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All viral hepatitis can have acute sx with RUQ pain, jaundice w/itching, dark urine, and clay stools; this will be ___ (conjugated) hyperbilirubinemia Viral hepatitis can cause false positive ___ (don't confuse with syphilis) Hepatits E (hepevirus) is naked +ssRNA with outbreaks in resource-limited areas; this is self-limited acute infection similar to HepA, *but [HY] with hepatic failure in ___ with mortality rates as high as 25%* Immune Reconstitution: if HIV is tx without tx HepB, can cause severe liver damage (do HepB testing before HIV therapy) *Two [HY] extrahepatic manifestations of HepB are ___ (fever, fatigue, abd pain, melena, neuropathy, rash) and ___ dz (membranous nephropathy w/nephrotic syndrome)* Patients w/HBV may have hepatitis flare that is actually ___ superinfection (Dx with serum HDAg, HDV RNA)

All viral hepatitis can have acute sx with RUQ pain, jaundice w/itching, dark urine, and clay stools; this will be direct (conjugated) hyperbilirubinemia Viral hepatitis can cause false positive VDRL (don't confuse with syphilis) Hepatits E (hepevirus) is nake +ssRNA with outbreaks in resource-limited areas; this is self-limited acute infection similar to HepA, *but [HY] with hepatic failure in pregnancy with mortality rates as high as 25%* Immune Reconstitution: if HIV is tx without tx HepB, can cause severe liver damage (do HepB testing before HIV therapy) *Two [HY] extrahepatic manifestations of HepB are polyarteritis nodosa (fever, fatigue, abd pain, melena, neuropathy, rash) and glomerular dz (membranous nephropathy w/nephrotic syndrome)* Patients w/HBV may have hepatitis flare that is actually HDV superinfection (Dx with serum HDAg, HDV RNA)

Alpha thalassemia is an abnormal copy of alpha chains (note: two copies on each chromosome 16, four genes total); alpha thalassemias are usually d/t *gene ___ of alpha chains* One missing alpha chain --> alpha thalassemia ___ (no sx) --- Two missing genes --> alpha thalassemia ___ (mild microcytic anemia w/no sx); alpha thalassemia minor is common in Asians and Africans - Africans are more likely to have ___ configuration, Asians are more likely to have ___ configuration (more dangerous for offspring) --- Three missing genes --> ___ dz - excess beta globin forms hemoglobin H (4 beta chains - ONLY SEEN w/THREE ALPHA CHAINS MISSING), which is useless d/t high O2 affinity (can't pass to tissues); pts p/w microcytic anemia + *abnormal RBC deformability w/___vascular hemolysis (+ splenomegaly, indirect hyper___ - DIFFERNTIATION FROM IDA!!*) Tx for HbH dz is *splenectomy + ___ (risk of iron overload)* --- Four missing genes --> hemoglobin ___ (not compatible w/life) - cannot form HbF, forms Hgb Barts w/four gamma chain (extremely high affinity for O2 --> can't deliver to tissues); will manifest w/h___ f___ + fetal death

Alpha thalassemia is an abnormal copy of alpha chains (note: two copies on each chromosome 16, four genes total); alpha thalassemias are usually d/t *gene deletion of alpha chains* One missing alpha chain --> alpha thalassemia minima (no sx) --- Two missing genes --> alpha thalassemia minor (mild microcytic anemia w/no sx); alpha thalassemia minor is common in Asians and Africans - Africans are more likely to have trans configuration, Asians are more likely to have cis configuration (more dangerous for offspring) --- Three missing genes --> HbH dz - excess beta globin forms hemoglobin H (4 beta chains - ONLY SEEN w/THREE ALPHA CHAINS MISSING), which is useless d/t high O2 affinity (can't pass to tissues); pts p/w microcytic anemia + *abnormal RBC deformability w/extravascular hemolysis (+ splenomegaly, indirect hyperbilirubinemia - DIFFERNTIATION FROM IDA!!*) Tx for HbH dz is *splenectomy + transfusions (risk of iron overload)* --- Four missing genes --> hemoglobin barts (not compatible w/life) - cannot form HbF, forms Hgb Barts w/four gamma chain (extremely high affinity for O2 --> can't deliver to tissues); will manifest w/hydrops fetalis + fetal death

Alpha-1 Antitrypsin deficiency results in e___ overactivity in lungs --> ___ emphysema in lower lobes (different from smokers - centriacinar emphysema in upper lobes) *[HY] A1-AT deficiency also l/t liver c___ 2/2 P___ of AAT in endoplasmic reticulum of hepatocytes* CLASSIC CASE: *young* COPD pt (40s) w/emphysematous changes most prominent at base - will ask about *___acinar involvement*, pts should NEVER smoke!

Alpha-1 Antitrypsin deficiency results in elastase overactivity in lungs --> panacinar emphysema in lower lobes (different from smokers - centriacinar emphysema in upper lobes) *[HY] A1-AT deficiency also l/t liver cirrhosis 2/2 POLYMERIZATION of AAT in endoplasmic reticulum of hepatocytes* CLASSIC CASE: *young* COPD pt (40s) w/emphysematous changes most prominent at base - will ask about *PANacinar involvement*, pts should NEVER smoke!

Alzheimer's is most common dementia, resulting from degeneration of cortex and loss of ___ cortical activity; *amyloid can be broken down to beta product (normally alpha), leading to dz; ___ enhances beta, while ___ decreases beta*; Down Syndrome is risk factor; on microscopy --> neurofibrillary ___ + tau protein + amyloid plaques Multi-Infarct Dementia results from multiple small strokes, *leading to ___ progression of sx* Lewy Body Dementia is collection of alpha-synuclein in basal ganglia (___) and cortex (___); classic triad is ___, then PD, hallucinations; *know what a Lewy body looks like!* Pick's disease is frontotemporal dementia, leading to ___ changes and aphasia; microscopy reveals ___ tau proteins (Pick bodies) CJD is prion disease --> *rapid onset dementia* with startle myoclonus, *spike-wave EEG complexes, and spongiform brain appearance

Alzheimer's is most common dementia, resulting from degeneration of cortex and loss of ACh cortical activity; *amyloid can be broken down to beta product (normally alpha), leading to dz; ApoE4 enhances beta, while ApoE2 decreases beta*; Down Syndrome is risk factor; on microscopy --> neurofibrillary tangles + tau protein + amyloid plaques Multi-Infarct Dementia results from multiple small strokes, *leading to stepwise progression of sx* Lewy Body Dementia is collection of alpha-synuclein in basal ganglia (Parkinsonism) and cortex (dementia); classic triad is dementia, then PD, hallucinations; *know what a Lewy body looks like!* Pick's disease is frontotemporal dementia, leading to behavior changes and aphasia; microscopy reveals spherical tau proteins CJD is prion disease --> *rapid onset dementia* with startle myoclonus, *spike-wave EEG complexes, and spongiform brain appearance

Amino acids are broken down into alpha ketoacids + NH3; NH3 is toxic to brain - must be converted to urea by kidneys In muscle, AA + alpha ketoglutarate combine to form alpha-ketoacid + glutamate (glutamate now carrying NH3) - this step requires B6 as cofactor There are two major methods for transfer of nitrogen from glutamate to liver for excretion in urea cycle: 1) glutamine synthesis (glutamate + NH4 --> glutamine, requires GLUTAMINE SYNTHETASE - in liver, glutamine can go back to glutamate --> urea cycle) 2) alanine cycle (glutamate [w/NH3] + pyruvate --> alanine [alanine now carrying NH3] + alpha-ketoglutarate; alanine goes to liver and combines with alpha-ketoglutarate --> pyruvate + glutamate; *THESE ARE SAME REACTIONS BUT IN REVERSE!*) The fact that pyruvate is produced in liver and consumed in skeletal muscle is huge for gluconeogenesis - pyruvate can be converted in glucose in liver, which is transferred to skeletal muscle to be used to produce pyruvate, which can be combined w/glutamate --> alanine (maintains cycle - deemed *CORI CYCLE*)

Amino acids can either be glucogenic or ketogenic (or both) Note that if converted to acetyl-CoA, that AA can *only be ketogenic (CANNOT be converted to oxaloacetate for use in gluconeogenesis)*; ketogenic AAs include leucine and lysine (*Loose Lies; DKA is a Loose Lose sitch*) Methionine, Histidine, and Valine are gluconeogenic (*Met His Valentine, who is SWEET*)

Amphetamines are stimulants (___ sympathomimetic) that increase dopamine/NE levels (promote release & prevent reuptake); intoxication --> hyperalert state w/SNS stimulation (tachy, HTN, mydriasis), fever, agitation Caffeine is stimulant that acts as antagonist of ___ receptors --> release of dopamine/NE + ___ (2/2 renal adenosine blockade); NOTE (CV tie-in): can't take caffeine (+ theophylline) before ___ 2/2 caffeine blocking adenosine receptor Nicotine is CNS stimulant --> activates SNS (2/2 nicotinic receptors in autonomic ganglia, adrenal medulla); withdrawal peaks at ___d, resolves after ___w To promote smoking cessation, assess *___ TO QUITTING* and *SET A ___* (bupropion, varenicline can be used)

Amphetamines are stimulants (indirect sympathomimetic) that increase dopamine/NE levels (promote release & prevent reuptake); intoxication --> hyperalert state w/SNS stimulation (tachy, HTN, mydriasis), fever, agitation Caffeine is stimulant that acts as antagonist of adenosine receptors --> release of dopamine/NE + diuresis (2/2 renal adenosine blockade); NOTE (CV tie-in): can't take caffeine (+ theophylline) before chemical stress test 2/2 caffeine blocking adenosine receptor Nicotine is CNS stimulant --> activates SNS (2/2 nicotinic receptors in autonomic ganglia, adrenal medulla); withdrawal peaks at 3-4d, resolves after 3-4w To promote smoking cessation, assess *BARRIERS TO QUITTING* and *SET A QUIT DATE* (bupropion, varenicline can be used)

Ampulla of Vater empties into the major d___ (halfway along 2nd part of duodenum), which delineates foregut to midgut (pt where celiac trunk transitions to ___) S___ surrounds major duodenal papilla - controls flow of bile/pancreatic enzymes; Sphincter of oddi syndrome is narrowing of SoO - p/w RUQ pain +/- recurrent pancreatitis that can be *exacerbated w/___*

Ampulla of Vater empties into the major duodenal papilla (halfway along 2nd part of duodenum), which delineates foregut to midgut (pt where celiac trunk transitions to SMA) Sphincter of Oddi surrounds major duodenal papilla - controls flow of bile/pancreatic enzymes; Sphincter of oddi syndrome is narrowing of SoO - p/w RUQ pain +/- recurrent pancreatitis that can be *exacerbated w/OPIOIDS*

Amyloidosis can l/t: *Renal: ___ syndrome* *Cardiac*: ___ cardiomyopathy --> arrhythmias + *wall thickening + ___ EKG (UNIQUE - different from HoCM!)* Neurologic: neuropathy Musculoskeletal: ___ GI: m___ (enlarged t___), hepatomegaly, malabsorption)

Amyloidosis can l/t: *Renal: nephrotic syndrome* *Cardiac*: restrictive cardiomyopathy --> arrhythmias + *wall thickening + low voltage EKG (UNIQUE - different from HoCM!)* Neurologic: neuropathy Musculoskeletal: CTS GI: macroglossia (enlarged tongue), hepatomegaly, malabsorption)

Amyloidosis is pathologic buildup of amyloid proteins in extracellular tissues (brain, kidneys, heart) All amyloid forms ___ and appears pink on standard biopsy - must differentiate with *Congo Red stain (___ on polarized light, d/t beta-sheets!)* Amyloid deposition can be localized (i.e., *Alzheimer's, T2DM, medullar thyroid cancer, isolated atrial amyloidosis, systemic senile [age-related] amyloidosis*) or diffuse (primary, secondary, and dialysis related) Senile (age-related) amyloidosis is d/t overproduction of *___ [getting older, stuff happens]* - usually seen in older pts (duh) and predominantly involves cardiac ventricles --> ___ Familial amyloidosis is d/t *___ [presents young, d/t mutation]* --> deposition in ___ (can tx w/liver transplant)

Amyloidosis is pathologic buildup of amyloid proteins in extracellular tissues (brain, kidneys, heart) All amyloid forms ___ sheets and appears ___ on standard biopsy - must differentiate with *___ stain (apple-green birefringence on polarized light, d/t beta-sheets!)* Amyloid deposition can be ___ (i.e., Alzheimer's, T2DM, medullar thyroid cancer, isolated atrial amyloidosis, systemic senile [age-related] amyloidosis) or diffuse (*primary, secondary, and dialysis related*) Primary (AL - A___ L___ chain) amyloidosis is a ___ cell malignancy l/t overproduction of ___ that deposit in tissue and form amyloid - can occur alone or in a/w MultMyel or WaldMac Secondary (AA, Amyloid A) amyloidosis occurs in chronic___ conditions (RA, AS, IBD) that l/t overproduction *serum ___ A proteins (which are acute phase reactants)* - can see in *F___ M___ F___ (major cause of death, tx with c___)* Dialysis-related amyloidosis results is 2/2 buildup of ___ (not removed in dialysis) --> bone, joint, and tendon deposition --> *c___ syndrome*

Amyloidosis is pathologic buildup of amyloid proteins in extracellular tissues (brain, kidneys, heart) All amyloid forms beta-pleated sheets and appears pink on standard biopsy - must differentiate with *Congo Red stain (apple-green birefringence on polarized light, d/t beta-sheets!)* Amyloid deposition can be localized (i.e., Alzheimer's, T2DM, medullar thyroid cancer, isolated atrial amyloidosis, systemic senile [age-related] amyloidosis) or diffuse (*primary, secondary, and dialysis related*) Primary (AL - Amyloid Light chain) amyloidosis is a plasma cell malignancy l/t overproduction of light chains that deposit in tissue and form amyloid - can occur alone or in a/w MultMyel or WaldMac Secondary (AA, Amyloid A) amyloidosis occurs in chronic inflammatory conditions (RA, AS, IBD) that l/t overproduction *serum amyloid A proteins (which are acute phase reactants)* - can see in *FAMILIAL MEDITERRANEAN FEVER (major cause of death, tx with colchicine)* Dialysis-related amyloidosis results is 2/2 buildup of beta-2-microglobulin (not removed in dialysis) --> bone, joint, and tendon deposition --> *carpal tunnel syndrome*

Anal canal is divided by pectinate (dentate, anocutaneous) line Above line, rectum is derived from ___ w/___ epithelium; Blood supply is ___ rectal aa (branch of IMA) and drainage is to superior rectal vv (can swell in ___); Innervation is visceral (*___ pain!*) --> internal hemorrhoids); Lymph drains to internal iliac nodes; Cancer above this line is ___ (rare) Below line, rectum is derived from ___ w/___ epithelium; Blood supply is internal pudendal aa (off iliac) and drainage is to IVC (does not drain to portal system); Innervation is somatic (*VERY PAIN___!*) --> external hemorrhoids; Lymph drains to superficial ___ nodes; Cancer below this line is s___ (MC) Imperforate anus (hindgut and ectoderm fail to fuse) is a/w ___ malformations (i.e., renal agenesis) and p/w failure to p___

Anal canal is divided by pectinate (dentate, anocutaneous) line Above line, rectum is derived from hindgut w/columnar epithelium; Blood supply is superior rectal aa (branch of IMA) and drainage is to superior rectal vv (can swell in portal HTN); Innervation is visceral (*no pain!*) --> internal hemorrhoids); Lymph drains to internal iliac nodes; Cancer above this line is adenocarcinoma (rare) Below line, rectum is derived from ectoderm w/stratified squamous epithelium; Blood supply is internal pudendal aa (off iliac) and drainage is to IVC (does not drain to portal system); Innervation is somatic (*VERY PAINFUL!*) --> external hemorrhoids; Lymph drains to superficial inguinal nodes; Cancer below this line is squamous cell carcinoma (MC) Imperforate anus (hindgut and ectoderm fail to fuse) is a/w GU malformations (i.e., renal agenesis) and p/w failure to pass meconium

Anemia of chronic disease occurs in a/w inflammation - seen in RA, lymphoma, etc.; AoCD is often ___, can be normocytic or microcytic (d/t low iron availability) AoCD is triggered by cytokines + inadequate EPO level + lack of availability of iron (*trapped in storage form by ___ - acute phase reactant!!*) H___ is acute phase reactant produced in liver w/anti-bacterial properties; hepcidin binds f___ in m___ and inhibits transport (*iron gets trapped in macrophages as ___ --> ferritin rises!*) Tx: fix underlying problem (doesn't respond to iron) Dx: low serum iron, high serum ferritin (trapped by *___*)

Anemia of chronic disease occurs in a/w inflammation - seen in RA, lymphoma, etc.; AoCD is often MILD, can be normocytic or microcytic (d/t low iron availability) AoCD is triggered by cytokines + inadequate EPO level + lack of availability of iron (*trapped in storage form by HEPCIDIN - acute phase reactant!!*) Hepcidin is acute phase reactant produced in liver w/anti-bacterial properties; hepcidin binds ferroportin in macrophages and inhibits transport (*iron gets trapped in macrophages as FERRITIN --> ferritin rises!*) Tx: fix underlying problem (doesn't respond to iron) Dx: low serum iron, high serum ferritin (trapped by *HEPCIDIN*)

Aneuploidy occurs 2/2 meiotic nondisjunction; if ___ --> diploid daughters (mixed genes, mom + dad copies) + empty daughters; if ___ --> 50% normal + 25% diploid (no gene mixing, 2 mom or 2 dad copies) + 25% empty Meiotic NDJ errors are common cause of trisomy - can determine NDJ in genotyping (dad 21A, mom 21B + 21C; baby 21ABC --> Mei___ NDJ, baby 21ABB --> Mei___ NDJ) Uniparental disomy is two copies of one 'rents chromosome and no copies of other 'rents chromosome (rare - requires abnormalities in both gametes); if 21AA --> isodisomy (Mei___ error), if 21 BC --> heterodisomy (Mei___ error) UniDis has normal phenotype, but increased risk for AR dz Robertsonian Translocation is fusion of long arms of two acrocentric (centromeres are close together) chroms (loss of short arms); t14:21 is most common and has six outcomes (___ [#] --> spont abort, ___ [#] --> norm, ___ [#] --> carrier, ___ [#] --> trisomy 21)

Aneuploidy occurs 2/2 meiotic nondisjunction; if Mei1 --> diploid daughters (mixed genes, mom + dad copies) + empty daughters; if Mei2 --> 50% normal + 25% diploid (no gene mixing, 2 mom or 2 dad copies) + 25% empty Meiotic NDJ errors are common cause of trisomy - can determine NDJ in genotyping (dad 21A, mom 21B + 21C; baby 21ABC --> Mei1 NDJ, baby 21ABB --> Mei2 NDJ) Uniparental disomy is two copies of one 'rents chromosome and no copies of other 'rents chromosome (rare - requires abnormalities in both gametes); if 21AA --> isodisomy (Mei2 error), if 21 BC --> heterodisomy (Mei1 error) UniDis has normal phenotype, but increased risk for AR dz Robertsonian Translocation is fusion of long arms of two acrocentric (centromeres are close together) chroms (loss of short arms); t14:21 is most common and has six outcomes (3 --> spont abort, 1 --> norm, 1 --> carrier, 1 --> trisomy 21)

Angiotensin II has several mechanisms to increase Na-H2O reabsorption: 1) direct PCT reabsorption through Na-H exchange (you know this from sketchy), 2) aldosterone release (you know this from sketchy) and *3) the ___ effect* When AII constricts efferent arteriole, there is less ___ pressure in the capillary beyond that point; additionally, oncotic pressure increases d/t AII-mediated efferent arteriole constriction (increases GFR --> increased H2O filtered --> ___ blood vessel oncotic pressure); both of these are deemed *capillary effect and increase Na and H2O resorption*

Angiotensin II has several mechanisms to increase Na-H2O reabsorption: 1) direct PCT reabsorption through Na-H exchange (you know this from sketchy), 2) aldosterone release (you know this from sketchy) and *3) the capillary effect* When AII constricts efferent arteriole, there is less hydrostatic pressure in the capillary beyond that point; additionally, oncotic pressure increases d/t AII-mediated efferent arteriole constriction (increases GFR --> increased H2O filtered --> increased blood vessel oncotic pressure); both of these are deemed *capillary effect and increase Na and H2O resorption*

Anti-phospholipid antibodies can occur in patients w/lupus Three important clinical consequences: 1) increased risk of venous and *___ thrombosis*, 2) increased ___, and 3) false positive ___ The three anti-phospholipid antibodies include anti-c___ (responsible for syphilis false-positive), lupus ___ (interferes w/PTT - gives false sense of hypocoaguability when actually hypercoaguable), and anti-Beta2 glycoprotein Patients w/Anti-PLA will be young and p/w ___ and DVT; *women will have recurrent ___*

Anti-phospholipid antibodies can occur in patients w/lupus Three important clinical consequences: 1) increased risk of venous and *arterial thrombosis*, 2) increased PTT, and 3) false positive syphilis The three anti-phospholipid antibodies include anti-cardiolipin (responsible for syphilis false-positive), lupus anticoagulant (interferes w/PTT - gives false sense of hypocoaguability when actually hypercoaguable), and anti-Beta2 glycoprotein Patients w/Anti-PLA will be young and p/w stroke and DVT; *women will have recurrent fetal losses*

Antiphospholipid syndrome l/t three important clinical consequences: 1) increased risk of venous *AND ___* thrombosis (including *recurrent ___*), 2) prolonged ___, 3) false-positive ___ Three antiphospholipid Abs include 1) anti-___(FP syphilis test), 2) *___ (l/t prolonged PTT - how it gets its name)*, and 3) anti-beta2 glycoprotein To meet APLS dx, need one ___ criteria (one of the Abs) + one ___ criteria (thrombosis or spontaneous abortion) Lupus anticoagulant binds *___ in PTT test that is required for clotting and interferes with test!*; to identify presence of lupus anticoagulant, *DO A ___ STUDY!!* Hemophilia ___ correct w/mixing study; Lupus anticoagulant ___ correct w/mixing study ^Anti-cardiolipin and anti-beta2 glycoprotein can be identified w/ELISA

Antiphospholipid syndrome l/t three important clinical consequences: 1) increased risk of venous *AND ARTERIAL* thrombosis (including *recurrent fetal losses*), 2) prolonged PTT, 3) false-positive RPR/VDRL Three antiphospholipid Abs include 1) anti-cardiolipin (FP syphilis test), 2) *lupus anticoagulant (l/t prolonged PTT - how it gets its name)*, and 3) anti-beta2 glycoprotein To meet APLS dx, need one lab criteria (one of the Abs) + one clinical criteria (thrombosis or spontaneous abortion) Lupus anticoagulant binds *phospholipid in PTT test that is required for clotting and interferes with test!*; to identify presence of lupus anticoagulant, *DO A MIXING STUDY!!* Hemophilia will correct w/mixing study; Lupus anticoagulant will not correct w/mixing study ^Anti-cardiolipin and anti-beta2 glycoprotein can be identified w/ELISA

Antiplatelet drugs include ASA, ___ blockers (-grel), IIb/IIIa inhibitors, PDE inhibitors - recall that thromboxane ___, ADP, IIb/IIIa aggregation, and low cAMP all contribute to platelet activation ASA *irreversibly* inhibits COX --> no ___ (from AA) [use for CAD, stroke] ADP blockers (-grel) irreversibly block ___ --> no ADP-induced aggregation Rare SE of P2Y12 blockers is T___; tigacrelor is only *reversible* P2Y12 blocker (can cause dyspnea) PDE inhibitors increase ___ --> decreased platelet activation [dipyramidole, cilostazole (also raises cAMP in vascular smooth muscle --> vasodilation --> *use in cl___*] IIb/IIIa receptor blockers --> prevent platelet ___ (via IIb/IIIa) [can l/t thrombocytopenia - monitor ___!] ^NOTE: COX prevents TXA and prostaglandin production --> shifts to production of ___ --> allergic rxn effect ^NOTE: NSAIDs all inhibit COX --> decreased ___ synthesis --> decreased platelet activation ("blood thinner", ASA is only irreversible NSAID)

Antiplatelet drugs include ASA, ADP blockers (-grel), IIb/IIIa inhibitors, PDE inhibitors - recall that thromboxane A2, ADP, IIb/IIIa aggregation, and low cAMP all contribute to platelet activation ASA *irreversibly* inhibits COX --> no TXA2 (from AA) [use for CAD, stroke] ADP blockers (-grel) irreversibly block P2Y12 --> no ADP-induced aggregation Rare SE of P2Y12 blockers is TTP; tigacrelor is only *reversible* P2Y12 blocker (can cause dyspnea) PDE inhibitors increase cAMP --> decreased platelet activation [dipyramidole, cilostazole (also raises cAMP in vascular smooth muscle --> vasodilation --> *use in claudication*] IIb/IIIa receptor blockers --> prevent platelet aggregation (via IIb/IIIa) [can l/t thrombocytopenia - monitor platelet count!] ^NOTE: COX prevents TXA and prostaglandin production --> shifts to production of leukotrienes --> allergic rxn effect ^NOTE: NSAIDs all inhibit COX --> decreased TXA2 synthesis --> decreased platelet activation ("blood thinner", ASA is only irreversible NSAID)

___ (anatomy?) of lungs have high V/Q (~3, ventilation is low, flow is lower --> relative incr. in ventilation, relatively ___ O2/low CO2) ___ (anatomy?) of lungs have low V/Q (~0.6, ventilation is high, flow is higher --> relative decr. in ventilation) W/exercise, ventilation will incr. greater than blood flow --> V/Q will approach 1 *[HY] In TB, ___ lesions are seen d/t TB liking highly ___ areas of body* Some V/Q mismatch examples worth knowing: *intracardiac shunt --> pure shunt (___ correction w/O2), inhaled peanut --> V/Q=___ (shunt), pulmonary embolism --> V/Q=___ (dead space)*

Apex of lungs have high V/Q (~3, ventilation is low, flow is lower --> relative incr. in ventilation, relatively high O2/low CO2) Base of lungs have low V/~ (~0.6, ventilation is high, flow is higher --> relative decr. in ventilation) W/exercise, ventilation will incr. greater than blood flow --> V/Q will approach 1 *[HY] In TB, apical lesions are seen d/t TB liking highly oxygenated areas of body* Some V/Q mismatch examples worth knowing: *intracardiac shunt --> pure shunt (no correction w/O2), inhaled peanut --> V/Q=0 (shunt), pulmonary embolism --> V/Q=infinity (dead space)*

Appendicitis occurs when opening to cecum becomes obstructed (adults - fecaliths, children - lymphoid ___); *pain starts periumbilical (poor ___ localization) --> RLQ (when ___ peritoneum is involved)* A diverticulum is blind pouch extending from GI tract d/t breakdown of *___ mucosa (false diverticulum)*, often where ___ recta penetrates muscularis of colon; diverticulosis is when many diverticula are present, usually 2/2 chronic straining to pass stool (chronic ___ - low fiber diet); often asymptomatic but can lead to *diverticulitis* Diverticulitis is inflammation of diverticulum, classically w/*___ abdominal pain (+ rebound tenderness)*, fever, leukocytosis, and *occult blood*; tx w/Abx +/- surgery Diverticulitis complications include 1) a___ (diverticulitis that does not improve after abx), 2) bowel obstruction, 3) f___ (commonly bladder w/*pneumaturia, fecaluria*), 4) perforation (*rigid abdomen*)

Appendicitis occurs when opening to cecum becomes obstructed (adults - fecaliths, children - lymphoid hyperplasia); *pain starts periumbilical (poor visceral localization) --> RLQ (when parietal peritoneum is involved)* A diverticulum is blind pouch extending from GI tract d/t breakdown of *muscularis mucosa (false diverticulum)*, often where vasa recta penetrates muscularis of colon; diverticulosis is when many diverticula are present, usually 2/2 chronic straining to pass stool (chronic constipation - low fiber diet); often asymptomatic but can lead to *diverticulitis* Diverticulitis is inflammation of diverticulum, classically w/*LLQ abdominal pain (+ rebound tenderness)*, fever, leukocytosis, and *occult blood*; tx w/Abx +/- surgery Diverticulitis complications include 1) abscess (diverticulitis that does not improve after abx), 2) bowel obstruction, 3) fistula (commonly bladder w/*pneumaturia, fecaluria*), 4) perforation (*rigid abdomen*)

Aspergillus form ___ angled branching septated hyphae with ___ on the tips *Lymph tissue in patients with aspergillus ABPA (seen in asthma and CF patients) reveals increased Th___ CD4+ T-cells, interleukins (IL-___, IL-___ - synthesized by Th2 cells!), ___philia (d/t interleukin production), and ___ Ab production (d/t eosinophils - type ___ HS rxn)* Cr___ can be cultured on Sabouraud's agar (selective for FUNGI)

Aspergillus form acute angled branching septated hyphae with conidiophores on the tips *Lymph tissue in patients with aspergillus ABPA (seen in asthma and CF patients) reveals increased Th2 CD4+ T-cells, interleukins (IL-4, IL-5 - synthesized by Th2 cells!), eosinophilia (d/t interleukin production), and IgE Ab production (d/t eosinophils - type I HS rxn)* Cryptococcus can be cultured on Sabouraud's agar (selective for FUNGI)

___ PNA is seen in pts w/seizures, alcohol, neuromuscular weakness (ALS) Bugs causing A-PNA are *___ (peptostreptococcus, prevotella, bacteroides - same bugs cause lung abscess)*, Klebsiella, Staph - tx w/___ Klebsiella PNA will present w/___ sputum Lung abscess (caused by above) will present as contained space in lungs w/___ level - tx w/clindamycin ___ is interstitial pneumonia - AIDS-defining illness, use silver stain of BAL to dx; tx w/TMP-SMX (can use dapson), ppx w/___ at CD4<200

Aspiration PNA is seen in pts w/seizures, alcohol, neuromuscular weakness (ALS) Bugs causing A-PNA are *anaerobes (peptostreptococcus, prevotella, bacteroides - same bugs cause lung abscess)*, Klebsiella, Staph - tx w/clindamycin Klebsiella PNA will present w/currant-jelly sputum Lung abscess (caused by above) will present as contained space in lungs w/air fluid level - tx w/clindamycin PCP is interstitial pneumonia - AIDS-defining illness, use silver stain of BAL to dx; tx w/TMP-SMX (can use dapson), ppx w/TMP-SMX at CD4<200

Asthma is reversible bronchoconstriction, usually 2/2 allergic stimulus (type ___ HS rxn) often associated w/atopic conditions Trigger avoidance is huge part of tx *Aspirin* can l/t aspirin-exacerbated respiratory dz (AERD); *[HY] this dz is d/t overproduction in ___ (aspirin is COX inhibitor --> shunts AA to leukotriene, dysregulation of arachidonic acid metabolism) - tx is leukotriene receptor ___ (montelukast)*, will also see chronic s___ + nasal polyps Asthma sx are episodic w/decreased inspiratory:expiratory ratio (longer time spent ___ past obstruction) + reduced peak flow - can cause pulsus paradoxus Path: *C___ spiral (whorled mucous plugs + epithelial cells)* and *C___-Leyden crystals*

Asthma is reversible bronchoconstriction, usually 2/2 allergic stimulus (type I HS rxn) often associated w/atopic conditions Trigger avoidance is huge part of tx *Aspirin* can l/t aspirin-exacerbated respiratory dz (AERD); *[HY] this dz is d/t overproduction in LEUKOTRIENES (aspirin is COX inhibitor --> shunts AA to leukotriene, dysregulation of arachidonic acid metabolism) - tx is leukotriene receptor antagonist (montelukast)*, will also see chronic sinusitis + nasal polyps Asthma sx are episodic w/decreased inspiratory:expiratory ratio (longer time spent inhaling past obstruction) + reduced peak flow - can cause pulsus paradoxus Path: *Curschmann's spiral (whorled mucous plugs + epithelial cells)* and *Charcot-Leyden crystals*

___ are a major part of reactive gliosis An important marker for astrocytes and astrocytomas is ___ ___ infects astrocytes in HIV patients HIV can also persist in ___ in patients

Astrocytes are a major part of reactive gliosis An important marker for astrocytes and astrocytomas is GFAP JC Virus infects astrocytes in HIV patients HIV can also persist in microglia in patients

At puberty, ___ contributes to penis/scrotum/seminal vesicle enlargement, pubic and underarm hair, and voice deepening - on the face, androgens stimulate ___ (via growth of sebaceous glands - also seen in PCOS and CAH w/androgen excess); it can also mediate growth spurt, though this is mediated *via ___* In adults, androgens stimulate ___ growth (finasteride can be used for tx of BPH - prevents testosterone --> DHT conversion), lowered HDL/___ LDL, and *androgenic alopecia (male pattern balding - driven by DHT , use fi___! [and minoxidil lol])* Exogenous testosterone (body builders) is available to tx male hypogonadism --> increased muscle mass + increased bond density; adverse effects include ___ hematocrit, acne, balding, small testes, *___ (conversion to estrogen)*, and worsening BPH, as well as fall in sperm count (exogenous testosterone cannot penetrate ___ & suppresses LH for endogenous testosterone) ___ can block androgen receptors & decrease androgen production (via 17-alpha-hydroxylase) --> gynecomastia; in women, take advantage of these effects to tx hirsutism, alopecia, and acne (eplerenone does not have these effects)

At puberty, testosterone contributes to penis/scrotum/seminal vesicle enlargement, pubic and underarm hair, and voice deepening - on the face, androgens stimulate acne (via growth of sebaceous glands - also seen in PCOS and CAH w/androgen excess); it can also mediate growth spurt, though this is mediated *via ESTROGEN* In adults, androgens stimulate prostate growth (finasteride can be used for tx of BPH - prevents testosterone --> DHT conversion), lowered HDL/increased LDL, and *androgenic alopecia (male pattern balding - driven by DHT , use finasteride! [and minoxidil lol])* Exogenous testosterone (body builders) is available to tx male hypogonadism --> increased muscle mass + increased bond density; adverse effects include increased hematocrit, acne, balding, small testes, *gynecomastia (conversion to estrogen)*, and worsening BPH, as well as fall in sperm count (exogenous testosterone cannot penetrate testes & suppresses LH for endogenous testosterone) Spironolactone can block androgen receptors & decrease androgen production (via 17-alpha-hydroxylase) --> gynecomastia; in women, take advantage of these effects to tx hirsutism, alopecia, and acne (eplerenone does not have these effects)

*Amphotericin side effects include fever/chills, phlebitis (pain/inflammation of vein), hypotension/arrhythmias, NEPHROTOXICITY (including ___ RTA), nephrogenic diabetes insipidus, electrolyte derangements (hypo___, hypo___), and anemia* *NYSTATIN is highly toxic when given IV - never used systemically, but can be used for "swish and swallow" for ___ as well as ___ (KNOW THESE FOR STEP!)* *GRISEOFULVIN is not safe in three demographics: pre___, ___ disease, and porphyria patients*

*Amphotericin side effects include fever/chills, phlebitis (pain/inflammation of vein), hypotension/arrhythmias, NEPHROTOXICITY (including distal [type I] RTA), nephrogenic diabetes insipidus, electrolyte derangements (hypomagnesemia, hypokalemia), and anemia* *NYSTATIN is highly toxic when given IV - never used systemically, but can be used for "swish and swallow" for thrush and diaper rash (KNOW THESE FOR STEP!)* *GRISEOFULVIN is not safe in three demographics: pregnancy, liver disease, and porphyria patients*

*C botulinum has many different variants of toxin, some of which are carried by ___* *C perfringens produces alpha toxin, a phospholipase that acts on lecithin - degrades ___ in cell membranes to cause ___; C perfringens can cause late-onset food poisoning 2/2 consuming ___ that need to grow and produce toxin (contrast to S aureus and B cereus)* *C difficile produces exotoxins A and B, which destroy ___ elements of GI cells --> pseudomembrane* *B anthracis is the only bacteria with ___ capsule (NOT polysaccharide), which contains ___ and prevents phagocytosis; B anthracis is seen in farm workers and causes ___ (2/2 edema factor) surrounding BLACK ___*

*C botulinum has many different variants of toxin, some of which are carried by bacteriophages* *C perfringens produces alpha toxin, a phospholipase that acts on lecithin - degrades phospholipids in cell membranes to cause hemolysis; C perfringens can cause late-onset food poisoning 2/2 consuming spores that need to grow and produce toxin (contrast to S aureus and B cereus)* *C difficile produces exotoxins A and B, which destroy cytoskeleton elements of GI cells --> pseudomembrane* *B anthracis is the only bacteria with polypeptide capsule (NOT polysaccharide), which contains D-glutamate and prevents phagocytosis; B anthracis is seen in farm workers and causes EDEMA (2/2 edema factor) surrounding BLACK ULCER*

*Cholera causes a toxin-mediated disease, permanently activating ___ leading to elevated ___; IMPORTANTLY, this toxin is carried by ___ (i.e., lysogenic)* Haemophilus ducreyi causes a pain___ genital ulcer (different from syphilis - pain___), tx with azithromycin/CTX *Y enterocolitica can cause inflammation around ___ nodes --> mesenteric adenitis that mimics ___*

*Cholera causes a toxin-mediated disease, permanently activating Gs leading to elevated cAMP; IMPORTANTLY, this toxin is carried by bacteriophage (i.e., lysogenic)* Haemophilus ducreyi causes a PAINFUL genital ulcer (different from syphilis - painless), tx with azithromycin/CTX *Y enterocolitica can cause inflammation around appendix/mesenteric nodes --> mesenteric adenitis that mimics appendicitis*

*Disseminated Intravascular Coagulation*: widespread activation of clotting cascade w/diffuse ___ (platelets AND fibrin) --> ischemia; platelets and clotting factors are *CONSUMED* and RBC destruction --> anemia DIC is always 2/2 another process, including ___ emergencies (*___ fluid contains TISSUE FACTOR --> activates coagulation cascade*), sepsis (LPS activates coagulation), malignancy (*ESPECIALLY ___!*), rattlesnake bites (venom contains thrombin-like glycoproteins) DIC dx is (*all abnormal*) w/prolonged PT/PTT, thrombocytopenia, ___ fibrinogen, ___ (anemia + elevated LDH/haptoglobin), schistocytes on smear, elevated D-dimer Tx: treat underlying d.o, also *FFP, RBCs, platelets, cryoprecipitate* --- ___ has thrombocytopenia + MAHA + prolonged PT/PTT ___ has thrombocytopenia + MAHA w/fever and confusion ___ has thrombocytopenia + MAHA w/child and diarrheal illness ___ has thrombocytopenia

*Disseminated Intravascular Coagulation*: widespread activation of clotting cascade w/diffuse thrombi (platelets AND fibrin) --> ischemia; platelets and clotting factors are *CONSUMED* and RBC destruction --> anemia DIC is always 2/2 another process, including obstetric emergencies (*amniotic fluid contains TISSUE FACTOR --> activates coagulation cascade*), sepsis (LPS activates coagulation), malignancy (*ESPECIALLY APML!*), rattlesnake bites (venom contains thrombin-like glycoproteins) DIC dx is (*all abnormal*) w/prolonged PT/PTT, thrombocytopenia, low fibrinogen, MAHA (anemia + elevated LDH/haptoglobin), schistocytes on smear, elevated D-dimer Tx: treat underlying d.o, also *FFP, RBCs, platelets, cryoprecipitate* --- DIC has thrombocytopenia + MAHA + prolonged PT/PTT TTP has thrombocytopenia + MAHA w/fever and confusion HUS has thrombocytopenia + MAHA w/child and diarrheal illness ITP has thrombocytopenia

*Follicular Adenoma*: benign thyroid nodule of follicular cells that is *___ by fibrous capsule (FNA cannot distinguish btwn it and...* *Follicular ___*: thyroid cancer of follicular cells that *invades thyroid capsule/vasculature* (FNA cannot determine capsular invasion - *monitor pathology over time*) Most carcinomas spread through lymph, *but FC spreads ___* --- *Papillary Carcinoma*: MC thyroid cancer with *___ exposure as risk factor (cover thyroid in OR)*; p/w painless thyroid nodule with excellent prognosis *HISTO: p___ bodies, O___ A___ Nuclei [Papi, Moma adopt Orphan], nuclear grooves (coffee beans)* --- *Medullary Carcinoma*: cancer of ___ cells that produce calcitonin --> *[HY] can present as hypocalcemia*; A/w MEN___ and ___ (RET mutation) *[HY] On biopsy, will see ___ (stains Congo red)* --- *___ Carcinoma*: shitty everything (old pts, awful histo, poor prognosis) *Will be tested for understanding of anatomy (esophagus --> ___, recurrent laryngeal nn --> ___, trachea --> ___)* Don't confuse w/Riedel's (will be seen in young pt w/___ thyroid)

*Follicular Adenoma*: benign thyroid nodule of follicular cells that is *completely surrounded by fibrous capsule (FNA cannot distinguish btwn it and...* *Follicular Carcinoma*: thyroid cancer of follicular cells that *invades thyroid capsule/vasculature* (FNA cannot determine capsular invasion - *monitor pathology over time*) Most carcinomas spread through lymph, *but FC spreads hematogenously* --- *Papillary Carcinoma*: MC thyroid cancer with *prior radiation exposure as risk factor (cover thyroid in OR)*; p/w painless thyroid nodule with excellent prognosis *HISTO: psamMOMA bodies, Orphan Annie Nuclei [Papi, Moma adopt Orphan], nuclear grooves (coffee beans)* --- *Medullary Carcinoma*: cancer of parafollicular (C) cells that produce calcitonin --> *[HY] can present as hypocalcemia*; A/w MEN2A and 2B (RET mutation) *[HY] On biopsy, will see AMYLOID (stains Congo red)* --- *Anaplastic Carcinoma*: shitty everything (old pts, awful histo, poor prognosis) *Will be tested for understanding of anatomy (esophagus --> dysphagia, recurrent laryngeal nn --> hoarseness, trachea --> dyspnea)* Don't confuse w/Riedel's (will be seen in young pt w/Rock hard thyroid)

*HSV-1 will cause acute infection, then live in latent state in the ___ GANGLIA* (causes temporal lobe encephalitis) *HSV-2 will cause acute infection, then live in latent state in the ___ GANGLIA* (causes meningitis) *VZV will cause acute infection, then live in latent state in the ___ GANGLIA* - VZV can reactivate in patients with IBD EBV expresses gp350/220 that binds to B-cell receptor CD21 - CD21 is B-cell receptor for C___ fragment of complement --> allows for EBV entrance into cells EBV + ___ may result in diffuse maculopapular rash that does not represent allergic reaction EBV symptoms with negative monospot --> ___ mononucleosis *HY: rhabdovirus has bullet-shaped envelope that forms "___ bodies" in neurons/___ cells; virus binds ___ receptors on peripheral nerves and migrate to CNS*

*HSV-1 will cause acute infection, then live in latent state in the TRIGEMINAL NERVE GANGLIA* (causes temporal lobe encephalitis) *HSV-2 will cause acute infection, then live in latent state in the LUMBOSACRAL GANGLIA* (causes meningitis) *VZV will cause acute infection, then live in latent state in the DORSAL ROOT GANGLIA* - VZV can reactivate in patients with IBD EBV expresses gp350/220 that binds to B-cell receptor CD21 - CD21 is B-cell receptor for C3d fragment of complement --> allows for EBV entrance into cells EBV + penicillin may result in diffuse maculopapular rash that does not represent allergic reaction EBV symptoms with negative monospot --> CMV mononucleosis *HY: rhabdovirus has bullet-shaped envelope that forms "Negri bodies" in neurons/Purkinje cells; virus binds ACh receptors on peripheral nerves and migrate to CNS*

*HY: E coli have ___ that allow attachment to urinary tract --> UTIs/pyelo; Neisseria gonorrhea has pili that display ___ --> reinfection with different strains of gonorrhea* ___ components include coat (outermost layer that is keratin-like and impermeable to chemicals), cortex/core wall (inner layer that is peptidoglycan-heavy), and dipicolinic acid (help with heat resistance) ___ and ___ species form spores (anthracis, cereus, perfringens, tetani, botulinum)

*HY: E coli have pili/fimbriae that allow attachment to urinary tract --> UTIs/pyelo; Neisseria gonorrhea has pili that display antigenic variation --> reinfection with different strains of gonorrhea* Spore components include coat (outermost layer that is keratin-like and impermeable to chemicals), cortex/core wall (inner layer that is peptidoglycan-heavy), and dipicolinic acid (help with heat resistance) Bacillus and Clostridium species form spores (anthracis, cereus, perfringens, tetani, botulinum)

*HY: HIV gp___ mutates rapidly leading to antigenic variation; V3 loop is highly immunogenic and will mount Ab response, though Ab neutralization is difficult 2/2 ___* HIV time course highlights: 1) initial spike in viral load correlates with acute HIV syndrome, 2) ___ T-cells are most important in clinical latency period, and 3) viral load set point (i.e., where VL sets after acute syndrome) is correlative with disease severity

*HY: HIV gp120 mutates rapidly leading to antigenic variation; V3 loop is highly immunogenic and will mount Ab response, though Ab neutralization is difficult 2/2 variation* HIV time course highlights: 1) initial spike in viral load correlates with acute HIV syndrome, 2) CD8 T-cells are most important in clinical latency period, and 3) viral load set point (i.e., where VL sets after acute syndrome) is correlative with disease severity

*HY: depression has affects on sleep phys, such that REM starts ___ after onset (___ REM latency), increased ___ sleep, and decreased ___ sleep* ___ are physical events/unwanted experiences occurring with sleep; can be REM- (*sleep ___*) and nREM-related nREM d/o's occur in ___ (earlier in night when more N3 sleep occurs) and include sleep walking, sleep terrors, sleep eating disorders; importantly, *no recollection by pt*; tx with benzos (decreases ___ sleep)

*HY: depression has affects on sleep phys, such that REM starts quicker after onset (decreased REM latency), increased REM sleep, and decreased N3 sleep* Parasomnias are physical events/unwanted experiences occurring with sleep; can be REM- (*sleep paralysis*) and nREM-related nREM occur in N3 (earlier in night when more N3 sleep occurs) and include sleep walking, sleep terrors, sleep eating disorders; importantly, *no recollection by pt*; tx with benzos (decreases N3 sleep)

*Idiopathic Thrombocytopenic Purpura*: disorder of decreased platelet survival, often 2/2 *anti-___ antibodies* --> consumption by *___* [remember bolded for Step 1] Can be 2/2 autoimmune d.o (SLE), viral illness (HIV), malignancy (CLL) Tx: steroids, IVIG, *s___ for refractory tx* --- *Thrombotic Thrombocytopenic Purpura*: disorder of small vessel thrombus formation --> platelet consumption --> thrombocytopenia, all 2/2 decreased activity *___* --> decreased cleavage of *vWF ___* --> *free floating vWF multimers* --> overactive platelet adhesion + aggregation --> *___!!* TTP is usually 2/2 *acquired Abs against ___* - large vWF multimers accumulate in areas of high shear stress (i.e., small vessels) l/t obstruction TTP is an example of microangiopathic hemolytic anemia w/___ LDH, low haptoglobin, and *___ on peripheral smear (also seen in HUS, DIC)* (also thrombocytopenia + ___ PT/PTT [differentiates from DIC]) TTP p/w Fever, Anemia (MAHA), Thrombocytopenia, ___, and Neuro sx (AMS) [FAT RN + petechial bleed] --- *Hemolytic Uremic Syndrome*: very similar to TTP (MAHA, thrombocytopenia, AKI) but *without fever or ___ sx (TTP focused on kidneys!) and with bloody diarrhea + child*

*Idiopathic Thrombocytopenic Purpura*: disorder of decreased platelet survival, often 2/2 *anti-GPIIb/IIIa antibodies* --> consumption by *splenic macrophages* [remember bolded for Step 1] Can be 2/2 autoimmune d.o (SLE), viral illness (HIV), malignancy (CLL) Tx: steroids, IVIG, *splenectomy for refractory tx* --- *Thrombotic Thrombocytopenic Purpura*: disorder of small vessel thrombus formation --> platelet consumption --> thrombocytopenia, all 2/2 decreased activity *ADAMTS13* --> decreased cleavage of *vWF MULTIMER* --> *free floating vWF multimers* --> overactive platelet adhesion + aggregation --> *THROMBOSIS!!* TTP is usually 2/2 *acquired Abs against ADAMTS13* - large vWF multimers accumulate in areas of high shear stress (i.e., small vessels) l/t obstruction TTP is an example of microangiopathic hemolytic anemia w/elevated LDH, low haptoglobin, and *SCHISTOCYTES on peripheral smear (also seen in HUS, DIC)* (also thrombocytopenia + normal PT/PTT [differentiates from DIC]) TTP p/w Fever, Anemia (MAHA), Thrombocytopenia, Renal failure, and Neuro sx (AMS) [FAT RN + petechial bleed] --- *Hemolytic Uremic Syndrome*: very similar to TTP (MAHA, thrombocytopenia, AKI) but *without fever or CNS sx (TTP focused on kidneys!) and with bloody diarrhea + child*

*Man*tle cell lymphoma is B-cell malignancy that *EXPRESSES CD___ (UNIQUE - also seen in CLL!)* seen in older *men* w/poor prognosis Classic translocation seen is *___ (Cyclin D1:IgG heavy chain --> overexpression of ___ --> cells promoted from G1 to S phase)*

*Man*tle cell lymphoma is B-cell malignancy that *EXPRESSES CD5 (UNIQUE - also seen in CLL!)* seen in older *men* w/poor prognosis Classic translocation seen is *t11;14 (Cyclin D1:IgG heavy chain --> overexpression of cyclin D1 --> cells promoted from G1 to S phase)*

*T-Cell Subpopulations:* Th1: *cell-mediated* immunity - macrophages secrete IL-___ (*drives Th1 production*); Th1 activates CD___ T-cells and ___, promotes Ig___ subclasses (opsonizing/complement) Th1 produces *IL-___* (drives *T-cell growth, both CD4/8* - also NKs [less HY]) and *___* (activates macrophages [GRANULOMA FORMATION]; suppresses Th2 cells) NOTE: macrophages and Th1 cells are basically having a bro-fest - Th1 activates M-Phage w/IFN, M-Phage activates Th1 w/IL12 (number stimulated by number!) Th2: humoral immunity, activate B-cells to promote antibodies (Ig___, Ig___) Th2 produces *IL-___ (MAJOR CYTOKINE - activates Th2 & suppresses Th1; promotes IgE production)*, IL-5 (Ig___ production, activates EOs), IL-10 (weird one - ___-inflammatory cytokine, atTENuates response) Th1 and Th2 both have activators (1: IFN, IL-12; 2: IL-4), inhibitors (1: IL-4, IL-10; 2: IFN)

*T-Cell Subpopulations:* Th1: cell-mediated immunity - macrophages secrete IL-12 (*drives Th1 production*); Th1 activates CD8 T-cells and macrophages, promotes IgG subclasses (opsonizing/complement) Th1 produces *IL-2* (drives *T-cell growth, both CD4/8* - also NKs [less HY]) and *IFN-gamma* (activates macrophages [GRANULOMA FORMATION]; suppresses Th2 cells) NOTE: macrophages and Th1 cells are basically having a bro-fest - Th1 activates M-Phage w/IFN, M-Phage activates Th1 w/IL12 (number stimulated by number!) Th2: humoral immunity, activate B-cells to promote antibodies (IgE, IgA) Th2 produces *IL-4 (MAJOR CYTOKINE - activates Th2 & suppresses Th1; promotes IgE production)*, IL-5 (IgA production, activates EOs), IL-10 (weird one - anti-inflammatory cytokine, atTENuates response) Th1 and Th2 both have activators (1: IFN, IL-12; 2: IL-4), inhibitors (1: IL-4, IL-10; 2: IFN)

*T-cells only recognized biomolecule ___* T-cells are useless until they encounter a___ cells, which present antigen on self-MHC After activation by APC, T-cells then recognize Ag via T-cell receptor (made up of alpha and beta chains) that is linked to *CD___ (seen in CD4 and CD8 cells!! Diff from B-cells!!)*; TCRs are encoded by genes that can rearrange for diversity (V___ w/hypervariable domains) CD4 T-cells are activated by APCs (dendritic cells, macrophages, *___-cells*) via antigen presentation on MHC2 binding to TCR and CD4 IMPORTANTLY: MHC2 is bound to "i___ c___" in APC endoplasmic reticulum, which *prevents APC host antigens (i.e., self-antigens) from binding on MHC2 (a way of protecting from autoimmune dz); once MHC2 merges w/lysosome, i___ c___ is released --> MHC2 binds foreign antigen --> MHC2 goes to surface* CD4 T-cells also require ___ protein (on APC) to bind CD28 (on T-cell) for co-stimulation (another mechanism to prevent autoimmunity) - will have three total bonds: 1) ___-MHC2, 2) ___-MHC2, 3) B7-CD___(B7xCD4=?) When activated, CD4 T-cells can 1) stimulate B-cells (class ___), 2) stimulate CD8 T-cells, 3) activate macrophages

*T-cells only recognized biomolecule PEPTIDE CHAINS* T-cells are useless until they encounter antigen-presenting cells, which present antigen on self-MHC After activation by APC, T-cells then recognize Ag via T-cell receptor (made up of alpha and beta chains) that is linked to *CD3 (seen in CD4 and CD8 cells!! Diff from B-cells!!)*; TCRs are encoded by genes that can rearrange for diversity (VDJC w/hypervariable domains) CD4 T-cells are activated by APCs (dendritic cells, macrophages, *B-cells*) via antigen presentation on MHC2 binding to TCR and CD4 IMPORTANTLY: MHC2 is bound to "invariant chain" in APC endoplasmic reticulum, which *prevents APC host antigens (i.e., self-antigens) from binding on MHC2 (a way of protecting from autoimmune dz); once MHC2 merges w/lysosome, invariant chain is released --> MHC2 binds foreign antigen --> MHC2 goes to surface* CD4 T-cells also require B7 protein (on APC) to bind CD28 (on T-cell) for co-stimulation (another mechanism to prevent autoimmunity) - will have three total bonds: 1) TCR-MHC2, 2) CD4-MHC2, 3) B7-CD28 When activated, CD4 T-cells can 1) stimulate B-cells (class switching), 2) stimulate CD8 T-cells, 3) activate macrophages

*The most common method of suicide is via ___* The SAD PERSONS scale is used to determine suicide risk (___) ECT can be used for tx of refractory depression; *importantly, main side effect to know is ___*; ECT can be used safely in pregnancy

*The most common method of suicide is via firearms* The SAD PERSONS scale is used to determine suicide risk (sex - male, age - young or old, depression - hx, prior attempt, ethanol/drugs, rational thinking loss [psychosis], sickness - medical illness, organized plan, no spouse - lack of social support, stated intent) ECT can be used for tx of refractory depression; *importantly, main side effect to know is AMNESIA*; ECT can be used safely in pregnancy

*___ Order Elimination*: constant rate of elimination over time (no dependence/variance with [drug], *no half-life*) - called zero order b/c: Rate = A x [Drug]^0; *this is seen with a___, phenytoin, aspirin* *___ Order Elimination*: rate varies w/[Drug] - % change over a given time is constant *(half-life!)* - called first order b/c: Rate = A x [Drug]^1; most drugs follow 1st order elimin. *___-Dependent Elimination*: drugs metabolized quickly to point that elimination is determined by blood flow to organ (usually liver) - deemed "high extraction" drugs (morphine is classic ex.); *pts w/Heart Failure have dec. clearance* (1st order) *___-Dependent Elimination*: rate of elimin. is constant when [drug] is running at Vmax rate (i.e., concentration is huge and enzymes are saturated) - when happens, zero order elimination occurs (zero order)

*Zero Order Elimination*: constant rate of elimination over time (no dependence/variance with [drug], *no half-life*) - called zero order b/c: Rate = A x [Drug]^0; *this is seen with alcohol, phenytoin, aspirin* *First Order Elimination*: rate varies w/[Drug] - % change over a given time is constant *(half-life!)* - called first order b/c: Rate = A x [Drug]^1; most drugs follow 1st order elimin. *Flow-Dependent Elimination*: drugs metabolized quickly to point that elimination is determined by blood flow to organ (usually liver) - deemed "high extraction" drugs (morphine is classic ex.); *pts w/Heart Failure have dec. clearance* (1st order) *Capacity-Dependent Elimination*: rate of elimin. is constant when [drug] is running at Vmax rate (i.e., concentration is huge and enzymes are saturated) - when happens, zero order elimination occurs (zero order)

*[HY] AST is a ___ protein, ___ is mitochondrial toxin, alcoholic hepatitis --> AST >> ALT* AlkPhos can be elevated in non-liver conditions (p___ [placenta], thyroid, bone) If unsure if AlkPhos elevation is d/t gallbladder dz --> g___, specific to gallbladder dz & *elevated in heavy alcohol consumption* *Others (+ levels in liver dz)*: albumin (___), PT (___), PTT (___), glucose (___), platelets (___)

*[HY] AST is a mitochondrial protein, alcohol is mitochondrial toxin, alcoholic hepatitis --> AST >> ALT* AlkPhos can be elevated in non-liver conditions (pregnancy [placenta], thyroid, bone) If unsure if AlkPhos elevation is d/t gallbladder dz --> gamma-glutamyl transpeptidase (GGT), specific to gallbladder dz & *elevated in heavy alcohol consumption* *Others (+ levels in liver dz)*: albumin (low), PT (high), PTT (high), glucose (low), platelets (low)

*[HY] ___ is responsible for normal anion gap of 8-16 - a low anion gap can be d/t hypo___, as well as m___ m___ (IgG is cationic [+])* The delta-delta only applies to anion-gap metabolic acidosis and is used *to detect a secondary ___ acid-base disorder (Winter's formula is for ___)* - note that anion gap increase should be similar to fall in HCO3 -Delta AG = AG - 12 -Delta HCO3 = 24 - [HCO3] Delta-Delta = [Delta AG]/[Delta HCO3] 1-2 = Normal <1 = secondary ___ (HCO3 too low) >2 = secondary ___ (HCO3 too high - could also indicate prior respiratory acidosis w/HCO3 compensation)

*[HY] Albumin is responsible for normal anion gap of 8-16 - a low anion gap can be d/t hypoalbuminemia, as well as multiple myeloma (IgG is cationic [+])* The delta-delta only applies to anion-gap metabolic acidosis and is used *to detect a secondary metabolic acid-base disorder (Winter's formula is for RESPIRATORY)* - note that anion gap increase should be similar to fall in HCO3 -Delta AG = AG - 12 -Delta HCO3 = 24 - [HCO3] Delta-Delta = [Delta AG]/[Delta HCO3] 1-2 = Normal <1 = secondary non-AG metabolic acidosis (HCO3 too low) >2 = secondary metabolic alkalosis (HCO3 too high - could also indicate prior respiratory acidosis w/HCO3 compensation)

*[HY] COX___ expression is increased in colon cancer; D___ gene is mutated in advanced CRC* Microsatellite instability pathway is seen in ___-sided (proximal) tumors - *can arise de novo w.o polyp, different from adenoma-carcinoma sequence* ___ = segments of DNA w/repeated sequence --> tendency to overlap (stable = successive divisions have same length microsatellites) Major regulation for microsatellite is ___ system - mutations in MMR enzymes --> microsatellite instability ___ is mutation in MMR system (e.g., MLH1; 80% lifetime CRC risk, less than FAP) - carries increased risk of ovarian, stomach cancer

*[HY] COX2 expression is increased in colon cancer; DCC (Deleted in Colon Cancer) gene is mutated in advanced CRC* Microsatellite instability pathway is seen in right-sided (proximal) tumors - *can arise de novo w.o polyp, different from adenoma-carcinoma sequence* Microsatellite = segments of DNA w/repeated sequence --> tendency to overlap (stable = successive divisions have same length microsatellites) Major regulation for microsatellite is mismatch repair system - mutations in MMR enzymes --> microsatellite instability HNPCC is mutation in MMR system (e.g., MLH1; 80% lifetime CRC risk, less than FAP) - carries increased risk of ovarian, stomach cancer

*[HY] ___ expression is increased in colon cancer; ___ gene is mutated in advanced CRC* Chromosomal instability pathway (adenoma-carcinoma sequence) l/t CRC over many years d/t somatic mutations - most commonly *___-sided tumors* Step 1: ___ mutation (TSG) --> beta catenin can activate oncogenes --> increased risk for *POLYPS* Step 2: ___ mutation (oncogene) --> aberrant cell signaling --> *POLYP formation (adenoma)* Step 3: ___ mutation (TSG) --> unregulated tumor cell growth (*colon cancer*) ___ is germline mutation of APC (chrom5) --> always l/t colon cancer (do a colectomy)

*[HY] COX2 expression is increased in colon cancer; DCC gene is mutated in advanced CRC* Chromosomal instability pathway (adenoma-carcinoma sequence) l/t CRC over many years d/t somatic mutations - most commonly *left-sided tumors* Step 1: APC mutation (TSG) --> beta catenin can activate oncogenes --> increased risk for *POLYPS* Step 2: KRAS mutation (oncogene) --> aberrant cell signaling --> *POLYP formation (adenoma)* Step 3: p53 mutation (TSG) --> unregulated tumor cell growth (*colon cancer*) FAP is germline mutation of APC (chrom5) --> always l/t colon cancer (do a colectomy)

*[HY] Carbonic anhydrase inhibitors (acetazolamide) reduce urinary c___ excretion; usually, c___ inhibits kidney stone formation; accordingly, acetazolamide can l/t kidney stones* Loop diuretics have two effects to promote diuresis: 1) increased sodium excretion and 2) decreased medullary o___ g___ Thiazide diuretics are notorious for causing hypon___, d/t preventing sodium reabsorption but keeping H2O reabsorption intact (maintain normal medullary gradient w/calcium resorption)

*[HY] Carbonic anhydrase inhibitors (acetazolamide) reduce urinary citrate excretion; usually, citrate inhibits kidney stone formation; accordingly, acetazolamide can l/t kidney stones* Loop diuretics have two effects to promote diuresis: 1) increased sodium excretion and 2) decreased medullary osmotic gradients Thiazide diuretics are notorious for causing hyponatremia, d/t preventing sodium reabsorption but keeping H2O reabsorption intact (maintain normal medullary gradient w/calcium resorption)

*[HY] Chronic steroid use can lead to skin effects (skin ___ + easy ___), Cushingoid appearance (___ obesity + buffalo hump + moon face), bone effects (___), eye effects (___), ___ effects (weakness, myopathy), and metabolic effects (hyper___); a feared complication of long-term steroid use is a___ of the hip; can develop ___ if d/c'ed abruptly*

*[HY] Chronic steroid use can lead to skin effects (skin thinning + easy bruising), Cushingoid appearance (truncal obesity + buffalo hump + moon face), bone effects (osteoporosis), eye effects (cataracts), muscle effects (weakness, myopathy), and metabolic effects (hyperglycemia); a feared complication of long-term steroid use is avascular necrosis of the hip; can develop adrenal crisis if d/c'ed abruptly*

*[HY] Colchicine has three unique, somewhat unrelated uses: gout, ___, and F___ M___ F___* *[HY] Allopurinol (and febuxostat) can abruptly change serum uric acid levels and precipitate g___ - start w/NSAIDs and/or colchicine* XO inhibitors (allopurinol, febuxostat) can increase levels of aza___ and 6-___ because those drugs are metabolized by XO

*[HY] Colchicine has three unique, somewhat unrelated uses: gout, pericarditis, and Familial Mediterranean Fever* *[HY] Allopurinol (and febuxostat) can abruptly change serum uric acid levels and precipitate gout attack - start w/NSAIDs and/or colchicine* XO inhibitors (allopurinol, febuxostat) can increase levels of azathioprine and 6-MP because those drugs are metabolized by XO

*[HY] Ezetimibe blocks intestinal brush border action in the intestines to decrease cholesterol absorption!*

*[HY] ___ is loss of proximal tubule function --> impaired resorption of solutes (HCO3, glucose, AAs, phosphate)* *Fanconi syndrome presents similar to diabetes: polyuria + polydipsia 2/2 diuresis from glucose, but with NORMAL ___* *FS will also p/w ___, 2/2 loss of HCO3* *Hypo___ and hypop___ will be present + AAs in urine (especially unique!)* *Fanconi syndrome can be inherited (a/w cystinosis - LyStDi with inability to break down ___) or acquired (lead poisoning, multiple myeloma, drugs)*

*[HY] Fanconi syndrome is loss of proximal tubule function --> impaired resorption of solutes (HCO3, glucose, AAs, phosphate)* *Fanconi syndrome presents similar to diabetes: polyuria + polydipsia 2/2 diuresis from glucose, but with NORMAL SERUM GLUCOSE* *FS will also p/w non anion gap metabolic acidosis, 2/2 loss of HCO3* *Hypokalemia and hypophosphatemia will be present + AAs in urine (especially unique!)* *Fanconi syndrome can be inherited (a/w cystinosis - LSD with inability to break down cystine) or acquired (lead poisoning, multiple myeloma, drugs)*

*[HY] GERD is 2/2 failure of the ___*, leading to reflux esophagitis (inflammation of epithelial layer) w/mucosal erythema and edema Biopsy will reveal *[buzzwords] basal zone ___, lamina propria ___, and neutrophils/___ in mucosal layer* GERD RFs include alcohol, smoking, obesity, and hiatal hernia GERD p/w chest pain (worse after meals + lying flat), dysphagia, and *respiratory sx (adult-onset ___)* Long-term, GERD can l/t ulcers (replaced w/fibrous tissue), healed by *S___*, and *___ ESOPHAGUS (metaplasia of squamous epithelium --> ___ epithelium [non-ciliated columnar epithelium w/G___ cells] @ squamocolumnar junction) - dx w/endoscopy (red/pink appearance) + biopsy* Tx w/*PPIs (first line)* and H2 blockers

*[HY] GERD is 2/2 failure of the LES*, leading to reflux esophagitis (inflammation of epithelial layer) w/mucosal erythema and edema Biopsy will reveal *[buzzwords] basal zone hyperplasia, lamina propria elongation, and neutrophils/EOSINOPHILS in mucosal layer* GERD RFs include alcohol, smoking, obesity, and hiatal hernia GERD p/w chest pain (worse after meals + lying flat), dysphagia, and *respiratory sx (adult-onset asthma)* Long-term, GERD can l/t ulcers (replaced w/fibrous tissue), healed by *STRICTURES*, and *BARRETT'S ESOPHAGUS (metaplasia of squamous epithelium --> intestinal epithelium [non-ciliated columnar epithelium w/Goblet cells] @ squamocolumnar junction) - dx w/endoscopy (red/pink appearance) + biopsy* Tx w/*PPIs (first line)* and H2 blockers

*[HY] Granulomatous inflammation can be ___ (cheese-like substance; TB) or non-caseating (___); it is a type ___ (___-mediated) hypersensitivity rxn* *[HY] Granulomatous inflammation involves ___ (cell type?)* *[HY] CXR will show ___ lymphadenopathy (occurs in TB and sarcoid)* *[HY] ___ foci will form as a result of subpleural granulomas in mid-to-lower lungs; ghon foci + hilar lymph node --> Ghon ___ (highly suggestive of TB)* *[HY] Reactivation TB classically causes cavitation w/caseous and liquefactive necrosis, p/w hemoptysis and ___ LOBE lesion (seen in REACTIVATION TB d/t V/Q RATIO!!)* ___ (fungal ball) can grow in pre-formed TB cavities

*[HY] Granulomatous inflammation can be caseating (cheese-like substance; TB) or non-caseating (sarcoid); it is a type IV (cell-mediated) hypersensitivity rxn* *[HY] Granulomatous inflammation involves MACROPHAGES* *[HY] CXR will show hilar lymphadenopathy (occurs in TB and sarcoid)* *[HY] Ghon foci will form as a result of subpleural granulomas in mid-to-lower lungs; ghon foci + hilar lymph node --> Ghon complex (highly suggestive of TB)* *[HY] Reactivation TB classically causes cavitation w/caseous and liquefactive necrosis, p/w hemoptysis and UPPER LOBE lesion (seen in REACTIVATION TB d/t V/Q RATIO!!)* Aspergillus (fungal ball) can grow in pre-formed TB cavities

*[HY] High altitude has low pO2 --> ___ventilation w/low pCO2 (resp. alk.)*; high altitude also triggers E___ production +/- chronic *hypoxic* vasoconstriction w/p___ hypertension 2,3-BPG levels also increase; 2,3-BPG causes ___ shift, alkalosis causes ___ shift, both cancel each other out *[HY] During exercise, CO2 production and O2 consumption increase - ___ O2 and CO2 stay normal, but ___ O2 falls and CO2 rises* *CO2 is powerful cerebral vaso___ (much better than hypoxemia)*; in panic attacks, hyperventilation --> cerebral vasoconstriction --> CNS sx CO2 is also major stimulus for breathing rate; COPD pts lose this stimulus d/t chronic hyper___ - O2 level becomes major stimulus (careful when giving 100% O2!)

*[HY] High altitude has low pO2 --> hyperventilation w/low pCO2 (resp. alk.)*; high altitude also triggers EPO production +/- chronic *hypoxic* vasoconstriction w/pulmonary hypertension 2,3-BPG levels also increase; 2,3-BPG causes right shift, alkalosis causes left shift, both cancel each other out *[HY] During exercise, CO2 production and O2 consumption increase - arterial O2 and CO2 stay normal, but venous O2 falls and CO2 rises* *CO2 is powerful cerebral vasodilator (much better than hypoxemia)*; in panic attacks, hyperventilation --> cerebral vasoconstriction --> CNS sx CO2 is also major stimulus for breathing rate; COPD pts lose this stimulus d/t chronic hypercapnia - O2 level becomes major stimulus (careful when giving 100% O2!)

*[HY] Know how to read MR of knee for Step1 - patella is anterior, ACL will angle anteriorly (___ condyle to ___ tibia), PCL will angle posteriorly (___ condyle to ___ tibia) - LAMP; menisci are ___ (color?) triangular structures* Know ___ (distal bone of joint moves away from midline - knock kneed Gus w/incr. passive abduction of knee in ___ tear) and ___ (distal bone of joint moves toward midline - bow legged w/incr. passive adduction in ___ tear) ACL tears are usually 2/2 noncontact athletic injury w/"pop" in knee and exaggerated ___ movement of tibia, look for ant. drawer or Lachman sign; PCL tears are usually 2/2 ___ injuries w/exaggerated ___ movement of tibia, look for post. drawer sign Meniscal tears p/w pain + swelling that are worse w/___ and McMurray test positive (lat. men. is ___ rotation, med. men. is ___ rotation, LIME) Unhappy triad is ___ (3) w/lateral force + planted foot

*[HY] Know how to read MR of knee for Step1 - patella is anterior, ACL will angle anteriorly (lateral condyle to anterior tibia), PCL will angle posteriorly (medial condyle to posterior tibia) - LAMP; menisci are black triangular structures* Know Valgus (distal bone of joint moves away from midline - knock kneed Gus w/incr. passive abduction of knee in MCL tear) and Varus (distal bone of joint moves toward midline - bow legged w/incr. passive adduction in LCL tear) ACL tears are usually 2/2 noncontact athletic injury w/"pop" in knee and exaggerated ant. movement of tibia, look for ant. drawer or Lachman sign; PCL tears are usually 2/2 dashboard injuries w/exaggerated post. movement of tibia, look for post. drawer sign Meniscal tears p/w pain + swelling that are worse w/pivoting and McMurray test positive (lat. men. is internal rotation, med. men. is external rotation, LIME) Unhappy triad is ACL, MCL, medial meniscal tear w/lateral force + planted foot

*[HY] Negative urine anion gap in setting of non-anion gap metabolic acidosis (trying to eliminate H+ via NH4 - negative indicates large amount of unmeasured NH4) --> ___* *[HY] Positive urine anion gap in setting of non-anion gap metabolic acidosis (trying to eliminate H+ via NH4 - positive indicates not much unmeasured NH4) --> ___*

*[HY] Negative urine anion gap in setting of non-anion gap metabolic acidosis (trying to eliminate H+ via NH4 - negative indicates large amount of unmeasured NH4) --> GI cause* *[HY] Positive urine anion gap in setting of non-anion gap metabolic acidosis (trying to eliminate H+ via NH4 - positive indicates not much unmeasured NH4) --> RTA*

*[HY] ___ is malignant bone tumor of osteoblasts (bimodal age distribution); path. reveals pleomorphic, osteoid-producing cells; usually seen in ___ of long bones* *XR reveals ___ triangle and/or ___ sign; RFs include prior radiation, P___ Dz for older pts, inherited conditions (Rb, Li-Fraumeni)* *Tx: en bloc (entire tumor + healthy tissue) resection + [HY] ___ (neo + adj)* Ewing sarcoma is of undifferentiated primitive neuroectoderm cells (path of small, blue cells) - youngest age of presentation; ES is in ___ of long bones; classic x-ray finding is onion skinning ES presentation looks like osteomyelitis w/negative cx *[HY] Most ES cases are 2/2 translocation of chroms ___ (EWSR1 [22] next to FLI1 [111] - detect w/FISH)* Bone tumors p/w bone pain + NORMAL LABS

*[HY] Osteosarcoma is malignant bone tumor of osteoblasts (bimodal age distribution); path. reveals pleomorphic, osteoid-producing cells; usually seen in METAPHYSIS of long bones* *XR reveals Codman triangle and/or Sunburst sign; RFs include prior radiation, Paget's Dz for older pts, inherited conditions (Rb, Li-Fraumeni)* *Tx: en bloc (entire tumor + healthy tissue) resection + [HY] chemotherapy (neo + adj)* Ewing sarcoma is of undifferentiated primitive neuroectoderm cells (path of small, blue cells) - youngest age of presentation; ES is in diaphysis of long bones; classic x-ray finding is onion skinning ES presentation looks like osteomyelitis w/negative cx *[HY] Most ES cases are 2/2 translocation of chroms 11 and 22 (EWSR1 [22] next to FLI1 [111] - detect w/FISH)* Bone tumors p/w bone pain + NORMAL LABS ^Pat Ewing wore 33 (11 + 22) - was ONIONS from 3

*[HY] Synovial joints have articular cartilage containing type ___ collagen; synovium secretes synovial fluid containing ___ acid*; Synovium has relatively low WBC (200-2000) In OA, hyaline cartilage breaks down; additionally, abnormal function of c___ plays a role (proliferate in OA w/inadequate repair) X-ray findings of OA: 1) joint space narrowing, 2) subchondral sclerosis, 3) subchondral cysts, 4) osteophytes OA often involves DIP, PIP, and 1st CMC joint (*NOT ___!!!*) - ___ w/Heberden nodes (pointing "here!"), Bouchard nodes of ___ (remember: OA occurs at end of our lives --> joints involved are end of fingers) Knee, spine, hip are often affected w/joint pain (worse @ ___ of day), stiffness, and decr. ROM; most important modifiable RF is weight Tx: activity, NSAIDs, injection, steroids, TKA/THA Hemochromatosis can mimic OA, but pt will be younger w/high serum ___

*[HY] Synovial joints have articular cartilage containing type II collagen; synovium secretes synovial fluid containing hyaluronic acid*; Synovium has relatively low WBC (200-2000) In OA, hyaline cartilage breaks down; additionally, abnormal function of chondrocytes plays a role (proliferate in OA w/inadequate repair) X-ray findings of OA: 1) joint space narrowing, 2) subchondral sclerosis, 3) subchondral cysts, 4) osteophytes OA often involves DIP, PIP, and 1st CMC joint (*NOT MCP!!!*) - DIP w/Heberden nodes (pointing "here!"), Bouchard nodes of PIP (remember: OA occurs at end of our lives --> joints involved are end of fingers) Knee, spine, hip are often affected w/joint pain (worse @ end of day), stiffness, and decr. ROM; most important modifiable RF is weight Tx: activity, NSAIDs, injection, steroids, TKA/THA Hemochromatosis can mimic OA, but pt will be younger w/high serum ferritin

*[HY] Theophylline toxicity manifests w/___ effects, n___ (seizures) - theophylline is like caffeine, think of it as having too much coffee! Can also see cardiotoxicity 2/2 blocking adenosine receptors, death is 2/2 arrhythmias* *Pt on theophylline for asthma/COPD who comes in w/SVT will NOT respond to ___, d/t theophylline blocking adenosine receptor!* Roflumilast (PDE-4 inhibitor) can be used for COPD treatment

*[HY] Theophylline toxicity manifests w/GI effects, neurotoxicity (seizures) - theophylline is like caffeine, think of it as having too much coffee! Can also see cardiotoxicity 2/2 blocking adenosine receptors, death is 2/2 arrhythmias* *Pt on theophylline for asthma/COPD who comes in w/SVT will NOT respond to adenosine, d/t theophylline blocking adenosine receptor!* Roflumilast (PDE-4 inhibitor) can be used for COPD treatment

*[INCREDIBLY HY - BONE TURNOVER] Bone turnover is modulated by signals (both stim. and inhib.) from osteo___ (-clast is slave to -blast)* *RANK is receptor on -___, when bound --> stimulated w/synthesis of N___* *RANK-L is ligand on ___, stimulate -clasts* *___ is decoy receptor for RANK-L - binds RANK-L to inhibit -clasts (via -blast binding)* *M-CSF is secreted by -blasts, also stimulates -clasts* *KEY PTS: more RANK-L/___ --> more -clast activity; more ___ --> less -clast activity*

*[INCREDIBLY HY - BONE TURNOVER] Bone turnover is modulated by signals (both stim. and inhib.) from osteoBLASTS (-clast is slave to -blast)* *RANK is receptor on -clasts, when bound --> stimulated w/synthesis of NF-k-B* *RANK-L is ligand on -blasts, stimulate -clasts* *OPG is decoy receptor for RANK-L - binds RANK-L to inhibit -clasts (via -blast binding)* *M-CSF is secreted by -blasts, also stimulates -clasts* *KEY PTS: more RANK-L/M-CSF --> more -clast activity; more OPG --> less -clast activity*

-Gastritis --> mucosal inflammation -Erosion --> loss of epithelium (extends to muscularis mucosa) -Ulcer --> loss of mucosal layer (can extend in submucosa/muscular layer) --- Gastritis can be acute (acidic damage w/___ infiltration) or chronic (autoimmune/H pylori w/___) Gastritis can be d/t 1) too much acid or 2) too little protection (ACh [vagus nn] + histamine stimulate acid; p___ inhibit acid) Acute gastritis can be d/t: 1) ___ (block prostaglandin production - see above) 2) Alcohol (directly damages mucosa) 3) C__ (inhibits epithelial cell replication) 4) H. pylori (also chronic) 5) ___ ulcer (seen in burn pts d/t loss of blood flow --> mucosal damage/gastritis) [cuRling --> buRn] 6) ___ ulcer (seen w/increased ICP --> vagal stimulation --> gastritis) [cuShing --> iSEEp] 7) ___ ulcers (poor perfusion --> decreased mucosal burn similar to #6 - PPx w/PPIs)

-Gastritis --> mucosal inflammation -Erosion --> loss of epithelium (extends to muscularis mucosa) -Ulcer --> loss of mucosal layer (can extend in submucosa/muscular layer) --- Gastritis can be acute (acidic damage w/neutrophil infiltration) or chronic (autoimmune/H pylori w/lymphocytes) Gastritis can be d/t 1) too much acid or 2) too little protection (ACh [vagus nn] + histamine stimulate acid; prostaglandins inhibit acid) Acute gastritis can be d/t: 1) NSAIDs (block prostaglandin production - see above) 2) Alcohol (directly damages mucosa) 3) Chemotherapy (inhibits epithelial cell replication) 4) H. pylori (also chronic) 5) Curling's ulcer (seen in burn pts d/t loss of blood flow --> mucosal damage/gastritis) 6) Cushing's ulcer (seen w/increased ICP --> vagal stimulation --> gastritis) 7) Stress ulcers (poor perfusion --> decreased mucosal burn similar to #6 - PPx w/PPIs)

-Gastritis --> mucosal inflammation -Erosion --> loss of epithelium (extends to muscularis mucosa) -Ulcer --> loss of mucosal layer (can extend in submucosa/muscular layer) --- Gastritis can be acute (acidic damage w/neutrophil infiltration) or chronic (autoimmune/H pylori w/lymphocytes) Type ___ (autoimmune) gastritis (aka, pernicious anemia) is d/t autoimmune destruction of gastric p___ cells --> loss of intrinsic factor --> ___ deficiency Type A l/t chronic inflammation of *gastric B___/F___ (where parietal cells are found!)* - a/w women, HLA-DR, and *increased risk of gastric ___ (THINK - chronic inflammation --> intestinal metaplasia, [HY] ___ CELLS will appear in stomach!!)* Type ___ (MC, infxn) gastritis (H pylori) mostly occurs in the stomach *___ (differentiating factor!)*; H pylori produces *___, which keeps alkali environment for bug to grow*; alkali environment --> gastrin release (from G-cells) --> increased acid production Type B can l/t ___ lymphoma and gastric adenocarcinoma (see above - both can induce GA, one can induce ML); Dx is via biopsy or *urea breath test* or stool Ag; Tx is w/triple therapy (+ confirmation of eradication)

-Gastritis --> mucosal inflammation -Erosion --> loss of epithelium (extends to muscularis mucosa) -Ulcer --> loss of mucosal layer (can extend in submucosa/muscular layer) --- Gastritis can be acute (acidic damage w/neutrophil infiltration) or chronic (autoimmune/H pylori w/lymphocytes) Type A (autoimmune) gastritis (aka, pernicious anemia) is d/t autoimmune destruction of gastric parietal cells --> loss of intrinsic factor --> B12 deficiency Type A l/t chronic inflammation of *gastric BODY/FUNDUS (where parietal cells are found!)* - a/w women, HLA-DR, and *increased risk of gastric adenocarcinoma (THINK - chronic inflammation --> intestinal metaplasia, [HY] GOBLET CELLS will appear in stomach!!)* Type B (MC, infxn) gastritis (H pylori) mostly occurs in the stomach *ANTRUM (differentiating factor!)*; H pylori produces *urease, which keeps alkali environment for bug to grow*; alkali environment --> gastrin release (from G-cells) --> increased acid production Type B can l/t MALT lymphoma and gastric adenocarcinoma (see above - both can induce GA, one can induce ML); Dx is via biopsy or *urea breath test* or stool Ag; Tx is w/triple therapy (+ confirmation of eradication)

CLASSIC BOARDS QUESTION: in what patients (3 disorders) is metoclopramide contraindicated in? Remember: a D2 antagonist

-Known seizure d.o (metoclopramide lowers seizure threshold) -Parkinson's dz (worsen dopamine depletion) -Bowel obstruction (increases GI motility, BAD when obstructed)

CLASSIC CASE: surfer with flu-like illness + conjunctival suffusion and jaundice CLASSIC BOARDS QUESTION: patient treated for syphilis with penicillin and develops flu-like syndrome, what happened? Other species of ___ (hermsii, turicatae, recurrentis) can cause relapsing fever, *2/2 ___ that occurs when bacteria is growing inside the body, allowing bug to evade immune response --> fever returns* *Swabbing a chancre or condyloma in syphilis reveals abundant ___ on dark-field microscopy*

-LEPTOSPIROSIS -JARISCH-HERXHEIMER REACTION, killed bacteria cause immune response Other species of Borellia (hermsii, turicatae, recurrentis) can cause relapsing fever, *2/2 antigenic variation that occurs when bacteria is growing inside the body, allowing bug to evade immune response --> fever returns* *Swabbing a chancre or condyloma in syphilis reveals abundant treponema on dark-field microscopy*

-Low cortisol --> hypo___, N/V -Low aldosterone --> hypovolemia/shock, hyperkalemia, high renin -High aldosterone --> hyper___, hypo___, low renin -Androgen excess --> ___ genitalia (XX), ___ puberty (XY) -Androgen deficiency --> normal development (XX), ambiguous genitalia (XY) -*All CAH will have hyperpigmentation 2/2 high ACTH!* --- ___ deficiency results in cortisol deficiency, excess androgens and mineralocorticoids (not aldosterone, but *11-deoxycorticosterone*) Similar to 21-hydroxylase, but with *hypertension and hypokalemia d/t mineralocorticoid activity (this is what they would test)*

-Low cortisol --> hypoglycemia, N/V -Low aldosterone --> hypovolemia/shock, hyperkalemia, high renin -High aldosterone --> hypertension, hypokalemia, low renin -Androgen excess --> ambiguous genitalia (XX), precocious puberty (XY) -Androgen deficiency --> normal development (XX), ambiguous genitalia (XY) -*All CAH will have hyperpigmentation 2/2 high ACTH!* --- 11-hydroxylase deficiency results in cortisol deficiency, excess androgens and mineralocorticoids (not aldosterone, but *11-deoxycorticosterone*) Similar to 21-hydroxylase, but with *hypertension and hypokalemia d/t mineralocorticoid activity (this is what they would test)*

-Low cortisol --> hypo___, N/V -Low aldosterone --> hypovolemia/shock, hyperkalemia, high renin -High aldosterone --> hypertension, hypokalemia, low renin -Androgen excess --> ambiguous genitalia (XX), precocious puberty (XY) -Androgen deficiency --> normal development (___), ambiguous genitalia (___) -*All CAH will have hyperpigmentation 2/2 high ACTH!* --- ___ deficiency results in deficient cortisol and androgens, excess aldosterone production *Low androgens is unique!! Often diagnosed at puberty (XX: no secondary sex characteristics; XY: phenotypic female w/amenorrhea*

-Low cortisol --> hypoglycemia, N/V -Low aldosterone --> hypovolemia/shock, hyperkalemia, high renin -High aldosterone --> hypertension, hypokalemia, low renin -Androgen excess --> ambiguous genitalia (XX), precocious puberty (XY) -Androgen deficiency --> normal development (XX), ambiguous genitalia (XY) -*All CAH will have hyperpigmentation 2/2 high ACTH!* --- 17-hydroxylase deficiency results in deficient cortisol and androgens, excess aldosterone production *Low androgens is unique!! Often diagnosed at puberty (XX: no secondary sex characteristics; XY: phenotypic female w/amenorrhea*

-Low cortisol --> hypo___, N/V -Low aldosterone --> hypovolemia/___, hyper___, ___ renin -High aldosterone --> hypertension, hypokalemia, low renin -Androgen excess --> ambiguous genitalia (XX), precocious puberty (XY) -Androgen deficiency --> normal development (XX), ambiguous genitalia (XY) -*All CAH will have hyperpigmentation 2/2 high ACTH!* --- ___ deficiency results in cortisol + aldosterone deficiency, androgen excess ___ is MC CAH (90%) - can have classic (0% enzyme activity, *severe manifestations of shock and hyperkalemia 1-2w after birth*) or non-classic (~30% activity) Screened for w/17-hydroxyprogesterone!

-Low cortisol --> hypoglycemia, N/V -Low aldosterone --> hypovolemia/shock, hyperkalemia, high renin -High aldosterone --> hypertension, hypokalemia, low renin -Androgen excess --> ambiguous genitalia (XX), precocious puberty (XY) -Androgen deficiency --> normal development (XX), ambiguous genitalia (XY) -*All CAH will have hyperpigmentation 2/2 high ACTH!* --- 21-hydroxylase deficiency results in cortisol + aldosterone deficiency, androgen excess 21-hydroxylase is MC CAH (90%) - can have classic (0% enzyme activity, *severe manifestations of shock and hyperkalemia 1-2w after birth*) or non-classic (~30% activity) Screened for w/17-hydroxyprogesterone!

CLASSIC CASE: neutropenic cancer patient with fever, chills (bacteremia) who develops black lesions on chest/back? CLASSIC CASE: mild cough, watery diarrhea, confusion 2/2 hyponatremia, and negative bacteria on gram stain? Bacteroides fragilis is an *___ic* GNR that is normal GI flora; it can cause polymicrobial infection that starts in ___, such as peritonitis, intraabdominal abscess, lung abscess (tx with ___)

-PSEUDOMONAS - ECTHYMA GANGRENOSUM -LEGIONELLA (tx with fluoroquinolone or macrolide) Bacteroides fragilis is an *ANAEROBIC* GNR that is normal GI flora; it can cause polymicrobial infection that starts in GI tract, such as peritonitis, intraabdominal abscess, lung abscess (tx with metronidazole)

*BETA LACTAMASE SENSITIVITY: rank in terms of most to least sensitive - aztreonam, carbapenems, cephalosporins (all gens), penicillin? *What causes Red Man Syndrome with vanc infusion?* Nitrofurantoin is used for UTIs in pregnancy (avoid ___ 2/2 NTDs) and can trigger hemolysis in ___ patients

-Penicillin^ -1st --> 4th Cephalosporins -Aztreonam^^ -Carbapenems ^Anti-staph penicillins (naf-, ox-) resist staph penicillinase ^^GN coverage only --- Direct activation of MAST CELLS --> *HISTAMINE RELEASE* (does not require sensitization --> can develop with first admin) --- Nitrofurantoin is used for UTIs in pregnancy (avoid TMP-SMX 2/2 NTDs) and can trigger hemolysis in ___ patients

Cells releasing following hormones: Somatostatin, Cholecystokinin, Glucose-dependent insulinotropic peptide (GIP), Secretin?

-Somatostatin - D-cells (found all over stomach/small intestine) -CCK - I-cells (duodenum/jejunum) -GIP - K-cells (duodenum/jejunum) -Secretin - S-cells (duodenum/jejunum) ^Some Crazy Girls S^^^ DIKS --- -Gastrin - G-cells (easy - antrum of stomach) --- -Motilin, VIP are found all over (like somatostatin!)

1st deg/superficial burns involve ___ only - painful, red, and *blanch w/pressure* (no blisters, heals in 1w) 2nd deg/part. thickn. burns involve epid. + some ___ - blisters, pain, blanch w/pressure (heal 1-3w) Full thickn. (also 2nd) burns involve epid. + most ___ - yellow/white, pain to pressure ONLY, and *___ blanching* (will scar) 3rd/4th deg. involve entire epid./derm. +/- subQ fat *[HY] UV___ radiation (as opposed to UV____ radiation) is most effective at causing sunburn --> damage to e___ + d___ (sunburn cells are keratinocytes undergoing apoptosis)*

1st deg/superficial burns involve epiderm. only - painful, red, and *blanch w/pressure* (no blisters, heals in 1w) 2nd deg/part. thickn. burns involve epid. + some derm. - blisters, pain, blanch w/pressure (heal 1-3w) Full thickn. (also 2nd) burns involve epid. + most derm. - yellow/white, pain to pressure ONLY, and *no blanching* (will scar) 3rd/4th deg. involve entire epid./derm. +/- subQ fat *[HY] UVB (uv-Burn) radiation (as opposed to UVA radiation) is most effective at causing sunburn --> damage to epid. + derm. (sunburn cells are keratinocytes undergoing apoptosis)*

CLASSIC CASE: female child with masculinization at puberty (or male child with ambiguous genitalia) with blind vagina, no uterus, bilateral undescended testes, and normal testosterone levels? Que pasa?

5-ALPHA REDUCTASE DEFICIENCY (no DHT --> no external genitalia in XY patient)

A 2x2 table is useful in risk quantification (dz +/-, exposure +/-, then A-B-C-D in quadrants), can calculate *[HY]*: risk of dz, risk ratio, odds ratio, attributable risk, # needed to harm Risk of dz is (A/[A+B]) for exposed, (C/[C+D]) for unexposed R___ is [risk w/exposure]/[risk w.o exposure] - ranges from 0 (protective) to infinity (harmful), usually come from ___ study; *often asked to calc. RR on exams!* O___ (from ___ study) is [odds exposure-dz]/[odds exposure-no-dz] or *[(A/C)/(B/D)]*, essentially asking "if dz, odds of exp.? if no dz, odds of exp.?" - 1=exposure equal, >1=exposure inc. in dz, <1=exposure dec. in dz Risk ratio is preferred to odds ratio (RR not available in case-control studies, i.e., rare dzs) - RR not valid in CC studies *d/t dependence on # of cases/controls selected*^, ___ will not change (*this point comes up on exams!!*) NOTE: can use *rare dz assumption* to get RR from OR in very rare dz, d/t A & C <<< B & D (*can use case control study to determine RR*); Rare Dz is prevalence <10% *CLASSIC Q: case-control study design, RR reported, is this valid? YES if dz is ___!!* Attributable risk is diff. btwn risk in unexposed and risk in exposed (literally subtract %s); A___ R___ P___ represents % dz explained by RF (i.e., 80% lung ca. explained by smoking) - ARP = [(RR-1)/RR] # needed to harm = # pts exposed for outcome to develop (NNH = 1/AR; AR 20% --> NNH = 5)

A 2x2 table is useful in risk quantification (dz +/-, exposure +/-, then A-B-C-D in quadrants), can calculate *[HY]*: risk of dz, risk ratio, odds ratio, attributable risk, # needed to harm Risk of dz is (A/[A+B]) for exposed, (C/[C+D]) for unexposed Risk ratio is [risk w/exposure]/[risk w.o exposure] - ranges from 0 (protective) to infinity (harmful), usually come from cohoRt study; *often asked to calc. RR on exams!* Odds ratio (from case-contrOl study) is [odds exposure-dz]/[odss exposure-no-dz] or *[(A/C)/(B/D)]*, essentially asking "if dz, odds of exp.? if no dz, odds of exp.?" - 1=exposure equal, >1=exposure inc. in dz, <1=exposure dec. in dz Risk ratio is preferred to odds ratio (RR not available in case-control studies, i.e., rare dzs) - RR not valid in CC studies *d/t dependence on # of cases/controls selected*^, OR will not change (*this point comes up on exams!!*) NOTE: can use *rare dz assumption* to get RR from OR in very rare dz, d/t A & C <<< B & D (*can use case control study to determine RR*); Rare Dz is prevalence <10% *CLASSIC Q: case-control study design, RR reported, is this valid? YES if dz is RARE!!* Attributable risk is diff. btwn risk in unexposed and risk in exposed (literally subtract %s); Attributable Risk Percentage represents % dz explained by RF (i.e., 80% lung ca. explained by smoking) - ARP = [(RR-1)/RR] # needed to harm = # pts exposed for outcome to develop (NNH = 1/AR; AR 20% --> NNH = 5) ^If confused - B&B Biostats --> Risk Quant --> 10:00

A normal Babinski sign is ___ toes; an abnormal response indicates ___ damage (importantly - upgoing Babinski is normal in infants) Primitive reflex (___ - 6) are present at birth, but dissipate at 1yr or less

A normal Babinski sign is downgoing toes; an abnormal response indicates UMN damage (importantly - upgoing Babinski is normal in infants) Primitive reflex (Moro, Rooting, Sucking, Palmar, Plantar, Galant) are present at birth, but dissipate at 1yr or less

CLASSIC CASE: adult w/recurrent, unexplained abdominal pain attacks + abnormal urine color and confusion/neuropathy - que pasa? what neurotoxins are causing disorder?

ACUTE INTERMITTENT PORPHYRIA *PORPHOBILINOGEN and delta-ALA (buildup in heme synthesis pathway - "should know for Step 1 of your boards" per Dr Ryan)*

CLASSIC PRESENTATION: fever + rash, oliguria, increased BUN/Cr, eosinophils in urine days to weeks after starting drug?

ACUTE INTERSTITIAL NEPHRITIS

ACh SYNAPSES: ACh is stored in vesicles; when depolarization happens, *___ at nerve terminal* leads to exocytosis of vesicles and release of ACh into synapse Hemicholinium blocks ___ uptake into neurons; vesamicol blocks CHaT from packaging ___ into vesicles Botulism is a toxin that targets this process (via cleavage of SNARE) and manifests with 3 Ds: ___

ACh SYNAPSES: ACh is stored in vesicles; when depolarization happens, *Ca influx at nerve terminal* leads to exocytosis of vesicles and release of ACh into synapse Hemicholinium blocks choline uptake into neurons; vesamicol blocks CHaT from packaging ACh into vesicles Botulism is a toxin that targets this process (via cleavage of SNARE) and manifests with 3 Ds: diplopia, dysphagia, and dysphonia

ADHD (4x more likely in boys) requires: 1) freq sx of ___, 2) present in >1 ___ (home/school), 3) x6mo, 4) present <___y of age, 5) impair social function, 6) excessive for development *Tx includes ___* (methylphenidate, amphetamine - increase CNS monoamine levels by blocking reuptake of NE/Dopa), *___* (selective NE re-uptake inhibitor - no dopamine fx --> less abuse potential), and *alpha-2 agonists* (clonidine, ___ - activate alpha-2A receptors in prefrontal cortex)

ADHD (4x more likely in boys) requires: 1) freq sx of hyperactivity, 2) present in >1 setting (home/school), 3) x6mo, 4) present <12y of age, 5) impair social function, 6) excessive for development *Tx includes stimulants* (methylphenidate, amphetamine - increase CNS monoamine levels by blocking reuptake of NE/Dopa), *atomoxetine* (selective NE re-uptake inhibitor - no dopamine fx --> less abuse potential), and *alpha-2 agonists* (clonidine, guanfacine - activate alpha-2A receptors in prefrontal cortex)

CLASSIC CASE: young adult w/HTN + hematuria, renal failure, and a family history of sudden death - que pasa?

ADPKD (family likely died from SAH 2/2 berry aneurysm)

___ is 2/2 chronic infxn of biliary tree (can be cryptosporidium or CMV induced) --> strictures of biliary tract --> RUQ pain + fever/jaundice --- ___ is massive gallstone that goes through GB wall --> fistula w/small intestine, goes on to tumble to ileocecal valve --> obstruction Classic imaging finding: *___ in biliary tree (2/2 fistula allowing air from bowel to gallbladder)* --- Gallbladder carcinoma is adenocarcinoma 2/2 chronic inflammation in gallbladder (chronic cholecystitis --> *___ gallbladder*); can be seen in pts w/chronic Salmonella typhi infxn

AIDS cholangiopathy is 2/2 chronic infxn of biliary tree (can be cryptosporidium or CMV induced) --> strictures of biliary tract --> RUQ pain + fever/jaundice --- Gallstone ileus is massive gallstone that goes through GB wall --> fistula w/small intestine, goes on to tumble to ileocecal valve --> obstruction Classic imaging finding: *air in biliary tree (2/2 fistula allowing air from bowel to gallbladder)* --- Gallbladder carcinoma is adenocarcinoma 2/2 chronic inflammation in gallbladder (chronic cholecystitis --> *porcelain gallbladder*); can be seen in pts w/chronic Salmonella typhi infxn

CLASSIC CASE: asthma/CF pt w/recurrent episodes of cough, fever, malaise + brown mucus plugs/hemoptysis; pt will have eosinophilia, high IgE, and bronchiectasis on imaging (PFTs --> obstructive pattern)?

ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS

CLASSIC CASE: asthma/CF patient with recurrent episodes of cough, fever, and malaise with brownish mucus/hemoptysis and a peripheral eosinophilia with high IgE - what does biopsy show?? CLASSIC CASE: DKA patient with severe sinusitits?

ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS - will see Th2 CD4+ T-cells (produce IL-4, IL-5 --> eosinophilia --> IgE production) Dx: skin testing Tx: steroids --- MUCORMYCOSIS (invades through cribriform plate

CLASSIC PRESENTATION: 50y pt with slowly progressive arm weakness, dysphagia to solids/liquids, and combined flaccid/spastic muscles with no sensory symptoms

ALS

ANP and BNP are released in response to increased volume (myocyte ___) --> *oppose actions of RAAS (vasodilation, diuresis, relax vascular smooth muscle)* PTH acts on ___ to increase calcium resorption; PTH acts on ___ to decrease phosphate resorption (also stimulates activation of vitamin D) EPO is released from *___ cells* of peritubular capillary and released in response of hypoxia; pts w/renal failure can develop normocytic anemia 2/2 low EPO Dopamine is synthesis in PCT

ANP and BNP are released in response to increased volume (myocyte stretch) --> *oppose actions of RAAS (vasodilation, diuresis, relax vascular smooth muscle)* PTH acts on DCT to increase calcium resorption; PTH acts on PCT to decrease phosphate resorption (also stimulates activation of vitamin D) EPO is released from *interstitial cells* of peritubular capillary and released in response of hypoxia; pts w/renal failure can develop normocytic anemia 2/2 low EPO Dopamine is synthesis in PCT

ANX DISORDERS: OCD is recurrent thoughts/urges (O) and behaviors to relieve Os (C); importantly, behaviors are *___ - distressing and in conflict with goals of ego* (egosyntonic in ___); tx is CBT + SSRIs and ___ (TCA) Body ___ disorder is preoccupation with appearance, focusing on nonexistent/minor defects w/repetitive behavior similar to OCD PTSD follows traumatic event w/HARD sx (___); sx must last >1mo and tx includes SSRIs (*+ ___ for nightmares*) Acute stress disorder is similar, but sx last ___ and may have dissociative sx (tx with CBT) Separation anxiety disorder is seem in children and often manifests with *___ sx (HA, nausea)*; tx with CBT

ANX DISORDERS: OCD is recurrent thoughts/urges (O) and behaviors to relieve Os (C); importantly, behaviors are *EGODYSTONIC - distressing and in conflict with goals of ego* (egosyntonic in OCPD); tx is CBT + SSRIs and clomipramine (TCA) Body dysmorphic disorder is preoccupation with appearance, focusing on nonexistent/minor defects w/repetitive behavior similar to OCD PTSD follows traumatic event w/HARD sx (hyperarousal, avoidance, re-experiencing event, distress); sx must last >1mo and tx includes SSRIs (*+ prazosin for nightmares*) Acute stress disorder is similar, but sx last <1mo and may have dissociative sx (tx with CBT) Separation anxiety disorder is seem in children and often manifests with *physical sx (HA, nausea)*; tx with CBT

ANX DISORDERS: Panic attacks last minutes-to-an hour and are associated with physical sx (palp, sweating); unique sx include ___ (items in room look foggy/unreal) and ___ (out-of-body experience) Panic Disorder is recurrent, unexpected panic attacks w/o trauma/phobia trigger; attacks are followed by 1+ month of persistent ___ and ___ behavior; RFs include female, genetics, hx of abuse, and life stress Phobias are of specific object/situation with *___ behavior* and subsets include SAD and agoraphobia *(fear of ___ - not afraid of scrutiny/embarrassment); sx must last >6mo and tx is behavioral therapy (systematic ___ and ___ therapy) GAD is chronic, persistent anxiety about many events/activities lasting >6mo (>50% of days); must also have 3+ of C-FIRST: ___

ANX DISORDERS: Panic attacks last minutes-to-an hour and are associated with physical sx (palp, sweating); unique sx include derealization (items in room look foggy/unreal) and depersonalization (out-of-body experience) Panic disorder is recurrent, unexpected panic attacks w/o trauma/phobia trigger; attacks are followed by 1+ month of persistent concern/worry and avoidance behavior; RFs include female, genetics, hx of abuse, and life stress Phobias are of specific object/situation with *avoidance behavior* and subsets include SAD and agoraphobia *(ear of leaving safe place - not afraid of scrutiny/embarrassment); sx must last >6mo and tx is behavioral therapy (systematic desensitization and exposure therapy) GAD is chronic, persistent anxiety about many events/activities lasting >6mo (>50% of days); must also have 3+ of C-FIRST: concentration difficulty, fatigue, irritability, restlessness, sleep disturbance, tension (muscles)

AR pedigrees will see dz skip generations, M/F affected ___, few ppl w/dz, and parents w.o dz having child w/dz (parents are carriers); *if risk of carrier is 1/50 in F, 1/100 in M, then (1/___ chance both 'rents are carriers) x (1/___ chance both alleles passed) = 1/20,000 affected by dz* AD pedigree do not skip generations, M/F affected equally, 50% offspring w/dz, and *M-to-M transmission of dz (r/o ___ conditions)* I___ dominance --> hetero phenotype (less sev) different from homo (more sev); achondroplasia (AD) in which Dd --> dwarfism, dd --> lethal; familial hypercholesterolemia in which Cc --> 350-550, cc --> 650-1000

AR pedigrees will see dz skip generations, M/F affected equally, few ppl w/dz, and parents w.o dz having child w/dz (parents are carriers); *if risk of carrier is 1/50 in F, 1/100 in M, then (1/5000 chance both 'rents are carriers) x (1/4 chance both alleles passed) = 1/20,000 affected by dz* AD pedigree do not skip generations, M/F affected equally, 50% offspring w/dz, and *M-to-M transmission of dz (r/o X-linked dom conditions)* Incomplete dominance --> hetero phenotype (less sev) different from homo (more sev); achondroplasia (AD) in which Dd --> dwarfism, dd --> lethal; familial hypercholesterolemia in which Cc --> 350-550, cc --> 650-1000

Abetalipoproteinemia is AR disorder in MTP --> *can't form ApoB48 or ApoB100!* Can't secrete chylomicrons from intestines --> steatorrhea + fat soluble vitamin deficiency Can't secrete VLDL from liver (B100) --> absent VLDL PRESENTATION: infant with steatorrhea, distension, failure to thrive + fat soluble vitamin deficiencies (*vitE - ataxia, weakness, hemolysis; vitA - poor vision*) BIOPSY: lipid accumulation in enterocytes LABS: absent-to-low VLDL, IDL, LDL, triglycerides, cholesterol, vitamin E; peripheral smear will show acanthocytosis (spiky membrane d/t abnormal lipids F-ing with membrane) NOTE: no problems with HDL, does not contain ApoB proteins!

A___ (validity) is how close data matches reality; P___ (reliability) is how close repeat measures match each other ___ tests have low SDs Random measurement errors reduce ___; Systemic errors reduce ___ ROC curves are used to find appropriate cutoff that maximizes sens./spec. (graphed as ___ [TP rate] on Y and 1-___ [FP rate] on X) - closer to up/left corner = better, more AUC = better Likelihood ratios tell us how much probably shifts with + or - test (how much pre-to-post test probably changes in event of test result); LRs are characteristics of test that don't vary with prevalence, LRs require sens. and spec. to calculate, and need to know pre-test prob. to use LRs +LR: [___/(1-___)]; -LR: [(1-sens.)/spec.] If asked *"what is likelihood of dz if (+) test?" --> asking for PPV!, will probs ask directly if they want +LR or -LR*

Accuracy (validity) is how close data matches reality; Precision (reliability) is how close repeat measures match each other Precise tests have low SDs Random measurement errors reduce precision; Systemic errors reduce accuracy ROC curves are used to find appropriate cutoff that maximizes sens./spec. (graphed as sens. [TP rate] on Y and 1-spec. [FP rate] on X) - closer to up/left corner = better, more AUC = better Likelihood ratios tell us how much probably shifts with + or - test (how much pre-to-post test probably changes in event of test result); LRs are characteristics of test that don't vary with prev., LRs require sens. and spec. to calculate, and need to know pre-test prob. to use LRs +LR: [sens./(1-spec.)]; -LR: [(1-sens.)/spec.] If asked *"what is likelihood of dz if (+) test?" --> asking for PPV!, will probs ask directly if they want +LR or -LR*

Achondroplasia is 2/2 F___ gene mutation (80% spontaneous - hetero --> dz, homo --> death) FGFR3 is GOF mutation, resulting in defective e___ (inhibits chondrocyte proliferation - limbs short, torso/head nml) Mucopolysaccharidoses (Hunter's/Hurler's) l/t inability to metabolize GAGS - chondrocytes normally degrade GAGS; in MPS, c___ die --> short stature + malformed bones

Achondroplasia is 2/2 FGFR3 gene mutation (80% spontaneous - hetero --> dz, homo --> death) FGFR3 is GOF mutation, resulting in defective endochondral ossification (inhibits chondrocyte proliferation - limbs short, torso/head nml) Mucopolysaccharidoses (Hunter's/Hurler's) l/t inability to metabolize GAGS - chondrocytes normally degrade GAGS; in MPS, chondrocytes die --> short stature + malformed bones

Acinar (means *berry*) cells of pancreas secrete enzymes + fluid; Ductal cells modify fluid (add water) and secrete ___ (neutralizes stomach juice) Pancreatic fluid composition varies w/flow rate: low flow --> high Cl, ___ HCO3; high flow --> low Cl, ___ HCO3 (Flow Follows hcO) [NOTE: Na, K values don't change] Reason for bicarb is bc bicarb is only secreted in small ducts (early), then reabsorbed in large ducts (late); when this process is sped up, secretion can occur but resorption cannot! S___ (secreted by S-sells) is the main stimulus for HCO3 secretion (in response to acid in duodenum)

Acinar (means *berry*) cells of pancreas secrete enzymes + fluid; Ductal cells modify fluid (add water) and secrete bicarb (neutralizes stomach juice) Pancreatic fluid composition varies w/flow rate: low flow --> high Cl, low HCO3; high flow --> low Cl, high HCO3 (Flow Follows hcO) [NOTE: Na, K values don't change] Reason for bicarb hesi/hey is bc bicarb is only secreted in small ducts (early), then reabsorbed in large ducts (late); when this process is sped up, secretion can occur but resorption cannot! Secretin (secreted by S-sells) is the main stimulus for HCO3 secretion (in response to acid in duodenum)

Acne is inflammation of hair follicles + sebaceous glands (exocrine glands); 1) SGs enlarge at puberty and sebum production is driven by *___ (men>women, PCOS women>healthy women, androgen insensitivity --> ___ acne)*; 2) elevated sebum + keratin block ducts and *bact. grow (sebum is growth medium for bact. - P___ acnes)*; 3) *c___ (debris blocking sebac. duct)* allow bact. growth & inflammation Acne affects most hormone-responsive glands (face) Tx: benzoyl peroxide +/- Abx (clindamycin, erythromycin) +/- *___* - dec. keratin production --> less follicle occlusion (*VERY teratogenic - use OCP +/- preg. test*)

Acne is inflammation of hair follicles + sebaceous glands (exocrine glands); 1) SGs enlarge at puberty and sebum production is driven by *ANDROGNES(men>women, PCOS women>healthy women, androgen insensitivity --> no acne)*; 2) elevated sebum + keratin block ducts and *bact. grow (sebum is growth medium for bact. - Propionibacterium acnes)*; 3) *comedones (debris blocking sebac. duct)* allow bact. growth & inflammation Acne affects most hormone-responsive glands (face) Tx: benzoyl peroxide +/- Abx (clindamycin, erythromycin) +/- *retinoids* - dec. keratin production --> less follicle occlusion (*VERY teratogenic - use OCP +/- preg. test*)

Acute Intermittent Porphyria (*autosomal ___*, low penetrance) is deficiency in PBGD (3rd step in heme synthesis pathway) AIP p/w acute intermittent attacks when por___ builds up - occurs whenever heme synthesis is upregulated (RECALL: ALA-synthase, rate-limiting step of heme synthesis, is step before PBGD! - accordingly, both rxn being slow --> more buildup of *por___ + ___ [both NEUROtoxins]*) aiP is Precipitated by medications that *induce ___ system (griseofulvin, Phenobarbital)*, alcohol, smoking, and starvation aiP attacks (5 Ps) p/w Painful ___, Port-___ Pee, Poly___, Psychological disturbance in response to Precipitating P450 inducer Dx: measure *___ + ___ DURING ATTACKS!* Tx: hemin (inhibits ALA synthase in heme synthesis!)

Acute Intermittent Porphyria (*autosomal DOMINANT*, low penetrance) is deficiency in PBGD (3rd step in heme synthesis pathway) AIP p/w acute intermittent attacks when porphobilinogen builds up - occurs whenever heme synthesis is upregulated (RECALL: ALA-synthase, rate-limiting step of heme synthesis, is step before PBGD! - accordingly, both rxn being slow --> more buildup of *porphobilinogen + ALA [both NEUROtoxins]*) aiP is Precipitated by medications that *induce P450 system (griseofulvin, Phenobarbital)*, alcohol, smoking, and starvation aiP attacks (5 Ps) p/w Painful abdomen, Port-wine Pee, Polyneuropathy, Psychological disturbance in response to Precipitating P450 inducer Dx: measure *porphobilinogen + ALA DURING ATTACKS!* Tx: hemin (inhibits ALA synthase in heme synthesis!)

Acute Lymphoblastic Leukemia is dz of children (~4y) and p/w fever, bone pain (2/2 ___ expansion), adenopathy + hepatosplenomegaly, HA + N/V, and peripheral -penias Peripheral blood will show *___* on smear (special CD testing to distinguish lymphoblasts vs myeloblasts) Most (~75%) of ALL are pre-___-cell malignancy, will be CD10+ (sometimes CD19+ or CD20+) and ___+ (DNA polymerase in T-/B-cell blasts and *NOT found in m___*) ALL has high cure rate, but "sanctuary sites" cannot be penetrated well by chemotherapy and relapse may occur there (testes, CNS) *[HY] Chromosomal abnormalities seen include Philadelphia chromosome - BCR-ABL (___, seen in adults and a/w ___ prognosis - know this b/c outcomes in adults is worse]) and TEL-AML [___, seen in children and a/w good prognosis - know this b/c outcomes in children are better]* Risk of ALL is significantly increased in children with ___ (trisomy 21 - greater chance for t12;21 [not really, but think of it this way to help remember association/translocation!]) --- T-cell ALL is seen in ___ males (teens to 20s) and often presents as *___ on CXR (___ involvement, site of T-cell development)!* Tumor compression may l/t *s___ syndrome + dyspnea*, T-cell markers are different (CD___+, *NOT CD10!!*) ^Developing B-cells are CD10+; developing T-/B-cells are TdT+; T-cell CDs are generally <10, B-cell CDs are generally >10

Acute Lymphoblastic Leukemia is dz of children (~4y) and p/w fever, bone pain (2/2 marrow expansion), adenopathy + hepatosplenomegaly, HA + N/V, and peripheral -penias Peripheral blood will show *lymphoblasts* on smear (special CD testing to distinguish lymphoblasts vs myeloblasts) Most (~75%) of ALL are pre-B-cell malignancy, will be CD10+ (sometimes CD19+ or CD20+) and TdT+ (DNA polymerase in T-/B-cell blasts and *NOT found in myeloblasts*) ALL has high cure rate, but "sanctuary sites" cannot be penetrated well by chemotherapy and relapse may occur there (testes, CNS) *[HY] Chromosomal abnormalities seen include Philadelphia chromosome (BCR-ABL [t9;22, seen in adults and a/w poor prognosis - know this b/c outcomes in adults is worse]) and TEL-AML [t12;21, seen in children and a/w good prognosis - know this b/c outcomes in children are better]* Risk of ALL is significantly increased in children with Down syndrome (trisomy 21 - greater chance for t12;21 [not really, but think of it this way to help remember association/translocation!]) --- T-cell ALL is seen in adolescent males (teens to 20s) and often presents as *a mediastinal mass on CXR (thymus involvement, site of T-cell development)!* Tumor compression may l/t *superior vena cava syndrome + dyspnea*, T-cell markers are different (CD7+, *NOT CD10!!*) ^Developing B-cells are CD10+; developing T-/B-cells are TdT+; T-cell CDs are generally <10, B-cell CDs are generally >10

Acute Myelogenous Leukemia is malignancy of myeloblasts *seen in ___ men* - sx largely stem from *___ suppression (anemia --> fatigue, weakness, pallor; thrombocytopenia --> bleeding; neutropenia --> infxns)* Peripheral blood smear will show *-penias + -___ (myeloblasts - will not see lymphoid CDs [CD3, 7, 10, etc], but will be ___-POSITIVE!!), -blasts may contain ___ (pathognomonic - accumulation of MPO --> can cause DIC!!)* Most important AML subtype is *APML (where ya see ___) - d/t t[15;17] --> ___ (promyelocytic leukemia gene + retinoic acid receptor alpha gene)* APML has 1) abnormal retinoic acid receptor (promyelocytes can't mature --> *tx w/___ (all trans retinoic acid) --> induces maturation) and 2) high incidence of ___ (release of MPO in Auer rods --> DIC, common presentation!)

Acute Myelogenous Leukemia is malignancy of myeloblasts *seen in adult men* - sx largely stem from *bone marrow suppression (anemia --> fatigue, weakness, pallor; thrombocytopenia --> bleeding; neutropenia --> infxns)* Peripheral blood smear will show *-penias + -BLASTS (myeloblasts - will not see lymphoid CDs [CD3, 7, 10, etc], but will be MPO-POSITIVE!!), -blasts may contain AUER RODS (pathognomonic - accumulation of MPO --> can cause DIC!!)* Most important AML subtype is *APML (where ya see Auer rods) - d/t t[15;17] --> PML-RARA (promyelocytic leukemia gene + retinoic acid receptor alpha gene)* APML has 1) abnormal retinoic acid receptor (promyelocytes can't mature --> *tx w/ATRA (all trans retinoic acid) --> induces maturation) and 2) high incidence of DIC (release of MPO in Auer rods --> DIC, common presentation!)

Acute pancreatitis classically p/w epigastric pain that radiates to the ___; May see ___ sign (umbiliCus ecchymosis) and Grey Turner Sign (flank ecchymosis) Path. is blocked pancreatic outflow --> *"___" of pancreas by trypsin* Dx: amylase and lipase (>3x ULN, *___ more specific*), epigastric pain, or classic CT findings (pancreas + edema) - need 2 of 3 Two most common causes of AP are 1) ___ (obstructing Ampulla of Vater) and 2) ___; other causes? (I GET SMASHED) -Auto-immune pancreatitis --> *[HY] IgG___-positive p___ cells!! (AUTO - 4 letters, Pancreatitis - cells)* -Children restrained by seatbelt --> ___-induced -Infection --> mumps-induced -Drugs --> GLP-1 agonist (exenatide)-induced (also sulfa drugs, 6-MP, valproate) -Electrolyte --> hypercalcemia-induced -Metabolic --> hyper___-induced -Procedure --> ERCP-induced

Acute pancreatitis classically p/w epigastric pain that radiates to the back; May see Cullen's sign (umbiliCus ecchymosis) and Grey Turner Sign (flank ecchymosis) Path. is blocked pancreatic outflow --> *"autodigestion" of pancreas by trypsin* Dx: amylase and lipase (>3x ULN, *lipase more specific*), epigastric pain, or classic CT findings (pancreas + edema) - need 2 of 3 Two most common causes of AP are 1) gallstones (obstructing Ampulla of Vater) and 2) alcohol; other causes? (I GET SMASHED) -Auto-immune pancreatitis --> *[HY] IgG4-positive plasma cells!! (AUTO - 4 letters, Pancreatitis - cells)* -Children restrained by seatbelt --> trauma-induced -Infection --> mumps-induced -Drugs --> GLP-1 agonist (exenatide)-induced (also sulfa drugs, 6-MP, valproate) -Electrolyte --> hypercalcemia-induced -Metabolic --> hypertriglyceridemia-induced -Procedure --> ERCP-induced *^Idiopathic (POSTERIOR DUODENAL ULCER), Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion, Hyperglycemia/Hypertriglyceridema (>1000), ERCP, Drugs*

___ are bands of scar tissue in peritoneal cavity (often 2/2 surgery) - can go on to cause 1) bowel obstruction, 2) ___ in women, 3) chronic abdominal/pelvic pain; tx w/lysis of adhesions operation Intussusception is "telescoping" of intestine into its own lumen - can compromise blood supply and l/t *___ STOOL*; common in children near the ileocecal junction *[HY] For intuss. to happen, there must be a ___ (intestine trapped & dragged by peristalsis) - includes M___, lymphoid hyperplasia, A___ [very HY], and tumors (in adults)* ___ is twisting of bowel around mesentery --> obstruction/infarction; can occur @ sigmoid or cecum --> coffee bean sign (*Midgut volvulus in Minors, Sigmoid volvulus in Seniors*) SBO causes include (ABC) adhesions, bulge (hernia), and cancer; LBO causes include tumor, adhesion, volvulus; Dx w/upright x-ray --> *___ w/dilated bowel loops*

Adhesions are bands of scar tissue in peritoneal cavity (often 2/2 surgery) - can go on to cause 1) bowel obstruction, 2) infertility in women, 3) chronic abdominal/pelvic pain; tx w/lysis of adhesions operation Intussusception is "telescoping" of intestine into its own lumen - can compromise blood supply and l/t *CURRANT JELLY STOOL*; common in children near the ileocecal junction *[HY] For intuss. to happen, there must be a lead point (intestine trapped & dragged by peristalsis) - includes Meckel's, lymphoid hyperplasia, ADENOVIRUS [very HY], and tumors (in adults)* Volvulus is twisting of bowel around mesentery --> obstruction/infarction; can occur @ sigmoid or cecum --> coffee bean sign (*Midgut volvulus in Minors, Sigmoid volvulus in Seniors*) SBO causes include (ABC) adhesions, bulge (hernia), and cancer; LBO causes include tumor, adhesion, volvulus; Dx w/upright x-ray --> *air fluid levels w/dilated bowel loops*

Adrenal crisis is *ACUTE* adrenal insufficiency d/t abrupt loss of cortisol and aldosterone - main manifestation is ___ (also hypoglycemia, N/V, confusion) Adrenal crisis often occurs when an acute increase in adrenal function is needed, but cannot be met (i.e., trauma in pt w/adrenal insufficiency); in pts who take chronic steroids, must administer *___* *A [HY] cause of acute adrenal insufficiency is ___ syndrome - bilateral adrenal hemorrhage 2/2 meningococcemia*

Adrenal crisis is *ACUTE* adrenal insufficiency d/t abrupt loss of cortisol and aldosterone - main manifestation is shock (also hypoglycemia, N/V, confusion) Adrenal crisis often occurs when an acute increase in adrenal function is needed, but cannot be met (i.e., trauma in pt w/adrenal insufficiency); in pts who take chronic steroids, must administer *stress dose steroids* *A [HY] cause of acute adrenal insufficiency is Waterhouse-Friderichsen syndrome - bilateral adrenal hemorrhage 2/2 meningococcemia*

Adrenal glands each have three arteries (superior, middle, inferior) and one vein (left drains to renal vein --> ___ course) Adrenal gland is divided into two structures: cortex and medulla Cortex is derived from ___oderm and has three histologic layers: zona glomerulosa (___ - aldosterone), zona fasciculata (___ - cortisol), zona reticularis (___ - testosterone) [Go Find Rex, Make Good Sex] Mineralocorticoid (aldosterone) key effect is on kidneys, production stimulated by RAA system (increase ___ resorption, ___ excretion) Glucocorticoids (cortisol) bind intra___ receptors --> ___ translocation --> gene expression, production stimulated by ACTH (CRH --> ACTH --> cortisol) Adrenal androgens (testosterone) make up 50% of androgens in women (overactive in CAH), production stimulated by ACTH Medulla is derived from ___ and secretes epinephrine and norepinephrine (SNS control)

Adrenal glands each have three arteries (superior, middle, inferior) and one vein (left drains to renal vein --> longer course) Adrenal gland is divided into two structures: cortex and medulla Cortex is derived from mesoderm and has three histologic layers: zona glomerulosa (mineral - aldosterone), zona fasciculata (gluco - cortisol), zona reticularis (andro - testosterone) [Go Find Rex, Make Good Sex] Mineralocorticoid (aldosterone) key effect is on kidneys, production stimulated by RAA system (increase Na/H2O resorption, K/H excretion) Glucocorticoids (cortisol) bind intracellular receptors --> nucleus translocation --> gene expression, production stimulated by ACTH (CRH --> ACTH --> cortisol) Adrenal androgens (testosterone) make up 50% of androgens in women (overactive in CAH), production stimulated by ACTH Medulla is derived from neural crest and secretes epinephrine and norepinephrine (SNS control)

Adrenal insufficiency is insufficient ___ production; can be either primary (*Addison's dz*) or secondary Primary AI is d/t failure of adrenal gland - cortisol and aldosterone will be ___ and ACTH will be ___; MC cause is autoimmune adrenalitis (Ab to 21-___) and TB Secondary AI is failure of pituitary ACTH release - only cortisol will be low (aldosterone will be normal) Symptoms of adrenal insufficiency stem from: Loss of ___: weakness, fatigue, weight loss, *___ HYPOTENSION*, N/V/D, abdominal pain, *hypoglycemia* Loss of ___ (in primary): hyperkalemia, acidosis, hypovolemia (2/2 sodium loss) High ACTH (in primary): ___ (2/2 melanocyte stimulating hormone sharing precursor protein as ACTH) - think John Kennedy

Adrenal insufficiency is insufficient cortisol production; can be either primary (*Addison's dz*) or secondary Primary AI is d/t failure of adrenal gland - cortisol and aldosterone will be low and ACTH will be high; MC cause is autoimmune adrenalitis (Ab to 21-hydroxylase) and TB Secondary AI is failure of pituitary ACTH release - only cortisol will be low (aldosterone will be normal) Symptoms of adrenal insufficiency stem from: Loss of Cortisol: weakness, fatigue, weight loss, *POSTURAL HYPOTENSION*, N/V/D, abdominal pain, *hypoglycemia* Loss of Aldosterone (in primary): hyperkalemia, acidosis, hypovolemia (2/2 sodium loss) High ACTH (in primary): hyperpigmentation (2/2 melanocyte stimulating hormone sharing precursor protein as ACTH) - think John Kennedy

After activation, B-cells have two fates: 1) ___ cell or 2) ___cell Plasma cells travel to spleen/bone marrow to secrete a shitload of antibodies, then die after a few days Memory B-cell (only produced through T-cell dependent activation of B-cells)

After activation, B-cells have two fates: 1) plasma cell or 2) memory B-cell Plasma cells travel to spleen/bone marrow to secrete a shitload of antibodies, then die after a few days Memory B-cell (only produced through T-cell dependent activation of B-cells)

After eating, ___ cells produce lots of HCl (via carbonic anhydrase) to pump into stomach - lots of HCO3 is also generated --> goes to serum (alkaline tide) Parietal cells have apical H+/K+ ATPase exchange pump - stimulated by ACh (M3 - Gq), Gastrin (CCKb - G___), histamine (H2 - Gs); inhibited by somatostatin (Gi) and *prostaglandins (G___) [why NSAIDs incr. acid production --> ulcer]* Vomiting loses HCl --> metabolic alkalosis (look for ___ urinary chloride! - low in vomiting 2/2 losing in secretions, high in di___ use 2/2 blocking NaCl resorption)

After eating, parietal cells produce lots of HCl (via carbonic anhydrase) to pump into stomach - lots of HCO3 is also generated --> goes to serum (alkaline tide) Parietal cells have apical H+/K+ ATPase exchange pump - stimulated by ACh (M3 - Gq), Gastrin (CCKb - Gq), histamine (H2 - Gs); inhibited by somatostatin (Gi) and *prostaglandins (Gi)* Vomiting loses HCl --> metabolic alkalosis (look for low urinary chloride! - low in vomiting 2/2 losing in secretions, high in diuretics 2/2 blocking NaCl resorption)

Aldosterone escape is phenomenon in which elevated aldosterone --> Na/H2O retention --> fluid retention Myocyte stretch will occur --> ___ release --> sodium and free water ___ Net Result: diuresis to normal volume status (*will not see ___ in hyperaldosterone state!*) IMPORTANTLY: urinary chloride will be ___!

Aldosterone escape is phenomenon in which elevated aldosterone --> Na/H2O retention --> fluid retention Myocyte stretch will occur --> ANP release --> sodium and free water excretion Net Result: diuresis to normal volume status (*will not see edema in hyperaldosterone state!*) IMPORTANTLY: urinary chloride will be increased!

