Step 1

Child motor development 12-36 months

"Child" Cruises - takes first steps (12 months) Climbs stairs (18 months) Cubes stacked - number = age (yr) x 3 Cultured - feeds self with fork and spoon by 20 months) Kicks ball - 24 months

Child motor development 3-5 years

"Don't" Drive - tricycle (3 wheels at 3 years) Drawings - copies line or circle, stick figure (4 years) Dexterity - hops on one foot (4 years) -uses buttons or zippers, grooms self (5 years)

Atrial fibrilation

10% of aortic stenosis patients -> atrial fibrillation -exacerbates already impaired cardiac output because preload decreases

Multiple endocrine neoplasia type I

3 P's -parathyroid -pituitary -pancreatic TUMORS mutation of MEN1 gene -menin -> tumor suppressor gene AD

Amyotrophic lateral sclerosis

40-60 UMN and LMN lesions UMN muscle weakness spastic paralysis clasp knife rigidity HYPERreflexia babinski sign LMN Flaccid paralysis Hypotonia Muscle atrophy Fasciculations downgoing plantar reflexes Congenital SOD1 mutation that causes apoptosis of motor neurons most die within 5 years

Turner syndrome

45 X 99% are spontaneously aborted in utero 75% are mosaics 45X/46XX 45X/46XY Single most important cause of primary amenorrhea Short stature because of deletion of SHOX gene on X-chromosome Neck webbing Streak ovaries Coarctation of aorta cystic hygroma (posterior neck mass) lymphedema

Maintenance dose

= [(concentration in plasma, desired) x Clearance] / bioavailability

Refsum disease

AR Disorder of alpha-oxidation (only occurs in peroxisome) Phytanic acid not metabolized to pristanic acid PW -Scaly skin -ataxia -cataracts/night blindness -shortening of the 4th toe -epiphyseal dysplasia Tx -diet -plasmapheresis

Zellweger syndrome

AR disorder of peroxisome biogenesis due to mutated PEX genes PW -hypotonia -seizures -hepatomegaly -early death

Cholangiocarcinoma

Adenocarcinoma of the bile duct epithelial cells -can be intra or extra hepatic East asia -liver fluke Clonorchis sinensis -risk factor very aggressive Metastasis early Fever, weight loss, night sweats Histology -mucin and glands

Streptococcus viridans

Adhere to fibrin-platelet aggregates -more likely to adhere to previous lesions (mitral valve prolapse, ect.) Gram - Dextran production that helps them adhere Normal mouth flora

Insulin dependent cells

Adipocytes Muscle cells

Bacillus cereus

Aerobic and spore forming FOOD poising -> reheated fried rice

PECAM-1

Aides in transmigration of leukocytes

Tricyclic antidepressants

Amitriptyline, Desipramine, Doxepin Messy antidepressant drugs that hit a lot of receptors Toxicity: Increase norepinephrine & serotonin concentrations in synaptic cleft muscarinic and alpha receptor antagonist Sodium channel blocker Tachycardia Seizures Hypotension arrythmeias Give sodium bicarbonate to reverse sodium channel blockade

Medullary thyroid cancer

Amorphous proteinaceous material -> amyloid -> medullary thyroid carcinoma arises from neuroendocrine parafollicular C cells of the thyroid produce calcitonin -> leads to amyloid synthesis associated with MEN 2A and 2B

Meigs syndrome

Ascites Pleural effusion Ovarian fibroma (tumor) Granulosa-Theca tumor

Beta-2 agonists

Beta-2 relaxes the uterus Ritodrine Terbutaline Tx -prevents preterm labor

Cholestyramine

Bile acid resins Colestipol Colesevelam Bind bile acids in intestinal lumen and prevents their reabsorption Liver compensates by increasing cholesterol synthesis (upregulates HMG-CoA reductase) Upregulation of LDL receptors Causes increase of serum triglycerides (increased VLDL) So these are really only good for isolated LDL increase Increased chance of galstones from increased produciton GI upset (constipation and bloating) Steatorrhea and impaired fat aborption (vitamin k) decreased absorption of statins so they have to be given 4 hours apart

Duodenal atresia

Bilious vomiting Presents like small bowel obstruction because it is Double bubble - air in stomach and proximal duodenum Downs syndrome association

Fondaparinux

Binds antithrombin III with higher specific than LMWH

Neural tube

Brain Spinal cord Posterior pituitary pineal gland Retina

IgA nephropathy

Burger's disease 1-2 days after respiratory infection Episodic hematuria Diffuse proliferation -> membranoproliferative glomerulonephritis Mesangial granular pattern due to immune complex deposition Treat: -glucocorticoids

Epithelial ovarian tumors

CA-125 -> also elevated in endometriosis and other things that disrupt epithelial membrane ->can be used to track progress, not specific enough to be diagnostic RF -BRCA I and II -anything that causes repeated damage of epithelium -> OVULATION when the follicle BURSTS out of epithelium lol -nulliparity due to no breaks in ovarian cycle -endometriosis protective factors -breast feeding -OCPs -pregnancy -all cause ovulation to take a break PW -malignant pleural effusions Serous cystadenocarcinoma Mucinous cystadenocarcinoma Brenner tumor Endometrioid ovarian cancer

Huntington Disease

CAG repeats Huntington protein gain of function leads to increased histone deacetylation

Vesicular trafficking proteins

COP1: Golgi -> Golgi (retrograde) cis-Golgi -> ER COPII: ER -> cis-Golgi (anterograde) TWO steps forward (anterograde) ONE step back (retro) Clathrin: trans-Golgi -> lysosomes Plasma membrane -> endosomes (receptor mediated endocytosis (eg. LDL receptor activity

Bile obstruction

COnjugated bilirubinemia Pale stools -no fat absorption Dark urine -bilirubin in the urine

CREST phenomenon

Calcinosis Raynaud's phenomenon Esophogeal dysmotility Sclerodactyly Telangiectasias Anti-centromere specific for CREST and found 40% Anti-DNA topoisomerase 1 (Scl-70) antibodies

Nifedipine

Calcium channel blocker Safe in pregnancy Side effects: -lightheadedness -headaches -peripheral edema because arterioles preferentially dilate, leading to increased hydrostatic pressure in capillaries and edema -Reflex tachycardia that can cause ischemia, don't use immediately post MI

Pseudogout

Calcium pyrophosphate deposition disease calcium pyrophosphate crystals in synovial fluid Knee joint most common site Neutrophilic predominace P's pyrophospate parallel positive

Chagas diseas

Cardiomegaly transmitted by Triatoma (reduviid) bugs, "kissing bugs" Trypnosoma cruzi myocarditis dysmotility of hollow organs such as esophogus

Mediastinal and diaphragmatic pleural pain

Carried by the phrenic nerve

Gastric lymphoma

Caused by: -MALT (h pylori) -EBV Marginal B cell and diffuse large B cell (50:50)

Chronic pancreatitis

Causes -cystic fibrosis PW -calcified concretions throughout the pancreas -pseudocysts -steatorrhea -vitamine ADEK deficiency -type 1 diabetes (islets of langerhans destroyed) Complications -pancreatic adenocarcinoma

Large bowel obstruction

Causes -malignancy - PW -abdominal pain -distension -tinkling bowel sounds -air fluid levels

Dimercaprol

Chelating agent for mercury exposure

Usual CSF flow

Choroid plexus found in all 4 ventricles Lateral ventricles -> interventricular foramina -> third ventricle -> cerebral aqueduct (of Sylvius) -> Fourth ventricle -> EITHER lateral foramen of Luschka to subarachnoid space OR medial foramen of Magendie to subarachnoid space Then back to systemic circulation via arachnoid granulations

Tetanus

Circulating antibodies neutralize toxin

Primary Effusion lymphoma

Co-infection with HHV-8 and HIV Presents in the pleural, periotoneum, or pericardial spaces

Vibrio spp.

Comma shaped bacteria Vibrio cholera: Profuse watery diarrhea Rice water Fecal-orally via poor sanitation fimbriae to attach secretes cholera toxin- increased cAMP. binds to and constituently activates adenylyl cyclase. Activates Gs pathway, increased water into lumen grows on alkaline media Acid labile!! oxidase positive Vibrio parahaemolyticus: contaminate oysters Vibrio vulnificus: Contaminate oysters

Neurocysticercosis

Common in central and south america Ingestion of Tania solium eggs (pork tapeworm) excreted in feces of human carriers PW -Seizures -Focal neurologic symptoms, intracranial hypertension (CSF obstruction) -Cysts on MRI -Eosinophilia -increased ESR Tx -Albendazole

Serous cystadenocarcinoma

Commonly bilateral contain cysts lined by tube-like ciliated columnar cells CA-125 -> also elevated in endometriosis and other things that disrupt epithelial membrane ->can be used to track progress, not specific enough to be diagnostic RF -BRCA I and II -anything that causes repeated damage of epithelium -> OVULATION when the follicle BURSTS out of epithelium lol -nulliparity due to no breaks in ovarian cycle -endometriosis protective factors -breast feeding -OCPs -pregnancy -all cause ovulation to take a break PW -malignant pleural effusions

Anaplastic thyroid carcinoma

Commonly occurs in the elderly (>65 years) Near 100% mortality RAS Invades local neck structures can cause compression of trachea

Dermatomyositis

Cutaneous manifestations: Gottron papules (red flat topped papules over bony prominences especially on hands Heliotrope rash (erythromus eruption on upper eyelids or periorbital skin) Malar rash Theory of pathogenesis -upregulation of type 1 interferon Obliteration of capillaries Anti-Jo most specific Antinuclear antibodies often elevated Increased creatinine kinase Perimysial inflammation with perimysial atrophy Inflammatory disorder of skin and skeletal muscle Some cases are associated with carcinoma (gastric particularly) -ovarian -lung -colorectal -NHL Bilateral muscle weakness (cant comb hair) Treat with corticosteroids

Nitroprusside overinfusion

Cyanide toxicity Give sodium thiosulfate to replenish sulfur donors (rhodanese) that detoxify cyanide

Germ cell ovarian tumors

Cystic teratomas -endoderm, ectoderm, mesoderm -abdominal pain -ovarian torsion Struma Ovarii -contain functioning thyroid tissue -hyperthyroidism -thyroid follicles with eosinophilic material, just like thyroid Dysgerminomas -most common ovarian cancer in children -serum beta-hCG elevated -LDH elevated -fried egg cells on histology Yolk sac tumor -AFP elevated -malignant -grow fast, get big -ovarian torsion -Schiller-Duval bodies

busulfan

Cytotoxic alkylating agent DNA intrastrand crosslinks Conditioning agent used prior to bone marrow transplant -causes severe bone marrow suppression Hyperpigmentation -busulfan tan AEs -lung toxicity -acute lung injury -interstitial fibrosis -alveolar hemorrhage

nitrosoureas

Cytotoxic alkylating agents highly lipophilic -> cross BBB -> brain cancer treatment carmustin lomustin streptozosin AEs -convulsion -dizziness -ataxia -neurotoxicity

Dopamine receptors

D1 -Gs -renal vasculature -> increases GFR, RBF, and sodium excretion D2 -Gi dopamine also has pressor effects through action at Alpha 1 and Beta 1 receptors D > B > A

Cystic fibrosis

DeltaF508 mutation in the cystic fibrosis -most common mutation causes impaired post-translational processing which is detected by the ER and the protein is degraded -less common mutations change the pore and affect other sites transmembrane conductance regulator (CFTR) protein The chloride absorption in sweat also determines the sodium and water absorption, so with impaired chloride secretion you get excess salt excretion in sweat -> hyponatremia in blood

Multiple sclerosis

Demyelinating disorder autoimmune disorder Destroys oligodendrocytes May involve autoreactive helper T cells -cytotoxic T cells also in inflammatory reaction -macrophages present relapsing-remitting pattern white women most common RF -HLA-DR2 -prevalence increases as you move away from the equator (sunlight is protective against development) PW -FATIGUE especially after hot shower or hot environments or sweating hard -optic neuritis (most common cause) -> marcus-gunn pupil -sensory symptoms -> decreased touch and vibration -decreased facial sensations -clasp-knife rigidity -Lhermitte's sign -> electrical shock running down spine upon flexion of neck -intention tremors Marcus-Gunn pupil -Affected eye will appear to dilate when light is shone on it -constricts, just not as much as other eye, so it appears to dilate Intranuclear opthalmoplegia -lesion in MLF -horizontal eye movement impaired -affected eye doesn't know when other is abducting -nystagmus -convergence will be normal Dx -multiple neuronal deficits that can't be described by a single lesion -if these different symptoms are seen throughout time and space -> get MRI (diagnostic) -demyelinating plaques on MRI -lumbar puncture can be used to diagnose too (oligonal clones) Tx -immunomodulating drugs -methotrexate -cyclophosphamide -interferon beta -natalizumab -gluteramir -high dose IV steroids for acute flairs

Acute infectious arthritis

Differential: Staph or gonorrhea

Sjogren's Syndrome

Dry eyes and dry mouth -immune destruction of lacrimal and salivary gland -much more common in women (9:1) -keratoconjunctivitis sicca (dry eyes) -xerostomia (dry mouth) HLA-DR HLA-DQ Presents with: -dry eyes -dry mouth -arthritis -raynaud -serositis? -vaginal dryness from destruction of exocrine glands increased risk of non-hodgkins lymphoma Infection with EBV thought to be trigger Damage to exocrine glands (from infection or genetic mutation) may lead to the release of self antigens -> development of self-reactive lymphocytes -Sever inflammation Autoantibodies -anti-SSA (anti-Ro) no direct damage -anti-SSE (anti-La) no direct damage Lymphocytic infiltrate in lacrimal and salivary gland -can even have germinal centers -lacrimal gland destruction -> lack of tears -> drying, inflammation and erosion of the cornea (keratoconjunctivitis sicca) -similar process in mouth Diagnosis: -presence of anti-SSA Ro or anti-SSE La with dry eyes or dry mouth treat: -pilocarpine -artificial tears and saliva -immunosuppressants can be used (methotrexate, rituximab, ect)

SNRI's

Duloxetine Venlafaxine inhibit presynaptic reuptake of serotonin and norepi Take up to 2 months to have maximal effect Treats: -diabetic neuropathy -panic disorder -chronic pain (low back pain, osteoarthritis, ect) -fibromyalgia -PTSD AE's -hypertension (increased adrenergic transmission) -withdrawal leads to flu-like symptoms

Liver cirrhosis

End point for inflammatory hepatic diseases Irreversible fibrosis of the liver MOA -stellate cells in the perisinusoidal space (space of Disse) activate and become myofibroblasts -Liver stem cells create new hepatocytes -> stranded in nodules because they are trapped by fibrosis -> regenerative nodules (for septae that look like chicken wire -compression of sinusoids -> increased sinusoidal pressure -> portal hypertension -Fibrosis -> thicker extracellular matrix -> shrinks fenestrations -> decreased exchange of solutes between blood and hepatocytes -> decreased detoxification of blood Liver can't make albumin and clotting factors -coagulopathy (check PT time (extrinsic) and INR) -> factor VII is used up first -hypoalbuminemia -> peripheral edema, hypocalcemia in serum although total is the same (calcium binds to albumin) Vitamin D synthesis is decreased Decreased gluconeogenesis and glycogenolysis -hypoglycemia Detoxification impaired -impaired secretion of conjugated bilirubin into bile -> leaks back into blood stream -> conjugated hyperbilirubinemia (as liver fails more, it cant even conjugate -> mixed hyperbilirubinemia -ammonia builds up because the liver cant process efficiently -> increased serum ammonia and decreased urea -> hepatic encephalopathy (asterixis) results from conversion of aromatic amino acids into false neurotransmitters because they cant be metabolized into urea -Treatment -> Lactalose is used to lower the pH environment of small intestines, can't absorb ammonia and its eliminated in stool Histology RF -chronic alcoholism (most common) -Hep B and C -Alpha-1 antitrypsin deficiency PW -Elevated serum estrogen -> gynecomastia -estrogen also causes palmar erythema -hypoalbuminemia -portal hypertension -Varices from venous dilation -hemorrhoids -Caput medusae -Splenomegaly -ASCITES (can get infected) -Splenic dysfunction -> platelet aggregation -> thrombocytopenia -Altered mental status (spontaneous bacterial peritonitis = SBP, usually caused by E coli) -hyperaldosteronism (liver can't break down aldosterone) -> hypokalemia, hypernatremia hepatorenal syndrome Hepatopulmonary syndrome

HSV1 and HSV2

Enveloped DNA virus Double stranded linear replicates in the nucleus Intranuclear inclusion bodies (Cowdry bodies) that look like targets Transmitted by sex, saliva, and vertical transmission to baby Herpetic whitlow -more common in dentists because of hands in mouth -vesicles on finger HSV1 -usually confined to upper half of body -Cold sores (herpes labialis) - gingivostomatitis -Keratoconjunctivitis -snake like ulcers on cornea (serpiginous) -Temporal lobe encephalitis that causes hemorrhage and necrosis of medial temporal lobe -Most common cause of sporadic encephalitis in USA -Remains latent in the trigeminal ganglia -Dew drops on a rose petal appearance or RAISED vesicles with an erythematous base -erythema multiforme (one of the most common causes) HSV2 -Genital -Herpes genitalis -Painful vesicular lesion -Painful inguinal lymphadenopathy -latent in the sacral ganglia -Aseptic meningitis in adolescents and adults PCR is the test of choice for diagnosis Old test used to be Tzank smear Acyclovir and Valcyclovir

PCSK9 inhibitor

Evolovamab Binds Protease produced by liver that leads to the degradation of hepatocyte LDL receptors

Hemophilia B

Factor IX deficiency X-linked recessive Affects intrinsic pathway Prolonged aPTT 'Coagulopathic' bleeding

Rivaroxaban

Factor Xa inhibitor

Vitamin K deficiency

Factors 2, 7, 9, 10 Usually synthesized by colonic bacteria from vegetables Liver VKOR activates vitamin K -> cofactor for gamma-glutamyl-carboxylase (activates Vitamin K-dependent factors) Deficiency Usually seen in infants -GI tract lack intestinal flora -decreased utilization by the liver -breast milk contains very little vitamin K -presents as hemorrhagic disease of the newborn (intracranial hemorrhage, retroperitoneal bleeding, death) -newborns are routinely given vitamin K injections (not in home births and they can refuse) Adults -diseases that cause malabsorption (inflammatory bowel disease, chronic pancreatitis, etc) -antibiotics can cause by killing gut GI that synthesizes vitamin K -cirrhosis -"coagulopathic' bleeding -reduced factor VII -treat with FFP

Transposition of the great arteries

Failure of spiraling during development NEED PDA or VSD or ASD Keep PDA open

After 14 days MI

Fibroblasts Strong scar tissue reduces risk of rupture Scar formation can cause conduction abnormalities and fatal ventricular arrhythmias

Actinomyces Isrealii

Filamentous branching rod Obligate Anaerobe Normal mouth flora Dental work can lead to opportunistic infection Sinus tracks drain thick yellow pus from infecitons Yellow sulfur granules Treatment: Penicillin G

Ebolavirus

Filoviridae RNA with helical capsid enveloped Hemorrhagic fever petechial rash End organ failure Usually fatal Hypovolemic shock Direct contact with monkeys (possible vector) or fruit bats (possible viral reservoir) Healthcare workers can get it from working with infected It is VERY infectious

Marburgvirus

Filoviridae RNA with helical capsid enveloped usually fatal Hemorrhagic fever

Stimulation of gluconeogenesis

First enzyme (pyruvate carboxylase) directly stimulated by acetyl-CoA (increased from fatty acid oxidation)

Thyrotoxicosis in pregnancy

First trimester: PTU after: Methimazole because it is less teratogenic Both antithyroid medications block thyroid peroxidase

Carbamazepine

First-line therapy for trigeminal neuralgia Diplopia Ataxia agranulocytosis Broad spectrum inducer of CYP450

LMN lesions

Flaccid paralysis Hypotonia Muscle atrophy Fasciculations downgoing plantar reflexes

Hepatitis C virus

Flaviviridae Positive sense, enveloped, RNA virus Transmission through blood transfusions back in the day IV drug users STD Antigenic variability of envolope proteins No proofreading leads to high antigenic variation (no 3-5 exonuclease) Hepatitis Acute stage inflammation can lead to jaundice RUQ pain Increased liver enzymes 60-80% of Hep C infections become chronic Cirrhosis of the liver Or liver can go into frenzy reproducing and cause hepatocellular carcinoma ALT rises and falls by 6 months Anti HCV will be present in both acute and chronic, and they soon become ineffective because of how much virus mutates Chronic: viral RNA persists after 6 months, and you will see cryoglobulins that precipitate out in cooler temperature and lymphocytes in portal vein Old way to treat: ribavirin and interferon alpha Protease inhibitors may be used Integrase inhibitor?

Focal segmental glomerulosclerosis

Focal - affects some glomeruli Segmental - not all parts of glomerulus are affected Podocyte effacement and fusion Poor response to steroid Can be caused by viral agents Or heroine abuse, diabetes, vasculitis, sickle cell can frequently progress to end stage kidney disease

Estrogen therapy

For menopause RAISES free T4 1. Estrogen increases TBG -> free T4 decreases 2. Thyroid senses this -> increased TSH and T4 3. now there is more total T4 in the serum (bound and free)

Nicotinic acetylcholine receptros

Found -directly on adrenal glands -ganglia (pre and post) -muscle

12-24 hours post MI

Frank coagulation necrosis structural outline of dead cells is preserved Loss of nuclei Pale cardiomyocytes Contraction bands can be seen on histology (return of blood flow -> abnormally high intracellular Ca2+ -> hypercontraction of dead cardiomyocytes) Neutrophils can be seen in area of infarct

Flumazenil

GABAa receptor antagonist (at the site benzodiazepines bind) Used for treatment of benzodiazepine toxicity Side effects: Seizures, withdrawal

D2 receptor

Gi coupled

Rapid acting insulin

Glulisine Aspart Lispro modified to not polymerize into hexamers like regular insulin

Selective muscarinic antagonists

Glycopyrrolate hyoscyamine Propantheline can be used to treat side effects from MG -blocks excessive acetylcholine in the gut

trastuzmab

HER2 receptor blocker monoclonal antibody Tx -HER2 positive breast cancer AEs -Infusion reaction (headache, fever, skin rash, dyspnea, hypotension)

Lesch-Nyhan Syndrome

HGPRT deficiency Cant use salvage pathway PW -Dystonia -Choreoathetosis -Self-mutilation PRPP synthase is the enzyme right before it GOUT

Heparin induced thrombocytopenia

HIT Quantitative platelet disorder Autoimmune destruction of platelets after administration of heparin Much more likely in unfractionated heparin Major cause of thrombocytopenia is phagocytosis of IgG coated platelets at the spleen Fever, chills, tachycardia, necrotic skin lesion Type 1 -mild -transient -observation usually Type II -Autoantibodies against platelet factor 4-heparin complex -These autoantibodies also attach directly to platelets via their Fc region -binding platelet causes degranulation -> more cytokines -> more platelet factor 4, cytokines, and ADP -> clot formation -Serious and life threatening -DVT -pulmonary embolism -arterial occlusion less frequently Treat with an anticoagulate OTHER THAN HEPARIN -argatroban (thrombin inhibitor) -bivalrudin (thrombin inhibitor)

p16 stain

HPV-related squamous cell carcinoma

Clinical manifestations of CHF

Hemosiderin-laiden macrophages "heart failure cells" Dyspnea on exertion Cardiomegaly on CXR S3 -more common in systolic failute -blood rushing into volume overloaded ventricle (volume that wasn't ejected last time) S4 -more common in diastolic failure -blood hitting stiff poorly compliant ventricular wall - Left sided: -orthopnea, laying down increases venous return -> more fluid in the lungs -peribronchial edema causes wheezing ("cardiac asthma") -pulmonary edema looks like fluffy bilateral "batwing" shape opacities on CXR -Kerley B lines (fluid accumulation between lobes) -dilated atrium -> irregularly irregular heart beat -left sided HF causes damage to pulmonary vascular endothelium -> decreased NO -> vasoconstriction -mitral regurgitation Right sided: -most common cause is left sided HF -pools in gravity dependent areas -tricuspid regurgitation -Kussmaul sign -deep breath shows paradoxical JVD pressure increase (usually decreases because this increases venous return to the heart, but in CHF the heart is backed up) -Nutmeg liver

HBeAg

Hep B marker (soluble protein that is a marker of viral replication and increased infectivity) Increased risk of vertical transmission (20% -> 95%)

Hepatitis B virus

Hepadnaviridae Enveloped DNA virus Partially double stranded DNA to intermediate single stranded RNA then back to double progeny DNA Sex and sharing blood products Transmitted during delivery Only 5-10% of adults develop into chronic infection Newborns however have a 90% chance Polyarteritis nodosa Purpuric rash with non-blanching lesions Arthralgia Kidney damage caused by polyarteritis nodosa Membranous glomerulonephritis (thickened glomerular membrane) Membranoproliferative glomerulonephropathy - TRAM TRACK appearance ALT is higher in viral hepatitis ALT is normal early in neonatal hepatitis Titer levels of antigens!!! HBsAg - marker of active disease HBeAg- next one that appears, means you're infectious With these two you have symptomes Anti-HBc- Hep b core antibody is positive during the window period Anti-HBe- Low infectivity Anti-HBs- indicated recovery, and seen in vaccinated So immunized people wont be positive for anti-HBc or anti-HBe, where as recovering patients will Hep B is a risk factor for Cirrhosis hepatocellular carcinoma Hep D cant cause any disease without Hep B Hep D is an enveloped negative sense circular RNA virus Hep D requires HBsAg to be infectious Co-infection: transmitted at same time Superinfection: Hep D transmitted after Hep B infection Treatment: Acute cases usually clear up by themselves Antivirals like lamivudine Interferon therapy NRTI's Histology -HBsAG accumulates in liver cells -> fine, granular, eosinophilic cytoplasm Give at risk kids immunoglobulins

Transplant rejection

Hyper-acute -minutes to hours -preformed antibodies against graft already present in circulation -> gross mottling and cyanosis -> arterial fibrinoid necrosis -> capillary thrombotic occlusion Acute -usually less than 6 months -exposure of donor antigens induces humoral/ cell mediated response -> C4d deposition ->neutrophilic infiltrate -> necrotizing vasulitis Chronic -months to years -chronic, low grade immune response refractory to immunosuppressants -> vascular wall thickening -> luminal narrowing -> interstitial fibrosis -> parenchyma atrophy

Diffuse proliferative glomerulonephritis

Hypercellularity of mesangium Wire looping Lupus causes -Immune complex (anti-DNA - DNA complex) -> granular pattern Usually progresses to CKD Treat with: Glucocorticoids

Prostacyclin analogues

Iloprost Epoprostenol first line agent for pulmonary hypertension prolonges survival

Primary immunodeficiencies

Increased susceptibility to infection Increased autoimmune diseases -regulation of self is messed up too Increased risk for cancer -T cells don't monitor well -lymphoma is most common (NHL) -gastrointestinal carcinoma Usually present 6 months to 2 years -IgG thru placenta - IgA thru breast milk Live vaccines are counterindicated Bruton disease

Amantadine

Increases dopamine in CNS through unknown mechanism Likely increases dopamine synthesis and release as well as inhibiting uptake

Mastitis

Inflammation of breast ducts common in breastfeeding pain inflammation fibrosis can be present if its bad

Fomepizole

Inhibits alcohol dehydrogenase, renal elimination of parent compound

Acetazolamide

Inhibits carbonic anhydrase prevents reabsorption of bicarbonate Catalyzes H2CO3 -> CO2 + H2O -lets bicarb be reabsorbed, turns to CO2 that can diffuse back into the cell, then CA inside turns it back into bicarb and traps it there Sodium exchanged for proton -> proton binds to bicarb to make carbonic acid -> turned to CO2 by CA -> diffuses in cell -> converted back to bicarb by CO2 -> pumped back into blood Works at PCT Causes diuresis Sodium excretion Tx -glaucoma (decreases aqueous humor production, bicarb is important) -decreased CSF production (bicarb is important) -mountain sickness AEs -metabolic acidosis (normal gap) Type II (defect in bicarb resorption...) -hypokalemia -Sulfa drug -> sulfa reactions

Isoniazid

Inhibits mycolic acid synthesis Has to be activated by intracellular catalase peroxidase -resistance by down regulating Kat G Need pyrazinamide -> vitamin B6, since isoniazid promotes its excretion Tx -can be used alone in latent TB infection -4 for 2 months (rifampin, isoniazid, pyrazinamide, ethambutol) 2 for 4 (rifampin, isoniazid) AEs -metabolized by liver enzyme N-acetyltransferase -> slow acetylators have higher risk of side effects -hepatotoxicity -asymptomatic rise in aminotransferases -drug induced lupus -anion gap acidosis -inhibits cytochromeP450

Congenital hypothyroidism

Initially normal at birth symptoms develop as maternal T4 wanes Lethargy Enlarged Fontanelle Protruding tongue umbilical hernia Poor feeding Constipation Dry Skin Jaundice

Gastric adenocarcinoma

Intestinal type most common RF: -chronic atrophic gastritis is biggest risk factor -Nitrosamines in preserved foods -EBV Diffuse type -E-cadherin + -can form glandular structures and turn into exophytic mass -Loss of E-cadherin -> less organized -> can invade

Toxoplasma gondii

Intracellular parasitic protozoan approximately 30% carry toxo CATS, CAT POOP!! Oocysts in feces, cat feces Ring enhancing lesions on CT or MRI Encephalitis Cysts in undercooked meat Clinical symptoms: Flu-like mostly asymptomatic in healthy Pregnant!! Congenital toxo -hydrocephalis -Chorioretinitis -intracranial calcifications -congenital deafness Diagnosis with serology (positive doesn't indicate active infection) or biopsy looking for intramuscular cysts Treatment Sulfadiazine and pyrimethamine Prophylaxis at <100 CD4+ count Trimethoprim and sulfamethoxazole (bactrim)

3-14 days post MI

Invasion of macrophages Removing debris The more they remove the weaker the myocardium gets Ischemia of the papillary muscle causes necrosis and rupture (posteromedial papillary muscle of the left ventricle, supplied by posterior descending artery of the right coronary) Mostly all ruptures occur during this time Scar tissue has NOT developed yet

HHV-8

Kaposi's sarcoma -AIDS defining illness Herpesviridae Erythematous lesions on the nose, extremities, and mucous membranes like within GI tract Most common is on the hard palate Can cause a B cell lymphoma (primary effusion lymphoma) Arise from primitive mesenchymal cells Causes proliferation of vascular Through dysregulation of VEGF Endemic in africa Old russian men get it Kaposi's lesions can look like bacillary angiomatosis from cat scratch fever (bartonella) Have to examine microscopically

Most commonly involoved artery in MI

LAD -septal rupture -holosystolic murmur

Leukocyte adhesion deficiency

LAD Absence of CD18 (necessary to form integrins) Persistent leukocytosis because they cannot migrate into tissue Autosomal recessive Recurrent bacterial infection -Particularly skin and mucosa -skin abcesses, otitis media, peridontitis -most patients have lost all teeth by adult hood Poor wound healing -delayed separation of the umbilical cord

Septic abortion

Leads to staph infections or gram - bacilli RF -pregnancy termination with retained products of conception

Common varied immunoglobulin defeciency

Low but not absent IgG Low levels of mature B cells Plasma cell differentiation is impaired Appears typically in early adulthood

CNS metastasis

Lung > breast > melanoma Nodular solid ring enhancing tumors Multiple Area of central necrosis Edema

Selegiline

MAO-B inhibitor (selectively metabolizes dopamine)

Topoisomerase II

Makes double stranded DNA breaks to relieve both negative and positive supercoiling

Plasmodium spp.

Malariae: Quartan fever cycle fever occurs on day 1, then 72 hours later on day 4 Vivax and Ovale: produce dormant hypnozoites hide in liver Tertian fever cycle fever on first day, then 48 hours later on day 3 Falciparum: Irregular fever patterns Cerebral malaria occlude vessels leading to kidney and lungs parasitized RBCs occlude arteries banana shaped Diagnosis: blood smear with giemsa stain Treatment: -quine's -Chloroquine Blocks plasmodium heme polymerase -Primaquine (added to prevent disease relapse G6PD deficiency is contraindication BUT they are all resistant in african areas SO use -Mefloquine prophylactic medication -Atovaquone -Proguanil can be used for travelers in chloroquine resistant countries Severe infections (usually from falciparum) -Artemisinins -Sickle cell is protective -Diniquine cinchonism and tinitis Anopheles mosquitoes carry sporozoites sporozoites travel to the liver and mature to trophozoites Rupture of hepatocyte and release of merozoites that infect RBCs -Ring form of immature schizont in RBC -After merozoite infects RBCs it can form gametocyte

Pyloric stenosis

Males more than females PW -projectile non-bileous vomiting after eating Hypertrophy of pyloric sphincter

Angiosarcoma

Malignant neoplasm of hepatic vascular endothelial cells -also occurs in head and neck express CD31 can cause life threatening hemorrhage RF -arsenic -vaporized PVC polyvinyl chloride

Maculopapular rash that starts on face and moves downwards

Measles (Rubella) German measles (rubella)

Enterobacter spp.

Multidrug resistance Nosocomial infections Cause pneumonia and UTIs Ferment lactose Enterodactyl! Motile

Serratia marcescens

Multidrug resistance Nosocomial infections Cause pneumonia and UTIs Ferment lactose Does so very slowly so it can come up negative Tri-serratia-tops Motile red pigment -> shower stains

Klebsiella pneumoniae

Multidrug resistance Nosocomial infections Cause pneumonia and UTIs Ferment lactose Three A's : alcoholics, abscesses, aspiration Capsule (polysaccharide) Currant-jelly sputum Immotile Urease positive

Mesoderm

Muscles Connective tissue Bone Cartilage Serosal linings Peritoneum Cardiovascular system Lymphatic system Spleen Hemopoietic cells Kidney Ureters Internal genitalia Adrenal cortex

CK-MB

Myocardi-BUM Can be used to diagnose reinfarction due to relatively short time of rise and fall

Hypertrophic cardiomyopathy

Myocardial hypertrophy Thick-walled and hypercontractible Septum is REALLY big, can even block blood from leaving the left ventricle S4 heart sound Treatment -slowing down blood across obstruction is good thing, helps more get out -beta blockers (negative inotropes, decreasing ejection acceleration) -CCBs (prolonged diastole from AV node inhibition) -Surgical management of obstruction if possible Contraindicated -Non-dihydropyridines -vasodilators -ACE inhibitors -diuretics Diastolic failure Friedreich's ataxia HOCM is autosomal dominant Mutated proteins: -Beta myosin heavy chain -myosin-binding protein C -Troponin T Tangled, disorganized myofibrils -abhorrent organization -> abhorrent conduction Typically manifests during adolescent growth spurt Systolic anterior motion of mitral valve -one leaflet of mitral valve is open -> regurg Valsalva reduces preload and even tighter space for blood to squeeze through Leg lift (increase preload) -> blood back to heart -> bigger chamber -> more room for blood to get out of LV -> decrease murmur Increase afterload -> slower blood velocity across obstruction -> decreased murmur

Pauci-immune RPGN

NO immunoglobulin or complement deposition -most patient will show ANCA in their serum

Abacavir

NRTI used in HIV/AIDS Abacavir hypersensitivity reaction -strongly associated with HLA-B*57:01 allele -delayed type IV hypersensitivity reaction -fever -malaise -GI symptoms -delayed rash

Phenytoin

Narrow spectrum antiepileptic drug Prolongs inactivation of sodium channels Megaloblastic anemia Increase in PDGF -> gingival growth Hirsutism Inducer of CYP450

Hyponatremia

Nausea Vomiting Cerebral edema Seizures Coma CANT CORRECT TO QUICKLY Sodium demyelinating disease -> locked in syndrome (pontine demyelination)

Gout

Needle shaped urate crystals negatively birefringent yellow under polarized light acute flares resolve within a few weeks chronic disease with relapsing remitting pattern RF -hyperuricemia -increased break down of purines -under-excretion of uric acid is most common cause (under-excretion is idiopathic) -HGPRT (Lesch-Nyhan syndrome inborn error of metabolism) -Massive cell lysis -tumor lysis syndrome -loop diuretics -eating a lot of red meat -alcohol PW -great toe swelling -inflammation of joint -pannus -tophus formations (accumulations of crystals outside joints) Tx -allopurinol -colchicine

Sucralfate

Negatively charged sulfated polysaccharide complexed with aluminum hydroxide Aides in ulcer healing -binds positively charged protons and forms a physical barrier between acid and damaged mucosa -also inhibits pepsin in the presence of stomach acid -binds bile salts -neutralizes acid

Acute lymphoblastic leukemia

Neoplastic lymphoid cells arise in the bone marrow -> cells leak into peripheral circulation (as opposed to lymphoid cells that form OUTSIDE bone marrow) Most common cancer in children -peak incidence 2-5 years Which precursor is mutated determines the type B cell ALL most common T-cell ALL usually occurs in male teenagers between 15-20 -usually presents with mediastinal mass (SVC syndrome possible LymphoBLASTS on peripheral smear PAS stain -> glycogen in membrane TdT positive (present in all immature lymphocytes, myeloblasts are negative) - TdT is required for VDJ recombination in developing lymphocytes Risk factors: -Downs syndrome Diagnosis of acute lymphoblastic LEUKEMIA -greater than 25% blasts in the bone marrow +/- lymphoid mass (common manifestation in b cell ALL Diagnosis of acute lymphoblastic LYMPHOMA -greater than 25% blasts in the bone marrow and presence of lymphoid mass (common manifestation of T-cell ALL) Clinical manifestation -fatigue -easy bruising or bleeding -fever (due to infection or leukemia itself) -leukocytosis Mets to CNS and testicles Chemotherapy and in some bone marrow transplant Good prognosis

Acetylcholinesterase inhibitors

Neostigmine (not common) (Quaternary - no BBB) Pyridostigmine - used for long term treatment (Q) Edrophonium (transient) (Q) Physostigmine (Tertiary -> crosses BBB) Organophosphates Galantamine -> used to treat Alzheimer's Rivastigmine-> used to treat Alzheimer's Donepezil -stigmine indirect acting cholinomimetics -increase acetylcholine at the synapse -boosts endogenous acetylcholine use Tx -myasthenia gravis -can reverse neuromuscular blockade (after anesthesia) -urinary retention AEs -

Post streptococcal glomerulonephritis

Nephritic syndrome After pharyngitis OR skin infection Immune complex deposition Subendothelial immune complex deposition Subepithelial humps Young kid with hematuria 1-3 weeks after skin or pharyngeal infection Leukocyte infiltration Adult onset is the worst prognostic factor, kidneys rarely recover

Wilms tumor

NephroBLASToma Commonly caused by loss of function mutations in WT1 or WT2 both on chromosome 11 Solitary, unilateral, encapsulated Asymptomatic abdominal mass is presentation mostly HTN due to excess renin producion Most are sporadic Hereditary WAGR and DENYS-DRASH -WT1 mutation or deletion -one hit already - WAGR = WILMS tumor, aniridia, genitourinary malformations, mental retardation -DD syndrome -> hypo genitalia Beckwith-Wiedemann syndrome -WT2 inherited mutation -Macroglossia -encephalocele

Diabetic nephropathy

Nephrotic syndrome due to non-enzymatic glycosylations Nodular glomerulosclerosis Kimmelsteil-Wilson nodules - pink round deposits in laminated mesangial matrix Obliterated capillaries with hylin deposition

Hirschprung's disease

Neural crest cells fail to migrate Congenital megacolon Loss of innervation to colon Always involved rectum

Neural crest

Neural ganglia adrenal medulla Schwann cells Pia mater Arachnoid mater Aorticopulmonary septum Endocardial cushion Branchial arches (bone and cartilage) Skull bones Melanocytes

Carcinoid tumors

Neuroendocrine tumors Ileum is most common site Most common malignancy of the appendix Bronchial carcinoid tumors -most common primary lung tumor in kids Most are asymptomatic PW: -appendicitis -small bowel obstruction -vascular telangectasia -secretory diarrhea -Affects right side of heart Give Beta-2 agonist to carcinoid patient (because you think its asthma) -> severe hypotension Diagnosed with 5-HIAA urinalysis -breakdown product of serotonin Treat -surgical excision -octreotide for symptomatic relief

Conversion disorder

Neurologic symptoms incompatible with any known disorder, often associated with acute onset of stress

Dystonia

Neurological movement disorder characterized by sustained, involuntary muscle contractions

Norepinepherine

Neurotransmitter vasoconstriction -> increased MAP and BP -> reflexive bradycardia Tx -septic shock

Zaleplon

Non-habit forming sleeping aid bind GABA-A receptor at benzo site short duration of action metabolized rapidly by CYP450 system good in inducing sleep, may not be good at maintaining less likely to cause tolerance physical dependence is less less withdrawal symptoms serum half life may be extended in adults AEs -cognitive deficits -falls and fractures -impaired performance of daily living tasks -DONT MIX with antihistamines, benzos, or barbs Rescue with flumazenil

Renal tubular acidosis type I

Normal anion gap acidosis (distal RTA) Caused by dysfunctional H+ ATPase within intercalated cells -doesn't bind with ammonia to make ammonium -> LOW urine ammonium -basic pH in urine Hypokalemia -K+ is excreted instead of H+ Calcium phosphate stones -metabolic acidosis -> increased bone resorption -> increased calcium in serum -> in urine -> stones Urine citrate is low -getting used up binding serum acid Causes -autoimmune (RA or sjogren's syndrome) -hypercalciuria -lithium -amphotericin B

Renal tubular acidosis type II

Normal anion gap acidosis Proximal RTA Bicarb is usually reabsorbed at the PCT -carbonic anhydrase is important DECREASED bicarb reabsorption in PCT -wasting in urine -metabolic acidosis -self limitied (serum and bicarb stabilize -> rest of tubule can eventually make up at a lower level of bicarb) hypokalemia (excessive bicarb binds sodium -> collecting duct -> sodium exchanged for potassium) Fanconi syndrome -MM -cysplatin -expired tetracyclins -acetazolamide therapy

Hepatic encephalopathy

Normal glutamate-glutamine cycle is impaired due to hyperammonemia Astrocytes swell -> impaired release of glutamine (usually taken up by neurons and converted to NT glutamate) -> decreased glutamate in neurons -> disruption of excitatory neurotransmission and encephalopathy results

Rickettsia spp.

Obligate intracellular Can't make CoA or NAD+ Coccobacillary shape (weakly gram -) Weil-felix test - tests for rickettsia species Headache and fever on early infection VASCULITIS with possible associated rash Treatment: Doxycycline

Rickettsia prowazekii

Obligate intracellular Poor gram staining Requires NAD+ and CoA Treatment: doxycycline Rash: STARTS IN MIDDLE -> moves OUTWARDS LICE spread prowazekii Causes epidemic typhus Causes pneumonia Encephalitis Very serious infections can cause coma

Basophilic stippling

Occurs due to build up of ribosomes due to an inability to degrade RNA Causes -Lead poisoning inhibits erythrocyte 5' nucleotidase -Thalassmia's -myelodysplastic syndrome Blue punctate dots in the cytoplasm of RBCs

CMV esophagitis

Occurs in IMMUNOCOMPROMISED PW -odynophagia or dysphagia -endoscopy shows linear and shallow ulcerations in the lower esophagus that sometimes diffusely involve the esophagus -Tissue biopsy shows enlarged cells with basophilic or eosinophilic intranuclear inclusion bodies

Uric acid crystal precipitation

Occurs in the collecting tubule due to low urine pH

Effect modification

Occurs when the effect of an exposure on an outcome is modified by another variable -can be identified using stratified analysis, as the different strata will have different measures of association

Somatostatin

Octreotide is synthetic analog Slows GI motility Stops -GH secretion -Gastrin secretion -Insulin secretion -glucagon secretion Tx -gastric adenoma -Pituitary GH adenoma -Gigantism -Acromegaly -VIPoma -Carcinoid syndrome (ileal tumor with hepatic metastasis) -insulinoma -glucagonoma AEs -nasuea -vomiting -abdominal pain -steatorrhea -gallstones -> acute cholecystitis

Blastomyces dermatitidis

Ohio river valley Great lakes East coast Dimorphic fungi yeast in the heat mold in the cold Broad based budding Majority are subclinical CXR: patchy infiltrate with lesions or cavities In Immunocompromised: systemic infection to skin and bone KOH wet stain Urine antigen test Azoles for local infections Itraconazole Systemic: amphotericin B

Hemrrhoids

Older patients Opiods Columnar above (endoderm, autonomic innervation from inferior hypogastric plexus -> no pain) -goes to portal vein -internal hemorrhoids (blood seen on stool during bowel movement) Squamous below(ectoderm, somatic innervation from inferior rectal nerve -> pain) -goes to internal iliac vein -external hemorrhoids

Fish Oil

Omega-3 fatty acids Lowers triglycerides by decreaseding VLDL and apoB production

Vitalline duct

Omphalomesenteric duct -> connects ileum to yolk sac during fetal life Supposed to degenerate can form meckel's diverticulum

Mumps

Orchitis (unilateral) Parotitis (mumps replicates in the parotid glands) rarely associated with morbilliform rash VF: Hemagglutinin Fusion protein Neuraminidase

Phenylketonuria

PKU Autosomal recessive PW -intellectual disability -gait or posture abnormality -eczema -musty body odor Caused by mutation in phenylalanine hydroxylase -build up of phenylalanine causes toxicity to cells

Omenprazole

PPI -lansoprazole, rabeprazole -directly inhibit gastric secretion by blocking H+ ATPase Treat -GERD first line -peptic and duodenal ulcers first line AE -increased risk of c diff infections -decreased Ca++, Mg++, and Fe++ absorption

Illeus

Paralytic or adynamic illeus

Secondary adrenal insufficiency

Pituitary isn't secreting ACTH Low cortisol preserved mineralocorticoid function (renin axis)

Megaloblastic Anemia

Result of DNA/RNA asynchrony -DNA maturation and cell division is delayed, while RNA translation and protein production continues -cytoplasmic region of cell continues to grow -nuclear portion lags behind in growth, can't divide either Bone marrow is hypercellular -> abnormal RBCs undergo apoptosis or phagocytosis in the bone marrow -> fewer RBCs in circulation -> megaloblasts and anemia -unusually low reticulocyte count, because problem is in the bone marrow itself Megaloblasts -seen in bone marrow aspirate -large oval cells with abundant basophilic cytoplasm -nucleus contains lacy chromatin hypersegmented neutrophils (more than 5 lobes) -all cell lines are messed up from impaired DNA formation Folate deficiency -Vitamin B9 -dark leaf vegetables -Dietary folate -> dihydrofolate -> tetrahydrofolate (DHFReductase) -> methyl groups added to tetrahydrofolate -> purine and pyrimidine synthesis -in deficiency, DNA synthesis comes to a halt -liver stores of folate can last for months -Risk factors -Drinking only goats milk (has low folate) -short gut syndrome -alcoholism (extra fast because it spoils liver stores) -Glossitis (sore, swollen tongue) -MTHFR (methyl-tetrahydrofolate reductase), removes one carbon from tetrahydrofolate, and donates to homocysteine, making methionine -Homocysteine builds up in blood -Folate cycle is how your body ships methyls around Vitamin B12 deficiency (cobalamin) -liver holds 1000 day supply of B12 -needs intrinsic factor -absorbed in ileum -coenzyme that aides in methyltransferase reaciont -presents like folate deficiency -can't convert homocysteine to methionine -Folate can't re-enter the cycle -> no more purine and pyrimidine synthesis -Also important cofactor for methylmalonyl CoA mutase (MethylMalonic Acid -> succinyl CoA) -fatty acid breakdown results in production of MMA -Risk factors -vegan diet -alcoholics with poor nutrition -achlorhydria (no acid, no activated pepsin, vitamin B12 trapped in food) -pernicious anemia (no intrinsic factor, no absorption) -Crohn's disease -Diphyllobothrium latum tapeworm from fish -causes demylination -subacute combined degeneration -> injury to both dorsal and lateral columns due to demylination -degeneration of motor pathways in the lateral pyramidal tracts (weakness and paralysis) -avoid treating vitamin B12 deficiency with folate (corrects anemia, but can worse neurological symptoms) High homocysteine levels are associated with a hypercoagulable state (cardiovascular, cerebrovascular disease)

Erythema multiforme

Target lesions Associated with herpes simplex infection can involve oral mucosa caused by sulfas mycoplasm infection Immune cell-mediated attack involves palms and soles

Intussusception

Telescoping of bowel most common in young children surgical emergency (impaired venous return -> ischemic necrosis of bowel) Ileocolic junction is most common point -RLQ mass Currant jelly stools (blood and mucus)

Hernias

Weakening of fibromuscular tissue Congenital or acquired (surgery, elevation in intra abdominal pressure -> weight lifting etc) RF -age -weight lifting -pregnancies -surgery incarcerated hernia -ischemia -venous and lymphatic impaired drainage -> pressure -> ischemia -bowel necrosis -> perforation -> sepsis\ Direct -goes directly through hesselbach triangle -MEDIAL to inferior epigastric vessels Indirect -goes indirectly the inguinal canal -lateral to inferior epigastric vessels -most are due to congenital defect in processus vaginalis -covered by all layers

Tubular carcinoma of breast

Well formed tubules infiltrating the stroma

Secretin paradoxically stimulating gastrin release

Zollinger-Ellison syndrome

Creatinine clearance rate

[(Urine creatinine) x (Volume)] / (Plasma creatinine)

p-ANCA

anti-myeloperoxidase (perinuclear)

c-ANCA

anti-proteinase-3

Passive aggression

avoiding conflict by expressing hostility covertly

Acanthosis

epidermal thickening elongated rete ridges

gp41

facilitates HIV fusion

Pilocarpine

increases salivary secretion causes contraction of ciliary body -> stimulates outflow of humor also activates sphincter pupillae muscle -> miosis and reduced pressure Tx -glaucoma

TNF-alpha

most important mediator of sepsis

Courvoisier sign

non-tender, palpable gallbladder sign of cancer

Varicose veins

predispose to skin ulcers

Lens of the eye

type IV collagen

Child social development 3-5 years

"Forget, they're still" Freedom - comfortably spends part of day away from mother (3 years) Friends - cooperative play, has imaginary friends (4 years)

Child verbal/cognitive development 3-5 years

"Learning" Language - 1000 words (3 zeros by age 3) -uses complete sentences and prepositions (4 years) Legends - can tell detailed stories (4 years)

Child verbal/cognitive development 0-12 months

"Observing" Orients - first to voice (4 months) -> then to name and gestures (9 months) Object permanence (9 months) Oratory - says "mama" and "dada" (10 months)

Child motor development 0-12 months

"Parents" -Primitive reflexes disappear -Moro (by 3 months) -Rooting (by 4 months) -Babinski (by 1 year) -Posture -> lifts head up prone (1 month) -> rolls and sits (by 6 months) -> crawls (by 8 months) -> stands (by 10 months) -> walks (1 year to 1.5 years) -Picks ->passes toys from hand to hand (6 months) -> Pincer grasp (10 months) -Points to objects (12 months)

Child social development 12-36 months

"Rearing" Recreation - parallel play (24-36 months) Rapprochement - moves away from and returns to mother (24 months) Realization - core gender identity formed (36 months)

Child social development 0-12 months

"Start" Social smile (2 months) Stranger anxiety (6 months) Separation anxiety (9 months)

Child verbal/cognitive development 12-36 months

"Working" Age 2 - two word sentences -50-200 word vocabulary Age 3 - three word sentences

basal cell carcinoma

"pearly papules" waxy appearance and rolled edges with central depression and ulceration clusters of dark basal cell like tumor cells with palisading nuclei at the periphery` "superficial multicentric"

