UWorld Questions

Triad of ascending cholangitis

jaundice, fever, RUQ pain

Explain the flow of calcium in cardiac muscle cell.

Intracellular calcium increases when VG L type calcium channels are opened and calcium flows into the cell. The ryanodine R is bound by calcium and also opens SR calcium channels to increase intracellular calcium by 100-fold. This calcium binds troponin C and kicks off tropomyosin so that actin and myosin can interact. Now that contraction has happened, we need to relax. So, the main way is Na/Ca2+ exchanger which sends out one calcium for taking in three sodium (high ECF gradient), this is the main method via the NCX channel. Another method, is SR Ca2+ ATPase SERCA which sends Ca2+ into the SR.

How much exocrine pancreas must be removed before a clinical problem develops?

>90%... it has a secretory reserve of glandualr tissue... Until they get malabsorption... Monosaccharides, however, need no enzyme to break them up in the small intestine... they enter epithelial cells of the small intestine via sodium-dependent cotransport or facilitated diffusion. D-xylose is a monosaccharide that is absorbed directly w/o pancreas enzymes and can bed to test brush border absorptive function. This can also decrease absorption if there is bacterial overgrowth of the small intestine.

Falciform Ligament

Attaches the Liver to the Anterior Body Wall... it is a derivative of the embryonic ventral mesentery and contains the round ligament.... Remnant of fetal umbilical vein

What are the syndromes for lacunar strokes?

1. Pure Motor Hemiparesis... posterior limb of internal capsule OR basal pons 2. Pure Sensory Stroke... Ventroposterolateral or Ventroposteromedial thalamus 3. Ataxia-Hemiplegia Syndrome... Posterior limb of internal capsule or basal pons 4. Dysarthria-Clumsy Hand Syndrome... Genu of internal capsule or basal pons... Small infarcts on CT ischemic may not be visible initially (<15mm)... After several weeks, cavitary spaces form.

What are the two pathways of purine synthesis? What do cells use more of?

1. Salvage Pathway 2. De Novo Synthesis Cells undergoing large/rapid amounts of proliferation/cell growth require de novo purine synthesis.

second most common CAHyperplasia, what makes things hypertensive

11 deoxycorticosterone pushes the hypokalemia and mild HTN weak MC In females, androgen excess --> ambiguous genitalia ~17 hydroxylase deficiency... boys undervirilized (ambiguous), girls normal genitalia. Hypertension and hypokalemia and no puberty!! ~5alpha reductase deficiency... girls normal, guys ambiguous genitalia ~21 hydroxylase deficiency... girls amibiguous and babies w/ hypotension/hyperkalemia

When do you vacc for MMR?

12-15 months ~Measles (rubeola) and German measles (rubella) both cause maculopapular rash on head and neck spread downward.

How do corticospinal fibers work??

1st oder located in premotor and motor cortex of frontal lobe (brodman 6 and 4)... Descend through internal capsule, midbrain and pons and continue to form the pyramids on the anterior aspect of the medulla. In the medulla, 90% decussate to form the lateral corticospinal tract... Those that don't decussate = anterior corticospinal tract.

Chron's Disease fistulas

2 adjacent loops of bowel = enteroenteric fistula... between a bowel and another organ (bladder or vagina) OR b/w bowel and skin of abdominal wall (enterocutaneous fistula) Even anus too, perianal fistulas It also forms abscesses

When does pH reach normal in situations of high altitude sickness?

2 days bicarb events pH out... will still have low O2 and CO2 from hyperventilation though.

Presentation of ankylosing spondylitis

2 month insidious onset of dull low back pain and morning stiffness. No trauma.. APAP and spinal manipulation don't help.. SLeeping on the side at night because pain. Limited anterior flexion of spine. Narrow sacroiliac joints.

Difference in presentation b/w 21 hydroxylase deficiency and aromatase deficiency

21 hydroxylase --> salt wasting hypotension in newborn.. amibiguous genitalia aromatase --> ambiguous genitalia and high androgen low estrogen in baby w/ maternal hirsutism/virilization. Affected newborn girls of aromatase will have normal internal genitalia and ambiguous/male type external. = clitoromegaly OR female pseudohermaphrodism. Men w/ aromatase def will have tall stature and osteoporosis but no genital abnormalities. (helps close bone plates and protect bones)

Post Op urinary retention

25% of patients after lower abdominal surgery. Normal post void residual volum eis <50ccs... Anesthesia and algesia cause over-distention of the bladder, decreased micturition reflex, decreased contractiliity of bladder detrussor muscle and incomplete emptying. tx w/ bethanechol

What is normal vocab for age 2?

50-200 words and 2-word phrases.. If less, could be an isolated language disorder... Language is the most common delayed milestone, 10-15% of age 2 kids. Most will catch up at preschool (prevalence falls to 5%)... Persistent deficits at risk for writing/reading/learning disorders in school. Could have a hearing exam as well and speech/language evaluation.

Patient with new high altitutude involvement, what happens to pH PaO2 and PaCO2 and plasma HCO3 after 2 days?

7.5 pH, 60 mmHg O2, 20 mmHg PaCO2, 15 plasma HCO3 Tissue hypoxia induced hyperventiilation drives down PaCO2n --> alkalosis Renal compensation takes 1-2 days.

What way does the pH go in patients w/ lactase deficiency, esp after gastroenteritis?

= lactose intolerance not lactase deficiency actually sir Most common cause is lactase nonpersistence (esp in Asian/Afircans) This however, if after infx, is secondary lactase deficiency --> acquired condition after bacterial overgrowth, infection, chron's) injury to brush border Incomplete hydrolysis means that lactose can be fermented by gut bacteria into short chain fatty acids (acetate, butyrate, propionate)... these acidfy the stool

What blood alcohol level is intoxicated and what is for motor impairment/blackout

>100mg/dL 0.1% then >200 0.2%

What can excessive alcohol consumption in someone who only drinks occasionally induce?

AFib (absent P waves, varying R-R intervals, narrow QRS), frbrillatory waves... Holiday Heart Syhndrome

What are the three most common cardiac anomalies seen in Down's?

ASD, VSD, Complete Atrioventricular Canal

If you have a gall stone ileus, what would you expect to find on imaging?

Air in the biliary tree = pneumobilia

Bone growth

As bone grows, osteoblasts near growth plates secrete matrix material, when they become trapped in the ossified material, they become osteocytes, that remain connected to each other by gap junctions, termed canaliculus.... Central Haversian canal w/ BV is encircled by multiple concentric lamellae of bony matrix that each contains lacunae filled w/ osteocytes and EC bone fluid. Delicate canaliculi radiate from each lacuna to create a reticular network w/ adjacent lacunae. These cytoplasmic processes send sigals to and exchange nutrients and waste products w/ osteocytes w/ neightboring lamellae via gap junctions Osteocytes maintain structure of mineralized miatrix and control short-term release and deposition of calcium. 1) plasma calcium concentratio main regulation 2) PTH and calcitonin indirectly regulate metabolic activity 3) sense mechanical stresses and send signal to modulate the activity of surface osteoblasts (helping to regulate bony remodeling

How to culture legionella?

BCYE is the name for buffered charcoal yeast extract agar w/ L-cysteine and iron. Oten gets into natural bodies of water, municipal water supplies and water-based cooling systems. Aerosols as well. Nosocomial from showers/baths, cooling towers, NG tubes, ventilators, nebulizers, respiratory therapy...

Which bone drug works through RANKL, how does Bisphosphonates work?

BPs attach to hydroxyapatite binding sites on bone surfaces and inhibit osteoclasts bone resoprtion also cause apoptosis and decrease precursors Denosumab binds RANKL and inhibits binding to RANK on OClasts reducing differentiation and survival of osteoclasts.

What organism has maltese cross signs?

Babesiosis... normocytic, normochromic anemia w/ ring and cross shaped intraerythrocytic inclusions.