All amino acids (except glycine) have L- and D-configurations - only L forms are used in amino acids NOTE: pKa is pH at which concentration of dissociated and intact AAs is EQUAL (i.e., pH > pKa --> more dissociated acid [H+ and A-]; pH < pKa --> more together acid [HA]) AAs are unique in that they have multiple different pKa's (one for NH3 group and one for COOH group) - some side chains even have a pKa (three pKa's), make these molecules charged At normal plasma pH (7.4), can determine what charge an AA will have based on pKa value; most AAs are uncharged at normal pH d/t NH3 and COOH, but will be charged if side chain is charged Histidine, Lysine, and Arginine are basic AAs (His Lies ARe basic; *histidine is kinda a faker w/pKa of 6, usually no charge at body pH*) - they pull H+ out of solution to become positively charged and raise pH; *basic amino acids (arginine and lysine) are concentrated in HISTONES (bind NEGATIVE phosphate backbone of DNA)* Aspartate and Glutamate are acidic AAs (this should be obvious based on their names) Proline is an AA to know, given that it has a rigid R-group *making it useful in COLLAGEN*

All reproductive hormones are st___ hormones (synthesized form cholesterol) that are poorly soluble --> carried by *___ (SHBGs)* - at their target organs, reproductive hormones cross bilayer and bind intracellular receptors to exert effect *[HY] SHBGs bind ___ more than ___, which can lead to estrogen amplification* Note that only free hormones exert clinical effect and increased SHBG --> ___ free androgens/estrogens; Accordingly, with increased SHBG, more ___ are bound and unable to exert effect --> free ___ > free ___ These effects are seen clinically when *h___ and estrogens increase SHBG (estrogen effects), while hypo___, ___ syndrome, and androgens decreases SHBG (androgen effects)* In cirrhosis, liver can't excrete estrogen --> excess estrogen increases ___ expression --> increased effects of estrogen seen in cirrhosis (gynecomastia, ___ angiomata/nevi, palmar ___)

All reproductive hormones are steroid hormones (synthesized form cholesterol) that are poorly soluble --> carried by *sex-hormone binding globulin (SHBGs)* - at their target organs, reproductive hormones cross bilayer and bind intracellular receptors to exert effect *[HY] SHBGs bind androgens more than estrogens, which can lead to estrogen amplification* Note that only free hormones exert clinical effect and increased SHBG --> decreased free androgens/estrogens; Accordingly, with increased SHBG, more androgens are bound and unable to exert effect --> free estrogen > free androgen These effects are seen clinically when *hyperthyroidism and estrogens increase SHBG (estrogen effects), while hypothyroidism, nephrotic syndrome, and androgens decreases SHBG (androgen effects)* In cirrhosis, liver can't excrete estrogen --> excess estrogen increases SHBG expression --> increased effects of estrogen seen in cirrhosis (gynecomastia, spider nevi, palmar erythema)

At rest, alveolar pressure = atmospheric pressure; w/exhalation, alveolar pressure ___, w/inhalation, alveolar pressure decreases Lungs tendency is to collapse (pull inward/recoil) - chest wall tendency is expansion (spring outward) Accordingly, at rest, these two are in equilibrium at ___(capacity?); when graphed (Y-axis=volume, X-axis=pressure), pressure-volume relationship of respiratory system is combination of lungs and chest wall (y-intercept is f___r___c___ - where forces of chest wall and lungs are balanced, lung in=chest out - pressure inside system is ZERO) NOTE: because lungs have tendency to collapse, *p___s___ (btwn lung and chest wall) must have negative pressure to keep alveoli open*; *transpulmonary pressure* is [(alveolar pressure) - (intrapleural pressure, often negative)] - must be ___(pos/neg?) to hold airway open (this is just another way to word concept - don't overthink this)

At rest, alveolar pressure = atmospheric pressure; w/exhalation, alveolar pressure increases, w/inhalation, alveolar pressure decreases Lungs tendency is to collapse (pull inward/recoil) - chest wall tendency is expansion (spring outward) Accordingly, at rest, these two are in equilibrium at FRC; when graphed (Y-axis=volume, X-axis=pressure), pressure-volume relationship of respiratory system is combination of lungs and chest wall (y-intercept is functional residual capacity - where forces of chest wall and lungs are balanced, lung in=chest out - pressure inside system is ZERO) NOTE: because lungs have tendency to collapse, *pleural space (btwn lung and chest wall) must have negative pressure to keep alveoli open*; *transpulmonary pressure* is [(alveolar pressure) - (intrapleural pressure, often negative)] - must be POSITIVE to hold airway open (this is just another way to word concept - don't overthink this)

At the DCT, ___ can act on Na-Ca basolateral pump to increase activity, driving low intracellular calcium concentration and promoting calcium resorption --- Increased sodium delivery to collecting duct (loop diuretics, thiazide diuretics) --> increased ___ excretion Importantly, both aldosterone and ADH act on the ___ --- In the nephron, the PCT and descending limb are permeable to ___; the DCT and ascending limb are ___ to water; the collecting duct has variable permeability to water depending on ___ availability Main physiologic stimuli for ADH release is *___ (secondary stimulus is volume loss, "non-osmotic release of ADH")* NOTE: *u___ resorption also increases in response to increased ADH (only in second half of collecting duct)*

At the DCT, PTH can act on Na-Ca basolateral pump to increase activity, driving low intracellular calcium concentration and promoting calcium resorption --- Increased sodium delivery to collecting duct (loop diuretics, thiazide diuretics) --> increased potassium excretion Importantly, both aldosterone and ADH act on the collecting duct --- In the nephron, the PCT and descending limb are permeable to water; the DCT and ascending limb are impermeable to water; the collecting duct has variable permeability to water depending on ADH availability Main physiologic stimuli for ADH release is *hyperosmolarity (secondary stimulus is volume loss, "non-osmotic release of ADH")* NOTE: *urea resorption also increases in response to increased ADH (only in second half of collecting duct)*

Atopic dermatitis (___) is chronic d/o with flares/remission - its a HS rxn, but not known what type (don't need to know) Usually eczema is 2/2 extrinsic rxn (environmental Ags) and p/w red, itchy rash in children SPEC. FEATS.: most pts have elevated Ig___ levels and family hx atopic dz, commonly co-occurs with allergic rhinitis and asthma (___ march) In babies --> develops on face; in children --> develops at ___ surfaces (antecub./popliteal fossas) w/thickened plaques --- Contact dermatitis (poison ivy, detergents) is similar to eczema, but is *localized to area of skin contact w/allergen (i.e., band-aid)* - CD is type ___ HS rxn, tx w/steroids --- Drug rash are delayed rxn to drug (pcn abx), leading to maculopapular rash w.o systemic sx; can occur days-to-weeks after starting drug and is a type IV (___-cell) HS rxn (think of delay in sx!) --- SJS-TEN is severe skin rxn (a type ___ HS rxn) that is triggered by drugs --> necrosis of epidermis + Nikolsky sign (also seen in Staph Scalded Skin, Pephigus Vulgaris) Usually flu-like prodrome --> *[HY] starts with lesions to ___* --> spread, then sloughing of skin w/mucosal involvement

Atopic dermatitis (eczema) is chronic d/o with flares/remission - its a HS rxn, but not known what type (don't need to know) Usually eczema is 2/2 extrinsic rxn (environmental Ags) and p/w red, itchy rash in children SPEC. FEATS.: most pts have elevated IgE levels and family hx atopic dz, commonly co-occurs with allergic rhinitis and asthma (atopic march) In babies --> develops on face; in children --> develops at flexor surfaces (antecub./popliteal fossas) w/thickened plaques --- Contact dermatitis (poison ivy, detergents) is similar to eczema, but is *localized to area of skin contact w/allergen (i.e., band-aid)* - CD is type IV HS rxn (need to FORm bond w/allergen), tx w/steroids --- Drug rash are delayed rxn to drug (pcn abx), leading to maculopapular rash w.o systemic sx; can occur days-to-weeks after starting drug and is a type IV (T-cell) HS rxn (think of delay in sx!) --- SJS-TEN is severe skin rxn (a type IV HS rxn) that is triggered by drugs --> necrosis of epidermis + Nikolsky sign (also seen in Staph Scalded Skin, Pephigus Vulgaris) Usually flu-like prodrome --> *[HY] starts with lesions to face/chest* --> spread, then sloughing of skin w/mucosal involvement

Attachment (loving human interaction) is necessary for normal development ___ D/o --> detached child unresponsive to caregiving that appears withdrawn ___ D/o --> little/no reluctance to interact with adults, hugging/sitting on lap of strangers

Attachment (loving human interaction) is necessary for normal development Reactive Attachment D/o --> detached child unresponsive to caregiving that appears withdrawn Disinhibited Social Engagement D/o --> little/no reluctance to interact with adults, hugging/sitting on lap of strangers

Autism Spectrum Disorder is abnormal social skills (must occur in multiple settings), repetitive behavior ___ (insist on sameness and routines), and limited ___ (intense obsessions with certain objects) *[HY] sx must be present in ___ development (often before 2y of age)* Subset of ASD are savants - exceptional skills in one area ASD is 4x more common in males and *manifests with increased ___* ASD is associated with ___ syndrome and ___ males (both associated with SEX CHROMOSOME) Tx involves *___ INTERVENTION with occupational/speech therapy (no specific medical therapy)

Autism Spectrum Disorder is abnormal social skills (must occur in multiple settings), repetitive behavior patterns (insist on sameness and routines), and limited interests (intense obsessions with certain objects) *[HY] sx must be present in early development (often before 2y of age)* Subset of ASD are savants - exceptional skills in one area ASD is 4x more common in males and *manifests with increased head circumference* ASD is associated with fragile X syndrome and double Y males (both associated with SEX CHROMOSOME) Tx involves *EARLY INTERVENTION with occupational/speech therapy (no specific medical therapy)

Autoimmune hepatitis is MC in middle-aged women, p/w asymptomatic --> acute liver dz --> cirrhosis; *look for ___ ABs* --- ___ is diffuse liver injury 2/2 hypoperfusion; p/w marked elevation of AST/ALT (into 1000s with APAP overdose and viral hepatitis) and *zone ___ necrosis (ischemia!)* --- ___ overdose can cause massive increase in AST/ALT (1000s, along with viral hepatitis) Tx of APAP Overdose: *[HY] use activated charcoal, but also ___ - replenishes levels of ___ in liver! - glutathione eliminates toxic metabolite NAPQI*

Autoimmune hepatitis is MC in middle-aged women, p/w asymptomatic --> acute liver dz --> cirrhosis; *look for ANTI-SMOOTH MUSCLE ABs* --- Shock liver is diffuse liver injury 2/2 hypoperfusion; p/w marked elevation of AST/ALT (into 1000s with APAP overdose and viral hepatitis) and *zone III necrosis (ischemia!)* --- APAP overdose can cause massive increase in AST/ALT (1000s, along with viral hepatitis) Tx of APAP Overdose: *[HY] use activated charcoal, but also N-ACETYLCYSTEINE - replenishes levels of glutathione in liver! - glutathione eliminates toxic metabolite NAPQI*

Autoregulation of the kidney maintains constant GFR and renal plasma flow (RPF) over a wide range of pressures - this is accomplished via 1) ___ mechanism and 2) ___ feedback 1) Myogenic mechanism is ability of afferent arteriole to constrict in response to ___ blood pressure - ___ RPF and GFR (really just keeps it normal) 2) Tubuloglomerular feedback is ___ sensing by macula densa (part of JG apparatus) l/t afferent arteriole vasoconstriction when ___ is high NOTE: severe volume loss --> BP and RPF are lower than can be compensated for by auto-regulatory mechanisms of kidney --> ___ GFR + ___ BUN/Cr (pre-renal azotemia)

Autoregulation of the kidney maintains constant GFR and renal plasma flow (RPF) over a wide range of pressures - this is accomplished via 1) myogenic mechanism and 2) tubuloglomerular feedback 1) Myogenic mechanism is ability of afferent arteriole to constrict in response to HIGH blood pressure - lowers RPF and GFR (really just keeps it normal) 2) Tubuloglomerular feedback is NaCl sensing by macula densa (part of JG apparatus) l/t afferent arteriole vasoconstriction when NaCl is high NOTE: severe volume loss --> BP and RPF are lower than can be compensated for by auto-regulatory mechanisms of kidney --> decreased GFR + increased BUN/Cr (pre-renal azotemia)

B AND T CELL IMMUNODEFICIENCIES: *Severe Combined Immunodeficiency*: most common form is X-linked mutation of IL-2 receptor (IL2RG mut), may also see *a___ deaminase deficiency ([semi-HY d/t biochem tie in] high adenosine --> high dATP, which inhibits ribonucleotide reductase - makes deoxyribonucleotides for DNA synthesis)* or *RAG mutation (VDJ recombination defect)*; results in loss of cell-mediated + humoral immunity (*entire loss of T- and B-cell areas --> loss of ___ (CXR?), loss of g___ in nodes*) Pts are severely susceptible to infxn - b___ boy; p/w recurrent thrush, failure to thrive Labs: identified on NBS, decreased T-cell receptor excision circles (___s, bubble boy with T-Rex) --- *Ataxia Telangiectasia*: defect in ___ gene (AutRec) on chrom11 --> impaired NHEJ --> hypersensitivity to *___*; p/w child having ataxia + telangiectasias (duh), and in immune system, will see recurrent infxns (sinopulmonary) and ___ (*lymphomas*) Labs: *low Ig___*, elevated AFP --- *Hyper IgM Syndrome (X-rec)*: defective ___ on T-cells --> inability to c___ s___ by B-cells; p/w recurrent sinopulmonary infections starting in infancy (S pneumo + H flu) - can see PJP, cryptosporidium, CMV Labs: normal IgM, *___ IgG/IgA/IgE* --- *Wiskott-Aldrich Syndrome*: defect in WAS gene (X-rec) --> abnormal *T-cell ___ maintenance (BuZzWoRd)* --> defective antigen presentation; p/w Thrombocytopenia (*+ p___ and bleeding - UNIQUE!*, Eczema, Recurrent infxns (WATER) Labs: elevated IgE, IgA (think ECZEMA)

B AND T CELL IMMUNODEFICIENCIES: *Severe Combined Immunodeficiency*: most common form is X-linked mutation of IL-2 receptor (IL2RG mut), may also see *adenosine deaminase deficiency ([semi-HY d/t biochem tie in] high adenosine --> high dATP, which inhibits ribonucleotide reductase - makes deoxyribonucleotides for DNA synthesis)* or *RAG mutation (VDJ recombination defect)*; results in loss of cell-mediated + humoral immunity (*entire loss of T- and B-cell areas --> loss of thymic shadow, loss of germinal centers in nodes*) Pts are severely susceptible to infxn - bubble boy; p/w recurrent thrush, failure to thrive Labs: identified on NBS, decreased T-cell receptor excision circles (TRECs) --- *Ataxia Telangiectasia*: defect in ATM gene (AutRec) on chrom11 --> impaired NHEJ --> hypersensitivity to *ionizing radiation*; p/w child having ataxia + telangiectasias (duh), and in immune system, will see recurrent infxns (sinopulmonary) and malignancies (*lymphomas*) Labs: *low IgA*, elevated AFP --- *Hyper IgM Syndrome (X-rec)*: defective CD40L on T-cells --> inability to class switch by B-cells; p/w recurrent sinopulmonary infections starting in infancy (S pneumo + H flu) - can see PJP, cryptosporidium, CMV Labs: normal IgM, *markedly decreased IgG/IgA/IgE* --- *Wiskott-Aldrich Syndrome*: defect in WAS gene (X-rec) --> abnormal *T-cell CYTOSKELETON maintenance (BuZzWoRd)* --> defective antigen presentation; p/w Thrombocytopenia (*+ petechiae and bleeding - UNIQUE!*, Eczema, Recurrent infxns (WATER) Labs: elevated IgE, IgA (think ECZEMA)

B-CELL IMMUNODEFICIENCIES (*all p/w sinpulmonary and GI sx*): *X-Linked (Bruton's) Agammaglobulinemia*: defect in ___ gene --> no l___ chains produced --> recurrent bacterial respiratory, sinus, ear, and GI infections (MUCOSAL Ab!!) *starting at ___ old (when mom's Abs are wiped out - unique!)* Key findings: *no ___-cells (absence of CD19, CD20, BCR)* + scant germinal centers + *___ antibodies* + Tx: IVIG (live vaccines contraindicated) --- *Selective IgA Deficiency*: MC, cause unknown; mostly Asymptomatic, but can have Airway (sinusitis, PNA, OM), A$$hole (*severe ___*) sx; also risk of ___ w/transfusion (rxn to IgA Abs); a/w Autoimmune dz (RA, SLE) Dx: low serum ___ (<7) w/normal IgG/IgM Special: can cause *false-positive ___ test (unique!)* or false negative celiac dz test (anti-TTG Ig___ Ab is test of choice) --- *Common Variable Immunodeficiency*: defect in B-cell differentiation w/unknown cause; can present in ___ (age?) w/o family history; can present similar to XLA (not x-linked so may be seen in females, also *later onset which is unique!*) Labs: low ___ cells, low Ig (usually IgG, but *variable as name suggests*) Special: increased frequency of A-Immune dz, *l___ (unique!)*

B-CELL IMMUNODEFICIENCIES (*all p/w sinpulmonary and GI sx*): *X-Linked (Bruton's) Agammaglobulinemia*: defect in BTK gene --> no light chains produced --> recurrent bacterial respiratory, sinus, ear, and GI infections (MUCOSAL Ab!!) *starting at 6mo (when mom's Abs are wiped out - unique!)* Key findings: *no B-cells (absence of CD19, CD20, BCR)* + scant germinal centers + *no antibodies* + Tx: IVIG (live vaccines contraindicated) --- *Selective IgA Deficiency*: MC, cause unknown; mostly Asymptomatic, but can have Airway (sinusitis, PNA, OM), A$$hole (*severe giardiA*) sx; also risk of Anaphylaxis w/transfusion (rxn to IgA Abs); a/w Autoimmune dz (RA, SLE) Dx: low serum IgA (<7) w/normal IgG/IgM Special: can cause *false-positive pregnancy test (unique!)* or false negative celiac dz test (anti-TTG IgA Ab is test of choice) --- *Common Variable Immunodeficiency*: defect in B-cell differentiation w/unknown cause; can present in adulthood w/o family history; can present similar to XLA (not x-linked so may be seen in females, also *later onset which is unique!*) Labs: low plasma cells, low Ig (usually IgG, but *variable as name suggests*) Special: increased frequency of A-Immune dz, *lymphoma (unique!)*

B-CELL RECEPTOR: B-cell receptor has two portions (Fab and Fc) and two chains (___ and ___) and two portions for antigen binding - the BCR forms a pentamer in Ig___ antibodies Heavy chains have three ___ regions and one ___ region; Light chains have ___ constant region and ___ variable region The Fab region is ___ terminus, Fc portion is ___ terminus (also Constant); disulfide bridges exist btwn heavy chains (@ hinge) and heavy-light chains (x2) *[HY] Complement binds at the ___ constant domain; Macrophages and Protein A bind @ ___-___ interface* ^Fc (Constant, Carboxy terminal, Complement binding, Confers isotype [IgG, IgM])

B-CELL RECEPTOR: B-cell receptor has two portions (Fab and Fc) and two chains (light and heavy) and two portions for antigen binding - the BCR forms a pentamer in IgM antibodies Heavy chains have three constant regions and one variable region; Light chains have one constant region and one variable region The Fab region is NH3 terminus, Fc portion is Carboxy terminus (also Constant); disulfide bridges exist btwn heavy chains (@ hinge) and heavy-light chains (x2) *[HY] Complement binds at the 2nd constant domain; Macrophages and Protein A bind @ constant2-constant3 interface* ^Fc (Constant, Carboxy terminal, Complement binding, Confers isotype [IgG, IgM])

B-cell surface proteins include CD___ (binds CD40___), MHC2, and ___ (binds CD28; also CD19, CD20, CD21) B-cell Abs include IgG, IgA, IgE, IgM - these are determined by Fc portion of Ab (during class switching, will be part of gene rearrangement in heavy chain - similar to VDJ rearrangement) Antibodies have three functions: 1) op___, 2) ne___, 3) complement activation ("c___ pathway") Protein A (seen in S. aureus) is key virulence factor expressed on cell membranes - binds ___ portion of IgG (protects from opsonization) Class switching is how B-cells change to different type of antibody (*start with IgM!*); triggers for class switching include cytokines (IL___ in Th2 response), T-cell binding

B-cell surface proteins include CD40 (binds CD40L), MHC2, and B7 (binds CD28; also CD19, CD20, CD21) B-cell Abs include IgG, IgA, IgE, IgM - these are determined by Fc portion of Ab (during class switching, will be part of gene rearrangement in heavy chain - similar to VDJ rearrangement) Antibodies have three functions: 1) opsonization, 2) neutralization, 3) complement activation ("classical pathway") Protein A (seen in S. aureus) is key virulence factor expressed on cell membranes - binds Fc portion of IgG (protects from opsonization) Class switching is how B-cells change to different type of antibody (*start with IgM!*); triggers for class switching include cytokines (IL4/5 in Th2 response, T-cell binding)

CLASSIC OVERDOSE PRESENTATION: CNS depression with normal vital signs? ANOTHER ONE: depressed respiratory rate with decreased bowel sounds, miosis? WITHDRAWAL: restlessness, *yawning, rhinorrhea, lacrimation, and piloerection*?

BENZODIAZEPINES (rarely cause respiratory depression + death, pts appear drunk w/o vital signs) OPIOIDS (remember that loperamide is used to constipate --> decreased BSs) OPIOID WITHDRAWAL

BLOTS: southern --> DNA, northern --> RNA, western --> prots. (So Dumb, Nobody Really Wants Proteins) South: uses probe (SS-DNA, complementary DNA - cDNA) to identify DNA in sample; STEPS: 1) R___ endonucleases cleave DNA, 2) gel electrophoresis separates DNA by size, 3) blotting (transfer to filter paper), 4) add probe & wash unbound probe (bound probe can be identified) SBs can be used for Restriction Fragment Length Polymorphisms (RFLP) - restriction nucs. cut DNA at specific sequence, l/t fragments of DNA w/different lengths (diff. genes break up into diff. lengths of fragments); Can use RFLP for *___ ANEMIA! (1.15kb --> normal beta, 1.35kb --> sickle beta)* North: same technique, but used to identify RNA - useful for studying gene ___ (mRNA levels) West: same technique but used for proteins, instead of probe use antibody; can be used to detect antibodies ^Southwestern: used to study DNA-prot. interaction (don't need to know that well - Western blot w/DNA probe)

BLOTS: southern --> DNA, northern --> RNA, western --> prots. (So Dumb, Nobody Really Wants Proteins) South: uses probe (SS-DNA, complementary DNA - cDNA) to identify DNA in sample; STEPS: 1) restriction endonucleases cleave DNA, 2) gel electrophoresis separates DNA by size, 3) blotting (transfer to filter paper), 4) add probe & wash unbound probe (bound probe can be identified) SBs can be used for Restriction Fragment Length Polymorphisms (RFLP) - restriction nucs. cut DNA at specific sequence, l/t fragments of DNA w/different lengths (diff. genes break up into diff. lengths of fragments); Can use RFLP for *SICKLE CELL ANEMIA! (1.15kb --> normal beta, 1.35kb --> sickle beta)* North: same technique, but used to identify RNA - useful for studying gene expression (mRNA levels) West: same technique but used for proteins, instead of probe use antibody; can be used to detect antibodies ^Southwestern: used to study DNA-prot. interaction (don't need to know that well - Western blot w/DNA probe)

BPPV is d/t ___ Vestibular neuritis is neuropathy of CN8 after ___ Meniere's Disease is ___ that causes three classic symptoms: ___; treatment is avoiding high salt foods +/- diuretics

BPPV is d/t calcium debris in semicircular canals Vestibular neuritis is neuropathy of CN8 after virus Meniere's Disease is endolymph fluid accumulation that causes three classic symptoms: tinnitus, SNHL, and vertigo; treatment is avoiding high salt foods +/- diuretics

Babies are subject to neonatal jaundice d/t 1) increased bilirubin (more RBCs w/shorter lifespan), 2) decreased U___ (UGT) activity (takes ~14w to mature) Unconjugated bilirubin can l/t ___ --> tx w/phototherapy (conjugates bili for excretion in urine)

Babies are subject to neonatal jaundice d/t 1) increased bilirubin (more RBCs w/shorter lifespan), 2) decreased UDP-glucuronyl transferase activity (takes ~14w to mature) Unconjugated bilirubin can l/t kernicterus --> tx w/phototherapy (conjugates bili for excretion in urine)

Bacteria are prokaryotes that lack nucleus; cell wall is key component - target for immune system and antibiotics (GP is thicc with lipotechoic acid, GN is thin and surrounded by outer and inner membrane w/___ space) *___* triggers immune reaction in GPs GNs contains periplasmic space (b/w CM and outer membrane) that contains enzymes (beta-___!); *outer membrane is made of LPS (lipid A + O antigen) --> VERY immunogenic! (___ triggers cytokine release)* *HY: peptidoglycan is made up of NAM-NAG sugars; importantly, peptides ATTACH TO ___; sugar/peptide backbones make chains, which are cross-linked by peptide cross-bridges* Electron transport and oxidative phosphorylation occur in the ___ (lipid bilayer internal to CW) *UNIQUE*: mycoPLASMA has no cell wall (does not take GS); mycoBACTERIA has cell wall with ___ acid (does not take GS --> used Ziehl-___); chlamydia lacks ___ acid (does not GS)

Bacteria are prokaryotes that lack nucleus; cell wall is key component - target for immune system and antibiotics (GP is thicc with lipotechoic acid, GN is thin and surrounded by outer and inner membrane w/periplasmic space) *LTA* triggers immune reaction in GPs GNs contains periplasmic space (b/w CM and outer membrane) that contains enzymes (beta-lactamase!); *outer membrane is made of LPS (lipid A + O antigen) --> VERY immunogenic! (lipid A triggers cytokine release)* *HY: peptidoglycan is made up of NAM-NAG sugars; importantly, peptides ATTACH TO NAM (Merge); sugar/peptide backbones make chains, which are cross-linked by peptide cross-bridges* Electron transport and oxidative phosphorylation occur in the cell membrane (lipid bilayer internal to CW) UNIQUE: mycoplasma has no cell wall (does not take GS); mycobacteria has cell wall with mycolic acid (does not take GS --> used Ziehl-Neelsen); chlamydia lacks muramic acid (does not GS)

Bacterial Growth Phases: lag, ___ (Abx have greatest effect), stationary, and death ___ is direct DNA uptake by bacteria from surrounding environment Conjugation is transfer from one cell to another via pilus (transferred via plasmids - circular DNA separate from chromosomal DNA); *___ can be excised --> moved to plasmid, mechanism of ___ transfer* Transduction is transfer of DNA via bacteriophage (Generalized/Lytic cycle --> random host DNA picked up and transferred to another bact; *Specialized/___ cycle --> bacteriophage DNA incorporates into bacterial DNA, then transfer of specific ___ DNA that was next to incorporated bacteriophage DNA - certain triggers induce genome expression, giving bact new abilities*) Lysogenic toxins include *___ (classic one)*, shiga-toxin, cholera, botulinum CLASSIC SCENARIO: strain A requires X, strain B requires Y, cultured without X or Y, DNAase added, bacteria grow --> what process occurred?

Bacterial Growth Phases: lag, growth (Abx have greatest effect), stationary, and death Transformation is direct DNA uptake by bacteria from surrounding environment Conjugation is transfer from one cell to another via pilus (transferred via plasmids - circular DNA separate from chromosomal DNA); *transposons can be excised --> moved to plasmid, mechanism of resistance transfer* Transduction is transfer of DNA via bacteriophage (Generalized/Lytic cycle --> random host DNA picked up and transferred to another bact; *Specialized/Lysogenic cycle --> bacteriophage DNA incorporates into bacterial DNA, then transfer of specific host DNA that was next to incorporated bacteriophage DNA - certain triggers induce genome expression, giving bact new abilities*) Lysogenic toxins include *DIPHTHERIA*, shiga-toxin, cholera, botulinum --- CONJUGATION (DNAase destroyed free floating DNA --> can't be transformation)

Bacterial capsules are sticky layer that allows for host attachment, protects against phagocytosis; most are made of polysaccharide *EXCEPT ___ (D-glutamate)*; capsule is often conjugated and used for vaccines (N meninigitis, S pneumo, H ___) ___ rxn used to identify encapsulated bugs (rabbit antiserum added to sample --> capsule swells) IMMUNOLOGY: B-cells secrete capsular antibodies --> triggers phagocytosis (need Ab to be phagocytized) and complement cascade; *HY: loss of ___ predisposes to recurrent encapsulated infxns (___ as well 2/2 loss of splenic phagocytes, which eat bugs tagged with Abs)* NOTE: glycocalyx is different (irregular, slimy/fuzzy vs. distinct capsule); glycocalyx is used to adhere to surfaces (___ biofilms)

Bacterial capsules are sticky layer that allows for host attachment, protects against phagocytosis; most are made of polysaccharide *EXCEPT B. anthracis (D-glutamate)*; capsule is often conjugated and used for vaccines (N meninigitis, S pneumo, H flu) Quellung rxn used to identify encapsulated bugs (rabbit antiserum added to sample --> capsule swells) IMMUNOLOGY: B-cells secrete capsular antibodies --> triggers phagocytosis (need Ab to be phagocytized) and complement cascade; *HY: loss of Abs/B-cells/complement predisposes to recurrent encapsulated infxns (asplenia as well 2/2 loss of splenic phagocytes, which eat bugs tagged with Abs)* NOTE: glycocalyx is different (irregular, slimy/fuzzy vs. distinct capsule); glycocalyx is used to adhere to surfaces (S epidermidis biofilms)

___ (2/2 str. basale overgrowth) is MC skin ca. that is slow-growing, rare mets. (lowest met. potential) BCC appears as *"___" papule or nodule (shiny app.)* w/telangectasias that may ulcerate w/crusty center; path. reveals *nests of "basaloid" dark cells in dermis + "___ nuclei"* Superficial BCC is variant w/light red-pink plaque and scale

Basal cell carcinoma (2/2 str. basale overgrowth) is MC skin ca. that is slow-growing, rare mets. (lowest met. potential) BCC appears as *"pearly" papule or nodule (shiny app.)* w/telangectasias that may ulcerate w/crusty center; path. reveals *nests of "basaloid" dark cells in dermis + "palisading nuclei"* Superficial BCC is variant w/light red-pink plaque and scale

Basilar artery stroke (ventral pontine stroke) results in locked-in syndrome with quadriplegia and ability to only ___ - can see similar scenario with ___ ___ stroke (lateral pons) results in loss of vestib nuc (nystagmus), spinothal tract (contra pain/temp loss), spinal V nuc (ipsilat face pain/temp loss), symp tract (Horner's), *facial nuc (facial droop + ant tongue taste loss)*, and *coch nuc (___ loss)* ___ stroke (lateral medulla) results in many similar sx (nystagmus, Horner's, contra pain/temp, ipsilat face pain/temp) *but with ___ 2/2 nuc ambig loss* ASA stroke results in loss of everything but *___ in spinal cord* and medial medullary syndrome in brainstem (corticospinal tract, medial lemniscus, and *CN12 - ___ deviation*)

Basilar artery stroke (ventral pontine stroke) results in locked-in syndrome with quadriplegia and ability to only blink - can see similar scenario with central pontine myelinolysis AICA stroke (lateral pons) results in loss of vestib nuc (nystagmus), spinothal tract (contra pain/temp loss), spinal V nuc (ipsilat face pain/temp loss), symp tract (Horner's), *facial nuc (facial droop + ant tongue taste loss)*, and *coch nuc (hearing loss)* PICA stroke (lateral medulla) results in many similar sx (nystagmus, Horner's, contra pain/temp, ipsilat face pain/temp) *but with hoarseness 2/2 nuc ambig loss* ASA stroke results in loss of everything but *vibration/proprioception in spinal cord* and medial medullary syndrome in brainstem (corticospinal tract, medial lemniscus, and *CN12 - tongue deviation*)

Beta ___ is absence of beta globin chain synthesis - there are only two genes for beta chain on chrom11 (four for alpha chain) Beta thalassemia is d/t *___ in beta gene (NOT deletions like in alpha thalassemia)* - because of this, there is a wide spectrum of dz depending on the mutation (B0 --> no function, B1 --> some function) Beta thalassemia is particularly common in ___ countries (*Italy, Greece, France, Turkey*) --- Beta thalassemia minor is single abnormal gene that is underproduced, but with enough beta globin that there are *___ symptoms (mild anemia on bloodwork)* Dx: Hgb electrophoresis w/*___ (KNOW THIS!)!* --- Beta thalassemia major is two abnormal beta globin genes - pts develop anemia in 1st year of life (when ___ begins to wane) - pts develop erythropoeisis w/___ chain tetramers Four Features of B-Thal-Maj: 1) hypochromic microcytic anemia, 2) abnormal RBC shapes *(microcytosis, ___cytosis, basophilic stippling, target cells)*, 3) erythroid ___ *(expansion of bone marrow --> "chipmunk facies", c___ c___ appearance)*, 4) extramedullary hematopoiesis (___megaly) Beta-thall major is exquisitely sensitive to parvovirus B19 Dx: electrophoresis (low or absent ___, increased ___ and HbF) Tx: transfusions (pts at risk for iron overload)

Beta thalassemia is absence of beta globin chain synthesis - there are only two genes for beta chain on chrom11 (four for alpha chain) Beta thalassemia is d/t *MUTATIONS in beta gene (NOT deletions like in alpha thalassemia)* - because of this, there is a wide spectrum of dz depending on the mutation (B0 --> no function, B1 --> some function) Beta thalassemia is particularly common in Mediterranean countries (*Italy, Greece, France, Turkey*) --- Beta thalassemia minor is single abnormal gene that is underproduced, but with enough beta globin that there are *no symptoms (mild anemia on bloodwork)* Dx: Hgb electrophoresis w/*increased HbA2 (KNOW THIS!)!* --- Beta thalassemia major is two abnormal beta globin genes - pts develop anemia in 1st year of life (when HgbF begins to wane) - pts develop erythropoeisis w/alpha chain tetramers Four Features of B-Thal-Maj: 1) hypochromic microcytic anemia, 2) abnormal RBC shapes *(microcytosis, anisopoikilocytosis, basophilic stippling, target cells)*, 3) erythroid hyperplasia *(expansion of bone marrow --> "chipmunk facies", crew cut appearance)*, 4) extramedullary hematopoiesis (hepatosplenomegaly) Beta-thall major is exquisitely sensitive to parvovirus B19 Dx: electrophoresis (low or absent HbA, increased HbA2 and HbF) Tx: transfusions (pts at risk for iron overload)

Bias is systematic error in a study (think of chemical exposure increasing HAs) H___ Effect: study pts/investigators behave different bc being studied (common in behavior studies, i.e., pt studied for exercise capacity starts working out more) P___ Effect (observer-expectancy eff.): researcher influences outcome of study to be positive d/t belief in tx (unique to investigator driving positive benefit) L___ T___ Bias: screen test identifies dz earlier --> makes survival appear longer (i.e., detect breast lump 2y early, expectancy is 2y longer) Recall Bias: surveyed on events that can't remember P___ Bias: one group receives procedure --> gets more care/attention than non-proc. group L___-Look Bias: pts with sev. dz don't get studied bc they die (i.e., healthy pts can fill out survey easier) Observer Bias: investigators know exposure status of pt M___ Bias: sloppy research technique (i.e., BP not measured correctly)

Bias is systematic error in a study (think of chemical exposure increasing HAs) Hawthorne Effect: study pts/investigators behave different bc being studied (common in behavior studies, i.e., pt studied for exercise capacity starts working out more) Pygmalion Effect (observer-expectancy eff.): researcher influences outcome of study to be positive d/t belief in tx (unique to investigator driving positive benefit) Lead Time Bias: screen test identifies dz earlier --> makes survival appear longer (i.e., detect breast lump 2y early, expectancy is 2y longer) Recall Bias: surveyed on events that can't remember Procedure Bias: one group receives procedure --> gets more care/attention than non-proc. group Late-Look Bias: pts with sev. dz don't get studied bc they die (i.e., healthy pts can fill out survey easier) Observer Bias: investigators know exposure status of pt Measurement Bias: sloppy research technique (i.e., BP not measured correctly)

Bias is systematic error in a study (think of chemical exposure increasing HAs) S___ Bias: groups differ in ways other than exposure (i.e., plant worker w/exposure compared to gen. pop. w.o exposure), also see this with *study volunteers*; if groups differ by one factor (smoking) --> confounding A___ Bias (select. subtype): pts lost to follow-up unequally btwn groups (pts that die) S___ Bias (select. sub.): pts in trial not representative of actual practice (i.e., HF study with average age of 30) *[HY] C___ Bias: unmeasured factor confounds study results (i.e., alcoholics appear to get lung cancer, but actually they smoke more - smoking --> confounding); can identify confounding bias w/STRATIFIED ANALYSIS (divide group by confounder to determine rates) - may be shown this on exam! if ___ goes away after dividing into subgroups --> confounding* *[HY] Mechanisms for avoiding confounding inc. r___ and m___ (careful selection of control pts)*

Bias is systematic error in a study (think of chemical exposure increasing HAs) Selection Bias: groups differ in ways other than exposure (i.e., plant worker w/exposure compared to gen. pop. w.o exposure), also see this with *study volunteers*; if groups differ by one factor (smoking) --> confounding Attrition Bias: pts lost to follow-up unequally btwn groups (pts that die) Sampling Bias: pts in trial not representative of actual practice (i.e., HF study with average age of 30) *[HY] Confounding Bias: unmeasured factor confounds study results (i.e., alcoholics appear to get lung cancer, but actually they smoke more - smoking --> confounding); can identify confounding bias w/STRATIFIED ANALYSIS (divide group by confounder to determine rates) - may be shown this on exam! if RR goes away after dividing into subgroups --> confounding* *[HY] Mechanisms for avoiding confounding inc. randomization and matching (careful selection of control pts)*

Bile is composed of bilirubin, bile salts, and cholesterol - balance of these components keeps bile fluid (NOT precipitate) Bilirubin (pigment - ___) stones (radio___ - think PIGMENTED) are 2/2 ___ bilirubin buildup; accordingly, any rise in indirect bili --> bili stones RFs include: -Extravascular ___ -Cirrhosis (poor bili conjugation) -Biliary tree infxns (bacterial glucuronidase can convert direct bili --> indirect bili, *remember glucuronidase does this in intestine for enterohepatic circulation!*)

Bile is composed of bilirubin, bile salts, and cholesterol - balance of these components keeps bile fluid (NOT precipitate) Bilirubin (pigment - black) stones (radioopaque) are 2/2 unconjugated bilirubin buildup; accordingly, any rise in indirect bili --> bili stones RFs include: -Extravascular hemolysis -Cirrhosis (poor bili conjugation) -Biliary tree infxns (bacterial glucuronidase can convert direct bili --> indirect bili, *remember glucuronidase does this in intestine for enterohepatic circulation!*)

Bile is composed of bilirubin, bile salts, and cholesterol - balance of these components keeps bile fluid (NOT precipitate) MC gallstones are ___ gallstones (radiolucent) - classically seen in 40y obese pts; when seen in elderly --> think GB ___ RFs include (*remember the balance of bili, bile salts, and chole!*): 1) Excess ___/cholesterol (estrogen promotes cholesterol synthesis; females, pregnancy/multiparity, obesity) 2) Altered lipid metabolism 3) Loss of ___ (cirrhosis, Crohn's dz [terminal ileum inflammation --> can't reabsorb bile salts], CF, clofibrate, bile acid resins) Can also remember 4Fs for RFs: fat, female, fertile, 40y

Bile is composed of bilirubin, bile salts, and cholesterol - balance of these components keeps bile fluid (NOT precipitate) MC gallstones are cholesterol gallstones (radiolucent) - classically seen in 40y obese pts; when seen in elderly --> think GB cancer RFs include (r*emember the balance of bili, bile salts, and chole!*): 1) Excess estrogen/cholesterol (estrogen promotes cholesterol synthesis; females, pregnancy/multiparity, obesity) 2) Altered lipid metabolism 3) Loss of bile salts (cirrhosis, Crohn's dz [terminal ileum inflammation --> can't reabsorb bile salts], CF, clofibrate, bile acid resins) Can also remember 4Fs for RFs: fat, female, fertile, 40y

Bile salts help w/___ absorption - triglycerides are broken to FAs via pancreatic lipase, FAs are not soluble in water --> bile emulsifies lipids (suspend them in water) by surrounding lipids --> more surface area for pancreatic l___ Bile acids (cholic acid, chenodeoxycholic acid - both synthesized from cholesterol) are conjugated w/tau___ and gly___ to be made hydrophilic Rate limiting step of bile synthesis is catalyzed by ___-alpha ___

Bile salts help w/lipid absorption - triglycerides are broken to FAs via pancreatic lipase, FAs are not soluble in water --> bile emulsifies lipids (suspend them in water) by surrounding lipids --> more surface area for pancreatic lipase Bile acids (cholic acid, chenodeoxycholic acid - both synthesized from cholesterol) are conjugated w/taurine and glycine to be made hydrophilic Rate limiting step of bile synthesis is catalyzed by 7-alpha hydroxylase

___ is idiopathic biliary obstruction in neonates (bile ducts do not form) - p/w jaundice, dark urine, and pale ("a___") stools; RUQ US will reveal *absent gallbladder* --- Cholangiocarcinoma is rare cancer of bile duct e___ - key RFs are conditions with chronic inflammation of biliary tract: 1) *primary ___ cholangitis* and 2) *C___ (Chinese liver fluke) infxn*

Biliary atresia is idiopathic biliary obstruction in neonates (bile ducts do not form) - p/w jaundice, dark urine, and pale ("acholic") stools; RUQ US will reveal *absent gallbladder* --- Cholangiocarcinoma is rare cancer of bile duct epithelium - key RFs are conditions with chronic inflammation of biliary tract: 1) *primary sclerosing cholangitis* and 2) *Clonorchis sinensis (Chinese liver fluke) infxn*

Biliary cirrhosis is liver damage 2/2 biliary obstruction - Primary biliary is biliary cirrhosis *___ extra-hepatic obstruction*; this is an autoimmune d.o *[HY] involving ___-cell attack on small INTER___ BILE DUCTS - also will see ___ inflammation! (NOTE: PSC --> UC, nongranulomatous; PBC isn't w/Crohn's, but hopefully helps remember granulomas/what goes where)* PBC is common in women and p/w *fatigue + ___/itching (precedes jaundice!!) that is worse @ night* *[HY] PBC is a/w other autoimmune d.o, most commonly ___* PBC Labs: AlkPhos high, *positive ___ antibodies!*, hyperlipidemia (w/xanthomas) PBC Imaging: *absence of biliary obstruction - NO ___ (w/this presentation, obstruction is on ddx, but absence endorse PBC)* Tx: urso___ acid (PSC doesn't have medical tx)

Biliary cirrhosis is liver damage 2/2 biliary obstruction - Primary biliary is biliary cirrhosis *WITHOUT extra-hepatic obstruction*; this is an autoimmune d.o *[HY] involving T-cell attack on small INTERLOBULAR BILE DUCTS - also will see GRANULOMATOUS inflammation!* PBC is common in women and p/w *fatigue + PRURITUS/itching (precedes jaundice!!) that is worse @ night* *[HY] PBC is a/w other autoimmune d.o, most commonly Sjogren's* PBC Labs: AlkPhos high, *positive anti-mitochondrial antibodies!*, hyperlipidemia (w/xanthomas) PBC Imaging: *absence of biliary obstruction - NO dilation (w/this presentation, obstruction is on ddx, but absence endorse PBC)* Tx: ursodeoxycholic acid (PSC doesn't have medical tx)

Biliary colic is episodic RUQ pain w/*radiation to ___* - occurs when GB contracts against stone; pain is especially worse after fatty meals (*CCK release*) Acute ___ is inflammation of gallbladder after stone in *CYSTIC duct* --> obstruction --> inflammation + wall ___; p/w RUQ pain, fever, leukocytosis - also look for Murphy's sign Chronic cholecystitis is chronic, untreated cholecystitis --> chronic inflammation --> *___ gallbladder, high risk of gallbladder ___!!* Acalculous cholecystitis is NOT d/t gallstones - seen w/gallbladder ischemia & stasis in ___ pts ___ is d/t stone blocking bile flow + bacteria ascending biliary tree - *Charcot's triad (___) & Reynold's pentad (+ ___)*; MC bugs are GNs (E coli, Klebsiella, Enterobacter), but *can see Clonorchis sinensis (helminth - look for ___!!)* - tx w/Abx (Zosyn) + biliary drainage (ERCP) ___ is d/t gallstone in common bile duct --> jaundice + elevated LFTs (can lead to *CHOLANGITIS*)

Biliary colic is episodic RUQ pain w/*radiation to R shoulder* - occurs when GB contracts against stone; pain is especially worse after fatty meals (*CCK release*) Acute cholecystitis is inflammation of gallbladder after stone in *CYSTIC duct* --> obstruction --> inflammation + wall thickening; p/w RUQ pain, fever, leukocytosis - also look for Murphy's sign Chronic cholecystitis is chronic, untreated cholecystitis --> chronic inflammation --> *porcelain gallbladder, high risk of gallbladder carcinoma!!* Acalculous cholecystitis is NOT d/t gallstones - seen w/gallbladder ischemia & stasis in critically ill pts Ascending/Acute cholangitis is d/t stone blocking bile flow + bacteria ascending biliary tree - *Charcot's triad (fever, RUQ pain, jaundice) & Reynold's pentad (+confusion, hypotension)*; MC bugs are GNs (E coli, Klebsiella, Enterobacter), but *can see Clonorchis sinensis (helminth - look for EOSINOPHILIA!!)* - tx w/Abx (Zosyn) + biliary drainage (ERCP) Choledocolithiasis is d/t gallstone in common bile duct --> jaundice + elevated LFTs (can lead to *CHOLANGITIS*)

Bilirubin is metabolized version of ___; heme is engulfed by macrophages and converted to biliverdin, then bilirubin (not soluble - carried by ___ to liver) In liver, bilirubin is conjugated w/glucuronic acid via *U___ g___ (UGT)*, which increases solubility for excretion In intestines, conjugated bilirubin undergoes two conversions via bact. enzymes: 1) returns to ___ bili (via *beta-glucuronidase - important in pathogenesis of BILIRUBIN STONES*) and 2) unconj. bili. --> ___ Urobilinogen has two fates: 1) excretion in feces (80-90% - converted to s___ beforehand) or 2) reabsorption by intestines (can be converted to urobilin for urinary output - yellow color) ^NOTE: direct --> conjugated --> soluble, indirect --> unconjugated --> insoluble (vowels run together)

Bilirubin is metabolized version of heme; heme is engulfed by macrophages and converted to biliverdin, then bilirubin (not soluble - carried by albumin to liver) In liver, bilirubin is conjugated w/glucuronic acid via *UDP glucuronyltransferase (UGT)*, which increases solubility for excretion In intestines, conjugated bilirubin undergoes two conversions via bact. enzymes: 1) returns to unconjugated bili (via *beta-glucuronidase*) and 2) unconj. bili. --> urobilinogen Urobilinogen has two fates: 1) excretion in feces (80-90% - converted to stercobilin beforehand) or 2) reabsorption by intestines (can be converted to urobilin for urinary output - yellow color) ^NOTE: direct --> conjugated --> soluble, indirect --> unconjugated --> insoluble (vowels run together)

Bioavailability (F) is % of drug that reaches systemic circulation unchanged *[HY] IV administration results in ___% bioavailability; PO administration always results in <100% bioavailability, 2/2 incomplete absorption AND first ___ metabolism* 1st Pass Metab.: oral drugs absorbed --> liver --> rapidly metabolized --> dec. amnt that reaches circulation (*[HY] 1st Pass Metab. can be reduced in ___ --> incr. [drug]*) Bioavailability can be graphed with IV vs. oral admin.; Bioavailability = ([AUC Oral]/[AUC IV]) x 100

Bioavailability (F) is % of drug that reaches systemic circulation unchanged *[HY] IV administration results in 100% bioavailability; PO administration always results in <100% bioavailability, 2/2 incomplete absorption AND first pass metabolism* 1st Pass Metab.: oral drugs absorbed --> liver --> rapidly metabolized --> dec. amnt that reaches circulation (*[HY] 1st Pass Metab. can be reduced in liver dz --> inc. [drug]*) Bioavailability can be graphed with IV vs. oral admin.; Bioavailability = ([AUC Oral]/[AUC IV]) x 100

Blood blister is 2/2 bleeding in dermis w/intact epidermis; looks similar to vasc. tumors - ddx formed based on pt characteristics ___ is tumor of blood/lymph vessels (lymphangiosarcoma v. hemangiosarcoma v. benign hemangioma) - malig. lesions carry poor progn.; angiosarcomas seen in L___ (a/w vinyl chloride exp.) and breast (s/p XRT, seen after mastectomy w/lymphedema), but most common in skin dermis (dermis is where BVs are; seen in head/neck, male predominance, old age) Bacillary Angiomatosis is 2/2 ___, seen in AIDS --> numerous red/purple nodules (bacterial - ___ [cell type?]) Kaposi Sarcoma is 2/2 ___, seen in AIDS --> numerous red/purple nodules (viral - ___ [cell type?]) Pyogenic granuloma is ben. vasc. tumor 2/2 hyperplasia of BVs d/t growth stimuli (*classic stimuli: tr___, pr___*) - often bleed profusely and are removed surgically

Blood blister is 2/2 bleeding in dermis w/intact epidermis; looks similar to vasc. tumors - ddx formed based on pt characteristics Angiosarcoma is tumor of blood/lymph vessels (lymphangiosarcoma v. hemangiosarcoma v. benign hemangioma) - malig. lesions carry poor progn.; angiosarcomas seen in liver (a/w vinyl chloride exp.) and breast (s/p XRT, seen after mastectomy w/lymphedema), but most common in skin dermis (dermis is where BVs are; seen in head/neck, male predominance, old age) Bacillary Angiomatosis is 2/2 Bartonella, seen in AIDS --> numerous red/purple nodules (bacterial - NEUTROPHILS) Kaposi Sarcoma is 2/2 HHV-8, seen in AIDS --> numerous red/purple nodules (viral - LYMPHOCYTES) Pyogenic granuloma is ben. vasc. tumor 2/2 hyperplasia of BVs d/t growth stimuli (*classic stimuli: trauma, pregnancy*) - often bleed profusely and are removed surgically

Blood blister is 2/2 bleeding in dermis w/intact epidermis; looks similar to vasc. tumors - ddx formed based on pt characteristics ___ hemangioma is ben. proliferation of capillaries in middle-to-elder age pts - usually multiple lesions on trunk Cystic ___ is congen. malformation seen in bebes w/cyst containing lymph - identified on prenatal US (inc. risk for Down's, Turner's, miscarriage) ___ body is structure in dermis that cont. smooth muscle cells --> reg. skin temp. by shunting blood away from surface in cold (preserves heat, seen in *in hands and feet!*); ___ tumor is ben. growth of SMCs in *f___/t___* - pink/purple nodule that are PAINFUL when exposed to ___! Strawberry hemangioma are benign proliferation of BVs seen in *___* - involute within years Nevus simplex is *capillary ___ (not tumor!)* seen in babies - common on eyelids or nape of neck ("stork bite") and fade within years Nevus flammeus is *malformation* of dermal capillaries/venules - often unilateral and blanches with pressure; importantly, *does NOT regress and is seen in ___ Syndrome*

Blood blister is 2/2 bleeding in dermis w/intact epidermis; looks similar to vasc. tumors - ddx formed based on pt characteristics Cherry hemangioma is ben. proliferation of capillaries in middle-to-elder age pts - usually multiple lesions on trunk Cystic hygroma is congen. malformation seen in bebes w/cyst containing lymph - identified on prenatal US (inc. risk for Down's, Turner's, miscarriage) Glomus body is structure in dermis that cont. smooth muscle cells --> reg. skin temp. by shunting blood away from surface in cold (preserves heat, seen in *in hands and feet!*); Glomus tumor is ben. growth of SMCs in *fingers/toes* - pink/purple nodule that are PAINFUL when exposed to COLD! Strawberry hemangioma are benign proliferation of BVs seen in *BABIES* - involute within years Nevus simplex is *capillary malformation (not tumor!)* seen in babies - common on eyelids or nape of neck ("stork bite") and fade within years Nevus flammeus is *malformation* of dermal capillaries/venules - often unilateral and blanches with pressure; importantly, *does NOT regress and is seen in Sturge-Weber Syndrome*

Blood products include ___ (plasma removed), platelets (rxns less common than those with RBCs), ___ (administered to correct clotting factor deficiencies, will correct PT/PTT), ___ (contains lots of fibrinogen - give after trauma) --- Acute hemolytic transfusion reaction is feared complication of blood transfusion, in which preformed antibodies attack donor RBCs (type ___ HS rxn) - Direct Coombs Test will be ___ This is life-threatening reaction l/t massive hemolysis of transfused RBCs, potentially l/t D___ Usual cause is *system or clerical error* --- Anaphylaxis (type ___ HS rxn) can occur in *___ deficiency - anti-IgA IgE antibodies react --> anaphylaxis* Tx: stop transfusion + epinephrine --- Febrile non-hemolytic transfusion reaction is d/t ___ in blood products - no other systemic symptoms are seen --- T___ is sudden onset hypoxemia during transfusion w/fever, chills and infiltrates on chest x-ray TRALI is d/t ___ activation by blood products (some pts predisposed w/PMNs in lungs --> PMNs are activated by blood product --> release cytokines --> increased capillary permeability --> ___ edema)

Blood products include pRBCs (plasma removed), platelets (rxns less common than those with RBCs), FFP (administered to correct clotting factor deficiencies, will correct PT/PTT), cryoprecipitate (contains lots of fibrinogen - give after trauma) --- Acute hemolytic transfusion reaction is feared complication of blood transfusion, in which preformed antibodies attack donor RBCs (type II HS rxn) - Direct Coombs Test will be positive This is life-threatening reaction l/t massive hemolysis of transfused RBCs, potentially l/t DIC Usual cause is *system or clerical error* --- Anaphylaxis (type I HS rxn) can occur in *IgA deficiency - anti-IgA IgE antibodies react --> anaphylaxis* Tx: stop transfusion + epinephrine --- Febrile non-hemolytic transfusion reaction is d/t cytokines in blood products - no other systemic symptoms are seen --- Transfusion related acute lung injury is sudden onset hypoxemia during transfusion w/fever, chills and infiltrates on chest x-ray TRALI is d/t neutrophil activation by blood products (some pts predisposed w/PMNs in lungs --> PMNs are activated by blood product --> release cytokines --> increased capillary permeability --> pulmonary edema)

Blood type testing involves taking pts blood, mixing with antibodies to antigens (anti-A, anti-B), then watch for ___ Once you know pts blood type, test for other rare antibodies - *type and screen* In type and screen, recipient ___ is mixed with standard ___ that contain many antigens - if no agglutination --> pt lacks Abs, if agglutination --> pt has Abs to less common antigens If patient has abnormal type and screen (i.e., ___ occurs), must *determine which antibody is present* In subsequent transfusions, test ___ blood for specific antigen that pt has antibodies to (challenging in pts with long transfusion history - SCA, beta thalassemia major) --- *Type and ___* is more specific - mix pts serum w/*potential donor* RBCs and look for agglutination (if none --> transfuse)

Blood type testing involves taking pts blood, mixing with antibodies to antigens (anti-A, anti-B), then watch for agglutination Once you know pts blood type, test for other rare antibodies - *type and screen* In type and screen, recipient serum is mixed with standard RBCs that contain many antigens - if no agglutination --> pt lacks Abs, if agglutination --> pt has Abs to less common antigens If patient has abnormal type and screen (i.e., agglutination occurs), must *determine which antibody is present* In subsequent transfusions, test donor blood for specific antigen that pt has antibodies to (challenging in pts with long transfusion history - SCA, beta thalassemia major) --- *Type and Cross* is more specific - mix pts serum w/*potential donor* RBCs and look for agglutination (if none --> transfuse)

Body is 60% water, 40% non-water Total body water is 33% extracellular, 67% intracellular Extracellular fluid is 25% plasma, 75% interstitial fluid *___* has important renal properties bc it stays in *EXTRACELLULAR* space (10g inulin, equilibrium concentration is ___g/L, extracellular fluid space = 40L) *___* has important renal properties bc it stays in *PLASMA*

Body is 60% water, 40% non-water Total body water is 33% extracellular, 67% intracellular Extracellular fluid is 25% plasma, 75% interstitial fluid *Inulin* has important renal properties bc it stays in *EXTRACELLULAR* space (10g inulin, equilibrium concentration is 0.25g/L, extracellular fluid space = 40L) *Radiolabeled albumin* has important renal properties bc it stays in *PLASMA*

Bone marrow transplants have unique problems as grafted cells *must replenish all cell lines* Two unique probs: 1) rejection of new cells and 2) ___ versus ___ dz GVHD is when ___ (donor or recipient?) T-cells react to ___ (donor or recipient?) cells (*opposite of rejection - tissue is rejecting body!*); this presents with rash (skin), diarrhea/abdominal pain (GI tract), and elevated LFTs/bilirubin (liver) In some patients (i.e., leukemia), small amount of GVHD may be a good thing as grafted (donor) cells kill remaining host (recipient - malignant) cells (*graft-vs-___ effect*) GVHD is type ___ HS rxn

Bone marrow transplants have unique problems as grafted cells *must replenish all cell lines* Two unique probs: 1) rejection of new cells and 2) graft versus host dz GVHD is when donated (grafted) T-cells react to recipient cells (*opposite of rejection - tissue is rejecting body!*); this presents with rash (skin), diarrhea/abdominal pain (GI tract), and elevated LFTs/bilirubin (liver) In some patients (i.e., leukemia), small amount of GVHD may be a good thing as grafted (donor) cells kill remaining host (recipient - malignant) cells (*graft-vs-leukemia effect*) GVHD is type IV HS rxn

Bowel atresia and stenosis can present prenatally w/___ and in neonatal period w/___ vomiting Duodenal atresia is d/t *failure to recanalize the duodenum* - *[HY] x-ray will show "___" sign and is [HY] a/w ___* Jejunal/ileal/colonic atresia is believed to be d/t ischemic necrosis of intestine --> resorption of necrotic tissue --> blind end of bowel; bowel distal to blind end may be curled ("___ atresia"), x-ray may show "triple bubble" (dilated stomach, duodenum, *proximal ___ [unique from duodenal atresia]*) Hypertrophic pyloric stenosis is palpable *___-shaped* mass that leads to *___ non-bilious vomiting* at 2-6w of age; HPS is most common in ___ born males; dx w/US

Bowel atresia and stenosis can present prenatally w/polyhydramnios and in neonatal period w/bilious vomiting Duodenal atresia is d/t *failure to recanalize the duodenum* - *[HY] x-ray will show "Double-bubble" sign and is [HY] a/w Down's syndrome* Jejunal/ileal/colonic atresia is believed to be d/t ischemic necrosis of intestine --> resorption of necrotic tissue --> blind end of bowel; bowel distal to blind end may be curled ("apple peel atresia"), x-ray may show "triple bubble" (dilated stomach, duodenum, *proximal jejunum [unique from duodenal atresia]*) Hypertrophic pyloric stenosis is palpable *olive-shaped* mass that leads to *PROJECTILE non-bilious vomiting* at 2-6w of age; HPS is most common in first born males; dx w/US

Brachial plexus (Randy, Tre, DJ, Cal, are Names) has 5 nerves: ___ (5) Axillary nn. (C5-C6, from post. cord) innervates deltoid (also teres minor) and provides ___ sensation; lesion (2/2 ___ humerus fx or ___ shoulder dislocation) p/w loss of sensation and no shoulder a___ Radial nn. (C5-T1, from post. cord) innervates ___ compartments (arm, wrist, fingers) and provides ___ hand/forearm sensation; lesion (2/2 "Saturday night palsy", crutches, ___ humerus fx) p/w wrist drop and sensory loss to post. hand/forearm (NOTE: can change based on location of lesion, proximal lesion may involve triceps w.o sensory loss) Musculocutaneous nn. (C5-C7) innervates biceps and sensation to ___ forearm; lesions are rare, but w/weak flexion and lat. forearm sensory loss (also loss of ___ reflex - C5-6) Median nn. (C5-T1) and ulnar nn. (C8-T1) lesions are covered elsewhere (but w/predictable presentation)

Brachial plexus (Randy, Tre, DJ, Cal, are Names) has 5 nerves: axillary, radial, median, ulnar, musculocutaneous Axillary nn. (C5-C6, from post. cord) innervates deltoid and provides deltoid sensation; lesion (2/2 prox. humerus fx or ant. shoulder dislocation) p/w loss of sensation and no shoulder abduction Radial nn. (C5-T1, from post. cord) innervates extensor compartments (arm, wrist, fingers) and provides post. hand/forearm sensation; lesion (2/2 "Saturday night palsy", crutches, midshaft humerus fx) p/w wrist drop and sensory loss to post. hand/forearm (NOTE: can change based on location of lesion, proximal lesion may involve triceps w.o sensory loss) Musculocutaneous nn. (C5-C7) innervates biceps and sensation to lat. forearm; lesions are rare, but w/weak flexion and lat. forearm sensory loss (also loss of biceps reflex - C5-6) Median nn. (C5-T1) and ulnar nn. (C8-T1) lesions are covered elsewhere (but w/predictable presentation)

Brachial plexus has trunks (upper and lower) and long thoracic nn. Upper trunk (C5-C6) injury (___ palsy) is 2/2 excessive angle at neck/shoulder, usually 2/2 birth trauma (macrosomia l/t shoulder dystocia); lose ___ nn. (deltoid), ___ nn. (biceps), and ___ nn. (infraspinatus) - p/w flat shoulder, extended/pronated elbow, internally rotated arm Lower trunk (C8-T1) injury (___ palsy) is 2/2 excessive abduction of arm, usually 2/2 falling from tree; lose ___ nn. and ___ nn. (intrinsic hand muscles - long flexors spared) - p/w complete ___ hand (flexed IP joints, extended MCP joints) Thoracic Outlet Syndrome is compression of lower trunk 2/2 *[HY] ___ rib (+ clavicle @ scalene triangle)*; p/w Klumpke palsy + arm ___ Long Thoracic nn. (C5-C7) innervates serratus anterior (pulls scapula against rib cage); lesion of LTN results in ___ scapula

Brachial plexus has trunks (upper and lower) and long thoracic nn. Upper trunk (C5-C6) injury (Erb's palsy) is 2/2 excessive angle at neck/shoulder, usually 2/2 birth trauma (macrosomia l/t shoulder dystocia); lose axillary nn. (deltoid), musculocutaneous nn. (biceps), and suprascapular nn. (infraspinatus) - p/w flat shoulder, extended/pronated elbow, internally rotated arm Lower trunk (C8-T1) injury (Klumpke palsy) is 2/2 excessive abduction of arm, usually 2/2 falling from tree; lose ulnar nn. and median nn. (intrinsic hand muscles - long flexors spared) - p/w complete clawed hand (flexed IP joints, extended MCP joints) Thoracic Outlet Syndrome is compression of lower trunk 2/2 *[HY] cervical rib (+ clavicle @ scalene triangle)*; p/w Klumpke palsy + arm swelling Long Thoracic nn. (C5-C7) innervates serratus anterior (pulls scapula against rib cage); lesion of LTN results in winged scapula

Branched chain amino acids (Isoleucine, Leucine, Valine - I Love Vermont) depends on alpha-ketoacid dehydrogenase for metabolism (aka, BCKDC - branched chain ketoacid dehydrogenase complex) BCKDC requires B1 as cofactor (B1ranches on Vermont trees) Deficiency in BCKDC --> *maple syrup urine dz* (AR dz with five phenotypes); p/w elevated alpha ketoacids + branched chain AAs in plasma, sweet smelling urine (2/2 isoleucine alpha-ketoacid in urine) MSUD can l/t neurotoxicity Dx: branched chain AAs (valine, leucine, isoleucine) elevated in plasma Tx: dietary restriction of BC-AAs + B1 supplementation

___ is psychotic sx that fully remit w/in one month; usually follows after stressful event in women Schizoaffective Disorder is schizophrenia + mania/depression; to differentiate from mood d/o w/psychotic features, SD MUST HAVE ___ ___ is delusion x1mo or longer, otherwise, no abnormal behavior (i.e., believe being followed x2mo, can't be convinced otherwise - SETH SMITH) - this may occur with Folie a deux Postpartum Psychosis usually occurs in women with known psychiatric disorder (MC: ___), occurring 2w after delivery; delusions often involve baby and are related to patient's mood; *HY: women must be ___, d/t risk of self-harm (tx with meds and ECT)*

Brief Psychotic Disorder is psychotic sx that fully remit w/in one month; usually follows after stressful event in woman Schizoaffective Disorder is schizophrenia + mania/depression; to differentiate from mood d/o w/psychotic features, SD MUST HAVE psychosis alone (x2w) Delusional Disorder is delusion x1mo or longer, otherwise, no abnormal behavior (i.e., believe being followed x2mo, can't be convinced otherwise - SETH SMITH) - this may occur with Folie a deux Postpartum Psychosis usually occurs in women with known psychiatric disorder (MC: bipolar), occurring 2w after delivery; delusions often involve baby and are related to patient's mood; *HY: women must be hospitalized, d/t risk of self-harm (tx with meds and ECT)*

Bronchiectasis is daily purulent sputum production with *large airway D___ and small airway C___ (obstructive lung dz)* Pts are subject to recurrent ___ (Pseudomonas), hemoptysis, clubbing Bronchiectasis can stem from obstruction, smoking, CF, *[HY] ___ syndrome, Allergic Bronchopulmonary A___* (all have to due w/mucus production/poor ciliary activity) *Kartagener's is 2/2 d___ mutation --> abnormal cilia function (dynein pull microtubules together to produce movement), will also see chronic sinusitis, i___, s___ i___* *___ is hypersensitivity rxn to aspergillus (only affects immunocompromise w/asthma or CF) - pts have EOSINOPHILIA + IgE*

Bronchiectasis is daily purulent sputum production with *large airway DILATION and small airway CONSTRICTION (obstructive lung dz)* Pts are subject to recurrent infxn (Pseudomonas), hemoptysis, clubbing Bronchiectasis can stem from obstruction, smoking, CF, *[HY] Kartagener's syndrome, Allergic Bronchopulmonary Aspergillosis* (all have to due w/mucus production/poor ciliary activity) *Kartagener's is 2/2 dynein mutation --> abnormal cilia function (dynein pull microtubules together to produce movement), will also see chronic sinusitis, infertility, situs inversus* *ABPA is hypersensitivity rxn to aspergillus (only affects immunocompromise w/asthma or CF) - pts have EOSINOPHILIA + IgE*

Brown-Sequard Syndrome is loss of ___ from trauma Patients lose ___ on contralateral side and ___ on ipsilateral side (@ level of injury, have complete sensory loss) If lesion is above T1 --> ___

Brown-Sequard Syndrome is loss of half the spinal cord from trauma Patients lose pain/temp on contralateral side and motor/prop/vibration on ipsilateral side (@ level of injury, have complete sensory loss) If lesion is above T1 --> Horner's syndrome

Bullous pemphigoid is 2/2 autoantibodies to ___ (hold cells to BM - pemphigus vulgaris is 2/2 Abs to ___, hold cells together) Bullae are subepidermal (makes sense given hemidesmosomes) and nonacantholytic (acant. is classic feature of ___) - clinically, bullae are *___ fragile, tense and rupture less (diff. from PV)* On biopsy, will see eosinophils and *immunofluorescence w/line along ___ (makes sense)!* BP is most common in elderly and *___ involves mouth (diff. from PV) and ___ Nikolsky's sign (diff. from PV)* - tx w/immunosuppressants

Bullous pemphigoid is 2/2 autoantibodies to hemidesmosomes [Balls and Hair] (hold cells to BM - pemphigus vulgaris is 2/2 Abs to desmosomes [Vagina and Dick], hold cells together) Bullae are subepidermal (makes sense given hemidesmosomes) and nonacantholytic (acant. is classic feature of PV) - clinically, bullae are *less fragile, tense and rupture less (diff. from PV)* On biopsy, will see eosinophils and *immunofluorescence w/line along basement membrane (makes sense)!* BP is most common in elderly and *rarely involves mouth (diff. from PV) and no Nikolsky's sign (diff. from PV)* - tx w/immunosuppressants

Burkitt's Lymphoma is B-cell malignancy w/aggressive and rapid course; three key distinctions to know for Step 1 are: 1) ___ morphology, 2) ___ association, and 3) C-___ translocation BL has two forms: endemic form (Africa, New Guinea; *[HY] classically p/w mass in the ___*) and sporadic form (also in children, but in ___) 1) Know how to recognize starry sky appearance for BL - 2/2 sheets of lymphocytes interspersed w/macrophages picking up debris that accumulates rapidly ("___ macrophages") 2) ___ infects B-cells --> l/t Burkitt's lymphoma (*a/w ___ form primarily - this is seen in Sketchy w/African kid*), remember that EBV uses CD___ to gain entry to cells (endemic BL expresses CD21) 3) Classic translocation is t___ (c-Myc:IgG Heavy Chain --> overproduction of c-Myc --> excessive growth)

Burkitt's Lymphoma is B-cell malignancy w/aggressive and rapid course; three key distinctions to know for Step 1 are: 1) starry sky morphology, 2) EBV association, and 3) C-myc translocation BL has two forms: endemic form (Africa, New Guinea; *[HY] classically p/w mass in the mandible*) and sporadic form (also in children, but in abdomen) 1) Know how to recognize starry sky appearance for BL - 2/2 sheets of lymphocytes interspersed w/macrophages picking up debris that accumulates rapidly ("tingible body macrophages") 2) EBV infects B-cells --> l/t Burkitt's lymphoma (*a/w ENDEMIC form primarily - this is seen in Sketchy w/African kid*), remember that EBV uses CD21 to gain entry to cells (endemic BL expresses CD21) 3) Classic translocation is t8;14 (c-Myc:IgG Heavy Chain --> overproduction of c-Myc --> excessive growth)

CLASSIC SCENARIO: abdominal pain, flushing, diarrhea, and pulmonic/tricuspid valve dz --> que pasa? treatment?

CARCINOID SYNDROME Tx: surgical excision + hepatic resection, then *octreotide*

CD8 T-cells (like CD4) react to unique Ags, require APC for activation, and have TCR a/w CD3 CD8 T-cells (unlike CD4) react to Ag on MHC1 - most human cells have MHC1 (don't require macrophages/dendritic cells) - important for intracellular organisms MHC1 binds TCR and CD8 and contains one ___ chain + one b___-m___ CD8 activation requires two stimuli: 1) TCR binding MHC1 w/Ag and 2) CD8 binding MHC1 w/Ag Once active, CD8 T-cell functions to kill infected cell via insertions of p___, insertion of granzymes (activate caspases --> apoptosis), insertion of granulysin, or *production of F___ ligand (binds F___ on cell surface --> activate ca___ --> extrinsic pathway of apoptosis*)

CD8 T-cells (like CD4) react to unique Ags, require APC for activation, and have TCR a/w CD3 CD8 T-cells (unlike CD4) react to Ag on MHC1 - most human cells have MHC1 (don't require macrophages/dendritic cells) - important for intracellular organisms MHC1 binds TCR and CD8 and contains one heavy chain + one beta-microglobulin CD8 activation requires two stimuli: 1) TCR binding MHC1 w/Ag and 2) CD8 binding MHC1 w/Ag Once active, CD8 T-cell functions to kill infected cell via insertions of perforins, insertion of granzymes (activate caspases --> apoptosis), insertion of granulysin, or *production of Fas ligand (binds Fas on cell surface --> activate caspase --> extrinsic pathway of apoptosis*)

CF is AR genetic dz that is d/t mutated ___ gene (codes for chloride channel - pumps Cl into lumen --> draws Na and H2O to hydrate mucus; in sweat glands, CFTR resorbs NaCl, mutation --> salty sweat) *Most common CF mutation is ___* (removes phenylalanine from protein --> abnormal ___ of protein to cell membrane - *have prot., but not functional*) CF manifests w/thick mucus in lungs w/hyperinflation and obstructive pattern (*[HY] recurrent ___ infxns*) and GI tract (impaired flow of bile + pancreatic secretions --> foul-smelling steatorrhea, ___ vitamin deficiency, *meconium ileus w/air-fluid levels*) Can also see biliary dz (pale/clay stools, hepatomegaly, cirrhosis), *[HY] INFERTILITY d/t absent ___ - can't transport sperm, can have kids w/IVF*

CF is AR genetic dz that is d/t mutated CFTR gene (codes for chloride channel - pumps Cl into lumen --> draws Na and H2O to hydrate mucus; in sweat glands, CFTR resorbs NaCl, mutation --> salty sweat) *Most common CF mutation is delta F508* (removes phenylalanine from protein --> abnormal trafficking of protein to cell membrane - *have prot., but not functional*) CF manifests w/thick mucus in lungs w/hyperinflation and obstructive pattern (*[HY] recurrent Pseudomonal infxns*) and GI tract (impaired flow of bile + pancreatic secretions --> foul-smelling steatorrhea, fat-soluble vitamin deficiency, *meconium ileus w/air-fluid levels*) Can also see biliary dz (pale/clay stools, hepatomegaly, cirrhosis), *[HY] INFERTILITY d/t absent VAS DEFERENS - can't transport sperm, can have kids w/IVF*

CF is diagnosed w/sweat chloride test (use pilocarpine - ___ agonist - to induce sweating), look for ___ chloride level (CFTR can't bring Cl back into sweat glands!) CF Tx: inhaled ___ (lots of DNA in mucus), ivacaftor (only for G551D mut.), Abx (for exacerbations), lung transplant, ___ enzyme replacement, fat-soluble vitamin replacement

CF is diagnosed w/sweat chloride test (use pilocarpine - ACh-M agonist - to induce sweating), look for high chloride level (CFTR can't bring Cl back into sweat glands!) CF Tx: inhaled DNAse (lots of DNA in mucus), ivacaftor (only for G551D mut.), Abx (for exacerbations), lung transplant, pancreatic enzyme replacement, fat-soluble vitamin replacement

CLASSIC SCENARIO: patient on MAO inhibitor goes out to dinner for pizza --> hypertensive urgency, what's hatnin'? *HY: what can happen with SNRIs that isn't seen in SSRIs?* What are unique "side effects" of bupropion not seen in SSRIs?" CLASSIC BOARDS QUESTION: what medication decreases lithium levels? what is most common SE of lithium? WHAT YOU SHOULD KNOW: how do antipsychotics exert their effect (receptor, 2nd messenger)? HIGH YIELD: most common drug-induced hyperprolactinemia? What are two special side effects of clozapine?

CHEESE EFFECT (tyramine is sympathomimetic that is broken down by MAO in GI tract; when can't, tyramine gets into blood --> hypertensive crisis) --- INCREASED BP (2/2 norepinephrine effects) --- Can help with smoking cessation and improve sexual dysfunction (also stimulating --> lowers seizure threshold) --- THIAZIDE DIURETICS (also NSAIDs, ACE-i's - potassium-sparing diuretics decrease Li levels) TREMOR --- D2 BLOCKADE --> INHIBITED Gi --> INCREASED cAMP --- ANTIPSYCHOTICS (2/2 dopamine blockade - dopamine inhibits prolactin production AGRANULOCYTOSIS and SEIZURES

CLASSIC CASE: child w/recurrent thrush and diaper rash with adrenal failure and hypoparathyroidism?

CHRONIC MUCOCUTANEOUS CANDIDIASIS (2/2 AIRE mutation!)

COLLATERALS: ___ ischemia from vessel occlusion is rare 2/2 anastamoses btwn superior pancreaticoduodenal (celiac trunk) and inferior pancreaticoduodenal (SMA) aa M___ connects SMA and IMA - provides protection of ischemia via *occlusion/t___* in splenic flexure Rectal ischemia from occlusion is rare 2/2 collaterals btwn superior rectal (___) and middle rectal (___) aa Mesenteric ischemia is ischemia of ___ (life threatening), while ischemic colitis is ischemia of ___ (not severe - can spontaneously resolve) Mesenteric ischemia can occur 2/2 embolism (*___, LV thrombus*) or arterial thrombosis (a___) or *non-occlusive ischemia d/t UNDERPERFUSION (seen in shock, affects WATERSHED areas of colon - ___ flexure & ___ junction)* Classic finding of mesenteric ischemia is *___ out of proportion to exam (no peritoneal signs)* + ___ blood - will see leukocytosis + lactic acidosis Chronic mesenteric ischemia (*think of mesenteric angina!*) is seen in older pts w/atherosclerotic risk factors (smoking, DM) - pts develop *FEAR OF ___ (pain worsens w/increased blood demand) --> weight ___*

COLLATERALS: Gastric ischemia from vessel occlusion is rare 2/2 anastamoses btwn superior pancreaticoduodenal (celiac trunk) and inferior pancreaticoduodenal (SMA) aa Marginal aa of Drummond connects SMA and IMA - provides protection of ischemia via *occlusion/thrombus* in splenic flexure Rectal ischemia from occlusion is rare 2/2 collaterals btwn superior rectal (IMA) and middle rectal (iliac) aa Mesenteric ischemia is ischemia of intestines (life threatening), while ischemic colitis is ischemia of colon (not severe - can spontaneously resolve) Mesenteric ischemia can occur 2/2 embolism (*Afib, LV thrombus*) or arterial thrombosis (atherosclerosis) or *non-occlusive ischemia d/t UNDERPERFUSION (seen in shock, affects WATERSHED areas of colon - splenic flexure & rectosigmoid junction)* Classic finding of mesenteric ischemia is *pain out of proportion to exam (no peritoneal signs)* + occult blood - will see leukocytosis + lactic acidosis Chronic mesenteric ischemia (*think of mesenteric angina!*) is seen in older pts w/atherosclerotic risk factors (smoking, DM) - pts develop *FEAR OF EATING (pain worsens w/increased blood demand) --> weight loss*

CONJUGATE GAZE (looking left): ___ FEF --> ___ PPRF --> left ___ nucleus --> left lateral rectus (via CN6) + right ___ nucleus --> right medial rectus INO is weak adduction on horizontal gaze 2/2 lesions of ___ (convergence is spared, d/t no MLF involvement); the laterality of INO is determined by eye involved (i.e., right horizontal gaze --> left eye doesn't work --> ___ INO); the unaffected eye develops nystagmus High yield cause of INO is MS, 2/2 ___ being highly myelinated ___ palsy is weak abduction of ipsilateral eye (i.e., right gaze --> right eye can't look right) PPRF (medial pons lesion) leads to gaze palsy in both eyes (i.e., right PPRF lesion --> neither eye can look right); this will be similar if CN6 ___ is affected One and a half syndrome is damage to ___, leading to conjugate gaze palsy on ipsilateral side and INO on contralateral side FEF lesion leads to deviation towards the ___ side of lesion

CONJUGATE GAZE (looking left): Right FEF --> left PPRF --> left CN6 nucleus --> left lateral rectus (via CN6) + right CN3 nucleus --> right medial rectus INO is weak adduction on horizontal gaze 2/2 lesions of MLF (convergence is spared, d/t no MLF involvement); the laterality of INO is determined by eye involved (i.e., right horizontal gaze --> left eye doesn't work --> left INO); the unaffected eye develops nystagmus High yield cause of INO is MS, 2/2 MLF being highly myelinated CN6 palsy is weak abduction of ipsilateral eye (i.e., right gaze --> right eye can't look right) PPRF (medial pons lesion) leads to gaze palsy in both eyes (i.e., right PPRF lesion --> neither eye can look right); this will be similar if CN6 nucleus is affected One and a half syndrome is damage to PPRF and MLF, leading to conjugate gaze palsy on ipsilateral side and INO on contralateral side FEF lesion leads to deviation towards the ipsilateral side of lesion

COPD Exacerbation: tx w/steroids, antibiotics, and nebulizer (albuterol +/- ipratropium), can tx chronic COPD based on GOLD criteria (goes off GOLD scoring) - PRN bronchodilator --> add long-acting bronchodilator --> add ICS --> add ___ (a/w incr. survival w/O2 sat <88%)/surgery Asthma Exacerbation: tx w/nebulized albuterol, steroids, +/- ipratropium, can tx chronic asthma based on sx - ___ --> + ICS --> + LABA --> incr. ICS dose --> oral steroids

COPD Exacerbation: tx w/steroids, antibiotics, and nebulizer (albuterol +/- ipratropium), can tx chronic COPD based on GOLD criteria (goes off FEV1 scoring) - PRN bronchodilator --> add long-acting bronchodilator --> add ICS --> add oxygen (a/w incr. survival w/O2 sat <88%)/surgery Asthma Exacerbation: tx w/nebulized albuterol, steroids, +/- ipratropium, can tx chronic asthma based on sx - SABA --> + ICS --> + LABA --> incr. ICS dose --> oral steroids

CPPD is in elderly pts w/no gender preference (different from gout) - can present w/asymptomatic dz, acute arthritis, and chronic joint dz Asymptomatic p/w *c___ (calcification of hyaline cartilage)* Acute arthritis (pseudogout) classically involves knee (similar to gout), classically occurring after p___ - get synovial fluid, will see ___ birefringent rhomboid crystals (*blue when parallel - opposite to gout!*) Chronic joint dz (pseudo-OA) is progressive cartilage deterioration Joint trauma, *hyperparathyroidism*, hemochromatosis (in addition to iron-arthritis) are a/w CPPD Tx: joint injection, NSAIDs, colchicine (can use for prophylaxis), THA/TKA for severe cases

CPPD is in elderly pts w/no gender preference (different from gout) - can present w/asymptomatic dz, acute arthritis, and chronic joint dz Asymptomatic p/w *chondrocalcinosis (calcification of hyaline cartilage)* Acute arthritis (pseudogout) classically involves knee (similar to gout), classically occurring after parathyroidectomy - get synovial fluid, will see positively birefringent rhomboid crystals (*blue when parallel - opposite to gout!*) Chronic joint dz (pseudo-OA) is progressive cartilage deterioration Joint trauma, *hyperparathyroidism*, hemochromatosis (in addition to iron-arthritis) are a/w CPPD Tx: joint injection, NSAIDs, colchicine (can use for prophylaxis), THA/TKA for severe cases

Calcium stones can be calcium oxalate (MC) or calcium phosphate Key RFs are hypercalcemia and *hyper___ (can be seen in C___ dz, gastric bypass pts)*; MC etiology is idiopathic hypercalciuria; other RFs include ethylene glycol and VitC abuse Calcium stones are radio___ on XR (think BONE) Crystals will appear *___ SHAPED* Tx: large --> surgery; for recurrent stones, thiazide diuretics (l/t calcium resorption) or citrate (binds calcium) NOTE: more Na in diet --> more Ca in urine --> more likely to develop STONES

Calcium stones can be calcium oxalate (MC) or calcium phosphate Key RFs are hypercalcemia and *hyperoxalemia (can be seen in Crohn's dz, gastric bypass pts)*; MC etiology is idiopathic hypercalciuria; other RFs include ethylene glycol and VitC abuse Calcium stones are radiopaque on XR (think BONE) Crystals will appear *ENVELOPE SHAPED* Tx: large --> surgery; for recurrent stones, thiazide diuretics (l/t calcium resorption) or citrate (binds calcium) NOTE: more Na in diet --> more Ca in urine --> more likely to develop STONES

Candida is normal flora of the mouth, intestine, skin, and vagina and *is a common contaminant of ___ cultures (no such thing as candida pneumonia)* Candida can form two *HIGH YIELD* structures: *germ tubes (___ with ___ growing out) and ___ (elongated budding yeast cells)* Mutations in *___ genes* can result in *T-cell dysfunction*, such that T-cells fail to react to candida antigens and patients have chronic mucocutaneous candidiasis (chronic skin, mucous membrane candida infections) - *look for child with recurrent ___ and ___* NOTE: T-cells are important for mucosal defense against Candida (HIV patients get ___), while neutrophils are important for systemic defense (HIV patients RARELY get ___, but candidemia occurs in chemo patients)

Candida is normal flora of the mouth, intestine, skin, and vagina and *is a common contaminant of sputum cultures (no such thing as candida pneumonia)* Candida can form two *HIGH YIELD* structures: *germ tubes (yeast with hyphae growing out) and pseudohyphae (elongated budding yeast cells)* Mutations in AIRE genes can result in T-cell dysfunction, such that T-cells fail to react to candida antigens and patients have chronic mucocutaneous candidiasis (chronic skin, mucous membrane candida infections) - look for child with recurrent thrush and diaper rash NOTE: T-cells are important for mucosal defense against Candida (HIV patients get thrush), while neutrophils are important for systemic defense (HIV patients RARELY get candidemia, but candidemia occurs in chemo patients)

Capacity is ability to comprehend info about illness to make choices; 4 key components: U___ (dz and tx), expression of C___ (can comm. y or n), appreciate F___ (understand how dz/tx affects them), & R___ (compare options/understand consequ) Decision must a) be consistent, b) not influenced by m___ d/o (think psych!), and 3) no AMS; disabled pts (tris21) does not preclude capacity If lack capacity --> a) advanced directive (living will or power of attorney [assigned surrogate - what would pt want?]) or b) surrogate (no AD/PoA --> 1. ___ , 2. adult ___, 3. parents, 4. adult sibs, 5. other) *Brain death is diff --> life support can be withdrawn in ___ of surrogate agreement* Competency is different - *IT IS A LEGAL JUDGEMENT, NOT FOR MDs!*

Capacity is ability to comprehend info about illness to make choices; 4 key components: understanding (dz and tx), expression of choice (can comm. y or n), appreciate facts (understand how dz/tx affects them), & reasoning (compare options/understand consequ) Decision must a) be consistent, b) not influenced by mood d/o, and 3) no AMS; disabled pts (tris21) does not preclude capacity If lack capacity --> a) advanced directive (living will or power of attorney [assigned surrogate - what would pt want?]) or b) surrogate (no AD/PoA --> 1. spouse, 2. adult kids, 3. parents, 4. adult sibs, 5. other) *Brain death is diff --> life support can be withdrawn in absence of surrogate agreement* Competency is different - *IT IS A LEGAL JUDGEMENT, NOT FOR MDs!*

C___ binds heme (240x stronger than O2) to block O2 binding sites - also allosteric modifies that makes Hgb more likely to hold on to O2 (left shift, can't deliver to tissues) CO poisoning p/w nonspecific sx + *cherry red lips*; can't dx w/pulse oximetry - send c___ level (>15% suggests poisoning) - tx w/O2 M___ is when Hgb iron is oxidized to Fe3+ - cannot bind O2 (also makes it so remaining Fe2+ can't release O2 to tissue - LEFT shift) Acquired methemegolbinemia is 2/2 many drugs (local anesthetics [benzocaine], nitric oxide, dapsone) - tx w/m___ CLASSIC: endoscopy patient receiving benzocaine spray for throat analgesia develops dyspnea after procedure, also with c___b___ blood and SpO2 80-90% Cyanide binds Fe3+ in cells - blocks ETC in mitochondria --> anabolic metabolism --> lactic acidosis (tx w/n___ - generate methemoglobin and Fe3+ pulls cyanide from mitochondria)

Carbon monoxide binds heme (240x stronger than O2) to block O2 binding sites - also allosteric modifies that makes Hgb more likely to hold on to O2 (left shift, can't deliver to tissues) CO poisoning p/w nonspecific sx + *cherry red lips*; can't dx w/pulse oximetry - send carboxyhemoglobin level (>15% suggests poisoning) - tx w/O2 Methemoglobinemia is when Hgb iron is oxidized to Fe3+ - cannot bind O2 (also makes it so remaining Fe2+ can't release O2 to tissue - LEFT shift) Acquired methemegolbinemia is 2/2 many drugs (local anesthetics [benzocaine], nitric oxide, dapsone) - tx w/methylene blue CLASSIC: endoscopy patient receiving benzocaine spray for throat analgesia develops dyspnea after procedure, also with chocolate brown blood and SpO2 80-90% Cyanide binds Fe3+ in cells - blocks ETC in mitochondria --> anabolic metabolism --> lactic acidosis (tx w/nitrites - generate methemoglobin and Fe3+ pulls cyanide from mitochondria)

Carcinoid (cancer-like) tumors are made of ___ cells and are found all over, but especially small intestine Carcinoid tumors secrete ___ --> responsible for most sx Carcinoid tumor + these sx = carcinoid syndrome; most occur in GI tract, but liver and ___ can inactivate most serotonin; accordingly, *can't get carcinoid syndrome w/o metastatic dz to ___* (also reason valvular dz is always *___-sided*) Tryptophan can be converted to serotonin (not usually, but happens in carcinoid tumors) - *tryptophan deficiency can occur (sx come from tryptophan using all Vit___ [niacin] --> ___)* Carcinoid heart dz is 2/2 ___ deposition in tricuspid/pulmonic valve --> stenosis/regurg Dx: ___ in urine (metabolite of serotonin)

Carcinoid (cancer-like) tumors are made of neuroendocrine cells and are found all over, but especially small intestine Carcinoid tumors secrete serotonin --> responsible for most sx (diarrhea, flushing, valvular lesions) Carcinoid tumor + these sx = carcinoid syndrome; most occur in GI tract, but liver and lung can inactivate most serotonin; accordingly, *can't get carcinoid syndrome w/o metastatic dz to liver* (also reason valvular dz is always *RIGHT-sided*) Tryptophan can be converted to serotonin (not usually, but happens in carcinoid tumors) - *tryptophan deficiency can occur (sx come from tryptophan using all VitB3 [niacin] --> PELLAGRA)* Carcinoid heart dz is 2/2 fibrous deposition in tricuspid/pulmonic valve --> stenosis/regurg Dx: 5-HIAA in urine (metabolite of serotonin)

Cardiac mm. has many similarities to skeletal mm. (striated, sarcomeres, Act-Myo, tropon-tropom, T-tub/SarcRetic) - different in other ways In cardiac myocytes, T-tub/SarcRetic complexes form d___ instead of t___; cardiac mm. is involuntary, depolarized by p___ cells (not motor nn.), and has gap junctions (*spreads depolarization*!) ActPot. is also different - phase 2 (not present in SkeMus) is dictated by *___ influx via L-type Ca channels* (low affinity for DHP CCBs [amlodipine], high affinity for non-DHP CCBs [dilt, verap]) - Ca enters cell via plasma membrane --> Ca triggers SR ___ release via ryanodine receptor (*Ca-triggered Ca release, unique to cardiac mm.!*) More ___ entry into cell --> harder contraction (target for non-DHP CCBs, digoxin); SNS incr. contractility via incr. intracellular ___ (Gs stimulation) --> PKA activation --> more Ca into cell (think of milrinone) Lusitropy is myocardial relaxation - mediated by S___ (faster contraction --> faster relaxation); SERCA is regulated by *P___ - SERCA inhibitor (PLB is phosphorylated by PKA --> allows SERCA to do its thing), SNS incr. contractility and relaxation!*

Cardiac mm. has many similarities to skeletal mm. (striated, sarcomeres, Act-Myo, tropon-tropom, T-tub/SarcRetic) - different in other ways In cardiac myocytes, T-tub/SarcRetic complexes form diad instead of triad; cardiac mm. is involuntary, depolarized by pacemaker cells (not motor nn.), and has gap junctions (*spreads depolarization*!) ActPot. is also different - phase 2 (not present in SkeMus) is dictated by *Ca influx via L-type Ca channels* (low affinity for DHP CCBs [amlodipine], high affinity for non-DHP CCBs [dilt, verap]) - Ca enters cell via plasma membrane --> Ca triggers SR Ca release via ryanodine receptor (*Ca-triggered Ca release, unique to cardiac mm.!*) More Ca entry into cell --> harder contraction (target for non-DHP CCBs, digoxin); SNS incr. contractility via incr. intracellular cAMP (Gs stimulation) --> PKA activation --> more Ca into cell (think of milrinone) Lusitropy is myocardial relaxation - mediated by SERCA (faster contraction --> faster relaxation); SERCA is regulated by *PHOSPHOLAMBAN - SERCA inhibitor (PLB is phosphorylated by PKA --> allows SERCA to do its thing), SNS incr. contractility and relaxation!*

Not a HY Card: Care transitions (i.e., hospital --> home) can predispose to bad things (do a ___ rec to prevent) Antimicrobial stewardship monitors use of abx to prevent drug-___ ___ is communication tool from nurse to MD (Situation - what happening?, Background - who pt?, Assessment - labs/vitals, Recommendation - what do?) Quality measures of hospitals include readmission rate *(different based on ___ payers, -CARE: HF, seps, pneumo; -CAID: mood d/o, schizo, diab; PRIVATE: chemo, mood d/o, surg comp; UNINSURE: mood d/o, EtOH, diab)*, pressure ulcer, DVT, SS-Infxn, CL-Infxn, VA-Pneumo, and never events (surg - wrong site, patient, procedure, foreign body, incompatible blood) Pro___ measure is process that leads to outcomes (i.e., DVT prophylaxis rate); Out___ measures are # of outcomes (i.e., DVT rates)

Care transitions (i.e., hospital --> home) can predispose to bad things (do a med rec to prevent) Antimicrobial stewardship monitors use of abx to prevent drug-resistance SBAR is communication tool from nurse to MD (Situation - what happening?, Background - who pt?, Assessment - labs/vitals, Recommendation - what do?) Quality measures of hospitals include readmission rate *(different based on insurance payers, -CARE: HF, seps, pneumo; -CAID: mood d/o, schizo, diab; PRIVATE: chemo, mood d/o, surg comp; UNINSURE: mood d/o, EtOH, diab)*, pressure ulcer, DVT, SS-Infxn, CL-Infxn, VA-Pneumo, and never events (surg - wrong site, patient, procedure, foreign body, incompatible blood) Process measure is process that leads to outcomes (i.e., DVT prophylaxis rate); Outcome measures are # of outcomes (i.e., DVT rates)

Catecholamine (dopamine, norepinephrine, epinephrine) degradation is accomplished via MAO and COMT - epi/norepi --> VMA, dopa --> HVA COMT and MAO are each needed for all three catecholamines to be broken down, go in either order

Celiac dz is autoimmune condition, resulting in small intestinal villi destruction; CD is d/t intolerance of *gliadin (part of gluten) after deamidation by t___*, deamidated gliadin presented to T-cells --> type ___ hypersensitivity rxn CD is a/w HLA-DQ___, HLA-DQ___ - whites from Europe CD targets small intestine w/3 *[HY] histo findings: ___ of villi, ___ hyperplasia, lymphocytes of l___* Abs seen in CD are *[HY] Ig___ anti-___ Ab (highest accuracy, but some pts deficient in IgA - measure Ig___ if Ig___ low!), anti-endom___ Ab* CD most commonly affects ___ (contr. to tropical sprue) --> farting, bloating, steatorrhea, IDA; other associations include *dermatitis herpetiformis ([HY] Ig___ deposition in DERMAL ___! - think of above Ig mentioned!), osteoporosis, iron-deficiency anemia, T-cell lymphoma (T-cells involved with pathogenesis!)/small bowel malignancy (look for pt w/worsening sx on gluten-free diet!)*

Celiac dz is autoimmune condition, resulting in small intestinal villi destruction; CD is d/t intolerance of *gliadin (part of gluten) after deamidation by tissue transglutaminase*, deamidated gliadin presented to T-cells --> type IV hypersensitivity rxn CD is a/w HLA-DQ2, HLA-DQ8 - whites from Europe CD targets small intestine w/3 *[HY] histo findings: blunting of villi, crypt hyperplasia, lymphocytes of lamina propria* Abs seen in CD are *[HY] IgA anti-TTG Ab (highest accuracy, but some pts deficient in IgA - measure IgG if IgA low!), anti-endomysial Ab* CD most commonly affects duodenum (contr. to tropical sprue) --> farting, bloating, steatorrhea, IDA; other associations include *dermatitis herpetiformis ([HY] IgA deposition in DERMAL PAPILLAE!), osteoporosis, iron-deficiency anemia, T-cell lymphoma (T-cells involved with pathogenesis!)/small bowel malignancy (look for pt w/worsening sx on gluten-free diet!)*

Celiac trunk supplies ___ structures (esophagus to prox. duodenum + liver, GB, part of pancr. spleen) - three major branches are s___, l___, c___ Lesser curvature is supplied by left gastric and right gastric (br. from ___ hepatic aa) Greater curvature is supplied by left ___ (br. of splenic aa) and right gastroepiploic (br. of g___ aa. from common hepatic aa.) Cardia of stomach is supplied by ___ gastric aa (from splenic aa) and lower esophagus is supplied by esophageal branches (of left gastric aa) Stomach blood supply is relevant w/ULCERS - ulcer of lesser curvature --> ___ aa bleed; ulcer of posterior duodenal --> g___ aa bleed (br. of common hepatic aa) Cardia of stomach is vulnerable to ischemia w/s___ aa occlusion, 2/2 s___ aa [*these s. arteries are DIFFERENT*] being only blood supply (rest of stomach has DUAL!) Hepatoduodenal ligament connects liver to duodenum and contains three structures: p___, p___, c___; w/Pringle's maneuver, clamp that ligament - if bleeding stops --> blood coming from those vessels, if bleeding continues --> IVC or hepatic veins

Celiac trunk supplies foregut structures (esophagus to prox. duodenum + liver, GB, part of pancr. spleen) - three major branches are splenic, left gastric, and common hepatic Lesser curvature is supplied by left gastric and right gastric (br. from proper hepatic aa) Greater curvature is supplied by left gastroepiploic (br. of splenic aa) and right gastroepiploic (br. of gastroduodenal aa. from common hepatic aa.) Cardia of stomach is supplied by short gastric aa (from splenic aa) and lower esophagus is supplied by esophageal branches (of left gastric aa) Stomach blood supply is relevant w/ULCERS - ulcer of lesser curvature --> left gastric aa bleed; ulcer of posterior duodenal --> gastroduodenal aa bleed (br. of common hepatic aa) Cardia of stomach is vulnerable to ischemia w/splenic aa occlusion, 2/2 short gastric aa being only blood supply (rest of stomach has DUAL!) Hepatoduodenal ligament connects liver to duodenum and contains three structures: proper hepatic aa (branch of common hepatic aa), portal vein, cystic duct; w/Pringle's maneuver, clamp that ligament - if bleeding stops --> blood coming from those vessels, if bleeding continues --> IVC or hepatic veins

Cell cycle is divided into interphase (includes G1 - growth, S - synthesis, G2 - growth) and mitosis G1: synthesis of proteins/organelles, driven by mitogens (stimulate cell division via C___ D___ K___, different from growth factors which inc. size of cell) S: synthesis of DNA (chromosomes --> two ___) G2: growth in preparation for mitosis G0: occurs w/absence of mitogen stimulation (most cells in body - neurons, skeletal muscle; bone marrow, GI epith., hair are never in G0 --> susceptible to chemo.) M: most rapid portion, divided into ___ (chroms. condense and spindles form), ___ (chroms organize on spindle), ___ (chroms line up on metaphase plate), ___ (chroms separate), telophase/cytokinesis (cell divides + spindle breaks down

Cell cycle is divided into interphase (includes G1 - growth, S - synthesis, G2 - growth) and mitosis G1: synthesis of proteins/organelles, driven by mitogens (stimulate cell division via cyclin dependent kinases, different from growth factors which inc. size of cell) S: synthesis of DNA (chromosomes --> two sister chromatids) G2: growth in preparation for mitosis G0: occurs w/absence of mitogen stimulation (most cells in body - neurons, skeletal muscle; bone marrow, GI epith., hair are never in G0 --> susceptible to chemo.) M: most rapid portion, divided into prophase (chroms. condense and spindles form), prometaphase (chroms organize on spindle), metaphase (chroms line up on metaphase plate), anaphase (chroms separate), telophase/cytokinesis (cell divides + spindle breaks down

Cells regulate cell cycle through "checkpoints", inc. *G1-S (commitment to cell cycle)*, G2-M, and M phase - cell will arrest if conditions inappropriate Checkpoints depend on C___ (activated by cyclins [regulatory proteins, levels vary during cycle]), cyclin-CDK complex phosphorylate regulatory proteins and allow progression through cycle G1-S: mitogens activate CDKs via inc. cyclin levels --> activate E2F transcription factors (bind to DNA promoter regions and activate genes for S phase) via Rb phosphorylation; ___ normally inhibited via binding to ___ (a TSG) - CDKs release this bind and allow cell cycle progression P___ and P___ can block Rb phosphorylation --> prevent cell cycle progression KEY PT: G1-S progression is stimulated by Rb-E2F NOTE: Rb (TSG) mutation --> retinoblastoma, unregulated cell growth via E2F activity

Cells regulate cell cycle through "checkpoints", inc. *G1-S (commitment to cell cycle)*, G2-M, and M phase - cell will arrest if conditions inappropriate Checkpoints depend on cyclin-dependent kinases (activated by cyclins [regulatory proteins, levels vary during cycle]), cyclin-CDK complex phosphorylate regulatory proteins and allow progression through cycle G1-S: mitogens activate CDKs via inc. cyclin levels --> activate E2F transcription factors (bind to DNA promoter regions and activate genes for S phase) via Rb phosphorylation; E2F normally inhibited via binding to Rb (a TSG) - CDKs release this bind and allow cell cycle progression P53 and P21 can block Rb phosphorylation --> prevent cell cycle progression KEY PT: G1-S progression is stimulated by Rb-E2F NOTE: Rb (TSG) mutation --> retinoblastoma, unregulated cell growth via E2F activity

___ is impaired respiratory effort - pts hypoventilate when awake, have apnea when asleep (seen w/ CNS dz, ALS, polio, narcotics); can be a/w ___ breathing (HF and stroke pts), in which there is cyclic breathing w/delayed detection/response to PaCO2 changes ___ is decreased air flow despite effort to breath d/t soft tissue pharyngeal collapse - strongest RF is *___*; can lead to HTN, pulm. HTN (2/2 low O2), arrhythmias w/sudden death; dx w/polysomnography (sleep study), tx w/weight loss, CPAP, upper airway surgery *[HY] OSA w/chronic hypoxia can lead to E___ release --> p___*

Central sleep apnea is impaired respiratory effort - pts hypoventilate when awake, have apnea when asleep (seen w/ CNS dz, ALS, polio, narcotics); can be a/w Cheyne-Stokes breathing (HF and stroke pts), in which there is cyclic breathing w/delayed detection/response to PaCO2 changes Obstructive sleep apnea is decreased air flow despite effort to breath d/t soft tissue pharyngeal collapse - strongest RF is *OBESITY*; can lead to HTN, pulm. HTN (2/2 low O2), arrhythmias w/sudden death; dx w/polysomnography (sleep study), tx w/weight loss, CPAP, upper airway surgery *[HY] OSA w/chronic hypoxia can lead to EPO release --> polycythemia*

Central tendency is center of normal distribution with three ways to characterize: mean, median, mode; mode is always highest pt on curve (if even dist. --> mean = median = mode); *[HY] ___ is least likely to be affected by outliers* Data can be skewed - negative skew has tail pointing ___, positive skew has tail pointing ___ (mode=highest pt, ___=farthest from mode toward tail, ___=between mode & mean) Dispersion is how widely data is spread with several ways to characterize: SD, variance (SD^2), SEM (SD/[root(N)]), Z-score, CIs *[HY] ___% of data is captured by +/- 1SD, ___% captured by +/- 2SD, ___% captured by +/- 3SD* (HOW ASK: 200 students tested, mean = 80, SD = 5, how many scored >90? N=___) S___ E___ or M___ is how precisely you know true pop. mean (i.e., smaller SEM --> more representative of true mean; big SD --> big SEM [need more samples for small SEM]; larger N --> lower SEM, more repr. of pop.) ___ is SDs away from mean ([score - mean]/SD)' ___ is range in which X% (usually 95%) of repeat measures would be expected to fall - used to estimate pop mean from sample data set (mean of 10 samples is X, how confident that mean of 1M samples is also X? --> 95% CI of Y - Z) - calculated as (mean +/- [1.96 x SEM]) *NOTE: ___ is for given dataset, ___ is an INFERRED VALUE for true mean of population - how close our dataset represents population!! LOOK OUT for the number 95%!!*

Central tendency is center of normal distribution with three ways to characterize: mean, median, mode; mode is always highest pt on curve (if even dist. --> mean = median = mode); *[HY] Mode is least likely to be affected by outliers* Data can be skewed - negative skew has tail pointing negative, positive skew has tail pointing positive (mode=highest pt, mean=farthest from mode toward tail, median=between mode & mean) Dispersion is how widely data is spread with several ways to characterize: SD, variance (SD^2), SEM (SD/[root(N)]), Z-score, CIs *[HY] 68% of data is captured by +/- 1SD, 95% captured by +/- 2SD, 99.7% captured by +/- 3SD* (HOW ASK: 200 students tested, mean = 80, SD = 5, how many scored >90? N=5) StErr of Mean is how precisely you know true pop. mean (i.e., smaller SEM --> more representative of true mean; big SD --> big SEM [need more samples for small SEM]; larger N --> lower SEM, more repr. of pop.) Z-score is SDs away from mean ([score - mean]/SD)' CI is range in which X% (usually 95%) of repeat measures would be expected to fall - used to estimate pop mean from sample data set (mean of 10 samples is X, how confident that mean of 1M samples is also X? --> 95% CI of Y - Z) - calculated as (mean +/- [1.96 x SEM]) *NOTE: SD is for given dataset, CI is an INFERRED VALUE for true mean of population - how close our dataset represents population!! LOOK OUT for the number 95%!!*

Charcot-Marie-Tooth a peripheral nerve disorder in which leg muscles become wasted; classic presentation is weakness with ___

Charcot-Marie-Tooth a peripheral nerve disorder in which leg muscles become wasted; classic presentation is weakness with severe LE/foot deformities

Cholecystokinin (I-cells) has two major effects: 1) ___ contraction and 2) ___ enzyme secretion (via CCK receptors on vagus nerve, vagus nn. --> pancreas), as well as sphincter of Oddi ___ [MAKES SENSE - want all these things to happen at the same time!] CCK is released in response to FAs and AAs (should make sense - want gallbladder to contract when we eat) CCK can be used in HIDA scan to stimulate gallbladder contraction --> GB e___ f___

Cholecystokinin (I-cells) has two major effects: 1) gallbladder contraction and 2) pancreatic enzyme secretion (via CCK receptors on vagus nerve, vagus nn. --> pancreas), as well as sphincter of Oddi relaxation [MAKES SENSE - want all these things to happen at the same time!] CCK is released in response to FAs and AAs (should make sense - want gallbladder to contract when we eat) CCK can be used in HIDA scan to stimulate gallbladder contraction --> GB ejection fraction

Cholestasis is disrupted bile flow to intestines - p/w ___ (conjugated) hyperbilirubinemia and elevated alkaline phosphatase^; Sx of cholestasis are jaundice, itching, dark urine, and ___-colored stools (long term: fat soluble vitamin deficiency) Best test for cholestasis: RUQ ultrasound (if dilated ducts --> ___hepatic bile flow obstruction - stones, pancreatic mass, biliary stricture; if normal ducts --> ___hepatic cholestasis - PBC, cholestasis of pregnancy, erythromycin) ^*[HY] Know cholestatic pattern vs hepatocellular pattern*

Cholestasis is disrupted bile flow to intestines - p/w direct (conjugated) hyperbilirubinemia and elevated alkaline phosphatase^; Sx of cholestasis are jaundice, itching, dark urine, and clay-colored stools (long term: fat soluble vitamin deficiency) Best test for cholestasis: RUQ ultrasound (if dilated ducts --> extrahepatic bile flow obstruction - stones, pancreatic mass, biliary stricture; if normal ducts --> intrahepatic cholestasis - PBC, cholestasis of pregnancy, erythromycin) ^*[HY] Know cholestatic pattern vs hepatocellular pattern*

Cholesteryl esters are cholesterol + fatty acid (conversion via ACAT), allowing for efficient transferring of cholesterol ApoB48 is required for *B4 fat you've 8 (ate) can be secreted from enterocytes in chylomicrons* ApoC-II (apoC-LL) is required for *lipoprotein lipase activation (cofactor Lipoprotein Lipase!)* ApoE binds liver receptors --> mediates reuptake in liver --- Two main lipoproteins secreted by liver are VLDL and HDL HDL functions as scavenger protein (*A-I is main apolipoprotein [good cholesterol is A1 - activates LCAT!] - others include ApoE and ApoCII*) that brings cholesterol back to liver in form of cholesterol esters (converted by LCAT - needs A1) --- LDL only has ApoB100 - binds LDL receptors --> uptake (seen in blood vessels); note that LDL has relatively high density of cholesterol > triglycerides (reason its bad!)

___ (Blue Bloater; obstructive lung dz) is chronic productive cough for 3mo over >2y - strongly a/w smoking (clinical dx) Will see hypertrophy of ___ secreting glands (Reid Index: thickness of glands:total wall thickness, >50% in bronchitis); mucous plugs bronchi --> ___ risk ChronBronch p/w hyper___, hypo___ (shunting - O2 doesn't help!), dyspnea, poly___, & pulm. HTN w/right HF; exam --> wheezing + crackles +/- cyanosis (d/t shunting) ___ is chronic bronchitis and/or chronic emphysema (also asthma)

Chronic bronchitis (obstructive lung dz) is chronic productive cough for 3mo over >2y - strongly a/w smoking (clinical dx) Will see hypertrophy of mucous secreting glands (Reid Index: thickness of glands:total wall thickness, >50% in bronchitis); mucous plugs bronchi --> infxn risk ChronBronch p/w hypercapnia, hypoxemia (shunting - O2 doesn't help!), dyspnea, polycythemia, & pulm. HTN w/right HF; exam --> wheezing + crackles +/- cyanosis (d/t shunting) COPD is chronic bronchitis and/or chronic emphysema (also asthma) ^Bronchitis - Bronchi Bloated

Chronic lymphocytic leukemia is a disorder of naiive ___ (NOT blasts) with a characteristic immunophenotype: *CD___+ and CD20+ (combines T- and B-cell markers!)* CLL is a d.o of ___ (old or young?) patients and most commonly presents w/asymptomatic pt + lymphocytosis - pts are often observed without treatment The peripheral smear hallmark of CLL *is ___ CELLS* CLL (d.o of B-cells) can lead to ___ --> recurrent infxns, autoantibodies to leukemic cells --> ___ Feared complication of CLL is transformation to *d___ (watch for pt with known CLL + rapid growth of single lymph node)*

Chronic lymphocytic leukemia is a disorder of naiive lymphocytes (NOT blasts) with a characteristic immunophenotype: *CD5+ and CD20+ (combines T- and B-cell markers!)* CLL is a d.o of older patients and most commonly presents w/asymptomatic pt + lymphocytosis - pts are often observed without treatment The peripheral smear hallmark of CLL *is SMUDGE CELLS* CLL (d.o of B-cells) can lead to hypogammaglobulinemia --> recurrent infxns, autoantibodies to leukemic cells --> AIHA Feared complication of CLL is transformation to *diffuse large B-cell lymphoma (watch for pt with known CLL + rapid growth of single lymph node)*

Chronic myeloid/myelogenous leukemia is a malignant disorder of ___ progenitor cells, resulting in dysregulated production of ___ (neuts, basos, and eos) - CML is a class of myeloproliferative disorder CML manifests with massive peripheral blood leukocytosis (>100k) of all ___ (*increased ___ is rare finding!*) CML progresses through chronic phase (years, asymptomatic w/minimal blasts) --> accelerated phase (months, rising wbc) --> blast crisis (*converts to ___ w/>20% blasts in periphery/bone marrow - can be lymphoblasts [ALL] or myeloblasts [AML]*) CML can easily be mistaken for left-shift (leukemoid rxn to infxn) - can distinguish w/l___ (*absent in CML - low score = ___*) Dx for CML is now done w/*genetic testing for ___ (constitutively active RTK)*; accordingly, can tx w/___

Chronic myeloid/myelogenous leukemia is a malignant disorder of myeloid progenitor cells, resulting in dysregulated production of granulocytes (neuts, basos, and eos) - CML is a class of myeloproliferative disorder CML manifests with massive peripheral blood leukocytosis (>100k) of all granulocytes (*increased basos is rare finding!*) CML progresses through chronic phase (years, asymptomatic w/minimal blasts) --> accelerated phase (months, rising wbc) --> blast crisis (*converts to acute leukemia w/>20% blasts in periphery/bone marrow - can be lymphoblasts [ALL] or myeloblasts [AML]*) CML can easily be mistaken for left-shift (leukemoid rxn to infxn) - can distinguish w/leukocyte alkaline phosphatase (*absent in CML - low score = CML*) Dx for CML is now done w/*genetic testing for PHILADELPHIA CHROMOSOME (t9;22 - BCR-ABL, constitutively active RTK)*; accordingly, can tx w/imatinib

Chronic pancreatitis is RF for pancreatic ___ (others: >50y, smoking, diabetes - *NOT ___, CLASSIC TRICK Q!*) - BRCA2 gene is a/w pancreatic ca Pancreatic adenocarcinoma is more common @ ___ (head, tail?) of pancreas; classic presentation is *___ jaundice (also fatigue, dark urine, ___-stools, steatorrhea) - look for Courvoisier sign (enlarged, nontender gallbladder + jaundice), carries poor prognosis Trousseau's Syndrome is migratory superficial ___ (redness + induration that migrates) and occurs d/t h___ state K___ (chrom12p oncogene) is most frequent mutation (adeno-carcino sequence in colon ca), SMAD4 (chrom18q TSG) is sometimes seen Tumor Markers: ___ (followed for tx) - historically CEA was used

Chronic pancreatitis is RF for pancreatic cancer (others: >50y, smoking, diabetes - *NOT ALCOHOL, CLASSIC TRICK Q!*) - BRCA2 gene is a/w pancreatic ca Pancreatic adenocarcinoma is more common @ head of pancreas; classic presentation is *painless jaundice (also fatigue, dark urine, clay-stools, steatorrhea) - look for Courvoisier sign (enlarged, nontender gallbladder + jaundice), carries poor prognosis Trousseau's Syndrome is migratory superficial thrombophlebitis (redness + induration that migrates) and occurs d/t hypercoaguable state KRAS (chrom12p oncogene) is most frequent mutation (adeno-carcino sequence in colon ca), SMAD4 (chrom18q TSG) is sometimes seen Tumor Markers: CA19-9 (followed for tx) - historically CEA was used

Chronic pancreatitis is fibrosis/calcification of pancreas 2/2 recurrent bouts of acute pancreatitis (i.e., alcohol, C___) - CT will show *___ pancreas* Pts will p/w chronic abdominal pain that is worse w/meals (fear of ___ --> weight loss); amylase/lipase may be normal (fibrotic tissue doesn't produce enzymes) Rare complications include: *___ Vein Thrombosis*: pancreas lies next to splenic vein, chronic inflammation --> thrombosis --> *gastric ___!* (look for pt w/chronic pancreatitis + upper GI bleed & splenomegaly) *Pancreatic ___*: fat malabsorption + steatorrhea + fat-soluble vitamin deficiency +/- diabetes

Chronic pancreatitis is fibrosis/calcification of pancreas 2/2 recurrent bouts of acute pancreatitis (i.e., alcohol, CF) - CT will show *calcified pancreas* Pts will p/w chronic abdominal pain that is worse w/meals (fear of eating --> weight loss); amylase/lipase may be normal (fibrotic tissue doesn't produce enzymes) Rare complications include: *Splenic Vein Thrombosis*: pancreas lies next to splenic vein, chronic inflammation --> thrombosis --> *gastric varices!* (look for pt w/chronic pancreatitis + upper GI bleed & splenomegaly) *Pancreatic Insufficiency*: fat malabsorption + steatorrhea + fat-soluble vitamin deficiency +/- diabetes

Cingulate gyrus, hippocampus, fornix, amygdala, and mamillary bodies all make up the ___ Kluver-Bucy (primitive behavior with hyperorality+ visual agnosia) is damage to ___ Anterograde amnesia stems from ___ lesion - this are is highly sensitive to hypoxia Wernicke-Korsakoff^ is d/t ___ deficiency (often in alcoholism), resulting in atrophy of ___; the Wernicke triad is ___; Korsakoff is known for ___ (make things up d/t inability to remember) ^NOTE: do not give glucose before thiamine - thiamine is cofactor in glucose metabolism and can worsen deficiency

Cingulate gyrus, hippocampus, fornix, amygdala, and mamillary bodies all make up the limbic system Kluver-Bucy (primitive behavior with hyperorality+ visual agnosia) is damage to amygdala Anterograde amnesia stems from hippocampal lesion - this are is highly sensitive to hypoxia Wernicke-Korsakoff^ is d/t thiamine deficiency (often in alcoholism), resulting in atrophy of mammillary bodies; the Wernicke triad is visual disturbances/nystagmus, ataxia, and confusion; Korsakoff is known for confabulation (make things up d/t inability to remember) ^NOTE: do not give glucose before thiamine - thiamine is cofactor in glucose metabolism and can worsen deficiency

Cirrhosis and HF can cause hypervolemic hyponatremia w/high ADH and high Uosm SIADH, hypothyroid, and secondary adrenal dz (cortisol suppresses ADH; retained aldosterone --> retained ECV) can cause euvolemic hyponatremia w/high ADH and high Uosm Dehydration, diuretics, and primary adrenal dz (cortisol suppresses ADH; lost aldosterone --> lost ECV) can cause hypovolemic hyponatremia w/high ADH and high Uosm Polydipsia and diet can cause euvolemic hyponatremia w/low ADH and low Uosm Renal failure can cause hypervolemic OR euvolemic hyponatremia w/low ADH and high Uosm (REMEMBER: low ADH is appropriate response to hyponatremia - in other cases where ADH is HIGH, is d/t low ECV [non-osmotic release of ADH] or inappropriate ADH release) Tx: fluid restriction +/- vaptan drugs (do NOT correct too quickly - avoid CPM w/quadriplegia +/- death)

Cirrhosis is irreversible, end-stage liver dz that can be 2/2 viral hepatitis, alcohol, or NASH; cirrhosis results in shrunken liver that is replaced by fibrosis & nodules Clinically, cirrhosis p/w: *HYPER___ (asterixis, confusion)* - tx w/low protein diet + *L___ (makes colon acidic --> NH3 in colon becomes NH4+ --> NH4+ is shat out --> decreases NH3 levels)*, + other common findings of liver dysfunction (jaundice, hypoglycemia, coagulopathy, *HYPO___ [ascites, edema]*) A number of sx can develop d/t elevated estrogen (*estrogen can make skin red*): ___ angiomata, palmar ___, and g___ ___ HTN can also develop 2/2 cirrhosis (fibrosis is not distensible) - gastric varices, caput medusa, hemorrhoids, upper GI bleeds Cirrhosis can have large impact on capillary fluid shifts - oncotic pressure decreases (loss of ___) and hydrostatic pressure increases (portal ___ - *must have portal HTN to get ascites!*); both effects drive fluid out of circulation!!

Cirrhosis is irreversible, end-stage liver dz that can be 2/2 viral hepatitis, alcohol, or NASH; cirrhosis results in shrunken liver that is replaced by fibrosis & nodules Clinically, cirrhosis p/w: *hyperammonemia (asterixis, confusion)* - tx w/low protein diet + *LACTULOSE (makes colon acidic --> NH3 in colon becomes NH4+ --> NH4+ is shat out --> decreases NH3 levels)*, + other common findings of liver dysfunction (jaundice, hypoglycemia, coagulopathy, *HYPOALBUMINEMA [ascites, edema]*) A number of sx can develop d/t elevated estrogen (*estrogen can make skin red*): spider angiomata, palmar erythema, and gynecomastia Portal HTN can also develop 2/2 cirrhosis (fibrosis is not distensible) - gastric varices, caput medusa, hemorrhoids, upper GI bleeds Cirrhosis can have large impact on capillary fluid shifts - oncotic pressure decreases (loss of albumin) and hydrostatic pressure increases (portal HTN - *must have portal HTN to get ascites!*); both effects drive fluid out of circulation!!

Classic osteo___ lesion is multiple myeloma; classic osteo___ lesion is prostate cancer ___ is small tumor of appendicular skeleton (arms/legs) of young men - p/w bone pain @ night that is relieved w/aspirin; will appear at diaphyseal cortex OOs are ___ tumor that secrete non-mineralized bone matrix, surrounded by rim of woven bone; X-ray will show radiolucent core surrounded by reactive bone ___ is larger (>2cm) osteoblast tumor in vertebra, ___ to NSAIDs (basically larger OO) Osteomas of skull/mandible can occur w/G___ syndrome (FAP variant) - *tumors often precede colon sx* Giant cell tumor is benign tumor of osteoclasts occurring *[HY] in ___* - stromal cells express high RANK-L --> giant osteoclasts

Classic osteolytic lesion is multiple myeloma; classic osteoblastic lesion is prostate cancer Osteoid osteoma is small tumor of appendicular skeleton (arms/legs) of young men - p/w bone pain @ night that is relieved w/aspirin; will appear at diaphyseal cortex OOs are osteoblast tumor that secrete non-mineralized bone matrix, surrounded by rim of woven bone; X-ray will show radiolucent core surrounded by reactive bone Osteoblastoma is larger (>2cm) osteoblast tumor in vertebra, unresponsive to NSAIDs (basically larger OO) Osteomas of skull/mandible can occur w/Gardner's syndrome (FAP variant) - *tumors often precede colon sx* Giant cell tumor is benign tumor of osteoclasts occurring *[HY] in EPIPHYSIS* - stromal cells express high RANK-L --> giant osteoclasts

Classic presentation for diabetes is poly___ + ___ Diagnosis for diabetes requires: 1) Random plasma glucose >___ + hyperglycemic sx 2) Fasting blood glucose >___ 3) HbA1c >___% (non-enzymatic glycation of beta-chains at valine terminals!) 4) Two-hour glucose tolerance test w/glucose >___ (often used for gestational diabetes d/t insulin resistance being normal in pregnancy)

Classic presentation for diabetes is polyuria + polydipsia Diagnosis for diabetes requires: 1) Random plasma glucose >200 + hyperglycemic sx 2) Fasting blood glucose > 126 3) HbA1c > 6.5% (non-enzymatic glycation of beta-chains at valine terminals!) 4) Two-hour glucose tolerance test w/glucose >200 (often used for gestational diabetes d/t insulin resistance being normal in pregnancy)

Classical conditioning involves unconditioned stimulus + response and conditioned stimulus + response; in CC, response is usually ___ (clinical example of CC is enuresis alarms) Operant conditioning involves a behavior d/t reward or punishment; OC enforces or decreases ___ behavior In OC, reinforcement *___* frequency of behavior and punishment *___* frequency of behavior -___ --> give reward for good behavior -___ --> spanking to decrease behavior -___ --> clean room to avoid scolding -___ --> take away iPad to decrease naughtiness

Classical conditioning involves unconditioned stimulus + response and conditioned stimulus + response; in CC, response is usually involuntary (clinical example of CC is enuresis alarms) Operant conditioning involves a behavior d/t reward or punishment; OC enforces or decreases voluntary behavior In OC, reinforcement *INCREASES* frequency of behavior and punishment *DECREASES* frequency of behavior -Positive reinforcement --> give reward for good behavior -Positive punishment --> spanking to decrease behavior -Negative reinforcement --> clean room to avoid scolding -Negative punishment --> take away iPad to decrease naughtiness

Clearance is *___*. of blood cleared of drug (i.e., volume that contained X amount of drug); Cx (L/min) = ([excretion rate, mg/min]/[___, mg/L]) - can also calculate via volume of distribution (Vd) w/elimination constant (Ke), Cx = (Vd x Ke) NOTE: higher Vd --> ___ clearance (THINK 'BOUT IT: if kidneys remove same mass [g] of drug, but that drug is over greater volume distr. in subject A than in subject B, the subj. A will have more volume of drug cleared --> greater clearance) Usually, clearance is used to calculate Ke such that Ke = ___ Cx can also be calculated using AUC (Cx = [DOSE, mg]/[AUC, (mg x min) / L]) *[HY] Clearance = [(0.7 x Vd) / ___]* Clearance occurs via kidneys or liver (kidney/liver dz --> clearance falls --> toxicity occurs, adjust dose)

Clearance is *VOLUME*. of blood cleared of drug (i.e., volume that contained X amount of drug); Cx (L/min) = ([excretion rate, mg/min]/[plasma concentration, mg/L]) - can also calculate via volume of distribution (Vd) w/elimination constant (Ke), Cx = (Vd x Ke) NOTE: higher Vd --> greater clearance (THINK 'BOUT IT: if kidneys remove same mass [g] of drug, but that drug is over greater volume distr. in subject A than in subject B, the subj. A will have more volume of drug cleared --> greater clearance) Usually, clearance is used to calculate Ke such that Ke = ([Cx]/[Vd]) Cx can also be calculated using AUC (Cx = [DOSE, mg]/[AUC, (mg x min) / L]) *[HY] Clearance = [(0.7 x Vd) / T-0.5]* Clearance occurs via kidneys or liver (kidney/liver dz --> clearance falls --> toxicity occurs, adjust dose)

Clinical bilirubin measures include: 1) serum (total, direct, undirect), 2) urine urobilinogen (normally small amount), 3) urine conjugated bilirubin (normally absent) Four general causes of hyperbilirubinemia: hemolysis, biliary obstruction, liver dz, "special causes" Hemolysis (or large hematoma present) --> elevated ___ bilirubin, ___ urine bilirubin detected (unconj. can't cross glomerulus), ___ urobilinogen Biliary obstruction (cholestasis) has normal conjugation --> elevated ___ bilirubin, ___ urinary direct bilirubin (*dark urine*), ___ urine urobilinogen (+ cholestatic liver pattern + *___-colored stools [no stercobilin]!*) Primary liver dz (don't rely on bili results) --> mixed hyperbilirubinemia, variable urobilinogen levels (elevated early d/t difficulty excreting after resorption, sometimes elevated urinary direct bilirubin, decreased late d/t less bilirubin making it to intestines)

Clinical bilirubin measures include: 1) serum (total, direct, undirect), 2) urine urobilinogen (normally small amount), 3) urine conjugated bilirubin (normally absent) Four general causes of hyperbilirubinemia: hemolysis, biliary obstruction, liver dz, "special causes" Hemolysis (or large hematoma present) --> elevated unconjugated bilirubin, no urine bilirubin detected (unconj. can't cross glomerulus), increased urobilinogen Biliary obstruction (cholestasis) has normal conjugation --> elevated direct bilirubin, elevated urinary direct bilirubin (*dark urine*), absent urine urobilinogen (+ cholestatic liver pattern + *clay-colored stools [no stercobilin]!*) Primary liver dz (don't rely on bili results) --> mixed hyperbilirubinemia, variable urobilinogen levels (elevated early d/t difficulty excreting after resorption, sometimes elevated urinary direct bilirubin, decreased late d/t less bilirubin making it to intestines)

Clinical trial features: control, randomization, blinding (best evidence of efficacy comes from studies with these features) ___: one group receives therapy, other does not Randomization: subj. randomly assigned to tx arm or no tx arm (all variables other than tx should be equal - *[HY] should eliminate ___, limit select. bias*) ___: control given placebo - subj. unaware of tx v. no tx (single - only pts; double - pts and providers; triple - subj., prov., and analysts unaware) *[HY] Data from CTs can be represented in several ways: if drug --> 30% mortality, no drug --> 50% mort.:* *-___ RR: 50% - 30% = 20%* *-___ RR: ARR/Placebo = 40% (bigger # --> sexier in papers* *-# Needed to Tx: 1/___ = 5* Meta-Analysis increase statistical power (limited 2/2 pooled studies being diff.) Phase I: small # *___ (healthy or sick?) PTS* (safety, toxicity) Phase II: small # *___ PTS* (efficacy, dosing, SEs) Phase III: large # sick pts from diff. centers Phase IV: *POST-MARKETING* study (think ranitidine)

Clinical trial features: control, randomization, blinding (best evidence of efficacy comes from studies with these features) Control: one group receives therapy, other does not Randomization: subj. randomly assigned to tx arm or no tx arm (all variables other than tx should be equal - *[HY] should eliminate confounding, limit select. bias*) Blinding: control given placebo - subj. unaware of tx v. no tx (single - only pts; double - pts and providers; triple - subj., prov., and analysts unaware) *[HY] Data from CTs can be represented in several ways: if drug --> 30% mortality, no drug --> 50% mort.:* *-Absolute RR: 50% - 30% = 20%* *-Relative RR: ARR/Placebo = 40% (bigger # --> sexier in papers* *-# Needed to Tx: 1/ARR = 5* Meta-Analysis increase statistical power (limited 2/2 pooled studies being diff.) Phase I: small # *HEALTHY PTS* (safety, toxicity) Phase II: small # *SICK PTS* (efficacy, dosing, SEs) Phase III: large # sick pts from diff. centers Phase IV: *POST-MARKETING* study (think ranitidine)

Coagulation factor inhibitors inhibit activity and/or increase clearance of clotting factor; MC is inhibitor of factor ___ Inhibitors can occur in a/w malignancy, post-partum, autoimmune d.o P/w sx similar to hemophilia - *do a mixing study (will correct in ___, will not correct w/___)* Tx w/prednisone

Coagulation factor inhibitors inhibit activity and/or increase clearance of clotting factor; MC is inhibitor of factor VIII Inhibitors can occur in a/w malignancy, post-partum, autoimmune d.o P/w sx similar to hemophilia - *do a mixing study (will correct in hemophilia, will not correct w/inhibitor)* Tx w/prednisone

Cocaine has two key physio effects: *1) local anesthetic (blocks ___ channels) and 2) inhibits ___ reuptake* Cocaine intoxication --> increased energy, less sleep, alert, and euphoria; also hallucinations (CLASSICALLY ___ - bugs on skin), *___ (VS?)*, anxiety, chest pain Signs of coke intox --> *___ pupils*, tachy, HTN Tx with benzos; avoid ___

Cocaine has two key physio effects: *1) local anesthetic (blocks sodium channels) and 2) inhibits monoamine (dopamine, 5HT, NE) reuptake* Cocaine intoxication --> increased energy, less sleep, alert, and euphoria; also hallucinations (CLASSICALLY tactile - bugs on skin), *FEVER*, anxiety, chest pain Signs of coke intox --> *DILATED pupils*, tachy, HTN Tx with benzos; avoid beta blockers (unopposed alpha effects)

___ is acquiring + understanding knowledge; cognitive d/o's (delirium, dementia) are inability to acquire knowledge and understanding Dementia is irreversible, chronic/slowly progressive cognitive decline (2/2 AD, multi-infarct, Lewy Body, Pick, CJD, etc); part of w/u should r/o ___ (HPI), ___ (check endo lab), neurosyphilis, vitamin deficiency, HIV; EEG will be ___ Delirium is reversible, acute + waxing/waning course w/loss of attn, disorg thinking, hallucinations (2/2 infxn, EtOH, dementia in unknown setting); EEG will be ___

Cognition is acquiring + understanding knowledge; cognitive d/o's (delirium, dementia) are inability to acquire knowledge and understanding Dementia is irreversible, chronic/slowly progressive cognitive decline (2/2 AD, multi-infarct, Lewy Body, Pick, CJD, etc); part of w/u should r/o depression, hypothyroid, neurosyphilis, vitamin deficiency, HIV; EEG will be normal Delirium is reversible, acute + waxing/waning course w/loss of attn, disorg thinking, hallucinations (2/2 infxn, EtOH, dementia in unknown setting); EEG will be abnormal

Collagen undergoes extensive post-translational modification Alpha chains are synthesized in rER (contain signal molecules - ___collagen), then enter ER lumen (d/t signal sequence directing, now referred to as pro-alpha chains) In ER lumen, pro___ and lys___ are hydroxylated (hydroxylase requires ___ --> can manifest with *SCURVY* if deficient), some hydroxylysines are ___ (Scurvy is 2/2 defective pro-alpha chains, can't form triple helix --> fragile BVs w/bleeding & bruising, poor wound healing, shitty teeth) After glycosylation, propeptides (extra AA at N and C ends of pro-alpha chains in *fibrillar collagens*) help form ___ bonds to stabilize alpha chain triple helix formation (now is *___COLLAGEN*) Procollagen goes through Golgi --> excreted via exocytosis --> propeptides are cleaved at both ends --> *___COLLAGEN (individual triple helix w/o propeptides, no crosslinks)* Tropocollagen is less soluble than procollagen, fibrils start to self-assemble and strengthened by *lysine crosslinking (catalyzed by ___ - requires copper)* - fibrils form collagen fibers (bundles of triple helices) Menkes Dz (X-linked) is mut. in ATP7A gene --> impaired copper absorption --> dec. lysyl oxidase activity; *CLASSIC FEAT.: male child with sparse/brittle/"kinky" ___*, will also see CNS features + poor growth ^Pre: OG, Pro: propeptides added, Tropo: propeptides removed, Fibrils: lysine crosslinking occurs

Collagen undergoes extensive post-translational modification Alpha chains are synthesized in rER (contain signal molecules - pre-procollagen), then enter ER lumen (d/t signal sequence directing, now referred to as pro-alpha chains) In ER lumen, prolines and lysines are hydroxylated (hydroxylase requires vitamin C --> can manifest with *SCURVY* if deficient), some hydroxylysines are glycosylated (Scurvy is 2/2 defective pro-alpha chains, can't form triple helix --> fragile BVs w/bleeding & bruising, poor wound healing, shitty teeth) After glycosylation, propeptides (extra AA at N and C ends of pro-alpha chains in *fibrillar collagens*) help form disulfide bonds to stabilize alpha chain triple helix formation (now is *PROCOLLAGEN*) Procollagen goes through Golgi --> excreted via exocytosis --> propeptides are cleaved at both ends --> *TROPOCOLLAGEN (individual triple helix w/o propeptides, no crosslinks)* Tropocollagen is less soluble than procollagen, fibrils start to self-assemble and strengthened by *lysine crosslinking (catalyzed by lysyl oxidase - requires copper)* - fibrils form collagen fibers (bundles of triple helices) Menkes Dz (X-linked) is mut. in ATP7A gene --> impaired copper absorption --> dec. lysyl oxidase activity; *CLASSIC FEAT.: male child with sparse/brittle/"kinky" hair*, will also see CNS features + poor growth ^Pre: OG, Pro: propeptides added, Tropo: propeptides removed, Fibrils: lysine crosslinking occurs

Competitive inhibitors compete for same site on enz. as subst.; Non-competitive inhibitors bind different (allosteric) site on enz. --> changes shape so can't bind subs. anymore (enz. destroyer) Lots of [S] will overcome ___ inhibitors, but not ___ inhibitors A comp. inhibitor will raise ___ (Vmax or Km?) and keep same ___ (REMEMBER: add enough [S] --> will overcome com. inhib.) A non-comp. inhibitor will keep ___ the same and lower ___ (REMEMBER: non-comp. inhib. basically inactivate/remove enzyme - don't change affinity) On Lin.-Burk Plot, adding a comp. inhib. will result in: x-int (-1/Km) will shift ___ (R or L?), y-int (1/Vmax) will ___ [*Km goes up*] On Lin-Burk Plot, adding non-comp. inhib. will result in: x-int (-1/Km) will ___, y-int (1/Vmax) will shift ___ [*Vmax goes down*]

Competitive inhibitors compete for same site on enz. as subst.; Non-competitive inhibitors bind different (allosteric) site on enz. --> changes shape so can't bind subs. anymore (enz. destroyer) Lots of [S] will overcome comp. inhibitors, but not non-comp. inhibitors A comp. inhibitor will raise Km and keep same Vmax (REMEMBER: add enough [S] --> will overcome com. inhib.) A non-comp. inhibitor will keep Km the same and lower Vmax (REMEMBER: non-comp. inhib. basically inactivate/remove enzyme - don't change affinity) On Lin.-Burk Plot, adding a comp. inhib. will result in: x-int (-1/Km) will shift right, y-int (1/Vmax) will not change [*Km goes up*] On Lin-Burk Plot, adding non-comp. inhib. will result in: x-int (-1/Km) will not change, y-int (1/Vmax) will shift up/increase [*Vmax goes down*]

Complement is a system of hepatically synthesized plasma proteins that have role in innate immunity - *most abundant complement protein is C___, which is converted to C___b --> bacterial binding --> MAC & bacterial death (all complement activation involves C3 --> C3b)* Three pathways for complement (all of which end in C3b --> MAC): alternative, lectin, classic A___ (innate): C3b spontaneously made - unstable and broken down quickly unless it binds amino/hydroxyl group on pathogens, commonly including *___, fungal cell wall, viral envelops*; once stable --> positive feedback loop (C3b binds complement protein ___ --> binds complement protein ___ --> protein B clipped --> C___ [C3 CONVERTASE] --> more C3b!!) Lectin (innate): mannose binding lectin (___) circulates w/MASPs bind *surfaces containing m___ (many bacteria)*, MBL-MASP bind mannose --> C___ converted to C2b + C___ converted to C4b --> C___ (*C3 CONVERTASE* --> more C3b --> MAC!) Classical (adaptive): Ab-Ag complexes bind C___ --> C2 cleaved to C2b + C4 cleaved to C4b --> C2bC4b (*C3 CONVERTASE* --> more C3b --> MAC!) C1 is large complex consisting of many proteins (C1q, C1r, C1s C1-inhibitor) - for C1 to activate, must bind *two F___ portions of antibody that are close together (heavy chain constant 2 and heavy chain constant 3! - also explains why Ig___ is such a potent complement activator!)* --> C1-inhibitor falls off --> C1r + C1s active --> *create C3 convertase (C___)* ^NOTE: C-reactive protein activates early classical pathway that can bind C1

Complement is a system of hepatically synthesized plasma proteins that have role in innate immunity - *most abundant complement protein is C3, which is converted to C3b --> bacterial binding --> MAC & bacterial death (all complement activation involves C3 --> C3b)* Three pathways for complement (all of which end in C3b --> MAC): alternative, lectin, classic Alternative (innate): C3b spontaneously made - unstable and broken down quickly unless it binds amino/hydroxyl group on pathogens, commonly including *LPS, fungal cell wall, viral envelops*; once stable --> positive feedback loop (C3b binds complement protein B --> binds complement protein D --> protein B clipped --> C3bBb [C3 CONVERTASE] --> more C3b!!) Lectin (innate): mannose binding lectin (MBL) circulates w/MASPs bind *surfaces containing mannose (many bacteria)*, MBL-MASP bind mannose --> C2 converted to C2b + C4 converted to C4b --> C2bC4b (*C3 CONVERTASE* --> more C3b --> MAC!) Classical (adaptive): Ab-Ag complexes bind C1 --> C2 cleaved to C2b + C4 cleaved to C4b --> C2bC4b (*C3 CONVERTASE* --> more C3b --> MAC!) C1 is large complex consisting of many proteins (C1q, C1r, C1s C1-inhibitor) - for C1 to activate, must bind *two Fc portions of antibody that are close together (heavy chain constant 2 and heavy chain constant 3! - also explains why IgM is such a potent complement activator!)* --> C1-inhibitor falls off --> C1r + C1s active --> *create C3 convertase (C2bC4b)* ^NOTE: C-reactive protein activates early classical pathway that can bind C1

Compliance is characteristic of lung (for given change in ___, how much does ___ change?) - compliant lung requires small amount of diaphragm effort --> ___ volume increase (easy to move lung in and out); noncompliant (stiff) lung requires large amount of diaphragm effort --> small volume increase Decreased lung compliance is seen in f___, edema, and pneumonia Increased lung compliance is seen in e___ ("floppy lungs") Air moving thru lungs encounters resistance (50% by trachea, then highest in *m___ bronchi [turbulent flow]*, lowest in terminal bronchioles)

Compliance is characteristic of lung (for given change in pressure, how much does volume change?) - compliant lung requires small amount of diaphragm effort --> large volume increase (easy to move lung in and out); noncompliant (stiff) lung requires large amount of diaphragm effort --> small volume increase Decreased lung compliance is seen in fibrosis, edema, and pneumonia Increased lung compliance is seen in emphysema ("floppy lungs") Air moving thru lungs encounters resistance (50% by trachea, then highest in *medium bronchi [turbulent flow]*, lowest in terminal bronchioles)

ConTis is composed of collagen, elastin, fibrillin Collagen consists of triple helix of alpha chains - 42 genes for alpha chains, different combos --> different collagen types; Col is rich is Pro-Lys-Gly AAs (___ > Pro/Lys) TypeI Col (90% of Col) is found in *___* (also skin, cornea, tendons) - defective TypeI Col --> ___; TypeII Col is found in ___; Type III Col is found in skin/BVs (abnormal in ___) [NOTE: *I-III are fibrillar Col*]; TypeIV Col is *non-fibrillar col* that is found in basement membrane (lens, cochlea) - defective TypeIV Col --> A___ Syndrome (alpha3,4,or 5 chains), an X-L d/o w/hematuria (glomerulus BM loss), hearing loss (BM in cochlea), vision chgs (BM in eye) Scl___ is AI d.o w/fibroblast activation --> excess collagen deposition OI is defective collagen production; TypeI OI (least severe) is defective TypeI Col (COL1A1, COL1A2), Type___ is lethal in utero, types III and IV also exist; Clinically, OI manifests w/multiple fx, ___ sclera, ___ loss (mal/inc/stap fxs), dentinogenesis imperfecta (discolored teeth) EhlDanSyn is 2/2 defective col. synthesis and affects joints/skin (OI affects bones!); Classic EDS is type ___ Col. defect (COL5A1, COL5A2), Vascular EDS is type ___ Col. defect (COL3A1); Clinically, see joint hypermobility, hyperextensible skin, easy bruising, cigarette paper scars, MVP - VascEDS can have CNS (___) aneurysms, life-threatening form of EDS (death: 48y)

ConTis is composed of collagen, elastin, fibrillin Collagen consists of triple helix of alpha chains - 42 genes for alpha chains, different combos --> different collagen types; Col is rich is Pro-Lys-Gly AAs (Gly > Pro/Lys) TypeI Col (90% of Col) is found in *BONE* (also skin, cornea, tendons) - defective TypeI Col --> osteogenesis imperfecta; TypeII Col is found in cartilage; Type III Col is found in skin/BVs (abnormal in EhlDanSyn) [NOTE: *I-III are fibrillar Col*]; TypeIV Col is *non-fibrillar col* that is found in basement membrane (lens, cochlea) - defective TypeIV Col --> Alport Syndrome (alpha3,4,or 5 chains), an X-L d/o w/hematuria (glomerulus BM loss), hearing loss (BM in cochlea), vision chgs (BM in eye) Scleroderma is AI d.o w/fibroblast activation --> excess collagen deposition OI is defective collagen production; TypeI OI (least severe) is defective TypeI Col (COL1A1, COL1A2), TypeII is lethal in utero, types III and IV also exist; Clinically, OI manifests w/multiple fx, blue sclera, hearing loss (mal/inc/stap fxs), dentinogenesis imperfecta (discolored teeth) EhlDanSyn is 2/2 defective col. synthesis and affects joints/skin (OI affects bones!); Classic EDS is type V Col. defect (COL5A1, COL5A2), Vascular EDS is type III Col. defect (COL3A1); Clinically, see joint hypermobility, hyperextensible skin, easy bruising, cigarette paper scars, MVP - VascEDS can have CNS (berry) aneurysms, life-threatening form of EDS (death: 48y)

ConTis is composed of collagen, elastin, fibrillin ___ is main component of elastic fibers (allow stretch/recoil) - important in arteries (50% of aorta) and lungs; Elastin cont. Gly-Lys-Pro (like collagen) that are non-hydroxylated and non-glycosylated (unlike col.); Elastin is secreted as ___, then crosslinked (similar to col.) Alpha-1-AT Deficiency is dec. AAT protein (normally inhibits ___) --> excessive breakdown of elastin --> *E___ in lungs (lack of lung recoil)* Williams Syndrome is deletion of long Chrom7 (lose portion of elastin gene) --> elfin appear. + *s___ aortic stenosis w/histo revealing loss of ELASTIN!* Fibrillin is major component of microfibrils (abundant in aorta) - fibrillin deficiency manifests w/___ (FBN1 gene) Clinically, MFS manifests as tall w/long wingspan (abnormal CT allows bones to grow excessively long), pectus excavatum, hypermobile joints (wrist + thumb sign), cataracts (early age, pre-senile), lens dislocation (*___ward and ___ward, think of TALL w/LONG ARMS*), mitral valve prolapse, and *aortic ___ (w/cystic medial necrosis, cysts/necrosis in medial layer of aorta)*