4-12 hours post MI

"wavy fibers" (non-contractile muscle fibers being pulled by adjacent contractile fibers Might see VERY early signs of coagulation necrosis

Cushing's Syndrome

-> fat redistribution -> thin skin -> obesity -> insulin resistance -hypertension -central muscel weakness -striae, especially over areas of weight gain -skinny arms and legs -central obesity -OSTEOPOROSIS -immunosuppresion -impaired wound healing -neutrophil excess Exogenous glucocorticoids is most common cause Small cell carcinoma of the lung Dx -late night salivary cortisol - should be low -early morning cortisol -dexamethasone suppression rest, low does to suppress physiologic hypercortisolism, but not tumors secreting, HIGH does will suppress pituitary adenoma, but a lung SCC will not be suppressed Tx -mifopristone -metyrapone -mitotane Bilateral adrenectomy -> nelsons syndrome -> drop in cortisol makes pituitary freak out -> mass effect from growth

First-generation antipsychotics

-azine suffix Treats: Schizophrenia -good with positive symptoms, not so good with negative Acute psychosis Acute agitation and aggression (haloperidol) Lipophilic -> extended serum half life -> large volume of distribution (trifluoperazine, fluphenazine, chlorpromazine, thioridazine) -lower potency - antimuscarinic and antihistaminergic activity as well -> atropine symptoms Haloperidol -high potency -treats acute psychosis in bipolar disorder Extrapyramidal symptoms

Sertoli-leydig

-benign or malignant -occur at any age -produce androgens -> hirsutism -tubular structures lined by round sertoli cells

Fluoroquinolones

-floxacin Levofloxacin Ciprofloxacin Moxifloxacin Inhibits bacterial topoisomerase -DNA gyrase bacteriocidal divalent and trivalent cations decrease absorption Tx -good gram negative coverage -UTIs (especially pseudomonas) -gastrointestinal pathogens -empiric treatment for pyelonephritis -Shigella -Salmonella (and its osteomylitis) -E. coli -Campylobacter -Bacillus anthracis -community acquired pnemonia -walking pnemonia AEs -prolonged QT -Torsades -tendon and cartilage damage in the elderly -teratogenic

Leukotriene blockers

-kast suffix Montelukast, zafirlukast -LTD4 inhibitors -orally taken

Beta blockers

-lol suffix Non-selecitve Propanolol Beta-1 selective Metoprolol Atenolol Betaxolol Esmolol Acebutolo Beta with some alpha blocking Carvidilol Labedalol -> Hypertensive emergency Partial beta blocking Pindalol Acetbutalol MOA -antagonizes beta-1 receptors in heart -decrease cardiac contractility -decreased activity at AV node -> heart block -decreases cardiac oxygen consumption -inhibits renin secretion from JGA (has beta-1 receptors) Tx -chronic stable angina -acute MI -chronic heart failure (NOT ACUTE) -PREVENTS CARDIAC REMODELING ->life extending treatment -HOCM -migraines -graves disease -glaucoma AEs -heart block -bradyarrythmias -exacerbate asthma and COPD -impotence

Protease inhibitors

-navir suffix Indinavir -nephrolithiasis HIV needs proteases to cleave gene products POL gene codes for proteases -resistance comes from this modification never used as monotherapy, resistance can form quickely not phosphorylated Tx - AEs -hyperglycemia -dislipidemia -lipodystrophy

Vemurafenib

-nib suffix = small molecule kinase inhibitor BRAF inhibitor Tx -V600E BRAF positive melanoma

Sorafenib

-nib suffix = small molecule kinase inhibitor -tyrosine kinase inhibitor inhibits VEGFR Tx -renal cell -hepatocellular AEs -hyperkeratosis -rashes -increased risk of hemorrhage

Theco-fibromas

-present in perimenopausal women -MEIGS syndrome -> ascites, pleural effusion, ovarian tumor -abundant yellow filled cytoplasm

ACE inhibitors

-pril suffix Block conversion of angiotensinogen I to II, blocking release of aldosterone -> lowering BP Reduce long term progression of heart failure Prolong survivability reduce remodeling (angiotensin II is main mediator)a Tx -HTN -heart failure (especially with diabetes) -acute MI -slow progression of diabetic nephropathy -albuminuria and high blood pressure AEs -creatinine bump -COUGH -contraindicated in hereditary angioedema -teratogenic -contraindicated in CKD -NSAID use -hyperkalemia

Granulosa-theca tumors

-produce estrogen -precocious puberty -unopposed estrongen -> endometrial hyperplasia and increased risk for tumor formation -INHIBIN -tumor marker for these cells -Call-exner bodies -> cuboidal cells -> rosette pattern, eosinophilic center -> coffee bean nuclei -appear yellow on histology due to lipid content -favorable survival rates, technically malignant though

Sunitinib

-tinib suffix = small molecule tyrosine kinase inhibitor inhibits VEGFR Tx -renal cell -GIST AEs -hyperkeratosis -rashes -increased risk of hemorrhage

Imatinib

-tinib suffix = small molecule tyrosine kinase inhibitor BCR-ABL in CML is blocked -has tyrosine kinase domain blocks c-kit too Tx -CML -GIST AEs -fluid retention -ankle and periorbital edema

Erlotinib

-tinib suffix = small molecule tyrosine kinase inhibitor EGFR -blocks the tyrosine kinase domain here Tx -non-small cell lung cancer AEs -papulopustular acneiform -diarrhea

Vasopressin receptor antagonists

-vaptans Conivaptan Tolvaptan ADH can't put aquaporins in luminal membrane Can't correct sodium too fast -> demyelination Tx -SIADH

Pneumoconioses

1-5 micron sized particles are engulfed by alveolar macrophage Coal worker's pneumoconiosis Silicosis -Silicon nodules form in the upper lung fields -weakly birefringent under polarized light -cystically dilated airways -top down involvement -concentric nodules -become more susceptible to TB Asbestosis -mesothelioma -found in insulation in old buildings -slow progressive diffuse pulmonary fibrosis -pleural plaque formation at bases (benign, does not lead to mesothelioma)

Herniations

1. subfalcine herniation -under the falx cerebri line -compresses ACA -> contralateral loss of motor and sensory function 2. transtentorial herniation -brainstem moves down past the tentorium cerebelli 3. Uncul herniation -medial temporal lobe herniates down -CN III compressed -> down and out pupil due to IV and VI working alone -> parasympathetic fibers compressed -> unopposed sympathetic -> blown pupil -can also compress PCA -> contralateral homonymous hemianopsia with macular sparing -> compresses contralateral cerebral peduncle next -> hemiparesis of ipsilateral side 4. Tonsillar herniation -compression of brainstem structures -> cardiorespiratory arrest Tx -sit the patient up, gravity helps drain CSF -Hyperventilation -> PCO2 is vasodilator, lowering PCO2 causes vasoconstriction and lowers ICP (only works acutely as brain adapts) -Mannitol pulls water out of intracellular space

Lewy body dementia

1/4 cases of dementia more common in males Lewy bodies -round, eosinophilic cytoplasmic inclusions composed of alpha-synuclein pw -decline in cognitive function

Neurons post-infarction timeline

12-24 hours following infarction -neurons develop vacuolated, eosinophilic cytoplasm as nuclei shrink and break apart (karyorrhexis) -appearance of "red neurons" ~24 hours -> neutrophils show up in injured paranchema -> inflammation, degradation, and phagocytosis of cellular debris -> DNAses, proteinases 1 week -astrocytes start to proliferate to and provide structural support surrounding the area of liquefactive necrosis (reactive gliosis) -form new blood vessels at the periphery of lesion -glial scar is the final form

Ischemic stroke

12-24 hours: "red neurons", eosinophilic cytoplasm, pyknotic nuclei, loss of nissel substance 24-72: Neutrophilic infiltration 3-7 days: Macrophage/microglia infiltration, phagocytosis begins 1-2 weeks: Reactive gliosis, vascular proliferation around necrotic area >2 weeks: glial scar formation

Antihistamines

1st gen: Chlorpheniramine hydroxyzine meclizine promethazine -block H1 -lipophilic -easily cross blood brain barrier -antagonize many different types of receptors -peripheral and central muscarinic receptors -treat extrapyramidal effects of antipsychotics -serotonin receptors in the CNS -> stimulate appetite and weight gain -alpha 1 receptors -side effects -drowsiness -dizziness and hypotension -cognitive impairment in the elderly -treatment -motion sickness, -acute dystonia 2nd generation: Fexofenadine cetirizine loratidine -dont cross BBB -not as much antagonism of other receptors, especially antimuscarenis

Chlorpheniramine

1st generation antihistamine

Osmolality and sodium disorders

2/3 of total body fluid is intracellular -potassiums dominates 1/3 is extracellular -25% of that is blood plasma -75% is interstitial (lymph) -sodium dominates Estimate osmolality by multiplying Na+ by 2 2xNa+ + [glucose]\18 + [BUN]/2.8 Normal is ~290 Secretory diarrhea -loss of isotonic fluid -hypovolemic -extracellular volume loss -hypovolemic euronatremia -body tries to conserve volume Too much IV fluids -extravascular compartment expands -hypervolemic normonatrimic Diuretics (or hypoaldosteronism) -hypovolemia -hyponatremia -ADH release to save more water -> loss of sodium greater than loss of water -fluid shift towards intracellular compartment SIADH -Hyponatremia -transient hypervolemia -> kidney compensation -> euvolemic CHF -> volume conservation -> release of ADH (cirrhosis and loss of albumin, nephrotic syndrome, can cause too) -more water gained than sodium -hyponatremia -hypervolemia -intracellular expansion MORE WATER LOSS THAN SODIUM NOW -> hypernatremia Vomiting, osmotic diarrhea, -loss of water greater than sodium -hypernatremia -Hypovolemic as water comes out of intracellular compartment Diabetes inspidus -resistance to or decreased ADH -water loss -> more concentrated -> hypernatremia -increased water intake leads to euvolemic hypernatremia Excess sodium conjugates given (like in antibiotics or some other therapy) -increased osmolality -hypervolemic hypernatremia Increased osmolality in the blood draws water from tissues -hyperglycemia in diabetes or DKA -hyperglycemia -> solution of serum sodium concentration -> falsely normal or low serum sodium level

Potassium disorders

3.5-5 mEq/L ~4 mEq/L Loop and thiazide diuretics -increase sodium delivery to the collecting duct -> exchanged for potassium -> hypokalemia Primary hyperaldosteronism Hypercortisolism Congenital adrenal hyperplasia Secondary hyperoldosteroism -CHF -Cirrhosis -Nephrotic syndrome RTA types 1 and 2 hypomagnesemia can inhibit potassium absorption Insulin Beta-2 agonists Hypokalemia -muscle weakness -decreased deep tendon reflexes -ascending paralysis -illius (sleepy lazy gut syndrome) -Inverted T waves on EKG -prominent U waves Hyperkalemia -Chronic kidney disease -> decreased potassium filtration -ACE inhibitors, ARBs -Spironolactone -amiloride and triemterine -Hypoaldosteronism (addison's, -Type IV RTA -rapid cell turnover -> intracellular potassium -insulin insufficiency (type 1 diabetes) -beta blockers -Acidosis (H+ exchanged for K+) -Super high T waves early on -QRS may start to widen (sine wave) -torsades -muscle weakness -reduced deep tendon reflex -ascending paralysis

Finasteride

5-alpha reductase inhibitor treats BPH treats prostate cancer (with leuprolide) can treat androgenic alopecia -these patients have increased 5-alpha reductase naturally

Papillary thyroid carcinoma

85% of all thyroid carcinomas Women:Men 3:1 MAPK signaling pathway Solitary or multifocal Early spread to cervical lymph nodes Form papillae Lack colloid or follicles Typically unencapsulated PSAMMOMA BODIES!! -dystrophic calcification -swirled eosinophilic appearance -50% of papillary carcinomas Orphan Annie's eyes RAS mutation

t(1/2)

= (0.7 x Vd) / CL

Power of study

= 1 - beta (beta = probability of concluding that there is no difference) ability to detect a difference between two groups when such a difference actually exists

Attributable risk percent in the exposed

= 100 x [(risk in exposed - risk in unexposed)/risk in exposed]

NPV

= TN / (TN + FN) true negatives / everyone who tested negative

PPV

= TP / (TP + FP) true positives / everyone who tested positive

Cardiac output

= rate of oxygen consumption / arteriovenous oxygen consumption difference

Prostate cancer

A lot of people have them don't really kill a lot of people die with them, not of them posterior lobe peripheral zone -very convenient for palpation PSA can be used for monitoring of recurrance

Sympathetic adrenergic receptors

A1 -Gq, IP3/DAG -increases peripheral arterial resistance -> increased MAP -increases constriction of venous system -> increased venous return -activation of pupillary dilator muscle -> mydriasis -urinary sphincter and prostatic smooth muscle contraction -> urinary retention A2 -Gi -> reduced cAMP -sympathoLYTICS -reduce BP -role in local negative feedback -decreases insulin release -decreases lipolysis -work on ciliary body -> decrease aqueous humor production -brimonidine -> treats glaucoma B1 -Gs -> increased cAMP -increases intracellular calcium in SA node, increasing activity and heart rate -JGA cells -> release renin -> increase BP B2 -Gs -> increased cAMP -> protein kinase A -bronchial smooth muscle cells -> bronchodilation -vasoDILATION -> decreases SVR (will have compensatory tachycardia) -increased lipolysis (on adipocytes) -increased gluconeogenesis by the liver -increased insulin secretion (on pancreatic beta cells) -> hypokalemia -increased aqueous humor production (on

Paroxysmal nocturnal hemoglobinuria

ACQUIRED mutation in the PIGA gene on X chromosome PIGA gene codes for first step in production of GPI anchor protein (holds other proteins to cell surface) -lose CD55 and CD59 -> complement activation runs RAMPANT -> RBCs get effed Pancytopenia Dark urine in the morning -mild respiratory acidosis during slow breathing during sleep (normal process but in PNH is sufficient to initiate complement activation Increased risk of large vein thrombosis Diagnose with flow cytometry looking for deficiency in CD55 and CD 59

Peutz-Jeghers syndrome

AD mutation in tumor suppressor gene) multiple non-neoplastic hamartomatous polyps throughout the GI system) Hyperpigmentation of mucocutaneous surfaces

Pneumocystis jirovecii

AIDS patients respiratory transmission asymptomatic in healthy individuals AIDS defining illness associated with CD4 count of <200 Diffuse interstitial pneumonia Not productive cough, no consolidation Ground glass appearance in lungs Bronchoalveolar lavage Silver stain that shows disc shaped yeast Prophylaxis at <200 CD4+ Treatment: (same as prophylaxis) -bactrim (trimethoprim and sulfamethoxazole) -Sulfa allergy? pentamidine

Subacute lymphocytic thyroiditis

AKA silent thyroiditis, painless thyroiditis Thought to be a transient variant form of Hashimoto's early phase has high anti-thyroid antibodies -> transient hyperthyroidism as cells lyse seen in postpartum women within a year of giving birth Some patients will develop chronic autoimmune thyroiditis years later (Hashimoto's)

Colon cancer sequence

APC inactivation -> hyperproliferative epithelium KRAS activation -> adenoma p53 inactivation -> adenocarcinoma

NRTIs

Abacavir -hypersensitivity reaction associated with HLA-B 57:01 allele Didanosine -dose dependent pancreatitis Emtricitabine Iamivudine -peripheral neuropathy -treats Hep B Stavudine -peripheral neuropathy -lipodystrophy Tenofovir -nucleotide -doesn't need phosphorylation to become active -treats hep B Zidovudine -Safe during pregnancy -nucleoside -myelosuppression -granulocytopenia -lipodystrophy Nucleosides or nucleotides some have -dine suffix Competitive inhibition of reverse transcriptase -inhibition of 3' to 5' phosphodiester formation -incorporte into growing strand and halt Many need to be phosphorylated to become active Tx -HIV AEs -mitochondrial toxicity -lactic acidosis

GP IIb/IIIa receptor blocker

Abciximab eptifibatide - short acting tirofiban - short acting Stop fibrinogen interacting with platelets to aggregate Can cause thrombocytopenia Increased bleeding time

Chronic lymphocytic leukemia

Abnormal proliferation of mature B lymphocytes in bone marrow Average age over 60 Follows indolent course Neoplastic cells exhibit increased expression of the proto-oncogene BCL2 (inhibits apoptosis -> promotes cell survival B-cell markers -CD 19 and higher -can express CD5, usually on T cells Presents with -asymptomatic usually with leukocytosis -smudge cell (fragile cells that collapse upon preperation of smear) -lymphadenopathy -hepatomegaly -splenomegaly -CLL can present as Small lymphocytic lymphoma (SLL) -hypogammaglobulinemia (usually IgA, IgG, IgM) -anemia -thrombocytopenia

Mycobacterium tuberculosis

Acid-fast Waxy, fatty acids (mycolic acid) carbol fuchsin stain 2-6 weeks for growth (lowenstein-jensen medium) Obligate aerobe Transmitted through respiratory droplets If it can't be cleared by immune system it resides in macrophages Glycolipids cause clumping of bacteria into serpentine shapes - CORD factor, makes it virulence Increased TNF-alpha to activate macrophages, this allows bacteria to remain walled off in granulomas Sulfatides: allows them to survive inside macrophages, prevent phagolysosome fusion and bacteria doesn't get exposed to lysozymes Ineffective lysosomes and phagosomes Progression of TB: Primary infection can have 3 outcomes 1) healed latent infection 2) systemic infection (miliary TB) 3) reactivation of TB 1) Primary -> lower or middle lobes of lung. healed lesions become fibrotic and calcified, along with hilar lymph nodes -> GHON complex!! Prolonged fever, most commonly in children, most resolve and become latent (TB skin test to test for latent infection) BCG vaccine can cause false positive PPD skin test Caseating granulomas, necrotic macrophages 2) Miliary TB -> fulminant multiorgan failure of immigrant Potentially lethal 3) reactivation of latent infection Most people don't reactivate 5-10% do immunosuppression usually causes, decrease of TNF-alpha secretion Reactivation in the upper lobes Night sweats, bloody cough, cough Many patients experience cachexia - wasting TNF alpha promotes wasting can involve skeletal system -> pott's disease, soft tissue lesions in bone (vertebral bodies) CNS -> meningitis or tuberculoma (cavitary lesion in brain) Treatment: RIPE Rifampin Isoniazid Pyrazinamide Ethambutol Prophylaxis -> Rifampin and Isoniazid for 9 months

DIC

Acquired coagulopathy Excessive clotting and bleeding Prolonged bleeding time Can be caused by sepsis -gram-negative sepsis (neisseria meningitidis, ect) is most common cause because bacterial proteins and lipopolysaccharides activate coagulation Can be caused by hypercoagulable conditions -obstetric complications -malignancy -trauma 'Platelet' type bleeding -petechiae -ecchymoses -mucocutaneous bleeding -oozing from IVs or arterial lines Can cause venous thrombi -most commonly in iliofemoral veins +/- pulmonary emboli Labs: -fibrin degregation products (D Dimer) -low levels on protein C and thrombin Treat: -FFP (vWF, coagulation factors, protein C) -Cryoprecipitate (fibrinogen) -thrombocytopenia? -> platelets -anemia? -> RBCs -For treating thrombosis, you have to be very careful -> may use heparin but monitoring is tough depending on underlying etiology, mortality is 40-80%

Antiphospholipid syndrome

Acquired thrombosis disorder Causes clots in both venous and arterial systems Autoantibodies against cardiolipin and other phospholipids/proteins -anticardiolipin antibodies cause false positive on VDLR Secondary antiphospholipid syndrome -can be due to SLE Lupus anticoagulant -promotes clotting in the body -inhibits clotting when tested in lab (how it got bad name) -aPTT prolonged Anti-beta2-glycoprotein -most strongly associated with actually developing antiphospholipid syndrome Antiphospholipid SYNDROME -presence of antiphospholipid antibodies is not enough to diagnose -have to have symptoms of thrombosis too -TIA -ischemic stroke -coronary arteries affected -can present with non-bacterial Thrombotic Endocarditis (thrombosis -> damage to valve endothelium -> activation of complement and platelets -> valve vegetations -can present with pregnancy-related ygen complications (miscarriages, severe preeclampsia, microthrombi in placenta impair nutrient and oxygen delivery to fetus

Sarcoidosis

Activated macrophages express 1-alpha-hydroxylase which convertes inactive to active vitamin D TH1 cells, IL-2, IFN-gamma Young african american female Multisystem granulomatous disease -non-caseating CD4+ helper T cells are activated Can cause anergy to type IV hypersensitivity reactions Granulomas contain giant multinucleated cells Schaumann bodies in granuloma -> purple spot Lung involvement -> granulomas can be found in interstitium, also in hilar and paratracheal lymphadenopathy (potato nodes) Present with -incedental -dry cough -progressive dyspnea -malaise -fever -anorexia -skin lesions present in a quarter of cases -> erythema nodosum (red raised painful nodes on anterior legs) can be painful -subcutaneous nodules that are painless (granulomas) -Lupus pernio violaceous rash on nose and cheeks

Calcitriol

Activates osteoblasts and clasts -overall bone turnover Activated vitamin D Tx -osteoporosis -psoriasis (topical)

Valproate

Acute mania (first-line) Maintenance therapy Can be combined with Lithium if either is not effective alone

Lithium

Acute mania and maintenance in bipolar MOA -inhibit signal transduction pathways (inositol triphosphate pathway and other protein kinase pathways) AE's -acute lithium toxicity -GI (vomiting ect -chronic -tremor -neurologic symptoms (confusion and ataxia) -reversible thyroid inhibition in most patients -> lithium induced hypothyroidism -Lithium induced diabetes insipidus -> frequent nighttime voiding Cleared renally (exclusively) -thiazides cause increased lithium -NSAIDs cause increased lithium Teratogenic Atrialization of the right ventricle -> Ebstein's anomaly (ASD and malformed tricuspid) -> later in childhood present with fatigue and avoidance of outside activities Diagnose: Tricuspid regurg on ECHO

Tubulointerstitial nephritis

Acute renal interstitial inflammation Causative agents -Furosemide -penicillins -cephalosporins -Sulfonamides Drug induced tubulointerstitial nephritis can be type 1 hypersensitivity mediated -Also type IV

Mitral stenosis

Acute rheumatic fever Annular calcification (incidental finding of aging)

Parotits

Acute viral or bacterial infection of the parotid gland Staph Risk factors: dehydration intubation medications that decrease salivary flow (anticholinergics) Presents: Swelling that extends to the mandible trismus dysphagia fever chills increased amylase

Vitamin A overdose

Acute: Nausea Vomiting Vertigo Blurred vision Chronic: Alopecia Dry skin Hyperlipidemia hepatotoxicity hepatosplenomegaly visual difficulties Teratogenic: Microcephaly Cardiac anomalies Fetal death

Rheumatoid arthritis

Affects PIP, MCP, MTP SPARES DIP Cervical spine involvement Positive rheumatoid factor and anti-CCP antibody systemic inflammation pathenogenesis -not well understood -may involve increased citrulline production from stimulated macrophages -> antigen presentation and activation of CD4+ cells -> infiltrate joints -common finding is anti-cyclic citrullinated peptide antibodies Pan RF -female -HLA DR-4 PW -Rheumatoid factor (IgM antibody) -> deposits in joint tissue (type III reaction) -neutrophils in joint space -pannus formation (hyperplasia and degranulation tissue formation inside rheumatoid joints -> can get so bad it fuses joints together -SYMMETRIC pain -worse in the morning -improves with movement -swan-neck deformity of fingers -subluxation of joint -ankylosis (fusion) of neck joints -rheumatoid nodules on skin (can appear in lungs too) -Anti-nuclear antibodies (not specific) -elevated ESR and CRP in active disease3 Can lead to -interstitial fibrosis -rare granulocytosis Tx -glucocorticoids -methotrexate

Multiple myeloma

Age 70 Plasma cells infiltrate multiple sites throughout the skeletal system IgG 70% SPEP -single narrow peak in gamma globulin region (M spike) Produce lots of free light chains -smaller, secreted in urine -Bence Jones proteins Can cause amyloidosis -eosinophilic deposits -apple green birefringence congo red stain Histology -lots of RER due to secreted proteins Presents with: -lytic lesions throughout skeletal system -back pain due to vertebral fractures -punched out lesions on x rays (imbalance of osteoclast to osteoblast activity, thought to be) -normocytic normochromic anemia due to tumor replacement by tumor cells -fatigue, pallor -neoplastic cells decrease production of normal antibodies -> recurrent infections -Kidney injury (bence jones proteins bind uromodulin in urine -> precipitate as dense casts -> obstruct renal tubules) -Fanconi syndrome (type 2 renal acidosis) -hypercalcemia -> deposits in kidney -patchy neural involvement Particularly susceptible to proteasome inhibitors Predisposed by MGUS -monoclonal gammaglobintosis of unknown significant predisposed by solitary plasmacytoma

Pneumothorax

Air gets into the pleural space -loss of negative intrapleural pressure Sharp pain provoked by deep inspiration Spontaneous primary pneumothorax -> tall thin guy in 20's (smoker Secondary spontaneous pneumothorax -COPD, empysema -apical subpleural blebs -parenchymal destruction from metastasis -airway pressure from mechanical ventilation -improper catheter insertion -hyperresonance on percussion Tension pneumothorax -flap like tear that lets air enter but not exit -compression of mediastinal structures -deviation of trachea AWAY from affected side -requires immediate needle decompression (midclavicular 2nd intercostal space) Dullness to percussion on affected side: Hemothorax -ruptured intrathoracic aneurysm Chylothorax -fluid is rich in triglycerides -form supernatant in test tube after refridgeration -blockage of thoracic duct

Dentate line

Aka pectinate line Columnar above (endoderm, autonomic innervation from inferior hypogastric plexus -> no pain) -goes to portal vein -internal hemorrhoids (blood seen on stool during bowel movement) Squamous below(ectoderm, somatic innervation from inferior rectal nerve -> pain) -goes to internal iliac vein -external hemorrhoids

Hereditary fructose intolerance

Aldolase B deficiency Fructose-1-phosphate builds up, toxic to cell

Patent urachus

Allantois remnant connects bladder to umbilicus presents with urine discharge from the umbilicus

Disease-modifying antirheumatic drugs (DMARDs)

Allieviate pain and swelling and long term joint necrosis Methotrexate (first line) Sulfasalazine hydroxychloroquine minocycline TNF-alpha inhibitors Typically take weeks to work, prednisone for fast relief

Alpha 1 antitrypsin deficiency

Alpha 1 antitrypsin secreted by liver usually inhibits neutrophil elastase in lungs Without it neutrophil elastase is uninhibited and cleaves elastin in the lungs -> increased compliance and emphysema Liver damage from accumulated misfolded alpha 1 antitrypsin

phenoxybenzamine

Alpha-1 and alpha-2 IRREVERSIBLE antagonist COVALENTLY binds Tx -cocaine toxicity -pheochromocytoma -tyramine hypertension AEs -Orthostatic hypotension -reflex tachycardia

phentolamine

Alpha-1 and alpha-2 REVERSIBLE antagonist causes vasodilation Tx -cocaine toxicity -pheochromocytoma -tyramine hypertension AEs -Orthostatic hypotension -reflex tachycardia

prazosin

Alpha-1 antagonist Tx -BPH AEs -Orthostatic hypotension -reflex tachycardia

alpha methyldopa

Alpha-2 agonist Alpha 2 -> Gi Sympatholytic CNS affect -> decrease sympathetic tone Safe in pregnancy Tx -hypertension -hypertensive emergency -ADHD (refractory to stimulants) -Tourette's AEs -lupus like syndromew

Clonidine

Alpha-2 agonist Alpha 2 -> Gi Sympatholytic CNS affect -> decrease sympathetic tone Tx -hypertension -hypertensive emergency -ADHD (refractory to stimulants) -Tourette's AEs

tizanadine

Alpha-2 agonist muscle relaxant

mirtazapine

Alpha-2 antagonist -effects at other receptors too atypical antidepressant Tx -depression AEs -Orthostatic hypotension -reflex tachycardia -BPH

Entacapone

Also Tolcapone (works in periphery and CNS) COMT inhibitor in periphery -blocks inactivation of L-DOPA -more effective L-DOPA treatment AEs -hepatic failure

Tissue plasminogen activator

Alteplase, reteplase, tenecteplase Naturally released by endothelial cells to curb thrombus formation Enhance plasminogen -> plasmin -> cleaves fibritic clot

Metronidazole

Anaerobe coverage intra-abdominal infection Free radicals damage bacterial DNA -bactericidal Tx -Entamoeba histolytica -Giardia -Trichomonas (treat both patient and partner) -Gardnerella -can be substituted for amoxicillin in helicobacter triple therapy -C diff pseudomembranous colitis AEs -ingestion of alcohol results in disulfiram-like reaction

Clindamycin

Anaerobic coverage binds to 50S subunit, inhibiting translocation excellent penetration into abcesss Tx -staph -strep -group A strep -soft tissue infections -MRSA -Bacteroides fragilis -clostridium perferingens -severe inflammatory acne (topical) -polymicrobial female genital tract infections -gentamicin paired with clindamycin for broad coverage -Garderella vaginosis infections AEs -diarrhea -C. Diff infections

Polygenic inheritance

Androgenetic alopecia Epilepsy Glaucoma Hypertension Ischemic heart disease Schizophrenia Type 2 diabetes

Surface ectoderm

Anterior pituitary Lens Cornea Inner ear sensory organs olfactory epithelium Nasal and oral epithelial linings salivary glands Epidermis, sweat, and mammary glands

Axillary nerve injury

Anterior shoulder dislocations

Goodpasture's disease

Anti-GBM antibodies Involvement of pulmonary capillary bed lead to hemoptysis Linear pattern on immunofluorescence (antibodies binding as much of GBM as it can)

Resistance to orthomyxovirus

Antibodies to hemagglutinin is most important

Vomiting

Area postrema in the fourth ventricle is chemoreceptor trigger zone -outside BBB -contains D2 receptors -metoclopramide is a D2 antagonist -also NK1 (neurokinin1) Area postrema projects to the NTS (nucleus tractus solitarius) -> other medullary nuclei to coordinate the vomiting process 5 major receptors invovled 1. M1 muscarinic 2. D2 Dopaminergic 3. H1 histaminergic 4. 5-HT3 serotinergic 5. Neurokinin 1 GI irritation causes serotonin release serotonin receptors on vagal afferents -> NTS Vestibular system also communicates -contains H1 histamine receptors (coupled to Gq) -scopolamine can treat this type of nausea

Lymphocytic choriomeningitis Virus

Arenaviridae Single stranded negative sense RNA virus Enveloped Ambisense Helical shaped capsid Two circular segments Grainy appearance on electron microscope, Arena means sandy Rodent transmission Meningoencephalitis Fever Inactivated by heat Inactivated by irradiation

Medullary thyroid carcinoma

Arise from parafollicular C cells Sporadic - most 5th to 6th decade Genetic - 20% MEN2A MEN2B Calcitonin can be used as a marker Can also produce VIP (diarrhea), serotonin (flushing), ACTH (Cushing's) Dense secretory granules Amyloid deposits (congo red staining, green under polarized light) PW -painless neck mass

Tolulene

Aromatic Hydrocarbon exposure via inhalation or ingestion high doses cause CNS depression Facilitate catecholamine-induced arrythmias Gasoline, paint, polish, airplane glue Liver and kidney damage drowsiness ataxia slurred speech

Cholangitis

Ascending -caused by migrating bacteria from SI -E coli, enterococci, clostridium, bacteroides Charcot's triad -RUQ, jaundice, fever chronic gallbladder inflammation -> dystrophic calcification -> carcinoma Stones can erode through wall -> fistula between biliary tract and adjacent small bowel -could lead to gallstone ileus (obstruction of the ileum by gallstone) -air in the biliary tree is suspicious

Hyperpituitarism

Associated with -McCune-Albright syndrome (spontaneous somatic mutation -> genetic mosaicism) -MEN1 PW -ca

Nasopharyngeal carcinoma

Associated with EBV Commonly seen in adults from Southern China and children from Africa

Pauci-RPGN

Associated with anti-neutrophilic antibodies -p-ANCA -c-ANCA Wegeners Microscopic angiopathies

Lichen planus

Associated with chronic hep c purple polygonal papules can present in mouth or other non vulvar regions white net like plaque very small chance of developing into vulvlar squamous cell carcinoma

Naegleria Fowleri

Associated with freshwater Enters through the cribriform plate Nuchal rigidity and fevers Encephalitis and meningitis Primary amoebic meningoencephalitis Rapidly fatal disease with poor prognosis Water sports also nasal lavages and eye contacts Diagnosis by Lumbar puncture Treatment: amphotericin B

Digital clubbing

Associated with hypoxia Lung diseases: Lung caner (especially large-cell carcinoma), tuberculosis, cystic fibrosis, bronchiectasis, pulmonary hypertension, empyema, copd, ATT deficiency (leading to COPD) Heart diseases: cyanotic congenital heart disease (5T's, Truncus arteriosus, Transposition of the great arteries, total anomalous pulmonary venous conneciton, tricupsid atresia, especially tetralogy of fallot) and bacterial endocarditis Other: inflammatory bowel disease (chron's disease, ulcerative colitis), hyperthyroidism, and malabsorption

Li-Fraumeni Syndrome

Associated with tumors in: bone brain adrenal glands breast p53 mutation

Viral protease inhibitors

Atazanavir, Darunavir, indinavir, lopinavir, ritonavir -metabolic side effects (hyperglycemia especially) -navir endings

Intestinal ischemia

Atrial fibrillation -> clot thrown to mesenteric arteries -> intestinal ischemia Rupture of plaques -> SMA thrombus Hypovolemia -> watershed areas in intestine get ischemic -splenic flexure (SMA and IMA) -IMA and rectal arteries near sigmoidal colon PW -severe abdominal pain out of proportion to exam -loss of bowel sounds -post prandial abdominal pain RF -angiodysplasia (painless hematochezia)

Bordetella pertussis

Attaches to respiratory epithelium with pilis (filamentous hemagglutinin) Bordatella toxin Ribosylation of Gi, disabling it -> causes rise in cAMP Also inhibits lymphocyte migration into tissues, causing lymphocytosis Adenylate cyclase toxin: (edema factor in bacillus) Tracheal toxin: part of peptidoglycan wall of pertussis that damages respiratory epithelium Clinical findings: paroxysmal phase: Whooping cough (from inspiration after you cough your brains out) third phase: convalescent phase, reduction of symptoms 100 day cough - phases can go on for months Treat: Macrolides Acellular vaccine: purified antigens of bacteria DTaP vaccine (diphtheria, tetanus, acellular pertussis

RSV

Attaches to the respiratory epithelium through G protein MOST COMMON CAUSE in infants: Bronchiolitis pneumonia VF: Fusion protein Ribavirin used in adults, not in children or pregnant women Palivizumab Seal bark cough Inspiratory stridor VF: fusion protein hemagglutinin NA Croup X-ray: "Steeple sign"

Lambert-Eaton Myasthenic Syndrome

Autoantibodies against presynaptic voltage gated calcium channels -IgG RF -paraneoplastic syndrome -small cell lung cancer PW -muscle weakness -repeated stimulation of motor neuron overcomes inhibition (calcium builds up eventually) -dry mouth -impotence

Vitiligo

Autoimmune attack on melanocytes

Polymyositis

Autoimmune destruction of muscle tissue Proximal symmetrical muscle weakness Upregulation of MHC1 on sarcolemma (membrane of myocytes) Presentation of autoantigens to CD8 T cells Autoantibody to histidyl-tRNA transferase -AKA Anti-Jo, anti-tRNA, antisynthetase antibodies -no evidence of tissue injury Endomysial inflammation myalgias Can present with interstitial lung disease Elevated creatine kinase Treat -corticosteroids -immunosuppressants if bad

Hashimoto's thyroiditis

Autoimmune disease Myxedema -> macroglossus -> myxedema coma (cardiovascular collapse) confusions, lethargy, hypothermia that may progress to coma downregulation of LDL receptors -> hyperlipidemia downregulation of beta receptors in the heart Hypothyroidism in mother can lead to congenital hypothyroidism (cretinism) -pot-belly -protruding umbilicus -pallor -puffy face -protuberant tongue May be associated with adrenal insufficiency Type IV hypersensitivity Type II also contributes -anti-thyroglobulin antibodies -anti-thyroid peroxidase antibodies -anti-TSH antibodies that BLOCKS RF -iodine deficiency -Celiac disease -diabetes type 1 -HLA-DR3 -HLA-DR5 PW -weight gain -cold intolerance -painless goiter -hyporeflexia -decreased BMR -muscle weakness -fatigue -myalgias -irregular mences -Loss or delay of deep tendon reflex (can't let go after handshake) -Transient hyperparathyroidism as cells lyse Dx -TSH serum level should be high in primary -T4 should be low Tx -Levothyroxine histology -germinal centers in thyroid tissue -> predisposes to non-hodgkin B-cell lymphoma -Hurthle cells (oxyphil cells) contain granular eosinophilic granules -interstitial fibrosis of gland -> primary lymphoma of the thyroid

Grave's disease

Autoimmune disease -IgG antibodies that bind to TSH receptors and ACTIVATE -type II hypersensitivity reaction Hypermetabolic state -> Hyperthermia, weight loss, flushed skin, muscle weakness (proximal), sweating, heat intolerance Sympathetic overstimulation -> increased beta receptors, direct sympathetic effect of thyroid hormone -deer-in-headlights or staring gaze from overstimulation of eye muscles -increased cardiac contractility, tachycardia, palpitations -systolic hypertension PW -brisk, exaggerated deep tendon reflexes -increased gut motility -increased bone resorption leads to hypercalcemia, osteoporosis -can lead to life threatening thyroid storm (thyrotoxicosis) -> fever, tachycardia, vomiting, diarrhea, CNS dysfunction. Can be caused by discontinuing meds, surgery, infection, etc. Tx with antiadrenergic drugs (alpha blockers before beta), propylthiouracil, potassium iodide, and corticosteroids. -Grave's ophthalmopathy (bulging of eyes) due to TSH receptors on orbital fibroblasts -> tissue remodeling, fat deposition, and inflammation (Helper T cells release cytokines) -> excess hyaluronic acid -> edema and swelling behind eyes -Waxy edema with dark purple or brown papules from hyaline accumulations Histology -T-cell lymphocytic infiltrate -SCALLOPED appearance of colloid as it pulls away from surrounding parenchyma RF -HLA-B8 -HLA-DR3 -physiologically stressful event -IgG anti-TSH antibodies Tx -radioactive iodine ablation -surgery -medical therapy with methimazole or propylthiouracil

Familial adenomatous polyposis

Autosomal dominant thousands of polyps in colon defective APC tumor supressor gene on chromosome 5 almost 100% chance to progress to adenomas Gardner syndrome

Ataxia-telangiectasia

Autosomal recessive combined B and T cell deficiency damage in ATM gene -usually surveys and repairs DNA leads to cerebellar atrophy early in life Serum IgA is low Elevated serum AFP

Chediak-Higashi syndrome

Autosomal recessive syndrome consisting of immunodeficiency, albinism, and neurological defects diagnosed in childhood Defect in neutrophil phagosome function

Macrolides

Azithromycin Clarithromycin Eryrthromycin Inhibits the 50S subunit of bacterial ribosome Bacteriostatic Tx -Bordetella pertussis (prophylaxis for close contacts) -Bartonella (cat scratch) -Azithromycin and clarithromycin for community acquired pneumonia (Strep pneumoniae, H influenzae, moraxella) -used in patients with penicillin allergy -walking pneumonia (mycoplasm, chlamydia, legionella) -azithromycin treats urethitis, cervicitis -erythromycin treats PID -clarithromycin treats babesia infections -mycobacterium avium -> prophylaxis at CD4 under 50 -triple therapy in h. pylori (with amoxicillin, PPI) AEs -Diarrhea from increased GI motility -jaundince -prolonged QT -Torsades -inhibits CYP450

Monobactams

Aztreonam single beta lactam ring activity only against aerobic gram negative rods resistant to most beta lactamases Tx -pseudomonas -serious systemic infections with gram negatives

Coronary artery dilation in CAD

BAD Atherosclerotic arteries are already maximally dilated, so giving a dilator dilates others, diverting blood flow AWAY from ischemic area

Chronic myelogenous leukemia

BCR-ABL fusion gene Philadelphia chromosome -truncated chromosome 22 created by a balanced reciprocal translocation between 9 and 22 (contains BCR-ABL gene) Constitutively activated receptor TYROSINE kinase Proliferation of more mature granulocyte progenitor cells (eosinophils, neutrophils basophils) Promyelocytes, myelocytes, metamyelocytes, neutrophils Insidious (slow, unnoticed) disease onset median age: 65 years Risk factors: -chemotherapy -ionizing radiation -exposure to benzene (plastic, rubber tire industry) -all the myeloproliferative disorders can turn into CML Clinical presentation: -anemia -splenomegaly (due to extramedullary hematopoiesis) Over time CML progresses to a more aggressive accelerated stage -> more immature, more abnormal -thrombocytopenia -> Blast crisis stage (difficult to control, similar to AML) Leukemoid reaction -> WBC count over 50,000 -benign -can be confused -WBC are composed mostly of neutrophils -Bands Treat: 1. Imatinib 2. Dasatinib 3. Nilotinib

Popliteal cyst

Baker cyst enlarged semimembranous bursa seen in young children and old people benign accumulation of bursal fluid that builds up secondary to motion at the joint can mess with common fibular (peroneal) nerve because it lies immediately adjacent to the tendon of the biceps femoris and can be injured when draining it

Osteochondroma

Benign lateral outgrowth cartilage cap Overlying cartilage can turn into osteochondrosarcoma Teenagers and elderly Familial retinoblastoma

Osteoid Osteoma

Benign tumor of osteoblasts surrounded by rim of reactive bone Produces osteoid Resolves with aspirin occur in cortex Radiofrequency ablation Arises in cortex (outermost portion) of long bones (femur) adults <25 years of age

Berylliosis

Beryllium dust found in nuclear and aerospace industries -A lot like sarcoidosis

Statins

Best at lowering LDL increases HDL decreased serum triglycerides Simvastatin, atorvastatin, rosuvastatin Most effective at preventing further cardiac events -Improve survival -initiate immediately after acute coronary syndromes regardless of lipid levels -also reduces risk of cardiovascular events in diabetes and those with peripheral artery disease -also reduces risk of strokes in those with history Teratogenic Side effects -myopathy (presents as proximal symmetrical muscle weakness or soreness, can have trouble raising arms above head, getting up from chair, ect) -CK can be elevated -mild elevations in liver enzymes Metabolized by CYP450

Fibrates

Best at lowering triglycerides lowers LDL/VLDL raises HDL (increase apoproteins A1 and A2 by hepatocytes Activates PPAR-alpha -> decreased hepatic VLDL production and increased LPL activity Combined with statins the chance of myopathy is increased

Niacin

Best at raising HDL (~30%) Lowers LDL/VLDL lowers triglycerides Vitamin B3 Harmless cutaneous flushing and sensation of warmth Decreased renal excretion of uric acid -> gout Can cause: Hyperglycemia Hyperuricemia Elevated LFTs

Class II antiarrhythmics

Beta blockers Block sympathetic input into the heart -decrease cAMP -> closure of membrane calcium channels -prolong phase 4 of nodal action potential -> decreased sinus rate -> prolonged conduction time and effective refractory period Serious bradyarrhythmia if also with AV conduction defect Beta blockers prevent rapid ventricular response in atrial flutter and fibrillation Treats: -supraventricular arrhythmias -A fib -A flutter

Amoxicillin

Beta lactam antibiotic -> interfere with transpeptidation reaction of bacterial cell wall synthesis -> penicillin binding protein forms peptidoglycan cross links (penicillin binds here and prevents this) Aminopenicillin increased activity against gram negative bacteria Sensitivity to beta lactamases -often paired with beta lactamase inhibitor like clavuanate oral availability prophylaxis for asplenic patients prophylaxis before dental procedures Tx -strep throat -sinusitis (strep pneumo, H influenzae, moraxella catarrhalis) -respiratory tract infections -triple therapy for H pylori -Lyme disease -GI and UTI gram negative rods AEs -rash -SJS -drug induced liver injury -skin rashes when prescribed for viral illness

Ampicillin

Beta lactam antibiotic -> interfere with transpeptidation reaction of bacterial cell wall synthesis -> penicillin binding protein forms peptidoglycan cross links (penicillin binds here and prevents this) IV adminitration Sensitivity to beta lactamases -often paired with beta lactamase inhibitor like clavuanate Tx -serious anaerobic infections -aspiration pneumonia -enterococcus (resistance through beta lactamases) -listeria -GI and UTI gram negative rods AEs -rash -SJS -drug induced liver injury -skin rashes when prescribed for viral illness

Penicillin

Beta lactam antibiotic -> interfere with transpeptidation reaction of bacterial cell wall synthesis -> penicillin binding protein forms peptidoglycan cross links (penicillin binds here and prevents this) Oral penicillin V is acid stable Penicillin G is given IV Resistance from beta lactamases -plasmid DNA Tx -staph -strep -strep pharyngitis -rheumatic fever -strep viridans -Group B strep -actinomyces isrealii -clostridium perfringens -Pasteruella multocida -Syphilis (treponema pallidum) -meningitis from niesseria AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Ticarcillin

Beta lactam antibiotic -> interfere with transpeptidation reaction of bacterial cell wall synthesis -> penicillin binding protein forms peptidoglycan cross links (penicillin binds here and prevents this) Sensitivity to beta lactamases -often paired with beta lactamase inhibitor like clavuanate Tx -Anaerobic infections -aspiration pneumonia -PSEUDOMONAS AEs -rash -SJS -drug induced liver injury -skin rashes when prescribed for viral illness

Piperacillin

Beta lactam antibiotic -> interfere with transpeptidation reaction of bacterial cell wall synthesis -> penicillin binding protein forms peptidoglycan cross links (penicillin binds here and prevents this) Sensitivity to beta lactamases -often paired with beta lactamase inhibitor like clavuanate, tazobactam Tx -Anaerobic infections -aspiration pneumonia -PSEUDOMONAS AEs -rash -SJS -drug induced liver injury -skin rashes when prescribed for viral illness

Dobutamine

Beta-1 agonist heart effects -> increased rate -> contractility -> CO increased used to temporarily keep heart going in shock used in cardiac stress test too

Isoproterenol

Beta-1 and Beta-2 agonist Increases contractility Decreases MAP (beta-2 effect) Decreases diastolic pressure -> increases pulse pressure (diff between systolic and diastolic) Tx -

Asthma therapy

Beta-2 agonists (-rol) -albuterol -terbutaline -dose inhalers for acute symptom relief Low dose inhaled corticosteroids -beclomethasone -budesonide -fluticasone -block inflammation and cellular infiltration Leukotrienes blockers Ziluten - LOX blocker Long acting beta 2 agonists (LABA) -formoterol -salmeterol Methylxanthins -increased cAMP by inhibiting phosphodiesterase -bronchialsmooth muscle relaxation -orally -not used anymore -> narrow therapeutic index, have to closely monitor so you don't have cardiac events Omalizumab -mast cell inhibitor -adjunctive therapy -binds to Fc on IgE to prevent mast cells from becoming sensitized Epinephrine can be used to treat acute severe attack

Peroxisome

Beta-oxidation of very-long-chain fatty acids alpha-oxidation (only happens in peroxisome) Catabolism of branched-chain fatty acids, amino acids, ethanol Synthesis of cholesterol, bile acids, and plasmalogens (important membrane phospholipid, especially in white matter of brain)

Subdural hematoma

Between dura mater and arachnoid membrane Cresent shape -> cross suture lines Caused by tearing of bridging veins -rapid movement of brain -infants have delicate veins -> shaken baby syndrome -elderly have cortical atrophy that stretch veins -> more prone to rupture Warfarin predisposes usually much more benign -You can have chronic subdural hematoma -> causes headache, seizure, cognitive impairment Can have acute on chronic

Esophagus on CT

Between the trachea and the vertebral bodies usually collapsed with no visual lumen

Failed lateral fusion of the paramesonephric ducts

Bicornuate uterus Double uterus and cervix

Small vessel vasculitis

Big vessels not affected obviously PALPABLE PURPURA from small vessel inflammation -raised, non-blanching, diffuse erythematous papules and plaques Glomerulonephritis Rapidly progressive kind also -crescent formation Wegener's (granulomatosis with polyangitis) -systemic necrotizing vasculitis -central necrosis usually present in granulomas -TRIAD - nose, lungs and kidneys (chronic rhinosinusitis, yellowish hemorrhagic pulmonary nodules, and -WECENERS, lots of C -c-ANCA -treat with cyclophosphamide Microscopic polyangitis -Likes to hit vessels of lungs and kidneys -RPGN -Looks like wegeners, p-ANCA instead of c-ANCA -no granulomas Churg-Strauss syndrome -eosinophilic granulomatosis with polyangiitis -ASTHMA (present in virtually every patient) -allergic rhinitis -nasal polyps -atopic dermatitis -pleural effusion -pANCA Heoch-Schonlein purpura -usually seen in children -Most present in spring or fall, almost NONE in summer -defective mucosal immunity? Mechanism not known -IgA everywhere!! -IgA deposition throughout body -deposition in the mesangium of glomeruli -> glomerulonephritis resembling IgA nephrothy (hematuria and occasional proteinuria) Cryoglobulinemia -Type III hypersensitivity -precipitates when body temp drops below ??? -IgG-IgM that bind to each others Fc region -association with Hep C infection -Multiple myloma -Lupus -IgM in glomerulus -> glomerulonephritis Goodpasture syndrome -Type II hypersensitivity reaction -antibodies directed against the alpha-3 chain of type IV collagen in glomerular basement membranes -can see IgG lining up along the basement membrane (linear pattern of immunofluorescense -crescentic glomerulonephritis -Also react with type IV collagen in alveolar basement membrane

Chronic kidney disease

Bilaterally shrunken with a red-brown granular surface Stages 1-5 5 is end stage 3 months of reduced GFR Causes: -Hypertension (MOST COMMON) -chronic glomerulonephritis conditions -Bilateral renal stenosis Adaptive hyperfiltration -as nephrons burn out, others try to pick up the work and eventually burn out too (insidious onset) -advanced scarring of glomeruli and interstitial fibrosis CKD can cause metabolic acidosis (impaired H+ excretion, bicarb reabsorption, hyperpotassiemia) Causes fluid retention Waxy casts in the urine CKD can cause hyperphosphatemia (decreased filtration) -> hypocalcemia -can cause hypovitaminosis D due to decreased activity of 1-alpha-hydroxylase Secondary hyperparathyroidism (due to hypocalcemia) -> osteofibrosis cystica UREMIA -nasuea -asterixis (tremulousness and cognitive changes) -platelet dysfunction -PERICARDITIS (serous and hemorrhagic -encephalopathy, seizures, coma, and death at high levels -peripheral neuropathy -itchiness -treat: gapapentin, SSRIs, Coronary artery disease is associated with CKD -not just due to atherosclerosis -CKD is an independent risk factor

Benzodiazapines

Bind to GABA-A receptor -inhibitory neurotransmitter (chloride channel) -benzodiazapines potentiate -> more depression (good for seizures, ect) -INCREASE IN FREQUENCY OF OPENING!! -alcohol also binds here (chronic alcoholism leads to down regulation of channel -> if alcohol is abruptly taken away -> not enough inhibition -> seizures....treat with benzodiazepines) Side Effects Potential to cause dependence Tolerance develops (increase dose to have same effect) Withdrawal symptoms are opposite of effects -seizures, anxiety, ect Anterograde amnesia Elderly patients are more sensitive to side effects -olam suffix -short acting -pam suffix -Long acting form active metabolites in the liver -long half lives IV benzodiazapines -epilepsy -status epilepticus -anesthesia (muscle relaxation, amnesia) -conscious sedation -> patient can maintain airway and follow commands Treat: -status epilepticus -alcohol withdrawal (one of the most common causes of seizures in adults) -sleepwalking and night terrors in children -treat spasticity caused by upper motor neuron disorders -> sedation at these doses -generalized anxiety disorder -panic disorder

Citrate

Binds calcium in urine and gets excreted -protects from stone formation Acidosis can cause hypocitraturia from buffering

Linezolid

Binds to 50S ribosomal subunit Big gun Tx -Staph and strep -VRE -MRSA (nosocomial) AEs -Optic neuropathy -thrombocytopenia -stocking-and-glove peripheral neuropathy -serotonin syndrome

Rabies encephalitis

Binds to nicotinic acetylcholine receptors Presentation: Agitation Disorientation pharyngospasm photophobia Coma death Dysphagia with hypersalivation leads to mouth foaming

Histoplasma capsulatum

Bird or bat dropping Mid western and central US respiratory transmission Rapid histoplamsa serum antigen test and urine test Histoplasma is much smaller than a RBC Dimorphic -Mold in the cold -yeast in the heat Usually subclinical can cause pneumonia with granulomas that calcify, espicially in hilar regions (looks like TB) You will see ovoid cells within macrophages Erythema nodosum In immunocompromised; Hepatosplenomegaly Spleen Fungus targets reticuloendothelial systems because it infects macrophages, so these organs are commonly affected Treatment: Local: Azole drugs -fluconazole -ketoconazole Systemic; -amphotericin B

Yersinia pestis

Black plague Gram - Fleas transmit (on rodents) Buboes (boils) DIC - endotoxin -> necrosis of digits Yersinia associated outter proteins - macrophage and neutrophil affected -> impaired phagocytosis and cytokine secretion Tetracyclines! Killed vaccine

Furosemide

Blocks NaClK cotransporter in Volume excretion Good in CHF Thick ascending loop Reduce lumen positive potential that drove magnesium and calcium absorption -hypocalcemia -hypomagnesia Most potent diuretic, so its first line in decompensated heart failure Potassium wasting Dose related hearing loss Tx -symptomatic treatment of acute decompensated heart failure -pulmonary edema from HF -ascites in liver failure -heart failure (chronic) -severe hypertension AEs -ototoxicity (usually reversible after stopping treatment) -dehydration -contraction alkalosis

Ezetimibe

Blocks intestinal absorption of cholesterol Restricts liver's access to exogenous cholesterol, so liver will upregulate its production, and LDL receptors will be upregulated Rare increased in transaminases Can cause diarrhea or steatorrhea

Carbidopa

Blocks peripheral conversion of L-DOPA to dopamine by blocking dopa decarboxylase -can't cross BBB, doesn't affect actual treatment

Babesia spp.