What are the intracellular pathogens (bacteria, 10) (fungi, 2), (protozoa, 5)

Bacteria... chlamydia, francisella, legionella, listeria, mycobaterium, N gonorrhea, nocardia, rickettsia, salmonella typhi, yersinia pestis Cryptococcus neoformans Histo capsulatum Cryptosporidium pavum Leishmania Plasmodium Toxo Gondii Trypanosoma Need cell-mediated immunity to remove them.

What does protein A of S aureus do?

Binds Fc portion of IgG Lives on the cell wall

How to know if PCV or physiologic secondary polycythemia from plasma volume and RBC mass?

Both have high RBC mass, but plasma volume high in PCVera... PV is myeloproliferative disease of plurpotent hematopoeitic stem cells (95% of PV have V617F mutation of JAK2)... Replaces valine w/ Phe... more sensitive to growth factors like EPO and TPO... Elevated platelet count and WBC count as well, increased pruritis from histamine release of basophils... gouty arthritis from cell turnover all indicate... p/w ruddy face and splenomegaly... Dx is low EPO levels, BM aspirate w/ JAK2 mutation... Tx is serial phlebotomy.

Lead poisoning in children

Brain = Loss of milestones, cognitive impairment, behavioral problems, encephalopathy GI = constipation, abdominal pain, decreased VitD Renal = interstitial nephritis Heme = Anemia Dust/Paint in homes built < 1978... Lead binds to sulfhydryl groups on proteins, replaces calcium in calcium dependent cellular functions and inhibits enzymes in heme synthesis. Dx w/ blood lead levels... effects irreversible... Urine gamma-aminolevulinic acid is also elevated (heme synthesis substrate)

Most important prognostic factor for melanoma?

Breslow depth (dstaince from granular cell layer to the deepest melanoma cells). Early radial growth is low risk but the atypical deep growth of dense, atypical, nuclei clustered cells is scary. Usually deep depth lesions are palpable nodularity. ~Multinucleated giant melanocytes suggets lentigo maligna, common pigmented lesions in elderly melanoma in siut

How does estrogen increase myometrial excitability?

By upregulating connexin-43 and oxytocin R... connexin increases gap junctions oxytocin R mediate calcium transport by ligand-activated calcium channels.

Who is the culprit in achondroplasia?

Chondrocytes autosomal dominant mutation.. Exagerrated inhibition of chondrocyte proliferation. Macrocephaly, frontal bossing, rhizomelia (short limbs), trident hand, genu varum (bowing)

Epi affected by Pituitary???

Cortisol increases expression of Phenylethanolamine-N-methyltransferase (PNMT) in the adrenal medulla to increase epinephrine release.

Drug resistance to HAART at Pol gene...

Could be an increase in transcription of reverse transcriptase... can also get mutations that make RT resistant to drugs if asking about humoral response, that more has to do w/ env (gp41,120 glycoproteins)

What drugs cause drug-induced parkinsonism?

D2 R blockers of nitgrostriatal pathway -antipsychotics (1st gen > 2nd gen) -antiemetics/gastric motility agents (prochlorperazine/metoclopramide) p/w rigidity/bradykinesia, tremor (rest/postural), masked facies Tx = decrease offending drug or discontinue.. also trihexyphenidyl or benztropine.

Supracondylar fracture, what is injured???

DEPENDS If anterolateral humerus... radial nerve and radial artery If anteromedial... brachial artery and median nerve... all run anterior...

What is DiGeorge associated w/ in heart defects what about Down's?

DiG = Tet of Fallot, Truncus Arteriosus, Transposition of GA Down's = ostium primum, single AV valve, ASD and VSD. Single AV valve leads to AV valve regurgitation type auscultation findings and increased pulmonary venous return.

Dantrolene

Direct-acting skeletal muscle relaxant... (inhibits calcium ion release from sarcoplasmic reticulum of skeletal muscle) Cyproheptadine is used for serotonin syndrome... it is a serotonin receptor antagonist.

Drug Induced liver Injury

Due to inhaled anesthetics is common. Inhaled anesthetic heptatotoxicity is most frequently w/ halothane... Most common worlwide... In US no longer use it, instead enflurane, isoflurane, desflurane, sevoflurane. Hepatocellular pattern of liver injury... Mild ALTs to fulminant hepatitis. Causes atrophy to liver and shrunken on biopsy. Widespread centrilobular necrosis and inflammation of portal tracts. HSN reaction to the drug is the idea. Fever, anorexia, n, myalgias, arthralgias, rash... Tender HM w/ jaundice... Prolonged prothrombin and elevates ALTs, leukocytosis, eosinophilia. Factor 7 goes first. Albumin decrease is seen more chronically not w/ this condition. (half life is like 20 days)

What is eptifibatide, cilostazol?

E is a GP2b/3a inhibitor useful in patients w/ ACS but not stable CHD C is a phosphodiesterase inhibitor for symptomatic PVD.

Proteins involved in ECM...

E-cadherins keep adhesion for cell... Adhere to basement membrane w/ lamins Invade basement membrane as a tumor w/ proteolytic enzymes like protease, metallorproteinases, cathepsin D ~Carboxypeptidases cleave peptide bonds (synthesize propeptides to peptides) ~Acid hydrolases are functioning lysosomal enzymes at acidic pH.

Ethosuximide side effects:

EFGHIJ Ethosuximide Fatigue GI Symptoms Headache Itching Johnson-Syndrome (SJS)

What is a good initial assessment for GCA?

ESR or CRP!! actually get them About half patients w/ GCA have Polymyalgia Rheumatica... Ocular manifestations is like dimming vision, amaurosis, diplopia, blurry vision etc. These ESR and CRP are highly sensitive and almost always significantly elevated in GCA. Then get temporal artery biopsy.

How to test for supraspinatus muscle injury?

Empty can test ... abduction of humerus in parallel to axis of scapula w/ 30 degree forward flexion while in full internal rotation

SIBO affect on absorption

Enteric bacteria can produce vitamins (vitamin K and folate), inhibit proliferation of pathogenic bacteria and digest unabsorbed sugars/convert them to fatty acids. A roux-en-Y gastric bypass creates a small gastric pouch which is removed from the remained of the stomach and attached to the jejunum via a gastrojejunal anastmosis. Larger bypassed portion of stomach/duod are reattached to the jejunum distally. This creates a closed-ended GD limb in which bacteria can proliferate and ferment any food that may be diverted this way... p/w n/bloating, abd discomfort, malabsorption ~SIBO causes cobalamin deficiency, due to decreased intestinal absorption of IF-bound B12, iron def due to decreased absorption through intestinal mucosal injury from toxins/Bile acids, ADE malabsorption, zinc deficiency due to small intestine malabsorption

What bacteria has a relevant endotoxin?

Enterobacteriaceae has an endotoxin Lipid A (part of LPS membrane) released en masse w/ antibiotic therapy during gram negative sepsis... scary

What is another name for Churg Straus, finger involvement?

Eosinophilic granulomatosis w/ polyangitis late onset asthma, rhinosinusitis and eosinophilia --> kidneys GI or CV system... Often can get mononeuritis multiplex from perineural vasculitis. will have NP MPO (p-ANCA). Can get pulmonary infiltrates and sinus paranasal abnormalities.

What are some common coagulopathies?

Factor VIII deficiency results in Hemophilia A... just long aPTT Factor XI deficiency rare autosomal recessive hemophilia C. Really only matters after surgery/rauma. Long aPTT Hageman Factor Deficiency (Factor XII)... auto rec, no significance clinically even though long aPTT vWF carries factor VIII (protecting it from degradation) and mediator of platelet adhesion to endothelium)... it p/w long bleeding time w/ long to normal aPTT

What is the fastest to slowest rates of depolarization in heart

Fastest = Purkinje system, then atrial muscle, then ventricular muscle then AV node slowest... so lowest distance traveled/second AV = 0.05m/sec V m = 0.3 A m = 1.1 P = 2.2 m/s

What happens to the cervix in gonococcal cervicitis?