ConTis is composed of collagen, elastin, fibrillin Elastin is main component of elastic fibers (allow stretch/recoil) - important in arteries (50% of aorta) and lungs; Elastin cont. Gly-Lys-Pro (like collagen) that are non-hydroxylated and non-glycosylated (unlike col.); Elastin is secreted as tropoelastin, then crosslinked (similar to col.) Alpha-1-AT Deficiency is dec. AAT protein (normally inhibits elastase) --> excessive breakdown of elastin --> *EMPHYSEMA in lungs (lack of lung recoil)* Williams Syndrome is deletion of long Chrom7 (lose portion of elastin gene) --> elfin appear. + *supravalvular aortic stenosis w/histo revealing loss of ELASTIN!* Fibrillin is major component of microfibrils (abundant in aorta) - fibrillin deficiency manifests w/Marfan syndrome (FBN1 gene) Clinically, MFS manifests as tall w/long wingspan (abnormal CT allows bones to grow excessively long), pectus excavatum, hypermobile joints (wrist + thumb sign), cataracts (early age, pre-senile), lens dislocation (*upward and outward, think of TALL w/LONG ARMS*), mitral valve prolapse, and *aortic aneurysm/dissection (w/cystic medial necrosis, cysts/necrosis in medial layer of aorta)*

CHILDHOOD DISORDERS: ___ is violation of others' rights, aggression to people/animal, and destruction of property (adults: Antisocial PD) ___ is angry/irritable child that argues with authority figures (less severe than CD) - must occur with non-sibling, cause problems at school, and not be 2/2 substances, depression, bipolar (tx with CBT) ___ (new dx) is *frequent temper outbursts at least 3x/week in at least 2 settings* (behavior out of proportion to situation)

Conduct Disorder is violation of others' rights, aggression to people/animal, and destruction of property (adults: Antisocial PD) Oppositional Defiant Disorder is angry/irritable child that argues with authority figures (less severe than CD) - must occur with non-sibling, cause problems at school, and not be 2/2 substances, depression, bipolar (tx with CBT) Disruptive Mood Dysregulation Disorder (new dx) is *frequent temper outbursts at least 3x/week in at least 2 settings* (behavior out of proportion to situation)

C___ report what % of resamples would fall within range determined by study (usually 95% confidence); CI is determined by SD and # of subjects; usually repr. as "95% chance next sample would fall btwn X and Y" CI calc: mean +/- (1.96 x [SD/(ROOT[N])]) *DON'T CONFUSE SD W/ConInt!! Do they want to know range where 95% of samples fall (___)? Do they want to know range in which you are 95% confident a resample would fall (___)?* Odds/Risk ratios are reported with CIs - *if range includes 1.0 --> null hypot. is ___ (i.e., can't confidently declare significance)* Mean difference between two groups can be calculated with CIs - *if CI includes 0 --> no significant difference btwn groups (null hypot. ___)* Can report group means with CIs - *if two groups have CIs that overlap --> no significant difference btwn groups (null hypot. ___)*

Confidence Intervals report what % of resamples would fall within range determined by study (usually 95% confidence); CI is determined by SD and # of subjects; usually repr. as "95% chance next sample would fall btwn X and Y" CI calc: mean +/- (1.96 x [SD/(ROOT[N])]) *DON'T CONFUSE SD W/ConInt!! Do they want to know range where 95% of samples fall (mean +/- 2SDs)? Do they want to know range in which you are 95% confident a resample would fall (ConInt)?* Odds/Risk ratios are reported with CIs - *if range includes 1.0 --> null hypot. is not rejected (i.e., can't confidently declare significance)* Mean difference between two groups can be calculated with CIs - *if CI includes 0 --> no significant difference btwn groups (null hypot. not rejected)* Can report group means with CIs - *if two groups have CIs that overlap --> no significant difference btwn groups (null hypot. not rejected)*

Correlation (Pearson) Coefficient (r) determines measure of linear correlation btwn two variables (i.e., lifespan and smoking) - represents strength of association btwn two variables (btwn -1.0 and 1.0, 0 = no relationship) Negative coefficient --> ___ relationship (more smoking, low lifespan); Positive coefficient --> ___ relationship (more smoking, high lifespan) p-value can be reported to indicate significant vs. insignificant correlation Coefficient of Determination (___) is indicative of % of variation in y explained by x (i.e., r^2 = 0.6, 60% of variation in y can be explained by x, 60% of variation in lifespan can be explained by how much you smoke)

Correlation (Pearson) Coefficient determines measure of linear correlation btwn two variables (i.e., lifespan and smoking) - represents strength of association btwn two variables (btwn -1.0 and 1.0, 0 = no relationship) Negative coefficient --> inverse relationship (more smoking, low lifespan); Positive coefficient --> direct relationship (more smoking, high lifespan) p-value can be reported to indicate significant vs. insignificant correlation Coefficient of Determination (r^2) is indicative of % of variation in y explained by x (i.e., r^2 = 0.6, 60% of variation in y can be explained by x, 60% of variation in lifespan can be explained by how much you smoke)

Cortisol is poorly soluble in plasma and exists bound to ___ (levels of CBG increase with high ___ levels --> pregnancy [similar to TH and TBG, estrogen and SHBG!]) Cortisol levels increase during periods of stress - accordingly, follow circadian rhythm (highest in ___ when we need to wake up and fight bears) *CORTISOL EFFECTS (think stress, A BIG FIB):* Appetite: ___ (need calories to fight bears) Blood Pressure: *maintains BP (MAJOR EFFECT, think adrenal crisis) via increased ___ (adrenergic receptor?) sensitivity* Insulin Resistance: ___genic (to get hyperglycemia for brain fuel) ___ (Lipolysis, Proteolysis): increased (increases G6P, PEPCK synthesis - more brain fuel); also leads to characteristic *___ deposition* Fibroblast Activity: decreased - don't want to divert energy to wound healing (l/t poor wound ___, decreased ___ synthesis, s___) *Inflammatory/Immune Response (reason for drug)*: don't want to divert energy to replicating T-/B-cells (blocks neutrophil migration [neutrophilia], block histamine release, eosinopenia); also *inactivates ___ ("like to ask about"), which mediates response to TNF-alpha* Bone Formation: decreased (2/2 decreased ___ activity, don't need it in times of stress)

Cortisol is poorly soluble in plasma and exists bound to cortisol binding globulin (levels of CBG increase with high estrogen levels --> pregnancy) Cortisol levels increase during periods of stress - accordingly, follow circadian rhythm (highest in morning when we need to wake up and fight bears) *CORTISOL EFFECTS (think stress, A BIG FIB):* Appetite: increased (need calories to fight bears) Blood Pressure: *maintains BP (MAJOR EFFECT, think adrenal crisis) via increased alpha-1 sensitivity* Insulin Resistance: diabetogenic (to get hyperglycemia for brain fuel) Gluconeogenesis (Lipolysis, Proteolysis): increased (increases G6P, PEPCK synthesis - more brain fuel); also leads to characteristic *fat deposition* Fibroblast Activity: decreased - don't want to divert energy to wound healing (l/t poor wound healing, decreased collagen synthesis, striae) *Inflammatory/Immune Response (reason for drug)*: don't want to divert energy to replicating T-/B-cells (blocks neutrophil migration [neutrophilia], block histamine release, eosinopenia); also *inactivates NF-kappa-B ("like to ask about"), which mediates response to TNF-alpha* Bone Formation: decreased (2/2 decreased osteoblast activity, don't need it in times of stress)

C___ Study: subj. randomly assigned to sequence of tx (i.e., pt receives placebo x8w, then drug x8w, or vice-versa - NEED washout period) - mechanism to eliminate bias *[HY] E___ M___: NOT a point of bias, but effect results of study (i.e., 3rd factor that alters effect); drug A is shown to inc. risk of DVT - to cause DVT, drug A req. gene X - gene X is an effect modifier; do a stratified analysis!* *[HY] Difference btwn confounding and effect mod.: confounding is 3rd variable that E___ effect on outcome (i.e., no real effect of exposure on outcome - after stratified analysis, no RR exists); EM is 3rd variable that M___ effect only in one group - there is real effect of exp. on outcome, but requires presence of 3rd variable (after stratified analysis, RR persists)!!* L___ P___: not form of bias, but occurs when dz takes long time and studies of drug is shorter than time period for dz to develop (i.e., studying ASA post-MI for only 1 month)

Crossover Study: subj. randomly assigned to sequence of tx (i.e., pt receives placebo x8w, then drug x8w, or vice-versa - NEED washout period) - mechanism to eliminate bias *[HY] Effect Modification: NOT a point of bias, but effect results of study (i.e., 3rd factor that alters effect); drug A is shown to inc. risk of DVT - to cause DVT, drug A req. gene X - gene X is an effect modifier; do a stratified analysis!* *[HY] Difference btwn confounding and effect mod.: confounding is 3rd variable that ELIMINATES effect on outcome (i.e., no real effect of exposure on outcome - after stratified analysis, no RR exists); EM is 3rd variable that MAINTAINS effect only in one group - there is real effect of exp. on outcome, but requires presence of 3rd variable (after stratified analysis, RR persists)!!* Latent Period: not form of bias, but occurs when dz takes long time and studies of drug is shorter than time period for dz to develop (i.e., studying ASA post-MI for only 1 month)

Cushing Syndrome Diagnosis: 1. Can screen w/24h urine free cortisol OR late night salivary cortisol; *[HY] Can also do a ___-dose dexamethasone suppression test! Give 1mg @ bedtime, then measure cortisol in AM - should be low, but in Cushing's syndrome, cortisol remains high (adenomas, tumors do not suppress cortisol production!)* 2. Establish Cause. Once Cushing's syndrome is confirmed, measure serum ___ - ACTH-dependent (Cushing dz, ectopic ACTH [small cell lung cancer]) and ACTH-independent (steroid therapy, adrenal adenoma). ACTH ___ in dependent causes, ACTH ___ in independent causes (consider adrenal CT). 3. If ACTH-dependent (ectopic ACTH [lung cancer] or pituitary adenoma), do *___ dexamethasone suppression test (3mg)* - should ___ in Cushing's Dz (get MRI brain) and ___ in ectopic ACTH (get chest CT)

Cushing Syndrome Diagnosis: 1. Can screen w/24h urine free cortisol OR late night salivary cortisol; *[HY] Can also do a low-dose dexamethasone suppression test! Give 1mg @ bedtime, then measure cortisol in AM - should be low, but in Cushing's syndrome, cortisol remains high (adenomas, tumors do not suppress cortisol production!)* 2. Establish Cause. Once Cushing's syndrome is confirmed, measure serum ACTH - ACTH-dependent (Cushing dz, ectopic ACTH [small cell lung cancer]) and ACTH-independent (steroid therapy, adrenal adenoma). ACTH high in dependent causes, ACTH low in independent causes (consider adrenal CT). 3. If ACTH-dependent (ectopic ACTH [lung cancer] or pituitary adenoma), do *high dose dexamethasone suppression test (3mg)* - should suppress in Cushing's Dz (get MRI brain) and not suppress in ectopic ACTH (get chest CT)

Cushing Syndrome has numerous manifestiations, including hyper___, hyper___, diabetes (2/2 insulin resistance), and ___ suppression (think of what steroids are used for); other features include moon facies, buffalo hump, osteoporosis, ___ obesity, skin changes (striae); d/t suppressed ___ release, women develop amenorrhea and hirsutism, while men develop ED Causes of Cushing's syndrome include ACTH independent causes (glucocorticoid therapy, adrenal ___) or ACTH dependent (Cushing's dz, ectopic ACTH [___ cancer]) *NOTE: ___ is 2/2 ACTH-dependent Cushing's syndrome (ACTH binds melanocyte-stimulating hormone receptors)* ^hyperCholesterolemia, Urinary free cortisol, Skin changes (striae, thinning), Hypertension, Immunsuppression, Neoplasm (Cushing Dz can cause CushSynd), Growth restriction (in children), Sugar (hyperglycemia 2/2 insulin resistance)

Cushing Syndrome has numerous manifestiations, including HTN, hyperglycemia, diabetes (2/2 insulin resistance), and immune suppression (think of what steroids are used for); other features include moon facies, buffalo hump, osteoporosis, truncal obesity, skin changes (striae); d/t suppressed GnRH release, women develop amenorrhea and hirsutism, while men develop ED Causes of Cushing's syndrome include ACTH independent causes (glucocorticoid therapy, adrenal adenoma) or ACTH dependent (Cushing's dz, ectopic ACTH [small cell lung cancer]) *NOTE: hyperpigmentation is 2/2 ACTH-dependent Cushing's syndrome (ACTH binds melanocyte-stimulating hormone receptors)* ^hyperCholesterolemia, Urinary free cortisol, Skin changes (striae, thinning), Hypertension, Immunsuppression, Neoplasm (Cushing Dz can cause CushSynd), Growth restriction (in children), Sugar (hyperglycemia 2/2 insulin resistance)

Cyclosporine and tacrolimus (no sketchy - consider YouTube) are drugs that inhibit ___ (normally activates NFAT, an important transcription factor for cytokines); both are used in autoimmune dz and to prevent organ rejection Importantly, both drugs are metabolized by P450 (many drug-drug interactions) Most limiting side effect of both is ___ (d/t vasconstriction of afferent and efferent arterioles) and HTN (use d___ - impairs P450 system --> raises drug levels, so can lower dose and tx HTN at same time); also hyperuricemia, hyperglycemia, neurotoxicity (cyclosporine: hirsutism + gingival hyperplasia) --- Sirolimus (no sketchy) is used in kidney transplants + ___-eluting stents; it inhibits ___ by binding FK binding protein SEs: pancytopenia, hyperlipidemia, hyperglycemia --- *[HY] Be careful for azathioprine/6-MP toxicity with ___*

Cyclosporine and tacrolimus (no sketchy - consider YouTube) are drugs that inhibit calcineurin (normally activates NFAT, an important transcription factor for cytokines); both are used in autoimmune dz and to prevent organ rejection Importantly, both drugs are metabolized by P450 (many drug-drug interactions) Most limiting side effect of both is nephrotoxicity (d/t vasconstriction of afferent and efferent arterioles) and HTN (use diltiazem - impairs P450 system --> raises drug levels, so can lower dose and tx HTN at same time); also hyperuricemia, hyperglycemia, neurotoxicity (cyclosporine: hirsutism + gingival hyperplasia) --- Sirolimus (no sketchy) is used in kidney transplants + drug-eluting stents; it inhibits mTOR by binding FK binding protein SEs: pancytopenia, hyperlipidemia, hyperglycemia --- *[HY] Be careful for azathioprine/6-MP toxicity with xanthine oxidase inhibitors (allopurinol)*

Cystinuria is AR disorder of renal PCT transporter --> can't reabsorb Cystine, Ornithine, Lysine, Arginine (COLA) --> cystinuria w/main problem being KIDNEY STONES (hexagonal crystals) Tx: urine alkalization, methionine free diet

Cytoskeleton cont. microfilaments (actin), intermediate fil., and microtubules Microfilaments are ___ polymers found under CM - maintain cell shape + movement, found in *m___ of intestinal cells* and *sarcomere thin fils.* Intermediate fils. maintain cell shape/structure and *are used as tumor markers/IHC staining!* Vimentin (IF) is found in mesenchymal tissue (connective tiss. - fibroblasts, skeletal musc./Z-disks, adipocytes - not organs) - because of location, Vimentin is *common tumor marker in S___ (liposarcoma, leiomyosarcoma), but can be found in non-sarcoma tumors* Desmin (IF) is muscle filament (part of Z-disk w/Vimentin) that can be used as marker for m___ tumors Keratin (IF) is ___ cell filament used to diagnose epithelial tumors (used in SqCeCa) Neurofilaments (IF) are found in neurons (esp. axons) - seen in CNS tumors GFAP (IF) is astrocyte filament that is seen in ___blastoma + ___cytoma

Cytoskeleton cont. microfilaments (actin), intermediate fil., and microtubules Microfilaments are actin polymers found under CM - maintain cell shape + movement, found in *microvilli of intestinal cells* and *sarcomere thin fils.* Intermediate fils. maintain cell shape/structure and *are used as tumor markers/IHC staining!* Vimentin (IF) is found in mesenchymal tissue (connective tiss. - fibroblasts, skeletal musc./Z-disks, adipocytes - not organs) - because of location, Vimentin is *common tumor marker in SARCOMAS (liposarcoma, leiomyosarcoma), but can be found in non-sarcoma tumors* Desmin (IF) is muscle filament (part of Z-disk w/Vimentin) that can be used as marker for muscle tumors Keratin (IF) is epithelial cell filament used to diagnose epithelial tumors (used in SqCeCa) Neurofilaments (IF) are found in neurons (esp. axons) - seen in CNS tumors GFAP (IF) is astrocyte filament that is seen in glioblastoma + astrocytoma

DEFENSE MECHANISMS (mature/healthy): ___ is using negative emotions in positive way (i.e., aggressive person becomes boxer) ___ is practice of concern for others to relieve own anxiety (i.e., cancer survivors helping others with same dz) ___ is conscious defense mechanism to ignore stressful thoughts (i.e., "I'm not going to think about that now") ___ is relieving anxiety with jokes/laughter (i.e., medical student making jokes about studying)

DEFENSE MECHANISMS (mature/healthy): Sublimation is using negative emotions in positive way (i.e., aggressive person becomes boxer) Altruism is practice of concern for others to relieve own anxiety (i.e., cancer survivors helping others with same dz) Suppression is conscious defense mechanism to ignore stressful thoughts (i.e., "I'm not going to think about that now") Humor is relieving anxiety with jokes/laughter (i.e., medical student making jokes about studying)

DNA damage (not muts) can occur via de___ (removal of purine bases) and de___ (*conversion of cytosine NH2 to C=O, Cyt --> Ura*), also others that are less HY; double-strand repair mechanisms (needed when exogenous damage - ionizing radiation) include homologous end joining and NHEJ HEJ uses ___ template to repair DS break NHEJ uses many proteins to re-join broken ends (no template used, ___ [highly or not highly?] error-prone); F___ Anemia is inherited aplastic anemia w/errors in DNA repair enzymes (can be seen w/impaired NHEJ); *CLASSIC NHEJ condition is A___ T___ 2/2 ATM mutation --> DNA hypersensitivity to ionizing radiation (high risk of cancer)*

DNA damage (not muts) can occur via depurination (removal of purine bases) and deamination (*conversion of cytosine NH2 to C=O, Cyt --> Ura*), also others that are less HY; double-strand repair mechanisms (needed when exogenous damage - ionizing radiation) include homologous end joining and NHEJ HEJ uses sister chromosome template to repair DS break NHEJ uses many proteins to re-join broken ends (no template used, highly error-prone); Fanconi Anemia is inherited aplastic anemia w/errors in DNA repair enzymes (can be seen w/impaired NHEJ); *CLASSIC NHEJ condition is ataxia telangiectasia 2/2 ATM mutation --> DNA hypersensitivity to ionizing radiation (high risk of cancer)*

DNA damage (not muts) can occur via depurination (removal of purine bases) and deamination (*conversion of cytosine NH2 to C=O, Cyt --> Ura*), also others that are less HY; single-strand repair mechanisms include base excision, nucleotide excision, mismatch repair ___ recognizes specific base errors (deamination, oxidation, open rings) and fixes in any phase of cell cycle; 1) remove damaged base via DNA glycosylase (leaves site apurinic or apyrimidinic - AP), 2) "nick" AP nucleotide to remove (AP ___nuclease --> 5', AP L___ --> 3'), 3) DNApol adds new nucleotide (to 3' hydroxyl terminus) and 4) DNA ligase seals strand Nucleotide excision repair removes "bulky" DNA damage (cyclobutane pyrimidine ___) in G1 phase only; Endonucleases remove mult. nucleotides and DNApol + DNAlig fill gap; *[HY] defective NER leads to ___ - extreme sensitivity to UV rays (easy sunburning, freckles, skin cancer)* Mismatch repair identifies incorrectly placed nucleotides (not damage, not recognized by BER or NER) in *[HY] the ___ phase (after DNA synthesis!)*; MMR is important for M___ stability (MSs: DNA segments w/many repeating nucleotides, prone to DNA slippage) and keep stable # of microsatellites in DNA (*microsatellite instability occurs with MMR deficiency, seen in ___ - germline mut. of DNA MMR prots [MLH1 and MSH2]*)

DNA damage (not muts) can occur via depurination (removal of purine bases) and deamination (*conversion of cytosine NH2 to C=O, Cyt --> Ura*), also others that are less HY; single-strand repair mechanisms include base excision, nucleotide excision, mismatch repair Base excision repair recognizes specific base errors (deamination, oxidation, open rings) and fixes in any phase of cell cycle; 1) remove damaged base via DNA glycosylase (leaves site apurinic or apyrimidinic - AP), 2) "nick" AP nucleotide to remove (AP endonuclease --> 5', AP lyase --> 3'), 3) DNApol adds new nucleotide (to 3' hydroxyl terminus) and 4) DNA ligase seals strand Nucleotide excision repair removes "bulky" DNA damage (cyclobutane pyrimidine dimer) in G1 phase only; Endonucleases remove mult. nucleotides and DNApol + DNAlig fill gap; *[HY] defective NER leads to XERODERMA PIGMENTOSUM - extreme sensitivity to UV rays (easy sunburning, freckles, skin cancer)* Mismatch repair identifies incorrectly placed nucleotides (not damage, not recognized by BER or NER) in *[HY] the S/G2 phase (after DNA synthesis!)*; MMR is important for microsatellite stability (MSs: DNA segments w/many repeating nucleotides, prone to DNA slippage) and keep stable # of microsatellites in DNA (*microsatellite instability occurs with MMR deficiency, seen in HNPCC - germline mut. of DNA MMR prots [MLH1 and MSH2]*)

DNA damage can arrest cell division via signaling pathways: ___ pathway (activated by DblStr breaks, mut --> AtaxTelang) and ___ pathway (SingStr breaks), both of which phosphorylate prots. --> cell cycle arrest P53 prot. is major target of ATM/ATR systems and is phosphorylated after DNA damage (prevents P53 breakdown --> incr. P53 activity) - P53 induces transcription of P21 --> P21 binds CDKs to inhibit activity --> block progression through cell cycle P53 and P21 are both considered ___ (TSG or oncogenes?) KEY PT: G1-S progression is inhibited by DNA damage NOTE: P53 (TSG) mutation --> L___-F___ syndrome

DNA damage can arrest cell division via signaling pathways: ATM pathway (activated by DblStr breaks, mut --> AtaxTelang) and ATR pathway (SingStr breaks), both of which phosphorylate prots. --> cell cycle arrest P53 prot. is major target of ATM/ATR systems and is phosphorylated after DNA damage (prevents P53 breakdown --> incr. P53 activity) - P53 induces transcription of P21 --> P21 binds CDKs to inhibit activity --> block progression through cell cycle P53 and P21 are both considered TSGs KEY PT: G1-S progression is inhibited by DNA damage NOTE: P53 (TSG) mutation --> Li-Fraumeni syndrome

DNA ___ is solid struct. (glass, plastic) containing thousands of DNA sequences (probes), used to test sample of DNA labeled w/fluorescent markers - if hybridize --> computer detects which probes bind sample MAs can be used to identify gene ___ (which genes are active in cells?), copy number variation (which cells contain inc/dec copies of gene? - compares fluorescence intensity to sample, sample > reference --> more copies), *___ (single nucleotide changes in gene)* FISH uses fluorescent lighting to identify binding of cDNA segments (like MAs) - fluor. DNA probe binds specific gene site --> localizes gene to chromosome --> determines which ___ contains gene (will be looking at karyotype, use when cells are in *METAPHASE*) FISH used to compare test cells to normal cells - identifies *microdeletions (DiGeorge, no fluorescence @ 22q11), ___locations, d___tions*

DNA microarray is solid struct. (glass, plastic) containing thousands of DNA sequences (probes), used to test sample of DNA labeled w/fluorescent markers - if hybridize --> computer detects which probes bind sample MAs can be used to identify gene expression (which genes are active in cells?), copy number variation (which cells contain inc/dec copies of gene? - compares fluorescence intensity to sample, sample > reference --> more copies), *SNPs (single nucleotide changes in gene)* FISH uses fluorescent lighting to identify binding of cDNA segments (like MAs) - fluor. DNA probe binds specific gene site --> localizes gene to chromosome --> determines which chrom. contains gene (will be looking at karyotype, use when cells are in *METAPHASE*) FISH used to compare test cells to normal cells - identifies *microdeletions (DiGeorge, no fluorescence @ 22q11), translocations, duplications*

DNA pol. cannot initiate replication without ___ (short nucleotide sequence); DNA ___ makes primers from RNA contained in enzyme; RNA pol. does not require primer DNA pol. adds triphosphate nucleotides by cleaving triphosphate bonds (provides energy for rxn) and adding to 3' end (@ hydroxyl group; i.e., *DNA rep. always goes ___' --> ___'*) Bcuz of DNA directionality, need to have leading strand and lagging strand; lead. str. goes about its business, lag. str. ends up with ___ fragments At end of DNA repl., RNA primers are removed and replaced w/DNA (Prok: DNApol-1; Euks: DNApol-Delta); DNA ___ unites Okazaki fragments by creating phosphodiester bonds DNApol can perform proofreading via ____ activity (REMEMBER: this is opposite normal direction) - significantly reduces error rate in DNA rep ___ helps in lag. str. (no place for RNA primer) by recognizing telomere sequence (TTAGGG), adding sequence to new DNA strands.; telomerase uses RNA template to do this ("RNA-dep-DNA-pol", sim. to reverse transcriptase!) - extends DNA, avoids loss of genes; telomerase found in abundance in hematopoietic stem cells KEY PTS: *___ strand* replication is continuous, *___ strand* replication is discontinuous (Okazaki fragments, DNA ligase); DNA rep. is semi-conservative (i.e., new DNA contains one ___, one ___ strand)

DNA pol. cannot initiate replication without primer (short nucleotide sequence); DNA primase makes primers from RNA contained in enzyme; RNA pol. does not require primer DNA pol. adds triphosphate nucleotides by cleaving triphosphate bonds (provides energy for rxn) and adding to 3' end (@ hydroxyl group; i.e., *DNA rep. always goes 5' --> 3'*) Bcuz of DNA directionality, need to have leading strand and lagging strand; lead. str. goes about its business, lag. str. ends up with Okazaki fragments At end of DNA repl., RNA primers are removed and replaced w/DNA (Prok: DNApol-1; Euks: DNApol-Delta); DNA ligase unites Okazaki fragments by creating phosphodiester bonds DNApol can perform proofreading via 3' to 5' exonuclease activity (REMEMBER: this is opposite normal direction) - significantly reduces error rate in DNA rep Telomerase helps in lag. str. (no place for RNA primer) by recognizing telomere sequence (TTAGGG), adding sequence to new DNA strands.; telomerase uses RNA template to do this ("RNA-dep-DNA-pol", sim. to reverse transcriptase!) - extends DNA, avoids loss of genes; telomerase found in abundance in hematopoietic stem cells KEY PTS: *Leading strand* replication is continuous, *lagging strand* replication is discontinuous (Okazaki fragments, DNA ligase); DNA rep. is semi-conservative (i.e., new DNA contains one old, one new strand)

DOSE RESP. CURVES: *___* have sim. structure to agonist, but produce less than full effect (*dec. Emax --> less efficacy*) Single agonist dose + [inc. dose of partial agonist (x-axis)] vs. [% binding (y-axis)] is often shown on graph - partial agonist has gradually higher %binding over inc. dose up to 100% (KePo: if agonist present, can add enough part. agon. to bump agonist off) Single agonist dose + [inc. dose of partial agonist (x-axis)] vs. [response (y-axis)] can also be shown on graph - results in ___ total response at high dose of part. agonist (makes sense based on earlier graph - agonist is displaced by part. agonist, which has lower efficacy) Pindolol/Acebutolol (*[HY] can cause ___ via vasoconstriction*), Buprenorphine, Aripiprazole, and Clomiphene are all partial agonists

DOSE RESP. CURVES: *Partial Agonists* have sim. structure to agonist, but produce less than full effect (*dec. Emax --> less efficacy*) Single agonist dose + [inc. dose of partial agonist (x-axis)] vs. [% binding (y-axis)] is often shown on graph - partial agonist has gradually higher %binding over inc. dose up to 100% (KePo: if agonist present, can add enough part. agon. to bump agonist off) Single agonist dose + [inc. dose of partial agonist (x-axis)] vs. [response (y-axis)] can also be shown on graph - results in dec. total response at high dose of part. agonist (makes sense based on earlier graph - agonist is displaced by part. agonist, which has lower efficacy) Pindolol/Acebutolol (*[HY] can cause angina via vasoconstriction*), Buprenorphine, Aripiprazole, and Clomiphene are all partial agonists

DOSE RESP. CURVES: Imagine measuring sympathetic activity in presence of beta blocker If BB is ___ antagonist, results in rightward shift of dose response curve (higher EC50 - less potent, no change in Emax - same efficacy) If BB is ___ antagonist, results in downward shift of dose response curve (same EC50 - no change in potency, lower Emax - decreased efficacy) *___* can result in rightward shift of graph in setting of low concentration of non-comp. antagonist (*no change in Emax!! this is believed to be d/t "spare receptors" becoming activated to overcome non-comp. ant.; if inc. [non-comp. ant.] --> expected dec. in Emax!*)

DOSE RESP. CURVES: Imagine measuring sympathetic activity in presence of beta blocker If BB is competitive antagonist, results in rightward shift of dose response curve (higher EC50 - less potent, no change in Emax - same efficacy) If BB is non-competitive antagonist, results in downward shift of dose response curve (same EC50 - no change in potency, lower Emax - decreased efficacy) *Spare Receptors* can result in rightward shift of graph in setting of low concentration of non-comp. antagonist (*no change in Emax!! this is believed to be d/t "spare receptors" becoming activated to overcome non-comp. ant.; if inc. [non-comp. ant.] --> expected dec. in Emax!*)

DRUG METABOLISM: Many liver rxns biotransform drugs to make lipophilic substances hydrophilic (excretable); rxns can be phase I or phase II Phase I: ___ rxn that *create active metabolites - phase I can slow in ___ pts, phase I includes cyp-P450 system* Statins and warfarin are metabolized by P450; if P450 inhibited --> drug levels ___ (*more dangerous - watch for cyclosporine, macrolides, -azoles*); if P450 induced --> drug levels ___ Phase II: ___ rxns (glucuronidation, acetylation) that produce polar, inactive metabolites that are excreted; "slow-acetylators" have dec. levels of excretion ^See induce/inhibit P450 drug list in your resources folder

DRUG METABOLISM: Many liver rxns biotransform drugs to make lipophilic substances hydrophilic (excretable); rxns can be phase I or phase II Phase I: redox + hydrolysis rxn that *create active metabolites - phase I can slow in elderly pts, phase I includes cyp-P450 system* Statins and warfarin are metabolized by P450; if P450 inhibited --> drug levels rise (*more dangerous - watch for cyclosporine, macrolides, -azoles*); if P450 induced --> drug levels fall Phase II: conjugation rxns (glucuronidation, acetylation) that produce polar, inactive metabolites that are excreted; "slow-acetylators" have dec. levels of excretion ^See induce/inhibit P450 drug list in your resources folder

Deletion syndromes are usually 2/2 error in c___ in meiosis (i.e., unbalanced exchange of genes) - most are sporadic Cri-du-chat is partial deletion of short arm of chrom5 (5p-), manifesting with DevDelay + "cry like ___ (mewing)" + microcephaly + wide eyes, low ears; many pts also have CongHeartDz Williams Synd is partial deletion of long arm of chrom7 (7q-), which includes ___ protein ("haploinsufficiency" - insufficient amnt of protein); classic "___" facial appearance + DevDelay + hyperCALCEMIA + *___ w/strangers & adults*; *unusual ConHeartDz is ___ aortic stenosis* Thymic aplasia (DiGeorge) is partial deletion of short arm of chrom22 (22q-)

Deletion syndromes are usually 2/2 error in crossover in meiosis (i.e., unbalanced exchange of genes) - most are sporadic Cri-du-chat is partial deletion of short arm of chrom5 (5p-), manifesting with DevDelay + "cry like cat (mewing)" + microcephaly + wide eyes, low ears; many pts also have CongHeartDz *[Cri-du-CAT, Cri-du-CINCO, Cri-du-CONGENITAL]* Williams Synd is partial deletion of long arm of chrom7 (7q-), which includes elastin protein ("haploinsufficiency" - insufficient amnt of protein); classic "elfin" facial appearance + DevDelay + hyperCALCEMIA + *friendliness w/strangers & adults*; *unusual ConHeartDz is SUPRAvalvular aortic stenosis* *[7 Elves and Friends Will Eliminate Superman]* Thymic aplasia (DiGeorge) is partial deletion of short arm of chrom22 (22q-)

Dermatitis herpetiformis is a/w C___ dz w/herpes-like lesions (papules/vesicles) that are *pruritic and found on ___ (F or E?) surfaces* Path. is 2/2 Ig___ deposition (think about dz!) in *dermal p___* - Abs are triggered by gluten cross-reacted at skin Biopsy reveals microabscesses at papillae tips w/neuts. Immunofluorescence reveals Ig___ deposition at tips of d___ papillae

Dermatitis herpetiformis is a/w Celiac dz w/herpes-like lesions (papules/vesicles) that are *pruritic and found on extensor surfaces* Path. is 2/2 IgA deposition in *dermal papillae (papillae similar to villi of intestines)* - Abs are triggered by gluten cross-reacted at skin Biopsy reveals microabscesses at papillae tips w/neuts. Immunofluorescence reveals IgA deposition at tips of dermal papillae

Dermatopathology describes microscopic findings of skin biopsies H___ is thickening of str. corneum d/t excess keratin (seen in guitar callus, psoriasis) P___ is hyperkeratosis with *retained nuclei in str. corneum* (indicates hyperproliferation - seen in psoriasis and cancer) H___ is thickening of *str. granulosum and [HY] IS SEEN IN L___ P___!* Spongiosis is edema of epidermis A___ is loss of connection btwn keratinocytes (usually via desmosomes) --> "rounded" keratinocytes --> detached/free floating from epidermis; *[HY] key feat. in p___ v___!* A___ is diffuse epidermal hyperplasia with *[HY] elongated rete ridges 2/2 spinous layer thickening* - can see acanthosis nigricans w/insulin resistance and malign. (gastric adenocarcinoma)

Dermatopathology desc. microscopic findings of skin biopsies Hyperkeratosis is thickening of str. corneum d/t excess keratin (seen in guitar callus, psoriasis) Parakeratosis is hyperkeratosis with *retained nuclei in str. corneum* (indicates hyperproliferation - seen in psoriasis and cancer) Hypergranulosis is thickening of *str. granulosum and [HY] IS SEEN IN LICHEN PLANUS!* Spongiosis is edema of epidermis Acantholysis is loss of connection btwn keratinocytes (usually via desmosomes) --> "rounded" keratinocytes --> detached/free floating from epidermis; *[HY] key feat. in pemphigus vulgaris!* Acanthosis is diffuse epidermal hyperplasia with *[HY] elongated rete ridges 2/2 spinous layer thickening* - can see acanthosis nigricans w/insulin resistance and malign. (gastric adenocarcinoma)

Differences btwn means being true (vs d/t chance) depends on 3 factors: diff. btwn means, scatter of data, # subjects tested - hypothesis testing calculates probs. that two difference btwn means is true v. chance using these 3 factors ___ difference --> more likely real; *___ scatter --> more likely d/t chance*; ___ tested --> more likely real ___ hypot (H0) --> lab test does NOT distinguish btwn dz and no dz; ___ hypot (H1) --> lab test DOES distinguish btwn dz and no dz Four Outcomes: --Difference exists and experiment detects (H1 true) - *P___* --No difference exists and experiment does not detect (H0 true) --No difference exists but experiment detects (H1 true) --> *type ___ error [arrogance in test, believe drug has benefit when it does not, reject null hypot. when shouldn't have (don't do unless alpha < 0.05) - false ___]* --Difference exists but experiment does not detect (H0 true) --> *type ___ error [bonehead running test, false ___, accept null hypothesis when shouldn't have - miss difference that's there], can get type II error if too few pts* *P___* is chance of detecting difference that exists (rejecting null hypothesis), power = (1 - beta); *[HY] Power ___ with more samples, large difference of means, and less scatter of data* In study design, little control over scatter and diff btwn means; do control # of subjects and can do *p___ c___* to find # of subj. needed for study to get high power

Differences btwn means being true (vs d/t chance) depends on 3 factors: diff. btwn means, scatter of data, # subjects tested - hypothesis testing calculates probs. that two difference btwn means is true v. chance using these 3 factors Bigger difference --> more likely real; *Greater scatter --> more likely d/t chance*; More tested --> more likely real Null hypot (H0) --> lab test does NOT distinguish btwn dz and no dz; Alt hypot (H1) --> lab test DOES distinguish btwn dz and no dz Four Outcomes: --Difference exists and experiment detects (H1 true) - *POWER* --No difference exists and experiment does not detect (H0 true) --No difference exists but experiment detects (H1 true) --> *type I (alpha) error [arrogance in test, believe drug has benefit when it does not, reject null hypot. when shouldn't have (don't do unless alpha < 0.05) - false positive]* --Difference exists but experiment does not detect (H0 true) --> *type II (beta) error [bonehead running test, false negative, accept null hypothesis when shouldn't have - miss difference that's there], can get type II error if too few pts* *Power* is chance of detecting difference that exists (rejecting null hypothesis), power = (1 - beta); *[HY] Power increases with more samples, large difference of means, and less scatter of data* In study design, little control over scatter and diff btwn means; do control # of subjects and can do *power calculation* to find # of subj. needed for study to get high power ^Alpha error differs from p-value - want alpha low before accepting study result as true, want p-value low before accepting difference is real

Diffuse large B-cell lymphoma (MC NH lymphoma) is B-cell malignancy usually seen in older adults *[HY] DLBCL is considered an ___ illness and is seen when ___ gets really low* Mutation seen in DLBCL are ___, ___ (*B-Cell Lymphoma 2 and 6*) Biopsy is not HY, but will reveal obliterated lymph node architecture Tx: ___ (CD20 Ab)

Diffuse large B-cell lymphoma (MC NH lymphoma) is B-cell malignancy usually seen in older adults *[HY] DLBCL is considered an AIDS-defining illness and is seen when CD4 count gets really low* Mutation seen in DLBCL are BCL2, BCL6 (*B-Cell Lymphoma 2 and 6*) Biopsy is not HY, but will reveal obliterated lymph node architecture Tx: rituximab (CD20 Ab)

Diffusion-Perfusion Limitations: graphs represent PartPres of gas in blood as it moves along capillary that passes alveoli In ___-limited gases (*asymptote hit*), the only way for more gas to be exchanged (i.e., diffuse across membrane) is to *add more blood for gas to enter* (e.g., O2 in healthy lung, N2O) In ___-limited gases, membrane is significant barrier to gas diffusing into blood - gas-to-alveoli concentration cannot equilibrate by time blood reaches end of capillary (e.g., CO, O2 in emphysema/fibrosis/exercise - in exercise, blood is pumping faster --> less time to pick up O2) Because CO is *___-LIMITED*, can use to determine diffusion function of lungs by calculating CO exhaled (nml: 75-140%, dz: <40%) ^NOTE: partial pressure in blood cannot exceed that of alveoli

Diffusion-Perfusion Limitations: graphs represent PartPres of gas in blood as it moves along capillary that passes alveoli In perfusion-limited gases (*asymptote hit*), the only way for more gas to be exchanged (i.e., diffuse across membrane) is to *add more blood for gas to enter* (e.g., O2 in healthy lung, N2O) In diffusion-limited gases, membrane is significant barrier to gas diffusing into blood - gas-to-alveoli concentration cannot equilibrate by time blood reaches end of capillary (e.g., CO, O2 in emphysema/fibrosis/exercise - in exercise, blood is pumping faster --> less time to pick up O2) Because CO is *DIFFUSION-LIMITED*, can use to determine diffusion function of lungs by calculating CO exhaled (nml: 75-140%, dz: <40%) ^NOTE: partial pressure in blood cannot exceed that of alveoli

Diplococci differentiated by maltose fermentation (MACCONKEY AGAR; mening --> ferments and ___, gono --> nope and ___) GNRs that ferment lactose are differentiated by speed (citrobact and serratia are ___) GNRs that don't ferment lactose differentiated by oxidase (Pseudo, HPylori --> ___; Shigella, Salmonella, Proteus --> ___) GN comma shaped oxidase positive differentiated by growth condition (grow at 42C --> ___; grow in alkaline media --> ___)

Diplococci differentiated by maltose fermentation (MACCONKEY AGAR; mening --> ferments and pink, gono --> nope and colorless) GNRs that ferment lactose are differentiated by speed (citrobact and serratia are slow) GNRs that don't ferment lactose differentiated by oxidase (Pseudo, HPylori --> pos; Shigella, Salmonella, Proteus --> neg) GN comma shaped oxidase positive differentiated by growth condition (grow at 42C --> Campylobacter; grow in alkaline media --> Vibrio)

Disruption of urea cycle --> hyperammonemia (seen in liver dz) High ammonia depletes alpha-ketoglutarate, alpha ketoglutarate can't be used for TCA cycle Hyperammonemia p/w CNS dysfunction (cerebral edema, tremor flapping tremor [asterixis], AMS); tx w/low protein diet and *LACTULOSE* --- Ornithine transcarbamylase deficiency (MC urea cycle disorder) is *Xrec condition* that p/w high *carbamoyl phosphate, ammonia, and OROTIC ACID* OTC deficiency presents in childhood w/sx of hyperammonemia (somnolence, poor feeding, coma) *DONT CONFUSE W/OROTIC ACIDURIA!! Orotic Aciduria is d/o of pyrimidine synthesis - p/w high orotic acid and NORMAL AMMONIA!!* OTC deficiency is urea cycle disorder, orotic aciduria is pyrimidine synthesis disorder --- Citrullinemia is arginosuccinate synthase deficiency --> elevated citrulline and ammonia, low arginine

Disruption of urea cycle --> hyperammonemia (seen in liver dz) High ammonia depletes alpha-ketoglutarate, alpha ketoglutarate can't be used for TCA cycle Hyperammonemia p/w CNS dysfunction (cerebral edema, tremor flapping tremor [asterixis], AMS); tx w/low protein diet and *LACTULOSE* --- Ornithine transcarbamylase deficiency (MC urea cycle disorder) is Xrec condition that p/w high *carbamoyl phosphate, ammonia, and OROTIC ACID* OTC deficiency presents in childhood w/sx of hyperammonemia (somnolence, poor feeding, coma) *DONT CONFUSE W/OROTIC ACIDURIA!! Orotic Aciduria is d/o of pyrimidine synthesis - p/w high orotic acid and NORMAL AMMONIA!!* OTC deficiency is urea cycle disorder, orotic aciduria is pyrimidine synthesis disorder --- Citrullinemia is arginosuccinate synthase deficiency --> elevated citrulline and ammonia, low arginine

___ is detachment from reality (vs psychosis which is loss of reality); it often follows trauma for coping ___ is seen in women w/sexual abuse before age 6; this disorder occurs with other psych disorders (PTSD) Depersonalization Derealization Disorder is feeling detached from ___ and surrounding ___; disorder is often triggered by trauma ___ Amnesia is inability to recall autobiographical memories after major trauma/stress; DA usually follows trauma + a new stressor Dissociative ___ is sudden travel/wandering in dissociated state (i.e., new job/state of residence after stressor)

Dissociation is detachment from reality (vs psychosis which is loss of reality); it often follows trauma for coping Dissociative Identity Disorder is seen in women w/sexual abuse before age 6; this disorder occurs with other psych disorders (PTSD) Depersonalization Derealization Disorder is feeling detached from self and surrounding world; disorder is often triggered by trauma Dissociative Amnesia is inability to recall autobiographical memories after major trauma/stress; DA usually follows trauma + a new stressor Dissociative Fugue is sudden travel/wandering in dissociated state (i.e., new job/state of residence after stressor)

___ is most common liveborn chrom abn, MC intellect disab; dysmorphic feats include flat face & nasal bridge, low-set small ears, short neck, and brachycephaly (post. skull is flat) Eye features include prominent epicanthal folds + upslanting palpebral fissures + b___ spots (white spots on iris) Hands have *T___ palmar crease* and feet have *"sandal gap"*; will also appreciate ___tonia Congenital heart dz occur in half pts (endocardial cushion defects - primum ASD, VSD [*HY: ___ mur*]); GI anomalies seen in 5% (MC: d___ atresia; also Hirschsprung dz); Alzheimer's occurs often and earlier (2/2 AFP on chrom21); DS incurs inc. risk of malignancy (A___, M7 subtype of AML)

Down Synd is most common liveborn chrom abn, MC intellect disab; dysmorphic feats include flat face & nasal bridge, low-set small ears, short neck, and brachycephaly (post. skull is flat) Eye features include prominent epicanthal folds + upslanting palpebral fissures + brushfield spots (white spots on iris) Hands have *TRANSVERSE palmar crease* and feet have *"sandal gap"*; will also appreciate hypotonia Congenital heart dz occur in half pts (endocardial cushion defects - primum ASD, VSD [*HY: holosystolic mur*]); GI anomalies seen in 5% (MC: duodenal atresia; also Hirschsprung dz); Alzheimer's occurs often and earlier (2/2 AFP on chrom21); DS incurs inc. risk of malignancy (ALL, M7 subtype of AML)

Down Synd often occurs 2/2 meiotic nondisjunction (usually meiosis I of *___*); Robertsonian Translocation can occur and has *high recurrence risk within families!! (may see on question)*; rarely, mitotic error can occur (normal fert --> mitosis in early development leads to 3 copies of C21 --> replicate --> somatic m___, milder feats of DS, no assoc w/advance maternal age) DS screening definitive test is fetal karyotype via CVS or amniocentesis (INVASIVE!); other screening includes ultrasound (poorly formed nasal bones, nuchal translucency) and maternal serum testing (1st trim: ___ PAPP-A and ___ b-hCG; 2nd trim: ___ AFP and estriol, ___ b-hCG and inhibin A)

Down Synd often occurs 2/2 meiotic nondisjunction (usually meiosis I of *mother*); Robertsonian Translocation can occur and has *high recurrence risk within families!! (may see on question)*; rarely, mitotic error can occur (normal fert --> mitosis in early development leads to 3 copies of C21 --> replicate --> somatic mosaicism, milder feats of DS, no assoc w/advance maternal age) DS screening definitive test is fetal karyotype via CVS or amniocentesis (INVASIVE!); other screening includes ultrasound (poorly formed nasal bones, nuchal translucency) and maternal serum testing (1st trim: low PAPP-A and high b-hCG; 2nd trim: low AFP and estriol, high b-hCG and inhibin A)

Drug A is administered --> rise in HR and MAP Drug A + Drug B administered --> rise in HR and fall in MAP What are drugs A and B?

Drug A: epinephrine Drug B: phenoxybenzamine When phenoxybenzamine is given, Beta effects dominate --> decreased SVR, decreased DBP, decreased MAP (HR remains high d/t B1 activity)

Drug-induced lupus can be seen with i___, h___, and p___ (positive ANA and everything); dangerous complications (i.e., renal, CNS involvement) are rare Key feature is anti-his___ Ab (rarely seen in true lupus) --- Neonatal lupus occurs in 1-2% of babies w/mother who have auto-immune dz (also seen in ___ - believed to be do to anti-Ro and anti-La) NL presents with rash (multiple red/circle lesions on face) and *congenital ___ (scary - p/w bradycardia requiring pacemaker)*

Drug-induced lupus can be seen with isoniazid, hydralazine, and procainamide (positive ANA and everything); dangerous complications (i.e., renal, CNS involvement) are rare Key feature is anti-histone Ab (rarely seen in true lupus) --- Neonatal lupus occurs in 1-2% of babies w/mother who have auto-immune dz (also seen in Sjogren's - believed to be do to anti-Ro and anti-La) NL presents with rash (multiple red/circle lesions on face) and *congenital heart block (scary - p/w bradycardia requiring pacemaker)*

During meiosis, chromosomes genetic recombine (crossover - never a direct copy of 'rents) If same chromosome + far away + crossover --> ___ (same or diff.?) combos/rates (results in parental [same genes] and recombinant version [exchanged genes]); if same chromosome + close + crossover --> ___ (S or D?) combos, ___ (S or D?) rates (lower rates of recombination) Recombination Frequency is frequency of recombined genes (0 [lil rec] to 0.5 [lots of rec]); *KEY POINT: recombination frequency is proportional to ___ apart* - this can be used to track frequency of recombination, then use frequency to determine relative location; Linkage is ___ (direct or inverse?) of RF - more linked --> closer together --> ___ (hi or lo?) RF Linkage Disequilibrium is used to study genes close together (can't do fam studies --> need large popul); large pops should have rates of AB, Ab, etc. similar to that of allele rate (i.e., A=0.7, B=0.5, AB=0.35); if disagree (i.e., AB=0.7) --> *disequilibrium, genes likely ___ (close or far?)!* LD is greatest at ___ entry into pop., fades with population growth; different pops --> different degrees of LD

During meiosis, chromosomes genetic recombine (crossover - never a direct copy of 'rents) If same chromosome + far away + crossover --> same combos/rates (results in parental - same genes - and recombinant version - exchanged genes); if same chromosome + close + crossover --> same combos, different rates (lower rates of recombination) Recombination Frequency is frequency of recombined genes (0 [lil rec] to 0.5 [lots of rec]); *KEY POINT: recombination frequency is proportional to distance apart* - this can be used to track frequency of recombination, then use frequency to determine relative location; Linkage is inverse of RF - more linked --> closer together --> lower RF Linkage Disequilibrium is used to study genes close together (can't do fam studies --> need large popul); large pops should have rates of AB, Ab, etc. similar to that of allele rate (i.e., A=0.7, B=0.5, AB=0.35); if disagree (i.e., AB=0.7) --> *disequilibrium, genes likely close together!* LD is greatest at first entry into pop, fades with population growth; different pops --> different degrees of LD

EATING DISORDERS: Anorexia often co-exists with other psych disorders (dep, anx), which will improve with ___ (esp. depression); AN also carries increased mortality from ___ *AN also has significant medical effects with decreased GnRH --> decreased ___ --> functional hypothalamic ___; decreased ___ density (2/2 low estrogen); pancytopenia; hypo___ (no energy to concentrate urine) with low GFR and ___ creatinine (no muscle mass to produce creatinine)* AN exam reveals bradycardia/hypotension, decreased bowel sounds, and hair loss + *___ (body hair?)* REFEEDING SYNDROME will occur if introducing food to quickly 2/2 *___ (low levels at baseline --> give glucose --> metab activated --> immediate decline in phosphate)* - can lead to cardiac fatalities

EATING DISORDERS: Anorexia often co-exists with other psych disorders (dep, anx), which will improve with weight restoration (esp. depression); AN also carries increased mortality from malnutrition *AN also has significant medical effects with decreased GnRH --> decreased LH/FSH --> functional hypothalamic amenorrhea; decreased bone density (2/2 low estrogen); pancytopenia; hyponatremia (no energy to concentrate urine) with low GFR and low creatinine (no muscle mass to produce creatinine)* AN exam reveals bradycardia/hypotension, decreased bowel sounds, and hair loss + *LANUGO* REFEEDING SYNDROME will occur if introducing food to quickly 2/2 *HYPOPHOSPHATEMIA (low levels at baseline --> give glucose --> metab activated --> immediate decline in phosphate)* - can lead to cardiac fatalities

EATING DISORDERS: Bulimia is binge eating + inappropriate ___ (vomiting, laxatives, exercise, fasting); patient must engage in binging 1x/week for at least 3mo BN may manifest with contraction alkalosis and hypokalemia; importantly, *___ is always low!* Physical exam will show ___ swelling, dental erosion, and *Russell's sign (___ scarring)* Binge eating disorder is similar to BN, but without inappropriate compensation (manifests with weight gain); *HY: first-line treatment in ___ (NOT ___!)*

EATING DISORDERS: Bulimia is binge eating + inappropriate compensation (vomiting, laxatives, exercise, fasting); patient must engage in binging 1x/week for at least 3mo BN may manifest with contraction alkalosis and hypokalemia; importantly, *URINE CHLORIDE is always low!* Physical exam will show parotid swelling, dental erosion, and *Russell's sign (knuckle scarring)* Binge eating disorder is similar to BN, but without inappropriate compensation (manifests with weight gain); *HY: first-line treatment in CBT (NOT drugs!)*

EEG is ___ in dementia and ___ in delirium Delirium is common in dementia patients in unknown setting, but has many other triggers; tx is with haloperidol, which can lead to ___ side effects Triad of dementia is ___(can't communicate), ___ (trouble doing jobs), and ___ (can't interpret senses - recognize people/objects, interpret full bladder)

EEG is NORMAL in dementia and ABNORMAL in delirium Delirium is common in dementia patients in unknown setting, but has many other triggers; tx is with haloperidol, which can lead to EPS side effects Triad of dementia is aphasia (can't communicate), apraxia (trouble doing jobs), and agnosia (can't interpret senses - recognize people/objects, interpret full bladder)

EIEC ___ intestinal mucosa to cause bloody diarrhea; it looks similar to Shi___, but does not produce a ___ EPEC does not produce inflammation, but does blunt ___ and prevent absorption; diarrhea occurs in ___ (P=pediatrics) *Gram negative sepsis (i.e., E. coli) is driven by endotoxin ___*; a common scenario would be elderly patient with catheter Fecal leukocytes + RBCs --> ___ infection (except EHEC) Fecal mucous + epithelial cells --> ___-mediated disease/virus *H pylori is associated with malignancy ___, a B-cell cancer in the stomach*

EIEC invades intestinal mucosa to cause bloody diarrhea; it looks similar to Shigella, but does not produce a toxin EPEC does not produce inflammation, but does blunt villi and prevent absorption; diarrhea occurs in children (P=pediatrics) *Gram negative sepsis (i.e., E. coli) is driven by endotoxin LPS*; a common scenario would be elderly patient with catheter Fecal leukocytes + RBCs --> invasive infection (except EHEC) Fecal mucous + epithelial cells --> toxin-mediated disease/virus *H pylori is associated with malignancy MALT lymphoma, a B-cell cancer in the stomach*

ELISA detects Ags/Abs in serum based on color change rxn - 1) add serum to plate (Ag sticks to plate) and wash, 2) add Ab to that Ag (Ab is labeled with enzyme) and wash, 3) add substrate for enzyme (color change --> Ag present!) [this is ___ ELISA - INDIRECT uses 2nd Ab that binds first Ab, 2nd Ab has enzymes --> same method to identify, but enzyme-Ab INDIRECTLY bound to Ag] ___ ELISA is similar to above, but plate is coated w/capture Ab (makes sandwich w/Ag being meat) - highly specific (unlikely to bind wrong Ag w/2 Abs), works w/complex samples Competitive ELISA is different - sample + primary Ab incubated, Ag-Ab complexes form - more Ab-Ag binding --> less free Ab; Mix is added to Ag coated plates and unbound Ab binds Ag --> wash --> 2nd Ab added --> add substrate, watch for color change (more color change --> ___ Ag - *this is where comp. is different!!*) ELISA can be used for HIV Ab detection (usually indirect, *comes w/Ag attached to well --> look for Abs to attach*), HIV p24 Ag detection as well (sandwich ELISA)

ELISA detects Ags/Abs in serum based on color change rxn - 1) add serum to plate (Ag sticks to plate) and wash, 2) add Ab to that Ag (Ab is labeled with enzyme) and wash, 3) add substrate for enzyme (color change --> Ag present!) [this is DIRECT ELISA - INDIRECT uses 2nd Ab that binds first Ab, 2nd Ab has enzymes --> same method to identify, but enzyme Ab INDIRECTLY bound to Ag] Sandwich ELISA is similar to above, but plate is coated w/capture Ab (makes sandwich w/Ag being meat) - highly specific (unlikely to bind wrong Ag w/2 Abs), works w/complex samples Competitive ELISA is different - sample + primary Ab incubated, Ag-Ab complexes form - more Ab-Ag binding --> less free Ab; Mix is added to Ag coated plates and unbound Ab binds Ag --> wash --> 2nd Ab added --> add substrate, watch for color change (more color change --> LESS Ag - *this is where comp. is different!!*) ELISA can be used for HIV Ab detection (usually indirect, *comes w/Ag attached to well --> look for Abs to attach*), HIV p24 Ag detection as well (sandwich ELISA)

CLASSIC CASE: patient returning from developing country with bloody diarrhea and RUQ pain for several weeks? HIGH YIELD: why does Trypanosoma bruceii cause recurrent fevers? CLASSIC QUESTION: patient has Lyme disease, what other disease are you worried about?

ENTAMOEBA HISTOLYTICA (w/liver cysts) VARIANT SURFACE GLYCOPROTEINS (antigenic variation) BABESIA (both transmitted by Ixodes tick)

EPO is synthesized in kidney ___ cells of peritubular capillary (renal cortex) and released in response to ___; renal failure --> decreased EPO --> *normocytic anemia w/inappropriately low ___ count* --- Aplastic anemia is *failure or destruction of h___ s___ cells* in the bone marrow (*acellular/hypocellular b___*) --> pancytopenia Accordingly, two hallmarks are 1) pancytopenia and 2) ___ bone marrow w/fat infiltration ApAn p/w fatigue/pallor (anemia), ___ (thrombocytopenia), recurrent infxns (leukopenia) ApAn has many causes: -Idiopathic: unknown trigger, but *autoimmune mediated^* -Radiation -Drugs: *___ (rubber factories, shoe repair shops)*, chloramphenicol, *methimazole/PTU* -Viruses: EBV, hepatitis -*___ anemia: DNA repair defect w/short stature, cafe-au-lait spots, malformed thumbs (increased risk of malignancy)* ^Tx: anti___ globulin (antibodies against human T-cells), cyclosporine

EPO is synthesized in kidney interstitial cells of peritubular capillary (renal cortex) and released in response to hypoxia; renal failure --> decreased EPO --> *normocytic anemia w/inappropriately low reticulocyte count* --- Aplastic anemia is *failure or destruction of hematopoietic stem cells* in the bone marrow (*acellular/hypocellular bone marrow*) --> pancytopenia Accordingly, two hallmarks are 1) pancytopenia and 2) acellular/hypocellular bone marrow w/fat infiltration ApAn p/w fatigue/pallor (anemia), bleeding/petechiae (thrombocytopenia), recurrent infxns (leukopenia) ApAn has many causes: -Idiopathic: unknown trigger, but *autoimmune mediated^* -Radiation -Drugs: *BENZENE (rubber factories, shoe repair shops)*, chloramphenicol, *methimazole/PTU* -Viruses: EBV, hepatitis -*Fanconi anemia: DNA repair defect w/short stature, cafe-au-lait spots, malformed thumbs (increased risk of malignancy)* ^Tx: antithymocyte globulin (antibodies against human T-cells), cyclosporine

EQUAL PRESSURE POINT: In forced expiration, intrapleural pressure rises (e.g., 60mmHg) and is transmitted to alveoli; b/c alveoli already have a tendency to collapse w/___ward pressure (e.g., 30mmHg inward), total alveolar pressure rises (e.g., 90mmHg); this increase in pressure keeps alveoli open during forced expiration Upstream in bronchioles, air encounters resistance and intraluminal pressure drops - at a point where intraluminal pressure is less than intrapleural pressure (*___*, i.e., <60mmHg), airway can collapse; in healthy lungs, this occurs in ___ airway to prevent collapse - in dz lungs, this occurs distally and can collapse bronchioles

EQUAL PRESSURE POINT: In forced expiration, intrapleural pressure rises (e.g., 60mmHg) and is transmitted to alveoli; b/c alveoli already have a tendency to collapse w/inward pressure (e.g., 30mmHg inward), total alveolar pressure rises (e.g., 90mmHg); this increase in pressure keeps alveoli open during forced expiration Upstream in bronchioles, air encounters resistance and intraluminal pressure drops - at a point where intraluminal pressure is less than intrapleural pressure (*EQUAL PRESSURE POINT*, i.e., <60mmHg), airway can collapse; in healthy lungs, this occurs in cartilaginous airway to prevent collapse - in dz lungs, this occurs distally and can collapse bronchioles

ESOPHAGEAL HISTOLOGY: Mucosal layer (most differentiating) contains ___ epithelium (not keratinized) Muscular layer is s___ in upper 1/3rd (voluntary) and s___ in lower 2/3rds (smooth) --- Stomach is split into cardia, fundus, body, antrum, and pylorus HISTOLOGY: Stomach mucosa contains (*gastric p___ & gastric g___ [found in L___ - cont. parietal, chief, G, mucous neck cells]*) - pit:gland ratio changes based on area of stomach! --- Colon produces lots of mucus - rich in ___ cells; Histologically, colon is characterized by ___ without villi

ESOPHAGEAL HISTOLOGY: Mucosal layer (most differentiating) contains stratified squamous epithelium (not keratinized) Muscular layer is striated in upper 1/3rd (voluntary) and smooth in lower 2/3rds (smooth) --- Stomach is split into cardia, fundus, body, antrum, and pylorus HISTOLOGY: Stomach mucosa contains (*gastric pits & gastric glands [found in LamProp - cont. parietal, chief, G, mucous neck cells]*) - pit:gland ratio changes based on area of stomach! --- Colon produces lots of mucus - rich in Goblet cells; Histologically, colon is characterized by crypts without villi

ETHICAL PRINCIPLES: ___: most important, allows pt to make decisions about body - *if a patient declines medical care, okay to ask "___" but don't judge/threaten/scold/scare (how will be tested)* ___: providers must act in best interests of pts, but *superseded by autonomy* ___: do no harm (balance risks v. benefits) ___: treat pts fairly and equally and use resources equitably (seen w/triage process) For noncompliant and/or emotional pts --> try to understand ___ (avoid scold/threat, telling pts to calm down)

ETHICAL PRINCIPLES: Autonomy: most important, allows pt to make decisions about body - *if a patient declines medical care, okay to ask "why" but don't judge/threaten/scold/scare (how will be tested)* Beneficence: providers must act in best interests of pts, but *superseded by autonomy* Non-Maleficence: do no harm (balance risks v. benefits) Justice: treat pts fairly and equally and use resources equitably (seen w/triage process) For noncompliant and/or emotional pts --> try to understand WHY (avoid scold/threat, telling pts to calm down)

Ectopia lentis (lens dislocation) can be 2/2 systemic disease: Marfan syndrome (___ defect) causes ___ lens dislocation (think tall features in MFS); homocystinuria (cystathione beta synthase defect) causes ___ lens *Aldose reductase converts glucose --> ___ (and galactose --> galactitol); normally this enzyme has low activity, but in diabetes (and galactose metab disorders^), high level accumulate --> increased lens osmolarity --> ___* ^Classic galactosemia, galactokinase deficiency (childhood onset cataracts)

Ectopia lentis (lens dislocation) can be 2/2 systemic disease: Marfan syndrome (fibrillin defect) causes upward/outward lens dislocation; homocystinuria (cystathione beta synthase defect) causes downward/inward lens *Aldose reductase converts glucose --> sorbitol (and galactose --> galactitol); normally this enzyme has low activity, but in diabetes (and galactose metab disorders^), high level accumulate --> increased lens osmolarity --> cataracts* ^Classic galactosemia, galactokinase deficiency (childhood onset cataracts)

Edward Synd (t18, 3:1 F:M) have IUGR and *very small, abnormal head (prominent ___)* and *clenched fists w/___ fingers and "rockerbottom feet"*; CHD is 50%, GI dfx in 75% (ES>>DS^; Meckel's, malrotation); most dx by US, but can use maternal screening (1st T: ___ PAPP-A and b-hCG; 2nd T: ___ AFP, estriol, b-hCG, inhibitin A - E=Everything) Patau Synd (t13, very rare/sev) is dx on fetal US 2/2 severe dz with low life expectancy; will see eye abnormalities (___), cleft lip/palate, post-axial polydactyly (extra digit away from midline, i.e., ulnar), and holoprosencephaly (alobar brain); CHD in 80% of cases Both (+ DS) a/w advanced ___ age 2/2 meiotic ___, share common feats. (intellect disab, phys deform, cong heart dfx)

Edward Synd (t18, 3:1 F:M) have IUGR and *very small, abnormal head (prominent occiput)* and *clenched fists w/overlapping fingers and "rockerbottom feet"*; CHD is 50%, GI dfx in 75% (ES>>DS^; Meckel's, malrotation); most dx by US, but can use maternal screening (1st T: low PAPP-A and b-hCG; 2nd T: low AFP, estriol, b-hCG, inhibitin A - E=Eliminate quad screen) Patau Synd (t13, very rare/sev) is dx on fetal US 2/2 severe dz with low life expectancy; will see eye abnormalities (micro-/anophthalmia), cleft lip/palate, post-axial polydactyly (extra digit away from midline, i.e., ulnar), and holoprosencephaly (alobar brain); CHD in 80% of cases Both (+ DS) a/w advanced maternal age 2/2 meiotic nondisjunction, share common feats. (intellect disab, phys deform, cong heart dfx) ^GI Dfx much more common in Edward than DS

___ is portion of extracellular fluid that is contained in arterial system to maintain tissue perfusion (*much different than total body water!*) ECV is modified by volume, cardiac output, and vascular resistance Importantly, low ECV --> low BP --> *activated ___ and ___* (seen in hemorrhage, heart failure [low CO], cirrhosis [low SVR])

Effective circulating volume is portion of extracellular fluid that is contained in arterial system to maintain tissue perfusion (*much different than total body water!*) ECV is modified by volume, cardiac output, and vascular resistance Importantly, low ECV --> low BP --> *activated SNS and RAAS* (seen in hemorrhage, heart failure [low CO], cirrhosis [low SVR])

___^ is maximal *effect* a drug can produce (morphine > aspirin w/pain control) ___^ is amount of drug needed for effect (5mg drug A produces same effect as 50mg drug B - A more potent than B) Dose response curves can be graded or quantal: Graded --> outcome on continuum (i.e., BP); Quantal --> outcome binary (i.e., is HA gone?) Graded Curves: inc. dose (x-axis) --> inc. efficacy (y-axis) to Emax (Emax representative of efficacy, asymptote on graph), higher Emax --> more ___; [drug] with 1/2EMax --> EC50 (representative of ___), lower EC50 --> more potent drug, leftward shift of curve --> ___ potent drug Quant. Curves: % patients (y-axis) inc. as dose (x-axis) inc. - can determine ___ (dose where 50% pts achieve benefit) and ___ (dose where 50% pts exp. adverse response) and ___ (dose where 50% pts die) -Therapeutic Index: ___ (higher number --> better) -Therapeutic Window: range btwn minimum effective dose and minimum toxic dose (warfarin, digoxin, lithium, theophylline all have low TI/TW --> *why we monitor levels for SEs!!* ^Know how to identify on charts

Efficacy^ is maximal *effect* a drug can produce (morphine > aspirin w/pain control) Potency^ is amount of drug needed for effect (5mg drug A produces same effect as 50mg drug B - A more potent than B) Dose response curves can be graded or quantal: Graded --> outcome on continuum (i.e., BP); Quantal --> outcome binary (i.e., is HA gone?) Graded Curves: inc. dose (x-axis) --> inc. efficacy (y-axis) to Emax (Emax representative of efficacy, asymptote on graph), higher Emax --> more efficacious; [drug] with 1/2EMax --> EC50 (representative of potency), lower EC50 --> more potent drug, leftward shift of curve --> more potent drug Quant. Curves: % patients (y-axis) inc. as dose (x-axis) inc. - can determine ED50 (dose where 50% pts achieve benefit) and TD50 (dose where 50% pts exp. adverse response) and LD50 (dose where 50% pts die) -Therapeutic Index: LD50/ED50 (higher number --> better) -Therapeutic Window: range btwn minimum effective dose and minimum toxic dose (warfarin, digoxin, lithium, theophylline all have low TI/TW --> *why we monitor levels for SEs!!* ^Know how to identify on charts

DEFENSE MECHANISMS (immature/unhealthy): ___ is avoiding emotions by bad behavior (i.e., adolescent engaging in promiscuous sex during parents' divorce) ___ is refusing to accept unpleasant reality ___ is directing emotions on another person ___ is detachment from reality (i.e., DID) ___ is "motivated forgetting" of one particular memory (i.e., forgetting rape, difficult childhood) ___ is failure to develop beyond growth stage (i.e., thumb sucking into adolescence) ___ is emphasizing positive thoughts and de-emphasizing negative thoughts (i.e., all family vacays were amazing) ___ is mimicking behavior of someone else (i.e., kid bullied at school --> goes home to bully sibling)

Ego defenses minimize anxiety and adapt to stressful situations Acting Out is avoiding emotions by bad behavior (i.e., adolescent engaging in promiscuous sex during parents' divorce) Denial is refusing to accept unpleasant reality Displacement is directing emotions on another person Dissociation is detachment from reality (i.e., DID) Repression is "motivated forgetting" of one particular memory (i.e., forgetting rape, difficult childhood) Fixation is failure to develop beyond growth stage (i.e., thumb sucking into adolescence) Idealization is emphasizing positive thoughts and de-emphasizing negative thoughts (i.e., all family vacays were amazing) Identification is mimicking behavior of someone else (i.e., kid bullied at school --> goes home to bully sibling)

Ehrlichia is transmitted by Lone ___ tick, white tail deer are principal reservoir; classically will see berry-like inclusions in monocytes (Morulae) 2/2 obligate ___ nature; presentation includes flu-like illness, ___penia, and ___penia (dx with ___ stain - used to dx intracellular bacteria, tx with ___) Anaplasma is very similar to Ehrlichia with two exceptions: 1) morula seen in granulocytes (NOT ___) and 2) tick vector is ___ tick (same as Lyme, Babesiosis) Rickettsia typhi (murine typhus) is transmitted from rat fleas to humans; common in developing world, causing flu-like illness + rash (starts trunk --> spreads out); this is ENDEMIC typhus (epidemic typhus is Rickettsia ___)

Ehrlichia is transmitted by Lone Star tick, white tail deer are principal reservoir; classically will see berry-like inclusions in monocytes (Morulae) 2/2 obligate intracellular nature; presentation includes flu-like illness, leukopenia, and thrombocytopenia (dx with Giemsa stain - used to dx intracellular bacteria, tx with doxy) Anaplasma is very similar to Ehrlichia with two exceptions: 1) morula seen in granulocytes (NOT monocytes) and 2) tick vector is Ixodes tick (same as Lyme, Babesiosis) Rickettsia typhi (murine typhus) is transmitted from rat fleas to humans; common in developing world, causing flu-like illness + rash (starts trunk --> spreads out); this is ENDEMIC typhus (epidemic typhus is Rickettsia prowazekii)

Elderly person with recurrent hemorrhagic strokes should raise concern for ___ Enlarged lateral ventricle with normal 3rd/4th ventricle should raise concern for ___ clot 2/2 intraventricular hemorrhage --> treat with VP shunt; this is usually a ___ problem in infants (highly vascular area, poor autoregulation in infants)

Elderly person with recurrent hemorrhagic strokes should raise concern for cerebral amyloid angiopathy Enlarged lateral ventricle with normal 3rd/4th ventricle should raise concern for foramen of Monro clot 2/2 intraventricular hemorrhage --> treat with VP shunt; this is usually a germinal matrix problem in infants (highly vascular area, poor autoregulation in infants)

EmPhysema (Pink Puffer; obstructive lung dz) is damage to ___ tissue (proteases >> anti-proteases) - seen in smokers (___ lobes - smoke rises up) and ___ (lower lobes) Loss of alveoli l/t loss of alveolar ___ recoil (*small airways collapse on exhalation --> air t___*) Emphysema p/w cough, hyperventilation, cor pulmonale, and *___ chest (d/t air trapping) + ___ lips (d/t trying to keep airways open)* *[HY] Smoking --> ___ emphysema (primarily affecting respiratory bronchioles, spares alveoli - S/S); A-1-AT deficiency --> ___ emphysema (affects respiratory bronchioles + alveoli)* Path: thin ___ spaces + alveolar enlargement ___ is chronic bronchitis and/or chronic emphysema (also asthma)

EmPhysema (Pink Puffer; obstructive lung dz) is damage to alveolar tissue (proteases >> anti-proteases) - seen in smokers (upper lobes - smoke rises up) and alpha-1 antitrypsin deficiency (lower lobes) Loss of alveoli l/t loss of alveolar elastic recoil (*small airways collapse on exhalation --> air trapping*) Emphysema p/w cough, hyperventilation, cor pulmonale, and *barrel chest (d/t air trapping) + pursed lips (d/t trying to keep airways open)* *[HY] Smoking --> centriacinar emphysema (primarily affecting respiratory bronchioles, spares alveoli - S/S); A-1-AT deficiency --> panacinar emphysema (affects respiratory bronchioles + alveoli)* Path: thin septal spaces + alveolar enlargement COPD is chronic bronchitis and/or chronic emphysema (also asthma) ^Emphysema - alveoli Enlarge

EndoRet is folded membrane that is continuous w/nuclear membrane and is site of prot./lipid synthesis - ___ER is site for prot. synthesis (studded w/membrane-bound ribosomes that make prots. for ___ [not free ribosomes, those in cytosol & makes prots. used by cell]) while ___ER is site for lipid/steroid synthesis and detoxification Lots of ___ER in secreting cells (e.g., plasma cells, beta cells) while ___ER is abundant in detoxify./steroid cells (e.g., hepatocytes, adrenals, gonads) Golgi app. is where prots. leave ER (via vesicles) for protein modification/sorting for next destination (Cis-G faces rER, Tra-G faces cytosol) Golgi can modify N-oligosacch. (attached to ___) on asparagine, O-oligosacch. (attached to ___) to serine/threonine, and mannose-6-phos. to ___ prots. (protects prots. from degradation, directs prots. to location)

EndoRet is folded membrane that is continuous w/nuclear membrane and is site of prot./lipid synthesis - rER is site for prot. synthesis (studded w/membrane-bound ribosomes that make prots. for secretion [not free ribosomes, those in cytosol & makes prots. used by cell]) while sER is site for lipid/steroid synthesis and detoxification Lots of rER in secreting cells (e.g., plasma cells, beta cells) while sER is abundant in detoxify./steroid cells (e.g., hepatocytes, adrenals, gonads) Golgi app. is where prots. leave ER (via vesicles) for protein modification/sorting for next destination (Cis-G faces rER, Tra-G faces cytosol) Golgi can modify N-oligosacch. (attached to nitrogen) on asparagine, O-oligosacch. (attached to oxygen) to serine/threonine, and mannose-6-phos. to lysosomal prots. (protects prots. from degradation, directs prots. to location)

E___ is how long bones are developed from cartilage - anlagen (cartilage mold) forms and as mold grows, chondrocytes die --> osteoblasts come in from blood to form bone @ center (diaphysis), BVs penetrate & -blasts begin laying down matrix for ossification (___ center of ossification); @ epiphysis, BVs penetrate & -blasts laydown matrix for ossification (s___ center of ossification); these two meet in adolescence to form *g___* First type of bone formed is w___ - disorganized collagen fiber w/relatively weaker bone (seen in adults after fx); woven bone is later remodeled to l___ bone - structured & stronger Membranous ossification (w.o cartilage mold) is used for ___ bones (i.e., skull, facial bones)

Endochondral ossification is how long bones are developed from cartilage - anlagen (cartilage mold) forms and as mold grows, chondrocytes die --> osteoblasts come in from blood to form bone @ center (diaphysis), BVs penetrate & -blasts begin laying down matrix for ossification (primary center of ossification); @ epiphysis, BVs penetrate & -blasts laydown matrix for ossification (secondary center of ossification); these two meet in adolescence to form *growth plate* First type of bone formed is woven - disorganized collagen fiber w/relatively weaker bone (seen in adults after fx); woven bone is later remodeled to lamellar bone - structured & stronger Membranous ossification (w.o cartilage mold) is used for flat bones (i.e., skull, facial bones)

Endocrine pancreas is made up of islets, which contain ___ cells (insulin - central), ___ cells (glucagon- peripheral), and ___ cells (somatostatin - peripheral) Insulin is a *___* hormone that is synthesized as ___insulin (made on ribosomes of rER), which is cleaved to ___ insulin and transported to Golgi; proinsulin is cleaved to insulin and ___ before being released via exocytosis Mature insulin is made of ___ and ___ chain connected by ___ bridges - the C-peptide ("connecting") used to attach insulin chains, but can be used as proxy for insulin production Insulin is released when beta cells take in glucose via ___^ transporters - once inside the cell, glucose produces ATP, which blocks ___ channels --> raises resting membrane potential --> *voltage-gated ___ channels open, promote exocytosis of insulin!* ___ receptors increase insulin release while ___ (adrenergic receptors?) receptors decrease insulin release - when epinephrine is released, alpha-2 effect dominates in pancreas --> ___ plasma glucose for fight-or-flight response ^NOTE: GLUT-2 and ___ (catalyzes first step in glucose metabolism) are found in beta cells and liver

Endocrine pancreas is made up of islets, which contain beta cells (insulin - central), alpha cells (glucagon- peripheral), and delta cells (somatostatin - peripheral) Insulin is a *protein* hormone that is synthesized as preproinsulin (made on ribosomes of rER), which is cleaved to proinsulin and transported to Golgi; proinsulin is cleaved to insulin and C-peptide before being released via exocytosis Mature insulin is made of alpha and beta chain connected by disulfide bridges - the C-peptide ("connecting") used to attach insulin chains, but can be used as proxy for insulin production Insulin is released when beta cells take in glucose via GLUT2^ transporters - once inside the cell, glucose produces ATP, which blocks potassium channels --> raises resting membrane potential --> *voltage-gated calcium channels open, promote exocytosis of insulin!* Beta-2 receptors increase insulin release while alpha-2 receptors decrease insulin release - when epinephrine is released, alpha-2 effect dominates in pancreas --> raised plasma glucose for fight-or-flight response ^NOTE: GLUT-2 and glucokinase (catalyzes first step in glucose metabolism) are found in beta cells and liver

Endometrium has three phases of menstrual cycle: proliferative phase (follicular phase of ovary) and secretory phase After menstruation, endometrium enters ___ phase (stimulated by *___* - 10x thicker w/growth of glands, stroma, etc.) After ovulation, endometrium enters ___ phase (stimulated by *___* - prepares endometrium for implantation of embryo), numerous secretions + formation of *___ arteries* If implantation does not occur --> *___ (vasoconstriction of spiral arteries + apoptosis)*

Endometrium has three phases of menstrual cycle: proliferative phase (follicular phase of ovary) and secretory phase After menstruation, endometrium enters proliferative phase (stimulated by *estrogen* - 10x thicker w/growth of glands, stroma, etc.) After ovulation, endometrium enters secretory phase (stimulated by *progesterone* - prepares endometrium for implantation of embryo), numerous secretions + formation of *spiral arteries* If implantation does not occur --> *menstruation (vasoconstriction of spiral arteries + apoptosis)*

Endosomes are membrane-bound cell compartments f/b endocytosis; examples include receptor-mediated endo., pinocytosis, phagocytosis Endosomes can transport contents to lysosomes (sometimes back to CM --> release contents) Lysosomes are very acidic and contain acid ___ (req. acidic environ. to function), which breakdown substrates via ___ addition; enzyme deficiency --> L___ S___ dz w/macromolecule buildup Peroxisomes cont. oxidative enzymes and generate H2O2, also cont. *___* which oxidizes substances w/H2O2 (detoxifies substances in liver, inc. ethanol), also complete beta oxidation of FAs ___ destroy aberrant proteins - have barrel structure and require ATP; most prots. are marked for destruction (___tion!)

Endosomes are membrane-bound cell compartments f/b endocytosis; examples include receptor-mediated endo., pinocytosis, phagocytosis Endosomes can transport contents to lysosomes (sometimes back to CM --> release contents) Lysosomes are very acidic and contain acid hydrolase (req. acidic environ. to function), which breakdown substrates via H2O addition; enzyme deficiency --> lysosomal storage dz w/macromolecule buildup Peroxisomes cont. oxidative enzymes and generate H2O2, also cont. *CATALASE* which oxidizes substances w/H2O2 (detoxifies substances in liver, inc. ethanol), also complete beta oxidation of FAs Proteasomes destroy aberrant proteins - have barrel structure and require ATP; most prots. are marked for destruction (ubiquitination!)

Eosinophils, Mast Cells (blood), and Basophils (tissue - same cells) are all members of innate immunity All are activated/triggered by Ig___ Abs (important w/parasites) and are involved in allergic rxn EOs: discharge contents onto parasites in response to IgE Ab; stimulated by IL-___ from Th___ cells; high counts are seen w/helminth infxn (also atopic dz) Mast/Basos: bind Fc portion of IgE Ab --> degranulation (*h___*) --- ___ cells (also Innate IS) are professional APCs found in skin/mucosal membranes; DCs migrate to lymph nodes to activate T-cells ("communicator" btwn innate and adaptive IS)

Eosinophils, Mast Cells (blood), and Basophils (tissue - same cells) are all members of innate immunity All are activated/triggered by IgE Abs (important w/parasites) and are involved in allergic rxn EOs: discharge contents onto parasites in response to IgE Ab; stimulated by IL-5 from Th2 cells; high counts are seen w/helminth infxn (also atopic dz) Mast/Basos: bind Fc portion of IgE Ab --> degranulation (*histamine*) --- Dendritic cells (also Innate IS) are professional APCs found in skin/mucosal membranes; DCs migrate to lymph nodes to activate T-cells ("communicator" btwn innate and adaptive IS)

Ephedrine and amphetamines promote release of ___ from neuron Cocaine enhances monoamine neurotransmitter activity (i.e., dopamine, NE, serotonin) by blocking presynaptic ___; this leads to generalized ___ (SNS or PNS?) activation (i.e., HTN, tachycardia) Cocaine also blocks Na channels in nerves, giving it local ___ effect Treatment for cocaine intoxication is benzodiazepines (avoid beta blockers --> unopposed ___ stimulation)

Ephedrine and amphetamines promote release of NE from neuron Cocaine enhances monoamine neurotransmitter activity (i.e., dopamine, NE, serotonin) by blocking presynaptic reuptake pumps; this leads to generalized sympathetic activation (i.e., HTN, tachycardia) Cocaine also blocks Na channels in nerves, giving it local anesthetic effect Treatment for cocaine intoxication is benzodiazepines (avoid beta blockers --> unopposed alpha stimulation)

Epi Studies Goal: determine if exposure is a/w dz (HTN --> stroke), ex. incl. *cross-sectional*, case-control, and cohort studies CSS: pts studied based on being part of group (New Yorkers), freq. of RFs/dz is identified (how many NYs smoke? how many NYs have lung ca.?); *[HY] CSS is ___ in time, pts not followed for months!* Main outcome for CSS is *P___* (i.e., 50% NYs smoke, 25% NYs have Lung Ca.) - may find higher in one group (50% men smoke vs. 25% women); CANNOT determine RR or OR (i.e., how much smoking inc. risk of lung ca., odds of getting lung ca.) To identify CSS on STEP, look for 1) absence of ___, 2) report of dz p___ (may include for several cohorts), 3) absence of RRs/ORs, 4) pts selected randomly (NOT by dz/exposure) Likely Qs: what type of study? what can be determined (*P___*)?

Epi Studies Goal: determine if exposure is a/w dz (HTN --> stroke), ex. incl. *cross-sectional*, case-control, and cohort studies CSS: pts studied based on being part of group (New Yorkers), freq. of RFs/dz is identified (how many NYs smoke? how many NYs have lung ca.?); *[HY] CSS is snapshot in time, pts not followed for months!* Main outcome for CSS is *PREVALENCE* (i.e., 50% NYs smoke, 25% NYs have Lung Ca.) - may find higher in one group (50% men smoke vs. 25% women); CANNOT determine RR or OR (i.e., how much smoking inc. risk of lung ca., odds of getting lung ca.) To identify CSS on STEP, look for 1) absence of time period, 2) report of dz prevalence (may include for several cohorts), 3) absence of RRs/ORs, 4) pts selected randomly (NOT by dz/exposure) Likely Qs: what type of study? what can be determined (*PREVALENCE*)?

Epi Studies Goal: determine if exposure is a/w dz (HTN --> stroke), ex. incl. cross-sectional, *case-control*, and cohort studies ___: compares ppl w/dz vs. ppl w/o dz (i.e., lung ca. vs. no lung ca., opposite of COHORT study, which would look at smokers v. non-smokers) CCS are strong when considering ___ dz; Main outcome of CCS is *___ RATIO (remember: pts are identified by dz vs. no dz) For CCS, want to ensure good matching (i.e., pts identical with exception of dz - reduces confounding) Likely Qs: what type of study? what can be determined (*___ RATIO*)? NOTE: don't confuse with randomized trial, in which exposure (i.e., receiving drug) is determined randomly

Epi Studies Goal: determine if exposure is a/w dz (HTN --> stroke), ex. incl. cross-sectional, *case-control*, and cohort studies CCS: compares ppl w/dz vs. ppl w/o dz (i.e., lung ca. vs. no lung ca., opposite of COHORT study, which would look at smokers v. non-smokers) CCS are strong when considering rare dz; Main outcome of CCS is *ODDS RATIO (remember: pts are identified by dz vs. no dz) For CCS, want to ensure good matching (i.e., pts identical with exception of dz - reduces confounding) Likely Qs: what type of study? what can be determined (*ODDS RATIO*)? NOTE: don't confuse with randomized trial, in which exposure (i.e., receiving drug) is determined randomly ^NOTE: CASE control studies view patients based on their CASE (i.e., dz); *also: case conrOl --> Odds ratio*

Epi Studies Goal: determine if exposure is a/w dz (HTN --> stroke), ex. incl. cross-sectional, case-control, and *cohort studies* ___: demonstrate powerful epi evidence; compares group w/exposure to group without (*pts are identified by EXPOSURE/RISK FACTOR! - diff. from case-control*) --> did exposure change likelihood of dz? Can be prosp. or retros. Main outcome is ___ (i.e., 50% smokers get lung ca., 10% non-smokers get lung ca., RR: 5) To identify Cohort on STEP, look for 1) time period, 2) report of r___, 3) pts identified by RF/exposure (smokers v. nonsmokers, NOT lung ca. vs. no lung ca.) Main problem w/cohort studies: *don't work w/___ dz (follow 1000 ppl for evidence of dz --> likely won't see dz) --> consider case control study* Likely Qs: what type of study? what can be determined (*RELATIVE RISK*)?

Epi Studies Goal: determine if exposure is a/w dz (HTN --> stroke), ex. incl. cross-sectional, case-control, and *cohort studies* Cohort: demonstrate powerful epi evidence; compares group w/exposure to group without (*pts are identified by EXPOSURE/RISK FACTOR! - diff. from case-control*) --> did exposure change likelihood of dz? Can be prosp. or retros. Main outcome is relative risk (i.e., 50% smokers get lung ca., 10% non-smokers get lung ca., RR: 5) To identify Cohort on STEP, look for 1) time period, 2) report of relative risk, 3) pts identified by RF/exposure (smokers v. nonsmokers, NOT lung ca. vs. no lung ca.) Main problem w/cohort studies: *don't work w/rare dz (follow 1000 ppl for evidence of dz --> likely won't see dz) --> consider case control study* Likely Qs: what type of study? what can be determined (*RELATIVE RISK*)? ^NOTE: COHORT studies place pts into COHORTS based on RFs (i.e., smoking); *also: cohoRt --> Relative risk*

Epithelial cells adhere to ___ membrane - anchors ECs to connective tissue (know apical/basolateral terminology) BM has two layers: ___ lamina (collection of extracell. matrix proteins secreted by ECs - includes *laminin and [HY] type ___ collagen [leads to Goodpasture's/Alport]*) and ___ lamina (anchors bas. lam. to connect. tissue) Epithelial cells are joined by: tight junc., adherens junc., gap junc., desmosomes Tight junct. seal two cells together to form barrier to paracellular movement btwn cells; these are most ___ (apical or basolateral?) adhesion Adherens junct. are found below tight junct. and anchor cells together ("belts"); major protein in adh. junct. is ___ (attaches to ___ filaments in cells) - E-cadherin is lost in some breast ca. --> m___ Desmosomes are "spots" (as opposed to belts) of cell-cell attachment common in skin; desmos. are attachment of ___ (made up of keratin) via cadherins (p___ v___ --> Ab to desmos.) Hemidesmosomes attach intermed. filaments to basement membrane via *___ (NOT cadherins)* (bullous pemphigoid --> Ab to hemidesmos.) ___ have channel connections (allow communication of sm. molecules) made up of connexin proteins

Epithelial cells adhere to basement membrane - anchors ECs to connective tissue (know apical/basolateral terminology) BM has two layers: basal lamina (collection of extracell. matrix proteins secreted by ECs - includes *laminin and [HY] type IV collagen (leads to Goodpasture's/Alport) and reticular lamina (anchors bas. lam. to connect. tissue) Epithelial cell junctions are joined by: tight junc., adherens junc., gap junc., desmosomes Tight junct. seal two cells together to form barrier to paracellular movement btwn cells; these are most apical adhesion Adherens junct. are found below tight junct. and anchor cells together ("belts"); major protein in adh. junct. is CADHERIN (attaches to actin filaments in cells) - E-cadherin is lost in some breast ca. --> metastasis [*Actin - Adherins - Cadherin*] Desmosomes are "spots" of cell-cell attachment common in skin; desmos. are attachment of intermediate filaments (made up of keratin) via cadherins (pemphigus vulgaris --> Ab to desmos.) Hemidesmosomes attach intermed. filaments to basement membrane via *integrins (NOT cadherins)* (bullous pemphigoid --> Ab to hemidesmos.) Gap junct. have channel connections (allow communication of sm. molecules) made up of connexin proteins *^Figure here is major key - reviews entire B&B vid* *^^Dick (desmo) goes with Vagina (Vulgaris); Hair (hemi) goes with Balls (bullous)*

Erysipelas develop through break in skin --> bact. enter Erysipelas is infxn of *___ dermis (impetigo --> only epi.)!* - usually 2/2 GAS w/fever, chills, rash with *___ demarcation*, usually of face Cellulitis is infxn of *___ dermis +/- subQ fat!* - usually 2/2 GAS or S. aureus in elderly pts *w/___-defined borders, expansion, and slower onset than ery.* Skin abscess is collection of pus walled-off in dermis/subQ space 2/2 S. aureus - req. I&D

Erysipelas develop through break in skin --> bact. enter Erysipelas is infxn of *superficial dermis (impetigo --> only epi.)!* - usually 2/2 GAS w/fever, chills, rash with *clear demarcation*, usually of face Cellulitis is infxn of *deep dermis +/- subQ fat!* - usually 2/2 GAS or S. aureus in elderly pts *w/ill-defined borders, expansion, and slower onset than ery.* Skin abscess is collection of pus walled-off in dermis/subQ space 2/2 S. aureus - req. I&D

Erythema multiforme is skin d/o a/w infxns (HSV, M pneumoniae) - also drugs, cancers Path. is unclear, but is a type ___ (think of the name!) HS rxn Clinically, is red lesion w/many different *forms (think of the name!)*; lesions are similar for one pt but differ btwn pts; classically, lesions start on backs of hands/feet (contrast w/SJS --> starts on ___), then spread centrally Hallmark lesion is "___ lesion" (dark center --> surrounding red rings) TYPICAL CASE: pt w/acute eruption of oral/genital ___ eruption, then EM skin eruption 2w later (no tx)

Erythema multiforme is skin d/o a/w infxns (HSV, M pneumoniae) - also drugs, cancers Path. is unclear, but is a *type IV HS rxn (multiFORme)* Clinically, is red lesion w/many different forms (think of the name!); lesions are similar for one pt but differ btwn pts; classically, lesions start on backs of hands/feet (contrast w/SJS --> starts on face), then spread centrally Hallmark lesion is "target lesion" (dark center --> surrounding red rings) TYPICAL CASE: pt w/acute eruption of oral/genital HSV eruption, then EM skin eruption 2w later (no tx)

Esophageal cancer (squamous cell or adeno-) p/w *progressive dysphagia (___ --> ___)* + weight loss +/- hematemesis; esophagus lacks serosa --> rapid extension, poor prognosis; both have smoking as RF, Barrett's is only RF for ___ Adenocarcinoma is MC esophageal cancer in US - *need GERD --> ___ --> glandular epithelium in ___ 1/3rd of esophagus* Squamous cell carcinoma is MC esophageal cancer worldwide - results from process that damages upper esophagus (___ food, alcohol, lye ingestion, Zenker's, webs, achalasia); accordingly esophageal SCC is usually seen in *___ esophagus (unique)!* D/t location, SCC can present w/voice sx (___ voice) +/- cough

Esophageal cancer (squamous cell or adeno-) p/w *progressive dysphagia (solids --> liquids)* + weight loss +/- hematemesis; esophagus lacks serosa --> rapid extension, poor prognosis; both have smoking as RF, Barrett's is only RF for adenocarcinoma Adenocarcinoma is MC esophageal cancer in US - *need GERD --> Barrett's --> glandular epithelium in lower 1/3rd of esophagus* Squamous cell carcinoma is MC esophageal cancer worldwide - results from process that damages upper esophagus (hot food, alcohol, lye ingestion, Zenker's, webs, achalasia); accordingly esophageal SCC is usually seen in *upper/middle esophagus (unique)!* D/t location, SCC can present w/voice sx (hoarse voice) +/- cough

Esophageal webs/rings are extension/protrusion of mucosa into lumen (___=circumferential, ___=not circumferential); webs MC in upper, rings MC in lower Schatzki Ring is ring @ ___ junction --> dysphagia to solids Plummer-Vinson syndrome is classic triad of IDA, *___ tongue*, and esophageal web All are associated w/increased risk of ___ of esophagus (let food sit and be all carcinogen-y)

Esophageal webs/rings are extension/protrusion of mucosa into lumen (ring=circumferential, web=not circumferential); webs MC in upper, rings MC in lower Schatzki Ring is ring @ squamocolumnar junction --> dysphagia to solids Plummer-Vinson syndrome is classic triad of IDA, *beefy red tongue*, and esophageal web All are associated w/increased risk of SCC of esophagus (let food sit and be all carcinogen-y)

Essential tremor occurs with intentional movement and *gets better with ___* (tx with propranolol or primidone) Resting tremor occurs at rest and is seen in ___ Intention tremor is zig-zag movement when doing FNF and is seen in ___ dysfunction Wing-beating tremor is seen in ___ disease

Essential tremor occurs with intentional movement and *gets better with alcohol* (tx with propranolol or primidone) Resting tremor occurs at rest and is seen in PD Intention tremor is zig-zag movement when doing FNF and is seen in cerebellar dysfunction Wing-beating tremor is seen in Wilson's disease

Excitation-Contraction coupling is SkeMusc contraction (via Ca) linked to action potential (i.e., musc. contracts when cell depolarizes) - neuron depolarize --> ACh release, bind ligand-gated ___ channel --> musc. depolarize --> contraction SkeMusc depolarize is d/t ___ entry, repolarize is d/t ___ exit T-tubule depolarization is key for c___ release from SR Dih___ is protein that spans T-tubule to SarcRetic (*not targeted by CCBs d/t low affinity on SkelMusc*) - conformational change w/depolarization l/t opening of r___ receptor on terminal cisternae Ryanodine receptors *release c___ to initiate contraction!* - S___ is responsible for transferring cytosol calcium back to SarcRetic (process requires ATP) *[HY] Malignant hyperthermia is d/t abnormal ___ receptors - excessive Ca release --> lots of ___ consumed by SERCA for Ca reuptake --> tissue damage (Tx w/dantrolene - ryanodine antag.)*

Excitation-Contraction coupling is SkeMusc contraction (via Ca) linked to action potential (i.e., musc. contracts when cell depolarizes) - neuron depolarize --> ACh release, bind ligand-gated Na channel --> musc. depolarize --> contraction SkeMusc depolarize is d/t sodium entry, repolarize is d/t potassium exit T-tubule depolarization is key for calcium release from SR Dihydropyridine is protein that spans T-tubule to SarcRetic (*not targeted by CCBs d/t low affinity on SkelMusc*) - conformational change w/depolarization l/t opening of ryanodine receptor on terminal cisternae Ryanodine receptors *release calcium to initiate contraction!* - SERCA is responsible for transferring cytosol calcium back to SarcRetic (process requires ATP) *[HY] Malignant hyperthermia is d/t abnormal ryanodine receptors - excessive Ca release --> lots of ATP consumed by SERCA for Ca reuptake --> tissue damage (Tx w/dantrolene - ryanodine antag.)*

Exotoxin has two components: A (active --> causes illness) and B (binding --> binds cells); exotoxin often not part of chromosome (plasmid-encoded or *bacteriophage-encoded in ___ bug?*) Protein synthesis inhibitors include diphth and pseudo (___ added to EF2 --> inactivated), shiga toxin (binds ___ ribosome; both Shigella and EHEC [*nontoxic Shigella strains still cause dz, likely 2/2 GI ___*; EHEC is noninvasive and all toxin, baby --> HUS]) Fluid secretion toxins (NOTE: Cl secretion into GI tract ~ water in GI tract, Cl secreted ~ [cAMP or cGMP]) include ETEC (Labile tox --> inc ___; Stable tox --> inc ___), B anthrax (Edema tox --> inc ___), V cholera (Chol tox --> act Gs) Phagocytosis inhibitors include Pertussis tox (inhibit Gi --> inc cAMP in ___ --> impaired neut recruitment) Neurotoxins include C bot and C tet - both act on ___ protein (T --> Renshaw cells [inhibitory cells] --> rigid paralysis; B --> NMJ --> flaccid paralysis) CM lysis toxins include C perf (a toxin --> ___ --> eventual low O2 environment favorable for bug) and GAS (sl-O --> beta hemolysis; ASO Abs used to confirm infxn) Superantigens activate a shitload of T-cells (S aureus and GAS) --> TSS (UNIQUE - will see sepsis + *sunburn rash + ___ GI?*)

Exotoxin has two components: A (active --> causes illness) and B (binding --> binds cells); exotoxin often not part of chromosome (plasmid-encoded or *bacteriophage-encoded in DIPHTHERIA*) Protein synthesis inhibitors include diphth and pseudo (ADP-ribose added to EF2 --> inactivated), shiga toxin (binds 60s ribosome; both Shigella and EHEC [*nontoxic Shigella strains still cause dz, likely 2/2 GI invasion*; EHEC is noninvasive and all toxin, baby --> HUS]) Fluid secretion toxins (NOTE: Cl secretion into GI tract ~ water in GI tract, Cl secreted ~ [cAMP or cGMP]) include ETEC (Labile tox --> inc cAMP; Stable tox --> inc cGMP), B anthrax (Edema tox --> inc cAMP), V cholera (Chol tox --> act Gs) Phagocytosis inhibitors include Pertussis tox (inhibit Gi --> inc cAMP in neuts --> impaired neut recruitment) Neurotoxins include C bot and C tet - both act on SNARE protein (T --> Renshaw cells [inhibitory cells] --> rigid paralysis; B --> NMJ --> flaccid paralysis) CM lysis toxins include C perf (a toxin --> lecithinase --> eventual low O2 environment favorable for bug) and GAS (sl-O --> beta hemolysis; ASO Abs used to confirm infxn) Superantigens activate a shitload of T-cells (S aureus and GAS) --> TSS (UNIQUE - will see sepsis + *sunburn rash + diarrhea*)

___ is gradual weakening of conditioned response (see in classical condit, operant condit) ___ is repeated exposure --> less response (i.e., child becoming less nervous for MD visits) ___ is repeated exposure --> more response (i.e., child becoming more nervous for MD visits) ___ is unconscious projection by patient onto others (i.e., patient responding to therapist as they would to parent 2/2 therapist taking on parent role); countertransference is opposite (i.e., clinician projecting onto patient - seeing patient as son/daughter)

Extinction is gradual weakening of conditioned response (see in classical condit, operant condit) Habituation is repeated exposure --> less response (i.e., child becoming less nervous for MD visits) Sensitization is repeated exposure --> more response (i.e., child becoming more nervous for MD visits) Transference is unconscious projection by patient onto others (i.e., patient responding to therapist as they would to parent 2/2 therapist taking on parent role); countertransference is opposite (i.e., clinician projecting onto patient - seeing patient as son/daughter)

Extravascular hemolysis occurs in the liver and *___* Spleen's job is to remove poorly ___ RBCs w/cords of Billroth in red pulp (old cells can't deform --> phagocytosed by ___); hemolytic disorders --> increased splenic removal of RBCs Intravascular hemolysis often occurs in small blood vessels (thrombus - microangiopathic) or large vessels (mechanical heart valves) Key lab test that can differentiate btwn intravascular and extravascular hemolysis is ___ (binds free Hgb, much lower in intravascular hemolysis)

Extravascular hemolysis occurs in the liver and *SPLEEN* Spleen's job is to remove poorly deformable RBCs w/cords of Billroth in red pulp (old cells can't deform --> phagocytosed by macrophages); hemolytic disorders --> increased splenic removal of RBCs Intravascular hemolysis often occurs in small blood vessels (thrombus - microangiopathic) or large vessels (mechanical heart valves) Key lab test that can differentiate btwn intravascular and extravascular hemolysis is haptoglobin (binds free Hgb, much lower in intravascular hemolysis)

FAMILIAL DYSLIPIDEMIAS: *Type I, Hyperchylomicronemia:* AR disorder w/*LPL deficiency (also ApoC-II [cofactor])* --> markedly elevated TGs + chylomicrons --> recurrent pancreatitis + hepatomegaly + xanthomas (can't have ANY fat, but normal life otherwise) *Type II, Hypercholesterolemia:* *autosomal DOMINANT disorder* w/*absent LDL receptors* --> markedly high LDL (>700 in homozygotes) --> severe atherosclerosis --> MI in 20s *Type III, Dysbetalipoproteinemia:* AR disorder w/Apo-E2 subtype of ApoE (*ApoE - Apo-thrEE*) --> chylomicrons + VLDL accumulate --> elevated total cholesterol + TGs --> premature atherosclerosis + palmar xanthomas *Type IV, Hypertriglyceridemia:* *autosomal DOMINANT* disorder of overproduction of VLDL --> elevated VLDL + TGs --> recurrent pancreatitis + T2DM

FAP is germline mutation in ___ --> leads to CRC in 100% of cases Special variants of FAP include: ___ Syndrome (bumpy dz): polyposis + *osteomas (especially mandible)*, skin cysts, connective tissue growths, retinal pigment hypertrophy Turcot Syndrome (brainy dz): polyposis + ___ tumors (mostly medulloblastomas + gliomas)

FAP is germline mutation in APC --> leads to CRC in 100% of cases Special variants of FAP include: Gardner's Syndrome (bumpy dz): polyposis + *osteomas (especially mandible)*, skin cysts, connective tissue growths, retinal pigment hypertrophy Turcot Syndrome (brainy dz): polyposis + brain tumors (mostly medulloblastomas + gliomas)

FRONTAL LOBE: The ACA supplies ___ areas of the homunculus; the MCA supplies the ___ and ___ of the homunculus The FEFs perform ___ movements and a FEF lesion results in eyes deviated ___ Anterior 2/3rds is ___, responsible for inhibition/judgement (Phineas Gage) Broca's ("Broken") speech area is located in the ___ hemisphere and does speech ___ (damage --> ___ aphasia)

FRONTAL LOBE: The ACA supplies leg areas of the homunculus; the MCA supplies the upper limb and face of the homunculus The FEFs perform saccadic (back-forth) movements and a FEF lesion results in eyes deviated ipsilaterally Anterior 2/3rds is prefrontal cortex, responsible for inhibition/judgement (Phineas Gage) Broca's ("Broken") speech area is located in the LEFT hemisphere and does speech production (damage --> expressive aphasia)

___ (three are sex-related) all have the same alpha subunit; importantly, these are all protein hormones that act on a GPCR with ___ second messenger system

FSH, LH, TSH, and hCG all have the same alpha subunit; importantly, these are all protein hormones that act on a GPCR with cAMP second messenger system

___ blocks alternative pathway on host cells so complement doesn't kill own cells (accelerates decay of C3 convertase [C3bBb], cleaves and inactivates C3b) Factor H can be used by cancer and bacteria (H flu, N men, Strep, PSeudo) to evade alternative pathway

Factor H blocks alternative pathway on host cells so complement doesn't kill own cells (accelerates decay of C3 convertase [C3bBb], cleaves and inactivates C3b) Factor H can be used by cancer and bacteria (H flu, N men, Strep, PSeudo) to evade alternative pathway

Factor VIII is unique in that it 1) is produced in ___ cells (not liver) and 2) circulates bound to ___ (also produced in endothelial cells) which prolongs its half life; factor VIII is released from ___ in response to vascular injury vWF is synthesized by endothelial cells and ___ (platelet precursor - found in alpha granules) - it is released when activated platelets degranulate, as well as when ___ cells are damaged vWF has three roles in hemostasis: 1) carrier protein for factor ___, 2) binding ___ to endothelium, 3) binding activated platelets together (a___) --- Vitamin K is required for many clotting factor synthesis (*___ - 6*); VitK deficiency --> bleeding (rationale for WARFARIN therapy, VitK antagonist)

Factor VIII is unique in that it 1) is produced in endothelial cells (not liver) and 2) circulates bound to vWF (also produced in endothelial cells) which prolongs its half life; factor VIII is released from vWF in response to vascular injury vWF is synthesized by endothelial cells and megakaryocytes (platelet precursor - found in alpha granules) - it is released when activated platelets degranulate, as well as when endothelial cells are damaged vWF has three roles in hemostasis: 1) carrier protein for factor VIII, 2) binding platelets to endothelium, 3) binding activated platelets together (aggregation) --- Vitamin K is required for many clotting factor synthesis (*II, VII, IX, X, C, S*); VitK deficiency --> bleeding (rationale for WARFARIN therapy, VitK antagonist)

Factor XII requires k___ for normal function; kinins contribute to inflammation and are considered link btwn ___ and inflammation ___ is vasodilator that increases vascular permeability + pain Bradykinin is degraded by ___ - using ___ can cause angioedema 2/2 elevated bradykinins; bradykinins are also broken down by C1 inhibitor protein - deficiency --> *hereditary ___ (do NOT give ACEi!!)* BIG PICTURE: factor XII activates clotting and produces ___ (requires prekallikrein [PK] and HMWK to function) Prekallikrein Deficiency p/w markedly prolonged ___, but no bleeding problems

Factor XII requires kinins for normal function; kinins contribute to inflammation and are considered link btwn coagulation and inflammation Bradykinin is vasodilator that increases vascular permeability + pain Bradykinin is degraded by ACE - using ACEi can cause angioedema 2/2 elevated bradykinins; bradykinins are also broken down by C1 inhibitor protein - deficiency --> *hereditary angioedema (do NOT give ACEi!!)* BIG PICTURE: factor XII activates clotting and produces bradykinin (requires prekallikrein [PK] and HMWK to function) Prekallikrein Deficiency p/w markedly prolonged PTT, but no bleeding problems

Familial Hypocalciuric Hypercalcemia is *autosomal ___* disorder of abnormal calcium sensing receptors (higher than normal set point for calcium) --> more renal resorption of calcium --> ___ serum calcium + ___ urine calcium + normal PTH Tx: nothing (*different from primary hyperparathyroidism!*)

Familial Hypocalciuric Hypercalcemia is *autosomal DOMINANT* disorder of abnormal calcium sensing receptors (higher than normal set point for calcium) --> more renal resorption of calcium --> raises serum calcium + lowers urine calcium + normal PTH Tx: nothing (*different from primary hyperparathyroidism!*)

Fastidious organism require special nutrients to grow (H flu, Legionella) Blood agar is non-___ (many orgs grow), enriched (blood has nutrients), and ___ (different bugs grow in different patterns, esp. STREP - alpha [pneumo, viridans], beta [GAS, GBS], gamma [entero, bovis]); Pseudomonas is also beta hemolytic and produces ___-metallic colonies Chocolate agar (RBCs that are lysed - contains factor ___ and factor ___) is used for H flu; NOTE: H flu may grow on blood agar if ___ is present

Fastidious organism require special nutrients to grow (H flu, Legionella) Blood agar is non-selective (many orgs grow), enriched (blood has nutrients), and differential (different bugs grow in different patterns, esp. STREP - alpha [pneumo, viridans], beta [GAS, GBS], gamma [entero, bovis]); Pseudomonas is also beta hemolytic and produces green-metalic colonies Chocolate agar (RBCs that are lysed - contains factor V and factor X) is used for H flu; NOTE: H flu may grow on blood agar if Staph is present

___ embolism is a/w long bone fractures, in which fat travels to lungs --> small artery infarctions; classic triad is h___, n___, p___ Amniotic fluid embolism is usually during labor or shortly postpartum - often fatal 2/2 DIC and massive inflammation; has two phases: 1) respiratory distress + hypoxemia + hypotension and 2) hemorrhage + DIC (seizures can occur) Air embolism is 2/2 nitrogen bubbles precipitating in vasculature (can be seen in ascending divers or central line placement)

Fat embolism is a/w long bone fractures, in which fat travels to lungs --> small artery infarctions; classic triad is hypoxemia (ARDS), neurologic abnormalities (AMS), and petechiae Amniotic fluid embolism is usually during labor or shortly postpartum - often fatal 2/2 DIC and massive inflammation; has two phases: 1) respiratory distress + hypoxemia + hypotension and 2) hemorrhage + DIC (seizures can occur) Air embolism is 2/2 nitrogen bubbles precipitating in vasculature (can be seen in ascending divers or central line placement)

___ malabsorption can l/t steatorrhea w/greasy, foul-smelling stools that float Carb malabsorption can l/t ___ diarrhea (2/2 ___ effect of carbs) Protein malabsorption can l/t ___ Watery diarrhea can be ___ (cholera) or ___ (lactose intolerance) - use stool osmotic gap (elevated in osmotic [>50], low in secretory - [290 - (2*Na) - (2*K)])

Fat malabsorption can l/t steatorrhea w/greasy, foul-smelling stools that float Carb malabsorption can l/t watery diarrhea (2/2 osmotic effect of carbs) Protein malabsorption can l/t edema Watery diarrhea can be secretory (cholera) or osmotic (lactose intolerance) - use osmotic gap (elevated in stool osmotic [>50], low in secretory - [290 - (2*Na) - (2*K)])

Features of a "good match" for transplant include 1) same ___ type, 2) same (or close) MHC1 and MHC2 molecules, 3) negative cross-matching screen (test of donor ___ vs. recipient ___ --> screen for antibodies) If donor cells express different MHC1, ___ cells will react; additionally, if donor organ has vascular endothelial cells that express different MHC2 from host, those may be attacked as well HLA is what we use to match - MHC1: HLA-A, HLA-B, HLA-C; MHC2: HLA-DR, HLA-DM, HLA-DO, HLA-DP, HLA-DQ; HLA-___, HLA-___, HLA-DR are most important (b/c each comes with pair, sometimes will hear "perfect 6/6 match") Each pt receives two sets of HLA genes en bloc (i.e., as a set) from each parent - accordingly, *[common question] siblings have ___% chance of being a perfect match (also ___% chance of being completely different)*

Features of a "good match" for transplant include 1) same blood type, 2) same (or close) MHC1 and MHC2 molecules, 3) negative cross-matching screen (test of donor cells vs. recipient plasma --> screen for antibodies) If donor cells express different MHC1, CD8+ T-cells will react; additionally, if donor organ has vascular endothelial cells that express different MHC2 from host, those may be attacked as well HLA is what we use to match - MHC1: HLA-A, HLA-B, HLA-C; MHC2: HLA-DR, HLA-DM, HLA-DO, HLA-DP, HLA-DQ; HLA-A, HLA-B, HLA-DR are most important (b/c each comes with pair, sometimes will hear "perfect 6/6 match") Each pt receives two sets of HLA genes en bloc (i.e., as a set) from each parent - accordingly, *[common question] siblings have 25% chance of being a perfect match (also 25% chance of being completely different)*

Flow cytometry is *used to analyze cells by size and surface proteins* (uses laser & photodetector); forward scatter --> ___ (small in lymphocytes [small cells]), side scatter --> G___ (high in granulocytes) FC can be used w/antibody staining (specific Abs to prots. that are tagged to fluorochrome --> FC detects fluorochrome, indicates presence of prot.) Clinically, FC can detect fetal-maternal hemorrhage (Abs for hemoglobin ___, if present --> fetal hemorrhage) FC can also detect *____* w/Abs labeled for GPI-anchored prots. (DAF/CD55, CD59) --> reduced/absent on RBCs in PNH

Flow cytometry is *used to analyze cells by size and surface proteins* (uses laser & photodetector); forward scatter (small in lymphocytes [small cells]) --> size, side scatter --> granularity (high in granulocytes) FC can be used w/antibody staining (specific Abs to prots. that are tagged to fluorochrome --> FC detects fluorochrome, indicates presence of prot.) Clinically, FC can detect fetal-maternal hemorrhage (Abs for hemoglobin F, if present --> fetal hemorrhage) FC can also detect *paroxysmal nocturnal hemoglobinuria* w/Abs labeled for GPI-anchored prots. (DAF/CD55, CD59) --> reduced/absent on RBCs in PNH

___ is B-cell malignancy of follicle-forming B-cells seen in adults Biopsy (not HY) will show massive follicles forming FL has characteristic genetic hallmark - *___, resulting in Ig-Heavy-Chain (heavily expressed):___ --> overexpression of BCL-2 (BCL-2 normally blocks apoptosis) --> uncontrolled B-cell growth* FL p/w indolent course w/waxing and waning sx that sometimes don't need tx Feared outcome is transformation to ___ To distinguish follicular lymphoma from reactive lymphadenopathy, look for *___ (more common in LAD d/t dying cells that don't express BCL2) and BCL2 staining (positive in ___)*

Follicular lymphoma is B-cell malignancy of follicle-forming B-cells seen in adults Biopsy (not HY) will show massive follicles forming FL has characteristic genetic hallmark - *t14;18, resulting in Ig-Heavy-Chain (heavily expressed):BCL-2 --> overexpression of BCL-2 (BCL-2 normally blocks apoptosis) --> uncontrolled B-cell growth* FL p/w indolent course w/waxing and waning sx that sometimes don't need tx Feared outcome is transformation to DLBCL To distinguish follicular lymphoma from reactive lymphadenopathy, look for *macrophages (more common in LAD d/t dying cells that don't express BCL2) and BCL2 staining (positive in FL)*

Fundamental principle of confidentiality is info *should only be disclosed with pt P___ (includes spouse/kids, other MDs, govt authorities)* Exceptions: 1) emergency (can tell fam "___ info" of location/general condition if in pts best interests, no specifics), 2) potential for harm (if 3rd party not warned, what will happen? e.g., psych pt with HI, *SEXUAL PARTNERS* of ___ pts [only if pt does not do so themselves after encouragement by MD]), 3) reportable illness (TB, syphilis, gon, measles, mumps), 4) abuse^ (child & elder - *tested by pt w/suspic injuries --> INTERVIEW ___ [MD protected if report & wrong]) Driving w/elderly person should be *discussed with pt/family*; driving w/seizures requires ___-free interval (*ANSWER ON STEP: consult with state ___ for interval!*) ^*NOTE: domestic violence is NOT reported - providers should be supportive, make sure pt feels safe at home, and (HY) ensure pt has ___ if emergency arises*

Fundamental principle of confidentiality is info *should only be disclosed with pt permission (includes spouse/kids, other MDs, govt authorities)* Exceptions: 1) emergency (can tell fam "directory info" of location/general condition if in pts best interests, no specifics), 2) potential for harm (if 3rd party not warned, what will happen? e.g., psych pt with HI, *SEXUAL PARTNERS* of STI pts [only if pt does not do so themselves after encouragement by MD]), 3) reportable illness (TB, syphilis, gon, measles, mumps), 4) abuse^ (child & elder - *tested by pt w/suspic injuries --> INTERVIEW ALONE [MD protected if report & wrong]) Driving w/elderly person should be *discussed with pt/family*; driving w/seizures requires seizure-free interval (*ANSWER ON STEP: consult with state DMV for interval!*) ^*NOTE: domestic violence is NOT reported - providers should be supportive, make sure pt feels safe at home, and (HY) ensure pt has safe space if emergency arises*

CLASSIC PRESENTATION: pt from Turkey who p/w jaundice, dark urine, and anemia after exposure to fava beans?

G6PD (key enzyme in HMP shunt, which synthesizes NADPH to protect RBCs from oxidative damage) deficiency (*Xrec*, MC human enzyme d.o) results in increased toxicity to H2O2 (d/t NADPH deficiency) --> hemolysis Common triggers for H2O2 production include infection (macrophages generate free radicals), *drugs (sulfas, dapson, isoniazid, anti-malarials), and FAVA beans* G6PD deficiency p/w recurrent hemolysis *+ BACK PAIN* after exposure to triggers (RBCs become rigid --> consumed by splenic macrophages [extravascular]) G6PD has a high prevalence in Africa, Asia, and Mediterranean [Turkey, Greece, Italy, France, Spain] (may protect against malaria) Two classic findings on peripheral smear include *Heinz bodies (oxidized hemoglobin) and bite cells (phagocytic removal by macrophages)* Dx: fluorescent spot test

___ (key enzyme in HMP shunt, which synthesizes NADPH to protect RBCs from oxidative damage) deficiency (*___*, MC human enzyme d.o) results in increased toxicity to H2O2 (d/t NADPH deficiency) --> hemolysis Common triggers for H2O2 production include infection (macrophages generate free radicals), *drugs (sulfas, dapsone, isoniazid, anti-malarials), and ___ beans* G6PD deficiency p/w recurrent hemolysis *+ ___ PAIN* after exposure to triggers (RBCs become rigid --> consumed by ___ macrophages [extravascular]) G6PD has a high prevalence in Africa, Asia, and ___ [Turkey, Greece, Italy, France, Spain] (may protect against malaria) Two classic findings on peripheral smear include *___ bodies (oxidized hemoglobin) and ___ cells (phagocytic removal by macrophages)* Dx: fluorescent spot test

GASTRIN: produced by G-cells in mucosa of a___ in response to distension, alkalinization, AAs, vagal stimulation (___ - atropine doesn't affect); act on parietal cells and 1) stimulate acid secretion, 2) stimulate growth of gastric mucosa, and 3) increase gastric motility Gastrin can also act on ___ cells to secrete histamine, which acts on parietal cells (most important) *[HY] ___ are gastrin-secreting tumors that cause Zollinger-Ellison Syndrome; these tumors occur in duodenum or pancreas --> abdominal pain, diarrhea/steatorrhea (excess acid can't be neutralized), ulcers (DISTAL ___), GERD refractory to tx; path. will reveal ___ mucosa!* *Dx gastrinoma w/fasting gastrin (>10x limit) + ___ test (gastrinoma G-cells stimulated by secretin --> gastrin levels rise; normally G-cells inhibited by secretin)* *Tx w/Octreotide - ___ analog*

GASTRIN: produced by G-cells in mucosa of antrum in response to distension, alkalinization, AAs, vagal stimulation (GRP - atropine doesn't affect); act on parietal cells and 1) stimulate acid secretion, 2) stimulate growth of gastric mucosa, and 3) increase gastric motility Gastrin can also act on ECL cells to secrete histamine, which acts on parietal cells (most important) *[HY] Gastrinoma are gastrin-secreting tumors that cause Zollinger-Ellison Syndrome; these tumors occur in duodenum or pancreas --> abdominal pain, diarrhea/steatorrhea (excess acid can't be neutralized), ulcers (DISTAL DUODENUM), GERD refractory to tx; path. will reveal hypertrophied mucosa!* *Dx gastrinoma w/fasting gastrin (>10x limit) + secretin test (gastrinoma G-cells stimulated by secretin --> gastrin levels rise; normally G-cells inhibited by secretin)* *Tx w/Octreotide - somatostatin analog*

GI tract (epithelium/glands of GI tract, liver, pancreas, trachea) come from ___ Surrounding structures (stroma [GI connective tissue], muscles, peritoneum, *___ [unique!]*) come from mesoderm In development, GI tube will form ___gut (esophagus to Ampulla of Vater), ___gut (Ampulla of Vater to splenic flexure), and ___gut (spenic flexure to anus) - importantly, all are supplied by different arteries (celiac trunk, SMA, IMA); At this stage, entire yolk sac has basically converted to digestive tube *except the vitelline duct, which should disappear*

GI tract (epithelium/glands of GI tract, liver, pancreas, trachea) come from endoderm Surrounding structures (stroma [GI connective tissue], muscles, peritoneum, *SPLEEN [unique!]*) come from mesoderm In development, GI tube will form foregut (esophagus to Ampulla of Vater), midgut (Ampulla of Vater to splenic flexure), and hindgut (spenic flexure to anus) - importantly, all are supplied by different arteries (celiac trunk, SMA, IMA); At this stage, entire yolk sac has basically converted to digestive tube *except the vitelline duct, which should disappear*

CLASSIC CASE *[HY one too]: new onset diabetes + red blistering rash to the genitals, buttocks, groin?*

GLUCAGONOMA (necrolytic migratory erythema)

GP Cocci can be differentiated (staph v strep) via ___ test (staph +, strep -); this enzyme does H2O2 --> H2O + O2 (bubbles); *patients with CGD are sensitive to cat+ organisms (2/2 loss of ___ oxidase --> cannot generate H2O2 for burst) - organisms are Staph, Pseudo, Serratia, Nocardia, and Aspergillus Staph aureus vs other staph --> use ___ test; Staph aureus will also grow yellow on ___ salt agar (2/2 mannitol fermentation) CoNS differentiated by ___ sensitivity (epi --> sens, sapro --> resist) B-hemolytic strep differentiated by ___ (GAS --> sens, GBS --> resist) a-hemolytic strep differentiated by ___ (pneumo --> sens, viri --> resist) g-hemolytic strep differentiated by growth in NaCl agar (entero --> ___, bovis --> ___); both grow on bile agar --> brown/black appearance

GP Cocci can be differentiated (staph v strep) via catalase test (staph +, strep -); this enzyme does H2O2 --> H2O + O2 (bubbles); *patients with CGD are sensitive to cat+ organisms (2/2 loss of NADPH oxidase --> cannot generate H2O2 for burst) - organisms are Staph, Pseudo, Serratia, Nocardia, and Aspergillus Staph aureus vs other staph --> use coagulase test; Staph aureus will also grow yellow on mannitol salt agar (2/2 mannitol fermentation) CoNS differentiated by novobiocin sensitivity (epi --> sens, sapro --> resist) B-hemolytic strep differentiated by bacitracin (GAS --> sens, GBS --> resist) a-hemolytic strep differentiated by optochin (pneumo --> sens, viri --> resist) g-hemolytic strep differentiated by growth in NaCl agar (entero --> grow, bovis --> no); both grow on bile agar --> brown/black appearance

Gastric carcinoma (95% adeno) has poor prognosis - p/w dyspepsia, abd pain, weight loss; two types: intestinal and diffuse Generally, will p/w *a___ n___ (insulin resistance), Leser-Trelat (explosive s___), Virchow Node (L supra___ node), Krukenberg tumor (o___ tumor not d/t ovary source, mets from gastric adeno. - SIGNET CELLS!), Sister Mary Joseph nodule (periumbilical nodule), Blumer shelf (digital rectal mass) --- INTESTINAL: Grossly, looks like large ulcer w/irregular margins in *___ curvature (where most gastric ulcers are!)* Histo: similar to colonic adenocarcinoma 2/2 ___ metaplasia (*seen w/H. pylori, autoimmune gastritis - cause chronic inflammation!*) RFs: men, smoking, alcohol, *n___ (seen in meats - think of man who eats meat, smokes, drinks)*, *type A blood* --- DIFFUSE: Not a/w anything - appears as *DIFFUSELY* thickened stomach (l___ p___ - l/t early satiety) d/t E-ca___ mut. Histo: *malignant mucus cells w/Si___ Ri___ Cells!!*

Gastric carcinoma (95% adeno) has poor prognosis - p/w dyspepsia, abd pain, weight loss; two types: intestinal and diffuse Generally, will p/w *acanthosis nigricans (insulin resistance), Leser-Trelat (explosive seborrheic keratosis), Virchow Node (L supraclavicular node), Krukenberg tumor (ovarian tumor not d/t ovary source, mets from gastric adeno. - SIGNET CELLS!), Sister Mary Joseph nodule (periumbilical nodule), Blumer shelf (digital rectal mass) --- INTESTINAL: Grossly, looks like large ulcer w/irregular margins in *lesser curvature (where most gastric ulcers are!)* Histo: similar to colonic adenocarcinoma 2/2 intestinal metaplasia (*seen w/H. pylori, autoimmune gastritis - cause chronic inflammation!*) RFs: men, smoking, alcohol, *nitrosamines (seen in meats - think of man who eats meat, smokes, drinks)*, *type A blood* --- DIFFUSE: Not a/w anything - appears as *DIFFUSELY* thickened stomach (linitis plastica - l/t early satiety) d/t E-cadherin mut. Histo: *malignant mucus cells w/Signet Ring Cells!!*

Generation of antibody diversity is done via random recombination of VJ genes (___-chain) and VDJ genes (___-chain[heavy>light], V: 50 genes, D: 25 genes, J: 6 genes), random combinations of heavy & light chains --> more diversity (*KEY POINT: small number of genes --> millions of receptors*) - this process occurs in bone marrow (pre-infection) and will determine what B-cell receptor is expressed During infection, B-cells go to lymph nodes - class switching happens and somatic hyper___ is seen in B-cells late during inflammation/infection; there is a high mutation rate in VDJ genes --> B-cells require re-stimulation for ongoing proliferation --> strongest binding B-Cell Receptor will survive (*"___ maturation"*)

Generation of antibody diversity is done via random recombination of VJ genes (light-chain) and VDJ genes (heavy-chain, V: 50 genes, D: 25 genes, J: 6 genes), random combinations of heavy & light chains --> more diversity (*KEY POINT: small number of genes --> millions of receptors*) - this process occurs in bone marrow (pre-infection) and will determine what B-cell receptor is expressed During infection, B-cells go to lymph nodes - class switching happens and somatic hypermutation is seen in B-cells late during inflammation/infection; there is a high mutation rate in VDJ genes --> B-cells require re-stimulation for ongoing proliferation --> strongest binding B-Cell Receptor will survive (*"affinity maturation"*)

Gifts from companies are acceptable if educational and low value (<$___) - no cash, tix, vacays; no definitive rules for gifts from pts, but don't accept LARGE gifts (or poor m___ state pt) Honoraria is fees paid to physicians by industry (usually to promote research to other MDs) - fees must be fair and reasonable and *must be ___* MDs can decline care for pt, but once relationship starts cannot refuse care (*MC: MD doesn't want to perform abortion --> ___ to another MD*) ___ (how often?) disclose errors to patients Don't give care to family/friends with exception to emergency *If family is present for office visit, politely ask for time ___ with pt (don't ask pt if they want fam present)*

Gifts from companies are acceptable if educational and low value (<$100) - no cash, tix, vacays; no definitive rules for gifts from pts, but don't accept LARGE gifts (or poor mental state pt) Honoraria is fees paid to physicians by industry (usually to promote research to other MDs) - fees must be fair and reasonable and *must be disclosed* MDs can decline care for pt, but once relationship starts cannot refuse care (*MC: MD doesn't want to perform abortion --> refer to another MD*) Always disclose errors to patients Don't give care to family/friends with exception to emergency *If family is present for office visit, politely ask for time alone with pt (don't ask pt if they want fam present)* ^ALSO: always deny romantic relationships with patients (duh)

What disease is atropine contraindicated in?

Glaucoma - muscarinic antagonism decreases fluid outflow

Glioblastoma is most common primary brain tumor in adults, occurring in cerebral cortex with expression of ___; *histology reveals ___ appearance (necrosis surrounded by cells lining along edge)* Meningioma is 2nd MC adult brain tumor, occurring near surfaces of brain ("extra-___" - not brain tissue, arise from arachnoid cells) - these are benign with common RF being prior head ___; *parasagittal meningioma --> compresses leg homunculus to mimic ___ stroke*; microscopy reveals ___ bodies ___ (3rd MC) classically occur in CN8, also affecting structures at cerebellopontine angle (CN7); these tumors stain positive for S-100 Neurofibromas are associated with NF, also a/w Lisch nodules and Cafe-Au-Lait spots; NF2 leads to bilateral ___, meningiomas (MISME)

Glioblastoma is most common primary brain tumor in adults, occurring in cerebral cortex with expression of GFAP; *histology reveals pseudopallisading appearance (necrosis surrounded by cells lining along edge)* Meningioma is 2nd MC adult brain tumor, occurring near surfaces of brain ("extra-axial" - not brain tissue, arise from arachnoid cells) - these are benign with common RF being prior head radiation; *parasagittal meningioma --> compresses leg homunculus to mimic ACA stroke*; microscopy reveals psammoma bodies Schwannomas (3rd MC) classically occur in CN8, also affecting structures at cerebellopontine angle (CN7); these tumors stain positive for S-100 Neurofibromas are associated with NF, also a/w Lisch nodules and Cafe-Au-Lait spots; NF2 leads to bilateral schwannomas, meningiomas (MISME)

Glucagon is protein hormone (single polypeptide chain) that is synthesized by alpha cells in response to ___ plasma glucose Glucagon increases ___ (*not muscle*) glycogen breakdown (should make sense - muscle still needs glucose) and increases ___ Glucagon will ___ lipolysis and promotes amino acid uptake in *___* for use in gluconeogenesis Glucagon receptor is a ___ (different from insulin - RTK), activates adenylyl cyclase --> increased cAMP --> PKA activation Glucagon receptors are (predictably) found primarily in ___ Clinically, glucagon can be used as 1) 2nd line treatment for hypoglycemia and 2) ___ overdose (activates adenylyl cyclase --> accomplishes what beta receptors do, but through different mechanism - BACK DOOR)

Glucagon is protein hormone (single polypeptide chain) that is synthesized by alpha cells in response to low plasma glucose Glucagon increases liver (*not muscle*) glycogen breakdown (should make sense - muscle still needs glucose) and increases gluconeogenesis Glucagon will increase lipolysis and promotes amino acid uptake in *liver* for use in gluconeogenesis Glucagon receptor is a GPCR (different from insulin - RTK), activates adenylyl cyclase --> increased cAMP --> PKA activation Glucagon receptors are (predictably) found primarily in liver Clinically, glucagon can be used as 1) 2nd line treatment for hypoglycemia and 2) beta blocker overdose (activates adenylyl cyclase --> accomplishes what beta receptors do, but through different mechanism - BACK DOOR)

___ (beta-cell enzyme) is the 1st step of glycolysis (also found in liver) - it has a high Km and high Vm, so it can convert lots of glucose to ___ but needs high concentration of glucose GLUT-2 (found in ___, kidney, and ___ cells) is bidirectional glucose transporter; in beta cells, allows glucose in/out based on plasma levels (helps determine ___ release!)

Glucokinase (beta-cell enzyme) is the 1st step of glycolysis (also found in liver) - it has a high Km and high Vm, so it can convert lots of glucose to G6P but needs high concentration of glucose GLUT-2 (found in liver, kidney, and beta cells) is bidirectional glucose transporter; in beta cells, allows glucose in/out based on plasma levels (helps determine insulin release!)