Blood related symptoms Tick transmitted Ixodes tick, Northeast distribution Higher risk in sickle cell patients Most people are scarcely symptomatic Hemolytic anemia -can lead to jaundice Irregularly cycling fevers Diagnosed by thick blood smear Maltese cross appearance Atovaquone or azithromycin

Shigella spp.

Bloody diarrhea Green colonies when plated on Hektoen agar Immotile ACID STABLE, don't need as much as salmonella facultative intracellular M cells in peyer's patches phagocytose Shigella, it then escapes the phagolysosome and uses the host cells actin to make actin rocket Fecal blood and leukocytes Infection in children can precipitate Hemolytic uremic syndrome -> Shiga toxin damages glomerulus in kidney, activates platelets and dropping serum count group of platelets lyses RBCs as they pass by Shiga toxin binds to 60s ribosomal subunit

mitochondrial myopathies

Blotchy red muscle fibers on Gomori trichrome stain "Red ragged fiber disease" Myoclonic epilepsy Leber optic neuritis mitochondrial encephalopathy with stroke-like episodes and lactic acidosis Maternal inheritance

Mitral regurgitation

Blowing holosystolic best heard over cardiac apex and may radiate to axilla S3 Causes -papillary muscle rupture following MI Acute increase in EDV due to blood shooting back into atrium through regurg Hyperacute -CO plumets -severe hypotension Chronic -increased EF to maintain CO (some is now wasted through effed valve Treat -Diuresis

Right-to-left shunts

Blue babies Truncus arteriosus (one outflow track) -failure of septation -improper neural crest migration Transposition of great arteries -two completely separate tracks -Needs PDA, VSD, ASD, somewhere to cross -diabetes in mother a risk factor Tricuspid Atresia - Tetrology of Fallot -most common -tetrad of mutations -PROVe -pulmonary stenosis (dictates severity of disease) -Right ventricular hypertrophy -Overriding Aorta (more central than usual, neural crest cell problem) -VSD TAPVR

Insulin independent cells

Brain Kidney Liver Intestine Red blood cells

Paracoccidioides brasiliensis

Brazil and south america Multiple buds that radiate out from central vacuole (captain's wheel) Much bigger than RBCs Dimorphic Respiratory droplets transmission Coughing, lymphadenopathy, granulomas in lungs, mucosal ulcers in URT (gums in mouth) Local: itraconazole Systemic: amphotericin B

Leishmania spp.

Braziliensis -cutaneous leishmaniasis -Sand Flies are the vector -Promastegoat - infectious form -in host it becomes amastigote Donovani -Visceral leishmaniasis: most common is spleen, bone, and liver -Black fever or kala-azar Treated: -Stibogluconate -amphotericin B

Psyllium

Bulk-forming laxative -indigestible hydrophilic colloid -> absorbs water -> distention -> peristalsis

Complement system disorders

C1 complement inhibitor deficiency -autosomal dominant -bradykinin production is UNCONTROLLED ( no C1 inhibitor -> increased kallikrein activation -> increased conversion of kininogen to bradykinin) -widespread angioedema -angioedema in GI tract presents as nausea and vomiting, abdominal pain, and diarrhea -C4 falls because its being used up C2 deficiency is most common (C1, C3, C4 deficiency is extremely similar) -increase susceptibility to encapsulated bacteria -Very high risk of SLE (theory is that complement helps clear immune complexes, so these build up like in lupus with deficiencies) Late complement deficiency (C5-C9 deficiencies) -Cant form MAC complex -susceptible to neisseria meningitidis Paroxysmal nocturnal hemoglobinuria -overactive complement -No CD55 and CD59 that inhibit complement cascade

Nasal transepithelial potential difference

CFTR secretes Cl- into the lumen and also has tonic inhibitory effect on the opening of the ENaC, which decreases Na+ resorption into the cell In defective CFTR, Cl- secretion will be impaired -> ENaC inhibition impaired -> more Na+ into cell

Secondary hyperparathyroidism

CKD -> decreased vitamin D activation -> decreased calcium absorption from the gut -> hypocalcemia -> parathyroids secrete PTH Parathyroid hyperplasia Labs -low calcium, low vitamin D, high PTH Bone disease from increased bone resorption -> longstanding secondary -> TERTIARY -Marked parathyroid hyperplasia -REALLY high parathyroid hormone regardless of calcium Tx -parathyroidectomy

Lead

CNS toxicity Lead encephalopathy: HA, confusion, clumsiness, insomnia, fatigue, & impaired concentration Thought to disrupt calcium signaling Treat with chelators calcium gluconate

Barbiturates

CNS, pulmonary depression Addiction Antiseizure agent occasionally Bind to allosteric site on GABA-A receptor and facilitate -> neuronal hyperpolarization, depression AFFECTS THE DURATION OF CHANNEL OPENING Long serum half life -> hangover effects ACTIVATE CYP450 Hypotension Coma in elderly Thiopental -IV for induction of anesthesia -management of seizures -highly lipid soluble -> rapid onset -duration 5-10 mins due to drug redistribution (rapid decrease in plasma) Phenobarbitol -antiseizure -can depress cardiac and respiratory function -second or third line agent because administration is slow, has bad side effects Primidone -treats seizure and essential tremor

Complete Hydatidiform Mole

COMPLETELY a mole -no developed fetal parts REAAAAALLLLYYYY high beta-hCG -orders of magnitude higher than what you would expect in normal pregnancy formed by fertilization of empty ovum -haploid 23X sperm fertilizes empty egg -> duplicates and forms 46XX zygote -46XY if two separate sperm fertilize empty ovum at the same time RF -extremes of maternal age -history of miscarriage PW -enormous uterus -bleeding early in pregnancy -"snowstorm" pattern on ultrasound -hyperemesis -hyperthyroidism (beta-hCG is similar to thyroid hormone) -theca-lutean cysts -early preeclampsia p57 negative overexpression of paternal genes significant risk after surgery -> malignant transformation into choriocarcinoma ->or other gestational trophoblastic neoplasm

Communicating Hydrocephalus

CSF can flow Dysfunction of the arachnoid granulations RF -inflammation and fibrosis from meningitis, subarachnoid hemorrhage Causes -high ICP Tx Ventriculoperitoneal shunt

Cinacalcet

Calcimimetic Binds to calcium-sensing receptor on parathyroid gland -> decreases production of PTH\

Wilson's disease

Can cause cystic degeneration of the putamen as well as damage to other basal ganglia structures

Ladd's bands

Can cause midgut volvulus Fibrous bands

Membranoproliferative glomerulonephritis

Can cause nephritic and nephrotic Hypercellularity Enlarged, lobular glomeruli GMB thickening! -splits membrane in two (ingrowth of mesangial cells into basement membrane) -Tram-tracking Caused by -viral infections -autoimmune disease -monoclonal neoplasms Immune complexes form in subendothelial space

Middle cerebral artery infarct

Can cause wernicke's or broca's aphasia

Mitral valve regurgitation

Can lead to severe hypotension and shock Holosystolic murmur Causes -acute rheumatic fever -Infective endocarditis (aortic and mitral most affected) If chronic the heart can compensate -has to increase ejection fraction to compensate for backflow -Eccentric hypertrophy -> decompensated congestive heart failure MID-SYSTOLIC CLICK if patient does valsalva

Early septic shock

Can present with an afebrile patient (especially elderly)

Vasectomy

Can still have viable sperm (because of sperm in distal vas defrens to cut) up to a month after

Restrictive lung disease

Can't get air into lungs due to impaired ability of lungs to expand Decreased TLC FEV1/FVC is near or above 80% -both are reduced, but FVC is reduced more Interstitial lung disease -dry crackles -velcro rales -diffuse reticulo-nodular opacities (diffuse, bilateral opacities) -sarcoidosis DLCO is low in intrinsic restictive lung disease only, because diffusion surface is destoryed During pleural effusion, protein can get into pleural space and impede movement Neuromuscular diseases that impair diaphragm movement Kyphoscoliosis and ankylosing spondylitis can restrict chest wall expansion and cause restrictive lung disease Extrathoracic fat can limit chest wall expansion -obesity hypoventilation syndrome -> high PaCO2, low PaO2 -can lead to cor pulmonale and right heart failure

HIV-associated esophagitis

Candida albicans -> pseudomembranes HSV-1 -> small vesicles and punched out ulcers CMV -> linear ulcerations

Echinocandins

Capsofungin micafungin anidulafungin act at fungal cell wall inhibits the synthesis of beta-1-3-glucan in the fungal cell wall IV for systemic candidaisis Tx -candida -aspergillis

Cisplatin

Carboplatin (less ototoxic) oxaliplatin (least ototoxic) cytotoxic platinum analogs -crosslink DNA Tx -solid malignancies -non-small cell lung cancer -small cell lung cancer -testicular cancer -ovarian cancer -bladder cancer AEs -ototoxicity -peripheral neuropathy -nephrotoxic -> AKI or ATN -> GIVE AMIFOSTINE -> also SALINE diuresis -neurotoxic (cisplatin especially) -myelosuppression

Carcinoid heart disease

Carcinoids are well-differentiated neuroendocrine tumors found most commonly in the distal small intestines and proximal colon. Strong propensity for for metastasis to the liver Secrete Histamine, serotonin, and VIP Lead to excessive secretion of serotonin -stimulates fibroblast growth and fibrogenesis -plaque-like fibrous tissue on endocardium -> tricuspid regurgitation 5-hydroxyindoleacetic acid (5-HIAA) is an end product of serotonin metabolism, will be elevated in a 24-hour urinary test

Class I antiarrhythmics

Cardiac cycle: Phase 0 -> upstroke, Na+ influx Phase 2 -> plateau, Ca2+ dominates Phase 3 -> repolarization, K+ dominates Sodium channel blockers -slow the upstroke of the action potential State-dependence (use-dependence) -tissues getting used more are blocked more readily (makes sense, most bind to inactivated sodium channels I.E. they need to be fired) Action in purkinje fibers No action at SA or AV node Wide QRS on ECG -slow down stroke, decrease conduction velocity of the action potential -widening increases with tachycardia, more use = more binding Supraventricular and ventricular arrhythmias Treat: -Wolff-parkinson-white syndrome (supraventricular tachycardia involving accessory pathways outside usual path) IC > IA > IB IA: -Quinidine Thrombocytopenia -Procainamide -Disopyramide Can exacerbate heart failure -Can cause torsades de pointe IB: -Phenytoin -Lidocaine best for ischemia induced ventricular arrhythmias more selective for channels in open state, so it targets ventricle because it's action potential is longer bind the least strongly of class I modest slowing of phase 0, little use dependence because it doesn't build up -Mexiletine IC: -Propafenone -flecainide -class IC binds the strongest, dissociates the slowest, and show the most use-dependence -don't affect action potential duration -can restore and maintain normal cardiac rhythm -contraindicated if history of structural or ischemic heart disease Side effects:

IgA proteases

Carried by: N gonorrhoeae N meningitidis Strep pneumo H influenzae

Aspergillus fumigatus

Catalase positive Aflatoxins - carcinogenic, especially in hepatocellular carcinoma Acute angle branching to discriminate from mucor (that has 90 degree angles) Forms conidiophores with fruiting bodies looks like Aspergillum, tool used to spray holy water Transmitted by inhalation Clinical manifestations: -Allergic bronchopulmonary aspergillosis: asthma and wheezing. Patients show increased IgE -Aspergilloma: ball of fungus in the lungs, associated with TB cavities. They are gravity dependent, in an upright CXR they will be at the bottom -Angioinvasive aspergillosis: affects immunocompromised patients. Invades blood vessels and disseminates throughout the body. Fever, cough, hemoptysis, kidney failure, endocarditis, ring enhancing lesions in the brain, Necrosis around the nose (happens in mucor too) Treatment: Voriconazole Aspergillomas need to be surgically debrided amphotericin B for angioinvasive disease

Senna

Cathartic agent stimulates GI movement causes melanosis coli (dark brown colored stool)

malignant (necrotizing) external otitis

Caused almost exclusively by pseudomonas Severe ear pain, discharge, potential hearing loss osteomyelitis of TMJ and base of skull can develop

Dilated cardiomyopathy

Causes -viral myocarditis (coxsackie type B, parvo, adenoa) -Chagas -genetic: usually autosomal dominant, although the muscular dystrophies are X linked -toxic exposures -Doxorubicin (free radicals) -anthracyclins (free radicals) -alcohol -excess iron that gets deposited in heart )heriditary hemochromotosis, or frequent blood transfusions\

Entamoeba histolytica

Causes amebiasis two main life cycle stages 1. cyst form (infectious when ingested, also more prevalent in men who have sex with men) Right lobe of liver is most common for amoebic abscesses Puss in abscess has consistency of anchovy paste RUQ pain large and tender liver Ulcerations in colon with intestinal amoebiasis Bloody diarrhea Flask shaped lesions Stool O&P for diagnosis Trophozoites with endocytosed red blood cells under microscope ELISA antigen test on stool or serum Meronidazole Paramycin - luminal agent to eliminate cysts Iodoquinol

IL-4

Causes class switching from IgM to IgE

Fourth generation cephalosporins

Cefepime broad spectrum penetrates CNS Pseudomonas serious systemic infections Resistance -altered PBPs -extended spectrum beta lactamases AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Fifth generation cephalosporins

Ceftaroline broad spectrum MRSA coverage Resistance -altered PBPs -extended spectrum beta lactamases AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Third generation cephalosporins

Ceftriaxone Cefotaxime Ceftaz(azzzz)idime -> pseudomonas(azzzzz) killa Vancomycin added too for MRSA coverage Resistance -altered PBPs -extended spectrum beta lactamases Tx -MENINGITIS!!! -community and hospital acquired pnemonia -Extended gram negative coverage -HENS -H flu -Neisseria -Serratia -Otitis -pneumonitis -URIs -Peritonitis (not first line) -Gram positive cocci -Staph -Strep -cellulitis -abscesses -pharyngitis -PEK UTI bugs -Proteus -E coli -Klebseilla -Salmonella -Shigella -SERIOUS HOSPITAL INFECTIONS -First line treatment for gonorrhea -LYME DISEASE AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Second generation cephalosporins

Cefuroxime Cefotetan Cefoxitin Resistance -altered PBPs -extended spectrum beta lactamases Tx -Extended gram negative coverage -HENS -H flu -Neisseria -Serratia -Otitis -pneumonitis -URIs -Peritonitis (not first line) -Gram positive cocci -Staph -Strep -cellulitis -abscesses -pharyngitis -PEK UTI bugs -Proteus -E coli -Klebseilla AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Sulfa drugs

Celecoxib Furosemide bumetanide torsemide hydrochlorothiazide indapamide metolazone acetazolamide chlorthalidone Zonisamide topiramate trimethoprim/sulfamethoxazole sumatriptan tamsulosin sotalol dronedarone

Benign prostatic hyperplasia

Cell hyperplasia smooth muscle cells cause urinary obstruction bilateral hydronephrosis diffuse, symmetrically enlarged prostate not a risk factor for prostate cancer Tx -alpha 1 antagonists -alpha 5 reductase inhibitors

First generation cephalosporins

Cephalexin Cefazolin Cefazolin for surgical prophylaxis Resistance -altered PBPs -extended spectrum beta lactamases Tx -Gram positive cocci -Staph -Strep -cellulitis -abscesses -pharyngitis -PEK UTI bugs -Proteus -E coli -Klebseilla AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Trypanosoma cruzi

Chagas disease Reduviid bug or "kissing bug" MEGAcolon Dilated cardiomyopathy Megaesophagus Diagnosed by blood smear to visualize mobile trypanosomes Chronic chagas can be diagnosed via serology and clinical symptoms Trypanosomes can be found within cardiac myocytes on biopsy Burrows into the endocardium Nifurtimox

Succimer

Chelation agent for mercury exposure

cetuximab

Chimeric monoclonal antibody Binds EGFR -tyrosine kinase Tx -Colorectal cancer -squamous cell carcinoma AEs -Infusion reaction (headache, fever, skin rash, dyspnea, hypotension) -papulopustular acniform rash

Galstones

Cholesterol Bilirubin 7-alpha-hydroxylase makes bile salts Black stones = hemolysis Brown stones = infection (bacteria unconjugate stones 4 F's -Fat -Forty -Fertile -Female Estrogen increased synthesis of cholesterol RF -somatostatin -TPN -hemolysis -decreased bladder motility -fasting -Crohn's PW -waxing and waning RUQ pain from gallbladder contraction (CCK release)

Gallstones

Cholesterol stones -too much cholesterol pigment stones -too much bilirubin

Hairy cell leukemia

Chronic B cell neoplasm Middle aged men Fine, hair-like cytoplasmic projection Stain for Tartrate-resistant acid phosphatase (TRAP) Massive splenomegaly Dry tap on bone marrow biopsy due to extensive myelofibrosis

Chronic tubulointerstitial nephritis

Chronic NSAID use Analgesics NSAIDS -> free radical damage Bilaterally small scarred kidneys Lead exposure Autoimmune diseases -Sjogren's syndrom -SLE -> concurrent glomerular disease

Ankylosing spondylitis

Chronic inflammatory condition HLA-B27 serotype Stiffness and fusion (ankylosis) of axial joints Sacroilliac and apophyseal joints most commonly affected Can limit chest wall expansion leading to hypoventilation Ascending aortitis Anterior Uveitis

Deep vein thrombosis

Chronic venous insufficiency can cause lipodermatosclerosis -> fibrosis of the subcutaneous tissue, starts at medial ankle Causes hyperventilation (manifest as tachypnea and dyspnea) from activation of chemoreceptors and pulmonary irritant sensors -> activation of respiratory centers -> respiratory alkalosis Dual blood supply for most central lung tissues, but peripheral have less of a dual supply and are more vulnerable to infarct Westermark sign -> hyperlucency from decreased perfusion Severe PE can cause increased pulmonary resistance from constriction of hypo-oxygenated area Saddle embolus -> occludes left and right pulmonary arteries and kills you almost instantly -spiral CT angiography if you suspect it -Then anticoagulate -thrombolytics like tPA Virchow's triad -stasis -hypercoagubility -epithelial injury

Eosinophilic granulomatosis with polyangiitis

Churg-Strauss syndrome Small to medium vessel vasculitis last onset asthma asymmetric multifocal neuropathy (wrist drop common) antibodies against neutrophil myeloperocidase

CYP450 inhibitors

Ciprofloxacin Macrolides verapamil Acetaminophen NSAIDs Antibiotics (metronidazole) Antifungals Amiodarnone Cimetidine Cranberry Juice Ginkgo Biloba Vitamine E Omeprazole Thyroid hormone SSRIs

JC polyomavirus

Circular, double stranded naked DNA virus John-cunninghame Progressive multifocal leukoencephalopathy -CNS demyelination disease -fatality is 50% -multifocal brain lesions -Non-enhancing lesions Over half the population has JC virus, but intact immune system has no problem with it Immunocompromised get PML AIDS patients with less than 200 CD4 get affected

BK polyomavirus

Circular, double stranded naked DNA virus Nephropathy hemorrhagic cystitis Transplant patients (especially renal and bone) BK is named after a renal transplant patient

Abetalipoproteinemia

Clear cells on jejunal biopsy Caused by impaired formation of apolipoprotein B Autosomal recessive MTP gene loss of function PW -malabsorption -acanthocytes (thoryny pointy RBCs)

Blood urea nitrogen

Cleared by the kidney Final product of nitrogen breakdown -amino acids -pyrimidines 7-20 mg/dL normally decrease in GFR -> increase in BUN Reabsorbed at the PCT Increased BUN/Cr ratio (> 15) -Pre renal AKI -Kidney not the issue -hypovolemia -hemorrhage -decreased fraction excretion of sodium (FENa) -UOsm > 500 -> concentrating urine to preserve volume -AND postrenal -stones (two), BPH, anything that can block urine flow Normal BUN/Cr ratio (not super high, < 15) -Because both are elevated -intrinsic kidney injury -FENa is high, unable to reabsorb sodium -kidney is not good at reabsorbing -muddy casts -acute interstitial nephritis -glomerulonephritis -UOsms are low, cant concentrate Decreased BUN/Cr ratio -

Selective IgA deficiency

Clinical features: -usually asymptomatic -Recurrent sinopulmonary, gastrointestinal infections -autoimmune disease -anaphylaxis during transfusions (form antibodies to IgA, and react with small amounts of IgA) Diagnosis -low or absent serum IgA levels -normal IgG and IgM levels

Rapidly progressive glomerulonephritis

Clinical syndrome Crescent formation that causes rapid decline in kidney function -Obliteration of Bowman's space Immune-complex mediated glomerulonephritis can lead to RPGN (granular deposits) Segmental necrosis and breaks in the glomerular basement membrane

ADP platelet inhibitors

Clopidogrel Ticagrelor Prasugrel ticlodipine -> neutopenia, granulocytopenia irreversibly block ADP P2-Y12 receptor Reduce cardiovascular events

Necrotizing fasciitis

Clostridium perfringens -alpha toxin: lecithinase (phospholipase C) that lyses RBCs platelets, leukocytes, and endothelial cells Strep pyo Symptoms: -skin discoloration -fever -mental changes -sepsis -severe pain can present with crepitus due to methane`

VSD in TOF

Comes from deviation of the infundibular septum

Hydrocele

Communicating -incomplete obliteration of the processus vaginalis (peritoneal tissue that travels with the testis through inguinal canal during development -> fluid from peritoneal cavity can flow into tunica vaginalis Noncommunicating -sac just hangs out in the bigger sac transilluminates

Choledocal cysts

Congenital (majority) most present before age 10 RUQ mass Jaundice Abdominal pain Surgically resected because they can lead to obstruction Chronic cholestasis -> increased chance for stones

DiGeorge Syndrome

Congenital defect in thymus development T cells cant mature (develop in BM) ABSENT mature CD3 T cells Extremely vulnerable to viral, fungal, and intracellular pathogens abnormal development of third and fourth pharyngeal pouches -parathyroid gland hyperplasia -> hypocalcemia (no PTH) -> Tetany -Abnormal facies -cleft palat -cyanotic congenital heart diseases (truncus arteriosus and tetralogy of fallot) Absent thymic shadow Lymph nodes have poorly developed paracortex (where T cells reside) Deletion of 22q11

Spinal muscular atrophy

Congenital degeneration of the anterior horn -affects bilaterally Infantile SMA = Werdnig Hoffman disease

Tumor necrosis factor alpha

Contributes to cachexia (muscle wasting) -along with IL-1beta and IL-6

Hypercortisolism

Cortisol secreting tumors -adenomas -carcinoma (rarer) -nodular hyperplasia of zona fasciculata (rarer) Cushing syndrome symptoms -skin atrophy and striae -fat redistribution -moon facies -insulin resistance PW -low ACTH level -contralateral adrenal atrophy

Omphalmocele

Covered by peritoneum associated -cardiac abnormalitites -trisomies

Transverse carpel ligament

Cut to relieve carpel tunnel syndrome

Candida albicans

Cutaneous and systemic fungal infections Part of normal flora Catalase positive chronic granulomatous disease patients are particularly susceptible Most common cause of opportunistic mycoses Dimorphic- pseudohyphae and budding yeast at 25 budding hyphae with germ tube (true hyphae) at 37 Diaper rash Oral candidiasis - immunocompromised or using steroid inhalers Can be scrapped off Esophagitis White pseudomembranes CD4 <100 Diabetes predisposes Antibiotics and OCPs can cause yeast infections in women pH of 4 and lower Candidal endocarditis in drug users because it can grow in types of heroin azoles for local amphotericin B for systemic Nystatin swish! Caspofungin for resistance

Ropinirole

D2 dopamine receptor agonist Tx -parkinsons -restless leg syndrome AEs -rock n roll side effects -> increased pleasure seeking, gambling, sexual activity, risky behavior

Metoclopromide

D2 receptor antagonist treats nausea AR -drowsiness in elderly -extrapyramidal side effects (dystonia, akathisia, parkinsonian features) -QT prolongation -torsades

Desmopressin

DDAVP Stimulates endothelial cells to release vWF and VIII Treats -hemophilia A and von Willebrand's disease -Night enuresis (decreased urine production) AEs -hyponatremia

Clear cell adenocarcinoma of vagina

DES exposure is very strong link

Sulfonureas

DM type 2 Inhibit potassium ATPase channel -> depolarizes -> calcium release -> insulin release 1st gen -tolbutamide -chlorpropamide -long duration of action, rarely used 2nd gen -glipizide -glyburide -glimepriride -short duration of action -less chance of hypoglycemia AE -hypoglycemia -weight gain -1st gen disulferam

Cytomegalovirus

DNA virus Herpesviridae Latent in mononuclear cells reactivated by immunosuppression Trasmitted in every way possible Most common viral illness in kids BLUEBERRY MUFFIN RASH jaundice hepatosplenomegaly #1 cause of Sensorineural hearing loss in kids #1 congenital viral infection #1 cause of congenital mental retardation Periventricular calcification Ventriculomegaly Intracranial calcifications can cause seizures 80-90% are asymptomatic Hydrops fetalis Transplant patients and AIDS patients are at risk for CMV pneumonia Buffy coat culture then plate with fluorescent antibodies AIDS <50 CD4 count! CMV retinitis -> full thickness retinal necrosis "pizza pie" necrosis CMV esophagitis with linear ulcerations CMV colitis Owl's eyes inclusions when CMV infects stuff TREATMENT: Ganciclovir phoscarnet- UL97 gene mutation that makes it resistant to gancyclovir CMV mononucleosis in immunocompetent patients

Gliptins

DPP-4 inhibitor Citagliptin saxagliptin linagliptin increased endogenous GLP-1 secretion delayed gastric emptying decreased post prandial glucose rise AE -pharyngitis -URTI's -increaesed risk of pancreatitis

Acute gastritis

Damaged gastric mucosa -toxic -viral -can't protect itself against nutrients NSAIDS -direct irritation to cells of mucosa -inhibit COX enzymes -> decreased prostaglandins -> mucosal blood flow and production decreased

Doxorubicin

Danarubicin anti-tumor antibiotic anthracyclin analogue MOA -generate oxygen free radicals through Iron dependent process -also intercalates Tx -numerous solid and hematologic malignancies AEs -cardiotoxicity -dilated cardiomyopathy -> give DEXRAZOXANE (iron chelating agent) -mucositis -stomatitis -alopecia

Lung tissue aging

Decrease in chest wall compliance as a result of stiffening from rib calcification and from increased thoracic curvature due to osteoporosis and osteoarthritis Lung compliance increases due to loss of elastic recoil leads to significant increase in residual volume TLC unchanged because decrease in chest wall compliance counter balances increase in lung compliance

Wrinkles

Decrease in collagen fibril production

Respiratory acidosis

Decreased breathing leads to buildup of CO2 -> decreased pH Kidney compensated by increasing bicarb production, retention Causes -COPD -> chronically retain CO2 -Obstructive sleep apnea -opiods -restrictive lung diseases (pulmonary fibrosis, obesity, scholiosis, pleural edema) -Neurological disorders

Gemfibrozil

Decreases hepatic clearance of statins, increases myalgias

Metformin

Decreases hepatic gluconeogenesis decreases glucose absorption in the gut increases glucose use by peripheral tissues AE -lactic acidosis -anorexia -nasuea -vomiting -diarrhea

Cystinuria

Defective channel protein for absorption of COLA a.a.'s -cystine -ornithine -lysine -arginine cant absorb from renal tubule -> cystine stones

Ehlers-Danlos syndrome

Deficiency in procollagen peptidase (cleaves terminal propeptides from procollagen in the extracellular matrix) Presents with Joint laxity, hyperextensible skin, fragile tissue

Kawasaki disease

Desquamating rash of hands and feet Fever longer than 11 days conjunctivitis cervical lymphadenopathy Oral lesions dry lips strawberry tongue

Long acting insulin

Detemir Glargine last 24 hours basal insulin

Hypoparathyroidism

DiGeorge syndrome 22q11 deletion 3rd and 4th pharyngeal pouch PW -Hyperphosphatemia -hypocalcemia -perioral numbness, numbness of hands and feet -Muscle cramps and twitchs -Trousseau sign (hand spasms when BP cuff) -Chvostek's sign (tapping facial nerve causing twitching)

Pulmonary artery catheters

Diagnosis of pulmonary hypertension Right atrium -> right ventricle -> pulmonary artery -> branch of pulmonary artery Ballon inflated, obstructs, creating a continuous static column of blood between the catheter tip and the LEFT ATRIUM This is called the pulmonary artery occlusion pressure (PAOP, or PCWP wedge presssure) that closely reflects LEFT atrial and left ventricular end-diastolic pressure

Emphysema

Diffuse bilateral wheezing Pink puffer Distant heart sounds Diminished lung sounds FEV1 goes down a lot Increased PaCO2 from trapped air, less PaO2, -> vasoconstriction and pulmonary hypertension

Membranous glomerulopathy

Diffuse thickening of the glomerular basement membrane Autoantibodies against phospholipase A2 receptor on Podocytes -> leads to subepithelial deposits -> Spike and dome pattern!! (basement membrane reaches out and engulfs immune complexes) Can be secondary to viral infections (Hep B and C) Can be caused by many chronic diseases Immunofluorescence leads to granular deposits along the basement membrane

Class V antiarrhythmic

Digoxin -increases AV node refractory rate -rate control, prevents rapid ventricular response to A fib of flutter -Direct parasympathetic activity via stimulation of the vagus nerve - Adenosine -interacts with A1 receptors on myocardium and the SA and AV nodes -activation supresses inward calcium current -> hyperpolarization -activation increases K+ outward current -most inhibitory effects at AV node (increased refractory period, decreased conduction) -high grade heart block -first line agent for acute supraventricular arrhythmias (PVST) -A2 receptor activation dilates coronary arteries -SE -Sense of impending doom -Cutaneous flushing -Shortness of breath -Chest pain -headache -hypotension Magnesium -treats torsades Potassium -hypo or hyperkalemia can cause arrhythmias -hyperkalemia -> peaked T wave -hypokalemia: renal abnormalitites, severe muscle weakness, glucose intolerance, ECG: U wave at the end of the T wave

Hydronephrosis

Dilated renal pelvis and ureter blocking of the tubes -> stagnant urine -> UTIs Pressure back up -> pressure atrophy -> renal papillary necrosis Can be diagnosed with Ultrasound -enlarged kidneys Vesicoureteral reflux can lead to hydronephrosis -perpendicular insertion into bladder increases chances -> also more UTI's Iatrogenic Striking flank pain -> stones Urolithaisis -> gross hematuria BPH!!!!!

Gastic varicies

Dilated veins in fundus of stomach -> splenic vein thrombosis RF -chronic pancreatitis Portal hypertension can cause

Phosphodiesterase inhibitors

Dipyridamole cilostazol - treats claudication due to peripheral artery disease Increases cAMP -impairs function of platelets

Flutamide

Directly blocks testosterone receptor competitive binding Cyproterone and spironolactone have same MOA

Pramipexole

Directly stimulates dopamine receptors Used in parkinson's initial treatment Dopamine agonist D3 dopamine receptor Tx -parkinsons -restless leg syndrome

Amyloidosis

Diseases caused by aggregations of misfolded proteins Beta sheets that clump green birefringence on congo red stain Amyloid can deposit in the glomeruli -progresses to total obliteration of the glomerulus -nephrotic syndrome cardiac amyloidosis -pink homongenous material autonomic neuropathy numbness liver involvment causes massive enlargement -spleen too can deposit in vessels and make them fragile -> trauma Can deposit in -lung -joints -nerve and cause carpel tunnel -neurologic Causes -multiple myeloma Reactive systemic amylodosis -AA amyloids made up of SSA fragments -after inflammation Hemodialysis amylodiosis -beta-2 microglobin (component of MHC 1) -happens in people with kidney disease that cant filter it -commonly affects osteoarthritic surfaces -carplle ligament of wrist Senile cerebral amyloidosis -accumulation in brain -Abeta amyloid extracellular in brain derived from AAP -cerebral amyloid angiopathy -> spontaneous cerebral hemorrhage Heritable amyloidosis -Familial mediterranean fever -autosomal recessive -constititively active PYRIN gene that results in chronic inflammation -causes reactive amyloidosis -Familial amyeloidotic polyneuropathy -motor, sensory, or autonomic neuropathy -can deposit in myocardium

Golgi apparatus

Distribution center -proteins and lipids from the ER enter, are modified, and sent to vesicles and plasma membrane Modifies -N-oligosaccarides on asparagine -O-oligosaccarides on serine and threonine Mannose-6-phosphate to proteins = trafficking to lysosomes

Laxative

Does not directly stimulate GI motility Osmotic laxatives -non or poorly absorbable materials that draw water into the lumen, distend the colon, and facilitate peristalsis Bulk-forming laxative -indigestible hydrophilic colloid -> absorbs water -> distention -> peristalsis) Stool softener -surfactant agent that stimulates penetration of stool by water and lipids AE -diarrhea -dehydration

Clinical trial phases

Does the drug SWIM? Phase 1 - small number of healthy volunteers or patients with disease of interest -is it SAFE -Assess safety, toxicity, pharmacodynamics, and pharmacokinetics Phase 2 - Moderate number of patients with disease of interest -does it WORK? -Assesses treatment efficacy, optimal dosing, and adverse affects Phase 3 - Large number of patients randomly assigned either to treatment under investigation or to the best available treatment (or placebo) -is it an IMPROVEMENT? -compares the new treatment to the current standard of care Phase 4 - Postmarketing surveillance of patients after treatment is approved -Can result in treatment being withdrawn from MARKET -detects rare or long-term adverse effects

Bacterial DNA polymerase III

Does traditional replication in the 5' -> 3'

Renal blood flow autoregulation

Done mostly through afferent arteriole constriction

HPV

Double stranded naked DNA virus 1-4: verruca vulgaris = cutaneous common wart 6,11 - low risk -condyloma acuminata: anogenital warts -recurrent respiratory papillomatosis (laryngeal papillomatosis) 16, 18, 31, 33 - HIGH risk associated with anogenital squamous cell carcinomas HPV vaccine covers 6, 11, 16, 18 Gardasil - inactivated subunit vaccine HPV proteins E6: proteolysis of p53 E7: proteolysis of Retinoblastoma protein Post-coital bleeding -> cervical carcinoma Koilocytes immunosuppressed people are more at risk

Tissue nematodes

Dracunculus medinensis: -Dracula -Infection by drinking contaminated water that contains copepods containing larvae -painful skin ulcer from which adult worm emerges -Pull out worm slowly with matchstick LOL -Metronidazole can speed it up but doesn't do much -eosinophilia Onchocerca volvulus: -Fly man -Rivers in africa, central america, and south america -fly bites skin and deposits larvae -scattered puruitic papules that can become hyper or hypo pigmented -River Blindness -larvae can get to eye and cause blindness -eosinophilia -Ivermectin Wuchereria bancrofti: -elephantitis -long standing lymphedema -Lymphadenopathy -transmitted by mosquitos -organisms seen on thick blood smear -eosinophilia -TREATMENT: Diethylcarbamazine Toxocara canis: -wolfman -dog or cat feces -parasitic larvae get into human and dont mature, they continue to circle in the body -larvae can cause blindness if they get to the eye -larvae migrans -Albendazole Loa loa: -Edema -local subcutaneous swellings -larvae can be seen in conjunctiva -African eye worm -Blood smear -transmitted by deer flies -eosinophilia -Treatment: diethylcarbamazine -albendazole

SMA syndrome

Duodenom is compressed between aorta and SMA

Aortic regurgitation

Dystrophic calcification Tertiary syphilis Giant cell arteritis Takayasu's Marfan, Ehlers-Danlos (collagen disorders) Compensatory eccentric hypertrophy Lower than normal diastolic pressure (blood going back into ventricle) High systolic due to compensatory SV increase de Musset sign (head bobs due to wide pulse pressure) Blowing decrescendo murmur best heard at the left sternal border in the 3rd or 4th ICS

Acute interstitial nephritis

Edema Eosinophilia Eosinophiluria White blood cell casts Oliguria BUN and creatinine elevated Fever

Silicosis

Eggshell calcifications Calcifications of the rim of hilar nodes Impairs macrophage function -increased risk of TB

Prostaglandin analogues

Endogenous prostaglandins produced by COX-1 and COX-2 alprostadil -injections for ED -PGE1 analogue -vasodilator Misoprostol -promotes mucus secretion -high doses can prevent gastric acid secretion -promotes uterine contraction -> category X teratogen -bad AEs, diarrhea and abdominal pain Dinoprostone -promotes uterine contraction PGF-2alpha -latanoprost -travoprose -used in glaucoma

volatile anesthetics

Enflurane Isoflurane Halothane -> highly soluble, slow onset, slow recovery all are fluorinated AEs -decrease respiration -decrease cerebral blood flow -halothane can be hepatotoxic -enflurane can be nephrotoxicity and cause convulsions -MALIGNANT HYPERTHERMIA

Streptokinase

Enhance plasminogen -> plasmin -> cleaves fibritic clot Can cause anaphylaxis, very rare

Low molecular weight heparins

Enoxaparin, deltaparin, tenzaparin Same MOA as heparin (binds antithrombin III) -inhibits factor Xa with less of an effect on thrombin Long half life, easy to administer Does not require routine monitoring Renal elimination Less likely to cause HIT Good for early stages of pregnancy Do not cross placenta short elimination time Protamine sulfate does not work as well on LMWH

Rabies virus (Rhabdovirus)

Enveloped Bullet shaped virus Helical capsid Squirrels, skunks, foxes, bats, raccoons Binds to nicotinic acetylcholine receptors in the postsynaptic membrane of neuromuscular junction Travels in retrograde direction along peripheral nerves Travels to the dorsal root ganglia to get access to CNS Increased salivary production Excruciating spasm of the muscles of the pharynx -> dysphagia These two make the crazy drooling appearance Rabies encephalitis Fever Negri bodies in neurons - eosinophilic cytoplasmic inclusions in purkinje cells of hippocampus or hippocampus Killed vaccine should be given after being bitten to develop active immunity Also give preformed antibodies (passive immunization)

Alcoholic hepatits

Ethanol -> acetaldehyde (NAD+ converted to NADH) -impaired beta oxidation from low NAD+ Acetaldehyde -> acetate (NAD+ -> NADH) -> chronic shortage of NAD+ results in fatty acid buildup in the liver (steatosis) alcohol is most common cause -reversible if alcohol stops Micro and macrosteatosis -macro -> nucleus is pushed to the periphery of cell Zone 3 is the area first to develop fatty change (central lobular zone) -> steatohepatitis! Neutrophil influx in response to inflammation Hangover caused by buildup of acetaldhyde CYP450 will detoxify too when its high Alcoholic hepatitis is usually reversible -> can progress to cirrhosis -> hepatocellular carcinoma Histology -Filament clumping due to damage -Mallory bodies (eosinophilic clumped intermediate filaments) -hepatocytes ballon and swell -fibrosis will start near central vein (zone 3) PW -Fatty liver -large painful liver -fever -leukocytosis -AST and ALT elevated (AST/ALT is high, 2:1) -elevated GGT -

Systemic sclerosis

Excessive fibrosis in multiple tissues Characteristic autoantibodies -Anti-DNA topoisomerase 1 (Scl-70) Also called scleroderma because of skin involvement Raynaud's CREST syndrome in limited sclerosis -Calcinosis cutis -Raynaud -Esophageal hypomotility -Sclerodactyly -Telangiectasias (cutaneous lesions formed by dilated blood vessels, especially on the face, upper trunk, and hands Subset -limited systemic sclerosis (usually restricted to hands and face -diffuse systemic sclerosis (rapid progression, visceral and skin involvement) Diffuse -Sclerodactyly -> progressive fibrosis of hands and fingers -perivascular lymphocytic infiltrate -fibrosis throughout the dermis -nodular subcutaneous calcifications Likely result of genetic and environmental factors -lol -may involve endothelial damage (viral or toxic) -> release of self-antigens -> self-reactive lymphocytes IL-13 and TGF-beta -activate fibroblasts -deposit collagen -repeated events lead to intimal fibrosis and narrowing of the lumen Pulmonary fibrosis Increased renin and angiotension due to decreased renal perfusion

Paget's disease

Excessive osteoclast activity followed by compensatory increased osteoblast activity Hearing problems because of skull deformities Mixed sclerosis and lucency on scan M-CSF and RANK-L important for differentiation

Interferon gamma

Exert antiviral effects immunomodulatory molecules released from virally infected cells Tx -CGD AEs -Flu like symptoms

Interferon beta

Exert antiviral effects immunomodulatory molecules released from virally infected cells Tx -relapsing type MS AEs -flu like symptomes

Interferon alpha

Exert antiviral effects immunomodulatory molecules released from virally infected cells Tx -Hep B -Hep C -Hairy cell leukemia -malignant melanoma -Kaposi sarcoma -condyloma accuminata caused by HPV -RCC AEs -flu like syndrome -myalgias -malase -myelosuppression -lupus

Liver angiosarcoma

Express CD 31 (PECAM1, platelet endothelial cell adhesion molecule) Related to arsenic exposure, and polyvinyl chloride

1-3 days post MI

Extensive coagulation necrosis Even more neutrophils Lots of pale blue lymphocytes between cardiomyocytes Early onset pericarditis Inflammation overlies area of necrosis only generally short-lived

Juvenile acromegaly

Extremely tall stature Pituitary gigantism Andre the giant PW -macrognathia -macrocephaly -macroglossia -hypertrophy of oralpharyngeal soft tissues -big hands and feet -frontal bossing -visceromegaly -hypertension -LV hypertrophy -aortic regurgitation -hypogonadism due to high prolactin Sequelae -increased polyp and colorectal cancer GHomas are made up of mammosomatotroph cells -> prolactin is high too -> hypogonadism etc

Hemophilia A

Factor VIII deficiency X-linked recessive -> almost exclusively in men Disrupts intrinsic and common pathway (decreased activation of factor X) Bleeding into joints, intramuscular bleeding, intracranial bleeding Dental procedures can cause hemorrhage factor XIII levels have to get to 5% to get bleeding, and 1% to get severe bleeding Getting several transfusions can lead to autoantibodies against factor VIII SLE can make antibodies to VIII -> acquired hemophilia Penicillin can cause anti-factor VIII antibodies -Mixing study: normal serum added to patients serum -> antibodies inactivate factor VIII -> aPPT does not correct Treat: 1. Desmopressin -induces platelets and endothelial cells to release factor 8

Tracheoesophogeal fistula

Failure of septation H type -tube connecting type C -esophogeal atresia -distal esophogus grows out of trachea -undigested non-bilious vomit -abdominal distension from air flow into stomach -aspiration type pnemonia -polyhydramnios because baby cant swallow VACTERAL associate -vertebral -anal -cardiac -tracheoesophageal fistual -renal -limb

Colonic diverticula

False diverticula (dont invovle all layers) Most common in sigmoid colon RF -Chronic constipation Diverticular bleeding -painless hematochezia -vasa recta injury Diverticulitis

Brucella spp.

Farm animals reservoir gram - bacteria recent consumption of milk and cheese facultative intracellular Fever (undulate) chills anorexia Enlargement of spleen, liver, and lymph nodes Osteomyelitis (chronic brucella infection) Treatment: Doxycycline + rifampin

West Nile Virus

Febrile viral illness Rash Neurologic manifestations Encephalitis FLACCID PARALYSIS RNA flavivirus transmitted by mosquitoes

Giardia lamblia

Fecal oral transmission of cysts Poorly purified drinking water -foul smelling diarrhea -Steatorrhea from stimulating massive mucus production that impairs absorption Distinct trophozoite stage -flagellated pear shaped, smiley face lookin' ass boy -attach to intestines -hikers and campers -presence of trophozoites in stool is diagnostic -O&P: ovas and parasites in stool -ELISA test to detect stool antigen -Metronidazole

Opiates

Fentanyl - postoperative and chronic pain Tramadol (weak agonist, also inhibits norepinepherin and serotonin reuptake, good for neuropathic pain) Morphine Hydromorphone act at mu-opioid receptor g proteins -in neurons, causes potassium channels to open causing hyperpolarization -also closes voltage gated calcium channels -> prevalence release of pain signals to brain (e.g. glutamate, acetylcholine, norepinephrine, serotonin, substance P) causes -analgesia -sedation -cough suppressant (codeine is like da best, dextromethorphan too -> NMDA receptor antagonism) AEs -respiratory depression -> respiratory acidosis -constipation!!!!!!!!!!!!!!!!!!!!!!!!!!!! -miosis -opiate induced hyperalgesia with chronic use -Contraction of smooth muscle cells of the sphincer of Oddi -> spasm and an increase in common bile duct pressures Tolerance to everything but constipation and miosis Opioid withdrawal -rhinorrhea -lacrimation -yawning -hyperventilation -hyperthemia -muscle aches -vomiting -diarrhea -anxiety

Neisseria meningitidis

Ferments Maltose (specific to this neisseria species) First colonize nasopharynx Polysaccharide capsule (vaccine uses this, type b not included) Patients with sickle cell are more susceptible LOS proteins -> bleb off organism and cause massive inflammatory response -> leaky capillaries -> hypovolemia -> shock Adrenals can infarct from vasoconstriction (WATERHOUSE-Friderichsen syndrome) Thrombocytopenia leading to DIC Third generation cephalosporin- ceftriaxone Close contacts prophylaxis -> rifampin

Dementia

Frontal areas affect behavior temporal is more speech Frontotemporal type is heritable -50's-60's -speech affected -Pick bodies!! -hyperphosphorylated tau -intracellular inclusions -TDP-43 (abnormal ubiquitination) accumulates -PW -language distrubance -behavioral changes -hyperorality Vascular dementia -multiple ischemic infarcts to the brain takes a toll on cognitive ability -every subsequent event progresses dementia HIV-related dementia -predominantley in untreated patients with advanced diseases -inflammatory activation of microglial cells -multinucleated giant cells from microglial fusion -neuronal damage as a result of cytokines

Transketolase

Fructose-6-phosphate -> ribose-5-phosphate Nucleic acid synthesis Pentose phosphate pathway

Iron metabolism

Function iron -in hemoglobin and enzymes -2/3's of total iron Stored Iron -ferritin -hemosiderin -in bone marrow macrophages Iron absorbed in duodenum -stored in duodenal enterocytes in the form of ferritin -transported into the blood through feroportin -binds to transferrin in the plasm -liver senses increased iron and releases hepcidin (inhibits further iron absorption, locks iron INCIDE cells)

Corticosteroid biosynthesis

G -> Aldosterone F -> Cortisol R -> Testosterone ACTH stimulates desmolase -> cholesterol to pregnenolone PREGNENOLONE IS GODFATHER ADRENAL MOLECULE precursor to all adrenal hormones 17-hydroxylase is uppermost in pathway and can move things left to right Glomerulosa pregnenolone -> progesterone (from 3-beta hydroxysteroid dehydrogenase) progesterone -> 11-decorticosterone (21-hydroxylase) -> corticosterone (11-hydroxylase) -> aldosterone (via 18-hydroxylase) angiotensin II dependent) Fasiculata pregnenolone -> 17-hydroxypregnenolone (17-hydroxylase) -> 17-hydroxyprogesterone (3-beta hydroxysteroid dehydrogenase) -> 11-deoxycortisol (21-hydroxylase) -> cortisol (11-hydroxylase) Reticularis pregnenolone -> 17-hydroxypregnenolone (17-hydroxylase) -> DHEA (17-hydroxylase again) -> androstenedione (3-beta hydroxysteroid dehydrogenase) -> testosterone (oxidoreductase)

Pegvisomant

GH antagonist treats acromegaly, giantism

GIST

GI stromal tumor From interstitial cells of Cajal gain of function mutations in c-KIT (tyrosine kinase) Well circumscribes, fleshy, mucosal tumors

Endoderm

Gastrointestinal tract Liver Pancreas Lungs Thymus Parathyroids Thyroid follicular cells Middle ear epithelium Bladder Urethra

E. Coli

General: Lactose fermenter - pink on MacConkey agar Encapsulated K antigen in capsule used for serotyping Green on EMB agar Catalase positve Fimbrae - needed for UTI #1 cause of UTIs Leading cause of gram - sepsis Neonatal meningitis is it has K capsule ETEC: Traveler's diarrhea trasmitted by water recent travel to mexico Montezuma's revenge heat labile -> increases cAMP heat stabile -> increases cGMP Watery diarhhea EHEC: Hemorrhagic undercooked hamburger bloody diarhhea Doesn't ferment sorbitol Shiga like toxin -> Hemolytic uremic sydrome (shiga-like toxin damages epithelial cells of glomerulus, causes aggregation of platelets that then lyse RBCs as they pass by O157:H7

Vasculitis with granuloma formation

Giant cell arteritis Takayasu's arteritis

Treatment resistant schizophrenia

Give clozapine

Antithrombin III deficiency

Give direct thrombin inhibitors (-rudin and -gatran suffixes -heparin will not work obviously

Nitroprusside toxicity

Give sulfur containing compounds Sodium thiosulfate Helps get rid of cyanide toxicity

Raloxifene

Given for: Postmenopausal osteoporosis AE: Hot flashes Venous thromboembolism Mixed agonist/antagonist

Small bowel Adenocarcinoma

Glandular structures Duodenum RF -lynch syndrome -familial adenomatous polyposis -Peutz-Jeghers syndrome (AD mutation in tumor suppressor gene) multiple non-neoplastic hamartomatous polyps throughout the GI system) -Crohn's disease

Clostridium tetani

Gram + Obligate anaerobe Spore forming Puncture wounds Reservoir is in soil Spastic paralysis Risus sardonicus - "evil grin" or lockjaw symptoms Tetanus toxin travels retrograde to the spinal cord Protease that cleaves SNARE Gaba and glycine are inhibited, uncontrolled firing of neurons Renshaw cells Vaccine is toxin conjugated to protein

Corynebacteria diptheriae

Gram + Y or V shape metachromatic Toxin has two subunits, A and B: A is active, B is binding causes ADP ribosylation of elongation factor 2 Pseudomembranes in oral mucosa Lymphadenopathy so strong that it makes neck look thick - bulls neck Cardiotoxic - myocarditis, arrhythmia, heart block Can damage the myelin of nerves need to culture or do toxin assay to diagnose Tellurite agar Elek's test - IMMIGRANTS, most are vaccinated Toxoid vaccine routinely administered in US

Nocardia asteroides

Gram + Filamentous branching rod Obligate AEROBE Soi reservoir Acid fast stain stains a bit, mycolic acids, carbolfuchsin stain Catalase positive (chronic granulomatous disease - cant deal with catalase positive as much) Urease positive Men more than women affected symptoms: Immunocompromised (impaired cell mediated immunity) Pulmonary- pneumonia with lung abscess formation, cavitary lesions in lung, disseminates from here CNS- affinity for neural tissue -> brain abscesses Cutaneous- indurated lesions Treatment: Sulfonamides!!!