Friable cervix w/ easy bleeding (esp post coital)... Dx w/ Nucleic Acid Amplification Test Up to 20% of cases of PID are from tubal factor infertility due to permanent scarring from salpingitis.

What is usually found for NT at the splice sites?

GU at the 5' splice site AG at the 3' splice site.

What anti-glomerular basement membrane antibody causes renal failure?

Goodpasture's w/ crescent formation on light Micro

HIV positive dude w/ a single ulcerated lesion in rectum

HPV dude... anal squamous cellc arcinoma... Pain itching, rectal bleeding. Anal cancers are ulcerative in >50% of cases

Rheumatoid Arteritis

HSN vasculitis affecting arterioles and arteries of any size. Produces visceral infarctions after long-standing Rheum Arthritis.

Give kid sucrose, gets sick, has aldolase B def, what is the major worry?

HYPOGLYCEMIA... bc GNG is impaired form F1P accumulation.

How would vWB disease present differently from ITP?

ITP super low platelets, vWD would have normal platelets.

Where are leads placed on a biventricular pacemaker?

If 3 leads are used... first 2 are in the Ratrum and Rventricle... Third is for the LV... RA/RV go from left subclavian and SVC to chambers. However, LV lead is harder... Pass LV pacing lead from RAtrium into the coronary sinus which resides in the atrioventricular groove on the posterior aspect of the heart. It is then advanced into one of the lateral venous tributaries in order to optimize LV pacing.

What do fibrates do?

Increase LPL activity to hydrolyze TGs in CMs and VLDL and also decrease production of VLDL by liver... Fish oil also decreases VLDL production. and inhibits synthesis of apoB

How does obesity hypoventilation affect blood gases?

Increase in Co2 production from increased mass/surface area... decrease in O2 from hypoventilation

What does being outdoors do for vitamin D???

Increases conversion of 7-dehydrocholesterol to Vitamin D2 and vitamin D3 = ergocalciferol and cholecalciferol Provitamin D3 undergoes thermal isomerization by absorbing UVB rays

Sign seen in all cases of constrictive pericarditis

Kussmaul sign... Restriction of filling in RV capacity, backs up in JVD. Can also cause a pericardial knock (sharper more accentuate sound heart early early in diastole)

What channels open in myocardial Calcium action potential to drive calcium plataeu?

L type K+ efflux from cells drives the return to resting potential.

How do blood distributions play out for the heart?

LAD gives the anterior and left lateral surfaces blood... in 85% of people, RCA gives off posterior descending artery... Right dominant circulatory people! 10% it is the circumflex PDA supplies the posterior interventricular groove and posterior 1/3 of IV septum and MOST of the inferior wall of the LV Inferior surface of the heart is 2/3 left ventricle and 1/3 right ventricle (separated by groove) Right Marginal hits most of RVentricle

In afib where does the thromboembolus originate?

LAtrial Appendage.. small saclike structure in the LAtrium susceptible to thrombus formation... 90% of them are int hese LAA when nonvalvular AFib. Impaired ventricle think LV apical thrombus.

Langhans Cell versus Langerhans cell

Langhans cells = multinucleated giant cell w/ horseshoe-shaped arrangement of multiple nuclei derived from the monocytic cell line in granulomatous inflammation. Lanherhans is a DC in skin/mucous membranes. Langerhans take up antigen by constant endocytosis and pinocytosis, then present to T cell. They have racquet shaped intracytoplasmic granules.

What arteries are most affected in claudication??

Large artery atherosclerosis. Fixed atheromas of lipid-filled intimal plaques that bulge into the arterial lumen. Prevent increase in blood flow during exercise... Thigh cluadication of ipsilateral external iliac or common femoral or both Aortoiliac or internal iliac --> interal pudendal claudication --> ED

What is associated w/ AIDS lymphomas?

Latent EBV is present in upt to 90% ofnormal individuals, with reactivation during immunosuppression --> Burkitt and AIDS primary CNS lymphoma... Decrease in cytotoxic lymphocytes specific to EBV. Tx w/ antiretroviral therapy.

Layers passed lateral abdominal wall and anterior midline abdominal wall

Lateral... Skin, Camper Fascia (fat), External Oblique,Investing fascia, Internal Oblique, investing fascia, Transversus, investing fascia, Transversalis Fascia, Extraperitoneal Fat Anterior... skin, camper fascia, anterior abdominal apopneurosis, anterior abdominal muscles, transversalis fascia, extraperitoneal fat, baldder Get to bladder for obstruction devacuation in a suprapubic cystostomy.

Why is intussusception a problem?

Leads to impaired venous return from invaginated segment leading to ischemia and subsequent necrosis of the intestinal wall. Most typical is ileocecal junction. Most common in kids <2 years old. Often viral infection. >2 years old, often a Meckel Diverticulum, foreign body, tumor. P/W colicky, intermittent abdominal pain, n/v/, currant jelly stools.

How does C perfringens toxin work?

Lecithinase splits phospholipid molecules... Hydrolyzes lecithin containing lipoprotein complexes in cell membrnaes causing cell lysis, tissue necrosis and edema...

What things shift the O2-Hbg Dissociation Curve?

Left = Decreased H+, Decreased 2,3-BPG, decreased temperature... opposite for right.. and that is moving PO2(50) If you move max up or down think capacity... Anemia is severe causes lactic acidosis which means low pH and shift to the right.

Hemorragic cystitis after breast cancer chemo

Likely cyclophosphamide --> hemorrhagic cystitis... Caused by a nitrogen mustard-based chemo agent. Ifosfamide also an option These are metabolized by the kidney into acrolein, which is excreted from the urine... Acrolein is toxic to uroepithelial cells and can cause death/necrosis Prevent w/ hydration and coadministration of mesna (2-mercaptoethanesulfonate) binds and inactivated toxic metabolites..

What is the pathologically deadly component of Neisseria Meningitidis?

Lipo-Oligosaccharide (LOS)... LPS is found in gram neg enteric rods (different) These are both endotoxins that cause toxicity when released by shedding of outer membrane. Endotoxins bind TLR-4 on monocytic/dendritic cells --> IL1/IL6/TNFalpha release --> endothelial damage, capillary leakage, hemorrhagic necrosis

Grief vs. Depression

MDepressive =five of the following 9... -sleep disturbance, appetite change, low energy, psychomotor changes, low mood, anhedonia, guilt, focus/concentration difficulty, suicidal ideation -low mood or anhedonia must be present -duraiton >=2 weeks -social/occupational dysfunction -suicidality related to hopelessness/worthlessness Grief =normal -loss, emptiness, symptoms revolve around the deceased, functional decline but less evere, waves of greif at reminders. -worthlessness, self-loathing, guilt, suicidality less common -thoguhts of dying involve joining the deceased -intensity decreases with weeks-months -feelings of loss mixed w/ positive memories.

What makes up MHC class 1?

MHC class 1 protein consists of a single heavy chain and an associated beta2 microglobulin. They are highly polymorphic, allowing them to present a variety of antigens. After entering a cell, virus releases core proteins, some viral polypeptides are processed and combined w/ MHC1 at the RER, then exported to Golgi and eventually surface.

How do macrophages work in TB?

MPs travel to pulmonary lyjmph nodes where they present mycobacterial antigens to naive CD4 helper t cells and secrete IL-12 to differentiate them into Th1. Th1 migrate to sites of infection where they release IFN-gamma to activate macrophages. This improves ability to kill ingested mycobacteria and also allows them to produce TNF-alpha.

NMS symptoms

Malignant FEVER Myoglobinuria Fever Encephalopathy Unstable Vitals Increased Enzymes (CK) Muscle Rigidity

Which drugs work on the tyrosine DOPA pathway?