Glucose-dependent *insulinotropic* peptide (GIP) is released by K-cells and stimulates ___ release (also blunts acid secretion; UNIQUE: GIP is released in response to ___ (only one with all three)! [I-->Insulinotropic!] *[HY] Because of GIP, ___ glucose is metabolized faster than ___ glucose (IV glucose does not stimulate GIP release!)*

Glucose-dependent *insulinotropic* peptide (GIP) is released by K-cells and stimulates insulin release (also blunts acid secretion; UNIQUE: GIP is released in response to FAs, AAs, and glucose (only one with all three)! *[HY] Because of GIP, oral glucose is metabolized faster than IV glucose (IV glucose does not stimulate GIP release!)*

___ from hypothalamus --> FSH/LH from pituitary --> estrogen/progesterone or testosterone Note that GnRH is peptide hormone released in *___ manner* - changes LH/FSH release from pituitary GnRH acts on G___ protein system w/IP3 2nd messenger ___ is GnRH agonist (amino acid substitution --> longer half-life) that can initially act as agonist, but chronic treatment --> ___regulation of GnRH receptor (pituitary desensitization) --> suppresses ovarian follicular growth/ovulation (chemically induced menopause); several uses for leuprolide: 1. Stimulation of LH/FSH when given in pulsatile manner (creates ___ for IVF) 2. Continuous administration for ___ of LH/FSH release (endometriosis, uterine fibroids, prostate cancer, precocious puberty) --- K___ Syndrome is absence of GnRH-secreting neurons from hypothalamus - it primarily affects males and p/w *hypogonadism + ___ (neurons migrate from olfactory bulb)*, delayed puberty, small testes

GnRH from hypothalamus --> FSH/LH from pituitary --> estrogen/progesterone or testosterone Note that GnRH is peptide hormone released in *pulsatile manner* - changes LH/FSH release from pituitary GnRH acts on Gq protein system w/IP3 2nd messenger Leuprolide is GnRH agonist (amino acid substitution --> longer half-life) that can initially act as agonist, but chronic treatment --> downregulation of GnRH receptor (pituitary desensitization) --> suppresses ovarian follicular growth/ovulation (chemically induced menopause); several uses for leuprolide: 1. Stimulation of LH/FSH when given in pulsatile manner (creates LH surge for IVF) 2. Continuous administration for suppression of LH/FSH release (endometriosis, uterine fibroids, prostate cancer, precocious puberty) --- Kallman Syndrome is absence of GnRH-secreting neurons from hypothalamus - it primarily affects males and p/w *hypogonadism + anosmia (neurons migrate from olfactory bulb)*, delayed puberty, small testes

Goal in pyrimidine synthesis is to create CMP, UMP and TMP OVERVIEW: glutamine --> carbamoyl phosphate --> orotic acid --> UMP --> CMP + TMP 1) make carbamoyl phosphate (*synthesized from GLUTAMINE + ATP + CO2!*) - catalyzed by carbamoyl phosphate synthetase II 2) make *orotic acid (uses ASPARTATE)* 3) make UMP (requires *PRPP + orotic acid*) 4) add phosphates to get UTP 5) can make CTP from UTP - can also make dTMP (another card covers this - think MTX sketchy scene) All pyrimidine rings are made from carbamoyl phosphate + aspartate! Orotic aciduria is defect in UMP synthase enzyme --> stopped in step 2, can't create UMP! Key findings in orotic aciduria include orotic acid in urine (duh) and *megaloblastic anemia (hypersegmented neutrophils w/ no response to B12/folate - DIFFERENTIATES FROM ORNITHINE TRANSCARBAMYLASE DEFICIENCY! - OTC also has high ammonia levels, look for lethargy + coma)* and growth retardation - tx w/uridine (bypasses UMP synthase!) With orotoic acidUria, think * U U U (UMP synthase, Uridine tx, U better get this right)*

Goodpasture's vs. Small Vessel Vasculitis: Goodpasture's is Ab to type ___ collagen (type II HS rxn) seen in glomerular BM and alveoli Pts present w/hemoptysis + nephritic syndrome (similar to vasculitis), *but with positive i___ biopsy (REMEMBER: Goodpasture's is Ig-mediated, Vasculitis is ANCA-mediated) CLASSIC CASE - GOODPASTURE'S: young male w/hemoptysis + hematuria with positive immunofluorescent staining and ___ ANCA CLASSIC CASE - VASCULITIS: patient w/hemoptysis + hematuria with ___ immunofluorescent staining and ___ ANCA

Goodpasture's vs. Small Vessel Vasculitis: Goodpasture's is Ab to type IV collagen (type II HS rxn) seen in glomerular BM and alveoli Pts present w/hemoptysis + nephritic syndrome (similar to vasculitis), *but with positive immunofluorscence biopsy (REMEMBER: Goodpasture's is Ig-mediated, Vasculitis is ANCA-mediated) CLASSIC CASE - GOODPASTURE'S: young male w/hemoptysis + hematuria with positive immunofluorescent staining and negative ANCA CLASSIC CASE - VASCULITIS: patient w/hemoptysis + hematuria with negative immunofluorescent staining and positive ANCA

Growth hormone (somatotropin) is a protein hormone released in ___ manner (in response to GHRH, *exercise, sleep*) that leads to linear growth in childhood - GH is inhibited by somatostatin and I___ GH receptor is membrane-bound (duh - its a protein hormone) that activates JACK2 (RTK) --> phosphorylates ___ residues --> alters gene expression The liver contains many GH receptors - in liver, GH --> ___ (mediates many GH effects, *measure IGF-1 as proxy of GH function!*) GH Itself: -___ glucose uptake by cells ("diabetogenic" like glucagon - makes glucose available to brain for growing) -___ lipolysis (available for brain) IGF-1 Effects: -___ stimulation for linear growth -Muscle stimulation for increased mass -Organ stimulation for ___ size

Growth hormone (somatotropin) is a protein hormone released in pulsatile manner (in response to GHRH, *exercise, sleep*) that leads to linear growth in childhood - GH is inhibited by somatostatin and IGF-1 GH receptor is membrane-bound (duh - its a protein hormone) that activates JACK2 (RTK) --> phosphorylates tyrosine residues --> alters gene expression The liver contains many GH receptors - in liver, GH --> IGF-1 (mediates many GH effects, *measure IGF-1 as proxy of GH function!*) GH Itself: -Decreases glucose uptake by cells ("diabetogenic" like glucagon - makes glucose available to brain for growing) -Increases lipolysis (available for brain) IGF-1 Effects: -Chondrocyte stimulation for linear growth -Muscle stimulation for increased mass -Organ stimulation for increased size

Growth hormone deficiency in child --> failure to grow; GH deficiency in adult --> ___ fat + ___ lean body mass + fatigue GH deficiency is MC d/t pituitary tumor (___ effect or radiation therapy) - tx w/synthetic GH and monitor w/serum IGF-1 --- GH excess is most commonly d/t somatotroph (pituitary) adenoma - will p/w HA + b___ h___; GHRH-secreting tumors can happen, but are rare GH excess in children --> ___ GH excess in adults --> ___, p/w enlarged jaw + coarse facial features (enlarged nose + frontal bones + enlarged hands and feet, "*___ increasing*"); additionally, because GH decreases glucose uptake in cells (want more sugar for growing brain) --> can develop insulin ___ + diabetes Acromegaly can l/t visceral organ enlargement, synovial tissue/cartilage enlargement (joint pain), and cardiovascular dz (___ - errthang gets big) Dx: serum ___, oral glucose tolerance test w/inability to suppress GH Tx: ___ (monitor IGF-1)

Growth hormone deficiency in child --> failure to grow; GH deficiency in adult --> increased fat + decreased lean body mass + fatigue GH deficiency is MC d/t pituitary tumor (mass effect or radiation therapy) - tx w/synthetic GH and monitor w/serum IGF-1 --- GH excess is most commonly d/t somatotroph (pituitary) adenoma - will p/w HA + bitemporal hemianopsia; GHRH-secreting tumors can happen, but are rare GH excess in children --> gigantism GH excess in adults --> acromegaly, p/w enlarged jaw + coarse facial features (enlarged nose + frontal bones + enlarged hands and feet, "*shoe size increasing*"); additionally, because GH decreases glucose uptake in cells --> can develop insulin resistance + diabetes Acromegaly can l/t visceral organ enlargement, synovial tissue/cartilage enlargement (joint pain), and cardiovascular dz (cardiomyopathy - errthang gets big) Dx: serum IGF-1, oral glucose tolerance test w/inability to suppress GH Tx: octreotide (monitor IGF-1)

Guillain-Barre syndrome is acute (days-to-weeks) ___ muscle weakness 2/2 Schwann cell destruction (___neurium); ___ failure is the most concerning outcome ___ dysfunction can also occur with tachycardia, urinary retention, and ___ leading to SCD Common infectious causes include ___ and ___ CSF demonstrates ___ protein level with ___ cell count Treatment involves ___ support, plasmapheresis, and ___

Guillain-Barre syndrome is acute (days-to-weeks) ascending muscle weakness 2/2 Schwann cell destruction (endoneurium); respiratory failure is the most concerning outcome Autonomic dysfunction can also occur with tachycardia, urinary retention, and arrhythmias leading to SCD Common infectious causes include Campylobacter and CMV CSF demonstrates elevated protein level with normal cell count Treatment involves respiratory support, plasmapheresis, and IVIG

HEREDITARY HEMOCHROMATOSIS: -Labs: ___ iron, ___ ferritin, ___ transferrin, ___ transferrin saturation -Biopsy: P___ blue staining (blue granules d/t iron dep.) -Imaging: "___" appearance of liver -Diagnosis: genetic testing for ___282___ mutation -Treatment: p___ + iron-chelating agents (rarely used, usually saved for secondary hemochromatosis 2/2 transfusion - deferoxamine)

HEREDITARY HEMOCHROMATOSIS: -Labs: elevated iron, elevated ferritin, decreased transferrin, elevated transferrin saturation -Biopsy: Prussian blue staining (blue granules d/t iron dep.) -Imaging: "black" appearance of liver -Diagnosis: genetic testing for C282Y mutation -Treatment: phlebotomy + iron-chelating agents (rarely used, usually saved for secondary hemochromatosis 2/2 transfusion - deferoxamine)

HEREDITARY THROMBOPHILIAS (*all autosomal ___*): Factor V Leiden l/t factor V that is not inactivated by ___ - factor V is activated longer --> hypercoagulability FVL mutation is a ___ mutation resulting in a single AA change (guanine --> adenine, Arg506Gln) Can l/t DVT, cerebral vein thrombosis, and *recurrent ___ loss* --- ___ gene mutation is 2/2 point mutation (guanine --> adenine) that l/t increased production of thrombin --> increased risk of venous clots --- Antithrombin ___ deficiency can be inherited or acquired (liver dz, nephrotic syndrome, DIC) - results in *___ resistance (diminishes increase in PTT when given heparin)* --- Protein C or S deficiency l/t inability to activate factors ___ and ___ When these pts are given warfarin, *l/t warfarin-induced ___ (warfarin --> marked decrease in protein ___ --> thrombosis of skin tissue)*

HEREDITARY THROMBOPHILIAS (*all autosomal DOMINANT*): Factor V Leiden l/t factor V that is not inactivated by protein C - factor V is activated longer --> hypercoagulability FVL mutation is a point mutation resulting in a single AA change (guanine --> adenine, Arg506Gln) Can l/t DVT, cerebral vein thrombosis, and *recurrent pregnancy loss* --- Prothrombin 20210 gene mutation is 2/2 point mutation (guanine --> adenine) that l/t increased production of thrombin --> increased risk of venous clots --- Antithrombin III deficiency can be inherited or acquired (liver dz, nephrotic syndrome, DIC) - results in *heparin resistance (diminishes increase in PTT when given heparin)* --- Protein C or S deficiency l/t inability to activate factors V and VIII When these pts are given warfarin, *l/t warfarin-induced skin necrosis (warfarin --> marked decrease in protein C --> thrombosis of skin tissue)*

HIP MUSCLES: -Flexors: *___*, TFL, sartorius, pectineus -Extensors: ___, hamstrings (semiM., semiT.) -___: glut. med. and glut. min. -___: add. magnus, add. longus, add. brevis -___: glut. max., piriformis, obturator internus -IntRot: glut. med., glut. min., TFL (not a HY motion)

HIP MUSCLES: -Flexors: *iliopsoas*, TFL, sartorius, pectineus -Extensors: glut. max., hamstrings (semiM., semiT.) -Abductors: glut. med. and glut. min. -Adductors: add. magnus, add. longus, add. brevis -ExtRot: glut. max., piriformis, obturator internus -IntRot: glut. med., glut. min., TFL (not a HY motion)

HIT is a type ___ HS rxn d/t Abs against heparin-PF4 complexes - this p/w abrupt drop in platelets (>50% original) + ___ thrombosis (can dx w/HIT Ab testing); pts w/HIT must d/c heparin and *start a new anti-___ drug (i.e., direct thrombin inhibitor), d/t hypercoaguable state!* --- LMWH does not require PTT monitoring - however, if obese/renal failure, can check anti ___ levels --- Dabigatran is a direct ___ inhibitor --- Only drugs that affect thrombin time are direct thrombin inhibitors and ___ heparin (both affect thrombin directly) --- Warfarin functions to inhibit vitamin K epoxide reductase; vitamin K comes from green leafy vegetables (K1 form) and ___ (K2 form) Warfarin skin necrosis is more common in patients w/*__ deficiency* Congenital warfarin syndrome (i.e., teratogenic effects of warfarin) p/w ___ hypoplasia Benefit to warfarin to NOACs is cost and no ___ agents for NOACs (in development - can reverse warfarin w/FFP + VitK)

HIT is a type II HS rxn d/t Abs against heparin-PF4 complexes - this p/w abrupt drop in platelets (>50% original) + arterial/venous thrombosis (can dx w/HIT Ab testing); pts w/HIT must d/c heparin and *start a new anti-thrombotic drug (i.e., direct thrombin inhibitor), d/t hypercoaguable state!* --- LMWH does not require PTT monitoring - however, if obese/renal failure, can check anti Xa levels --- Dabigatran is a direct thrombin inhibitor --- Only drugs that affect thrombin time are direct thrombin inhibitors and unfractionated heparin (both affect thrombin directly) --- Warfarin functions to inhibit vitamin K epoxide reductase; vitamin K comes from green leafy vegetables (K1 form) and GI bacteria (K2 form) Warfarin skin necrosis is more common in patients w/*protein C deficiency* Congenital warfarin syndrome (i.e., teratogenic effects of warfarin) p/w limb hypoplasia Benefit to warfarin to NOACs is cost and no reversal agents for NOACs (in development - can reverse warfarin w/FFP + VitK)

HODGKIN SUBTYPES: Nodular Lymphocyte Predominant (not in FirstAid): rare variant of HL w/Reed Sternberg variant ("___" LP cells), express CD___ (not CD15 or CD30 seen in traditional HL) --- *Nodular Sclerosing*: MC type w/___ tissue surrounding RS cells --> nodules; more common in ___ (M or W?) (*unique!*) and often p/w *___ mass on CXR!* - slow growing lymphoma w/best prognosis --- *Mixed Cellularity*: look for ___ --- *Lymphocyte Rich*: ___ prognosis --- *Lymphocyte Depleted*: ___ prognosis

HODGKIN SUBTYPES: Nodular Lymphocyte Predominant (not in FirstAid): rare variant of HL w/Reed Sternberg variant ("popcorn" LP cells), express CD20 (not CD15 or CD30 seen in traditional HL) --- *Nodular Sclerosing*: MC type w/fibrous tissue surrounding RS cells --> nodules; more common in women (*unique!*) and often p/w *mediastinal mass on CXR!* - slow growing lymphoma w/best prognosis --- *Mixed Cellularity*: look for eosinophils --- *Lymphocyte Rich*: good prognosis --- *Lymphocyte Depleted*: shitty prognosis

CLASSIC CASE: farmer/bird handler w/cough, dyspnea, chest tightness + diffuse crackles on lung exam; what is going on? what is underlying mechanism?

HYPERSENSITIVITY PNEUMONITIS - dx is challenging, but tx is avoiding triggers Mixed type III/IV HS rxn to environmental antigens Can lead to irreversible fibrosis if can't avoid triggers

HYPERTHYROID D/Os: *Grave's Dz*: autoimmune dz w/TSHr antibodies; p/w *___ (bulging eyes) and ___ myxedema [KNOW THESE TWO]*, d/t *[HY] T-cells activating ___ --> fibroblast secretion of ___!)* Dx: exophthalmos + hyperthyroid labs Tx: beta blockers, thionamides --> radioactive iodine or surgery *Thyroid Storm Tx*: ___, thionamides (PTU, methimazole), ___ (Wolf-Chaikoff), steroids NOTE: Grave's ophthalmopathy can be persistent - continue treating w/steroids, radiation, or surgery --- *Thyroid Adenoma/Toxic Multinodular Goiter*: nodule(s) in thyroid that functions independently (mutated ___ --> do not respond to TSH, constitutively active); on exam, palpable thyroid nodule + hyperthyroid labs Tx: radioactive iodine or surgery NOTE: radioactive iodine reveals "___" nodule --> usually thyroid adenoma --- *Jod-Basedow PhenomenON (oppo. to WolChaik)*: iodine-induced ___ - occurs when pt w/iodine deficiency or toxic adenoma is given large amount of iodine (amiodarone, contrast dye) --- Amiodarone can can cause hyperthyroidism via two mechanisms: type I) amiodarone provides iodine to those w/pre-existing thyroid adenoma (___) or type II) amiodarone-induced ___

HYPERTHYROID D/Os: *Grave's Dz*: autoimmune dz w/TSHr antibodies; p/w *exophthalmos (bulging eyes) and pretibial myxedema [KNOW THESE TWO]*, d/t *[HY] T-cells activating fibroblast --> fibroblast secretion of GAGs!)* Dx: exophthalmos + hyperthyroid labs Tx: beta blockers, thionamides --> radioactive iodine or surgery *Thyroid Storm Tx*: propranolol, thionamides (PTU, methimazole), SSKI (Wolf-Chaikoff), steroids NOTE: Grave's ophthalmopathy can be persistent - continue treating w/steroids, radiation, or surgery --- *Thyroid Adenoma/Toxic Multinodular Goiter*: nodule(s) in thyroid that functions independently (mutated TSHr --> do not respond to TSH, constitutively active); on exam, palpable thyroid nodule + hyperthyroid labs Tx: radioactive iodine or surgery NOTE: radioactive iodine reveals "hot" nodule --> usually thyroid adenoma --- *Jod-Basedow PhenomenON (oppo. to WolChaik)*: iodine-induced hyperthyroidism - occurs when pt w/iodine deficiency or toxic adenoma is given large amount of iodine (amiodarone, contrast dye) --- Amiodarone can can cause hyperthyroidism via two mechanisms: type I) amiodarone provides iodine to those w/pre-existing thyroid adenoma (Jod-Basedow) or type II) amiodarone-induced thyroiditis

HYPERTHYROID SYMPTOMS: Metabolic: ___ intolerance, increased sweat, weight loss Skin/Hair: warm/moist skin, fine hair and nails, ___ myxedema (in Graves dz) MSK: thyrotoxic myopathy (*proximal muscle weakness w/___ CK*) Cardiovascular: tachycardia w/*___ (check TSH in new onset ___)* Neuropsychiatric: hyperactivity, restlessness, anxiety, insomnia, tremors GI: ___ (errthang speeds up) --- Thyroid Storm (thyrotoxicosis) is life-threatening hyperthyroidism usually precipitated by acute event (Grave's + trauma), leading to massive catecholamine surge --> fever w/delirium, tachycardia (*death from ___*), hyperglycemia, hypocalcemia

HYPERTHYROID SYMPTOMS: Metabolic: heat intolerance, increased sweat, weight loss Skin/Hair: warm/moist skin, fine hair and nails, pretibial myxedema (in Graves dz) MSK: thyrotoxic myopathy (*proximal muscle weakness w/normal CK*) Cardiovascular: tachycardia w/*ARRHYTHMIAS (check TSH in new onset Afib)* Neuropsychiatric: hyperactivity, restlessness, anxiety, insomnia, tremors GI: diarrhea (errthang speeds up) --- Thyroid Storm (thyrotoxicosis) is life-threatening hyperthyroidism usually precipitated by acute event (Grave's + trauma), leading to massive catecholamine surge --> fever w/delirium, tachycardia (*death from arrhythmia*), hyperglycemia, hypocalcemia

HYPOTHYROID SYMPTOMS: Metabolic: ___ intolerance, decreased sweat, weight gain, hyponatremia (SIADH) Skin/Hair: dry/cool skin, ___ hair and nails, periorbital/facial ___ (non-pitting edema of the skin d/t hyaluronic acid deposits in dermis --> draws water out --> SWELLING) MSK: hypothyroid myopathy (*___ muscle weakness w/___ CK*), CTS Cardiovascular: bradycardia Neuropsychiatric: lethargy, fatigue, depression, hyporeflexia GI: ___ (errthang slows down) --- Goiter occurs when high ___ (usually hypothyroid state - trying to get more T3/T4 going, but can't - TSH stimulates thyroid growth)

HYPOTHYROID SYMPTOMS: Metabolic: cold intolerance, decreased sweat, weight gain, hyponatremia (SIADH) Skin/Hair: dry/cool skin, coarse/brittle hair and nails, periorbital/facial myxedema (non-pitting edema of the skin d/t hyaluronic acid deposits in dermis --> draws water out --> SWELLING) MSK: hypothyroid myopathy (*proximal muscle weakness w/elevated CK*), CTS Cardiovascular: bradycardia Neuropsychiatric: lethargy, fatigue, depression, hyporeflexia GI: constipation (errthang slows down) --- Goiter occurs when high TSH (usually hypothyroid state - trying to get more T3/T4 going, but can't - TSH stimulates thyroid growth)

HYPOTHYROIDISM D/Os: *Endemic ___*: d/t iodine deficiency - seen in mountainous area d/t iodine runoff; chronically elevated TSH --> thyroid hypertrophy --- *Iodine Excess*: Wolff-Chaik*OFF* effect (___ inhibited by high iodide) NOTE: goitrogen is substance that inhibits TH production; most common is iodine but most *[HY] is ___ (psych drug)* --- *___ (drug?) Hypothyroidism*: excess iodine --> WC-effect, normal pts can usually "escape" this effect after several weeks on drug --- *Congenital Hypothyroidism (formerly cretinism*: childhood depletion in thyroid hormone (thyroid dysgenesis, *iodine deficiency*, IEM) --> cretinism w/ abnormal ___ growth + ___ maturation Can p/w (3 Ps) poor brain development + poor bone development + *protruding ___ (umbilical hernia)* --- *Iatrogenic hypothyroidism* can be 2/2 thyroid surgery (for Grave's or malignancy), radioiodine therapy, neck radiation (___ lymphoma, SCC of neck) --- *Plus late ___ (Hashimoto's, Riedel, subacute granulomatous) - covered in a different card*

HYPOTHYROIDISM D/Os: *Endemic Goiter*: d/t iodine deficiency - seen in mountainous area d/t iodine runoff; chronically elevated TSH --> thyroid hypertrophy --- *Iodine Excess*: Wolff-Chaik*OFF* effect (organification inhibited by high iodide) NOTE: goitrogen is substance that inhibits TH production; most common is iodine but most *[HY] is lithium (psych drug)* --- *Amiodarone Hypothyroidism*: excess iodine --> WC-effect, normal pts can usually "escape" this effect after several weeks on drug --- *Congenital Hypothyroidism (formerly cretinism*: childhood depletion in thyroid hormone (thyroid dysgenesis, *iodine deficiency*, IEM) --> cretinism w/ abnormal bone growth + CNS maturation Can p/w (3 Ps) poor brain development + poor bone development + *protruding umbilicus (umbilical hernia)* --- *Iatrogenic hypothyroidism* can be 2/2 thyroid surgery (for Grave's or malignancy), radioiodine therapy, neck radiation (Hodgkin's lymphoma, SCC of neck) --- *Plus late THYROIDITIS (Hashimoto's, Riedel, subacute granulomatous) - covered in a different card*

Hairy Cell Leukemia is a rare chronic (mature) ___-cell malignancy with peripheral smear revealing lymphocytes w/"hair-like" cytoplasm projections (look for CD___) HCL p/w *massive ___ d/t engorged red pulp (w/malignant cells - can p/w abdominal pain)*, "___ tap" on bone marrow (d/t *bone marrow fibrosis/obliteration)*, and *t___ (___ - catches bear from sketchy?) staining* *Tx: cladribine (purine analog)* ^TRAPped in Hairy situation

Hairy Cell Leukemia is a rare chronic (mature) B-cell malignancy with peripheral smear revealing lymphocytes w/"hair-like" cytoplasm projections (look for CD103) HCL p/w *massive splenomegaly d/t engorged red pulp (w/malignant cells - can p/w abdominal pain)*, "dry tap" on bone marrow (d/t *bone marrow fibrosis/obliteration)*, and *tartrate-resistant acid phosphatase (TRAP) staining* *Tx: cladribine (purine analog)* ^TRAPped in Hairy situation

Half-life is time required to change amount of drug by 1/2 (i.e., time for [drug] to fall 50%) Depends on ___ and Clearance (T-0.5 = [0.7 x Vd] / [CL]) - in general, takes 4 half-lives for drug to no longer have effect NOTE: *[HY] w/repeat dosing, takes ~___ doses to reach steady state* ___ Dose: give just enough to replace what was eliminated ___ Dose: give lots right away to get to steady state quickly (used when T-0.5 is high) For MD: dose Rate = Elimination Rate = ([Drug conc.] x [Clearance]) (if bioavailability is <100% [i.e., oral admin.], then divide target dose by bioavailability to make up for amount lost [Dose Rate / F], [[Drug] x [Clearance]] / F) *[HY] LD = ([steady state drug conc.] x Vd) / F* For LD: *[HY] ([steady state drug conc.] x ___) / ___* *[HY] In kidney/liver dz, ___ dose may fall (prolongs T-0.5), but ___ dose is unchanged*

Half-life is time required to change amount of drug by 1/2 (i.e., time for [drug] to fall 50%) Depends on Vd and Clearance (T-0.5 = [0.7 x Vd] / [CL]) - in general, takes 4 half-lives for drug to no longer have effect NOTE: *[HY] w/repeat dosing, takes ~4-5 doses to reach steady state* Maintenance Dose: give just enough to replace what was eliminated Loading Dose: give lots right away to get to steady state quickly (used when T-0.5 is high) For MD: dose Rate = Elimination Rate = ([Drug conc.] x [Clearance]) (if bioavailability is <100% [i.e., oral admin.], then divide target dose by bioavailability to make up for amount lost [Dose Rate / F], [[Drug] x [Clearance]] / F) *[HY] LD = ([steady state drug conc.] x Vd) / F* For LD: *[HY] ([steady state drug conc.] x Vd) / F* *[HY] In kidney/liver dz, maintenance dose may fall (prolongs T-0.5), but loading dose is unchanged*

Hardy-Weinberg Law (used in pop. studies) is used to derive genotypes from allele freq (used to study SINGLE GENES with mult. forms); *EX: A=0.4, a=0.6 (GENES; A+a=___) --> AA=0.16, Aa=0.48 (2Aa), aa=0.36 (INDIVIDUALS; A^2 + 2Aa + a^2 = ___) [know how to get there intuitively!]*; HWL useful in AR dz (if sick from dz, will come to attn - *will be how tested*) Assumptions to HW Law: large pop., random mating, no muts, no migration in/out, no natural selection; if assumptions met --> allele freq doesn't change over generations ("HW equilibrium") EX: AR Dz A (aa) present in 1/4500 kids (1/4500 = 0.0002 = aa; sqrt[0.0002] = 0.015 = a; A = ___); accordingly, carrier freq. is (2 x A x a) = ~0.03 (3% of pop are carriers!); in rare Dz (A~1), Aa=___ X-linked rec dz is unique (XnY, XdY, XnXd, XdXd) - must consider males and females separately; b/c males have one X, A=healthy males and a=dz males; among females, AA=healthy females, 2Aa=carrier females, aa=dz females

Hardy-Weinberg Law (used in pop. studies) is used to derive genotypes from allele freq (used to study SINGLE GENES with mult. forms); *EX: A=0.4, a=0.6 (GENES; A+a=1^) --> AA=0.16, Aa=0.48 (2Aa), aa=0.36 (INDIVIDUALS; A^2 + 2Aa + a^2 = 1) [know how to get there intuitively!]*; HWL useful in AR dz (if sick from dz, will come to attn - *will be how tested*) Assumptions to HW Law: large pop., random mating, no muts, no migration in/out, no natural selection; if assumptions met --> allele freq doesn't change over generations ("HW equilibrium") EX: AR Dz A (aa) present in 1/4500 kids (1/4500 = 0.0002 = aa; sqrt[0.0002] = 0.015 = a; A = 1 - 0.015 = 0.985); accordingly, carrier freq. is (2 x A x a) = ~0.03 (3% of pop are carriers!); in rare Dz (A~1), Aa=2[a] X-linked rec dz is unique (XnY, XdY, XnXd, XdXd) - must consider males and females separately; b/c males have one X, A=healthy males and a=dz males; among females, A*A=healthy females, 2A*a=carrier females, a*a=dz females

Hemoglobin C is rare mutation of beta gene in which glutamate is replaced by ___ (E6K, not E6V); because lysine is more polar than valine, sx are more mild than that of sickle cell anemia Hemoglobin C induces dehydration in RBCs, manifesting with *HbC ___ on smear - will also see elevated MCHC* HbSC is one S and one C gene - pts are at risk for same complications as SCD, but with ___ frequency of complications (i.e., milder dz)

Hemoglobin C is rare mutation of beta gene in which glutamate is replaced by LYSINE (E6K, not E6V); because lysine is more polar than valine, sx are more mild than that of sickle cell anemia Hemoglobin C induces dehydration in RBCs, manifesting with *HbC crystals on smear - will also see elevated MCHC* HbSC is one S and one C gene - pts are at risk for same complications as SCD, but with lower frequency of complications (i.e., milder dz)

Hemolysis causes a normocytic anemia (non-hemolytic normocytic anemia is 2/2 decreased ___^ [low iron, low EPO, abnormal marrow]) Hemolytic anemias can be ___ (i.e., something extrinsic to RBC [Abs, mechanical trauma, RBC infxn - AIHA, MAHA]) or ___ (i.e., something intrinsic to RBC [hereditary spherocytosis, G6PD deficiency, sickle cell, HgbC, PK deficiency, PNH]) Hemolytic anemias can also be classified based on where hemolysis occurs (intravascular vs. extravascular [liver and ___]) Any hemolytic anemia will p/w *normocytic anemia + ___ LDH (glycolysis enzyme that spills out of broken RBCs) + ___ reticulocyte count^ (usually 1-2% peripheral blood - increases to compensate for hemolysis) + elevated unconjugated bilirubin (remember - can lead to pigmented, radiopaque stones) +/- ___ haptoglobin (free haptoglobin functions to bind Hgb - Haptoglobin is much lower in ___VASCULAR hemolysis) +/- hemoglobinuria (seen in ___VASCULAR hemolysis --> more free Hgb, can l/t Hgb in urine w.o RBCs [also seen in rhabdo])* Reticulocyte count is KEY for distinguishing normocytic anemias! If low (<2%) --> decreased ___, if high (>2%) --> increased ___ *MUST USE CORRECTED RETIC COUNT: %retics x [HCT/45]* (retic % goes up in anemia d/t lower hct, need to correct for this!)

Hemolysis causes a normocytic anemia (non-hemolytic normocytic anemia is 2/2 decreased production^ [low iron, low EPO, abnormal marrow]) Hemolytic anemias can be extrinsic (i.e., something extrinsic to RBC [Abs, mechanical trauma, RBC infxn - AIHA, MAHA]) or intrinsic (i.e., something intrinsic to RBC [hereditary spherocytosis, G6PD deficiency, sickle cell, HgbC, PK deficiency, PNH]) Hemolytic anemias can also be classified based on where hemolysis occurs (intravascular vs. extravascular [liver and spleen]) Any hemolytic anemia will p/w *normocytic anemia + elevated LDH (glycolysis enzyme that spills out of broken RBCs) + increased reticulocyte count^ (usually 1-2% peripheral blood - increases to compensate for hemolysis) + elevated unconjugated bilirubin (remember - can lead to pigmented, radiopaque stones) +/- decreased haptoglobin (free haptoglobin functions to bind Hgb - Haptoglobin is much lower in INTRAVASCULAR hemolysis) +/- hemoglobinuria (seen in INTRAVASCULAR hemolysis --> more free Hgb, can l/t Hgb in urine w.o RBCs [also seen in rhabdo])* Reticulocyte count is KEY for distinguishing normocytic anemias! If low (<2%) --> decreased production, if high (>2%) --> increased destruction *MUST USE CORRECTED RETIC COUNT: %retics x [HCT/45]* (retic % goes up in anemia d/t lower hct, need to correct for this!)

Hemophilias are ___(inheritance?) d.o and include Hemophilia A (factor VIII deficiency) and Hemophilia B (factor IX deficiency) Hemophilia p/w spontaneous, easy bruising + recurrent ___ bleeds; in hemophilia, ___ will be prolonged (factors VIII and IX are part of ___ pathway) - all other tests will be normal Tx w/factor replacement or *___ in hemophilia A (increases vWF & factor VIII levels, both stored in Weibel-Palade bodies of endothelial cells - also used in vWF dz, central DI, en___)* C___ has historically been used to tx hemophilia A - contains factor VIII and fibrinogen (also factor XIII, vWF), now primarily used for DIC and massive trauma

Hemophilias are X-rec d.o and include Hemophilia A (factor VIII deficiency) and Hemophilia B (factor IX deficiency) Hemophilia p/w spontaneous, easy bruising + recurrent joint bleeds; in hemophilia, PTT will be prolonged (factors VIII and IX are part of extrinsic pathway) - all other tests will be normal Tx w/factor replacement or *DESMOPRESSIN in hemophilia A (increases vWF & factor VIII levels, both stored in Weibel-Palade bodies of endothelial cells - also used in vWF dz, central DI, enuresis)* Cryoprecipitate has historically been used to tx hemophilia A - contains factor VIII and fibrinogen (also factor XIII, vWF), now primarily used for DIC and massive trauma

___ is benign liver tumor of epithelial cell, commonly seen in women taking anabolic steroids (body builders) or OCPs (*may rupture during pregnancy --> shock*, may remove tumor prior to preg.) ___ are most common benign liver tumor composed of vascular spaces w/thrombus - can lead to fatal hemorrhage w/biopsy (try to avoid this) Hepatic Angiosarcomas are malignant vascular tumor *a/w v___ (PVC plastic) and a___ exposure!* ___ is common in women and is *hyperplastic rxn of hepatocytes to aberrant artery* - will see central stellate scar on imaging

Hepatic Adenoma is benign liver tumor of epithelial cell, commonly seen in women taking anabolic steroids (body builders) or OCPs (*may rupture during pregnancy --> shock*, may remove tumor prior to preg.) Hepatic Hemangioma are most common benign liver tumor composed of vascular spaces w/thrombus - can lead to fatal hemorrhage w/biopsy (try to avoid this) Hepatic Angiosarcomas^ are malignant vascular tumor *a/w vinyl chloride (PVC plastic) and arsenic exposure!* [Angiosarcoma is Vascular, a/w Arsenic & Vinyl chloride] Focal nodular hyperplasia is common in women and is *hyperplastic rxn of hepatocytes to aberrant artery* - will see central stellate scar on imaging ^Angiosarcoma is Vascular, a/w Arsenic & Vinyl chloride

Hepatocellular carcinoma is usually seen ISO c___ l___ dz (hepatitis B/C, alcoholic cirrhosis, Wilson's dz, hemochromatosis, alpha-1 anti-trypsin deficiency) ___ can also cause HCC 2/2 aflatoxin that contaminates corn, soybean, and peanuts (not seen in industrialized countries) HCC is often asymptomatic (*screen high risk pts as mentioned above!*), may see abnormal LFTs, hepatomegaly, liver failure Large HCC can cause *___ (high metabolic rate --> eat up the glucose)*, erhtyrocytosis, and *___ Syndrome (hypercoaguable state + compression on venous structures = hepatic vein occlusion; TRIAD: abrupt onset abdominal pain, ascites, hepatomegaly)* HCC lab marker includes elevated ___ (not specific - can be elevated in chronic liver dz); primary dx is via imaging + biopsy Mets can go to *___* via hematogenous spread (sometimes bone)

Hepatocellular carcinoma is usually seen ISO chronic liver dz (hepatitis B/C, alcoholic cirrhosis, Wilson's dz, hemochromatosis, alpha-1 anti-trypsin deficiency) Aspergillus can also cause HCC 2/2 aflatoxin that contaminates corn, soybean, and peanuts (not seen in industrialized countries) HCC is often asymptomatic (*screen high risk pts as mentioned above!*), may see abnormal LFTs, hepatomegaly, liver failure Large HCC can cause *hypoglycemia (high metabolic rate --> eat up the glucose)*, erhtyrocytosis, and *Budd-Chiari Syndrome (hypercoaguable state + compression on venous structures = hepatic vein occlusion; TRIAD: abrupt onset abdominal pain, ascites, hepatomegaly)* HCC lab marker includes elevated AFP (not specific - can be elevated in chronic liver dz); primary dx is via imaging + biopsy Mets can go to *LUNG* via hematogenous spread (sometimes bone) ^Hepatic --> Hematogenous spread

Hereditary hemochromatosis is AR dz of iron metabolism 2/2 mutation in H___ gene (C___Y substitution [may also see H63D] on chrom6) [Hereditary FE] Enterocytes absorb iron (in Fe___+ form - all heme iron is this way, free Fe3+ must be reduced by Vit___), but very few ways to get rid of iron ___ mutation --> unregulated iron absorption of both heme and non-heme iron --> iron accumulation HH presents in adulthood (later in females 2/2 menstruation) w/*___ dz (cirrhosis, HCC), ___ (diabetes), skin [termed BRONZE DIABETES]* - can also infiltrate heart (___-CM), j___, and testes (impotence) *[HY] HH pts should avoid ___ (accelerates liver dz) and Vit___ (increases iron absorption!)* Secondary hemochromatosis (not d/t mutation) can be seen in blood transfusions - seen in ___ (organ system?) d/o requiring chronic transfusions (thalassemia, MDS, leukemia, SCA)

Hereditary hemochromatosis is AR dz of iron metabolism 2/2 mutation in HFE gene (C282Y substitution [may also see H63D] on chrom6) Enterocytes absorb iron (in Fe2+ form - all heme iron is this way, free Fe3+ must be reduced by VitC), but very few ways to get rid of iron HFE mutation --> unregulated iron absorption of both heme and non-heme iron --> iron accumulation HH presents in adulthood (later in females 2/2 menstruation) w/*liver dz (cirrhosis, HCC), pancreas (diabetes), skin [termed BRONZE DIABETES]* - can also infiltrate heart (Dilated-CM), joints, and testes (impotence) *[HY] HH pts should avoid alcohol (accelerates liver dz) and VitC (increases iron absorption!)* Secondary hemochromatosis (not d/t mutation) can be seen in blood transfusions - seen in hematologic d/o requiring chronic transfusions (thalassemia, MDS, leukema, SCA) ^Vocab: ferritin --> iron storage protein in plasma; hemosiderin --> iron storage product in macrophages (not measured clinically, but seen on path slides)

Hereditary spherocytosis (*autosomal ___*) is d/t defect in *RBC proteins (___ [MC, begins w/SP], ankyrin, band 3, protein 4.2) that l/t RIGID membrane* O2 carrying function is normal, but pts have problems d/t *chronic destruction in ___ --> splenomegaly + hyperbilirubinemia, jaundice, and pigment (bilirubin) gallstones* Classic labs are *___ MCHC (higher volume:surface area ratio than normal), ___ RDW (membrane loss is gradual over time)*, low-to-normal MCV (reticulocytes have high MCV --> average is ~normal) Pts are at risk for aplastic crisis d/t *___ inxn (infects progenitor cells --> retic count can't keep up with hemolysis)* *[HY] ___ are what will help you differentiate HS vs. G6PD (NOT seen in G6PD!)* Dx: osmotic ___ test (increased fragility in spherocytes d/t poor ability to swell in hypotonic solution!) Tx: splenectomy (will result in ___-Jolly bodies on peripheral smear) [HS has cardiovascular tie in, d/t increased viscosity of blood --> increased ___ to flow --> necessitates increased contractility]

Hereditary spherocytosis (*autosomal DOMINANT*) is d/t defect in *RBC proteins (SPECTRIN [MC, begins w/SP], ankyrin, band 3, protein 4.2) that l/t RIGID membrane* O2 carrying function is normal, but pts have problems d/t *chronic destruction in spleen --> splenomegaly + hyperbilirubinemia, jaundice, and pigment (bilirubin) gallstones* Classic labs are *elevated MCHC (higher volume:surface area ratio than normal), high RDW (membrane loss is gradual over time)*, low-to-normal MCV (reticulocytes have high MCV --> average is ~normal) Pts are at risk for aplastic crisis d/t *Parvovirus B19 inxn (infects progenitor cells --> retic count can't keep up with hemolysis)* *[HY] Spherocytes are what will help you differentiate HS vs. G6PD (NOT seen in G6PD!)* Dx: osmotic fragility test (increased fragility in spherocytes d/t poor ability to swell in hypotonic solution!) Tx: splenectomy (will result in Howell-Jolly bodies on peripheral smear) [HS has cardiovascular tie in, d/t increased viscosity of blood --> increased resistance to flow --> necessitates increased contractility]

Heyde's Syndrome (not HY) is GI bleeding a/w aortic stenosis - pts w/aortic stenosis have increased risk of *___ (vascular malformations of GI tract)* + deficiency of vWF (*high shear stress of aortic stenosis --> uncoiling of vWF --> overactivity of ___*) Sx improve after aortic valve surgery

Heyde's Syndrome (not HY) is GI bleeding a/w aortic stenosis - pts w/aortic stenosis have increased risk of *angiodysplasia (vascular malformations of GI tract)* + deficiency of vWF (*high shear stress of aortic stenosis --> uncoiling of vWF --> overactivity of ADAMTS13*) Sx improve after aortic valve surgery

Hgb A contains two alpha, two beta, and four heme molecules (A2 has two ___, F has two ___); heme contains iron in middle w/porphyrin ring surrounding (___ binds oxygen) 2,3-BPG promotes O2 release from Hgb (___ O2 affinity --> ___ O2 delivery to tissues, useful in highly metabolic states that need rightward shift of O-H-D-C) Hgb can exist as Taut form (___ O2 affinity - release O2 in Tissues that need O2 [low pH, high CO2]) or Relaxed form (___ O2 affinity - pick up O2 from Respiratory tract [high pH, low CO2]) HgB has sigmoidal shape curve d/t *c___ (1st O2 molecule makes 2nd O2 molecule more likely to bind - increases affinity for 2nd molecule), an example of a___ protein effect (POSITIVE ALLOSTERIC EFFECT)* Other allosteric effectors include pH, temperature, 2,3-BPG, CO2 (right shift [more likely to unload O2] - acidic [___ H+], ___ pCO2, ___ 2,3-BPG, ___ altitude, ___ temperature; *High ACE BATs RIGHT-handed*) Hgb F (higher O2 affinity) has left-shift

Hgb A contains two alpha, two beta, and four heme molecules (A2 has two delta, F has two gamma); heme contains iron in middle w/porphyrin ring surrounding (iron binds oxygen) 2,3-BPG promotes O2 release from Hgb (decrease O2 affinity --> increase O2 delivery to tissues, useful in highly metabolic states that need rightward shift of O-H-D-C) Hgb can exist as Taut form (low O2 affinity - release O2 in Tissues that need O2 [low pH, high CO2]) or Relaxed form (high O2 affinity - pick up O2 from Respiratory tract [high pH, low CO2]) HgB has sigmoidal shape curve d/t *cooperativity (1st O2 molecule makes 2nd O2 molecule more likely to bind - increases affinity for 2nd molecule), an example of allosteric protein effect (POSITIVE ALLOSTERIC EFFECT)* Other allosteric effectors include pH, temperature, 2,3-BPG, CO2 (right shift [more likely to unload O2] - acidic [high H+], high pCO2, high 2,3-BPG, high altitude, high temperature; *High ACE BATs RIGHT-handed*) Hgb F (higher O2 affinity) has left-shift

High risk polyps include ___ histology, high grade dysplasia, multiple polyps, >1cm MC colonic polyp is ___ polyp - common @ rectosigmoid junction w/normal cellular structure (no dysplasia) w/"saw tooth" or serrated pattern - no change in screening Adenomatous polyps are dysplastic w/malignant potential - can be classified by shape (___ [broad base attached to colon] or ___ [attached via stalk]) and histology (tubular or villous) Histology is more important - tubular (MC) for tubules; ___ are often sessile and have high risk of malignant transformation Polyps are most often asymptomatic, but can p/w diarrheal illness - villous adenomas can cause *excessive mucous secretion + hypokalemia* (not super HY)

High risk polyps include villous histology, high grade dysplasia, multiple polyps, >1cm MC colonic polyp is hyperplastic polyp - common @ rectosigmoid junction w/normal cellular structure (no dysplasia) w/"saw tooth" or serrated pattern - no change in screening Adenomatous polyps are dysplastic w/malignant potential - can be classified by shape (sessile [broad base attached to colon] or pedunculated [attached via stalk]) and histology (tubular or villous) Histology is more important - tubular (MC) for tubules; villous are often sessile and have high risk of malignant transformation Polyps are most often asymptomatic, but can p/w diarrheal illness - villous adenomas can cause *excessive mucous secretion + hypokalemia*

Hirschsprung dz is congenital d/o a/w Down's; *[HY] HD is d/t failure of m___ of ___ cells (derived from n___ c___) in colon plexuses --> absent A___ and M___ plexus (no peristalsis can happen)* HD p/w dilated bowel behind obstruction + failure to pass meconium w/*no stool in rectal ___ (stool can't get to disease colon)*; classic imaging finding is *"transition zone" of normal (___) bowel to abnormal (___) bowel* Dx w/*rectal suction biopsy b/c [HY] ___ is ALWAYS involved & need to see submucosa to identify absence of ___ cells* Common Mut: ___ (RET in REcTum)

Hirschsprung dz is congenital d/o a/w Down's; *[HY] HD is d/t failure of migration of ganglion cells (derived from neural crest) in colon plexuses --> absent Auerbach's and Meissner's plexus (no peristalsis can happen)* HD p/w dilated bowel behind obstruction + failure to pass meconium w/*no stool in rectal vault (stool can't get to disease colon)*; classic imaging finding is *"transition zone" of normal (dilated) bowel to abnormal (narrow) bowel* Dx w/*rectal suction biopsy b/c [HY] rectum is ALWAYS involved & need to see submucosa to identify absence of ganglion cells* Common Mut: RET (RET in REcTum)

Histidine can be converted to histamine (require B6) -- Glycine can be converted to porphyrin --> heme (requires B6) *[HY] All carbon and nitrogen in porphyrin ring come from GLYCINE (AA) and SUCCINYL CoA (TCA cycle intermediate)* --- Arginine can be metabolized to creatinine, urea, and nitric oxide --- Glutamate can serve as excitatory neurotransmitter, or can be converted to GABA (inhibitory) via glutamate decarboxylase (requires B6 as cofactor)

Homocysteine, Cysteine, and Methionine are all related (methionine - essential, cysteine - nonessential [synthesized from methionine], homocysteine - nonstandard) Methionine is used to generate SAM; when SAM is used (Norepi --> Epi), you are left with homocysteine; homocysteine + serine --> cystathionine (via cystathionine synthase, requires B6) --> cysteine SUMMARY: methionine --> SAM --> homocysteine --> cystathionine --> cysteine --- Homocysteine is usually 5-15 micromoles/L; elevated homocysteine levels --> CV risk Severe homocysteine levels (*Homocystinuria*) are usually 2/2 defects in homocysteine metabolism enzymes (AR disorders) Homocystinuria usually p/w marfanoid habitus, lens dislocation, osteoporosis, *early atherosclerosis, mental retardation, blood clots (BOLD is UNIQUE to HOMOCYSTINURIA!!)* [Homocysteinuria, Osteoporosis, Marfanoid, Ocular dislocation (down and in), CV dz - HOMOCystinrua] Classic cause of homocysteinuria is *cystathionine synthase deficiency!* Tx: avoid methionine, increase cysteine and B6 --- Can also see homocysteinuria w/methionine synthase deficiency or MTHFR deficiency

Hypernatremia can be d/t 1) water loss or 2) diabetes insipidus Acquired diabetes insipidus can be d/t hypercalcemia, hypokalemia, *lithium, and amphotericin B* Sx of DI include polyuria + polydipsia Key test in DI is Uosm, which will be markedly low When you suspect dx --> fluid restrict and look for urine concentration and/or hypernatremia If kidneys respond to desmopressin --> central DI (tx w/desmopressin); If no response --> nephrogenic DI Thiazide diuretics and NSAIDs can also be used to tx DI

Hyperphosphatemia may p/w calci___ (renal stones, calcium deposit in medial artery layer) - can be d/t tumor lysis syndrome, rhabdomyolysis, *chronic kidney disease, and hypo___* Hypophosphatemia p/w *WEAKNESS (commonly ___ muscle weakness)* - can be 2/2 hyperparathyroidism, DKA, *___ syndrome*, and urinary wasting (Fanconi syndrome) --- Hypermagnesemia p/w *___ reflexes (remember nurse checking reflexes in PreE pts @ night during OBGYN!)*, bradycardia, hypotension, lethargy, and *hypo___ (2/2 CaSR sensing Mg as Ca --> less PTH release)* - most important cause of hypermagnesemia is kidney disease Hypomagnesemia p/w tetany, *[HY] HYPO___, HYPO___ (2/2 CaSR not working as well [needs some Mg to function] --> less PTH release), + arrhythmias (torsade de pointes)* - hypomagnesemia can be d/t GI losses, renal losses (loop diuretics + alcoholics), drugs (foscarnet, omeprazole)

Hyperphosphatemia may p/w calciphylaxis (renal stones, calcium deposit in medial artery layer) - can be d/t tumor lysis syndrome, rhabdomyolysis, *chronic kidney disease, and hypoparathyroidism* Hypophosphatemia p/w *WEAKNESS (commonly respiratory muscle weakness)* - can be 2/2 hyperparathyroidism, DKA, *refeeding syndrome*, and urinary wasting (Fanconi syndrome) --- Hypermagnesemia p/w *decreased reflexes (remember nurse checking reflexes in PreE pts @ night during OBGYN!)*, bradycardia, hypotension, lethargy, and *hypocalcemia (2/2 CaSR sensing Mg as Ca --> less PTH release)* - most important cause of hypermagnesemia is kidney disease Hypomagnesemia p/w tetany, *[HY] HYPOKALEMIA, HYPOCALCEMIA (2/2 CaSR not working as well [needs some Mg to function] --> less PTH release), + arrhythmias (torsade de pointes)* - hypomagnesemia can be d/t GI losses, renal losses (loop diuretics + alcoholics), drugs (foscarnet, omeprazole)

Hypo- and hypernatremia both effect the brain: ___ sodium --> fluid drawn into brain (cerebral edema), ___ sodium --> fluid drawn into tissues (cerebral shrinkage) Hyponatremia --> malaise, stupor, coma, and seizures Three key diagnostic tests for hyponatremia are: 1) plasma osmolality, 2) urine sodium, and 3) urine osmolality 1) Key solute in plasma osmolality is sodium - osmolality should be ___ in HYPOnatremia (check to make sure this is the case) Hyponatremia + high plasma osmolality --> hyper___ or m___ (both osmoles that draw water out of cells --> hyponatremia) Hyponatremia + normal plasma osmolality --> hyperlipidemia or hyperproteinemia (*pseudohyponatremia*) If low --> --- 2) Urinary sodium (low value --> low sodium intake/excess free water) --- 3) Urinary osmolality (low Uosm --> dilute, high Uosm --> concentrated)

Hypo- and hypernatremia both effect the brain: low sodium --> fluid drawn into brain (cerebral edema), high sodium --> fluid drawn into tissues (cerebral shrinkage) Hyponatremia --> malaise, stupor, coma, and seizures Three key diagnostic tests for hyponatremia are: 1) plasma osmolality, 2) urine sodium, and 3) urine osmolality 1) Key solute in plasma osmolality is sodium - osmolality should be LOW in HYPOnatremia (check to make sure this is the case) Hyponatremia + high plasma osmolality --> hyperglycemia or mannitol (both osmoles that draw water out of cells --> hyponatremia) Hyponatremia + normal plasma osmolality --> hyperlipidemia or hyperproteinemia (*pseudohyponatremia*) If low --> --- 2) Urinary sodium (low value --> low sodium intake/excess free water) --- 3) Urinary osmolality (low Uosm --> dilute, high Uosm --> concentrated)

Hypoparathyroidism is inappropriately low PTH secretion (i.e., not d/t hypercalcemia) - will p/w ___calcemia + low PTH Sx of hypocalcemia include neuromuscular irritability (N/T of hands, *peri___ tingling*) + tetany (*___ sign and Chvostek's sign*) MC cause is ___ (*look for post-op thyroidectomy pt who p/w N/T*), but can see it in other causes (hemochromatosis, Wilson's cancer) Autoimmune Polyendocrine Syndrome type I is a mutation in ___ --> hypoparathyroidism (+ adrenal insufficiency, recurrent candida infxns, chronic mucocutaneous candidiasis - if you don't have AIRE your body will CHAR) ___ can also cause hypoparathyroidism (triad: hypocalcemia, recurrent infxns, congenital heart defects)

Hypoparathyroidism is inappropriately low PTH secretion (i.e., not d/t hypercalcemia) - will p/w hypocalcemia + low PTH Sx of hypocalcemia include neuromuscular irritability (N/T of hands, *perioral tingling*) + tetany (*Trousseau's sign and Chvostek's sign*) MC cause is surgical excision (*look for post-op thyroidectomy pt who p/w N/T*), but can see it in other causes (hemochromatosis, Wilson's cancer) Autoimmune Polyendocrine Syndrome type I is a mutation in AIRE --> hypoparathyroidism (+ adrenal insufficiency, recurrent candida infxns, chronic mucocutaneous candidiasis - if you don't have AIRE your body will CHAR) Thymic aplasia (DiGeorge) can also cause hypoparathyroidism (triad: hypocalcemia, recurrent infxns, congenital heart defects)

Hypopituitarism is dysfunction of pituitary - can be 2/2 mass (nonfunctional adenoma, *c___*) or ischemia/injury/hemorrhage Most importantly, lose ACTH function --> low cortisol --> *___ (no salt wasting)*, will also have hypothyroidism + hypogonadism Craniopharyngioma is a benign, nonsecreting tumor derived from *remnants of ___* seen in children - compression --> hypopituitarism, bitemporal hemianopsia ___ is enlarged sella turcica (partially filled w/CSF) --> pituitary compression & hypopituitarism (seen in obese women w/HTN) ___ is sudden hemorrhage of pituitary (usually 2/2 existing adenoma), p/w sudden severe HA + bitemporal hemianopsia + diplopia (CN3 compression) + *shock (cortisol loss)* ___ is ischemic infarct of pituitary following postpartum hemorrhage (pituitary enlarges in pregnancy 2/2 prolactin release --> sudden hypotension [postpartum hemorrhage] --> hypopituitarism); if severe --> shock, if mild --> ___ Brain radiation can lead to hypopituitarism (i.e., nasopharyngeal carcinoma)

Hypopituitarism is dysfunction of pituitary - can be 2/2 mass (nonfunctional adenoma, *craniopharyngioma*) or ischemia/injury/hemorrhage Most importantly, lose ACTH function --> low cortisol --> *shock (no salt wasting)*, will also have hypothyroidism + hypogonadism Craniopharyngioma is a benign, nonsecreting tumor derived from *remnants of Rathke's Pouch* seen in children - compression --> hypopituitarism, bitemporal hemianopsia Empty Sella Syndrome is enlarged sella turcica (partially filled w/CSF) --> pituitary compression & hypopituitarism (seen in obese women w/HTN) Pituitary Apoplexy is sudden hemorrhage of pituitary (usually 2/2 existing adenoma), p/w sudden severe HA + bitemporal hemianopsia + diplopia (CN3 compression) + *shock (cortisol loss)* Sheehan Syndrome is ischemic infarct of pituitary following postpartum hemorrhage (pituitary enlarges in pregnancy 2/2 prolactin release --> sudden hypotension [postpartum hemorrhage] --> hypopituitarism); if severe --> shock, if mild --> failure to lactate Brain radiation can lead to hypopituitarism (i.e., nasopharyngeal carcinoma)

Hypothalamic syndrome, often caused by ___ (Rathke's pouch tumor) that also causes ___ hemianopsia, results in ___ (loss of ADH), ___ (loss of CRH), obesity, and loss of temp regulation

Hypothalamic syndrome, often caused by craniopharyngioma (Rathke's pouch tumor) that also causes bitemporal hemianopsia, results in DI (loss of ADH), fatigue (loss of CRH), obesity, and loss of temp regulation

IBD (autoimmune d.o) both have slight female predominance in young, white, Jewish pts - both cause relapsing-remitting bloody diarrhea *[HY] Crohn's involves G___ T___ inflammation involving ANY PORTION OF GI TRACT (mouth-to-anus)* *___* is most common location of CD (can lead to *malabsorption of B12, bile salts)* - can mimic appendicitis; often *spares the rectum* Grossly, will see *___ lesions (not a straight march), ___ mucosa (stones are normal - fissures are transmural inflammation), creeping fat (2/2 transmural inflammation), strictures (2/2 transmural inflammation --> S___ SIGN)* Microscopically, will see *g___* and *t___ inflammation* Complications can include *___ (d/t transmural inflammation)* and adenocarcinoma (only if colon involved) Smoking *___ Crohn's outcomes* Extra-intestinal manifestations include *migratory polyarthritis (large joints), kidney stones (fat malabsorption --> calcium binding --> hypocalcemia --> HIGH OXALATE l/t STONES)*, ankylosing spondylitis, and uveitis Labs may show *anti-___ antibodies (ASCA)* *[HY] T-cell response in Crohn's is Th___ (think GRANULOMAS!)*

IBD (autoimmune d.o) both have slight female predominance in young, white, Jewish pts - both cause relapsing-remitting bloody diarrhea *[HY] Crohn's involves GRANULOMATOUS TRANSMURAL inflammation involving ANY PORTION OF GI TRACT (mouth-to-anus)* *Terminal ileum* is most common location of CD (can lead to *malabsorption of B12, bile salts)* - can mimic appendicitis; often *spares the rectum* Grossly, will see *skip lesions (not a straight march), cobblestone mucosa (stones are normal - fissures are transmural inflammation), creeping fat (2/2 transmural inflammation), strictures (2/2 transmural inflammation --> STRING SIGN)* Microscopically, will see *granulomas* and *transmural inflammation* Complications can include *fistulas (d/t transmural inflammation)* and adenocarcinoma (only if colon involved) Smoking *worsens Crohn's outcomes* Extra-intestinal manifestations include *migratory polyarthritis (large joints), kidney stones (fat malabsorption --> calcium binding --> hypocalcemia --> HIGH OXALATE l/t STONES)*, ankylosing spondylitis, and uveitis Labs may show *anti-saccharomyces cerevisiae antibodies (ASCA)* *[HY] T-cell response in Crohn's is Th1 (think GRANULOMAS!)* ^*BOLD* is different from UC! ^For Crohn's, think of a Creepy Fat Granny Skipping down a Cobblestone road away from the wRECk

IBD (autoimmune d.o) both have slight female predominance in young, white, J___ pts - both cause relapsing-remitting bloody diarrhea Ulcerative colitis forms ulcer in *colon alone (never involves ___)* w/autoimmune inflammation of *___ + ___ *; it always *starts in ___ (LLQ pain is classic)* Grossly, can see *___ (healing of ulcers), loss of HAUSTRA (lead-pipe appearance)* Microscopically, will see *crypt ___* Extra-intestinal features include pyoderma gangrenosum/erythema nodosum, *p___ (liver?)*, ankylosing spondylitis, uveitis Feared complication is *toxic ___ (will see distension + fever + shock - also seen in C diff) - can perforate* and adenocarcinoma (do a colectomy) Smoking *___ UC outcomes* Labs may show *p-ANCA* *[HY] T-cell response in UC is Th___ (think NO GRANULOMAS!)* Can use *sulfasalazine to tx (doesn't become 5-ASA until reaching colon to encounter colonic bacteria - watch for oligospermia in men)*

IBD (autoimmune d.o) both have slight female predominance in young, white, Jewish pts - both cause relapsing-remitting bloody diarrhea Ulcerative colitis forms ulcer in *colon alone (never involves small intestine)* w/autoimmune inflammation of *mucosa + submucosa*; it always *starts in rectum (LLQ pain is classic)* Grossly, can see *pseudopolyps (healing of ulcers), loss of HAUSTRA (lead-pipe appearance)* Microscopically, will see *crypt abscesses* Extra-intestinal features include pyoderma gangrenosum/erythema nodosum, *primary sclerosing cholangitis*, ankylosing spondylitis, uveitis Feared complication is *toxic megacolon (will see distension + fever + shock - also seen in C diff) - can perforate* and adenocarcinoma (do a colectomy) Smoking *improves UC outcomes* Labs may show *p-ANCA* *[HY] T-cell response in UC is Th2 (think NO GRANULOMAS!)* Can use *sulfasalazine to tx (doesn't become 5-ASA until reaching colon to encounter colonic bacteria - watch for oligospermia in men)* ^*BOLD* is different from Crohn's!

IIH classically manifests with *___* in a overweight woman of childbearing age - dx is via spinal tap (opening pressure) and tx is ___ NPH causes classic triad of *___* - tx is VP shunt

IIH classically manifests with *PULSATILE TINNITUS* in a overweight woman of childbearing age - dx is via spinal tap (opening pressure) and tx is acetazolamide NPH causes classic triad of *URINARY INCONTINENCE, GAIT DISTURBANCE, AND DEMENTIA (wet, wobbly, wacky)* - tx is VP shunt

IL-___ receptor deficiency results in inability for T-cells to differentiate to Th1 cells (IL-12 secreted by macrophages) - results in low ___ (secreted by Th1) and increased susceptibility to mycobacterium and salmonella (___ macrophage bugs!) - tx w/exogenous IFN-gamma IFN-gamma receptor deficiency is similar - macrophages are not stimulated --> disseminated my___ and/or salmonella dz - tx w/continuous anti-TB therapy + stem cell transplant (IFN-gamma NOT effective)

IL-12 receptor deficiency results in inability for T-cells to differentiate to Th1 cells (IL-12 secreted by macrophages) - results in low IFN-gamma (secreted by Th1) and increased susceptibility to mycobacterium and salmonella (intracellular macrophage bugs!) - tx w/exogenous IFN-gamma IFN-gamma receptor deficiency is similar - macrophages are not stimulated --> disseminated myobacterial and/or salmonella dz - tx w/continuous anti-TB therapy + stem cell transplant (IFN-gamma NOT effective)

IMMUNE OVERVIEW: Innate immune system (macrophages, neutrophils, complement) are 2nd barrier to infxn (behind skin/mucous membranes) - ___ immune system (T-cells, B-cells) are 3rd barrier ___ is faster, non-specific, with no memory (big, dumb jock - you in past); ___ is slow, specific, with memory (nerd - you now) When bact. gets to body, innate cells (macrophages, neuts) can react immediately (to "free antigen"); adaptive immune cells (T-cells) can do NOTHING until chatting w/a___p___ c___ CD is found on different immune cells - allow for identification (also receptors + cell binding) Cytokines also come into play and include: -Chemokines: attract immune cells (chemotaxis) -I___: IL-1, IL-2 -T___: can cause tumor death -Transforming Growth Factor (TGF) -I___: interfere w/viral replication (virions)

IMMUNE OVERVIEW: Innate immune system (macrophages, neutrophils, complement) are 2nd barrier to infxn (behind skin/mucous membranes) - adaptive immune system (T-cells, B-cells) are 3rd barrier Innate is faster, non-specific, with no memory (big, dumb jock - you in past); Adaptive is slow, specific, with memory (nerd - you now) When bact. gets to body, innate cells (macrophages, neuts) can react immediately (to "free antigen"); adaptive immune cells (T-cells) can do NOTHING until chatting w/antigen-presenting cell CD is found on different immune cells - allow for identification (also receptors + cell binding) Cytokines also come into play and include: -Chemokines: attract immune cells (chemotaxis) -Interleukins: IL-1, IL-2 -Tumor Necrosis Factor: can cause tumor death -Transforming Growth Factor (TGF) -Interferons: interfere w/viral replication (virions)

INFLAMMATORY MYOPATHIES: A-Immune conditions (polymyositis, dermatomyositis) that are dx w/muscle biopsy, tx w/immunosuppression (steroids first, others later); both classically manifest w/*muscle p___ (diff. from polymyalgia rheumatica) + SYMMETRIC PROXIMAL muscle weakness* Labs will demonstrate elevated ___, positive ANA, *anti-___ (histidyl t-RNA synthetase) Ab*, & others (anti-SRP, anti-Mi-2) Polymyositis is *___ (fiber) inflammation w/CD___+ T-cells!* Dermatomyositis is *___ (fascicle) inflammation w/CD___+ T-cells!* - will also present w/heliotrope rash (discoloration of upper eyelid) + grotton papules (scaly papules on hands), both pathognomonic for dermatomyositis (*CAN PRESENT W/MALAR RASH! BE ALERT!*) IMs (DM > PM) are a/w *a___ risk*

INFLAMMATORY MYOPATHIES: A-Immune conditions (polymyositis, dermatomyositis) that are dx w/muscle biopsy, tx w/immunosuppression (steroids first, others later); both classically manifest w/*muscle pain (diff. from polymyalgia rheumatica) + SYMMETRIC PROXIMAL muscle weakness* Labs will demonstrate elevated CK, positive ANA, *anti-Jo-1 (histidyl t-RNA synthetase) Ab*, & others (anti-SRP, anti-Mi-2) Polymyositis is *ENDOMYSIAL (fiber) inflammation w/CD8+ T-cells!* Dermatomyositis is *PERIMYSIAL (fascicle) inflammation w/CD4+ T-cells!* - will also present w/heliotrope rash (discoloration of upper eyelid) + grotton papules (scaly papules on hands), both pathognomonic for dermatomyositis (*CAN PRESENT W/MALAR RASH! BE ALERT!*) IMs (DM > PM) are a/w *adenocarcinoma risk* ^*Phy Ed is @ 8, we DiP out @ 4*

INHERITED PLATELET DISORDERS: *Glanzmann's Thrombasthenia*: functional deficiency of ___ receptors, leading to mucosal bleeds (i.e., epistaxis); dx is made w/blood smear (*___ platelets, GPIIb/IIIa a___ platelets!!*), can also do platelet aggregometry (bleeding time prolonged as well) --- *Bernard Soulier Syndrome*: deficiency of ___ platelet receptors --> platelets cannot bind vWF to adhere and initiate platelet activation; p/w epistaxis and other mucosal bleeds Dx: prolonged bleeding time, thrombocytopenia, *___ PLATELETS ON SMEAR* --- *Wiskott-Aldrich Syndrome*: thrombocytopenia *+ ___ dysfunction (X-linked d.o w/Thrombocytopenia, E___, and Recurrent ___ - WATER)* Mutation in WAS gene - T-cell ___ maintenance

INHERITED PLATELET DISORDERS: *Glanzmann's Thrombasthenia*: functional deficiency of GPIIb/IIIa receptors, leading to mucosal bleeds (i.e., epistaxis); dx is made w/blood smear (*isolated platelets, GPIIb/IIIa aggregate platelets!!*), can allso do platelet aggregometry (bleeding time prolonged as well) --- *Bernard Soulier Syndrome*: deficiency of GPIb platelet receptors --> platelets cannot bind vWF to adhere and initiate platelet activation; p/w epistaxis and other mucosal bleeds Dx: prolonged bleeding time, thrombocytopenia, *ENLARGED PLATELETS ON SMEAR* --- *Wiskott-Aldrich Syndrome*: thrombocytopenia *+ immune dysfunction (X-linked d.o w/Thrombocytopenia, Eczema, and Recurrent infxns - WATER)* Mutation in WAS gene - T-cell cytoskeleton maintenance

CLASSIC PRESENTATION: fever + oliguria with increased BUN/Cr ration, eosinophils in urine, and WBC + WBC casts in urine?

INTERSTITIAL NEPHRITIS (2/2 PCN hypersensitivity reaction - watch for new meds)

IgA protease is expressed by three bacteria: S ___, H ___, N___ Endotoxin (LPS - fat [immunogenic ___ A] and sugar) is released when GN bact die (as opposed to exotoxin - protein - is secreted); endotoxin triggers TNF and IL-1 release; endotoxin is heat ___ *HY HY HY: LPS activates macrophages via ___ --> IL1 [fever], TNF [fever, hypotension], ___ [hypotension]; activates complement --> C___a [hypotension, edema], C___a [neuts/chemotaxis]; activates tissue factor --> coagulation/___*

IgA protease is expressed by three bacteria: S pneumo, H flu, Neisseria Endotoxin (LPS - fat [immunogenic lipid A] and sugar) is released when GN bact die (as opposed to exotoxin - protein - is secreted); endotoxin triggers TNF and IL-1 release; endotoxin is heat stable *HY: LPS activates macrophages via CD14 --> IL1 [fever], TNF [fever, hypotension], NO [hypotension]; activates complement --> C3a [hypotension, edema], C5a [neuts/chemotaxis]; activates tissue factor --> coagulation/DIC*

IgM is first antibody produced and is potent activator of c___ (classical pathway - lots of Fc to bind C1), but weak o___ (too big, but has greatest *avidity* of all antibodies d/t more binding sites) IgG is major antibody produced in secondary response (memory B-cells) and functions as *excellent opsonin for ___*; it is the only antibody that crosses placenta; IgG is crucial for ___ bacteria (capsule makes bacteria resistant to phagocytosis, opsonized w/IgG --> can phagocytose) Ig___ is main antibody of mucosal surfaces (GI tract, respiratory tract) that exists in plasma as monomer, but after transport through epithelial cells, becomes linked via *secretory component (___-chain)*; accordingly, IgA does not fix complement (not an issue! should coat pathogens so they cannot invade surfaces) and does not produce significant inflammation; secreted in mother's milk to prevent GI infxns in babies Some bacteria express IgA ___ (S. pneumo, H. flu, Neisseria) --> allows colonization of mucosal surfaces Ig___ binds mast cells and eosinophils for defense against parasites (too large for phagocytosis --> mast cells find IgE and degranulate); IgE does not activate complement; IgE mediates allergic rxns

IgM is first antibody produced and is potent activator of complement (classical pathway - lots of Fc to bind C1), but weak opsinin (too big, but has greatest *avidity* of all antibodies d/t more binding sites) IgG is major antibody produced in secondary response (memory B-cells) and functions as *excellent opsonin for macrophages*; it is the only antibody that crosses placenta; IgG is crucial for encapsulated bacteria (capsule makes bacteria resistant to phagocytosis, opsonized w/IgG --> can phagocytose) IgA is main antibody of mucosal surfaces (GI tract, respiratory tract) that exists in plasma as monomer, but after transport through epithelial cells, becomes linked via *secretory component (J-chain)*; accordingly, IgA does not fix complement (not an issue! should coat pathogens so they cannot invade surfaces) and does not produce significant inflammation; secreted in mother's milk to prevent GI infxns in babies Some bacteria express IgA protease (S. pneumo, H. flu, Neisseria) --> allows colonization of mucosal surfaces IgE binds mast cells and eosinophils for defense against parasites (too large for phagocytosis --> mast cells find IgE and degranulate); IgE does not activate complement; IgE mediates allergic rxns

___ is loss of bowel peristalsis --> constipation/obstipation, often caused by narcotics or post-operative ___ syndrome is ileus-like ("pseudo-obstruction") w/dilated colon in absence of lesion; a/w narcotic use and sedentary lifestyle (severe illness, hospitalized pt) ___ is functional bowel disorer with completely normal intestinal structure w/recurrent abdominal pain (3d/month x3mo) + improvement w/defecation, change in stool frequency, onset a/w change in stool appearance Necrotizing enterocolitis is neonatal d.o --> intestinal necrosis + obstruction; major risk factor is *___ * - will see *P___ I___ on x-ray (air in bowel wall)* ___ is aberrant BV in GI tract (common in cecum/right-sided colon) that can cause lower GI bleeding (hematochezia); Hereditary Hemorrhagic Telangectasia (*autosomal ___*) l/t development of telangiectasia THROUGHOUT GI TRACT (mouth to rectum) - will see nosebleeds, GI bleeds, iron deficiency (+ telangiectasia on ___)

Ileus is loss of bowel peristalsis --> constipation/obstipation, often caused by narcotics or post-operative Ogilvie syndrome is ileus-like ("pseudo-obstruction") w/dilated colon in absence of lesion; a/w narcotic use and sedentary lifestyle (severe illness, hospitalized pt) IBS is functional bowel disorer with completely normal intestinal structure w/recurrent abdominal pain (3d/month x3mo) + improvement w/defecation, change in stool frequency, onset a/w change in stool appearance Necrotizing enterocolitis is neonatal d.o --> intestinal necrosis + obstruction; major risk factor is *PREMATURITY* - will see *PNEUMATOSIS INTESTINALIS on x-ray (air in bowel wall)* Angiodysplasia is aberrant BV in GI tract (common in cecum/right-sided colon) that can cause lower GI bleeding (hematochezia); Hereditary Hemorrhagic Telangectasia (*autosomal DOMINANT*) l/t development of telangiectasia THROUGHOUT GI TRACT (mouth to rectum) - will see nosebleeds, GI bleeds, iron deficiency (+ telangiectasia on lips)

Impetigo is superficial skin infxn in which neuts. collect beneath str. ___ --> macules/papules that rupture --> erosions, dried sebum --> "honey-crust" (conatgious, isolate + abx!) Impetigo contagiosa (non-bullous) is MC, affecting face/extremities and caused by S. aureus and GAS --> honey-crusted lesions Bullous impetigo is seen on the trunk of children and caused by S. aureus (strains causing bullous express ex___ toxin that *[HY] destroys keratinocyte attachments by cleaving ___ 1 complex [desmosome protein that links keratinocytes together] - affects str. g___ --> bullous impetigo) Ex___ toxin can lead to Scalded Skin Syndrome (3-7d old, sloughing of skin, intraepidermal damage --> heals w.o scar; look for N___ sign and tx with abx)

Impetigo is superficial skin infxn in which neuts. collect beneath str. corneum --> macules/papules that rupture --> erosions, dried sebum --> "honey-crust" (conatgious, isolate + abx!) Impetigo contagiosa (non-bullous) is MC, affecting face/extremities and caused by S. aureus and GAS --> honey-crusted lesions Bullous impetigo is seen on the trunk of children and caused by S. aureus (strains causing bullous express exfoliative toxin that *[HY] destroys keratinocyte attachments by cleaving desmoglein 1 complex [desmosome protein that links keratinocytes together] - affects str. granulosum --> bullous impetigo) Exfoliative toxin can lead to Scalded Skin Syndrome (3-7d old, sloughing of skin, intraepidermal damage --> heals w.o scar; look for Nikolsky's sign and tx with abx)

Important deactivators of coagulation cascade are: antithrombin ___, proteins C & S, and TFPI Antithrombin III is inhibitor of serine proteases (serpin), acting on factors *___ (VitK dependent + 2 more...)*; ATIII is produced by liver --> activated by endothelium via *___ sulfate (rationale for heparin drug therapy)*; ATIII deficiency --> ___coaguable state Proteins C and S are both synthesized in liver; Protein S is cofactor for protein C; Protein C is activated (APC) by *thrombomodulin*, a cell membrane protein found on *healthy ___ cells (i.e., don't wanna clot when endothelium is healthy; thrombomodulin binds thrombin - complex activates protein C); APC inactivates factors ___ and ___ *Some patients are born w/protein C deficiency --> ___coaguable; some patients born w/factor V mutation so can't be inactivated by protein C --> ___coaguable* TFPI inactivates factor X via 1) direct binding and 2) binding TF-VIIa complex; not much clinical significance, but TFPI increases w/he___ administration

Important deactivators of coagulation cascade are: antithrombin III, proteins C & S, and TFPI Antithrombin III is inhibitor of serine proteases (serpin), acting on factors *II, VII, IX, X, XI, and XII*; ATIII is produced by liver --> activated by endothelium via *heparan sulfate (rationale for heparin drug therapy)*; ATIII deficiency --> hypercoaguable state Proteins C and S are both synthesized in liver; Protein S is cofactor for protein C; Protein C is activated (APC) by *thrombomodulin*, a cell membrane protein found on *healthy endothelial cells (i.e., don't wanna clot when endothelium is healthy; thrombomodulin binds thrombin - complex activates protein C); APC inactivates factors V and VIII *Some patients are born w/protein C deficiency --> hypercoaguable; some patients born w/factor V mutation so can't be inactivated by protein C --> hypercoaguable* TFPI inactivates factor X via 1) direct binding and 2) binding TF-VIIa complex; not much clinical significance, but TFPI increases w/heparin administration

Important innate immune components include: p___ (macrophages [primary] and neutrophils [on-call]), *C___*, NK cells, eosinophils, mast cells/basophils Innate IS, in general, recognizes molecules that are "foreign" (Pathogen-Associated Molecular Patterns - PAMPs), recognizing through pattern recognition receptors (*T___, TLRs*) TLRs recognize PAMPs --> secrete cytokines Special PAMPs that Innate IS can react to include *___ (LPS, binds [HY] CD___, triggering TLR4 --> cytokines^)* and *peptidoglycan (via N___receptors [INTRACELLULAR] --> cytokines)*, mannose, lipoteichoic acid (GPs), dsRNA, unmethylated DNA

Important innate immune components include: phagocytes (macrophages [primary] and neutrophils [on-call]), *COMPLEMENT*, NK cells, eosinophils, mast cells/basophils Innate IS, in general, recognizes molecules that are "foreign" (Pathogen-Associated Molecular Patterns - PAMPs), recognizing through pattern recognition receptors (*Toll-Like Receptors, TLRs*) TLRs recognize PAMPs --> secrete cytokines Special PAMPs that Innate IS can react to include *endotoxin (LPS, binds [HY] CD14, triggering TLR4 --> cytokines^)* and *peptidoglycan (via NOD receptors [INTRACELLULAR] --> cytokines)*, mannose, lipoteichoic acid (GPs), dsRNA, unmethylated DNA ^: IL-1, IL-6, IL-8, TNF

Important renal function measures include GFR, renal plasma flow, filtration fraction, filtered load, and renal clearance ___ is the mass of a substance that is cleared per minute (plasma concentration [mg/mL] x GFR [mL/min]) - reported in mg/min ___ is the amount of substance pee-ed out per unit time (urine concentration [meq/mL] x urine flow [mL/hr]) - reported in meq/hr ___ is volume of blood "cleared" of substance X per minute ([urine concentration of X x urine flow rate]/plasma concentration of X) - reported in L/min Renal clearance can be used to calculate ___ using *inulin* - inulin is neither absorbed nor secreted, such that all inulin that is filtered leaves the body; accordingly, *___ of inulin = GFR = ([urine concentration of inulin x urine flow rate]/plasma concentration of inulin) Clinically, we use ___ to measure GFR (VERY small amount of secretion, so slightly overestimates GFR, but close enough) - note that if plasma creatinine doubles --> 50% reduction in GFR Note that if clearance of substance X < GFR --> net ___; clearance of substance X > GFR --> net ___ ^NOTE: measure RPF using PAH

Important renal function measures include GFR, renal plasma flow, filtration fraction, filtered load, and renal clearance Filtered load is the mass of a substance that is cleared per minute (plasma concentration [mg/mL] x GFR [mL/min]) - reported in mg/min Excretion rate is the amount of substance pee-ed out per unit time (urine concentration [meq/mL] x urine flow [mL/hr]) - reported in meq/hr Renal clearance is volume of blood "cleared" of substance X per minute ([urine concentration of X x urine flow rate]/plasma concentration of X) - reported in L/min Renal clearance can be used to calculate GFR using *inulin* - inulin is neither absorbed nor secreted, such that all inulin that is filtered leaves the body; accordingly, *clearance of inulin = GFR = ([urine concentration of inulin x urine flow rate]/plasma concentration of inulin) Clinically, we use creatinine to measure GFR (VERY small amount of secretion, so slightly overestimates GFR, but close enough) - note that if plasma creatinine doubles --> 50% reduction in GFR Note that if clearance of substance X < GFR --> net resorption; clearance of substance X > GFR --> net secretion ^NOTE: measure RPF using PAH

Imprinting is epigenetic phenomenon --> alteration in gene exp; it occurs in gametogenesis prior to fert and occurs via ___ (base?) methylation; imprinted genes --> only one allele expressed (*PWS, AS, chrom 15q11-q13*) ___ copy abn --> LOF PWS gene on dad Chrom15 --> PWS (NOT expressed on maternal Chrom15); 75% d/t deletion of dad gene, 25% d/t maternal uniparental ___; will see obese child with hypotonia, hyper___, hypogonadism, and *___ intellectual disability* ___ copy abn --> LOF UBE3A gene on dad Chrom15 --> AS (*NOT expressed on paternal Chrom15); only 5% are d/t paternal uniparental disomy (NDJ less common in sperm than oocytes); will see *frequent l___ing*, seizures, and *___ intellectual disability*

Imprinting is epigenetic phenomenon --> alteration in gene exp; it occurs in gametogenesis prior to fert and occurs via cytosine methylation; imprinted genes --> only one allele expressed (*PWS, AS, chrom 15q11-q13*) Paternal copy abn --> LOF PWS gene on dad Chrom15 --> PWS (NOT expressed on maternal Chrom15); 75% d/t deletion of dad gene, 25% d/t maternal uniparental disomy; will see obese child with hypotonia, hyperphagia, hypogonadism, and *mild intellectual disability* Maternal copy abn --> LOF UBE3A gene on dad Chrom15 --> AS *NOT expressed on paternal Chrom15); only 5% are d/t paternal uniparental disomy (NDJ less common in sperm than oocytes); will see *frequent laughing*, seizures, and *severe intellectual disability* ^happy mommy, fat daddy

In Euks., hnRNA (pre-mRNA) undergoes three modifications before leaving nuc.: 5' capping, intron splicing, 3' polyadenylation 5' capping is addition of ___ to 5' end - distinguishes mRNA from other RNA! RNA is divided into introns and exons - ___ are spliced out and stay IN nucleus, while ___ EXit nucleus (5' splice site: GU, 3' splice site: AG); One gene can make many prots. d/t alternative splicing snRNPs (short RNA polymers + prots., also called U-RNAs d/t high U content) combine with mRNA to form spliceosome - intron loop is formed ("___") and released to remove intron, exons are then joined (NOTE: anti-Sm Ab in ___ is against snRNPs, anti-RNP Ab in Mixed C___ T___ Dz is against *U1 RNA*!) 3' polyadenylation starts in transcr. when polyadenylation signal (AATAA) is hit, then some nucleotides then CA; many prots. bind mRNA (CSF binds ___, CstF binds ___) and stop transcr., then ___ (PAP) adds ~200 adenosine nucs. to 3' end of mRNA (no template needed)

In Euks., hnRNA (pre-mRNA) undergoes three modifications before leaving nuc.: 5' capping, intron splicing, 3' polyadenylation 5' capping is addition of 7-methylguanosine to 5' end - distinguishes mRNA from other RNA! RNA is divided into introns and exons - introns are spliced out and stay IN nucleus, while exons EXit nucleus (5' splice site: GU, 3' splice site: AG); One gene can make many prots. d/t alternative splicing snRNPs (short RNA polymers + prots., also called U-RNAs d/t high U content) combine with mRNA to form spliceosome - intron loop is formed ("lariat") and released to remove intron, exons are then joined (NOTE: anti-Sm Ab in SLE is against snRNPs, anti-RNP Ab in Mixed Connective Tissue Dz is against *U1 RNA*!) 3' polyadenylation starts in transcr. when polyadenylation signal (AATAA) is hit, then some nucleotides then CA; many prots. bind mRNA (CSF binds AAUAA, CstF binds CA) and stop transcr., then Poly-A polymerase (PAP) adds ~200 adenosine nucs. to 3' end of mRNA (no template needed)

In HF (low CO) and cirrhosis (low SVR), the body perceives a low ECV in the setting of high TBW; ADH is *chronically elevated* d/t non-osmotic release of ADH --> high Uosm Hyponatremia can also be seen in advanced renal failure d/t kidneys inability to excrete free water normally, even in the setting of low ADH (p/w higher than normal Uosm, usually >200mOsmol/kg) KEY POINT: high Uosm indicates abnormal response to hyponatremia Diuretics can also l/t hyponatremia w/variable urinary findings (thiazide diuretics are more likely, d/t maintenance of medullary osmotic gradient High ADH can cause hyponatremia and common etiologies include vomiting, diarrhea, sweating, SIADH, adrenal insufficiency [cortisol suppresses ADH], hypothyroidism SIADH can be seen d/t drugs (carbamazepine, cyclophosphamide), paraneoplastic syndrome (small cell lung cancer), CNS dz, pulmonary dz; in SIADH, pts are euvolemic d/t downregulation of RAAS SIADH Tx: fluid restriction (+/- demeclocycline) --- Psychogenic polydipsia can cause hyponatremia w/hallmark being *low Uosm* Tea and toast diet, beer drinkers (beer potomania) can also l/t hyponatremia

In Restrictive lung dz, flow-volume loop shifts ___ (lung volume starts at ___ point - still has similar shape d/t similar lung mechanics, just decr. volume) In obstructive lung dz, flow-volume loop shifts ___ (lung volume starts at ___ point) w/more gradual downslope (difficulty getting air out) - will also have ___ peak (trouble getting air out - can't breath out as fast) ^Difficult to get FEV1 from FV loops

In Restrictive lung dz, flow-volume loop shifts Right (lung volume starts at lower point - still has similar shape d/t similar lung mechanics, just decr. volume) In obstructive lung dz, flow-volume loop shifts left (lung volume starts at higher point) w/more gradual downslope (difficulty getting air out) - will also have lower peak (trouble getting air out - can't breath out as fast) ^Difficult to get FEV1 from FV loops

In cirrhosis, hypoalbuminemia --> decreased ___ pressure --> ___ ECV At the same time, nitric oxide and other vaso))) are upregulated --> splanchnic vasodilation --> *FALL IN ___ (hallmark!)* --> fall in BP --> fall in ECV (double whammy) Fall in ECV --> activation of ___ --> increased Na/H2O absorption --> *___ total body water (ascites, edema)* ^Along w/heart failure, cirrhosis is classic condition that leads to ___ ECV with ___ TBW [cirrhosis is d/t *LOW SVR!!*)

In cirrhosis, hypoalbuminemia --> decreased oncotic pressure --> decreased ECV At the same time, nitric oxide and other vasodilators are upregulated --> splanchnic vasodilation --> *FALL IN SVR (hallmark!)* --> fall in BP --> fall in ECV (double whammy) Fall in ECV --> activation of RAAS/ADH --> increased Na/H2O absorption --> *increased total body water (ascites, edema)* ^Along w/heart failure, cirrhosis is classic condition that leads to decreased ECV with increased TBW [cirrhosis is d/t *LOW SVR!!*)

In early development, midgut is open to yolk sac; by week 5, connection w/yolk sac begins to narrow and becomes *v___*, which normally disappears but can persist to cause anomalies ___ diverticulum is MC congenital GI pathology (*persistent remnant of vitelline duct*); MD is a *___ diverticulum (contains all layers of bowel - MucSubmucMusc*); *[HY] MD often contains ___* MD usually has no sx (incidental finding - think Dr. Zamora), but can present w/ulceration, pain, and bleeding d/t *___ tissue* Rule of 2s: 2x more likely in men, 2% of population, 2 inches long, within 2 feet of ileocecal valve Dx: ___ scan (tracer taken up by gastric cells in diverticulum) Vitelline duct anomalies can also be cysts, sinus, persistent duct

In early development, midgut is open to yolk sac; by week 5, connection w/yolk sac begins to narrow and becomes *vitelline duct*, which normally disappears but can persist to cause anomalies Meckel's diverticulum is MC congenital GI pathology (*persistent remnant of vitelline duct*); MD is a *TRUE diverticulum (contains all layers of bowel - MucSubmucMusc*); *[HY] MD often contains ectopic gastric tissue* MD usually has no sx (incidental finding - think Dr. Zamora), but can present w/ulceration, pain, and bleeding d/t *ectopic gastric tissue* Rule of 2s: 2x more likely in men, 2% of population, 2 inches long, within 2 feet of ileocecal valve Dx: Technetium scan (tracer taken up by gastric cells in diverticulum) Vitelline duct anomalies can also be cysts, sinus, persistent duct

In fetus, development of testes requires functional Y chromosome - ___ gene produces testis determining factor (chromosomal sex), while internal/external genitalia requires ___ (testosterone/estrogen) Internal male genitalia is derived from m___ ducts (seminal vesicles, epididymis, vas deferens) and is dependent on *___* External male genitalia is derived from ur___ sinus (penis, scrotum, prostate, bladder) and is dependent on *___*

In fetus, development of testes requires functional Y chromosome - SRY gene produces testis determining factor (chromosomal sex), while internal/external genitalia requires hormones (testosterone/estrogen) Internal male genitalia is derived from mesonephric ducts (seminal vesicles, epididymis, vas deferens) and is dependent on *TESTOSTERONE* External male genitalia is derived from urogenital sinus (penis, scrotum, prostate, bladder) and is dependent on *DHT*

In foregut development, the lung buds off of the esophageal foregut ("lung bud"); eventually, tracheoesophageal septum divides bud --> matures into separate trachea and esophagus Abnormal formation of septum --> pathology, most commonly *esophageal a___* when septum deviates *___* Three types: ___ (MC, prominent gastric bubble), pure EA (___ gastric bubble), and H-type (___ gastric bubble) In esophageal atresia (pure or EA w/TEF), baby cannot swallow --> ___ (drooling, choking, vomiting --> *CANNOT PASS ___ INTO STOMACH!*)

In foregut development, the lung buds off of the esophageal foregut ("lung bud"); eventually, tracheoesophageal septum divides bud --> matures into separate trachea and esophagus Abnormal formation of septum --> pathology, most commonly *esophageal atresia* when septum deviates *posteriorly* Three types: EA w/TEF (MC, prominent gastric bubble), pure EA (no gastric bubble), and H-type (prominent gastric bubble) In esophageal atresia (pure or EA w/TEF), baby cannot swallow --> polyhydramnios (drooling, choking, vomiting --> *CANNOT PASS NG TUBE INTO STOMACH!*)

In gout, uric acid deposition in joints triggers phagocytosis by ___ --> inflammation; three things create perfect gout storm: hyperuricemia, cool ___, genes Will most often see gout at 1st MTP joint of toe or knee - multiple attacks will lead to painless ___; longstanding gout can also l/t uric acid kidney stones and/or chronic renal failure Primary gout (not d/t other dz or med) can be triggered by diet and alcohol; this is b/c uric acid comes from p___ (purine --> hypoxanthine --> uric acid via *xanthine oxidase*) - seafood/meat is rich in purines --> high uric acid; Alcohol also incr. activity of URAT-1 --> URAT-1 resorbs ___ in kidney Secondary gout can be d/t ___ dz (decr. UA excretion - renal failure, volume depletion, diuretics), myeloproliferative d.o (excess turnover --> purines!), L___ Syndrome (HGPRT - lost purine salvage pathway, one of only causes of juvenile gout), Von Gierke's Dz (G___ deficiency) Dx: arthrocentesis w/WBC 20k-50k and *___ birefringence needles* (ye*ll*ow under para*ll*el light, blue under perpendicular)

In gout, uric acid deposition in joints triggers phagocytosis by macrophages --> inflammation; three things create perfect gout storm: hyperuricemia, cool temperatures, genes Will most often see gout at 1st MTP joint of toe or knee - multiple attacks will lead to painless tophi; longstanding gout can also l/t uric acid kidney stones and/or chronic renal failure Primary gout (not d/t other dz or med) can be triggered by diet and alcohol; this is b/c uric acid comes from purines (purine --> hypoxanthine --> uric acid via *xanthine oxidase*) - seafood/meat is rich in purines --> high uric acid; Alcohol also incr. activity of URAT-1 --> URAT-1 resorbs uric acid in kidney Secondary gout can be d/t kidney dz (decr. UA excretion - renal failure, volume depletion, diuretics), myeloproliferative d.o (excess turnover --> purines!), Lesch-Nyhan Syndrome (HGPRT - lost purine salvage pathway, one of only causes of juvenile gout), Von Gierke's Dz (G6P deficiency) Dx: arthrocentesis w/WBC 20k-50k and *negative birefringence needles* (ye*ll*ow under para*ll*el light, blue under perpendicular)

In hypersensitivity rxn, first contact --> sensitization, second contact --> hypersensitivity Type I HS rxn (allergies) are d/t pre-formed IgE antibodies that are bound to ___, which attach antigen --> *mast cell degranulation w/___ --> vasodilation + broncho___ + vascular permeability* (IgE in susceptible pts is d/t B-cell class switching [driven by *Th2 cells & IL-___!*]) - importantly, complement is not involved Type I HS rxn manifests w/urticaria, rhinitis/wheezing, conjunctivitis, and diarrhea (can have early sx d/t leukotrienes & prostaglandins, late sx d/t c___); anaphylaxis is systemic rxn that can be deadly --> tx w/___ A___ is genetic predisposition to HS rxns (urticaria, rhinitis, asthma) - will see family hx Ex: anaphylaxis, allergic asthma Dx: skin test for wheal Tx: desensitization (gradually administer more allergen - IgE --> Ig___ response)

In hypersensitivity rxn, first contact --> sensitization, second contact --> hypersensitivity Type I HS rxn (allergies) are d/t pre-formed IgE antibodies that are bound to mast cells, which attach antigen --> *mast cell degranulation w/histamine --> vasodilation + bronchospasm + vascular permeability* (IgE in susceptible pts is d/t B-cell class switching [driven by *Th2 cells & IL-4!*]) - importantly, complement is not involved Type I HS rxn manifests w/urticaria, rhinitis/wheezing, conjunctivitis, and diarrhea (can have early sx d/t leukotrienes & prostaglandins, late sx d/t cytokines); anaphylaxis is systemic rxn that can be deadly --> tx w/epinephrine Atopy is genetic predisposition to HS rxns (urticaria, rhinitis, asthma) - will see family hx Ex: anaphylaxis, allergic asthma Dx: skin test for wheal Tx: desensitization (gradually administer more allergen - IgE --> IgG response)

In portal HTN, increase in portal pressure can *dilate ___ vessels that connect portal veins to systemic veins!* Swelling of collaterals at the: Umbilicus: ___ (2/2 epigastric vv [portal] and paraumbilical vv [systemic]) Esophagus: ___ (p/w hematemesis; 2/2 esophageal varices, collaterals connect esophageal vv [portal] and left gastric vv [systemic]) Stomach: ___ (p/w melena; 2/2 gastric varices, collaterals connect left gastric/splenic vv [portal] and short gastric vv [systemic]) Rectum: ___ (*ABOVE dentate line - painless!*; 2/2 mid/inferior rectal vv [portal] and superior rectal vv [systemic]) Portal HTN can also l/t hypersplenism w/___penia

In portal HTN, increase in portal pressure can *dilate collateral vessels that connect portal veins to systemic veins!* Swelling of collaterals at the: Umbilicus: caput medusa (2/2 epigastric vv [portal] and paraumbilical vv [systemic]) Esophagus: upper GI bleeding (p/w hematemesis; 2/2 esophageal varices, collaterals connect esophageal vv [portal] and left gastric vv [systemic]) Stomach: upper GI bleeding (p/w melena; 2/2 gastric varices, collaterals connect left gastric/splenic vv [portal] and short gastric vv [systemic]) Rectum: internal hemorrhoids (*ABOVE dentate line - painless!*; 2/2 mid/inferior rectal vv [portal] and superior rectal vv [systemic]) Portal HTN can also l/t hypersplenism w/thrombocytopenia

In the adrenal gland, ACTH stimulates *___*, converting cholesterol to pregnenolone and starting the process of aldosterone/cortisol synthesis; ___ inhibits desmolase Ketoconazole is also a potent inhibitor of ___, which is important for Fasciculata --> Reticularis (i.e., enzyme that takes takes pathway to Reticularis for Androgens) conversion and results in feminization (g___) Ketoconazole can also inhibit 17-alpha-hydroxylase, which is important for Glomerulosa --> Fasciculata conversion and results in decreased ___ production (used to tx Cushing's) [NOTE: ketoconazole inhibits step leading to every layer!] ___ stimulates aldosterone synthase, driving aldosterone production

In the adrenal gland, ACTH stimulates *desmolase*, converting cholesterol to pregnenolone and starting the process of aldosterone/cortisol synthesis; ketoconazole inhibits desmolase Ketoconazole is also a potent inhibitor of 17,20-lyase, which is important for Fasciculata --> Reticularis conversion and results in feminization (gynecomastia) Ketoconazole can also inhibit 17-alpha-hydroxylase, which is important for Glomerulosa --> Fasciculata conversion and results in decreased cortisol production (used to tx Cushing's) [NOTE: ketoconazole inhibits step leading to every layer!] Angiotensin II stimulates aldosterone synthase, driving aldosterone production

In transcription, template strand allows for RNA synthesis in 5' to 3' direction, yielding RNA strand that is complementary to template strand (can look to other DNA strand as well [*___ Strand*] with U substituted for T in transcript) RNA types include mRNA (specify AAs for proteins), ___ (form ribosomes), tRNA (transfer AAs to proteins), *___RNA ^ (regulate gene expression via targeting mRNA --> bind via base pairing --> remove poly-A tail --> mRNA degradation [endonuclease]/stop translation)*, siRNA^ (also regulate gene expression), snRNA (splicing of pre-mRNA) RNApol synthesizes RNA from DNA and *does not require ___ (DNApol does)* - RNApol binds ___ region directly and opens double helix (requires transcription factors to function) Proks have one RNApol (rifampin inhibits); Euks have RNApol1 (most rRNA), RNApol___ (mRNA - workhorse), RNApol3 (rRNA 5S); Alpha amantin (found in 'shrooms) inhibits RNApol___, actinomycin D also inhibits RNApol Proks have one transcription factor (sigma factor); Euks have multiple (___IID, ___IIB, etc.) ^I = interfering

In transcription, template strand allows for RNA synthesis in 5' to 3' direction, yielding RNA strand that is complementary to template strand (can look to other DNA strand as well [*Coding Strand*] with U substituted for T in transcript) RNA types include mRNA (specify AAs for proteins), rRNA (form ribosomes), tRNA (transfer AAs to proteins), *miRNA^ (regulate gene expression via targeting mRNA --> bind via base pairing --> remove poly-A tail --> mRNA degradation [endonuclease]/stop translation)*, siRNA^ (also regulate gene expression), snRNA (splicing of pre-mRNA) RNApol synthesizes RNA from DNA and *does not require primer (DNApol does)* - RNApol binds promoter region directly and opens double helix (requires transcription factors to function) Proks have one RNApol (rifampin inhibits); Euks have RNApol1 (most rRNA), RNApol2 (mRNA - workhorse), RNApol3 (rRNA 5S); Alpha amantin (found in 'shrooms) inhibits RNApol2, actinomycin D also inhibits RNApol Proks have one transcription factor (sigma factor); Euks have multiple (TFIID, TFIIB, etc.) ^I = interfering

In translation, AAs are added from ___-terminal to ___-terminal; prot. synthesis has three stages: initiation, elongation, termination Four binding sites for ribosomes: mRNA, ___-site (AA binding w/charged tRNA), ___-site (tRNA attached to protein chain), ___-site (exit or tRNA) Initiation begins w/AUG (codes methionine), which binds directly to P-site (bypasses A); GTP is hydrolyzed for this process to occur Elongation requires GTP for energy and uses elongation factors; Bact.: EF-Tu and EF-G, Euks: EF1 and *EF___ [target for diphtheria/pseudo toxin]*) undergoes 4 steps: 1) charged tRNA binds ___-site, 2) AA in A site joined to peptide chain in P site (prot. now in A site; process is catalyzed by ___ - "ribozyme" - via peptidyl transferase activity), 3) ribosome moves down mRNA and tRNAs bump over a site (prot. back in P site) and 4) tRNA leaves E site Translation terminates when stop codon (UAA, UAG, UGA) is reached, which codes for R___ factors - water is added to protein chain to finish process Post-Trans. modification include phosphorylation (via ___), glycosylation (yields glyco___), hydroxylation, methylation, acetylation, ubiquitination Chaperones are prots. that bind other prots. to facilitate folding; classic example is *heat ___ proteins*, which inc. with stress --> stabilize prots. --> can survive stressful situations

In translation, AAs are added from N-terminal to C-terminal; prot. synthesis has three stages: initiation, elongation, termination Four binding sites for ribosomes: mRNA, A-site (AA binding w/charged tRNA), P-site (tRNA attached to protein chain), E-site (exit or tRNA) Initiation begins w/AUG (codes methionine), which binds directly to P-site (bypasses A); GTP is hydrolyzed for this process to occur Elongation (requires GTP for energy and uses elongation factors; Bact.: EF-Tu and EF-G, Euks: EF1 and *EF2 [target for diphtheria/pseudo toxin]*) undergoes 4 steps: 1) charged tRNA binds A-site, 2) AA in A site joined to peptide chain in P site (prot. now in A site; process is catalyzed by ribosome - "ribozyme" - via peptidyl transferase activity), 3) ribosome moves down mRNA and tRNAs bump over a site (prot. back in P site) and 4) tRNA leaves E site Translation terminates when stop codon (UAA, UAG, UGA) is reached, which codes for releasing factors - water is added to protein chain to finish process Post-Trans. modification include phosphorylation (via kinase), glycosylation (yields glycoproteins), hydroxylation, methylation, acetylation, ubiquitination Chaperones are prots. that bind other prots. to facilitate folding; classic example is *heat shock proteins*, which inc. with stress --> stabilize prots. --> can survive stressful situations

___ = # new cases per year [Inc. Rate = (# new cases)/(total pop - ppl w/dz (*shouldn't be counted as "at risk")*]; ___ = # cases present at any one pt in time [Prev. Rate = (# cases)/(population at risk)] For chronic dz, prev. >> incid.; when new drugs improve survival, incid. is unchanged - prev. ___ Sensitivity = [___/(___ [all pts w/dz])]; Specificity = [___/(___ [all pts w.o dz])]; *if using 2x2 table --> left side for sens., right side for spec.* For overlapping graphs, midpoint maximizes sens./spec.; also, degree of overlap limits sens./spec. *[HY] ___ tests are good at ruling out dz, ___ tests are good at ruling in dz (SPIN and SNOUT); sens. and spec. are characteristics of test and remain CONSTANT for any p___ (diff. from PPV/NPV)* Screen with sensitive test (or when you don't wanna miss cases), confirm with specific test TYPIC. Q: *test is neg. in 80% of ppl w.o dz, what is spec.? 80% = TN and spec., FP = 20%*

Incidence = # new cases per year [Inc. Rate = (# new cases)/(total pop - ppl w/dz [*shouldn't be counted as "at risk")*]; Prevalence = # cases present at any one pt in time [Prev. Rate = (# cases)/(population at risk)] For chronic dz, prev. >> incid.; when new drugs improve survival, incid. is unchanged - prev. increases Sensitivity = [TP/(TP + FN [all pts w/dz])]; Specificity = [TN/(TN + FP)]; *if using 2x2 table --> left side for sens., right side for spec.* For overlapping graphs, midpoint maximizes sens./spec.; also, degree of overlap limits sens./spec. *[HY] Sensitive tests are good at ruling out dz, specific tests are good at ruling in dz (SPIN and SNOUT); sens. and spec. are characteristics of test and remain CONSTANT for any prevalence (diff. from PPV/NPV)* Screen with sensitive test (or when you don't wanna miss cases), confirm with specific test TYPIC. Q: *test is neg. in 80% of ppl w.o dz, what is spec.? 80% = TN and spec., FP = 20%*

Increased COX2 expression is well-described in colon cancer - rationale for ___ therapy for reducing CRC risk (also increases risk of bleeding/ulcers) ___ gene (chrom18q) indicates shitty prognosis; most common met site is liver ___-sided (MSI, HNPCC) p/w iron-deficiency anemia, weight loss, and "exophytic" tumor (doesn't obstruct --> Apple core sign) ___-sided (AdCarSeq, FAP) p/w LLQ pain, blood-streaked stool, & circumferential lesions w/change in stool ___ (pencil-thin stools) Strep bovis bacteremia/endocarditis is strongly a/w colon cancer (CLASSIC Q: strep bovis bacteremia --> what next? *___*) ___ is tumor marker used for CRC (use to measure tx response)

Increased COX2 expression is well-described in colon cancer - rationale for ASA therapy for reducing CRC risk (also increases risk of bleeding/ulcers) DCC gene (chrom18q) indicates shitty prognosis; most common met site is liver Right-sided (MSI, HNPCC) p/w iron-deficiency anemia, weight loss, and "exophytic" tumor (doesn't obstruct --> Apple core sign) Left-sided (AdCarSeq, FAP) p/w LLQ pain, blood-streaked stool, & circumferential lesions w/change in stool caliber (pencil-thin stools) Strep bovis bacteremia/endocarditis is strongly a/w colon cancer (CLASSIC Q: strep bovis bacteremia --> what next? *COLONOSCOPY*) CEA is tumor marker used for CRC (use to measure tx response)

Infectious esophagitis can be 2/2 ___ (white membranes + pseudohyphae on biopsy), ___ ("punched out" ulcers), and ___ (linear ulcers, AIDS) Eosinophilic esophagitis is rxn to food allergens --> dysphagia + food impaction w/poor response to tx and *lots of ___ on biopsy!* Achalasia is inability to relax LES (*[HY] 2/2 loss of ganglion cells in ___ plexus*) - can be caused by chronic ___ Dz (Trypanosoma cruzi); Achalasia p/w *complete dysphagia to ___* + bad breath; Dx w/swallow study (*___ sign*) or esophageal manometry --> ___ LES tone (different from scleroderma!)

Infectious esophagitis can be 2/2 Candida (white membranes + pseudohyphae on biopsy), HSV-1 ("punched out" ulcers), and CMV (linear ulcers, AIDS) Eosinophilic esophagitis is rxn to food allergens --> dysphagia + food impaction w/poor response to tx and *lots of eosinophils on biopsy!* Achalasia is inability to relax LES (*[HY] 2/2 loss of ganglion cells in Auerbach's [myenteric] plexus*) - can be caused by chronic Chagas Dz (Trypanosoma cruzi); Achalasia p/w *complete dysphagia to solids and liquids* + bad breath; Dx w/swallow study (*Bird's Beak sign*) or esophageal manometry --> high LES tone (different from scleroderma!)

Inferior cerebellar peduncle is major pathway into cerebellum from spine, carrying ___ proprioception information (middle cerebellar peduncle carries fibers from contralateral pons); superior cerebellar peduncle carries info out to ___/___ Climbing and mossy fibers carry info to cerebellum and synapse on ___ cells and ___ nuclei; Purkinje cells project to deep nuclei and are inhibitory (___), while deep nuclei project out of cerebellum Deep nuclei include (M --> L) ___

Inferior cerebellar peduncle is major pathway into cerebellum from spine, carrying IPSILATERAL proprioception information (middle cerebellar peduncle carries fibers from contralateral pons); superior cerebellar peduncle carries info out to red nucleus/thalamus Climbing and mossy fibers carry info to cerebellum and synapse on Purkinje cells and deep nuclei; Purkinje cells project to deep nuclei and are inhibitory (GABA), while deep nuclei project out of cerebellum Deep nuclei include (M --> L) fastigial, globose, emboliform, and dentate (get an F, get your GED)

Informed consent must include benefits, risks, and ___ - *must be in language pt understands (___ family)*; consent is implied in emergency (i.e., unconscious trauma pt) ___ privilege is withholding info when disclosure could lead to dangerous psych threat (often for psych pts at risk of harm); can NOT withhold distressing results (violates a___ - i.e., fam not wanting it given, can't lie to get pt to adhere to tx) If pt doesn't wanna know risks, that's okay, *but understand W___ and get W___* Parent/guardian signs consent for minors except in special situations (EMERGENCY - *___ (give or nah?) blood in JehWit parents*; EMANCIPATION; SPECIAL - sex stuff^, s___ abuse)

Informed consent must include benefits, risks, and alternatives - *must be in language pt understands (NOT family)*; consent is implied in emergency (i.e., unconscious trauma pt) Therapeutic privilege is withholding info when disclosure could lead to dangerous psych threat (often for psych pts at risk of harm); can NOT withhold distressing results (violates autonomy - i.e., fam not wanting it given, can't lie to get pt to adhere to tx) If pt doesn't wanna know risks, that's okay, *but understand WHY and get WAIVER* Parent/guardian signs consent for minors except in special situations (EMERGENCY - *GIVE blood in JehWit parents*, EMANCIPATION, SPECIAL - sex stuff^, substance abuse) ^Prenatal care, STDs, contraception

Inguinal canal runs on top of and parallel to the inguinal canal (crosses femoral vessels) - testes descend w/spermatic cord through inguinal canal to scrotum; in females, inguinal canal contains r___ Entrance to inguinal canal is d___, exit is s___, floor is inguinal ligament Three layers to spermatic cord are: internal spermatic fas. (from ___ fas.), cremaster mm (from ___ oblique), and external spermatic fas. (from ___ oblique) [remember ICE TIE] --- Indirect hernias (MC) go through *inguinal canal via ___ inguinal ring* (follow path of testes - also goes through superficial inguinal ring) and originate *___ to epigastric BVs*; IHs are covered by ___ of spermatic fascia IHs are congenital defect 2/2 patent p___ vaginalis --- Direct hernias protrude through *H___ triangle (ing. ligament, inferior epigastric vessels, rectus abdominis)* only passing through superficial inguinal ring and originate *___ to epigastric vessels*; DHs will only be covered by ___ spermatic fascia DHs are 2/2 t___ fascia breakdown

Inguinal canal runs on top of and parallel to the inguinal canal (crosses femoral vessels) - testes descend w/spermatic cord through inguinal canal to scrotum; in females, inguinal canal contains round ligament Entrance to inguinal canal is deep inguinal ring, exit is superficial inguinal ring, floor is inguinal ligament Three layers to spermatic cord are: internal spermatic fas. (from transversalis fas.), cremaster mm (from internal oblique), and external spermatic fas. (from external oblique) [remember ICE TIE] --- Indirect hernias (MC) go through *inguinal canal via deep inguinal ring* (follow path of testes - also goes through superficial inguinal ring) and originate *LATERAL to epigastric BVs*; IHs are covered by all layers of spermatic fascia IHs are congenital defect 2/2 patent processus vaginalis --- Direct hernias protrude through *Hesselbach's triangle (ing. ligament, inferior epigastric vessels, rectus abdominis)* only passing through superficial inguinal ring and originate *MEDIAL to epigastric vessels*; DHs will only be covered by external spermatic fascia DHs are 2/2 transversalis fascia breakdown

___ passes from ASIS to pubic symphysis - femoral aa is ~halfway between (remember NAVL mneumonic) Neurovascular bundle passes through femoral triangle - superior border: i___, medial border: a___, lateral border: s___ Femoral ___ (below inguinal ligament) contains femoral artery, vein, and lymphatics (lymphatics are in femoral ring) - femoral ___ is opening to femoral canal (site of femoral hernias and a component of femoral sheath) Bc FHs pass through femoral ___, which is medial aspect of femoral sheath, FHs are always ___ to femoral vessels; bowel protrudes below the inguinal ligament FHs are more common in ___ (M or F?) and carry high risk of incarceration/strangulation

Inguinal ligament passes from ASIS to pubic symphysis - femoral aa is ~halfway between (remember NAVL mneumonic) Neurovascular bundle passes through femoral triangle - superior border: inguinal ligament, medial border: adductor magnus, lateral border: sartorius Femoral sheath (below inguinal ligament) contains femoral artery, vein, and lymphatics (lymphatics are in femoral ring) - femoral ring is opening to femoral canal (site of femoral hernias and a component of femoral sheath) Bc FHs pass through femoral ring, which is medial aspect of femoral sheath, FHs are always medial to femoral vessels; bowel protrudes below the inguinal ligament FHs are more common in women and carry high risk of incarceration/strangulation

Inherited C3 deficiency leads to recurrent infxns to ___ bacteria (Pneumo, Hflu) and autoimmune dz (REMEMBER: classic pathway starts with ___ complexes and is crucial for clearing them; in C3 deficiency, can't clear --> buildup --> *glomerulonephritis 2/2 ___ deposition [type III hypersensitivity]*) C5-C9 (terminal complement pathway deficiency) p/w impaired defense against encapsulated bugs, but not as bad (still produce C3___ --> anaphylatoxin, C3___ --> opsonin for m___); main problem in C5-9 deficiency is *recurrent ___ infxns* Hereditary Angioedema (___ deficiency) p/w recurrent episodes of swelling and facial edema w.o urticaria (C1-inhibitor can break down b___, deficiency --> excess b___); dx w/low C4; *[HY] NEVER give these pts ___ d/t synergistic effect of excess bradykinin (ACEi inhibit bradykinin breakdown)* CH50 test is ___ assessment of complement (is it working - Y/N); C3 or C4 level is ___ assessment of complement (low in many complement mediated dz - lupus, MPGN, PSGN)

Inherited C3 deficiency leads to recurrent infxns to encapsulated bacteria (Pneumo, Hflu) and autoimmune dz (REMEMBER: classic pathway starts with Ag-Ab complexes and is crucial for clearing them; in C3 deficiency, can't clear --> buildup --> *glomerulonephritis 2/2 IC deposition [type III hypersensitivity]*) C5-C9 (terminal complement pathway deficiency) p/w impaired defense against encapsulated bugs, but not as bad (still produce C3a --> anaphylatoxin, C3b --> opsonin for macrophages); main problem in C5-9 deficiency is *recurrent Neisseria infxns* Hereditary Angioedema (C1-inhibitor deficiency) p/w recurrent episodes of swelling and facial edema w.o urticaria (C1-inhibitor can break down bradykinin, deficiency --> excess bradykinin); dx w/low C4; *[HY] NEVER give these pts ACE-inhibitors d/t synergistic effect of excess bradykinin (ACEi inhibit bradykinin breakdown)* CH50 test is qualitative assessment of complement (is it working - Y/N); C3 or C4 level is quantitative assessment of complement (low in many complement mediated dz - lupus, MPGN, PSGN)

Insulin has several effects that are predictable (think high sugar environment) -___ glucose uptake in adipose and muscle tissue -___ glycogen synthesis (activates glycogen synthase) -___ gluconeogenesis (increases fructose-2,6-bisphosphonate levels) -___ triglyceride synthesis^ (activates acetyl-CoA carboxylase, inhibits hormone sensitive ___ - HSL also acted on by glucagon and epinephrine for OPPOSITE effect) -___ lipolysis -___ protein synthesis^ -Increases sodium retention (not HY) -Lowers potassium (d/t cellular uptake - enhanced ___ pump activity in skeletal muscle, reason for giving in hyperkalemia) -Inhibits glucagon release ^Insulin promotes weight gain

Insulin has several effects that are predictable (think high sugar environment) -Promotes glucose uptake in adipose and muscle tissue -Stimulates glycogen synthesis (activates glycogen synthase) -Inhibits gluconeogenesis (increases fructose-2,6-bisphosphonate levels) -Increases triglyceride synthesis^ (activates acetyl-CoA carboxylase, inhibits hormone sensitive lipase - HSL also acted on by glucagon and epinephrine for OPPOSITE effect) -Inhibits lipolysis -Increases protein synthesis^ -Increases sodium retention (not HY) -Lowers potassium (d/t cellular uptake - enhanced Na-K-ATPase pump activity in skeletal muscle, reason for giving in hyperkalemia) -Inhibits glucagon release ^Insulin promotes weight gain

Insulin receptor is tetramer made up of two ___ units (binds insulin) and two beta units (transmembrane, connected to t___ k___), connected by disulfide bonds 1. Insulin binds receptor --> activates ___ domains within receptor complex 2. Tyrosine ___ (i.e., receptor phosphorylates self) 3. After phosphorylation, RTK binds substrates (insulin receptor substrate - IRS1, IRS2) 4. Downstream signaling via PIK3 or RAS/MAP-Kinase 4a. PIK3 *upregulates ___ transporter (in muscles, fat)* 4b. Insulin receptors activate RAS ___-protein, triggering RAS/MAP-K --> *modify gene expression/cell growth* --- Insulin-dependent organs include ___ and ___ (use GLUT-4 transporters, which requires insulin for express) Insulin-independent organs include B___, RBCs, I___, Cornea, K___, Liver, Islet (beta) cells, Placenta, Spermatocytes (BRICK LIPS)

Insulin receptor is tetramer made up of two alpha units (binds insulin) and two beta units (transmembrane, connected to tyrosine kinase), connected by disulfide bonds 1. Insulin binds receptor --> activates RTK domains within receptor complex 2. Tyrosine autophosphorylation (i.e., receptor phosphorylates self) 3. After phosphorylation, RTK binds substrates (insulin receptor substrate - IRS1, IRS2) 4. Downstream signaling via PIK3 or RAS/MAP-Kinase 4a. PIK3 *upregulates GLUT4 transporter (in muscles, fat)* 4b. Insulin receptors activate RAS G-protein, triggering RAS/MAP-K --> *modify gene expression/cell growth* --- Insulin-dependent organs include muscle and fat (use GLUT-4 transporters, which requires insulin for express) Insulin-independent organs include Brain, RBCs, Intestines, Cornea, Kidney, Liver, Islet (beta) cells, Placenta, Spermatocytes (BRICK LIPS)

Insulinomas lead to *___ hypoglycemia (hallmark)* --> confusion, odd behavior, SNS activation symptoms (tremor, palpitations) Dx is by measure fasting insulin, ___, ___insulin levels (r/o exogenous insulin administration, NOTE: sulfonylureas [and maybe others?] will lead to elevated insulin AND C-peptide as they increase endogenous insulin release) --- Glucagonomas l/t glucose ___ (looks like diabeetus) This will p/w weight loss + *[HY] ___ (red blistering rash that is itchy/painful, flucutates in severity and is found on genitals/buttocks/groin)* Dx is by measuring plasma glucagon levels Tx is w/somatostatin analogs (___) --- *Both these tumors are seen in MEN type ___!*

Insulinomas lead to *fasting hypoglycemia (hallmark)* --> confusion, odd behavior, SNS activation symptoms (tremor, palpitations) Dx is by measure fasting insulin, C-peptide, proinsulin levels (r/o exogenous insulin administration, NOTE: sulfonylureas [and maybe others?] will lead to elevated insulin AND C-peptide as they increase endogenous insulin release) --- Glucagonomas l/t glucose intolerance (looks like diabeetus) This will p/w weight loss + *[HY] necrolytic migratory erythema (red blistering rash that is itchy/painful, flucutates in severity and is found on genitals/buttocks/groin)* Dx is by measuring plasma glucagon levels Tx is w/somatostatin analogs (octreotide) --- *Both these tumors are seen in MEN type I!*

DEFENSE MECHANISMS (immature/unhealthy): ___ is avoiding emotions through reasoning (i.e., stating divorce stats) ___ is isolating destressing memory/event while not experiencing emotions (i.e., describe rape without sadness) ___ is conflicting with others in non-confrontational manner ___ is attributing own feelings/emotions to others (i.e., cheater accusing others of cheating) ___ is distorting events so outcome is positive (i.e., glad I got fired) ___ is engaging in opposite behavior to unwanted feelings (i.e., crave alcohol --> preach abstinence) ___ is reverting to behavior of younger person (i.e., stressed adult watching cartoons when upset) ___ is categorizing others at extremes (i.e., all good or all bad; *seen in borderline personality disorder*)

Intellectualization is avoiding emotions through reasoning (i.e., stating divorce stats) Isolation is isolating destressing memory/event while not experiencing emotions (i.e., describe rape without sadness) Passive Aggression is conflicting with others in non-confrontational manner Projection is attributing own feelings/emotions to others (i.e., cheater accusing others of cheating) Rationalization is distorting events so outcome is positive (i.e., glad I got fired) Reaction Formation is engaging in opposite behavior to unwanted feelings (i.e., crave alcohol --> preach abstinence) Regression is reverting to behavior of younger person (i.e., stressed adult watching cartoons when upset) Splitting is categorizing others at extremes (i.e., all good or all bad; *seen in borderline personality disorder*)

Intraperitoneal structures (covered by mesentery) include: ___ Retroperitoneal structures include (SAD PUCKER): ___ Peritoneal cavity is divided into greater and lesser sac; greater sac is entire width of abdomen from diaphragm to pelvic floor; lesser sac is closed space behind liver/stomach/lesser omentum (___ is opening btwn two sacs)

Intraperitoneal structures (covered by mesentery) include: *stomach, appendix, liver, spleen, jejunum, ileum; 1st part of duodenum; transverse colon, sigmoid colon, part of rectum; tail of pancreas* Retroperitoneal structures include (SAD PUCKER): *Suprarenal (adrenal) glands, AORTA and IVC (important for bleeding!!), Duodenum (not 1st part), Pancreas (head and body), Ureters, Colon (ascending and descending), Kidneys, Esophagus, Rectum (part)* Peritoneal cavity is divided into greater and lesser sac; greater sac is entire width of abdomen from diaphragm to pelvic floor; lesser sac is closed space behind liver/stomach/lesser omentum (epiploic foramen is opening btwn two sacs)

___ stroke generally has gradual onset (over hours), while ___ is more sudden (over minutes) TPA benefit window is ___-hours; after stroke, patients get aspirin for prophylaxis, EKG to look for afib, echo to look for source of embolism (i.e., PFO), and carotid ultrasound (surgery if stenosis >___%)

Ischemic stroke generally has gradual onset (over hours), while hemorrhagic is more sudden (over minutes) TPA benefit window is 3-hours; after stroke, patients get aspirin for prophylaxis, EKG to look for afib, echo to look for source of embolism (i.e., PFO), and carotid ultrasound (surgery if stenosis >70%)

CLASSIC CASE: newborn baby w/deformed teeth/face, diffuse rash, and recurrent *cold* skin abscesses - labs show elevated IgE, que pasa? What's the defect?

JOB'S SYNDROME (HYPER IgE) Defective Th17 cells --> impaired *neutrophil recruitment (why abscesses are cold!)*

Juvenile polyps are benign tumors (h___) that occur in children - can cause painless bleeding after auto-amputation; can be part of *Juvenile Polyposis Syndrome (>10) - although benign polyps, can l/t colon cancer* Peutz-Jeghers syndrome is *autosomal ___ d.o* w/mulitple hamartomas throughout GI tract w/pigmented spots on lips/buccal mucosa - increased risk of breast, GI cancer

Juvenile polyps are benign tumors (hamartomas) that occur in children - can cause painless bleeding after auto-amputation; can be part of *Juvenile Polyposis Syndrome (>10) - although benign polyps, can l/t colon cancer* Peutz-Jeghers syndrome is *autosomal DOMINANT d.o* w/mulitple hamartomas throughout GI tract w/pigmented spots on lips/buccal mucosa - increased risk of breast, GI cancer

CLASSIC CASE: child w/recurrent sinus/ear infxns, chronic cough, bronchiectasis on chest CT, obstruction on PFTs, situs inversus --> what's the abnormality/mutation?