Pasteurella multocida

Gram - Catalase positve Oxidase positive Encapsulated Grows well in 5% sheep blood agar Safety pin staining Found in respiratory tract of small animals (cats and dogs, bites can transmit) Cellulitis occurs 24 hours after bite Osteomyelitis Treatment: Penicillin usually use beta lactam to prevent resistance

Yersinia enterocolitica

Gram - Transmitted through puppy feces Toddlers commonly infected -> puppy poop and contaminated milk products Cold resistant Diarrhea (bloody) Can mimic appendicitis Tetracyclines!

Neisseria species

Gram - diplococci Oxidase positive Heated blood agar - chocolate agar to culture VPN agar (Thayer martin agar) Patients with deficiency MAC complex are particularly susceptible Virulence factors: Pilus - antigenic variation

Pseudomonas aeruginosa

Gram - rod encapsulated catalase positive Blue and green pigment - biocidin pyoverdine ( can even turn wounds blue) fruity, grape-like odor Obligate aerobe Cystic fibrosis respiratory failure pneumonia osteomyelitis - IV drug users and diabetics Burn patients indwelling catheter infections (nosocomial UTI's) Skin lesions: Pruritic, papular pustular folliculitis (hot tub folliculitis) Sepsis -> toxin that causes cutaneous necrosis (ecthyma gangrenosum) Otitis externa -> swimmers ear -Malignant otitis externa seen in ELDERLY DIABETIC PATIENTS Exotoxin A -> ribosylation of elongation factor 2 Treatment: Piperacillin + tazobactam Aminoglycosides (can be used in combination with beta lactams) fluoroquinolones (UTIs)

Bartonella Henselae

Gram -, but you need warthin starry stain Cat scratch disease fever can also involve regional lymph nodes - painful large nodes in axilla Immunocompetent bacillary angiomatosis Immunocompromised raised red vascular lesions all over skin Kaposi's sarcoma is very similar, both present with red lesions skin biopsy and stain will make bartonella distinciton Doxycylin Azithromycin can be used Macrolides

Gardnerella vaginalis

Gram variable rod Grayish-white discharge with fishy odor that comes out of vulva pH > 4.5 KOH Whiff test Metronidazole

Somatotropin

Growth hormone JAK tyrosine kinase / STAT pathway Insulin-like growth factor mediates the growth promoting effects of GH Anabolic effects in muscle Catabolic effects in adipose cells Only really helps growth in those with GH deficiency Tx -GH deficiency -Idiopathic short stature in kids -Prader-Willi syndrome -Turner syndrome

D1 receptor

Gs coupled

Chronic gastritis

H. pylori infection -Can cause acute and chronic -Spreads from the antrum to the body of the stomach -inflammation of gastric mucosa -mucosal atrophy -> chronic atrophic gastritis -> metaplasia -> gastric mucosa to goblet cells (more intestinal like) -> MALT -appear blue due to lymphocytes -> can transform into gastric lymphoma -Urease test to see if infected -urea breath test Autoimmune destruction of parietal cells and intrinsic factor -> decreased secretion of gastric acid -> hyperplasia of G cells -> more gastrin -> megaloblastic anemia Gastric cancer

Histamine reactions

H1 receptor coupled to Gq protein Histamine increases nasal and bronchial mucus production -increases vascular permeability -constriction of bronchioles Type 1 hypereaction -urticaria -bronchoconstriction -

Supine hypotension syndrome

Happens in pregnant women When lying supine, uterus is right on top of IVC and compresses it -> less blood return to the heart

Ventricular wall aneurysm

Happens over fibrotic scar tissue 4-18 weeks post MI Can cause systolic heart failure (CHF) Wont rupture Increases chance of arrhythmias Cant cause clots and throw thrombi

ARDS

Happens usually shortly after an inciting event -could be acute pancreatitis to chest pain hypoxemia -not corrected with oxygen supplementation bilateral diffuse crackles Pulmonary edema 1. pressure increase causing leakage 2. damage to capillaries themselves -left sided heart failure causing backup -mitral stenosis causing increased left atrial pressure -fluid overload (CHF, renal failure) TRALI -transfusion related acute lung injury -happens within 6 hours of transfusion -moa not well understood Neutrophils release reactive oxygen species proteases -damage to capillary endothelium causes bloody cellular protein rich exudate to fill alveoli (ARDS exudative phase) -injury to type II pneumocytes causes decreased surfactant -> alveolar collapse (atelectasis) Diffuse hyalin membrane line the small airways -exudate mixing with cellular debris Proliferative phase -type II pneumocytes proliferate -pulmonary edema resolves -resynthesis of surfactant and differentiation into type I pneumocytes -> replenished endothelium BNP in CHF, NOT ARDS, use to distinguish -also usually see S3 and S4 in CHF, not ARDS

Angelman Syndrome

Happy puppet syndrome Jerky, wide-based gait ataxia Seizures Inappropriate outbursts of laughter Mental retardation Deletion in MATERNALLY derived chromosome 15

Hawthorne effect

Hawthorne is a pretentious man -get over yourself observer bias people change their behavior when they know they are being observed screw hawthorne

Neonatal vitamin K deficiency

Healthy children need vitamin K supplementation presents with: ICH -> ICP -> enlarging head circumference, bulging fontanel, downward-driven eyes

Cryptococcus neoformans

Heavily encapsulated main virulence factor making them unable to be phagocytized Pigeon droppings Soil Enters through inhalation and Urease positive Cough, dyspnea, and other serious lung infections Can spread to CSF and cause meningitis MOST COMMON CAUSE OF FUNGAL MENINGITIS -Fever -cryptococcal pneumonia -meningitis Bronchopulmonary washings that are stained with mucicarmine (red) or methenamine silver stain Lumbar puncture and india ink for CSF suspicion -Cryptococcal yeast with halos Latex agglutination test to detect polysaccular capsular antigen CSF pathology -soap bubble lesions in the gray matter of the brain Treatment: Joint therapy with amphotericin B and Flucytosine, followed by Fluconazole

Vitamine A supplementation

Helps in measles infections Protects against eye damage Measles deplete vitamine A stores

Nephritic syndrome

Hematuria (tea or cola colored urine) -RBC casts (dysmorphic RBCs and casts = glomerular bleeding) Periorbital edema Proteinuria (usually around >150mg/day, not 3.5 grams like nephrotic) Immune complex deposition -mostly deposit at the subendothelial or mesangial layer -granular -> local activation of complement cascade -> C5a chemotactic agent -> neutrophils -leads to low C3 -> glomerular capillary damage that leads to hematuria and AKI BUN rises Creatinine rises Oliguria

Sickle cell disease

Hemoglobin S (HbS) Missense mutation in the BETA globin gene (on chromosome 11) Glutamic acid -> valine (increases hydrophobic interaction between hemoglobin molecules -> polymerize and overlap) Deoxy form polymerizes, so under low oxygen concentrations more polymerizing will happen -acidosis (makes hemoglobin give up its oxygen -> deoxy -> polymer) RBC can recover after polymerization, but it can only go thru these cycles so many times Mostly extravascular hemolysis and some intravascular Autosomal recessive Severity depends on number of HbS copies -1 affected allele -> sickle cell trait, very little hemolysis and anemia. Under EXTREME circumstances significant sickling can occur -if combined with another hemoglobin deficiency it can present like sickle cell disease -2 copies -> sickle cell disease -happens after 6 months of age, when shift from hemoglobin F to S is complete -sickle cells adhere to each other -spleen become congested and swells early in childhood -Howell Jolly bodies (purple dots of old DNA in RBC cytosol) due to splenic fatigue (spleen usually is all over this easy peasy) -Autosplenectomy by adulthood -> encapsulated bacteria can't be captured and engulfed -splenic sequestration -> large blockage in spelnic circulation -> tender spleen -> hypotension -Aplastic crisis (infection with parvovirus B19) -Reticulocyte count is HIGH in splenic sequestration, LOW in aplastic crisis -vasoocclusion -permanent necrosis and deformity of hands and feet -avascular necrosis of femoral head -Acute chest syndrome -> respiratory distress, severe chest pain, can be fatal -ischemic stroke -Priapism if penile veins are occluded -hematuria due to vaso occlusion and small infarcts in kidney -extramedullary hematopoiesis -> chipmunk facies and crew cut appearance Electrophoresis -Sickle cell trait -primarily HbA1 band, smaller HgS band -Sickle cell DISEASE -primarily HbS -No HbA1 -HbF Treatment -hydroxyurea -> increases HbF (activates expression of gamma subunit gene)

Wilson disease

Hepatocytes cannot transport copper into bile for excretion Mutation in hepatocyte copper-transporting ATPase Serum ceruloplasmin is low (normally transports copper in blood) -> deposits in tissue -> makes total serum copper low Kayser-Fleischer rings -coppos colored rings encircling periphery of iris Half of patients will have hepatosplenomegaly and cirrhosis Can cayse -hemolytic syndrome -dysarthria -parkinsonian symptoms -hemi ballismus PW -urine copper elevated -Kayser-Fleischer rings -low serum copper -low ceruloplasmin Treat with -penicillamine (chelates in gut)

Osler-Weber-Rendu syndrome

Hereditary hemorrhagic telangiectasia Recurrent severe nose bleeds GI bleeding Hematuria Autosomal dominant Congenital telangiectasias to the skin and mucous membranes Mucosal involvement affects the lips, oronasopharynx, respiratory tract, gastrointestinal tract, or urinary tract Rarely can occur in the brain, liver, and spleen

Lynch syndrome

Hereditary nonpolyposis colon cancer Increases the risk of EPITHELIAL ovarian, colon, and endometrial cancer

Epstein-Barr virus

Herpesviridae Double stranded DNA Infectious mononucleosis Primarily transmitted through saliva Tender lymphadenopathy Reactive cytotoxic CD8+ T cells Atypical lymphocytes Splenomegaly due to T-cell proliferation Targets B lymphocytes in new infection EBV remains latent in B cells Binds to CD21 to infect B cells Pharyngitis and tonsil exudates Mono is usually asymptomatic in children People with mono who get treated with Amoxicillin or ampicillin and causes a maculopapular rash, not allergic, mechanism not fully understood B cell lymphoma Hodgkin's lymphoma - Reed-Sternberg cells that look like "owl's eyes" Endemic Burkitt lymphoma - large lesion in the jaw Sporadic Burkitt lymphoma - T(8:14) Nasopharyngeal carcinoma associated with asian EBV patients Oral hairy leukoplakia - most common in HIV, not a precancerous lesion EBV secretes anti-sheep IgM (monospot test) Mainly supportive therapy They cannot play contact sports due to splenic rupture

Varicella-zoster virus

Herpesviridae Enveloped DNA virus Respiratory droplet transmission Chicken pox Shingles- reactivation occurs with stress, immunocompromised, age vesicular, itchy rash on face and trunk in combination with the rash pattern as a mixture of lesions occurring in crops "dew drops on a rose petal" Lesions usually in different stages of healing Extremely painful rash Postherpetic neuralgia - pain after the rash subsides Remains latent in dorsal root ganglia Herpes Zoster Ophthalmicus - vision loss possible if V1 dermatome affected Congenital varicella syndrome -Limb hypoplasia -cutaneous scarring in a dermatomal pattern -blindness Tzanck smear of the base of a vesicle may demonstrate multinucleated giant cells Live attenuated Zoster vaccine -can give to AIDS patients if CD4 > 200 Acyclovir Famciclovir treatment for shingles Valacyclovir

Tay-Sachs disease

Hexosaminidase A deficiency -> accumulation of GM2 ganglioside (cell membrane glycolipid PW -progressive neurologic deterioration -weakness -seizures -blindness -spacsticity -macrocephaly -cherry-red macula spot

Respiratory alkalosis

High pH Low PaCO2 Causes -high altitude (low O2 -> stimulate breathing -> blow off CO2) -aspirin (directly stimulates respiratory centers)

Metabolic alkalosis

High pH Serum bicarb is high Body tries to compensate with -respiratory acidosis Causes -vomiting (loss of HCl from stomach -> retention of bicarb) -diuretics (reabsorption of sodium and chloride are reduced -> exchanged for H+ in collecting tubule -> H+ excreted -chloride excretion too -(isotonic saline rescues both) -aldosterone leads to H+ excretion and Na+ resorption -> alkalosis if its too high Gotta check urine chloride -Low = vomiting/ nasogastric aspiration or prior diabetic use -High: ->current diuretic use -> Bartter & Gitelman syndromes -> excessive mineralocorticoid activity (primary hyper aldosteronism, Cushing disease, ectopic ACTH production)

Urticaria

Hives Transient hypersensitivity IgE-mediated degranulation of mast cells On biopsy: Edema of the superficial dermis

Epinepherine

Hormone Acts on all A1, A2, B1, B2 Beta > alpha -especially at low doses Effects -decreases diastolic pressure at low doses, increased doses increase Tx -first line for anaphylactic shock

Congenital kidney diseases

Horseshoe kidney -Turner's syndrome (10%) -More likely to get Wilms tumor -Kidney gets caught on first median blood vessel as it ascends -increased risk of kidney stone Renal Agenesis -no kidneys! -if only one, asymptomatic -Potter's sequence due to no amniotic fluid -most die right after birth due to respiratory distress Hematuria and stones and UTI's Renal dysplasia -can even have bone and cartilage in kidney

Pityriasis versicolor

Hot, humid conditions, worse after tanning Malassezia yeast species spaghetti and meatball appearance on light microscopy KOH prep Damages melanocytes through lipolysis Stays in the stratum corneum Immunocompromised: Neonates receiving TPN Lipid infusion where the fungus grows and then enters the body systemically Selsun blue! - selenium sulfate

Gestational diabetes

Human placental lactogen (secreted by syncytiotrophoblast) Increases insulin resistance in the mother -> increases glucose delivery to fetus Delivery resolves after baby (more specifically placenta) is gone increased risk of DM type 2

Actinic Keratoses

Hyperkeratosis Parakeratosis (retention of nuclei in the stratum corneum) atypical keratinocytes may have pigmented irregularities and dialated blood vessels Small percentage will progress to SCC

Hyperthyroidism

Hypermetabolic state -> Hyperthermia, weight loss, flushed skin, muscle weakness (proximal), sweating, heat intolerance Sympathetic overstimulation -> increased beta receptors, direct sympathetic effect of thyroid hormone -deer-in-headlights or staring gaze from overstimulation of eye muscles -increased cardiac contractility, tachycardia, palpitations -systolic hypertension PW -brisk, exaggerated deep tendon reflexes -increased gut motility -increased bone resorption leads to hypercalcemia, osteoporosis -can lead to life threatening thyroid storm (thyrotoxicosis) -> fever, tachycardia, vomiting, diarrhea, CNS dysfunction. Can be caused by discontinuing meds, surgery, infection, etc. Tx with antiadrenergic drugs (alpha blockers before beta), propylthiouracil, potassium iodide, and corticosteroids. Toxic adenomas can secrete T4 without TSH stimulation -> surgery or radioactive iodine

Hypercalcemia

Hyperparathyroidism!! -Stones, moans, groans -adenoma -Secondary -> CKD (hyperplasia can go wrong and cause hypersecretion) Ectopic malignancy -Ectopic PTHrP production -Squamous cell lung cancer -renal cell carcinoma -Low endogenous PTH because of calcium inhibition -no lytic lesion Secondary to osteolytic mets -breast -squamous cell lung cancer -multiple myeloma!! Familial hypocalciuric hypercalcemia -renal calcium receptors -autosomal dominant -kidney cant see calcium levels -> just ramps up and reabsorbs calcium -low 24 hour calcium excretion with hypercalcemia -thiazides can cause a mild hypercalcemia Toxic ingestion of vitamin D Granulomatous diseases Sarcoidosis

Menetrier's disease

Hyperplasia of mucus-secreting cells results in decreased number of acid-secreting glands -> Decreased protein digestion Presents: Nasuea vomiting early satitey Melena hematemesis Increased risk of GASTRIC ADENOCARCINOMA

Narcolepsy

Hypocretin-1 and hypocretin-2 deficiency Cataplexy Recurrent lapses into sleep

HPA

Hypothalamus -Thyrotropin releasing hormone -Corticotropin-releasing hormone -somatostatin -dopamine anterior Pituitary -FSH -LH -ACTH -TSH -Prolactin -GH posterior pitutiary -ADH -oxytocin Adrenals

Tertiary adrenal insufficiency

Hypothalamus isn't secreting corticotropin releasing hormone causes -chronic steroid therapy -> chronic negative feedback RAAS function is preserved

Mediators of inflammation

IL-1 IL-6 TNF-alpha Main mediators

Giant cell arteritis

IL-6 Jaw claudication can cause blindness with thrombus to ophthalamic artery

Cavernous hemangioma complication

INTRACEREBRAL hemorrhage

Ketamine

IV anesthetic dissociative amnesia rapid induction Inhibition of NMDA receptor complex AEs -unpleasant emergence reactions -> vivid colorful dreams, hallucinations, out of body experiences

Etomidate

IV anesthetic rapid induction preserves cardiovascular stability after bolus injections MOA: GABA-A potentiate chloride current

Propofol

IV anesthetic rapid induction and maintenance Lipophilic rapidly enter brain and spinal cord -> rapid induction MOA: GABA-A potentiate chloride current

Clevidipine

IV calcium channel blocker Hypertensive crisis

Nicardipine

IV calcium channel blocker Hypertensive crisis

Isolated IgA deficiency

IgA secreting B cells cant develop most common (1/700 caucasians) Most are asymptomatic Recurrent sinopulmonary infections Anaphylactic reactions to transfusion reactions -Think IgA is foreign protein

Carbapenems

Imipenem Ertapenem Meropenem Doripenem anaerobic infections -peritonitis pseudomonas penetrates CSF hospital acquired pnemonia Usually used when bug proves resistant Inhibited by dehydropeptidases in the renal tubules -> give cilastin to prevent this resistant to even extended beta lactamases AEs -skin rash -lowers seizure threshold

Levodopa

Immediate precursor to dopamine Crosses the BBB L-DOPA -> decarboxylation (by dopa decarboxylase) to dopamine (dopa decarboxylase in periphery causes GI effects, and cardiac arrhythmias, and postural hypotension, plus behavioral changes -> hallucinations ect) -carbidopa prevents this Has a wearing off effect, when does winds down you can get bradykinesia) -response fluctuations Therapeutic window narrows as disease progresses AEs -Dyskinesia -choreoathetosis of face and distal extremities -Contraindicated in psychotic patients

Autoimmune diseases

Immune system inappropriately reacting to self antigen Certain HLA alleles are associated -Code for MHC antigen -HLA B27 -HLA Triggers -infection -molecular mimicry -drugs (procainamide, hydralazine, isoniazid) -cigarette smoke -> rheumatoid arthritis -intracellular contents that the immune system isn't usually exposed to (when cells lyse)

Mucor spp

Immunocompromised patients Diabetics spore inhalation DKA is most predisposing factor NON septate 90 degree angle branching (unlike aspergillosis which is acute) Cross shaped Likes to invade blood vessels and penetrate the cribriform plate of the skull to get to CNS Rhinocerebral mucopsycoses Black eschar on face Necrosis of nasal cavity and eyes Death is likely Treatments: surgical debridement of necrotic tissue Amphotericin B

Chronic granulomatosus disease

Impaired degradation of ingested microbes within the phagolysosome -life threatening infections -number of different genetic mutations - most common is X-linked recessive No NADPH oxidase!!! -No release of free oxygen molecules -> no superoxide -> minimal hydrogen peroxide -> minimal respiratory burst -Catalase positive organisms can break down hydrogen peroxide -> able to live in phagolysosome even better -Aspergillus, serratia, staph aureus GRANULOMAS!!! In any organs -Cause in CGD is unknown -impaired phagocytes release much more cytokines -> granulomas -hyperactive macrophages -> multinucleated giant cells Dihydrorhodamine flow cytometry test -presence of superoxide converts dihydrorhodamine to rhodamine (a fluorescent green compound) -CGD will have diminished color Nitroblue Tetrazolium test -Exposure of NBT to superoxide -> production of blue dye -CGD will have less or no blue substance

Essential tremor

Improves with alcohol use Tx -Propranolol (thought to work through central nervous system effects)

Kussmal breathing

In DKA to breathe off excess acetone

Burr cell

In Pyruvate Kinase deficiency bumpy cell membrane due to the stiff cell architecture

Chloride shift

In RBCs As bicarb diffuses out chloride diffuses in to maintain neutrality venous RBCs will have much lower chloride content

Kappa/lamda ratio

In a healthy individual, the total kappa to lambda ratio is roughly 2:1 in serum (measuring intact whole antibodies) or 1:1.5 if measuring free light chains. a highly divergent ratio indicative of neoplasm

Sickle-cell disease complications

In a patient with pain in a specific bone area, with fever, leukocytosis, predominance of neutrophils -> OSTEOMYELITIS not aseptic necrosis

Acromegaly

In adults -epiphyseal plates have closed -non-linear bone growth PW -macrognathia -macrocephaly -macroglossia -hypertrophy of oralpharyngeal soft tissues -big hands and feet -frontal bossing -visceromegaly -hypertension -LV hypertrophy -aortic regurgitation Sequelae -increased polyp and colorectal cancer Diagnosis -oral glucose test (usually suppresses GH, in tumor GH will not decrease) Tx -surgical removal -somatostatin -cabergoline

I-cell disease

Inclusion cell disease Mucolipidosis type II Inherited lysosomal storage disorder Defect in N-acetylglucosaminyl-1-phosphotransferase -> failure of the Goldi to phosphorylate mannose residues -> proteins are secreted extracellularly instead of delivered to lysosome PW -coarse facial features -gingival hyperplasia -clouded corneas -restricted joint movements -claw hand deformities -kyphoscoliosis -high plasma levels of lysosomal enzymes -often fatal in childhood

AV shunts

Increase preload, because return back to the heart is increased (resistant arterioles bypassed) Decreased afterload (resistant arterioles bypassed)

Down Syndrome

Increased inhibin on maternal serum screen -decreased AFP

Diverticulitis

Infection and inflammation of diverticulum Perforation of diverticulum Sigmoid PW -fever -nausea -vomiting -LLQ tenderness -pain DW -CT with contrast Can cause abcess formation CAn cause obstruction Can cause fistula (colon-bladder most common) -> pneumoturia, stool in urine

anemia of chronic disease

Inflammation and cytokines inhibit the release of iron Causes hepcidin release from the liver Iron stores in marrow will be high -increased serum ferritin Transferrin is low TIBC is low Caused by -Rheumatoid arthritis -inflammatory bowel disease -malignancy -alchoholics

Myocarditis

Inflammatory damage to myocardium -U.S. most common is viral (coxsackie B) -blue inflammatory infiltrate seen on histology -can lead to dilated cardiomyopathy -> systolic heart failure Fever, dyspnea, fatigue Can mimic MI Release of troponins and CK-MB Can cause arrhythmias Causes: -cross reactive antibodies -viral (coxsackie B, parvo, adeno, HIV, HH6) -toxins (alcohol, CO, cocaine, diuretics, antibiotics, diphtheria toxin) -Chagas disease, trypanosoma cruzi -bacteria (rickettsia, mycoplasma, borrelia burgdorferi- manifests as heart block usually) -drug hypersensitivity myocarditis (sulfa drugs, furosemide, HCTZ, ampicillin, azithromycin, zidovudine) with eosinophilic infilitrate -autoimmune (SLE, scleroderma, wegener's, takayasu, rheumatic fever)

Rifampin

Inhibits RNA polymerase activated by CYP450 Tx -prophylaxis for n. minigitidis -prophylaxis for H. flu -used in RIPE therapy for tuberculosis AEs -hepatotoxicity -harmless production of orange body fluids

Warfarin

Inhibits V-KOR, preventing oxidized vitamin K from returning to its reduced and active form Factor VII goes down first because it has shortest half life Factor II takes the longest (~3 days) Oral administration PT monitoring Goal is 2-3 for INR Cannot be given in pregnancy Substrate of CYP450 Early hypercoagulable state due to short half life of protein C -> HEPARIN BRIDGE Administering vitamin K to reverse will not be immediate because factors still have to be synthesized -> FFP has all the clotting factors already

Nephrotic syndrome

Initial injury to glomerular basement membrane or podocytes Podocyte effacement -slit diaphragm disruption depletion -cytokines implicated Marked proteinuria - >3.5 -hypoalbuminemia -> edema -> increased liver synthesis of proteins -> hyperlipidemia Oval fat bodies Hypercoagulable state (due to loss of antithrombin III in urine) Hypogammaglobulinemia -> immunocompromised Frothy urine Causes: -Amyloidosis -> obliterates glomerular capillaries

Trochlear nerve palsy

Innervates the superior oblique muscle which usually causes the eye to intort (internally rotate) and depress while adducted Particularly susceptible to injury due to its long course and small caliber Vertical diplopia most noticeable when the eye looks down and towards the nose Chin tuck and head tilt to compensate

Appendicitis

Inspissated fecalith (hard poop stone) In children commonly due to lymph hyperplasia from infection Sealed off appendix -> accumulated mucus -> increased pressure -> lymphatics and veins obstructed -> ischemic and necrotic -> inflammation -> bacterial invasion -> abscess formation and perforation PW -colicy periumbilical pain -> RLQ pain (involvement of parietal peritoneum

Cell adhesion

Integrins on cell connect to fibronectin which connects to collagen Anchors cells

Trichinella spiralis

Intestinal nematode found in undercooked meat (pork and bear) Fever, vomiting, periorbital edema Severe myalgia from the larvae forming cysts in the striated muscle cell Muscle inflammation Eosinophilia

Primary Hypothyroidism

Iodine deficiency -not as big a problem because of ionization of salt -still most common cause worldwide -> deficiency leads to hyperplasia of thyroid tissue (repeated TSH stimulation) -> nodular and enlarged thyroid -when iodine is reintroduced it can cause hyperthyroidism or even thyrotoxicosis -> eventual fibrosing of thyroid Thyroiditis

Topotecan

Irinotecan topoisomerase I inhibitor -. blocks S phase Tx -ovarian cancer -SC lung cancer -Irinotecan -> colon cancer AEs -myelosuppresion -diarrhea

Ring sideroblasts

Iron accumulating in mitochondria, and mitochondria accumulate around nucleus -> ring around nucleus Causes -Thalassemia's -lead poisoning (only in BM, not periphery) -iron overload states

Borrelia burgdorferi

Ixodes deer tick-transmitted Northeastern US Early, stage 1: localized skin lesion (bull's eye rash), fever, chils early, disseminated stage 2: fever chills migratory myalgia and arthralgia, heart block, bilateral bell's palsy late disseminated stage 3: chronic migratory, arthritis and encephalopathy (memory difficulty, cognitive slowing) White footed mouse and white tailed dear Wright stain Giemsa stain treat: Doxycycline and Ceftriaxone

Primary myeloibrosis

JAK2 constitutively activating mutation Prominent fibrosis of the bone marrow Begins with a hyperproliferative phase -> hypercellular bone marrow with increased granulocytes and megakaryocytes) Megakaryocyte atypia -> release growth factors into surroundings -> stimulate fibroblast growth -> collagen deposition -> bone marrow fibrois

Polycythemia vera

JAK2 constitutively activating mutation -increase in hemoglobin, hematocrit, and RBC count -activated STAT Relative polycythemia with hypovolemia -> hematocrit increases -EPO is normal Clinical presentation -abdominal pain -hyperuricemia (excessive RBCs -> increased break down -> increased purine metabolism -> uric acid -Bone marrow can burn out -> myelofibrosis -severe hepatomegaly Transformation to AML Risk factors: -chronic hypoxemia (cyanotic congenital heart disease, sleep apnea, COPD) -renal cell carcinoma -> EPO secretion

Essential thrombocythemia

JAK2 constitutively activating mutation -increased risk of bleeding (thought to be vWF defect) -aspirin to decrease thrombotic eventslko

Ruxolitinib

JAK2 inhibitor can be useful in the treatment of myeloproliferative neoplasms -especially polycythemia vera and myelofibrosis

Giant cell arteritis

Jaw claudication Headache Visual disturbances Polymyalgia rheumatica Tests: Elevated ESR & C reactive protein

Cranial nerve V motor lesion

Jaw deviates TOWARD side of lesion due to unopposed force from the opposite pterygoid muscle

Hyper-IgE syndrome

Job syndrome Mutation in STAT3 gene -JAK/STAT signal transduction messed up Th17 Helper T cells are deficient (due to mutations in STAT3) Cold skin abscesses and absence of fever during systemic infection -lack of neutrophil chemotaxis -> absent inflammatory response to infection Recurrent skin infections Coarse facies Elevated eosinophil count Hyper-IgE is associated symptome, not thought to cause all this stuff

Rationalization

Justifying behavior to avoid difficult truths

Cranial nerve XII lesion

LMN lesion tongue deviates TOWARDS side of lesions ("lick your wounds") due to weakened tongue muscle on affected side

Ziluten

LOX inhibitor Can cause hepatic damage

Central diabetes insipidus

Lack of ADH secretion from posterior pituitary -supraocular nuclei ADH usually acts to reabsorb water at the collecting duct -> lower serum osmolality - released when serum is hypertonic or in hypovolemic states ADH stimulates v1 and v2 peripheral receptors v1 -vascular smooth muscle -Gq -> increased calcium -contraction v2 -kidney -Gs proteins -upregulates aquaporin channels PW -dilute copious urine -polyuria -patients usually drink water to avoid hypernatremia RF -thought to be autoimmmune -tumors in the brain affecting hypothalamus Serum osmolality rises as free water is shed Administering ADH test -Kidneys are fine, can use ADH, and water is conserved Tx -exogenous ADH

Chlamydia spp

Lack of muramic acid obligate intracellular Elementary bodies: outside, infectious Reticular bodies: replicate inside, active dividing form, make inclusion bodies in cells that can be visualized Giemsa stain NAAT - nucleic acid amplification test Trachomatis Types: A-C are blindness -leading cause of blindness D-K are STI -Watery discharge L1-L3 are LVG -painless genital ulcer, then tender lymphadenopathy with draining nodes Can progress to PID Late onset conjunctivitis (1-2 weeks) pneumonia in newborns Reactive arthritis - maladaptive immune response - cant see cant pee cant climb a tree Pneumoniae: Walking pneumonia, more common in elderly Psittaci: Also transmits pneumonia PARROTS! Doxycycline AND ceftriaxone (gonorrhea co-infection)

Unfractionated heparin

Large negatively charged sulfated polymer Binds antithrombin III in blood and catalyzes inactivation of numerous clotting factors -thrombin -factor Xa -XIa -IXa? Monitor aPTT (intrinsic pathway) Prevents clots from forming Antibodies against heparin bound to platelet factor 4 causes heparin induced thrombocytopenia (HIT), a paradoxical hypercoagulable state Hypoaldosteronism leading to hyperkalemia Type 4 renal tube acidosis Osteoporosis Protamine sulfate to un-do heparin therapy -positively charged peptide that binds to heparin

Pox virus

Largest known DNA virus Comes with all the proteins it needs Makes their own envelopes instead of taking them from host ONLY DNA virus that replicates in the cytoplasm (has DNA dependent RNA polymerase so it doesn't need the one in the nucleus) Dumbbell shaped core Guarnieri bodies are sites of viral replication in cytoplasm Smallpox virus -Raised blisters on skin and mucosal surfaces -Lesions are all the same age in small pox (unlike HVZV) Cowpox virus -gives immunity to smallpox Molluscum contagiosum -flesh colored dome shaped umbilicated lesions (little dimple in the middle) -not on palms and soles of feet -commonly found on popliteal fossa, core, antecubital fossa -usually doesn't spread unless the person is immunocompromised

Strongyloides stercoralis

Larvae penetrate through skin, travel through blood to the lungs then to the small intestine Lays eggs into intestinal wall so they can hatch and go to the lungs Repeated penetration to the GI can cause infection and diffuse dissemination of gut flora Larvae in the stool Treatment: Albendazole Ivermectin

Left-to-Right shunts

Late cyanosis, pink babies Congenital rubella infection can cause Prostaglandins keep PDA open Indomethacin closes PDA May be lifesaving though if another heart defect is present (Transposition of the great arteries) MACHINE LIKE MURMUR -present during systolic and diastolic Widened pulse pressure VSD -Most common in childhood -systolic ejection murmur -failure to thrive in the newborn -fetal alcohol syndrome predisposes ASD -Rarely closes on its own -Ostium secundum doesn't close -Foramen ovale stays open -INCOMPLETE FUSION of septum primum and secundum leaves PFO -Flow with every atrial contraction -Flow can reverse ("paradoxical" embolism can cause stroke) -wide fixed splitting of S2 (right side always overloaded from high pressure left side spillover) -bubble study PDA Turn blue in adolescence from pulmonary hypertension reversing the shunt

Mitral prolapse

Leaflets billow up like parachute into left atrium Marfan's Ehlers-Danlos Osteogenesis Imperfecta Mid systolic click

Branched amino acids

Leucine Isoleucine Valine Breakdown of these is THIAMINE dependent

Bipolar II

Like Bipolar but less sever Called hypomania - like mania but you do sleep a little bit, are able to hold down a job usually -no psychosis depressive disorders

Probenacid

Limits nephrotoxicity of cidofovir Blocks tubular secretion AEs -prevents excretion of other drugs, leading to higher plasma volumes (penicillins, methotrexate, NSAIDs)

Premortum thrombus

Lines of zhan composed of platelets

Post-renal AKI

Lithiasis Benign prostatic hyperplasia Prolonged obstruction leads to intrinsic renal damage

Squamous cell lung carcinoma

Located centrally (sentral) Almost exclusively in smokers Metaplasia columnar -> squamous -temporary if toxin is temporary Second most common dysplasia -> mitotic figure, messed up cells, N/C ratio is huge Paraneoplastic syndrome: Hypercalcemia from PTH-like secretion

Small cell carcinoma

Located centrally (sentral) Almost exclusively in smokers Neuroendocrine tumor Worst prognosis Sheets of round blue basophilic cells with scant cytoplasm Granular chromatin (salt n pepper) Positive for neuroendocrine markers (chromogranin) Metastasis early Paraneoplastic syndrome: SIADH Fluid retention hyponatremia LEMS (antibodies against voltage gated calcium channels) -> decreased acetylcholine and proximal muscle weakness Cerebellar degeneration and encephalomylitis (probably from more autoantibody formation) Cushing syndrome from ACTH-like release

Henoch-Schoen purpura

Looks like IgA nephropathy

Ascaris lumbricoides

Lumberman Bloodstream -> lungs -> GI tract -malnutrition -most likely to cause respiratory symptoms -intestinal obstruction Diagnose: -Eggs in the feces -eosinophilia Treatment -albendazole (causes microtubule dysfunction), can actually induces obstruction when they all die

Lipoprotein metabolism

Lumenal absorption of free fatty acids and cholesterol Packaged into lipoprotein called chylomicron (triglycerides = 3FFAs and glycerol, and cholesterol) Cholesterol converted into cholesterol ester (more soluble) All chylomicrons have Apolipoprotein that aide in the creation, metabolism, and absorption of these molecules Apolipoprotein A B C E - aide in reuptake by the liver, interacts with hepatic LDL receptor to endocytose Lipoprotein lipase in extrahepatic tissue hydrolyzes triglycerides in chylomicrons to release FFAs VLDL is main export vehicle from liver (60% triglycerides, then -has B100 -bad cholesterol -lead to triglyceride deposition in arteries and other tissues -hydrolyzed by LPL, leading to FFAs for tissues and storage in adipose tissue -forms some IDLs that head back to the liver, but most go on to LDLs? LDLs are formed as VLDLs continually lose triglycerides and cholesterol esters -higher proportion of cholesterol ester -main source of cholesterol for the rest of the body -cells with not enough cholesterol upregulate LDL receptor and vice versa HDL -Good cholesterol -contain mostly protein by weight -extracts cholesterol from peripheral tissue cell membrane in the form of free cholesterol (its then converted into cholesterol ester by lecithin cholesterol acyltransferase (LCAT)) -> makes its mature HDL molecule -delivers cholesterol back to the liver -transfers cholesterol esters to LDL and VLDL to be transported back to liver (through cholesteryl ester transfer protein) -HDL can deliver directly to liver through scavenger 1 receptor Mevalonic acid is intermediate in hepatic cholesterol synthesis Most bile is recycled (secreted by gal bladder and reabsorbed by ileum)

Hereditary nonpolyposis colorectal cancer

Lynch syndrome most common familial colorectal cancer cause autosomal dominant Mismatch repair genes mutations -MSH2 -MLH1 -tumor suppressor genes

Ketogenic amino acids

Lysine Leucine

Streptococcus pyogenes

M protein prevents phagocytosis JONES criteria Bacitracin sensitive Beta hemolytic Impetigo

Minimum alveolar concentration

MAC -dose that makes 50% of patients unresponsive to painful stimuli ED50 on dose effect curve -find where effect is 50% -> find value the lower the MAC, the higher the potency

Macrocytosis

MCV > 100 alcohol abuse

Vancomycin

MRSA coverage MOA -binds to D-ala-D-ala oligopeptides and prevents cell wall synthesis -> altered PBPs ineffective -> resistance to beta lactamases IV adminitration combined with ceftriaxone for meningitis prophylaxis Resistance -> cell wall made of D-ala-D-lac Tx -MRSA resistant osteomylitis -MRSA -staph epidermidis -enterococcus AEs -Red man syndrome ->infusion related flushing related to histamine release -DRESS syndrome

Daptomycin

MRSA coverage ineffective for pnemonia -inactivated by surfactant MOA -punches holes in bacterial cell membrane -> cell lyses Tx -MRSA -Enterococcus AEs -myopathy

Melatonin

MT1 and MT2 receptors are in the suprachiasmatic nucleus of the hypothalamus Ramelteon is synthetic analogue Aides in sleep Tx -insomnia

Fidaxomicin

Macrocyclic antibiotic (related to macrolides) inhibits sigma subunit of RNA polymerase activity against c diff

Leprosy treatment

Macrolide -azithromycin or clarithromycin -combined with ethambutol

Phagocytic cell disorders

Macrophage physiology -In phagolysosome: NADPH is high energy electron carrier -> uses its electron to generate Superoxide ion which goes on to make hydrogen peroxide -> damage to microbes

Hyperaldosteronism

Made in glomerulosa sodium reabsorption H+ and K+ excretion Primary -adenoma -> well-circumscribed, small, solitary, SPIRONOLACTONE bodies -bilateral idiopathic hyperaldosteronism -> zona glomerulosa is hyperplastic -carcinoma of the adrenal gland -ectopic secretion from tumor Secondary -renin oversecretion (conditions with peripheral edema aka CHF, cirrhosis, nephrotic syndrome -> low intravascular volume -> renin secretion) PW -hypertension -hypokalemia usually mild -metabolic alkalosis ANP and BNP release from hypervolemia Tx -spironolactone (aldosterone antagonist) -low sodium diet

Schizoaffective disorder

Major depressive or manic episode concurrent with symptoms of schizophrenia lifetime history of delusions, hallucinations for greater than 2 weeks in the absence of major depressive or manic episode Mood symptoms are present for majority of illness Not due to substances or medication

Inflammatory leukocyte accumulation

Margination: Increased vascular leakage -> hemoconcentration and decreased wall shear stress -> improved contact of neutrophils with endothelial lining Rolling: Neutrophils roll on the endothelium via the loose binding of sialylated carbohydrate groups (Sialyl Lewis X or PSGL-1) to L-selectin on NEUTROPHILS of E-selectin/P-selectin on endothelial cells (cytokines stimulation greatly increases expression of endothelial selectins) Activation: slow rolling allows the leukocytes to sample the chemokines secreted by the inflamed tissue -> activates integrins by inducing a signaling cascade that results in a conformational change in the integrins necessary for binding Tight adhesion and crawling: Neutrophils become firmly attached to the endothelium by binding CD 18 beta 2 integrins (Mac-1 and LFA-1) to intercellular adhesion molecule-1 (ICAM-1) Transmigration: Integrin attachment to platelet endothelial cell adhesion molecule 1 (PECAM-1) found primarily at the intercellular junctions of endothelial cells

Glutamine

Metabolism produces ammonia and bicarbonate Important buffer system for the blood Used in lactic acidosis

Vitamin B12 deficiency

Methylmalonic acid buildup (cant make succinyl-coa) Exertional dyspnea Fatigue pallor Megaloblastic anemia Abnormal myeline synthesis -> degeneration of -Dorsal columns of the spinal cord (gait abnormalities) -Lateral corticospinal tracts (UMN signs, spastic paralysis, hyperreflexia, babinski sign) -peripheral nerves VB12 = hydroxocovalamine

IBS

Middle aged women Vague abdominal pain relieved with defecation Changes in stool consistancy Constipation dominant and diarrhea dominant

Sumatriptan

Migraine therapy Acute treatment 5-HTb and 5-HTd agonist -located on meningeal vessels ->vasoconstriction -> prevents release of CGRP, substance P, neurokinin A from trigeminal -> inhibits pain pathwyay AEs -coronary vasospasm -contraindicated in patient with angina

Visceral carcinoma

Migratory thrombophlebitis = Trousseau syndrome Hypercoagulability because adenocarcinoma's produce a thromboplastin-like substance Seen in: visceral adenocarcinomas of the pancreas, colon, and lung

Prolactinoma

Milky nipple discharge (galactorrhea) prolactin inhibits GnRH -> decreased FSH and LH release -> hypogonadism PW -hypogonadism -amenorrhea -infertility Postmenopausal PW -Mass effect symptoms In men -decreased testosterone -decreased libido -hypogonadism Tx -bromocriptine -cabergoline -D2 receptor agonists -> inhibit prolactin cells

Spironolactone

Mineralocorticoid Action in collecting duct K+ sparing diuretic Antagonizes the glucocorticoid receptor Useful in treatment of heart failure, also can be used in combination with other diuretics do blunt potassium loss REDUCES CARDIAC REMODELING Possible hyperkalemia Inhibit aldosterone in collecting duct -> type 4 renal tubular acidosis Inhibits 17alpha-hydroxylase (testosterone synthesis pathway) -treat androgen excess in PCOS -causes gynecomastia -decreased libido

Eplerenone

Mineralocorticoid Action in collecting duct K+ sparing diuretic Antagonizes the glucocorticoid receptor Useful in treatment of heart failure, also can be used in combination with other diuretics do blunt potassium loss REDUCES CARDIAC REMODELING Possible hyperkalemia Inhibit aldosterone in collecting duct -> type 4 renal tubular acidosis

Amiloride

Mineralocorticoid Action in collecting duct K+ sparing diuretic Inhibits Na+ resorption through ENaC Treatment of heart failure, also can be used in combination with other diuretics do blunt potassium loss Treatment of Li+ induced nephrogenic diabetes insipidus Treatment of Liddle's syndrome Possible hyperkalemia Inhibit aldosterone in collecting duct -> type 4 renal tubular acidosis

Triamterene

Mineralocorticoid Action in collecting duct K+ sparing diuretic Inhibits Na+ resorption through ENaC Treatment of heart failure, also can be used in combination with other diuretics do blunt potassium loss Treatment of Liddle's syndrome Possible hyperkalemia Inhibit aldosterone in collecting duct -> type 4 renal tubular acidosis

Tetracyclines

Minocycline Doxycycline Inhibit 30s ribosomal subunit -bind reversibly broad spectrum absorption in proximal SI and stomach Chelate metals -absorption is reduced if given with metals Resistance -efflux pump -also some alter binding site on ribosome Tx -MRSA -various gram + and - -Critters! -Ricketssia -Ehrlichia -Francisella -Borrelia -Yersinia -chlamydial cervicitis -urethiritis -PID -walking pnemonia -acne AEs -discolor teeth in young children -vomiting -diarhea -photosensitivity of skin in systemic administration -Fanconi's syndrome from expired tetracyclines

Hemoglobin C

Missense mutation in BETA globin gene Glutamic acid -> lysine in position 6 Homozygote has mild hemolytic anemia hexagonal crystals precipitate SIckle cell + Hemoglobin C = Hemoglobin SC disease -autosomal recessive -two copies -> similar to sickle cell disease

Extravascular hemolysis

Misshapen RBCs become trapped in the Cords of Billroth Cleared by splenic macrophages -hemoglobin remains sequestered, so hemoglobin is not released into blood and urin -converted to unconjugated bilirubin -excretion in bile causes formation of Urobilinogen in GI -> more reabsorbed -> more excreted in urine Excessive bilirubin can lead to gallstones Elevated LDH Elevated reticulocyte count (>3%) Splenomegaly from expansion of the red pulp MCV will probably not change much

Thyroid malignancies

More likely to be malignant in males and children PW -cold nodules RF -radiation to the neck

Cystic kidney disease

More likely to get hematuria and stones and UTI's Renal dysplasia -can even have bone and cartilage in kidney Autosomal dominant -adult presentation -Polycystin-1 on chromosome 16 -Polycystin-2 on chromosome 4 -flank pain -hematuria -HTN -saccular aneurysms in the circle of Willis -pancreatic cysts Autosomal recessive -symptomatic in early childhood -diffuse small cysts -develop in collecting ducts (cysts are lined with cuboidal cell -Potter sequence -Cysts form in the liver, too -> malformation of developing biliary system -> hepatomegaly, hepatic fibrosis Medullary sponge disease -cysts in collecting duct

Partial Hydatidiform Mole

More messed up one Contains fetal parts 69XXX 69XXY 69XYY Two sperm one egg -maternal and paternal DNA are present -p57 positive (maternal DNA present) Uterus NOT really big -partial mole doesn't grow well slightly high beta-hCG -> less side effects RF -extremes of maternal age -history of miscarriage -some chorionic villi will be enlarged, but not all overexpression of paternal genes

Colorectal cancer

Most are adenocarcinomas -third most common cancer overall in men and women -most common GI tract tumor -second leading cause of death from cancer -30 times lower in developing countries APC defective -> e-cadherin mutations, K-RAS oncogene mutations -> basement membrane invasion -> ADENOCARCINOMA DCC gene (deleted in colon cancer gene lol) -activates apoptosis normally -immortality! COX-2 upregulation -use of aspirin associated with less occurance RF -most are sporadic -FAP - PW -Iron deficiency -hematechezia -obstruction -apple core lesion on CT -Increased CEA

Congenital cardiac pathology

Most are sporadic

Diffuse large B cell

Most common adult lymphoma 1/3rd have translocation of 14:18 like follicular Another third have mutation in BCL-6 gene transcription regulation protein histology: sheets of large B cells EBV and HIV co-infection can cause AIDS defining illness Most common CNS lymphoma

Iron deficiency anemia

Most common anemia worldwide Risks -vegetarian diet low in iron (most common worldwide) -chronic unchecked bloodloss (most common in US), very common in pregnant women who bleed a bunch -in developing countries think parasites -autoimmune gastritis -h. pylori gastritis -small bowel inflammation and injury At first you see normochromic, normocytic cells Then microcytic hypochromic Transferrin is elevated Transferrin saturation is decreased TIBC is increased Fatigue, weakness, skin pallor Increase in CO to compensate for decreased oxygen carrying capacity Atrophic glossitis -> smooth red tongue Spoon-shaped nails Pica -> drive to eat ice Can lead to Plummer-Vinson syndrome -dysphagia -esophageal webs -iron deficiency

Polycystic ovary syndrome

Most common cause of anovulation -can cause infertility PW -insulin resistance -amenorrhea -obesity -infertility Tx -first line is weight loss, which can reverse the symptoms -OCPs to decrease risk of hyperplasia and cancer -Metformin

Lung cancer

Most common cause of cancer death (not most common cancer occurrence tho) Most cancers found in lungs are mets Risk factors -smokeing -radiation -pulmonary fibrosis -toxins (asbestos, radon, metals, aromatic hydrocarbons) Peak incidence -50s-60s Presents with -weight loss -chest pain (especially in younger patients) -decreased appetitie -progressive dyspnea -coughing (especially central tumors) -hemoptysis Commonly cause pleural and pericardial effusions (regional tumor spread) Pancoast syndrome -regional spread to superior pulmonary sulcus -invasion of brachial plexus C8 D2, pain and muscle waisting in ulnar and medial distribtion -Horner's syndrome -> ptosis, anhydrosis, miosis SVC syndrome from mediastinal involvement

Porphyria cutanea tarda

Most common disorder of heme synthesis Abdominal pain Neuropsychiatric manifestations Photosensitivity due to accumulation of porphyrinogens that react with oxygen on excitation by light

Acute tubular necrosis

Most common form of AKI Ischemia of tubule cells MI -> hypoperfusion -> prerenal AKI -> intrinsic kidney damage Muddy brown casts (necrotic tubular cells) -accumulate in tubular lumen and block -> further reducing GFR PCT and ascending loop of henle Patchy necrosis on histology Initially -Kidney is ok, whatever is causing ATN is maine feature Maintenance -kidney problems predominate -metabolic abnormalities -creatinine and BUN accumulate Recovery phase -1 to 2 weeks after insult to kidney -tubular reepithelialization -production of dilute copius urine -all minerals decrease

Homocystinuria

Most common inborn error of methionine metabolism Autosomal recessive deficiency of cystathionine beta-synthase -requires pyridoxine PW -age 3-10 with ectopia lentis (dislocated lens) -Intellectual disability -Marfanoid habitus (elongated limbs, arachnodactyly, scholiosis) -Thrombotic occlusions Tx -methionine restriction -Pyridoxine

Aortic stenosis

Most common lesion affecting aortic valve Calcific degeneration of the aortic valve associated with endothelial and fibroblast death Concentric hypertrophy due to increased afterload Atrial fibrillation due to LA dilation Crescendo-decrescendo systolic murmur -Squatting increases (increased preload, more blood flowing across stenotic valve) -Standing up decreases Weak, slow rising pulse More severe aortic stenosis = more later crescendo (close to S2 Hemolytic anemia -schistocytes on blood smear Can cause fixed cardiac output, heart can increase in times of exertion -can cause angina Risk factors: Bicuspid aortic valve Rheumatic fever - MOST COMMON in developed world