Metyrosine inhibits conversion to DOPA Reserpine inhibits adding NE to vesicles TCAs and Cocaine inhibit reuptake of NT by NET *Cocaine actually inhibits reuptake of Norepi, Dopamine and Serotonin... patients have HTN, tachycardia, agitation, but also light responsive mydriasis

Muscle glycogenolysis during contraction

Muscle contraction causes increased Calcium Epinephrine causes increased cAMP... along w/ glucagon and epinephrine in the liver causing increased cAMP... Both Ca/cAMP cause phosphorylase kinase to phosphorylate glycogen phosphorylase a... which converts glycogen to glucose-1-P AMP increases this conversion in muscle ATP and G6P decrease this conversion everywhere Overall synchronization of skeletal muscle contraction (increased Ca2+) and glycogen breakdown for energy provides energy for contraction

What is the point of lowest O2 content in the blood and the body?

NOT pulmonary artery, though it is last.. that is ~40 mmHg O2.. the coronary sinus is actually ~25mmHg... makes sense, because it is the highest demand from coronary veins... Coronary sinus actually feeds into the RA on its own, not part of IVC/SVC 1) LV is perfused only during diastole due to compression of blood vessels in sytole 2) extraction is super high... 60-75% of blood. 3) myocardial O2 demand and coronary blood flow are tightly coupled. There is little capacity to increase O2 extraction w/ exercise because it is already maxing out.

What is the difference b/w specificity and NPV?

NPV is the probability of not having a disease when the test is negative. Prevalence of a disease in a population may be used as an estimate for pretest probability of having the disease in patients who closely resemble the population. A patient w/ high pretest probability will have a low NPV w/ a negative test... whereas a patient with low pretest probability will ahve a high NPV w/ test. *Specificity/Sensitivity are intrinsic characteristics of a test, their values are fixed and do not vary w/ pretest probability. NPV better for patient centered questiosn

What are the three main cells involved in COPD?

NPs, MPs, CD8 T cells... These cells release enzymes and proteases such as neutrophil elastase that cause alveolar damage and reduce ciliary motion, increasing mucus secretion by goblet cells. Also these cells have declined ability to phagocytose -> contributing to higher infections.

How does colchicine stop gout flares?

Obviously microtubules polymerization is inhibited by binding tubulin protein. But, it specifically messes up chemotaxis, phagocytosis, and degranulation... Reduces LKT B4 as well. Adv Effects = nausea, abdominal pain, diarrhea. Don't use in elderly or severe renal dysfunction

What brain problem associated w/ Coarctation of Aorta?

Often happens w/ other congenital anomlies OR berry aneurysms of CoW...

How are pro-carcinogens metabolized in body?

P450 monooxygenase system in hepatic microsomes and ER of varied tissues.... CP450 metabolizes steroids, alcohols, toxins and other foreign substances --> soluble for excretion... ~Glutathione S transferase is involved in detox of some chemical carciniogens...

Patient presents w/ abdominal discomfort, weight loss, loose stools... You get an intestinal biopsy looking for a microorganism... which one should you check for with what stain that YOU will forget?

PAS stain for Tropheryma whippelii...An actinomycete.. PAS + and diastase resistant. PAS is good because the periodic acid oxidizes C-C bonds forming aldehydes that produce brilliant magenta color when reacting w/ fuchsin-sulfurous acid... PAS is good for polysaccharides of fungal cell wall, mucosubstances of epithelia and basement membrnaes... Diastase can be used in conjunction to see glycogen (skin, liver, parathyroid, cardiac muscle)... It basically digests glycogen to maltose and glucose (two sugars easily washed from sections during processing (giving a negative image).. abdominal discomfort, greasy stool, weight loss.. MP w/ PAS positive granules.. small intestine, joints, nervous system all involved... Proliferates only in MPs -> provokes no inflammatory response.. Has enlarged, foamy MPs packed w/ rod-shaped bacilli that is diastase-resistant... Often middle aged Caucasian males. p/w diarrhea, weight loss, arthropathy, polyarthritis, psych and cardiac abnormalities... antbx

What is upregulated in transformed glioblastoma?

PDGF

Where do beta blockers affect EKG?

PR interval... beta blockers slow AV nodal conduction (except sotalol which has class 3 properties, beta blockers do not have any effects on QRS/QT)

What tumors appear w/ psammoma bodies?

Papillary Thyroid Carcinoma, Mesothelioma, Papillary Serious Carcinoma of Ovary or Endometrium

Who is buproprion contraindicated for?

People w/ hx of seizures or current/prior diagnosis of bullemia or anorexia nervosa... Food restriction and excessive exercise suggest possibility of this.

Burning grass then come in w/ anticholinergic toxicity, what is the treatment?

Physostigmine!! probably from atropine/scopolamine in burned Jimson weed. (these are anticholinergic compounds) Pesticides on the other hand are organophophates aka cholinesterase inhibiors... Atropine is used to counteract these excess muscarinic effects also use pralidoxime for the paralysis due to nicotinic overactivation.

How does DiGeorge affect the lymph nodes?

Poor development of paracortex... Thymus is gonzo. Major deficiency in T lymphocytes. Predisposed to fungal, protozoan, intracellular bacterial pathogens

Timeline of ovulation

Primary OOcyte arrested in Prophase 1 of meiosis Secondary OOcyte arrested in Metaphase 2 of meiosis Approx 36 hours after LH levels rise, a secondary oocyte is released from the ovarian follicle. Secondary oocyte remains frozen in metaphase 2 until that fertilization. Until it completes to mature oocyte (ovum) and second polary body.

Patient w/ Chron's can be treated an alternative way

Pro and Anti inflammatory cytokines balance is essential for homeostasis... Over production of pro is Chron's. IL10 has antiinflammatory though and an increase in that could bring th einflammation down... IL10 and TGFbeta are both anti inflammatory. IL10 reduces production of TH1 and MHC 2 production...

What does a dilated coronary sinus indicate??

Probably pulmonary hypertension, because the flow backs up in the RAtrium. CS runs in the left atrioventricular groove on the posterior aspect of the heart and opens into the R atrium b/w the IVC and tricuspid valve.

What cell can't use ketones?

RBCs... no mitochondria

Panic Disorder

Recurrent & Unexpected Panic Attack w/ >=4 of these: -cx px, palpitations, SOB, choking -trembling, sweating, nausea, chills -dizziness, paresthesias -derealization, depersonalization -fear of losing control/dying Worry about attacks avoidance behavior Tx = benzos immediately (unless SADisorder Hx) also always SSRI/SNRI long term w/ cognitive behavior therapy

What is the main problem w/ MGravis at the neuron level?

Reduced amplitude of motor end plate potential, NOT reduce action potential amplitude. End plate potential never reaches threshold. Muscle is not depolarized. Synaptic concentrations of Ach are unaffected though. Look for fatiguability Decreased compound muscle action potential amplitude (summer action potentials of all muscle fibers in a motor unit) Decreases nujmbers of functional Ach R...

Treatments for PtSD

SSRI, SNRI, trauma-focused cognitive behavioral therapy and prazosin for nightmares. SSRI best.

What determines amount of shunting in T of F?

SVR: PVR ratio.. squatting increases SVR and increases pulmonary oxygenated blood flow

What stimulates creation of NO in the coronary endothelium?

Shear stress, Ach, bradykinin make Arg + O2 into NO + citrulline.. NO goes on to positively enhance guanylate cyclase for cGMP

What cardio drugs prolong QT interval?

Sotalol... aka Class1A and Class III digoxin actually shortens QT... Hypokalemia and Hypomagnesemia can also cause... Methadon, antipsychotics, some macrolides/FQs

Diagnosing fungi based on lab culture...

Sporothrix = 25 branching hyphae, round/cigar shaped budding yeast Coccidioides = hyphae at 25, 37 forms thick walled spherules filled w/ endospores Histo = 25, branchign hyphae... bx = oval yeast cells w/in macrophages Blasto = 25, branching hyphae... bx = large, round yeast w/ doubly refractile wall and single broad-based bud ParaC = 25, multiple blastoconidia, bx reveas cells covered in blastoconidia

How does Chron Disease change the wall?