KARTAGENER'S SYNDROME 2/2 DYNEIN MUTATION

Kidneys are derived from ___ germ layer; in utero, three structures form, but after degeneration of two, only one becomes adult kidney The ___ forms and degenerates by week 4; the ___ is the interim kidney for 1st trimester, but degenerates (forms vas deferens in males); the ___ forms at week 5 and forms the adult kidney ~weeks 32-36 These structures form off of the ___ duct - pronephros is cranial, metanephros is caudal, and mesonephros is in btwn Two key structures form adult kidney: 1) ___ (outgrowth of mesonephric duct - becomes ureter, pelvis, calyxes, collecting ducts) and 2) m___ m___ (mesodermal tissue that becomes glomerulus-to-distal tubule) Wilms tumor (MC renal malignancy in children) is proliferation of *m___ m___ (a/w WT1 mutation!)*

Kidneys are derived from mesoderm germ layer; in utero, three structures form, but after degeneration of two, only one becomes adult kidney The pronephros forms and degenerates by week 4; the mesonephros is the interim kidney for 1st trimester, but degenerates (forms vas deferens in males); the metonephros forms at week 5 and forms the adult kidney ~weeks 32-36 These structures form off of the mesonephric duct - pronephros is cranial, metanephros is caudal, and mesonephros is in btwn Two key structures form adult kidney: 1) ureteric bud (outgrowth of mesonephric duct - becomes ureter, pelvis, calyxes, collecting ducts) and 2) metanephric mesenchyme (mesodermal tissue that becomes glomerulus-to-distal tubule) Wilms tumor (MC renal malignancy in children) is proliferation of *metanephric mesenchyme (a/w WT1 mutation!)*

Klinefelter (47 XXY) is usually 2/2 m___ n___ of either parent; 48 XXXY can happen, more severe; 46 XY --> 47 XXY can occur with somatic m___ (2/2 mitotic nondisjunction after fert., less sev) Males are feminized - primary h___ (delayed pub., low testosterone, high FSH/LH, small testes - ratio of est:test determines severity), genital abnormalities (cryptorchidism, hypospadia, micropenis), long legs/arms (extra copy of S___ gene on X-chromosome --> important for long bone growth), "eunuchoid body shape", learning disabilities, quiet personalities *[HY] Klinefelter patients can have B___ B___ found in nucleus of cells (not normally seen in males)*

Klinefelter (47 XXY) is usually 2/2 meiotic nondisjunction of either parent; 48 XXXY can happen, more severe; 46 XY --> 47 XXY can occur with somatic mosaicism (2/2 mitotic nondisjunction after fert., less sev) Males are feminized - primary hypogonadism (delayed pub., low testosterone, high FSH/LH, small testes - ratio of est:test determines severity), genital abnormalities (cryptorchidism, hypospadia, micropenis), long legs/arms (extra copy of SHOX gene on X-chromosome --> important for long bone growth), "eunuchoid body shape", learning disabilities, quiet personalities *[HY] Klinefelter patients can have Barr Body found in nucleus of cells (not normally seen in males)*

Knee is classic synovial joint w/surrounding synovial-lined sacs called bursa; prepatellar bursitis is inflamm. of prepatellar bursa ("___ knee") that p/w pain with activity + swelling/warmth anterior to patella (tx w/NSAIDs and ice) Popliteal (Baker's) cyst is fluid collection in bursa btwn gastroc. and semimembranosus; this bursa communicates w/___ space and is present in chronic joint dz (___, rheumatoid arthritis); rupture can cause acute pain and mimics ___ ___r is pain/swelling @ tibial tubercle 2/2 overuse; *this attachment is site of ___ ossification center of tibia* *Patellar fracture presents w/inability to ___ knee against gravity*

Knee is classic synovial joint w/surrounding synovial-lined sacs called bursa; prepatellar bursitis is inflamm. of prepatellar bursa ("housemaid's knee") that p/w pain with activity + swelling/warmth anterior to patella (tx w/NSAIDs and ice) Popliteal (Baker's) cyst is fluid collection in bursa btwn gastroc. and semimembranosus; this bursa communicates w/synovial space and is present in chronic joint dz (osteoarthritis, rheumatoid arthritis); rupture can cause acute pain and mimics DVT Osgood-Schlatter is pain/swelling @ tibial tubercle 2/2 overuse; *this attachment is site of secondary ossification center of tibia* *Patellar fracture presents w/inability to extend knee against gravity*

L5 nerve root syndrome causes pain down ___ leg S1 NRS causes pain down ___ leg with weakness in ___ and loss of ___

L5 nerve root syndrome causes pain down lateral leg S1 NRS causes pain down back of leg with weakness in plantarflexion and loss of ankle reflex

LARGE VESSEL VASCULITIS: *___* inflammation + large artery narrowing; Tx with steroids *Temporal (Giant Cell) Arteritis*: narrowing of temporal artery (usually in ___) --> *headache*, *jaw ___*; feared outcome is *BLINDNESS (___ occlusion - often what is asked)* Classically seen w/elevated ESR, confirmation is w/*temporal aa biopsy (shows ___ inflammation - often what is asked)* Strong a/w p___ --- *Takayasu's Arteritis*: granulomatous thickening of ___ and branches (usually in *young ___ woman*), classic sx of *weak ___ in one arm ("pulseless dz")* d/t narrowing of proximal great vessels (BP difference), may show aortogram on Step 1! Will see elevated ESR and *___ inflammation*

LARGE VESSEL VASCULITIS: *granulomatous* inflammation + large artery narrowing; Tx with steroids *Temporal (Giant Cell) Arteritis*: narrowing of temporal artery (usually in old woman) --> *headache*, *jaw claudication*; feared outcome is *BLINDNESS (ophthalmic aa occlusion - often what is asked)* Classically seen w/elevated ESR, confirmation is w/*temporal aa biopsy (shows granulomatous inflammation - often what is asked)* Strong a/w polymyalgia rheumatica --- *Takayasu's Arteritis*: granulomatous thickening of aortic arch and branches (usually in *young Asian woman*), classic sx of *weak pulses in one arm ("pulseless dz")* d/t narrowing of proximal great vessels (BP difference), may show aortogram on Step 1! Will see elevated ESR and *granulomatous inflammation*

LEMS is a paraneoplastic syndrome (___) 2/2 Abs to *___synaptic Ca channels* LEMS presents w/slow-onset, symmetric proximal muscle weakness (diff. from MG, which p/w *___ SYMPTOMS*; weakness improves with repeated contraction, diff. from MG) - this is also seen in myositis, but LEMS will have *normal labs (no CK/CRP elevation, which is seen in myositis)* LEMS also presents w/*a___ dysfunction (DIFF. from MG - in MG, problem is w/muscle receptor; in LEMS, problem is w/ACh release and affects entire body)* - this p/w dry mouth, constipation, and impotence

LEMS is a paraneoplastic syndrome (small cell lung cancer) 2/2 Abs to *PREsynaptic Ca channels* LEMS presents w/slow-onset, symmetric proximal muscle weakness (diff. from MG, which p/w *EYE SYMPTOMS*; weakness improves with repeated contraction, diff. from MG) - this is also seen in myositis, but LEMS will have *normal labs (no CK/CRP elevation, which is seen in myositis)* LEMS also presents w/*autonomic dysfunction (DIFF. from MG - in MG, problem is w/muscle receptor; in LEMS, problem is w/ACh release and affects entire body)* - this p/w dry mouth, constipation, and impotence

Lactose intolerance is lactase deficiency (BB enzyme) --> lactose in small bowel --> ___ diarrhea Histology: *perfectly normal* Cause: *lactase non-___ (falls w/aging - congenital deficiency is rare)*; LI can be 2/2 mucosal injury (bacterial overgrowth, infxn, IBD) - will see histology that reflects cause Dx: clinical, but can use *lactose breath hydrogen test (if undigested, bacteria ferment lactose --> generate ___ --> [+] if H+ is high on exhalation!)*

Lactose intolerance is lactase deficiency (BB enzyme) --> lactose in small bowel --> osmotic diarrhea Histology: *perfectly normal* Cause: *lactase non-persistence (falls w/aging - congenital deficiency is rare)*; LI can be 2/2 mucosal injury (bacterial overgrowth, infxn, IBD) - will see histology that reflects cause Dx: clinical, but can use *lactose breath hydrogen test (if undigested, bacteria ferment lactose --> generate hydrogen --> [+] if H+ is high on exhalation!)*

Lacunar strokes are small strokes associated with HTN that often *___ in initial CT scan* and lack cortical signs (aphasia, agnosia, hemianopsia); LSs can damage internal capsule, thalamus, basal ganglia, pons 2/2 occlusion of ___ arteries There are five subtypes: pure motor (post limb int caps), pure sensory (VPL thal), sensorimotor, ataxic hemiparesis, and dysarthria-clumsy hand syndrome Hemiballism is a lacunar stroke subtype 2/2 ___ damage

Lacunar strokes are small strokes associated with HTN that often don't show in initial CT scan and lack cortical signs (aphasia, agnosia, hemianopsia); LSs can damage internal capsule, thalamus, basal ganglia, pons 2/2 occlusion of lenticulostriate arteries There are five subtypes: pure motor (post limb int caps), pure sensory (VPL thal), sensorimotor, ataxic hemiparesis, and dysarthria-clumsy hand syndrome Hemiballism is a lacunar stroke subtype 2/2 subthalamic nucleus damage

Langerhans Cell Histocytosis (hystiocyte - connective tissue macrophage; Langerhans cell - dendritic cell) is a clonal proliferation of *dendritic cells of myeloid origin, expressing ___ and ___ ("most likely questions you will see on exam")* Malignant Langerhans cells will have *___ on electron microscopy (tennis racket - "other thing they will want you to know")* LCH p/w child who has sx in the bone (*___ bone lesions*) and ___ (*rash*) - in event of pathologic bone fx, you might think osteosarcoma but *biopsy will show ___ cells + eosinophils*

Langerhans Cell Histocytosis (hystiocyte - connective tissue macrophage; Langerhans cell - dendritic cell) is a clonal proliferation of *dendritic cells of myeloid origin, expressing S-100 and CD1a ("most likely questions you will see on exam")* Malignant Langerhans cells will have *Birbeck granules on electron microscopy (tennis racket - "other thing they will want you to know")* LCH p/w child who has sx in the bone (*lytic bone lesions*) and skin (*rash*) - in event of pathologic bone fx, you might think osteosarcoma but *biopsy will show Langerhans cells + eosinophils*

Layers of the gut wall included (MSMS): mucosa, submucosa, muscularis externa, serosa Mucosa includes epithelium, l___ (contains glands), and m___ mucosa Submucosa contains connective tissue and Meissner's (s___) plexus (MP is lost in *Hirschsprung's dz*) Muscularis contains inner ___ layer and outer ___ layer - also contains Auerbach's plexus (btwn layers, lost in *a___*) Serosa contains layers of surface epithelial cells (mesothelium - secretes lubricating fluid), except ___ structures (SAD PUCKER, surrounded by adventicia - not lubricated) NOTE: erosion --> mucosa only; ulcer --> mucosa + submucosa +/- muscularis

Layers of the gut wall included (MSMS): mucosa, submucosa, muscularis externa, serosa Mucosa includes epithelium, lamina propria (contains glands), and muscularis mucosa Submucosa contains connective tissue and Meissner's (submucosal) plexus (MP is lost in *Hirschsprung's dz*) Muscularis contains inner circular layer and outer longitudinal layer - also contains Auerbach's plexus (btwn layers, lost in *achalasia*) Serosa contains layers of surface epithelial cells (mesothelium - secretes lubricating fluid), except retroperitoneal structures (SAD PUCKER, surrounded by adventicia - not lubricated) NOTE: erosion --> mucosa only; ulcer --> mucosa + submucosa +/- muscularis

Lead poisoning can be caused by inhalation from industrial work in adults and eating ___ in children Lead poisoning can l/t microcytic anemia, d/t lead inhibiting heme synthesis (*delta-ALA ___ and ferrochelatase*); accordingly, a key lab finding is *elevated ___ and proto___!* LP p/w Lead Lines (*blue pigment on ___ line*), Encephalopathy (behavioral issues, developmental delay)/Erythrocyte stippling, A___ pain/Anemia, and wrist/foot ___ *[LEAD]* Dx: low plasma lead, *[know the following] high ___, high proto___* Blood Smear: *BASOPHILIC ___ (lead also inhibits pyrimidine 5' nucleotidase --> accumulation of pyrimidines/RNA in RBCs)* Tx: chelation therapy (dimercaprol, EDTA, succimer)

Lead poisoning can be caused by inhalation from industrial work in adults and eating lead paint in children Lead poisoning can l/t microcytic anemia, d/t lead inhibiting heme synthesis (*delta-ALA dehydratase and ferrochelatase*); accordingly, a key lab finding is *elevated delta-ALA and protoporphyrin!* LP p/w Lead Lines (*blue pigment on gum-tooth line*), Encephalopathy (behavioral issues, developmental delay)/Erythrocyte stippling, Abdominal pain/Anemia, and wrist/foot Drop *[LEAD]* Dx: low plasma lead, *[know the following] high delta-ALA, high protoporphyrin* Blood Smear: *BASOPHILIC STIPPLING (lead also inhibits pyrimidine 5' nucleotidase --> accumulation of pyrimidines/RNA in RBCs)* Tx: chelation therapy (dimercaprol, EDTA, succimer)

Legionella can cause pneumonia (lobar, atypical), outbreaks @ hotels w/*contaminated ___* - *look for ___ SYMPTOMS and ___! - also confusion + no bact. on gram stain (need BCYE agar)* Mycoplasma can cause atypical pneumonia in ___ residents & ___ recruits - *look for ___ AIHA and Stevens-Johnsons Syndrome* Influenza can cause secondary ___ 2/2 *Strep pneumo, Staph - cause of death related to influenza!* CMV can cause pneumonia in transplant pts on immunosuppressive drugs - look for *___ intranuclear inclusions on path!* ___ can cause LRI in infants (bronchiolitis, pneumonia) w/*wheezing* - tx w/Ribavirin and prevent w/Palivizumab in pre-term infants (monclonal Ab against F-protein)

Legionella can cause pneumonia (lobar, atypical), outbreaks @ hotels w/*contaminated water* - *look for GI SYMPTOMS and HYPONATREMIA! - also confusion + no bact. on gram stain (need BCYE agar)* Mycoplasma can cause atypical pneumonia in dorm residents & military recruits - *look for cold AIHA and Stevens-Johnsons Syndrome* Influenza can cause secondary bacterial pneumonia 2/2 *Strep pneumo, Staph - cause of death related to influenza!* CMV can cause pneumonia in transplant pts on immunosuppressive drugs - look for *Owl Eye intranuclear inclusions on path!* RSV can cause LRI in infants (bronchiolitis, pneumonia) w/*wheezing* - tx w/Ribavirin and prevent w/Palivizumab in pre-term infants (monclonal Ab against F-protein)

Leptomininges are ___ mater and are what is inflamed in meningitis Hallmark of meningitis is ___ rigidity; may also seen Kernig sign (knee extension, K --> Knee) and Brudzinski's sign (lift head) *During LP, needle goes through skin, ligaments, dura, and arachnoid - it does NOT pierce the ___* Bacterial meningitis --> elevated ___, ___ prot, ___ glu Viral meningitis --> elevated ___, ___ prot, ___ glu Fungal/TB meningitis --> elevated ___, ___ prot, ___ glu

Leptomininges are pia and arachnoid mater and are what is inflamed in meningitis Hallmark of meningitis is nuchal rigidity; may also seen Kernig sign (knee extension, K --> Knee) and Brudzinski's sign (lift head) *During LP, needle goes through skin, ligaments, dura, and arachnoid - it does NOT pierce the PIA MATER* Bacterial meningitis --> elevated PMNs, elevated prot, low glu Viral meningitis --> elevated lymphs, normal/high prot, normal glu Fungal/TB meningitis --> elevated lymphs, elevated prot, low glu

Leukemias are malignant proliferation of WBC w/*___ WBC in peripheral blood (vs lymphoma)* Leukemias can be acute vs chronic (differentiated by onset of sx and involvement of -blasts) and myelogenous vs lymphoid (differentiated by cells of origin) Myeloid: myeloblasts (AML) or myeloproliferative d/o (RBCs - ___, granulocytes - ___, plts - ___) Lymphoid: lymphoblasts (acute lymphoblastic leukemia) or B-cells/T-cells (chronic lymphocytic leukemia) or lymph node lymphocytes (lymphomas) or plasma cells (multiple myeloma)

Leukemias are malignant proliferation of WBC w/*elevated WBC in peripheral blood (vs lymphoma)* Leukemias can be acute vs chronic (differentiated by onset of sx and involvement of -blasts) and myelogenous vs lymphoid (differentiated by cells of origin) Myeloid: myeloblasts (AML) or myeloproliferative d/o (RBCs - polycythemia vera, granulocytes - CML, plts - essential thrombocytosis) Lymphoid: lymphoblasts (acute lymphoblastic leukemia) or B-cells/T-cells (chronic lymphocytic leukemia) or lymph node lymphocytes (lymphomas) or plasma cells (multiple myeloma)

Lichen Planus is flat skin lesion w/unknown pathogen *that is associated with Hep___*; sx include *intense ___, but minimal pain (differentiating factor)* - wrists/ankles are common sites LP often has *mucosal involvement with Wichham striae - white dots/lines 2/2 hypergranulosis*; path. will reveal *H___ (inc. thickness of granular layer, LP is classic cause of this) and "sawtooth pattern" of rete ridges* P___ R___ is self-limited eruption of skin lesions (resolves 2-3mo); begins with *"herald patch"* (single red, round, well-demarc. lesion), then days later develop *multiple lesions on trunk* (follow skin lines on back --> *"C___ T___ distribution"*)

Lichen Planus is flat skin lesion w/unknown pathogen *that is associated with HepC*; sx include *intense itchiness, but minimal pain (differentiating factor)* - wrists/ankles are common sites LP often has *mucosal involvement with Wichham striae - white dots/lines 2/2 hypergranulosis*; path. will reveal *HYPERGRANULOSIS (inc. thickness of granular layer, LP is classic cause of this) and "sawtooth pattern" of rete ridges* Pityriasis Rosea is self-limited eruption of skin lesions (resolves 2-3mo); begins with *"herald patch"* (single red, round, well-demarc. lesion), then days later develop *multiple lesions on trunk* (follow skin lines on back --> *"Christmas tree distribution"*)

Light reflex starts with 1. CN2, 2. pretectal nuc, and 3. bilateral EW nuc Marcus Gunn Pupil is relative APD that is dx via swinging flashlight test; the classic cause is optic neuritis 2/2 ___ Accommodation reflex has three steps: convergence, accommodation, and ___ (complex circuit - don't know it) Argyll Robertson Pupil, 2/2 ___, involves pretectal nuc; subsequently, pupil constricts to accommodation but not light --> ___

Light reflex starts with 1. CN2, 2. pretectal nuc, and 3. bilateral EW nuc Marcus Gunn Pupil is relative APD that is dx via swinging flashlight test; the classic cause is optic neuritis 2/2 multiple sclerosis Accommodation reflex has three steps: convergence, accommodation, and miosis (complex circuit - don't know it) Argyll Robertson Pupil, 2/2 syphilis, involves pretectal nuc; subsequently, pupil constricts to accommodation but not light --> syphilis

Live attenuated vaccines are less virulent bugs --> induce strong cell-mediated response; some risk of infection and can't give <1y (___ prevent response); ex: MMR ___ vaccine is just antigen - generates strong humoral response (weaker than live-attenuated), but has no risk of infection Oral vaccine stimulates GI mucosal immunity (i.e., largely Ig___ response) that can be useful for bugs like Polio, Rotavirus IM vaccine --> tissue response --> Ig___ ___ immunization is just giving antibodies (rabies, tetanus)

Live attenuated vaccines are less virulent bugs --> induce strong cell-mediated response; some risk of infection and can't give <1y (mom's Abs prevent response); ex: MMR Killed vaccine is just antigen - generates strong humoral response (weaker than live-attenuated), but has no risk of infection Oral vaccine stimulates GI mucosal immunity (i.e., largely IgA response) that can be useful for bugs like Polio, Rotavirus IM vaccine --> tissue response --> IgG Passive immunization is just giving antibodies (rabies, tetanus)

Liver abscess is usually 2/2 bacteria (bacteremia, cholangitis [Klebsiella]), but two *[HY] causes are e___ (protozoa) and e___ (helminth)* Entamoeba is 2/2 eating ___ in contaminated water --> blood diarrhea + hepatomegaly Echinococcus is 2/2 fecal-oral ingestion of eggs --> *___* liver cysts

Liver abscess is usually 2/2 bacteria (bacteremia, cholangitis [Klebsiella]), but two *[HY] causes are entamoeba histolytica (protozoa) and echinococcus (helminth)* Entamoeba is 2/2 eating cysts in contaminated water --> blood diarrhea + hepatomegaly Echinococcus is 2/2 fecal-oral ingestion of eggs --> *MASSIVE* liver cysts

Low ADH --> low Uosm; high ADH --> high Uosm In the setting of hyponatremia, urine should be diluted; if urine is diluted, cause is likely outside the kidney; if urine is not diluted, kidneys are not responding appropriately or too much ADH is around

Lower respiratory tract is trachea down; resp. tract can also be divided into conducting zone (humidifies air) and respiratory zone (gas exchange - starts @ ___ bronchioles + alveoli) Alveoli are small sacs surrounded by capillaries - facilitate in gas exchange; alveoli have two cell types: type I pneumocytes (97% of cells - thin for gas exchange) and *[HY] type II p___ that produces ___ (lecithin) - also proliferate and are key for ___ regeneration* (also Clara cells, but w/unknown function) Surfactant prevents alveoli collapse by reducing s___ t___^ In fetal lungs <35w, lecithin/s___ ratio is <2.0 (immature lungs - can't keep alveoli open yet) - lecithin shoots up ~35w; give preterm babies *b___* to stimulate surfactant production ^Distending pressure (pressure needed to keep sphere open) = 2 x ([surface tension] / [radius]) - as radius goes down, distending pressure increases (takes more pressure to keep small sphere open - small sphere is easier to collapse); ST decreases as alveoli shink --> distending pressure remains same

Lower respiratory tract is trachea down; resp. tract can also be divided into conducting zone (humidifies air) and respiratory zone (gas exchange - starts @ respiratory bronchioles + alveoli) Alveoli are small sacs surrounded by capillaries - facilitate in gas exchange; alveoli have two cell types: type I pneumocytes (97% of cells - thin for gas exchange) and *[HY] type II pneumocytes that produces SURFACTANT (lecithin) - also proliferate and are key for injury regeneration* (also Clara cells, but w/unknown function) Surfactant prevents alveoli collapse by reducing surface tension^ In fetal lungs <35w, lecithin/sphingomyelin ratio is <2.0 (immature lungs - can't keep alveoli open yet) - lecithin shoots up ~35w; give preterm babies *betamethasone* to stimulate surfactant production ^Distending pressure (pressure needed to keep sphere open) = 2 x ([surface tension] / [radius]) - as radius goes down, distending pressure increases (takes more pressure to keep small sphere open - small sphere is easier to collapse); ST decreases as alveoli shink --> distending pressure remains same

Lumbosacral plexus (L: T12-L4, S: L4-S4) has many nerves: Sciatic (L4-S3, remember - obt. and fem. nn. end @ L4): splits into common peroneal and tibial; M - gets hamstrings *and a___ (1/2)* Common Peroneal (L4-S2): M - *biceps femoris ___ (knee flexion)*, lateral leg mm. (superficial - *___*), anterior leg mm. (deep - *___*), S - dorsum of foot; injury (2/2 trauma to *lateral aspect of leg/f___ fx*) l/t *foot ___ and sensory loss of dorsal foot* Tibial (L4-S3): M - LH of BF (knee flex.), posterior calf mm. (*___, ___*), S - sole of foot/heel (*travels thru ___ under medial mal.*); lesion (2/2 knee trauma, Baker's cyst, *tarsal tunnel synd.*) l/t pain on foot sole and inability to walk on toes Pudendal (S2-S4): M - genital mm. (perineum, ext. sphincters, levator ani), S - perineum + penis/clitoris; lesion (2/2 ___ stretching, cycling) l/t decr. sensation and incontinence (use pudendal nn. block @ ischial spine of pelvis)

Lumbosacral plexus (L: T12-L4, S: L4-S4) has many nerves: Sciatic (L4-S3, remember - obt. and fem. nn. end @ L4): splits into common peroneal and tibial; M - gets hamstrings *and adductor magnus (1/2)* Common Peroneal (L4-S2): M - *biceps femoris short head (knee flexion)*, lateral leg mm. (superficial - *eversion*), anterior leg mm. (deep - *dorsiflexion*), S - dorsum of foot; injury (2/2 trauma to *lateral aspect of leg/fibular neck fx*) l/t *foot drop and sensory loss of dorsal foot* Tibial (L4-S3): M - LH of BF (knee flex.), posterior calf mm. (*plantarflexion, inversion*), S - sole of foot/heel (*travels thru tarsal tunnel under medial mal.*); lesion (2/2 knee trauma, Baker's cyst, *tarsal tunnel synd.*) l/t pain on foot sole and inability to walk on toes Pudendal (S2-S4): M - genital mm. (perineum, ext. sphincters, levator ani), S - perineum + penis/clitoris; lesion (2/2 childbirth stretching, cycling) l/t decr. sensation and incontinence (use pudendal nn. block @ ischial spine of pelvis)

Lumbosacral plexus (L: T12-L4, S: L4-S4) has many nerves: I GLO F (note how vertebral levels go - easier to understand when written this way) + sciatic and others Iliohypogastric (T12-L1): M - transverse abdominis & internal oblique, S - suprapubic (hypogastric) region; lesion (2/2 abd. surgery w/sutures trapping nn.) l/t pain @ ___ radiating to ___ region Genitofemoral (L1-L2): M - cremaster, S - scrotum/labia & medial thigh; lesion (2/2 lap. surgery w/retractor blades) l/t decr. sensation and *absent ___* Lateral Femoral Cutaneous (L2-L3): S - anterolateral thigh; damage (2/2 tight clothing, fatness) l/t decr. sensation over anterolateral thigh (*___*) Obturator (L2-L4, obturare - to close): M - adductors, S - medial thigh; damage (2/2 pelvic surgery w/trocars) l/t weak a___ and ___ thigh numbness Femoral (L2-L4): M - knee extensors & *hip flexors*, S - anterior thigh & *medial leg (saphenous - can be damaged in CABG)*; damage (2/2 pelvic fx) l/t weak leg extension & *[HY] decr. ___* (can do femoral nn. block, but need to remember NAVL - palp. aa. and go lateral)

Lumbosacral plexus (L: T12-L4, S: L4-S4) has many nerves: I GLO F (note how vertebral levels go - easier to understand when written this way) + sciatic and others Iliohypogastric (T12-L1): M - transverse abdominis & internal oblique, S - suprapubic (hypogastric) region; lesion (2/2 abd. surgery w/sutures trapping nn.) l/t pain @ surgical site radiating to suprapubic region Genitofemoral (L1-L2): M - cremaster, S - scrotum/labia & medial thigh; lesion (2/2 lap. surgery w/retractor blades) l/t decr. sensation and *absent cremaster reflex* Lateral Femoral Cutaneous (L2-L3): S - anterolateral thigh; damage (2/2 tight clothing, fatness) l/t decr. sensation over anterolateral thigh (*meralgia paresthetica*) Obturator (L2-L4, obturare - to close): M - adductors, S - medial thigh; damage (2/2 pelvic surgery w/trocars) l/t weak adduction and medial thigh numbness Femoral (L2-L4): M - knee extensors & *hip flexors*, S - anterior thigh & *medial leg (saphenous - can be damaged in CABG)*; damage (2/2 pelvic fx) l/t weak leg extension & *[HY] decr. patellar reflex* (can do femoral nn. block, but need to remember NAVL - palp. aa. and go lateral)

Lung Pressure Zones: At apex, pressure of blood vessels is low (d/t gravity); at base, pressure of blood vessels is high Throughout lungs, pressure in alveoli is SAME Theoretically, alveolar pressure could become high enough to compress vessels --> ___ (theoretical concept seen in some dz states, but tested on) NOTE: ___ (BV?) pressure > ___ (BV?) pressure In apex (Zone 1), P___ > P___ > P___ In middle (Zone 2), P___ > P___ > P___ In base (Zone 3), P___ > P___ > P___

Lung Pressure Zones: At apex, pressure of blood vessels is low (d/t gravity); at base, pressure of blood vessels is high Throughout lungs, pressure in alveoli is SAME Theoretically, alveolar pressure could become high enough to compress vessels --> dead space (theoretical concept seen in some dz states, but tested on) NOTE: artery pressure > vein pressure In apex (Zone 1), PA > Pa > Pv In middle (Zone 2), Pa > PA > Pv In base (Zone 3), Pa > Pv > PA

Lung capacities are sum of two volumes; terms to know are tidal volume, inspiratory reserve volume, expiratory reserve volume, residual volume - inspiratory capacity, expiratory reserve capacity, functional residual capacity, vital capacity, total lung capacity V___ is [volume of air x respiratory rate] - can go to alveoli (good for gas exchange) or ___ (wasted ventilation) - dead space can be anatomic (conducting portion - nose, trachea) or physiologic (alveoli that don't exchange gas, seen in apex - increases in dz)

Lung capacities are sum of two volumes; terms to know are tidal volume, inspiratory reserve volume, expiratory reserve volume, residual volume - inspiratory capacity, expiratory reserve capacity, functional residual capacity, vital capacity, total lung capacity Ventilation is [volume of air x respiratory rate] - can go to alveoli (good for gas exchange) or dead space (wasted ventilation) - dead space can be anatomic (conducting portion - nose, trachea) or physiologic (alveoli that don't exchange gas, seen in apex - increases in dz)

Lupus is a classic example of type ___ HS rxn with wide ranging, episodic sx - these Ag-Ab complexes overactivate ___ Accordingly, labs often show positive ANA antibodies (sensitive, but not specific) and ___ complement (C3/C4); antibodies that are specific for SLE include anti-___ and anti-Smith (*biochem tie in - Smith is anti-___; snRNPS combine with RNA transcript --> ___ --> intron splicing*) Sx in SLE come in flares and include Rash (malar [sunlight exposure], discoid), Arthritis, ___ (pleuritis, pericarditis), Hematologic d.o (-penias *2/2 type ___ HS rxn*), Oral/nasopharyngeal ___, Renal dz (*common cause of death - DPGN [nephr___tic] and MPGN [nephr___tic]*) , Photosensitivity (malar rash), Antinuclear antibodies, Immunologic d.o (w/anti-___, anti-dsDNA, antiphospholipid), Neurologic d.o (psychosis, seizures) [RASH OR PAIN] ___ Endocarditis is non-bacterial inflammation of the left-sided valves, *classically affecting ___ SIDES of the mitral valve* [LSE in SLE] Can see anti-phospholipid syndrome in SLE (anti-c___, ___ anticoagulant, anti-___ glycoprotein) COD: renal failure, infection (immunosuppressant drugs), coronary dz

Lupus is a classic example of type III HS rxn with wide ranging, episodic sx - these Ag-Ab complexes overactivate complement Accordingly, labs often show positive ANA antibodies (sensitive, but not specific) and low complement (C3/C4); antibodies that are specific for SLE include anti-dsDNA and anti-Smith (*biochem tie in - Smith is anti-snRNP; snRNPS combine with RNA transcript --> spliceosome --> intron splicing*) Sx in SLE come in flares and include Rash (malar [sunlight exposure], discoid), Arthritis, Serositis (pleuritis, pericarditis), Hematologic d.o (-penias *2/2 type II HS rxn*), Oral/nasopharyngeal ulcers, Renal dz (*common cause of death - DPGN [nephritic] and MPGN [nephrotic]*) , Photosensitivity (malar rash), Antinuclear antibodies, Immunologic d.o (w/anti-Smith, anti-dsDNA, antiphospholipid), Neurologic d.o (psychosis, seizures) [RASH OR PAIN] Libman-Sacks Endocarditis is non-bacterial inflammation of the left-sided valves, *classically affecting BOTH SIDES of the mitral valve* [LSE in SLE] Can see anti-phospholipid syndrome in SLE (anti-cardiolipin, lupus anticoagulant, anti-B2 glycoprotein) COD: renal failure, infection (immunosuppressant drugs), coronary dz

Lye are alkali substances (i.e., sodium hydroxide) that can be ingested by children incidentally (household cleaners); Lye can l/t liquefactive necrosis --> esophageal ___ in later life Esophageal varices are dilated submucosal veins, usually 2/2 cirrhosis - can lead to *u___ G___ b___ + death in cirrhotics (screen w/endoscopy, tx w/banding/ligation)* Mallory-Weiss syndrome is *[HY] damage to esophageal ___ at GE junction (linear lacerations)!* - p/w painful hematemesis in pt w/severe, chronic vomiting (alcoholic, bulimia) BoerHaave Syndrome is *[HY] ___ rupture of esophagus 2/2 severe, chronic vomiting* - will see ___ in mediastinum (pneumomediastinum); more severe that MalWeisSyn Zenker's Diverticulum is a ___ diverticulum that occurs d/t herniation of *mucosa/submucosa tissue @ ___ Triangle (btwn thyropharyngeus & cricopharyngeus)* - commonly results d/t inability of *___ mm to relax* --> increased pressure --> turd pokes out; p/w *AWFUL ___, dysphagia, aspiration in elderly guy*; dx w/swallow study

Lye are alkali substances (i.e., sodium hydroxide) that can be ingested by children incidentally (household cleaners); Lye can l/t liquefactive necrosis --> esophageal strictures in later life Esophageal varices are dilated submucosal veins, usually 2/2 cirrhosis - can lead to *upper GI bleed + death in cirrhotics (screen w/endoscopy, tx w/banding/ligation)* Mallory-Weiss syndrome is *[HY] damage to esophageal MUCOSA ONLY at GE junction (linear lacerations)!* - p/w painful hematemesis in pt w/severe, chronic vomiting (alcoholic, bulimia) BoerHaave Syndrome is *[HY] transmural rupture of esophagus 2/2 severe, chronic vomiting* - will see air in mediastinum (pneumomediastinum); more severe that MalWeisSyn Zenker's Diverticulum is a false diverticulum that occurs d/t herniation of *mucosa/submucosa tissue @ Killian Triangle (btwn thyropharyngeus & cricopharyngeus)* - commonly results d/t inability of *cricopharyngeus mm to relax* --> increased pressure --> turd pokes out; p/w *AWFUL breath, dysphagia, aspiration in elderly guy*; dx w/swallow study

Lymphomas commonly present as enlarged, *pain___* lymph node (pain___ suggests infxn) + B-symptoms; cervical nodes are MC involved, followed by *___ spread (unique from NHL) and ___ extranodal involvement (unique from NHL)* Dx is made with node biopsy - if Reed-Sternberg cells are present --> *___ lymphoma* Reed-Sternberg cells or usually derived from B-cells and have *large, multi-lobed nuclei ("___")*; unlike normal B-cells, RS cells rarely express CD19, 20, 21 - instead, express *CD___ and CD___!* What's unique about HL is that malignant cells (RSCs) are ___ of cells present - RSCs release *shitload of ___ --> generate reactive cells + MORE B-SYMPTOMS THAN nHL!* - also, macrophages are activated and *[HY] can lead to ___ 2/2 ___ hydroxylase activity in macrophages* RFs include *___ infxn*, immunosuppression, AI dz (RA, SLE) When dz is limited --> HL highly curable (___ is strongest predictor of prognosis) Subtypes include: nodular sclerosis, lymphocyte rich, mixed cellularity, lymphocyte depleted, and nodular lymphocyte predominant

Lymphomas commonly present as enlarged, *painLESS* lymph node (painFUL suggests infxn) + B-symptoms; cervical nodes are MC involved, followed by *predictable spread (unique from NHL) and w.o extranodal involvement (unique from NHL)* Dx is made with node biopsy - if Reed-Sternberg cells are present --> *Hodgkin lymphoma* Reed-Sternberg cells or usually derived from B-cells and have *large, multi-lobed nuclei ("owl-eyed")*; unlike normal B-cells, RS cells rarely express CD19, 20, 21 - instead, express *CD15 and CD30!* What's unique about HL is that malignant cells (RSCs) are minority of cells present - RSCs release *shitload of cytokines --> generate reactive cells + MORE B-SYMPTOMS THAN nHL!* - also, macrophages are activated and *[HY] can lead to hypercalcemia 2/2 1-alpha hydroxylase activity in macrophages* RFs include *EBV infxn*, immunosuppression, AI dz (RA, SLE) When dz is limited --> HL highly curable (stage is strongest predictor of prognosis) Subtypes include: nodular sclerosis, lymphocyte rich, mixed cellularity, lymphocyte depleted, and nodular lymphocyte predominant

MAC can cause severe disseminated disease in AIDS patients *(CD4 <___)* with fever, sweats, abdominal pain, diarrhea, weight loss with no ___ findings (differentiates from TB); give ___ when CD4 <50 Mycobacterium Kansasii causes similar pathology to ___, but is less virulent (tx similarly) Deficiency in ___ receptor leaves patients incapable of differentiating *T-cells to Th1 cells*, thus no ___ can be produced; decreased ___ cellular activity leaves patients susceptible to disseminated Salmonella and nonTB mycobacteria (___ organisms), but can treat with IFN-y

MAC can cause severe disseminated disease in AIDS patients *(CD4 <50)* with fever, sweats, abdominal pain, diarrhea, weight loss with no lung findings (differentiates from TB); give azithromycin when CD4 <50 M Kansasii causes similar pathology to TB, but is less virulent (tx similarly) Deficiency in IL-12 receptor leaves patients incapable of differentiating T-cells to Th1 cells, thus no IFN-y can be produced; decreased Th1 cellular activity leaves patients susceptible to disseminated Salmonella and nonTB mycobacteria (intracellular organisms), but can treat with IFN-y

MEDIUM VESSEL VASCULITIS: *Kawasaki Disease*: common in *___ children* w/skin (involving palms/soles), lips, and tongue involvement ("___") [C___, Rash, A___, Strawberry tongue, H___ changes, fever - CRASH and burn on Kawasaki] Feared complication of KD *(and is often question worthy) is ___* Tx: IVIG + ASA NOTE: sx are similar to Scarlet Fever (sandpaper skin, Strawberry tongue, and *sore throat before other sx [differentiating factor!]*) --- *Buerger's Disease (thromboangiitis obliterans)*: male s___s w/heaving smoking history --> poor blood flow to hands and feet --> *GANGRENE (___ of digits)*; also Raynaud's, intermittent claudication, superficial nodular phlebitis (tender nodules over ___) Tx: smoking cessation --- *Polyarteritis Nodosa*: ___-mediated (*UNIQUE! - type III HS rxn, only one!*) seen in HepB pts w/widespread dz (nerves --> motor/sensory deficits, skin --> nodules/purpura, ___ --> r___ failure); can l/t aneurysms + ___ on kidney arteriogram (*rosary sign, 2/2 transmural inflammation of vessel wall --> ___ necrosis*) LOOK FOR: HepB+ pt w/bizarre sx including ___, skin deficits, purpura, renal failure w.o urinary casts Dx: renal angiogram +/- biopsy Tx: steroids + cyclophosphamide

MEDIUM VESSEL VASCULITIS: *Kawasaki Disease*: common in *Asian children* w/skin (involving palms/soles), lips, and tongue involvement ("strawberry tongue") [Conjunctivitis, Rash, Adenopathy, Strawberry tongue, Hand/foot changes, fever - CRASH and burn on Kawasaki] Feared complication of KD *(and is often question worthy) is coronary aneurysms* Tx: IVIG + ASA NOTE: sx are similar to Scarlet Fever (sandpaper skin, Strawberry tongue, and *sore throat before other sx [differentiating factor!]*) --- *Buerger's Disease (thromboangiitis obliterans)*: male smokers w/heaving smoking history --> poor blood flow to hands and feet --> *GANGRENE (autoamputation of digits)*; also Raynaud's, intermittent claudication, superficial nodular phlebitis (tender nodules over vein) Tx: smoking cessation --- *Polyarteritis Nodosa*: immune complex-mediated (*UNIQUE! - type III HS rxn, only one!*) seen in HepB pts w/widespread dz (nerves --> motor/sensory deficits, skin --> nodules/purpura, kidneys --> renal failure); can l/t aneurysms + constrictions on kidney arteriogram (*rosary sign, 2/2 transmural inflammation of vessel wall --> fibrinoid necrosis*) LOOK FOR: HepB+ pt w/bizarre sx including nerve, skin deficits, purpura, renal failure w.o urinary casts Dx: renal angiogram +/- biopsy Tx: steroids + cyclophosphamide

MEN1 is *autosomal ___* d.o of multiple endocrine glands 2/2 mutation in *___ (menin - a TSG gene, 2-hit hypothesis!)* MEN1 is characterized by three Ps: p___ adenoma, (MC - *first finding in most pts, WILL BE HOW IT IS PRESENTED IN A QUESTION!* - hyperparathyroidism + kidney stones), p___ adenoma (*this one is unique and differentiates from MEN2s*), and p___ tumor (*also differentiates - look for ZES!*) --- KEY POINT: pituitary adenoma or pancreatic tumor (only one!)

MEN1 is *autosomal DOMINANT* d.o of multiple endocrine glands 2/2 mutation in *MEN1 (menin - a TSG gene, 2-hit hypothesis!)* MEN1 is characterized by three Ps: parathyroid adenoma, (MC - *first finding in most pts, WILL BE HOW IT IS PRESENTED IN A QUESTION!* - hyperparathyroidism + kidney stones), pituitary adenoma (*this one is unique and differentiates from MEN2s*), and pancreatic tumor (*also differentiates - look for ZES!*) --- KEY POINT: pituitary adenoma or pancreatic tumor (only one!)

MEN2A (medullary tumors) is *autosomal ___* d.o of multiple endocrine glands 2/2 mutation in ___ (oncogene w/GOF on chrom10 - Hirschsprung is LOF) MEN2A is characterized by two Ps (+ one other medullary): p___ adenoma (*overlap with MEN1*), p___ (medullary + P; overlap w/MEN2B), and m___ (*overlap w/MEN2B; of parafollicular cells [C-cells --> calcitonin], also a P*) - NO PHYSICAL FINDING AS SEEN IN 2B!!! *IMPORTANTLY ("often comes up on board exams"), pts often have ___ young to eliminate chance for MTC!* --- KEY POINT: no pituitary adenoma (1), no marfanoid/mucosal neuromas (2B)

MEN2A (medullary tumors) is *autosomal DOMINANT* d.o of multiple endocrine glands 2/2 mutation in RET (oncogene w/GOF on chrom10 - Hirschsprung is LOF) MEN2A is characterized by two Ps (+ one other medullary): parathyroid adenoma (*overlap with MEN1*), pheochromocytoma (medullary + P; overlap w/MEN2B), and medullary thyroid carcinoma (*overlap w/MEN2B; of parafollicular cells [C-cells --> calcitonin], also a P*) - NO PHYSICAL FINDING AS SEEN IN 2B!!! *IMPORTANTLY ("often comes up on board exams"), pts often have thyroidectomy young to eliminate chance for MTC!* --- KEY POINT: no pituitary adenoma (1), no marfanoid/mucosal neuromas (2B)

MEN2B (medullary tumors + PHYSICAL EXAM FINDINGS) is *autosomal ___* d.o of multiple endocrine glands 2/2 mutation in RET (oncogene w/___ on chrom10 - Hirschsprung is LOF) MEN2B is characterized by 1P: p___ (P + medullary; overlap w/MEN2A), m___ (*overlap w/MEN2A; of parafollicular cells [C-cells --> calcitonin], also a P*) + PHYSICAL EXAM FINDINGS!! (*M___ + M___*) *IMPORTANTLY ("often comes up on board exams"), pts often have ___ young to eliminate chance for MTC!* --- KEY POINT: look for Marfanoid/Mucosal neuromas

MEN2B (medullary tumors + PHYSICAL EXAM FINDINGS) is *autosomal DOMINANT* d.o of multiple endocrine glands 2/2 mutation in RET (oncogene w/GOF on chrom10 - Hirschsprung is LOF) MEN2B is characterized by 1P: pheochromocytoma (P + medullary; overlap w/MEN2A), medullary thyroid carcinoma (*overlap w/MEN2A; of parafollicular cells [C-cells --> calcitonin], also a P*) + PHYSICAL EXAM FINDINGS!! (*Marfanoid body habitus + Mucosal neuromas*) *IMPORTANTLY ("often comes up on board exams"), pts often have thyroidectomy young to eliminate chance for MTC!* --- KEY POINT: look for Marfanoid/Mucosal neuromas

CLASSIC CASE: pt w/suspected ingestion + confusion and *[HY] visual symptoms with gapped metabolic acidosis* - que pasa? how do we treat? --- CLASSIC CASE: suspected ingestion + high AG acidosis w/flank pain and oliguria (acute renal failure) - que pasa? how do we treat? --- CLASSIC CASE: suspected ingestion + no acidosis - que pasa?

METHANOL INGESTION Tx: inhibit alcohol dehydrogenase (use fomipizole or ethanol) --- ETHYLENE GLYCOL INGESTION Tx: inhibit alcohol dehydrogenase (use fomipizole or ethanol) --- ISOPROPYL ALCOHOL INGESTION

MG is A-Immune dz 2/2 Abs to *___synaptic ACh receptor*; clinically, p/w muscle fatigability, as well as d___ and p___ + bulbar sx (speech, chewing, swallowing) Tx MG w/*ACh-E inhibitors to incr. ACh levels in synapse!* MG flare can be d/t too high dose or too low dose - use Tensilon Test (edrophonium - short-acting ACh-E inhibitor); if improvement --> increase dose, if no improvement --> lower dose (cholinergic crisis) *[HY] Edrophonium can cause complications d/t p___ hyperactivity (DUMBELS)* Most MG pts have abnormal t___ - MG often resolves w/t___; COMMON Q: new onset MG --> get mediastinal imaging

MG is A-Immune dz 2/2 Abs to *POSTsynaptic ACh receptor*; clinically, p/w muscle fatigability, as well as diplopia and ptosis + bulbar sx (speech, chewing, swallowing) Tx MG w/*ACh-E inhibitors to incr. ACh levels in synapse!* MG flare can be d/t too high dose or too low dose - use Tensilon Test (edrophonium - short-acting ACh-E inhibitor); if improvement --> increase dose, if no improvement --> lower dose (cholinergic crisis) *[HY] Edrophonium can cause complications d/t parasympathetic hyperactivity (DUMBELS)* Most MG pts have abnormal thymus - MG often resolves w/thymectomy; COMMON Q: new onset MG --> get mediastinal imaging

CLASSIC CASE: old grandmother with abdominal pain + bone pain + altered mental status + metabolic alkalosis - que pasa?

MILK ALKALI SYNDROME (antacid overdose, sx 2/2 hypercalcemia) Hypercalcemia --> inhibits Na-K-Cl2 pump (essentially like being on loop diuretic) --> contraction alkalosis (+ base already consumed in antacid)

CLASSIC PRESENTATION: pt with DKA who, in recovery, develops fever, headache, and eye pain?

MUCORMYCOSIS

Macrocytic anemias can be d/t abnormal DNA synthesis (*___ anemia*) or other (liver dz, alcohol, reticulocytosis) Megaloblastic anemias are where RBCs grow, but cannot divide *d/t abnormal ___ synthesis* Megaloblastic anemias manifest w/anemia, large RBCs, and *[HY - DEFINING FEATURE] h___ n___ (WBCs can't divide d/t decreased DNA synthesis)* Megaloblastic anemias can be d/t *f___, B12*, drugs (MTX, 5-FU, hydroxyurea, zidovudine) Non-megaloblastic macrocytic anemias can be d/t ___ dz or a___ (unknown cause, but can use macrocytosis to determine if pt is heavy drinker) Reticulocytosis could cause macrocytic anemia, but would need 20% retic count (not HY)

Macrocytic anemias can be d/t abnormal DNA synthesis (*megaloblastic anemia*) or other (liver dz, alcohol, reticulocytosis) Megaloblastic anemias are where RBCs grow, but cannot divide *d/t abnormal DNA synthesis* Megaloblastic anemias manifest w/anemia, large RBCs, and *[HY - DEFINING FEATURE] hypersegmented neutrophils (WBCs can't divide d/t decreased DNA synthesis)* Megaloblastic anemias can be d/t *folate, B12*, drugs (MTX, 5-FU, hydroxyurea, zidovudine) Non-megaloblastic macrocytic anemias can be d/t liver dz or alcoholism (unknown cause, but can use macrocytosis to determine if pt is heavy drinker) Reticulocytosis could cause macrocytic anemia, but would need 20% retic count (not HY)

Macrophages are *soldiers/guardians* of innate immunity (produced in bone marrow as ___) - enter tissues and given different names (microglia, osteoclasts, etc.) Macrophages have three main functions: 1) Phagocytosis: engulf pathogens into phagosome --> fuse w/___(*cont. ROSs/superoxide, reactive nitrogen intermediates, proteases/nucleases*) --> bact. death Some pathogens block this process (TB - ___ factor prevents phag-lyse fusion); also C___ Syndrome (phag-lyse can't fuse) 2) Cytokine production: macs. exist as resting (remove debris - osteoclasts) or active ("primed" - exposed to bact.) - when active (via LPS, peptidoglycan - IFN-gamma also activates macs), secrete *IL-___ and ___ (MOST IMPORTANT)*, also IL-6, IL-8, IL-12 IL-1 and TNF-alpha increase synthesis of *endothelial ___ molecules (allow neuts. to enter inflamed tissue)*; IL-1 (macrophage is 1st cell activated) is *___(--> fever^)*; TNF-alpha --> vascular ___, *acts as cachectin (inhibits utilization of FAs)*, and intravascular coagulation (DIC) IL-6^ stimulates ___, IL-8^ attracts ___ (cleanup), IL-12 facilitates granulomas (Th___ response) 3) Antigen presentation

Macrophages are *soldiers/guardians* of innate immunity (produced in bone marrow as monocytes) - enter tissues and given different names (microglia, osteoclasts, etc.) Macrophages have three main functions: 1) Phagocytosis: engulf pathogens into phagosome --> fuse w/lysosome (*cont. ROSs/superoxide, reactive nitrogen intermediates, proteases/nucleases*) --> bact. death Some pathogens block this process (TB - cord-like factor prevents phag-lyse fusion); also Chediak-Higashi Syndrome (phag-lyse can't fuse) 2) Cytokine production: macs. exist as resting (remove debris - osteoclasts) or active ("primed" - exposed to bact.) - when active (via LPS, peptidoglycan - IFN-gamma also activates macs), secrete *IL-1 and TNF-alpha (MOST IMPORTANT)*, also IL-6, IL-8, IL-12 IL-1 and TNF-alpha increase synthesis of *endothelial adhesion molecules (allow neuts. to enter inflamed tissue)*; IL-1 (mac is 1st cell activated) is *pyrogen (--> fever^)*; TNF-alpha --> vascular leak, *acts as cachectin (inhibits utilization of FAs)*, and intravascular coagulation (DIC) IL-6^ stimulates APR, IL-8^ attracts neutrophils (cleanup), IL-12 facilitates granulomas (Th1 response) 3) Antigen presentation ^Hot T-Bone stEAK (for IL-1 through IL-6); Clean up on aisle 8!

Main sx of musc dystrophy is progressive muscle weakness (incl. *Duchenne [MC], Becker*, Myotonic - TriNucRep, on another card); Duchenne and Becker are both ___ d/o involving DMD and dystrophin prot. *[HY] Most muts are ___; DMD --> ___ mut with early stop codon, truncated prot.; BMD --> non-___ mut w/some functional prot. and less sev. dz* DMD is X-rec (all ___ are aff.; 67% of DMD cases are 2/2 mother carriers, 90% in BMD; this is vs. mut of fertilized egg) mutation of DMD gene (encodes for dystrophin - attaches actin to transmembrane prots. alpha- and beta-dystroglycan) Loss of dystrophin --> myonecrosis --> *___ elevation (+/- AST, ALT)*; presentation is ___ muscle weakness of lower extremities (running, jumping) +/- *___ sign w/waddling gait and pseudohypertrophy of ___ (fat/connective tissue - also classic muscle biopsy sign)*; dystrophin is found in cardiac muscle, can lead to cardiomyopathy (sysHF, AV block) Dx: elevated CK, then genetic testing PCR (historically Western blot - absent in DMD, altered in BMD)

Main sx of musc dystrophy is progressive muscle weakness (incl. *Duchenne [MC], Becker*, Myotonic - TNR, on another card); Duchenne and Becker are both X-linked d/o involving DMD and dystrophin prot. *[HY] Most muts are deletions; DMD --> frameshift mut with early stop codon, truncated prot.; BMD --> non-frameshift mut w/some functional prot. and less sev. dz* DMD is X-rec (all males are aff.; 67% of DMD cases are 2/2 mother carriers, 90% in BMD; this is vs. mut of fertilized egg) mutation of DMD gene (encodes for dystrophin - attaches actin to transmembrane prots. alpha- and beta-dystroglycan) Loss of dystrophin --> myonecrosis --> *CK elevation (+/- AST, ALT)*; presentation is proximal muscle weakness of lower extremities (running, jumping) +/- *Gower's sign w/waddling gait and pseudohypertrophy of calf (fat/connective tissue - also classic muscle biopsy sign)*; dystrophin is found in cardiac muscle, can lead to cardiomyopathy (sysHF, AV block) Dx: elevated CK, then genetic testing PCR (historically Western blot - absent in DMD, altered in BMD)

Major regulators of sodium balance are 1) antidiuretic hormone, 2) sympathetic nervous system and 3) renin-angiotensin aldosterone system ___ (electrolyte?) is the major determinant of ECV - ECV can be estimated based on BP and a major indicator of low ECV is orthostatic hypotension A low ECV activates RAAS and SNS --> sodium and water retention Chronic sodium/water retention can l/t increased TBW, but may not necessarily l/t higher ECV (HF - low ___ and low ECV, cirrhosis - low ___ and low ECV) ADH is primarily released in response to high ___, but can be released in response to very low ___ ("non-osmotic release of ADH") NOTE: water intake can be regulated to maintain normal ECV w/___; sodium intake cannot be regulated as well to maintain normal ECV (no ADH for sodium), such that sodium intake expands ECV (think about eating sodium heavy meal --> get bloated vs. drinking a lot of fluids --> pee it out right away) When ECV is low --> SNS and RAAS are activated; when ECV is high --> SNS and RAAS are inhibited (regulates SODIUM balance, but does NOT bring ECV back to normal - only thing that will return to normal ECV is be decreasing sodium consumption) KEY POINTS: high sodium intake --> ___ ECV (weight gain, HTN); low sodium intake --> ___ ECV (weight loss, improves HTN)

Major regulators of sodium balance are 1) antidiuretic hormone, 2) sympathetic nervous system and 3) renin-angiotensin aldosterone system Sodium is the major determinant of ECV - ECV can be estimated based on BP and a major indicator of low ECV is orthostatic hypotension A low ECV activates RAAS and SNS --> sodium and water retention Chronic sodium/water retention can l/t increased TBW, but may not necessarily l/t higher ECV (HF - low CO and low ECV, cirrhosis - low SVR and low ECV) ADH is primarily released in response to high plasma osmolarity, but can be released in response to very low ECV ("non-osmotic release of ADH") NOTE: water intake can be regulated to maintain normal ECV w/ADH; sodium intake cannot be regulated as well to maintain normal ECV (no ADH for sodium), such that sodium intake expands ECV - think about eating sodium heavy meal --> get bloated vs. drinking a lot of fluids --> pee it out right away When ECV is low --> SNS and RAAS are activated; when ECV is high --> SNS and RAAS are inhibited (regulates SODIUM balance, but does NOT bring ECV back to normal - only thing that will return to normal ECV is be decreasing sodium consumption) KEY POINTS: high sodium intake --> expanded ECV (weight gain, HTN); low sodium intake --> decreased ECV (weight loss, improves HTN)

Malaria starts with bite of anopheles mosquito and ___zoites (infectious form) travel to liver; *patients remain ___ for ~1 month!* Sporozoites invade ___ (cell?) and mature to multi-nucleated *___ (multiple nuclei, ready to rupture to daughter cells)*; schizonts rupture --> release *___ZOITES*, which leave liver to invade ___ Inside RBCs, ___ozoites form (this form of the bug can be visualized as ___ form RBCs); inside RBCs, trophozoites mature to schizonts (digest RBC proteins to cause disease) and schizonts burst to release merozoites again, resulting in RBC lysis (*reason for regular cyclic fevers*) *Plasmodium ___ is most severe malarial infection, primarily because P falciparum invades RBCs of any ___ (others only reticulocytes)* *Use Giemsa or Wright stain to identify malaria - will see trophozoite ___ or ___* *Malaria drugs can trigger anemia in ___ patients*

Malaria starts with bite of anopheles mosquito and sporozoites (infectious form) travel to liver; *patients remain asymptomatic for ~1 month!* Sporozoites invade hepatocytes and mature to multi-nucleated *SCHIZONTS (multiple nuclei, ready to rupture to daughter cells)*; schizonts rupture --> release *MEROZOITES*, which leave liver to invade RBCs Inside RBCs, trophozoites form (this form of the bug can be visualized as ring form RBCs); inside RBCs, trophozoites mature to schizonts (digest RBC proteins to cause disease) and schizonts burst to release merozoites again, resulting in RBC lysis (*reason for regular cyclic fevers*) *Plasmodium falciparum is most severe malarial infection, primarily because P falciparum invades RBCs of any age (others only reticulocytes)* *Use Giemsa or Wright stain to identify malaria - will see trophozoite ring or schizont* *Malaria drugs can trigger anemia in G6PD patients*

Male ___ cells pull cholesterol from serum and produce testosterone (NOTE: can also get androgens from adrenal cortex, more important in ___); testosterone can be converted to the more potent DHT via ___ (many androgenic effects are mediated by DHT, d/t potency) ___ inhibits 5-alpha-reductase (used for *prosthetic hyperplasia* and *androgenic alopecia*) In adipose tissue, testosterone can also be converted to estradiol via *___* DHT is required for *___ GENITALIA in men*; accordingly, 5-alpha reductase deficiency manifests with patient who is XY with ___ external genitalia, ___ internal genitalia (epididymis, vas deferens, seminal vesicles) are normal

Male Leydig cells pull cholesterol from serum and produce testosterone (NOTE: can also get androgens from adrenal cortex, more important in females); testosterone can be converted to the more potent DHT via 5-alpha-reductase (many androgenic effects are mediated by DHT, d/t potency) Finasteride inhibits 5-alpha-reductase (used for *prosthetic hyperplasia* and *androgenic alopecia*) In adipose tissue, testosterone can also be converted to estradiol via *aromatase* DHT is required for *EXTERNAL GENITALIA in men*; accordingly, 5-alpha reductase deficiency manifests with patient who is XY with female external genitalia, male internal genitalia (epididymis, vas deferens, seminal vesicles) are normal

Many drugs are weak acids or weak bases; drugs are filtered by glomerulus and *[HY] ___ form of drug gets trapped in urine after filtration (i.e., HA <-> A + H, ___ gets trapped and excreted)* *[HY] Accordingly, urine pH affects drug excretion - weak acid drugs are more excreted in ___ urine, weak bases are more excreted in ___ urine (i.e., want to do to urine what is opposite of drug to excrete - think Michaelis Menten of HA <-> A + H, add H, shifts equation left, A less excreted)* Weak acid drug examples: phenobarbital, aspirin (give sodium ___ to favor excretion in overdose); Weak base drug examples: amphetamines, quinidine, phencyclidine

Many drugs are weak acids or weak bases; drugs are filtered by glomerulus and *[HY] ionized form of drug gets trapped in urine after filtration (i.e., HA <-> A + H, A gets trapped and excreted)* *[HY] Accordingly, urine pH affects drug excretion - weak acid drugs are more excreted in alkaline urine, weak bases are more excreted in acidic urine (i.e., want to do to urine what is opposite of drug to excrete - think Michaelis Menten of HA <-> A + H, add H, shifts equation left, A less excreted)* Weak acid drug examples: phenobarbital, aspirin (give sodium bicarbonate to favor excretion in overdose); Weak base drug examples: amphetamines, quinidine, phencyclidine

M___ Zone lymphoma is B-cell malignancy w/extranodal involvement common in *chronic ___ disorders (i.e., Sjogren's - salivary glands, Hashimoto's - thyroid, H. pylori - MALT lymphoma)* --- Small Lymphocytic Lymphoma are same malignant cells as CLL (*CD___ + CD20 - UNIQUE!*) - difference is degree of lymphocytosis (CLL if >___, SLL if <___)

Marginal Zone lymphoma is B-cell malignancy w/extranodal involvement common in *chronic inflammatory disorders (i.e., Sjogren's - salivary glands, Hashimoto's - thyroid, H. pylori - MALT lymphoma)* --- Small Lymphocytic Lymphoma are same malignant cells as CLL (*CD5 + CD20 - UNIQUE!*) - difference is degree of lymphocytosis (CLL if >5000, SLL if <5000)

Median nerve lesion leads to loss of ___ flex/abd/opp (thenar mm. - "ape hand") and clawing of lateral two digits (___ loss); Proximal (knock out ___) median nn. lesions can lead to Pope's Blessing (hand of benediction) when making a fist (lateral two fingers stay extended) Median nn. lesions at the wrist can be 2/2 trauma (laceration, CTS) and is w.o wrist deviation; median nn. lesions at the elbow can be 2/2 ___ humerus fx and is w/s___ forearm (pronator teres knocked out), weak flexion, and *[HY] ___ deviation (flex. carpi ulnar. maintained) Recurrent br. of median nn. can be damaged 2/2 superficial lacerations - *manifests with ___ thumb but normal sensation*

Median nerve lesion leads to loss of thumb flex/abd/opp (thenar mm. - "ape hand") and clawing of lateral two digits (lumbrical loss); Proximal (knock out FDP) median nn. lesions can lead to Pope's Blessing (hand of benediction) when making a fist (lateral two fingers stay extended) Median nn. lesions at the wrist can be 2/2 trauma (laceration, CTS) and is w.o wrist deviation; median nn. lesions at the elbow can be 2/2 supracondylar humerus fx and is w/supinated forearm (pronator teres knocked out), weak flexion, and *[HY] ulnar deviation (flex. carpi ulnar. maintained) Recurrent br. of median nn. can be damaged 2/2 superficial lacerations - *manifests with immobile thumb but normal sensation*

Meiosis (only in germ cells, diploid --> haploid) has two steps: Meiosis I (separation of ___) starts w/replication to create sister chromatids, then crossover, then division (now haploid, 1n); In meiosis II, ___ separate Males undergo spermatogenesis (spermato___ [mit] prim spermatocyte [mei1] sec spermatocyte [mei2] sperma___ [spermiogenesis] spermatozoa) Females undergo oogenesis - primary oocytes *form in utero, arrest in ___ of meiosis I until puberty (drawn out process --> vulnerable to errors)*; @ puberty, a few prim oocytes complete Mei1 each cycle --> sec oocytes, Mei2 begins and arrests in ___ (if fertilized --> complete Mei2) Aneuploidy (abn. # chroms) occurs 2/2 meiotic nondisjunction; if Mei1 --> ___loid daughters (mixed genes, mom + dad copies) + empty daughters; if Mei2 --> 50% ___loid + 25% ___loid (no gene mixing, 2 mom or 2 dad copies) + 25% empty

Meiosis (only in germ cells, diploid --> haploid) has two steps: Meiosis I (separation of homologous chroms) starts w/replication to create sister chromatids, then crossover, then division (now haploid, 1n); In meiosis II, sister chromatids separate Males undergo spermatogenesis (spermatogonium [mit] prim spermatocyte [mei1] sec spermatocyte [mei2] spermatid [spermiogenesis] spermatozoa) Females undergo oogenesis - primary oocytes *form in utero, arrest in prophase of meiosis I until puberty (drawn out process --> vulnerable to errors)*; @ puberty, a few prim oocytes complete Mei1 each cycle --> sec oocytes, Mei2 begins and arrests in metaphase (if fertilized --> complete Mei2) Aneuploidy (abn. # chroms) occurs 2/2 meiotic nondisjunction; if Mei1 --> diploid daughters (mixed genes, mom + dad copies) + empty daughters; if Mei2 --> 50% haploid + 25% diploid (no gene mixing, 2 mom or 2 dad copies) + 25% empty

Melanin is derived from tyrosine (synthesized by melanocytes) via tyrosinase Deficiency in tyrosinase (or tyrosine transporters) --> *decreased melanin* --> *oculocutaneous albinism (pale skin, blonde hair, blue eyes, SUNBURNS + SKIN CANCER)* *Chediak-Higashi* is deficiency in tyrosine transporter --> oculocutaneous albinism (type II)

Melanin protects skin from UV radiation and *[HY] is formed from AA t___; [HY] Melanocytes produce melanin (from melanosomes) and are derived from ___* - they are found in basal layer of epidermis (str. ___), transfer melanin to keratinocytes Freckles are areas of skin with inc. amnts of ___ (normal melanocyte number/density) Albinism is AR dz of absent/reduced melanin synthesis d/t decreased ___ (think of AA!) activity (normal # of melanocytes) - pts have inc. risk of sunburns and skin cancer (no UV protection) ___ (oppo. of albinism) is acquired hyperpigmentation, p/w irregular tan/dark macules on face in sun-exposed areas (MC: women w/dark complexion); classically, melasma comes on with P___ or OCP use ("mask of pregnancy", thought to be related to estrogen - will resolve after pregnancy) Vitiligo is acquired, localized pigment disorder with *autoimmune destruction of ___!* - asymptomatic symmetric depigmented macules/patches (*CLASSIC PRESENTATION IN WHITES: failure to ___ in localized region*), tx w/steroids +/- immunosuppressants

Melanin protects skin from UV radiation and *[HY] is formed from AA tyrosine; [HY] Melanocytes produce melanin (from melanosomes) and are derived from neural crest* - they are found in basal layer of epidermis (str. basale), transfer melanin to keratinocytes Freckles are areas of skin with inc. amnts of MELANIN (normal melanocyte number/density) Albinism is AR dz of absent/reduced melanin synthesis d/t decreased tyrosinase activity (normal # of melanocytes) - pts have inc. risk of sunburns and skin cancer (no UV protection) Melasma (oppo. of albinism) is acquired hyperpigmentation, p/w irregular tan/dark macules on face in sun-exposed areas (MC: women w/dark complexion); classically, melasma comes on with pregnancy or OCP use ("mask of pregnancy", thought to be related to estrogen - will resolve after pregnancy) Vitiligo is acquired, localized pigment disorder with *autoimmune destruction of melanocytes!* - asymptomatic symmetric depigmented macules/patches (*CLASSIC PRESENTATION IN WHITES: failure to tan in localized region*), tx w/steroids +/- immunosuppressants

Melanoma (2/2 melanocyte overgrowth) is highly malig. skin ca. - use ABCDE crit. to identify -S___ S___ subtype (75%) starts superf., then spreads side to side (not deep) -N___ subtype (~20%) grows vertically --> early invasion, met., death (50% of melan. deaths) -Lentigo (~3%) is confined to epidermis, looks like large freckle, *slow-growing* but can go from lentigo --> lentigo maligna (growing) --> lentigo maligna melanoma (invades dermis) -Acral lentiginous (~3%) is on hands/feet of *___-skinned pts (UNIQUE!)* Dx is via biopsy (not HY) w/*tumor marker S___ positive (highly specific, low sens.)* Prognosis: tumor starts growing radially, then ___ - inc. depth of tumor --> inc. risk of met. (Breslow thickness); met. via heme and lymph to lung, liver, brain Tx: excision w/*wide margins* Genetics: ~half melanomas are 2/2 ___ mutations (oncogene) --> cell proliferation; 90% BRAF mutations are *___ mutations, which you can tx w/vemurafenib and dabrafenib*

Melanoma (2/2 melanocyte overgrowth) is highly malig. skin ca. - use ABCDE crit. to identify -Superficial spreading subtype (75%) starts superf., then spreads side to side (not deep) -Nodular subtype (~20%) grows vertically --> early invasion, met., death (50% of melan. deaths) -Lentigo (~3%) is confined to epidermis, looks like large freckle, *slow-growing* but can go from lentigo --> lentigo maligna (growing) --> lentigo maligna melanoma (invades dermis) -Acral lentiginous (~3%) is on hands/feet of *dark-skinned pts (UNIQUE!)* Dx is via biopsy (not HY) w/*tumor marker S100 positive (highly specific, low sens.)* Prognosis: tumor starts growing radially, then vertically - inc. depth of tumor --> inc. risk of met. (Breslow thickness); met. via heme and lymph to lung, liver, brain Tx: excision w/*wide margins* Genetics: ~half melanomas are 2/2 BRAF mutations (oncogene) --> cell proliferation; 90% BRAF mutations are *V600E mutations, which you can tx w/vemurafenib and dabrafenib*

___ is hyperplasia of stomach mucous cells --> loss of acid (achlorhydria) --> protein loss ("protein-losing enteropathy") --> hypoalbuminemia (w/swelling) Can l/t gastric a___ (think about it - its a d.o of hyperplasia!!) Rugae appear markedly hypertrophied

Menetrier Disease is hyperplasia of stomach mucous cells --> loss of acid (achlorhydria) --> protein loss ("protein-losing enteropathy") --> hypoalbuminemia (w/swelling) Can l/t gastric adenocarcinoma (think about it - its a d.o of hyperplasia!!) Rugae appear markedly hypertrophied

Mesentery (derived from ___oderm) is a double layer of peritoneum that suspends abdominal organs from cavity walls and carries BVs - ___ organs are enclosed by mesentery, while ___ are only covered on anterior wall Two types of mesentery form in fetus: dorsal and ventral ___: gut moves away from posterior wall in development --> dorsal mesentery lengthens btwn gut and posterior wall --> dorsal mesentery covers most abdominal structures Ventral: only exists from bottom esophagus-stomach-duodenum; derived from septum transversum and *___ grows into mesentery!* - in adults, exists as ___ omentum and ___ ligament Greater omentum hangs from ___ curvature of stomach and covers intestines - derived from mesogastrium/mesoderm *[HY] Lesser omentum hangs from liver-to-stomach and is derived form ___*

Mesentery (derived from MESoderm) is a double layer of peritoneum that suspends abdominal organs from cavity walls and carries BVs - intraperitoneal organs are enclosed by mesentery, while retroperitoneal are only covered on anterior wall Two types of mesentery form in fetus: dorsal and ventral Dorsal: gut moves away from posterior wall in development --> dorsal mesentery lengthens btwn gut and posterior wall --> dorsal mesentery covers most abdominal structures Ventral: only exists from bottom esophagus-stomach-duodenum; derived from septum transversum and *LIVER grows into mesentery!* - in adults, exists as lesser omentum and falciform ligament Greater omentum hangs from greater curvature of stomach and covers intestines - derived from mesogastrium/mesoderm *[HY] Lesser omentum hangs from liver-to-stomach and is derived form VENTRAL MESENTERY*

Metabolic alkalosis (high HCO3) occurs d/t losing H+ or gaining HCO3 - common causes include ___ (vomiting, loop diuretics), hypokalemia, antacid use, and hyperaldosteronism Contraction (2/2 vomiting): decreased ECV activates RAAS --> increased H+ ___ + HCO3 generation in PCT (*via a___!*) and increased HCO3 generation in collecting duct (*via aldosterone!*) Hyperaldosteronism: 2/2 adrenal hyperplasia, adenoma - p/w hypokalemic metabolic alkalosis d/t above mechanisms (*look out for ___ HTN!*) ___kalemia: H-K exchange channel can be disrupted by hypokalemia, such that low K --> more H+ shift into cells --> alkalosis Vomiting: classically presents as ___kalemic, ___chloremic metabolic alkalosis w/*___ urine chloride! (differentiates from vomiting vs other causes of alkalosis [hyperaldosteronism] - look out for young woman w/surreptitious vomiting!)* Antacid Use: milk alkali syndrome - excess intake of calcium carbonate --> hypercalcemia --> inhibit ___ transporter in TAL + decreased ADH resorption = volume contraction + alkalosis from antacid! ^NOTE: loop and thiazide diuretics cause BOTH contraction + hypokalemia + *increased Na delivery to collecting duct (--> more H+ and K+ excretion)* - also look for *surreptitious diuretic use (test for w/diuretic screen)* NOTE: ___ syndrome looks like a pt on loop diuretic, ___ syndrome looks like a pt on thiazide diuretic

Metabolic alkalosis (high HCO3) occurs d/t losing H+ or gaining HCO3 - common causes include contraction (vomiting, loop diuretics), hypokalemia, antacid use, and hyperaldosteronism Contraction (2/2 vomiting): decreased ECV activates RAAS --> increased H+ excretion + HCO3 generation in PCT (*via angiotensin II!*) and increased HCO3 generation in collecting duct (*via aldosterone!*) Hyperaldosteronism: 2/2 adrenal hyperplasia, adenoma - p/w hypokalemic metabolic alkalosis d/t above mechanisms (*look out for resistant HTN!*) Hypokalemia: H-K exchange channel can be disrupted by hypokalemia, such that low K --> more H+ shift into cells --> alkalosis Vomiting: classically presents as hypokalemic, hypochloremic metabolic alkalosis w/*low urine chloride! (differentiates from vomiting vs other causes of alkalosis [hyperaldosteronism] - look out for young woman w/surreptitious vomiting!)* Antacid Use: milk alkali syndrome - excess intake of calcium carbonate --> hypercalcemia --> inhibit Na-K-Cl2 transporter in TAL + decreased ADH resorption = volume contraction + alkalosis from antacid! ^NOTE: loop and thiazide diuretics cause BOTH contraction + hypokalemia + *increased Na delivery to collecting duct (--> more H+ and K+ excretion)* - also look for *surreptitious diuretic use (test for w/diuretic screen)* NOTE: Bartter syndrome looks like a pt on loop diuretic, Gitelman syndrome looks like a pt on thiazide diuretic

Metaiodobenzylguanidine (MIBG) is chemical analog of norepinephrine that can be used for dx of pheochromocytoma and neuroblastoma; this drug concentrates in sympathetic tissues and is labeled with radioactive iodine --> will concentrate in tumors and emit radiation *[HY - and all you need to know for this card] During this test, ___ must be protected - give ___ for thyroid to take up instead of damaging radioactive substance*

Metaiodobenzylguanidine (MIBG) is chemical analog of norepinephrine that can be used for dx of pheochromocytoma and neuroblastoma; this drug concentrates in sympathetic tissues and is labeled with radioactive iodine --> will concentrate in tumors and emit radiation *[HY - and all you need to know for this card] During this test, thyroid must be protected - give potassium iodide for thyroid to take up instead of damaging radioactive substance*

Michaelis-Menten Kinetics determines velocity of rxn as a function of substrate concentration (i.e., more substrate --> velocity increases to Vmax); add more substrate --> more product formation at faster V (@ Vmax, enzymes are saturated - *only way to inc. Vmax is to add ___*) Velocity (V) = (___ x [S])/(___+ [S]) Km has same units as [S] and at some point, Km = [S]; at that point, V=(Vmax/2) NOTE: to reach Vmax, Km has to be small relative to [S]; accordingly, smaller Km is --> Vmax reached at ___ (high or low?) concentration (substrate binds easily - high affinity substr. for enz.) KEY PTS: Km is characteristic of subs./enz.; Vmax depends on [enzyme] Lineweaver Burk plot is (1/V) on Y and (1/[S]) on X; ___ is y-int., ___ is x-int., slope is Km/Vm EXAM Qs: what is Vmax (asymptote)? how inc. Vmax (add enzyme)? what is Km ([S] at which point V = [Vmax/2])? on LB plot, what is Vm (y-int), Km (x-int)?

Michaelis-Menten Kinetics determines velocity of rxn as a function of substrate concentration (i.e., more substrate --> velocity increases to Vmax); add more substrate --> more product formation at faster V (@ Vmax, enzymes are saturated - *only way to inc. Vmax is to add enzyme*) Velocity (V) = (Vmax x [S])/(Km + [S]) Km has same units as [S] and at some point, Km = [S]; at that point, V=(Vmax/2) NOTE: to reach Vmax, Km has to be small relative to [S]; accordingly, smaller Km is --> Vmax reached at low concentration (substrate binds easily - high affinity substr. for enz.) KEY PTS: Km is characteristic of subs./enz.; Vmax depends on [enzyme] Lineweaver Burk plot is (1/V) on Y and (1/[S]) on X; Vm is y-int., Km is x-int., slope is Km/Vm EXAM Qs: what is Vmax (asymptote)? how inc. Vmax (add enzyme)? what is Km ([S] at which point V = [Vmax/2])? on LB plot, what is Vm (y-int), Km (x-int)?

Microtubules are polymers of tubulin (alpha and beta - heterodimer) that grow out from centrosome (give + and - end w/+ away from cent.); MTs have ___ - grow slowly and rapidly disassemble MTs allow molecular motor proteins to bind and move along MTs - ___ moves towards (+) end (axonal transport), ___ moves towards (-) end Cilia and flagella (built from MTs + dynein) allow mobility - Cilia (short) move mucus in RespTra, Flagella (long) allow sperm motility *[HY] For Cil/Flag, MTs and prots form axoneme (___x___ pattern w/9 doublet MTs surrounding 1 doublet) that is secured to CM via basal body (9 fused ___lets)* *Axonemal ___ forms bridges btwn MTs, activated dynein pulls neighboring doublets (req. ___) and sliding of doublets --> Cil/Flag bending* Primary Ciliary Dyskinesia is 2/2 dynein gene mutation (cilia/flagella can't beat) --> rhinosinusitis, ___ (men-sperm flag., women-no fall. tube cilia); PCD can manifest with Kartagener's Syndrome - triad of chronic sinusitis, bronchiectasis, S___ I___ MTs also important for mitosis (duh); Many drugs act on MTs (cancer - vincristine, paclitaxil; gout - colchicine; ID - griseofulvin, mebendazole)

Microtubules are polymers of tubulin (alpha and beta - heterodimer) that grow out from centrosome (give + and - end w/+ away from cent.); MTs have dynamic instability - grow slowly and rapidly disassemble MTs allow molecular motor proteins to bind and move along MTs - Kinesin moves towards (+ - S --> SEE YA!) end (axonal transport), Dynein moves towards (-) end Cilia and flagella (built from MTs + dynein) allow mobility - Cilia (short) move mucus in RespTra, Flagella (long) allow sperm motility *[HY] For Cil/Flag, MTs and prots form axoneme (9x2 pattern w/9 doublet MTs surrounding 1 doublet) that is secured to CM via basal body (9 fused triplets)* *Axonemal dynein forms bridges btwn MTs, activated dynein pulls neighboring doublets (req. ATP) and sliding of doublets --> Cil/Flag bending* Primary Ciliary Dyskinesia is 2/2 dynein gene mutation (cilia/flagella can't beat) --> rhinosinusitis, infertility (men-sperm flag., women-no fall. tube cilia); PCD can manifest with Kartagener's Syndrome - triad of chronic sinusitis, bronchiectasis, situs inversus MTs also important for mitosis (duh); Many drugs act on MTs (cancer - vincristine, paclitaxil; gout - colchicine; ID - griseofulvin, mebendazole)

Mood disorders occur along the spectrum of depression --> mania Depression is characterized by SIG E CAPS (___) - need 5 x 2w period *WITHOUT EVIDENCE OF ___* *HY: depressed patients have ALTERED SLEEP RHYTHMS - REM starts ___ (___REM latency) with ___ (inc or dec?) total REM sleep (normalizes on anti-___)* Atypical depression has unique features, including mood ___ (feel better when good things happen), eating/sleeping all the time, ___ feeling in limbs, and sensitivity to ___; still tx with SSRIs (can use MAOi-s)

Mood disorders occur along the spectrum of depression --> mania Depression is characterized by SIG E CAPS (sleep changes, interest lost, guilt, energy lost, concentration lost, appetite changes, psychomotor agit/reta, suicidal ideation) - need 5 x 2w period *WITHOUT EVIDENCE OF MANIA* *HY: depressed patients have ALTERED SLEEP RHYTHMS - REM starts sooner (decreased REM latency) with more total REM sleep (normalizes on anti-depressants)* Atypical depression has unique features, including mood reactivity (feel better when good things happen), eating/sleeping all the time, heavy feeling in limbs, and sensitivity to rejection; still tx with SSRIs (can use MAOi-s)

Mood disorders occur along the spectrum of depression --> mania Mania is characterized by elevated mood and energy, think DIG FAST (___) - need 3+ x1w for dx Hypomania is similar, but with *little/no ___ in functioning* with inflated self-esteem and more energy, but productive - need sx x4d with *NO ___ sx (if psychosis --> mania)* Any patient with manic/hypomanic episode has bipolar disorder^; ___ is any patient with manic episode +/- depression/hypomania; ___ is hypomania + depression (*NO mania*); typical course follows mania-hypomania-depression with periods of euthymia ^Do NOT tx with SSRIs --> *triggers manic episode!*; tx with mood ___

Mood disorders occur along the spectrum of depression --> mania Mania is characterized by elevated mood and energy, think DIG FAST (distractibility, irresponsibility/disinhibition, grandiosity, flight of ideas, agitation, sleep less, talk too much [pressured speech]) - need 3+ x1w for dx Hypomania is similar, but with *little/no impairment in functioning* with inflated self-esteem and more energy, but productive - need sx x4d with *NO psychotic sx (if psychosis --> mania)* Any patient with manic/hypomanic episode has bipolar disorder^; BP1 is any patient with manic episode +/- depression/hypomania; BP2 is hypomania + depression (*NO mania*); typical course follows mania-hypomania-depression with periods of euthymia ^Do NOT tx with SSRIs --> *triggers manic episode!*; tx with mood stabilizers

Mood disorders occur along the spectrum of depression --> mania Some pts with severe MDs (MDD, BPD) develop psychotic features; *importantly, MD w/psychotic features has psychosis ONLY ___ - psychosis w/o mood sx --> ___ disorder* ___ disorder is mild mania + mild depression x2y; sx come and go with ups and downs, but occur >50% of time and are never absent >2mo ___ disorder is low-grade depression (less severe, more chronic) with sx occurring most of time for at least 2y and no sx free period for >2mo Grief is normal response to loss (w/ ___ stages +/- visions/voices of dead person); persistent grief disorder *lasts >___ (HY)* Postpartum mood disorders include postpartum blues (*sx last <___!!*, tx is supportive), postpartum depression (*sx last >___!!*, tx is SSRIs + CBT), and postpartum psychosis

Mood disorders occur along the spectrum of depression --> mania Some pts with severe MDs (MDD, BPD) develop psychotic features; *importantly, MD w/psychotic features has psychosis ONLY w/mood sx - psychosis w/o mood sx --> schizoaffective disorder* Cyclothymic disorder is mild mania + mild depression x2y; sx come and go with ups and downs, but occur >50% of time and are never absent >2mo Persistent Depressive disorder is low-grade depression (less severe, more chronic) with sx occurring most of time for at least 2y and no sx free period for >2mo Grief is normal response to loss (w/ DABDA stages +/- visions/voices of dead person); persistent grief disorder *lasts >6mo (HY)* Postpartum mood disorders include postpartum blues (*sx last <2w!!*, tx is supportive), postpartum depression (*sx last >2w!!*, tx is SSRIs + CBT), and postpartum psychosis

Moraxella (GN diplococci) colonizes the airway and causes ___ (along with H flu and Strep pneumo) *Both Neisseria species can be treated with ___* *Key features of N gonorrhea is antigenic variation of ___ proteins (no long-term immunity after infection --> re-infection likely)* *Campylobacter is a leading cause of acute diarrhea in children worldwide 2/2 ___ transmission; Campylobacter is common trigger of ___, a demyelinating disease with ascending weakness*

Moraxella (GN diplococci) colonizes the airway and causes otitis media (along with H flu and Strep pneumo) *Both Neisseria species can be treated with ceftriaxone* *Key features of N gonorrhea is antigenic variation of pilus proteins (no long-term immunity after infection --> re-infection likely)* *Campylobacter is a leading cause of acute diarrhea in children worldwide 2/2 fecal-oral transmission; Campylobacter is common trigger of Guillain Barre, a demyelinating disease with ascending weakness*

Most cocci are GP with very few GN cocci (Neisseria and ___ - not a sketchy bug); GP rods are also rare (corynebacteria, clostridium, listeria, bacillus) Two bacteria are pleomorphic (many shapes): ___ (also intracellular pathogens) *HY: ___ makes GP bacteria purple*; bugs that don't stain well include treponema (too thin), mycobacteria (mycolic acids), mycoplasma (no CW), and intracellular bacteria (rickettsia, chlamydia, legionella - mostly intracellular) For intracellular pathogens (plasmodium, trypanosomes, + above listed), use ___ stain; for mycolic acid bugs (TB, nocardia), use ___ (acid fast) stain; use silver stain for PCP, Legionella, and H Pylori Some bugs have special colors (Staph --> ___; Pseudomonas --> ___; ___ --> red; Actinomyces --> yellow-orange with ___ granules)

Most cocci are GP with very few GN cocci (Neisseria and Moraxella); GP rods are also rare (corynebacteria, clostridium, listeria, bacillus) Two bacteria are pleomorphic (many shapes): Rickettsia and Chlamydia (also intracellular pathogens) *HY: thicc cell wall of peptidoglycan makes GP bacteria purple*; bugs that don't stain well include treponema (too thin), mycobacteria (mycolic acids), mycoplasma (no CW), and intracellular bacteria (rickettsia, chlamydia, legionella - mostly intracellular) For intracellular pathogens (plasmodium, trypanosomes, + above listed), use Giemsa stain; for mycolic acid bugs (TB, nocardia), use Ziehl-Neelsen (acid fast) stain; use silver stain for PCP, Legionella, and H Pylori Some bugs have special colors (Staph --> gold; Pseudomonas --> blue-green; Serratia --> red; Actinomyces --> yellow-orange with sulfur granules)

Most lipid absorption occurs in jejunum (bile acids not resorbed w/lipids) - pass to ___, where 95% are resorbed (5% eliminated - major mechanism of c___ elimination) Bile acid ___ (cholestyramine, colestipol) retain bile acids in stool --> lower cholesterol (NASTY side effects) 3rd function of bile salts (lipid absorption, cholest. elimination) is as antimicrobial - loss of bile salts in liver dz --> bacterial overgrowth (*[HY] bile salts are believed to disrupt bact. ___*)

Most lipid absorption occurs in jejunum (bile acids not resorbed w/lipids) - pass to terminal ileum, where 95% are resorbed (5% eliminated - major mechanism of cholesterol elimination) Bile acid resins (cholestyramine, colestipol) retain bile acids in stool --> lower cholesterol (NASTY side effects) 3rd function of bile salts (lipid absorption, cholest. elimination) is as antimicrobial - loss of bile salts in liver dz --> bacterial overgrowth (*[HY] bile salts are believed to disrupt bact. cell membranes*)

M___ is released by cells in stomach, intestine, colon - promotes motility in fasting state *KEY POINT: e___ binds motilin receptors --> treats gastroparesis*

Motilin is released by cells in stomach, intestine, colon - promotes motility in fasting state *KEY POINT: erythromycin binds motilin receptors --> treats gastroparesis*

___ is failure of Mullerian duct to form (absent upper vagina and uterus); ovaries are normal --> estrogen + progesterone + LH + FSH are all normal --- Most common cause of secondary amenorrhea is ___, but can also develop in thyroid dz, prolactinoma, *anorexia (2/2 GnRH dysfunction)*, menopause, *PCOS*, and Cushing's syndrome In menopause, ovaries stop producing estrogen (still get some from adipose tissue) and inhibin - ___ will be high! Menopause l/t hot flashes, vaginal atrophy, ___ (bones?) Hormone replacement therapy can be used to relieve hot flashes and improve bone density (may increase risk ___ and/or breast cancer) --- NOTE: amenorrhea workup - low FSH --> ___ (high LH:FSH), high FSH --> ___, normal FSH --> ___

Mullerian dysgenesis is failure of Mullerian duct to form (absent upper vagina and uterus); ovaries are normal --> estrogen + progesterone + LH + FSH are all normal --- Most common cause of secondary amenorrhea is pregnancy, but can also develop in thyroid dz, prolactinoma, *anorexia (2/2 GnRH dysfunction)*, menopause, *PCOS*, and Cushing's syndrome In menopause, ovaries stop producing estrogen (still get some from adipose tissue) and inhibin - FSH will be high! Menopause l/t hot flashes, vaginal atrophy, osteoporosis Hormone replacement therapy can be used to relieve hot flashes and improve bone density (may increase risk thrombosis and/or breast cancer) --- NOTE: amenorrhea workup - low FSH --> PCOS (high LH:FSH), high FSH --> menopause, normal FSH --> Mullerian dysgenesis

Multicystic Dysplastic Kidney dz is d/t abnormal ___ btwn ureteric bud (part of mesonephric duct) and mesenchyme --> kidney replaced w/cysts that have no functional tissue If unilateral --> contralateral kidney can compensate; if bilateral --> Potter's syndrome (not compatible w/life) *MDK is a ___ occurrence - not inherited* --- *[HY] Autosomal recessive polycystic kidney dz occurs in ___ - if bilateral --> ___ syndrome* *If child survives, will have renal failure + HTN, in addition to HEPATIC FIBROSIS w/___* --- *[HY] Autosomal dominant polycystic kidney dz occurs in ___ - born w/tiny cysts at birth that are not detectable --> enlarge over time* *ADPKD is 2/2 mutation in ADPKD1 and ADPKD2; ADPKD is an autosomal ___ disorder* *[HY] ADPKD is a/w ___ (can l/t subarachnoid hemorrhage), liver cysts, and m___ (heart?)* --- Medullary cystic kidney dz (*autosomal ___* - also called AD Tubulointerstitial Kidney dz) causes tubulointerstitial fibrosis and progressive renal insufficiency w/inability to concentrate urine Kidneys will appear ___

Multicystic Dysplastic Kidney dz is d/t abnormal interaction btwn ureteric bud (part of mesonephric duct) and mesenchyme --> kidney replaced w/cysts that have no functional tissue If unilateral --> contralateral kidney can compensate; if bilateral --> Potter's syndrome (not compatible w/life) *MDK is a SPONTANEOUS occurrence - not inherited* --- *[HY] Autosomal recessive polycystic kidney dz occurs in CHILDREN - if bilateral --> Potter's syndrome* *If child survives, will have renal failure + HTN, in addition to HEPATIC FIBROSIS w/PORTAL HTN* --- *[HY] Autosomal dominant polycystic kidney dz occurs in ADULTS - born w/tiny cysts at birth that are not detectable --> enlarge over time* *ADPKD is 2/2 mutation in ADPKD1 and ADPKD2; ADPKD is an autosomal DOMINANT disorder* *[HY] ADPKD is a/w berry aneurysms (can l/t subarachnoid hemorrhage), liver cysts, and mitral valve prolapse* --- Medullary cystic kidney dz (*autosomal DOMINANT* - also called AD Tubulointerstitial Kidney dz) causes tubulointerstitial fibrosis and progressive renal insufficiency w/inability to concentrate urine Kidneys will appear SMALL and SHRUNKEN

Multiple Myeloma is a malignancy of plasma cells that produce ___ in excess; MM commonly occurs in older folks MM is *highly dependent on IL-___!!*; MM predominantly results in overproduction of Ig___ (50% of cases), Ig___ (20% of cases), and some cases of light-chain only (*KEY POINT: excess ___ chain production in MM, can lead to ___ + renal damage*) Clinically, MM p/w *bone pain/fractures (osteoclasts stimulated from MM cytokines --> ___ lesions) + hyper___ (from lesions) + __ failure (overwhelmed by light chains + hypercalcemia) + anemia (bone marrow replaced w/plasma cells + renal failure) + recurrent infxns (can't produce normal Ig)* XR will show *"___"* lesions + pathologic fractures of vertebrae; peripheral blood smear will show *___ formation* MM carries increased risk of *am___* Dx of MM is done w/serum protein electrophoresis (SPEP) - look for *___ in gamma fraction (all the way to right of SPEP)*, can also run ___ (urine - detects *Bence Jones proteins [name for urine light chains]*); confirmed w/bone marrow analysis --> >10% monoclonal plasma cells w/___-face chromatin

Multiple Myeloma is a malignancy of plasma cells that produce immunoglobulin in excess; MM commonly occurs in older folks MM is *highly dependent on IL-6!!*; MM predominantly results in overproduction of IgG (50% of cases), IgA (20% of cases), and some cases of light-chain only (*KEY POINT: excess light chain production in MM, can lead to amyloidosis + renal damage*) Clinically, MM p/w *bone pain/fractures (osteoclasts stimulated from MM cytokines --> lytic lesions) + hypercalcemia (from lesions) + renal failure (overwhelmed by light chains + hypercalcemia) + anemia (bone marrow replaced w/plasma cells + renal failure) + recurrent infxns (can't produce normal Ig)* XR will show *"punched out"* lesions + pathologic fractures of vertebrae; peripheral blood smear will show *Rouleaux formation* MM carries increased risk of *amyloidosis* Dx of MM is done w/serum protein electrophoresis (SPEP) - look for *M-spike in gamma fraction (all the way to right of SPEP)*, can also run UPEP (urine - detects *Bence Jones proteins [name for urine light chains]*); confirmed w/bone marrow analysis --> >10% monoclonal plasma cells w/clock-face chromatin

Myco. TB is obligate aerobe that prefers reactivating in ___ lobe of lungs - also facultative intracellular that infects ___ TB virulence factors include "___ factor" (help TB evade immune response - cause granuloma formation), s___ (inhibit phagosome-lysosome fusion), catalase-peroxidase (resist host cell oxidation) Most (90%) will clear bacteria from body --> ___ (potential to reactivate), dz heals by fibrosis (PPD ___) Some (10% - immunocompromised) will develop primary active infxn in chemo pts (fever, cough, pleuritic CP), can progress to ___ dz (reactivation TB can do this too); Miliary TB --> bones (*___ dz*), heart (*___ pericarditis*) *[HY] 2-4w after infxn, cell-mediated immune response is mounted w/Th___ CD___ T-cells, ___-gamma, and macrophages/CD8+ T-cells*

Myco. TB is obligate aerobe that prefers reactivating in upper lobe of lungs - also facultative intracellular that infects macrophages TB virulence factors include "cord factor" (help TB evade immune response - cause granuloma formation), sulfatides (inhibit phagosome-lysosome fusion), catalase-peroxidase (resist host cell oxidation) Most (90%) will clear bacteria from body --> latent (potential to reactivate), dz heals by fibrosis (PPD positive) Some (10% - immunocompromised) will develop primary active infxn in chemo pts (fever, cough, pleuritic CP), can progress to miliary dz (reactivation TB can do this too); Miliary TB --> bones (*Pott's dz*), heart (*constrictive pericarditis*) *[HY] 2-4w after infxn, cell-mediated immune response is mounted w/Th1 CD4 T-cells, IFN-gamma, and macrophages/CD8+ T-cells*

___ is abnormal myeloid progenitor cells --> ineffective hematopoiesis w/anemia, thrombocytopenia, and neutropenia Dx: bone marrow biopsy w/dysplasia (*<___% blasts - can progress to >20% blasts --> ___!*) MDS is a/w environmental factors (years after ___, chemo)

Myelodysplastic Syndromes (MDS) is abnormal myeloid progenitor cells --> ineffective hematopoiesis w/anemia, thrombocytopenia, and neutropenia Dx: bone marrow biopsy w/dysplasia (*<20% blasts - can progress to >20% blasts --> AML!*) MDS is a/w environmental factors (years after radiation, chemo)

Myeloproliferative disorders include CML, PV, ET, and myelofibrosis The characteristic mutation in CML is ___; characteristic mutation in remaining three is ___ mutation JAK2 is cytoplasmic ___ - mutation --> elevated ___ phosphorylation --> hypersensitivity to cytokines --> more growth + longer survival --- Polycythemia Vera (JAK2) is disorder of increased RBCs (*must exclude other causes: ___ and EPO tumors [___]*); in PV, EPO is ___ and PaO2 is ___ Basic mechanisms underlying sx of PV are 1) increased RBC mass (--> HTN + flushing) and 2) ___ (increased viscosity + increased platelets) Classic presentation for PV is *intense ___ after ___ (aquagenic pruritis - know it!)*; also may see red/puffy skin, *DVT (classically B___)* Complications: *___ phase (exhausted marrow --> ___)*, leukemia (usually AML), *GOUT (excess purines!)* Tx: phlebotomy, hydroxyurea

Myeloproliferative disorders include CML, PV, ET, and myelofibrosis The characteristic mutation in CML is Philadelphic chromosome; characteristic mutation in remaining three is JAK2 mutation JAK2 is cytoplasmic RTK - mutation --> elevated RTK phosphorylation --> hypersensitivity to cytokines --> more growth + longer survival --- Polycythemia Vera (JAK2) is disorder of increased RBCs (*must exclude other causes: hypoxia and EPO tumors [RCC]*); in PV, EPO is low and PaO2 is normal Basic mechanisms underlying sx of PV are 1) increased RBC mass (--> HTN + flushing) and 2) thrombosis (increased viscosity + increased platelets) Classic presentation for PV is *intense itching after shower (aquagenic pruritis - know it!)*; also may see red/puffy skin, *DVT (classically Budd-Chiari syndrome)* Complications: *spent phase (exhausted marrow --> myelofibrosis)*, leukemia (usually AML), *GOUT (excess purines!)* Tx: phlebotomy, hydroxyurea

Myeloproliferative disorders include CML, PV, ET, and myelofibrosis; characteristic mutation in remaining PV, ET, and myelofibrosis is JAK2 mutation JAK2 is cytoplasmic RTK - mutation --> elevated RTK phosphorylation --> hypersensitivity to cytokines --> more growth + longer survival --- Primary myelofibrosis (i.e., not 2/2 another condition - seen in PV spent phase, chronic leukemias) is 2/2 atypical ___ --> *TGF-___ and PDGF* --> *___ activity* --> excessive *___* deposition Primary myelofibrosis therefore p/w *MASSIVE ___ for extramedullary hematopoiesis (rxn to marrow fibrosis) --> LUQ pain, early satiety;* also fatigue + weight loss Peripheral blood smear will show *___ RBCs (deformed when squeezed out of fibrotic marrow!) and leukoerythroblastosis (inappropriate release of immature cells into peripheral blood - ___ and ___ precursors found in blood) + severe anemia (Hgb <10) w/normal WBC and platelets

Myeloproliferative disorders include CML, PV, ET, and myelofibrosis; characteristic mutation in remaining PV, ET, and myelofibrosis is JAK2 mutation JAK2 is cytoplasmic RTK - mutation --> elevated RTK phosphorylation --> hypersensitivity to cytokines --> more growth + longer survival --- Primary myelofibrosis (i.e., not 2/2 another condition - seen in PV spent phase, chronic leukemias) is 2/2 atypical megakaryocytes --> *TGF beta and PDGF* --> *FIBROBLAST activity* --> excessive *COLLAGEN* deposition Primary myelofibrosis therefore p/w *MASSIVE splenomegaly for extramedullary hematopoiesis (rxn to marrow fibrosis) --> LUQ pain, early satiety;* also fatigue + weight loss Peripheral blood smear will show *teardrop RBCs (deformed when squeezed out of fibrotic marrow!) and leukoerythroblastosis (inappropriate release of immature cells into peripheral blood - erythroid and granulocyte precursors found in blood) + severe anemia (Hgb <10) w/normal WBC and platelets

N-linked oligosaccharides are synthesized and added to ___ of prots. (d/t extra Nitrogen on asp.) in the rER, then modified in Golgi O-linked oligosaccharides are added *in the G___!* - sugars are added to serine/threonine (d/t extra oxygen) - mucins have lots OLOs Mannose-6-phosphate is added to proteins that are destined for ___ (e.g., acid hydrolase enzymes) - process disrupted in *I-cell dz* ICD is lysosomal storage dz w/failure of Golgi processing - ___ is not found on lysosomal proteins (2/2 deficiency in NA1P) --> hydrolases secreted outside cell, lysosomes contain inclusions (I in ICD is inclusions) of undigested GAGs and lipids

N-linked oligosaccharides are synthesized and added to asparagine of prots. (d/t extra Nitrogen on asp.) in the rER, then modified in Golgi O-linked oligosaccharides are added *in the Golgi app.!* - sugars are added to serine/threonine (d/t extra oxygen) - mucins have lots OLOs Mannose-6-phosphate is added to proteins that are destined for lysosomes (e.g., acid hydrolase enzymes) - process disrupted in *I-cell dz* ICD is lysosomal storage dz w/failure of Golgi processing - M6P is not found on lysosomal proteins (2/2 deficiency in NA1P) --> hydrolases secreted outside cell, lysosomes contain inclusions (I in ICD is inclusions) of undigested GAGs and lipids

Naked RNA viruses (4) include calici (___), hepe (___), reo (___), and picorna (PERCH); in general, naked viruses are more durable (fecal-oral trans) than enveloped viruses (mosquito trans); all naked viruses are + sense (enveloped can be either) w/icosahedral capsid (enveloped are helical) HepE is similar to ___ (fecal-oral transmission, non-enveloped, + ssRNA that is linear, icosahedral capsid) HTLV is diploid + sense RNA, enters CD4 TCs, and RNA is transcribed to DNA --> inc to cell DNA (similar to ___); at this point, differs from HIV - *T-cells proliferate --> T-cell ___ (NHL variant); HTLV a/w IVDU* Yellow Fever can mimic alcoholism with ___ >> ___; characteristic path finding is ___man bodies

Naked RNA viruses (4) include calci (Norwalk), hepe (HEV), reo (rotavirus), and picorna (PERCH); in general, naked viruses are more durable (fecal-oral trans) than enveloped viruses (mosquito trans); all naked viruses are + sense (enveloped can be either) w/icosahedral capsid (enveloped are helical) HepE is similar to Calicivirus (fecal-oral transmission, non-enveloped, + ssRNA that is linear, icosahedral capsid) HTLV is diploid + sense RNA, enters CD4 TCs, and RNA is transcribed to DNA --> inc to cell DNA (similar to HIV); at this point, differs from HIV - *T-cells proliferate --> T-cell leukemia-lymphoma (NHL variant); HTLV a/w IVDU* Yellow Fever can mimic alcoholism with AST >> ALT; characteristic path finding is Councilman bodies

Narcolepsy is 2/2 decreased neuropeptides from lateral hypothalamus (___ - can test CSF, but used for research mainly); autoimmune hypothesis is death of orexin neurons *d/t [HY] strong association with HLA-___* Manifestations include sleep attacks + daytime sleepiness, but *not tired when ___ (diff from sleep apnea!)*; may also see *CATAPLEXY* in response to ___ (loss of tone w/o LOC); hypnagogic hallucinations may also occur Pts may complain of sleep paralysis (___ sleep while awake - paralyzed in REM) Tx: modafinil, methylphenidate, amphetamine, *___ (GABA metabolite and gamma-hydroxybutyrate salt that reduces cataplexy)*

Narcolepsy is 2/2 decreased neuropeptides from lateral hypothalamus (orexin-A, orexin-B - can test CSF, but used for research mainly); autoimmune hypothesis is death of orexin neurons *d/t [HY] strong association with HLA-DQB1* Manifestations include sleep attacks + daytime sleepiness, but *not tired when waking in morning (diff from sleep apnea!)*; may also see *CATAPLEXY* in response to strong emotions (loss of tone w/o LOC); hypnagogic hallucinations may also occur Pts may complain of sleep paralysis (REM sleep while awake - paralyzed in REM) Tx: modafinil, methylphenidate, amphetamine, *sodium oxybate (GABA metabolite and gamma-hydroxybutyrate salt that reduces cataplexy)*

Natural Killer cells have two key roles: 1) kill human cells infected by virus and 2) produce ___ to activate macrophages MHCI is important for CD8-mediated immunity - some viruses have adapted to ___ MHCI, which is what NK cells are primed to find! Important NK cell CD markers include: 1) CD___ (binds Fc --> antibody-dependent cell-mediated cytotoxicity,ADCC) and 2) CD56 (aka, NCAM - ID for NK cells) In ADCC, a cell is coated w/Abs, then destroyed by *NON-___ (i.e., not macrophage or neutrophil), classically NK-cells (recognize Fc by CD___) or ___ (recognize Fc on IgE for parasites, which are too big for phagocytosis!)* NK-cells are *___ (myeloid/lymphocyte?)*, but do not mature in thymus, have no memory, and do not require antigen presentation (*unique from other lymphocytes - T- and B-cells*)

Natural Killer cells have two key roles: 1) kill human cells infected by virus and 2) produce IFN-gamma to activate macrophages MHCI is important for CD8-mediated immunity - some viruses have adapted to downregulate MHCI, which is what NK cells are primed to find! Important NK cell CD markers include: 1) CD16 (binds Fc --> antibody-dependent cell-mediated cytotoxicity, ADCC) and 2) CD56 (aka, NCAM - ID for NK cells) In ADCC, a cell is coated w/Abs, then destroyed by *NON-PHAGOCYTES (i.e., not macrophage or neutrophil), classically NK-cells (recognize Fc by CD16) or EOs (recognize Fc on IgE for parasites, which are too big for phagocytosis!)* NK-cells are *LYMPHOCYTES*, but do not mature in thymus, have no memory, and do not require antigen presentation (*unique from other lymphocytes - T- and B-cells*)

___ is infxn of fascia (muscle fascia + subQ fat) w/destruction of tissue above fascia; clinically, see skin color changes +/- bullae and pain out of proportion to exam (minor rash, exquisite tenderness - eventually pain stops 2/2 nerve destruction) ___ can occur 2/2 gas formation from bact. NF carries high mortality rate 2/2 quick spread along fascia (fascia has poor blood supply) - req. urgent surgical debridement Type I is ___, common in diabetics/immunocompromise and following surgery; type II is ___ (Staph or GAS) that occurs in healthy people after injury KNOW: minor skin trauma OR diabetic/recent surgery --> redness & warmth w/extreme pain, fever, hypotension

Nec fasc is infxn of fascia (muscle fascia + subQ fat) w/destruction of tissue above fascia; clinically, see skin color changes +/- bullae and pain out of proportion to exam (minor rash, exquisite tenderness - eventually pain stops 2/2 nerve destruction) Crepitus can occur 2/2 gas formation from bact. NF carries high mortality rate 2/2 quick spread along fascia (fascia has poor blood supply) - req. urgent surgical debridement Type I is polymicrobial, common in diabetics/immunocompromise and following surgery; type II is monomicrobial (Staph or GAS) that occurs in healthy people after injury KNOW: minor skin trauma OR diabetic/recent surgery --> redness & warmth w/extreme pain, fever, hypotension

Neonatal respiratory distress syndrome is atelectasis 2/2 immature lungs --> hypoxemia and hypercapnia; RFs include pre___, maternal diabetes (insulin decreases surfactant production), C-s___ (no compression stress to stimulate surfactant) NRDS can lead to complications, all of which are *[HY] related to o___ problem*: 1) bronchopulmonary dysplasia (O2 ___), 2) PDA (___ keeps shunt open), 3) retinopathy of prematurity (O2 --> free radicals --> neo___ --> blindness)

Neonatal respiratory distress syndrome is atelectasis 2/2 immature lungs --> hypoxemia and hypercapnia; RFs include prematurity, maternal diabetes (insulin decreases surfactant production), C-section (no compression stress to stimulate surfactant) NRDS can lead to complications, all of which are *[HY] related to oxygen problem*: 1) bronchopulmonary dysplasia (O2 toxicity), 2) PDA (hypoxia keeps shunt open), 3) retinopathy of prematurity (O2 --> free radicals --> neovascularization --> blindness)

Nephrotic syndrome can lead to hyperlipidemia, as well as alcoholism, pregnancy, beta blockers, and HCTZ Signs of marked hyperlipidemia include xanthomas (plaques of lipid-laden histiocytes/macrophages) - look for tendinous xanthoma (over Achilles); may also see corneal arcus (lipid deposit in cornea)

Neuroblastoma is the most common tumor of adrenal medulla and almost always occurs in *CHILDREN (younger --> better prognosis)* - it is derived from *sympathetic n___ cells (like pheo)* and can arise anywhere in SNS, but usually is found in adrenals Symptoms are usually 2/2 ___ - can synthesize catecholamines, but rarely cause sx like pheos (can still diagnose w/urinary metanephrines) Rare feature of neuroblastoma is *O___ M___ A___ (OMA), a rare paraneoplastic syndrome w/rapid eye movements, rhythmic jerking, and ataxia* N-m___ is proto-oncogene that is overexpressed in some tumors - like older age, this mutation is a/w poor prognosis Histology will reveal *H___-W___ rosettes*

Neuroblastoma is the most common tumor of adrenal medulla and almost always occurs in *CHILDREN (younger --> better prognosis)* - it is derived from *sympathetic neural crest cells (like pheo)* and can arise anywhere in SNS, but usually is found in adrenals Symptoms are usually 2/2 mass effect - can synthesize catecholamines, but rarely cause sx like pheos (can still diagnose w/urinary metanephrines) Rare feature of neuroblastoma is *opsoclonus-myoclonus-ataxia (OMA), a rare paraneoplastic syndrome w/rapid eye movements, rhythmic jerking, and ataxia* N-myc is proto-oncogene that is overexpressed in some tumors - like older age, this mutation is a/w poor prognosis Histology will reveal *Homer-Wright rosettes*

Neurocutaneous disorders are genetic disorders of skin, nerves, and eye (structures derived from *ECTODERM*) Neurofibromatosis is AD d/o of NF1 and NF2 genes, resulting in nerve tumors w/skin and eye findings NF1 encodes for neurofibromin (TSG) on chrom___, which restricts RAS function (RAS overactivity --> tumor); NF1 has 100% penetrance with variable e___ (some pts - mild, others - severe) NF1 manifests w/NEUROFIBROMAS of nerves, ___ nodules in eye (brown iris spots), ___ spots (light brown macules) + a___ freckles in skin; NF1 can lead to ___ gliomas, bone abnormalities (long bones curvy), and intellectual impairment, as well as HTN (ren. art. sten., pheo.) and malignancy (peripheral nerve sheath tumor) NF2 (less common) is AD mutation in NF2, leading to CNS tumors *w/BILATERAL ___ (acoustic neuromas, CNVIII) and meningiomas*, hearing loss + tinnitus + ataxia in child

Neurocutaneous disorders are genetic disorders of skin, nerves, and eye (structures derived from *ECTODERM*) Neurofibromatosis is AD d/o of NF1 and NF2 genes, resulting in nerve tumors w/skin and eye findings NF1 encodes for neurofibromin (TSG) on chrom17, which restricts RAS function (RAS overactivity --> tumor); NF1 has 100% penetrance with variable expressivity (some pts - mild, others - severe) NF1 manifests w/NEUROFIBROMAS of nerves, Lisch nodules in eye (brown iris spots), cafe-au-lait spots (light brown macules) + axillary freckles in skin; NF1 can lead to optic gliomas, bone abnormalities (long bones curvy), and intellectual impairment, as well as HTN (ren. art. sten., pheo.) and malignancy (peripheral nerve sheath tumor) NF2 (less common) is AD mutation in NF2, leading to CNS tumors *w/BILATERAL SCHWANNOMAS (acoustic neuromas, CNVIII) and meningiomas*, hearing loss + tinnitus + ataxia in child

Neurocutaneous disorders are genetic disorders of skin, nerves, and eye (structures derived from *___DERM*) Sturge-Weber Syndrome is congenital vascular disorder of capillaries that is acquired, *NOT ___*; SWS is 2/2 spont. mut. in GNAQ gene after f___ (somatic mutation --> m___) Three cardinal manifestations are: *Nevus ___ (port-wine stain)*: malform. of dermal capil. and venules in 1st/2nd CNV distribution, leading to slow/low blood flow and pink/red patch *Leptomeningeal Angioma*: capil.-venous malform. of pia/arachnoid mater on *[HY] ___ side as NeFl* - may cause s___, hemiparesis, headaches *Glaucoma*: infancy/early adulthood w.o known patho. --> vision impaired

Neurocutaneous disorders are genetic disorders of skin, nerves, and eye (structures derived from *ECTODERM*) Sturge-Weber Syndrome is congenital vascular disorder of capillaries that is acquired, *NOT INHERITED*; SWS is 2/2 spont. mut. in GNAQ gene after fert. (somatic mutation --> mosaicism) Three cardinal manifestations are: *Nevus Flammeus (port-wine stain)*: malform. of dermal capil. and venules in 1st/2nd CNV distribution, leading to slow/low blood flow and pink/red patch *Leptomeningeal Angioma*: capil.-venous malform. of pia/arachnoid mater on *[HY] same side as NeFl* - may cause seizures, hemiparesis, headaches *Glaucoma*: infancy/early adulthood w.o known patho. --> vision impaired

Neurocutaneous disorders are genetic disorders of skin, nerves, and eye (structures derived from *ECTODERM*) Tuberous sclerosis is cancer syndrome characterized by *___ - benign malformation of cells/tissue* TSC is AD (80% cases are de novo) w/variable expressivity - TSC1: hamartin & TSC2: tuberin, both of which inhibit m___ (mutation --> cells overgrow in *SIZE*) TSC manifests with tumors in multiple organ systems --> *s___ (main clinical feature 2/2 CNS tumors CORTICAL TUBERS, SUBEPENDYMAL NODULES)*, "ash leaf spots" (___pigmentation), shagreen patch ("orange peel"), u___ fibromas TSC pts can develop *subependymal giant cell astrocytoma @ interventricular foramen, which [HY] can obstruct ___ --> ___* TSC pts can develop ___myomas, tumor of muscle cells embedded in ventricular wall (rare sx, but seen in 90% of cases) TSC pts can develop renal angio___, proliferation of cells around vessel --> growth + hemorrhage, renin-dependent HTN, and CKD

Neurocutaneous disorders are genetic disorders of skin, nerves, and eye (structures derived from *ECTODERM*) Tuberous sclerosis is cancer syndrome characterized by *HAMARTOMAS - benign malformation of cells/tissue* TSC is AD (80% cases are de novo) w/variable expressivity - TSC1: hamartin & TSC2: tuberin, both of which inhibit mTOR (mutation --> cells overgrow in *SIZE*) TSC manifests with tumors in multiple organ systems --> *seizures (main clinical feature 2/2 CNS tumors CORTICAL TUBERS, SUBEPENDYMAL NODULES)*, "ash leaf spots" (hypopig.), shagreen patch ("orange peel"), ungual fibromas TSC pts can develop subependymal giant cell astrocytoma @ interventricular foramen, which *[HY] can obstruct ventricles --> HYDROCEPHALUS* TSC pts can develop rhabdomyomas, tumor of muscle cells embedded in ventricular wall (rare sx, but seen in 90% of cases) TSC pts can develop renal angiomyolipomas, proliferation of cells around vessel --> growth + hemorrhage, renin-dependent HTN, and CKD

Neurocutaneous disorders are genetic disorders of skin, nerves, and eye (structures derived from *___DERM*) von Hippel-Lindau Dz is 2/2 mutation of VHL gene (TSG) on chrom3; *[HY] VHL functions to ubiquitinate of H___ I___ F___ (i.e., post-translational modification), which tags protein for destruction - without this process, cells behave as if ___oxic --> induce blood vessel growth* VHL manifests with *multiple hema___ (benign clumps of capill.)* in CNS (cerebellum, spinal cord, retina) VHL can also manifest with renal/adrenal tumors (cysts, ___, pheo.) NOTE: VHL is "classic example" of two-hit hypothesis

Neurocutaneous disorders are genetic disorders of skin, nerves, and eye (structures derived from *ECTODERM*) von Hippel-Lindau Dz is 2/2 mutation of VHL gene (TSG) on chrom3; *[HY] VHL functions to ubiquitinate hypoxia-inducible factor (i.e., post-translational modification), which tags protein for destruction - without this process, cells behave as if hypoxic --> induce blood vessel growth* VHL manifests with *multiple hemangioblastomas (benign clumps of capill.)* in CNS (cerebellum, spinal cord, retina) VHL can also manifest with renal/adrenal tumors (cysts, RCC, pheo.) NOTE: VHL is "classic example" of two-hit hypothesis

Neutrophils (backup to macrophages) are drawn from blood to tissue by cytokines & macrophages *[HY] Neutrophils in blood undergo (SIP - Selectin, Integrin, PECAM):* *1) ___ (slow down - ___ ligands on neuts bind E-selectin or P-selectin on endothelial cells [E-/P-selection expression is induced by IL-___ and TNF-alpha])* *2) ___(___ on neutrophils [expression induced by LPS/C5a] bind ICAM on endothelial cells)* *3) ___ (neuts bind PECAM-1 btwn endothelial cells)* *4) MIGRATION (to site of inflammation, brought there by ___ [complement] or IL-8 [macrophages])* Neutrophils have small granules (specific/secondary - can be released into ___ space) and large granules (azurophilic/primary - only fuse w/___); Also know band-form (immature neutrophils - seen in acute infxn, "left shift") *IMPORTANTLY: neutrophils ___ present antigens (in contrast to macrophages!)* Opsonins (attracters) for neutrophils include IL-8, C5a, IgG

Neutrophils (backup to macrophages) are drawn from blood to tissue by cytokines & macrophages *[HY] Neutrophils in blood undergo (SIP - Selectin, Integrin, PECAM):* *1) ROLLING (slow down - selectin ligands on neuts bind E-selectin or P-selectin on endothelial cells [E-/P-selection expression is induced by IL-1 and TNF-alpha])* *2) CRAWLING (INTEGRIN on neutrophils [expression induced by LPS/C5a] bind ICAM on endothelial cells)* *3) TRANSMIGRATION (neuts bind PECAM-1 btwn endothelial cells)* *4) MIGRATION (to site of inflammation, brought there by C5a [complement] or IL-8 [macrophages])* Neutrophils have small granules (specific/secondary - can be released into extracellular space) and large granules (azurophilic/primary - only fuse w/phagosome); Also know band-form (immature neutrophils - seen in acute infxn, "left shift") *IMPORTANTLY: neutrophils do NOT present antigens (in contrast to macrophages!)* Opsonins (attracters) for neutrophils include IL-8, C5a, IgG(

Newborn (0-6mo) mening --> ___ (GBS, Eco, List) Children/young adults --> ___ (SPneu, NMening, HFlu, Entero, HSV) Elderly (>60y) --> ___ (SPneu, GNRs, List)

Newborn (0-6mo) mening --> ampicillin + gentamicin (GBS, Eco, List) Children/young adults --> CTX + vanc (SPneu, NMening, HFlu, Entero, HSV) Elderly (>60y) --> CTX + vanc + ampicillin (SPneu, GNRs, List)

Non-AG metabolic acidosis can be d/t (HARDASS): Hyperalimentation/Hyperchloremia, Addison's dz (loss of aldosterone), RTA, Diarrhea, Acetazolamide, Spironolactone, Saline (decreased RAAS activity 2/2 increased volume status) --- Anion gap metabolic acidosis can be d/t (MUDPILES): Methanol, Uremia, DKA, Propylene glycol, Iron/INH, Lactic acidosis, Ethylene glycol, Salicylates Methanol --> formic acid (*___ loss*) ___ (advanced kidney dz) --> kidneys can't excrete organic acids DKA --> ketoacid buildup Iron poisoning --> toxic effect to GI tract + lactic acidosis & ferric anions Shock/ischemia/*m___* --> lactate buildup Ethylene glycol --> unmeasured anions glycolate + oxalate (extremely ___toxic) *[HY] S___ --> accumulation of pyruvate, lactate, ketoacids after inhibition of TCA cycle (+ respiratory ___)*

Non-AG metabolic acidosis can be d/t (HARDASS): Hyperalimentation/Hyperchloremia, Addison's dz (loss of aldosterone), RTA, Diarrhea, Acetazolamide, Spironolactone, Saline (decreased RAAS activity 2/2 increased volume status) --- Anion gap metabolic acidosis can be d/t (MUDPILES): Methanol, Uremia, DKA, Propylene glycol, Iron/INH, Lactic acidosis, Ethylene glycol, Salicylates Methanol --> formic acid (*vision loss*) Uremia (advanced kidney dz) --> kidneys can't excrete organic acids DKA --> ketoacid buildup Iron poisoning --> toxic effect to GI tract + lactic acidosis & ferric anions Shock/ischemia/*metformin* --> lactate buildup Ethylene glycol --> unmeasured anions glycolate + oxalate (extremely nephrotoxic) *[HY] Salicylates --> accumulation of pyruvate, lactate, ketoacids after inhibition of TCA cycle (+ respiratory alkalosis)*

Non-Hodgkin lymphoma (unlike Hodgkin) often involves many lymph nodes w/*___ spread + extranodal involvement (___ prognosis - Non-Hodgkin is Not what I want)* Key diagnostic distinction of NHL vs. HL is Reed Sternberg cells; if RSCs --> ___, if none --> ___ NHL often involves Waldeyer's ring of mouth (not HY, but helpful to distinguish - HL doesn't involve WR) Note that (in general), lymphomas occur in adults, while leukemias are more seen in children NHL are primarily malignancies of ___-cells (T-cell still happen, but rare); in NHL, malignant cells obliterate lymph node architecture Examples of NHL include: -B: follicular, marginal cell, mantle zone, diffuse large b cell, small lymphocytic lymphoma, Burkitt's -T: adult T-cell lymphoma, cutaneous T-cell lymphoma

Non-Hodgkin lymphoma (unlike Hodgkin) often involves many lymph nodes w/*noncontiguous spread + extranodal involvement (worse prognosis - Non-Hodgkin is Not what I want)* Key diagnostic distinction of NHL vs. HL is Reed Sternberg cells; if RSCs --> HL, if none --> NHL NHL often involves Waldeyer's ring of mouth (not HY, but helpful to distinguish - HL doesn't involve WR) Note that (in general), lymphomas occur in adults, while leukemias are more seen in children NHL are primarily malignancies of B-cells (T-cell still happen, but rare); in NHL, malignant cells obliterate lymph node architecture Examples of NHL include: -B: follicular, marginal cell, mantle zone, diffuse large b cell, small lymphocytic lymphoma, Burkitt's -T: adult T-cell lymphoma, cutaneous T-cell lymphoma

Non-depolarizing neuromuscular blockers (rocuronium, tubocararine, atracurium) are competitive antagonists of ___ receptor, leading to paralysis; these drugs can cause massive ___ release --> hypotension + compensatory tachycardia Reversing ND-NMBA involves inhibiting ___ to increase synaptic ACh levels

Non-depolarizing neuromuscular blockers (rocuronium, tubocararine, atracurium) are competitive antagonists of Ach-N receptor, leading to paralysis; these drugs can cause massive histamine release --> hypotension + compensatory tachycardia Reversing ND-NMBA involves inhibiting AChE to increase synaptic ACh levels

Nonalcoholic fatty liver disease p/w asymptomatic ___ pt with abnormal LFTs (ALT > AST); can improve w/weight loss, but may progress to cirrhosis/HCC Budd-Chiari syndrome is thrombosis of *___ vein* (2/2 myeloproliferative d.o, HCC, OCP/pregnancy, hypercoaguable state); p/w abdominal pain, ascites, hepatomegaly; biopsy demonstrates centrilobular (zone ___) congestion, hemorrhage, and necrosis; BCS can cause *___ liver (mottled appearance d/t chronic edema, also seen in heart failure ["cardiac cirrhosis"])* Portal vein thrombosis is rare cause of abrupt portal HTN, p/w acute abdominal pain, ___megaly +/- *bleeding gastric varices* - importantly, liver biopsy will be ___ (portal vein is before entry into liver!)

Nonalcoholic fatty liver disease p/w asymptomatic obese pt with abnormal LFTs (ALT > AST); can improve w/weight loss, but may progress to cirrhosis/HCC Budd-Chiari syndrome is thrombosis of *hepatic vein* (2/2 myeloproliferative d.o, HCC, OCP/pregnancy, hypercoaguable state); p/w abdominal pain, ascites, hepatomegaly; biopsy demonstrates centrilobular (zone III) congestion, hemorrhage, and necrosis; BCS can cause *nutmeg liver (mottled appearance d/t chronic edema, also seen in heart failure ["cardiac cirrhosis"])* Portal vein thrombosis is rare cause of abrupt portal HTN, p/w acute abdominal pain, splenomegaly +/- *bleeding gastric varices* - importantly, liver biopsy will be NORMAL (portal vein is before entry into liver!)

___ is the main NT for sympathetic system (exceptions: sweat glands --> ___ receptors; adrenal glands --> ___ receptors; dopamine for renal, etc.) ___ receptors are the main system for parasympathetic nervous system; ___ receptors are main system for somatic muscle NOTE: nicotinic receptors are in 1st synapse for SNS and PNS, but have little effects clinically

Norepinephrine is the main NT for sympathetic system (exceptions: sweat glands --> ACh M; adrenal glands --> ACh N; dopamine for renal, etc.) Muscarinic acetylcholine receptors are the main system for parasympathetic nervous system; nicotinic acetylcholine receptors are main system for somatic muscle NOTE: nicotinic receptors are in 1st synapse for SNS and PNS, but have little effects clinically

Not a HY Card: Infxn precautions include standard, ___ (infxn spread by touch [*C diff, MRSA, infectious diarrhea (rota/noro)*] - gloves, gown), DROPLET (spread by talk [*N m___*] - facemask, gloves, gown), A___ (as said [*TB, measles*] - N95 or respirator) Root cause analysis is used to identify cause of serious adverse events (wrong drug administered --> MD/RN error? label issue? admin issue? *Swiss Cheese Model*); Failure mode & effects analysis identifies how process might fail ___ SAE happens Act___ Errors occur at end of process (bedside operator administers wrong drug); Latent Errors occur away from bedside (overworked RNs) Timeout and Checklist are crucial for QI in procedures Tri___ is pt event that mandates response (CP, low O2); Rapid Response Team is provider group that responds to trigger with formal assessment Forcing function are action beneficial to safety (verify allergy before order meds), but can lead to WORKAROUND for efficiency purposes; FFs are part of Human Factors Design (accounts for human nature errors) - also standardization, simplification End goal is Culture of Safety + High Reliability Organization

Not a HY Card: Infxn precautions include standard, CONTACT (infxn spread by touch [*C diff, MRSA, infectious diarrhea (rota/noro)*] - gloves, gown), DROPLET (spread by talk [*N meningitidis*] - facemask, gloves, gown), AIRBORNE (as said [*TB, measles*] - N95 or respirator) Root cause analysis is used to identify cause of serious adverse events (wrong drug administered --> MD/RN error? label issue? admin issue? *Swiss Cheese Model*); Failure mode & effects analysis identifies how process might fail BEFORE SAE happens Active Errors occur at end of process (bedside operator administers wrong drug); Latent Errors occur away from bedside (overworked RNs) Timeout and Checklist are crucial for QI in procedures Trigger is pt event that mandates response (CP, low O2); Rapid Response Team is provider group that responds to trigger with formal assessment Forcing function are action beneficial to safety (verify allergy before order meds), but can lead to WORKAROUND for efficiency purposes; FFs are part of Human Factors Design (accounts for human nature errors) - also standardization, simplification End goal is Culture of Safety + High Reliability Organization

Nucleotide = phosphate group attached; Nucleoside = no phosphate group RNA = two OH groups; DeOXY-NA = one OH group Cytosine methylation inactivates TRANSCRIPTION - lots of unmethylated CG --> immune response Bacterial methylation (on adenine and cytosine) is different (*protects from bacteriophages*); non-methylated DNA is destroyed by endonucleases --- Chromatin is DNA plus proteins and allows condensation of DNA into chromosomes; Chromatin proteins include *HISTONES (repeated DNA + histone units = nucleosome)* Histones contain BASIC, POSITIVELY CHARGED (lysine and arginine) AAs to bind to negatively charged DNA; H1 sits outside of nucleosome and ties together "beads on string" --- *Histones become clinically relevant in DRUG-INDUCED LUPUS (fever + joint pains + rash after starting drug) - most pts with drug-induced lupus [hydralazine, procainaide, isoniazid] have ANTI-HISTONE ANTIBODIES! (normal lupus = anti-dsDNA Abs - reason disorders look similar!)* --- Heterochromatin is condensed and genes do not transcribe well; Euchromatin is less condensed and genes transcribe fine --- Histone acetylation = adding acetyl group --> removes positive charge from histone --> *ALLOWS FOR TRANSCRIPTION!*

Nucleotides are synthesized as monophosphates, converted to triphosphate form to be incorporated into DNA Adenine pairs with thymine (___ bonds), cytosine pairs with guanine (___ bonds); 5' end has phosphate and 3' end has ___ group; adenine and guanine are ___, while thymine and cytosine are ___ DNA repl. starts w/___ unwinding helix (uses ATP) at origin or replication (rich in ___-___ bonds 2/2 fewer bonds), then ___ bind and stabilize DNA strands DNA pol. carries out rest of DNA repl. process (Prok: I-IV, III - primary, I - removes RNA primers; Euk: Greek lettering) Topoisomerase prevents DNA tangling by breaking DNA, then resealing; Top1 breaks ___ strands, while Top2 breaks ___ strands; quinolones abx target prok. topo., many chemo drugs target euk. topo.

Nucleotides are synthesized as monophosphates, converted to triphosphate form to be incorporated into DNA Adenine pairs with thymine (2 bonds), cytosine pairs with guanine (3 bonds); 5' end has phosphate and 3' end has hydroxyl group; adenine and guanine are purines, while thymine and cytosine are pyrimidines DNA repl. starts w/helicase unwinding helix (uses ATP) at origin or replication (rich in A-T bonds 2/2 fewer bonds), then SSBPs bind and stabilize DNA strands DNA pol. carries out rest of DNA repl. process (Prok: I-IV, III - primary, I - removes RNA primers; Euk: Greek lettering) Topoisomerase prevents DNA tangling by breaking DNA, then resealing; Top1 breaks single strands, while Top2 breaks both strands; quinolones abx target prok. topo., many chemo drugs target euk. topo.

Nucleotides can be obtained via diet and via biochemical synthesis (direct synthesis AND salvage pathways) Ingredients for purine synthesis include 1) ribose phosphate, 2) amino acids, and 3) carbons (tetrahydrofolate, CO2) PURINE SYNTHESIS: 1) Create PRPP 2) PRPP --> IMP (nucleotide w/hypoxanthine base!) *[HY] NOTE: glutamine and aspartate donate nitrogens to purines, glycine contributes carbons + nitrogen group as well, CO2 contributes to a carbon group, tetrahydrofolate contributes two carbon groups* RLS: glutamine PRPP amidotransferase (inhibited by AMP, GMP, IMP) *NOTE: ribivirin and mycophenolate inhibit IMP dehydrogenase --> can't go from IMP to GMP (T- and B-cells w/mycophenolate!)*

Organ donation requires 3rd ___ to discuss w/families (MD is confl. of inter. 2/2 "giving up" on pt) ___ entails no CPR or shocks i.s.o. cardiac arrest (other tx can be given - ICU care, surgery) A___ C___ P___ is deciding care prior to incapacitation (ideally done w/PCP, but can be done on admission - VERY important in patients with chronic illness [cancer, HF, COPD]) All research is reviewed by IRB and requires informed consent; prisoners can be a part of research; ___ disclosures must be given to pts if funded by company Pregnant women ___ (can or nah?) refuse tx even if baby's health is impacted Consent before procedure must be conducted by someone familiar with procedure (i.e., NOT medical students) - can be done via telephone, but requires ___

Organ donation requires 3rd party to discuss w/families (MD is conf of int 2/2 "giving up" on pt) DNR entails no CPR or shocks iso cardiac arrest (other tx can be given - ICU care, surgery) Advanced care planning is deciding care prior to incapacitation (ideally done w/PCP, but can be done on admission - VERY important in patients with chronic illness [cancer, HF, COPD]) All research is reviewed by IRB and requires informed consent; prisoners can be a part of research; financial disclosures must be given to pts if funded by company Pregnant women can refuse tx even if baby's health is impacted Consent before procedure must be conducted by someone familiar with procedure (i.e., NOT medical students) - can be done via telephone, but requires witness

Orientation (DPS - ___ - lost in that order) is lost in cognitive d/o's Amnesia is loss of memory often 2/2 CNS injury; ___ amnesia is loss of past memories; anterograde amnesia is inability to make memories Wernicke-Korsakoff is classic cause of amnesia; W: acute ___; K: permanent neuro condition 2/2 repeated W events; both associated with ___ deficiency and alcoholism; *[HY] WKS is associated with atrophy of ___* KS manifests with ___ (can't remember --> make up) + amnesia (A > R)

Orientation (DPS - date, place, self - lost in that order) is lost in cognitive d/o's Amnesia is loss of memory often 2/2 CNS injury; retrograde amnesia is loss of past memories; anterograde amnesia is inability to make memories Wernicke-Korsakoff is classic cause of amnesia; W: acute encephalopathy; K: permanent neuro condition 2/2 repeated W events; both associated with B1 deficiency and alcoholism; *[HY] WKS is associated with atrophy of mammillary bodies* KS manifests with confabulation (can't remember --> make up) + amnesia (A > R)

Osteitis Deformans (Paget's Dz) is *focal* d.o common in older pts w/excessive bone r___ --> abnormally large, deformed bone PD evolves through phases: ___ (osteocytes break down bone), ___ (osteolytic + -blastic), osteosclerotic (bone formation dominates - *hyper___* occurs) Pathologic hallmark is m___ pattern of lamellar bone w/cement lines PD p/w "c___" fracture +/- bone pain or bowing, enlarged skull (increased ___ size), deafness (CN compression) Complications of PD include *[HY] ___ failure 2/2 AV fistula in new bone*, as well as risk of osteosarcoma Labs: ___ AlkPhos; Tx: bisphosphates and calcitonin

Osteitis Deformans (Paget's Dz) is *focal* d.o common in older pts w/excessive bone remodeling --> abnormally large, deformed bone PD evolves through phases: osteolytic (osteocytes break down bone), mixed (osteolytic + -blastic), osteosclerotic (bone formation dominates - *hypervascularity* occurs) Pathologic hallmark is mosaic pattern of lamellar bone w/cement lines PD p/w "chalkstick" fracture +/- bone pain or bowing, enlarged skull (increased hat size), deafness (CN compression) Complications of PD include *[HY] high-output heart failure 2/2 AV fistula in new bone*, as well as risk of osteosarcoma Labs: high AlkPhos; Tx: bisphosphates and calcitonin

Osteitis fibrosa cystica is bone dz of ___ (usually 2/2 parathyroid adenoma) w/bone pain + fractures; labs reveal ___ PTH, high Ca, ___ phosphate X-ray reveals 1) subperiosteal bone resorption and 2) ___ tumors (osteoclastomas) Renal osteodystrophy is bone dz 2/2 renal failure that p/w secondary hyperparathyroidism - will see high PTH and ___ PO4 (UNIQUE!)

Osteitis fibrosa cystica is bone dz of hyperparathyroidism (usually 2/2 parathyroid adenoma) w/bone pain + fractures; labs reveal high PTH, high Ca, low phosphate X-ray reveals 1) subperiosteal bone resorption and 2) brown tumors (osteoclastomas) Renal osteodystrophy is bone dz 2/2 renal failure that p/w secondary hyperparathyroidism - will see high PTH and high PO4 (UNIQUE!)

Osteoblast activity markers include alk. phos., osteocalcin (on-collagen bone matrix protein), type I procollagen; Alk Phos creates ___ environment for calcium deposition (REMEMBER: acidosis stimulates osteoclasts --> hypercalcemia) PTH has multiple effects on bone (resorption and formation) - continuous admin. --> bone ___ predominates of c___ bone; once daily bolus --> bone ___ predominates in t___ bone (lots of trabecular bone in SPINE, use teriparatide) -___ contain PTH receptors (incr. bone mass); -clasts have no PTH receptors (activated indirectly via -blasts), PTH --> -blasts --> M-CSF and RANK-L expression ___ also affect bone - close growth plate at puberty and incr. bone density (reason for osteoporosis in post-menopausal women) - estrogens induce apoptosis of -clasts (incr. OPG, decr. RANK and M-CSF)

Osteoblast activity markers include alk. phos., osteocalcin (on-collagen bone matrix protein), type I procollagen; Alk Phos creates alkaline environment for calcium deposition (REMEMBER: acidosis stimulates osteoclasts --> hypercalcemia) PTH has multiple effects on bone (resorption and formation) - continuous admin. --> bone resorption predominates of cortical bone; once daily bolus --> bone formation predominates in trabecular bone (lots of trabecular bone in SPINE, use teriparatide) -blasts contain PTH receptors (incr. bone mass); -clasts have no PTH receptors (activated indirectly via -blasts), PTH --> -blasts --> M-CSF and RANK-L expression Estrogens also affect bone - close growth plate at puberty and incr. bone density (reason for osteoporosis in post-menopausal women) - estrogens induce apoptosis of -clasts (incr. OPG, decr. RANK and M-CSF)

O___ is cartilage-capped bone spur (2/2 cartilage-forming tumor) - *[HY] osteochondromas are lateral projection of ___ (stop growing with GP closure)* Fibrous dysplasia is benign tumor of woven bone surrounded by f___ - occur in medulla/diaphysis (*histology - Chinese character trabeculae*) Simple bone cysts are fluid-filled spaces in young adult - rarely involve surgery, but can l/t ___ fx Only tumor in bones of hand/feet is a c___ - benign tumor of cartilage (malignant - chondrosarcoma) Langerhans Cell Histiocytosis has bone variant (eosinophilic granuloma) that p/w bone mass in skull of kids (biopsy w/Langerhans cells + *E___*) Bone tumors p/w bone pain + NORMAL LABS

Osteochondroma is cartilage-capped bone spur (2/2 cartilage-forming tumor) - *[HY] osteochondromas are lateral projection of growth plate (stop growing with GP closure)* Fibrous dysplasia is benign tumor of woven bone surrounded by fibroblasts - occur in medulla/diaphysis (*histology - Chinese character trabeculae*) Simple bone cysts are fluid-filled spaces in young adult - rarely involve surgery, but can l/t path. fx Only tumor in bones of hand/feet is a chondroma - benign tumor of cartilage (malignant - chondrosarcoma) Langerhans Cell Histiocytosis has bone variant (eosinophilic granuloma) that p/w bone mass in skull of kids (biopsy w/Langerhans cells + *EOSINOPHILS*) Bone tumors p/w bone pain + NORMAL LABS

O___ is incr. bone density 2/2 defective osteoclast activity; infantile form is most severe and 2/2 *c___ anhydrase II mutation (-clasts can't function)* Bones in osteopetrosis are prone to fx d/t loss of flexibility - excess bone can also overgrow bone marrow --> p___ w/extramedullary hematopoesis (h___); excess skull bone --> CN compression w/vision loss Osteoclasts are derived from macrophages - stem cell transplant can be curative

Osteopetrosis is incr. bone density 2/2 defective osteoclast activity; infantile form is most severe and 2/2 *carbonic anhydrase II mutation (-clasts can't function)* Bones in osteopetrosis are prone to fx d/t loss of flexibility - excess bone can also overgrow bone marrow --> pancytopenia w/extramedullary hematopoesis (hepatosplenomegaly); excess skull bone --> CN compression w/vision loss Osteoclasts are derived from macrophages - stem cell transplant can be curative

Osteoporosis affects ___ bone > ___ bone (d/t high surface area - more for -clasts to work with); high trabecular content in spine, hip, and wrist (site of osteoporotic breaks) Women start with lower peak bone mass, then have accelerated bone loss after menopause (loss of estrogen stimulation - estrogen usually inhibits osteoclasts); ___ activity can increase bone mass *[HY] Ca, PTH, AlkPhos are ___ in primary (senile) osteoporosis* Steroids, phenobarb/phenytoin/carbamazepine (via P450 enzymes --> incr. breakdown of VitD), levothyroxine (hyperthyroidism --> osteoporosis/fracture) can all cause secondary osteoporosis; malabsorption syndromes (celiac, Crohn's, UC) can cause 2nd osteoporosis Dx is based on fragility fx (fall from standing height), vertebral compression fx (loss of height), T-score <___ on DXA scan

Osteoporosis affects trabecular bone > cortical bone (d/t high surface area - more for -clasts to work with); high trabecular content in spine, hip, and wrist (site of osteoporotic breaks) Women start with lower peak bone mass, then have accelerated bone loss after menopause (loss of estrogen stimulation - estrogen usually inhibits osteoclasts); weight-bearing activity can increase bone mass *[HY] Ca, PTH, AlkPhos are normal in primary (senile) osteoporosis* Steroids, phenobarb/phenytoin/carbamazepine (via P450 enzymes --> incr. breakdown of VitD), levothyroxine (hyperthyroidism --> osteoporosis/fracture) can all cause secondary osteoporosis; malabsorption syndromes (celiac, Crohn's, UC) can cause 2nd osteoporosis Dx is based on fragility fx (fall from standing height), vertebral compression fx (loss of height), T-score <2.5 on DXA scan

Ovaries have three phases of menstrual cycle: follicular phase (menses/proliferate phase of endometrium), ovulation, luteal phase (secretory phase of endometrium) In follicular phase, ___ pulse frequency increases --> FSH production --> *___ production* (feeds back to initially decrease FSH/LH levels) - over time, estrogen leads to selection of one dominant follicle [NOTE: Follicular phase can Fluctuate in length - reason for different length cycles] Mid-cycle, there is a switch from ___ feedback to ___ feedback for estrogen on hypothalamus --> GnRH pulses increase --> *___* --> OVULATION [*___ is mild, unilateral pain for hours-to-days that lines up w/mid-cycle pain*] After ovulation, corpus luteum forms (luteal phase) and secretes *___ (prepares uterus for implantation)*, which feeds back on pituitary --> FSH/LH levels fall; eventually, corpus luteum degrades --> *___* (if fertilization occurs --> hCG maintains corpus luteum for ~12w until placenta is sufficient)

Ovaries have three phases of menstrual cycle: follicular phase (menses/proliferate phase of endometrium), ovulation, luteal phase (secretory phase of endometrium) In follicular phase, GnRH pulse frequency increases --> FSH production --> *estradiol production* (feeds back to initially decrease FSH/LH levels) - over time, estrogen leads to selection of one dominant follicle [NOTE: Follicular phase can Fluctuate in length - reason for different length cycles] Mid-cycle, there is a switch from negative feedback to positive feedback for estrogen on hypothalamus --> GnRH pulses increase --> *LH surge* --> OVULATION [*Mittelschmerz is mild, unilateral pain for hours-to-days that lines up w/mid-cycle pain*] After ovulation, corpus luteum forms (luteal phase) and secretes *progesterone (prepares uterus for implantation)*, which feeds back on pituitary --> FSH/LH levels fall; eventually, corpus luteum degrades --> *MENSTRUATION* (if fertilization occurs --> hCG maintains corpus luteum for ~12w until placenta is sufficient)

PARIETAL LOBE: Contains sensory cortex and damage to right parietal lobe can lead to ___ Baum's loop is here and can cause "___" when damaged TEMPORAL LOBE: Wernicke's ("Wacky") speech area is in ___ hemisphere and does speech ___ (damage --> ___ aphasia) Olfactory bulb is here and can be involved in temporal lobe ___ Meyer's loop is here and can cause "___" when damaged (MCA stroke) Amygdala is here, can lead to ___ when damaged (primitive behavior)

PARIETAL LOBE: Contains sensory cortex and damage to right parietal lobe can lead to spatial neglect (can't perceive left side) Baum's loop is here and can cause "pie on the floor" when damaged TEMPORAL LOBE: Wernicke's ("Wacky") speech area is in LEFT hemisphere and does speech comprehension (damage --> fluent aphasia) Olfactory bulb is here and can be involved in temporal lobe epilepsy Meyer's loop is here and can cause "pie in the sky" when damaged (MCA stroke) Amygdala is here, can lead to Kluver-Bucy Syndrome when damaged (primitive behavior)

CLASSIC SCENARIO: pt w/chronic hemolysis (sickle cell, hereditary spherocytosis, beta thalassemia major) p/w worsening anemia + *LOW RETICULOCYTE COUNT*?

PARVOVIRUS B19 (infxn of RBC progenitor cells)

CASE DESCRIPTION: sickle cell patient with LOW reticulocyte count - what's going on? how do we treat? BOARD BUZZWORD: "flesh-colored domes"?

PARVOVIRUS B19 INFXN (normal retic count is 0.5-1.5%), Tx with TRANSFUSION MOLLESCUM CONTAGIOSUM (2/2 poxvirus)

PCP has 2 MOAs: 1) antagonizes ___ (like ketamine) and 2) inhibits reuptake of ___ (like cocaine); manifestations include AMS + psychosis, agitated + ___ behavior, HTN + tachy; fatalities 2/2 trauma (loss of pain/sensation) - tx w/benzos or Haldol LSD causes a trip w/expanded consciousness, ___ (blending of senses), depersonalization; LSD can cause *___* - hallucinate after stopping drug ___ (ecstasy) is amphetamine variant (HTN, tachy) that increases release of serotonin/inhibits reuptake in brain; patients develop euphoria and *___ (teeth grinding)*; can cause *[HY] ___ (inc fluid intake + inc ADH secretion) --> seizures* and hepatotoxicity ; withdrawal --> dep, anx, jaw soreness

PCP has 2 MOAs: 1) antagonizes NMDA (like ketamine) and 2) inhibits reuptake of monoamines (like cocaine); manifestations include AMS + psychosis, agitated + violent behavior, HTN + tachy; fatalities 2/2 trauma (loss of pain/sensation) - tx w/benzos or Haldol LSD causes a trip w/expanded consciousness, synesthesia (blending of senses), depersonalization; LSD can cause *FLASHBACKS* - hallucinate after stopping drug MDMA (ecstasy) is amphetamine variant (HTN, tachy) that increases release of serotonin/inhibits reuptake in brain; patients develop euphoria and *BRUXISM (teeth grinding)*; can cause *[HY] HYPONATREMIA (inc fluid intake + inc ADH secretion) --> seizures* and hepatotoxicity ; withdrawal --> dep, anx, jaw soreness

PCR is lab technique to amplify copies of DNA in sample (can determine if DNA is present, how much is there) Ingredients: sample, DNApol, primer (SS-DNA segment), nucleotides Technique: ___ (denatures DNA to single strands), ___ (primer anneals complimentary DNA if present), ___ (DNApol elongates), repeat ___ is done in presence of fluorescent dye - amount of dye taken up is proportional to amount of DNA in sample (i.e., more rapid fluorescence detected --> more DNA in sample) PCR used clinically in situations where very ___ amounts of DNA are present (HSV encephalitis, HIV viral load)

PCR is lab technique to amplify copies of DNA in sample (can determine if DNA is present, how much is there) Ingredients: sample, DNApol, primer (SS-DNA segment), nucleotides Technique: heat (denatures DNA to single strands), cool (primer anneals complimentary DNA if present), warm (DNApol elongates), repeat rtPCR is done in presence of fluorescent dye - amount of dye taken up is proportional to amount of DNA in sample (i.e., more rapid fluorescence detected --> more DNA in sample) PCR used clinically in situations where very small amounts of DNA are present (HSV encephalitis, HIV viral load)

PHAGOCYTE IMMUNODEFICIENCIES (*INNATE IMMUNITY DEFECTS!*): *Leukocyte Adhesion Deficiency (AutRec, "way to test neutrophil migration")*: defective neutrophil/lymphocyte migration 2/2 CD18 (LFA-1) i___ --> impaired chemotaxis Will p/w (LAD) *LATE separation of ___ +/- infection*, Absent ___, Dysfunctional neutrophils (recurrent skin + mucosal bacteria infxns) Labs: ___ neutrophil count (can't migrate out of blood!) --- *Chediak-Higashi Syndrome*: defect in ___ (LYSosome is Trash) --> *microtubule dysfunction* --> *LYSOSOME can't fuse w/PHAGOSOME!* P/w (PLAIN) Progressive neurodegeneration (w/c bound usually), Lymphohistiocytosis, *___ (OCULOCUTANEOUS - pigment granules are also f'ed up, fair skin, blond hair, blue eyes), Infxns (recurrent - usually Staph and Strep), Neuropathy Smear: giant ___ in granulocytes --- *Chronic Granulomatous Dz*: defect in ___ oxidase --> can't form ROS or respiratory burst for phagosome in neutrophils (usually generates H2O2 from O2); accordingly, bacteria that don't have ___ (ie., bring own H2O2 and can't break it down) don't cause a problem, but bacteria *with ___ (which breaks down H2O2) are problem* P/w increased susceptibility to catalase (+) organisms (Staph, Pseudomonas, Serratia, Nocardia, Aspergillus - SPANS) Dx: lack of ___ on nitroblue tetrazolium dye test

PHAGOCYTE IMMUNODEFICIENCIES (*INNATE IMMUNITY DEFECTS!*): *Leukocyte Adhesion Deficiency (AutRec, "way to test neutrophil migration")*: defective neutrophil/lymphocyte migration 2/2 CD18 (LFA-1) integrin --> impaired chemotaxis Will p/w (LAD) *LATE separation of umbilical cord +/- infection*, Absent pus, Dysfunctional neutrophils (recurrent skin + mucosal bacteria infxns) Labs: elevated neutrophil count (can't migrate out of blood!) --- *Chediak-Higashi Syndrome*: defect in LYST --> *microtubule dysfunction* --> *LYSOSOME can't fuse w/PHAGOSOME!* P/w (PLAIN) Progressive neurodegeneration (w/c bound usually), Lymphohistiocytosis, *Albinism (OCULOCUTANEOUS - pigment granules are also f'ed up, fair skin, blond hair, blue eyes), Infxns (recurrent - usually Staph and Strep), Neuropathy Smear: giant granules in granulocytes --- *Chronic Granulomatous Dz*: defect in NADPH oxidase --> can't form ROS or respiratory burst for phagosome in neutrophils (usually generates H2O2 from O2); accordingly, bacteria that don't have catalase (ie., bring own H2O2 and can't break it down) don't cause a problem, but bacteria *with catalase (which breaks down H2O2) are problem* P/w increased susceptibility to catalase (+) organisms (Staph, Pseudomonas, Serratia, Nocardia, Aspergillus) Dx: lack of blue on nitroblue tetrazolium dye test

CLASSIC BOARDS QUESTION: pt w/DKA + respiratory failure --> what do you check?

PHOSPHORUS (B&B Diabetes 10:30)

PONTINE STROKES: Medial pontine damages CST, CN6, and CN7 --> contra hemipar, ipsi facial weak, CN6 palsy, & gaze palsy to affected side Lateral pontine can damage vestib nuclei, spinothal tract, spinal V nucleus, symp tract, facial nuc, and coch nuc --> nystagmus, contra pain/temp loss, ipsi facial pain/tem loss, Horner's, ipsi facial droop, and deafness (classically caused by AICA stroke) (consider deleting me)

PONTINE STROKES: Medial pontine damages CST, CN6, and CN7 --> ___ hemipar, ___ facial weak, CN6 palsy, & gaze palsy ___ side Lateral pontine can damage vestib nuclei, spinothal tract, spinal V nucleus, symp tract, facial nuc, and coch nuc --> nystagmus, ___ pain/temp loss, ___ facial pain/tem loss, Horner's, ___ facial droop, and deafness (classically caused by ___ stroke)

CLASSIC CASE: pt p/w sx of portal HTN (varices, caput medusa, bleeding gastric varices, hypersplenism, internal hemorrhoids) with normal biopsy - que pasa?

PORTAL VEIN THROMBOSIS

CLASSIC SCENARIO: GI symptoms (N/V/D and abdominal pain) + darkening skin - what's up?

PRIMARY ADRENAL INSUFFICIENCY (Addison's Dz)

CLASSIC CASE: young woman w/Sjogren's and elevated AlkPhos + anti-mitochondrial Abs + SEVERE ITCHING --> what is it? how treat?