Hepatocellular carcinoma

Most common malignancies in liver are METS -lung, colon, HCC is most common primary Monitor AFP inactivation of tumor suppressor gene is key component of pathogenesis -integration of viral hepatitis DNA -also viral proteins activate signal transduction pathways and inactivate p53 protein RF -Cirrhosis is number 1 cause -men (2:1) -hep C -alcoholic cirrhosis -NAFLD -PBC primary biliary cholangitis -PSC primary sclerosing cholangitis -Aflatoxin (aspergillus flavus) -> mutates p53 -exposure to azo dyes (paints, leather working etc) Histology -bile containing pseud-canaliculi (globs of bile) -giant cells -> multinucleated hepatocytes with enlarge nucleoli and prominent nucleoli PW -chronic symptoms are masked -may present with acute decompensated symptoms -Vascular invasion can occlude large vessels in hepatic veins -> venous congestion and portal hypertension -> BUDD-CHIARI SYNDROME -> can go ALL THE WAY TO THE RIGHT HEART -Mets to lungs -> hemoptysis -mets to intra abdominal lymph nodes

Minimal change disease

Most common nephrotic syndrome in children (90%) Podocyte effacement and fusion Things look normal on histology Usually several weeks after some trigger -infections, drugs, fever, allergies, etc. Proteinuria Hypoalbuminemia (selectively) Treatment short course of corticosteroid therapy

Hepatic hemangioma

Most common overall benign Dilated, vascular spaces filled with blood, lined with a single layer of epithelium -very fragile -held together with just a bit of fibrous tissue -> commonly called cavernous aka cavernous hemangioma RF -young, healthy women PW -mostly asymptomatic -incidental -can lyse and cause RUQ pain histology -dilated cystic spaces filled with RBCs

HSP

Most common vasculitis in children 3-10 ages mostly Often occurs following infection TYPE III hypersensitivity Circulating IgA-antigen immune complexes -deposit in the walls of small vessels and the renal mesangium -> neutrophil and lymphocyte recruitment LEADS TO -palpable purpura -organ dysfunction usually self limited

Hereditary spherocytosis

Most commonly due to SPECTRIN defect Spectrin attaches the external phospholipid membrane to the cytoskeleton Causes extravascular normocytic hemolytic anemia RBCs lose vesicles of membrane in the spleen -> small RBCs and increased RBC distribution width No central pallor Less flexible -> trapped in spleen -> phagocytized Osmotic fragility test (lyses very easily under changing osmolality) INCREASED MCHC -> less volume, same hemoglobin -> higher concentration Jaundice Splenomegaly Can cause hydrops fetalis Aplastic crisis (especially if infected with parvo B19)

Large and medium vessel vasculitis

Most vasculitis thought to be autoimmune Inflammation can lead to narrowing of the lumen and tissue ischemia (bruits) Can cause aortic aneurysms and aortic root dilation -> aortic regurgitation Inflammation of the carotid and cerebral arteries can lead to neurologic symptoms (syncope, vertigo, and visual changes) giant cell arteritis -Vision loss like curtain being pulled over -granulomatous inflammation in central retinal artery and posterior ciliary -patchy and segmental inflammation -fragmentation of the elastic lamina due to inflammation and medial fibrosis -diagnosis confirmed with temporal artery biopsy Takayasu's -asian women under 40 -predilection for aortic arch and its proximal branches (though inflammation can affect abdominal and cerebral vessels) -similar on histology to GCA -luminal narrowing of renal arteries -> renal hypoperfusion -> severe renovascular hypertension Kawasaki disease -young asian males -erythema and swelling of the hands and feet -inflammation of the coronary vessels can lead to coronay aneurysms -Conjuctival injection -desquamative rash on trunk -Adenopathy (cervical) -strawberry tonge -TREAT with IVIG and aspirin (prevents thrombus, only illness you use aspirin in kids) -MI in young kid Thromboangitis obliterans -strong association with tobacco smoke -exact moa unknown -macrophages -lumen of vessel obliterated Polyarteritis nodosa -diffuse vasculitis of medium and small vessels involving multiple organs -acute flares and remittances with a background of chronic inflammation -> lesions of varying age and severity -strong association with hepatitis C and especially hepatitis B -immune hypersensitivity type III (immune complex) -Segmental, transmural necrotizing inflammation -> microaneurysm formation and alternating areas of stricture and dilation (string of beads appearance) -non-granulomatous mixed inflammatory infiltrate of entire vessel wall -leads to fibrinoid necrosis in vessels -renal involvement causes hypertension -renal vessel involvement can lead to glomerulonephritis, renal infarction, AKI, and chronic kidney disease -1/3 of patients will develop skin changes like subcutaneous nodules, palpable purpura, livedo reticularis (purplish reticular discoloration of the skin) Cerebral changes limb claudication diagnosed with ct treatment -glucicorticoids

Salmonella enteritidis

Motile H2S positive (black colonies on hektoen agar) encapsulated acid labile (easily degraded in stomach) need a ton to seed intestines, or if the patient is on a PPI Chicken Inflammatory diarrhea Type 3 secretion system - detects eukaryotic cells and secretes a protein that helps with infection Invades lymphatics, gets phagocytized by macrophages and carried into the blood facultative intracellular, doesnt require it

Salmonella Typhi

Motile H2S positive (black colonies on hektoen agar) encapsulated acid labile (easily degraded in stomach) need a ton to seed intestines, or if the patient is on a PPI Harboured in galbladder Typhoid mary red macules on abdomen 1# cause of osteomyelitis in those with sickle cell Pea-soup diarrhea Vaccine FLUOROQUNILONE

Pudendal nerve

Motor and sensory innervation to the perineal region S2-S4, passes between the piriformis and coccygeus muscles as it exits the greater sciatic foramen Then reenters near the ischial spine Vulnerable to stretch injury here

Clostridium perfringens

Motorcycle accidents deep, penetrating wounds from military combat Spore former Gas gangrene - crepitus, crackling from consuming carbohydrates Alpha toxin - lecithinase causes damage to cell membranes, can lead to RBC hemolysis DOUBLE zone of hemolysis Treatment IV penicillin G Food posing late onset, spores have to germinate

Halogenated inhaled anesthetics

Much more likely to cause acute hepatitis Metabolized by CYP450 to reactive metabolites

Chronic bronchetectesis

Mucus gland hyperplasia Goblet cell metaplasia and proliferation

Intrinsic kidney injury

Muddy casts Acute interstitial nephritis Glomerulonephritis BUN and Creatinine increased

Hodgkin Lymphoma

Mutated B lymphocyte in germinal center (or just having left germinal center) ->proliferation of CLONAL B cells Liver and spleen contain germinal centers too, can arise here Most commonly in the cervical, supraclavicular, or mediastinal lymph nodes ALWAYS displays Reed-Sternberg cells (cells with two nuclear lobes containing an acidophilic nucleolus surrounded by a clear zone) looks like owl's eyes Reed-Sternberg cells are sparse but always present Mostly lymphocytes, eosinophils, neutrophils, fibroblasts, ect CD 15 and CD 30 Bimodal age distribution, 20 and 65 Risk factors -family history of autoimmune disease (unclear why) Presents as -B symptoms (fever, weight loss, drenching night sweats) -mediastinal mass Subtypes 1. Nodular Sclerosis -distinct nodules of inflammatory cells with fibrous collagen in between -lacunar Reed-Sternberg cells -> reaction of cytoplasm during slide fixation -> ring of clear space "lacunae" around the nucleus 2. Mixed cellularity -more common in developed countries -EBV infection (especially if coinfection with HIV) -Predominates in abdominal lymph nodes and spleen -nodules without fibrous septae 3. Lymphocyte predominant "non-classic" hodgkin's lymphoma -contains almost no Reed-Sternberg cells -lymphohistocytic cells express CD19 and CD 20 -nuclei look like popped popcorn 4.Lymphocyte rich 5.Lymphocyte delpleted

Aminoglycosides

Neomycin Streptomycin Tobramycin Paromomycin Gentamicin Amikacin Acts on bacterial ribosome 30S subunit Halts translation Has to be coupled with cell wall active drugs to penetrate (beta lactams, vancomycin) transported into bacteria via an aerobic process IV administration Resistance -inactivated by acetylation enzyme Tx -aerobic gram negative bacteria -neomycin remains active in GI tract -> used in bowel prep -paromomycin -> luminal agent against parasites -streptomycin -> tularemia caused b Fancisella, plague caused by Yersinia -Gentamicin -> resistant gram negative infections -> Enterobacter, Serratia, Klebsiella -Septicemia -nosocomial RTI -complicated UTI -intra- abdominal infection -psuedomonas (gentamycin, Tobramycin, amikacin) -Enterococcus AEs -Ototoxicity -nephrotoxicity -ATN

Prader-Willi Syndrome

Neonatal hypotonia genital hypoplasia and hypogonadism mental retardation Short stature Profound hyperphagia Small hands and feet Deletion in PATERNALLY derived chromosome 15

Islet cell tumors

Neuroendocrine tumors More rare than adenocarcinoma of pancreas Insulinoma (most common) Beta cell tumor rarely malignant present early PW -HYPOGLYCEMIA from excess insulin -feeling better after eating -Whipple's triad -high c-peptide Glucagonoma alpha cell PW -hyperglycemia -GI upset -weight loss Cause -venous thrombosis -> DVT or PE -Necrolytic migratory erythema Gastrinoma -over acidification of the stomach -originate from duodenum or pancreas -Zollinger-Ellison syndrome -> GERD, peptic ulcer disease, ulcers in jejunum (specific) -unresponsive to conventional therapies -malabsorption -> diarrhea VIPomas -secrete VIP vasoactive intestinal peptide -stimulates secretion of water, electrolytes, and bicarbonate by the small intestine and pancreas -large volume watery diarrhea -hypovolemia -hypokalemia -achlorhydria (low HCl in the stomach, inhibition by VIP) Somatostatinoma -inhibits secretion of insulin, glucagon, cholecystokinin, gastrin, VIP -least common -insulin inhibited more than glucagon -hyperglycemia MEN 1 syndrome

NNRTIs

Nevirapine Efavirenz Delavirenz Don't need to be phosphorylated Tx -HIV AEs -flu-like symptoms -hepatic failure can occur within 6 weeks -CNS symptoms -dizziness -drowsiness -headache -insomnia -nightmares -psychoses -teratogenic (delavirenz) -varying effects on CYP450 system -Skin rash -SJS

Preeclampsia

New onset HTN after 20 weeks gestation (def. of gestational HTN) PLUS proteinuria OR signs of end organ dysfunction headache and vision changes Swollen liver -> abdominal pain -elevated transaminases Starts with abnormal placentation abnormal blood flow to the placenta Fetus releases inflammatory mediators -> causes decreased production of vasodilators and increased production of vasoconstrictors in mom

Gestational hypertension

Nifedipine

Nitrates

Nitroglycerin Isosorbide mononitrate/dinitrate - oral preparations for more long term coverage Antianginal therapy Prinzmetal angina therapy Symptomatic relief in chronic stable angina Sublingual nitroglycerin administration Can be used in hypertensive emergency Reduces pulmonary edema in lungs Metabolized and release nitric oxide -> increases cGMP in vascular smooth muscle cells -> decreased intracellular calcium -> decreased activity of myosin light chain kinase (dephosphorylation) -> decreased activity with actin Some vasodilation of arteries very mild dilation of arterioles Decreased preload -reduced wall stress -less blood to move -myocardial oxygen demand decreased Should be avoided in right sided MI Side effects: -hypotension -> reflex tachycardia (pair with beta blocker to stop) -headaches -flushing -methemoglobinemia nitrate free interval for tolerance avoid in phosphodiesterase 5 inhibitors contraindicated in HOCM

0-4 hours post MI

No changes

Focal nodular hyperplasia (hepatocyte)

Nodular star pattern from solitary area of hepatocyte proliferation -normal appearing hepatocytes around lesion benign condition -can occasionally have symptoms if the lesion is large RF -female (10x more common) -OCP could be -estrogen excess (pregnancy)

Rifaximin

Non absorbable antibiotic alters Gi flora Decreases GI ammonia production Usually given with Lactulose, which is digested and turns GI more acidic, favoring ammonia -> ammonium (not absorbed)

Verapamil

Non-dihydropyridine Greatest cardiac effects Reduce cardiac contractility, reducing cardiac output Decrease activity at SA and AV nodes Treat -hypertension -stable angina -vasospastic angina (CCBs first line) -Migraines Side effects: -lightheadedness -headaches -peripheral edema because arterioles preferentially dilate, leading to increased hydrostatic pressure in capillaries and edema -Reflex tachycardia -gingival hypertrophy -contraindicated in patients with risk of heart block -contraindicated in overt heart failure

Diltiazem

Non-dihydropyridine Has mild vasodilatory effect Reduce cardiac contractility, reducing cardiac output Decrease activity at SA and AV nodes Treat: -hypertension -stable angina -vasospastic angina

Class IV antiarrhythmics

Non-dihydropyridine CCBs Rate control at SA and AV nodes Block activated and inactivated calcium channels -prolong phase 4 of nodal action potential -> decreased sinus rate -> prolonged conduction time and effective refractory period Can cause heart block Treats A fib and A flutter -prevents rapid ventricular response in atrial fib and flutter Decreases atrioventricular conduction Only useful in supraventricular arrhythmias Prolong the PR interval on ECG Diltiazem Verapamil

Chronic diabetes mellitus complications

Non-enzymatic glycation -glucose covalently bonds to proteins -> advanced glycation products (AGE) -vascular injury when they bind to extracellular matrix proteins in the vessel wall -> makes them crosslink -> things get tangled and trapped like LDLs (accelerate atherosclerosis) AGEs can bind to RAGEs (receptors of advanced glycated products) -triggers release of growth factors and inflammatory cytokines, maybe even ROS's -AGEs form in epithelial cells Diffuse glomerular basement membrane proliferation -thicker and leakier -> GLOMERULOSCLEROSIS due hyaline deposition (Kimmelstiel-Wilson nodules) -> albuminuria Concentric layers of hyaline around the basement membranes of capillaries -> reduces the integrity of capillaries -> leakage of plasma proteins -leads to CKD EYE -microaneurysms (early sign) -increased vascular permeability leads to visable exudates -> flame hemorrhages -"cotton wool spots" from small areas of microinfarction -neovascular proliferation can block humor flow -> glaucoma -retinal detachment Risk factor for atherosclerosis (chronic inflammation and lipid oxidation) Also for peripheral artery disease Sorbitol accumulates -> osmotic damage to fibers of the lens -> opacification -> Osmotic damage to myelin -> peripheral neuropathy -usually proprioception and vibration go first -> charcot joints Cranial nerve neuropathy Autonomic neuropathy -> gastroparesis Impotence Bladder dysfunction More prone to fungal infections -Mucor -pseudomonas -> malignant external otitis

Zopiclone

Non-habit forming sleeping aid bind GABA-A receptor at benzo site short duration of action good in inducing sleep AND maintaining less likely to cause tolerance physical dependence is less less withdrawal symptoms serum half life may be extended in adults AEs -cognitive deficits -falls and fractures -impaired performance of daily living tasks -DON'T MIX with antihistamines, benzos, or barbs Rescue with flumazenil -can precipitate withdrawal seizures

Zolpidem

Non-habit forming sleeping aid bind GABA-A receptor at benzo site short duration of action metabolized rapidly by CYP450 system good in inducing sleep, may not be good at maintaining less likely to cause tolerance physical dependence is less less withdrawal symptoms serum half life may be extended in adults AEs -cognitive deficits -falls and fractures -impaired performance of daily living tasks -DONT MIX with antihistamines, benzos, or barbs Rescue with flumazenil

Parathyroid gland disorders

Normal -Chief cells that secrete parathyroid hormone -Raises serum calcium Primary hyperthyroidism -MEN1 (adenoma), MEN2A (diffuse hyperplasia) -old women

Neural tube defects

Normal -neural tube forms at 4 weeks Low folate duh Elevated levels of acetylcholinesterase in amniotic fluid (because the tube is leaking) Anterior -anencephaly (polyhydramnios) -encephalocele (sac-like protrusion through the skull) not lethal, tho many defects Posterior -more common -Spina bifida occulta (tuft of hair, non-fusion -meningocele (CSF filled cyst, meninges herniate thru -myelomeningocele ( neural tissue herniates thru too)

Renal tubular acidosis type III

Normal anion gap acidosis

Renal tubular acidosis type IV

Normal anion gap acidosis Deficiency of aldosterone Hyperkalemia ->inhibits ammonia production in PCT ->Intracellular alkalosis -K+ traded for H+ -stops making ammonia -> cant excrete H+ as well Causes -decreased aldosterone synthesis -aldosterone resistance -low renin levels -> decreased aldosterone synthesis (diabetic nephropathy, NSAIDs, cyclosporine -> injured JGA -> low renin) -ACE inhibitors -Heparin (direct toxic effect on zona glomerulosa) -primary adrenal insufficiency) -Spironolactone, amiloride, triamterene (aldosterone resistance)

Hypocalcemia

Normal ~9 Acidosis -albumin takes up H+ to buffer -> calcium cant bind -> hypercalcemia Alkalosis - PTH disorders -hypoparathyroidism -> hypocalcemia, hyperphosphatemia -Albright hereditary osterodystorpgy (G protein involved in PTH signaling is impaired) PTH resistance (Hypoparathyroidism with elevated parathyroid hormone) genetic imprinting causes it to be inherited through mother Deficiency of Vitamin D -CKD (where vitamin D activation occurs) -> Hyperphosphatemia and hypocalcemia Elevated citrate, albumin, or phosphate can bind calcium -> hypocalcemia Medications -phoscarnate (chelates -loop diuretics -bisphosphenates -Cinecalcet -> increases threshold for PTH release, can overshoot at cause hypocalcemia -pancreatitis -> fat and fatty acids -> bind calcium

Pulomonary Anthracosis

Normal, asymptomatic pigmentation of the lung tissue and hilar lymph nodes

Autoimmune hemolytic anemia

Normocytic anemia (usually) Cold -IgM autoantibodies against RBC surface antigens -only bind below 30 degrees celsius (extremities) -RBC clumps in hands, feet, and ears Warm -IgG against RBC surface antigens -bind and activate complement system -MAC complex formation -> intravascular hemolysis -Act as opsonins -Can lead to bite cells -> smaller membrane can cause morphing into spherocytes -> extravascular hemolysis Most are idiopathic Penicillin can cause warm AIHA ALE can cause warm AIHA In children -> viral infection can cause WARM AIHA Cold AIHA usually associate with viral in adults (especially mycoplasma pneumonia and EBV) Lymphomas can cause AIHA

G6PD deficiency

Normocytic anemia (usually) Rate limiting enzyme in the pentose phosphate pathway (synthesis of FA's and cholesterol, generating NADPH in the process) Decreased active glutathione (can't protect against oxidative damage) -hemoglobin becomes exposed to more oxidative damage -> Heinz bodies -Heinz bodies chewed off by macrophages -> bite cells -> eventual extravascular hemolysis Usually asymptomatic until exposure to an outside agent -drugs (primaquine, dapsone, trimethoprime-sulfamethoxazole, fava beans) -infection Protection from malaria

Calicivirus

Norovirus/Norwalk virus is most common Calicivirus Cruise ship virus diarrhea RNA positive strand virus Naked virus Polyprotein that needs to be cleaved by viral proteases Young children in day care centers and schools Consumption of shellfish that are handled and served raw Viral gastroenteritis that can cause explosive watery diarrhea MOST COMMON cause of viral gastroenteritis

Clostridium Difficile

Nosocomial diarrhea C. Diff can grow easy in hospital patients because they are on antibiotics Clindamycin CAUSES c diff Exotoxin A- binds to brush boarder of intestines and causes inflammation, cell death, and watery diarrhea Exotoxin B- depolymerizes actin which leads to enterocyte death and necrosis, also yellowish gray exudate that creates pseudomembranes that cover colonic mucosa Assay to detect toxin in stool Treatment: Oral vancomycin - Thats where the C Diff is Metronidazole

Howell-Jolly bodies

Nuclear DNA remnant inclusions -normally removed by spleen -> show up in ASPLENIC patients

Incidence

Number of NEW cases

Child neglect

Number one cause of death in children related to mistreatment followed by physical abuse

B cell isotype switching

Occurs in germinal centers in lymph nodes Requires interaction of the CD40 receptor on activated B cells with CD40 ligand (CD154) Modulated by cytokines -IL-2, 4, 5, 6 -IFN-gamma

Primary hyperparathyroidism

Older women mostly Hypercalcemia Hypersecretion of PTH by parathyroid Moans, stones, bones, groans, psychiatric overtones MEN1 (adenoma) MEN2A (diffuse hyperplasia) Direct effect on kidneys -increased calcium resorption -phosphate excretion -high vitamin D -Type II renal tubular acidosis by impairing bicarb reabsorption in PCT (non-anion gap) Hypercalcemia -> hypercalciuria -> stones Polyuria and poly Calcium deposition in various tissues -Injures pancrease Confusion, anxiety, seizures Groans - constipation and hypersecretion of acid leading to peptic ulcer disease Activated osteoclasts resorb bone -> increased serum calcium -> elevated alk phos -> biopsy will show subperiosteal resorption with cystic degeneration Tx -parathyroidectomy

Muscarenic scetylcholine receptors

On end organs M1 -Gq -IP3/DAG -> increased Ca++ -nerves -CNS M2 -Gi -inhibits cAMP production -on heart -atria -SV node -AV node -slows down heart -> paraympathetic activity on M3 -Gq -IP3/DAG -> increased Ca++ -glands -smooth muscle -> stimulate release of NO -> drops blood pressure

Mantle cell lymphoma

Originate from mantle zones of lymphoid follicles 11:14 translocation -cyclin D1 gene

Lactulose

Osmotic laxative -non or poorly absorbable materials that draw water into the lumen, distend the colon, and facilitate peristalsis Sorbitol too non-absorbable sugar colonic bacteria digest it -> flatulence Tx -hepatic encephalopathy (can't detoxify ammonia in this state, and lactulose promotes the excretion of GI produced ammonia)

Polyethylene glycol

Osmotic laxative -non or poorly absorbable materials that draw water into the lumen, distend the colon, and facilitate peristalsis Used before GI endoscopic procedures Balanced with electolytes

Magnesium hydroxide/citrate

Osmotic laxative -non or poorly absorbable materials that draw water into the lumen, distend the colon, and facilitate peristalsis milk of magnesia prolonges use in patients with renal insufficiency can lead to hypermagnesemia

Osgood-Schlatter disease

Oversuse injury of the secondary ossification center (apophysis) of the tibial tuberosity

Folate metabolism

PABA is intermediate in folate synthesis Dihydroreductase Tetrahydroreductase Donate Deficiencies manifest as -megaloblastic anemia

Para-aminohippuric acid

PAH freely filtered at bowman's capsule MAJORITY is secreted in the PCT

Abnormal uterine bleeding

PALM COEIN Poly Adenomyosis Leiomyoma Malignancy Coagulation disorder Ovulatory Endometrial Iatrogenic Not otherwise specified

Crohn's disease

PATCHY, SKIP LESIONS Cobblestone appearance Mouth to anus Small bowel most common place Anti-saccharomyces cerevisiae antibodies Non-caseating granulomas String sign Fistulas Transmural inflammation of the bowel -ALL layers of bowls abdominal pain(RLQ)

Nephrotoxic AKI

PCT is most often injured -> its the site that the toxins hit first Toxic agents: Aminoglycosides Heme pigments

Left dominant circulation

PDA comes off the left circumflex artery AV nodal artery comes off dominant artery, so left circumflex in this case too

Tetralogy of Fallot

PROVe Pulmonic stenosis right ventricular hypertrophy overriding aorta ventricular septal defect Worsening cyanosis difficulty feeding More severe the pulmonary stenosis, the worse the prognosis Squatting helps

Varicocele

PW -aching in left scrotum testicular atrophy and decreased fertility can follow

Respiratory alkalosis from high altitudes

PaO2 can be as low as 60 mmHg pH ~ 7.50 PaCO2 ~ 20 HCO3 ~ 15

Esophageal ulcer

Pain with swallowing Long term GERD can cause

Aneurisms

Palpable, pulsatile abdominal mass Screening ultrasound in men smokers over 65 Distal embolization of thrombus withing aortic aneurysm can cause acute limb ischemia True aortic aneurysm = ALL layers involved False = only involves adventitia Focal area of dilation Most occur below renal arteries Aortic arch is second most common Many patients also have atherosclerosis, even at the site of the aneurysm (unclear if they directly cause one another) Inflammatory cells infiltrate in vessel wall (seen in cystic medial degeneration) -Degradation of elastic lamina -degradation of extracellular matrix by metalloproteinases -smooth muscle apoptosis and necrosis -> accumulation of mucopolysaccharide Risk factors: -atherosclerosis -smoking -age -hypertension -Marfan's -bicuspid aortic valve -turner's -family history -septic emboli from endocarditis that can seed the aortic wall -temporal arteritis -Takayasu arteritis -tertiary syphilis (starts with destruction of vasa vasorum which perfuses 2/3rd of aortic wall Can compress surrounding structures if they get big enough -can obstruct ureters -> hydronephrosis and postrenal kidney injury -tracheal compression -> cough ,dyspnea, wheezing -compress recurrent laryngeal nerve and cause hoarseness -compress esophagus -> dysphagia Rupture of AA is reaaaaaaaally bad 50% mortality -severe acute flank pain -retroperitoneal hemorrhage AA's extending proximally can involve aortic root and cause aortic regurgitation (diastolic decrescendo murmur) which can lead to heart failure AA's extending proximally may involve coronary arteries -> ischemic heart disease -stroke also because these proximal lesions are in the right spot to throw clots up the carotid to the brain Diameter >6cm = risk of rupture Thoracic aortic aneurysm rupture presents with acute, tearing, chest pain radiating to back

Multiple endocrine neoplasia type 2A

Parathyroid Pheochromocytoma Medullary thyroid carcinoma mutation in RET -codes for receptor tyrosine kinase -neural crest cell AD Gain of function RET mutation (tyrosine kinase)

Gastroschisis

Paraumbilical herniation through ventral abdominal wall Next to umbilicus, not through it No peritoneum Guts spill directly out

Parinaud syndrome

Parinaud syndrome -> vertical gaze palsy syndrome that presents with "setting sun sign" due to compression of the tectum & superior colliculi

Lipid A

Part of LPS O antigen, core poly saccharide, and lipid A lipid A is responsible for the toxic properties that lead to gram negative sepsis and endotoxic septic shock Induces shock by activation of macrophages and granulocytes -> IL-1, prostaglandins, TNF-alpha, interferon

Aortic dissection

Partial tear HTN most important predisposing factor Young people? connective tissue disorders Iatrogenic damage from cardiac catheterization Tearing posterior pain Can extend all the way down to iliac arteries Stanford system: -Type A aortic dissections = occur in ASCENDING aorta -Type B, descending DeBakey -Type I: both ascending and descending -Type II: asceding only -type III: descending distal to the left subclavia artery

Indirect Coombs test

Patients serum -> add RBCs -> add Coombs reagent (antibody that attaches to antibodies) -> agglutination is positive result

Pilocytic astrocytoma

Pediatric tumor mostly infratentorial (under tentorium cerebelli) Most common in children hairlike projections grade I astrocytoma (benign) Activations of BRAF gene are common posterior fossa, cerebellum well circumscribed solid and cystic components Rosenthal fibers GFAP+ PW -headache -seizure -focal neurologic defects -nausea -vomiting -infant: decreased feeding, irritibility -obstructive hydrocephalus RF -tuberous sclerosis -NF type 1

Ependymoma

Pediatric tumor mostly infratentorial (under tentorium cerebelli) arise from cells that line the ventricular system most common from roof of 4th ventricle obstructive hydrocephalus can be found anywhere along spinal tract perivascular pseudorosettes ependymal rosettes (not always present, but diagnostic) PW -headache -seizure -focal neurologic defects -nausea -vomiting -infant: decreased feeding, irritibility -obstructive hydrocephalus RF -tuberous sclerosis -NF type 1

Medulloblastoma

Pediatric tumor mostly infratentorial (under tentorium cerebelli) positive for synaptophysin and neuron specific enolase cerebellum is common area extend into the 4th ventricle MYC amplification (poor prognosis) small blue cells many mitotic figures Homer-Wright rosettes small blue cells surrounding acellular pink neurophil drop metastasis -nodules form along spinal cord - PW -headache -seizure -focal neurologic defects -nausea -vomiting -infant: decreased feeding, irritibility -obstructive hydrocephalus -ataxia RF -tuberous sclerosis -NF type 1

peptic ulcer disease

Penetrate past muscularis mucosa into the submucosa Chronic NSAID use -synergistic risk factors Melana

non small cell carcinoma (large cell)

Peripherally located Large undifferentiated anaplastic cells with huge nuclei and prominent nucleoli -Probably from adeno or squamous carcinoma cells that have become so undifferentiated that they cannot be recognized Form peripherally in sheets or nests Metastasis early Very resistant to chemotherapy

Adenocarcinoma

Peripherally located Most common in those with no smoking history Women Under 40 Most common lung cancer Glandular tissue -acinar, papillary, mucinous Adenomatous hyperplasia -> adenocarcinoma in situ (hasn't crossed BM, tall columnar cells that spread across alveolar wall aka Lepidic growth pattern, means rind-like or membrane-like) May look like hazy consolidation and pneumonia-> adenocarcinoma Produce mucin -> copious sputum production Are hyperchromatic Paraneoplastic syndrome: Digital clubbing from hypertrophic osteoarthropothy

Bronchiectasis

Permanent dilation of bronchi or bronchioles Caused by recurrent infections -destroy elastic tissue -tumors causing obstruction leading to infection beyond -primary ciliary dyskinesia (cant clear mucus) -TB (post infectious bronchiectasis is most common) Primarily affects lower lobes Productive cough (cup fulls)

Fibular fracture

Peroneal nerve damage deep peroneal nerve innervates dorsiflexors of foot superficial peroneal nerve provides sensory innervation to dorsum of foot

Cardiac pacemaker cells

Phase 4 -funny Na+ channel leaks sodium in -T-type Ca channel opens first, helps depolarization Phase 0 -L-type Ca opens next and rapid depolarization occurs Phase 3 -K+ outward repolarizes

Multiple endocrine neoplasia type 2B

Pheochromocytoma medullary thyroid carcinoma mucosal neuromas (small collections of neural tissue on tongue, lips and buccal mucosa) associated -marfanoid habitus -RET gene AD Gain of function RET mutation Marfanoid habitus -lordosis

Sildenafil

Phosphodiesterase 5 inhibitor increases cGMP -> dephosphoylates MLC Kinase -> vasodilation ED Pulmonary hypertension

Poliovirus

Picornaviridae Positive sense RNA virus Naked virus Fecal Oral transmission Acid Stable Enters through GI Replicates in lymphoid tissue (lymph nodes and Peyer's patches) Then goes to anterior horn of the spinal corn Asymmetric paralysis Myalgia decreased deep tendon reflexes respiratory insufficiency from paralysis of diaphragm Can also cause aseptic meningitis Salk vaccine - killed vaccine (parentral - no IgA) Sabien vaccine - attenuated LIVE vaccine (IgA immunity, however more dangerous because the virus can be shed fecally where it could possibly revert to regular virus and infect others) U.S. uses killed Salk vaccine

Hepatitis A virus

Picornaviridae RNA positive sense RNA virus Acid stable Fecal orally Naked virus Shed in feces and contaminates drinking water Inactive Hep A: chlorine, bleach, UV radiation, or boil the water Shellfish that were caught in contaminated waters Common route of transmission in US Commonly seen in travelers to endemic areas (southern hemisphere especially) Hepatitis Jaundice in adults Anicteric hepatitis in young Smokers with hep A develop aversion to smoking One month duration of symptoms Self-limiting No carrier state Vaccine - inactivated

Coxsackievirus A & B

Picornaviridae RNA positive strand virus Naked virus Coxsackie A: Hand foot and mouth disease Red vesicular rash Aseptic meningitis helmet Infection common in summer time Coxsackie B: Dilated cardiomyopathy Devils grip (bornholm's disease / pleurodynia) - extreme sharp pain in the lower chest, usually unilateral Treatment is supportive only

Rhinovirus

Picornaviridae RNA positive-sense virus Respiratory transmission (not fecal oral like all other picornaviridae) and fomites Naked virus Acid Labile Attaches to ICAM-1 Grows best in cooler temperature (upper respiratory tract with cool air flowing in and out) URI's Soooooo many serotypes Can't make vaccine No treatments

Thrombocytopenia

Platletest under 150,000 Bleeding risk doesn't rise until you are under 50,000 Spontaneous bleeding doesn't occur until under 20,000 No effect on PT/aPTT

Sturge-Weber syndrome

Port wine stain -nevus flammus -facial capillary malformation -mutation in GNAQ gene -> G alpha q protein -IP3/DAG pathway messed up -V1 and maxillary most affected mosaicism leptomeningeal angiomas -affect arachonoid mater -grow into subarachnoid space -compresses brain parenchyma -compression necrosis -calcifcations -seizures Episcleral hemangiomas -glaucoma -visual changes Intellectual disability tends to be progressive disorder Tx -reduce seizure frequency -laser therapy for face stain

Coronavirus

Positive sense RNA helically encapsulated virus SARS -acute bronchitis that can lead to acute respiratory MERS also can cause common cold replicates in the cytoplasm like all other RNA positive sense virus

Gabapentin

Postherpetic neuralgia Fibromyalgia Neuropathic pain Does dependent sedation Ataxia Bad for older patients Gabapentin DOES NOT bind to gaba receptors

Osteoporosis

Postmenopausal -decreased estrogen (stimulates PW -fractures of vertebral column -kyphosis -dowingers hump (stooped over posture) -femoral neck fracture RF -smoking -steroids -cushing syndrome -heparin -PPIs Dx -DEXA scan for bone density -T score between negative 1 and negative 2.5 -one of the fragility fractures is diagnositic Tx -bisphosphonates -Raloxifen -weight bearing therap

Class III antiarrhythmics

Potassium channel blockers -prolong phase 2 and 3 of the cardiac action potential -> prolonged refractory period Treat -both supraventricular arrhythmias and ventricular -A fib -A flutter Amiodarone -exhibits qualities of all classes of antiarrhtyhmics -accumulates in many tissues -brain: tremor, ataxia, peripheral neuropathy, sleep disturbances -Gray corneal microdeposits (can rarely cause halos in vision or blindness -hypothyroidism -hyperthyroidism -Must do thyroid test before starting -Pulmonary fibrosis -can cause heart block -can induce heart failure -hypersensitivity hepatitis -LESS CHANCE OF TORSADES than others Sotalol -beta blocker -torsades "till I die" -tilide suffix ( Dofetilide -torsades Ibutilide -torsades

Hydralazine

Potent vasodilator -> reflexive tachycardia Safe in pregnancy Combines with nitroglycerin to treat heart failure (AA's) Can cause drug induced lupus like syndrome

Oligohydramnios

Potter's sequence -Clubbed feet -Flat facies caused by -malformation of the kidney -anything that causes decreased urine -ARB or ACE inhibitor exposure in utero -posterior urethral valves

Glucocorticoids

Prednisone, prednisolone, methylprednisolone, dexamethasone, fludrocortisone Inhibits phospholipase A2 -releases arachidonic acid usually -> LOX and COX inflammatory pathways -anti-inflammatory Inhibits NF-Kappa B -> no IL-2 and TNF-alpha -> no WBC differentiation -> no neutrophil adhesion molecule stimulation -> demargination and decreased migration of neutrophils -> can't get to places of antigen presentation Reduce peripheral lymphocyte counts within minutes -lymphocytes go into spleen, bone marrow Peripheral antagonism of insulin -> insulin resistance Increases hepatic glycogen storage Promote catabolism at peripheral tissue Impaired wound healing Immunosuppresion DMARDs Tx -Inflammatory conditions -Rheumatoid arthritis (its a DMARD) -Addison's disease (adrenal insufficiency) -Give calcium and vitamin D supplementation AEs -Can cause hypocalcemia -Fluid retention and hypertension -Hypokalemia -Acute adrenocortical insufficiency upon cessation -Hyperglycemia -Hyperlipidemia -Elevated glucagon -Osteoporosis -Decreased osteoblastic bone formation -increased osteoclastic bone resorption -Adrenal cortical atrophy with chronic exogenous use -muscle weakness, moon facies, central adiposity, thinning of skin, abdominal striae, impaired wound healing (Cushing's syndrome symptoms) -hypomania, confusion, hallucinations (glucocorticoid induced psychosis)

Secondary amenorrhea

Pregnancy most frequent cause Acquired GnRH deficiency -severely low caloric intake -vigorous strenuous exercise -female athlete triad: amenorrhea, disordered eating, and hypocalcemia from low vitamin D intake Prolactinoma Hypothalamic and pituitary dysfunction

Celiac disease

Presence of IgA antibodies against tissue transglutaminase, which is concentrated in intestinal smooth muscle Linkage with HLA DQ2 and DQ8 alleles Triggered by ingestion of gliaden, a component of gluten Immune response causing villous atrophy Dermatitis due to epidermal transglutaminase Itchy, red, vesicular rash prominent on extensor surfaces Strong association with metabolic bone disease, even in patients with no overt GI symptoms

Pericarditis

Presentation -fever -tachycardia -Pleuritic chest pain (worse with swallowing, deep breaths, better when leaning forward) -friction rub (doesn't disappear when breath is held) -Diffuse ST elevation on ECG -pleural effusion (exudative inflammatory fluid; can be hemorrhagic - think malignancy) -cardiac tamponade if effusion is fast enought -Beck's triad: JVD, hypotension, muffled heart sounds -Pulsus paradoxus: IVS bows out to left upon deep inspiration, LV can't pump and pulse drops Causes -viral (MOST common) -autoimmune (SLE -bacterial -MI -acute pericarditis overlying necrotic area -Dressler's -Uremic pericarditis -malignant pericarditis

Dressler's syndrome

Presents weeks to months post MI Fever leukocytosis PERICARDITIS Friction rub

Intracranial hypertension

Pressure is usually aroun 15 mmHg >20mmHg is INTRACRANIAL HYPERTENSION CPP = MAP - ICP -if ICP gets to high, no perfusion to the brain Symptoms -Altered mental status -Confusion -Seizures -Coma -Vomiting -PAPILLEDEMA (swelling of optic disc) -> can lead to permanent vision loss -diplopia due to stretching of cranial nerve VI -Cushing's reflex -> HTN, bradycardia, irregular respirations (late sign that signals impending brain herniation) -HERNIATIONS RF -cerebral edema ->intracellular cerebral edema due to hyponatremia -hydrocephalus due to increased vascular permeability leading to leakage into extracellular space Dx -Effacement of the sulci due to increased pressure smushing nooks and crannies -> turns more homogenous -PAPILLEDEMA (swelling of optic disc) Tx - Idiopathic ICHTN -most commonly affects obese women of childbearing age -pathogenesis is thought to involve increased drainage of CSF thru arachnoid granulations -All-trans retinoic acid is risk factor -tetracyclines and isotretinoin too -headaches, papilledema, diplopia, pulsatile tinnitus -High opening pressure on lumbar tap

Interferon-gamma

Primarily secreted by T lymphocytes Activates macrophages, increases MHC1 expression

Primary amenorrhea

Primary -never had a menstrual period by age 15 -or 13 if no other secondary sexual characteristics -Congenital GnRH deficiency -> Kallmann syndrome: anosmia (absent sense of smell). Total lack of estrogen, no secondary sex characteristics either -Ovarian dysfunction: FSH and LH will be elevated -Turner's syndrome Structural -Mullerian duct agenesis -> Mullerian ducts usually develop into uterus, fallopian tubes, upper 1/3rd of vagina -> not present -imperforate hymen: failure of central hymen to degenerate (fully developed secondary sexual characteristics

Kartagener Syndrome

Primary ciliary dyskinesia Immotile cilia due to dynein arm defect AR decreased male and female fertility PW -bronchiectasis -recurrant sinusitis -chronic ear infections -conductive hearing loss -situs inversus

Collecting duct

Principle cell exchanges sodium, potassium, water -ENaC on luminal side -Na+/K+ ATPase on basolateral side -resorption of Na+ creates negative luminal potential that facilitates K+ excretion

Sertoli-leydig tumor

Produce androgens hirsutism, cliteromegaly, voice changes Tubular structures lined by round sertoli cells Males and females

Leukotrienes

Product of LOX pathway C4 B4 - potent chemoattractant D4 - bronchoconstrictor E4 - bronchoconstrictor CysLT1 -receptor

Slipped capital femoral epiphysis

Progression left femoral head deformity Obese adolescent

Acute myeloid leukemia

Proliferation of immature granulocyte and monocyte precursors (myeloblasts) in the bone marrow Acute = rapid disease onset and progression Clinical presentation -functional pancytopenia -actual count may be high, but all the white blood cells are effed, non-functioning -> you are counting blasts -weakness -fatigue Myeloblasts must account for 20% of BM cells or peripheral blood Myeloblasts contain abundant basophilic cytoplasm (with faint granules); large folded or bilobed nuclei (with multiple dark nucleoli) In some subtypes -> AUER Rods (indicate partial myeloid differentiation) 8 subtypes (most are so rare they are not tested) By type of cell that proliferates 1. Acute promyelocytic leukemia (APL) -immature myeloid cells with abundant Auer rods -can lead to DIC due to secretion of tissue factor by promyelocytes -can be treated with all-trans-retinoic acid (vitamin A analog that signals neoplastic promyelocytes to differentiate into mature neutrophils 2.

Non-Hodgkin Lymphoma

Proliferation of mature B cells Usually non-contiguous distribution Extranodal involvement is common No Reed-Sternberg cells Classic B cell lymphoma/leukemia symptoms -night sweats -weight loss -fever Burkitt lymphoma -very aggressive B cell lymphoma -gene translocation -8 -> 14 overexpression of myc protein -mitotic figures Follicular lymphoma Mantle cell lymphoma Diffuse large B cell lymphoma Primary effusion lymphoma

Rasburicase

Protects organs during chemotherapy by converting uric acid into more soluble metabolite Recombinate version of urate oxidase

Sixth aortic arch

Proximal pulmonary arteries On left -> ductus arteriosus

Lambert-Eaton syndrome

Proximal weakness (gait alteration, difficulty arising from chair, climbing stairs) Cranial nerve involvement is present in >60% of patients antibodies against presynaptic calcium channels approximately half have associated malignancies (small cell lung cancer is classic)

Dermatitis herpetiformis

Pruritic papules and vesicles with an erythematous base tends to involve forearms/elbows, knees, and buttocks strongly associated with gluten-sensitive enteropathy (eliminate gliadin to remiss) Deposits of IgA and C3

Internal capsule stroke

Pure motor weakness affecting the contralateral arm, leg, and lower face UMN signs -contralateral spasticity, or increased tone, hyperreflexia, and a positive babinski sign

Foscarnet

Pyrophosphate analog Used in ganciclovir- resistant CMV infections Chelates calcium Induces renal wasting of magnesium -> hypomagnesemia These changes can lead to seizures Tx -resistant HSV, CMV, VZV AEs -Delerium -Confusion -Vertigo -hallucinations -hypocalcemia -all worse with IV administration -hypomagnesia -hypokalemia -renal insufficency

Coxiella Burnetii

Q fever No rash! Obligate intracellular Transmitted to humans via aerosol transmission or a vet who helped delivery a baby farm animal Pneumonia and headache Fever HEPATITIS! Infection is usually self-limited myocarditis if its chronic

Von Willebrand disease

Quantitative deficiency in vWF Autosomal dominant

Immune thrombocytopenia

Quantitative platelet disorder Group of disorders caused by IgG autoantibodies against glycoprotein 2b/3a receptors on platelets -in children, thought to be caused by abnormal autoimmune response to viral infection and typically affects children from 2-5 years old (slight male predominance) -usually self-limited in children Platelet bleeding -petechia -epistaxis -easy bruising In adults -many potential causes -chronic courses with episodic flares -young women in their 20's and 30's -diagnoses requires isolated thrombocytopenia with no other abnormal findings -corticosteroids and IVIg -IVIg - a bunch of antibodies confuse the body and it stops making autoantibodies? lol -can step it up to splenectomy and rituximab -diagnosis of exclusion

Hemolytic-uremic syndrome

Quantitative platelet disorder HUS thrombotic microangiopathy Diffuse platelet activation -> thrombocytopenia Thrombosis of the microcirculation increases shear force on erythrocytes -> hemolysis -> microangiopathic hemolytic anemia (MAHA) -Schistocytes -increased LDH, bilirubin -increased reticulocyte production Most common Enterohemorrhagic E. coli (EHEC) causes 90% of cases (bloody diarrhea, abdominal pain, vomiting, undercooked meat, shiga-like toxin production) -NEVER TREAT WITH ANTIBIOTICS -> lysis of cells causes release of all the toxin at once and can cause complete renal failure Shiga toxin -> capillary endothelial damage -> MAHA Acute Kidney Injury

Leptospira interrogans

Question mark Rodents and dogs, transmitted through urine, humans get it when they swim in contaminated water WATER sports Symptoms Conjunctivitis -> red without the puss WEIL'S disease Affects kidney and liver Jaundice

Intravascular hemolysis

RBCs lyse inside blood vessels -LDH directly into bloodstream -increased serum hemoglobin (haptoglobin binds to some and this complex is taken up by the liver -> haptoglobin drops to undetectable levels) -hemoglobin or methemoglobin in the urine -> hemoglobinuria and dark brown urine Severe intravascular hemolysis can cause acute tubular necrosis (ATN) heme from lysed RBCs -> tubular obstruction, direct toxicity, and vasoconstriction -> kidney injury AKI due to ATN -> elevated BUN and creatinine Unconjugated hyperbilirubinemia Urinary Urobilinogen Reticulocyte count elevated (>3%) usually causes normocytic anemia (80-100)

Asthma

REVERSIBLE intermittent airway obstruction Chronic bronchial inflammation with eosinophils Type 1 hypersensitivity Charco-Layden crystals- thin needle like concentrations of eosinophil proteins -found in eosinophils Allergen activated TH2 cells -> IL-5 -> eosinophil activation Bronchoconstriction Nocturnal cough Severe acute asthma can cause pulsus paradoxus FEV1/FVC =.7 Late phase -4-8 hours after early -eosinophils, neutrophils, and t cells -epithelial cells secrete chemotaxin -eosinophils release major basic protein that damages epithelial cells -can lead to airway remodeling respiratory acidosis from CO2 buildup in lungs

Breast cancer

RF -BRCA 1 and 2 -Li-Fraumeni syndrome -nulliparity -older age at first pregnancy - breastfeeding is protective against breast cancer ER+ -can treat with tamoxifen PR+ - HER2+ -tyrosine kinase -EGF receptor Triple negative breast cancer carries worse prognosis Tx -SERMs:Raloxifene, tamoxifen (agonist in uterus)

Bunyaviridae

RNA negative strand enveloped virus 3 circular segments Most are arboviruses Members: Hantavirus -rodents and their excrement -deer mouse is reservoir (robo virus) -pulmonary edema from capillary leak -Pre-renal azotemia -Hemorrhagic fever California encephalitis virus -seizures -encephalitis -Aedes mosquito Rift valley fever virus -seizures -encephalitis -Aedes mosquito

Flaviviridae overview

RNA positive sense Enveloped virus Non-segmented Members: Hepatits C -hepatitis Dengue fever -Aedes Aegypti vector -infects the bone marrow -thrombocytopenia -hemorrhagic fever -can lead to renal failure -supportive therapy, hydration -secondary infection with a different phenotype can lead to more severe illness, possibly due to antibody-dependent enhancement of the infection, enhanced immune complex deposition, and/or accelerated T cell response Yellow fever -Aedes mosquito vector -Jaundice -back ache -bloody diarrhea -bloody vomiting -live attenuated vaccine for travelers West Nile virus -birds are resevoir -Mosquito vector -Encephalitis is major complication -myelitis that can lead to flaccid paralysis -seizures and coma if it gets bad enough -Supportive therapy

Togaviridae

RNA virus, positive sense enveloped Transmitted via respiratory droplets Arbovirus arthropod borne virus Western equine encephalitis Eastern Equine encephalitis Venezuelan equine -no treatment for these, so protective gear is most effective Rubella -german measles -Childhood exanthem -Congenital mental retartdation microcephaly deafness cataracts jaundice BLUEBERRY MUFFIN RASH patent ductus arterioses pulmonic stenosis CLASSIC TRIAD: congenital cataracts, sensorineural deafness, patent ductus arteriosus -childhood Mild fever tender postauricular and occipital lymphadenopathy maculopapular rash beginning on face and spreading downward Rash moves fast, present for around 3 days, and doesn't coalesce -adult Lymphadenopathy and fever Arthritis and myalgia Vaccine - MMR Live, attenuated which induces both humoral and cell mediated immunity HIV patients should only receive vaccine if their CD4 is over 200 Do not give to pregnant woman Long polyprotein cleaved by proteases

Picornaviridae overview

RNA viruses Positive sense Fecal oral transmission Polyprotein product that gets cleaved into smaller subunits Members: Hepatitis A Hepatosplenomegaly Enteroviruses: Poliovirus Coxsackie A and B Echovirus Aseptic meningitis Viral meningitis (children particularly susceptible): CSF glucose is normal, no organisms, elevated protein Rhinovirus Common cold RESPIRATORY INFECTION URI

Acid-base disturbances

ROME Respiratory opposite (low pH high bicarb) Metabolic equivalent (low pH low bicarb) Look at pH Lower than 7.4 -> acidotic Higher than 7.4 -> basic Look at pCO2 to differentiate between respiratory or metabolic -messed up pCO2 -> respiratory Respiratory acidosis -> kidney compensates by dumping more H+ and saving more bicarb (requires 3-5 days to have maximal effect) For simplicity, bicarb > 30 is seen in chronic compensated, < 30 is seen in acute uncompensated Metabolic acidosis -> compensate by hyperventilation Respiratory alkalosis -> delayed, kidneys compensate through bicarb loss Metabolic alkalosis -> hypoventiliation

Sporothrix Schenckii

ROSE THORN Also tree bark, bushed, plants Dimorphic fungus Branching hyphae Cigar shaped budding yeasts Local ulcer at site of trauma Then; ascending ulcer pattern along draining lymphatics Treatment: Itraconazole Saturated solution of potassium iodine

Francisella tularensis

Rabbits are reservoir Ticks (dermacenter) Aerosolized (can be used in bioterrorism) gram -, coccobacilli Facultative intracellular (cell mediated immunity) Painful ulcer at site of infection goes into macrophages, travels through lymph to nodes and causes granulomas with caseation necrosis Regional lymphadenopothy Treat: Streptomycin (aminoglycosides)

Cystine Stones

Radiolucent Acidic urine pH Defect in PCT reabsorption that causes increased cystine, ornithine, arginine, and lysine in the urine -only cystine is insoluable enough Can form staghorn calculi Flat hexagonal crystals on microscopy Sodium cyanide-nitroprusside urine test -urine will turn red-purple in positive test Chelating agent (penicillamine) can help

Uric acid stones

Radiolucent Increased urine uric acid concentration Decreased urine pH Causes -Gout -Leisch-Neienne syndrome -Rapid cell turnover (leukemias and lymphomas) -chemotherapy -> massive cell death -> tumor lysis syndrome -chronic diarrhea -> metabolic acidosis -> decreased urine pH Treatment -Alkalinization of the urine -Allopurinol Diamond red-brown crystals on microscopy

Magnesium ammonium phosphate stone

Radiopaque 2nd most common in adults MAP stones Struvite or staghorn calculi UTI with urease positive organism -urea -> ammonium + CO2 -increased pH decreased solubility of phosphate -Proteus -S. saprophiticus -Klebsiella Surgical removal may be necessary Antibiotics to treat

Calcium phosphate stones

Radiopaque More common in children Minority of calcium stones RTA type 1 -acidemia and alkaline urine environment promotes calcium precipitation Elevated pH promotes Treatment -Hydrochlorothiazide can help by increasing calcium resorption -hydration

Calcium oxalate stones

Radiopaque Supersaturation Most common stone High concentration in the renal tubule of either calcium or oxalate -Hypercalcemia (although most are normal) -Hypercalciuria with normocalcemia (most common cause) -> most common cause is absorptive calciuria (gut absorbs more and so more is excreted) -Hyperparathyroidism (primary or from malignancy) -Acidosis can cause hypercalciuria from phosphate buffer system -hypocitraturia -Diarrhea leading to metabolic acidosis -increased sodium intake leading to reduced Na+ and Ca++ reuptake from nephron through symporter Decreased calcium intake actually PRECIPITATES stones (due to increased oxalate absorption -> more oxalate in tubule) Pure vegan diet is rich in oxalate Fat malabsorption binds calcium in the gut -Crohn's disease (cobblestoning, skip lesions)

integrase inhibitors

Raltegravir -binds viral integrase -usually inserts viral DNA into host genome Tx -HIV AEs -rhabdomyolysis

Somatostatinoma

Rare pancreatic islet cell tumors that arise from delta cells Secrete somatostatin that inhibits secretion of secretin, cholecystokinin, glucagon, insulin, and gastrin. Patients present with hyperglycemia hypoglycemia steatorrhea gallbladder stones

MAO inhibitors

Really old drugs not used anymore Tranylcypromine phenelzine isocarboxazide Selegiline (MAO-B specific) MAO-A -Serotonin, norepinephrine, dopamine MAO-B -Dopamine MOA -prevent breakdown of monoamines (dopamine, serotonin, norepinephrine) -increase availability in synapse -irreversible AEs -If you eat cheese while on it, you can get tyramine excess -> dangerous hypertension -> give phentolamine -orthostatic hypotension -weight gain -most sexual side effect causing -don't use with SSRIs, TCAs ect Tx -depression (resistant, def not first line) -atypical depression

Mecasermin

Recombinant Insulin-like growth factor-1 AEs -hypoglycemia

Teriparatide

Recombinant PTH analog given subcutaneous daily OSTEOBLAST STIMULATOR (only one)

Ulcerative colitis

Recurrent episodes of rectal and colonic inflammation CONTINUOUS mucosa and submucosal involvement Lead pipe appearance (loss of haustra) pANCA elevation Fulminent colitis Toxic megacolon -inflammation extended to smooth muscle layer -> paralyzing -> megacolon -> perforation (50% mortality) abdominal pain increased risk of primary sclerosing cholangitis Migratory arthritis erythema nodosomse -> inflammation of fat cells renal calculi -> increased absorption of oxalate Eye disease Treat -5-ASA

Acute decompensated heart failure

Reduced cardiac output is sensed by body and SYMPATHETIC nervous activation is most contributory in compensatory stimulation (renin activity and BNP + ANP)

Intermediate acting insulin

Regular insulin - only one that can be given IV, for emergency DKA Neutral Protamine Hagedorn - NPH works within 30 min peaks within 2 hours less predictable

Acute pancreatitis

Release of pancreatic enzymes is very bad -premature activation of trypsinogen to trypsin -> activation of other enzymes -> tissue damage -pancreatic lipase -> fat necrosis -fatty acids bind with calcium and precipitate -> more inflammation -vicious cycle of more release and more digestion Gallstones are most common cause -common bile duct obstruction (choledocolithiasis) RF -alcoholism (direct toxic injury) -hypertriglyceridemia (>1000mg/dL) that can be toxic -diabetes -medications ( -Trauma (seatbelt trauma) -iatrogenic (endoscopic retrograde cholangiopancreatography) PW -pain radiating to back -nasua -vomiting -serum amylase is elevated -hypocalcemia -hypovolemia due to fluid around the abdomen -pseudocyst from all the calcified fat and inflammation (walls are not made of true epithelium, rather a fibrous -hemorrhage -ARDS (phospholipase released chews up surfactant in lungs) Can lead to acute necrotizing pancreatitis -acinar cells die from ischemia and release enzymes splenic vein thrombosis -pressure backs up to gastric veins -> gastric varices -> rupture and hematemesis and tarry stools Treat -preventative -dont eat to prevent further release

Antidiuretic hormone

Released by posterior pituitary increases water resorption at -V2 on basolateral membrane (Gs -> cAMP) collecting duct cells causes aquaporin to be put into luminal membrane -V2 receptors also on vascular endothelium -> stimulates endothelial cells to release vWF and VIII -Treats hemophilia A and von Willebrand's disease Has vasopressor properties as well -activates V1 (Gq -> IP3 -> DAG -> calcium) receptors on vascular smooth muscle -> vasoconstriction and increased BP Tx -Central diabetes insipidus (thiazide diuretics, amiloride for nephrogenic DI0

Bacterial DNA polymerase I

Removes DNA primers (RNA) with DNA 5' -> 3' exonuclease activity

Leukemoid reaction

Response to an infection Normal response Bone marrow can become hypercellular Increased bands and early immature neutrophils with Dohle bodies (light blue basophilic peripheral granules) Serum leukocyte alkaline phosphatase

Splinter hemorrhages

Result of microemboli Sign of infectious endocarditis Progressive fatigue

Adult T-cell leukemia

Result of viral infection of HTLV-1 -retrovirus that infects t lymphocytes -endemic in japan -reverse HIV -> uncontrolled proliferation of T helper cells presents with -hepatosplenomegaly -function immunocompromise -infiltrates skin often -> presents with red plaques and papules (appears similar to cutaneous T-cell lymphoma -lytic bone lesions -> hypercalcemia

HIV

Retroviridae Positive sense enveloped RNA virus Uses reverse transcriptase to make DNA from RNA Gag gene = p24, capsule for the RNA strands Env gene = gp 41 and 120 -> 420!! -41 is transmembrane -120 is outer glycoprotein Pol gene = reverse transcriptase HIV initially infects macrophages Prodrome consists of flu or mono-like symptoms -> lymphadenopathy fever can last for several weeks CD4+ cells are infected Latent for up to 10 years where its replicating in the lymph nodes Then there is a sharp drop in CD4 count, and after it goes below 200, you now have AIDS Can also be diagnosed if its above 200 with an AIDS defining illness HIV can cause a diffuse large B cell lymphoma Has to use CCR5 (early stages) and CXCR4 (later stages) coreceptors to enter ELISA test for screening Western blot to CONFIRM ELISA for baby will come up positive if mother has anti-HIV antibodies Western blot will be positive because of this In NEONATE you have to do RNA and DNA PCR amplification to see if the virus is actually there Combination therapy: NRTIs - nucleotide reverse transcriptase inhibitors, pose as nucleotide and halt further elongation -Zidovudine, can be used during pregnancy, reduces risk of transmission NNRTIs - non-nucleotide reverse transcriptase inhibitors Protease inhibitors - cant cleave proteins necessary for viral replication CCR5 inhibitor: Maraviroc!!!