Strictures = edema, fibrosis, then hypertrophy of muscularis mucosae which narrows lumen and can progress to obstruction Fistuals for communication Abscesses form when sinus tracts become walled off. Can perforate --> peritonitis.

What keeps the duodenum basic alkaline w/ secretions?

Submucosal Brenner Glands w/ alkaline mucus in duodenum and Epithelial cells of pancreatic ductules (high bicarb)

How would you describe bone of osteitis fibrosa cystica?

Superiosteal resorption w/ cystic degeneration Often involve cortical bone in the appendicular skeleton (pectoral girdle, pelvic girlde, limbs)... Subperiosteal thinning is characteristic... also get a salt and pepper skull w/ osteolytic cysts in long bones.

Why are arteriolar only relaxants not used alone?

They cause sympathetic compensation w/ RAAS, CO, HR and contractility leading to peripheral edema.

What is the time course for juvenile hemangiomas?

They first increase in size then regress. They are benign vascular tumors. Cutaneous strawberry -type capillary hemangioma. Unencapsulated aggregates of closely packed, thin walled capillaries. Common, 1/200 birhs. Can be multiple and on mucous membrnae,s subQ tissues. Can also occur in liver, spleen and kidneys. Lesions regress at or before puberty. Capillary usually at 1-3 years. 85% will regressed completely by age 7.

Patient on warfarin, falling down stairs due to knee buckling... Patellar reflex is diminished.

Think retroperitoneal hematoma on the psoas leading to weak quads and decreased sensation over anterior/medial thigh.

Patient w/ septic shock gets blood in the NG tube....

Think stress-related mucosal disease... acute gastric mucosal defects that develop in response to severe physiologic stress (shock, burns, sepsis, trauma, intracranial injury)... multiple small, 1cm circular lesions in the stomach ranging from superficial erosions to full thickness ulcers... That can perforate or bleed. Often due to impaired mucosal protection due to local ischemia... Caused by systemic hypotension and splanchnic vasoconstriction.. Proximal Duodenal Ulcers w/ severe trauma/burns = Curling Ulcers.. Esophagus, Stomach, Duodenum w/ intracranial injury are prone to perforation and are Cushing ulcers. Due to direct vagus nerve stimulation caused by elevated ICP, resulting in hypersecretion of gastric acid.

CAP pneumonia why the green sputum?

Tobacco incrases risk... NP myeloperoxidase is responsible for the green color of pus and sputum. It is a blue-green heme-based pigmented molcl contained w/in the azurophilic granules of NPs and catalyzes the production of hypochlorous acid from chloride and H2O2 during phagocytic respiratory burst.

What are patients at TPN at risk of?

Total Parenteral nutrition... gall stones!!! Normally enteral passage of fat and amino acids in the duodenum triggers release of CCK, leading to contraction of gall bladder. Absence of normal enteral stimulation leads to decreased CCK release and biliary stasis.

In patients w/ COPD long standing what drives respiration?

Usually have chronically high PaCO2 so the carotid receptors become tolerant to PaCO2 and oxygen is the main determinant of respiratory drive. Abnormal, because usually CO2 is the driver. When a patient has COPD they will have hypoxemia so will have chronically high RR, when administering O2, will see a big drop in RR Respiratory is in the medulla ~PaCO2 is the major stimulator of central R ~Peripheral mainly PaCO2 but also H+ and O2, but central more important for hypercapnia response ~Pulmonary stretch receptors include myelinated and unmyelinated C fibers in the lungs and airways... THese regulate duration of inspiration dependent on degree of lung distension = Hering-Breuer Reflex

When can minors provide their own consent?

Usually require parental consent for non-emergency medical treatment. I n most states, minors can consent to prenatal care, diagnosis and treatment fo STIs, contraception, drug/alcohol rehab, emergency care. These situations don't require parental consent. Emancipated minor = married, parent, homeless, financially independent, high school graduate, military 2/3 states require parental consent prior to abortion

Salmonella that causes typhoid fever

Usually travel to a foreign location. Week 1 = rising fever, bacteremia, relative bradycardia (pulse-temperature dissociation) Week2 = abdominal pain, rose spots on trunk/abdomen Week 3 = HSM, intestinal bleeding/perforation... Fecal-oral route. Enters via phagocytosis w/ M cells... Bacteria survive and prolifearte in Peyer's Patches... Affected patients are also risk for becoming chronic carriers, particularly those w/ cholelithiasis or other biliary tract abnormalities that allow S typhi to persist. NOT Salmonella Enteritidis

What anomalies often go w/ renal anomalies? in females

Uterine anomalies, development of paramesoN and mesoN ducts are linked... failed lateral fusion of PMN duct can result in various anomalies... Incomplete = bicornuate uterus... indentation in the center of the fundus!!! Complete lack of fusion is didelphys uterus (two) Failed involution of PMN duct --> longitudinal uterine septum. Patient w/ recurrent pregnancy loss screened w/ hysterosalpinogram (HSG) involves contrast injection through servix into uterus w/ pelvic xRAY... 2 unfused uterine horns w/ a central filling defect is bicornuate uterus or a longitudinal uterine septum... MRI distinguishes. Complete Agenesis of PMN duct = Mayer-Rokitansky-Kuster-Hauser Syndrome...

Septic arthritis test of choice?

WBC ct of synovial fluid, if >20,000-100,000) acute monoarticular arthritis w/ an effusion and decrease ROM... if a young male gonococcal... Can also gram stain/culture synovial fluid... Microscopy could exclude gout/pseudogout.

Gonorrhea reinfection???

WHen host produces antibodies against gonococcal pilli, mucosal adherence is inhibited. Structural genes for pilus then undergo antigenic variation at a high frequency; this recombination will yield new antigenic types of pili.

What antineutrophil cytoplasmic antibody is present w/ a vasculitis causing kidney disease?

Wegener's.. Renal involvement --> RPGN type 3... cough and hemoptysis w/ sinusitis/epistaxis. Crescents too

Where is somewhere weed a black eschar form B anthracis can present?

Your shoulder!! really anywhere on the skin... From exposure to animals. If cutaneous exposure to anthrax w/o occupational risk, suspect bioterrorism lol Growth of vegetative organisms w/in inoculation results in formation of edematous wound w/ central necrosis... B anthracis spreads via lymphatics to the bloodstream and multiplies in blood/tissue. Cutaneous anthrax more common than pulmonary. (5% of cases)

How would you describe the atypical lymphocyte in EBV?

abundant pale blue cytoplasm w/ a basophilic rim that is indented.

RCCs

account for 80-85% of primary renal tumors and arise from the renal cortex.. Often incidentally found on imaging.. Asymptomatic for awhile.. P/W hematuria, flank pain, abdominal mass, polycythemia... Hematuria is esp painless.

How does antioxidant use long term help things?

accumulation effect... >= 5 years statistically significant decreased stroke risk ~Rare disease assumption = diseases w/ low incidence rate in a population also have low prevalence... Odds ratio actually approximates RR when prevalence is low <10% ~Selection bias would be if one groups was also unhealthy and other was healthy, or attrition.

When would you use peroxidase staining?

acute leukemia differentiation and horseradish peroxidase is useful in immunoblotting.

Parotitis

acute viral or bacterial infection of the parotid gland.. most common is S aureus. RF = dehydration, intubation (elderly post op), meds that decrease saliva (anticholinergics), salivary flow obstruction (salivary calculi or neoplasm), recent teeth cleaning. Usually p/w firm erythematous post auricular swelling that extends to the mandible. Can get dysphagia, fever, chills as well. Confirmed w/ U/S or Ct P/W elevated amylase

Main cause of HCC in developing countries

aflatoxins contribute but main cause is HepB and HepC

Rodenticides affect on the body

aka arsenic... they contain brodifacoum (superwarfarin), a long acting 4-hydroxycoumarin derivative... By ingesting the rodenticide, this patient depleted her vitamin K dependent clotting factors, causing acquired coagulopathy... Leads to bleeding (GI hemorrhage w/ hematemesis) WIll get guaiac-positive stools and ecchymosis. 48 hours following ingestion Need to replenish coag factors so give FFP, all coa factors here also give vitamin K... If just abnormal coag tests but not bleeding, just give vitamin K ~Cryoprecipitate (FFP centrifugation/thawing) leads to factor VIII, factor XIII and vWF and fibrinogen... In warfarin overdose... vitamin K takes days, FFP effective revival but protamine ineffective In heparin overdose, vitamin K does not help, FFP is ineffective (actual harmful since has antithrombin III), protamine sulfate effective

What three cells make up the endocrine pancreas?

alpha glucagon cells, beta insulin cells, D somatostatin cells.