PRIMARY BILIARY CIRRHOSIS Tx: ursodeoxycholic acid (+/- liver transplant)

PUBLIC HEALTH: ___ prevent prevents dz from occurring (immunization); ___ prevent prevents disability (detect and tx early - screening mammogram); ___ prevent prevents long-term dz comp and maximize remaining function (cardiac rehab programs); ___ prevent avoids overuse of tx Medicare provides insurance for pts >65, disabled pts, pts on D___; broken down into part ___ (hospitals), part ___ (outpt tx), part C (complicated) part D (prescrip ___); Medicaid is jointly funded by state and fed govt Private insurance includes 1) ___ (cheap - insur hires MDs --> pts must go to those MDs), 2) ___ (expensive - see any MD but some cheaper ["in network"]), 3) POS (middle - specific PCP w/referrals out of network but higher copay) Insurance pays by 1) fee for service ($100/clinic visit), 2) salary ($100k to see all pts), 3) C___ (set fee paid to MD per pt; spend less $ than fee --> make $$$) *Hospice requires expected survival <6mo*

PUBLIC HEALTH: Primary prevent prevents dz from occurring (immunization); Secondary prevent prevents disability (detect and tx early - screening mammogram); Tertiary prevent prevents long-term dz comp and maximize remaining function (cardiac rehab programs); Quanternary prevent avoids overuse of tx Medicare provides insurance for pts >65, disabled pts, pts on dialysis; broken down into part A (hospitals), part B (outpt tx), part C (complicated) part D (prescrip drugs); Medicaid is jointly funded by state and fed govt Private insurance includes 1) HMO (cheap - insur hires MDs --> pts must go to those MDs), 2) PPO (expensive - see any MD but some cheaper ["in network"]), 3) POS (middle - specific PCP w/referrals out of network but higher copay) Insurance pays by 1) fee for service ($100/clinic visit), 2) salary ($100k to see all pts), 3) capitation (set fee paid to MD per pt; spend less $ than fee --> make $$$) *Hospice requires expected survival <6mo* ^*NOTE: emergency care must be provided w/w.o insurance!!*

___ reflects amount of O2 dissolved in blood (result of ABG via radial artery); Pulse oximeter measures % ___ of hemoglobin w/O2 (related to PaO2, but not same thing); Oxygen content is related to presence of Hgb + saturation of Hgb Hypoxia - low O2 delivery to tissues; Hypoxemia - low O2 content in blood (low Hgb saturation, low PaO2) Hypoxia can be caused by hypoxemia, but also h___ (normal O2 content in blood but can't get blood out), a___ (decreased O2 binding capacity d/t less Hgb - PaO2 and O2 saturation normal), CO poisoning (blocks O2 binding sites - *functional anemia by taking Hgb away from O2*) In CO poisoning, will have ___ alveolar PO2, ___PaO2, *but ___ O2 saturation that l/t HYPOXIA* - note that O2 sat. detector CANNOT distinguish CO or O2 bound to Hgb, which is why O2 sat is NORMAL in CO poisoning)

PaO2 reflects amount of O2 dissolved in blood (result of ABG via radial artery); Pulse oximeter measures % saturation of hemoglobin w/O2 (related to PaO2, but not same thing); Oxygen content is related to presence of Hgb + saturation of Hgb Hypoxia - low O2 delivery to tissues; Hypoxemia - low O2 content in blood (low Hgb saturation, low PaO2) Hypoxia can be caused by hypoxemia, but also heart failure (normal O2 content in blood but can't get blood out), anemia (decreased O2 binding capacity d/t less Hgb - PaO2 and O2 saturation normal), CO poisoning (blocks O2 binding sites - *functional anemia by taking Hgb away from O2*) In CO poisoning, will have normal alveolar PO2, normal PaO2, *but low O2 saturation that l/t HYPOXIA* - note that O2 sat. detector CANNOT distinguish CO or O2 bound to Hgb, which is why O2 sat is NORMAL in CO poisoning)

Pancreas is made of head (+ uncinate process), body, and tail Most pancreatic enzymes pass through Ampulla of Vater (some through ___ duct) Embryology of pancreas involves *___ buds off foregut (ventral and dorsal)* - ___ bud forms head, uncinate process, and main pancreatic duct; dorsal bud forms body, tail, ___ duct *___* is congenital anomaly of ventral bud (buds don't fuse --> surround duodenum --> *bowel obstruction*) *___* is failure of dorsal and ventral *DUCTS* to fuse - accessory duct drains pancreas body and tail (usually asymptomatic, but can develop pancreatitis) Pancreas is *___ RETROPERITONEAL, d/t being intraperitoneal in development --> fusing w/posterior wall*

Pancreas is made of head (+ uncinate process), body, and tail Most pancreatic enzymes pass through Ampulla of Vater (some through accessory duct) Embryology of pancreas involves *TWO buds off foregut (ventral and dorsal)* - ventral bud forms head, uncinate process, and main pancreatic duct; dorsal bud forms body, tail, accessory duct *Annular pancreas* is congenital anomaly of ventral bud (buds don't fuse --> surround duodenum --> *bowel obstruction*) *Pancreas divisum* is failure of dorsal and ventral *DUCTS* to fuse - accessory duct drains pancreas body and tail (usually asymptomatic, but can develop pancreatitis) Pancreas is *SECONDARILY RETROPERITONEAL, d/t being intraperitoneal in development --> fusing w/posterior wall*

Pancreatic enzymes are secreted by ___ cells of pancreatic duct; ___ is major stimulus for release (*makes sense - want gallbladder and pancreas releasing @ same time*), but ___ can also stimulate release (vagovagal reflex - afferent [senses acid in duodenum] and efferent [stimulates acinar cells via ACh] arms of reflex are both found w/in vagus nn.!) Pancreatic enzymes include: alpha-amylase, lipase, phospholipase A, colipase, proteases, trypsin Alpha ___ (secreted in active form - unique!) breaks down starch into oligosaccharides, which are further digested by ___ enzymes (rate-limiting step for carb digestion!); can be used to identify acute pancreatitis! Lipases (lipase, PLA-C, colipase) break triglycerides to FAs; PLA-C is activated by ___; lipase can be used to identify acute pancreatitis! Protein digestion enzymes (elastase, chymotrypsin, carboxypeptidase) are secreted as zymogens - activated by *___ (activated from trypsinogen via enterokinase)!!*; *[HY] Acute pancreatitis occurs when large amounts of trypsin activated --> ___ of pancreas itself!*

Pancreatic enzymes are secreted by acinar cells of pancreatic duct; CCK is major stimulus for release, but ACh can also stimulate release (vagovagal reflex - afferent [senses acid in duodenum] and efferent [stimulates acinar cells via ACh] arms of reflex are both found w/in vagus nn.!) Pancreatic enzymes include: alpha-amylase, lipase, phospholipase A, colipase, proteases, trypsin Alpha amylase (secreted in active form - unique!) breaks down starch into oligosaccharides, which are further digested by brush border enzymes (rate-limiting step for carb digestion!); can be used to identify acute pancreatitis! Lipases (lipase, PLA-C, colipase) break triglycerides to FAs; PLA-C is activated by trypsin; lipase can be used to identify acute pancreatitis! Protein digestion enzymes (elastase, chymotrypsin, carboxypeptidase) are secreted as zymogens - activated by *TRYPSIN (activated from trypsinogen via enterokinase)!!*; *[HY] Acute pancreatitis occurs when large amounts of trypsin activated --> auto-digestion of pancreas itself!*

Paracentesis can lead to ___ (infxn of ascitic fluid), usually 2/2 E Coli or Klebsiella SBP p/w abdominal pain and tenderness (usually after tap) w/ascitic PMNs >___/mL - tx w/cefo___ --- *[HY] ___ (perisinusoidal cell) cell is a storage site for retinoids (vitA metabolites) that are activated in chronic liver dz (i.e., ___); stellate cells secrete ___-beta and proliferate, producing ___ tissue and l/t CIRRHOSIS!!!*

Paracentesis can lead to spontaneous bacterial peritonitis (infxn of ascitic fluid), usually 2/2 E Coli or Klebsiella SBP p/w abdominal pain and tenderness (usually after tap) w/ascitic PMNs >250/mL - tx w/cefotaxime --- *[HY] Stellate (perisinusoidal cell) cell is a storage site for retinoids (vitA metabolites) that are activated in chronic liver dz (i.e., cirrhosis); stellate cells secrete TGF-beta and proliferate, producing fibrous tissue and l/t CIRRHOSIS!!!*

SLUDD: mneumonic for what? The sympathetic nervous system mostly constricts vessels except at ___ and ___ The parasympathetic dilates indirectly by stimulating ___ to release ___

Parasympathetic nervous system -Salivation -Lacrimation -Urination -Digestion -Defecation The sympathetic nervous system mostly constricts vessels except at muscle and liver The parasympathetic dilates indirectly by stimulating endothelium to release NO

Parathyroid glands (derived from ___ pharyngeal pouches) contain ___ cells that synthesize and secrete PTH, a protein hormone that binds surface receptor in bone and kidneys Net effects of PTH are to 1) ___ serum calcium, 2) ___ serum phosphate, 3) ___ urinary phosphate - some effects are directly d/t PTH, while others are VitD Calcium activates ___ and when not much is bound --> PTH secreted; Triggers for PTH secretion include 1) ___calcemia, 2) ___ phosphate, 3) ___ 1,25-VitD (active form) NOTE: Mg can also activate CaSR (both 2+ cations! - hypomagnesemia --> hyperparathyroidism, *unless ___ Mg [need some Mg for CaSR function] - can see hypocalcemia w/severe hypomagnesemia*) NOTE: hypocalcemia and hypomagnesemia can both cause prolonged ___

Parathyroid glands (derived from 3rd/4th pharyngeal pouches) contain chief cells that synthesize and secrete PTH, a protein hormone that binds surface receptor in bone and kidneys Net effects of PTH are to 1) increase serum calcium, 2) decrease serum phosphate, 3) increase urinary phosphate - some effects are directly d/t PTH, while others are VitD Calcium activates Ca-Sensing Receptors (CaSRs) and when not much is bound --> PTH secreted; Triggers for PTH secretion include 1) hypocalcemia, 2) high phosphate, 3) low 1,25-VitD (active form) NOTE: Mg can also activate CaSR (both 2+ cations! - hypomagnesemia --> hyperparathyroidism, *unless very low Mg [need some Mg for CaSR function] - can see hypocalcemia w/severe hypomagnesemia*) NOTE: hypocalcemia and hypomagnesemia can both cause prolonged QT-interval

___ cells (found in gastric glands) secrete HCl in stomach - low pH protects against infxn and denatures proteins; parietal cells are ___ (color?; eosinophilic) and found in glandular layer of glands (not pits) *[HY] Parietal cells are stimulated by 1) direct ___ (secreted by G-cells in atrum - CCKb receptor), 2) indirect gastrin (gastrin acts on ___ cells --> histamine --> stimulates parietal cells for acid secretion, rationale for histamine blockers), 3) vagal nerve stimulation^ (ACh-to-M3 receptors stimulate ___ cells, Gastrin-Releasing-Peptide [GRP]-to-___ cells)* [SO: two ways for gastrin to stimulate, two ways for vagus nn to stimulate] ^*Historically, vagotomy was used to tx ulcers; [HY] Atropine can block ___ cell HCl secretion, but does not block vagal stimulation of ___-cells --> gastrin --> HCl (bc stimulated by ___!!)* Parietal cells also secrete ___ for B12 absorption --- Stomach mucosa is protected by mucous and bicarb (secreted by n___ cells) --- Chief cells of stomach are found in gastric gland DEEP layer (dark-colored, basophilic) - CCs secrete ___ to digest proteins via vagus nerve stimulation

Parietal cells (found in gastric glands) secrete HCl in stomach - low pH protects against infxn and denatures proteins; parietal cells are *P*ink (eosinophilic) and found in glandular layer of glands (not pits) *[HY] Parietal cells are stimulated by 1) direct gastrin (secreted by G-cells in atrum - CCKb receptor), 2) indirect gastrin (gastrin acts on ECL cells --> histamine --> stimulates parietal cells for acid secretion, rationale for histamine blockers), 3) vagal nerve stimulation^ (ACh-to-M3 receptors stimulate parietal cells, Gastrin-Releasing-Peptide [GRP]-to-G cells)* [SO: two ways for gastrin to stimulate, two ways for vagus nn to stimulate] ^*Historically, vagotomy was used to tx ulcers; [HY] Atropine can block parietal cell HCl secretion, but does not block vagal stimulation of G-cells --> gastrin --> HCl (bc stimulated by GRP!!)* Parietal cells also secrete intrinsic factor for B12 absorption --- Stomach mucosa is protected by mucous and bicarb (secreted by neck cells) --- Chief cells of stomach are found in gastric gland DEEP layer (dark-colored, basophilic) - CCs secrete pepsin to digest proteins via vagus nerve stimulation

Paroxysmal Nocturnal Hemoglobinura is RBC destruction via *___* 2/2 loss of protective proteins on RBC membrane (CD___/DAF or CD___); PNH is an ACQUIRED mutation in RBC stem cells, l/t loss of *___ synthesis (serve as RBC membrane anchors to surface, when lost --> can't mount DAF/CD59 --> complement-mediate lysis)* - platelets and WBCs are also lysed PNH p/w hemolysis at ___, pancytopenia, fatigue/dyspnea (*[HY] ___ is lost in urine --> IDA is common finding in these pts!*); abdominal pain is also seen (*Hgb binds ___ --> increased smooth muscle tone --> abdominal pain*) Feared complication of PNH is *venous ___ in rare locations (i.e., ___ vein, mesenteric vein, cerebral vein, Budd-Chiari syndrome)* - pts are also at increased risk for ___ (THINK ABOUT IT - stem cells already mutated!) Dx: expected w/hemolysis + unexplained thrombosis, labs show evidence of hemolysis (LDH, low haptoglobin) w/___ Coombs test, confirm w/*flow cytometry for ___-anchored proteins* Tx: eculizumab (anti-___ antibody) - prevents intravascular hemolysis, but not extravascular hemolysis (C3 can still bind --> get effed by spleen)

Paroxysmal Nocturnal Hemoglobinura is RBC destruction via *complement* 2/2 loss of protective proteins on RBC membrane (CD55/DAF or CD59); PNH is an acquired mutation in RBC stem cells, l/t loss of *GPI anchor synthesis (serve as RBC membrane anchors to surface, when lost --> can't mount DAF/CD59 --> complement-mediate lysis)* - platelets and WBCs are also lysed PNH p/w hemolysis at night, pancytopenia, fatigue/dyspnea (*[HY] iron is lost in urine --> IDA is common finding in these pts!*); abdominal pain is also seen (*Hgb binds nitric oxide --> increased smooth muscle tone --> abdominal pain*) Feared complication of PNH is *venous thrombosis in rare locations (i.e., portal vein, mesenteric vein, cerebral vein, Budd-Chiari syndrome)* - pts are also at increased risk for AML (THINK ABOUT IT - stem cells already mutated!) Dx: expected w/hemolysis + unexplained thrombosis, labs show evidence of hemolysis (LDH, low haptoglobin) w/negative Coombs test, confirm w/*flow cytometry for GPI-anchored proteins* Tx: eculizumab (anti-C5 antibody) - prevents intravascular hemolysis, but not extravascular hemolysis (C3 can still bind --> get effed by spleen)

PartPres of O2 in alveoli (PAO2) is not same as that of inspired air (PiO2 - d/t mixing with CO2); PAO2 is also not same as PaO2 (d/t some blood not participating in gas exchange) Alveolar gas concentration (PAO2) = 150mmHg (PiO2) - ([Pa___]/___) A-a gradient can subsequently be calculated as PAO2 - PaO2, normal is 10-15mmHg (d/t shunting from thebesian/bronchial veins) Hypoxemia (decreased PaO2) w/normal A-a gradient is 2/2 not inhaling enough ___ (hypoventilation, high altitude) - tx w/O2 Hypoxemia w/high A-a gradient is 2/2 ___ not working (fibrosis, shunt, V/Q mismatch) ^0.8 = [CO2 produced]/[O2 consumed]

PartPres of O2 in alveoli (PAO2) is not same as that of inspired air (PiO2 - d/t mixing with CO2); PAO2 is also not same as PaO2 (d/t some blood not participating in gas exchange) Alveolar gas concentration (PAO2) = 150mmHg (PiO2) - ([PaCO2]/0.8) A-a gradient can subsequently be calculated as PAO2 - PaO2, normal is 10-15mmHg (d/t shunting from thebesian/bronchial veins) Hypoxemia (decreased PaO2) w/normal A-a gradient is 2/2 not inhaling enough O2 (hypoventilation, high altitude) - tx w/O2 Hypoxemia w/high A-a gradient is 2/2 alveoli not working (fibrosis, shunt, V/Q mismatch) ^0.8 = [CO2 produced]/[O2 consumed]

___ is only ssDNA virus Viral genome infectivity refers to whether or not viral nucleic acid is infectious on own (dsDNA and ___RNA; ___RNA is not infectious on own 2/2 lack of RdRp) Four RNA viruses have genomes segmented --> allows for reassortment and mixing into new virus to cause pandemics (BOAR: B___, O___ [flu], A___, R___ [rota]) 3 DNA viruses with circle genome are P___oma, Polyoma (J___/B___), Hepadna (HBV); all DNA viruses have icosahedral and replicate in nuc except POX (dumbell-shaped + cytoplasm - v big)

Parvovirus is only ssDNA virus Viral genome infectivity refers to whether or not viral nucleic acid is infectious on own (dsDNA and +RNA; -RNA is not infectious on own 2/2 lack of RdRp) Four RNA viruses have genomes segmented --> allows for reassortment and mixing into new virus (BOAR: Bunyavirus, Orthomyxovirus [flu], Arenavirus, Reovirus [rota]) 3 DNA viruses with circle genome are Papilloma, Polyoma (JC/BK), Hepadna (HBV); all DNA viruses have icosahedral and replicate in nuc except POX (dumbell-shaped + cytoplasm - v big)

Patients who lack A or B antigens (*which are made of ___ [macromolecule?]*) generate antibodies to those antigens by 4-6mos of age, d/t exposure to bacterial antigens w/similar structures - those Abs are Ig___; Importantly, these Abs are *naturally occurring* The Rh antigens (more than 50) are made up of transmembrane proteins - the most important Rh antigen is ___! Rh negative individuals can develop anti-D antibodies if exposed to D+ RBC - this can occur via transfusion or pregnancy; importantly, anti-D antibodies are *Ig___ - can cross placenta to affect baby!* Newborn hemolytic disease is classically caused by anti-D antibodies and can only occur in D- ___ and D+ ___ To develop newborn hemolytic dz, mother has first pregnancy w/exposed D+ RBCs at delivery, develops anti-___ IgG; if 2nd pregnancy has D+ RBCs --> hemolysis in utero Low Ab titer l/t mild hemolysis in baby; high Ab titer l/t h___ (*fluid everywhere - high output CHF, pleural edema, pericardial effusion, ascites*) Prevent newborn hemolytic dz by giving ___ immune globulin (Rhogam - IgG antibodies to D antigen) in 3rd trimester of D- mothers Can do maternal antibody screen (*___ Coombs Test - mix mom's serum w/RBCs that are D+, watch for blood clumping --> isoimmunization!*)

Patients who lack A or B antigens (*which are made of sugars*) generate antibodies to those antigens by 4-6mos of age, d/t exposure to bacterial antigens w/similar structures - those Abs are IgM; Importantly, these Abs are *naturally occurring* The Rh antigens (more than 50) are made up of transmembrane proteins - the most important Rh antigen is D! Rh negative individuals can develop anti-D antibodies if exposed to D+ RBC - this can occur via transfusion or pregnancy; importantly, anti-D antibodies are *IgG - can cross placenta to affect baby!* Newborn hemolytic disease is classically caused by anti-D antibodies and can only occur in D- mother and D+ father/baby To develop newborn hemolytic dz, mother has first pregnancy w/exposed D+ RBCs at delivery, develops anti-D IgG; if 2nd pregnancy has D+ RBCs --> hemolysis in utero Low Ab titer l/t mild hemolysis in baby; high Ab titer l/t hydrops fetalis (*fluid everywhere - high output CHF, pleural edema, pericardial effusion, ascites*) Prevent newborn hemolytic dz by giving anti-D immune globulin (Rhogam - IgG antibodies to D antigen) in 3rd trimester of D- mothers Can do maternal antibody screen (*Indirect Coombs Test - mix mom's serum w/RBCs that are D+, watch for blood clumping --> isoimmunization!*)

Pemphigus vulgaris is blistering condition with *[HY] pathologic finding of ___ (loss of connections btwn keratinocytes)* - PV involves skin and m___ Acantholysis is usually 2/2 loss of d___ (connect cells), leading to "rounded", freely-floating k___ (*again, [HY] to know this is seen in Pemphigus Vulgaris*) On path., will also see immunofl. for IgG in "___" (net-like) pattern (remember - its a T2HSrxn) Acant. develops 2/2 autoantibodies against desmoglein (component of desmosomes) - type ___ HS rxn; disrupts connections in str. spinosum --> Nikolsky's sign ___ Clinically, PV manifests with large, *F___* bullae that easily burst - few intact, will see scabs + *[HY] ___ bullae and ulcerations first!* - tx w/immunosuppressants

Pemphigus vulgaris is blistering condition with *[HY] pathologic finding of acantholysis (loss of connections btwn keratinocytes)* - PV involves skin and mouth Acantholysis is usually 2/2 loss of desmosomes (connect cells), leading to "rounded", freely-floating keratinocytes (*again, [HY] to know this is seen in Pemphigus Vulgaris*) On path., will also see immunofl. for IgG in "reticular" (net-like) pattern (remember - its a T2HSrxn) Acant. develops 2/2 autoantibodies against desmoglein (component of desmosomes) - type II (REMEMBER: Abs directed against body!) HS rxn; disrupts connections in str. spinosum --> Nikolsky's sign positive Clinically, PV manifests with large, *FLACCID* bullae that easily burst - few intact, will see scabs + *[HY] oral bullae and ulcerations first!* - tx w/immunosuppressants

Penicillin binding proteins bind Ala-Ala residues and link ___-to-alanine to crosslink cell wall (penicillin inhibits this step) Beta lactamase enzymes are produced by many gram negative bacteria (found in ___) and Staph aureus (___) Aminopenicillins have greater gram negative coverage due to penetration of ___ CHANNELS, allowing for extended spectrum against GNs *PCN, cephalosporin, and sulfonamides can cause various immunologic reactions: type I HS rxn includes acute ___; type II HS rxn includes IgG-induced ___ anemia; type III HS rxn includes ___; type IV HS rxn includes T-cell induced skin rash and ___*

Penicillin binding proteins bind Ala-Ala residues and link lysine-to-alanine to crosslink cell wall (penicillin inhibits this step) Beta lactamase enzymes are produced by many gram negative bacteria (found in periplasm) and Staph aureus (secreted) Aminopenicillins have greater gram negative coverage due to penetration of PORIN CHANNELS, allowing for extended spectrum against GNs *PCN, cephalosporin, and sulfonamides can cause various immunologic reactions: type I HS rxn includes acute anaphylaxis; type II HS rxn includes IgG-induced hemolytic anemia; type III HS rxn includes serum sickness; type IV HS rxn includes T-cell induced skin rash and interstitial nephritis*

Peptic ulcer dz is usually a solitary ulcer in ___ (90%) or ___ (10%) H. pylori infxn, NSAID use, and smoking are major RFs (nearly all related to H. pylori) - rare cause is ___ (primarily for duodenal ulcers, may occur in jejunum) Gastric: pain ___ w/meals (stimulates acid secretion); *[HY] MC location is ___ curvature, rupture --> left ___ aa bleeding*; only 70% a/w H. pylori (duodenal ~100%) - can be d/t *gastric ___ - biopsy to r/o* *Duodenum (MC)*: pain ___ w/meals (stimulates bicarb secretion from panc.), worsens @ night (empty stomach), are always benign, and has *[HY] ___ gland hypertrophy (remember - BGs produce basic fluid to protect duodenum from acidic stomach fluid)*; Posterior duodenal ulcers can *[HY] erode into ___ aa (upper GI bleed) and pancreas (pancreatitis)* Tx of Either: triple therapy (+ PPI empirically)

Peptic ulcer dz is usually a solitary ulcer in duodenum (90%) or antrum (10%) H. pylori infxn, NSAID use, and smoking are major RFs (nearly all related to H. pylori) - rare cause is ZES (primarily for duodenal u., may occur in jejunum) Gastric: pain worsens w/meals (stimulates acid secretion); *[HY] MC location is lesser curvature, rupture --> left gastric aa bleeding*; only 70% a/w H. pylori (duodenal ~100%) - can be d/t *gastric adenocarcinoma - biopsy to r/o* *Duodenum (MC)*: pain improves w/meals (stimulates bicarb secretion from panc.), worsens @ night (empty stomach), are always benign, and has *[HY] Brunner's gland hypertrophy (remember - BGs produce basic fluid to protect duodenum from acidic stomach fluid)*; Posterior duodenal ulcers can *[HY] erode into gastroduodenal aa (upper GI bleed) and pancreas (pancreatitis)* Tx of Either: triple therapy (+ PPI empirically)

P___ is outer membrane that contains BVs and sensory nerves; cortical bone is hard exterior bone (shell); trabecular (cancellous, spongy) is found @ ends of long bones - soft and flexible w/lots of surface area (key concept in bone resorption); medullary cavity contains marrow (shaft) *___ synthesize bone matrix* *___ (special macrophages) secrete acid and proteases* Osteocytes are osteoblasts buried in bone matrix Bone matrix is extracellular component of bone - synthesized by -blasts and rich in type ___ collagen, hydroxyapatite; matrix is first synthesized as ___ (non-mineralized proteinaceous substance), then mineralized w/calcium and phosphate

Periosteum is outer membrane that contains BVs and sensory nerves; cortical bone is hard exterior bone (shell); trabecular (cancellous, spongy) is found @ ends of long bones - soft and flexible w/lots of surface area (key concept in bone resorption); medullary cavity contains marrow (shaft) *Osteoblasts synthesize bone matrix* *Osteoclasts (special macrophages) secrete acid and proteases* Osteocytes are osteoblasts buried in bone matrix Bone matrix is extracellular component of bone - synthesized by -blasts and rich in type I collagen, hydroxyapatite; matrix is first synthesized as osteoid (non-mineralized proteinaceous substance), then mineralized w/calcium and phosphate

Personality Disorder (vs P Trait) *causes ___ or impaired function* *Cluster A (weird/Abnormal behavior)*, Cluster B (wild/Bitchy), Cluster C (wacky/Concerned) Paranoid PD is distrust of others (friends, family); *hallmark ego defense is ___ (accuse others of paranoia)* ___ is *CHOOSING social isolation* - more comfortable, do not enjoy relationships, asexual (differs from avoidant PD - don't want to socialize) Schizotypal PD is *FEAR* of social interactions, but hallmark is *___ (superstitious, telepathy)*; pts will have ideas of reference; key feature - *open to ___ (distinct from delusions)*

Personality Disorder (vs P Trait) *causes distress or impaired function* *Cluster A (weird/Abnormal behavior)*, Cluster B (wild/Bitchy), Cluster C (wacky/Concerned) Paranoid PD is distrust of others (friends, family); *hallmark ego defense is projection (accuse others of paranoia)* Schizoid PD is *CHOOSING social isolation* - more comfortable, do not enjoy relationships, asexual (differs from avoidant PD - don't want to socialize) Schizotypal PD is *FEAR* of social interactions, but hallmark is *odd beliefs/magic thinking (superstitious, telepathy)*; pts will have ideas of reference; key feature - *open to challenged beliefs (distinct from delusions)*

Personality Disorder (vs P Trait) *causes ___ or impaired function* Cluster A (weird/Abnormal behavior), *Cluster B (wild/Bitchy)*, Cluster C (wacky/Concerned) ___ PD is impulsivity and disregard for rights of others (common in men, often break law --> jail); child version is ___ D/o (~35% of ASPD had CD) Borderline PD is more common in women with hallmark being *unstable personal relationships (___ - defense mechanism?, stormy relationships, intense fear of ABANDONMENT)*; may see impulsivity and/or suicide gestures; *HY: tx with ___* ___ PD is desire to be *center of attn*; often women with sexually provocative behavior and c/f physical appearance ___ PD is inflated sense of self with no empathy for others

Personality Disorder (vs P Trait) *causes distress or impaired function* Cluster A (weird/Abnormal behavior), *Cluster B (wild/Bitchy)*, Cluster C (wacky/Concerned) Antisocial PD is impulsivity and disregard for rights of others (common in men, often break law --> jail); child version is Conduct D/o (~35% of ASPD had CD) Borderline PD is more common in women with hallmark being *unstable personal relationships (SPLITTING, stormy relationships, intense fear of ABANDONMENT)*; may see impulsivity and/or suicide gestures; *HY: tx with dialectical behavioral therapy* Histrionic PD is desire to be *center of attn*; often women with sexually provocative behavior and c/f physical appearance Narcissitic PD is inflated sense of self with no empathy for others

Personality Disorder (vs P Trait) *causes ___ or impaired function* Cluster A (weird/Abnormal behavior), Cluster B (wild/Bitchy), *Cluster C (wacky/Concerned)* ___ PD is avoidance of social interactions 2/2 feeling inadequate (differs from ___ - want to socialize, but can't) Obsessive-Compulsive PD is preoccupation with order and control (love to-do lists, always need plan, inflexible at work) - behaviors help achieve goals (*___ behaviors*) ___ PD is clingy behavior with low confidence (rarely alone, difficulty expressing opinion) - often pts involved in abusive relationships

Personality Disorder (vs P Trait) *causes distress or impaired function* Cluster A (weird/Abnormal behavior), Cluster B (wild/Bitchy), *Cluster C (wacky/Concerned)* Avoidant PD is avoidance of social interactions 2/2 feeling inadequate (differs from schizoid - want to socialize, but can't) Obsessive-Compulsive PD is preoccupation with order and control (love to-do lists, always need plan, inflexible at work) - behaviors help achieve goals (*egosyntonic behaviors*) Dependent PD is clingy behavior with low confidence (rarely alone, difficulty expressing opinion) - often pts involved in abusive relationships

Phenylalanine --> tyrosine (via phenylalanine hydroxylase) Tyrosine --> DOPA (via *tyrosine hydroxylase, ALSO requires BH4 as a cofactor [dihydropteridine reductase is back!]*); Metyrosine inhibitis tyrosine hydroxylase (think of Sketchy scene) DOPA --> dopamine (via DOPA decarboxylase - requires B6 as cofactor, *inhibited by CARBIDOPA*) Dopamine --> norepinephrine (via dopamine beta-hydroxylase, *uses VitC as cofactor!*) Norepinephrine --> epinephrine (via phenylethanolamine N-methyltransferase, *requires SAM as cofactor - SAM methylates things*) SAM is formed from methionine; When N --> E, SAM becomes homocysteine + adenosine; to regenerate methionine from homocysteine, *you need B12 and folate!* (*elevated homocysteine CAN BE D/T B12/FOLATE DEFICIENCY!!*) For those keeping score at home, cofactors are: BH4, B6, VitC, SAM

Phenylalanine is essential AA that is converted to tyrosine (tyrosine is non-essential, can be derived); P --> T conversion is done via phenylalanine hydroxylase (*requires tetrahydrobiopterin as cofactor [BH4]*) In P --> T, tetrahydrobiopterin (BH4) is converted to dihydrobiopterin (BH2) - requires re-conversion back to BH4 by *dihydropteridine reductase* *PHENYLALANINE to TYROSINE CONVERSION: will need PHENYLALANINE HYDROXYLASE and DIHYDROPTERIN REDUCTASE* --- Deficiency of Phenylalanine Hydroxylase --> *PKU (also seen w/defective BH4 cofactor), most common IEM seen in HUMANS --> accumulation of phenylalanine and deficiency of tyrosine* When phenylalanine cannot be converted to tyrosine, becomes converted to *phenylketones (toxic metabolites)*; p/w musty urine smell + CNS symptoms + pale skin, fair hair, blue eyes (*TYROSINE becomes MELANIN - LACKING MELANIN IN THIS DISORDER*) Tx of PKU requires dietary modification - restrict phenylalanine, *avoid aspartame (contains phenylalanine)*, tyrosine supplementation (tyrosine becomes essential in this d/o) Screen for PKU 2-3d after birth (allow maternal washout) --- ISO BH4 deficiency (instead of phenylalanine hydroxylase), will also have decreased synthesis of epinephrine, norepinephrine, serotonin, and *DOPAMINE (--> hyperprolactinemia)*; tx w/dietary restriction + BH4 supplementation + dopamine and serotonin precursors --- Maternal PKU can occur when women w/PKU consume too much phenylalanine --> teratogenic findings (microcephaly + growth restriction + congenital heart defects)

Pheochromocytoma is catecholamine-secreting tumor of *___ cells* of adrenal medulla (derivatives of *n___*) Clinically, p/w *e___ HTN + HA, palpitations, sweating* To diagnose, do 24hr urine collection for catecholamines and me___ (done by MAO [MAO-inhibitors] or COMT [COMT-inhibitors) To treat, do surgical removal of tumor but *pre-op management is crucial! - give pre-operative ___ (irreversible alpha blocker) to prevent hypertensive crisis*

Pheochromocytoma is catecholamine-secreting tumor of *chromaffin cells* of adrenal medulla (derivatives of *neural crest*) Clinically, p/w *episodic HTN + HA, palpitations, sweating* To diagnose, do 24hr urine collection for catecholamines and metanephrines (done by MAO [MAO-inhibitors] or COMT [COMT-inhibitors) To treat, do surgical removal of tumor but *pre-op management is crucial! - give pre-operative PHENOXYBENZAMINE (irreversible alpha blocker) to prevent hypertensive crisis*

Pilocytic astrocytoma (MC children brain tumor) arises from cerebellum that can be resected surgically; microscopically, will see ___ fibers that stain GFAP positive Medulloblastoma are malignant cerebellar brain tumors in children, leading to ___ ataxia; can develop "drop metastasis" in spinal cord; *histo demonstrates ___* Ependymomas arise in 4th ventricle and cause hydrocephalus with histo revealing pseudorosettes surrounding blood vessel Hemangioblastomas are vascular CNS tumors; *can produce ___ (--> polycythemia) and occur in ___ syndrome* Pineal tumors can compress pretectal area --> Parinaud syndrome (*paralysis of ___ gaze in children* + pseudo-___ pupils) + hydrocephalus

Pilocytic astrocytoma (MC children brain tumor) arises from cerebellum that can be resected surgically; microscopically, will see Rosenthal fibers that stain GFAP positive Medulloblastoma are malignant cerebellar brain tumors in children, leading to truncal ataxia; can develop "drop metastasis" in spinal cord; *histo demonstrates Homer-Wright Rosettes* Ependymomas arise in 4th ventricle and cause hydrocephalus with histo revealing pseudorosettes surrounding blood vessel Hemangioblastomas are vascular CNS tumors; *can produce EPO (--> polycythemia) and occur in VHL syndrome* Pineal tumors can compress pretectal area --> Parinaud syndrome (*paralysis of upward gaze in children* + pseudo-Argyll-Robertson pupils) + hydrocephalus

Plasma Cell Disorders (that aren't multiple myeloma): --- MGUS (___): asymptomatic overproduction of Ig (any type) - p/w abnormal SPEP w/___, but no end-organ damage Can progress to multiple myeloma, but MGUS itself is not symptomatic --- *Waldenstrom Macroglobulinemia*: B-cell lymphoma where tumor cells differentiate to *PLASMA cells --> Ig___ antibodies* Sx from WM primarily result from *___ symptoms [know this for Step 1!] - p/w ___ symptoms (HA, blurry vision, dizziness), Raynaud phenomenon, & ___ hemorrhages Hyperviscous syndrome in WM is *medical emergency that can l/t t___ - do emergent p___!* *Key distinction from multiple myeloma: NO ___ bone lesions*

Plasma Cell Disorders (that aren't multiple myeloma): --- MGUS (monoclonal gammopathy of undetermined significance): asymptomatic overproduction of Ig (any type) - p/w abnormal SPEP w/M-spike, but no end-organ damage Can progress to multiple myeloma, but MGUS itself is not symptomatic --- *Waldenstrom Macroglobulinemia*: B-cell lymphoma where tumor cells differentiate to *PLASMA cells --> IgM antibodies* Sx from WM primarily result from *hyperviscosity symptoms [know this for Step 1!] - p/w CNS symptoms (HA, blurry vision, dizziness), Raynaud phenomenon, & retinal hemorrhages Hyperviscous syndrome in WM is *medical emergency that can l/t thrombosis - do emergent plasmapheresis!* *Key distinction from multiple myeloma: NO osteolytic bone lesions*

Plasma osmolarity is ~275-295mOsm/kg; Importantly, *fluid only shifts between cells and extracellular fluid if there is a difference in osmolarity (cell in hypertonic solution --> cell ___, cell in hypotonic solution --> cell ___)* Addition (normal saline) or loss (hemorrhage) of isotonic fluid --> ___ (change or nah?) in ECF volume, ___ in ICF volume Infusion of hypotonic fluid (5% dextrose) --> ___ in ECF volume + ___ in ICF fluid volume Infusion of hypertonic fluid (mannitol) --> ___ in ECF volume + ___ in ICF fluid volume (+ ___ in interstitial fluid - mannitol remains in intravascular space)

Plasma osmolarity is ~275-295mOsm/kg; Importantly, *fluid only shifts between cells and extracellular fluid if there is a difference in osmolarity (cell in hypertonic solution --> cell dehydrates, cell in hypotonic solution --> cell swells)* Addition (normal saline) or loss (hemorrhage) of isotonic fluid --> change in ECF volume, no change in ICF volume Infusion of hypotonic fluid (5% dextrose) --> increase in ECF volume + increase in ICF fluid volume Infusion of hypertonic fluid (mannitol) --> increase in ECF volume + decrease in ICF fluid volume (+ decrease in interstitial fluid - mannitol remains in intravascular space)

___ (synthesized by liver) breaks down fibrin clot; it can be activated by tPA and urokinase (synthesized by ___ cells --> don't clot when endothelium is healthy) tPA is used as drug therapy in acute ___ and stroke; streptokinase is streptococcal protein that also acts as tPA to activate plasmin ___ and fibrin degradation productions (FDPs) are what is formed after plasmin breaks down fibrin clot; D-dimer contains crosslinked bond *made by factor ___* - accordingly, the presence of D-dimer indicates clot breakdown after crosslinking by factor XIII (used in DVT/PE) FDPs are not as reliable as they can be found without clot formation (i.e., FDPs still made when factor XIII not active, breaking down *___ not fibrin*) *[HY] Primary fibrinolysis is overactive ___ --> hyperfibrinolysis of ___ (not fibrin) --> increased FDPs and ___ D-dimer! In this process, plasmin can deplete clotting factors --> ___ PT/PTT (seen in prostate cancer w/urokinase release, cirrhosis w/loss of alpha-2 antiplasmin)*

Plasmin (synthesized by liver) breaks down fibrin clot; it can be activated by tPA and urokinase (synthesized by endothelial cells --> don't clot when endothelium is healthy) tPA is used as drug therapy in acute MI and stroke; streptokinase is streptococcal protein that also acts as tPA to activate plasmin D-dimer and fibrin degradation productions (FDPs) are what is formed after plasmin breaks down fibrin clot; D-dimer contains crosslinked bond *made by factor XIII* - accordingly, the presence of D-dimer indicates clot breakdown after crosslinking by factor XIII (used in DVT/PE) FDPs are not as reliable as they can be found without clot formation (i.e., FDPs still made when factor XIII not active, breaking down *fibrinogen not fibrin*) *[HY] Primary fibrinolysis is overactive plasmin --> hyperfibrinolysis of fibrinogen (not fibrin) --> increased FDPs and normal D-dimer! In this process, plasmin can deplete clotting factors --> increased PT/PTT (seen in prostate cancer w/urokinase release, cirrhosis w/loss of alpha-2 antiplasmin)*

Platelet alpha granules contain platelet factor 4, fibrinogen, and vWF (NOTE: granule contents mentioned once in FirstAid) PF-4 has numerous effects and is implicated in *heparin-induced thrombocytopenia, in which Abs form to ___ --> platelet activation --> diffuse t___ + t___ 2/2 consumption* Platelet ___ granules contain serotonin, ADP, calcium Serotonin is the basis for the *test of HIT (serotonin release assay) - ___ platelets are radiolabeled with serotonin --> pt serum and heparin added to cells --> ___ result in excessive serotonin release!* ADP binds ___ (also P2Y1), leading to drop in cAMP^ formation to activate platelets --> platelet ___ --> increased aggregation; P2Y12 receptor blockers are used to inhibit platelet activity Thromboxane A2 is also powerful platelet activator - TXA2 is derived from ___ via COX (rationale for *ASA as anti-platelet therapy!*) NOTE: bleeding time is test that specifically measures platelet function, not dependent on coagulation cascade! ^*NOTE: phosphodiesterase inhibitors are used to raise cAMP and block platelet activation!*

Platelet alpha granules contain platelet factor 4, fibrinogen, and vWF (NOTE: granule contents mentioned once in FirstAid) PF-4 has numerous effects and is implicated in *heparin-induced thrombocytopenia, in which Abs form to PF4-heparin complex --> platelet activation --> diffuse thrombosis + thrombocytopenia 2/2 consumption* Platelet dense granules contain serotonin, ADP, calcium Serotonin is the basis for the *test of HIT (serotonin release assay) - donor platelets are radiolabeled with serotonin --> pt serum and heparin added to cells --> HIT antibodies result in excessive serotonin release!* ADP binds P2Y12 (also P2Y1), leading to drop in cAMP^ formation to activate platelets --> platelet degranulation --> increased aggregation; P2Y12 receptor blockers are used to inhibit platelet activity Thromboxane A2 is also powerful platelet activator - TXA2 is derived from arachidonic acid via COX (rationale for *ASA as anti-platelet therapy!*) NOTE: bleeding time is test that specifically measures platelet function, not dependent on coagulation cascade! ^*NOTE: phosphodiesterase inhibitors are used to raise cAMP and block platelet activation!*

Platelets are derived from m___ in reaction to ___ (TPO) and can activate in response to endothelial injury or from stimuli of other activated platelets Formation of activated platelets (primary hemostasis) requires three steps: 1) ___ to sub-endothelium: vascular endothelium is damaged --> exposure of subendothelial collagen and ___ --> vWF binding to ___ on platelets (platelets adhere to subendothelial collagen) 2) ___ (platelet-platelet binding) - ___ receptor on platelets *becomes capable of binding (after adhesion), binds F___ or v___ for aggregation of other platelets (i.e., fibrinogen sandwich w/GPIIb/IIIa)* [basis for IIb/IIIa receptor blockers] 3) ___ (release of granule^ contents) - activated by binding subendothelial collagen --> secretion of stored substances to activate other platelets (i.e., activation of one platelet via subendothelial binding --> activation of many other platelets) ^Includes ___ (fibrinogen, vWF, platelet factor 4) and ___ (ADP, calcium, serotonin) granules

Platelets are derived from megakaryocytes in reaction to thrombopoietin (TPO) and can activate in response to endothelial injury or from stimuli of other activated platelets Formation of activated platelets (primary hemostasis) requires three steps: 1) Adhesion to sub-endothelium: vascular endothelium is damaged --> exposure of subendothelial collagen and vWF --> vWF binding to GP1b on platelets (platelets adhere to subendothelial collagen) 2) Aggregation (platelet-platelet binding) - GPIIb/IIIa receptor on platelets *becomes capable of binding (after adhesion), binds FIBRINOGEN or vWF for aggregation of other platelets (i.e., fibrinogen sandwich w/GPIIb/IIIa)* [basis for IIb/IIIa receptor blockers] 3) Secretion (release of granule contents) - activated by binding subendothelial collagen --> secretion of stored substances to activate other platelets (i.e., activation of one platelet via subendothelial binding --> activation of many other platelets) ^Includes alpha (fibrinogen, vWF, platelet factor 4) and dense (ADP, calcium, serotonin) granules

Pleural effusion is accumulation of fluid in pleural space --> blunting of costophrenic angle Three etiologies of P-Eff: Transudative: high pressure driving fluid into pleural space (either high hydrostatic pressure [HF] or low oncotic pressure [___ syndrome, cirrhosis]); *mostly f___* Exudative: d/t vascular leakage - seen in malignancy, infection, trauma; *mostly p___/gunk* Lymphatic: d/t thoracic duct injury - seen in trauma or malignancy; *mostly t___ (w/milky fluid) - use for dx* Test w/LIGHT'S CRITERIA (pleural and serum values) - Exudative if: -pProt:sProt > ___ -pLDH:sLDH > ___ -pLDH > ___

Pleural effusion is accumulation of fluid in pleural space --> blunting of costophrenic angle Three etiologies of P-Eff: Transudative: high pressure driving fluid into pleural space (either high hydrostatic pressure [HF] or low oncotic pressure [nephrotic syndrome, cirrhosis]); *mostly fluid* Exudative: d/t vascular leakage - seen in malignancy, infection, trauma; *mostly protein/gunk* Lymphatic: d/t thoracic duct injury - seen in trauma or malignancy; *mostly triglycerides (w/milky fluid) - use for dx* Test w/LIGHT'S CRITERIA (pleural and serum values) - Exudative if: -pProt:sProt > 0.5 -pLDH:sLDH > 0.6 -pLDH > 2/3 ULN

Pneumoconioses (*RESTRICTIVE* occupational lung dz) include coal-miner's lung, silicosis, and asbestosis Coal-miner's lung is d/t prolonged coal dust exposure (preference for ___ lobes) Silicosis is inhalation of silica (sandblasting, foundries, sandstone, mines) - *[HY] ___ (cell type?) react to silica --> fibroblasts --> c___ deposition; preference for ___ lobes, ___ can live in silicosis nodules (REMEMBER: TB also likes upper lobes!); high prevalence of bronchogenic carcinoma; ___ calcification of hilar lymph nodes (Silly Egg Sandwich i Found is Mine!)* Asbestosis is inhalation of asbestos fibers (shipbuilding, roofing, plumbing) and classically affects ___ lobes w/three problems: IntLunDz, pleural ___, lung cancer (br___ carcinoma >> mesothelioma) Asbestos CXR --> *pleural plaques*; Asbestos path --> ___ bodies (brown dumbbell rods)

Pneumoconioses (*RESTRICTIVE* occupational lung dz) include coal-miner's lung, silicosis, and asbestosis Coal-miner's lung is d/t prolonged coal dust exposure (preference for UPPER lobes) Silicosis is inhalation of silica (sandblasting, foundries, sandstone, mines) - *[HY] macrophages react to silica --> fibroblasts --> collagen deposition; preference for UPPER lobes, TB can live in silicosis nodules (REMEMBER: TB also likes upper lobes!); high prevalence of bronchogenic carcinoma; EGGSHELL calcification of hilar lymph nodes (Silly Egg Sandwich i Found is Mine!)* Asbestosis is inhalation of asbestos fibers (shipbuilding, roofing, plumbing) and classically affects lower lobes w/three problems: IntLunDz, pleural plaques, lung cancer (bronchogenic carcinoma >> mesothelioma) Asbestos CXR --> *pleural plaques*; Asbestos path --> ferruginous bodies (brown dumbbell rods) ^Asbestos is from Roof but affects Base; Silica/Coal/Berries are from Base but affect Roof

Pneumothorax is air in pleural space - can be: ___: rupture of apical subpleural bleb/cyst, common in tall/thin men Secondary: d/t dz lung (older pts w/underlying ___) ___: usually 2/2 trauma ("traumatic PNX") - air enters pleural space but cannot leave (think of flap example), high pressure builds --> compresses lung + mediastinal shift (*___ from affected side*) and vessel collapse (tx w/thoracentesis + CT placement) Classic presentation is sudden onset dyspnea w/pleuritic CP, dx w/CXR, tx w/___ (decreases nitrogen in capillary blood --> increases gradient that pulls nitrogen in pleural space back into blood!) +/- chest tube

Pneumothorax is air in pleural space - can be: Spontaneous: rupture of apical subpleural bleb/cyst, common in tall/thin men Secondary: d/t dz lung (older pts w/underlying COPD) Tension: usually 2/2 trauma ("traumatic PNX") - air enters pleural space but cannot leave (think of flap example), high pressure builds --> compresses lung + mediastinal shift (*AWAY from affected side*) and vessel collapse (tx w/thoracentesis + CT placement) Classic presentation is sudden onset dyspnea w/pleuritic CP, dx w/CXR, tx w/100% O2 (decreases nitrogen in capillary blood --> increases gradient that pulls nitrogen in pleural space back into blood!) +/- chest tube

Point Mutation: single base is switched to different base; can have transition (pur-pur, pyr-pyr swap - MC) or transversion (pur-pyr swap - less common); some pt mutations are less likely to alter AAs d/t *___ effect (UUU, UUC are same AA)* Pt muts. can be silent (often in 3rd position of codon - Wobble), ___ (early stop codon), or ___ (different AA); Sickle-Cell Anemia is classic ___ mutation in 6th codon of beta-globin gene (E6V 2/2 adenine-to-thymine switch) Insertion/Deletion Mutation: insertion/deletion of nucleotide (classic del. example - CF 2/2 delta ___, loss of phenylalanine); can result in *frameshift mut.* - alters reading frame of DNApol w/big change in final protein (truncated, elongated) Frameshift muts are seen in Tay Sachs dz (H___ A) and Duchenne MD (d___, more severe than Becker MD d/t frameshift mut) Slipped-Strand Mispairing (DNA slippage) occurs in areas of repeated nucleotide sequences w/inadequate mismatch repair - slippage in template --> ___ (del or ins? +/- FS), slippage in replicated strand --> ___ (del or ins? +/- FS); DNA slippage is implicated in trinucleotide repeat d/o's and microsatellite instability

Point Mutation: single base is switched to different base; can have transition (pur-pur, pyr-pyr swap - MC) or transversion (pur-pyr swap - less common); some pt mutations are less likely to alter AAs d/t *wobble effect (UUU, UUC are same AA)* Pt muts. can be silent (often in 3rd position of codon - Wobble), nonsense (early stop codon), or missense (different AA); Sickle-Cell Anemia is classic missense mutation in 6th codon of beta-globin gene (E6V 2/2 adenine-to-thymine switch) Insertion/Deletion Mutation: insertion/deletion of nucleotide (classic del. example - CF 2/2 delta F508, loss of phenylalanine); can result in *frameshift mut.* - alters reading frame of DNApol w/big change in final protein (truncated, elongated) Frameshift muts are seen in Tay Sachs dz (hexosaminidase A) and Duchenne MD (dystrophin, more severe than Becker MD d/t frameshift mut) Slipped-Strand Mispairing (DNA slippage) occurs in areas of repeated nucleotide sequences w/inadequate mismatch repair - slippage in template --> deletion (+/- FS), slippage in replicated strand --> insertion (+/- FS); DNA slippage is implicated in trinucleotide repeat d/o's and microsatellite instability

Polycystic ovarian syndrome causes secondary amenorrhea; *hyper___* is believed to alter hypothalamic pathway --> *increased ___ ratio*, ___ drives androstenedione levels from theca cells and can be converted to estrone in ___ tissue (*can't use granulosa cells d/t low FSH!*) --> decreases FSH further --> *an___* Clinically, PCOS manifests with symptoms of ___ excess: *hirsutism, acne, amenorrhea, infertility* w/cysts in ovaries (*unruptured follicles*) Complications related to PCOS include diabetes + a___ n___, as well as *increased risk of ___ cancer (d/t unopposed estrogens)* Tx: weight loss, *___ (suppress LH, estrogen can increase SHBG and decrease free androgens)*, spironolactone, metformin/TZDs

Polycystic ovarian syndrome causes secondary amenorrhea; *hyperinsulinemia* is believed to alter hypothalamic pathway --> *increased LH:FSH ratio*, LH drives androstenedione levels from theca cells and can be converted to estrone in adipose tissue (*can't use granulosa cells d/t low FSH!*) --> decreases FSH further --> *anovulation* Clinically, PCOS manifests with symptoms of androgen excess: *hirsutism, acne, amenorrhea, infertility* w/cysts in ovaries (*unruptured follicles*) Complications related to PCOS include diabetes + acanthosis nigricans, as well as *increased risk of endometrial cancer (d/t unopposed estrogens)* Tx: weight loss, *OCPs (suppress LH, estrogen can increase SHBG and decrease free androgens)*, spironolactone, metformin/TZDs

Polymyalgia Rheumatic is inflammatory d.o in older pts w/BILATERAL proximal muscle s___ (worse in morning) and *normal s___* - *[HY] strong a/w ___*; will see elevated ESR and CRP, tx w/steroids Fi___ is chronic, widespread MSK pain in young women w/psych d.o - dx clinically (point tenderness on exam), tx w/TCAs or SNRIs

Polymyalgia Rheumatic is inflammatory d.o in older pts w/BILATERAL proximal muscle stiffness (worse in morning) and *normal strength* - *[HY] strong a/w temporal arteritis*; will see elevated ESR and CRP, tx w/steroids Fibromyalgia is chronic, widespread MSK pain in young women w/psych d.o - dx clinically (point tenderness on exam), tx w/TCAs or SNRIs

Porphoryns are components of ___ (non-iron part); ___ are disorders of porphyrin synthesis, all from deficient enzymes in heme synthesis Interestingly, dz rarely cause anemia, but can lead to symptoms when porphyrins build up Heme is mostly produced in bone marrow (80%), but some is produced in liver and used in cytochrome P450 enzymes Heme synthesis begins in ___ (organelle?) with rate limiting step being the conversion of delta-aminolevulinic acid (via ___ - heme feeds back to inhibit this step when enough heme is made); middle pathway occurs in cytosol, then synthesis finishes back in mitochondria Two MC porphyrias are *1) acute ___ porphyria and 2) porphyria ___ tarda*

Porphoryns are components of heme (non-iron part); porphyrias are disorders of porphyrin synthesis, all from deficient enzymes in heme synthesis Interestingly, dz rarely cause anemia, but can lead to symptoms when porphyrins build up Heme is mostly produced in bone marrow (80%), but some is produced in liver and used in cytochrome P450 enzymes Heme synthesis begins in mitochondria with rate limiting step being the conversion of delta-aminolevulinic acid (via ALA-synthase - heme feeds back to inhibit this step when enough heme is made); middle pathway occurs in cytosol, then synthesis finishes back in mitochondria Two MC porphyrias are *1) acute intermittent porphyria and 2) porphyria cutanea tarda*

Porphyria Cutanea Tarda is MC porphyria and results from deficiency in uroporphyrinogen decarboxylase (*___* - 5th enzyme in pathway) UROD deficiency is usually *acquired - excess iron may play a role* In PCT, there is accumulation of uroporphyrinogen, which is oxidized to uro___; uroporphyrin can be transported to skin and causes skin damage on exposure to light Accordingly, PCT p/w *P___ w/hyperpigmentation and chronic BLISTERING skin lesions + "T___" urine (d/t urinary uroporphyrin)*, as well as bump in AST/ALT (d/t hepatic synthesis of porphyrins) Other factors that worsen dz include *___ and alcohol consumption (remember: hepatic synthesis of porphyrins)* Tx: phlebotomy, sun avoidance, +/- anti-malarials --- VAMPIRE HYPOTHESIS: pts avoid sun + "drink blood" as heme inhibits porphyrin synthesis --> stops sx

Porphyria Cutanea Tarda is MC porphyria and results from deficiency in uroporphyrinogen decarboxylase (*UROD* - 5th enzyme in pathway) UROD deficiency is usually *acquired - excess iron may play a role* In PCT, there is accumulation of uroporphyrinogen, which is oxidized to uroporphyrin; uroporphyrin can be transported to skin and causes skin damage on exposure to light Accordingly, PCT p/w *Photosensitivity w/hyperpigmentation and chronic BLISTERING skin lesions + "Tea-colored" urine (d/t urinary uroporphyrin)*, as well as bump in AST/ALT (d/t hepatic synthesis of porphyrins) Other factors that worsen dz include *hepC and alcohol consumption (remember: hepatic synthesis of porphyrins)* Tx: phlebotomy, sun avoidance, +/- anti-malarials --- VAMPIRE HYPOTHESIS: pts avoid sun + "drink blood" as heme inhibits porphyrin synthesis --> stops sx

___ (seen only in males) occur when tissue obstructs bladder outflow --> bilateral hydroureteronephrosis --> *oligohydramnios + Potter's syndrome* --- Horseshoe kidney is fusion of ___ poles of the kidneys, l/t kidneys that *[HY] cannot ascend past the ___ artery* Most pts are asymptomatic Horseshoe kidney is a/w chromosomal aneuploidy (notably ___ syndrome, ___ syndrome) and vesicoureteral reflux --- The ___ is an embryologic structure that connects the dome of the bladder to the umbilicus - the urachus should be obliterated at birth to become ___ ligament, but failed/incomplete obliteration can l/t: -Urine leak from umbilicus -Cyst/sinus/diverticulum formation -Infxns *[HY] Urachal remnants can l/t ___ OF BLADDER (cancer at dome of bladder* - p/w adult having pain___ hematuria + tumor at dome of bladder

Posterior urethral valves (seen only in males) occur when tissue obstructs bladder outflow --> bilateral hydroureteronephrosis --> *oligohydramnios + Potter's syndrome* --- Horseshoe kidney is fusion of inferior poles of the kidneys, l/t kidneys that *[HY] cannot ascend past the inferior mesenteric artery* Most pts are asymptomatic Horseshoe kidney is a/w chromosomal aneuploidy (notably Turner's syndrome, Down syndrome) and vesicoureteral reflux --- The urachus is an embryologic structure that connects the dome of the bladder to the umbilicus - the urachus should be obliterated at birth to become median umbilical ligament, but failed/incomplete obliteration can l/t: -Urine leak from umbilicus -Cyst/sinus/diverticulum formation -Infxns *[HY] Urachal remnants can l/t ADENOCARCINOMA OF BLADDER (cancer at dome of bladder* - p/w adult having painless hematuria + tumor at dome of bladder

Postinfectious encephalomyelitis is acute onset multifocal neurologic symptoms with rapid deterioration, often ~one month after ___ or ___ The most common histopathologic finding is ___ with inflammation and loss of myelin Imaging demonstrates ___ circles

Postinfectious encephalomyelitis is acute onset multifocal neurologic symptoms with rapid deterioration, often ~one month after infection or vaccines The most common histopathologic finding is perivenous infiltration with inflammation and loss of myelin Imaging demonstrates hypodense circles

___ is necessary for heart and skeletal muscles - accordingly, s/s of hyperkalemia include EKG changes (QRS ___ and peaked T-waves), arrhythmias, and muscle weakness Hyperkalemia can occur 2/2 increased K release from cells (___ [H-K exchanger], trauma, digoxin, insulin deficiency, beta blockers, CKD, type ___ RTA) Hypokalemia p/w EKG changes (___ waves and flattened T waves), arrhythmias, and muscle weakness Hypokalemia can occur 2/2 increased K entry into cells (hyperinsulinism [rationale for use of insulin to tx hyperkalemia], beta adrenergic activity, alkalosis), GI losses (vomiting), renal losses (diuretics, RTA [type ___]), and hypo___ (*can't correct hypoK until Mg is corrected!*)

Potassium is necessary for heart and skeletal muscles - accordingly, s/s of hyperkalemia include EKG changes (QRS widening and peaked T-waves), arrhythmias, and muscle weakness Hyperkalemia can occur 2/2 increased K release from cells (acidosis [H-K exchanger], trauma, digoxin, insulin deficiency, beta blockers, CKD, type IV RTA) Hypokalemia p/w EKG changes (U waves and flattened T waves), arrhythmias, and muscle weakness Hypokalemia can occur 2/2 increased K entry into cells (hyperinsulinism [rationale for use of insulin to tx hyperkalemia], beta adrenergic activity, alkalosis), GI losses (vomiting), renal losses (diuretics, RTA [type I and II]), and hypomagnesemia (*can't correct hypoK until Mg is corrected!*)

Potassium is necessary for heart and skeletal muscles - accordingly, s/s of hyperkalemia include EKG changes (QRS widening and peaked T-waves), arrhythmias, and weakness Hyperkalemia can occur 2/2 increased K release from cells (acidosis [H-K exchanger], trauma, digoxin, insulin deficiency, beta blockers)

Potter's Sequence is sequelae of findings when fetus is exposed to absent or decreased a___ f___ Recall that amniotic fluid is fetal urine - accordingly, severe ___ malfunction --> decreased amniotic fluid --> loss of fetal cushioning to external forces --> *abnormal face + abnormal limbs + abnormal ___ formation* Look for limb deformities, flat face, and ___ hypoplasia - often fatal Causes include chronic ___ insufficiency (can't get amniotic fluid to baby) and ___ dz (can't get amniotic fluid out - posterior urethral valves, bilateral renal agenesis, ARPKD) 2nd Trimester: renal dz 3rd Trimester: R___ O___ M___

Potter's Sequence is sequelae of findings when fetus is exposed to absent or decreased amniotic fluid Recall that amniotic fluid is fetal urine - accordingly, severe renal malfunction --> decreased amniotic fluid --> loss of fetal cushioning to external forces --> *abnormal face + abnormal limbs + abnormal lung formation* Look for limb deformities, flat face, and pulmonary hypoplasia - often fatal Causes include chronic placental insufficiency (can't get amniotic fluid to baby) and renal dz (can't get amniotic fluid out - posterior urethral valves, bilateral renal agenesis, ARPKD) 2nd Trimester: renal dz 3rd Trimester: ROM

Primary ___ leads to hypertension (young onset), hypokalemia, and metabolic alkalosis Most common cause is bilateral adrenal ___, can also be d/t adrenal adenoma (Conn syndrome) To dx: must have high plasma aldosterone and low plasma ___ activity; if high aldosterone and high plasma ___ activity --> secondary aldosteronism If problem is confined to one adrenal gland --> surgical removal (i.e., adenoma); if bilateral, *[HY] use ___ (blocks aldosterone)* Secondary hyperaldosteronism is seen in pts w/renovascular HTN, renin-producing tumors, and edematous states w/low ___ (cirrhosis, heart failure, nephrotic syndrome)

Primary hyperaldosteronism leads to hypertension (young onset), hypokalemia, and metabolic alkalosis Most common cause is bilateral adrenal hyperplasia, can also be d/t adrenal adenoma (Conn syndrome) To dx: must have high plasma aldosterone and low plasma renin activity; if high aldosterone and high plasma renin activity --> secondary aldosteronism If problem is confined to one adrenal gland --> surgical removal (i.e., adenoma); if bilateral, *[HY] use spironolactone (blocks aldosterone)* Secondary hyperaldosteronism is seen in pts w/renovascular HTN, renin-producing tumors, and edematous states w/low ECV (cirrhosis, heart failure, nephrotic syndrome)

Primary hyperparathyroidism is 2/2 overactive parathyroid glands Inappropriate secretion of PTH is classically caused by parathyroid adenoma/hyperplasia --> ___calcemia + ___phosphaturia + high PTH (___ bone resorption + high vitamin D) - NOTE: urinary calcium can still be normal or high d/t overwhelming serum calcium pHPT manifests w/sx of hypercalcemia ("stones, bones [bone pain], groans [abd pain + PUD], psychiatric overtones"); other sx include poly___ + dehydration Bony changes in hyperparathyroidism are termed osteitis fibrosa cystica - *___ bone resorption [BuZzWoRd]* --> ___ tumors (osteoclastomas) Tx: parathyroidectomy (*can damage ___ nn., develop post-op hypocalcemia*) --- Secondary hyperparathyroidism is 2/2 low calcium, classically in ___ failure pts; will see elevated PTH, low-normal calcium, ___ phosphate (kidneys can't clear) No symptoms of hypercalcemia (this is largely a normal response from parathyroid with shitty kidneys), can predispose to... --- Tertiary hyperparathyroidism is 2/2 renal failure - chronically low calcium --> chronically high PTH to point of ___ parathyroid (p/w VERY high PTH, ___calcemia, ___phosphatemia d/t shitty kidneys) Tx: parathyroidectomy

Primary hyperparathyroidism is 2/2 overactive parathyroid glands Inappropriate secretion of PTH is classically caused by parathyroid adenoma/hyperplasia --> hypercalcemia + hyperphosphaturia + high PTH (increased bone resorption + high vitamin D) - NOTE: urinary calcium can still be normal or high d/t overwhelming serum calcium pHPT manifests w/sx of hypercalcemia ("stones, bones [bone pain], groans [abd pain + PUD], psychiatric overtones"); other sx include polyuria + dehydration Bony changes in hyperparathyroidism are termed osteitis fibrosa cystica - *SUBPERIOSTEAL bone resorption [BuZzWoRd]* --> Brown tumors (osteoclastomas) Tx: parathyroidectomy (*can damage recurrent laryngeal nn., develop post-op hypocalcemia*) --- Secondary hyperparathyroidism is 2/2 low calcium, classically in renal failure pts; will see elevated PTH, low-normal calcium, high phosphate (kidneys can't clear) No symptoms of hypercalcemia (this is largely a normal response from parathyroid with shitty kidneys), can predispose to... --- Tertiary hyperparathyroidism is 2/2 renal failure - chronically low calcium --> chronically high PTH to point of autonomous parathyroid (p/w VERY high PTH, hypercalcemia, hyperphosphatemia d/t shitty kidneys) Tx: parathyroidectomy

Primary lymphoid organs (sites of lymphocyte formation) include ___ (B-cell) and ___ (T-cells); Secondary lymphoid organs (sites of B-/T-cell proliferation) include lymph nodes, spleen, Peyer patches Node has cortex, paracortex, and medulla; multiple afferent vessels carry lymph into node to percolate through --> exit through one efferent lymph channel In infxn, 1) d___ cells drain into node carrying processed antigens, 2) B-/T-cells look for unique antigen, 3) DCs present to lymphocytes, 4) proliferation of ___ immune response In cortex, lymphoid follicles are site of ___-cell activation; primary ___ are inactive (contain follicular dendritic cells and B-cells), while secondary follicles (*___ center*) are active w/B-cell growth + differentiation Paracortex has two key features: 1) contain ___-cells activated by dendritic cells + antigen and 2) contains high e___ v___ (endothelial cells are spaced out - allow B-/T-cell entry into node from blood); Paracortex is engorged in immune response (EBV) and is underdeveloped in D___ (think T-cell dysfunction!) Medulla has sinuses (contain m___ - filter lymph w/macrophages phagocytosing stray bugs) and c___ (btwn sinuses, contain plasma cells secreting antibodies) [ALL THREE CELL TYPES!]

Primary lymphoid organs (sites of lymphocyte formation) include bone marrow (B-cell) and thymus (T-cells); Secondary lymphoid organs (sites of B-/T-cell proliferation) include lymph nodes, spleen, Peyer patches Node has cortex, paracortex, and medulla; multiple afferent vessels carry lymph into node to percolate through --> exit through one efferent lymph channel In infxn, 1) dendritic cells drain into node carrying processed antigens, 2) B-/T-cells look for unique antigen, 3) DCs present to lymphocytes, 4) proliferation of adaptive immune response In cortex, lymphoid follicles are site of B-cell activation; primary follicles are inactive (contain follicular dendritic cells and B-cells), while secondary follicles (*germinal center*) are active w/B-cell growth + differentiation Paracortex has two key features: 1) contain T-cells activated by dendritic cells + antigen and 2) contains high endothelial venules (endothelial cells are spaced out - allow B-/T-cell entry into node from blood); Paracortex is engorged in immune response (EBV) and is underdeveloped in DiGeorge Medulla has sinuses (contain macrophages - filter lymph w/macrophages phagocytosing stray bugs) and cords (btwn sinuses, contain plasma cells secreting antibodies)

Primary sclerosing cholangitis is autoimmune disorder w/*fibrosis + ___ in biliary tree, involving ___- and ___-hepatic bile ducts (diff. from PBC!!)*; PSC is strongly a/w ___ (diff. from PBC!) PSC p/w UC pt with cholestatic complaints + *elevated Ig___ and positive ___-ANCA (also seen in UC)* PSC Biopsy: periductal fibrosis ("___ skin" fibrosis) Imaging (ERCP, MRCP) will demonstrate *strictures + dilations ("___")* Tx: monitor for cholangiocarcinoma (*increased risk*)

Primary sclerosing cholangitis is autoimmune disorder w/*fibrosis + STRICTURES in biliary tree, involving INTRA- and EXTRA-hepatic bile ducts (diff. from PBC!!)*; PSC is strongly a/w Ulcerative colitis (diff. from PBC!) PSC p/w UC pt with cholestatic complaints + *elevated IgM and positive p-ANCA (also seen in UC)* PSC Biopsy: periductal fibrosis ("onion skin" fibrosis) Imaging (ERCP, MRCP) will demonstrate *strictures + dilations ("BEADING")* Tx: monitor for cholangiocarcinoma (*increased risk*) ^Cirrhosis --> liver, Cholangitis --> bile ducts

Prolactin is under inhibitory control from the hypothalamus via ___ binding D2 receptors (destruction of hypothalamus --> ___prolactinemia); many substances affect prolactin release, notably *TRH such that ___thyroidism --> ___prolactinemia* In pregnancy, estrogen ___ prolactin release --> marked increase in lactotrophs during pregnancy Prolactin also ___ GnRH release in pregnancy (stops ovulation/menstruation!) Prolactin stimulates growth of mammary glands in breast but importantly, milk production is held until birth d/t ___ effect by *estrogen and progesterone* --- Dopamine agonists (cabergoline, bromocriptine) can be used to tx Parkinson's dz, but *will ___ prolactin release (can be used to benefit for prolactinoma!*) --- Pituitary adenomas can be of any cell type in anterior pituitary - most common secreting tumor is *prolactinoma* (women: a___, galactorrhea; men: h___ h___ [low LH/FSH, testosterone --> decreased libido, impotence, infertility]) Any pituitary adenoma can compress optic chiasm --> *b___ h___*! --- Dopamine antagonists (haloperidol, metoclopramide) --> ___prolactinemia (p/w sx similar to prolactinoma + *Parkinsonism*)

Prolactin is under inhibitory control from the hypothalamus via dopamine binding D2 receptors (destruction of hypothalamus --> hyperprolactinemia); many substances affect prolactin release, notably *TRH such that hypothyroidism --> hyperprolactinemia* In pregnancy, estrogen stimulates prolactin release --> marked increase in lactotrophs during pregnancy Prolactin also inhibits GnRH release in pregnancy (stops ovulation/menstruation!) Prolactin stimulates growth of mammary glands in breast but importantly, milk production is held until birth d/t inhibitory effect by *estrogen and progesterone* --- Dopamine agonists (cabergoline, bromocriptine) can be used to tx Parkinson's dz, but *will inhibit prolactin release (can be used to benefit for prolactinoma!*) --- Pituitary adenomas can be of any cell type in anterior pituitary - most common secreting tumor is *prolactinoma* (women: amenorrhea, galactorrhea; men: hypogonadotropic hypogonadism [low LH/FSH, testosterone --> decreased libido, impotence, infertility]) Any pituitary adenoma can compress optic chiasm --> *bitemporal hemianopsia*! --- Dopamine antagonists (haloperidol, metoclopramide) --> hyperprolactinemia (p/w sx similar to prolactinoma + *Parkinsonism*)

Promoters are DNA regions that aren't transcribed, but bind ___ (binding opens dbl helix --> transcription can occur) ___ box is common euk. promoter that binds transcription factors (TFIID), CAAT and GC box are others ___ increase rate of transcription (either up- or downstream of gene they regulate) - bind activators (special trans. factor) and stabilize RNApol; *enhancers can be many nucleotides away from gene, but are geometrically close d/t DNA coiling* ___ are opposite of enhancers - bind repressors (special trans. factor) Untranslated regions are at both ends of mRNA - 5' end is recognized by ribosomes for translation, 3' end is important for post-transcriptional gene ___ (i.e., influences whether mRNA becomes protein)

Promoters are DNA regions that aren't transcribed, but bind RNApol (binding opens dbl helix --> transcription can occur) TATA box is common euk. promoter that binds transcription factors (TFIID), CAAT and GC box are others Enhancers increase rate of transcription (either up- or downstream of gene they regulate) - bind activators (special trans. factor) and stabilize RNApol; *enhancers can be many nucleotides away from gene, but are geometrically close d/t DNA coiling* Silencers are opposite of enhancers - bind repressors (special trans. factor) Untranslated regions are at both ends of mRNA - 5' end is recognized by ribosomes for translation, 3' end is important for post-transcriptional gene expression (i.e., influences whether mRNA becomes protein)

___ dilate afferent arteriole to increase RPF - because ___ block PG production, afferent arteriole constricts --> *decreased RPF, decreased GFR, stable filtration fraction* ___ constricts the efferent arteriole preferentially - because ___ block AII production, efferent arteriole dilates --> *increased RPF, decreased GFR, decreased filtration fraction*

Prostaglandins dilate afferent arteriole to increase RPF - because NSAIDs block PG production, afferent arteriole constricts --> *decreased RPF, decreased GFR, stable filtration fraction* Angiotensin II constricts the efferent arteriole preferentially - because ACE-inhibitors block AII production, efferent arteriole dilates --> *increased RPF, decreased GFR, decreased filtration fraction*

Common causes of UTI: PEEKS Two bugs don't form nitrites - what are they? --- Mainstay tx for UTIs is ___ - use ___ in pregnancy Sterile pyuria may be a manifestation of ___ (not seen/cultured easily - do a GC probe) --- Differentiating lower UTI from pyelo includes flank pain/CVA tenderness, hematuria, *WBC ___*, and systemic symptoms --- Chronic pyelonephritis is d/t recurrent bouts of acute pyelo - pts develop scarring of kidneys, blunted ___, and *tubules containing eosinophilic casts --> "___ of tissue"*

Proteus, Enterococcus, *E coli (up to 90%)*, Klebsiella, Staph saprophyticus Staph saprophyticus and enterococcus --- Mainstay tx for UTIs is fluroquinolones - use nitroufrantoin in pregnancy Sterile pyuria may be a manifestation of chlamydia/gonorrhea (not seen/cultured easily - do a GC probe) --- Differentiating lower UTI from pyelo includes flank pain/CVA tenderness, hematuria, *WBC casts*, and systemic symptoms --- Chronic pyelonephritis is d/t recurrent bouts of acute pyelo - pts develop scarring of kidneys, blunted calyces, and *tubules containing eosinophilic casts --> "thyroidization of tissue"*

Protozoa exist in different stages throughout life cycle with important forms being ___ (feeding form, vulnerable form) and ___ stage (more durable form, usually present in feces) All GI protozoa are fecal-oral transmission (consumption of water cont. with ___) ___ deficiency leaves patients vulnerable to severe Giardia infection (giardiAAA), including ___ Agammaglobulinemia and Selective IgA Deficiency Entamoeba histolytica is different from Giardia in that it ___ bowel tissue to cause ___ diarrhea

Protozoa exist in different stages throughout life cycle with important forms being trophozoites (feeding form, vulnerable form) and cyst stage (more durable form, usually present in feces) All GI protozoa are fecal-oral transmission (consumption of water cont. with cysts) IgA deficiency leaves patients vulnerable to severe Giardia infection (giardiAAA), including Bruton's Agammaglobulinemia and Selective IgA Deficiency Entamoeba histolytica is different from Giardia in that it invades bowel tissue to cause bloody diarrhea

Pseudohypoparathyroidism is *autosomal ___ d.o (GNAS)* of unresponsive kidney/bone to PTH (*abnormal PTH ___*) - presents in childhood w/___calcemia + ___phosphatemia + *ELEVATED PTH (normal response, but bone/kidney can't respond!!)* Albright Hereditary Osteodystrophy is form of pseudohypoparathyroidism (*AUTOSOMAL ___*) that p/w short stature + *shortened ___!* (+ what's mentioned above obviously related abnormal PTH receptor)

Pseudohypoparathyroidism is *autosomal DOMINANT d.o (GNAS)* of unresponsive kidney/bone to PTH (*abnormal PTH receptor*) - presents in childhood w/hypocalcemia + hyperphosphatemia + *ELEVATED PTH (normal response, but bone/kidney can't respond!!)* Albright Hereditary Osteodystrophy is form of pseudohypoparathyroidism (*AUTOSOMAL DOMINANT*) that p/w short stature + *shortened 4th and 5th digits!* (+ what's mentioned above obviously related abnormal PTH receptor)

Psoriasis is chronic, inflamm. skin d.o w/well-demarcated plaques w/scaling on ___ (flex/ext?) surfaces; psoriasis is thought to be autoimmune d/t *strong association with HLA-___* Pathology shows acanthosis (epidermis thickening), parakeratotic scaling (retained ___ in str. corneum, indicates hyperprolif.), and munro microabscesses (neutrophils in str. corneum) Dermis blood vessels can get close to surface and when scale breaks --> bleeding (A___ sign) Clinically, psoriasis has nail pitting and onycholysis + psoriatic arthritis (33%)

Psoriasis is chronic, inflamm. skin d.o w/well-demarcated plaques w/scaling on extensor surfaces; psoriasis is thought to be autoimmune d/t *strong association with HLA-C (sCott C sCoop)* Pathology shows acanthosis (epidermis thickening), parakeratotic scaling (retained nuc. in str. corneum, indicates hyperprolif.), and munro microabscesses (neutrophils in str. corneum) Dermis blood vessels can get close to surface and when scale breaks --> bleeding (Auspitz sign) Clinically, psoriasis has nail pitting and onycholysis + psoriatic arthritis (33%)

Psychosis is loss of perception of reality in medical/psych d/o (delirium, schizophrenia); three cardinal manifestations are ___ Delusions are strongly held beliefs (determined by what pts say) that conflict with reality (___ - examples? [6], PERCS G) Disorganized Thought is demonstrated in ___ of speech (i.e., how patient says it); may see alogia (speech ___ - schizo), thought blocking, loosening of association, tangentiality, clanging, word salad, perseveration VHs are common in ___ and AHs are classic for ___; olfactory hallucinations are classic aura in ___; tactile hallucinations is feeling/sensation (insects on skin - seen in substance use); hypnagogic/hypnopompic halluc. are seen in ___

Psychosis is loss of perception of reality in medical/psych d/o (delirium, schizophrenia); three cardinal manifestations are delusions, disorganized thought, and hallucinations Delusions are strongly held beliefs (determined by what pts say) that conflict with reality (persecutory, grandiose, erotomaniac, somatic, reference, control) Disorganized Thought is demonstrated in patterns of speech (i.e., how patient says it); may see alogia (speech poverty), thought blocking, loosening of association, tangentiality, clanging, word salad, perseveration VHs are common in delirium and AHs are classic for schizophrenia; olfactory hallucinations are classic aura in temporal lobe epilepsy; tactile hallucinations is feeling/sensation (insects on skin - seen in substance use); hypnagogic/hypnopompic halluc. are seen in narcolepsy

CLASSIC FINDING: peripheral blood smear w/spherocytes and Howell-Jolly bodies - what's going on?

Pt is s/p SPLENECTOMY for HEREDITARY SPHEROCYTOSIS!

PulmEmb p/w pleuritic CP and respiratory distress - a massive PE can l/t sudden death and a small/chronic PE can l/t Pulm HTN PulmEmb is example of *dead space - V/Q=___* w/other V/Q disturbances (blood shunted to healthy parts of lung --> V/Q mismatch); *[HY] pts w/PulmEmb ___VENTILATE --> ___ PaO2 and ___ PCO2* PulmEmb can come from ___ (pain, edema, warmth of one leg) --> dx w/LE US DVT/PE can occur in h___ pts (2/2 immobility) --> SubQ heparin/LMWH prophylaxis PFO can lead to ___ w/DVT/PE PE on EKG can lead to ___ (deep S in I, Q-wave in III, inverted T in III) + pseudo-RBBB Dx is via CT-A (use ___ if low suspicion in Well's score)

PulmEmb p/w pleuritic CP and respiratory distress - a massive PE can l/t sudden death and a small/chronic PE can l/t Pulm HTN PulmEmb is example of *dead space - V/Q=infinity* w/other V/Q disturbances (blood shunted to healthy parts of lung --> V/Q mismatch); *[HY] pts w/PulmEmb HYPERVENTILATE --> low PaO2 and low PCO2* PulmEmb can come from DVT (pain, edema, warmth of one leg) --> dx w/LE US DVT/PE can occur in hospitalized pts (2/2 immobility) --> SubQ heparin/LMWH prophylaxis PFO can lead to stroke w/DVT/PE PE on EKG can lead to S1Q3T3 (deep S in I, Q-wave in III, inverted T in III) + pseudo-RBBB Dx is via CT-A (use D-dimer if low suspicion in Well's score)

Pulmonary artery is low pressure system (24/12) d/t not needing to go far; accordingly, walls of PA are ___ (little smooth muscle - little resistance - very distensible) In systemic circulation, low O2 --> vaso___ (maintains blood flow); in pulmonary circulation, low O2 --> vaso___ (shunts blood away from poorly ventilated areas, prevents shunting); this is key for fetal circulation! Rate of O2 diffusion depends on 1) p___ difference, 2) a___ of alveoli, and 3) t___ of alveoli Vgas (diffusion rate) = A x D(diffusion coefficient) x ([pressure difference]/[wall thickness]) In emphysema --> a___ falls In pulm. fibrosis --> t___ rises

Pulmonary artery is low pressure system (24/12) d/t not needing to go far; accordingly, walls of PA are thin (little smooth muscle - little resistance - very distensible) In systemic circulation, low O2 --> vasodilation (maintains blood flow); in pulmonary circulation, low O2 --> vasoconstriction (shunts blood away from poorly ventilated areas, prevents shunting); this is key for fetal circulation! Rate of O2 diffusion depends on 1) pressure difference, 2) area of alveoli, and 3) thickness of alveoli Vgas (diffusion rate) = A x D(diffusion coefficient) x ([pressure difference]/[wall thickness]) In emphysema --> area falls In pulm. fibrosis --> thickness rises

Pulmonary edema on CXR --> puffy white fields + enlarged heart + K___ B lines Pleural effusion on CXR --> blunting of ___ Pneumothorax on CXR --> ___density (excessive darkness) +/- midline shift Lobar PNA on CXR --> ___ localized to one lobe Interstitial fibrosis on CXR --> diffuse h___ whiteness TB/Sarcoid on CXR --> ___ lymphadenopathy Pulmonary nodule on CXR --> look for c___ lesion

Pulmonary edema on CXR --> puffy white fields + enlarged heart + Kerley B lines Pleural effusion on CXR --> blunting of costophrenic angle Pneumothorax on CXR --> hypodensity (excessive darkness) +/- midline shift Lobar PNA on CXR --> consolidation localized to one lobe Interstitial fibrosis on CXR --> diffuse honeycomb whiteness TB/Sarcoid on CXR --> hilar lymphadenopathy Pulmonary nodule on CXR --> look for coin lesion

___ is absence of erythroid precursors in bone marrow w/marked reduction in reticulocytes, but normal granulocytes and platelets PRCA is a/w some drugs and viral infxns *KEY ASSOCIATION: ___*

Pure red cell aplasia is absence of erythroid precursors in bone marrow w/marked reduction in reticulocytes, but normal granulocytes and platelets PRCA is a/w some drugs and viral infxns *KEY ASSOCIATION: thymoma*

Purines can either be excreted via uric acid or enter *salvage pathway* Purine salvage converts adenine, guanine, hypoxanthine back into nucleotides (AMP, GMP, IMP) - this step requires PRPP, which is incorporated into guanine or hypoxanthine to make GMP and IMP, respectively (6-MP/AZA mimic hypoxanthine/guanine --> added to PRPP by HGPRT --> inhibit multiple steps in de novo synthesis --> decrease IMP, AMP, GMP levels) For excretion, adenosine becomes inosine *via ADENOSINE DEAMINASE ENZYME!* - inosine can become hypoxanthine --> conversion to uric acid and excretion --- CLINICAL TIE IN: X-linked deficiency in HGPRT results in excess uric acid + ramped up purine de novo synthesis --> elevated PRPP and IMP levels

P___ K___ deficiency is a cause of intrinsic hemolytic anemia; pyruvate kinase is key enzyme in glycolysis for anaerobic metabolism (recall that RBCs don't have mitochondria & require PK for metabolism) PK deficiency --> rigid RBCs --> extravascular hemolysis in ___ PK deficiency classically presents as newborn w/extravascular hemolysis + splenomegaly On smear, will see ___ cells (Pointy Pyruvate)

Pyruvate Kinase deficiency is a cause of intrinsic hemolytic anemia; pyruvate kinase is key enzyme in glycolysis for anaerobic metabolism (recall that RBCs don't have mitochondria & require PK for metabolism) PK deficiency --> rigid RBCs --> extravascular hemolysis in spleen PK deficiency classically presents as newborn w/extravascular hemolysis + splenomegaly On smear, will see Burr cells (Pointy Pyruvate)

R lung has 3 lobes, L lung has 2 lobes (think of heart as lobe); aspiration is more likely to go to ___ lung (d/t ___ bronchus being wider, more vertical angle - think of heart being in way of left bronchus) ASPIRATION DESTINATION: If upright --> right ___ lobe; if supine --> right inferior lobe ___ segment R pulmonary artery passes a___ to R bronchus; L pulmonary artery passes s___ to L bronchus Diaphragm has three important segments running through: v___ (caval opening, T8), e___ (esophageal hiatus + *vagus nn.*, T10), a___ (aortic hiatus + thoracic duct & azygous vein, T12 - at T-1-2, its RedWhiteBlue) Phrenic nerve (C3-C5) innervates diaphragm; diaphragm irritation --> shoulder pain; phrenic nn. cut --> paradoxical diaphragm ___ + dyspnea Inspiratory mm. (neck) include scalenes, SCM; expiratory mm. (abdomen) include rectus, obliques, transverse abdominis, int. intercostals

R lung has 3 lobes, L lung has 2 lobes (think of heart as lobe); aspiration is more likely to go to R lung (d/t R bronchus being wider, more vertical angle - think of heart being in way of left bronchus) ASPIRATION DESTINATION: If upright --> right inferior lobe; if supine --> right inferior lobe superior segment R pulmonary artery passes anteriorly to R bronchus; L pulmonary artery passes superiorly to L bronchus Diaphragm has three important segments running through: vena cava (caval opening, T8), esophagus (esophageal hiatus + *vagus nn.*, T10), aorta (aortic hiatus + thoracic duct & azygous vein, T12 - at T-1-2, its RedWhiteBlue) Phrenic nerve (C3-C5) innervates diaphragm; diaphragm irritation --> shoulder pain; phrenic nn. cut --> paradoxical diaphragm elevation + dyspnea Inspiratory mm. (neck) include scalenes, SCM; expiratory mm. (abdomen) include rectus, obliques, transverse abdominis, int. intercostals ^NOTE: common carotide bifurcates C4, trachea bifurcates T4, aorta bifurcates L4

CLASSIC CASE: young child (<2y) w/fever, runny nose - develops cough + wheezing a few days later?

RSV

Radiculopathy is compression of nerve root at spine (2/2 disc herniation, spondylolisthesis, stenosis); herniated disc is d/t *___ breakdown w/___ bulging*, often occurring posteriorly d/t *[HY] thinner/weaker ___ ligament and thicker ___ longitudinal ligament along vertebral bodies* Spinal stenosis occurs d/t intervertebral discs shrinking, *facet joint arthritis w/bone spurs, and ligamentum flavum ___* - in stenosis, pain will be worse w/standing & walking (*neurogenic claudication - similar to vascular, but ___ when resting and ___ w/flexed posture*) Recall sciatic motor functions are to ___ knee and ___ hip - sciatica (lumbar radiculopathy) can impact these motor functions; commonly d/t herniated disc (compresses only one root), but can have *complete sciatic neuropathy 2/2 hip fracture/dislocation (posterior is most common), THA, or prolonged compression (knocks out all sciatic nn, tibial nn, peroneal nn function)*

Radiculopathy is compression of nerve root at spine (2/2 disc herniation, spondylolisthesis, stenosis); herniated disc is d/t *annulus fibrosus breakdown w/nucleus pulposus bulging*, often occurring posteriorly d/t *[HY] thinner/weaker posterior longitudinal ligament and thicker anterior longitudinal ligament along vertebral bodies* Spinal stenosis occurs d/t intervertebral discs shrinking, *facet joint arthritis w/bone spurs, and ligamentum flavum hypertrophy* - in stenosis, pain will be worse w/standing & walking (*neurogenic claudication - similar to vascular, but PERSISTS when resting and IMPROVES w/flexed posture*) Recall sciatic motor functions are to flex knee and extend/rotate hip - sciatica (lumbar radiculopathy) can impact these motor functions; commonly d/t herniated disc (compresses only one root), but can have *complete sciatic neuropathy 2/2 hip fracture/dislocation (posterior is most common), THA, or prolonged compression (knocks out all sciatic nn, tibial nn, peroneal nn function)*

___ is compression of nerve root at spine (2/2 disc herniation, spondylolisthesis, stenosis); herniated disc tend to compress nerve ___ disc (L3/L4 disc l/t L4 radiculopathy) L2/3/4 nerve roots lead to thigh/knee symptoms (supply f___ nn.) - pain in anterior thigh +/- *reduced ___ reflex* L5 radiculopathy (MC, L___ disc) l/t pain down ___ leg + weak foot ___ (can't walk on heels, affects common peroneal nn.) S1 radiculopathy (L___ disc) l/t pain down ___ leg + weak ___ (can't walk on toes & *ankle reflex lost!* - tibial nn. affected) Use straight leg raise test to look for lumbar radiculopathy (pain needs to go down leg)

Radiculopathy is compression of nerve root at spine (2/2 disc herniation, spondylolisthesis, stenosis); herniated disc tend to compress nerve below disc (L3/L4 disc l/t L4 radiculopathy) L2/3/4 nerve roots lead to thigh/knee symptoms (supply femoral nn.) - pain in anterior thigh +/- *reduced patellar reflex* L5 radiculopathy (MC, L4/5 disc) l/t pain down lateral leg + weak foot dorsiflexion (can't walk on heels, affects common peroneal nn.) S1 radiculopathy (L5/S1 disc) l/t pain down post. leg + weak plantarflexion (can't walk on toes & *ankle reflex lost!* - tibial nn. affected) Use straight leg raise test to look for lumbar radiculopathy (pain needs to go down leg)

___: crackles/pops when airway opens after collapse - seen in pulmonary edema (bases - HF), pneumonia, interstitial fibrosis Wheezes: air flowing through narrowed bronchi, classic cause is *___* (also seen in heart failure, bronchitis, obstruction) ___: coarse breath sounds - classic cause is *COPD* Bronchial Breath Sounds: high pitched lung sounds - seen in pneumonia ___: wheeze that is entirely inspiratory (UNUSUAL - usually d/t partial obstruction of larynx or trachea and is loudest over neck) - seen in laryngotracheitis (croup), epiglottitis, retropharyngeal abscess Pectoriloquy: sounds over chest are heard through stethoscope - indicates fluid in lungs (effusion, consolidation), includes bronchophony (voice sounds are heard), egophony Fremitus: vibration when pt says "99", increased --> pneumonia, decreased --> pleural effusion, pneumothorax, atelectasis

Rales: crackles/pops when airway opens after collapse - seen in pulmonary edema (bases - HF), pneumonia, interstitial fibrosis Wheezes: air flowing through narrowed bronchi, classic cause is *asthma* (also seen in heart failure, bronchitis, obstruction) Rhonchi: coarse breath sounds - classic cause is *COPD* Bronchial Breath Sounds: high pitched lung sounds - seen in pneumonia Stridor: wheeze that is entirely inspiratory (UNUSUAL - usually d/t partial obstruction of larynx or trachea and is loudest over neck) - seen in laryngotracheitis (croup), epiglottitis, retropharyngeal abscess Pectoriloquy: sounds over chest are heard through stethoscope - indicates fluid in lungs (effusion, consolidation), includes bronchophony (voice sounds are heard), egophony Fremitus: vibration when pt says "99", increased --> pneumonia, decreased --> pleural effusion, pneumothorax, atelectasis

Reactivation TB can happen in HIV, diabetes, or when starting ___ inhibitors (Etanercept) - check PPD before starting Dx Active TB: take ___ sputum samples, 8hrs apart for cx Dx Latent TB: TB skin testing (PPD), wait 48h --> measure induration diameter (*NOT ___!*); healthy (>15mm), high-risk (silicosis, IVDU, homeless - >10mm), immunocompromise (HIV - >5mm); *[HY] false negatives occur in immunosuppression/immunocompromise, dz lymph system (lymphomas, sarcoid)*, false positive in ___ vaccine Tx Latent TB: ___ x9mo Tx Active TB: 4 drugs for 2 months (RIPE), 2 drugs for 4 months (+ direct observation therapy); *[HY] main side effect of rifampin is r___ of fluids (not dangerous)*

Reactivation TB can happen in HIV, diabetes, or when starting TNF-alpha inhibitors (Etanercept) - check PPD before starting Dx Active TB: take 3 sputum samples, 8hrs apart for cx Dx Latent TB: TB skin testing (PPD), wait 48h --> measure induration diameter (*NOT ERYTHEMA!*); healthy (>15mm), high-risk (silicosis, IVDU, homeless - >10mm), immunocompromise (HIV - >5mm); *[HY] false negatives occur in immunosuppression/immunocompromise, dz lymph system (lymphomas, sarcoid)*, false positive in BCG vaccine Tx Latent TB: isoniazid x9mo Tx Active TB: 4 drugs for 2 months (RIPE), 2 drugs for 4 months (+ direct observation therapy); *[HY] main side effect of rifampin is red/orange discoloration of fluids (not dangerous)*

Recall that iron is absorbed in Fe___+ state - heme iron exists this way, Fe___+ state must be reduced to Fe2+ by vitamin ___ before absorption by *enterocytes via iron transporter ___* (major regulator of iron levels in body, d/t few mechanisms to excrete iron) Four clinical iron measurements are serum iron, total iron binding capacity (*___*), ferritin, and % saturation (% of transferrin that is bound - Fe/TIBC) Iron deficiency can be d/t lack of iron from gut (___fed newborns, malabsorption [Celiac dz, PPIs w/alkaline stomach that converts Fe2+ --> Fe3+]) or loss of iron via bleeding (menorrhagia, peptic ulcers, colon cancer [*any adult w/IDA NEED ___ workup*]) Pregnancy can lead to IDA d/t expansion of maternal Hgb mass and *increased ___ from fetus*; both pregnancy and OCPs can also increase plasma ___ (low % saturation, don't rely on it - use ferritin) Two rare causes of IDA include hookworms (*a___ d___*) and Plummer-Vinson Syndrome (triad of IDA, *ESOPHAGEAL ___*, and dysphagia + *b___ t___*)' Labs in IDA: low iron, low ferritin, high transferrin (TIBC), low % saturation, *elevated p___ (can't add to Fe to create heme --> levels buildup)* CBC: micro-to-normocytic, ___ RDW (*differentiation from thalassemias!*)

Recall that iron is absorbed in Fe2+ state - heme iron exists this way, Fe3+ state must be reduced to Fe2+ by vitamin C before absorption by *enterocytes via iron transporter ferroportin* (major regulator of iron levels in body, d/t few mechanisms to excrete iron) Four clinical iron measurements are serum iron, total iron binding capacity (*transferrin*), ferritin, and % saturation (% of transferrin that is bound - Fe/TIBC) Iron deficiency can be d/t lack of iron from gut (breastfed newborns, malabsorption [Celiac dz, PPIs w/alkaline stomach that converts Fe2+ --> Fe3+]) or loss of iron via bleeding (menorrhagia, peptic ulcers, colon cancer [*any adult w/IDA NEED colon cancer workup*]) Pregnancy can lead to IDA d/t expansion of maternal Hgb mass and *increased demand from fetus*; both pregnancy and OCPs can also increase plasma transferrin (low % saturation, don't rely on it - use ferritin) Two rare causes of IDA include hookworms (*ancylostoma duodenale*) and Plummer-Vinson Syndrome (triad of IDA, *ESOPHAGEAL WEBS*, and dysphagia + *beefy tongue*)' Labs in IDA: low iron, low ferritin, high transferrin (TIBC), low % saturation, *elevated protoporphyrin (can't add to Fe to create heme --> levels buildup)* CBC: micro-to-normocytic, increased RDW (*differentiation from thalassemias!*)

Recurrent laryngeal nerve compression leads to ___ This is classically caused by ___ and ___

Recurrent laryngeal nerve compression leads to hoarseness This is classically caused by dilated LA (mitral stenosis) and aortic dissection

Regulatory T-cells (CD25+) suppress CD4 and CD8 T-cell functions - accomplish this via anti-inflammatory cytokines (IL-___ and ___-beta, Both atTENuate immune response) Th17 T-cells are important for m___ immunity (GI tract) - recruit neutrophils and macrophages (loss of Th17 --> ___ bacteria sepsis) ___ T-cells elicit stronger immune rxn to new exposure (faster, more vigorous response - seen with PPD test when Th___ cells activated --> IFN-gamma --> skin macrophages activated; if no memory T-cells [i.e., no prior exposure] --> nothing happens) --- Superantigens directly link MHC to T-cells --> produce massive response without processing by APC --> huge release of IFN-gamma and IL-2 (seen in TSST, pyrogenic GAS toxin)

Regulatory T-cells (CD25+) suppress CD4 and CD8 T-cell functions - accomplish this via anti-inflammatory cytokines (IL-10 and TGF-beta, Both atTENuate immune response) Th17 T-cells are important for mucosal immunity (GI tract) - recruit neutrophils and macrophages (loss of Th17 --> GI bacteria sepsis) Memory T-cells elicit stronger immune rxn to new exposure (faster, more vigorous response - seen with PPD test when Th1 cells activated --> IFN-gamma --> skin macrophages activated; if no memory T-cells [i.e., no prior exposure] --> nothing happens) --- Superantigens directly link MHC to T-cells --> produce massive response without processing by APC --> huge release of IFN-gamma and IL-2 (seen in TSST, pyrogenic GAS toxin)

Renal agenesis is failure of ___ bud to develop --> absent kidney; *[HY] if unilateral, other kidney can compensate (hyperfiltration), but can lead to ___ --> renal failure*; if both kidneys --> o___ + ___ syndrome --- Multicystic dysplastic kidney is d/t abnormal ___-mesenchymal interaction (ureteric bud still forms), l/t kidney replaced with cysts; this is usually unilateral and l/t nonfunctional kidney --- Ureteropelvic junction is last connection to form in utero - if this forms improperly --> ___ (*common cause of unilateral kidney obstruction*) This results in narrowing of proximal ureter --> h___ --> poor urinary flow after birth (tx w/surgery) --- Duplex collecting system is bifurcation of ureteric bud --> poor urine flow --> *increased risk of ___ urinary stasis* & a/w vesicoureteral ___ --- Vesicoureteral reflux is retrograde urine flow from bladder to kidneys l/t *recurrent ___ (urinary stasis)* VUR can be primary (d/t abnormal closure of ureterovesical junction, *[HY] ___ ureters*) or secondary (high bladder pressure pushes urine backwards [i.e., posterior ___])

Renal agenesis is failure of ureteric bud to develop --> absent kidney; *[HY] if unilateral, other kidney can compensate (hyperfiltration), but can lead to FSGS --> renal failure*; if both kidneys --> oligohydramnios + Potter's syndrome --- Multicystic dysplastic kidney is d/t abnormal ureteric bud-mesenchymal interaction (ureteric still forms), l/t kidney replaced with cysts; this is usually unilateral and l/t nonfunctional kidney --- Ureteropelvic junction is last connection to form in utero - if this forms improperly --> UPJ obstruction (*common cause of unilateral kidney obstruction*) This results in narrowing of proximal ureter --> hydronephrosis --> poor urinary flow after birth (tx w/surgery) --- Duplex collecting system is bifurcation of ureteric bud --> poor urine flow --> *increased risk of UTIs (urinary stasis* & a/w vesicoureteral reflux --- Vesicoureteral reflux is retrograde urine flow from bladder to kidneys l/t *recurrent UTIs (urinary stasis)* VUR can be primary (d/t abnormal closure of ureterovesical junction, *[HY] duplex ureters*) or secondary (high bladder pressure pushes urine backwards [i.e., posterior ureteral valves])

Renal angiomyolipoma is a tumor of blood vessels, smooth muscle, and fat - this is seen in *___ (AD - look for brain tubers, hamartomas, seizures, ash-leaf spots)*

Renal angiomyolipoma is a tumor of blood vessels, smooth muscle, and fat - this is seen in *TUBEROUS SCLEROSIS (AD - look for brain tubers, hamartomas, seizures, ash-leaf spots)*

Renal cell carcinoma is an epithelial cell tumor arising from ___ cells; the classic triad is *___, palpable abdominal mass, and flank pain* in a fat male smoker RCC commonly invades the renal vein, *[HY] causing a ___ varicocele*; RCC metastasizes to lung and ___ RCC has several paraneoplastic syndromes: 1) *___* (2/2 EPO production), 2) *___* (2/2 PTHrP production), 3) *___* (2/2 renin production), 4) *___ syndrome* (2/2 ACTH production - will not suppress w/high dose dexamethasone suppression test) On histology, *[HY] RCC appears w/___ cells - its the most common type of kidney tumor* RCC is a/w sporadic deletion mutation of ___ on chrom3; inherited mutation --> VHL Dz w/triad of *RCC, ___omas (cerebellar + retinal)* Tx: RCC is poorly responsible to chemotherapy - can give recombinant IL-___ (aldesleukin - pt will look like they have the flu)

Renal cell carcinoma is an epithelial cell tumor arising from PCT cells; the classic triad is *hematuria, palpable abdominal mass, and flank pain* in a fat male smoker RCC commonly invades the renal vein, *[HY] causing a LEFT varicocele*; RCC metastasizes to lung and bones RCC has several paraneoplastic syndromes: 1) *polycythemia* (2/2 EPO production), 2) *hypercalcemia* (2/2 PTHrP production), 3) *HTN* (2/2 renin production), 4) *Cushing's syndrome* (2/2 ACTH production - will not suppress w/high dose dexamethasone suppression test) On histology, *[HY] RCC appears w/clear cells - its the most common type of kidney tumor* RCC is a/w sporadic deletion mutation of VHL on chrom3; inherited mutation --> VHL Dz w/triad of *RCC, hemangioblastomas (cerebellar + retinal)* Tx: RCC is poorly responsible to chemotherapy - can give recombinant IL-2 (aldesleukin - pt will look like they have the flu)

Renal clearance is volume of blood "cleared" of substance X per minute ([urine concentration of X x urine flow rate]/plasma concentration of X) - reported in L/min Renal plasma flow is determined using the substance *___ - 100% filtered & secreted by kidney!* (i.e., any PAH that enters kidney --> leaves as urine) NOTE: PAH slightly underestimates RPF d/t not all blood flow to kidney entering glomerulus (some goes to supply kidney Accordingly, renal plasma flow = ([___ concentration of PAH x urine flow rate]/___ concentration of PAH) Renal blood flow = (RPF/[1-___]) ^NOTE: measure GFR using inulin/creatinine

Renal clearance is volume of blood "cleared" of substance X per minute ([urine concentration of X x urine flow rate]/plasma concentration of X) - reported in L/min Renal plasma flow is determined using the substance *PAH - 100% filtered & secreted by kidney!* (i.e., any PAH that enters kidney --> leaves as urine) NOTE: PAH slightly underestimates RPF d/t not all blood flow to kidney entering glomerulus (some goes to supply kidney Accordingly, renal plasma flow = ([urine concentration of PAH x urine flow rate]/plasma concentration of PAH) Renal blood flow = (RPF/[1-Hct]) ^NOTE: measure GFR using inulin/creatinine

Renal tubular acidosis are rare disorders of nephron ion channels that cause ___-gap metabolic acidosis - p/w metabolic acidosis + abnormal potassium Type I (distal) RTA is a defect in ___ pump of intercalated cells in collecting duct - can't excrete acid + *can't resorb ___ d/t negative luminal potential generated (holds potassium in urine)* Type I RTA often manifests with *severely low ___ (can be <10)!* - urine pH will be ___ (>5.5 - can't acidify urine) and urine anion gap will be *___ (UNIQUE - not a lot of NH4 being excreted! [Na + K - Cl])* Type I RTA is *[HY HY] a/w ___ diseases (Sjogren's, RA) and a___ B* KEY SYMPTOMS: increased risk for calcium kidney stones (___ urine pH precipitates stone formation, + ___ state --> bone resorption) - may also present as growth failure in children

Renal tubular acidosis are rare disorders of nephron ion channels that cause non-anion-gap metabolic acidosis - p/w metabolic acidosis + abnormal potassium Type I (distal) RTA is a defect in H+ (1+) pump of intercalated cells in collecting duct - can't excrete acid + *can't resorb potassium d/t negative luminal potential generated (holds potassium in urine)* Type I RTA often manifests with *severely low HCO3 (can be <10)!* - urine pH will be high (>5.5 - can't acidify urine) and urine anion gap will be *positive (UNIQUE - not a lot of NH4 being excreted! [Na + K - Cl])* Type I RTA is *[HY HY] a/w autoimmune diseases (Sjogren's, RA) and amphotericin B* KEY SYMPTOMS: increased risk for calcium kidney stones (increased urine pH precipitates stone formation, + acidotic state --> bone resorption) - may also present as growth failure in children

Renal tubular acidosis are rare disorders of nephron ion channels that cause non-anion-gap metabolic acidosis - p/w metabolic acidosis + abnormal ___ (electrolyte?) Type II (proximal) RTA is a defect in PCT ___ reabsorption - this p/w *urine pH ___ (distal tubule can secrete H+ to compensate - can't do this in type I as defect is way downstream in CD!)* + ___kalemia (loss of HCO3 --> diuresis --> aldosterone activation --> K wasting) Type II RTA will not p/w ___ (different from type I RTA) Type II RTA can present as part of Fanconi syndrome

Renal tubular acidosis are rare disorders of nephron ion channels that cause non-anion-gap metabolic acidosis - p/w metabolic acidosis + abnormal potassium Type II (proximal) RTA is a defect in PCT bicarb (2-carb) reabsorption - this p/w *urine pH <5.5 (distal tubule can secrete H+ to compensate - can't do this in type I as defect is way downstream in CD!)* + hypokalemia (loss of HCO3 --> diuresis --> aldosterone activation --> K wasting) Type II RTA will not p/w kidney stones (different from type I RTA) Type II RTA can present as part of Fanconi syndrome

Renal tubular acidosis are rare disorders of nephron ion channels that cause non-anion-gap metabolic acidosis - p/w metabolic acidosis + abnormal ___ (electrolyte?) Type IV RTA is d/t inappropriate response to *___ (why it is seen w/aldosterone antagonists!!!!!)* Accordingly, type IV RTA is only RTA with *___KALEMIA!!*; urine pH will still be low Importantly, type IV RTA has impaired ___ (*hyper___ --> reduced production of NH3 in PCT*) --> *acidosis d/t less ___ excretion* Type IV RTA is seen in *___ renal dz (decreased renin production --> less aldosterone around), ACEi/ARB, NSAIDs, adrenal insufficiency, K-sparing diuretic, TMP-SMX (random one!)*

Renal tubular acidosis are rare disorders of nephron ion channels that cause non-anion-gap metabolic acidosis - p/w metabolic acidosis + abnormal potassium Type IV RTA is d/t inappropriate response to *ALDOSTERONE (why it is seen w/aldosterone antagonists!!!!!)* Accordingly, type IV RTA is only RTA with *HYPERKALEMIA!!*; urine pH will still be low Importantly, type IV RTA has impaired NH*4* excretion (*hyperkalemia --> reduced production of NH3 in PCT*) --> *acidosis d/t less NH4 excretion* Type IV RTA is seen in *diabetic renal dz (decreased renin production --> less aldosterone around), ACEi/ARB, NSAIDs, adrenal insufficiency, K-sparing diuretic, TMP-SMX (random one!)*

Renin is secreted by ___ cells (modified smooth muscle cells of afferent arteriole) - m___ is also part of JGA and is a portion of the distal tubule The role of renin is to convert angiotensinogen to angiotensin I; AI is converted to AII (via ACE in ___), which has the following effects (RAAS system): 1. Renal NaCl resorption 2. Arteriolar ___ 3. Adrenal aldosterone secretion NET RESULT: increased salt and water retention + increased BP Three stimuli for renin release include: 1. ___ perfusion pressure to kidney 2. Low ___ delivery to macula densa (macula densa can stimulate renin release from JGA, as well as constrict afferent arteriole ["___ feedback"]) 3. Sympathetic activation of ___ receptors

Renin is secreted by juxtaglomerular cells (modified smooth muscle cells of afferent arteriole) - macula densa is also part of JGA and is a portion of the distal tubule The role of renin is to convert angiotensinogen to angiotensin I; AI is converted to AII (via ACE in lungs), which has the following effects (RAAS system): 1. Renal NaCl resorption 2. Arteriolar vasoconstriction 3. Adrenal aldosterone secretion NET RESULT: increased salt and water retention + increased BP Three stimuli for renin release include: 1. Low perfusion pressure to kidney 2. Low NaCl delivery to macula densa (macula densa can stimulate renin release from JGA, as well as constrict afferent arteriole ["tubuloglomerular feedback"]) 3. Sympathetic activation of beta-1 receptors

Respiratory alkalosis (low pCO2) occurs 2/2 hyperventilation - this can be a result of panic attacks, pain, hypo___ (*high altitude*), and *ASA overdose* When pts ascend to high altitude, low pO2 triggers ___ventilation, which subsequently lowers pCO2 - after 1-2d, kidneys will compensate by excreting HCO3 (*rationale for ___ for altitude sickness - augments HCO3 excretion!*) *[HY] ASA causes two acid base disorders: 1) shortly after ingestion, salicylates stimulate the ___ to hyperventilate --> respiratory ___ and 2) salicylates cause accumulation of pyruvate/lactate/ketoacids --> ___; accordingly, pH can be variable, pCO2 will be ___, and HCO3 will be ___ - Winter's formula will predict a ___ CO2 than actual --> MIXED DISORDER* --- Respiratory acidosis (high pCO2) occurs 2/2 hypoventilation - this is seen in COPD, *___ (drugs?)*, and respiratory muscle weakness (myasthenia, ALS, Guillain-Barre)

Respiratory alkalosis (low pCO2) occurs 2/2 hyperventilation - this can be a result of panic attacks, pain, hypoxemia (*high altitude*), and *ASA overdose* When pts ascend to high altitude, low pO2 triggers hyperventilation, which subsequently lowers pCO2 - after 1-2d, kidneys will compensate by excreting HCO3 (*rationale for acetazolamide for altitude sickness - augments HCO3 excretion!*) *[HY] ASA causes two acid base disorders: 1) shortly after ingestion, salicylates stimulate the medulla to hyperventilate --> respiratory alkalosis and 2) salicylates cause accumulation of pyruvate/lactate/ketoacids --> AGMA; accordingly, pH can be variable, pCO2 will be low, and HCO3 will be low - Winter's formula will predict a higher CO2 than actual --> MIXED DISORDER* --- Respiratory acidosis (high pCO2) occurs 2/2 hypoventilation - this is seen in COPD, *narcotics*, and respiratory muscle weakness (myasthenia, ALS, Guillain-Barre)

Responses to acidosis include hyperventilation, myocardial contractility depression, cerebral vaso___ (increased ICP), CNS depression (CO2 is narcotic), ___kalemia (H-K exchange), and ___-shift of oxyhemoglobin dissociation curve (Bohr effect) Responses to alkalosis include hypoventilation, myocardial contractility depression, cerebral *vaso___ (decreased cerebral blood flow)*, hypokalemia, and ___-shift of oxyhemoglobin dissociation curve General approach to acid-base disorders includes: 1) check pH, 2) check HCO3 and pCO2, 3) determine acid-base disorder (met vs. resp, acid vs. alk), 4) for metabolic acidosis - calculate anion gap, 5) special formulas to check for mixed disorder (Winter's formula) Accelerated Version: 1) what's the acid-base disorder? 2) is there a second disorder (i.e., is compensation appropriate)? *WINTERS FORMULA: ___* NOTE: *body cannot compensate to normal pH - if normal pH + abnormal HCO3/pCO2 --> *MIXED DISORDER* NOTE: ___ compensation is rapid, ___ compensation takes a while - respiratory acid-base disorder will have delayed compensation by kidneys! In folks w/high altitude (chronic hyperventilation), pts develop chronically low bicarb

Responses to acidosis include hyperventilation, myocardial contractility depression, cerebral vasodilation (increased ICP), CNS depression (CO2 is narcotic), hyperkalemia (H-K exchange), and right-shift of oxyhemoglobin dissociation curve (Bohr effect) Responses to alkalosis include hypoventilation, myocardial contractility depression, cerebral *vasoconstriction (decreased cerebral blood flow)*, hypokalemia, and left-shift of oxyhemoglobin dissociation curve General approach to acid-base disorders includes: 1) check pH, 2) check HCO3 and pCO2, 3) determine acid-base disorder (met vs. resp, acid vs. alk), 4) for metabolic acidosis - calculate anion gap, 5) special formulas to check for mixed disorder (Winter's formula) Accelerated Version: 1) what's the acid-base disorder? 2) is there a second disorder (i.e., is compensation appropriate)? *WINTERS FORMULA: [(1.5 x [HCO3]) + 8] +/- 2* NOTE: *body cannot compensate to normal pH - if normal pH + abnormal HCO3/pCO2 --> *MIXED DISORDER* NOTE: respiratory compensation is rapid, metabolic compensation takes a while - respiratory acid-base disorder will have delayed compensation by kidneys! In folks w/high altitude (chronic hyperventilation), pts develop chronically low bicarb

Restrictive lung dz can be d/t 1) poor breathing m___ or 2) diffuse interstitial/parenchymal dz Poor mechanics will have ___ A-a gradient - may be seen in polio, MyasGrav, scoliosis, morbid obesity Diffuse interstitial/parenchymal dz will have ___ A-a gradient - imaging will demonstrate bilateral diffuse "h___" pattern (reticulonodular) DLCO can determine cause of RLD - normal DLCO --> ___, low DLCO --> ___ (problem w/diffusion) ILD can include IPF, ___ (work exposures - silicosis, asbestosis), sarcoid, RA, Goodpasture's, Wegener's, drug toxicity (am___, bleomycin, methotrexate)

Restrictive lung dz can be d/t 1) poor breathing mechanics or 2) diffuse interstitial/parenchymal dz Poor mechanics will have normal A-a gradient - may be seen in polio, MyasGrav, scoliosis, morbid obesity Diffuse interstitial/parenchymal dz will have elevated A-a gradient - imaging will demonstrate bilateral diffuse "honeycomb" pattern (reticulonodular) DLCO can determine cause of RLD - normal DLCO --> mechanics, low DLCO --> ILD (problem w/diffusion) ILD can include IPF, pneumoconioses (work exposures - silicosis, asbestosis), sarcoid, RA, Goodpasture's, Wegener's, drug toxicity (amiodarone)

Retinal detachment occurs when retina peels from ___ layer --> ischemia, photoreceptor degeneration; vision loss occurs in curtain-dropping fashion RD is commonly preceded by ___ detachment - vitreous shrinks with age, pulls on retina --> holes in retina/tears (manifests with floaters, light flashes) RFs for RD include myopia and prolif diabetic retinopathy

Retinal detachment occurs when retina peels from choroid layer --> ischemia, photoreceptor degeneration; vision loss occurs in curtain-dropping fashion RD is commonly preceded by posterior vitreous membrane detachment - vitreous shrinks with age, pulls on retina --> holes in retina/tears (manifests with floaters, light flashes) RFs for RD include myopia and prolif diabetic retinopathy

Rett Syndrome is developmental disorder in females who have normal development until 1-2y; hallmark is *___ of cognitive/motor skills* Manifestations include decel of ___ growth, loss of balance (ataxia)/motor skills, and *repetitive ___ movements* RS is ___ (inheritance?) disorder (boys die with only one copy, girls have some cells that express normal gene 2/2 random X-inactivation) of ___ gene (99% sporadic mutation)

Rett Syndrome is developmental disorder in females who have normal development until 1-2y; hallmark is *regression of cognitive/motor skills* Manifestations include decel of head growth, loss of balance (ataxia)/motor skills, and *repetitive hand movements* RS is X-linked dominant disorder (boys die with only one copy, girls have some cells that express normal gene 2/2 random X-inactivation) of MECP2 gene (99% sporadic mutation)

Reverse T3 (isomer of T3) are usually parallel to ___ (low T4 --> low rT3); the exception is *___*, seen in critically ill pts w/low TSH, low T3/T4, and rT3 (*rT3 ___ in CRITICAL ILLNESS*) If low TSH/T3/T4 + high rT3 --> ___ If low TSH/T3/T4 + low rT3 --> look for ___ hypothyroidism (pituitary tumor, hypothalamic tumor)

Reverse T3 (isomer of T3) are usually parallel to T4 (low T4 --> low rT3); the exception is *euthyroid sick syndrome*, seen in critically ill pts w/low TSH, low T3/T4, and rT3 (*rT3 rises in CRITICAL ILLNESS*) If low TSH/T3/T4 + high rT3 --> euthyroid sick syndrome If low TSH/T3/T4 + low rT3 --> look for central hypothyroidism (pituitary tumor, hypothalamic tumor)

Reye's syndrome causes liver failure + encephalopathy after ___ administration for children w/influenza, VZV (ASA believed to inhibit beta oxidation --> fatty changes in liver); Children now only given ASA in ___ Alpha-1-antitrypsin deficiency (co-dominant d.o, can be severe or moderate depending on homo- or heterozygous) results in ___ overactivation; can affect lungs (emphysema 2/2 ___), but in liver --> *[HY] pathologic ___ of AAT builds up in liver endoplasmic reticulum (think of what makes protein!) --> death of hepatocytes! - on biopsy, [HY] will see AAT ___ on ___ stain that ___ digestion w/diastase (unlike what is seen in glycogen storage dz!)*

Reye's syndrome causes liver failure + encephalopathy after aspirin administration for children w/influenza, VZV (ASA believed to inhibit beta oxidation --> fatty changes in liver); Children now only given ASA in Kawasaki Alpha-1-antitrypsin deficiency (co-dominant d.o, can be severe or moderate depending on homo- or heterozygous) results in protease overactivation; can affect lungs (emphysema 2/2 autodigestion), but in liver --> *[HY] pathologic polymerization of AAT builds up in liver endoplasmic reticulum (think of what makes protein!) --> death of hepatocytes! - on biopsy, [HY] will see AAT polymers on PAS stain that resists digestion w/diastase (unlike what is seen in glycogen storage dz!)*

Rhabdomyolysis is a syndrome d/t muscle necrosis - accordingly, pts need a cause of muscle damage, including *intense physical exercise (pt stuck in desert), crush injuries (trauma), and drugs (___)* When muscle damage occurs, muscle contents spill into plasma --> *ELEVATED C___ (hallmark!) and M___*; importantly, *hyper___ + hyperphosphatemia* are common (as well as hyperuricemia) *[HY] ___ has no allosteric interactions w/O2 (no sigmoidal curve - straight up, baby)* ___ is what leads to renal toxicity in rhabdo - it can obstruct tubules, is directly toxic to proximal tubular cells, and causes vasoconstriction in medulla (--> hypoxia); additionally, volume depletion (d/t intravascular volume efflux to dead muscle tissue) worsens sx Sx of rhabdo include muscle pain, weakness, and *___ urine 2/2 myglobin*; dx is made w/high CK (>1000), urinalysis will be positive for heme with *no ___* Intravascular calcium can deposit in damaged myocytes --> hypocalcemia; be careful about tx w/calcium as tx can release calcium from myocytes --> rebound ___calcemia!! Tx: volume resuscitation, tx electrolyte changes, *dialysis for hyperkalemia*

Rhabdomyolysis is a syndrome d/t muscle necrosis - accordingly, pts need a cause of muscle damage, including *intense physical exercise (pt stuck in desert), crush injuries (trauma), and drugs (sTaTiNs)* When muscle damage occurs, muscle contents spill into plasma --> *ELEVATED CREATINE KINASE (hallmark!) and MYOGLOBIN*; importantly, *hyperkalemia + hyperphosphatemia* are common (as well as hyperuricemia) *[HY] Myoglobin has no allosteric interactions w/O2 (no sigmoidal curve - straight up, baby)* Myoglobin is what leads to renal toxicity in rhabdo - it can obstruct tubules, is directly toxic to proximal tubular cells, and causes vasoconstriction in medulla (--> hypoxia); additionally, volume depletion (d/t intravascular volume efflux to dead muscle tissue) worsens sx Sx of rhabdo include muscle pain, weakness, and *dark urine 2/2 myglobin*; dx is made w/high CK (>1000), urinalysis will be positive for heme with *no RBCs* Intravascular calcium can deposit in damaged myocytes --> hypocalcemia; be careful about tx w/calcium as tx can release calcium from myocytes --> rebound hypercalcemia!! Tx: volume resuscitation, tx electrolyte changes, *dialysis for hyperkalemia*

Rheumatoid arthritis (type ___ HS rxn) involves inflammation of the synovium; synovium usually secretes h___ acid - in RA, an unknown trigger causes overproduction of ___ (rationale for DMARD infliximab!) and IL-___ in synovium The result of synovial inflammation is synovial hypertrophy with thickening into a ___, which erodes into cartilage and bone Classically, RA p/w *___ (different from OA)*, gradual onset pain, stiffness, and swelling that is worse in the morning (+/- fever) Classically, RA involves ___ and PIP joints of the hand (often tender to touch) - *the ___ joints are spared (different from OA)* Gross deformities seen in RA include ___ deviation (d/t swelling of MCPs) and swan-neck deformity (extended PIP, flexed DIP) RA, unlike OA, is a systemic dz - *need to know the systemic associations!*

Rheumatoid arthritis (type III HS rxn) involves inflammation of the synovium; synovium usually secretes hyaluronic acid - in RA, an unknown trigger causes overproduction of TNF and IL-6 in synovium The result of synovial inflammation is synovial hypertrophy with thickening into a pannus, which erodes into cartilage and bone Classically, RA p/w *SYMMETRIC (different from OA)*, gradual onset pain, stiffness, and swelling that is worse in the morning (+/- fever) Classically, RA involves MCP and PIP joints of the hand (often tender to touch) - *the DIP joints are spared (different from OA)* Gross deformities seen in RA include ulnar deviation (d/t swelling of MCPs) and swan-neck deformity (extended PIP, flexed DIP) RA, unlike OA, is a systemic dz - *need to know the systemic associations!*

Ribosomes can be found free in cytoplasm or bound to rER; ribosomes contain ___ and proteins - proks. have ___S ribosomes (50S and 30S subunits), which is different from human cells and allows for abx targets (e.g., aminoglycosides); euks. have ___S ribosomes (60S and 40S) tRNA are synthesized by RNApol3 and contain bases that are chemically modified; tRNA takes on ___ shape (secondary structure 2/2 base pairing within molecule); key portions include anticodon, D-loop, T-loop, and 3' end Anticodon contains 3 nucleotides that pairs complementary mRNA (codes for correct AA); D-loop contains dihydrouridine, which is recognized by aminoacyl-tRNA synthetase; T-loop contains T-sai-C (ribotymidine, pseudouridine, cytidine) sequence, which is necessary for tRNA to aTTach to r___ for translation; 3' end always ends in CCA w/hydroxyl of A attached to ___ Charging is process of linking AmAc to tRNA, which is catalyzed by A___A___-tRNA synthetase (requires ATP) Mischarged tRNA means wrong AA will go in for certain codon; this process can be fixed w/h___ editing, in which aminoacyl-tRNA synthetase scrutinizes the AA and if wrong --> hydrolyzes AA or tRNA

Ribosomes can be found free in cytoplasm or bound to rER; ribosomes contain rRNA and proteins - proks. have 70S ribosomes (50S and 30S subunits), which is different from human cells and allows for abx targets (e.g., aminoglycosides); euks. have 80S ribosomes (60S and 40S) tRNA are synthesized by RNApol3 and contain bases that are chemically modified; tRNA takes on cloverleaf shape (secondary structure 2/2 base pairing within molecule); key portions include anticodon, D-loop, T-loop, and 3' end Anticodon contains 3 nucleotides that pairs complementary mRNA (codes for correct AA); D-loop contains dihydrouridine, which is recognized by aminoacyl-tRNA synthetase; T-loop contains T-sai-C (ribotymidine, pseudouridine, cytidine) sequence, which is necessary for tRNA to bind to ribosomes for translation; 3' end always ends in CCA w/hydroxyl of A attached to AmAc Charging is process of linking AmAc to tRNA, which is catalyzed by aminoacyl-tRNA synthetase (requires ATP) Mischarged tRNA means wrong AA will go in for certain codon; this process can be fixed w/hydraulic editing, in which aminoacyl-tRNA synthetase scrutinizes the AA and if wrong --> hydrolyzes AA or tRNA

Rickets/osteomalacia are 2/2 low Ca or VitD intake, resulting in poor m___ of osteoid; osteoid is at sites of new bone growth (children: growth plates, RICKETS; adults: bone turnover, OSTEOMALACIA) In rickets, growth plates thicken d/t chondrocyte expansion towards epiphysis - osteoid is laid by -blasts, but not ___ (bones thicken w/distorted growth) Rickets p/w epiphyseal widening, bowed legs (genu varum), c___ swelling (rachitic rosary), and craniotabes (soft skull) Osteomalacia (adults or children) p/w bone pain/tenderness; two classic x-ray findings are pseudofractures and L___ zones (2/2 inadequately mineralized stress fractures + bone erosion by arterial pulsation) ___ deficiency can be 2/2 poor consumption in pregnancy, reduced sun exposure, and other malabsorption syndromes - Tx w/VitD and Ca Labs reveal low VitD/Ca, ___ PTH, ___ phosphate (2/2 PTH), ___ AlkPhos (-blasts working hard to lay osteoid)

Rickets/osteomalacia are 2/2 low Ca or VitD intake, resulting in poor mineralization of osteoid; osteoid is at sites of new bone growth (children: growth plates, RICKETS; adults: bone turnover, OSTEOMALACIA) In rickets, growth plates thicken d/t chondrocyte expansion towards epiphysis - osteoid is laid by -blasts, but not mineralized (bones thicken w/distorted growth) Rickets p/w epiphyseal widening, bowed legs (genu varum), costochondral swelling (rachitic rosary), and craniotabes (soft skull) Osteomalacia (adults or children) p/w bone pain/tenderness; two classic x-ray findings are pseudofractures and Looser zones (2/2 inadequately mineralized stress fractures + bone erosion by arterial pulsation) VitD deficiency can be 2/2 poor consumption in pregnancy, reduced sun exposure, and other malabsorption syndromes - Tx w/VitD and Ca Labs reveal low VitD/Ca, high PTH, low phosphate (2/2 PTH), high AlkPhos (-blasts working hard to lay osteoid)

Rifampin and Probenecid can compete w/bilirubin for uptake --> increased indirect bili ___ syndrome is mildly decreased UDP-glucuronyltransferase (UGT) function --> mild indirect hyperbilirubinemia (worse w/stress, exercise, illness) Crigler-Najjar (worse Gilbert's) is severely reduced or absent ___ (type I is more severe) --> unconjugated hyperbilirubinemia (can cross BBB) --> kernicterus; Can tx type II w/ph___ or clofibrate, both of which induce liver glucuronidation [GCDC - GC Difficulty Conjugating] ___ is defective liver excretion --> *D*irect hyperbilirubinemia + urinary direct bilirubin and w.o pruritis (can still excrete bile salts, differentiates from cholestasis; *grossly, will see DARK liver*) ___ syndrome is mildly defective liver excretion --> direct hyperbilirubinemia (w/*R*egular liver) [DR Excrete]

Rifampin and Probenecid can compete w/bilirubin for uptake --> increased indirect bili Gilbert's syndrome is mildly decreased UDP-glucuronyltransferase (UGT) function --> mild indirect hyperbilirubinemia (worse w/stress, exercise, illness) Crigler-Najjar (worse Gilbert's) is severely reduced or absent UGT (type I is more severe) --> unconjugated hyperbilirubinemia (can cross BBB) --> kernicterus; Can tx type II w/phenobarbital or clofibrate, both of which induce liver glucuronidation *D*ubin-Johnson is defective liver excretion --> *D*irect hyperbilirubinemia + urinary direct bilirubin and w.o pruritis (can still excrete bile salts, differentiates from cholestasis; *grossly, will see DARK liver*) *R*otor's syndrome is mildly defective liver excretion --> direct hyperbilirubinemia (w/*R*egular liver)

Risk factors for lung cancer include smoking, radiation (look out for pt w/hx of H___, ___ ca), environmental toxins CXR in lung cancer will demonstrate pulmonary nodule ("coin lesion") - 1st step: ___ w/prior imaging Lung ca. mets. to l___, a___, b___, b___ (Lungs Love Attacking Boneheads and Brainiacs, *ADRENALS ARE [HY]*) Benign pulm. nodules include ___ (80% of benign lesions - histo, coccidio, TB) or hamartomas Lung ca. can be divided into ___ cell (15% - BAD) and ___ cell (85% - LESS BAD) Lung ca. can l/t SPHERE of complications: Superior vena cava synd. (f___ swelling 2/2 SVC compression), Pancoast tumor (apex tumor --> subclavian compress --> arm swelling w.o face edema +/- Horner's)/Phrenic nn. compression (hemidiaphragm), Horner, Endocrine (p___ synd.), Recurrent laryng. nn. damage (hoarse), Effusions

Risk factors for lung cancer include smoking, radiation (look out for pt w/hx of Hodgkins, breast ca), environmental toxins CXR in lung cancer will demonstrate pulmonary nodule ("coin lesion") - 1st step: compare w/prior imaging Lung ca. mets. to liver, adrenals, bone, brain (Lungs Love Attacking Boneheads and Brainiacs, *ADRENALS ARE [HY]*) Benign pulm. nodules include granulomas (80% of benign lesions - histo, coccidio, TB) or hamartomas Lung ca. can be divided into small cell (15% - BAD) and non-small cell (85% - LESS BAD) Lung ca. can l/t SPHERE of complications: Superior vena cava synd. (facial swelling 2/2 SVC compression), Pancoast tumor (apex tumor --> subclavian compress --> arm swelling w.o face edema +/- Horner's)/Phrenic nn. compression (hemidiaphragm), Horner, Endocrine (paraneoplastic synd.), Recurrent laryng. nn. damage (hoarse), Effusions

Rotator cuff holds shoulder together: Supraspinatus provides initial abduction (0-15') and is innervated by suprascapular nn. (MC injury 2/2 impingement btwn humeral head and acromion, use empty can test); Infraspinatus performs ext. rot. and abduct., innervated by suprascapular nn. (injured in pitchers); Teres minor assists in ext. rot., innervated by axillary nn.; Subscapularis performs int. rot., innervated by upper and lower subscapular nn. Deltoid is primary shoulder abductor to 90' (trap/SerAnt abduct beyond 90') Ant. dislocation of shoulder can occur w/arm abduct., ext. rot., extended (throwing football) - can result in damage to *axillary nn. (runs below humeral head - weak abduction and sensory loss over deltoid)* Proximal humerus fx. can damage blood supply l/t AVN, may also damage axillary nn. w/similar findings ELBOW: lateral epicondylitis p/w pain on wrist extension, medial epicondylitis p/w pain on wrist flexion; axial traction on pronated forearm can l/t radial head subluxation (Nursemaid's - annular ligament slips over radius); *supracondylar fx in children can damage brachial aa. and median nn.*

Rule of 4s: 4CNs in medulla, pons, above medulla 4CNs divide into 12 and are midline (3, 4, 6, 12) - others are lateral 4 midline columns start with M (motor nuclei of midline CNs, motor pathway - CST, MLF, medial lemn) 4 lateral columns start with S (side; sympathetic, spinothalamic, sensory nuc of 5, spinocerebellar) ^CAVEATS: use ipsi loss of facial pain/temp (sens nuc of V) to localize laterally, NOT to pons; don't use vestib signs to localize to pons (okay to use deafness) ^^Consider drawing picture on test during Step1 (B&B Brainstem - 21:30)

Rule of 4s: 4CNs in medulla, pons, above medulla 4CNs divide into 12 and are midline (___) - others are lateral 4 midline columns start with M (___) 4 lateral columns start with S (side; ___) ^CAVEATS: use ipsi loss of facial pain/temp (sens nuc of V) to localize laterally, NOT to pons; don't use vestib signs to localize to pons (okay to use deafness) ^^Consider drawing picture on test during Step1 (B&B Brainstem - 21:30)

CLASSIC QUESTION: child with itchy anus, how do you diagnose? CLASSIC CASE: patient with recent travel, abdominal pain, and pulmonary symptoms with eosinophilia? CLASSIC CASE: skin findings + abdominal pain + cough? CLASSIC CASE: skin findings + skinny habitus (2/2 bug affecting nutritional status) + iron deficiency anemia? CLASSIC CASE: muscle weakness after eating undercooked meat? CLASSIC CASE: skin symptoms + keratitis, diagnosed by what? CLASSIC CASE: worm squiggling across eyeball + transient skin swellings? CLASSIC CASE: child playing in sandbox with cat/dog exposure with wheezing/dyspnea and RUQ pain/hepatomegaly?

SCOTCH TAPE TEST (Enterobius vermicularis) ASCARIS LUMBRICOIDES (bowel obstruction + pneumonia + eggs in stool) STRONGYLOIDES STERCORALIS HOOKWORM (ancylostoma duodenale, necator americanus) TRICHINELLA ONCHOCERCA VOLVULUS (river blindness) - SKIN SNIPS!! LOA LOA TOXOCARA

CLASSIC CASE: infant w/recurrent infections in multiple systems (otitis, GI, candida) with absent thymic shadow and normal calcium and normal heart?