Regression

Reverting to an earlier stage in development

hydroxyurea

Ribonucleotide reductase inhibitor -stops conversion of UDP to dUDP -blocks thymidine synthesis Chemo drug Rheumatoid arthritis increases fetal hemoglobin

CYP450 inducers

Rifampin Phenytoin Carbamazepine Ginseng St. John's Wort Oral contraceptives Phenobarbital

Myelodysplastic Syndromes

Ringed sideroblasts on peripheral smear -premature RBCs with iron deposits in mitochondria (dysfunctional mitochondria -> iron accumulates in mitochondrial matrix as ferritin, forming the rings) appears as ring around the nucleus Myelofibrosis Hypercellular marrow

Rickets

Risk factors: Exclusive breastfeeding inadequate sun exposure Maternal vitamin D deficiency manifestations: Craniotabes "ping pong ball" skull Delayed fontanel closure Hypertrphy of the costochondral joints widening and thickening of the wrists femoral and tibial bowing valgus deformity Defective cartilage formation at growth plates

Direct factor Xa inhibitors

Rivaroxaban Apixaban Treat venous thrombosis Fixed oral doses without the need for monitoring

Rickettsia rickettsii

Rocky mountain spotted fever CENTRIPETAL rash, also petechial Tick (dermacentor) transmitted Obligate intracellular Rash on HANDS and FEET Starts on hands and feet and goes central Giemsa stain Needs CoA and NAD+ Treat with doxycycline Myalgia, headache, fever

Primary empty sella syndrome

Roof caves in on gland obliterates pituitary secondary is from iatrogenic primary is from abnormal growth

HHV-6

Roseola Rose-six-ola DNA virus Herpesviridae Infects CD4 cells Can cause immunosuppression this way "Exanthem subitum" High fever - so high it can cause seizures (fever lasts 4 days about) THEN the rash, usually diffuse lacey and spares the face Affects kids 6 months to 2 years usually self limiting no treatment, just cooling

Reoviridae

Rotavirus Colorado tick fever virus Double stranded RNA virus Naked virus 11 segments on average (between 9-12) Rotavirus: Toxin mediated watery diarrhea NSP4 toxin Increased the chloride permeability Seasonal -> winter time Children are at risk -> classic is young child in day care #1 cause of severe diarrhea in young children Colorado tick fever virus: Fever, myalgia, vomiting No rash Treatment: Oral rehydration and supportive therapy Live attenuated oral vaccine is now part of routine care in US First does should be given before 3 months of age Thought to increase the risk of intussusception

Pacing of heart components

SA node: 60-100 beats per minute AV node: 45-55 beats per minute

Hypertensive emergency

SBP >180 DBP > 120 End organ damage Can't lower too fast (ischemic damage to tissues that have become accustomed to high BP), 10-20% over first hour, then further 5-15% over the next 23 hours Treat: -beta-1 antagonists (labetalol, -VASODILATORS to reduce afterload (toxic amount -> hypotension -> reflex tachycardia, increased renin) -Nicardipine, clevidipine (IV CCBs) to dilate arteries and decrease SVR -Nitroprusside (provide NO -> cGMP increase -> dephosphorylation of myosin light chain) and too much can cause cyanide poisoning

Parvovirus

SINGLE STRANDED naked DNA virus "slapped cheek" rash smallest DNA virus Respiratory droplet transmission Congenital transmission "fifth's disease" "Erythema infectiosum" Fever, then fever breaks Then slapped cheek rash Then lacy diffuse rash that moves downwards Classic: school teacher gets infected Arthritis Transient aplastic anemia (especially those with sickle cell disease) Only adipocytes left, which have a cobweb appearance on biopsy Baby in utero -hydrops fetalis: severe fetal anemia that leads to a severe version of CHF

Citalopram

SSRI first-line treatment for Generalized anxiety disorder

Selective serotonin reuptake inhibitors

SSRI's Fluoxetine Paroxetine Sertraline Citalopram Take up to 2 months to have maximal effect (depressive period as well) Treats: -depression -anxiety -OCD -PTSD -panic disorder -bulimia (not anorexia) -social anxiety disorder Inhibit SERT -> more serotonin at the synapse AE's -SIADH -sexual dysfunction -weight gain -drowsiness -insomnia -serotonin syndrome -> hypertension, hyperthermia, hyperreflexia and clonus (NMS has rigidity) -withdrawal leads to flu-like symptoms Save with cyproheptadine

LAD occlusion

ST elevation in mainly V1 and V2 if septum is ischemic V3 and V4 if its anterior left ventricular wall Proximal LAD occlusion that blocks whole thing would be V1-V4

Treponema pallidum

STD Spirochete Dark Field microscopy Direct sample from lesion Infection is usually diagnosed through blood tests -VDRL screening test Mixes patients serum with cardiolipin-cholesterol-lecithin antigen, presence of clumping indicates antibody against cardiolipin, which is nonspecific for a treponemal species -RPR rapid plasmin reagin Mono, RF, SLE, Leprosy, IV drug user can come up with false positives on VDRL FTA-Ab test - specific test to confirmatory Early: Primary - painless genital chancre (takes out nerves so it's painless) Secondary - systemic disease, maculopapular rash weeks to months after infection Condyloma latum Early latent Late: Tertiary - gummas - soft growths with firm necrotic center Tree-bark aorta, destroys vasa vasorum that supplies aorta with blood (damages small vessels just like in chancre) Tabes dorsalis - demyelination of nerves in dorsal columns of spinal cord that leads to a loss of vibration, proprioception, and discriminatory touch Argyll-robertson pupil - react to accommodation but no reaction to light Late latent Congenital: Saber shins Saddle shaped nose Hutchinson's teeth - notched incisors Mulberry molars - enamel outgrowths Treatment: PENICILLIN!!!! Allergic? Desensitize to allergic reaction then give or tetracycline Treatment can cause Jarisch-Herxheimer reaction - occurs within hours of treatment for a spirochete infection (syphilis, lyme disease, leptospirosis) -Rapid lysis of spirochetes causes release of bacterial lipoproteins into the bloodstream and triggers a strong immunogenic response

Neisseria gonorrheae

STI gram - diplococci obligate intracellular in PMNs Not encapsulated Affects genitalia of women and men men - urethritis, prostatitis, orchitis women - PID Fitz-hugh-curtis syndrome - violin string adhesions form from capsule to liver. This happens when infection seeds the peritoneum Asymmetric arthritis (usually knee) Purulent synovial fluid that doesn't gram stain Mom can pass infection onto baby, causing purulent conjunctivitis Ceftriaxone + doxy for chlamydia coinfection

Constrictive pericarditis

Scarring and fibrosis from pericarditis that leaves the pericardium stiff and non-distendable Presents like constrictive cardiomyopathy Heart can't fill during diastole Prominent Y descent Pericardial knock -ventricle hitting thickened parietal pericardium White brim calcium deposition in chronic constrictive pericarditis TB After open heart surgery Radiation therapy

Aripiprazole

Second generation antipsychotic -LOWER EXTRAPYRAMIDAL SYMPTOMS THAN FIRST GEN -Less prolactinemia -Less NMS Block D2 receptors in the CNS (weaker) Block serotonin receptors (5-HT 2A) (stronger) Block H1 receptors -> drowsiness Block alpha-1 receptors Blocks central and peripheral muscarinic receptors AEs -Weight gain -drowsiness -dyslipidemia -hyperglycemia -lowers seizure threshold -Elongation of QT interval (blocking of cardiac potassium channels) -> torsades

Olanzapine

Second generation antipsychotic -LOWER EXTRAPYRAMIDAL SYMPTOMS THAN FIRST GEN -Less prolactinemia -Less NMS Block D2 receptors in the CNS (weaker) Block serotonin receptors (5-HT 2A) (stronger) AEs -Weight gain -drowsiness -dyslipidemia -hyperglycemia -Elongation of QT interval (blocking of cardiac potassium channels) -> torsades

ziprasidone

Second generation antipsychotic -LOWER EXTRAPYRAMIDAL SYMPTOMS THAN FIRST GEN -Less prolactinemia -Less NMS Block D2 receptors in the CNS (weaker) Block serotonin receptors (5-HT 2A) (stronger) Block H1 receptors -> drowsiness Block alpha-1 receptors Blocks central and peripheral muscarinic receptors AEs -Weight gain -drowsiness -dyslipidemia (lowest risk) -hyperglycemia (lowest risk) -lowers seizure threshold -Elongation of QT interval (blocking of cardiac potassium channels) -> torsades

Quetiapine

Second generation antipsychotic -LOWER EXTRAPYRAMIDAL SYMPTOMS THAN FIRST GEN -Less prolactinemia -Less NMS Block D2 receptors in the CNS (weaker) Block serotonin receptors (5-HT 2A) (stronger) Block H1 receptors -> drowsiness (BAD) Block alpha-1 receptors Blocks central and peripheral muscarinic receptors AEs -Weight gain -drowsiness -dyslipidemia (BAD) -hyperglycemia (BAD) -lowers seizure threshold -Elongation of QT interval (blocking of cardiac potassium channels) -> torsades

clozapine

Second generation antipsychotic -LOWER EXTRAPYRAMIDAL SYMPTOMS THAN FIRST GEN -Less prolactinemia -Less NMS prototypical SGA Block D2 receptors in the CNS (weaker) Block serotonin receptors (5-HT 2A) (stronger) Block H1 receptors -> drowsiness (BAD) Block alpha-1 receptors Blocks central and peripheral muscarinic receptors (worst of all) treat positive and negative symptoms Tx -Schizophrenia -tourettes -depression (treatment resistant) AEs -Weight gain -drowsiness -dyslipidemia -hyperglycemia -neutropenia -agranulocytosis -lowers seizure threshold (worst)

risperidone

Second generation antipsychotic -LOWER EXTRAPYRAMIDAL SYMPTOMS THAN FIRST GEN -Less prolactinemia -Less NMS (this one is the least good at this tho) Block D2 receptors in the CNS (weaker) Block serotonin receptors (5-HT 2A) (stronger) Block H1 receptors -> drowsiness Block alpha-1 receptors Blocks central and peripheral muscarinic receptors Tx -can help manage OCD (adjunctive with SSRIs) -Tourette syndrome AEs -Weight gain -drowsiness -dyslipidemia -hyperglycemia -lowers seizure threshold -Elongation of QT interval (blocking of cardiac potassium channels) -> torsades

Fragile X syndrome

Second most common cause of low IQ after Downs CGG repeats 6-55 normal 55-200 premutation >200 full blown When you have so many repeats the body silences the gene -> methylation Large ears Long narrow face Prominent forehead Large chin High palate Hyperextensible joints large testicles mental retardation autism spectrum disorder ADD/ADHD

Secondary lactase deficiency

Secondary to inflammation -> old cells die -> new cells have low lactase levels

Parietal cells

Secrete HCl and intrinsic factor Respond to gastrinoma Stimulated by -Gastrin -Histamine (H2 Gs) -CCK cholecystokinin

Duodenal S cells

Secrete secretin that makes pancreas release bicarb

Type II pneumocytes

Secrete surfactant have the ability to proliferate in response to injury (for themselves and for type 1 pneumocytes which cannot regenerate)

Leptin

Secreted by adipocytes related to size decreased appetite MOA -decreased production of neuropeptide Y, a potent appetite stimulant, in hypothalamus -stimulates production of proopiomelanocortine (POMC) in arcuate nucleus -> produces alpha-MSH upon cleavage which inhibits food intake

IL-12

Secreted by macrophages when presenting antigen Stimulates differentiation into the Th1-subset Th1 then stimulate macrophages if you don't have IL-12 then you can use IFN-gamma to stimulate macrophages

Non-immune cell response to viral infection

Secretes type 1 interferons (alpha and beta) Autocrine/paracrine signaling HALTS protein synthesis -in the presence of double stranded RNA common to viral replicaiton -RNase L -> degrades all RNA in cell -protein kinase R -> degrades eIF-2 selectively inhibits infected cells

Anti-centromere antibodies

Seen in CREST syndrome

Eclampsia

Seizures with preeclampsia Tx MAGNESIUM SULFATE

Celecoxib

Selective COX-2 inhibitor Sulfa drug Rheumatoid arthritis

Cryptosporidium spp.

Severe watery diarrhea in AIDS patients Unicellular acid fast organisms complete their entire lifecycle within one animal and release cysts in stool Cysts are composed of 4 motile sporozoites Sporozoites attach to intestinal wall, cause diarrhea and small intestine damage Nitazoxanide treatment in immunocompetent for parasites Spiramycin - not FDA approved in US Treatment is usually supportive

Ewing Sarcoma

Sheets of small round blue cells in pseudorosettes CD99+ 11:22 translocation derived from neuroectoderm diaphysis usually in male children Onion-skin appearance Responds well to chemo starts in medullary bone PW -pain and swelling

Creatine kinase

Shows up in the serum as a result of cellular membrane damage (heart, brain, or skeletal muscle)

Osteoblastoma

Similar to osteoid osteoma arises in vertebrae presents as bone pain that does not respond to aspirin

Leukocytoclastic vasculitis

Skin rash that arises due to drug or pathogen exposure Known agents: Penicillin cephalosporins sulfas phenytoin allopurinol violaceous non blanching palpable purpura on lower extremities

Epidural Hematoma

Skull fractures are major cause -pterion (temple) Middle meningeal artery ruptures -branch of external carotid Elliptical shaped (cant cross suture lines) Increased pressure and pressure necrosis LUCID INTERVAL can be present Uncal herniation Blown CN III Tx -drill burr holes in skull

Prolonging PR interval

Slowing AV conduction PR interval is time between atrial firing and ventricular, so AV conduction is the key influencer here

Merkel Cell carcinoma

Small blue cell tumor similar to small cell carcinoma of lung trabecular, nested, or sheet-like arrangements of medium-sized cells Minimal cytoplasm, hyperchromatic nuclei Frequent mitoses, apoptoses

Chondroma

Small bones of hands and feet (like most benign cartilage tumors, malignant will occur centrally in pelvis or central skeleton) Arise in the medulla (like all cartilage tumors)

Reninoma

Small, rare tumor of the JGA cells -> secretes renin

Anti-smith antibodies

Smith protein normally complexes with snRNA in the cytoplasm, forming snRNPs that participate in splicing

Thalassemias

Some level of protection to malaria (likely due to increased ease of hemolysis when protozoa replicates in RBCs) Alpha -chromosome 16 -each chromosome has 2 alpha genes -1 alpha deletion (alpha thalassemia minima) -> silent carrier -2 alpha subunit deletions (alpha thalassemia trait or minor) can be trans or cis. Decreased hemoglobin level with increased RBC count, causes microcytic anemia with hypochromic RBCs -> usually mild anemia or asymptomatic -3 alpha subunit deletions (hemoglobin H disease -> alpha thalassemia intermedia) -> excess unpaired beta subunits start to form tetramers (hemoglobin H, binds oxygen too tightly and doesn't offload in tissues) -> hemoglobin H forms inclusion bodies and damages cell membrane and causes hemolysis -4 deletions -> alpha thalassemia MAJOR causes the formation of hemoglobin Bart's (100x the oxygen affinity of regular hemoglobin, can't deliver oxygen to tissues, also forms inclusion bodies that damage cell Beta -only 2 genes -mRNA splicing defects caused by mutations -> 1 subunit mutated -> beta thalassemia minor -> target cells, mild microcytic anemia -> excess alpha subunits precipitate and form inclusion bodies -> hemolysis in spleen (extravascular). Causes increased production of HbA2 (alpha and delta globins) Causes production of fetal hemoglobin (alpha and gamma globulins) -2 mutations, mild splicing defects -beta thalassemia intermedia -2 mutations, 2 stop codons -beta thalassemia major -alpha inclusions lead to severe extravascular hemolysis -> kidney releases EPO -> reticulocytes in bone marrow -> reticulocyte production in spleen and liver eventually -> hepatosplenomegaly Hematopoiesis can expand from medulla into bone cortex -> expansion of facial bones leading to 'chipmunk facies', expansion of skull causes 'crew cut' appearance Dramatic poikilocytosis (abnormal RBC morphology including microcytes, target cells, and teardrop cells -increased HbA2 (alpha and delta globins) -large amounts of HgF (alpha and gamma globulins) -HbA1 band is absent -iron overload (frequent transfusions, low levels of hepcidin leading to increased uptake, ect) -> hemochromatosis -aplastic crisis: near total failure to produce reticulocytes -> no new RBCs -> lose 20% of your oxygen carrying ability per day -> frequent transfusions -> bone marrow transplant can be curative

Noncommunicating hydrocephalus

Something is blocking CSF Obstructive RF -Chiari II malformations -congenital ToRCH infections (toxoplasmosis, rubella, CMV) causing scarring of the meninges -Colloid cyst that forms in third ventricles -> dilation of lateral ventricles -tumors in posterior fossa Tx Ventriculoperitoneal shunt

Coccidioides immitis

Southwestern US Inhalation of spore In dust, so dust storm kicks up a bunch San joaquin fever earthquakes kick up a bunch of dust Dimorphic fungus Spheroles of endospores inside the body Endospores are much bigger than RBCs Clinical features subclinical usually self limited pneumonia, fever, arthralgia CXR: usually unremarkable but can show cavities and nodules erythema nodosum is sign of robust immune response so its only seen in healthy Immunocompromised -Skin and lungs are common sites of infection -osteomyelitis -meningitis KOH stain or culture (takes a long time tho) Serology for antibody detection is also possible Treatment: Local: azoles like ketoconazole systemic: amphotericin B

Acute dystonia reaction

Spasmodic torticollis Extrapyramidal symptom Can be caused by initiation of antipsychotic medication Sudden involuntary contraction of a major muscle group Thought to result from D2 inhibition in the nigrostriatal pathway. Inhibitory effects of dopamine are usually balanced by muscarinic cholinergic (M1) neurons. With D2 blocked, M1 causes overexcitiation

Arginase deficiency

Spastic diplegia abnormal movements elevated arginine levels Mild or no hyperammonemia (unlike other urea cycle disorders) Arginase produces urea and ornithine frome arginine

Ectopic pregnancy

Specimen would reveal decidualized endometrium only, consistent with dilated, coiled endometrial glands and vascularized edematous stroma Changes occur due to progesterone Most common site 1. Ampulla 2. Ovaries 3. Abdominal cavity RF -DES exposure -inflammation -PID -Endometriosis PW -vaginal bleeding -can have life-threatening bleeding If the patient is stable, you can manage with methotrexate

Kaposi's sarcoma

Spindle-shaped tumor cells with small-vessel proliferation

Anal carcinoma

Squamous cell carcinoma -keratin pearls Basaloid -non keratinizing RF -HPV infection -HIV infection -smoking -immunocompromised -

Corticomedullary tract

Start in motor neurons in the cortex -> decussate in pyramidal tracts in the medulla -> lateral spinal tracts -> (UMN) synapse in anterior horn in spinal cord (LMN) Body of LMN cells are in anterior horn

Non-alcoholic fatty liver disease

Steatosis -> steatohepatitis -> cirrhosis Micro and macrovesicular steatosis RF -increased visceral adipose tissue -insulin resistance -more FFA's floating around, liver grabs more -METABOLIC SYNDROME -hypertension is increased risk of disease progression PW -RUQ pain -malaise -elevated liver enzymes, although not as high, and ALT is usually higher Histology -Neutrophil infiltration -mallory bodies -

Mastitis in the context of breastfeeding

Still suspect Staph aureus -not bacteriodies

LH

Stimulates THECA cells to increase androgen synthesis -> androstenedione and testosterone -> these go to granulosa cells causes one follicle to rupture and starts ovulation

Thyrotropin-releasing hormone

Stimulates release of TSH from pituitary Lactotrophs also have a TRH receptor, and so increased TRH (from hypothyroidism) will stimulate prolactin release -> amenorrhea, nipple discharge etc

Glycol docusate

Stool softener -surfactant agent that stimulates penetration of stool by water and lipids

Transfusion hypocalcemia

Stored packed blood has citrate in it to preserve it citrate can chelate calcium in the body

Trichomonas vaginalis

Strawberry cervix yellow green discharge Motile trophozoites on wet mount 4.5 pH and up Treat both partners Metronidazole to treat

Anal fissures

Stretching and tearing of the anal sphincter -most are posterior -anterior are associated with Crohn's

Measles

Subacute sclerosing panencephalitis (rare) Rash is usually erythematous, confluent, and maculopapular, and has a distribution that begins at the hairline and spreads inferiorly Koplik spots High fever 3c's: Cough, Coryza, and conjunctivitis

Left ventricular free wall rupture

Super fatal obstruction of LCA

Fungal infections

Superficial or cutaneous -Microsporum -Trichophyton -Epidermophyton

Finger drop

Supinator canal problem

Glioblastoma multiforme

Supratentorial Adults Astrocytoma grade IV more common in men frontal and temporal lobes common site thick peripheral RIM enhancement heavy surrounding edema small round cells high mitotic rate line up along bands on necrosis -> pseudopalisading necrosis positive for GFAP CP -when they are large enough to cause compression of surrounding parenchyma -seizures, blindness, paralysis, gait disturbances, high ICP -focal stuff RF

Oligodendroma

Supratentorial Adults 40-50 years old Most often in frontal and temporal lobes white matter frequently calcified sheets of fired egg cells round nuclei with abundant cytiplasm chicken-wire calcificfations GFAP positive slow growing usually can be operated on

Proteus mirabilis

Swarming motility Staghorn calculi (struvite stones) Urease positive -> produces alkaline environment that is perfect for the precipitation of struvite stones Fishy odor Sulfonamides!

Trematodes

Swimmers are at risk Access to the blodstream, then travel to the liver, then we poop and pee in water sources, where they infect snails (intermediate host) Migrate against portal flow to reach GI Like to reside in mesenteric veins Schistosoma mansoni: -Large lateral spine -GI Hemorrhage -portal hypertension -liver cirhossis -jaundice Schistosoma japonicum: -small spine Haematobium -Large terminal spine that can be seen on stool O&P -also goes against portal flow -hematuria -bladder cancer -Praziquantel Clonorchis sinensis -biliary fibrosis -snails intermediate host -Cholangiocarcinoma -Pigmented gallstones -Operculated eggs on O&P (little yamakas) -Praziquantel treatment Paragonimus westermani: -Chronic cough with bloody sputum -snail is intermediate host -Transmitted through eating crab -Stool O&P shows operculated eggs

Syncytiotrophoblast

Syncytio- part of name comes from the fact that it acts as one big cell secretes beta-hCG and human placental lactogen (HPL)

Elastin

Synthesized as large polypeptide precursor (tropoelastin) composed of about 700 mostly nonpolar amino acids -> Secreted into extracellular space where it interacts with microfibrils (fibrillin) that function as a scaffold -> Lysyl oxidase (requires copper) oxidatively deaminiates some of the lysine residues of tropoelastin, facilitating the formation of desmosine cross-links between neighboring polypeptides -> rubber like properties of elastin

Aldosterone

Synthesized in the adrenal cortex Intracellular receptor Affects gene transcription -increases ENaC, increasing resorption of Na+ -upregulated K+ luminal channels, increasing excretion

Congestive heart failure

Systolic heart failure -heart having trouble pumping in systole -ejection fraction is less than 40% (cardiac ultrasound) -end diastolic pressure is increased because there was already blood in there that didn't get pumped last time -end diastolic volume increased -CAD -> cardiac ischemia -> decreased contractility -> systolic heart failure -dilated cardiomyopathy -valvular deficiency -L->R shunting of blood Diastolic heart failure -ejection fraction preserved (>55%) -ventricle doesn't want to distend -diastolic pressure high -normal diastolic volume -long standing hypertension->pressure overload -> left ventricular hypertrophy -> diastolic heart failure (MOST common cause) -HOCM -concentric hypertrophy, increase in wall thickness and decrease in chamber size Compensatory mechanisms -ANP and BNP -RAAS and sympathetic nervous system will be activated which increases afterload -ADH increase will cause fluid overload -cardiac remodeling in response to hemodynamic changes during heart failure -prone to ischemia and arrhythmia Clinical manifestations:

Severe combined immunodeficiency

T and B cell X linked recessive mutation in cytokine receptors -IL-7 deficiency -> B and T cells cant mature Autosomal recessive mutation in ADA -abnormal purine metabolism -> decreased B and T cells -> SCID No globulins No T cells Thymic hypoplasia No germinal centers

Microcytic anemia

TAILS Thalassemia Anemia of chronic disease Iron deficiency Lead Sideroblastic anemia Mean corpuscular volume >80 Reticulocyte count is low (>3%) Smaller, paler cells Target cells (to much membrane to volume)

Keloid

TGF beta

Stroke

THROMBOTIC -can be acute or evolving -usually result of rupture of thrombosis of atherosclerotic plaques in the proximal circle of willis (MCA most common, vertebral arteries, and carotid bifurcation and internal carotid artery) RF -atherosclerosis -Giant cell arteritis -takayasu arteritis -vasospasm during migranes -sickle cell disease EMBOLIC -MCA is most common -symptom development is acute and severe -tPA can be given up to 4.5 hours after ischemic event -must be very careful with tPA, have to be sure there are NO BLEEDS RF -atrial fibrillation -valvular vegetations -hypercoagulable states -mural thrombus following MI -ASD -VSD -Patent foramen ovale HYPOXIC RF -hypotension -high altitudes -CO poisoning HEMORRHAGIC -20% of strokes RF -hypertension -> fibrinoid necrosis of cerebral vessels -> hyaline arteriosclerosis of cerebral vessels -> intracranial hemorrhage -cerebral amyloid angiopathy -astrocytomas and other brain tumors -vasculitis -Charcot-Bouchard microaneurysms in the lenticulostriate arteries (deep brain perforators originating from the ACA and MCA) TIAs -REVERSIBLE -ischemia WITHOUT infarction -leads to focal neurologic symptoms -and then COMPLETE resolution of symptoms because its reversible Ischemic stroke can lead to hemorrhagic stroke Dx -brain MRI is the best (DWI) -> can show ischemic changes in 30 mins or less -wedge shaped infarction form embolic strokes

Lung parameters

TLC - total lung capacity FEV1 - amount of air you can expel in one second Inspiratory volume - Air that can still be breathed in after normal respiration Tidal volume - Air that moves into lung with each quiet inspiration Expiratory reserve volume - air that can still be breathed out after normal respiration Residual volume - Air in lungs after maximal expiration Inspiratory capacity - IRV + TV Functional residual capacity - RV + EVR (Volume in lungs after normal expiration, includes RV, cannot be measured with spirometry) Vital capacity - TV + IRV + ERV (maximal amount of air that can be expired after a maximal inspiration) Total lung capacity - IRV + TV + ERV + RV (Volume of gas inside lungs after maximal inspiration)

Normal aging of lung

TLC - unchanged FVC - decreased Residual volume - increased

Specificity

TN/(TN + FP) ability to identify people without the disease people without disease who tested negative / all the people without the disease

Etanercept

TNF-alpha inhibitor used in RA treatment

Sensitivity

TP/(TP + FN) ability to identify people with disease people who tested positive who have disease / everyone who has disease

Thrombotic thrombocytopenic purpura

TTP Quantitative platelet disorder Thrombotic microangiopathy Diffuse platelet activation -> thrombocytopenia Thrombosis of the microcirculation increases shear force on erythrocytes -> hemolysis -> microangiopathic hemolytic anemia (MAHA) -Schistocytes -increased LDH, bilirubin -increased reticulocyte production Acquired version involves development of autoantibodies against the ADAMTS13 protease (normally responsible for cleaving large vWF complexes -> large vWF complexes activate/cross-link platelets -> intravascular thrombus) Pentad -thrombocytopenia -hemolytic anemia -AKI -Fever -neurologic symptoms

Piriformis

Takes up most of the great sciatic foramen

Direct Coombs Test

Taking patient washed RBCs -> add Coombs reagent (antibody that attaches to antibodies) -> agglutination is positive result

Cestodes

Tapeworm Taenia genus: Eating bad meat Taenia Saginata - cattle Taenia Solium - pig -hooks on proglottid heads of Taenia solium -malabsorption -ingesting adult worms does not infect brain, only eggs Neurocysticercosis -Taenia cestodes -Ingested Taenia eggs from water -goes to brain and form cystic brain lesions -Seizures -Swiss cheese on head CT -Immigrant or farmer with seizures of hydrocephalus Treatment: Praziquantel Albendazole if neurocysticercosis Diphyllobothrium latum -fish tapeworm -Causes diarrhea -B12 (cobalamin) deficiency leading to megaloblastic anemia -proglottid segments seen on stool O&P -Praziquantel -Niclosamide Echinococcus granulosus -Dogs are definitive host -sheep are intermediate host -incidental host humans from fecal oral transmission with dog feces -Hydatid cyst -Egg shell calcifications in cysts on liver CT -When cysts rupture you can get anaphylactic reaction and acute abdomen -eosinophilia

Rituximab

Targets CD20 Chimeric monoclonal antibody Tx -CLL -DMARD -immunosuppressive therapy -microscopic polyangiitis -Wegener's granulomatosis AEs -immunosuppression -may be associated with higher risk of progressive multifocal leukoencephalopathy -Infusion reaction (headache, fever, skin rash, dyspnea, hypotension) -serum sickness (fever, rash, arthralgia, within 7-10 days)

Extra-hepatic gluconeogenesis

The KIDNEY!!!! the kidney is capable of gluconeogenesis

Sex cord stromal tumors

Theco-fibromas -present in perimenopausal women -MEIGS syndrome -> ascites, pleural effusion, ovarian tumor -abundant yellow filled cytoplasm Granulosa-theca tumors -produce estrogen -precocious puberty -unopposed estrongen -> endometrial hyperplasia and increased risk for tumor formation -INHIBIN -tumor marker for these cells -Call-exner bodies -> cuboidal cells -> rosette pattern, eosinophilic center -> coffee bean nuclei -appear yellow on histology due to lipid content -favorable survival rates, technically malignant though Sertoli-leydig -benign or malignant -occur at any age -produce androgens -> hirsutism -tubular structures lined by round sertoli cells rare most are benign In females, sex cord gives rise to -theca cells -mesenchymal cells that fill in between follicles? not sex specific

Campylobacter jejuni

Thermophilic - 42 degrees C Reservoir - GI tract of animals (chickens, dogs, cattle) Bloody diarrhea Comma shaped gram - rod (bent rod) Oxidase positive Bacteremia - Invasive Reactive arthritis!! Guillain-barre syndrome demylenation ascending paralysis autoimmune response

Primary hypertension

Thiazide diuretics ACE inhibitors or ARBs Long acting CCBs Hydralazine - safe in pregnancy

Dynamics of atherosclerotic plaques

Thin-cap fibroatheroma - large necrotic core covered by thin fibrous cap Activated macrophages secrete MMPs that can destabilize and throw clot

Sporotrichosis

Thorn prick Forms subcutaneous nodules biopsy reveals granuloma consisting of histiocytes, multinucleated giant cells, and neutrophils, surrounded by plasma cells

Normal pressure hydrocephalus

Thought to be due to impaired CSF absorption by the arachnoid granulations Thought to be communicating type WET -> diuresis WACKY -> mental changes and dementia WOBBLY -> ataxia develops over a long time Ventricular enlargement -> stretches nerves and impairs conduction pressure is usually......NORMAL lol

Mycobacterium leprae

Thrives in cool temperatures -> predilection for extremities Acid fast bacteria mycolic acid carbol fuchsin stain Armadillo is reservoir Hansen's disease Two separate presentations 1) Tuberculoid TH1 cells, which promote cell mediated immunity -> body can contain bacteria within macrophages Tuberculin response (PPD skin test) DAPSONE and RIFAMPIN for 6 moths 2) Lepromatous TH2 cells response, which promote HUMORAL response Weak or non-existant cell mediated response, can't contain bacteria Symptoms: Symmetric neuropathy with glove and stocking pattern Numerous demarcated raised lesions on extensor surfaces (THEY ARE COOLER) Profound facial deformity Leonine facies DAPSONE, RIFAMPIN, and CLOFAZIMINE

HELLP syndrome

Thrombocytopenia Potentially anemia Schistocytes on peripheral smear ALT & AST elevated

Levothyroxine

Thyroid hormone agonist Treats hypothyroidism IV AEs -hyperthyroid symptoms

Propylthiouracil

Thyroid hormone antagonist Can be used in first trimester, then methimazole PTU inhibits TPO -can't oxidize iodine so it can undergo storage AEs -severe hepatotoxicity -liver failure -maculopapular rash -agranulocytosis -aplastic anemia -drug induced lupus -ANCA-associated vasculitis

Methimazole

Thyroid hormone antagonist less teratogenic than propylthiouracil, used after first trimester inhibits TPO -can't oxidize iodine so it can undergo storage 10x more potent than PTU AEs -agranulocytosis -aplastic anemia -drug induced lupus

Dermatophytes

Tinea Name means Skin plant Pruritic lesions Epidermophyton Trichophyton Microsporum Woods lamps can be used to diagnose Treatment: Clotrimazole Onychomycosis: Nail infection Often requires oral medication to be successful Treatment: Terbinafine Griseofulvin- GI side effects

Malassezia furfur

Tinea versicolor Pityriasis versicolor hypopigmentation due to bleach production from fungus Spaghetti and meatballs

Ipratropium

Tiotropium - longer action than ipratroprium antimuscarinic Bronchodilator Block M3 receptors in lungs -> no constriction -> dilation

Sudan III stain

To check the stool for fat malabsorption

Daily continuous valacyclovir

To suppress recurrent herpes infection

SIADH

Too much ADH Too much water reabsorption Dilute blood inappropriately concentrated urine (>100osm/dL) High urine sodium (>40mEq, increased volume -> ANP and BNP -> sodium excretion) PW -hyponatremia -hypo osmolality -euvolemic hyponatremia (euvolemia because body compensates) can cause altered mental status, seizure, coma, and death RF -head trauma -meningitis -stroke -pnemonia -small cell lung cancer -cyclophosphamide -carbamazipine -SSRIs -Immunosuppressant and chemotherapy agents -surgery Tx -Hypernatremic IV solution -Vaptans, conivaptan and tolvaptan -> directly inhibit the action of ADH with V2 blocking) -Demeclocycline blocks ADH at collecting tubule CAN'T RAISE SODIUM TOO FAST -demyelinating syndrome

Dense deposit disease

Tram tracking lobular glomerulus proliferation of glomerular and mesangial cells Overactivation of the alternative complement pathway Formation of autoantibodies -> C3 nephritic factor -> stabilizes C3 convertase -> overactivation of alternative pathway

Displacement

Transferring feelings to a more acceptable object

Dengue fever

Travel to Brazil MOSQUITO TRANSMITTED -Aedes aegypti Prevalent in tropical and subtropical regions PW -acute febrile illness -headache -retro-orbital pain -joint and muscle pain -can also PW hemorrhage, thrombocytopenia, leukopenia, and hemoconcentration

Cefepime

Treat Pseudomonas 4th gen cephalosporin

Nitroglycerin

Treat chronic stable angina reduces preload thru venodilation modest reduction in afterload due to arteriolar dilation mild coronary artery dilation and reduction of vasospasm

raloxifene

Treat osteoporosis SERM Estrogen prevents osteoclast differentiation Tx -Osteoporosis (postmenopausal) -Breast cancer -Uterine cancer

Bisphosphonates

Treat osteoporosis inhibits osteoclasts -chemically similar to pyrophosphate -> attach to hydroxyapatite on bone surface -> osteoclasts bind and can't break it down -> inhibited -osteoclast apoptosis alendronate, pamidronate, zoledronate first line treatment for osteoporosis AEs -esophagitis -transient hypocalcemia Tx -bisphosphonates -postmenopausal osteoporosis -Paget's disease

Calcitonin

Treat osteoporosis physiologic hormone Puts calcium IN bone (calcitonIN) Promotes kidney excretion of calcium ALL ACTIONS DROP SERUM CALCIUM (opposite of Tx -osteoporosis -Paget's disease AEs -hypocalcemia

Malathione

Treatment of lice

Lamotrigine

Treats Bipolar disorder

Nesiritide

Treats acute heart failure BNP analogue -> increases GMP in arteries and veins -> sodium loss through diuresis

Milrinone

Treats acute heart failure inhibits phosphodiesterase -> decreases breakdown of cAMP -> inotropic effect

Carbamazapine

Treats bipolar disorder

Clofazimine

Treats lepromatous leptosy

Dantrolene

Treats malignant hyperthermia muscle relaxant blocks ryanodine receptors

Scopolamine

Treats vestibular nausea and sea sickness antimuscarinic causes mydriasis blocks M1 receptors AEs -glaucoma

Friedreich ataxia

Trinucleotide repeat disease - GAA Pes cavus Ataxia kyphoscolosis hypertrophic cardiomyopathy autosomal recessive loss of function mutation in Frataxin gene lateral corticospinal tract -> lower extremity weakness

Patau syndrome

Trisomy 13 defect in fusion of the perchordal mesoderm midline structures affected Cleft palate holoprosenceophaly omphalocele

Edwards syndrome

Trisomy 18 PW -micrognathia -heart defects -prominent occiput -low-set ears -clenched hands -renal defects -limited hip abductions -rocker-bottom feet

Gastric ulcer

True ulcer -> involves submucosa (where blood vessels are) Increased vagal output -> increased gastric acid production -> Cushing ulcers biopsied to rule out malignancies

Trypanosoma brucei

Tsetse fly is vector sleeping sickness Western and Southeastern Africa Gambiense Rhodesiense Symptoms: Coma Cervical and axillary lymphadenopathy Recurrent fevers Trypomastigotes seen on blood smear Variable surface glycoprotein coats undergoing constant variation Motile with a single flagella Melarsoprol treatment - CNS infection Suramin treatment - peripheral blood infection

Nondepolarizing neuromuscular blocking agents

Tubocurarine Pancuronium Cisatracurium MOA -inhibit nicotinic ACh receptors at NMJ endplate -> used in anesthesia

Atherosclerosis

Tunica intima = layer adjacent to vessel lumen Risk factors: -diabetes -HTN -homocystine -tobacco -diabetes Foam cells are enlarged -oxidized LDL -lesion takes on the appearance of a fatty streak -release cytokines hyline aterioscelrosis -benign hypertension -diabetes Malignant hyperplasia -> hyperplastic arterosclerosis

Anorectal fistula

Tunnels that eventually become epithelialized RF -pelvic radiation -Crohn's disease

Coarctation of the aorta

Turner syndrome Bicuspid aortic valve Babies rely on flow through PDA, when it closes they will present with heart shock Rib notching High pressures up top Low pressures down low

Klinefelter syndrome

Two or more X chromosomes and one or more Y chromosome Primary hypogonadism in men (only consistent phenotype) Nondisjunction causes most Rarely diagnosed before puberty Gynecomastia Small penis Lower IQ Mitral valve prolapse Decreased testosterone Increased LH Increased FSH and estradiol Testicular atrophy

bethanecole

Tx -non-obstructive ileum -inactive bowel -non-obstructive urinary retention MOA -increase secretion and motor activity of the gut -relaxes bladder, stimulates voiding

Muscarenic agonist

Tx -non-obstructive ileum -inactive bowel -non-obstructive urinary retention -glaucoma MOA -increase secretion and motor activity of the gut -parasympathetic activity

Anaphylactic shock

Type 1 hypersensitivity reaction increased vascular permeability edema -> massive shift of fluid from intravascular to extravascular compartment Widespread mast cell and basophil degranulation -> histamine and tryptase release -tryptase is relatively specific to mast cells Receptors aggregate on antigen -> degranulation RF -insect stings -medications

Pompe disease

Type II glycogen storage disorder Acid alpha-glucosidase deficiency lysosomes can't break down glycogen PW -severe cardiomegaly (Pompe trashes the pump) -normal glucose levels -glycogen accumulation in lysosomes

McArdle disease

Type V glycogen storage disorder Muscle phosphorylase deficiency -cant take glucose of glycogen chain PW -weakness with exercise -fatigue with exercise -no rise in blood lactate levels after exercise

Transthyretin deposition

Type of amyloid deposition Mutations in the TTR gene can increase tendency to misfold, producing amyloid protein that infiltrates the myocardium

Conjugated bilirubin

UDP-glucuronyltransferase -> conjugated bilirubin (soluble) converted to urobilinogen by intestinal flora -> stercobilin (passed in stool, makes stool brown) Conjugated bilirubin in urine -> biliary problem causing backup High conjugated bilirubin Causes -choleolithiasis -blockages of bile flow (pancreatic mass, etc) -dubin johnson syndrome (mutation of intrahepatic bile duct membrane proteins) -biliary atresia

Glutamate-glutamine cycle

Under normal conditions, astrocytes take up excess glutamate in the synapse (preventing excess neuronal excitation) and it is converted to glutamine, which is released by astrocytes and taken up by neurons to make more glutamate When excess ammonia is present, glutamine production is increased by astrocytes -> excess glutamine accumulation leads to cellular swelling and impaired glutamine release -> less glutamine for neurons to convert to glutamate -> impaired excitatory transmission

Melana

Upper GI bleed At or before duodenum (before ligament of treitz)

Bladder cancer

Urothelial carcinoma (transitional cell) and Squamous cell carcinoma Urothelial -most common in US -hypercellular -hyperchromasia Squamous -metaplasia drop metastases usually due to systemic irritant that accumulates in blood RF -cigarette smoke -cyclophosphamide ->mesna to protect, binds to toxic metabolite? -urinary schistosomiasis -chronic UTIS PW -painless hematuria

Amyl nitrate

Used to treat cyanide poisoning oxidizes ferrous iron (Fe++) present in hemoglobin to ferric iron (Fe+++) -> generating methemoglobin -> high affinity for cyanide -> antidote to cyanide

Intellectualization

Using intellect to avoid uncomfortable feelings

Chronic lung transplant rejection

Usually involved the small airways months to years submucosal lymphocytic inflammation -airway obstruction and obliteration

Uterine atony

Uterus fails to contract after delivery -> most common cause of postpartum hemorrhage Can cause massive hemorrhage

Cranial nerve X lesion

Uvula deviates AWAY from side of lesion weak side collapses and uvula deviates away

Streptococcus pneumoniae

Vaccine is polysaccharide capsule lancet shaped diplococci #1 cause of MOPS Meningitis Otitis media Pneumonia Sinusitis Toxoid that cleaves IgA Treatment: Ceftriaxone

Distal intestinal atresia

Vascular event in utero No flow, no grow

Pancreatic adenocarcinoma

Very aggressive RF -smoking -male -chronic pancreatitis -alcoholism (calcified fat necrosis) -BRCA 1 and 2 -biliary obstruction -> jaundice Markers -CEA -CA 19-9 PW -K-RAS mutation -CDKN2A tumor suppressor gene mutation -Courvoisier's sign (nontender palpable gallbladder) -Jaundice -epigastric pain radiating to back -weight loss -fever -night sweats -palpable Virchow's node -periumbilical mass (Sister mary joseph sign) -superficial migratory thrombophlebitis (Trousseau's sign) Complications

Helicobacter pylori

Very common infection Motile Urease positive - breath test Oxidase positive (all curved rods) Causes ulcers duodenal ulcers Chronic infection causes increased acid production, either by inhibiting somatostatin or increasing gastrin Adenocarcinoma of the stomach MALToma - only cancer you can treat with antibiotics Triple therapy: PPI (omeprazole) Amoxicillin Macrolide (clarithromycin)

Vincristine

Vinblastine M phase specific cytotoxic vinca alkaloid -> inhibits microtubule productions and mitotic spindle assembly Tx -solid and lymphomas -ALL -MM -NHL, HL -rhabdomyosarcoma -neuroblastoma -Ewing's sarcoma -Wilm's tumor Vinblastin = breast, germ cell AE -neurotoxicity -peripheral neurophathy -paralytic ileus -constipation -alopecia

Mixed hyperbilirubinemia

Viral hepatits alcoholic hepatitis AST/ALT high

Protein A

Virulance factor in Staph cell wall Binds with the Fc portion of IgG at the complement binding site -> prevents activation

Riboflavin deficiency

Vitamin B2 in chronic alcoholics or severely malnourished Succinate dehydrogenase doesn't work (needs riboflavin)-> ETC messed up PW -angular stomatits -chelitits -glossitits -seborrheic dermatitis -eye changes

Pyrazinamide

Vitamin B6 Isoniazid promotes excretion Tx -adjunct in RIPE therapy for tuberculosis AEs -hepatotoxicity -can precipitate gout attacks -hyperuricemia -> needle shaped uric acid -

Biotin

Vitamin B7 Important cofactor for several carboxylase enzymes CO2 carrier Pyruvate -> oxaloacetate in gluconeogenesis Deficiency PW -mental status changes -myalgias -anorexia -chronic dermatologic changes -metabolic acidosis from increased pyruvate -> lactic acid