How do interferons alpha and beta affect neighboring cells?

alpha/beta bind type 1 interferon R on neighboring cells results in transcription of antiviral enzymes (halting protein synthesis) such as RNase L and protein kinase R (inactivates eIF-2 to stop translation initiation). Enzymes become active ONLY in presence of dsRNA... Selective inhibition once cells are infected.

What does phenylephrine do?

alpha1 agonist causes arterial vasoconstriction. Increase SVR and BP. Increase elicits and baroreceptor mediated increase in vagal tone, decreasing stroke volume and a slowed heart rate. Pulse pressure is decreased because of the reflexive decrease in SV and increased afterload

What two ways does spironolactone help mortality?

also eplerenone but regress myocardial fibrosis and improve ventricular remodeling. Don't use in patients w/ hyperkalemia or renal failure... often cause hyperkalemia/gynecomastia (more so spirono for second one)

Gingivitis, tibial subperiosteral hematoma, myopathy and dotted bumps on legs... in elderly...

ascorbic acid deficiency... Causes myalgias, subperiosteal hematoma, gingivitis and perifollicular hemorrhages... Scurvy Fruits and veggies mostly have it. Ptechial hemorrhages, hemarthrosis, impaired wound healing weakened immune system also possible Due to synthesis of collagen problems... need hydroxyproline, but can't form well.. Means lower strength collagen and defects in BV walls. Vitamin K deficiency is bleeding diathesis Zinc deficiency is acrodermatitis enteropathica, growth retardation, infertility. Linolenic acid deficinecy... fatty acid for AA... growth and neurovisual defects

What are the three short-acting insulins?

aspart, lispro, glulisine long acting = glargine/detemir Delayed onset of regular insulin is due to dimer/hexamer formation. Dimers/hexamers take time to disassociate after injection, causing absorption delay... Rapid-acting insulins were produced to overcome this. These monomeric insulins have improved postprandial life. Work with 15 minutes and peak at 45-75 minutes.

Low CSF 5-hydroxyindole-acetic acid

associated w/ impulsive, destructive behaviors, esp aggression and suicide and violence

Gaucher Disease

beta-glucocerebrosidase deficiency... glycolipid of leukocyte and erythrocyte membranes... Lipid-laden Mps (Gaucher cells) P/W bone pain due to bone marrow invasion/inflammation, abdominal distension due to HSM, easy bleeding, bruising, pallor, fatigue from pancytopenia.

How does nystatin work?

binds ergosterol, creating pores and leakage of fungal cell contents. Not absorbed in GI tract.

Where is alk phos found?

bone, liver, bile ducts, placenta elevated in biliary conditions, bone disease, leukemia/lymphoma

Features of FAD deficiency...

both made from riboflavin (B2).. sore throat, stomatitis, glossitis, normocytic anemia, seborrheic dermatitis

AV shunts affect on heart

byapsses arterioles (artery to vein directly)... arterioles are major source of resistance so decrease SVR... Congenital or aquired from dialysis/penetrating injuries)... Pulsatile mass w/ a thrill on palpation. Constant bruit Increase cardiac preload by increasing rate and volujme of blood flow back to the heart.. also decrease SVR. Decreased afterload.

Definition of Achylorhydria?

can't maintain normal gastric pH < 4. Higher risk for bacterial infection... Esp gastritis or long term ppi therapy can cause this. Vibrio grows on thiosulfate-citrate-bile salts-sucrose agar (TCBS)

Sudden loss of vision unilateral painless w/ cherry red macular spot

central retinal artery occlusion ~amaurosis fugax only lasts a few minutes ~Diabetic retinopathy is blurry vision, black spots, floaters, decreased peripheral vision... Acute vision loss if vitreous hemorrhage w/ neovascularization

Two drugs that cause muscle fiber atrophy

chronic corticosteroids or chloroquine

Vocal cords position when food irritates laynx and provokes cough...

closed while swallowing, closed after laryngeal irritation, open while coughing

What does matching patients w/ similar demographics in a study control for?

confounding variable!!

Symptom of lithium toxicity

confusion, agitation, ataxia, tremors/fasciculations Lithium excreted by kidneys, like sodium it is filtered and reabsorbed mostly in PTs... Any cause of decreased GFR (depletion, CHF, cirrhosis) can increase lithium retention... Thiazides limit sodium reabsorption in distal tubule leading to volume depletion.

What can cause pain when reaching over head and behind back .. left sided chest pain just under clavicle. near midline

costrochondritis worsens when you take a deep breath.. inflammation of the cartilage that connects rip to sternum. treat w/ physical therapy and NSAIDs difference from pleurisy because in pleursy the patient is SOB

How does hereditary orotic aciduria present?

de novo pyrimdine synthesis that results in physical and mental retardation... (low height/weight/DDelay), megaloblastic anemia, elevated urinary orotic acid levels... This last finding is also seen in ornithine transcarbamylase deficiency, but these patients have failure to thrive and hyperammonemic encephalopathy w/in the first few weeks of life (due to impaired urea synthesis) The main condition is due to a defect in UMP synthase, a polypeptide w/ 2 enzymatic domains (orotate phosphoribosyltransferase & OMP decarboxylase) that catalyze the final conversion of orotic acid to UMP... Impaired conversion of orotic acid to UJMP leads to large amounts of orotic acid in urine and features above... Uridine supplementation bypasses this enzymatic defect and improves symptoms... Uridine --> UJMP via nucleoside kinases.

What do amatoxins inhibit

death cap mushroom, mRNA synthesis. Absorbed by GI tract. Even 1 is life threatening. Enter liver via portal circulation by organic anion transporting polypeptide (OATP) and sodium taurocholate co transporter (NTCP) concentrates the toxin w/in the liver. Leads to apoptosis of liver cells... GI tract and proximal convoluted renal tubules also affected. Symptoms in 6-24 hours.. p/w abdominal pain, vomiting, severe cholera like diarrhea, blood and mucus. test for alpha-amantin

what drugs cause rta4?

decr aldosterone... 1) diabetic renal disease 2) ACEi/ARB 3) NSAIDs 4) Adrenal Insufficiency Aldosterol Resistance 1) Pot Sparing Diuretics 2) TMP/SMX

Severe asthma

decreased lung functions, symptoms during day, night, limiting activity, exacerbations needing oral steroids, frequent use of SABA. LABA and inhaled corticosteroids aren't doing the trick. Don't use LKT antagonists or theophylline not effective. SubQ omalimizumab. Recombinant humanized IgG1 antibody to bind IgE. inhibit action of IgE on mast/basophils.