SEVERE COMBINED IMMUNODEFICIENCY - DiGeorge is on differential, but kid is normal aside from shitty immune system

SKELETAL MM. TERMS: Skeletal and cardiac mm. are examples of s___mm. (smooth mm. is not) In skeletal mm., fiber=cell, myofibril=contractile structures, sarcolemma=plasma membrane (also know T-tubule, sarc. retic. [important for Ca storage], terminal cisternae [SR near T-tubule], ___ad) Sarcomeres are contractile structures within myofibrils, made up of actin and myosin; end of sarcomeres are Z-discs (contain v___ and d___ - IFs used as tumor markers), titin is cytoskeletal prot. (tethers myosin to Z-disc) ___-Band: only thin filam. (i is thin) ___-band: only thick filam. (H is thick) ___-line: Middle ___-Band: All the thick filam. (overlapping thick and thin-Allthick) Contraction --> smaller H-band, I-band, same size A-band***

SKELETAL MM. TERMS: Skeletal and cardiac mm. are examples of striated mm. (smooth mm. is not) In skeletal mm., fiber=cell, myofibril=contractile structures, sarcolemma=plasma membrane (also know T-tubule, sarc. retic. [important for Ca storage], terminal cisternae [SR near T-tubule], triad) Sarcomeres are contractile structures within myofibrils, made up of actin and myosin; end of sarcomeres are Z-discs (contain vimentin and desmin - IFs used as tumor markers), titin is cytoskeletal prot. (tethers myosin to Z-disc) I-Band: only thin filam. (i is thin) H-band: only thick filam. (H is thick) M-line: Middle A-Band: All the thick filam. (overlapping thick and thin) Contraction --> smaller H-band, I-band, same size A-band ^NOTE: contraction --> more overlap --> less filam. by selves (H-band, I-band)

SKELETAL MM.: Thin filas. are actin, troponin (___-calcium binding, ___-tropomyosin binding, ___-inhibits myosin-actin bind), tropomyosin (thick is myosin) THIN FILAS: ___ blocks Ac-My binding at rest - Ca entry stimulates Tropom. to drop off --> allows binding (skeletal mm. is *___-filament regulated*) THICK FILAS: myosin binds ATP --> hydrolysis (ATP --> ADP + P), assumes "___" position --> ___stroke (ADP + P drop off)

SKELETAL MM.: Thin filas. are actin, troponin (C-calcium binding, T-tropomyosin binding, I-inhibits myosin-actin bind), tropomyosin (thick is myosin) THIN FILAS: tropomyosin blocks Ac-My binding at rest - Ca entry stimulates Trop. to drop off --> allows binding (skeletal mm. is *THIN-filament regulated*) THICK FILAS: myosin binds ATP --> hydrolysis (ATP --> ADP + P), assumes "cocked" position --> power stroke (ADP + P drop off)

SKETCHY AFFIRMATION: -PTH in Kidney: ___ Ca resorption, ___ PO4 resorption, increased 1,25-VitD production -PTH in GI: ___ Ca and PO4 resorption (via VitD) -PTH in Bone: ___ Ca and PO4 resorption (directly + VitD) ^REMEMBER: ParaThyroid Hormone net effect is Phosphate Trashing Hormone --- Low dose once daily bolus of PTH --> ___ bone formation in trabecular bone (activate -blasts) Continuous administration of PTH --> ___ bone resorption in cortical bone (activate -blasts --> activate -clasts (via RANK-L:RANK and *___ [MACROPHAGE-CSF, -clasts are specialized macrophages!]*) --- PTHrP is synthesized in large amounts by some tumors (i.e., ___ carcinoma, ___ lung cancer) --> hypercalcemia

SKETCHY AFFIRMATION: -PTH in Kidney: increased Ca resorption, decreased PO4 resorption, increased 1,25-VitD production -PTH in GI: increased Ca and PO4 resorption (via VitD) -PTH in Bone: increased Ca and PO4 resorption (directly + VitD) ^REMEMBER: ParaThyroid Hormone net effect is Phosphate Trashing Hormone --- Low dose once daily bolus of PTH --> increased bone formation in trabecular bone (activate -blasts) Continuous administration of PTH --> increased bone resorption in cortical bone (activate -blasts --> activate -clasts (via RANK-L:RANK and *M-CSF [MACROPHAGE-CSF, -clasts are specialized macrophages!]*) --- PTHrP is synthesized in large amounts by some tumors (i.e., renal cell carcinoma, squamous cell lung cancer) --> hypercalcemia

SLEEP PHYSIOLOGY (BAT-D): -Awake eyes open --> ___ waves (low amp, high freq) -Awake eyes closed --> ___ waves (inc amp, more in sync) -Immediate sleep (N1) --> theta waves (variable) -After that (N2) --> theta waves w/K-complexes (sudden ___ inc) and sleep spindles (sudden ___ inc)^ -Later (N3) --> ___ waves (slow waves - hardest to wake, sleep walking occurs) -REM --> low voltage pattern (saw-toothed); coordinated by PPRF! In REM --> loss of ___ (paralysis), cannot sleep walk but do dream/nightmares, night boners Throughout night/cycles (90min), *REM ___ and N3 (deep sleep) ___* Drugs (EtOH, benzos, barbs) alter sleep architecture --> ___ N3 and REM

SLEEP PHYSIOLOGY (BAT-D): -Awake eyes open --> beta waves (low amp, high freq) -Awake eyes closed --> alpha waves (inc amp, more in sync) -Immediate sleep (N1) --> theta waves (variable) -After that (N2) --> theta waves w/K-complexes (sudden amp inc) and sleep spindles (sudden freq inc)^ -Later (N3) --> delta waves (slow waves - hardest to wake, sleep walking occurs) -REM --> low voltage pattern (saw-toothed); coordinated by PPRF! In REM --> loss of motor tone (paralysis), cannot sleep walk but do dream/nightmares, night boners Throughout night/cycles (90min), *REM increases and N3 (deep sleep) decreases* Drugs (EtOH, benzos, barbs) alter sleep architecture --> less N3 and REM ^N2 is teeth grinding + *largest percentage of sleep time (~50%)*

SMALL VESSEL VASCULITIS: IgA --> IgA mediated, other three --> ANCA-mediated; *ALL Tx w/STEROIDS + ___!* *IgA Vasculitis (HenSchoPurp)*: often *follows ___ in child (URI involves Ig___)* --> IgA complex + C___ deposition in skin, GI tract, kidneys P/w p___ p___ to buttocks/legs (skin), abdominal pain + melena (GI tract), nephritis (kidneys) Biopsy: Ig___ nephropathy Feared Outcome: renal failure --- *ANCA Dzs: eosinophilic granulomatosis w/polyangitis (Churg-Strauss), granulomatosis w/polyangitis (Wegener's), microscopic polyangitis - all lead to pulmonary involvement + renal C___ RPGN ([-] IF, pauci-immune, no Ig)!!* --- *Eosinophilic Granulomatosis w/Polyangitis*: adult-onset asthma w/sinusitis + neuropathy, labs demonstrate *___philia and ___-ANCA + IgE*; p/w *PALPABLE PURUPURA* Biopsy: *necrotizing ___ inflammation w/eosinophils* --- *Granulomatosis w/Polyangiitis [Wegener's]*: triad of sinusitis, otitis media, h___ (upper and lower airway involvement), + renal involvement (hematuria & RBC casts) + skin involvement (p___); *___-ANCA mediated (UNIQUE - others are ___-ANCA!*) [C-->Criminal] Biopsy: *necrotizing granulomas in lungs/vessels* --- *Microscopic Polyangiitis*: p/w hemoptysis, kidney failure, purpura - just like GwP but *without ___ dz! (i.e., sinusitis)* Labs/Biopsy: ___-ANCA mediated with *no granulomas on biopsy*

SMALL VESSEL VASCULITIS: IgA --> IgA mediated, other three --> ANCA-mediated; *ALL Tx w/STEROIDS + CYCLOPHOSPHAMIDE!* *IgA Vasculitis (HenSchoPurp)*: often *follows URI in child (URI involves IgA)* --> IgA complex + C3 deposition in skin, GI tract, kidneys P/w palpable purpura to buttocks/legs (skin), abdominal pain + melena (GI tract), nephritis (kidneys) Biopsy: IgA nephropathy Feared Outcome: renal failure --- *ANCA Dzs: eosinophilic granulomatosis w/polyangitis (Churg-Strauss), granulomatosis w/polyangitis (Wegener's), microscopic polyangitis - all lead to pulmonary involvement + renal CRESCENTIC RPGN ([-] IF, pauci-immune, no Ig)!!* --- *Eosinophilic Granulomatosis w/Polyangitis*: adult-onset asthma w/sinusitis + neuropathy, labs demonstrate *eosinophilia and p-ANCA + IgE*; p/w *PALPABLE PURUPURA* Biopsy: *necrotizing granulomatous inflammation w/eosinophils* --- *Granulomatosis w/Polyangiitis*: triad of sinusitis, otitis media, hemoptysis (upper and lower airway involvement), + renal involvement (hematuria & RBC casts) + skin involvement (palpable purpura); *c-ANCA mediated (UNIQUE - others are p-ANCA!*) [C-->Criminal] Biopsy: *necrotizing granulomas in lungs/vessels* --- *Microscopic Polyangiitis*: p/w hemoptysis, kidney failure, purpura - just like GwP but *without UPPER AIRWAY dz! (i.e., sinusitis)* Labs/Biopsy: p-ANCA mediated with *no granulomas on biopsy*

SPINAL CORD SYNDROMES: Classic presentation for polio is ___ child with febrile illness and ___ weakness Werdnig-Hoffman Disease is spinal muscular atrophy disease with classic finding being ___ MS damages cervical ___ matter of spinal cord ALS is UMN/LMN disease (___ and ___) with NO ___ SYMPTOMS; common COD is aspiration pneumo; familial cases are seen in ___ deficiency ASA stroke leads to intact posterior columns (___) and ___ paralysis, usually in ___ fashion ___ damages ST nerve fibers crossing center (can affect anterior horn/lateral horn), leading to symptoms at level of lesion - look for ___ on Step! Subacute combined degeneration results from ___ deficiency with demyelination of ___ and lateral motor tracts (___ signs)

SPINAL CORD SYNDROMES: Classic presentation for polio is unvaccinated child with febrile illness and flaccid weakness Werdnig-Hoffman Disease is spinal muscular atrophy disease with classic finding being tongue fasciculations MS damages cervical white matter of spinal cord ALS is UMN/LMN disease (CST and ventral horn) with NO SENSORY SYMPTOMS; common COD is aspiration pneumo; familial cases are seen in zinc copper superoxide dismutase deficiency ASA stroke leads to intact posterior columns (vibration, proprioception) and flaccid paralysis, usually in acute fashion Syringomyelia damages ST nerve fibers crossing center (can affect anterior horn/lateral horn), leading to symptoms at level of lesion - look for KYPHOSCOLIOSIS on Step! Subacute combined degeneration results from B12 deficiency with demyelination of posterior columns and lateral motor tracts (UMN signs)

SYSTEMIC COMPLICATIONS OF RA (what is commonly asked related to RA): Baker's Cyst: mimicker of ___ ___: pleuritis (lung) and pericarditis (heart) +/- effusion Subcutaneous (Rheumatoid) Nodules: palpable nodules in subQ tissue of skin in people *with positive ___*; common @ elbow and on biopsy, will be *central necrosis surrounded by ___ macrophages/lymphocytes* *[HY] Eye Involvement: e___ (red painful eye w/o discharge), s___ (more severe, deep ocular pain on eye m___, often bilateral w/dark red eyes; REMEMBER - episclera is more superficial --> not as bad), uveitis (anterior/posterior, can have floaters/vision loss)* Secondary Sjogren's: ___ glands --> dry mouth and eyes Osteoporosis: accelerated in RA and worsened w/___ Coronary Dz: increased risk in RA ___: 2/2 autoimmune dz (apple-green birefringence) Felty Syndrome: triad of RA + ___megaly + neutropenia; only seen in pts w/many years of severe dz

SYSTEMIC COMPLICATIONS OF RA (what is commonly asked related to RA): Baker's Cyst: mimicker of DVT Serositis: pleuritis (lung) and pericarditis (heart) +/- effusion Subcutaneous (Rheumatoid) Nodules: palpable nodules in subQ tissue of skin in people *with positive rheumatoid factor*; common @ elbow and on biopsy, will be *central necrosis surrounded by pallisading macrophages/lymphocytes* *[HY] Eye Involvement: episcleritis (red painful eye w/o discharge), scleritis (more severe, deep ocular pain on eye movement, often bilateral w/dark red eyes; REMEMBER - episclera is more superficial --> not as bad), uveitis (anterior/posterior, can have floaters/vision loss)* Secondary Sjogren's: salivary/lacrimal glands --> dry mouth and eyes Osteoporosis: accelerated in RA and worsened w/steroids Coronary Dz: increased risk in RA Amyloidosis: 2/2 autoimmune dz (apple-green birefringence) Felty Syndrome: triad of RA + splenomegaly + neutropenia; only seen in pts w/many years of severe dz

___ receives CSF The cavernous sinus is a large collection of veins that has structures through it (___ - 7); compression leads to cavernous sinus syndrome with HA, *___ eyes*, ocular paralysis, ___ syndrome, and sensory loss over V1/V2

Sagittal sinus receives CSF The cavernous sinus is a large collection of veins that has structures through it (CN3, 4, V1, V2, 6, sympathetic fibers, and internal carotid artery); compression leads to cavernous sinus syndrome with HA, *swollen eyes*, ocular paralysis, Horner's syndrome, and sensory loss over V1/V2

Salivary electrolytes are produced by acinar and ductal cells; ___ cells produce isotonic saliva (Na, Cl, K, HCO3 same as plasma), ___ cells remove NaCl and secrete K/___ (bicarb helps w/raises pH to protect against acid); Saliva becomes *___tonic w/higher concentration of K-HCO3 compared to plasma* Flow rate can influence saliva contents (faster rate --> less time for ductal modification --> ___ like plasma, also more HCO3 2/2 incr. metabolism and CO2 production); A___ also acts on salivary glands (incr. Na absorp. & K secr.) Saliva production is increased by ___ NS (via *muscarinic M1 and M3 receptors*) >> sympathetic NS; muscarinic antagonists (at___) --> dry mouth, muscarinic agonists (pi___, cholinesterase poisoning) --> wet mouth

Salivary electrolytes are produced by acinar and ductal cells; acinar cells produce isotonic saliva (Na, Cl, K, HCO3 same as plasma), ductal cells remove NaCl and secrete K/HCO3 (bicarb helps w/raises pH to protect against acid); Saliva becomes *HYPOtonic w/higher concentration of K-HCO3 compared to plasma* Flow rate can influence saliva contents (faster rate --> less time for ductal modification --> more like plasma, also more HCO3 2/2 incr. metabolism and CO2 production); Aldosterone also acts on salivary glands (incr. Na absorp. & K secr.) Saliva production is increased by parasympathetic NS (via *muscarinic M1 and M3 receptors*) >> sympathetic NS; muscarinic antagonists (atropine) --> dry mouth, muscarinic agonists (pilocarpine, cholinesterase poisoning) --> wet mouth

Sarcoidosis is immune-mediated granulomatous dz w/hallmark of *___ granulomas (not much dead tissue in granuloma - diff. from TB)* At cellular level, sarcoid is driven by *[HY] accumulation of Th___ CD___+ T-cells (high CD___/CD___ ratio in BAL fluid!)*, resulting in *IL-2/IFN-gamma secretion* Sarcoid p/w lung sx (cough, dyspnea), skin involvement (*look for e___ - painful tender nodules d/t panniculitis*), eye involvement (u___), *heart block (2/2 conduction dz)*, kidneys, CNS (*Bell's palsy, motor loss*) CXR/CT will demonstrate extensive *___ lymphadenopathy* Labs will demonstrate hyper___ (d/t 1-alpha hydroxylase activity --> incr. vitD levels) and high ___ levels *Black women more common!* - tx w/steroids, immunosuppressants

Sarcoidosis is immune-mediated granulomatous dz w/hallmark of *non-caseating granulomas (not much dead tissue in granuloma - diff. from TB)* At cellular level, sarcoid is driven by *[HY] accumulation of Th1 CD4+ T-cells (high CD4/CD8 ratio in BAL fluid!)*, resulting in *IL-2/IFN-gamma secretion* Sarcoid p/w lung sx (cough, dyspnea), skin involvement (*look for erythema nodosum - painful tender nodules d/t panniculitis*), eye involvement (uveitis), *heart block (2/2 conduction dz)*, kidneys, CNS (*Bell's palsy, motor loss*) CXR/CT will demonstrate extensive *hilar lymphadenopathy* Labs will demonstrate hypercalcemia (d/t 1-alpha hydroxylase activity --> incr. vitD levels) and high ACE levels *Black women more common!* - tx w/steroids, immunosuppressants

___ is MC injured carpal bone (usually 2/2 FOOSH) - p/w pain in snuff box; complications include AVN and nonunion 2/2 ___ of radial aa (especially common in waist fx); ___ dislocation can impinge median nn and cause CTS Carpal tunnel runs ___ transverse carpal ligament (flexor retinaculum), CTS is entrapment of CT and p/w *median nn dysfunction (motor loss of ___ muscles + lateral ___, sensory loss of lateral 3.5 fingers *but not thenar eminence d/t palmar cutaneous sensory nn.*) - look for Tinel sign (Tapping) or Phalen maneuver (Flex wrist) RFs include pregnancy, obesity, *[HY] ___ (33% of pts 2/2 enlarged hands/feet - look for increasing glove/shoe size), [HY] dialysis (2/2 dialysis-related ___ [beta-2 microglobulin])* Guyon's canal carries ulnar nn. and aa. into wrist (*[HY] Guyon's canal is ___ transverse carpal ligament - diff. from carpal tunnel*) - classically seen in cyclists and p/w loss of ___ of fingers (interossei), hypothenar mm. loss, and sensory loss to medial 1.5 digits Greenstick fx is ___ bone from fracture - does not extend through width of bone (often at distal radius); Torus (buckle) fx is when axial force applied to immature bone l/t ___ of cortex (toRuS - Remains Solid)

Scaphoid is MC injured carpal bone (usually 2/2 FOOSH) - p/w pain in snuff box; complications include AVN and nonunion 2/2 retrograde flow of radial aa (especially common in waist fx); Lunate dislocation can impinge median nn and cause CTS Carpal tunnel runs below transverse carpal ligament (flexor retinaculum), CTS is entrapment of Ct and p/w *median nn dysfunction (motor loss of thenar muscles + lateral lumbricals, sensory loss of lateral 3.5 fingers *but not thenar eminence d/t palmar cutaneous sensory nn.*) - look for Tinel sign (Tapping) or Phalen maneuver (Flex wrist) RFs include pregnancy, obesity, *[HY] acromegaly (33% of pts 2/2 enlarged hands/feet - look for increasing glove/shoe size), [HY] dialysis (2/2 dialysis-related amyloidosis [beta-2 microglobulin])* Guyon's canal carries ulnar nn. and aa. into wrist (*[HY] Guyon's canal is ABOVE transverse carpal ligament - diff. from carpal tunnel*) - classically seen in cyclists and p/w loss of abduction/adduction of fingers (interossei), hypothenar mm. loss, and sensory loss to medial 1.5 digits Greenstick fx is bent bone from fracture - does not extend through width of bone (often at distal radius); Torus (buckle) fx is when axial force applied to immature bone l/t buckling of cortex (toRuS - Remains Solid)

Scatter of data points relative to difference in means influences likelihood that difference is d/t chance vs. real (# data points also influences); Little scatter in data + means far apart = more likely difference in means is ___ (real or chance?) Three key tests compare groups: t-test, ANOVA, chi-square (NOTE: quantitative variables are reported as number [i.e., age]; categorical variables reported as *PERCENTAGES [i.e., X% take drug; BEWARE - don't confuse as quantitative!]*) T-test compares to two mean *___ (quant or cat?)* values (i.e., ages); yields p-value that is *chance ___ is correct (i.e., no difference btwn means)* - if p<0.05 --> reject null hypot., believe difference is statistically significant Common Qs: what test to compare quant. difference of means? what p makes test significant? if p is high, why is that the case (need more ___)? ANOVA compares >2 *___ (quant or cat?)* means (i.e., t-test w/3 groups) Chi-Sq compares 2+ *___ (quant or cat?)* variables (i.e., yes-no, low-med-hi - *BEWARE OF %s!!*)

Scatter of data points relative to difference in means influences likelihood that difference is d/t chance vs. real (# data points also influences); Little scatter in data + means far apart = more likely difference in means is real Three key tests compare groups: t-test, ANOVA, chi-square (NOTE: quantitative variables are reported as number [i.e., age]; categorical variables reported as *PERCENTAGES [i.e., X% take drug; BEWARE - don't confuse as quantitative!]*) T-test compares to two mean *QUANTITATIVE* values (i.e., ages); yields p-value that is *chance null hypothesis is correct (i.e., no difference btwn means)* - if p<0.05 --> reject null hypot., believe difference is statistically significant Common Qs: what test to compare quant. difference of means? what p makes test significant? if p is high, why is that the case (need more pts)? ANOVA compares >2 *QUANTITATIVE* means (i.e., t-test w/3 groups) Chi-Sq compares 2+ *CATEGORICAL* variables (i.e., yes-no, low-med-hi - *BEWARE OF %s!!*)

Schizophrenia is recurrent episodes of ___ (delus, disorg thot, halluc), ___ dysfunction (poor attn, learning, mems), and ___ sx Schizo has ___ hallucinations; delusions are fixed, false beliefs (paranoid, grandiose); disorganized thots manifest with ___ (changing topics frequently) or circumstantial speech (roundabout answers) ___ sx are absence of normal behaviors (flat affect, poverty of speech [alogia], asociality, anhedonia) - can persist despite tx Schizo occurs in young adults w/male predominance; RFs include living in urban areas, ___, OB complications, early pot use; schizo carries high risk of suicide Path involves excess central ___; gross path will reveal ___ ventricle enlargement; micro path reveals dendritic ___ loss Schizophrenia is dx by 2+ (delusion, hallucination, disorg speech [i.e., psychosis], disorg behavior, negative sx) x1mo, + cont signs x6mos; ___ d/o meets criteria for shizophrenia, but for <6mo

Schizophrenia is recurrent episodes of psychosis (delus, disorg thot, halluc), cognitive dysfunction (poor attn, learning, mems), and negative sx Schizo has auditory hallucinations; delusions are fixed, false beliefs (paranoid, grandiose); disorganized thots manifest with tangential (changing topics frequently) or circumstantial speech (roundabout answers) Negative sx are absence of normal behaviors (flat affect, poverty of speech [alogia], asociality, anhedonia) - can persist despite tx Schizo occurs in young adults w/male predominance; RFs include living in urban areas, immigration, OB complications, early pot use; schizo carries high risk of suicide Path involves excess central dopamine; gross path will reveal lateral ventricle enlargement; micro path reveals dendritic spine loss Schizophrenia is dx by 2+ (delusion, hallucination, disorg speech [i.e., psychosis], disorg behavior, negative sx) x1mo, + cont signs x6mos; schizophreniform d/o meets criteria for shizophrenia, but for <6mo

Scleroderma (systemic sclerosis) has complex pathophys involving endothelial damage --> *___ activation* --> *C___ deposition (taut skin w.o wrinkles)* SS usually affects middle-aged women in two distinct syndromes: ___ (2) Diffuse SS is diffuse skin thickening a/w Raynaud's phenomena (usually the initial presentation) and *early visceral organ involvement (___ dz --> renal failure [can present in acute crisis w/HTN, tx with ___], GI tract --> dysmotility, heart --> ___/myocarditis)*; amongst the most lethal organ involvements is ___ dz (--> pulmonary ___ + interstitial lung dz) - check for anti-___ Ab Limited SS (CREST) has limited skin involvement (hands, face) and five hallmark sx: ___ (calcium deposits in subQ tissue --> bumps on elbows, knees, fingers; look for x-rays) and *anti-C___ antibody*, Raynaud's phenomena, E___ dysmotility (difficulty swallowing [2/2 collagen deposition] + GERD [*esophageal ___TONIA - contrast to achalasia*]), Sclerodactyly (fibrosis of skin of hand --> puffy fingers, shiny skin, wood-feeling skin), Tel___ Limited SS has more benign clinical course, *but can still lead to PULMONARY DZ* ANA can be elevated in both forms; look for *anti-Scl70 (anti-___ I) in diffuse* Tx symptoms (not immunosuppressants)

Scleroderma (systemic sclerosis) has complex pathophys involving endothelial damage --> *fibroblast activation* --> *COLLAGEN deposition (taut skin w.o wrinkles)* SS usually affects middle-aged women in two distinct syndromes: Diffuse and Limited (CREST) Diffuse SS is diffuse skin thickening a/w Raynaud's phenomena (usually the initial presentation) and *early visceral organ involvement (renal dz --> renal failure [can present in acute crisis w/HTN, tx with ACEi], GI tract --> dysmotility, heart --> pericarditis/myocarditis)*; amongst the most lethal organ involvements is pulmonary dz (--> pulmonary HTN + interstitial lung dz) - check for anti-Scl70 Ab Limited SS (CREST) has limited skin involvement (hands, face) and five hallmark sx: Calcinosis (calcium deposits in subQ tissue --> bumps on elbows, knees, fingers; look for x-rays) and *anti-Centromere antibody*, Raynaud's phenomena, Esophageal dysmotility (difficulty swallowing [2/2 collagen deposition] + GERD [*esophageal HYPOTONIA - contrast to achalasia*]), Sclerodactyly (fibrosis of skin of hand --> puffy fingers, shiny skin, wood-feeling skin), Telangiectasia Limited SS has more benign clinical course, *but can still lead to PULMONARY DZ* ANA can be elevated in both forms; look for *anti-Scl70 (anti-topoisomerase I) in diffuse* Tx symptoms (not immunosuppressants)

Sebhorrheic dermatitis is red plaques with scale on ___/scalp; path. not understood; tx w/topical antifungals + corticosteroids Melanocytic nevus (mole) are benign melanocytic neoplasms (tan/brown, uniform, round, <6mm); moles can develop dysplasia --> melanoma (look out for ___ - criteria for concern?) Acquired (not congenital) moles can be ___ (growth along dermal-epidermal junct.), ___ (growth extends to dermis), ___ (found only in dermis) - REMEMBER: melanocytes normally exist on epi.-derm. junction Pseudofolliculitis barbae is inflammation from trapped hair that is a/w ___ (80% black men) ___ is common skin disorder of whites; its inflamm. skin condition with chronic redness of nose and cheeks +/- papules and pustules (*no comedones*) - pts may have facial flushing w/stimuli (EtOH) or phymatous rosacea (big, lumpy ___)

Sebhorrheic dermatitis is red plaques with scale on face/scalp; path. not understood; tx w/topical antifungals + corticosteroids Melanocytic nevus (mole) are benign melanocytic neoplasms (tan/brown, uniform, round, <6mm); moles can develop dysplasia --> melanoma (look out for ABCDE) Acquired (not congenital) moles can be junctional (growth along dermal-epidermal junct.), compound (growth extends to dermis), intradermal (found only in dermis) - REMEMBER: melanocytes normally exist on epi.-derm. junction Pseudofolliculitis barbae is inflammation from trapped hair that is a/w shaving (80% black men) Rosacea is common skin disorder of whites; its inflamm. skin condition with chronic redness of nose and cheeks +/- papules and pustules (*no comedones*) - pts may have facial flushing w/stimuli (EtOH) or phymatous rosacea (big, lumpy nose)

Seborrheic keratosis are benign tumors 2/2 *[HY] proliferation of ___ KERATINOCYTES* of the trunk w/characteristic "stuck-on" appearance; biopsy shows dark cells and keratin-filled "horn cysts" *Leser-Trelat Sign is explosive onset of multiple itchy SK lesions 2/2 [HY] ___ (___ is most common)*; if present in STEP1 Q --> investigate for g. adeno.) Verrucae are warts, cellular proliferation 2/2 HPV - biopsy shows *___ (cell type) w/cytoplasmic clearing* (vulgaris --> skin) Erythema nodosum is type ___ HS rxn and type of panniculitis (fat inflamm., subQ) - many triggers, incl. infxn (Strep), Crohn's, sarcoid, coccidiomycosis (remember Sketchy); clinically, nodules are *PAIN___ and on shins*; pathology reveals *___ panniculitis (inflamm. of septa btwn fat lobules)

Seborrheic keratosis are benign tumors 2/2 *[HY] proliferation of IMMATURE KERATINOCYTES* of the trunk w/characteristic "stuck-on" appearance; biopsy shows dark cells and keratin-filled "horn cysts" *Leser-Trelat Sign is explosive onset of multiple itchy SK lesions 2/2 [HY] malignancy (gastric adenocarcinoma is most common)*; if present in STEP1 Q --> investigate for g. adeno.) Verrucae are warts, cellular proliferation 2/2 HPV - biopsy shows *koilocytosis w/cytoplasmic clearing* (vulgaris --> skin) Erythema nodosum is type IV HS rxn and type of panniculitis (fat inflamm., subQ) - many triggers, incl. infxn (Strep), Crohn's, sarcoid, coccidiomycosis; clinically, nodules are *PAINFUL and on shins*; pathology reveals *septal panniculitis (inflamm. of septa btwn fat lobules)

Secondary adrenal insufficiency (problem is pituitary - decreased ___ secretion) is most often d/t ___ l/t pituitary atrophy - must WEAN pts off of steroids In secondary adrenal insufficiency, ___ have hyperpigmentation or hyperkalemia (RAAS intact)

Secondary adrenal insufficiency (problem is pituitary - decreased ACTH secretion) is most often d/t glucocorticoid therapy l/t pituitary atrophy - must WEAN pts off of steroids In secondary adrenal insufficiency, will not have hyperpigmentation or hyperkalemia (RAAS intact)

Secretin (S-sells) functions to ___ pH of small intestine - accordingly, released in response to H+ Secretin functions to increase pancreatic ___ secretion (allows pancreatic enzymes to function, protects small intestines) and suppress gastrin release --> decrease acid release into stomach (*not in ___!*) [Secretin Soothes Stomach]

Secretin (S-sells) functions to raise pH of small intestine - accordingly, released in response to H+ Secretin functions to increase pancreatic HCO3 secretion (allows pancreatic enzymes to function, protects small intestines) and suppress gastrin release --> decrease acid release into stomach (*not in GASTRINOMAS!*)

Secretory pathway is steps for secretory prots. (translation in cytosol --> rER lumen --> Golgi --> vesicle --> exocytosis) & relies on S___ S___ (found on N-terminal of translated prots.) which pull free ribosomes to ER membrane to create rER --> prots. can enter ER lumen SSs are recognized by ___ (SRPs), ribonucleoproteins found in cytosol (remove SSs --> move prot. to ER); rER has SRP receptor --> allows prot. to be translated into ER lumen Vesicles can be coated for different forms of transport - inc. clathrin, COPI, COPII Clathrin-coated vesicle transport from C___ M___ --> Golgi (receptor-mediated endocytosis w/clathrin-coated pits) COPI is Golgi-to-ER (___grade transport) and COPII is ER-to-Golgi (___grade transport)

Secretory pathway is steps for secretory prots. (translation in cytosol --> rER lumen --> Golgi --> vesicle --> exocytosis) & relies on signal sequences (found on N-terminal of translated prots.) which pull free ribosomes to ER membrane to create rER --> prots. can enter ER lumen SSs are recognized by signal recognition particles (SRPs), ribonucleoproteins found in cytosol (remove SSs --> move prot. to ER); rER has SRP receptor --> allows prot. to be translated into ER lumen Vesicles can be coated for different forms of transport - inc. clathrin, COPI, COPII Clathrin-coated vesicle transport from cell membrane --> Golgi (receptor-mediated endocytosis w/clathrin-coated pits) COPI is Golgi-to-ER (retrograde transport) and COPII is ER-to-Golgi (anterograde transport)

Sens./spec. don't answer "if neg. --> what is prob. I don't have dz?" - need PPV/NPV PPV = (___/[___ (all + tests)]) - top row of table; NPV = (TN/[TN + FN (all - tests)]) - bottom row of table *[HY SKILL] Test w/sens. = 80%, spec. = 50%, prev. = 40%; 1) create 100 pts and fill in table (___ w/dz, ___ w.o dz; ___ w/dz and + test, ___ w/dz and - test; ___ w.o dz and + test, ___ w.o dz and - test), 2) calc. PPV/NPV as needed* *[HY] PPV and NPV are HIGHLY DEPENDENT on ___ of dz (differ from sens./spec.) - PPV is higher when prev. is ___, NPV is higher when prev. is ___ (this is intuitive - think abnml EKG in young healthy person vs old unhealthy, more likely FP in young and TP in old)* In graph: moving cutoff changes PPV and NPV (if more strict/rightward shift --> raises PPV, if more liberal/leftward shift --> lowers PPV; exact opposite of NPV) *SAMPLE:* lower fasting glucose for diabetes dx --> what happens? sens: inc; spec: dec; PPV: dec; NPV: inc

Sens./spec. don't answer "if neg. --> what is prob. I don't have dz?" - need PPV/NPV PPV = (TP/[TP + FP (all + tests)]) - top row of table; NPV = (TN/[TN + FN (all - tests)]) - bottom row of table *[HY SKILL] Test w/sens. = 80%, spec. = 50%, prev. = 40%; 1) create 100 pts and fill in table (40 w/dz, 60 w.o dz; 32 w/dz and + test, 8 w/dz and - test; 30 w.o dz and + test, 30 w.o dz and - test), 2) calc. PPV/NPV as needed* *[HY] PPV and NPV are HIGHLY DEPENDENT on prevalence of dz (differ from sens./spec.) - PPV is higher when prev. is higher, NPV is higher when prev. is lower (this is intuitive - think abnml EKG in young healthy person vs old unhealthy, more likely FP in young and TP in old)* In graph: moving cutoff changes PPV and NPV (if more strict/rightward shift --> raises PPV, if more liberal/leftward shift --> lowers PPV; exact opposite of NPV) *SAMPLE:* lower fasting glucose for diabetes dx --> what happens? sens: inc; spec: dec; PPV: dec; NPV: inc

Separation Anxiety D/o is distress when separating home/parents w/worry about losing attachment figures; children will c/o *___* - tx w/CBT Tourette D/o is recurrent tics in motor/speech that *[HY] commonly co-occur with ___*; Dx: x1y, onset before ___y, multiple motor tics + >0.9 phonic tics; Tx: neuroleptics, ___ (VMAT-2 inhibitor - blocks reuptake of dopamine), clonidine/guanfacine (a2 agonists)

Separation Anxiety D/o is distress when separating home/parents w/worry about losing attachment figures; children will c/o *physical sx* - tx w/CBT Tourette D/o is recurrent tics in motor/speech that *[HY] commonly co-occur with psych disorders (ADHD, OCD)*; Dx: x1y, onset before 18y, multiple motor tics + >0.9 phonic tics; Tx: neuroleptics, tetrabenazine (VMAT-2 inhibitor - blocks reuptake of dopamine), clonidine/guanfacine (a2 agonists)

Seronegative Spondyloarthritis (arthritis w/negative RF) include PAIR: Psoriatic A, Ankylosing S, Inflammatory BD, Reactive A All SS are A-Immune conditions mediated by T-cells - they are all as___ ___arthritis (contrast with RA - symmetric polyarthritis), have axial spine inflamm. (SI joints, worse in morning), dactylitis (sausage fingers), and ___ (inflamm. @ tendon attachment) HLA-___ is *strongly a/w SSs (90% of AS cases, 50% PA cases)* AnkSpond is new bone formation in spine (ankylosis --> joint jusion) is seen in young males, p/w *inflammatory back pain that improves w/___* - look for *___(x-ray?)* Long-term complications include uveitis, aorititis (aortic ___), and restrictive lung dz (poor mobility) Labs in AnkSpond --> elevated ESR/CRP

Seronegative Spondyloarthritis (arthritis w/negative RF) include PAIR: Psoriatic A, Ankylosing S, Inflammatory BD, Reactive A All SS are A-Immune conditions mediated by T-cells - they are all asymmetric oligoarthritis (contrast with RA - symmetric polyarthritis), have axial spine inflamm. (SI joints, worse in morning), dactylitis (sausage fingers), and enthesitis (inflamm. @ tendon attachment) HLA-B27 is *strongly a/w SSs (90% of AS cases, 50% PA cases)*[itBin27y.o] AnkSpond is new bone formation in spine (ankylosis --> joint jusion) is seen in young males, p/w *inflammatory back pain that improves w/exercise* - look for *BAMBOO SPINE* Long-term complications include uveitis, aorititis (aortic regurg), and restrictive lung dz (poor mobility) Labs in AnkSpond --> elevated ESR/CRP

Seronegative Spondyloarthritis (arthritis w/negative RF) include PAIR: ___ All SS are A-Immune conditions mediated by T-cells - they are all asymmetric oligoarthritis (contrast with RA - symmetric polyarthritis), have axial spine inflamm. (SI joints, worse in morning), dactylitis (sausage fingers), and enthesitis (inflamm. @ tendon attachment) HLA-___ is *strongly a/w SSs (90% of AS cases, 50% PA cases)* PsorArt (33% psoriasis pts) will have *___ abnormalities (onycholysis, pitting)*; PA is asymmetric polyarthritis (diff. from RA - symmetric) w/*___ involvement (--> ___ deformity!)* IBD can l/t type I SS (<5 large joints w/___) or type II SS (>5 small joints w.o ___) ReacArt follows infxn (days-to-weeks), resolves after 12mo; usually follows GI/GU infxn (*e.g., C___*, but Shig, Camp, Ecoli, Salm, Chlam, Yersin - She Caught Every Student Cheating Yesterday and overREACTed) - often co-occurs w/conjunctivitis, urethritis (Reiter's - can't see/pee/tree)

Seronegative Spondyloarthritis (arthritis w/negative RF) include PAIR: Psoriatic A, Ankylosing S, Inflammatory BD, Reactive A All SS are A-Immune conditions mediated by T-cells - they are all asymmetric oligoarthritis (contrast with RA - symmetric polyarthritis), have axial spine inflamm. (SI joints, worse in morning), dactylitis (sausage fingers), and enthesitis (inflamm. @ tendon attachment) HLA-B27 is *strongly a/w SSs (90% of AS cases, 50% PA cases)*[itBin27y.o] PsorArt (33% psoriasis pts) will have *nail abnormalities (onycholysis, pitting)*; PA is asymmetric polyarthritis (diff. from RA - symmetric) w/*DIP involvement (--> pencil-in-cup deformity!)* IBD can l/t type I SS (<5 large joints w/GI sx) or type II SS (>5 small joints w.o GI sx)[I-->gI,2>1-->5joints] ReacArt follows infxn (days-to-weeks), resolves after 12mo; usually follows GI/GU infxn (*e.g., Chlamydia*, but Shig, Camp, Ecoli, Salm, Chlam, Yersin - She Caught Every Student Cheating Yesterday and overREACTed) - often co-occurs w/conjunctivitis, urethritis (Reiter's - can't see/pee/tree)

___ cells in men Support Sperm (regulate Spermatogenesis); Sertoli cells are stimulated by ___ and are supported by Leydig cell ___ (acts as paracrine; KEY POINT: need both FSH and LH for normal spermatogenesis) ___ between Sertoli cells form *blood-testis barrier (isolate sperm from autoimmune attack)* Sertoli cells also secrete *___, which inhibits FSH release from pituitary (respond to and inhibit fSh)* Sertoli cells also secrete *___*, which raises and maintains local testosterone levels (intra-testicular testosterone concentration is 100x peripheral levels - why exogenous testosterone --> fall in sperm count, can't tap into this awesomeness) In development, ___ cells produce *anti-Mullerian hormone --> degeneration of ___ (paramesonephric) ducts (fallopian tubes, uterus)* ___ is a mutation of the androgen receptor - SRY gene exists, TDF --> testicles, MIH --> no fallopian tubes/uterus, but no cellular response from androgens --> no ___ male genitalia; will p/w pubertal child who develops breasts, but amenorrhea, no ___ hair, and abdominal testes

Sertoli cells in men Support Sperm (regulate Spermatogenesis); Sertoli cells are stimulated by fSh and are supported by Leydig cell testosterone (acts as paracrine; KEY POINT: need both FSH and LH for normal spermatogenesis) Tight junctions between Sertoli cells form *blood-testis barrier (isolate sperm from autoimmune attack)* Sertoli cells also secrete *inhibin B, which inhibits FSH release from pituitary (respond to and inhibit fSh)* Sertoli cells also secrete *androgen-binding protein*, which raises and maintains local testosterone levels (intra-testicular testosterone concentration is 100x peripheral levels - why exogenous testosterone --> fall in sperm count, can't tap into this awesomeness) In development, Sertoli cells produce *anti-Mullerian hormone --> degeneration of Mullerian (paramesonephric) ducts (fallopian tubes, uterus)* Complete Androgen Insensitivity Syndrome (CAIS) is a mutation of the androgen receptor - SRY gene exists --> TDF --> testicles, MIH --> no fallopian tubes/uterus, no cellular response from androgens --> no internal or external male genitalia; will p/w pubertal child who develops breasts, but amenorrhea, no armpit/pubic hair, and abdominal testes

___ is obstruction of salivary flow by stones - seen in pts w/decreased flow through salivary glands (dehydration, anticholinergics) - tx w/NSAIDs and hydration ___ is infxn of salivary gland (often 2/2 sialolithiasis) - usually d/t Staph or anaerobes Mumps can p/w *PAROTITIS* - often bilateral --- Salivary tumors (usually benign & of parotid gland) can be malignant/invasive if painful w/CN___ involvement Pleomorphic adenoma is benign mixed tumor w/painless, mobile mass @ jaw angle; *[HY] pathology will reveal mixed ___ and ___ tissue cells*, RF is prior radiation therapy [PLaid is a MESs] Warthin's tumor is of parotid tumor and seen in *S___!* - on histology, *[HY] look for c___ filled w/fluid + lymph tissue forming ___ centers* [Germs Smoke Cysts in War] Mucoepidermoid carcinoma (malignant) is seen in pts w/prior radiation - *[HY] pathology will show mixed ___ and ___-secreting cells!* [MucoEpi - Mucous and Epithelium]

Sialolithiasis is obstruction of salivary flow by stones - seen in pts w/decreased flow through salivary glands (dehydration, anticholinergics) - tx w/NSAIDs and hydration Sialadenitis is infxn of salivary gland (often 2/2 sialolithiasis) - usually d/t Staph or anaerobes Mumps can p/w *PAROTITIS* - often bilateral --- Salivary tumors (usually benign & of parotid gland) can be malignant/invasive if painful w/CN7 involvement Pleomorphic adenoma is benign mixed tumor w/painless, mobile mass @ jaw angle; *[HY] pathology will reveal mixed epithelial and stromal tissue cells*, RF is prior radiation therapy [PLaid is a MESs - Pleomorphic adenomas have Mixed Epithelial and Stromal cells] Warthin's tumor is of parotid tumor and seen in *SMOKERS!* - on histology, *[HY] look for cysts filled w/fluid + lymph tissue forming germinal centers* [Germs Smoke Cysts in War] Mucoepidermoid carcinoma (malignant) is seen in pts w/prior radiation - *[HY] pathology will show mixed squamous and mucus-secreting cells!* [MucoEpi - Mucous and Epithelium]

Sickle cell anemia is AR disorder with abnormal beta-chains --> abnormal HbA; root cause is *abnormal beta globin gene (HbS; ___ mutation --> ___ (exact mut?), polar protein --> nonpolar protein)* If one abnormal beta chain --> sickle cell ___; if both abnormal beta chains --> sickle cell ___ When HbS is deoxygenated, it becomes poorly soluble --> p___ in hypoxic environments (+ dehydration and acidosis); RBCs form "crescents" (also cause ___ ESR) Sickle cell trait has no sickling, but can develop loss of ___ ability in the renal medulla + increased risk of renal medullary carcinoma Pts w/sickle cell trait do have protection against malaria (P. falciparum); IMPORTANTLY, *pts are ___ protected from infxn, but infxn is more mild - when infected --> increased clearance* Dx of SCA/SCT: electrophoresis (Dz: ___ HbA, 2-15% HgF, ~90% ___; Trait: 55% ___, 40% HbS), sickling test NOTE: some pts can be born w/1 sickle beta gene, 1 thalassemia beta gene - phenotype is dependent on severity of thalassemia mutation

Sickle cell anemia is AR disorder with abnormal beta-chains --> abnormal HbA; root cause is *abnormal beta globin gene (HbS; point mutation --> E6V, polar protein --> nonpolar protein)* If one abnormal beta chain --> sickle cell trait; if both abnormal beta chains --> sickle cell disease When HbS is deoxygenated, it becomes poorly soluble --> polymerization in hypoxic environments (+ dehydration and acidosis); RBCs form "crescents" (also cause decreased ESR) Sickle cell trait has no sickling, but can develop loss of concentrating ability in the renal medulla + increased risk of renal medullary carcinoma Pts w/sickle cell trait do have protection against malaria (P. falciparum); IMPORTANTLY, *pts are not protected from infxn, but infxn is more mild - when infected --> increased clearance* Dx of SCA/SCT: electrophoresis (Dz: no HbA, 2-15% HgF, ~90% HbS; Trait: 55% HbA, 40% HbS), sickling test NOTE: some pts can be born w/1 sickle beta gene, 1 thalassemia beta gene - phenotype is dependent on severity of thalassemia mutation

___ (found in bone marrow) are nucleated red cell precursors w/granules containing non-heme iron Sideroblastic anemia is microcytic anemia w/sideroblasts in peripheral blood! Sideroblastic anemia occurs when there is a failure to make ___ inside RBCs; accordingly, no protoporphyrin is around for iron to bind and make heme --> ___ accumulates in mitochondria Sideroblastic anemias are usually 2/2 toxins: *___ (its a mitochondrial toxin)*, ___ deficiency (cofactor for d-ALA synthase, RLStep of protoporphyrin synthesis - *look for TB pts taking Isoniazid!*), lead poisoning X-linked defect in ALA ___ gene can lead to congenital sideroblastic anemia; *IMPORTANTLY, [know this] this condition responds to tx w/___* Labs: microcytic anemia w/iron overload, low proto___ levels (unless d/t lead poisoning)

Sideroblasts (found in bone marrow) are nucleated red cell precursors w/granules containing non-heme iron Sideroblastic anemia is microcytic anemia w/sideroblasts in peripheral blood! Sideroblastic anemia occurs when there is a failure to make protoporphyrin inside RBCs; accordingly, no protoporphyrin is around for iron to bind and make heme --> iron accumulates in mitochondria Sideroblastic anemias are usually 2/2 toxins: *ALCOHOL (its a mitochondrial toxin)*, B6 deficiency (cofactor for d-ALA synthase, RLStep of protoporphyrin synthesis - *look for TB pts taking Isoniazid!*), lead poisining X-linked defect in ALA synthase gene can lead to congenital sideroblastic anemia; *IMPORTANTLY, [know this] this condition responds to tx w/VitB6* Labs: microcytic anemia w/iron overload, low protoporphyrin levels (unless d/t lead poisoning)

Single celled fungi are ___, while multicellular are molds/mushrooms; accordingly, fungi that can live as both are ___ (mold in cold, yeast in heat) There are three primary categories for fungal infections: pneumonia (histo, blasto, coccidio), skin infections (tinea, sporothirix), and opportunistic infections (candida, aspergillus, cryptococcus, mucormycosis, PJP) Pneumonia fungal infections are dimorphic (except coccidio) and will be mold in the cold and yeast in the heat; importantly, this means no transmission will occur ___ (transmission cannot occur from ___ form) - you get disease by inhaling fungus *IMPORTANTLY, many fungal pneumonias mimic ___* Aspergillus is opportunistic fungal infection that occurs in immunocompromised; it has no geographic preference and is NOT monomorphic (i.e., *WILL HAVE ___ - different from pneumonia fungi*); patients will be VERY sick (vs ___ pneumonias, which are less severe)

Single celled fungi are yeast, while multicellular are molds/mushrooms; accordingly, fungi that can live as both are dimorphic There are three primary categories for fungal infections: pneumonia (histo, blasto, coccidio), skin infections (tinea, sporothirix), and opportunistic infections (candida, aspergillus, cryptococcus, mucormycosis, PJP) Pneumonia fungal infections are dimorphic (except cocci) and will be mold in the cold and yeast in the heat; importantly, this means no transmission will occur person-to-person (transmission cannot occur from yeast form) - you get disease by inhaling fungus *IMPORTANTLY, many fungal pneumonias mimic TB* Aspergillus is opportunistic fungal infection that occurs in immunocompromised; it has no geographic preference and is NOT monomorphic (i.e., *WILL HAVE HYPHAE - different from pneumonia fungi*); patients will be VERY sick (vs fungal pneumonias, which are less severe)

Sjogren's is autoimmune destruction of salivary and lacrimal glands, p/w dry eyes (sensation of dirt/debris in eyes) and dry mouth (difficulty chewing dry food, cavities, *bad ___*) [sicca symptoms] Extraglandular dz includes xerosis (dry, skaly skin in axilla), arthralgias, ___ Sjogren's is lymphocyte-mediated A-Immune d.o (type ___ HS rxn) with biopsy demonstrating *lymphocytic si___ (BuZzWoRd! - lymphocytic infiltration of salivary glands)* - will result in bilateral ___ enlargement Sjogren's can be primary or secondary (often 2/2 Rheumatoid or SLE and *[HY] seen in half of pts with p___ b___ ___!*) Complications: *___ lymphoma (increased risk 2/2 inflammation in glands - look for UNILATERAL GLAND SWELLING THAT IS PERSISTENT!)*, ___ lupus (driven by anti-Ro/anti-La Abs - rash + congenital heart block) Antibodies: ANA (garbage), Rheumatoid Factor (better, seen in primary and secondary dz), *anti-___ (Ro) and anti-___ (La) antibodies (MONEY!)* Dx (not HY): Schirmer test (ocular signs), salivary testing (need subjective + objective evidence [testing or Abs]) Tx: good hygiene (tooth brushing to avoid cavities), pilo___

Sjogren's is autoimmune destruction of salivary and lacrimal glands, p/w dry eyes (sensation of dirt/debris in eyes) and dry mouth (difficulty chewing dry food, cavities, *bad breath*) [sicca symptoms] Extraglandular dz includes xerosis (dry, skaly skin in axilla), arthralgias, Raynaud's phenomenon Sjogren's is lymphocyte-mediated A-Immune d.o (type IV HS rxn) with biopsy demonstrating *lymphocytic sialadenitis (BuZzWoRd! - lymphocytic infiltration of salivary glands)* - will result in bilateral parotid enlargement Sjogren's can be primary or secondary (often 2/2 Rheumatoid or SLE and *[HY] seen in half of pts with primary biliary cirrhosis!*) Complications: *B-cell lymphoma (increased risk 2/2 inflammation in glands - look for UNILATERAL GLAND SWELLING THAT IS PERSISTENT!)*, neonatal lupus (driven by anti-Ro/anti-La Abs - rash + congenital heart block) Antibodies: ANA (garbage), Rheumatoid Factor (better, seen in primary and secondary dz), *anti-SSA (Ro) and anti-SSB (La) antibodies (MONEY!)* Dx (not HY): Schirmer test (ocular signs), salivary testing (need subjective + objective evidence [testing or Abs]) Tx: good hygiene (tooth brushing to avoid cavities), pilocarpine

Skin has three layers: epidermis (keratinocytes), dermis (connective tissue), subcutaneous fat/hypodermis Epidermis is divided into five layers (stratum): ___ (*Come Let's Get Some Beers*) Basalis has ___ cells Spinosum has *___ (connections btwn keratinocytes) that form spines* Granulosum contains granules (keratohyalin) --> stain ___ Lucidum is clear d/t containing dead skin cells Corneum has a___ cells, d/t being filled with keratin filaments *___ contains blood vessels --> where edema accumulates*

Skin has three layers: epidermis (keratinocytes), dermis (connective tissue), subcutaneous fat/hypodermis Epidermis is divided into five layers (stratum): corneum, lucidum, granulosum, spinosum, basale (*Come Let's Get Some Beers*) Basalis has stem cells Spinosum has *desmosomes (connections btwn keratinocytes) that form spines* Granulosum contains granules (keratohyalin) --> stain dark Lucidum is clear d/t containing dead skin cells Corneum has anucleated cells, d/t being filled with keratin filaments *Dermis contains blood vessels --> where edema accumulates*

Skin lesions can be primary (2/2 dz process - macule, papule, vesicle) or secondary (modification of primary lesion 2/2 trauma - scale, crust, erode, ulcer) Flat lesion can be <1cm (macule - freckle) or >1cm (___ - birthmark) Raised lesions can be <1cm (papule - mole) or >1cm (___ - psoriasis) Fluid-filled lesions (blisters) can be <1cm (vesicle - chickenpox) or >1cm (___ - bullous pemphigoid); ___ is pus-filled vesicle (acne) Wheal is *smooth*, elevated papule/rash that is *ITCHY d/t dermal edema* (seen in ___ of allergic rxn) ___ is secondary lesion 2/2 peeling/flaking of str. corneum ___ is secondary lesion 2/2 dried exudate of primary lesion (i.e., impetigo)

Skin lesions can be primary (2/2 dz process - macule, papule, vesicle) or secondary (modificationof primary lesion 2/2 trauma - scale, crust, erode, ulcer) Flat lesion can be <1cm (macule - freckle) or >1cm (patch - birthmark) Raised lesions can be <1cm (papule - mole) or >1cm (plaque - psoriasis) Fluid-filled lesions (blisters) can be <1cm (vesicle - chickenpox) or >1cm (bulla - bullous pemphigoid); pustule is pus-filled vesicle (acne) Wheal is *smooth*, elevated papule/rash that is *ITCHY d/t dermal edema* (seen in urticaria of allergic rxn) Scale is secondary lesion 2/2 peeling/flaking of str. corneum Crust is secondary lesion 2/2 dried exudate of primary lesion (i.e., impetigo)

Slow (type I) twitch mm. (appear red d/t ___) have slow time to peak tension, but have more myoglobin + mitochondria (oxidative phosphorylation) --> resists fatigue (postural muscles of ___)[One-slOw-myOglobin-Ox.phos.] Fast (type II) twitch mm. (appear white/pale) have fast time to peak tension, use a___ glycolysis d/t less myoglobin + mitochondria (muscles of eye)[fasT-Two] *1 Slow Red Ox* *2 Fast White Antelopes*

Slow (type I) twitch mm. (appear red d/t myoglobin) have slow time to peak tension, but have more myoglobin + mitochondria (oxidative phosphorylation) --> resists fatigue (postural muscles of spine) Fast (type II) twitch mm. (appear white/pale) have fast time to peak tension, use anaerobic glycolysis d/t less myoglobin + mitochondria (muscles of eye) *1 Slow Red Ox* *2 Fast White Antelopes*

Sm. muscle (___ striated) can change resistance to flow (blood vessels, intestines); SmoMusc differences from striated muscles include: do not need A___P___, demonstrate slow/sustained contraction, different mechanism by which Ca stimulates contraction In SmoMusc, ___ are modified to control contraction (*thick filament regulated - contrast to SkeMusc*); only *___ MLC stimulates contraction* (MLC-Kin --> stimulates contract., MLC-Phos --> prevents contract.) Calmodulin binds calcium, *CAM-Ca activates ___* (*this is how SmoMusc has different mechanism of Ca --> contract*) L-type Ca channels (bind dihydropyridines) allow Ca to enter cells - when blocked (-dipine drugs) --> vascular muscle relaxation (d/t less [Ca])

Sm. muscle (not striated) can change resistance to flow (blood vessels, intestines); SmoMusc differences from striated muscles include: do not need ActPots, demonstrate slow/sustained contraction, different mechanism by which Ca stimulates contraction In SmoMusc, myosin light chains are modified to control contraction (*thick filament regulated - contrast to SkeMusc*); only *phosphorylated MLC stimulates contraction* (MLC-Kin --> stimulates contract., MLC-Phos --> prevents contract.) Calmodulin binds calcium, *CAM-Ca activates MLC-Kin* (*this is how SmoMusc has different mechanism of Ca --> contract*) L-type Ca channels (bind dihydropyridines) allow Ca to enter cells - when blocked (-dipine drugs) --> vascular muscle relaxation (d/t less [Ca])

Small cell lung ca. is made of poorly differentiated small cells (*dark blue cells - neuroendocrine tumors w/___ mutation*), classically seen in male smokers with *___ (C or P?) lesion* B/c Small-CC is neuroendocrine tumor, there are many associated paraneoplastic syndromes (3 As: ACTH - ___, ADH - ___, Abs - ___) --- Squamous cell carcinoma is hilar (___ - C or P?) mass that produce keratin (*path: ___ like SCC of skin*) Squa-CC presents in male smokers and can lead to ___ secretion (*hyper___, stones/bones*) --- ___ is MC tumor in non-smokers (esp. women) and arises in periphery --- ___ is poorly differentiated large cells (central or peripheral) that carries poor prognosis - seen in smokers, tx w/surgery --- ___ is subtype of adenocarcinoma (mucinous + nonmucinous type) that appears like PNA on CXR, carries excellent prognosis --- Pleura is lined by ___ cells - can become malignant to cause mesothelioma (only RF is asbestos exposure), which carries poor prognosis

Small cell lung ca. is made of poorly differentiated small cells (*dark blue cells - neuroendocrine tumors w/MYC mutation*), classically seen in male smokers with *CENTRAL lesion* B/c Small-CC is neuroendocrine tumor, there are many associated paraneoplastic syndromes (3 As: ACTH - Cushing's, ADH - SIADH, Abs - LEMS) --- Squamous cell carcinoma is hilar (central) mass that produce keratin (*path: keratin pearls like SCC of skin*) Squa-CC presents in male smokers and can lead to PTHrP secretion (*hypercalcemia, stones/bones*) --- Adenocarcinoma is MC tumor in non-smokers (esp. women) and arises in periphery --- Large cell carcinoma is poorly differentiated large cells (central or peripheral) that carries poor prognosis - seen in smokers, tx w/surgery --- Bronchioalveolar carcinoma is subtype of adenocarcinoma (mucinous + nonmucinous type) that appears like PNA on CXR, carries excellent prognosis --- Pleura is lined by mesothelial cells - can become malignant to cause mesothelioma (only RF is asbestos exposure), which carries poor prognosis

Small intestine should be sterile - can develop bacterial ___, p/w bloating, flatulence, and discomfort (+/- chronic diarrhea) Bacterial overgrowth can be 2/2 altered ___ (diabetes, scleroderma) or partial/intermittent ___ (adhesions, Crohn's) Dx: lactulose test (bacteria will metabolize some --> a___ poo) Tx: abx *D-xylose will be abnormal (i.e., no serum Xylose rise; altered normal mucosa --> can't absorb)*

Small intestine should be sterile - can develop bacterial overgrowth, p/w bloating, flatulence, and discomfort (+/- chronic diarrhea) Bacterial overgrowth can be 2/2 altered motility (diabetes, scleroderma) or partial/intermittent obstruction (adhesions, Crohn's) Dx: lactulose test (bacteria will metabolize some --> acidic poo) Tx: abx *D-xylose will be abnormal (i.e., no serum Xylose rise; altered normal mucosa --> can't absorb)*

Small intestine will contain *___* on histology (can't see grossly) - differentiating factor, incr. surface area for absorption (contains some crypts [with goblet cells], but much smaller than colon); Villi are projections of *[HY] ___ layer* and also contain microvilli (epithelial cell membrane projections - hard to see microscopically) Grossly, small intestine contains ___ circulares (can see grossly) - *folds of mucosa and ___ layers!* Goblet cells are seen in small intest. (also large) - ___ in number from duodenum to ileum, *not normally seen in stomach (can occur w/intestinal m___)* Brunner's glands are found in ___ (layer?) and produce alkaline fluid to neutralize stomach acid (only found in ___ [anatomic location?]) - BGs thicken in peptic ulcer dz! Peyer's patches are lymph aggregates located in the submucosa that are found only in *___ (jejunum doesn't have PPs or BGs!)* Finally, small intestine can contain ___ - lymphatic channels within villi (important for fat absorption)

Small intestine will contain *VILLI* on histology (can't see grossly) - differentiating factor, incr. surface area for absorption (contains some crypts [with goblet cells], but much smaller than colon); Villi are projections of *[HY] MUCOSAL layer* and also contain microvilli (epithelial cell membrane projections - hard to see microscopically) Grossly, small intestine contains plicae circulares (can see grossly) - *folds of mucosa and submucosal layers!* Goblet cells are seen in small intest. (also large) - increase in number from duodenum to ileum, *not normally seen in stomach (can occur w/intestinal metaplasia)* Brunner's glands are found in submucosa and produce alkaline fluid to neutralize stomach acid (only found in duodenum) - BGs thicken in peptic ulcer dz! Peyer's patches are lymph aggregates located in the submucosa that are found only in *ileum (jejunum doesn't have PPs or BGs!)* Finally, small intestine can contain lacteal - lymphatic channels within villi (important for fat absorption)

SmoMusc tone has two major regulators that are *[HY]: c___ in cell and m___ phosphorylation* - can be modified by G-prots. and 2nd messengers (cAMP, cGMP, IP3) -IP3 --> ___ release from SR --> contraction (think of 3DAGS sketchy) -cAMP --> MLC kinase inhibition --> ___ (think of milrinone) -cGMP --> MLC phosphatase activation --> ___ (think of nesiritide) Accordingly, can derive: -Gs --> incr. cAMP --> -MLC-Kin and ___ -Gi --> decr. cAMP --> +MLC-Kin and ___ -Gq --> incr. IP3 --> ___ Nitric Oxide is synthesized *[HY] indirectly from ___ cells from L-arg___* - many stimuli for production (e.g., *AC___*, bradykinin, shear stress); once synthesized (by EndoCell), NO diffuses to SMCs --> activates guanylyl cyclase, GTP becomes cGMP --> MLC ___ active --> relaxation

SmoMusc tone has two major regulators that are *[HY]: calcium in cell and myosin light chain phosphorylation* - can be modified by G-prots. and 2nd messengers (cAMP, cGMP, IP3) -IP3 --> Ca release from SR --> contraction (think of 3DAGS sketchy) -cAMP --> MLC kinase inhibition --> relaxation (think of milrinone) -cGMP --> MLC phosphatase activation --> relaxation (think of nesiritide) Accordingly, can derive: -Gs --> incr. cAMP --> -MLC-Kin and relaxation -Gi --> decr. cAMP --> +MLC-Kin and contraction -Gq --> incr. IP3 --> contraction Nitric Oxide is synthesized *[HY] indirectly from endothelial cells from L-arginine* - many stimuli for production (e.g., *ACETYLCHOLINE*, bradykinin, shear stress); once synthesized (by EndoCell), NO diffuses to SMCs --> activates guanylyl cyclase, GTP becomes cGMP --> MLC phosphatase active --> relaxation

Sodium ___ (alka seltzer) can lead to alkalosis and/or fluid retention Calcium ___ (tums) can lead to hypercalcemia (can l/t constipation; use to tx hypocalcemia) - can also cause *Milk Alkali Syndrome (hypercalcemia + MetAlk [contraction alk + carbonate] + renal failure)* and *Acid Rebound (acid surge after antacid leaves stomach)* ___ Hydroxide can cause constipation (aluminum decrease GI motility) and hypophosphatemia (aluminum binds phosphate - use in renal failure, but can cause aluminum toxicity in renal pts) ___ hydroxide can l/t diarrhea (osmotic laxative) or hypermagnesemia (hypotension, bradycardia, cardiac arrest) - combine w/aluminum to form MAALOX (antacid w/balance constip./diarrhea effect) *T___, fluoroquinolones, isoniazid are poorly absorbed w/antacids!*

Sodium bicarbonate (alka seltzer) can lead to alkalosis and/or fluid retention Calcium carbonate (tums) can lead to hypercalcemia (can l/t constipation; use to tx hypocalcemia) - can also cause *Milk Alkali Syndrome (hypercalcemia + MetAlk [contraction alk + carbonate] + renal failure)* and *Acid Rebound (acid surge after antacid leaves stomach)* Aluminum Hydroxide can cause constipation (aluminum decrease GI motility) and hypophosphatemia (aluminum binds phosphate - use in renal failure, but can cause aluminum toxicity in renal pts) Magnesium hydroxide can l/t diarrhea (osmotic laxative) or hypermagnesemia (hypotension, bradycardia, cardiac arrest) - combine w/aluminum to form MAALOX (antacid w/balance constip./diarrhea effect) *Tetracyclines, fluoroquinolones, isoniazid are poorly absorbed w/antacids!*

Solutes in Renal Failure: Regulated solutes (Na, K) are tightly controlled such that there's little concentration change in renal failure Unregulated solutes (Cr, BUN) are not tightly regulated, such that plasma levels rise in renal failure KEY POINT: if GFR is cut in half, ___ won't change, but ___ will rise --- Filtered load is the mass of a substance that is cleared per minute (plasma concentration [mg/mL] x GFR [mL/min]) - reported in mg/min Accordingly, filtered load of Na and K will *___* in the setting of renal failure (excrete less), filtered load of BUN remains *EXACT SAME* --- Excretion rate is the amount of substance pee-ed out per unit time (urine concentration [meq/mL] x urine flow [mL/hr]) - reported in meq/hr Excretion of Na, K and BUN will all remain *___* --- Fractional excretion = [amount excreted]/[amount filtered] Accordingly, fraction excretion of Na and K will *___* while fractional excretion of BUN will remain *EXACT SAME* ^All this makes sense because even though you're filtering less, you want to keep Na and K the same concentration in plasma --> need to excrete same amount (= amount of intake) to maintain those plasma level

Solutes in Renal Failure: Regulated solutes (Na, K) are tightly controlled such that there's little concentration change in renal failure Unregulated solutes (Cr, BUN) are not tightly regulated, such that plasma levels rise in renal failure KEY POINT: if GFR is cut in half, Na and K won't change, but BUN and Cr will rise --- Filtered load is the mass of a substance that is cleared per minute (plasma concentration [mg/mL] x GFR [mL/min]) - reported in mg/min Accordingly, filtered load of Na and K will *DECREASE* in the setting of renal failure (excrete less), filtered load of BUN remains *EXACT SAME* --- Excretion rate is the amount of substance pee-ed out per unit time (urine concentration [meq/mL] x urine flow [mL/hr]) - reported in meq/hr Excretion of Na, K and BUN will all remain *EXACT SAME* --- Fractional excretion = [amount excreted]/[amount filtered] Accordingly, fraction excretion of Na and K will *INCREASE* while fractional excretion of BUN will remain *EXACT SAME* ^All this makes sense because even though you're filtering less, you want to keep Na and K the same concentration in plasma --> need to excrete same amount (= amount of intake) to maintain those plasma level

Somatic cells are most body cells (diploid) while ___ are reproductive cells (haploid); somatic cells replicate through m___ and gametes replicate through m___ G___ mutation is in gametes --> transmitted to offspring and found in every cell of body; S___ mutation is acquired during lifespan of cell --> not transmitted (think cancer) C___ --> both Contribute to phenotype (ABO grouping); alpha-1 AT deficiency displays codominance (M-normal, S-moderate, Z-severe), such that MM and ZZ display wildly different protein lvls P___ --> Proportion (Percentage) of allele that exPress phenotype (i.e., BRCA, AD dz w/incomplete penetrance) E___ --> variations in phenotype of gene (i.e., NF1 w/vastly different severities but 100% penetrance) P___ --> one gene mutation w/multiple phenotype effects (i.e., CF --> lungs, pancreas) G___ heterogeneity --> same phenotype from diff genes/muts; A___ heterogeneity (form of gen heterogeneity) --> one dz, mult genes, single location (e.g., CF); L___ heterogeneity --> mut at different loci lead to same phenotype (one dz, mult genes, mult locals; e.g., retinitis pigmentosa)

Somatic cells are most body cells (diploid) while gametes are reproductive cells (haploid); somatic cells replicate through mitosis and gametes replicate through meiosis Germline mutation is in gametes --> transmitted to offspring and found in every cell of body; Somatic mutation is acquired during lifespan of cell --> not transmitted (think cancer) Codominance --> both Contribute to phenotype (ABO grouping); alpha-1 AT deficiency displays codominance (M-normal, S-moderate, Z-severe), such that MM and ZZ display wildly different protein lvls Penetrance --> Proportion (Percentage) of allele that exPress phenotype (i.e., BRCA, AD dz w/incomplete penetrance Expressivity --> variations in phenotype of gene (i.e., NF1 w/vastly different severities but 100% penetrance) Pleiotropy --> one gene mutation w/multiple phenotype effects (i.e., CF --> lungs, pancreas) Genetic heterogeneity --> same phenotype from diff genes/muts; Allelic heterogeneity (form of gen heterogeneity) --> one dz, mult genes, single location (e.g., CF); Locus heterogeneity --> mut at different loci lead to same phenotype (one dz, mult genes, mult locals; e.g., retinitis pigmentosa)

___ is physical symptoms not explained by medical dz (RFs: female, less educated, minority, low SES) *HY: management of somatization involves regular visits with ___*; also r/o serious medical dz and avoid ___ sx ___ is somatic sx that cause distress + excessive time/energy devoted to sx that is persistent (>6mo) ___ is preoccupation of having undiagnosed illness with no sx (i.e., do I have cancer?) ___ D/o follows stressor --> voluntary neuro sx (inability to speak/move, blindness); exam demonstrates findings incompatible w/dz and La belle indifference (lack of concern for sx) Factitious (Munchausen) D/o is falsified sx (+/- tests/surgeries) done consciously for ___ (motive? pt feels better in sick role); RFs include female, unmarried, and ___ worker

Somatization is physical symptoms not explained by medical dz (RFs: female, less educated, minority, low SES) *HY: management of somatization involves regular visits with the same physicians*; also r/o serious medical dz and avoid debating sx Somatic Symptom Disorder is somatic sx that cause distress + excessive time/energy devoted to sx that is persistent (>6mo) Illness Anxiety D/o is preoccupation of having undiagnosed illness with no sx (i.e., do I have cancer?) Conversion D/o follows stressor --> voluntary neuro sx (inability to speak/move, blindness); exam demonstrates findings incompatible w/dz and La belle indifference (lack of concern for sx) Factitious (Munchausen) D/o is falsified sx (+/- tests/surgeries) done consciously for attention (pt feels better in sick role); RFs include female, unmarried, and healthcare worker ^MALINGERING: consciously falsified medical sx for secondary gain (i.e., worker's comp)

___ ("wet blanket") is released by D-cells throughout GI tract, but found in nerves throughout body (reason it has wide-ranging effects) Somatostatin production is ___ when pH is low (i.e., haven't eaten - don't want digestive enzymes); somatostatin production is ___ when pH is high (i.e., just ate - want digestive enzymes) Somatostatin release is ___ by vagus nerve (vagus is "rest and digest", want to digest --> want less somatostatin) ___ is somatostatin analog used in bleeding varices and rare tumors (VIPoma, carcinoid syndrome, acromegaly [inhibit GH release], glucagonoma, gastrinoma)

Somatostatin ("wet blanket") is released by D-cells throughout GI tract, but found in nerves throughout body (reason it has wide-ranging effects) Somatostatin production is increased when pH is low (i.e., haven't eaten - don't want digestive enzymes); somatostatin production is decreased when pH is high (i.e., just ate - want digestive enzymes) Somatostatin release is inhibited by vagus nerve (vagus is "rest and digest", want to digest --> want less somatostatin) Octreotide is somatostatin analog used in bleeding varices and rare tumors (VIPoma, carcinoid syndrome, acromegaly [inhibit GH release], glucagonoma, gastrinoma)

Some genes have variable number of trinuc repeats that varies; Trinuc repeat d/o have increased # of repeats Importantly, dz-ed gene demonstrates unstable repeat expansions; # of repeats increases from gen-to-gen (key point: genetic abnormality changes over time); this leads to A___ - dz severity worsens over generations (w/earlier onset) Fragile X Syndrome is ___ (inheritance?) d/o of ___ gene w/___ repeat (>200) that leads to DNA methylation and silencing of FMR1; FXS leads to intellectual disability with *hallmark being macroorchidism (big ole testes)* Friedreich's Ataxia is AR d/o ___ gene w/GAA repeats, leading to decreased frataxin in mitochondria (affects brain, heart [*HY: ___*], pancreas) Huntington's Dz is AD d/o of ___ gene w/___ repeat, leading to degeneration of basal ganglia --> chorea + dementia Myotonic Dystrophy is AD d/o with two types: type I - DMPK gene w/CTG expansion --> abn myotonic dystrophy protein kinase; type II - CNBP gene w/CCTG (tetranuc) repeats; manifests with musc weak/wast in 20s/30s and *M___* + long/narrow face and hollowed cheeks; MD is multi-system d/o (hypogonadism [low test, high FSH], cataracts, arrhythmia [AV block, AFib], frontal balding, lung issues)

Some genes have variable number of trinuc repeats that varies; Trinuc repeat d/o have increased # of repeats Importantly, dz-ed gene demonstrates unstable repeat expansions; # of repeats increases from gen-to-gen (key point: genetic abnormality changes over time); this leads to anticipation - dz severity worsens over generations (w/earlier onset) Fragile X Syndrome is X-dom d/o of FMR1 gene w/CGG repeat (>200) that leads to DNA methylation and silencing of FMR1; FXS leads to intellectual disability with *hallmark being macroorchidism (big ole testes)* *[Cojones Get Grand in Dominant Fragile Male Residents]* Friedreich's Ataxia is AR d/o frataxin gene w/GAA repeats, leading to decreased frataxin in mitochondria (affects brain, heart [*HY: HOCM*], pancreas) Huntington's Dz is AD d/o of HTT gene w/CAG repeat, leading to degeneration of basal ganglia --> chorea + dementia *[Chorea And Gonzo in the head]* Myotonic Dystrophy is AD d/o with two types: type I - DMPK gene w/CTG expansion --> abn myotonic dystrophy protein kinase; type II - CNBP gene w/CCTG (tetranuc) repeats; manifests with musc weak/wast in 20s/30s and *MYOTONIA* + long/narrow face and hollowed cheeks; MD is multi-system d/o (hypogonadism [low test, high FSH], cataracts, arrhythmia [AV block, AFib], frontal balding, lung issues)

Someone feeling fatigued after a hot shower should raise suspicion for ___ In MS, ___-cells react to myelin antigens, specifically ___; ___ is commonly released to recruit macrophages MS is a type ___ hypersensitivity reaction MS can present as ___, MLF syndrome (eye can't move ___ on lateral gaze), or bladder dysfunction

Someone feeling fatigued after a hot shower should raise suspicion for multiple sclerosis In MS, T-cells react to myelin antigens, specifically myelin basic protein; interferon-gamma is commonly released to recruit macrophages MS is a type IV hypersensitivity reaction MS can present as optic neuritis, MLF syndrome (eye can't move medially on lateral gaze), or bladder dysfunction

Spermatogenesis requires a temperature that is slightly lower than body temperature (*___ cells are particularly Sensitive*, Leydig cells less so --> testosterone production remains stable) Varicocele is a dilation of ___ of spermatic veins ("bag of worms" - worse w/valsalva), which can lead to infertility 2/2 increased temperature and poor blood flow; *[HY] Varicoceles are more common on ___ d/t venous drainage to ___, which can be compressed btwn aorta and SMA*; *[HY] Varicoceles are a/w ___ (cancer?), especially on right side* In cryptorchidism, testes can be exposed to higher than normal temperatures --> low sperm counts; *additionally, [HY] there are low ___ levels (secreted by ___ cells) --> high FSH* Cryptorchidism carries increased risk of ___ tumors, inguinal hernias, and *testicular torsion* Bilateral undescended testes can be *2/2 congenital adrenal hyperplasia w/XX pt + ambiguous genitalia - check ___ and ___ for impending adrenal crisis!*; testes may also be absent (agenesis, atrophy)

Spermatogenesis requires a temperature that is slightly lower than body temperature (*Sertoli cells are particularly Sensitive*, Leydig cells less so --> testosterone production remains stable) Varicocele is a dilation of pampiniform plexus of spermatic veins ("bag of worms" - worse w/valsalva), which can lead to infertility 2/2 increased temperature and poor blood flow; *[HY] Varicoceles are more common on left d/t venous drainage to left renal vein, which can be compressed btwn aorta and SMA*; *[HY] Varicoceles are a/w renal cell carcinoma, especially on right side* In cryptorchidism, testes can be exposed to higher than normal temperatures --> low sperm counts; *additionally, [HY] there are low inhibin levels (secreted by Sertoli cells) --> high FSH* Cryptorchidism carries increased risk of germ cell tumors, inguinal hernias, and *testicular torsion* Bilateral undescended testes can be *2/2 congenital adrenal hyperplasia w/XX pt + ambiguous genitalia - check ACTH and cortisol for impending adrenal crisis!*; testes may also be absent (agenesis, atrophy)

Spina bifida occulta --> missing bones with ___; meningocele --> meninges bulge but not cord; myelominingocele --> meninges + ___ bulge out (seen with ___); all these are 2/2 failur of caudal neural tube to close Anencephaly is failure of ___ neural tube to close and is not compatible with life; *fetus has ___-like appearance* and mother has polyhydramnios High ___ suggests NTD Holoprosencephaly is failure of ___ to close --> no hemispheres (seen in Patau, Edward's) with cleft lip/palate and cyclopia

Spina bifida occulta --> missing bones with tuft of hair; meningocele --> meninges bulge but not cord; myelominingocele --> meninges + cord bulge out (seen with Chiari malformation); all these are 2/2 failur of caudal neural tube to close Anencephaly is failure of rostral neural tube to close and is not compatible with life; *fetus has frog-like appearance* and mother has polyhydramnios High AFP suggests NTD Holoprosencephaly is failure of prosencephalon to close --> no hemispheres (seen in Patau, Edward's) with cleft lip/palate and cyclopia

Spirometry measures volume of air expired by time In restrictive lung dz, spirogram curve will look similar, but with lower total volume (have problem getting air ___ - starting w/___ air, *curve looks SIMILAR just ___*) In obstructive lung dz, spirogram curve will have much lower slope (have problem getting air ___, *curve looks ___*) In RLD, FEV1 and FVC decrease to same degree, FEV1/FVC is ___ In OLD, FEV1 decreases significantly more than FVC, *FEV1/FVC is ___* Spirometry cannot measure RV or FRC

Spirometry measures volume of air expired by time In restrictive lung dz, spirogram curve will look similar, but with lower total volume (have problem getting air in - starting w/less air, *curve looks SIMILAR just smaller*) In obstructive lung dz, spirogram curve will have much lower slope (have problem getting air out, *curve looks DIFFERENT*) In RLD, FEV1 and FVC decrease to same degree, FEV1/FVC is normal In OLD, FEV1 decreases significantly more than FVC, *FEV1/FVC is decreased* Spirometry cannot measure RV or FRC

Spleen functions to filter blood - white pulp (*blood exposed to B-/T-cells that can be activated if Ag's present + macrophages that can phagocytose*) that contains: 1) f___, 2) p___, and 3) m___ Follicles contain ___-cells (like in lymph node!) Periarteriolar lymphatic sheath (surround arteries) contain ___-cells (like Paracortex in lymph node!) Marginal zone (surrounds PALS) contains ___ that remove debris (*VERY important for removing e___ organisms!*) R___ (*filters blood to remove old RBCs + storage of platelets*) contains sinusoids - open endothelium that allow cells to pass in and out; when exiting sinusoids, encounter macrophages in splenic cords (macrophages phagocytose old RBCs) ^*KEY BUZZWORD FOR SPLEEN SINUSOID ENDOTHELIUM: ___-hoop endothelium*

Spleen functions to filter blood - white pulp (*blood exposed to B-/T-cells that can be activated if Ag's present + macrophages that can phagocytose*) that contains: 1) follicle, 2) periarteriolar lymphatic sheath, and 3) marginal zone Follicles contain B-cells Periarteriolar lymphatic sheath (surround arteries) contain T-cells Marginal zone (surrounds PALS) contains macrophages that remove debris (*VERY important for removing encapsulated organisms!*) Red pulp (*filters blood to remove old RBCs + storage of platelets*) contains sinusoids - open endothelium that allow cells to pass in and out; when exiting sinusoids, encounter macrophages in splenic cords (macrophages phagocytose old RBCs) ^*KEY BUZZWORD FOR SPLEEN SINUSOID ENDOTHELIUM: barrel-hoop endothelium*

Splenic dysfunction leads to increased risk of infxn by *e___ organisms*! Encapsulated organisms are resistant to phagocytosis via capsule - mechanism of clearing these pathogens is usually via m___ phagocytosis & complement (___ --> complement --> macrophage binding) In splenic dysfunction, m___-zone (area in splenic white pulp) macrophages are LOST; in addition, B-cells are lost --> decreased Ig___ --> decreased complement activation/opsonization --> less macrophage phagocytosis --> *increased susceptibility to infxn* *S___ is most dangerous asplenic infxn (50% mortality)*; others include H. flu, N. meningitidis, S. pyogenes, E. coli, Salmonella, *malaria and babesia (RBC infxn)* Asplenia can be found w/splenectomy, ITP, hereditary spherocytosis, sickle cell anemia Postsplenectomy findings include: H___ bodies (nuclear remnants), target cells, ___cytosis/___cytosis (can't sequester/remove)

Splenic dysfunction leads to increased risk of infxn by *encapsulated organisms*! Encapsulated organisms are resistant to phagocytosis via capsule - mechanism of clearing these pathogens is usually via macrophage phagocytosis & complement (IgG --> complement --> macrophage binding) In splenic dysfunction, marginal-zone (area in splenic white pulp) macrophages are LOST; in addition, B-cells are lost --> decreased IgM --> decreased complement activation/opsonization --> less macrophage phagocytosis --> *increased susceptibility to infxn* *Strep pneumo is most dangerous asplenic infxn (50% mortality)*; others include H. flu, N. meningitidis, S. pyogenes, E. coli, Salmonella, *malaria and babesia (RBC infxn)* Asplenia can be found w/splenectomy, ITP, hereditary spherocytosis, sickle cell anemia Postsplenectomy findings include: Howell-Jolly bodies (nuclear remnants), target cells, thrombocytosis/lymphocytosis (can't sequester/remove)

Squam. cell carcinoma can develop from premalignant ___ (sun exposure --> atypical epiderm. keratinocyte growth [AcKe]; incr. degree of dysplasia --> SCC) AKs are red/brown papules in sun-exposed area w/biopsy revealing hyper___ (thickening of str. corneum), epidermal cell dysplasia, and *[HY] ___KERATOSIS (retained nucs. in str. ___)* SCC arises from squams. in epidermis of older pts - <5% met. to regional nodes SCC appears as red, scaling plaque w/sharp borders --> ulceration, crusting, bleeding; classic pathology is *K___ P___!* RFs: sun exposure, chronic ___, chronic skin inflammation (burns, chronic ulcers, draining sinus), arsenic exposure K___ is benign SCC variant, appearing as dome-nodule w/central hyperkeratosis; classic course is rapid growth --> regression Bowen's Dz is SCC in situ (well-demarcated, scaly plaque)

Squam. cell carcinoma can develop from premalignant actinic keratosis (sun exposure --> atypical epiderm. keratinocyte growth [AcKe]; incr. degree of dysplasia --> SCC) AKs are red/brown papules in sun-exposed area w/biopsy revealing hyperkeratosis (thickening of str. corneum), epidermal cell dysplasia, and *[HY] PERAKERATOSIS (retained nucs. in str. corneum)* SCC arises from squams. in epidermis of older pts - <5% met. to regional nodes SCC appears as red, scaling plaque w/sharp borders --> ulceration, crusting, bleeding; classic pathology is *KERATIN PEARLS!* RFs: sun exposure, chronic immunosuppression, chronic skin inflammation (burns, chronic ulcers, draining sinus), arsenic exposure Keratoacanthoma is benign SCC variant, appearing as dome-nodule w/central hyperkeratosis; classic course is rapid growth --> regression Bowen's Dz is SCC in situ (well-demarcated, scaly plaque)

Staph saprophyticus is common cause of UTIs in ___ (nitrite negative on UTIs) Scarlet fever is maculopapular rash (sandpaper skin) following strep pharyngitis 2/2 skin reaction to erythrogenic toxin; *this toxin's gene is not found in bacterial genome, rather transferred by ___* Rheumatic fever will lead to ___ bodies (cardiac nodules with inflammatory cells) and ___ cells (macrophages with owl eye appearance); on Step 1, look for URI followed by joint pain or new ___ *Strep pneumo main virulence factor is ___, which prevents phagocytosis and is basis for vaccine; because of this factor, ___ and sickle cell patients are susceptible* Recent dental procedure + endocarditis --> ___ *Enterococcus is resistant to many antibiotics, especially VRE; UTIs will be negative for ___* *Strep bovis, Clostridium septicum --> ___*

Staph saprophyticus is common cause of UTIs in sexually active young women (nitrite negative on UTIs) Scarlet fever is rash following strep pharyngitis 2/2 skin reaction to erythrogenic toxin; *this toxin's gene is not found in bacterial genome, rather transferred by lysogenic bacteriophage* Rheumatic fever will lead to Aschoff bodies (cardiac nodules with inflammatory cells) and Anitschkow's cells (macrophages with owl eye appearance); on Step 1, look for URI followed by joint pain or new murmur *Strep pneumo main virulence factor is polysaccharide capsule, which prevents phagocytosis and is basis for vaccine; because of this factor, asplenic and sickle cell patients are susceptible* Recent dental procedure + endocarditis --> strep viridans *Enterococcus is resistant to many antibiotics, especially VRE; UTIs will be negative for nitrites* *Strep bovis, Clostridium septicum --> colon cancer*

Status epilepticus (seiz >30min, recurring seiz in <30min) can lead to arrhythmias and death 1st line tx is ___ (lorazepam), next is phenytoin or fosphenytoin, then go to phenobarbital (if still seizing --> general anesthesia) In AEDs, most teratogenic drug is ___ Many AEDs can also cause *dermatologic ___ (carbamazepine, phenytoin, lamotrigine)* Phenobarbital is contraindicated in porphyria

Status epilepticus (seiz >30min, recurring seiz in <30min) can lead to arrhythmias and death 1st line tx is benzos (lorazepam), next is phenytoin or fosphenytoin, then go to phenobarbital (if still seizing --> general anesthesia) In AEDs, most teratogenic drug is valproate Many AEDs can also cause *dermatologic Stevens-Johnson Syndrome (carbamazepine, phenytoin, lamotrigine)* Phenobarbital is contraindicated in porphyria

Struvite stones (2nd MC) arre a consequence of UTI w/___-positive bugs (Proteus, Staph saprophyticus, Klebsiella), which lead to alkaline urine *[HY] Struvite stones l/t ___ - require surgery to remove* Appear radio___ on XR (note: need to be radiopaque to be able to appreciate staghorn calculi) Crystals will appear as c___

Struvite stones (2nd MC) arre a consequence of UTI w/urease-positive bugs (Proteus, Staph saprophyticus, Klebsiella), which lead to alkaline urine *[HY] Struvite stones l/t staghorn calculi - require surgery to remove* Appear radiopaque on XR (note: need to be radiopaque to be able to appreciate staghorn calculi) Crystals will appear as coffin lids

CLASSIC PRESENTATION: problems walking, positive Romberg, spastic paresis in legs, and LE hyperreflexia with a positive Babinski

Subacute combined degeneration (tabes dorsalis + UMN damage)

Submucosal (Meissner's) plexus controls s___ & b___ flow Myenteric (Auerbach's) plexus controls GI m___ (found btwn longitudinal & circular muscle layers) Slow waves describe the slow, oscillating membrane potential of GI smooth muscle originating in intestinal cells of C___ (intestinal pacemaker cells) - membrane potential slowly rises near threshold --> APs may occur to induce contraction; slow waves essentially set maximum number of contractions per minute (testing less frequently - just be aware!)

Submucosal (Meissner's) plexus controls secretions & blood flow Myenteric (Auerbach's) plexus controls GI motility (found btwn longitudinal & circular muscle layers) Slow waves describe the slow, oscillating membrane potential of GI smooth muscle originating in intestinal cells of Cajal (intestinal pacemaker cells) - membrane potential slowly rises near threshold --> APs may occur to induce contraction; slow waves essentially set maximum number of contractions per minute (testing less frequently - just be aware!)

Substance abuse disorder requires 2+ criteria for 12mo period (includes tolerance + withdrawal); stages of change follow ___ phases (know 'em) Alcohol is a CNS depressant; biomarkers include ___ (2-6w return to normal) and ___ (1w return to normal); other signs in chronic EtOH abuse *[HY] include increased ___ (2/2 B12 deficiency) and ___ (vital sign)*; high enough BAC --> respiratory depression --> fatal EtOH WITHDRAWAL^: 1d: tremors, anxiety, palpitations, intact mental status 1-2d: ___ seizures, visual hallucinations, tactile hallucinations (bugs on skin) 3-5d: *[HY] ___* ^Tx with benzos based on ___ scale

Substance abuse disorder requires 2+ criteria for 12mo period (includes tolerance + withdrawal); stages of change follow PCPAM-relapse phases (know 'em) Alcohol is a CNS depressant; biomarkers include GGT (2-6w return to normal) and AST (1w return to normal); other signs in chronic EtOH abuse *[HY] include increased MCV (2/2 B12 deficiency) and HTN (vital sign)*; high enough BAC --> respiratory depression --> fatal EtOH WITHDRAWAL^: 1d: tremors, anxiety, palpitations, intact mental status 1-2d: TC seizures, visual hallucinations, tactile hallucinations (bugs on skin) 3-5d: *[HY] delirium tremens (altered mental status, agitation, fever, sweats, autonomic hyperactivity w/tachycardia + HTN - 20% mortality 2/2 hyperthermia, arrhythmia, electrolyte changes)* ^Tx with benzos based on CIWA scale

Succinylcholine is unique paralytic in that it is ___ neuromuscular blocker with strong ___ receptor agonism (not degraded by ACh-E), leading to sustained depolarization, desensitization, and preventing muscle contraction over time In phase 1 (depolarizing phase), muscle ___ and fasciculates; in phase 2 (sensitization phase), muscle is so stimulated that it is ___ and no longer reacts to ACh Importantly, succinylcholine has no reversal

Succinylcholine is unique paralytic in that it is depolarizing neuromuscular blocker with strong nicotinic ACh receptor agonism (not degraded by ACh-E), leading to sustained depolarization, desensitization, and preventing muscle contraction over time In phase 1 (depolarizing phase), muscle depolarizes and fasciculates; in phase 2 (sensitization phase), muscle is so stimulated that it is desensitized and no longer reacts to ACh Importantly, succinylcholine has no reversal

Superior Gluteal Nerve (L4-S1) innervates glut med and glut min (*hip ___*); damage (usually via IM injection in superiomedial region - go to upper outer quad.) l/t Trendelenburg sign (*weakness of hip abduction! - lesion is ___ side of hip drop*) Inferior Gluteal Nerve (L5-S2) innervates glut max (hip ___), damage results in difficulty climbing stairs/rising from chair Avascular necrosis is 2/2 blood vessel compromise (MC: femoral head, *major blood supply is ___ AA.*) and p/w groin pain and weight bearing difficulty; often 2/2 trauma, but can be d/t *s___ (med?)*, SLE, sickle cell, and alcohol ___ is seen in fat adolescents w/antalgic gait (scoop falling off cone); ___ is idiopathic AVN (poor blood flow) in child (more common in males)

Superior Gluteal Nerve (L4-S1) innervates glut med and glut min (*hip ABDUCTORS*); damage (usually via IM injection in superiomedial region - go to upper outer quad.) l/t Trendelenburg sign (*weakness of hip abduction! - lesion is opposite side of hip drop*) Inferior Gluteal Nerve (L5-S2) innervates glut max (hip EXTENSION), damage results in difficulty climbing stairs/rising from chair Avascular necrosis is 2/2 blood vessel compromise (MC: femoral head, *major blood supply is MEDIAL CIRCUMFLEX FEMORAL AA.*) and p/w groin pain and weight bearing difficulty; often 2/2 trauma, but can be d/t *steroids*, SLE, sickle cell, and alcohol SCFE is seen in fat adolescents w/antalgic gait (scoop falling off cone); Legg-Calve-Perthes is idiopathic AVN (poor blood flow) in child (more common in males)

Superoxide Dismutase (reduces free radicals) and Catalase (break down H2O2) allow bugs to survive in ___ environments; obligate aerobes use O2 to generate ATP and include: Pseudomonas, Myco TB, Nocardia *HY: 99% of gut & mouth flora are obligate ___ (lack 1+ enzymes)*; these bact produce gases and short-chain FAs --> foul ___ Several OAn situations to know include actinomyces (dental absc), *___ (abd absc - metronidazole)*, clostridium; also know *___ pneumo* (peptostreptococcus, fusobacterium, prevotella - ___ tx?) *HY: aminoglycosides don't work against obligate ___ 2/2 bugs not requiring ___ to enter cells* Facultative anaerobes include many common bact (Staph, Strep, E. coli) Obligate intracellular bact can't create own ATP --> need host CM (c___ - dx NAAT, r___ - dx serology)

Superoxide Dismutase (reduces free radicals) and Catalase (break down H2O2) allow bugs to survive in oxygen environments; obligate aerobes use O2 to generate ATP and include: Pseudomonas, Myco TB, Nocardia *HY: 99% of gut & mouth flora are obligate anaerobes (lack 1+ enzymes)*; these bact produce gases and short-chain FAs --> foul smell Several OAn situations to know include actinomyces (dental absc), *bacteroides (abd absc - metronidazole)*, clostridium; also know *asp pneumo* (peptostreptococcus, fusobacterium, prevotella - clindamycin) *HY: aminoglycosides don't work against obligate anaerobes 2/2 bugs not requiring O2 to enter cells* Facultative anaerobes include many common bact (Staph, Strep, E. coli) Obligate intracellular bact can't create own ATP --> need host CM (chlamydia - dx NAAT, rickettsia - dx serology)

CLASSIC PRESENTATION: patient with cuts/burns on hands that were not felt with loss of pinprick/temp in back, shoulders, and arms, +/- arm weakness +/- Horner's syndrome

Syringomyelia

T-CELL IMMUNODEFICIENCIES: *Thymic Aplasia (DiGeorge)*: *SPONTANEOUS (not familial)* 22q deletion --> failure of ___ and ___ pharyngeal pouch to form (c___ + abnormal facies + absent ___ + congenital heart defects + p___ gland - CATCH22); immune sx relate to lack of T-cells (equivalent to HIV/AIDS) - recurrent viral/fungal infxns Work-Up: *absence of ___ on CXR (also seen in SCID - kid looks normal in SCID)*, low T-cell count (duh) + *UNDERDEVELOPED T-CELL STRUCTURES ("like to ask about on Step 1" - ___ in nodes, p___ sheaths in spleen)*, hypoparathyroidism, hypocalcemia --- *Hyper IgE (Job) Syndrome*: STAT___ defect --> *deficient CD4+ Th17* --> *impaired neutrophil recruitment @ sites of infection*; p/w *___ (age?)* having Abscesses (described as *___* d/t lack of neutrophil recruitment), Baby teeth (two rows!), Coarse facies, Dermatologic problems (eczema), elevated igE, Fractures from minor trauma (*learn ABCDEFs to get a Job!*) Labs: elevated Ig___ + eosinophils, low IFN-gamma --- *Chronic Mucocutaneous Candidiasis*: defect in AIRE --> impaired cell-mediated immunity against ___ (not decreased amount --> dysfunction); p/w chronic *noninvasive (___) Candidal infxns of skin and mucous membranes (mouth, esophagus)* Special: a/w endocrine dysfunction (Hypo___, A___ insufficiency, Recurrent candida infxn - without AIRE, body will CHAR) NOTE: T-cells are big for mucosal defense, ___ are big for systemic dz (rarely see candidemia in CMC!) --- *IL-12 Receptor Deficiency*: decreased Th___ response (macrophages normally activate Th___ response via IL-12); p/w disseminated mycobacterial infxn (Th1 important for in___ bugs) Labs: decreased IFN-gamma

T-CELL IMMUNODEFICIENCIES: *Thymic Aplasia (DiGeorge)*: *SPONTANEOUS (not familial)* 22q deletion --> failure of 3rd and 4th pharyngeal pouch to form (cleft palate + abnormal facies + absent thymus + congenital heart defects + parathyroid gland - CATCH22); immune sx relate to lack of T-cells (equivalent to HIV/AIDS) - recurrent viral/fungal infxns Work-Up: *absence of thymus shadow on CXR (also seen in SCID - kid looks normal in SCID)*, low T-cell count (duh) + *UNDERDEVELOPED T-CELL STRUCTURES ("like to ask about on Step 1" - paracortex in nodes, peri-arteriolar sheaths in spleen)*, hypoparathyroidism, hypocalcemia --- *Hyper IgE (Job) Syndrome*: STAT3 defect --> *deficient CD4+ Th17* --> *impaired neutrophil recruitment @ sites of infection*; p/w *baby* having Abscesses (described as *COLD* d/t lack of neutrophil recruitment), Baby teeth (two rows!), Coarse facies, Dermatologic problems (eczema), elevated igE, Fractures from minor trauma (*learn ABCDEFs to get a Job!*) Labs: elevated IgE + eosinophils, low IFN-gamma --- *Chronic Mucocutaneous Candidiasis*: defect in AIRE --> impaired cell-mediated immunity against Candida (not decreased amount --> dysfunction); p/w chronic *noninvasive (mucosal) Candidal infxns of skin and mucous membranes (mouth, esophagus)* Special: a/w endocrine dysfunction (Hypoparathyroidism, Adrenal insufficiency, Recurrent candida infxn - without AIRE, body will CHAR) NOTE: T-cells are big for mucosal defense, neutrophils are big for systemic dz (rarely see candidemia in CMC!) --- *IL-12 Receptor Deficiency*: decreased Th1 response (macrophages normally activate Th1 response via IL-12); p/w disseminated mycobacterial infxn (Th1 important for intracellular bugs) Labs: decreased IFN-gamma

T-CELL MALIGNANCIES: *T-Cell Leukemia*: CD4+ malignancy a/w ___ (*a/w IVDU*) - will find anti-___ antibodies Seen in Japanese, Caribbean, and West African patients (where HTLV1 is common); *[HY] T-cell malignancies involve ___ - l/t ulcers +/- rash*; can also develop ___ bone lesions w/hyper___ (*in a question, beware of pt that looks like MM, but is from one of the regions described w/___ involvement, which is not seen in MM*) Prognosis is poor --- *Cutaneous T-Cell Lymphoma (mycosis fungoides)*: skin disorder of malignant T-cells P/w skin lesions (varying size/shape, indolent w/slow development over time, developing in *___ distribution*) ranging from localized lesions (MF) or diffuse symptoms (Sezary syndrome - ___form nuclei T-cells) Dx: *skin biopsy w/___ cells (what to know for Step 1)*

T-CELL MALIGNANCIES: *T-Cell Leukemia*: CD4+ malignancy a/w HTLV1 (*a/w IVDU*) - will find anti-HTLV1 antibodies Seen in Japanese, Caribbean, and West African patients (where HTLV1 is common); *[HY] T-cell malignancies involve SKIN - l/t ulcers +/- rash*; can also develop lytic bone lesions w/hypercalcemia (*in a question, beware of pt that looks like MM, but is from one of the regions described w/SKIN involvement, which is not seen in MM*) Prognosis is poor --- *Cutaneous T-Cell Lymphoma (mycosis fungoides)*: skin disorder of malignant T-cells P/w skin lesions (varying size/shape, indolent w/slow development over time, developing in *bathing trunk distribution*) ranging from localized lesions (MF) or diffuse symptoms (Sezary syndrome - cerebriform nuclei T-cells) Dx: *skin biopsy w/LYMPHOID cells (what to know for Step 1)*

T2DM is d/t insulin resistance in muscle, adipose, and liver tissue (pancreatic failure - IMPORTANT: early in dz, insulin is actually ___ as pancreas can compensate) Major RF for T2DM is obesity (___ and ___ fat >> subcutaneous fat, ___ >> pear); family history is also a strong RF Classic histo finding is *___ in pancreatic islets (amylin peptide is made by beta cells)*; classic exam finding w/insulin resistance is *___ (also look out for gastric adenocarcinoma)* [Not HY] Pathophys is believed to be d/t insulin receptor abnormalities - FAs may activate serine-threonine kinase which inhibit tyrosine phosphorylation; may also be d/t elevated TNF-alpha --- Hyperosmolar hyperglycemic syndrome is a life-threatening complication of T___DM In HHS, markedly elevated glucose (>600) --> diuresis + severe dehydration Unlike DKA, ___ ketones or acidosis present, but serum ___ (>320) is high (--> CNS dysfunction) HHS p/w polyuria + polydipsia, fatigue, and mental status changes; tx w/insulin and IVF

T2DM is d/t insulin resistance in muscle, adipose, and liver tissue (pancreatic failure - IMPORTANT: early in dz, insulin is actually high as pancreas can compensate) Major RF for T2DM is obesity (central and visceral fat >> subcutaneous fat, apple >> pear); family history is also a strong RF Classic histo finding is *amyloid in pancreatic islets (amylin peptide is made by beta cells)*; classic exam finding w/insulin resistance is *acanthosis nigricans (also look out for gastric adenocarcinoma)* [Not HY] Pathophys is believed to be d/t insulin receptor abnormalities - FAs may activate serine-threonine kinase which inhibit tyrosine phosphorylation; may also be d/t elevated TNF-alpha --- Hyperosmolar hyperglycemic syndrome is a life-threatening complication of T2DM In HHS, markedly elevated glucose (>600) --> diuresis + severe dehydration Unlike DKA, no ketones or acidosis present, but serum osmolarity (>320) is high (--> CNS dysfunction) HHS p/w polyuria + polydipsia, fatigue, and mental status changes; tx w/insulin and IVF

___ is major hormone produced by thyroid gland, but___ is more potent; T4 --> T3 conversion is accomplished in peripheral tissues via ___ *Wolf-Chaikoff Effect* is inhibition of ___ when there is too much iodide in our body (chaik*OFF*) - ___ (antiarrhythmic that contains iodine) can cause hypothyroidism via WoChaik effect, also mimics T4 --> competitive inhibition of ___ (decreased T3 --> elevated TSH) ___ is taken up in the thyroid gland (competes w/elemental iodine) and emits beta-decay - can be used for imaging (small dose) or destruction of thyroid tissue (large dose) ^___ and propranolol (weak) inhibit 5'-deiodinase

T4 is major hormone produced by thyroid gland, but T3 is more potent; T4 --> T3 conversion is accomplished in peripheral tissues via 5'-deiodinase *Wolf-Chaikoff Effect* is inhibition of organification when there is too much iodide in our body (chaik*OFF*) - Amiodarone (antiarrhythmic that contains iodine) can cause hypothyroidism via WoChaik effect, also mimics T4 --> competitive inhibition of 5'-deiodinase (decreased T3 --> elevated TSH) Radioactive iodine is taken up in the thyroid gland (competes w/elemental iodine) and emits beta-decay - can be used for imaging (small dose) or destruction of thyroid tissue (large dose) ^PTU and propranolol (weak) inhibit 5'-deiodinase

TH SYNTHESIS *[HY]*: 1. Iodide Uptake: ___ brings iodide in from blood (*NIS can take in other anions that inhibit iodide uptake - per___, per___*) 2. Oxidation of Iodide to I2: ___ catalyzes this step 3. Organification: TPO adds iodine to ___ residues on thyroglobulin to become MIT (one I) or DIT (two I) 4. Coupling Reaction: TPO catalyzes ___ added to ___ --> T3 or T4, respectively 5. Proteolysis: ___ (w/T3 and T4) is endocytosed, proteases break off TH for entry into plasma ^TPO antibodies can be seen in ___ ^PTU and methimazole inhibit TPO (*both can lead to AG___ - in Sketchy*)

TH SYNTHESIS *[HY]*: 1. Iodide Uptake: Na-I symporter (NIS) brings iodide in from blood (*NIS can take in other anions that inhibit iodide uptake - perchlorate, pertechenate*) 2. Oxidation of Iodide to I2: thyroid peroxidase (TPO) catalyzes this step 3. Organification: TPO adds iodine to tyrosine residues on thyroglobulin to become MIT (one I) or DIT (two I) 4. Coupling Reaction: TPO catalyzes [MIT or DIT] added to DIT --> T3 or T4, respectively 5. Proteolysis: thyroglobulin (w/T3 and T4) is endocytosed, proteases break off TH for entry into plasma ^TPO antibodies can be seen in Hashimoto's thyroiditis ^PTU and methimazole inhibit TPO (*both can lead to AGRANULOCYTOSIS - in Sketchy*)

THALAMIC NUCLEI: VPL: ___ info (pain, temp, touch, prop, vibr), relays info from tracts --> ___ VPM: ___ + ___ info, relays info from trigeminal/gustatory nuclei --> ___ LGN (light): ___ info MGN: ___ info VL: ___ info, relays from ___ --> motor cortex

THALAMIC NUCLEI: VPL: all sensory info (pain, temp, touch, prop, vibr), relays info from tracts --> somatosensory cortex VPM: facial sensory + taste info, relays info from trigeminal/gustatory nuclei --> somatosensory cortex LGN (light): vision info MGN: hearing info VL: motor info, relays from basal ganglia --> motor cortex

THYROID HORMONE EFFECTS: 7Bs ___ Maturation: think cretinism ___ Growth: think cretinism Beta Adrenergic: more ___ receptors on heart --> increased CO, HR, SV, contractility ___ Rate (energy burned if spent all day sleeping): increased via increasing ___ pumps (more ATP consumed) --> increased body temperature, respiratory rate (O2 demand) Blood Sugar: increased via g___ + g___ Break Down Lipids: *increased ___* + LDL-receptors on liver + cholesterol secretion in bile (overall decreases serum lipids) Babies: stimulate surfactant release (*also cretinism - mental retardation, coarse facial features, short stature, ENLARGED ___*) HYPOTHYROID: ___lipidemia, weight ___ HYPERTHYROID: ___glycemia, weight ___

THYROID HORMONE EFFECTS: 7Bs Brain Maturation: think cretinism Bone Growth: think cretinism Beta Adrenergic: more beta-1 receptors on heart --> increased CO, HR, SV, contractility Basal Metabolic Rate (energy burned if spent all day sleeping): increased via increasing Na-K ATPase pumps (more ATP consumed) --> increased body temperature, respiratory rate (O2 demand) Blood Sugar: increased via gluconeogenesis + glycogenolysis Break Down Lipids: *increased lipolysis* + LDL-receptors on liver + cholesterol secretion in bile (overall decreases serum lipids) Babies: stimulate surfactant release (*also cretinism - mental retardation, coarse facial features, short stature, ENLARGED TONGUE*) HYPOTHYROID: hyperlipidemia, weight gain HYPERTHYROID: hyperglycemia, weight loss

CLASSIC CASE: child/infant w/seizures, ash-leaf spots, and angiofibromas - what's going on? What else might this pt develop later in life? --- CLASSIC CASE: newborn w/port-wine stain + seizures + glaucoma?

TSC (hamartomas in multiple organ systems) BRAIN: cortical tubers, subependymal nodules, subependymal giant cell astrocytomas --> *HYDROCEPHALUS* SKIN: ash-leaf spots, angiofibromas, shagreen patch, ungual fibromas HEART: rhabdomyomas KIDNEY: angiomyolipomas --- STURGE-WEBER SYNDROME (look for leptomeningeal angioma)

CLASSIC CASE: pt w/Sjogren's dz + bilateral kidney stones, bicarb is 10, HYPOkalemia w/high urine pH + positive urine anion gap - que pasa? how do you treat --- CLASSIC CASE: diabetic pt w/unexplained hyperkalemia + non-gapped metabolic acidosis - que pasa? how do you treat?

TYPE I RTA (tx w/sodium bicarbonate) --- TYPE IV RTA (tx w/mineralocorticoid [fludrocortisone])

*[HY] What patients should avoid thiazolidinediones? What patient should avoid metformin? (comorbidities)*

TZDs (-glitazone) --> heart failure (edema) Metformin --> renal insufficiency (lactic acidosis)

Tamoxifen is a SERM that acts as a ___ at breast tissue and can be used for treatment and prevention Tamoxifen acts as an ___ at bone (--> increased bone density) and uterus (--> increased endothelial growth) Tamoxifen toxicity includes *increased risk of ___ (d/t increased clotting factor synthesis* and *___ hyperplasia/cancer* --- Aromatase inhibitors block aromatase --> decreased ___ synthesis (used in ER+ breast cancer in *postmenopausal women [pre-menopausal still have estrogen from ovaries, would make drugs obsolete]*) Aromatase inhibitors include anastr___, letr___, exemestane Adverse effects of aromatase inhibitors include osteoporosis --- Trastuzumab is ___ receptor antibody *[HY] Trastuzumab inhibits proliferation of tumor cells via ___ (i.e., NK cells)*

Tamoxifen is a SERM that acts as a competitive antagonist at breast tissue and can be used for treatment and prevention Tamoxifen acts as an agonist at bone (--> increased bone density) and uterus (--> increased endothelial growth) Tamoxifen toxicity includes *increased risk of DVT/PE (d/t increased clotting factor synthesis* and *endometrial hyperplasia/cancer* --- Aromatase inhibitors block aromatase --> decreased estrogen synthesis (used in ER+ breast cancer in *postmenopausal women [pre-menopausal still have estrogen from ovaries, would make drugs obsolete]*) Aromatase inhibitors include anastrozole, letrozole, exemestane Adverse effects of aromatase inhibitors include osteoporosis --- Trastuzumab is HER2 receptor antibody *[HY] Trastuzumab inhibits proliferation of tumor cells via antibody-dependent cell-mediated cytotoxicity (i.e., NK cells)*

Tension HA is bilateral, constant pain (without photo/phonophobia or aura) that is tx with NSAIDs Migraine HA is unilateral, throbbing pain (with photo/phonophobia +/- *visual aura - ___*, N/V); pathophys involves *irritation of ___*; tx is abortive (triptans - vasoconstrictor that is contraindicated in ___ and ___) or preventive (topiramate, valproate, propranolol) Cluster HA happens in male smokers with excruciating unilateral HA behind the eye with associated ___ sx (tearing, rhinorrhea, Horner's); they occur in clusters with *___ rhythm*, lasting 15min and *tx is with ___ and triptans*

Tension HA is bilateral, constant pain (without photo/phonophobia or aura) that is tx with NSAIDs Migraine HA is unilateral, throbbing pain (with photo/phonophobia +/- *visual aura - scintillating scotoma*, N/V); pathophys involves *irritation of CN5*; tx is abortive (triptans - vasoconstrictor that is contraindicated in CAD, Prinzmetal's) or preventive (topiramate, valproate, propranolol) Cluster HA happens in male smokers with excruciating unilateral HA behind the eye with associated autonomic sx (tearing, rhinorrhea, Horner's); they occur in clusters with *Circadian rhythm*, lasting 15min and *tx is with oxygen and triptans*

Testing for Adrenal Insufficiency: 1. 8AM serum cortisol (if ___ --> adrenal insufficiency, *go find the cause...*) 2. ACTH level (if ___ --> primary adrenal insufficiency; if ___ --> secondary adrenal insufficiency) --- ACTH stimulation test can also be used - administer ACTH and if no jump --> ___ AI (adrenal problem), if jump --> ___ AI (pituitary problem)

Testing for Adrenal Insufficiency: 1. 8AM serum cortisol (if low --> adrenal insufficiency, *go find the cause...*) 2. ACTH level (if high --> primary adrenal insufficiency; if low --> secondary adrenal insufficiency) --- ACTH stimulation test can also be used - administer ACTH and if no jump --> primary AI (adrenal problem), if jump --> secondary AI (pituitary problem)

Th1 response is important for intracellular infections (Ab [coming from Th___ response] are not useful d/t bug hiding in cell), including *TB (hides in macrophages, need Th1 --> ___)* and Listeria (*newborns and elderly have weak Th___ response --> VULNERABLE*) Granulomatous dz are driven from inflammation w/macrophages - Th1 cells secrete ___, which activates macrophages; macrophages secrete ___ --> maintains granuloma (*reason TNF-alpha inhibitors can reactivate TB!*) Leoprosy causes two dz depending on rxn: 1) mild tuberculoid (strong Th___ response --> contains infxn w/*___*) or 2) severe lepromatous (weak Th___ response --> for some reason, pts develop humoral response to intracellular bug, poorly contained --> Abs cannot contain --> diffuse skin lesions)

Th1 response is important for intracellular infections (Ab [coming form Th2 response] are not useful d/t bug hiding in cell), including *TB (hides in macrophages, need Th1 --> granulomas)* and Listeria (*newborns and elderly have weak Th1 response --> VULNERABLE*) Granulomatous dz are driven from inflammation w/macrophages - Th1 cells secrete IFN-gamma, which activates macrophages; macrophages secrete TNF-alpha --> maintains granuloma (*reason TNF-alpha inhibitors can reactivate TB!*) Leoprosy causes two dz depending on rxn: 1) mild tuberculoid (strong Th1 response --> contains infxn w/*GRANULOMAS*) or 2) severe lepromatous (weak Th2 response --> for some reason, pts develop humoral response to intracellular bug, poorly contained --> Abs cannot contain --> diffuse skin lesions)

___ is decreased or absent production of globin chains (alpha or beta) - all hemoglobins have alpha chain, second chain determines hemoglobin type (A - ___, A2 - ___, F - ___); thalassemias have spectrum of severity (minor or major) Hgb ___ can be used to diagnose hemoglobinopathies (thalassemia, sickle cell) Hgb will present with a normal RDW - *wide RDW will be seen in ___ anemia (distinguishing factor!)* NOTE: alpha and beta thalassemia is protective vs malaria (symptoms are ___)

Thalassemia is decreased or absent production of globin chains (alpha or beta) - all hemoglobins have alpha chain, second chain determines hemoglobin type (A - beta, A2 - delta, F - gamma); thalassemias have spectrum of severity (minor or major) Hgb electrophoresis can be used to diagnose hemoglobinopathies (thalassemia, sickle cell) Hgb will present with a normal RDW - *wide RDW will be seen in iron deficiency anemia (distinguishing factor!)* NOTE: alpha and beta thalassemia is protective vs malaria (symptoms are lessened)

Thayer-Martin (VPN) media is selective for ___ (Vanc kills GPs, Polymyxin kills GNs, Nystatin kill fungi) Corynebacterium requires Loeffler's media (selective) and ___ media (differential - grows gray-black) ___-Jensen is used for M tuberculosis (SLOW GROWING!) ___ agar is used for mycoplasma pneumonia (no CW --> poorly visualized); not used often, use serology, PCR, agglutinins instead MacConkey's agar is selective for GNs and differential for ___ fermenters (yes --> pink, no --> colorless); Eosin Methylene Blue as well, fermenters (E coli) grow ___ and nonfermenters are transparent Use sorbitol MacConkey agar for EHEC (cannot ferment sorbitol --> grows ___ instead of pink) Buffered Charcoa*L* Yeast grows ___} only; bug must be cultured to contain outbreaks

Thayer-Martin (VPN) media is selective for Neisseria (Vanc kills GPs, Polymyxin kills GNs, Nystatin kill fungi) Corynebacterium requires Loeffler's media (selective) and Tellurite media (differential - grows gray-black) Lowenstein-Jensen is used for M tuberculosis (SLOW GROWING!) Eaton's agar is used for mycoplasma pneumonia (no CW --> poorly visualized); not used often, use serology, PCR, agglutinins instead MacConkey's agar is selective for GNs and differential for lactose fermenters (yes --> pink, no --> colorless); Eosin Methylene Blue as well, fermenters (E coli) grow green and nonfermenters are transparent Use sorbitol MacConkey agar for EHEC (cannot ferment sorbitol --> grows COLORLESS instead of pink) Buffered Charcoa*L* Yeast grows *L*egionella only; bug must be cultured to contain outbreaks

The body's first line of defense against bleeding is vasoconstriction, which occurs in response to endothelial damage after *___ are released (endothelin-receptor blockers are used in p___ H___!)* Coagulation factors are proteins synthesized in ___ that activate to become s___ proteases (*protein cleavage enzymes that contain serine*) At the center of coagulation cascade is activation of factor ___, which will lead to fibrin formation (via factor II - thrombin; NOTE thrombin can amplify effect via *activating factors ___, VIII, ___, XIII [two showing are roman numeral + III!]*) Tissue factor is major activator of coagulation cascade - TF is constitutively expressed in s___-e___ cells (*NOT endothelial cells*), such that there is no significant contact w/circulating blood until endothelial damage occurs Once active --> TF binds factor ___ --> complex factor X (extrinsic - PT) Other pathway is intrinsic pathway, which ends in factor IXa-VIIIa complex to activate factor X (PTT) F___ is important for testing of coagulation system w/PTT (activates XI in response to contact w/negative charge), but physiologic significance is unclear Factor ___ crosslinks fibrin at conclusion of clot (requires calcium cofactor) Both pathways require c___ (cofactor - use EDTA tubes when collecting blood) and p___ to function; PTT test requires ___ charged substances (silica) to activate factor XII and form clot; PT test requires ___ to activate factor VII and form clot

The body's first line of defense against bleeding is vasoconstriction, which occurs in response to endothelial damage after *endothelins are released (endothelin-receptor blockers are used in pulmonary HTN!)* Coagulation factors are proteins synthesized in liver that activate to become serine proteases (*protein cleavage enzymes that contain serine*) At the center of coagulation cascade is activation of factor X, which will lead to fibrin formation (via factor II - thrombin; NOTE thrombin can amplify effect via *activating factors V, VIII, XI, XIII*) Tissue factor is major activator of coagulation cascade - TF is constitutively expressed in sub-endothelial cells (*NOT endothelial cells*), such that there is no significant contact w/circulating blood until endothelial damage occurs Once active --> TF binds factor VII --> complex factor X (extrinsic - PT) Other pathway is intrinsic pathway, which ends in factor IXa-VIIIa complex to activate factor X (PTT) Factor XII is important for testing of coagulation system w/PTT (activates XI in response to contact w/negative charge), but physiologic significance is unclear Factor XIII crosslinks fibrin at conclusion of clot (requires calcium cofactor) Both pathways require calcium (cofactor - use EDTA tubes when collecting blood) and phospholipids to function; PTT test requires negatively charged substances (silica) to activate factor XII and form clot; PT test requires TF to activate factor VII and form clot

The functional unit of the liver is a hexagonal lobule - at the center is the ___ vein (connects to hepatic vein), at the edges are triad w/hepatic artery, portal vein, and bile duct NOTE: liver has two blood supplies - ___ (80%) and ___ (20%) - but only one drainage (hepatic vein) As blood goes from PV to CV, it passes through three zones: Zone I (periportal): closest to blood supply - affected by ___/toxins, resistant to ___ Zone II (mid-zone): affected by ___ fever Zone III (peri-central): furthest from blood supply - vulnerable to i___ & *___ hepatitis (fat accumulation)*, also highest concentration of cytP450

The functional unit of the liver is a hexagonal lobule - at the center is the central vein (connects to hepatic vein), at the edges are triad w/hepatic artery, portal vein, and bile duct NOTE: liver has two blood supplies - portal veins (80%) and hepatic artery (20%) - but only one drainage (hepatic vein) As blood goes from PV to CV, it passes through three zones: Zone I (periportal): closest to blood supply - affected by hepatitis/toxins, resistant to ischemia Zone II (mid-zone): affected by ye*ll*ow fever Zone III (peri-central): furthest from blood supply - vulnerable to ischemia & *alcoholic hepatitis (fat accumulation)*, also highest concentration of cytP450

The glomeruli, proximal tubule, and distal tubule can be found in the kidney ___ The loop of Henle and collecting ducts can be found in the kidney ___ Urine collects in the kidney calyces The medullary pyramids meet the calyces at the renal ___ The pelvis collects urine from renal pyramids The arterial system of the kidney follows renal aa --> segmental aa --> inter___ aa --> a___ aa --> *inter___ aa* --> glomerulus Importantly, at the level of the glomerulus, there are *two ___ - afferent and efferent (UNIQUE)* The right kidney is slightly ___ than left kidney (pushed out of way by liver) The left renal vein is ___ (long or short?) than right renal vein (can l/t some pathology)

The glomeruli, proximal tubule, and distal tubule can be found in the kidney cortex The loop of Henle and collecting ducts can be found in the kidney medulla Urine collects in the kidney calyces The medullary pyramids meet the calyces at the renal papilla The pelvis collects urine from renal pyramids The arterial system of the kidney follows renal aa --> segmental aa --> interlobar aa --> arcuate aa --> *interlobular aa* --> glomerulus Importantly, at the level of the glomerulus, there are *two arterioles - afferent and efferent (UNIQUE)* The right kidney is slightly smaller than left kidney (pushed out of way by liver) The left renal vein is longer than right renal vein (can l/t some pathology)

The ovarian follicle is an egg surrounded by two layers of cells: ___ cells (inner) and ___ cells (outer) ___ cells take up cholesterol for conversion to andrestenedione (via desmolase) in response to LH; ___ cells take andrestenedione and convert it to estradiol (via ___) in response to FSH - also secrete ___ to suppress FSH [NOTE: FSH --> cAMP --> aromatase] ^Nothing Like That, Great Romanian Food --- Progesterone is synthesized by the ___ (also placenta, adrenal gland, testes) Many effects of progesterone are to oppose estrogen and prepare body for ___ Progesterone stimulates ___ phase of uterine cycle endometrium, thickens cervical ___ (prevents sperm entry), prevents uterine contractions, and raises body temperature (also inhibits FSH/LH release)

The ovarian follicle is an egg surrounded by two layers of cells: granulosa cells (inner) and theca cells (outer) Theca cells take up cholesterol for conversion to andrestenedione (via desmolase) in response to LH; Granulosa cells take andrestenedione and convert it to estradiol (via aromatase) in response to FSH - also secrete inhibin to suppress FSH [NOTE: FSH --> cAMP --> aromatase] ^Nothing Like That, Great Romanian Food --- Progesterone is synthesized by the corpus luteum (also placenta, adrenal gland, testes) Many effects of progesterone are to oppose estrogen and prepare body for pregnancy Progesterone stimulates secretory phase of uterine cycle endometrium, thickens cervical mucous (prevents sperm entry), prevents uterine contractions, and raises body temperature (also inhibits FSH/LH release)

The pituitary connects to the ___ of the hypothalamus The ___ pituitary (neurohypophysis) is derived from neural ___oderm - it is made up of two types of cells: ___ nuclei (secrete oxytocin, O-P) and ___ nuclei (ADH) The ___ pituitary (adenohypophysis) is derived from ___ - an outgrowth of the oral cavity The AP is made up of five cell types that make six different hormones (___ [corticotrophs], ___ [thyrotrophs], ___ [gonadotrophs], ___ [somatotrophs], ___ [lactotrophs]) - prolactin is unique in that it is inhibited (dopamine) while the others are stimulated by hypothalamic control

The pituitary connects to the median eminence of the hypothalamus The posterior pituitary (neurohypophysis) is derived from neural ectoderm - it is made up of two types of cells: paraventricular nuclei (secrete oxytocin, O-P) and supraoptic nuclei (ADH) The anterior pituitary (adenohypophysis) is derived from Rathke's pouch - an outgrowth of the oral cavity The AP is made up of five cell types that make six different hormones (ACTH [corticotrophs], TSH [thyrotrophs], LH/FSH [gonadotrophs], GH [somatotrophs], prolactin [lactotrophs]) - prolactin is unique in that it is inhibited (dopamine) while the others are stimulated by hypothalamic control

The ___ reabsorbs 100% of filtered glucose and AAs (also 2/3rds HCO3, Na, Cl, K, and PO4) - engine driving the PCT is Na-K-ATPase that creates low intracellular ___ concentration At PCT, ___ inhibits Na/PO4 cotransporter (increases urinary phosphate excretion); ___ stimulates Na/H exchange --> increased Na + H2O reabsorption (HCO3 too) *[HY] Glucose is completely reabsorbed at PCT via ___ cotransporter - in diabetes @ ___mg/dL --> glucose appears in urine; @ ___mg/dL --> all transporters saturated, urinary glucose increases in linear fashion* *[HY] In pregnancy, some glycosuria is normal d/t ___ GFR + ___ glucose reabsorption - NEED to use serum glucose testing for diabetes* NOTE: AAs should all be reabsorbed in PCT; in ___ dz, tryptophan transporter is deficient --> tryptophan deficiency --> niacin deficiency --> *PELLAGRA*

The proximal convoluted tubule reabsorbs 100% of filtered glucose and AAs (also 2/3rds HCO3, Na, Cl, K, and PO4) - engine driving the PCT is Na-K-ATPase that creates low intracellular sodium concentration At PCT, PTH inhibits Na/PO4 cotransporter (increases urinary phosphate excretion); ATII stimulates Na/H exchange --> increased Na + H2O reabsorption (HCO3 too) *[HY] Glucose is completely reabsorbed at PCT via Na-Glucose cotransporter - in diabetes @ 160mg/dL --> glucose appears in urine; @ 350mg/dL --> all transporters saturated, urinary glucose increases in linear fashion* *[HY] In pregnancy, some glycosuria is normal d/t increased GFR + decreased glucose reabsorption - NEED to use serum glucose testing for diabetes* NOTE: AAs should all be reabsorbed in PCT; in Hartnup dz, tryptophan transporter is deficient --> tryptophan deficiency --> niacin deficiency --> *PELLAGRA*

The spleen arises from dorsal ___ tissue of stomach (*___*) and bets blood supply from ___ (*like other foregut structures [stomach] which derive from ___*) Because of stomach rotation, spleen ends up on left side Retained connections btwn spleen and stomach exist w/___ ligament, which carries short gastric aa and left gastroepiploic aa

The spleen arises from dorsal mesodermal tissue of stomach (*MESODERM*) and bets blood supply from celiac trunk (*like other foregut structures [stomach] which derive from ENDODERM*) Because of stomach rotation, spleen ends up on left side Retained connections btwn spleen and stomach exist w/gastrosplenic ligament, which carries short gastric aa and left gastroepiploic aa

The superior mesenteric artery supplies ___ structures (duodenum to first 2/3rd of transverse colon) and, important, travels over duodenum SMA syndrome is a rare cause of bowel obstruction - occurs when there is massive ___ loss --> SMA squishes on ___ The inferior mesenteric artery supplies ___ structures (last 1/3rd of transverse colon to rectum)

The superior mesenteric artery supplies midgut structures (duodenum to first 2/3rd of transverse colon) and, important, travels over duodenum SMA syndrome is a rare cause of bowel obstruction - occurs when there is massive weight loss --> SMA squishes on duodenum The inferior mesenteric artery supplies hindgut structures (last 1/3rd of transverse colon to rectum)

The thin descending loop of Henle is impermeable to ___, but can absorb ___ --> concentrates urine; force drawing water out of loop is *___ hypertonicity in medullary interstitium (up to 1200mOsm in inner medulla)* *[HY] Three solutes responsible for increasing tonicity in medulla are ___; collecting duct is highly permeable to urea, maintaining this gradient* After turning up to ascending loop of Henle, the loop becomes impermeable to ___ but permeable to ___ --> NaCl reabsorbed (*most is reabsorbed in THICC ascending limb*)

The thin descending loop of Henle is impermeable to NaCl, but can absorb water --> concentrates urine; force drawing water out of loop is *increasing hypertonicity in medullary interstitium (up to 1200mOsm in inner medulla)* *[HY] Three solutes responsible for increasing tonicity in medulla are Na, Cl, and urea; collecting duct is highly permeable to urea, maintaining this gradient* After turning up to ascending loop of Henle, the loop becomes impermeable to water but permeable to NaCl --> NaCl reabsorbed (*most is reabsorbed in THICC ascending limb*)

The thymus is site of T-cell maturation (immature T-cells migrate from ___ to thymus); in thymus, T-cells express T-Cell Receptor and only ideal TCRs survive (i.e., bind MHC1 or MHC2, *don't bind ___*) The cortex does ___ selection (binding to MHC complexes), in which thymus epithelial cells express MHC and T-cell binding to MHC is tested (weak --> apoptosis, strong --> to the ___) The thymic medulla does ___ selection (binding to self-antigens), in which thymus epithelial cells/dendritic cells express *self-antigens* - if T-cell reacts to self antigen --> ___ ___ genes (autoimmune regulator) are responsible for expression of self antigens; mutations --> unique presentation (chronic mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency, recurrent candida infxns) ^Without AIRE, your body will CHAR

The thymus is site of T-cell maturation (immature T-cells migrate from bone marrow to thymus); in thymus, T-cells express T-Cell Receptor and only ideal TCRs survive (i.e., bind MHC1 or MHC2, *don't bind self-antigens*) The cortex does positive selection (binding to MHC complexes), in which thymus epithelial cells express MHC and T-cell binding to MHC is tested (weak --> apoptosis, strong --> to the medulla) The thymic medulla does negative selection (binding to self-antigens), in which thymus epithelial cells/dendritic cells express *self-antigens* - if T-cell reacts to self antigen --> apoptosis AIRE genes (autoimmune regulator) are responsible for expression of self antigens; mutations --> unique presentation (chronic mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency, recurrent candida infxns) ^Without AIRE, your body will CHAR

The two inhibitory neurotransmitters are ___ GABA binds to its receptor, allowing ___ to enter cell and hyperpolarize the membrane; GABA is synthesized by ___ and broken down by ___, both of which need ___ as a cofactor The major excitatory neurotransmitter is ___, which is indicated in ___ disease (excessive amount)

The two inhibitory neurotransmitters are GABA and glycine GABA binds to its receptor, allowing chloride to enter cell and hyperpolarize the membrane; GABA is synthesized by glutamate decarboxylase and broken down by GABA transaminase, both of which need B6 as a cofactor The major excitatory neurotransmitter is glutamate, which is indicated in Huntington's disease (excessive amount)

Thenar muscles (abductor poll. brevis, flexor poll. brevis, opponens poll.) are innervated by ___ nn. - will atrophy with median nn. lesion; Hypothenar muscles (opponens DM, flexor DM brevis, abductor DM) are innervated by ___ nn. - will atrophy w/lesions ___ mm. are responsible for abduction/adduction of fingers (dorsal - abduct, palmar - adduct; DAB PAD) - all are innervated by ___ nn. *[HY] ___ originate from tendons of FDP and flex @ MCP joints, extend @ ___ joints (form L-shape for Lumb.); medial two lumbs. have ___ innervation, lateral two lumbs. have ___ innervation; lumbrical loss l/t ___ fingers* Flexor digitorum profundus also flexes digits (extrinsic hand mm.) - innervation is ___ nn. (lateral 2) and ___ nn. (medial 2); Extensor digitorum primarily extends MCP joints (remember: lumbricals extend IPs) - innervation is ___ nn. Wrists flexors are flexor carpi radialis (___ nn.) and flexor carpi ulnaris (___ nn.), while wrist extensors are ext. carpi rad. longus, ext. carpi rad. brevis, ext. carpi uln. (___ nn.); damage to these structures l/t wrist deviation

Thenar muscles (abductor poll. brevis, flexor poll. brevis, opponens poll.) are innervated by median nn. - will atrophy with median nn. lesion; Hypothenar muscles (opponens DM, flexor DM brevis, abductor DM) are innervated by ulnar nn. - will atrophy w/lesions Interosseous mm. are responsible for abduction/adduction of fingers (dorsal - abduct, palmar - adduct; DAB PAD) - all are innervated by ulnar nn. *[HY] Lumbricals originate from tendons of FDP and flex @ MCP joints, extend @ IP joints (form L-shape for Lumb.); medial two lumbs. have ulnar innervation, lateral two lumbs. have median innervation; lumbrical loss l/t claw fingers* Flexor digitorum profundus also flexes digits (extrinsic hand mm.) - innervation is median nn. (lateral 2) and ulnar nn. (medial 2); Extensor digitorum primarily extends MCP joints (remember: lumbricals extend IPs) - innervation is radial nn. Wrists flexors are flexor carpi radialis (median nn.) and flexor carpi ulnaris (ulnar nn.), while wrist extensors are ext. carpi rad. longus, ext. carpi rad. brevis, ext. carpi uln. (radial nn.); damage to these structures l/t wrist deviation

Theoretical driving forces that determine GFR are 1) hydrostatic pressure and 2) oncotic pressure Hydrostatic pressure is largely determined by ___ (systemic) and ___ (local) vasoconstriction; oncotic pressure is largely determined by ___ *Dilation of afferent arteriole (accomplished by prostaglandins):* -___ blood in -___ renal plasma flow (RPF) -___ glomerular hydrostatic pressure -___ GFR -___ filtration fraction (GFR/RPF) *Constriction of efferent arteriole (accomplished by angiotensin II):* -___ blood out -___ RPF -___ glomerular hydrostatic pressure -___ GFR -___ filtration fraction *Increased oncotic pressure (increased protein - multiple myeloma)*: -Less blood drawn into proximal tubule -___ GFR -No change in RPF -___ filtration fraction *Increased pressure in Bowman's capsule (obstructed ureter):* -___ GFR -No change in RPF -___ filtration fraction

Theoretical driving forces that determine GFR are 1) hydrostatic pressure and 2) oncotic pressure Hydrostatic pressure is largely determined by BP and afferent arteriole/efferent arteriole vasoconstriction; oncotic pressure is largely determined by albumin *Dilation of afferent arteriole (accomplished by prostaglandins):* -Increased blood in -Increased renal plasma flow (RPF) -Increased glomerular hydrostatic pressure -Increased GFR -Unchanged filtration fraction (GFR/RPF) *Constriction of efferent arteriole (accomplished by angiotensin II):* -Decreased blood out -Decreased RPF -Increased glomerular hydrostatic pressure -Increased GFR -Increased filtration fraction *Increased oncotic pressure (increased protein - multiple myeloma)*: -Less blood drawn into proximal tubule -Decreased GFR -No change in RPF -Decreased filtration fraction *Increased pressure in Bowman's capsule (obstructed ureter):* -Decreased GFR -No change in RPF -Decreased filtration fraction

There are two types of B-cell activation: 1) T-cell dependent (only for proteins d/t T-cells only activated by proteins) and 2) T-cell independent (no proteins) For T-Cell Dependent (SEE PICTURE), need 1) crosslinking (multiple BCRs --> multiple antigens on surface) and 2) T-cell binding (B-cell presents Ag to T-cells via MHC2 + CD___-CD___L [required for CLASS SWITCHING from IgM - can't do in T-cell ___ pathway] + B___-CD28); this is most potent way to activate B-cells For T-cell Independent, there's *SO MANY antigens on pathogen surface --> activate B-cell w.o T-cell help* Key Points for TC-Indep-Act: 1) key for *non-___ antigens (especially polysaccharide capsules of bacteria & LPS)* and 2) generates a *___ RESPONSE (mostly Ig___, no memory)* CLINICAL CORRELATION: Conjugated vaccines are d/t polysaccharide antigens producing a WEAK RESPONSE (T-cell ___ pathway); conjugating to peptide antigen --> B-cells generate Ab to polysaccharide + protein Ag presented to B-cell --> T-cells boost B-cell response (*stronger vaccine!*) Conjugated vaccines exist for HiB, N meningitidis, S pneumo

There are two types of B-cell activation: 1) T-cell dependent (only for proteins d/t T-cells only activated by proteins) and 2) T-cell independent (no proteins) For T-Cell Dependent (SEE PICTURE), need 1) crosslinking (multiple BCRs --> multiple antigens on surface) and 2) T-cell binding (B-cell presents Ag to T-cells via MHC2 + CD40-CD40L [required for CLASS SWITCHING from IgM - can't do in T-cell independent pathway] + B7-CD28); this is most potent way to activate B-cells For T-cell Independent, theres's *SO MANY antigens on pathogen surface --> activate B-cell w.o T-cell help* Key Points for TC-Indep-Act: 1) key for *non-protein antigens (especially polysaccharide capsules of bacteria & LPS)* and 2) generates a *WEAKER RESPONSE (mostly IgM, no memory)* CLINICAL CORRELATION: Conjugated vaccines are d/t polysaccharide antigens producing a WEAK RESPONSE (T-cell independent pathway); conjugating to peptide antigen --> B-cells generate Ab to polysaccharide + protein Ag presented to B-cell --> T-cells boost B-cell response (*stronger vaccine!*) Conjugated vaccines exist for HiB, N meningitidis, S pneumo

There are two underlying mechanisms behind most diabetic complications: 1) ___ and 2) ___ accumulation Non-enzymatic glycation (seen in A1c) is glucose added to amino groups w.o enzyme --> crosslinked proteins (*___ products*) AGEs trap LDL in *large vessels* --> ___ (*CAD, CVA, PVD [claudication + poor wound healing]*) AGEs can cause *small vessel* dz (vessel ___ thickening) --> kidney dz (arteriolar damage/glomerular BM) In renal arterioles, diabetes l/t *hyaline arteriosclerosis (thickening of arterioles - also seen in HTN)* - can effect afferent arteriole (i___) and efferent arteriole (hyper___ --> albuminuria) (*[HY] e___ a___ is UNIQUE to diabetes!*) In glomerulus, T2DM can lead to two forms of glomerulosclerosis: *___ GS (specific to T2DM) results in nodules in periphery of glomerulus/mesangium (will see K___-W___ NODULE, know how to recognize!)*; Diffuse GS (also seen in HTN, aging) is d/t deposits of proteins (collagen IV) diffusely on BM of glomeruli capillary loops --> mesangial proliferation

There are two underlying mechanisms behind most diabetic complications: 1) non-enzymatic glycation and 2) sorbitol accumulation Non-enzymatic glycation (seen in A1c) is glucose added to amino groups w.o enzyme --> crosslinked proteins (*advanced glycosylation end products*) AGEs trap LDL in *large vessels* --> atherosclerosis (*CAD, CVA, PVD [claudication + poor wound healing]*) AGEs can cause *small vessel* dz (vessel basement membrane thickening) --> kidney dz (arteriolar damage/glomerular BM) In renal arterioles, diabetes l/t *hyaline arteriosclerosis (thickening of arterioles - also seen in HTN)* - can effect afferent arteriole (ischemia) and efferent arteriole (hyperfiltration --> albuminuria) (*[HY] efferent arteriosclerosis is UNIQUE to diabetes!*) In glomerulus, T2DM can lead to two forms of glomerulosclerosis: *Nodular GS (specific to T2DM) results in nodules in periphery of glomerulus/mesangium (will see KIMMELSTIEL-WILSON NODULE, know how to recognize!)*; Diffuse GS (also seen in HTN, aging) is d/t deposits of proteins (collagen IV) diffusely on BM of glomeruli capillary loops --> mesangial proliferation

There are two underlying mechanisms behind most diabetic complications: 1) non-enzymatic glycation and 2) ___ (glucose --> sorbitol -/-> fructose) Chronic hyperglycemia --> ___ accumulation, which acts as osmotic agent --> fluid accumulation ___ are MC in diabetics and are d/t sorbitol accumulation in lens Sorbitol can accumulate in ___ cells --> neuropathy (*"stocking glove" sensory sx, can l/t autonomic neuropathy [postural hypotension, delayed gastric emptying]*); neuropathy + PVD (d/t non-enzymatic glycation of large vessels) --> diabetic ___ dz + amputations Sorbitol accumulation in *___ of capillaries --> microaneurysms/hemorrhage in retina --> DIABETIC ___ (also look for cotton-wool spots, neo___)* - NOTE: non-enzymatic glycation is likely involved in retinopathy as well

There are two underlying mechanisms behind most diabetic complications: 1) non-enzymatic glycation and 2) sorbitol accumulation (glucose --> sorbitol -/-> fructose) Chronic hyperglycemia --> sorbitol accumulation, which acts as osmotic agent --> fluid accumulation Cataracts are MC in diabetics and are d/t sorbitol accumulation in lens Sorbitol can accumulate in Schwann cells --> neuropathy (*"stocking glove" sensory sx, can l/t autonomic neuropathy [postural hypotension, delayed gastric emptying]*); neuropathy + PVD (d/t non-enzymatic glycation of large vessels) --> diabetic foot dz + amputations Sorbitol accumulation in *PERICYTES of capillaries --> microaneurysms/hemorrhage in retina --> DIABETIC RETINOPATHY (also look for cotton-wool spots, neovascularization)* - NOTE: non-enzymatic glycation is likely involved in retinopathy as well

Three factors play into net excretion in kidney: 1) GFR, 2) ___, 3) ___ Total amount excreted = total filtered - total resorbed + total secreted Filtered (X) = [Plasma X] x [___] Excreted (X) = [Urine X] x [___] Filtered = Excreted --> no secretion/reabsorption Filtered > Excretion --> net ___ Filtered < Excretion --> net ___

Three factors play into net excretion in kidney: 1) GFR, 2) secretion, 3) reabsorption Total amount excreted = total filtered - total resorbed + total secreted Filtered (X) = [Plasma X] x [GFR] Excreted (X) = [Urine X] x [Urine Flow Rate] Filtered = Excreted --> no secretion/reabsorption Filtered > Excretion --> net resorption Filtered < Excretion --> net secretion

Three forms of CO2 transport from tissue to lungs: HCO3, bound to h___, dissolved C___ a___ is big for HCO3 conversion - also produces H+, which binds to Hgb --> ___ shift (B___ effect - helps Hgb unload O2 in metabolic states) H___ Effect^: in lungs, oxygenation of Hgb promotes dissociation of H+ from Hgb --> shifts equilibrium towards CO2 formation --> CO2 released from RBCs (i.e., in O2-___ environments, Hgb has low affinity for CO2; in O2-___ environments, Hgb has high affinity for CO2) Tissues: low O2, high CO2 and H+ - favors O2 ___loading (Bohr) and CO2 ___loading (Haldane) Lungs: high O2, low CO2 and H+ - favors O2 ___loading (Bohr) and CO2 ___loading (Haldane) ^*H*emoglobin *A*ffinity for carbon *(l)D(ane)*ioxide

Three forms of CO2 transport from tissue to lungs: HCO3, bound to hemoglobin, dissolved Carbonic anhydrase is big for HCO3 conversion - also produces H+, which binds to Hgb --> right shift (Bohr effect - helps Hgb unload O2 in metabolic states) Haldane Effect^: in lungs, oxygenation of Hgb promotes dissociation of H+ from Hgb --> shifts equilibrium towards CO2 formation --> CO2 released from RBCs (i.e., in O2-rich environments, Hgb has low affinity for CO2; in O2-poor environments, Hgb has high affinity for CO2) Tissues: low O2, high CO2 and H+ - favors O2 unloading (Bohr) and CO2 loading (Haldane) Lungs: high O2, low CO2 and H+ - favors O2 loading (Bohr) and CO2 unloading (Haldane) ^*H*emoglobin *A*ffinity for carbon *(l)D(ane)*ioxide

Three general causes of extrinsic hemolysis: *antibodies*, trauma/shearing, and RBC infxns --- *Autoimmune Hemolytic Anemia*: RBC destruction from autoantibodies --> RBC removal by ___ Warm (MC) AIHA is IgG Ab binding at body temp - s/sx are classic of anemia (fatigue, pallor, dyspnea, tachycardia) and ___vascular hemolysis (jaundice, splenomegaly); classic W-AIHA smear finding is *___+ agglutination (IgG Ab gets in way of macrophage --> only part is taken out --> more dense RBC)* Warm AIHA is often idiopathic, but can be seen in S___E, C___L, drugs (beta-lactams, alpha-methyldopa) Tx: steroids, splenectomy if refractory --- Cold AIHA is Ig___ Ab binding at <30C (fingertips, nose, ears) - s/sx are painful ___ w/purple discoloration When RBCs are warmed, IgM is lost; however, because IgM fixes complement better than IgG, ___ stays bound to RBCs (*important for Coombs test!*) Cold AIHA causes *___vascular hemolysis (C3-coated RBCs engulfed whole)* and can be seen in CLL, *but classically occurs in M pneumonia or EBV!* Tx: stay warm --- Coombs test (direct antiglobulin test) can be performed - patient's ___ + anti-IgG antiserum --> *agglutination (+) in Warm AIHA* (indicates RBCs are ALREADY BOUND by ___) - Cold AIHA will have DAT positive for ___ only (use anti-C3 Abs, not anti-IgG)!! INDIRECT antiglobulin test (indirect Coombs) is pt's ___ + random ___ --> look for Abs to RBC components (*not used for warm/cold AIHA, tests for Abs IN SERUM!! - can use for maternal-fetal testing*)

Three general causes of extrinsic hemolysis: *antibodies*, trauma/shearing, and RBC infxns --- *Autoimmune Hemolytic Anemia*: RBC destruction from autoantibodies --> RBC removal by spleen Warm (MC) AIHA is IgG Ab binding at body temp - s/sx are classic of anemia (fatigue, pallor, dyspnea, tachycardia) and extravascular hemolysis (jaundice, splenomegaly); classic W-AIHA smear finding is *spherocytes + agglutination (IgG Ab gets in way of macrophage --> only part is taken out --> more dense RBC)* Warm AIHA is often idiopathic, but can be seen in SLE, CLL, drugs (beta-lactams, alpha-methyldopa) Tx: steroids, splenectomy if refractory --- Cold AIHA is IgM Ab binding at <30C (fingertips, nose, ears) - s/sx are painful fingers/toes w/purple discoloration When RBCs are warmed, IgM is lost; however, because IgM fixes complement better than IgG, C3 stays bound to RBCs (*important for Coombs test!*) Cold AIHA causes *extravascular hemolysis (C3-coated RBCs engulfed whole)* and can be seen in CLL, *but classically occurs in M pneumonia or EBV!* Tx: stay warm --- Coombs test (direct antiglobulin test) can be performed - patient's RBCs + anti-IgG antiserum --> *agglutination (+) in Warm AIHA* (indicates RBCs are ALREADY BOUND by Abs) - Cold AIHA will have DAT positive for C3 only (use anti-C3 Abs, not anti-IgG)!! INDIRECT antiglobulin test (indirect Coombs) is pt's serum + random RBCs --> look for Abs to RBC components (*not used for warm/cold AIHA, tests for Abs IN SERUM!! - can use for maternal-fetal testing*)

Three general causes of extrinsic hemolysis: antibodies, *trauma/shearing*, and *RBC infxns* --- Shearing of RBCs in small blood vessels is d/t ___ in microvasculature --> narrowing MAHA is seen in TTP, HUS, and DIC, as well as *malignant ___ (d/t narrowing of vessels), aortic stenosis, mechanical heart valves* Classic blood smear finding is *___* --- ___ and ___ are classic infectious agents that can cause extrinsic hemolysis (will see Maltese cross and trophozoite rings, respectively)

Three general causes of extrinsic hemolysis: antibodies, *trauma/shearing*, and *RBC infxns* --- Shearing of RBCs in small blood vessels is d/t thrombi in microvasculature --> narrowing MAHA is seen in TTP, HUS, and DIC, as well as *malignant hypertension (d/t narrowing of vessels), aortic stenosis, mechanical heart valves* Classic blood smear finding is *schistocytes* --- Malaria and Babesia are classic infectious agents that can cause extrinsic hemolysis (will see Maltese cross and trophozoite rings, respectively)

Three major salivary glands include: p___ (behind angle of jaw - largest), sub___ (floor of mouth - secretes through Wharton's duct), sub___ (floor of mouth) Saliva consists of water and important immunologic aspects (Ig___, lysozymes - bact. cell wall, lactoferrin - prevent bact. growth) Saliva is important for ___ immunity; loss of saliva (Sjo___) --> dental ___ Digestive enzymes in saliva are ___ (inactive in stomach) and ___ - there are also pancreatic enzymes that do same thing

Three major salivary glands include: parotid (behind angle of jaw - largest), submandibular (floor of mouth - secretes through Wharton's duct), sublingual (floor of mouth) Saliva consists of water and important immunologic aspects (IgA, lysozymes - bact. cell wall, lactoferrin - prevent bact. growth) Saliva is important for innate immunity; loss of saliva (Sjogren's) --> dental caries Digestive enzymes in saliva are amylase (inactive in stomach) and lipase - there are also pancreatic enzymes that do same thing

Three mechanisms by which hypoxemia + high A-a gradient can be achieved: 1) *___ limitation*, 2) shunt, 3) V/Q mismatch Diffusion limitation (pulmonary f___) is seen when O2 can't leave alveoli for blood - results in hypoxemia usually ___ hypercapnia (CO2 can usually pass through diffusion limitation ___ readily) ___ correct w/100% O2 (increasing pressure gradient)

Three mechanisms by which hypoxemia + high A-a gradient can be achieved: 1) diffusion limitation, 2) shunt, 3) V/Q mismatch Diffusion limitation (pulmonary fibrosis) is seen when O2 can't leave alveoli for blood - results in hypoxemia usually w.o hypercapnia (CO2 can usually pass through diffusion limitation more readily) Will correct w/100% O2 (increasing pressure gradient)

Three mechanisms by which hypoxemia + high A=a gradient can be achieved: 1) diffusion limitation, 2) *s___*, 3) V/Q mismatch In normal lungs, ventilation = 4L/min, perfusion = 5L/min (of blood), normal V/Q = 0.8 If there is reduced ventilation, perfusion is wasted; extreme V/Q reduction (such that V/Q=0) --> venous blood gets to arterial system w.o oxygenation (*s___*) - shunting can be anatomic (AVM) or physiologic (alveoli not p___, seen in atelectasis!) Shunting results in PaO2<99%, pt will increase RR, which doesn't help PaO2 (d/t *MIXING of un___ + ___ blood*), but keeps CO2 normal ^V/Q=0 in *O*irway obstruction (shunt)

Three mechanisms by which hypoxemia + high A=a gradient can be achieved: 1) diffusion limitation, 2) shunt, 3) V/Q mismatch In normal lungs, ventilation = 4L/min, perfusion = 5L/min (of blood), normal V/Q = 0.8 If there is reduced ventilation, perfusion is wasted; extreme V/Q reduction (such that V/Q=0) --> venous blood gets to arterial system w.o oxygenation (*shunting*) - shunting can be anatomic (AVM) or physiologic (alveoli not perfused, seen in atelectasis!) Shunting results in PaO2<99%, pt will increase RR, which doesn't help PaO2 (d/t *MIXING of unoxygenated + oxygenated blood), but keeps CO2 normal

Three mechanisms by which hypoxemia + high A=a gradient can be achieved: 1) diffusion limitation, 2) shunt, 3) *___* In normal lungs, ventilation = 4L/min, perfusion = 5L/min (of blood), normal V/Q = 0.8 V/Q mismatch is somewhere on the spectrum of shunt (V/Q=___) to dead space (V/Q=___) - V/Q mismatch is usually referring to intermediate, though dead space/shunting are extremes Pulmonary e___ is classic example of V/Q mismatch, d/t less ventilation at fluid-filled alveoli - capillaries will mix w/O2-poor and O2-rich blood, leading to hypoxemia

Three mechanisms by which hypoxemia + high A=a gradient can be achieved: 1) diffusion limitation, 2) shunt, 3) V/Q mismatch In normal lungs, ventilation = 4L/min, perfusion = 5L/min (of blood), normal V/Q = 0.8 V/Q mismatch is somewhere on the spectrum of shunt (V/Q=0) to dead space (V/Q=infinity) - V/Q mismatch is usually referring to intermediate, though dead space/shunting are extremes Pulmonary edema is classic example of V/Q mismatch, d/t less ventilation at fluid-filled alveoli - capillaries will mix w/O2-poor and O2-rich blood, leading to hypoxemia

Three mechanisms by which hypoxemia + high A=a gradient can be achieved: 1) diffusion limitation, 2) shunt, 3) *V/Q mismatch* In normal lungs, ventilation = 4L/min, perfusion = 5L/min (of blood), normal V/Q = 0.8 When perfusion decreases, ventilation is wasted (i.e., gas going to places where can't be used); extreme perfusion decrease results in ___ (V/Q is infinity) - dead space can be anatomic (trachea) or physiologic (alveoli w.o functioning ___) With dead space, primary problem is *[HY]___ - PaO2 remains normal in PURE DEAD SPACE, PaO2 decreases in not-pure dead space (this is b/c flow increases to ___ parts of lung, creating V/Q mismatch such that flow [Q] outweighs ventilation [V] - perfusion-limited gas exchange)* Dead space can result 2/2 *p___ (obstruction to flow)*, fibrosis (destruction of alveolar capillaries) ^V/Q = oo (infinity) in blOOd flow obstruction (dead space)

Three mechanisms by which hypoxemia + high A=a gradient can be achieved: 1) diffusion limitation, 2) shunt, 3) V/Q mismatch In normal lungs, ventilation = 4L/min, perfusion = 5L/min (of blood), normal V/Q = 0.8 When perfusion decreases, ventilation is wasted (i.e., gas going to places where can't be used); extreme perfusion decrease results in dead space (V/Q is infinity) - dead space can be anatomic (trachea) or physiologic (alveoli w.o functioning capillaries) With dead space, primary problem is *[HY]HYPERCAPNIA - PaO2 remains normal in PURE DEAD SPACE, PaO2 decreases in not-pure dead space (this is b/c flow increases to healthy parts of lung, creating V/Q mismatch such that flow [Q] outweighs ventilation [V] - perfusion-limited gas exchange)* Dead space can result 2/2 *pulmonary embolism (obstruction to flow)*, fibrosis (destruction of alveolar capillaries)

Three mechanisms by which hypoxemia + high A=a gradient can be achieved: 1) diffusion limitation, 2) shunt, 3) V/Q mismatch Two primary ways to determine underlying mechanism of inadequate gas exchange: 1) response to ___ (increasing pressure gradient) and 2) presence of hyper___ *If no response to 100% O2 --> ___ (sick alveoli don't receive O2!)*; dead space and V/Q mismatch will correct Elevation is PaCO2 is d/t 1) increased production, 2) hypoventilation, 3) incr. d___ (PaCO2 ~ [CO2 production / (Tidal Volume - Dead Space)] *D___ causes hypercapnia (REMEMBER: dead space does not cause hypoxemia on own!)* d/t v___ being wasted; shunting and V/Q mismatch rarely cause hypercapnia (d/t hyperventilation fixing problem!)