Osteomalacia

Vitamin D deficiency is most common cause RF -poor diet -CKD -CF -celiac's disease -chronic pancreatitis PW -hyperparathyroidism (secondary) -valgus deformity

Vitamin E deficiency

Vitamin E primarily serves to protect fatty acids from being oxidized deficiency -> hemolytic anemia from RBCs popping -> neuromuscular disease because neurons are susceptible Presents like Friedrich ataxia -ataxia -loss of positional or vibration sense

Pellegra

Vitamin b3 (Niacin) deficiency photosensitive dermatitis

Thiamine

Vitamine B1 1. Pyruvate dehydrogenase (pyruvate -> acetyl-CoA 2. Alpha-ketogluterate dehydrogenase 3. Branched-chain alpha-ketoacid dehydrogenase 4. Transketolase Deficiency -Beriberi -> peripheral neuropathy, heart failure -Wernicke-Korsakoff syndrome

Neurofibromatosis type 1

Von recklinghausen disease NF1 tumor suppressor gene on chromosome 17 -> constitutive activation of RAS 100% penetrance variable expression CNS tumors autosomal dominant CAFESPOT Cafe-au-lait spots -freckling -skin folds Axillary freckling "eye" lisch nodules -form on iris and eye Scoliosis Pheochromocytoma "Tumor" Optic glioma Neural crest cells -stain with s-100 cutaneous neurofribroms

Parinaud syndrome pupils

WILL constrict due to accommodation not light

Mycoplasma pneumoniae

Walking pneumonia NO CELL WALL Has cholesterol in is membrane Patchy infiltrate in lungs that looks way worse than it it Young adults, especially those in close quarters Cold agglutinin (present in 50-70%) Eaton agar Treatment: Macrolides

Psoriasis

Well demarcated scaly erythematous plaques involving extensor surfaces of the extremities Psoriatic arthritis nail changes:yellow-brown color, pitting, thickening, or crumbling conjunctivitis, blepharitis or uveitis (slit lamp test) HLA-B27

Parathyroid adenoma

Well-encapsulated Hyperparathyroidism Hypercalcemia Surrounding parathyroid nodules atrophy Moans, stones, bones, groans, psychiatric overtones -mostly asymptomatic hypercalcemia tho

Parathyroid carcinoma

Well-encapsulated Hyperparathyroidism Hypercalcemia Surrounding parathyroid nodules atrophy Moans, stones, bones, groans, psychiatric overtones -mostly asymptomatic hypercalcemia tho Malignant and invade

Permissiveness

When one hormone allows another to exert its maximal effect

Renal ammoniagenesis

When the body is in acidosis -> glutamine is metabolize -> more ammonia to bind H+

Fibromuscular dysplasia

When the renal artery shows "strings on a bead" appearance alternating areas of stenosis and aneurysmal dilation

Thiazides

Work in the DCT -Active resorption of Ca regulated by PTH Blocks NaCl cotransporter Treats hypertension (mild to moderate) -reduces preload (amount heart has to pump) -need good end renal function -Chlorthalidone half life > hydrochlorothiazide half life Adjunctive treatment in CHF Treats nephrogenic diabetes insipidus Potassium wasting diuretic hyponatremia because with thiazides you don't mess up formation of high solute gradient in loop, so you can get water back better than with loop diuretics Side effects: -hyperglycemia -hypercalcemia (good for osteoporosis, can also unmask hypercalcemia from other causes) -hypocalciuria (good for renal stones) -hyperlipidemia -messes up lithium excretion -contraction alkalosis

Duchenne muscular dystrophy

X linked recessive mutation in dystrophin (stabilizes muscle fiber mechanically) Duchenne is complete absence of dystrophin Becker is partial dystrophin links actin cytoskeleton to cell membrane -anchor protien Gower's sign - uses hands to walk up legs dilated cardiomyopathy PW -pseusdohypertrophy of calves -muscle replaced with adipose tissue and necrosis -nuclei in center of cells instead of along periphery -presents early -elevated CK -muscle weakness -child unable to keep up -heart failure -dilated cardiomyopathy -arrythmias -death from respiratory failure around 20 Dx -muscle biopsy

Wiskott-Aldrich syndrome

X-linked Recessive 1. B and T cell primary immunodeficiency 2. thrombocytopenia 3. Eczema abnormal actin cytoskeleton reorganization -impaired migration, adhesion, and interaction with other cells Encapsulated bacteria IgG and IgM are low to normal IgA and IgE can be elevated Hyper IgM syndrome -B cells can make IgM but can't class switch -CD40 binding mediated (on helper T cells, they are CD40 deficient) -IgM will be super high

Bruton disease

X-linked agammaglobulinemia B cell primary immunodeficiency Pre B cells dont mature -no antibodies either -no B cells in peripheral blood -lack germinal centers -encapsulated organisms are particularly dangerous -> no antibody mediated phagocytosis labs show low globulin levels of all types Bruton tyrosine kinase protein usually signals B cells to mature Male infant gets a bunch of recurrent infections Candida injection with positive inflammatory response (T cell mediated) is diagnostic

Adrenoleukodystrophy

XR disorder of beta-oxidation Very long chain fatty acids build up in adrenal glands, white matter of brain, testes progressive disease can lead to adrenal gland crisis, coma, and death

Reye's syndrome

Young child who takes aspirin after a viral infection -> mitochondrial damage and decoupling Triad -encephalopathy -microvesicular fatty changes in liver -serum transaminase elevation Mitochondrial damage -> impaired beta-oxidation of fatty acids -> accumulation of fatty acids, inflammation, elevated transaminases -also impairs mitochondrial urea cycle, decreased metabolism of ammonia levels, increased serum levels of ammonia PW -clumsy baby (encephalopathy) -sleepy -> then seizures, vomiting, UMN signs -> can progress to coma and death (25% and up mortality No neutrophil infiltrate Elevated AST and ALT, not right ratio for alcohol

Transthyretin

a protein tetramer produced in the liver acts as a carrier of thyroxine and retinol mutations cause it to misfold -> amyloid protein deposition in the myocardium

Budd-chiari syndrome

abdominal pain ascites palpably enlarged liver due to venous congestion of the hepatic vein RF -clot in hepatic vein -HCC metastasis

Annular pancreas

abnormal migration of the ventral bud

Osteogenesis imperfecta

abnormal type 1 collagen autosomal dominant COL1 or COL2 mutations brittle weak bones that fracture with minimum force Type 2 is incompatible with life too many fractures intracranial hemorrhage affected babies die in utero Type 1 make normal collagen just less of it blue sclera small teeth that wear out quickly

Signal recognition particle

abundant cytosolic ribonucleoprotien that traffics proteins from the ribosome to the RER proteins accumulate in cytosol if this is deficient

Griseofluvin

accumulates in keratin containing tissues binds to fungal cell microtubules Tx -dermatophytic infections -dermatophytosis -tinea capitis AEs -activates CYP450

99m Tc-pertechnetate

accumulates in parietal cells can be used to diagnose Meckel Diverticulum

Organophophates

acetylcholinesterase inhibitor crosses BBB AEs -DUMBBELS -Diarrhea -Urination -Miosis -Bronchospasm -Bradycardia -Lacrimation -Salivation Pralidoxime to rescue, works in periphery mostly -regenerated acetycholinesterase in synapse

Chloramphenicol

acts on bacterial ribosome, inhibiting peptide bond formation and halting translation Used mostly in developing countries Tx -Rickettsia -meningitis -strep pneumo -h flu -niesseria meningitides AEs -Gray baby syndrome ->accumulates in newborns, flaccidity, hypothermia, shock -dose related reversible suppression of RBC production -aplastic anemia

Timolol

acts on respiratory EPITHELIUM Decreases aqueous humor production Tx -open angle glaucoma

Antibiotic-modifying enzymes

add chemical groups (acetyl, adenyl, phosphate) to a target drug The most common mechanism of aminoglycoside resistance -> can't bind to bacterial ribosome as well

Cosyntropin test

administer -> stimulates secretion of cortisol from the adrenals shows secondary adrenal insufficiency

Hepatopulmonary syndrome

again from increased NO liver unable to metabolize? In the lungs, excess NO and endothelin causes vasodilation -V/Q mismatch, O2 cant diffuse into blood before it flows away -hypoxemia -clubbing of the fingers

Baclofen

agonist at the GABA-B receptor Tx -MS -spacicity

Mucinous carcinoma of breast

aka colloid carcinoma 1% present with soft, gelatinous, well circumscribed masses

blood-gas partition coefficient

aka solubility less soluble drugs saturate faster -> rapid onset, rapid recovery low blood-gas partition coefficient, low solubility -> rapid onset

Infundibulopelvic ligament

aka suspensory ligament of the ovary Supplies blood to the ovary also contains ovarian nerve plexus ovaries can rotate around infundibulopelvic ligament and precipitate ovarian torsion

Phenylephrine

alpha-1 agonist activates pupillary dilator muscle -mydriasis Tx -nasal congestion (receptors in nasal mucosa) -pressor agent to increase BP, MAP (reflexive bradycardia, although not in elderly so its dangerous) -treat hypotension

Acarbose

alpha-glucosidase inhibitor prevents breakdown of carbs in intestines delay carbohydrate absorption less glucose in blood AE -diarrhea -flatulence -abdominal pain -all from increased carbs to gut bacteria -rarely prescribed because of this

Miglitol

alpha-glucosidase inhibitor prevents breakdown of carbs in intestines delay carbohydrate absorption less glucose in blood AE -diarrhea -flatulence -abdominal pain -all from increased carbs to gut bacteria -rarely prescribed because of this

Cimetidine

also ranitidine, famotidine, nizatidine inhibit acid secretion by parietal cells H2 receptor antagonist Treat -GERD -peptic and duodenal ulcers AE -elevated serum prolactin -> galactorrhea

Amniotic fluid embolism

amniotic fluid containing AA metabolites enters maternal circulation resulting in anaphylactic reaction

pramlintide

amylin analogue -amylin = islet amyloid polypeptide decreased glucagon, gastric emptying, and appetite works in type 1 and 2 AEs -GI symptoms -hypoglycemia

Ondansetron

antagonizes 5HT3 receptors on vagal afferents prevents nausea and vomiting due to GI upset -chemotherapy nausea Can cause serotonin syndrome

Diphenoxylate

anti-diarrheal agent activates mu receptor doesnt cross BBB Increases phasic movement (pushing down) which increases transit time increased water absorption Do not give with bloody diarrhea Tx -VIPoma -carcinoid tumor

Loperamide

anti-diarrheal agent activates mu receptor doesnt cross BBB Increases phasic movement (pushing down) which increases transit time increased water absorption Do not give with bloody diarrhea Tx -VIPoma -carcinoid tumor

Trimethoprim/sulfamethoxazole

anti-folate aka Bactrim SMX: PABA analogue that blocks first stem -dihydrojpterate synthase TMP: Blocks dihydrofolate reductase synergistic relationship bacteriostatic when separate bactericidal when together Tx -acute prostatitis -gram - -UTI bugs -gram + -MRSA -staph -Strep -Nocardia -PJP (prophylaxis too) -Toxoplasma Gondii AEs -cytopenias -pancytopenia -megaloblastic anemia -Heinz bodies -SJS -Type IV RTA -Kernicterus in neonates -displace drugs from albumin (increased action from drugs like warfarin) -also inhibit CYP450 -teratogenic -neural tube defects

Amphotericin B

anti-fungal Binds to ergosterol and forms pores in fungal membrane IV administration toxicity comes from non-selective binding to cholesterol administered intrathecally for CNS infections -seizures Often used with flucytosine Tx -every fungus pretty much -severe systemic fungal infection AEs 1. Infusion related immediate reactions -headache -hypotension -fever and chills -thrombophlebitis at injection site 2. Chronic cumulative toxicity -renal damage -type 1 RTA (impaired H+ secretion? -> hypokalemia ->hypomagnesia -Anemia due to kidney damage

Actinomycin D

anti-tumor antibiotic intercalates DNA -> blocks DNA and RNA synthesis AEs -alopecia -myelosuppression

Bleomycin

anti-tumor antibiotic intercalates between DNA generates oxygen free radicals through Iron dependent process Cell cycle specific -G2 AEs -pulmonary toxicity -skin toxicity (rash, atrophic striae, hyper pigmentation) -mucositis -stomatitis -alopecia

Anti-nuclear antibodies

antibodies against proteins usually found in the nucleus of cells

Terbinafine

antifungals inhibits fungal squalene epoxidase -accumulation of squalene Tx -dermatophytosis -tinea capitis -onychomycosis AEs -GI side effects -hepatic damage

Azoles

antifungals INHIBITS lanosterol conversion to ergosterol -by inhibiting fungal CYP450 Voriconizole -blurry vision -changes in color vision Tx -invasive aspergillosis -candida Fluconazole -mucocutaneous candidiasis -one time dose treats vaginal candidiasis -CNS penetration -coccidiodal meningitis Itraconazole -dimorphic fungi -histoplasmosis -blastomycosis -coccidioidomycosis -sporothrix -onychomycosis -dermatophytosis Clotrimazole -tinea -topical -vaginal candidaiasis Miconazole -tinea -topical -vaginal candidaiasis Ketoconazole -topical -dermatophytosis -inhibits 17,20 desmolase, which synthesizes cholesterol AEs -inhibits CYP450

Atropine

antimuscarinic Blocking DUMBBELS -block cholinergic, muscarinic effects Tx -reversal of lethal bradyarrythmias (M2), increases AV conduction AEs -Hot as a hare -Dry as a tea cracker -Full as a tea kettle -Blind as a bat -Mad as a hatter -

Oxybutynin

antimuscarinic blocks muscarenic receptors in bladder treat urinary incontinence

Tolterodine

antimuscarinic blocks muscarenic receptors in bladder treat urinary incontinence

Superoxide dismutase

antioxidant enzyme

Propylthiuracil

antithyroid medication blocks thyroid peroxidase -> inhibiting thyroid hormone synthesis may be used in first trimester of pregnancy, after that you want to use methimazole (less teratogenic) can cause agranulocytosis -presents with sore throat, fever, oral ulcerations, and other signs of infeciton -> discontinue medication immediately -> immunocompromised

Ribivirin

antiviral guanasine nucloeside analog needs to be phosphorylated Tx -Treats Hep C AEs -dose dependent hemolytic anemia

Lead time bias

apparent increase in survival time among patient ath undergo screening when they actually have an unchanged prognosis overall length of time from disease onset to death actually remains the same with or without earlier screening

Watershed infarcts

appear as BILATERAL wedge shaped ischemic areas spanning the length of the cerebrum

Pulmonary capillary wedge pressure

approximates the pressure in the left atrium

Giant cell tumor

arises in the epiphysis soap bubble appearance Locally aggressive

Cheyne-Stokes breathing

associated with advanced CHF cyclic breathing pattern in which apnea is followed by gradual increase then decrease Apnea causes build up of CO2 which triggers breathing that then overshoots and breathing is subdued Also seen in neurologic diseases (stroke, brain tumor, traumatic brain injury)

Nonbacterial thrombotic endocarditis

associated with advanced malignancy as well as antiphospholipid syndrome, lupus, and disseminated intravascular coagulation MOA: Thought to be endothelial injury caused by circulating cytokines -> trigger platelet deposition in the presence of a hypercoagulable state

Trichophyton rubrum

athlete's foot

Projection

attributing ones own feelings to others

Mirtazapine

atypical antidepressants used if SSRIs don't work for a patient Alpha-2 adrenergic receptor blocker ->increased presynaptic norepinephrine and serotonin release Blocks 5HT-2 and 5HT-3 receptors inhibits H1 receptor lack of sexual side effects AEs -weight gain -sedation -orthostatic hypotension -

Buproprion

atypical antidepressants used if SSRIs don't work for a patient Inhibits norepinephrine and dopamine -NET -DAT Less sexual side effects CNS activating effects Treats tobacco dependence AEs -seizures -contraindicated in bulimia

Trazodone

atypical antidepressants used if SSRIs don't work for a patient TrazaBONE antagonises alpha 1 receptor H1 receptor antagonist AEs -priapism (giant boners for more than 4 hours) -orthostatic hypotension -sedation -sexual dysfunction

Pemphigus vulgaris

autoantibody against desmosomes Intraepidermal cleavage tombstone cells along basal layer Flaccid bullae Oral mucosa involved

Primary sclerosing cholangitis

autoimmune destruction of bile ducts -exact cause unknown Intra and extrahepatic bile duct destruction RF -usually occurs in middle-aged men -HLA-DR gene association -p-ANCA PW -onion skin on histology from concentric fibrosis -beading appearance due to alternating dilation and sclerosis -Increased Alk phos, GGT, and conjugated bilirubin (classic cholestasis labs) -Pruritis -jaundice (late finding) -infection by gut bacteria (ascending cholagitis Increased risk for -cholangiocarcinoma (inflammation to bile ducts) -hepatocellular carcinoma (via progression to cirrhosis)

Primary sclerosing cholagnitis

autoimmune disease of intra- and extra-hepatic ducts

Myasthenia gravis

autoimmune disese antibodies against acetylcholine receptor on motor end plate (skeletal muscle NMJ) -> inactivated nicotinic ACh receptors ->complement activation causes destruction and depletion of receptors -> decreased neurotransmission Myesthenic crisis -respiratory failure requireing intubation -severe vulvar weakness -RF are magnesium, macrolides, fluroquninlones, infections, pregnancy edrophonium (tensilon) test RF -women ~ age 20 -Men older (60) -HLA B8 PW -progressive proximal weakness -ptosis -diplopia -worsen as day goes on -dysarthria -dysphagia -from impairment of muscles innervated by cranial nerves Look for thymoma Tx -acetylcholinesterase inhibitors

Primary biliary cholangitis

autoimmune mediated destruction of INTRAhepatic bile ducts -resulting from genetic and environmental injury to biliary epithelial mitochondria -> anti-mitochondria antibodies Granulomas form within the portal triad Alk phos elevated (all cholestasis) GGT elevated (all cholestasis) Conjugated hyperbilirubinemia Levels of immune proteins are elevated Can eventually lead to cirrhosis Increased risk of hepatocellular carcinoma Malabsorption of vitamins ADEK -poor fat absorption PW -most are asymptomatic -fatigue -hyperpigmentation from melanin deposition in the skin -Xanthomas and xanthelasmas from hypercholesterolemia -Pruritis RF -90% middle aged women -presence of other autoimmune disorders Diagnose -look for any other reason for blockage Treat -Ursodeoxycholic acid (from bear bile)

Neurofibromatosis type 2

autosomal dominant NF2 gene on chromosome 22 merlin tumor supressor gene bilateral acoutsic neuromas -> vertigo -> nystagmus trigeminal dyfunction multiple meningiomas cataracts spinal tumor -> motor or sensory dysfunction

Hereditary ellipsocytosis

autosomal dominant almost the same as spherocytosis Increases protection against malaria

Myotonic dystrophy

autosomal dominant inheritance CTG expansion anticipation PW -muscle weakness -muscle wasting -long narrow face due to temporal wasting -difficulty letting go of things -cataracts -testicular atrophy

Inclusion cell disease

autosomal recessive defects in protein targeting -cant signal with mannose to send things to lysosome -defective phosphotransferase enzyme causes extracellular

Ataxia telangiectasia

autosomal recessive mutation of ATM gene -DNA break repair telangectasias ataxia increased sinopulmonary infections

Pyruvate kinase deficiency

autosomal recessive pyruvate kinase turns phosphoenolpyruvate into pyruvate needed in glycolysis less ATP for RBCs decreases flexibility -> extravascular hemolysis Burr cells -bumpy cell membrane due to stiff architecture hemolytic anemia in newborn period hepatosplenomegaly later Splenectomy is a treatment -increases infection to encapsulated organisms tho

11 hydroxylase deficiency

autosomal recessive Hyperplasia (decreased cortisol -> ACTH release -> hyperplasia) Hyperpigmentation Hyperandrogenism -females present with ambigous genetalia -cliteromegaly -precosious hair growth -hirsuitism -acne -irregular menses and infertility no aldosterone no cortisol build up of 11-deoxycorticosterone (can exert mineralocorticoid effects) -> HYPERaldosteronism -HTN -hypokalemia

17 hydroxylase deficiency

autosomal recessive Steroid precursors are trapped in glomerulosa Can make a bunch of aldosterone no cortisol or androgens hyperaldosteronism hypogonadism hypocortisolism

21 hydroxylase deficiency

autosomal recessive >90% of cases of congenital adrenal hyperplasia Hyperplasia (decreased cortisol -> ACTH release -> hyperplasia) Hyperpigmentation Hyperandrogenism -females present with ambigous genetalia -cliteromegaly -precosious hair growth -hirsuitism -acne -irregular menses and infertility no aldosterone or cortisol can be made all shunted to androgen synthesis hyponatermia salt wasting hyperkalemia type IV renal acidosis increased renin

Ethambutol

bacteriostatic Tx -RIPE therapy for tuberculosis AEs -hepatotoxicity -red-green color blindness -optic neuritis

Necrotizing enterocolitis

begins when an infant starts feeding -> bacteria introduced into the gut overpower immune system Premature birth is biggest risk Bacteria invade bowel wall Pneumatosis intestinalis -pockets of gas in intestinal wall Causes bowel necrosis Mortality can be as high as 30%

Denial defense mechanism

behaving as if an aspect of reality does not really exist

CD receptor numbers

below 10 usually for T cells above 10 usually B cells

Fibroadenoma

benign breast tumor estrogen responsive -increase in pregnancy or lactation or just prior to ovulation painless mobil stromal proliferation can compress glandular ducts -> slits on histology

Essential fructosuria

benign condition Fructokinase deficiency Fructose can still be shunted to glycolysis

Renal angiomyolipoma

benign kidney tumor

Hepatic adenoma

benign liver mass Estrogen DEFINITELY stimulates this one Full of glycogen Normal hepatic architecture is NOT preserved lesions can be up to 30 cm (big) histology -tan appearence -areas of hemorrhage and necrosis RF -reproductive women -OCP administration (these were rare before OCPs came on market) -pregnancy -steroid use -Glycogen storage diseases -Type 1 Von Gierke's disease (glycogen causes?) taking away hormones will cause them to regress PW -usually asymptomatic -can present with hypotension and hypovolemic shock from rupture -> severe RUQ, surgical emergency 20% mortality Small risk of progressing into HCC

Leiomyomas

benign smooth muscle tumors of myometrium 30-50% of women reproductive age have them more common in blacks mostly asymptomatic mass effect can cause problem can have calcifications can cause infertility if in the right spot can cause heavy menstrual bleeding

Nafcillin

beta lactam antibiotic beta lactamase resistance -bulky R groups Naf for staph Resistance -altered PBPs -MRSA Tx -narrow spectrum -mild to moderate localized staph infections -Folliculitis -abcesses -systemic staph infections -staph osteomyelitis -tricuspid infection AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Dicloxacillin

beta lactam antibiotic beta lactamase resistance -bulky R groups Resistance -altered PBPs -MRSA Tx -narrow spectrum -mild to moderate localized staph infections -Folliculitis -abcesses -systemic staph infections -staph osteomyelitis -tricuspid infection AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Methicillin

beta lactam antibiotic beta lactamase resistance -bulky R groups Resistance -altered PBPs -MRSA Tx -narrow spectrum -mild to moderate localized staph infections -Folliculitis -abcesses -systemic staph infections -staph osteomyelitis -tricuspid infection AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Oxacillin

beta lactam antibiotic beta lactamase resistance -bulky R groups Resistance -altered PBPs -MRSA Tx -narrow spectrum -mild to moderate localized staph infections -Folliculitis -abcesses -systemic staph infections -staph osteomyelitis -tricuspid infection AEs -Type 1 IgE hyper reaction -autoimmune hemolytic anemia -drug induced interstitial nephritis

Gaucher disease

beta-glucocerebrosidase deficiency -accumulation of glucocerebrocidase Lipid laden macrophages Pancytopenia Most common genetic abnormality in Ashkenazi Jews PW -bone pain -pancytopenia -massive splenomegaly -hepatomegaly

Subarachnoid hemorrhage

between arachnoid mater and pia mater -where CSF is berry aneurysm -circle of willis (anterior cerebral and anterior communicating) -more frequent in postmenopausal women, drinkers, and smokers -Ehlers-Danlos type III collagen defect in vascular walls -ADPKD trauma vasculitis arteriovenous malformation Causes vasospasm of cerebral arteries

Ecchymoses

big bruises greater than 1 cm Purpura are 5mm - 1 cm Petechia are less than 5mm

Maraviroc

binds CCR5R -prevents entry Tx -HIV AEs -

Denosumab

binds RANK-L and inhibits osteoclasts activation Treat osteoporosis -Paget's disease

Unconjugated bilirubin

binds to albumin most common form in blood cant excrete in gut because lipophilicity would make it absorbed again (hepatobiliary circuit) UDP-glucuronyltransferase -> conjugated bilirubin (soluble) -babies have normal low level of this High unconjugated bilirubin -hemolysis -hemoglobinopathy -RBC structural defect -associated with increased urobilinogen

Gemcitabine

block DNA polymerase cytotoxic pyrimidine analogue

Cytarabine

block DNA polymerase hematologic malignancies AML NHL

Cladribine

block DNA polymerase purine analogue

Hyperviscosity syndrome

blood becomes more sludgier (increased viscosity) -> bood stasis -> thrombus Polycythemia Sickle cell Inherited thrombosis syndromes are usually autosomal dominant -Factor V leiden -prothrombin G20210A mutation -protein C/S deficiency -ATIII deficency -waldenstrom's macroglobulinemia (a type of non-Hodgkin lymphoma. The cancer cells make large amounts of an abnormal protein (called a macroglobulin). Another name for WM is lymphoplasmacytic lymphoma.) Factor V Leiden (protein C resistance) -most common in young caucasians -protein C can't destroy factor V (mutation eliminates binding spot) -> thrombus Prothrombin G20210A mutation -inherited -make more prothrombin than normal (4X) -more PE and embolisms -not that bad, UNLESS it is paired with another deficiency

myeloperoxidase

blue-green heme-based pigmented molecule contained within the azurophilic granules of neutrophils and catalyzes the production of hypochlorus acid from chloride and hydrogen peroxide during the respiratory burst Reason why sputum is green in bacterial pneumonia (red or rust colored sputum is from extravasation of blood)

Turcot syndrome

brain tumors FAP

Partial mu agonist

buprenorphine nalbuphine butorphanol can precipitate withdrawal symptoms when given to someone who has been using full agonists

Amlodipine

calcium channel blocker dihydropyridine dilated coronary arteries Treat: -hypertension -stable angina -vasospastic angina -Raynaud's phenomenon -vasospasm of cerebral arteries in SAH

Endometrial polyps

can cause AUB PW -light intermenstrual bleeding more likely to be malignant in postmenopausal women

Adipokines

can contribute to insulin resistance cytokines released by adipose cells

lichen sclerosis

can develop into vulvar squamous cell carcinoma smooth white plaques on parchment like tissue histology -thin epidermis overlying

Brain injury on non-dominant hand side

can present with hemineglect

Beck's Triad

cardiac tamponade presents with -muffled heart sounds -hypotension -JVD

Neurophysins

carrier proteins for oxytocin and vasopressin in the posterior pituitary

Umbilical vein

carries oxygenated blood back to fetus connects to IVC -> right atrium -> foramen ovale -> left atrium

Burkholderia cepacia

catalase positive bacteria RF -CGD

5' deiodinase

catalyzes T4 -> T3 in peripheral tissue Beta blockers inhibit this Glucocorticoids too

Hormone sensitive lipase

catalyzes the mobilization of stored triglycerides into free fatty acids and glycerol aids in ketone body formation and gluconeogenesis

Familial hypocalciuric hypercalcemia

cause by mutation in calcium-sensing receptors -G protein coupled Thinks there is low calcium, -> secrete parathyroid hormone The set point of calcium homeostasis is raised

Endometrial hyperplasia

caused by -unopposed estrogen (relative to progesterone) -estrogen replacement therapy -tamoxifen use (agonist in endometrium) -estrogen secreting tumor -anovulatory cycles (PCOS) -SERM

Primary adrenal insufficiency

causes -bilateral adrenal hemorrhage in anticoagulated patients or DIC -adrenal vein thrombosis in hypercoagulable states or malignancy -Waterhouse friderichsen symptom often due to N meningitidis -disseminated TB -> chronic primary adrenal insufficiency (most common worldwide) PW -loss of cortisol production -> decreased vascular tone -> hypotension and shock -nasua -fatigue -hypoaldosteronism -> hyperkalemia, hyponatremia, non-anion gap metabolic acidosis -type 4 renal acidosis -hypovolemia -> increased ADH and dilute solutes in serum -high ACTH Tx -

Hyperandrogenism

causes -congenital adrenal hyperplasia -11, 21, 17 hydroxylase deficiency

Pulmonary edema

causes decreased lung compliance like cardiac tamponade increased hydrostatic pressure around the lungs squeezes it

Ornithine translocase deficiency

causes defect in the hepatic urea cycle -> ammonia accumulates in the blodd Tx -protein restriction -phenylacetate provides another means for ammonia secretion Ornithine combines with carbamoyl phosphate in mitochondria to make citrulline (can be recycled)

Persistant nasal bleeding

cautery of the nasal septum will stop

Exudate

cell rich protein rich white out on xray

trihexyphenidyl

centrally acting antimuscarinic can improve parkinson's symptoms -not usually great with bradykinesia though

Benztropine

centrally acting antimuscarinic can improve parkinson's symptoms -not usually great with bradykinesia though AEs -sedation, agitation, hallucination, coma

Smoking

centriacinar emphysema oxidative injury to the respiratory bronchioles -> activation of resident alveolar macrophages -> inflammatory recruitment of neutrophils into affected airspace -> release proteases -> degrade the extracellular matrix

Addison's disease

chronic primary adrenal deficiency usually due to autoimmune destruction most commonly female RF -female -HLA B8, DR3, DR4 PW -fatigue -nasuea -hypotension -hypovolemia -salt and sugar cravings -hyperpigmentation of oral mucosa, face, hands, genitalia from increased ACTH -decreased pubic hair -decreased libido -irregular mences -amenorrhea -HIGH ATCH

Systemic mastocytosis

clonal mast cell proliferation Mutations in KIT receptor extensive histamine release -syncope -flushing -pruritus -abdominal cramps -diarrhea

bacterial vaginosis

clue cells

Heinz body

clumps of denatured, insoluble heme -> in spleen turn to bite cell G6PD deficiency

Tetrahydrobiopterin (BH4)

cofactor in the synthesis of serotonin, tyrosine, and DOPA

Increased CK-MB and troponin I

comes from membrane lipid peroxidation

Retinal artery

comes off ophthalmic (branch of INTERNAL carotid)

C-myc

common oncogene in Burkitt lymphoma t(8:14) Transcriptional activator controlling cell proliferation, differentiation, and apoptosis

Cavernous hemangioma

common to liver and CNS prone to hemorrhage no smooth muscle just endothelial cell layer

Hemangioblastoma

commonly affect the retina cerebellum spinal cord well circumscribed vascular lesions that do not invade fluid filled cysts ofen surround it smooth muscle and elastic fibers present PAS+ prone to rupture and hemorrhage retinal edema and detachment

Osteomyelitis

commonly affects the metaphysis of long bones -> contains slow-filling, sinusoidal vasculature that is conductive to microbial passage

Endometrioid ovarian cancer

commonly coexists with endometrial carcinoma tubular glands with many purple nuclei crammed together CA-125 -> also elevated in endometriosis and other things that disrupt epithelial membrane ->can be used to track progress, not specific enough to be diagnostic RF -BRCA I and II -anything that causes repeated damage of epithelium -> OVULATION when the follicle BURSTS out of epithelium lol -nulliparity due to no breaks in ovarian cycle -endometriosis protective factors -breast feeding -OCPs -pregnancy -all cause ovulation to take a break PW -malignant pleural effusions

Osteoma

composed of cortical bone common in head and neck no potential for malignancy associated with Gardner syndrome

Orbital floor

composed of zygomatic bone and axilla infraorbital nerve injured in fractures -> numbness of upper cheek, upper lip, upper gingiiva

Diaphragmatic hernia

compression of lungs by abdominal organs Pulmonary hypoplasia and hypertension hypoplasia of heart Mostly fatal

Wernicke-Korsakoff syndrome

confusion, ataxia, occulomotor abnormalities, permanent memory deficiets Adult beriberi -dry or wet depending on cardiac involvement -symmetrical peripheral neuropathy of distal extremities -Cardiac involvement includes cardiomyopathy, high-output congestive heart failure -peripheral edema -tachycardia Alcoholics

Chiari malformation type II

congenital defects of the posterior fossa -cerebellum -brainstem -craniocervical junction leads to downward displacement of the cerebellum into the spinal canal herniation of medulla, cerebellar tonsils, and vermis down into spinal canal Myelomeningiocele PW -headaches due to meningeal irritation -diziness -nystagmus -ataxia -UMN dysfunction

Chiari malformation type I

congenital defects of the posterior fossa -cerebellum -brainstem -craniocervical junction leads to downward displacement of the cerebellum into the spinal canal synringomyelia PW -headaches due to meningeal irritation -diziness -nystagmus -ataxia -UMN dysfunction

Integrin

connects to fibronectin to anchor -also collagen and laminin

Bacillus anthracis

contact with animals or facilities using animal products locally contaminated soil Black eschars Gram + rods in chains Protein capsule (poly-d glutamate) Obligate aerobes Spore forming Leathal factor- cleaves MAP kinase, leads to tissue necrosis because MAPK is needed for cell growth edema factor- increase cAMP, edema, prevents phagocytosis People working with wool get this Widening of the mediastinum Pulmonary hemorrhage - if you have this death is almost certain cutaneous anthrax- malignant pustules rupture and form a black eschar surrounded by edema death can occur from from bacteremia, meningitis, and pneumonia boxcar-shaped, gram positive rod Doxycycline or ciprofloxacin

Granulosa cells

convert androgens to estrogens

Heme oxygenase

converts heme (purple blue) to biliverdin (green)

Smith antigen

core protein of small nuclear ribonucleoproteins (snRNPs) anti-smith antibodies in 30% of SLE patients An ANA

Renal function tests

creatinine (0.6-1.2 normal) -filtered freely and hardly secreted, good for renal function -slight overestimation because its secreted jusssttttt a little bit

Acalculous cholecystitis

critically ill patients caused by bile stasis, not obstruction

Syringomelia

cystic dilation of th central canal of spinal cord trauma tumors obstructing CSF flow compresses the ANTERIOR WHITE COMMISSURE -> bilateral loss of pain and temperature sensation

cyclophosphamide

cytotoxic alkylating agent -> crosslinks DNA -has to be metabolyzed by CYP450 in liver Tx -cancers -nephrotic syndrome nephritic syndrome -vasculitis -autoimmune hemolytic anemia AEs -myelosuppression -bladder cancer (high grade transitional cell carcinoma) -hemorrhagic cystitis -> protect with mesna -SIADH -> hyponatremia -infertility and premature menopause -azoospermia (irreversible)

5-fluorouracil

cytotoxic pyrimidine analogue complexes with THF -stops DNA synthesis -dUMP can't get methylated to turn to thymidine (dTMP) (thymidilate synthase) Chemo drug -colorectal cancer #1 -breast -head and neck -liver -pancrease -basal cell cancers Rheumatoid arthritis AE -nausea and vomiting -hyperpigmentation -myelosuppression leucovorin does not help

Canagliflozin

dapagliflozin SGLT-2 inhibitors decrease resorption of glucose at PCT AEs -increased UTIs -Polyuria -vaginal candida infection

Lobular carcinoma in situ

dark round nuclei in cells in clusters in lobules no palpable mass no necrosis no calcifications Dx -lucky when you see it on breast biopsy for some other reason Tx -surgery

Cori disease

debranching enzyme deficiency Type III PW -hypoglycemia -hepatomegaly -ketoacidosis -muscle weakness -hypotonia -hepatic fibrosis ACCUMULATION OF GLYCOGEN with ABNORMALLY SHORT OUTER CHAINS -> cant debranch all the way

Gilbert syndrome

decreased activity of UDP-glucuronyltransferase -> conjugated bilirubin leads to increased unconjugated bilirubin autosomal recessive mild jaundice in times of stress

Chediak Higashi syndrome

defective fusion of phagosomes and lysosomes -> defective phagolysosome formation Autosmal recessive Lysosomal trafficking disrupted Neutrophils whith giant azurophilic granules that dont release properly -staph infections Occulocutaneous albanism -melanin doesn't transfer properly Neurological sensory deficets

Gastroparesis

delayed gastric emptying in the ABSENCE of a mechanical obstruction Nausea Stomach pain Early satiety Vagus nerve damage Metoclopromide to treat

Succinylcholine

depolarizing neuromuscular blockade Just sits on receptor, stimulating it constitutively Phase-1 block

Atopic eczematous dermatitis

dermal atrophy on punch biopsy after successful treatment because corticosteroids decrease production of extracellular matrix collagen and glycosaminoglycans Active disease shows intraepidermal vesicles, superficial epidermal hyperkeratosis

Beta-hCG in serum

detectable at 8 days after fertilization Looks like TSH and LH -and FSH

Hemithorax

deviation of trachea toward affected side

Methotrexate

dihydrofolate reductase inhibitor -irreversible -dihydrofolate can't get recycled back into tetrahydrofolate, cant get methylated, can't make dTMP) -stops DNA synthesis -dUMP can't get methylated to turn to thymidine (dTMP) (thymidilate synthase) Chemo drug -leukemias -lymphomas -breast cancer -head and neck cancer -lung cancer -invasive molar pregnancy -trophoblastic tumors -choriocarcinoma -psoriasis -IBD -SLE -Vasculitis -dermatomyositis -Rheumatoid arthritis AEs -megaloblastic anemia -myelosuppresion -pancytopenia -pulmonary fibrosis -hepatotoxicity - monitor LFTs -somatositis

Aliskiren

direct renin inhibitors Reduce long term progression of heart failure Prolong survivability reduce remodeling (angiotensin II is main mediator) Tx -HTN -heart failure (especially with diabetes) -slow progression of diabetic nephropathy -albuminuria and high blood pressure AEs -creatinine bump -COUGH -contraindicated in hereditary angioedema -teratogenic -contraindicated in CKD -NSAID use -hyperkalemia

Bivalirudin

direct thrombin inhibitor

ARBs

directly block angiotensin II receptor Reduce long term progression of heart failure Prolong survivability Reduce long term progression of heart failure Prolong survivability reduce remodeling (angiotensin II is main mediator)a Tx -HTN -heart failure (especially with diabetes) -slow progression of diabetic nephropathy -albumineria and high blood pressure -acute MI AEs -creatinine bump -COUGH -contraindicated in hereditary angioedema -teratogenic -contraindicated in CKD -NSAID use -hyperkalemia

Hamartomatous polyp

disorganized growth of mature cells benign Puetz-jeghers

Lateral medullary syndrome

disruption in posterior inferior cerebellar artery -branch of vertebral PW -vertigo -nystagmus -because vestibular nucleus is disturbed -ipsilateral face and contralateral body (spinal trigeminal and spinothalamic tract -bulbar weakness (dysphagia and dysphonia) due to injury of nucleus ambiguus) -ipsilateral horner syndrome

P body

distinct foci found within eukaryotic cells that are involved in mRNA regulation and turnover. Play a role in translation repression and mRNA decay -contain RNA nucleases Also play a role in RNA storage

Cidofovir

doesn't need to be phosphorylated Tx -acyclovir resistant HSV and VZV -CMV AEs -Delerium -Confusion -Vertigo -hallucinations -all worse with IV administration -

Migraine pain

due to activation of the trigeminal nerve in meninges -> release CGRP, substance P, neurokinin A

Limb girdle muscular dystrophy

due to defective caveolin (sarcolemma protein) that causes T tubules to be fewer, leads to uncoordinated muscle contraction

Fat necrosis of breast

due to trauma can present with mass

Familial Mediterranean fever

dysfunction of neutrophils -presents with episodes of fever and acute serosal inflammation -high SAA during attacks Dx -requires tissue biopsy

Plummer-Vinson syndrome

dysphagia esophageal webs iron deficiency iron supplementation helps reverse

Secondary hyperthyroidism

elevated T4 and TSH Pituitary adenoma -> hyperplasia -> goiter

FSH

elevated in the FOLLICULAR phase stimulates development of MULTIPLE follicles

Granulosa-theca tumor

elevated inhibin precocious puberty in children AUB in postmenopausal women Exner bodies - cuboidal granulosa cells in rosette pattern with eosinophilic center Coffee-bean nuclei Favorable survival Sertoli-leydig is counterpart male

AV node location

endocardial surface of the right atrium near the insertion of the septal leaflet of the tricuspid valve and the orifice of the coronary sinus

Bosentan

endothelial- receptor antagonist that blocks the effects of endothelin (causes vasoconstriction and endothelial proliferation) decreases pulmonary artery pressure and lessens the progression of vascular and right ventricular hypertrophy

Fusion inhibitors

enfuvirtide Treat HIV

Paclitaxel

enhance microtubule production and prevent their degradation -> inhibits cell division -> cell death M phase specific

Bullous Pemphigoid

epidermis on top dermis on bottom and fluid accumualtes in between linear deposition of IgG1 and C3

Charcot-Bouchard microaneurysms

especially common in the lenticulostriate arteries (deep brain perforators originating from the ACA and MCA)

Polyhydramnios

excessive amniotic fluid uterus is larger than expected caused by -decreased swelling of amniotic fluid -tracheoesophageal fistula -increased fetal urination -> from increased fetal cardiac output -> diabetes

Trigeminal nerve location

exits the brainstem at the lateral aspect of the mid-pons at the level of the middle cerebellar peduncles

Acting out defense mechanism

expressing unacceptable feelings through actions

Akathesia

extrapyramidal side effect associated with antipsychotic treatment PW -feelings of tension -marked physical restlessness -inability to sit stil

Listeria monocytogenes

facultative intracellular narrow zone of beta hemolysis Pregnant women get infected Cant heat cheese Motile, flagella, tumbling Actin rockets intracellularly Catalase positve Grows at low temperatures Ampicillin

Growth hormone deficiency

failure to grow in child cherub-like face decreased hair growth small genitalia delayed puberty delayed bone age (bone age < actual age) Tx -give recombinant growth hormone In adults -endocrine and metabolic effects -muscle wasting and obesity -decreased bone density and osteoporosis -Insulin-like growth factor 1 is LOW (normally secreted by liver in response to GH)

Peyronie disease

fibrous plaque of excessive collagen forms in tunica albuginea can cause erectile dysfunction corrected with surgery

Hippocampus

first site of ischemic injury in brain

Seborrheic keratoses

flat to raised waxy to greasy pigmented lesions with a "stuck on" appearance

68/95/99 rule

for normal distribution symmetry about its mean 68% of all observations lie within one standard deviation 95% within two 99.7% within three mean +- 1.96 x SDroot(n)

Reactive arthritis

formerly known as reiter syndrome Conjunctivitis, urethritis, arthritis Cant see cant pee cant climb a tree associated with chlamydial infection 70% or more Shigella Salmonella Yersinia Campylobacter Chlamydia inflammatory arthritis with predominance of neutrophils HLA-B27

Invasive lobular carcinoma

forms lines of invasive cells -no overt mass lesions more likely to be bilateral

Trophoblasts

forms the chorionic villi -part of placenta that derives from embryo -transfers oxygen and nutrients between mother and fetus composed of 1. SYNCYTIOtrophoblast 2.CYTOtrophoblast dysfunction of these cells usually involves -elevated beta-hCG

Cytotrophoblast

from embryo inner layer of chorionic villi

Krukenberg tumor

gastric cancer with metastases to the ovary often bilateral signet ring cells -mucin displacing nucleus against cell membrane

Burkitt lymphoma

gene translocation 8 -> 14 (c-myc overexpressed, growth-stimulating hormone) KI-67 -protein present only during cellular replication -fraction shows how quickly cancer is replicating -high KI-67 fraction Endemic in africa -jaw mass Sporadic in north america -rapidly growing abdominal mass Immunodeficiency related burkitt lymphoma -chronic infection with EBV -HIV related

Follicular Lymphoma

gene translocation of 14 -> 18 -overexpression of BLC2 antiapoptotic protein (prevents release of cytochrome C from mitochondrial membrane) Waxing and waning hypercellular nodules second most common middle age caucasians can progress to diffuse large cell

Absence seizures

generalized epilepsy children 4-10 brief staring spells automatisms like lip smacking or rhythmic blinking Can be provoked with hyperventilation 3-Hz spike wave complexes Ethosuximide inhibits t-type calcium channels in thalamic neurons Valproate can also be used if this isn't effective

Vasospasm due to Subarachnoid hemorrhage

give calcium channel blockers

Hyperglycemic Hyperosmolar non ketoacidosis

glucose >1000mg/dL osmotic diuresis hyponatremia hypovolemia hypovolemic shock serum osmolality 320-380 mOsm NOT ketoacidosis normal pH Sometimes even alkaline from contraction alkalosis

Primary hypogonadism

gonads themselves dysfunctional end organ dysfunction = primary disorder

Clostridium botulinum

gram + Improper canning of foods can allow for survival of spores, produce relatively heat-stable toxin Obligate anaerobe Flaccid paralysis Descending paralysis - eye problems can appear first, diplopia and ptosis Affects PNS not CNS because it cannot cross blood brain barrier Botulism toxin is the same as Tetanus toxin, just the type of neuron is different -> botulism affects motor neurons with acetylcholine (excitatory) so the result is flaccid paralysis Floppy baby syndrome - particularly worse because babies don't have the range of microorganisms in their gut to compete HONEY!