Clinical picture of VHL

deletion of VHL tumor suppressor on 3p p/w cerebellar hemangioblastomas, clear cell RCC, pheochromos... RCC in 40% major cause of death ~c-MYC is oncogene on chromosome 8 for Burkitts and diffuse large B cell

How are CFTR channels handled in CF?

deltaF508s are generated but misfolded and failure of glycosylation so targeted for the proteasome, the few that make it to the membrane don't function Lumacaftor and Ivacaftor both help w/ the folding and function of this CFTR protein Both have been shown to improve forced expiratory volume and decrease rates of pulmonary exacerbations THE PROTEIN CREATED, FROM THE MOST COMMON MUTATION, DELTAF508, IS A 3 BASE PAIR DELETION OF PHENYLALANINE FROM 508 (70%)... LEADS TO IMPAIRED POST TRANSLATIONAL PROCESSING OF CFTR (BAD GLYCOSYLATION AND FOLDING), DETECTED AT THE ER --> DEGRADED... THE PROTEIN IS ACTUALLY FUNCTIONAL IN THIS SCENARIO^

Succinylcholine

depolarizing NM blocking agent like ACh that attaches to nAChR and depolarizes the NM end plate... Succinylcholine tho is not degraded by ACHEsterase leads to continuous end plate potential. Leads to flaccid paralysis (phase 1 block). Eventually, w/ continued administration of succinylcholine, the continuous depolarization of endplate gives way to gradual repolarization as the nAChR becomes desensitized to the effects of succylcholine... THis is phase 2 block... Sodiujm influx also leads to potassiujm release.. Exaggerated hyperkalemia and life threatening arrhythmias. Pathoogies that upregulate muscle nAChRs and or rhabdomyolysis which can result in release of large maoujnts of potassium when succinylcholine is administered. Vecuronium or Rocuronium are better for these patients and myopathies and quadriplegia and guillain barreR

How to treat warfarin skin necrosis?

discontinue warfarin, give FFP OR protein c concentrate

what are the non selective alpha 1 blockers

doxazosin, terazosin, prazosin.. can be used for tx of HTN and BPH

How does ionizing radiation induce cell death?

ds DNA breaks and free radical formation from ionization fo water. Most pronounced in rapidly dividing cells less able to repairdamage. Cell death curve is a flat line on initial exposure followed by a steep increase in cell death as radiation dose increases.

What is the sequence of genomes of HBV replication?

dsDNA -> positive sense RNA template --> ds DNA progeny via RT.

How does TORCH of hep b work?

during delivery is when most transmission occurs, but transplacental infection can also occur... Maternal viral load/HBeAg status are strongest risk factors for infant infection... Infants forn to HBeAg positive women have a >90% chance of infection... Viral replication rapid in infant due to immature immune system... Leads to high viral loads and HbeAg levels... Immune tolerant phase of chronic HBV infeciton in which they are asymptomatic and have normal LFTs. Over time, chronic newborns are at high risk of cirrhosis and HCC. 90% chance of progression to chronic HepB... HepB Vaccine and Immunoglobulin right after delivery can prevent chronic infection. Hepatic injury from HepB is cellular immune response not virus. Absence of both HBsAg and anti-HBs at 2 months indicate no infection.

Presentation of silica

dyspnea on exertion, nodular densities on XRAY, calcified hilar lymph nodes, birefringent particles on biopsy... Mineral dust inhalation... 10-20 years after intial exposure an dhave calcification of hilar lymph nodes (eggshell) Silica particles surrounded by fibrou stissue. ~Beryllium = noncaseating granulomas without obvious particles

Presentation of acute exacerbation of obstructive pulmonary disease?

dyspnea, tachypnea, prolonged expiration, b/l wheezing, pulsus paradoxus... need to give beta-2-adrenergic R Asthma could also be a cause... Asthma or COPD in pulsus paradoxus w/o pericardial disease Drop in intrathoracic pressure becomes greatly exaggerated and transmitted.

What type of remodeling does mitral regurge cause

eccentric w/ LV hypertrophy sarcomeres added in series (dilated) so does ischemic heart disease, dilated CMOP, aortic/mitral regurge, ASD (of RV tho) aortic stenosis/chronic HTN cause concentric w/ sarcomeres added in parrallel.

What is effect modification?

effect of an exposure on an outcome is modified by another variable. Identified w/ stratified analysis (analyzing the cohort as a subgroups)...Different measures of association can be brought to light. NOT CONFOUNDING strata tells the difference W/ Effect modification, different strata will have different measures of association. W/ counfounding, stratification usually reveals no significant difference b/w the strata.

Adenomyosis

endometrial glandular tissue in th emyometriu. Middle aged parous females common. Heavy menstrual bleeding due to an increased endometrial surface area and dysmenorrhea. Physical exam shows uniformly enlarged uterus. Results from hormonal stimulation of endometrial gland tissue in the myometrium. Normal finding for a woman in day 21 of her menstrual cycle. Glands are spread throughout, no just in one lesion area... Uniformly distributed.

What is the path of the radial nerve?

enters the forearm anterior to the lateral epicondyle and divides into the superficial and deep branches.. Superficial = somatic sensory innervation to radial half of dorsal hand and Deep Branch innervates extensor compartment muscles in the forearm after passing through the supinator canal (b/w superficial and deep parts of supinator muscle) Deep continues to wrist to become posterior interosseous nerve, which innervates muscles of finger and thumb extension. Repetitive pronation/supination can cause injury to the radial nerve in this canal (screwdriver motion)... typicall weak finger/thumb extension. Triceps and extensor carpi radialis longus typically unaffected. (these branches come off proximal to supinator canal)

Where is lecithinase (alpha toxin) a virluence factor?

enzyme w/ phospholipase C activity (C perfringens)... increases platelet aggregation and adherence expression on leukocytes and endothelial cells leading to vasoocclusion and ischemic necrosis.

Histo of SJS/TEN

epidermal necrosis and subepidermal bullae

What does cytokeratin stain for?

epithelial vimentin is mesenchymal (sarcomas) Chromogranin A and synaptophysin are neuroendocrine

PTSD clinical features and treatment

exposure to life-threatening trauma nightmares, flashbacks, intrusive memories avoidance of reminders, amnesia for event emotional detachment, negative mood, decreased interest in activities sleep disturbance, hypervigilance, irritability duration >= 1 month tx = trauma-focused CBT -antidepressants (SSRI/SNRIs) Prazosin for nightmares. ~Acute Stress Disorder if it is the same as PTSD but for 3days-1month ~Adjustment Disorder... stress can be of any type/severity and results in symptoms of anxiety/depression that don't meet criteria for another disorder ~Psychotic disorder vs flashbacks... in flashbacks patients feel as if the traumatic event is recurring but reality testing is intact.

How does I cell disease present?

failure to thrive, developmental delay, coarse facial features, corneal clouding, HSMegaly, restricted joint mobility... Leads to deficient phosphorylation of mannose residues on certain glycoproteins in the Golgi Inclusion Cell Disease is an autosomal recessive lysosomal storage disorder. I-cell disease occurs due to defects in protein targeting. For lysosomes... Golgi body phosphotransferase catalyzes the phosphorylation of mannose residues on these proteins. If defective phosphorylation enzyme, these proteins will be sent extracellularly and accumulate. Also means accumulation of debris in lysosomes.

How does adenovirus present?

fecal-oral, direct contact, or respiratory droplet transmission. P/w outbreaks often. Pharyngoconjunctival fever w/ acute fever, cough congestion, pharyngitis, conjunctivitis. Pneumonia in a small percentage.

Prostatitis presentation

fever, chills, dysuria, obstructive urinary tract, spontaneous discharge, pain. Prostate is nodular or boggy and tender to palpation.

IVH in a premie born before 32 weeks

germinal matrix, esp if birth weight <1500g... usually w/in the first 5 postnatal days. Bulging anterior fontanelle, hypoTN, decerebrate posturing, tonic-clonic seizures, irregular respirations, coma Highly cellular/vascularized layer in the subventricular zone from which neurons and glial cells migrate out during brain development. Numerous thin-walled vessels lacking glial fibers that support other blood vessels throughout the brain, which contributes to risk of hemorrhage. Impaired autoregulation of blood flow in infants. From 24-32 it becomes less prominent.