Three mechanisms by which hypoxemia + high A=a gradient can be achieved: 1) diffusion limitation, 2) shunt, 3) V/Q mismatch Two primary ways to determine underlying mechanism of inadequate gas exchange: 1) response to 100% O2 (increasing pressure gradient) and presence of hypercapnia *If no response to 100% O2 --> shunting (sick alveoli don't receive O2!)*; dead space and V/Q mismatch will correct Elevation is PaCO2 is d/t 1) increased production, 2) hypoventilation, 3) incr. dead space (PaCO2 ~ [CO2 production / (Tidal Volume - Dead Space)] *Dead space causes hypercapnia (REMEMBER: dead space does not cause hypoxemia on own!)* d/t ventilation being wasted; shunting and V/Q mismatch rarely cause hypercapnia (d/t hyperventilation fixing problem!)

Three patterns of pneumonia: lobar, bronchopneumonia, interstitial (atypical) Bronchopneumonia is patchy inflammation of multiple lobules - classic bact. is S ___ (also H flu, Klebsiella) Interstitial (atypical, i.e., not pneumococcus) pneumonia is infiltrate of alveolar walls only - indolent course (m___, c___)

Three patterns of pneumonia: lobar, bronchopneumonia, interstitial (atypical) Bronchopneumonia is patchy inflammation of multiple lobules - classic bact. is S aureus (also H flu, Klebsiella) Interstitial (atypical, i.e., not pneumococcus) pneumonia is infiltrate of alveolar walls only - indolent course (mycoplasma, chlamydia)

Three patterns of pneumonia: lobar, bronchopneumonia, interstitial (atypical); Lobar pneumo. goes through four stages: 1. ___: 1-2d, alveolar capillaries dilate and exudate of bact. occurs 2. ___: 3-4d, exudate of RBCs/neutrophils/fibrin give lung red color 3. ___: 5-7d, uniformly gray d/t exudate of WBCs and *lysed RBCs - pneumococci starting to die (gray is sad, everything is dying)* 4. ___: 8+d, enzymatic digestion of exudate by macrophages, *[HY] ___ (cell type?) are key for regeneration*

Three patterns of pneumonia: lobar, bronchopneumonia, interstitial (atypical); Lobar pneumo. goes through four stages: 1. Congestion: 1-2d, alveolar capillaries dilate and exudate of bact. occurs 2. Red Hepatization: 3-4d, exudate of RBCs/neutrophils/fibrin give lung red color 3. Gray Hepatization: 5-7d, uniformly gray d/t exudate of WBCs and *lysed RBCs - pneumococci starting to die (gray is sad, everything is dying)* 4. Resolution: 8+d, enzymatic digestion of exudate by macrophages, *[HY] type II pneumocytes are key for regeneration*

Thrombin Time tests measures for 1) ___ of thrombin or 2) decreased ___ levels Abnormal ___ function leads to characteristic mucosal bleeding, skin bleeding, and petechiae Abnormal ___ leads to joint bleeding or deep tissue bleeding

Thrombin Time tests measures for 1) inhibitors of thrombin or 2) decreased fibrinogen levels Abnormal platelet function leads to characteristic mucosal bleeding, skin bleeding, and petechiae Abnormal coagulation factors leads to joint bleeding or deep tissue bleeding

Thyroid Hormone secretion is stimulated ty TSH secretion (anterior pituitary), which *[HY] binds to follicular cells to activate ___ second messenger system* - increases T3/4 release via 1) increased proteolysis of thyroglobulin, 2) rapid release of T3/4, and 3) thyroid cell ___ (think Goiter) TSH itself is controlled by TRH from hypothalamus Pregnancy has many effects on TH production: 1. Elevated estrogen --> increased ___ --> increased total T4 2. ___ stimulates thyroid (same subunit as TSH) --> increased free T4 (early in pregnancy) 3. Because of increased T4 --> decreased ___ (early in pregnancy)

Thyroid Hormone secretion is stimulated ty TSH secretion (anterior pituitary), which *[HY] binds to follicular cells to activate cAMP/PKA second messenger system* - increases T3/4 release via 1) increased proteolysis of thyroglobulin, 2) rapid release of T3/4, and 3) thyroid cell growth (think Goiter) TSH itself is controlled by TRH from hypothalamus Pregnancy has many effects on TH production: 1. Elevated estrogen --> increased TBH --> increased total T4 2. hCG stimulates thyroid (same subunit as TSH) --> increased free T4 (early in pregnancy) 3. Because of increased T4 --> decreased TSH (early in pregnancy)

Thyroid cancer usually presents as pain___ nodule w.o hyper-/hypothyroid symptoms (with differential being adenoma vs. cancer) FNA is usually done to biopsy and dx - ultrasound can also give nodule characteristics (borders, vascularity, calcifications) Radioactive iodine uptake can also be done with several results: 1) Diffuse, even uptake (___) 2) Diffuse, high uptake (___) 3) Diffuse, low uptake (___) 4) Multiple areas of high uptake (___) 5) Single "hot" nodule (___) 6) Single "cold" nodule (___)

Thyroid cancer usually presents as painless nodule w.o hyper-/hypothyroid symptoms (with differential being adenoma vs. cancer) FNA is usually done to biopsy and dx - ultrasound can also give nodule characteristics (borders, vascularity, calcifications) Radioactive iodine uptake can also be done with several results: 1) Diffuse, even uptake (normal) 2) Diffuse, high uptake (Grave's) 3) Diffuse, low uptake (Hashimoto's) 4) Multiple areas of high uptake (nodular goiter) 5) Single "hot" nodule (adenoma) 6) Single "cold" nodule (possibly cancer - cancer doesn't make hormone)

Thyroid contains two glands connected by the ___; the blood supply comes from superior (___ branch of external carotid) and inferior (thyrocervical trunk) thyroid aa The thyroid ___ (center of pharyngeal pouches) descends into neck; initially, it maintains connection to tongue via ___ (disappears later in development, but remnants include *foramen ___ and ___ lobe*) Some CHILDREN have *thyroglossal duct cyst (painless ___ mass* that *___ w/swallowing and/or tongue protrusion (think of connection!!)* Because of embryology, MC location for ectopic thyroid is *@ base of the ___ (presents w/tongue mass during puberty or pregnancy)*

Thyroid contains two glands connected by the isthmus; the blood supply comes from superior (1st branch of external carotid) and inferior (thyrocervical trunk) thyroid aa The thyroid diverticulum (center of pharyngeal pouches) descends into neck; initially, it maintains connection to tongue via thyroglossal duct (disappears later in development, but remnants include *foramen cecum and pyramidal lobe*) Some CHILDREN have *thyroglossal duct cyst (painless midline mass* that *moves up w/swallowing and/or tongue protrusion (think of connection!!)* Because of embryology, MC location for ectopic thyroid is *@ base of the tongue (presents w/tongue mass during puberty or pregnancy)*

Thyroid histology contains follicles (fill with *___*) which are lined w/*___ cells (synthesize thyroid hormone)* Thyroid hormones contain ___ (reason for iodizes salt - prevent deficiency); two forms are T3 and T4 (synthesized from tyrosine and iodine); plasma iod*IDE* (I-) needs to be oxidized to iod*INE* (I2) for thyroid hormone synthesis before it can be *ORGANIFIED* (added to ___) ___ (large protein produced by follicular cells w/many tyrosines) functions to aid T3 and T4 synthesis Thyroid also contains ___ cells, which secrete calcitonin --> lowers serum calcium

Thyroid histology contains follicles (fill with *colloid*) which are lined w/*follicular cells (synthesize thyroid hormone)* Thyroid hormones contain iodine (reason for iodizes salt - prevent deficiency); two forms are T3 and T4 (synthesized from tyrosine and iodine); plasma iod*IDE* (I-) needs to be oxidized to iod*INE* (I2) for thyroid hormone synthesis before it can be *ORGANIFIED* (added to tyrosine) Thyroglobulin (large protein produced by follicular cells w/many tyrosines) functions to aid T3 and T4 synthesis Thyroid also contains parafollicular (C) cells, which secrete calcitonin --> lowers serum calcium

Thyroiditis can cause transient ___thyroidism, followed by long-term ___thyroidism --- *Hashimoto Thyroiditis*: autoimmune d.o (*a/w HLA-DR5*) characterized by lymphocytic infiltration of thyroid gland; may find anti-___ or anti-___ anti bodies Histology will reveal *massive ___ infiltrate (+/- germinal centers) and ___ cells (enlarged eosinophilic follicular cells)* Commonly p/w woman who has enlarged non-tender thyroid w/gradual onset of thyroid function + labs c/w hypothyroidism Tx: thyroid replacement Special: *a/w increased risk of Non-___* --- *De Quervain's/Subacute/GRANULOMATOUS Thyroiditis*: *[HY] ___ inflammation of thyroid*; seen in young women w/*___ (unique!), enlarged thyroid* + classic thyroiditis picture (hyper- --> eu- --> hypothyroid) ^de quervAIN and ___AIN --- *Riedel's Thyroiditis*: ___ activation --> *FIBROUS tissue (HUGE part of pathophys) deposition in thyroid* --> *___ thyroid [BuZzWoRd - Rock=Riedel's*] (*often extending beyond thyroid --> parathyroid, ___ nn, trachea*) *A/w ___ plasma cells (along with autoimmune pancreatitis)* --- *___ thyroiditis* is mild self-limited variant of Hashimoto's <1y after delivery; *___ thyroiditis* is similar w/o pregnancy

Thyroiditis can cause transient hyperthyroidism, followed by long-term hypothyroidism --- *Hashimoto Thyroiditis*: autoimmune d.o (*a/w HLA-DR5*) characterized by lymphocytic infiltration of thyroid gland; may find anti-TPO or anti-thyroglobulin anti bodies Histology will reveal *massive lymphocytic infiltrate (+/- germinal centers) and Hurthle cells (enlarged eosinophilic follicular cells)* Commonly p/w woman who has enlarged non-tender thyroid w/gradual onset of thyroid function + labs c/w hypothyroidism Tx: thyroid replacement Special: *a/w increased risk of Non-Hodgkin lymphoma (large B-cell)* --- *De Quervain's/Subacute/GRANULOMATOUS Thyroiditis*: *[HY] granulomatous inflammation of thyroid*; seen in young women w/*TENDER (unique!), enlarged thyroid* + classic thyroiditis picture (hyper- --> eu- --> hypothyroid) ^de quervAIN and pAIN --- *Riedel's Thyroiditis*: fibroblast activation --> *FIBROUS tissue (HUGE part of pathophys) deposition in thyroid* --> *rock-hard thyroid [BuZzWoRd - Rock=Riedel's*] (*often extending beyond thyroid --> parathyroid, recurrent laryngeal nn, trachea*) *A/w IgG4 plasma cells (along with autoimmune pancreatitis)* --- *Postpartum thyroiditis* is mild self-limited variant of Hashimoto's <1y after delivery; *Painless thyroiditis* is similar w/o pregnancy

___ is important carrier for thyroid hormone (T4) - most T4 in plasma is bound to TBG; KEY POINT: less TBG --> ___ T4 (and T3) available to tissues TBG levels increase with ___ (pregnant and OCP pts can have elevated T4) Mechanism: rise in TBG --> ___ bound T4, ___ free T4 --> increased TSH --> increased total T4 --> increased free T4 (to normal) --> decreased TSH (to normal) TBG levels decrease in ___ failure (less protein produced, similar mechanism to above but in reverse) Thyroid hormone functions on thyroid receptors to modulate gene expression and *regulate metabolic activity and growth*

Thyroxine-Binding Globulin (TBG) is important carrier for thyroid hormone (T4) - most T4 in plasma is bound to TBG; KEY POINT: less TBG --> less T4 (and T3) available to tissues TBG levels increase with estrogen (pregnant and OCP pts can have elevated T4) Mechanism: rise in TBG --> more bound T4, less free T4 --> increased TSH --> increased total T4 --> increased free T4 (to normal) --> decreased TSH (to normal) TBG levels decrease in liver failure (less protein produced, similar mechanism to above but in reverse) Thyroid hormone functions on thyroid receptors to modulate gene expression and *regulate metabolic activity and growth*

___ = fungal skin/nail infection Dermatophytes = fungi that require ___ for growth Most tinea infxns are caused by dermatophytes *Tinea versicolor on KOH prep will show ___ AND ___ cells (--> spaghetti and meatballs)*

Tinea = fungal skin/nail infection Dermatophytes = fungi that require keratin for growth Most tinea infxns are caused by dermatophytes *Tinea versicolor on KOH prep will show hyphae AND yeast cells (--> spaghetti and meatballs)*

Transitional cell carcinoma (urothelial carcinoma of bladder) is MC urinary tract tumor - it can be seen in bladder, renal calyces, pelvises, and ureters Importantly, TCC is often multifocal and recurrent w/damage to entire urothelium RFs include Phenacetin, ___, Aromatic amines (hair coloring), and ___ [Pee SAC problems] Tx: platinum-based chemotherapy (cisplatin, carboplatin) --- Squamous cell carcinoma is a rare bladder cancer that requires chronic ___ of the bladder to develop (*like in any SCC*) Key RFs include smoking, chronic stones, S___ --- ___ is a very rare bladder cancer w/glandular proliferation of bladder Occurs in special circumstances (*URACHAL remnants*, long h/o cystitis, or bladder protrusion through abdominal wall)

Transitional cell carcinoma (urothelial carcinoma of bladder) is MC urinary tract tumor - it can be seen in bladder, renal calyces, pelvises, and ureters Importantly, TCC is often multifocal and recurrent w/damage to entire urothelium RFs include Phenacetin, Smoking, Aromatic amines (hair coloring), and Cyclophosphamide [Pee SAC problems] Tx: platinum-based chemotherapy (cisplatin, carboplatin) --- Squamous cell carcinoma is a rare bladder cancer that requires chronic inflammation of the bladder to develop (*like in any SCC*) Key RFs include smoking, chronic stones, Schistosoma haematobium --- Adenocarcinoma is a very rare bladder cancer w/glandular proliferation of bladder Occurs in special circumstances (*URACHAL remnants*, long h/o cystitis, or bladder protrusion through abdominal wall)

Transplant rejection can be: Hyperacute (minutes): caused by preformed ___ in recipient (i.e., Abs to ABO, HLA antigens - developed from previous exposure to foreign antigens [pregnancy, transfusion]) - prevented by *___-matching*; at a cellular level, blood vessel spasm --> intravascular coagulation --> ___ ("white rejection") Acute (weeks-to-months): recipient T-cells react to graft (via HLA); CD8+ T-cell-driven response and biopsy will show *infiltrates of ___ cells* (tx w/immunosuppression) Chronic (months-to-years): biopsy hallmark is *___*, especially in vessels (kidneys - glomeruli, heart - coronary arteries); complex, incompletely understood process w/type II and IV HS rxn (humoral + cellular), but host APCs presenting ___ peptides to host CD4+ T-cells may play a role

Transplant rejection can be: Hyperacute (minutes): caused by preformed antibodies in recipient (i.e., Abs to ABO, HLA antigens - developed from previous exposure to foreign antigens [pregnancy, transfusion]) - prevented by *cross-matching*; at a cellular level, blood vessel spasm --> intravascular coagulation --> ischemia ("white rejection") Acute (weeks-to-months): recipient T-cells react to graft (via HLA); CD8+ T-cell-driven response and biopsy will show *infiltrates of lymphocytes/mononuclear cells* (tx w/immunosuppression) Chronic (months-to-years): biopsy hallmark is *FIBROSIS*, especially in vessels (kidneys - glomeruli, heart - coronary arteries); complex, incompletely understood process w/type II and IV HS rxn (humoral + cellular), but host APCs presenting donor peptides to host CD4+ T-cells may play a role

Treatment for Cushing's Syndrome can be via surgery (if adrenal adenoma or pituitary adenoma) or medication (*___ - [HY]*) *Ketoconazole blocks 1st step in cortisol synthesis (___, which normally primes cholesterol for cycle); this is the step that occurs to get to the zona glomerulosa* *NOTE: ketoconazole also blocks 17,20-lyase --> ___*

Treatment for Cushing's Syndrome can be via surgery (if adrenal adenoma or pituitary adenoma) or medication (*ketoconazole - [HY]*) *Ketoconazole blocks 1st step in cortisol synthesis (DESMOLASE, which normally primes cholesterol for cycle); this is the step that occurs to get to the zona glomerulosa* *NOTE: ketoconazole also blocks 17,20-lyase --> gynecomastia*

Tropical sprue (occurs in tropics) has similar findings to Celiac (steatorrhea, blunting of villi), but *will involve ___ (CD primarily affects DUODENUM)* TS is a/w f___ and B___ deficiencies TYPICAL CASE: traveler to tropics w/chronic diarrhea and negative TTG Abs Tx: Abx and folate

Tropical sprue (occurs in tropics) has similar findings to Celiac (steatorrhea, blunting of villi), but *will involve entire intestine (CD primarily affects DUODENUM)* TS is a/w folate and B12 deficiencies TYPICAL CASE: traveler to tropics w/chronic diarrhea and negative TTG Abs Tx: Abx and folate

Tryptophan is used to synthesize serotonin (5-HT) - the first step is tryptophan --> 5-hydroxytryptophan (via tryptophan hydroxylase, requires BH4) --> 5HT (serotonin); serotonin can be converted to melatonin Normally, only 1% of tryptophan is converted to serotonin, *but up to 70% can be converted in cases of CARCINOID SYNDROME (diarrhea, valvular lesions, flushing) --> tryptophan deficiency* Serotonin is broken down by MAO --> 5-HIAA excreted in urine (*elevated in carcinoid syndrome!*) --- Other than serotonin/melatonin, tryptophan can be used to synthesize *niacin (B3)*, which is used to synthesize NADH/NADPH Hartnup dz is AR disorder of AA transporter in proximal tubule --> loss of tryptophan in urine --> sx of niacin deficiency (*pellagra - hyperpigmented rash on exposed skin areas, red tongue [glossitis], diarrhea/vomiting, CNS sx [three Ds - dementia, diarrhea, dermatitis]*) Tx: high protein diet + niacin supplement

Turner (X0) can occur d/t sperm lacking Xchrom (50% of cases) or d/t poxt-zygotic mitotic nondisjunction leading to m___ Turner syndrome (50% of cases, milder) General features: short stature (loss of SHOX gene --> give GH), broad "shield" chest, wide-spaced nipples, *webbed neck (2/2 lymph obstruction), swollen hands/feet (2/2 lymph obstruction)*, cystic hygroma (congenital lymphatic defect, collection of lymph in head/neck), and *(hallmark) primary hypogonadism with "___ OVARIES"* --> ___ inhibin B/estrogen, ___ LH/FSH, delayed puberty, *___ AMENNHOREA*; most women are infertile *[HY] 1/3rd of girls w/TS are born with ___ (cardiac?); 5-10% have ___ of the aorta --> high blood pressure in childhood* Renal manifestations (33% of pts) include *[HY] ___ kidney* Other issues include osteoporosis (2/2 no estrogen), T2DM, thyroid dz

Turner (X0) can occur d/t sperm lacking Xchrom (50% of cases) or d/t poxt-zygotic mitotic nondisjunction leading to mosaic Turner syndrome (50% of cases, milder) General features: short stature (loss of SHOX gene --> give GH), broad "shield" chest, wide-spaced nipples, *webbed neck (2/2 lymph obstruction), swollen hands/feet (2/2 lymph obstruction)*, cystic hygroma (congenital lymphatic defect, collection of lymph in head/neck), and *(hallmark) primary hypogonadism with "STREAK OVARIES"* --> dec. inhibin B/estrogen, inc. LH/FSH, delayed puberty, *PRIMARY AMENNHOREA*; most women are infertile *[HY] 1/3rd of girls w/TS are born with bicuspid aortic valve; 5-10% have coarctation of the aorta --> high blood pressure in childhood* Renal manifestations (33% of pts) include *[HY] horseshoe kidney* Other issues include osteoporosis (2/2 no estrogen), T2DM, thyroid dz

Two blood vessels determine pulmonary vascular resistance: alveolar and arteriolar vessels Increased lung volume stretches a___ vessels (longer, narrower --> incr. resistance), decreased lung volume narrows a___ vessels (incr. resistance); happy medium is at F___ - when PVR is lowest Pulm. HTN (MAP>25mmHg) manifests w/*[HY] loud ___* and dyspnea (can lead to cor pulmonale + death) PVR = ([Press. PA - Press. LA, i.e., change in pressure] / [CO]) Press. PA (pulm HTN!) = [PVR x CO] + Press. LA Accordingly, pulm HTN can develop from 1) incr. PVR^, 2) incr. ___ (ASD, VSD, PDA), 3) incr. ___ (heart failure, valve dz) ^Elevated PVR can be 2/2 COPD, pulmonary fibrosis, sleep apnea, HIV, chronic pulmonary emboli; *primary pulm. HTN (rare - young women) is 2/2 increased e___ (vasoconstrictor) and decreased NO - seen w/BMPR2 mutation, tx w/epoprostenol, bosentan, sildenafil*

Two blood vessels determine pulmonary vascular resistance: alveolar and arteriolar vessels Increased lung volume stretches alveolar vessels (longer, narrower --> incr. resistance), decreased lung volume narrows arteriolar vessels (incr. resistance); happy medium is at FRC - when PVR is lowest Pulm. HTN (MAP>25mmHg) manifests w/*[HY] loud P2* and dyspnea (can lead to cor pulmonale + death) PVR = ([Press. PA - Press. LA, i.e., change in pressure] / [CO]) Press. PA (pulm HTN!) = [PVR x CO] + Press. LA Accordingly, pulm HTN can develop from 1) incr. PVR^, 2) incr. CO (ASD, VSD, PDA), 3) incr. Press. LA (heart failure, valve dz) ^Elevated PVR can be 2/2 COPD, pulmonary fibrosis, sleep apnea, HIV, chronic pulmonary emboli; *primary pulm. HTN (rare - young women) is 2/2 increased endothelin (vasoconstrictor) and decreased NO - seen w/BMPR2 mutation, tx w/epoprostenol, bosentan, sildenafil*

Two major problems from sickled cells: 1) hemolytic anemia and 2) ___ of small blood vessels 1. Sickling of cells is reversible, but sickle-unsickle in circulation --> RBC ___ damage --> ___vascular hemolysis in spleen (+ some intravascular) Because of low Hgb, ___ is markedly elevated --> expansion of bone marrow --> face and skull abnormalities (*"___ facies", crewcut appearance*); pts are also extremely vulnerable to ___ infxn 2. Sickled cells can occlude microvasculature, classically affect *hands (d___), ___ (ortho), acute pain crises (MC; episodic acute pain d/t vaso-occlusion - ___, bones, etc.), splenic failure (d/t repeated splenic infarctions --> functional asplenia --> H___ on smear, risk of encapsulated infxns), acute chest syndrome (occlusion of ___ microvasculature - triggered by PNA), renal dysfunction (occlusion of vasa recta of medulla --> ___ necrosis)* Classically, SCA pts can develop osteomyelitis from ___ (encapsulated bacteria) Splenic sequestration crisis can also occur, in which splenic vaso-occlusion --> pooling of RBCs --> *rapidly enlarging spleen + hypovolemic ___* Tx: hydroxyurea, transfusions, immunizations

Two major problems from sickled cells: 1) hemolytic anemia and 2) vaso-occlusion of small blood vessels 1. Sickling of cells is reversible, but sickle-unsickle in circulation --> RBC membrane damage --> extravascular hemolysis in spleen (+ some intravascular) Because of low Hgb, EPO is markedly elevated --> expansion of bone marrow --> face and skull abnormalities (*"chipmunk facies", crewcut appearance*); pts are also extremely vulnerable to parvoB19 infxn 2. Sickled cells can occlude microvasculature, classically affect *hands (dactylitis), AVASCULAR NECROSIS (ortho), acute pain crises (MC; episodic acute pain d/t vaso-occlusion - abdomen, bones, etc.), splenic failure (d/t repeated splenic infarctions --> functional asplenia --> HOWELL-JOLLY BODIES on smear, risk of encapsulated infxns), acute chest syndrome (occlusion of pulmonary microvasculature - triggered by PNA), renal dysfunction (occlusion of vasa recta of medulla --> papillary necrosis)* Classically, SCA pts can develop osteomyelitis from Salmonella (encapsulated bacteria) Splenic sequestration crisis can also occur, in which splenic vaso-occlusion --> pooling of RBCs --> *rapidly enlarging spleen + hypovolemic shock* Tx: hydroxyurea, transfusions, immunizations

Two major steps in midgut development: herniation *through umbilical ring* (6th week) and rotation around ___ w/cecum in RLQ (~10th week) If midgut does not return to abdomen --> *OMPHALOCELE (Distinct Features: intestines ___ by PERITONEAL membrane; herniation through ___)*; babies have normal GI function but *a/w defects (___ [chrom abnormalities?], congenital heart defects, orofacial defects, neural tube defects)* Gastroschisis is extrusion of bowel through abdominal wall w/unclear mechanism; IMPORTANTLY: this will be a *___ abdominal wall defect that is ___ covered by peritoneum* - bad GI prognosis, but no associated defects Malrotation of gut can lead to bowel obstruction, ___ (small bowel twists around SMA --> ischemia --> obstruction; p/w distension and hematochezia), or left-sided colon

Two major steps in midgut development: herniation *through umbilical ring* (6th week) and rotation around SMA w/cecum in RLQ (~10th week) If midgut does not return to abdomen --> *OMPHALOCELE (Distinct Features: intestines COVERED by PERITONEAL membrane; herniation through umbilicus)*; babies have normal GI function but *a/w defects (trisomy 21/18/13, congenital heart defects, orofacial defects, neural tube defects)* Gastroschisis is extrusion of bowel through abdominal wall w/unclear mechanism; IMPORTANTLY: this will be a *paraumbilical abdominal wall defect that is not covered by peritoneum* - bad GI prognosis, but no associated defects Malrotation of gut can lead to bowel obstruction, volvulus (small bowel twists around SMA --> ischemia --> obstruction; p/w distension and hematochezia), or left-sided colon

Two-Hit Theory: mutations in TSG requires both genes to be mutated for cancer (first --> no dz, 2nd --> dz - "loss of h___"), classic example is *hereditary retinoblastoma (germline Rb mutation --> 2nd hit; multiple tumors vs sporadic retinoblastoma --> one tumor, not born w/first hit)*; other examples are HNPCC (germline mut in DNA ___ genes), ___ (APC gene), and Li-Fraumeni (SBLA ca syndrome, mut in TP___) Mosaicism is gene mutation in one cell that leads to line of mutated cells and mixture of cells; can have germline mosaicism (passed to offspring) and somatic mosaicism (differences in tissues/organs); ex: McCune-Albright Syndrome (*2/2 ___-ZYGOTIC somatic mut in G___ gene*, mut varies depending on tissue affected - germline mut is lethal) - P___ puberty, bone f___/deformity, skin pigmentation w/irregular (Coast of Maine) ___

Two-Hit Theory: mutations in TSG requires both genes to be mutated for cancer (first --> no dz, 2nd --> dz - "loss of heterozygosity"), classic example is *hereditary retinoblastoma (germline Rb mutation --> 2nd hit; multiple tumors vs sporadic retinoblastoma --> one tumor, not born w/first hit)*; other examples are HNPCC (germline mut in DNA MMR genes), FAP (APC gene), and Li-Fraumeni (SBLA ca syndrome, mut in TP53) Mosaicism is gene mutation in one cell that leads to line of mutated cells and mixture of cells; can have germline mosaicism (passed to offspring) and somatic mosaicism (differences in tissues/organs); ex: McCune-Albright Syndrome (*2/2 POST-ZYGOTIC somatic mut in GNAS gene*, mut varies depending on tissue affected - germline mut is lethal) - precocious puberty, bone fractures/deformity, skin pigmentation w/irregular (Coast of Maine) borders

Tx of acute pancreatitis involves three steps: 1) NPO, 2) IV fluids, and 3) pain control Complications include (DAMP CAN): -DIC -Abscess (*infxn of pancreatic ___*) -Multi-organ failure -___ (identified when acute pancreatitis doesn't resolve - persistent pain, no fall in amylase/lipase, *seen in lesser sac of abdomen, can rupture --> peritonitis*) -___ low (seen necrosis of fat) -ARDS (looks like pulmonary edema, *but w/NORMAL ___!*) -Necrosis of fat (inflammation of acute pancreatitis spreads to surrounding fat, *[HY] can lead to HYPO___/HYPO___ 2/2 saponification*)

Tx of acute pancreatitis involves three steps: 1) NPO, 2) IV fluids, and 3) pain control Complications include (DAMP CAN): -DIC -Abscess (*infxn of pancreatic pseudocyst*) -Multi-organ failure -Pseudocyst (identified when acute pancreatitis doesn't resolve - persistent pain, no fall in amylase/lipase, *seen in lesser sac of abdomen, can rupture --> peritonitis*) -Calcium low (seen necrosis of fat) -ARDS (looks like pulmonary edema, *but w/NORMAL PCWP!*) -Necrosis of fat (inflammation of acute pancreatitis spreads to surrounding fat, *[HY] can lead to HYPOCALCEMIA/HYPOMAGNESEMIA 2/2 saponification*)

Type I DM is autoimmune disorder (type ___ HS rxn), in which T-cells destroy beta cells of pancreas (will see ___ on biopsy) --> loss of insulin; Type I DM is a/w HLA-DR___ and HLA-___4 (4 - 3 = 1) T1DM presents in children w/symptomatic hyperglycemia (DKA) --> tx w/insulin DKA is common initial presentation of T1DM (*much ___ common than T2DM*) and is often precipitated by infxn/trauma, or when T1DM skips insulin therapy DKA PATHOPHYS: Low insulin (--> high glucagon) + high epinephrine --> high glucose High glucose --> high ___ (*fruity breath*) --> acidosis (*hyper___ [ARRHYTHMIA] + ___phosphatemia [acid shifts phosphate out of cells --> lost in urine --> MUSCLE WEAKNESS]*) --> decreased GI motility (*abd pain, N/V*) High glucose --> polyuria (*de___*) DKA PRESENTATION: Child w/___ pain, N/V, dehydration, hyperglycemia + hyperkalemia + anion gap metabolic acidosis w/*___ breathing to compensate*, fruity smell on breath Tx: insulin + IV fluids + *[HY] close monitoring of serum ___ (consider adding later in tx - also monitor glucose)*

Type I DM is autoimmune disorder (type IV HS rxn), in which T-cells destroy beta cells of pancreas (will see lymphocytes on biopsy) --> loss of insulin; Type I DM is a/w HLA-DR3 and HLA-DR4 (4 - 3 = 1) T1DM presents in children w/symptomatic hyperglycemia (DKA) --> tx w/insulin DKA is common initial presentation of T1DM (*much more common than T2DM*) and is often precipitated by infxn/trauma, or when T1DM skips insulin therapy DKA PATHOPHYS: Low insulin (--> high glucagon) + high epinephrine --> high glucose High glucose --> high ketones (*fruity breath*) --> acidosis (*hyperkalemia [ARRHYTHMIA] + hypophosphatemia [acid shifts phosphate out of cells --> lost in urine --> MUSCLE WEAKNESS]*) --> decreased GI motility (*abd pain, N/V*) High glucose --> polyuria (*dehydration*) DKA PRESENTATION: Child w/abd pain, N/V, dehydration, hyperglycemia + hyperkalemia + anion gap metabolic acidosis w/*Kussmaul breathing to compensate*, fruity smell on breath Tx: insulin + IV fluids + *[HY] close monitoring of serum potassium (consider adding later in tx - also monitor glucose)*

Type II HS rxn are autoimmune d.o in which antibodies are directed against our own tissue antigens; three mechanisms by which this occurs: 1) cellular destruction, 2) inflammation, or 3) cellular dysfunction 1) Cell is opsonized by antibodies --> phagocytosis (w/ or w.o complement) or ___ cell killing (*antibody-dependent cellular cytotoxicity*) (*T___ Reaction [CLASSIC], autoimmune hemolytic anemia [warm and cold]*) 2) Binding of Abs --> activation of complement cascade/Fc receptor-mediated inflammation (*R___ [CLASSIC], Go___ syndrome*) 3) Antibodies bind cell surface --> block downstream effects/goals of cell (*Pemphigus Vulgaris, M___ G___, Graves Dz*)

Type II HS rxn are autoimmune d.o in which antibodies are directed against our own tissue antigens; three mechanisms by which this occurs: 1) cellular destruction, 2) inflammation, or 3) cellular dysfunction 1) Cell is opsonized by antibodies --> phagocytosis (w/ or w.o complement) or NK cell killing (*antibody-dependent cellular cytotoxicity*) (*Transfusion Reaction [CLASSIC], autoimmune hemolytic anemia [warm and cold]*) 2) Binding of Abs --> activation of complement cascade/Fc receptor-mediated inflammation (*Rheumatic Fever [CLASSIC], Goodpasture syndrome*) 3) Antibodies bind cell surface --> block downstream effects/goals of cell (*Pemphigus Vulgaris, Myasthenia Gravis, Graves Dz*)

Type III HS rxn is 2/2 Ag-Ab complex formation --> complement formation + inflammation; two subtypes: serum sickness and arthrus reaction Serum Sickness (1-2w): IC in plasma deposit in many places --> systemic dz --> trigger immune response (fever, rash, arthralgias), labs demonstrate ___ C3/C4 Arthrus Reaction (4-10h): local reaction to IC deposition, seen after intradermal injection of antigen into pre-sensitized (i.e., w/circulating ___) individual --> immune complex formation --> local complement activation, edema, and fibrinoid necrosis (e.g., TDAP booster, insulin); IDed via immunofluorescent staining Ex: SLE, RA, *polyarteritis nodosa (HepB), PSGN*

Type III HS rxn is 2/2 Ag-Ab complex formation --> complement formation + inflammation; two subtypes: serum sickness and arthrus reaction Serum Sickness (1-2w): IC in plasma deposit in many places --> systemic dz --> trigger immune response (fever, rash, arthralgias), labs demonstrate low C3/C4 Arthrus Reaction (4-10h): local reaction to IC deposition, seen after intradermal injection of antigen into pre-sensitized (i.e., w/circulating IgG) individual --> immune complex formation --> local complement activation, edema, and fibrinoid necrosis (e.g., TDAP booster, insulin); IDed via immunofluorescent staining Ex: SLE, RA, *polyarteritis nodosa (HepB), PSGN*

Type IV hypersensitivity reaction is entirely ___-mediated (*NO ANTIBODIES!*) Can be 1) direct cell cytotoxicity (CD8+ T-cells kill targeted cells) or 2) inflammatory reaction (effector CD4+ T-cells recognize antigen and release inflammation-inducing cytokines) Ex: PPD injection for TB infection (body previously exposed --> ___ cells recognize antigen --> Th1 response to PPD), *c___ dermatitis, multiple sclerosis*

Type IV hypersensitivity reaction is entirely cell-mediated (*NO ANTIBODIES!*) Can be 1) direct cell cytotoxicity (CD8+ T-cells kill targeted cells) or 2) inflammatory reaction (effector CD4+ T-cells recognize antigen and release inflammation-inducing cytokines) Ex: PPD injection for TB infection (body previously exposed --> memory T-cells recognize antigen --> Th1 response to PPD), *contact dermatitis, multiple sclerosis*

Typical h/o child abuse is minor trauma --> major injury, history changing over time, or injuries blamed on ___ (will see bruises of different ages in odd places, fractures in different stages of healing) Classic findings in Shaken Baby Syndrome is ___ hemorrhages and/or ___ hematoma RFs for child abuse include parent (single/young, low education, substance use, psych illness) and child (unplanned/unwanted, disability) factors ___ is different in that it is abandonment of child (inadequate food, shelter, affection); ___ Child Syndrome is opposite --> trips to ER for minor complaints, constant worry about illness

Typical h/o child abuse is minor trauma --> major injury, history changing over time, or injuries blamed on siblings/pets (will see bruises of different ages in odd places, fractures in different stages of healing) Classic findings in Shaken Baby Syndrome is retinal hemorrhages and/or subdural hematoma RFs for child abuse include parent (single/young, low education, substance use, psych illness) and child (unplanned/unwanted, disability) factors Neglect is different in that it is abandonment of child (inadequate food, shelter, affection); Vulnerable Child Syndrome is opposite --> trips to ER for minor complaints, constant worry about illness

Tyrosine --> ___ --> ___ --> norepinephrine (calcium influx triggers NE release) Metyrosine inhibits ___ --> ___ ___ inhibits dopamine --> norepinephrine Cocaine inhibits reuptake of ___, dopamine, and serotonin; manifestations include ___ pupils, chest pain, and abnormal ___ mucosa

Tyrosine --> dopa --> dopamine --> norepinephrine (calcium influx triggers NE release) Metyrosine inhibits tyrosine --> dopamine Reserpine inhibits dopamine --> norepinephrine Cocaine inhibits reuptake of NE, dopamine, and serotonin; manifestations include dilated pupils, chest pain, and abnormal nasal mucosa

Tyrosine can be metabolized to homogentisic acid for breakdown in body --> fumarate and acetoacetate (accordingly, tyrosine [and phenylalanine] are glucogenic and ketogenic) Alkaptonuria is AR deficiency in homogentisic oxidase --> homogentisic acid levels accumulate --> polymerization to *DARK PIGMENT* --> pigmented skin + dark pee Alkaptonuria can p/w arthritis (polymers deposit in joints + cartilage, *calcification of intervertebral discs*) Dx: elevated HGA in urine/plasma *Tx [KNOW THIS]: dietary restriction of tyrosine and phenylalanine*

UMN damage (cortex, internal capsule, corticospinal tract) results in ___ LMN damage (brainstem for CNs, anterior horn of spinal cord) results in ___ UMNs decussate ___ (UMN lesion above decussation --> ___ weakness) Bulbar (CNV, VII, IX, XI, XII) palsy is ___ signs of damage to these nerves (i.e., ___ gag); pseudobulbar palsy is ___ signs (i.e., ___ gag)

UMN damage (cortex, internal capsule, corticospinal tract) results in spasticity/hyperreflexia (clasp knife spasticity) LMN damage (brainstem for CNs, anterior horn of spinal cord) results in flaccid paralysis/hyporeflexia and fasciculations UMNs decussate just below the medulla (UMN lesion above decussation --> contralateral weakness) Bulbar (CNV, VII, IX, XI, XII) palsy is LMN signs of damage to these nerves (i.e., absent gag); pseudobulbar palsy is UMN signs (i.e., exaggerated gag)

CLASSIC CASE: pt w/flank pain + hematuria w.o stone on x-ray - que pasa?

URIC ACID STONE (appears radiolucent on XR!)

Ulnar nn. lesions l/t a___ and hypothenar loss, as well as sensory loss to medial 1.5 digits Distal ulnar nn. lesion leads to ulnar claw when extending hand (loss of ___ - primary IP extensors) Ulnar nn. lesions at the wrist can be 2/2 lacerations or Guyon Canal compression; ulnar nn. lesions at the elbow can be 2/2 medial condyle fx (*p/w ___ deviation of wrist*) Ulnar Paradox: ulnar claw not seen w/proximal ulnar nn. lesions d/t loss of flexor digitorum profundus mm. (ulnar digits paralyzed w.o clawing)

Ulnar nn. lesions l/t abduction/adduction and hypothenar loss, as well as sensory loss to medial 1.5 digits Distal ulnar nn. lesion leads to ulnar claw when extending hand (loss of lumbricals - primary IP extensors) Ulnar nn. lesions at the wrist can be 2/2 lacerations or Guyon Canal compression; ulnar nn. lesions at the elbow can be 2/2 medial condyle fx (*p/w RADIAL deviation of wrist*) Ulnar Paradox: ulnar claw not seen w/proximal ulnar nn. lesions d/t loss of flexor digitorum profundus mm. (ulnar digits paralyzed w.o clawing)

Uncomplicated community-PNA w.o comorbidities --> tx w/___ (3-5d) Complicated community-PNA (w/COPD, CKD, diabetes, CHF, recent Abx use) --> tx w/___ (levofloxacin) Nosocomial PNA tends to be ___ resistant (E. coli, Klebsiella, Pseudomonas, MRSA) - need to cover MRSA + Pseudomonas (cefepime/ceftazidime, meropenem, piperacillin-tazobactam) Bad PNA can lead to ARDS - injury --> cytokines --> ne___ --> capillary + alveolar damage --> fluid pours into interstitium ARDS can be triggered by sepsis, PNA, aspiration, trauma, pancreatitis, and TRALI - CXR w/*WHITE OUT*; can look like pulmonary edema 2/2 HF, *but will have PCWP that is ___!* - low TV is only tx

Uncomplicated community-PNA w.o comorbidities --> tx w/macrolide (3-5d) Complicated community-PNA (w/COPD, CKD, diabetes, CHF, recent Abx use) --> tx w/fluoroquinolone (levofloxacin) Nosocomial PNA tends to be more resistant (E. coli, Klebsiella, Pseudomonas, MRSA) - need to cover MRSA + Pseudomonas (cefepime/ceftazidime, meropenem, piperacillin-tazobactam) Bad PNA can lead to ARDS - injury --> cytokines --> neutrophils --> capillary + alveolar damage --> fluid pours into interstitium ARDS can be triggered by sepsis, PNA, aspiration, trauma, pancreatitis, and TRALI - CXR w/*WHITE OUT*; can look like pulmonary edema 2/2 HF, *but will have PCWP that is NORMAL!* - low TV is only tx

Urea cycle is conversion of ammonia to urea for excretion in urine (*occurs only in liver*); Urea comes from ammonia, CO2, and aspartate 1st and 2nd step of urea cycle are in mitochondria 1 (*RLS*): NH4 + CO2 + ATP --> carbamoyl phosphate (*via carbamoyl phosphate synthetase I*); N-acetylglutamate is allosteric activator of CPS-I (*levels are elevated in fed state, i.e., when there's more protein - used to regulate cycle*) 2: carbamoyl phosphate + ornithine --> citrulline (*via ORNITHINE TRANSCARBAMYLASE - MC urea cycle enzyme deficiency!!*) 3-5: less important (citrulline --> aspartate --> arginosuccinate --> fumarate + arginine --> urea + ornithine), occurs in cytoplasm ^NOTE: carbamoyl phosphate synthetase II is used in *PYRIMIDINE SYNTHESIS!! (yields two products [T and C], while I yields one product [urea])* ^NOTE: citrulline is non-standard amino acid, but can be added to proteins via post-translational modification (anti-CCP antibodies seen in RA)

Uremia can lead to ___ dysfunction and bleeding, 2/2 uremic toxins inhibiting aggregation and adhesion of platelets Uremic pts will have prolonged ___ w/normal platelet count and coag labs --- Thrombocytopenia can cause bleeding problems (when plt-ct < ___) and can be d/t decreased production (chemo, leukemia), sequestration (splenomegaly, portal HTN), and destruction (ITP, TTP, HUS, DIC) --- *von Willebrand Disease*: deficient production of vWF - recall that vWF is synthesized by ___ cells + m___; vWF has two key roles in hemostasis: 1) carries factor ___ and 2) binds platelets to ___ after damage vWD is MC bleeding d.o (usually *autosomal ___*) and p/w easy bruising, skin bleeding, and *prolonged bleeding (epi___, men___)* vWD manifests w/increased ___ +/- increased PTT (d/t factor VIII decrease!!!), otherwise labs will be normal Dx: *r___ cofactor activity assay (no aggregation in vWD!)* Tx: dDAVP

Uremia can lead to platelet dysfunction and bleeding, 2/2 uremic toxins inhibiting aggregation and adhesion of platelets Uremic pts will have prolonged bleeding time w/normal platelet count and coag labs --- Thrombocytopenia can cause bleeding problems (when plt-ct < 10k) and can be d/t decreased production (chemo, leukemia), sequestration (splenomegaly, portal HTN), and destruction (ITP, TTP, HUS, DIC) --- *von Willebrand Disease*: deficient production of vWF - recall that vWF is synthesized by endothelial cells + megakaryocytes; vWF has two key roles in hemostasis: 1) carries factor VIII and 2) binds platelets to endothelium after damage vWD is MC bleeding d.o (usually *autosomal DOMINANT*) and p/w easy bruising, skin bleeding, and *prolonged bleeding (epistaxis, menorrhagia)* vWD manifests w/increased bleeding time +/- increased PTT (d/t factor VIII decrease!!!), otherwise labs will be normal Dx: *ristocetin cofactor activity assay (no aggregation in vWD!)* Tx: dDAVP

Uric acid stones are precipitated by acidic urine - *UA stones appear radio___ on XR (important - only one!)* RFs for uric acid stones include gout, leukemia/myeloproliferative dz, *chronic ___*, and hot/arid climates Crystals will appear *r___* Tx: *___ of urine (potassium bicarbonate), rarely can use allopurinol* [*MEDICAL THERAPY - NOT SURGERY, UNIQUE!!*] --- Cystine stones are seen in children w/cystinuria d/t inability to absorb cystine (may form ___ calculi) CLASSIC CASE TO KNOW: *CHILD* w/no history of *UTI* and *___ STONE* Tx: hydration + alkalization of urine

Uric acid stones are precipitated by acidic urine - *UA stones appear radiolucent on XR (important - only one!)* RFs for uric acid stones include gout, leukemia/myeloproliferative dz, *chronic diarrhea*, and hot/arid climates Crystals will appear *rhomboid* Tx: *alkalization of urine (potassium bicarbonate), rarely can use allopurinol* [*MEDICAL THERAPY - NOT SURGERY, UNIQUE!!*] --- Cystine stones are seen in children w/cystinuria d/t inability to absorb cystine (may form staghorn calculi) CLASSIC CASE TO KNOW: *CHILD* w/no history of *UTI* and *STAGHORN STONE* Tx: hydration + alkalization of urine

Urticaria (hives) are itchy, raised wheals +/- angioedema (deep mucocutaneous swelling), a classic manifestation of allergic skin rxn Urticaria are type ___ HS rxn 2/2 mast cell degranulation after Ag binds to Ig___ Abs on m___ cells leading to *[HY] ___ release* There are no changes to epidermis - just d___ edema + dilation of lymph vessels (for dermal drainage) Urticaria is usually self-limited - tx w/antihistamines +/- steroids (unless a/w anaphylaxis)

Urticaria (hives) are itchy, raised wheals +/- angioedema (deep mucocutaneous swelling), a classic manifestation of allergic skin rxn Urticaria are type I HS rxn 2/2 mast cell degranulation after Ag binds to IgE Abs on mast cells leading to *[HY] HISTAMINE release* There are no changes to epidermis - just dermal edema + dilation of lymph vessels (for dermal drainage) Urticaria is usually self-limited - tx w/antihistamines +/- steroids (unless a/w anaphylaxis) *^NOTE: urticaria is type I, all other skin HS rxns (contact dermatitis, SJS, drug rash) are type IV HS rxn!!*

VASCULITIS BUZZWORDS: Elderly female w/headache and jaw claudication --> ___ Asian female with decreased pulses --> ___ Asian child w/red rash and strawberry tongue --> ___ Smoker w/autoamputation of digits --> ___ HepB --> ___ Child with recent URI + melena --> ___ Adult w/new asthma, eosinophilia, and positive pANCA --> ___ Sinus, kidney, and lung involvement w/positive c-ANCA --> ___ Kidney and lung involvement + p-ANCA --> ___

VASCULITIS BUZZWORDS: Elderly female w/headache and jaw claudication --> temporal arteritis Asian female with decreased pulses --> Takayasu arteritis Asian child w/red rash and strawberry tongue --> Kawasaki dz Smoker w/autoamputation of digits --> Buerger's dz HepB --> polyarteritis nodosa Child with recent URI + melena --> Henoch Schonlein Purpura (IgA vasculitis) Adult w/new asthma, eosinophilia, and positive pANCA --> eosinophilic granulomatosis w/polyangitis (Churg-Strauss) Sinus, kidney, and lung involvement w/positive c-ANCA --> granulomatosis w/polyangitis (Wegener's) [C-->Criminal] Kidney and lung involvement + p-ANCA --> microscopic polyangiitis

CLASSIC CASE: adult w/long-standing watery diarrhea (no blood or pus) with no response to diet changes and high stomach pH? Treatment?

VIPoma Tx w/octreotide (often metastatic at presentation w/8y survival)

Vasculitis in inflammation of blood vessels (look for ___ in vessel walls), p/w systemic sx + organ dz specific sx of organs that are occluded Can be classified based on vessels involved: medium (p___ n___, Kawasaki, Buerger's), ___ (Churg-Strauss, Wegener's, microscopic polyangiitis, Henoch-Schonlein Purpura), and ___ (temporal arteritis, Takayasu arteritis) NOTE: ___ is raised purpura and *ONLY SEEN IN VASCULITIS* (purpura are red-purple skin lesions [d/t extravagation of blood] that do not blanch); non-palpable purpura (petechiae - small, ecchymoses - large) are seen in non-inflammatory conditions General vasculitis tx includes steroids +/- cyclophosphamide

Vasculitis in inflammation of blood vessels (look for leukocytes in vessel walls), p/w systemic sx + organ dz specific sx of organs that are occluded Can be classified based on vessels involved: medium (polyarteritis nodosa, Kawasaki, Buerger's), small (Churg-Strauss, Wegener's, microscopic polyangiitis, Henoch-Schonlein Purpura), and large (temporal arteritis, Takayasu arteritis) NOTE: palpable purpura is raised purpura and *ONLY SEEN IN VASCULITIS* (purpura are red-purple skin lesions [d/t extravagation of blood] that do not blanch); non-palpable purpura (petechiae - small, ecchymoses - large) are seen in non-inflammatory conditions General vasculitis tx includes steroids +/- cyclophosphamide

Vasoactive intestinal peptide (VIP) is neurocrine (synthesized in neurons) that can 1) ___ smooth muscle (important in LES), 2) ___ pH (stimulates HCO3 secretion, inhibits H+ secretion) VIPoma can develop - results in *WDHA syndrome (W___ D___ [secretory diarrhea - draws water w/tea-colored, odorless stool], H___ [d/t high volume diarrhea], A___ [absence of gastric acid - VIP effect])*

Vasoactive intestinal peptide (VIP) is neurocrine (synthesized in neurons) that can 1) relax smooth muscle (important in LES), 2) raise pH (stimulates HCO3 secretion, inhibits H+ secretion) VIPoma can develop - results in *WDHA syndrome (Watery Diarrhea [secretory diarrhea - draws water w/tea-colored, odorless stool], Hypokalemia [d/t high volume diarrhea], Achlorhydria [absence of gastric acid - VIP effect])*

Ventral hernias can include umbilical hernias or incisional hernias Hiatal hernias are through esophageal h___ (no bulge, but can l/t GERD) Type I (___) hiatal hernia is when cardia slides above diaphragm ("hourglass" appearance) Type II-IV are paraesophageal hernias and include part of the fundus - d/t defect in phrenoesophageal membrane; classic finding is b___ s___ in lung fields Congenital diaphragmatic hernia is congenital defect of diaphragm (*pleuroperitoneal membrane*) --> abdominal organs herniate into chest --> ___ hypoplasia

Ventral hernias can include umbilical hernias or incisional hernias Hiatal hernias are through esophageal hiatus (no bulge, but can l/t GERD) Type I (sliding) hiatal hernia is when cardia slides above diaphragm ("hourglass" appearance) Type II-IV are paraesophageal hernias and include part of the fundus - d/t defect in phrenoesophageal membrane; classic finding is bowel sounds in lung fields Congenital diaphragmatic hernia is congenital defect of diaphragm (*pleuroperitoneal membrane*) --> abdominal organs herniate into chest --> pulmonary hypoplasia

Vestibular dysfunction can lead to three (or four) typical symptoms: ___ Left/right and torsional/rotational nystagmus is seen with ___ vestibular dysfunction; causes are usually ___ (BPPV, Meniere's disease, vestibular neuritis) and patients usually have ___ sx Upbeat/downbeat nystagmus is seen with ___ vestibular dysfunction; causes are usually ___ (brainstem/cerebellar lesions lesions, infarct, stroke, tumor) and patients often have ___ sx Positional testing (Dix-Hallpike) leads to immediate nystagmus in ___ vertigo and delayed nystagmus in ___ vertigo (Epley maneuver can reverse)

Vestibular dysfunction can lead to three (or four) typical symptoms: vertigo, nystagmus, and N/V Left/right and torsional/rotational nystagmus is seen with peripheral vestibular dysfunction; causes are usually benign (BPPV, Meniere's disease, vestibular neuritis) and patients usually have no other sx Upbeat/downbeat nystagmus is seen with central vestibular dysfunction; causes are usually not benign (brainstem/cerebellar lesions lesions, infarct, stroke, tumor) and patients often have other CNS symptoms (diplopia, ataxia, weakness) Positional testing (Dix-Hallpike) leads to immediate nystagmus in central vertigo and delayed nystagmus in peripheral vertigo (Epley maneuver can reverse)

Virchow's Triad (___) are kept in check to prevent formation of thrombus Hypercoaguable states include post-___ (surgical endothelial damage, immobile - stasis, inflammation from surgery - hypercoaguable), trauma/hip fracture, long flight, malignancy, ___/OCPs, ___ syndrome (loss of ATIII), smoking, and *elevated homocysteine* Homocysteine is a/w both ___ AND venous clots - high levels can l/t endothelial injury and activation of clotting factors; high levels are d/t folate/B12/B6 deficiency and homo___, can be lowered with *___*

Virchow's Triad (endothelial damage, stasis of blood, hypercoagulability) are kept in check to prevent formation of thrombus Hypercoaguable states include post-op (surgical endothelial damage, immobile - stasis, inflammation from surgery - hypercoaguable), trauma/hip fracture, long flight, malignancy, pregnancy/OCPs, nephrotic syndrome (loss of ATIII), smoking, and *elevated homocysteine* Homocysteine is a/w both arterial AND venous clots - high levels can l/t endothelial injury and activation of clotting factors; high levels are d/t folate/B12/B6 deficiency and homocystinuria, can be lowered with *folate*

Viruses are nucleic acids surrounded by proteins (capsid) which may or may not be surrounded by envelope (lipid membrane acquired from *___*); capsid may be ___ (enveloped) or ___ (enveloped or naked - icosahedral are stable, don't need envelope) In general, env viruses cannot survive in environment --> no fecal-oral transmission RNA viruses are single stranded linear except 1) reovirus (___), 2) retroviruses (HIV, ___ - two copies single stranded), and 3) bunya-arena-delta virus (BAD - ___ DNA); most rep in cytoplasm (except influenza and retroviruses --> ___) Neg sense RNA viruses must carry enzyme (___-dep-___-pol) to convert (-) to (+) sense RNA before being translated; RdRp also accomplishes viral nucleic acid replication

Viruses are nucleic acids surrounded by proteins (capsid) which may or may not be surrounded by envelope (lipid membrane acquired from *HOST CELL*); capsid may be helical (enveloped) or icosahedral (enveloped or naked - icosahedral are stable, don't need envelope) In general, env viruses cannot survive in environment --> no fecal-oral transmission RNA viruses are single stranded linear except 1) reovirus (dsRNA), 2) retroviruses (HIV, HTLV - two copies single stranded), and 3) bunya-arena-delta virus (BAD - circular DNA); most rep in cytoplasm (except influenza and retroviruses --> nuc) Neg sense RNA viruses must carry enzyme (RNA-dep-RNA-pol) to convert (-) to (+) sense RNA before being translated; RdRp also accomplishes viral nucleic acid replication

Vitamin K deficiency manifests w/bleeding; VitK-dependent coagulation factors include factors ___ Key lab finding in VitK deficiency is *ELEVATED ___ (can see elevated ___, but less sensitive - bleeding time + platelets will be normal)*; PT is more sensitive because factor ___ has fastest half-life --> depletes faster VitK is produced by GI ___a - common causes of vitK deficiency: warfarin, antibiotics (deplete GI bacteria), newborns (sterile GI tract), malabsorption --- Large volume transfusions can dilute clotting factors --> coagulopathy (pRBCs are devoid of plasma/platelets) - tx w/___ --- *___ dz* l/t loss of clotting factors AND thrombopoietin --> coagulopathy!

Vitamin K deficiency manifests w/bleeding; VitK-dependent coagulation factors include factors II, VII, IX, and X Key lab finding in VitK deficiency is *ELEVATED PT/INR (can see elevated PTT, but less sensitive - bleeding time + platelets will be normal)*; PT is more sensitive because factor VII has fastest half-life --> depletes faster VitK is produced by GI bacteria - common causes of vitK deficiency: warfarin, antibiotics (deplete GI bacteria), newborns (sterile GI tract), malabsorption --- Large volume transfusions can dilute clotting factors --> coagulopathy (pRBCs are devoid of plasma/platelets) - tx w/FFP --- *Liver dz* l/t loss of clotting factors AND thrombopoietin --> coagulopathy!

Volatile acids (derived from CO2) are eliminated by ___; non-volatile acids (not from CO2 - from AA, FA metabolism) are eliminated by ___ Importantly, acid is buffered by *bicarbonate, which is replenished by kidneys (kidneys reabsorb HCO3 and excrete H in ___, also generate NEW bicarb in COLLECTING DUCT [how H is generated to be excreted!])* To protect kidneys from low pH, urine has two important buffers: 1) ___ acids and 2) ___ 1) Titratable acids are substances that absorb ___, including phosphate (H2PO4) 2) Ammonia can be generated by kidneys when ___ concentration is high (need ammonia d/t limited supply of titratable acid - dependent on diet); Ammonia is synthesized from g___ (amino acid?) and absorbs H+ in urine to become ammonium (NH4+) for excretion Net acid excretion = [Titratable Acids + NH4] - [HCO3] --> Acidosis results in ___ net acid excretion, alkalosis results in ___ net acid excretion *[HY] Any time kidneys are excreting more acid, they will excrete MORE ___ ACIDS AND ___ (i.e., compensation for acidosis)*

Volatile acids (derived from CO2) are eliminated by lungs; non-volatile acids (not from CO2 - from AA, FA metabolism) are eliminated by kidneys Importantly, acid is buffered by *bicarbonate, which is replenished by kidneys (kidneys reabsorb HCO3 and excrete H in PCT, also generate NEW bicarb in COLLECTING DUCT [how H is generated to be excreted!])* To protect kidneys from low pH, urine has two important buffers: 1) titratable acids and 2) ammonia 1) Titratable acids are substances that absorb protons, including phosphate (H2PO4) 2) Ammonia can be generated by kidneys when H+ concentration is high (need ammonia d/t limited supply of titratable acid - dependent on diet); Ammonia is synthesized from glutamine and absorbs H+ in urine to become ammonium (NH4+) for excretion Net acid excretion = [Titratable Acids + NH4] - [HCO3] --> Acidosis results in increased net acid excretion, alkalosis results in decreased net acid excretion *[HY] Any time kidneys are excreting more acid, they will excrete MORE TITRATABLE ACIDS AND AMMONIUM (i.e., compensation for acidosis)*

Volume of Distribution (Vd) is theoretical volume a drug occupies (determine by injecting dose and measuring concentration); *[HY] Vd = ([___]/[___])* NOTE: upon initial injection, drug concentration decreases rapidly 2/2 distribution in tissues before leveling out with steady decreasing slope; can extrapolate theoretical initial concentration if rapid distribution did not happen (C0) and use to find Vd (Vd = ([amount injected]/[___]) Vd is useful for drug dosing - if Efficacious Concentration @ 10mg/L, Vd is 10L, Dose = ___ Body compartments include Extracellular (33%) and Intracellular (67%); among EC --> Plasma (11.1%) and Interstitial (22.2%); Vd incr. when drug distributes to more fluid compartments! (i.e., drugs restricted to vasculature [large, nonpolar, *___-bound*^] have ___ Vd [e.g., warfarin] - drugs that accumulate in tissue [small, lipophilic] have ___ Vd [e.g., chloroquine]) ^Hypoalbuminemia (liver dz, nephrotic synd.) --> less plasma prot. binding --> more unbound drug goes to peripheral compartments --> ___ Vd (dosing requirement changes)

Volume of Distribution (Vd) is theoretical volume a drug occupies (determine by injecting dose and measuring concentration); *[HY] Vd = ([amt injected]/[plasma concentration of drug])* NOTE: upon initial injection, drug concentration decreases rapidly 2/2 distribution in tissues before leveling out with steady decreasing slope; can extrapolate theoretical initial concentration if rapid distribution did not happen (C0) and use to find Vd (Vd = ([amount injected]/[C0]) Vd is useful for drug dosing - if Efficacious Concentration @ 10mg/L, Vd is 10L, Dose = 10mg/L x 10L --> 100mg Body compartments include Extracellular (33%) and Intracellular (67%); among EC --> Plasma (11.1%) and Interstitial (22.2%); Vd incr. when drug distributes to more fluid compartments! (i.e., drugs restricted to vasculature [large, nonpolar, *protein-bound*^] have low Vd [e.g., warfarin] - drugs that accumulate in tissue [small, lipophilic] have high Vd [e.g., chloroquine]) ^Hypoalbuminemia (liver dz, nephrotic synd.) --> less plasma prot. binding --> more unbound drug goes to peripheral compartments --> inc. Vd (dosing requirement changes)

CLASSIC CASE: male infant, 6mo old w/eczema, bleeding + petechiae, and recurrent infections?

WISKOTT-ALDRICH SYNDROME (defect in WAS --> defective cytoskeleton in antigen presenting cells) ^WATER (Wiskott Aldrich Thrombocytopenia Eczema Recurrent infxns)

When C3 --> C3b (via alternative, lectin, classical pathway), C3a is also made - "a___toxin" that increases vascular permeability (same with C4a, C5a - *A*naphylaxis; C___ specifically recruits neutro*FI*lls) C3b can act as opsonin for m___ C3b can also form MAC (C5-9) - C3b cleaves ___ --> ___, which joins C6-9 (nice) to form MAC MAC does not attack human cells d/t decay accelerating factor (___/CD55) and MAC inhibitor protein (CD___) - especially important for RBCs, deficiency... Paroxysmal Nocturnal Hemoglobinuria is 2/2 CD5___ or CD5___ deficiency, p/w hemolysis with many downstream effects (anemia, renal failure, *thrombosis [d/t high Hgb]*; Hgb binds nitric oxide --> increased smooth muscle tone --> erectile dysfunction, dysphagia, abdominal pain) Classically, PNH p/w ___ @ night (+ fatigue, abdominal pain, and *thrombosis at weird spots [p___ vv, m___ vv, cerebral vv]*)

When C3 --> C3b (via alternative, lectin, classical pathway), C3a is also made - "anaphylatoxin" that increases vascular permeability (same with C4a, C5a - *A*naphylaxis; C5a specifically recruits neutro*FI*lls) C3b can act as opsonin for macrophages C3b can also form MAC (C5-9) - C3b cleaves C5 --> C5b, which joins C6-9 (nice) to form MAC MAC does not attack human cells d/t decay accelerating factor (DAF/CD55) and MAC inhibitor protein (CD59) - especially important for RBCs, deficiency... Paroxysmal Nocturnal Hemoglobinuria is 2/2 CD55 or CD59 deficiency, p/w hemolysis with many downstream effects (anemia, renal failure, *thrombosis [d/t high Hgb]*; Hgb binds nitric oxide --> increased smooth muscle tone --> erectile dysfunction, dysphagia, abdominal pain) Classically, PNH p/w hemolysis @ night (+ fatigue, abdominal pain, and *thrombosis at weird spots [portal vv, mesenteric vv, cerebral vv]*)

When pts p/w new onset ascites, ___ can determine cause (portal HTN vs leaky vasculature [i.e., malignancy]); need to pull fluid w/paracentesis Serum albumin - ascites albumin = SAAG SAAG > 1.1 --> ___ (ascites d/t high pressure driving fluid [NOT albumin] into peritoneum) SAAG < 1.1 --> ___ (fluid AND albumin leaking out) Tx ascites w/Na restriction, *___ (1st line)*, loop diuretics, therapeutic large volume paracentesis, TIPS (portal vein --> hepatic vein anastamosis)

When pts p/w new onset ascites, Serum Ascites Albumen Gradient can determine cause (portal HTN vs leaky vasculature [i.e., malignancy]); need to pull fluid w/paracentesis Serum albumin - ascites albumin = SAAG SAAG > 1.1 --> portal HTN (ascites d/t high pressure driving fluid [NOT albumin] into peritoneum) SAAG < 1.1 --> leaky vasculature/malignancy (fluid AND albumin leaking out) Tx ascites w/Na restriction, *spironolactone (1st line)*, loop diuretics, therapeutic large volume paracentesis, TIPS (portal vein --> hepatic vein anastamosis)

___ is infection w/Tropheryma whipplei --> small intestine involvement (also joints, brain, heart) Four Cardinal Features: ___, abdominal pain, weight loss, j___ pain (+hyperpigmentation, mesenteric lymphadenopathy) Biopsy: small intestine biopsy *[HY] w/___+ (stain?) ___ macrophages in lamina propria!* *D-xylose will be abnormal (i.e., no serum Xylose rise; altered normal mucosa --> can't absorb)*

Whipple Dz is infection w/Tropheryma whipplei --> small intestine involvement (also joints, brain, heart) Four Cardinal Features: diarrhea, abdominal pain, weight loss, joint pain (+hyperpigmentation, mesenteric lymphadenopathy) Biopsy: small intestine biopsy *[HY] w/PAS+ FOAMY macrophages in lamina propria!* *D-xylose will be abnormal (i.e., no serum Xylose rise; altered normal mucosa --> can't absorb)* ^PASs the Foamy Whipped cream CAN (Cardiac, Arthralgias, Neuro sx)

Wilm's Tumor is a renal malignancy in children d/t proliferation of m___ b___; will p/w child who has palpable flank mass, hematuria, and HTN (renin) WT is a/w ___ (type of mutation?) in WT1 TSG on chrom11; this is often sporadic, but can be inherited in *WAGR complex (Wilm's, A___, G___ malformation, mental Retardation)* Can also see WT in *___, which will p/w big baby (overgrowth) + big tongue (macroglossia) + big organs + big kidney (Wilm's) - tip off in Boards question will be ___ (BWS is 2/2 WT2 mutation)*

Wilm's Tumor is a renal malignancy in children d/t proliferation of metanephric blastema; will p/w child who has palpable flank mass, hematuria, and HTN (renin) WT is a/w LOF in WT1 TSG on chrom11; this is often sporadic, but can be inherited in *WAGR complex (Wilm's, Aniridia, Genitourinary malformation, mental Retardation)* Can also see WT in *Beckwith Wiedeman, which will p/w big baby (overgrowth) + big tongue (macroglossia) + big organs + big kidney (Wilm's) - tip off in Boards question will be HEMIHYPERPLASIA (BWS is 2/2 WT2 mutation)*

Wilson's dz is AR d.o of copper metabolism, d/t ___ mutation (copper transport protein for excretion found on chrom13) Normal metabolism: copper is excreted into bile after incorporation into ___ (transport molecule); in WD, can't excrete copper - accumulates in liver --> free radical production --> cirrhosis; Accordingly, dx is made by *decreased serum ___! (total serum copper is also ___ d/t low ceruloplasmin)* Copper in serum deposits in brain, cornea, kidney, and joints WD presents in young patient (12-24y) w/*___ (high risk of HCC)*, CNS features (basal ganglia deposition --> *___ tremor!*, depression), *___ Rings (diagnostic! - corneo-scleral junction browning)*, coombs-negative hemolytic anemia *CLASSIC BOARDS QUESTION: pt looks like WD, what test next? S___!* Tx: penicillamine - copper resin that promotes urinary excretion

Wilson's dz is AR d.o of copper metabolism, d/t ATP7B mutation (copper transport protein for excretion found on chrom13) Normal metabolism: copper is excreted into bile after incorporation into ceruloplasmin (transport molecule); in WD, can't excrete copper - accumulates in liver --> free radical production --> cirrhosis; Accordingly, dx is made by *decreased serum ceruloplasmin! (total serum copper is also reduced d/t low ceruloplasmin)* Copper in serum deposits in brain, cornea, kidney, and joints WD presents in young patient (12-24y) w/*cirrhosis (high risk of HCC)*, CNS features (basal ganglia deposition --> *WING-BEATING tremor!*, depression), *Kayser-Fleischer Rings (diagnostic! - corneo-scleral junction browning)*, coombs-negative hemolytic anemia *CLASSIC BOARDS QUESTION: pt looks like WD, what test next? SLIT-LAMP EXAM!* Tx: penicillamine - copper resin that promotes urinary excretion

Work of Breathing: ___ Resistance: slower you breathe --> less turbulence/resistance --> easier to breath ___ Resistance: rapid breathing takes less work to expand alveoli, d/t alveoli being relatively open (elasticity --> more open, easier to expand) Slower you breathe --> less ___ resistance Faster you breathe --> less ___ resistance ^Happy medium is ~15/min In restrictive lung dz, curve looks similar, but w/___ work of breathing In obstructive lung dz, curve shifts left (___ breaths/min., d/t increased airflow resistance)

Work of Breathing: Airflow Resistance: slower you breathe --> less turbulence/resistance --> easier to breath Elastic Resistance: rapid breathing takes less work to expand alveoli, d/t alveoli being relatively open (elasticity --> more open, easier to expand) Slower you breathe --> less airflow resistance Faster you breathe --> less elastic resistance ^Happy medium is ~15/min In restrictive lung dz, curve looks similar, but w/increased work of breathing In obstructive lung dz, curve shifts left (fewer breaths/min., d/t increased airflow resistance)

X-linked dz *always affects ___ (M or F?)*; X-rec usually don't affect females, X-dom can affect females; in pedigree, look for *only men affected, NO ___ TRANSMISSION*; classic example of X-rec is hemophilia A and B Females can have X-rec dz if father w/dz + female carrier, or ___ lyonization (LYON: random process in which one X-chrom condenses into heterochromatin --> DNA methylated --> ___ body; SKEW LYON: inactive healthy X > inactive unhealthy X) X-dom d/o MUST HAVE *every ___ of affected males w/dz*; key difference from AD: *no male-to-___ transmission!!*; F___ Syndrome is X-dom d/o Organs affected by mitochon d/o include CNS and skeletal muscle; mitochon have many copies of mtDNA and can have mix of norm/abn DNA (heteroplasmy); in pedigree, *look for mom passing mut to ___ - if homoplasmy --> all children, if heteroplasmy --> variable (more common)* Mitochondrial myopathies present w/w___, confusion, L-A___; *hallmark of mito-myop is ___ fibers 2/2 proliferation of mitochondria*

X-linked dz *always affects males*; X-rec usually don't affect females, X-dom can affect females; in pedigree, look for *only men affected, NO M-to-M TRANSMISSION*; classic example of X-rec is hemophilia A and B Females can have X-rec dz if father w/dz + female carrier, or skewed lyonization (LYON: random process in which one X-chrom condenses into heterochromatin --> DNA methylated --> Barr body; SKEW LYON: inactive healthy X > inactive unhealthy X) X-dom d/o MUST HAVE *every daughter of affected males w/dz*; key difference from AD: *no male-to-male transmission!!*; Fragile X Syndrome is X-dom d/o Organs affected by mitochon d/o include CNS and skeletal muscle; mitochon have many copies of mtDNA and can have mix of norm/abn DNA (heteroplasmy); in pedigree, *look for mom passing mut to ALL offspring - if homoplasmy --> all children, if heteroplasmy --> variable (more common)* Mitochondrial myopathies present w/weakness, confusion, L-Acidosis; *hallmark of mito-myop is red, ragged fibers 2/2 proliferation of mitochondria*

[HY] HOW TO IDENTIFY STUDY TYPES: 1) how were pts identified? (___: by location/group [New Yorkers]; ___: by RF/exposure [smokers]; ___: by dz [lung ca.]) 2) time period of study? (Cross Sect: ___ [snapshot in time], Cohort/Case: both use time period [retro. or prosp.]) 3) what is determined by study? (___: prevalence; ___: Relative risk; ___: Odds ratio)

[HY] HOW TO IDENTIFY STUDY TYPES: 1) how were pts identified? (Cross-Sect: by location/group [New Yorkers]; Cohort: by RF/exposure [smokers]; Case: by dz [lung ca.]) 2) time period of study? (Cross Sect: none [snapshot in time], Cohort/Case: both use time period [retro. or prosp.]) 3) what is determined by study? (Cross Sect: prevalence; CohoRt: Relative risk; Case ContrOl: Odds ratio)

dTMP (don't need ribonucleotide for thymidine) starts with UMP (remember: glutamine + CO2 --> carbamoyl phosphate, add aspartate --> orotic acid, add PRPP --> UMP) 1) UMP --> dUDP *(via ribonucleotide reductase - INHIBITED BY HYDROXYUREA!!)* 2) dUDP --> dUMP 3) dUMP --> dTMP via thymidylate synthase (adds carbon to dUMP!), requires FOLATE (THF) THF --> N5,N10-methylene THF w/carbon THAT WILL BE ADDED TO dUMP to make dTMP! --> DHF (after conversion of dUMP to dTMP) DHF --> THF is converted by DIHYDROFOLATE REDUCTASE (MTX target!) 5-FU inhibits thymidylate synthase directly after conversion to 5-FdUMP ("thymineless death", d/t inability to produce dTMP) NOTE: there is a pathway in which THF is "trapped" in N5-methyl THF form (can't get THF) --> B12 can convert back to THF, reason for megaloblastic anemia w/B12 deficiency! *[HY] Know how to differentiate B12 vs MMA!* *B12 --> neuro dysfunction, folate deficiency --> neuro intact* *B12 deficiency --> elevated MMA (need to B12 to fight in MMA) - MMA will be NORMAL in folate deficiency* *B12 or Folate deficiency --> elevated homocysteine (HomoFoloBolo)*

~80% of patients with rheumatoid arthritis have positive *rheumatoid factor ([HY] antibodies against ___ portion of IgG antibody*), though this has poor specificity (endocarditis, HepB/C, Sjogren's, SLE); a specific antibody for RA is anti-___ (anti-ACA) Citrulline is non-standard amino acid - not encoded into proteins, but can be added via post-translational modification Other lab findings in RA are elevated CRP and ESR, as well as *HLA-___ (DRs have 4-walled Rheum)* Can tx RA with a number of DMARDs (MTX, azathioprine, cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide [inhibits pyrimidine synthesis], *___ inhibitors*^) ^Infliximab, adalimumab, golimumab, etanercept (*can all cause reactivation TB - check a TB!!*)

~80% of patients with rheumatoid arthritis have positive *rheumatoid factor ([HY] antibodies against Fc portion of IgG antibody*), though this has poor specificity (endocarditis, HepB/C, Sjogren's, SLE); a specific antibody for RA is anti-cyclic citrullinated peptide (anti-ACA) Citrulline is non-standard amino acid - not encoded into proteins, but can be added via post-translational modification Other lab findings in RA are elevated CRP and ESR, as well as *HLA-DR4 (4-walled Rheum)* Can tx RA with a number of DMARDs (MTX, azathioprine, cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide [inhibits pyrimidine synthesis], *TNF-alpha inhibitors*^) ^Infliximab, adalimumab, golimumab, etanercept (*can all cause reactivation TB - check a TB!!*)

Uvea includes ___; uveitis can involve any of these three structures Anterior uveitis is termed ___/iridocyclitis; sx include pain and redness Intermediate uveitis is vitreous humor inflammation Posterior uveitis is chorioretinal inflammation; sx include floaters and decreased ___ (pain___) Uveitis can be infectious, mainly by agents that affect ___ (HSV, CMV, toxo), or systemic 2/2 autoimmune disease^ (remember: uvea is ___ layer, easier route for Abs/WBCs to enter and cause inflammation) ^Ank spond, react arthritis, JIA, rheumatoid, sarcoid, psoriatic arthritis, IBD

Uvea includes iris, ciliary body, and choroid; uveitis can involve any of these three structures Anterior uveitis is termed iritis/iridocyclitis; sx include pain and redness Intermediate uveitis is vitreous humor inflammation Posterior uveitis is chorioretinal inflammation; sx include floaters and decreased vision (painless) Uveitis can be infectious, mainly by agents that affect CNS (HSV, CMV, toxo), or systemic 2/2 autoimmune disease^ (remember: uvea is vascular layer, easier route for Abs/WBCs to enter and cause inflammation) ^Ank spond, react arthritis, JIA, rheumatoid, sarcoid, psoriatic arthritis, IBD

Presbycusis is age-related hearing loss due to degeneration of organ of Corti Long-term loud noise exposure can result in hearing loss with high-frequency loss first In Weber test, sound is louder in CHL and quieter in SNHL (NOTE: can't determine type of HL without knowing which ear is bad) In Rinne test, BC > AC in CHL; AC > BC in SNHL, but both AC and BC are decreased

___ is age-related hearing loss due to degeneration of organ of Corti Long-term loud noise exposure can result in hearing loss with ___ loss first In Weber test, sound is louder in ___ and quieter in ___ (NOTE: can't determine type of HL without knowing ___) In Rinne test, BC > AC in ___; AC > BC in ___, but both AC and BC are decreased

Where is the thalamus on coronal section? Where is the thalamus on axial section?

-Below lateral ventricles, surrounding the third ventricle -Medial to posterior limb of internal capsules ^Look up coronal

Kuh --> which CN? Mi --> which CN? La --> which CN?

-CN10 -CN7 -CN12

TREATMENT SCENARIOS: Boy with anaphylaxis? Man with septic shock? Man with MI and hypotension? Boy with asthma attack? Young man with rhinorrhea?

-Epinephrine -Norepinephrine -Dobutamine -Albuterol -Pseudoephedrine

Common side effect of alpha blockers? The primary determinant of SBP is ___, while the primary determinant of DBP is ___; peripheral vasoconstriction leads to reflex ___cardia, while peripheral vasodilation leads to reflex ___cardia A1 activation leads to vasoconstriction and reflex ___cardia A2 activation leads to decreased NE and bradycardia and hypotension B1 activation leads to ___cardia B2 activation leads to vaso___ and reflex ___cardia Isoproterenol can lead to significant increase in ___ pressure, d/t B1-mediated CO increase and B2-mediated vasodilation

-Hypotension + reflex tachycardia The primary determinant of SBP is cardiac output, while the primary determinant of DBP is peripheral resistance; peripheral vasoconstriction leads to reflex bradycardia, while peripheral vasodilation leads to reflex tachycardia A1 activation leads to vasoconstriction and reflex bradycardia A2 activation leads to decreased NE and bradycardia and hypotension B1 activation leads to tachycardia B2 activation leads to vasodilation and reflex tachycardia Isoproterenol can lead to significant increase in pulse pressure, d/t B1-mediated CO increase and B2-mediated vasodilation

Testing CN8, eyes move with head then adjust --> ipsi or contra lesion? Unconscious CN8, warm water normal? Warm water CN8 lesion? Warm water cortical lesion?

-Ipsilateral -Normal: slow away --> rapid back -CN8: no slow away -Cortical: slow away, but no rapid back ^COWS named for side of correction ^^Think of CN8 as pushing eye midline; stimulated --> contralateral deviation, inhibited --> ipsilateral deviation

Serotonin Syndrome: Triad, Treatment, and Differentiation from NMS

-Mental status changes (anxiety, delirium, restlessness) -Autonomic hyperactivity (diaphoresis, tachycardia, hyperthermia) -Neuromuscular abnormalities (tremor, clonus, hyperreflexia) -Tx: cyproheptadine ^NMS --> lead pipe rigidity; SS --> clonus

What is only sense that doesn't go through thalamus? What does an CN3 palsy look like? What does CN4 palsy look like? What does CN5 palsy look like (deviation and reflex)? What is unique features (+ others) of CN7 palsy? Hemodynamic effects of CN9 palsy (+ others)? Dysphagia, hoarseness, dysarthria --> which CN? -CN12 palsy --> which side?

-Smell -Eyeball is down (SR loss), out (MR loss), dilated pupil (parasymp loss), and ptosis (levator palpebrae loss) -Eye tilts outward --> head tilted away from side to compensate -Numb face, weak jaw deviated to affected side, loss of corneal reflex (CN5 sens, CN7 mot), +/- trigeminal neuralgia -Hyperacusis d/t stapedius paralysis (also loss of corn refl, loss of ant taste, facial droop) -Tachycardia, HTN - also loss of gag reflex, taste in posterior tongue -CN10 -TOWARDS affected side

ANESTHESIA: Molecules dissolved in blood have ___ anesthetic effect, while molecules not dissolved have ___ anesthetic effect (i.e., need to saturate blood to exert effect) - non-dissolved gases are referred to as partial pressure (PP rises quickly with less soluble molecules) The more soluble a molecule is in blood, the ___ it takes to take effect (i.e., ___ induction time) The partition coefficient lets us know how soluble a gas is - the higher coefficient, the ___ soluble, and the ___ induction time Lipid affinity is a measure of gas ___ (greater lipid affinity --> more potent) - halothane has large lipid affinity, while nitrous oxide has low lipid affinity; ___ is usually used to refer to affinity instead (lipid solubility = 1/MAC)

ANESTHESIA: Molecules dissolved in blood have no anesthetic effect, while molecules not dissolved have an anesthetic effect (i.e., need to saturate blood to exert effect) - non-dissolved gases are referred to as partial pressure (PP rises quickly with less soluble molecules) The more soluble a molecule is in blood, the longer it takes to take effect (i.e., slower induction time) The partition coefficient lets us know how soluble a gas is - the higher coefficient, the more soluble, and the slower induction time (higher, more, longer) Lipid affinity is a measure of gas potency (greater lipid affinity --> more potent) - halothane has large lipid affinity, while nitrous oxide has low lipid affinity; MAC is usually used to refer to affinity instead (lipid solubility = 1/MAC)

Activating muscarinic receptors can lead to lower BP via an indirect mechanism of stimulating ___ cells to release NO which bind vascular smooth muscle --> activate ___ cyclase --> ___ calcium --> vasodilation Any cholinergic medication can worsen two pre-existing conditions: ___ and gastric ___ (bronchoconstriction and increased acid production - think parasympathetic nervous system) Organophosphate poisoning is seen in ___ and manifests with fasciculations and cholinergic toxicity (know mneumonic and what stands for) Cholinergic antagonist toxicity also has a mneumonic... (know it)

Activating muscarinic receptors can lead to lower BP via an indirect mechanism of stimulating endothelial cells to release NO which bind vascular smooth muscle --> activate guanylate cyclase --> decreased calcium --> vasodilation Any cholinergic medication can worsen two pre-existing conditions: COPD and gastric ulcers (bronchoconstriction and increased acid production - think parasympathetic nervous system) Organophosphate poisoning is seen in farmers and manifests with fasciculations and cholinergic toxicity (know mneumonic and what stands for) -^DUMBELS: Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Lacrimation, Salivation -^^Red as a beet (sweat block --> hot), dry as a bone (no lacrimation, salivation, sweat), blind as a bat (mydriasis can trigger angle closure glaucoma), mad as a hatter (confusion), hot as a hare (same thing as red beet)

An epigastric rising sensation is classic aura for ___ epilepsy The temporal lobe is the most common site of partial seizures, 2/2 ___ (neuronal loss in hippocampus) Juvenile Myoclonic Epilepsy is gradual evolution of seizures over childhood - *hallmark is myoclonic jerks on ___ (shock-like movements of both arms)* Absence Epilepsy will be described as *child not paying attention in school with EEG showing ___ complex* - no post-ictal state in this disorder, tx with ethosuximide

An epigastric rising sensation is classic aura for medial temporal lobe epilepsy The temporal lobe is the most common site of partial seizures, 2/2 mesial temporal sclerosis (neuronal loss in hippocampus) Juvenile Myoclonic Epilepsy is gradual evolution of seizures over childhood - *hallmark is myoclonic jerks on awakening (shock-like movements of both arms)* Absence Epilepsy will be described as *child not paying attention in school with EEG showing 3 Hz spike-and-wave complex* - no post-ictal state in this disorder, tx with ethosuximide

Anterior horn --> ___ nerves Posterior horn --> ___ sensory nerves Lateral horn --> ___ nerves Spinothalamic tract --> ___ info Posterior column/medial lemniscus --> ___ Corticospinal tract --> ___

Anterior horn --> motor nerves Posterior horn --> pain/temp (STT) sensory nerves Lateral horn --> autonomic nerves Spinothalamic tract --> pain/temp info Posterior column/medial lemniscus --> vibration/proprioception Corticospinal tract --> motor

At rest, neurons have a voltage of ___ maintained by leak of ___ To depolarize, *___ channels* open and raise voltage to "threshold" voltage; they subsequently continue to open along axon in a process known as ___ At axon terminal, ___ channels open and trigger release of NTs To bring voltage back down, ___ leaves the cell

At rest, neurons have a voltage of -70mV maintained by leak of potassium To depolarize, sodium channels open and raise voltage to "threshold" voltage; they subsequently continue to open along axon in a process known as propagation At axon terminal, calcium channels open and trigger release of NTs To bring voltage back down, potassium leaves the cell

At rest, ___ (of SN) and ___ pour GABA onto thalamus (tonic inhibition of thalamus) so thalamus cannot stimulate cortex to activate brainstem/spinal cord Direct Pathway: cortex decides to make movement --> dumps glutamate onto ___ --> striatum dumps GABA on ___ and ___ --> thalamus no longer inhibited and can activate cortex (modifier: ___ is also activated by cortex --> amplifies striatum via ___) Indirect Pathway: cortex decides to make movement --> activates striatum --> dumps GABA on ___ --> GPe no longer inhibits ___ --> STN activates ___ to further inhibit thalamus (modifier: ___ is also activated by cortex --> amplifies striatum via ___) PC neurons are lost in ___

At rest, pars reticulata (of SN) and GP internus pour GABA onto thalamus (tonic inhibition of thalamus) so thalamus cannot stimulate cortex to activate brainstem/spinal cord Direct Pathway: cortex decides to make movement --> dumps glutamate onto striatum --> striatum dumps GABA on pars reticulata and GPi --> thalamus no longer inhibited and can activate cortex (modifier: PC is also activated by cortex --> amplifies striatum via D1) Indirect Pathway: cortex decides to make movement --> activates striatum --> dumps GABA on GPe --> GPe no longer inhibits STN --> STN activates GPi to further inhibit thalamus (modifier: PC is also activated by cortex --> amplifies striatum via D2) PC neurons are lost in Parkinson's

Ataxia telangiectasia manifests as early cerebellar atrophy with diffuse telangiectasias, repeated sinus/respiratory infections, and *high risk of ___* 2/2 DNA hypersensitivity to radiation (___ defect, which repairs double-stranded DNA breaks via NHEJ); lab values show elevated AFP and low/absent ___ (think recurrent sx) Friedreich's Ataxia is 2/2 ___ mutation, a mitochondrial protein with high levels in brain, heart, and pancreas (leading to ___ - 3)

Ataxia telangiectasia manifests as early cerebellar atrophy with diffuse telangiectasias, repeated sinus/respiratory infections, and *high risk of cancer* 2/2 DNA hypersensitivity to radiation (ATM defect, which repairs double-stranded DNA breaks via NHEJ); lab values show elevated AFP and low/absent IgA (think recurrent sx) Friedreich's Ataxia is 2/2 frataxin mutation, a mitochondrial protein with high levels in brain, heart, and pancreas (leading to ataxia, HOCM, and diabetes)

BASAL GANGLIA - label 'em on coronal: caudate nucleus, putamen, globus pallidus, subthalamic nuclei, substantia nigra The striatum is two structures (___) divided by internal capsule; the lentiform nucleus is made up of ___ BG functions to coordinate ___

BASAL GANGLIA - label 'em on coronal: caudate nucleus, putamen, globus pallidus, subthalamic nuclei, substantia nigra The striatum is two structures (putamen and caudate) divided by internal capsule; the lentiform nucleus is made up of putamen and globus pallidus BG functions to coordinate complex movement

BRAINSTEM SECTIONING: Cerebral aqueduct & cerebral peduncle --> midbrain Inferior olivary nucleus --> pons Neither --> medulla

BRAINSTEM SECTIONING: Cerebral aqueduct & cerebral peduncle --> ___ Inferior olivary nucleus --> ___ Neither --> ___

Berry aneurysms are associated with ADPKD, Ehlers-Danlos, and aortic coarctation, as well as age, HTN, smoking, and Afro-American AComm aneurysm can result in visual field defect ___; PComm aneurysm can result in ___ palsy Subarachnoid hemorrhage (2/2 berry aneurysm rupture) is bleeding between ___ mater; SAH presents with "worst HA of life" with sudden onset + ___ rigidity, but no focal deficits; spinal tap shows xantho___ Days after SAH clipping, re-bleeding is common and vasospasm can lead to worsened neuro symptoms (treated with ___)

Berry aneurysms are associated with ADPKD, Ehlers-Danlos, and aortic coarctation, as well as age, HTN, smoking, and Afro-American AComm aneurysm can result in visual field defect bitemporal hemaianopsia; PComm aneurysm can result in CN3 palsy Subarachnoid hemorrhage (2/2 berry aneurysm rupture) is bleeding between arachnoid and pia mater; SAH presents with "worst HA of life" with sudden onset + nuchal rigidity, but no focal deficits; spinal tap shows xanthochromia Days after SAH clipping, re-bleeding is common and vasospasm can lead to worsened neuro symptoms (treated with nimodipine)

Biceps reflex tests ___ Triceps reflex tests ___ Patella reflex tests ___ Achilles reflex tests ___ A 1+ reflex indicates a ___ lesion; a 3+ reflex indicates a ___ lesion

Biceps reflex tests C5 Triceps reflex tests C7 Patella reflex tests L4 Achilles reflex tests S1 A 1+ reflex indicates a LMN lesion; a 3+ reflex indicates a UMN lesion

Branch RVO is 2/2 compression of vein by retinal arterioles at ___ and is a/w arteriosclerosis; central RVO is a primary ___ disorder; RVO manifests with engorged retinal veins and hemorrhages RArteryO leads to ___ on exam (central macula surrounded by ischemia, also seen in Tay Sachs); RAO is commonly 2/2 ___ atherosclerosis, AFib, and temporal arteritis Macular degeneration results in loss of ___ vision (--> central scotoma); dry MD is slowly progressive *2/2 ___ accumulation (see pic) between ___ membrane (inner layer of choroid) and ___ (outer layer of retina)*; wet MD is rapid 2/2 break in ___ membrane leading to hemorrhage

Branch RVO is 2/2 compression of vein by retinal arterioles at AV crossing points and is a/w arteriosclerosis; central RVO is a primary thrombus disorder; RVO manifests with engorged retinal veins and hemorrhages RArteryO leads to cherry red spot on exam (central macula surrounded by ischemia, also seen in Tay Sachs); RAO is commonly 2/2 carotid artery atherosclerosis, AFib, and temporal arteritis Macular degeneration results in loss of central vision (--> central scotoma); dry MD is slowly progressive *2/2 drusen accumulation (see pic) between Bruch's membrane (inner layer of choroid) and retinal pigment epithelium (outer layer of retina)*; wet MD is rapid 2/2 break in Bruch's membrane leading to hemorrhage

CSF is produced by ___ cells of choroid plexus, absorbed by ___ in superior sagittal sinus Key Clinical Scenario: prior meningitis (leads to scarring), headache, papilledema, enlarged ventricles --> ___ Aqueductal stenosis can cause non-com hydro, common d/t ___ and presents with ___ head circumference Chiari II malformation can cause non-com hydro and are associated with ___ Dandy Walker can cause non-com hydro with ___, leading to hydrocephalus/macrocephaly and delayed development

CSF is produced by ependymal cells of choroid plexus, absorbed by arachnoid villi in superior sagittal sinus Key Clinical Scenario: prior meningitis (leads to scarring), headache, papilledema, enlarged ventricles --> communicating hydrocephalus Aqueductal stenosis can cause non-com hydro, common d/t intrauterine infection (rubella, CMV, toxo) and presents with enlarging head circumference Chiari II malformation can cause non-com hydro and are associated with myelomeningocele Dandy Walker can cause non-com hydro with massive 4th ventricle, leading to hydrocephalus/macrocephaly and delayed development

Chiari malformations is downward displacement of cerebellum CM1 is abnormal shape of cerebellar tonsils, resulting in displacement through foramen magnum, resulting in ___ headache, ataxia, and CN dysfunction; *CM1 is associated with ___* CM2 is downward displacement of vermis and tonsils, blocking aqueduct --> hydrocephalus (manifests with large head, distended ant font); *CM2 is associated with ___* ___ is poor development of cerebellum

Chiari malformations is downward displacement of cerebellum CM1 is abnormal shape of cerebellar tonsils, resulting in displacement through foramen magnum, resulting in cough headache, ataxia, and CN dysfunction; *CM1 is associated with syringomyelia* CM2 is downward displacement of vermis and tonsils, blocking aqueduct --> hydrocephalus (manifests with large head, distended ant font); *CM2 is associated with myelomeningocele* Dandy Walker is poor development of cerebellum

Epidural hematoma is 2/2 ___ rupture, often via traumatic injury and appears ___ on CT (can lead to midline shift, very deadly); this presents with loss of consciousness preceded by ___ interval Subdural hematoma is 2/2 ___rupture with blood b/w dura and arachnoid space that accumulates slowly; CT reveals ___-shaped bleed; classic presentation is old alcoholic on blood thinners that presents confused ~1w after fall SAH is 2/2 ___ rupture with bleeding b/w arachnoid and pia mater Hemorrhagic stroke (___ bleed) can occur 2/2 HTN, anti-coagulation, malignancy, or reperfusion of ischemic stroke; most hemorrhagic strokes affect non-cortical structures (putamen, cerebellum, thalamus, pons) Putamen stroke manifests with *contralateral hemiparesis (___ - structure?), contralateral hemisensory loss (thalamus), and ipsilateral gaze deviation (___)*

Epidural hematoma is 2/2 middle meningeal artery rupture, often via traumatic injury and appears convex on CT (can lead to midline shift, very deadly); this presents with loss of consciousness preceded by lucid interval Subdural hematoma is 2/2 bridging vein rupture with blood b/w dura and arachnoid space that accumulates slowly; CT reveals crescent-shaped bleed; classic presentation is old alcoholic on blood thinners that presents confused ~1w after fall SAH is 2/2 berry aneurysm rupture with bleeding b/w arachnoid and pia mater Hemorrhagic stroke (intraparenchymal bleed) can occur 2/2 HTN, anti-coagulation, malignancy, or reperfusion of ischemic stroke; most hemorrhagic strokes affect non-cortical structures (putamen, cerebellum, thalamus, pons) Putamen stroke manifests with *contralateral hemiparesis (IC), contralateral hemisensory loss (thalamus), and ipsilateral gaze deviation (FEF)*

HYPOTHALAMIC AREAS: Lateral: ___ (lesion --> anorexia), ___ by leptin (Lateral Lesion --> Lose Lateral Lumps) Ventromedial: satiety (lesion --> ___), ___ by leptin (Ventral lesion --> Very heaVy) Anterior (AC): ___ (lesion --> hyperthermia) - NOTE: IL-1/IL-6 released in infection increase hypothalamic set point --> fever Posterior (phuckin' hot): ___ (lesion --> hypothermia) Suprachiasmatic Nuc: ___ (think melatonin SketchyPharm) ___ nucleus makes ADH (loss --> central DI), while ___ nucleus makes oxytocin; both are stored and released in ___

HYPOTHALAMIC AREAS: Lateral: hunger (lesion --> anorexia), inhibited by leptin (Lateral Lesion --> Lose Lateral Lumps) Ventromedial: satiety (lesion --> hyperphagia), stimulated by leptin (Ventral lesion --> Very heaVy) Anterior: cooling (lesion --> hyperthermia) - NOTE: IL-1/IL-6 released in infection increase hypothalamic set point --> fever Posterior: heating (lesion --> hypothermia) Suprachiasmatic Nuc: circadian rhythm (think melatonin SketchyPharm) Supraoptic nucleus makes ADH (loss --> central DI), while paraventricular nucleus makes oxytocin; both are stored and released in posterior pituitary

In CNS infarction damage, there are no changes for ~12 hours First changes occur in neurons when ___ appear (indicates ischemia) 24-48h, neutrophils, macrophages, and microglia become involved leading to ___ Days to weeks, ___ eliminate debris and cysts form with ___ undergoing gliosis that form wall around cyst

In CNS infarction damage, there are no changes for ~12 hours First changes occur in neurons when red neurons appear (indicates ischemia) 24-48h, neutrophils, macrophages, and microglia become involved leading to liquefactive necrosis Days to weeks, macrophages eliminate debris and cysts form with astrocytes undergoing gliosis that form wall around cyst

In axonotmesis distal to neuron lesion, ___ degeneration occurs where ___ degenerates and ___ involutes (regrowth can occur if Schwann cells are intact) Proximal to lesion, ___ occurs in which cell body upregulates ___ for repair (cell body ___, chromatolysis occurs with disappearance of ___)

In axonotmesis distal to neuron lesion, Wallerian degeneration occurs where axon degenerates and myelin sheath involutes (regrowth can occur if Schwann cells are intact) Proximal to lesion, axonal reaction occurs in which cell body upregulates protein synthesis for repair (cell body swells, chromatolysis occurs with disappearance of Nissl bodies)

In cardiac muscle, Gs increases cAMP that leads to ___ contractility (via ___ influx; Gi --> ___ contraction) In smooth muscle, Gs increases cAMP that leads to ___ (via ___; Gi --> contraction) In smooth muscle, Gq increases calcium concentration that leads to ___

In cardiac muscle, Gs increases cAMP that leads to increased contractility (via calcium influx; Gi --> decreased contraction) In smooth muscle, Gs increases cAMP that leads to relaxation (via MLCK; Gi --> contraction) In smooth muscle, Gq increases calcium concentration that leads to contraction

In general, cerebellum controls ___ side (projects contra cortex, which projects contra arm/leg - double cross); left cerebellar lesion --> loss of ___ proprioception Midline cerebellar lesions (vermis, ___ nuclei, floculonodular node) affect ___, leading to falling while sitting; lateral cerebellar lesions (hemispheres, ___ nuclei) affect extremities and falls ___ A classic sign of any cerebellar lesion is cerebellar ataxia, manifesting as ___ (other signs include hypotonia and dyssynergia - loss of coordinated activity)

In general, cerebellum controls ipsilateral side (projects contra cortex, which projects contra arm/leg - double cross); left cerebellar lesion --> loss of left proprioception Midline cerebellar lesions (vermis, emboliform/globus/fastigial nuclei, floculonodular node) affect trunk, leading to falling while sitting; lateral cerebellar lesions (hemispheres, dentate nuclei) affect extremities and falls towards affected side A classic sign of any cerebellar lesion is cerebellar ataxia, manifesting as wide-based gait (other signs include hypotonia and dyssynergia - loss of coordinated activity)

Local anesthetics (benzocaine) can cause ___, a condition where Fe is oxidized to Fe3+; treatment is with ___ blue Classic Scenario: endoscopy patient receiving benzocaine spray for throat analgesia develops dyspnea after procedure, also with ___ blood and SpO2 ___%

Local anesthetics (benzocaine) can cause methemoglobinemia, a condition where Fe is oxidized to Fe3+; treatment is with methylene blue Classic Scenario: endoscopy patient receiving benzocaine spray for throat analgesia develops dyspnea after procedure, also with chocolate brown blood and SpO2 80-90%

Local anesthetics have an ___ form that can cross the membrane before combining with H+ to become charged (BH+); the charged form blocks ___ channel from inside cell, leading to impaired depolarization NOTE: ___ environments require more drug to take effect (more likely to become ___ in extracellular environment --> cannot cross cell membrane) Small myelinated fibers are first to be blocked (small unmyelinated next); because of this effect, ___ (small myelinated fibers) is lost first Because LAs block sodium channels, systemic administration can lead to hypotension, bradycardia, arrhythmias, and heart block; *___* is most cardiotoxic

Local anesthetics have an uncharged form that can cross the membrane before combining with H+ to become charged (BH+); the charged form blocks sodium channel from inside cell, leading to impaired depolarization NOTE: acidic environments require more drug to take effect (more likely to become charged in extracellular environment --> cannot cross cell membrane) Small myelinated fibers are first to be blocked (small unmyelinated next); because of this effect, pain (small myelinated fibers) is lost first Because LAs block sodium channels, systemic administration can lead to hypotension, bradycardia, arrhythmias, and heart block; *BUPIVACAINE* is most cardiotoxic

MCA strokes affect upper limb and face; if left-sided, will result in ___, while right-sided will result in ___ ACA strokes affect lower limb PCA strokes affect vision, potentially resulting in visual hallucinations/agnosia and *___lateral hemianopia with macular sparing (2/2 dual blood supply from PCA and ___)*; deep branches also supply the lateral thalamus, which can lead to contralateral ___ loss and proprioception but no motor deficits (can result in chronic pain) REMEMBER: upper face has dual UMN supply, while lower face has single UMN supply from contralateral motor cortex (MCA stroke --> ___ facial droop only)

MCA strokes affect upper limb and face; if left-sided, will result in aphasia, while right-sided will result in hemineglect ACA strokes affect lower limb PCA strokes affect vision, potentially resulting in visual hallucinations/agnosia and *contralateral hemianopia with macular sparing (2/2 dual blood supply from PCA and MCA)*; deep branches also supply the lateral thalamus, which can lead to contralateral sensory loss and proprioception but no motor deficits (can result in chronic pain) REMEMBER: upper face has dual UMN supply, while lower face has single UMN supply from contralateral motor cortex (MCA stroke --> lower facial droop only)

MEDULLARY STROKE SYNDROMES: Medial medullary syndrome damages CST, med lemn, and CN12 --> contra hemiparesis, contra prop/vib loss, flaccid tongue paralysis (classically d/t ASA stroke) Lateral medullary syndrome damages vestib nuclei, symp tract, spinothal tract, spinal V nuc, and NUC AMBIG --> nystagmus, Horner's, contra pain/temp, ipsi facial pain/temp, and HOARSENESS (unique; classically d/t PICA stroke) (consider deleting me)

MEDULLARY STROKE SYNDROMES: Medial medullary syndrome damages CST, med lemn, and CN12 --> contra ___, ___ prop/vib loss, flaccid ___ paralysis (classically d/t ___ stroke) Lateral medullary syndrome damages vestib nuclei, symp tract, spinothal tract, spinal V nuc, and NUC AMBIG --> nystagmus, Horner's, ___ pain/temp, ___ facial pain/temp, and ___ (unique; classically d/t ___ stroke)

MIDBRAIN STROKES: Benedikt Syndrome damages CN3, medial lemn, and red nuc --> oculomotor palsy (down and out), contralat prop/vibr loss, involunt movement Weber Syndrome damages CN3, corticosp, corticobulb --> oculomotor palsy, contralat hemipar, pseudobulb palsy (UMN CN weakness) Parinaud Syndrome damages post midbrain (sup collic + pretectal area) --> vertical gaze palsy, pseudo Argyll Robert pup (often stem from pinealoma/germinoma --> can lead to hydrocephalus) (consider deleting me)

MIDBRAIN STROKES: Benedikt Syndrome damages CN3, medial lemn, and red nuc --> oculomotor palsy (___), contralat ___ loss, involunt movement Weber Syndrome damages CN3, corticosp, corticobulb --> oculomotor palsy, contralat ___, pseudobulb palsy (___ CN weakness) Parinaud Syndrome damages post midbrain (sup collic + pretectal area) --> ___ gaze palsy, pseudo Argyll Robert pup (often stem from pinealoma/germinoma --> can lead to hydrocephalus)

Most CNS stems from germ layer ___ (surface --> pituitary, lens/cornea; tube --> brain/spinal cord; crest --> autonomics) Notocord triggers ectoderm to become crest/plate; plate involutes to become fold, which closes to form ___ - if it does not close --> ___ Brain development starts with three primary vesicles (prosencephalon, mesencephalon, rhombecephalon), which go on to form five secondary vesicles (telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon)

Most CNS stems from germ layer ectoderm (surface --> pituitary, lens/cornea; tube --> brain/spinal cord; crest --> autonomics) Notocord triggers ectoderm to become crest/plate; plate involutes to become fold, which closes to form tube - if it does not close --> spina bifida Brain development starts with three primary vesicles (prosencephalon, mesencephalon, rhombecephalon), which go on to form five secondary vesicles (telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon) ^B&B video is helpful for brain development! ^^Pros Miss Ramen, Toss Dice, Miss Most Myspace

Nitrous oxide will diffuse rapidly into airspaces, which is why it cannot be used in cases of ___ and abdominal distension Opioids act through the mu receptor, a GPCR with unclear 2nd messenger; this increases ___ efflux from cells, hyperpolarizing them and causing less pain transmission Importantly, while chronic opioid use can lead to tolerance with pain, sedation, and cough suppression, *___ and ___* never develop tolerance and persist with use Inhaled anesthetics (sevoflurane, desflurane) are usually used for ___ anesthesia

Nitrous oxide will diffuse rapidly into airspaces, which is why it cannot be used in cases of pneumothorax and abdominal distension Opioids act through the mu receptor, a GPCR with unclear 2nd messenger; this increases K efflux from cells, hyperpolarizing them and causing less pain transmission Importantly, while chronic opioid use can lead to tolerance with pain, sedation, and cough suppression, *constipation and miosis* never develop tolerance and persist with use Inhaled anesthetics (sevoflurane, desflurane) are usually used for maintenance anesthesia

PD is a degenerative disease involving loss of dopaminergic neurons of ___, *leading to pathologic hallmark of Lewy bodies in SN* Classic PD presentation is rest tremor (asymmetric), ___ (can't initiate movement), and ___ (exam?); PD patients taking cbd-lvd should avoid vit B6 as B6 converts L-dopa --> dopamine in periphery Huntington's disease is another movement disorder caused by degeneration of ___ (caudate + putamen), *specifically losing GABA neurons leading to ___ toxicity; brain imaging reveals enlarged ___ ventricles*; HD is trinucleotide repeat disorder involving ___ gene HD presents with sx in 30-40s with dementia, ___, and aggression Hemiballism is wild, flinging movements of one side ("go ballistic") 2/2 damage in ___ (lacunar stroke) Wilson's disease causes parkinsonism 2/2 copper deposition in basal ganglia, *classically presenting with ___ tremor*

PD is a degenerative disease involving loss of dopaminergic neurons of SN pars compacta, *leading to pathologic hallmark of Lewy bodies in SN* Classic PD presentation is rest tremor (asymmetric), bradykinesia (can't initiate movement), and cogwheeling; PD patients taking cbd-lvd should avoid vit B6 as B6 converts L-dopa --> dopamine in periphery Huntington's disease is another movement disorder caused by degeneration of striatum (caudate + putamen), *specifically losing GABA neurons leading to glutamate toxicity; brain imaging reveals enlarged lateral ventricles*; HD is trinucleotide repeat disorder involving HTT gene HD presents with sx in 30-40s with dementia, chorea, and aggression Hemiballism is wild, flinging movements of one side ("go ballistic") 2/2 damage in subthalamic nucleus (lacunar stroke) Wilson's disease causes parkinsonism 2/2 copper deposition in basal ganglia, *classically presenting with wing-beating tremor*

Papilledema is 2/2 increased ICP, which can manifest clinically as Cushing's Triad (___); severely increased ICP manifests with posturing (cerebral hemisphere --> decorticate, arms ___; brainstem --> decerebrate, arms ___) SubFALcine herniation results in cingulate gyrus extending under falx cerebri, bringing ACA with it --> contralateral ___ paresis Uncal herniation is medial temporal lobe crossing tentorium, compressing ___; this manifests with ___ compression (*"blown" pupil*), ipsilateral ___ collapse (*homonymous hemianopsia*), cerebral ___ compression (*contralateral paresis; opposite side/Kernohan's notch --> ipsilateral paresis*) Transtentorial herniation is herniation crossing tentorium cerebelli, usually a fatal condition with posturing Tonsillar herniation is cerebellar tonsils herniating through foramen magnum, usually 2/2 mass lesion; this is usually fatal

Papilledema is 2/2 increased ICP, which can manifest clinically as Cushing's Triad (HTN, bradycardia, irregular respiration); severely increased ICP manifests with posturing (cerebral hemisphere --> decorticate, arms flexed; brainstem --> decerebrate, arms extended) Subfalcine herniation results in cingulate gyrus extending under falx cerebri, bringing ACA with it --> contralateral leg paresis Uncal herniation is medial temporal lobe crossing tentorium, compressing midbrain; this manifests with CN3 compression (*"blown" pupil*), ipsilateral PCA collapse (*homonymous hemianopsia*), cerebral peduncle compression (*contralateral paresis; opposite side/Kernohan's notch --> ipsilateral paresis*) Transtentorial herniation is herniation crossing tentorium cerebelli, usually a fatal condition with posturing Tonsillar herniation is cerebellar tonsils herniating through foramen magnum, usually 2/2 mass lesion; this is usually fatal

Right visual field --> ___-sided retina --> either optic nerve --> optic chiasm (where ___ visual fields cross) --> ___ optic tract --> ___ of thalamus --> Meyer's loop (temporal lobe, ___ visual fields) or Baum's loop (parietal lobe, ___ visual fields) [MT BP; MP BT don't go together] Anopia (complete vision loss in one eye) --> optic ___ lesion (i.e., optic neuritis or amaurosis fugax) Bitemporal hemianopsia --> optic ___ lesion (i.e., pituitary tumor or AComm aneurysm) Homonymous hemianopsia --> optic ___ lesion or ___ stroke (left OT lesion --> right HH); macular sparing means PCA stroke 2/2 dual blood supply Quadrantic anopia --> Meyer's loop lesion (pie in the ___) or Baum's loop (pie in the ___)

Right visual field --> left-sided retina --> either optic nerve --> optic chiasm (where lateral visual fields cross) --> left optic tract --> LGN of thalamus --> Meyer's loop (temporal lobe, superior visual fields) or Baum's loop (parietal lobe, inferior visual fields) Anopia (complete vision loss in one eye) --> optic nerve lesion (i.e., optic neuritis or amaurosis fugax) Bitemporal hemianopsia --> optic chiasm lesion (i.e., pituitary tumor or AComm aneurysm) Homonymous hemianopsia --> optic tract lesion or PCA stroke (left OT lesion --> right HH); macular sparing means PCA stroke 2/2 dual blood supply Quadrantic anopia --> Meyer's loop lesion (pie in the sky) or Baum's loop (pie in the floor)

Sclera and cornea are continuous with one another; sclera is the site where ___ insert into eye Scleritis results in dark red eyes and "boring" pain with eye movement (think of where EOM insert) - 50% are associated with systemic disease (i.e., RA) The sclera is covered by conjunctiva, but cornea is not; accordingly, contact lens wearers can develop inflammation of cornea termed ___ (sight-threatening disorder) with foreign body sensation (HSV-1 can cause keratoconjunctivitis) Adenovirus causes ~85% of viral conjunctivitis with *___* discharge; bacterial conjunctivitis causes *___* discharge - neonatal conj prophylaxis includes erythromycin ointment; allergic conjunctivitis will be *___ (type I HS rxn)* *Corneal abrasions can be infected with ___ --> treat with ___ eye drops*

Sclera and cornea are continuous with one another; sclera is the site where EOM insert into eye Scleritis results in dark red eyes and "boring" pain with eye movement (think of where EOM insert) - 50% are associated with systemic disease (i.e., RA) The sclera is covered by conjunctiva, but cornea is not; accordingly, contact lens wearers can develop inflammation of cornea termed keratitis (sight-threatening disorder) with foreign body sensation (HSV-1 can cause keratoconjunctivitis) Adenovirus causes ~85% of viral conjunctivitis with *WATERY* discharge; bacterial conjunctivitis causes *PURULENT* discharge - neonatal conj prophylaxis includes erythromycin ointment; allergic conjunctivitis will be *BILATERAL (type I HS rxn)* *Corneal abrasions can be infected with Pseudomonas --> treat with cipro eye drops*

Sphincter pupillae is circular and contracts to cause ___; dilator pupillae is radially oriented and contracts to cause ___ Miosis is under ___ control and begins at EW nucleus --> CN3 --> ___ ganglion (synapse) --> sphincter pupillae (ACh M receptors); CN3 *IMPACTION (via ___ aneurysm)* --> mydriasis (+ down and out) - absence of mydriasis --> ___ damage (PS fibers on outside); Adie's tonic pupil is chronic mydriasis 2/2 ___ ganglion damage Mydriasis is under ___ control and starts 1) post hypothalamus to ciliospinal center of Budge, 2) exits T1 to sup cerv gang, and 3) goes through cavernous sinus with ICA to dilator pupillae; disruption at any point of this chain (apical lung tumor, aort diss, carotid diss, PICA stroke) --> ___, can use cocaine to dx

Sphincter pupillae is circular and contracts to cause miosis; dilator pupillae is radially oriented and contracts to cause mydriasis Miosis is under PNS control and begins at EW nucleus --> CN3 --> ciliary ganglion (synapse) --> sphincter pupillae (ACh M receptors); CN3 *IMPACTION (via PCOM aneurysm)* --> mydriasis (+ down and out) - absence of mydriasis --> ischemic damage (PS fibers on outside); Adie's tonic pupil is chronic mydriasis 2/2 ciliary ganglion damage Mydriasis is under SNS control and starts 1) post hypothalamus to ciliospinal center of Budge, 2) exits T1 to sup cerv gang, and 3) goes through cavernous sinus with ICA to dilator pupillae; disruption at any point of this chain (apical lung tumor, aort diss, carotid diss, PICA stroke) --> Horner's, can use cocaine to dx

___ (pain, temp): 1N is ___ to ___, 2N is ___ to ___ (decussation here), 3N is ___ to ___; damage to STT --> ___ loss ___ (vib, fine touch, prop): 1N is ___ to ___, 2N is ___ to ___ (decussation here in ___), 3N is ___ to ___; damage to DC in cord --> ___ loss (damage to brainstem --> ___ loss) Corticospinal Tract (motor): 1N is cortex to anterior horn of spinal cord (decussation in ___), 2N is anterior horn to muscle

Spinothalamic Tract (pain, temp): 1N is spinal root to cord, 2N is dorsal horn to thalamus (decussation here), 3N is VPL thalamus to cortex; damage to STT --> contralateral loss Dorsal Column (vib, fine touch, prop): 1N is spinal root to lower medulla, 2N is nucleus gracilis/cuneatus to thalamus (decussation here in lower medulla), 3N is VPL thalamus to cortex; damage to DC in cord --> ipsilateral loss (damage to brainstem --> contralateral loss) Corticospinal Tract (motor): 1N is cortex to anterior horn of spinal cord (decussation in lower medulla), 2N is anterior horn to muscle

CLASSIC PRESENTATION: patient with eccentric behavior that has difficulty walking, 5/5 strength, positive Romberg, wide-based gait, loss of ankle/knee reflexes, and pupils that react to accommodation but not light

Tabes dorsalis 2/2 tertiary syphilis

The blood brain barrier keeps bacteria and many drugs out; importantly, ___ (2) can't cross directly and use carrier-mediated transport proteins Circumventricular organs (i.e., ___ - chemoreceptor trigger zone in caudal 4th ventricle, OVLT, SFO, median eminence of hypothalamus) are vascular structures that do not contain ___ - allow point of communication between CNS and bloodstream

The blood brain barrier keeps bacteria and many drugs out; importantly, glucose and amino acids can't cross directly and use carrier-mediated transport proteins Circumventricular organs (i.e., area postrema - chemoreceptor trigger zone in caudal 4th ventricle, OVLT, SFO, median eminence of hypothalamus) are vascular structures that do not contain BBB - allow point of communication between CNS and bloodstream

The lens is an avascular structure with cells that undergo anaerobic metab and is surrounded by type ___ collagen The ciliary muscle controls lens accommodation, such that contraction --> relax of ___ --> accommodation (focus on near objects) ___ is lens stiffening with age --> can't focus on near objects (i.e., reading glasses) Myopia (nearsightedness) has focal point ___ to retina, either d/t eye that is too long or cornea with too much curvature --> fix with negative lens Hyperopia (farsightedness) has focal point ___ to retina, either d/t eye that is too short or cornea that is too flat --> fix with positive lens ___ has multiple focal points 2/2 uneven corneal curvature

The lens is an avascular structure with cells that undergo anaerobic metab and is surrounded by type IV collagen The ciliary muscle controls lens accommodation, such that contraction --> relax of zonules --> accommodation (focus on near objects) Presbyopia is lens stiffening with age --> can't focus on near objects (i.e., reading glasses) Myopia (nearsightedness) has focal point anterior to retina, either d/t eye that is too long or cornea with too much curvature --> fix with negative lens Hyperopia (farsightedness) has focal point posterior to retina, either d/t eye that is too short or cornea that is too flat --> fix with positive lens Astigmatism has multiple focal points 2/2 uneven corneal curvature

The ___ innervates the diaphragm, which can cause referred pain to ___ (d/t C3-C5 also innervating that area) and dyspnea/___ The ___ dermatome supplies the umbilicus, which can cause referred pain in ___ Dermatomes are important in ___ as virus lays dormant in ___, reactivating to cause shingles

The phrenic nerve (C3-C5) innervates the diaphragm, which can cause referred pain to shoulder (d/t C3-C5 also innervating that area) and dyspnea/hiccups The T10 dermatome supplies the umbilicus, which can cause referred pain in appendicitis Dermatomes are important in VZV as virus lays dormant in DRG, reactivating to cause shingles

The retina is supplied by choroid, the major focal point is the ___ Retinitis pigmentosa is loss of photoreceptors, resulting in visual loss in childhood (night/peripheral first); fundoscopy reveals ___ pattern Retinitis results in floaters and decreased vision with classic cause being CMV in AIDs/transplant patients; fundoscopy reveals ___ Diabetic retinopathy is 2/2 ___ degeneration --> microaneurysms --> rupture and hemorrhage More common is NON-prolif retinop leading to "dot-and-blot hemorrhage" and ___ spots (2/2 nerve infarction); prolif retinop occurs when retinal ischemia --> ___ (vessel prolif), which are friable and can cause retinal detachment (tx with laser, anti-VEGF inhibitors)

The retina is supplied by choroid, the major focal point is the macula Retinitis pigmentosa is loss of photoreceptors, resulting in visual loss in childhood (night/peripheral first); fundoscopy reveals bone-spicule pattern Retinitis results in floaters and decreased vision with classic cause being CMV in AIDs/transplant patients; fundoscopy reveals retinal hemorrhages and whitish appearance (pizza-pie) Diabetic retinopathy is 2/2 pericyte degeneration --> microaneurysms --> rupture and hemorrhage More common is NON-prolif retinop leading to "dot-and-blot hemorrhage" and cotton-wool spots (2/2 nerve infarction); prolif retinop occurs when retinal ischemia --> neovascularization (vessel prolif), which are friable and can cause retinal detachment (tx with laser, anti-VEGF inhibitors)

The trochlear nerve innervates ___, while the abducens nerve innervates ___ The SO moves the eye ___, while the IO moves the eye ___ Diplopia 2/2 nerve palsies is binocular (resolves with eye covered); monocular diplopia is usually 2/2 ___ CN3 palsy --> eye is down and out + ptosis +/- pupil dilation (if compressed by ___ aneurysm) CN4 palsy --> diplopia + eye tilted outward + difficulty looking down + *head tilting ___ affected side* CN6 palsy --> cannot abduct affected eye (may be medially deviated at rest), often 2/2 elevated ICP d/t long course of CN6 (i.e., ___ - overweight woman of childbearing age)

The trochlear nerve innervates superior oblique, while the abducens nerve innervates lateral rectus The SO moves the eye inward and downward, while the IO moves the eye outward and upward Diplopia 2/2 nerve palsies is binocular (resolves with eye covered); monocular diplopia is usually 2/2 astigmatism CN3 palsy --> eye is down and out + ptosis +/- pupil dilation (if compressed by PComm aneurysm) CN4 palsy --> diplopia + eye tilted outward + difficulty looking down + *head tilting away from affected side* CN6 palsy --> cannot abduct affected eye (may be medially deviated at rest), often 2/2 elevated ICP d/t long course of CN6 (i.e., pseudotumor cerebri - overweight woman of childbearing age)

The vitreous humor is back of eyeball; ___ humor is in front of eyeball and is divided into anterior and posterior chambers Aqueous humor is produced by ciliary ___, goes to trabecular network, and drains in Canal of Schlemm Intraocular pressure is determined by amount of aqueous humor - ___ produces fluid (B2) while ___ drains fluid Glaucoma is elevated IOP *and manifests with loss of ___ vision first, then ___ vision* CAG manifests with *"___"* eyeball and pain that is triggered when pupil ___ (i.e., dark room, scopolamine) - chronic CAG is 2/2 scarring with fewer sx OAG is far more common, manifests with disc cupping (increased ___ ratio)

The vitreous humor is back of eyeball; aqueous humor is in front of eyeball and is divided into anterior and posterior chambers Aqueous humor is produced by ciliary muscle, goes to trabecular network, and drains in Canal of Schlemm Intraocular pressure is determined by amount of aqueous humor - SNS produces fluid (B2) while PNS drains fluid Glaucoma is elevated IOP *and manifests with loss of peripheral vision first, then central vision* CAG manifests with *"ROCK HARD"* eyeball and pain that is triggered when pupil dilates (i.e., dark room, scopolamine) - chronic CAG is 2/2 scarring with fewer sx OAG is far more common, manifests with disc cupping (increased cup-to-disk ratio)

There are two types of cells that are highly sensitive to hypoxic damage: ___ cells of the hippocampus and ___ cells of cerebellum Watershed area infarcts occur after global hypoperfusion (i.e., massive MI) and result in ___ syndrome (can't move shoulders/thighs, spares face/hands/feet)

There are two types of cells that are highly sensitive to hypoxic damage: pyramidal cells of the hippocampus and Purkinje cells of cerebellum Watershed area infarcts occur after global hypoperfusion (i.e., massive MI) and result in man-in-a-barrel syndrome (can't move shoulders/thighs, spares face/hands/feet)

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