Haemophilus influenzae

gram - coccobacilli shape Chocolate agar with factor 5 (nicotinamide) and 10 (hematin) Primarily transmitted by aerosol transmission Pneumonia Meningitis - (type B capsule) Otitis media Epiglottitis - inspiratory stridor, drooling, "cherry red epiglottis" Splenectomy - sepsis Capsule is made up of PRP -polyribosylribitol phosphate Vaccinate against type B capsule that causes meningitis (2-18 months best time) Polysaccharide of haemophilus capsule conjugated to the diphtheria toxoid to increase immune response Treat: Beta-lactam antibiotic for systemic: ceftriaxone Rifampin for prophylaxis in close contacts

Tropheryma whippelii

gram positive actinomyces infects only macrophages -> no inflammation -> macrophages will show PAS+ granules and bacteria in phagolysosome

Subacute granulomatous thyroiditis

granulomatous inflammation of the thyroid widespread neutrophilic and lymphocytic infiltration of the gland multinucleated giant cells Women 30-50's Thought to follow viral infection HLA-B35 -thought to be a receptor for viral infection, body makes antibodies to it via molecular mimicry PW -acute PAINFUL goiter -pain swallowing -transient hyperthyroidism (2-8 weeks) -hypothyroid phase (2-8 weeks) usually asymptomatic -recovery

Intraductal papillomas

grow into lumen most common cause of bloody nipple discharge -result of twisting of the vascular stalk -papillary projections with vascular core benign -> risk of transformation into cancer

Adenomyosis

growth of deeper stratum basalis layer of endometrium grows into myometrium uniformly enlarged globular uterus can cause AUB -heavy prolonged menstrual bleeding -dysmenorrhea

human chorionic gonadotropin

hCG Binds to testicular tissue -> estradiol production Can cause gynecomastia in men

Actinic keratosis

half of SCC arises from AKs RF -UV light exposure -p53 mutation PW -hyperkeratosis -raised papules or plaques -sandpaper roughness -brown scale -on sun exposed areas

Tuberous sclerosis

hamartomas throughout the body 20x higher risk of cancer autosomal dominant mutation -TSC 1 -> hammartin -TSC 2 -> tuberin -> RAS constitutively active (GDP always on?) CNS hamartomas are pretty unique PW -seizures due to CNS hamartomas -IQ disability -angiofibroms -Ash-Leaf spots (hypopigmented areas) -fibroadenomas of face (adenoma sebaceum) -mitral regurgitation -interstitial fibrosis -renal angiomyolipomas (malignant transformation

Physostigmine

has CNS effects tertiary amine -> crosses BBB indirect acting cholinomimetics -increase acetylcholine at the synapse -boosts endogenous acetylcholine use Tx -ATROPINE OVERDOSE -myasthenia gravis -can reverse neuromuscular blockade (after anesthesia) -urinary retention AEs -DUMBBELS -Diarrhea -Urination -Miosis -Bronchospasm -Bradycardia -Lacrimation -Salivation

Embryonal carcinoma of testicles

hemorrhagic masses with areas of necrosis more common than in females sheets of atypical poorly differentiated cells

Idiopathic pulmonary fibrosis

honeycomb lungs -> alveoli collapse and proximal airways dilate

Leukoplakia

hyperkeratosis

Spinal stenosis

hypertrophy of the ligamentum flavum presents with lower extremity pain, numbness, weakness

Waldenstrom Macroglobulinemia

hyperviscosity syndrome caused by LymphoPlasmacytic Lymphoma neoplasm of mature B lymphocytes IgM 10% neoplasms on bone marrow Hyperviscosity causes -headaches -dizziness -tinnitus -deafness -confusion (due to sluggish blood flow in the CNS) -visual impairment due to tortuous retinal artery -peripheral neuropathy -tendency for bleeding because IgM messes with clotting factors -Raynaud phenomenon (urticaria, purpura, tissue necrosis) -lymphadenompathy -splenomegaly -anemia Treat: -plasmapheresis -chemotherapy

Sheehan syndrome

hypopituitarism seen in pregnancy increased estrogen leads to hyperplasia of prolactin-secreting cells Pituitary can more easily become ischemic PW -inability to lactate due to lack of prolactin

Eisenmenger syndrome

hypoxemia -release of EPO -> polycythemia Right ventricular hypertrophy due to increase afterload

Testicular seminoma

identicle to dysgerminomas in female homogenous testicular enlargement beta-hCG is elevated

Legg-calves perthes

idiopathic avascular bone necrosis in children (4-7) Limp of insidious onset Trendelenburg gait

Rhizopus spp

immunocompromised patients Diabetics Bread mold Spore inhalation DKA is most predisposing factor Likes to invade blood vessels and penetrate the cribriform plate of the skull to get to CNS

CNS lymphoma

immunocompromised state is most important risk factor Most common CNS malignancies in immunocompromised often display areas of necrosis

Medial longitudinal fasiculus

in the dorsal pons horizontal eye movement

Superior Colliculus

in the midbrain involved in pupillary reflex parasympathetic input to eye

obstructive sleep apnea

increase risk of pulmonary hypertension RF -thick neck -narrow airway

Qualitative platelet disorders

increased bleeding time skin and mucous membranes bleed -> easy bruising, petechiae, epistaxis Acquired: 1. Uremia -due to kidney disease 2. Trauma -coagulopathy is part of the triad of death -lactic acidosis and temperature regulation likely leads to bad platelet function 3. Diabetes -thrombotic complications Congenital 1. Bernard-Soulier syndrome -causes deficiency of GP1b (normally responsible for platelets adhering to vWF -> eventually leads to formation of platelet plug) receptors on platelet surface -autosomal recessive -giant platelets (GP1b is involved in process of platelet budding from megakaryocytes -> absence leads to formation of large platelets) -diagnose: ristocetin test is NEGATIVE (normally causes vWF to bind to GP1b) [also occurs in von willebrand's disease -> so you add normal serum with vWF, and if this returns platelet aggregation back to normal then the patient had von willibrand's disease] 2. Glanzmann thrombasthenia -GP2a/3b, located on platelet surface, is dysfunctional -> fibrinogen unable to bind -> reduced formation of platelet plug -> "platelet-like" bleeding pattern -This is what abciximab does essentially -Ristocetin test in POSITIVE (vWF and GP1b are normal) 3.Wiskott-Aldrich syndrome -X linked -mutation in 'Wiskott-Aldrich syndrome" protein (a cytoskeletal protein in platelets, B cells, T cells) -small deformed platelets -> phagocytosed by macrophages -> thrombocytopenia -> Purpura -IMMUNODEFICIENCY

Sclerosing adenosis

increased glandular tissue in lobules increased fibrous tissue -> sclerosis

GI bleeding

increased nitrogen in blood -from bacterial breakdown of heme products

IgG4 antibodies to phospholipase A2 receptor

indicative of membranous nephropathy

Cocaine

indirect sympathomimetic -enhance endogenous catecholamines -epinephrine, norepinephrine, dopamine MOA -inhibits NET and DAT -> accumulation at synapses Effects -tachycardia - addictive intoxication -agitated -tachycardic -dilated pupils -hypertension causes nasal mucosal atrophy coronary vasospasm -> myocardial ischemia no beta blockers without blocking alpha too

Amphetamine

indirect sympathomimetic -enhance endogenous catecholamines -epinephrine, norepinephrine, dopamine MOA -reverses pump of VMAT, -> pumps NT out of vesicle and back into synapse mood elevating effect alerting sleep-deferring increased attention to repetitive tasks appetite suppressing Tx -ADHD -narcolepsy

Methylphenidate

indirect sympathomimetic -enhance endogenous catecholamines -epinephrine, norepinephrine, dopamine MOA -reverses pump of VMAT, -> pumps NT out of vesicle and back into synapse mood elevating effect alerting sleep-deferring increased attention to repetitive tasks appetite supressing

Atomoxetine

indirect sympathomimetic -enhance endogenous catecholamines -epinephrine, norepinephrine, dopamine NET blocker Tx -ADHD

Modafinil

indirect sympathomimetic -enhance endogenous catecholamines -epinephrine, norepinephrine, dopamine treats narcolepsy stimulant fewer adverse effects than amphetamines

Sacroiliitis

inflammation of the sacroiliac joints presents with butt pain, hip pain, lower buttocks extending down the leg

Eczema

inflammatory skin disorder papulovesicular eruptions with erythema and edema Pruritus Exudates Crusting and scaling Excoriations from itching History (family too) of atopic disease asthma hay fever allergic rhinitis path reveals spongiosus characterize by increased width between cells of epidermis due to intercellular edema

Lead poisoning

inhibits heme synthesis -microcytic hypochromic anemia -SOB due to decreased oxygen delivery to tissues Basophilic stippling -inhibition of erythrocyte 5' nucleosidase -> ribosome aggregation due to inability to degrade RNA -> coarse blue punctate dots in the cytoplasm -seen in thalassemias and myelodysplastic syndrome

Estrogen

inhibits osteoclast differentiation -> prevents bone breakdown

Riedel's thyroiditis

intense inflammatory infiltrate of the thyroid -> spreads to local muscles, nerves, blood vessels ect -> cytokines released fibrosis of thyroid tissue over time -> fibrosis extended beyond thyroid capsule and into surrounding neck tissue Several forms of systemic fibrosis occur as well PW -hard, fixed, painless goiter -diffuse sclerosis of the neck -compression of trachea -hypothyroidism (TSH high, T4 low, fatigue, weight gain, cold intolerance, dry skin, brittle hair) -will have anti-thyroid antibodies, but most likely these are formed after destruction has begun

Neuromuscular blockers

interfere with transmission at NMJ -curiums atracurium mivacurium pancuronium vecuronium rocuronium cyclobenzaprine - centrally acting skeletal muscle relaxant structurally related to tricyclic antidepressants has strong anticholinergic side effects: xerostoma, mydriasis, tachycardia

IL-5

interleukin activates eosinophils

Invasive ductal carcinoma

invaded through basement membrane painless, fixed, hard breast mass with irregular boarders spiculated soft tissue mass microcalcifications on mammogram dense desmoplastic reaction in surrounding stroma

vulvar squamous cell carcinoma

keratin pearls intercellular bridges surgery or radiation inguinal lymph nodes HPV 16, 18

Breast feeding jaundice

lack of breast feeding lack of milk production lack of milk leads to slow bile excretion -> jaundice

Galactosemia

lack of galactokinase -Galactose builds up -> converted to galactitol -> osmotic agents cause cataracts Lack of glacatose-1-phosphate uridyl transferase -MUCH more serious -galactose-1-phosphate accumulates -> toxic metabolite -> hepatic and renal dysfunction -vomiting, lethargy, and failure to thrive

Nitrous oxide

laughing gas inhaled anesthetic N2O less soluble anesthetic -less soluble drugs saturate faster -> rapid onset, rapid recovery AEs -decrease respiration

Methylmalonyl-CoA mutase mutation

leads to build up of methylmalonic acid and propinoic acid can't turn methylmanoyl-CoA into succinyl-CoA (vitamin B12 dependent) PW -metabolic acidosis -hypoglycemia (overall increased metabolic rate leading to increased glucose utilization and toxic inhibition of gluconeogenesis) -urea cycle inhibited -> hyperammonemia

Restrictive cardiomyopathy

leads to filling problems ventricle is too stiff and can't stretch to fill diastolic failure JVD prominent Y descent Kussmal sign Causes -usually just one part of more systemic disease -amyloidosis -sarcoidosis -hemochromatosis (more usually dilated) -lysosomal storage diseases -Gauchy -> cerebrosites -Hurlers -> mucopolysacharrides -Fabry's -> glycolipids -myocardial fibrosis i.e. scleroderma -Radiation treatment to chest -endomyocardial fibrosis (most common worldwide and cause unknown) -endocardial fibroelastosis = proliferation of left ventricular endocardium (infants in 1st year of life in conjunction with congenital heart disease

Primary lactase deficiency

leads to more acidic stool -bacteria breakdown of lactose gives off acidic byproducts

L/S ratio

lecithin / sphingomyelin ratio -when its greater than 2, lungs are mature

Holoprosencephaly

left and right hemispheres fail to separate abhorrent midline signaling fetal alcohol syndrome associated spectrum from cleft palate to cyclopia

Frontal lobe lesions

left side = apathy and depression right side = disinhibited behavior

gp120

lets GIV gain access to CD4+ cell CXCR4 or CCR5

Mucinous cystadenocarcinoma

light pink, full of mucin, similar to cervical cells can secrete massive amounts of mucus into peritoneal cavity -> pseudomyxoma peritonei can be associated with brenner tumor CA-125 -> also elevated in endometriosis and other things that disrupt epithelial membrane ->can be used to track progress, not specific enough to be diagnostic RF -BRCA I and II -anything that causes repeated damage of epithelium -> OVULATION when the follicle BURSTS out of epithelium lol -nulliparity due to no breaks in ovarian cycle -endometriosis protective factors -breast feeding -OCPs -pregnancy -all cause ovulation to take a break PW -malignant pleural effusions

Cervical polyps

lined by mucus secreting columnar cells middle aged women around menopause can cause vaginal bleeding

ANP and BNP

linked to guanylyl cyclase that increases GMP

Exenatide

liraglutide GLP-1 agonists delayed gastric emptying decreased post prandial glucose rise

Congenital hydrocephalus

macrocephaly and a bulging fontanelle -> irritability, poor feeding, developmental delay -> permanent brain damage, seizure Ventriculoperitoneal shunt

Lung healing

maintenance of basement membrane integrity allows for resolution of pneumonia with no abnormalities in lung infections

Neutrophil myeloperoxidase

makes pus green in sputum during bacterial infections blue-green heme-based pigmented molecule contained within the azurophilic granules

Topoisomerase I

makes single-stranded nicks in DNA to relieve negative supercoiling

Paget disease of breast

malignant cells within the skin OVERLYING a breast carcinoma -> due to cells spreading through the lactiferous ducts and into the epidermis of the nipple malignant intraepithelial adenocarcinoma cells can also present on and near the genitals -vuvla -called extramammary Paget's disease

Squamous cell carcinoma

malignant proliferation of keratinocytes lower lip 5% metastasize to regional lymph node RF -UV light exposure -inflammation of skin (doesn't have to be sun exposed) -lichen sclerosis -burns -chronic immunosuppression PW -keratin pearls on histology

Mammary duct ectasia

mammary ducts blocked by debris pain inflammation fibrosis can be present if its bad

Temporomandibular joint disorder

mandibular nerve is involved -sensation to the TMJ and mandibular teeth -sensation to floor of mouth -inside of the cheeks -anterior tounge -skin over jaw motor fibers innervate -medial and lateral pterygoid -massater -temporalis -muscles of the floor of the mouth (mylohyoid) -tensor veli palatini -tensor tympani!!!! in EAR Jaw pain and otological symptoms

IgE-independent mast cell activation

mast cell degranulation can be caused by several drugs by activation of protein kinase A and PI3 kinase -> release of histamine, bradykinin, heparin, and a number of enzymes and chemotactic factors Drugs -Opiods -Radiocontrast agents -Vancomycin

Sublimation

mature defense mechanism Channeling impulses into socially acceptable behaviors

Suppression

mature defense mechanism Putting unwanted feelings aside to cope with reality

Rifabutin

may be added as a third agent in treatment of MAC infection activated by CYP450

diagnosing hyperthyroidism

measure serum T4

Enchondroma

men and women equally produce cartilage less than 3 cm medullary cavity commonly affect bones in hand and feet

Osteosarcoma

metaphysis Malignant cell producing osteois anaplasia + osteoid = osteosarcoma Usually distal femur or proximal tibia Drags periosteum off bone "Codman's angle"? Bimodal age distribution ~20 and >65 chemo: Adriamycin (doxorubicin) cis-platinum methotrexate ifosfamide RF -Retinoblastoma -radiation therapy

HIV-associated dementia

microglial nodules present <200 count Subcortical dementia usually presents first -attention, working memory, executive function etc.

breast milk jaundice

milk can contain materials that can inhibit UDP-glucuronyltransferase -> conjugated bilirubin

Acute Rheumatic Fever

mitral stenosis Strep pharyngitis is necessary before you can get RF Autoimmune disease -molecular mimicry Endocarditis (that can lead to valvular involvement) Valve damage can cause mitral regurgitation (new holosystolic murmur) Aortic regurgitation can also happen, less common (diastolic murmur) JONES criteria -joints -my-O-carditis -nodules -erythema marginatum -Sydenham chorea Histology -granuloma composed of group of activated macrophages, lymphocytes, -> multinucleated giant cell -Aschoff bodies -Anitschkow cells = activated macrophages with slender, ribbon-like nuclei may be seen in the granuloma of ARF Can detect antistreptolysin O Subsequent exposure causes repeated and worsening ARF

alemtuzumab

monoclonal antibody binds CD52 -depletes T and B cells -binds and causes apoptotic effect Tx -CLL AEs -Infusion reaction (headache, fever, skin rash, dyspnea, hypotension)

bevacizumab

monoclonal antibody binds VEGF Tx -metastatic cancers -colorectal cancer -lung cancer -wet macular degeneration -> retinal hypoxia stimulates VEGF production AEs -Infusion reaction (headache, fever, skin rash, dyspnea, hypotension) -serum sickness (fever, rash, arthralgia, within 7-10 days) -bleeding -thrombotic events -impaired wound healing

Craniopharyngioma

most common cause of hypopituitarism in children rathke pouch overgrowth commonly occur on stalk bitemporal hemianopsia compression usually slowly growing histology -3 components -calcified component -solid component -cystic component

Achondroplasia

most common form of dwarfism inherited defect in chondrocyte proliferation ->defective endochondrial ossification & abnormal epiphyseal growth plate function Gain of function mutation in FGFR3 -on chromosome 4 -tyrosine kinase receptor -usually responsible for inhibiting chondrocytes -> over inhibited Autosomal dominant Homozygous form is lethal

Gallbladder adenocarcinoma

most common gallbladder cancer -very deadly RF -chronic cholecystitis -dystrophic calcifications -> porcelain gallbladder Can for exophytic mass

Choriocarcinoma

most common gestational trophoblastic neoplasm malignant tumor arising from trophoblasts occurs after pregnancy histology -bulky -yellow-white -intrauterin mass -areas of necrosis and hemorrhage VERY sensitive to chemotherapy -methotrexate

Renal cell carcinoma

most common malignant renal tumor (85%) 6th and 7th decades of life Aggressive Early mets lungs and bones Flank pain, hematuria, palpable abdominal mass Clear cell carcinoma is most common type -high lipid and glycogen content Arise from cells of the PCT Associated with e Lindau gene -encodes for a tumor suppressor protein -2 hit model Unilateral, large, and well defined margins -satellite nodules can ascend the renal vein -> IVC -> right atrium -Lower extremity edema -Left sided varicocele from backup of blood into left testicular vein Produce renin Produce erythropoeitin -> polycemiam vera Produce PTH like peptide Produce ACTH like hormone Risk factors -obesity -smoking -hypertension -

Corpus luteum cysts

most common ovarian mass found in pregnant women usually regress spontaneously

Meningioma

most common primary CNS tumor 1/3 benign slow growing from arachnoid mater 40-60 year old women NF type II CP -when they are large enough to cause compression of surrounding parenchema -seizures, blindness, paralysis, gait disturbances, high ICP -focal stuff Histology -well circumscribed round tumors growing out from the dura (may remain attached via dural tail) -dural folds, tentorium cerebelli, venous sinuses -PSAMOMMA BODIES -whirled spindle cells easily treated with surgical removal

Small bowel obstruction

most common site (small lumen) RF -adhesions (prior abdominal surgery, infections, IBD) -Small bowel tumors - PW -Air in bowels (backup) -tinkling sound from abnormal peristalsis -air fluid levels within bowel loops -transition point (dilated proximal bowel to normal bowel distal to obstruction) Treat: -surgical -No eating, nutrition by fluids SBO likely to reoccur in IBD

Adenomatous polyps

most common type of colon polyp Increased chance of adenocarcinoma -larger are more likely Tubular adenomas villous adenomas -larger than tubules -more likely to become malignant

Ornithine transcarbamylase deficiency

most common urea cycle disorder Excess carbamoyl phosphate -> stimulates pyrimidine synthesis -> increase urinary orotic acid Hyperammonemia due to impaired ammonia excretion -> vomiting -> coma/confusion

Basal cell carcinoma

most common worldwide Upper lip lateral campus of eye RF -UV light exposure -age -fair skin -intense sporadic sun exposure (bad sun burn) more than chronic -chronic immunosuppresion -aresenic exposure -PTCH1 tumor suppressor gene PW -nuclear palisading edge -pearly papule with rolled boarders -telangectatsias -scaly red plaque generally slow growing invade surrounding structures over time

Tardive dyskinesia

movement disorder associated with long-term treatment with dopamine antagonist medication PW -repetitive, rhythmic, involuntary movements of the tongue, lips, face, trunk, and extremities

Naloxone

mu-opioid antagonist can reverse acute toxicity precipitates withdrawals

Naltrexone

mu-opioid antagonist can reverse acute toxicity precipitates withdrawals helps reduce cravings for alcohol and nicotine

Tourette disorder

multiple motor ticks and at least one vocal tick Motor: facial grimacing, blinking, head/neck jerking, shoulder shrugging, tongue protrusion, sniffline Vocal: grunts, snorts, throat clearing, barking, yelling, coprolalia (obscenities)

Langhans giant cell

multiple nuclei organized peripherally into the shape of a horseshoe nonspecific finding in granulomatous conditions

Bowenoid papules

multiple red papules on penis no risk of cancer

Systemic lupus erythematosus

multisystem autoimmune disease most commonly in young women (20-30s) -blacks and asians affected at higher rate HLA-DR HLA-DQ Estrogen stimulates cell-mediated immunity Androgens tend to be more immunosuppressive Anti-nuclear antigens -Anti-double stranded DNA (70% of patients, very specific) -anti-Smith antibodies (30%, specific) -anti-Ro (SSA) -anti-La (SSB) -anti-U1 RNP -anti-histone (very specific) Anti-phospholipid antibodies -present in 50% -hyper coagulable state -abortions -bloodclots -anti-cardiolipin causes false positive VDRL result Drug induced lupus -presents with arthralgias and faituge -no involvement of skin, kidney, or CNS Presents with -Hemolytic anemia -antibodies against platelets -antibodies against lymphocytes -immune complexes that deposit throughout the body (complement activation and tissue injury) -decreased C3 and C4 complement proteins -constitutional symptoms (fever, fatigue, weight loss) -kidney involvement (renal failure is most common cause of death) -glomerulonephritis -nephritic syndrome -nephrotic syndrome -skin involvement -malar rash (butterfly distribution, acute cutaneous lupus erythematosus -chronic cutaneous erythematous (photosynsetive rash) -> liquefactive necrosis and dermal epidermal junction (deposition of complex protein here) -migratory, symmetrical arthralgia -vasculitis -> palpable purpura -Raynaud phenomenon (cold temps -> vasospasm -> pale and cyanotic digits) -pericarditis (pleuritic chest pain, friction rub) -Libman-Sacks endocarditis (sterile verrucous endocarditis) -> aggregates of immune thrombi complexes, leukocytes, thrombi -CNS involvement (Cognitive impairment, strokes, seizures) from small vessel vasculopathy -> microscopic ischemia and infarction) Diagnosis -consensus clinical criteria -beyond scope of Step 1 Classic presentation -Young adult woman with malar rash, joint pain, and glomerulonephritis -some kind of cytopenia (anemia, leukopenia) -positive for at least one kind of autoantibody (anti-double stranded DNA, anti-Smith)

carbachol varenicline

muscarenic and nicotinic agonist Tx -glaucoma -smoking cessation

UMN lesions

muscle weakness spastic paralysis clasp knife rigidity HYPERreflexia babinski sign

Primary hemochromatosis

mutation in HFE protein (normally senses iron stores) -thinks iron is low all the time -> iron accumulation and toxicity

Gorlin's syndrome

mutation in PTCH ("patch", ch9q22.3) Nevoid BCC syncrome Tumor suppressor, two hit hypothesis

spinal muscular atrophy

mutation in survival motor neuron (SMN1) gene affects spliceosome function presents like floppy baby syndrome

Adenovirus

naked DNA virus Most common cause of tonsillitis Respiratory droplets are one mode of transmission Fecal oral route also Hemorrhagic cystitis Viral Conjunctivitis (pink eye) Live attenuated vaccine for military recruits

Methacholine challenge test

necessary to diagnose asthma FEV1 drops by at least 20%

Pheochromocytoma

neural crest cells -> chromaffin cells most common medullary adrenal tumor in adults rule of 10s 10% are bilateral 10% are malignant 10% occur outside the adrenals MEN2 VHL syndrome NF-1 (café-au-lait spots) secrete norepinephrine, epinephrine, and dopamine (EPISODIC) -> headaches -> tachycardia -> sweating -> hypertension -> palpitations -> chest pain -

Neuroblastoma

neural crest cells -> chromaffin cells most common medullary adrenal tumor in children can occur anywhere along the sympathetic chain (medulla is most common tho) N-myc mutation is common presents -abdominal pain -nasua -abdominal mass -can obstruct bowels -bone pain if mets -weight loss Opsoclonus-myoclonus syndrome

Alzheimer Disease

neurodegenerative disease tau protein (hyperphosphorylated, microtubule protein) amyloid beta -> forms aggregates and plaques RF -Down's syndrome: amyloid precursor protein (precursor to amyloid beta) is encoded on chromosome 21 -ApoE4 PW -memory deficits out of proportion to other impairments (especially recent memory) -planning and organizing impaired -spatiotemporal (getting lost in your own neighborhood) Imaging -hydrocephalus ex vacuo (from shrunken cortex, sulci appear narrow) -hippocampal atrophy on MRI is pretty much diagnostic Blood -decreased acetylcholine level due to decreased acetylcholine transferase (most noticeable in the nucleus basalis of maynard - participates in memory and cognition)

Parkinson's disease

neurodegenerative disease abnormal movement BRADYKINESIA postural instability shuffling gait dementia in late stages Loss of substantia niagara -> disinhibited striatum function -> activated subthalamic nucleus -> inhibition of thalamus and MOVEMENT IMPAIRMENT drug induced -anything that reduces amount of dopamine in brain -first-gen antipsychotics -drugs toxic to nigrostriatal Wilson's disease -copper binds dopamine Histology -pallor of nigra striatum

Creutzfeldt-Jakob Disease

neurodegenerative disease abnormal movement Mad cow disease -prion disease -abnormally folded protein catalyzes abnormal folding of others -> beta-sheets accumulate -> cell death -PrPsc (scrapies from disease first discovered in sheep) no treatment always fatal, usually within a year

Huntington's disease

neurodegenerative disease abnormal movement 30-50 Autosomal dominant 100% penetrance Loss of inhibitory neurotransmitter GABA is most common change seen -> excitement PW -Chorea!!! Rapid, nonvoluntary, arrhythmic movement of the limbs - atrophy of tissue Trinucleotide repeat expansion disease CAG more severe if mutated allele is from father disease gets worse with generations Ex vacuo dilation Caudate most affected Striatum Putamen (less so)

Rett syndrome

neurodevelopmental disorder in girls loss of motor and language skills Deceleration of head growth stereotypic hand movements

Mediators of COPD

neutrophils #1 Macrophages CD8+ T cells

Crigler-Najjar

no UDP-glucuronyltransferase -> conjugated bilirubin brain damage, severe jaundice, kernicterus (deposits in brain)

Myeloperoxidase deficiency

no myeloperoxidase -responsible for converting hydrogen peroxide into hypochlorous acid (bleach) -impaired pathogen destruction Most common (50x more common than CGD) respiratory burst is intact NBT test and dihydrorhodamine test are positive

Pituitary adenoma

non functioning hypopituitarism most common cause in adults mass effect PW headache compression of optic chiasm -> bitemporal hemianopsia (tunnel vision)

Sevelamer

non-absorbable phosphate polymer that binds phosphate in the GI tract -> decreases phosphate absorption Treats -hyperphosphatemia due to CKD

Damage to midbrain

nonreactive pupils to light stimulation -contains superior colliculus -> pretectal nucleus -> Edinger-Westphal nucleus -> these nuclei then project parasympathetic innervation through CN III When its knocked out you get unopposed sympathetic stimulation

Hydrocephalus ex vacuo

normal aging cerebral atrophy make ventricles look larger

Protein C/S deficiency

normally inactivates activated factor V and VIII -> suppressing clotting cascade NO WARFARIN -protein C and S are also vitamin K dependent -will lead to warfarin induced skin necrosis (thrombi)

Ethacrynic acid

not sulfamide drug furosemide like action Blocks NaClK cotransporter in Volume excretion Good in CHF Thick ascending loop Reduce lumen positive potential that drove magnesium and calcium absorption -> increased excretion -hypocalcemia (rare, compensation is good) -hypomagnesia Most potent diuretic, so its first line in decompensated heart failure Potassium wasting Dose related hearing loss

Sofosbuvir

nucleoside analog Tx -hep C

Choledocholithaisis

obstruction of common bile duct Alk phos is elevated Gamma glutamyl transpeptidase is elevated (specific to bile duct) Conjugated bilirubin is elevated Stone in the ampulla of vater can obstruct the common bile duct and the pancreatic duct (most common cause)

Graft vs host disease

occurs most often in bone marrow transplant can also occur in liver transplants -rich in lymphocytes

Iatrogenic Sciatic nerve injury

occurs when shot is given superiomedially in the glute should be given superiolaterally

Alkaptonuria

ochronosis urine turns black upon sitting in room air autosomal recessive Tyrosine -> fumarate IMPAIRED Deficiency of homogentisic acid dioxygenase -> no homogentisic acid metabolism -> excreted in urine and turns it black -> also binds collagen in various tissues -> black pigmentation

Ductal carcinoma in situ

often has prominent central necrosis microcalcifications most commonly diagnosed by mammography does not invade basement membrane by definition

Immature teratoma

often malignant males and females

High-affinity IgE receptor

on mast cells and basophils Normally binds Fc portion of circulating IgE When multivalent antigen comes in contact -> receptors aggregate -> non receptor tyrosine kinase activated -> degranulation

Mullerian-inhibiting factor

on the Y chromosome -Causes Mullerian ducts to regress (paramesonephric) -Causes mesonephric ducts develop into epididymus, ductus deferens, and seminal vesicles Not produced in female Absence of this factor will produce a female body type with 46XY

N-terminal collagen propeptide removal

only step that occurs extracellularly

Valacyclovir

oral nucleoside analog guanosine activated via viral thymidate kinase inhibits viral DNA polymerase DAILY suppressive therapy for recurrant HSV improved oral bioavailability more effective if given within three days of outbreak Tx -HSV -VZV AEs -Delerium -Confusion -Vertigo -hallucinations -all worse with IV administration

Acyclovir

oral nucleoside analog guanosine activated via viral thymidate kinase inhibits viral DNA polymerase IV for serious HSV and VZV infections Tx -HSV -HVH AEs -interstitial nephritis -crystalline nephropathy -Delerium -Confusion -Vertigo -hallucinations -all worse with IV administration

Famiciclovir

oral nucleoside analog guanosine activated via viral thymidate kinase inhibits viral DNA polymerase Tx -HSV -preferred treatment for VZV AEs -Delerium -Confusion -Vertigo -hallucinations -all worse with IV administration

Ganciclovir

oral nucleoside analog guanosine activated via viral thymidate kinase inhibits viral DNA polymerase resistance comes from mutating protein kinase Tx -HSV -VZV -CMV AEs -Delerium -Confusion -Vertigo -hallucinations -all worse with IV administration -myelosuppression

Influenza virus

orthomyxoviridae Negative sense RNA virus, enveloped All negatives must bring their own RNA polymerase to make positive strand All single stranded (except RIOVIRUS) All replicate in cytoplasm EXCEPT THIS ONE orthomyxovirus 8 virus segments (BOAR - Bunyavirus, orthomyxo, Arenavirus, Reovirus) Antigenic drift - point mutation that leads to new antigenic strains every season (epidemics) Antigenic shift - When the segments get reassorted (pandemics) Respiratory transmission Influenza A epidemics and pandemics antigenic drift and shift Influenza B endemic antigenic drift Influenza C Virulence factors: -Hemagglutinin: binds to sialic acid on cells in URT or RBC's, makes RBCs clump together. HA antigens are H1, H2, H3. Determines cell tropism. Anti HA antibodies protect you from infection with the same strain in the future -M2 protein: proton pump that creates the proper pH for viral uncoating. Amantadine and rimantadine inhibit M2 protein. No longer recommended because of high levels of resistance -Neuraminidase: cleaves the sialic acid to release the newly formed virions from the host cell Treat Oseltamivir/Anamivir: NA inhibitors, prevent the release of virions Live attenuated nasal spray vaccine Killed injected version of vaccine Pneumonia = major complication Staph or strep superinfection on top of viral Question stem: kid has flu and mom gives him aspirin NO!!! they can get Reyes syndrome which gives encephalitis, fatty liver, and liver failure Aspirin uncouples oxidative phosphorylation in liver cells

Mannitol

osmotic diuretic Works at PCT, loop of Henle Draws free water out of the eye -> decreases intraocular pressure AEs -pulmonary edema from expansion of extracellular volume

Paget disease of the bone

osteitis deformans rapid bone turnover grossly large by weak bone First phase: osteoclast dominant osteolytic Second: mixed osteoclast and osteoblast phase Third: PW -enlarged skull -hats don't fit -headaches -dizziness -chalk stick fracture -spinal stenosis -bone pain -elevated alk phos -shaggy dark areas of radiolucency

ACTH-producing adenoma

overproduction of cortisol -moon facies -cushing's syndrome -> fat redistribution -> thin skin -> obesity -> insulin resistance

Metabolic Acidosis

pH less than 7.35 Causes bicarb to decrease acutely (< 21 mEq/L) Compensation: -lungs kick in -Breathe off excess CO2 (PaCO2 is < 35 mmHG) - Low -pH -BiCarb -PaCO2 Anion gap: Sodium - bicarb - chloride = anion gap ~8-12 -increased anion gap = other organic acids in the blood taking its place INCREASED anion gap -MUDPILES -methanol -uremia -DKA -propylene glycol (antifreeze) -iron and isoniazid (ferric ions get hydrated and release protons) -lactate (hypoxia -> anaerobic metabolism -> lactic acid production) -ethylene glycol and ethanol -salicylates Hypercholremic normal anion gap acidosis -low bicarb is replaced by chlorine -diarrhea -RTA

Placenta previa

painless vaginal bleeding placenta covering cervical os most resolve before delivery -> if it persists, -extra monitoring and blood transfusions if necessary RF -Cesarean delivery previously -multiple gestation

measles

paramyxovirus family, genus Morbilliviruses Enveloped, helical, negative stranded RNA Replicates in the cytoplasm "rubeola" Incubation 7-18 days Cough, coryza, conjunctivitis Koplik's spots Maculopapular rash, centripetal distribution (starts on face and moves downward) Pneumonia Subacute sclerosing panencephalitis SSPE Virulence factors: Hemagglutinin Fusion protein: multinucleated giant cells You do not see a rash until you get an immune response, part of pathogenesis Histology: giant cells MMR is live attenuated virus Vitamin A reduces morbidity and mortality

Becker muscular dystrophy

partial Duchennes X linked recessive mutation in dystrophin (stabilizes muscle fiber mechanically) -somewhat functional PW -pseusdohypertrophy of calves -muscle replaced with adipose tissue and necrosis -nuclei in center of cells instead of along periphery -All of Duchennes stuff with later age of onset -elevated CK -muscle weakness -child unable to keep up -heart failure -dilated cardiomyopathy -arrythmias -death from respiratory failure usually live past 30 Dx -muscle biopsy

Varenicline

partial agonist of the alpha4beta2-nicotinic acetylcholine present in the CNS (thought to be responsible for the reinforcing effects of nicotine

Molluscum contagiosum

pearl-like umbilicated papules

Inflammatory breast cancer

peau d'orange -erythematous, thickened, dimpled, appearance of overlying skin -> due to lymphedema and inflammation -> tumor invades lymphatic vessels and blocks

Germ cell brain tumors

pediatric result of abnormal migration of embryonal cells Pinealoma is most common location germinoma is most common -similar to seminoma PW -hydrocephalus -Parinaud syndrome -> vertical gaze palsy syndrome that presents with "setting sun sign" due to compression of the tectum & superior colliculi

Chicken wire IgG and C3

pemphigus vulgaris

Charcot-Marie-Tooth disease

peripheral demyelinating disorder LMN symptoms -atrophy -progressive weakness hereditary autosomal dominant -structural proteins affected sensory loss genetic testing no cure supportive

Guillain-Barré disease

peripheral demyelinating disorder acute ascending paralysis molecular mimicry- RF -Campylobacter jejuni -viral infections -upper respiratory infections -HIV, EBV, CMV LMN symptoms Usually transient with ventilation support, nearly everyone survives Tx -plasma exchange to get rid of autoantibodies

Cardiac pacemaker action potential

phase 4: sodium leak phase 0: Calcium upstroke phase 3: potassium repolarization back to 4

Purine synthesis

phosphoribosyl pyrophosphate (PRPP) -> Ionosine monophosphate (IMP) -> AMP or GMP

Pellagra

photosensitive dermatitis diarrhea dementia secondary to NIACIN (Vitamin B3) deficiency -can't make NAD+

Follicular cysts

physiologic and usually resolve on their own can rupture and cause peritonitis though can also cause ovarian torsion

Rosiglitazone

pioglitazone Thiazolidinediones PPAR-gamma agonists upregulates adiponectin increases insulin sensetivitt AE -weight gain

Secondary endocrine disorder

pituitary is dysfunctioning secondary hypogonadism -> problem with FSH or LH

Placenta accreta

placenta grows into myometrium

Placenta Percreta

placenta implants past myometrium into serosa of uterine wall Placenta doesn't detach -> significant PPH -> can lead to DIC

Testicular torsion

poor fixation to tunica vaginalis is big risk factor can lead to arterial compression and ischemia absent cremasteric reflex

Medullary breast carcinoma

poorly-differentiated, small cells with prominent blue nuclei significant lymphocytic infiltrate

Acute intermittent porphyria

porphobillinogen deaminase deficiency nervous system dysfunction due to accumulation of early heme pathway intermediates PW -acutely, variable GI and neuro symptoms -abdominal pain -vomiting -peripheral neuropathy REDDISH URINE that DARKENS upon sitting darkens due to oxidation upon hitting air

Sturge-Weber disease

port-wine stain (a facial angioma, or nevus flammeus) neurocutaneous disorder usually in the distribution of a cranial nerve (V1 V2) capillary malformations absent red reflex - leukocoria glaucoma ipsilateral leptomeningeal angiomatosis, intellectual disabilities focal or generalized seizures pheochromocytomas

Herpes zoster infection

postherpetic neuralgia Dermatomal distribution

Chronic lymphedema

predisposes to angiosarcoma

Neutropenia

predisposes to gram - organisms like pseudomonas

Placenta abruptum

premature detachment of placenta from uterine wall PAINFUL vaginal bleeding RF -hypertension -smoking -cocaine use -painful prolonges uterine contractions PW -retroplacental hematoma on ultrasound Emergent C section required

Hypothyroidism

primary -thyroid is problem -High TSH -low T3 -low T4 secondary -pituitary is problem -low TSH -low T3 -low T4 tertiary -hypothalamus is problem PW -cold intolerance -

Osteopetrosis

problems maintaining bone osteoclasts cant make acidic environment autosomal dominant infantile malignant osteoporosis is often fatal PW -bone within bone on xray -pancytopenia -hearing loss if cranial nerve VIII is involved -facial nerve too

Valganciclovir

prodrug of ganciclovir with better bioavalaiblity as effective as IV ganciclovir in treating CMV retinitis Indicated in prophylaxis of immunocompromised patient Tx -CMV AEs -myelosuppresion

Sirolimus

proliferation signal inhibitor Targets mTOR -interrupts IL-2 signaling

Epithelial hyperplasia

proliferation that takes over breast ducts and lobules -> atypia can develop -> looks like carcinoma in situ

POMC

proopiomelanocortin Polypeptide precursor that goes through enzymatic cleavage and modification to produce 1. beta-endorphins 2. ACTH 3. MSH

Simeprevir

protease inhibitor Tx -hep C AEs -photosensitivity -rash

Bortezomib

proteasome inhibitor Lead to cell apoptosis Tx -MM

6-mercaptopurine

purine synthesis inhibitor cytotoxic purine analogue Activated by HGPRT Inactivated by XO treats hematologic malignancy chronic inflammatory conditions IBD, UC, Crohn's second line to methotrexate usually AE -myelosuppression -hepatitis

Azathioprine

purine synthesis inhibitor prodrug of 6-mercaptopurine HGPRT

Mycophenolate mofetil

purine synthesis inhibitor IMP dehydrogrenase inhibitor -> decreased GMP synthesis AEs -myelosuppression

Acne vulgaris

pustules, nodules, comedones, papules, cysts, scarring from previous lesions Tetracycline to treat (prevents binding of aminoacyl-tRNA to ribosomes

Hereditary orotic aciduria

rare autosomal recessive disorder of de novo protein synthesis -defect in UMP synthase (uridine 5'-monophosphate) ->catalyzes final conversion of orotic acid to UMP PW -physical and mental retardation Tx -uridine supplementation

Ménétrier disease

rare protein-losing gastropathy elderly MARKED hyperplasia of mucus-secreting cells -> hypersecretion of mucus -> decreased protein reabsorption -> loss of proteins PW -peripheral edema (low albumin) histology -hyperplasia of goblet cells

RANK-L

receptor activator of nuclear factor kappaB ligand Stimulated by PTH secretion binds to RANK on osteoclast -> activation

Cilostazole

reduces platelet activation by inhibiting platelet phosphodiesterase -> usually breaks down cAMP -> cAMP increase Causes -direct arteriolar dilation -inhibition of platelet aggregation

Cilostazol

reduces platelt aggregation by inhibiting platelet phosphodiesterase (enzyme that breaks down cAMP) Direct arterial vasodilator Great for peripheral arterial disease

Malignant hyperthermia

related to a defect in ryanodine receptors can be caused by -volatile anesthetics -succinylcholine causes -rhabdomyolysis

G Cells

release gastrin to stimulate parietal cells and enterochromaffin cells vagal stimulation to release gastrin

Enterochromaffin cells

release histamine to activate parietal cell respond to gastrin

Tryptase

released by mast cells in anaphylactic shock

Atrial natriuretic peptide

released from atrium in response to stretch decreases renin levels, promotes salt excretion because aldosterone decreases systemic vascular resistance promotes natriuresis which decreases preload increases GFR

GnRH

released from hypothalamus stimulates anterior pituitary to release LH and FSH

Brain natriuretic peptide

released from ventricle in response to stress decreases renin levels, promotes salts excretion because aldosterone decreases systemic vascular resistance promote natriuresis which decreases preload increases GFR

Holocrine exocrine gland

releases contents by lysis of cell membrane and release of cytoplasmic contents -sebaceous glands of skin -> plugging leads to inflammatory acne

Gardner duct cyst

remnants of the wolffian duct (mesonephric duct)

Chronic cholecystits

repeated mild acute event Rokitansky-ASchoff sinu (herniation of gallbladder mucosa into muscular wall)

Gluconeogenesis

requires GTP (like that formed during the succinyl-CoA -> succinate reaction

Nephrogenic diabetes insipidus

resistance to ADH in the kidneys Hereditary causes -insufficient numbers of V2 receptors -defective aquaporin channels PW -dilute copious urine -polyuria -patients usually drink water to avoid hypernatremia RF -LITHIUM THERAPY (enters the principal cells and prevents proper aquaporin formation) -hypercalcemia (mechanism unknown) Administering ADH test -the kidneys cant use it anyway -> still copious dilute urine Tx -Thiazides diuretics -> increase volume depletion -> upregulates volumes conservation in proximal nephron -triamterene can work too -low salt, low protein diet -> less urination

Reaction formation

responding in a manner opposite to one's actual feelings

Osteoarthritis

result of chronic local inflammation -cycle of cytokine release ->chondrocyte activation -> release of more cytokines and metalloproteases not curable PW -enlarged joint spaces -bone spurrs -swollen DIP -heberdens nodes -bruchards nodes -decreased range of motion improves with rest Tx -NSAIDS

Leucovorin

reverses effects of methotrexate doesn't require methylation folinic acid

Aminocaproic acid

reverses fibrinolysis

Tranexamic acid

reverses tPA

Necator americanus

rural southern US Hookworm infected by walking barefoot Travel to the lungs through blood where they get coughed up and you swallow it to get to the small intestine -Iron deficiency anemia -eggs in stool -eosinophils Treatment: pyrantel pamoate albendazole

Ancylostoma duodenale

rural southern US Hookworm infected by walking barefoot travel to the lungs where they get coughed up and swallowed to get to small intestine -Iron deficiency anemia -eggs in stool -eosinophils Treatment pyrantel pamoate albendazole

Concentric hypertrophy

sarcomeres add in parallel in response to increased afterload (HTN, stenotic valves) can lead to diastolic heart failure

Amifostine

scavenges free radicals protective of nephrotoxicity in -> cisplatin expensive

Inflammatory acne

sebaceous glands 1. keratinization of the hair follicle with formation of a keratin plug 2.Hypertrophy of the sebaceous glands with excess sebum production 3.Colonization of the glands with Propionibacterium acnes 4. bacterial hydrolysis of triglycerides in sebum, release of inflammatory fatty acids

menopause

secondary amenorrhea lasting more than a year not due to any other pathology hot flashes night sweats vaginal dryness bone density suffers

Plasma cell neoplasms

secrete monoclonal antibody that can be measured in plasma (M protein) 1. Multiple myeloma

Splitting defense mechanism

seeing others as only bad or good

Heinz bodies

seen in G6PD deficiency oxidative stress

Fenoldopam

selective dopamine 1 receptor agonist increases cAMP vasodilation (especially renal, mesenteric, and coronary) Only agent that increases renal profusion while lowering BP

Osteocytes

send signals and exchange nutrients through gap junctions

Simplex Chronicus

severe pruritus more itching, more scratching

Mixed connective tissue disease

shares a lot with SLE, systemic sclerosis, rheumatoid arthritis, and many others -Young adult women in 20-30w Anti-U1 ribonuclearprotein

Follicular thyroid adenoma

sheets of follicular cells surrounding colloid (similar to normal) Benign tumors that rarely secrete hormone

Fendolopam

short-acting, selective, peripheral dopamine-1 receptor agonist with little to no affect on alpha or beta vasodilation of most arterial beds -> decrease in systemic BP Renal vasodilation -> increased renal perfusion, diuresis, natriesis Especially beneficial in patients with acute kidney injury

Krukenberg Tumor

signet ring cells (mucin displacing nucleus against cell membrane) Gastric cancer metastatic to the ovaries

low serum maternal AFP

signifies aneuploidy -18 or 21

Meglitinide

similar to sulfonylureas repaglinide, nateglinide NOT sulfa drugs DM type 2 Inhibit potassium ATPase channel -> depolarizes -> calcium release -> insulin release AE -hypoglycemia weight gain

Mu receptor

site of opioid action Gi coupled -presynaptic: closure of voltage gated calcium channels -post: increased potassium efflux, hyper polarization

Embryonal rhabdomyosarcoma

skeletal muscle cancer of the vagina chemoradiation surgery

Osteochondroma

skeletally immature patients can look like polyps ->painful if stalk breaks cartilage cap grows slowly most common benign bone tumor distal femur is common site of occurance

Digoxin

slows ventricular firing rate during AF increased parasympathetic tone, which leads to inhibition of the AV node MOA: inhibition of the sodium potassium pump in vagal afferent fibers sensitizes arterial baroreceptors (carotid, aortic) and cardiac receptors = INCREASED vagal output renally cleared Tx -symptomatic treatment of chronic systolic heart failure AEs -Yellowish hue vision change -hypokalemia can increase digoxin binding (loop diuretics are often prescribed in these patients (CHF) too) -preventricular contractions -scooped concave ST segments on ECG -heart block

Lenticulostriate arteries

small vessel ischemic stroke -> lacunar infarcts -> deep basal ganglia -> internal capsule -> midbrain HYPERTENSION longstanding diabete Lipohyalinosis -> thickens wall of blood vessels

Gardner syndrome

soft tissue tumors FAP bone osteomas cutaneous lesions dental abnormalities

Endosomes

sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for future use

McCune-Albright syndrome

spontaneous somatic mutation -> genetic mosaicism Hyperpituitarism PW -Cafe-au-lait spots (usually unilaterally distributed) -precocious puberty -fibrous dysplasia

Acute cholecystitis

stone persistently blocking duct Mucus accumulates behind stone Phospholipase hydrolyzes biliary enzymes -> caustic substances -> mucosal inflammation -> increase in pressure -> occlusion of lymph and veins, eventually artery -> necrosis and perforation Murphy's sign (pain on deep inspiration) radioscintigraphy (aka HIDA scan) can be used to diagnose an impacted stone causing cholecystitis (radiotracer does not enter the gallbladder) E coli overgrowth PW -fever -leukocytosis -thickened bladder wall on ultrasound

Capillary hemangioma

strawberry hemangioma aggregates of closely packed, thin-walled capillaries Benign initially grow, then recede

Ecthyma gangrenosum

strongly associated with Pseudomonas aeruginosa Rf -neutropenia

Difenacoum

structurally similar to warfarin Super warfarin's Bleeding (2,7,9,10 are inhibited) Treatment with fresh frozen plasma and phytonadione (vitamin K)

Ecological study

studying populations -> not individuals

Bullous pemphigoid

subepidermal cleavage Tense bullae Caused by antibodies against hemidesmosomes

ACL tear

sudden decelerations or pivoting on an extended knee

Melanoma

superficial spreading melanoma -flat irregular macuals or plaques Lentigo -elderly with chronic sun exposure Acral lentiginous -dark skinned -palms -soles of feet -subungual (under nail bed) -killed bob marley -poor prognosis Malignant when it breaks through basement membrane -breslow thickness is most important prognostic factor for metastasis RF -UV light exposure -BRAF mutation (most common acquired) ->activated MAP-kinase ERK pathway -atypical nevi -familial (10%) -immunosuppresion PW -ABCDE -Asymmetric -boarder (irregular) -color -diameter bigger than 6mm -evolution -S100

Posteromedial papillary muscle

supplied by posterior descending artery

Sertoli cells

support sperm in response to FSH produce anti mullerian hormone which causes mullerian duct involution

Volvulus

surgical emergency Bowel twists around its mesentary -> strangulation -> ischemia and necrosis

Septic arthritis

synovial fluid WBC > 100,000 gonococcus most likely in younger

Legionella pneumophila

technically gram -, but you need to use silver stain to visualize Oxidase positive Buffered charcoal yeast extract with cystine and iron AGAR Clinical features: Legionnaires disease Smokers atypical pneumonia Unilobar infiltrate hyponatermia urine antigen test Pontiac fever fever and malase usually self limited Treatment: Macrolides fluoroquinolones

Etoposide

teniposide topoisomerase II inhibitor -can't seal double-stranded breaks that it creates -> blocks G2 Tx -solid and hematologic malignancies -testicular -small cell lung cancer -NHL and HL AEs -myelosuppression -alopecia

hydroxyl radical

the most harmful ROS

Number needed to harm

the number of people who must be treated before one additional adverse event occurs NNH = 1 / absolute risk increase

Endometriosis

theories -reverse mences through fallopian tube leads to endometrial tissue outside uterus -inappropriate stem cell differentiation is another theory common sites -serosal surface -rectouterine pouch of douglas PW -dyschezia -dysmenorrhea -powder burn lesions -flesh colored nodules can cause -infertility Tx -OCPs

Pralidoxime

to rescue in organophosphate poisoning, works in periphery mostly -regenerated acetycholinesterase in synapse doesn't work if its been bound for too long

Jaundice

too much bilirubin -natural product of heme breakdown

Amatoxins

toxin found in poisonous mushrooms Halt mRNA synthesis -> hepatic failure -> watery diarrhea -> renal failure urine testing for alpha-amanitin can confirm

Restless leg syndrome

treat with dopamine AGONIST -pramipexole

restless leg syndrome

treat with dopamine agonist pramipexole

Dandy-walker syndrome

triad 1. agenesis of cerebellar vermis 2. cystic dilation of the 4th ventricle 3.enlarged posterior fossa needs shunt due to hydrocephalus

McCune-Albright syndrome

triad of fiberous dysplasia (multiple osteolytic lesions of hip and pelvis) endocrine abnormalities, and cafe-au-lait spots GNAS mutation (alpha subunit of g protein) causing constituent activation precocious puberty

Leprosy

tuberculoid (TH1) least severe Lepromatous (TH2) (weak CMI response)

BRCA 1 and 2

tumor suppressor genes double strand break repair 2 -> most common presentation of male breast cancer

von Gierke disease

type 1 glycogen storage disorder Deficiency in glucose 6-phosphate Can't take phosphate off of glucose to release it into cirulation PW -hepatomegaly and steatosis -fasting hypoglycemia -lactic acidosis -hyperuricemia -hyperlipidemia

Contractures

unusually pronounced MMP activity results in excessive wound contraction Myofibroblast accumulation

Wallerian degeneration

upon axonal damage, axonal degeneration occurs and the myelin sheath breaks down distal to the site of injury usually begins within a few days after lesion onset

SA node location

upper anterior right atrium at the opening of the superior vena cava

hypospadias

urethral opening on ventral side of penis incomplete fusion of urogenital folds increased incidence of cryptorchidism related to bladder extrophy (congenital) surgery

Heterophile antibodies

used to diagnose EBV in vivo

methacholine

used to stimulate asthma in asthma testing cholinomimetic

Calcipotriene

used to treat Psoriasis Topical vitamin D analogue -bind vitamin D receptor (a nuclear transcription factor) that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte differentiation -> inhibits T cell proliferation and other inflammatory modulators

Flucytosine

used with amphotericin B Flourinated cytocine -> 5-Fluorouracil -halts DNA synthesis

Brenner tumor

usually benign nests of transitional-type epithelium -similar to urinary tract contain coffee bean nuclei CA-125 -> also elevated in endometriosis and other things that disrupt epithelial membrane ->can be used to track progress, not specific enough to be diagnostic RF -BRCA I and II -anything that causes repeated damage of epithelium -> OVULATION when the follicle BURSTS out of epithelium lol -nulliparity due to no breaks in ovarian cycle -endometriosis protective factors -breast feeding -OCPs -pregnancy -all cause ovulation to take a break PW -malignant pleural effusions

Hemochromatosis

usually diagnosed after menopause (because premenopausal women have low iron states from menses, pregnancy and breastfeeding) Acquired -multiple transfusions in those with RBC disorders (sickle cell, thalassemias) Hereditary -autosomal recessive -HFE gene on chromosome 6 -linked to HLA-A3 locus -most develop irreversible cirrhosis -increased risk of hepatocellular carcinoma Transferrin upregulated Liver should release hepcidin to reduce iron uptake, lock iron inside cell Hydroxyl free radicals RF -frequent transfusions -ineffective erythopoiesis -thalassemias -alcoholics (increased iron absorption from gut, implies they are still eating decently well) Histology -golden yellow granule in cytoplasm of cell -iron deposits in pancreas, liver, Labs -serum iron and ferritin levels increased PW -bronze diabetes -iron deposits in the pancreas cause diabetes mellitus -steatorrhea from lack of exocrine function -restrictive or dilated cardiomyopathy -secondary hypogonadism from iron deposition in the pituitary -chondrocalcinosis from iron in joint space Diagnose -liver biopsy, because thats where its most severe -genetic testing for mutated HFE allele Treat -phlebotomy -deferoxamine (chelation) to reduce levels

Costosternal syndrome

usually occurs after repetitive activities Reproduced with palpations also movements or certain positions

Lymphocytic hypophysitis

usually presents late in pregnancy lymphocytic infiltrate on histology swelling can cause compression -bitemporal hemianopsia

Von Willebrand Factor

vWF is exposed with endothelial injury, its located in the subendothelium Forms an adhesive Binds to GP1b on platelet and exposed collagen on endothelium, linking them together Also activates platelets -> degranulation and further activation of the coagulation cascade Prolonged bleeding time Prolonged aPTT Binds factor VIII in circulation and drastically prolongs its half life -> von Willebrand's disease causes prolonging of the aPTT pathway (defective intrinsic pathway) Heavy menstrual bleeding Aortic stenosis -shearing effect from narrowed valve Angiodysplasia combined with von Willebrand disease causes intractable GI bleeding Diagnose: Ristocetin test will be NEGATIVE, then add vWF and it will be POSITIVE

Hepatorenal syndrome

vasodilation of splanchnic vessels with vasoconstriction elsewhere in the body -> ischemic renal tissue Decreased Kupffer macrophages in liver -> less clearing of bacteria from GI, higher levels of bacteria in blood -> release of NO Pre-renal kidney injury must reverse hepatic syndrome often too late Mortality >80%

Enterobius Vermicularis

vermin lady -pin worms -female worms migrate down to anus and lay eggs -scotch tape on the anus Treatment -Pyrantel pamoate -Albendazole

Alpha ketogluterate

very important amino group acceptor

Scurvy

vitamin C deficiency presents with: Bleeding gums Ecchymoses & petechiae Impaired wound healing Impairs collagen hydroxylation which occurs in the RER

Charcot-Bouchard aneurysm

weakening of the vessel wall from progressive arteriolar hyalinization and fibrinoid necrosis -> CBA RF -HTN

Cranial nerve XI lesion

weakness turning head to contralateral side of lesion (SCM) Shoulder droop on side of lesions (trap) The left SCM contracts to help turn the head to the right

Phyllodes tumors

women in their 40's well-defined painless mobil masses