What on pap smear indicates inadequate sampling?

glandular endocervical cells (columnar cells w/ vacuolated and granular cytoplasm and prominent cell bords that form honeycomb pattern in clusters) ~Parabasal cells are round cells /w basophiilc cytoplasm finely granular chromatin in their nuclei and no visible nucleoli... high N/C ratio, dominant in post menopausla and postpartum women

What 2 things prevent C diff?

hand soap washing spores intact intestinal microbiome Antibiotic therapy is the most important risk factor beforehand... Cdiff can alter microbiome leading to potential overgrowth of pathogenic strains and clinical disease... very few anaerobes <10% actually invade intestinal microbiome. These suppress growth of Cdiff by competing for nutrients/adhesion sites w/ the gut.

Acute dystonia from EPS

happens after starting antipsychotics... usually 4 hours to 4 days later... Spasmodic torticollis is one example Oculogyric Crisis (forced, sustained elevation of the eyes) Opisthotonus (arching of back/head), Laryngospasm RF = young age, male sex, high potency first gen antipsychotic D2 antagonism of the nigrostriatal pathway... Inhibitor D2 are balanced by excitatory actions of muscarinic cholinergic neurons.. Strong dopaminergic blockade causes excess Ach resulting in EPS M1 R antagonist properties like benztropine or trihexyphenidyl or antihistamine like diphenydramine helps to re-establish balance.

Is botulism toxin heat stable or labile?

heat labile

What is GGT?

helps convert glutathione to glutamate, many places including the liver

Presentation of coagulopathy

hemarthroses, excessive bleeding w/ tooth extraction... coagulopathy = clotting factor deficiency generally p/w deep tissue bleeding into joints, muscles, subQ tissue. Platelet defects typically p/w mucocutaneous bleeding (epistaxis/petechiae)

What does haemophilus need to grow on agar?

hematin or NAD+ factor X or factor V... sheep blood agar does not allow Haemophilus to grow dur to insufficient nutrients and the V factor-inactivating enzymes in th emediujm Cross streak w/ s aureus though. H influenzae will grow around the streaks of beta hemolysis S aureus colonies because they secrete factor V into the medium and facilitate release of factor X during beta hemoloysis of erythrocytes. = Satellite Phenomenon

CKD what PTH and Ca you expect?

high PTH low Calcium

How does TEF present?

hours old child w/ feeding difficulties, failure to progress. Excessive drooling/coughing. Also when breastfeeding -> coughing, perioral cyanosis w/ O2 sat dropping. Prenatally can have polyhydramnios due to inability to swallow amniotic fluid... After birth --> choking, drooling, coughing, cyanosis w/ feeding (due to reflex aspiration)... Xray shows positioning of nasogastric tube in the esophageal atresic pouch after an attempt to reach to stomach... XRAY will show a sotmach bubble for airflow from tachea to distal esophagus pouch

How to decide what is causing HTN and hypokalemia

if high renin and high ald -renovascular HTN, malignant HTN, renin-secreting tumor, diuretics if low renin high ald -ald-tumor, B/L adrenal hyperplasia if low renin low ald -congenital adrenal hyperplasia, deoxycorticosterone producing adrenal tumor, Cushing's Syndrome, exogenous mineralocorticoids

How to know when something is ARDS not cardiogenic?

if pulmonary capillary wedge pressure is normal, then you know that it is noncardiogenic pulmonary edema

WHat is the scary long term complication of DKA?

if severe PaCO2 persists above the expected copmensated range, then pulmonary edema, respiratory fatigue, decreased mental status may lead to hypoventilation and hypercarbi respiratory failure

signs of social anxiety?

ill during interview, avoid eye contact, breif resposnes, anxious = blushing, sweating, trembling, tachycardia.. Specifier performance only is given to patients who only have performacne situation anxietyl

What type of vaccine is used for post exposure ppx in rabies?

inactivated vaccine also want to give rabies immune globulin. These vaccines are grown in a culture and inactvated by beta-propionolactone p/w hydrophobia, aerophobia, painful sapsms, progressive paralysis, coma, agitation, dysphagia, insomnia, headaches... patients die

Positively skewed...

increased # of observations w/ larger than expected magnitudes (extreme) that shift toward the right produces a longer slope of the curve tail, same opposite for neg Mean > Median > Mode for positive

Initially after smoking, will get...

increased mucus production/secretion, decreased activity of airway cilia, decreased alveolar macrophage function

Acute Decompensated HF, what is causing the symptoms of overload/cx px/SOB?

increased sympathetic NS activity BNP is not, it is helping, HF occurs when structural or functional cardiac disorder impairs ventricular filling/ejection reducing CO and leads to excessive ventricular filling pressures. Sympathetics --> stimulates RAAS --> ADH --> improve CO by increasing chronotropy and inotropy. 1) increased afterload from excessive vasoconstriction leads to fluid renetion/poor renal perfusion 2) high RAAS fluid retention leads toperipheral edema/pulmonary congestion (causes symptoms of circulatory overload) 3) bad cardiac remodeling occurs due secondary to hemodynamic stress, perpetuating a downward spiral of progressive cardiac dysfx.

Hf w/ increased endo diastolic and systolic pressures

indicates that diastolic failure is the problem, so look for conditions that reduce LV compliance Restrictive CMOPs do this (amyloidosis, sarcoidosis, hemochromatosis)... Transthyretin is a tetramer produced inthe liver and acts as a carrier of thyroxine and retinol... Mutations can lead to misfolding and amyloid protein that infiltrates the myocardium.

How do statins affect gall stones?

inhibit rate limiting step of cholesterol synthesis... less cholesterol, less risk of gall stones.

MOA of isoniazid

inhibits synthesis of mycolic acids

In patient w/ alcohol withdrawal, treatment?

insomnia, anxiety, tremulousness, autonomic hyperactivity... seizures w/in 12-48 hours and delirium tremens (48-96)... benzos first line. (diazepam or chlordiazepoxide are best because long acting) and they are self tapering. In patients w/ liver disease, use those that don't undergo oxidative metabolism in liver = Lorazepam, Oxazepam, Temazepam (LOT)

How does laryngomalacia present?

inspiratory stridor due to collapse of supraglottic structures during inspiration. Stridor is worse int he supine position and improves w/ upright positioning.

When suspect child abuse what is the next step?

interview child alone... if parents say no --> abuse If yes, ask open ended questions then move into suspected abuse... look for genital trauma, pathognomonic injuries, injuries of different stages of healing, bony tenderness, signs of swlling, unwillingness to use an extremity, skin lesions, retinal hemorrhages.

Which type of bond is irreversible and which is reversible for competitive antagnoists?

ionic is reversible, covalent is irreversible noncomp agonists change binding site by binding somewhere else and prevent agonist binding. ... comp antagonists shift Km higher but no effect on Vmax.. need higher doses to achieve same effect as before.

Patient w/ PUD has ruptured ulcer, gets gastrectomy.. what do you need to supplement moving forward?

iron, because acid needed and iron absorption occurs int he duodenum and proximal jejunum... Also give B12, folate, ADEK, calcium

Dexrazoxane...

iron-chelating agent, helps prevent anthracycline-induced cardiotoxicity (doxorubicin)

Afer 12-18 hours how do many small molecules feed into GNG?

lactate/alanine/glucogenic amino acids --> pyruvate... Glutamien and other glucogenic AA --> TCA cycle Overall shut to malate to get out of the Mitochondria, then malate to OAA then to PEP. Other unique enzymes to GNG are G6 Phosphatase bypasses hexokinase and also F16BPase (FBPase1) which bypasses PFK1

Where in thalamus does vision go?

lateral geniculate body... nasal vision of one eye goes ipsi temporal vision contral

Motor and sensory problems on one side w/ facial paralysis problems on that same side sparing forehead and mild dysarthria

mCA stroke

What cell is in fatty streaks?

macrophages

Types of dystonias

may affect a single muscle, a group of muscles or the entire body. Cervical dystonia = spasmodic torticollis. Blepharospasm is the second most common. Involuntary closure of the eyelids. Presents initially as uncontrollable blinking that eventually becomes complete closure of eyelids. Writer's cramp is a form that can affect the muscles of the hand. ~hiccups and hypnic jerks (when falling asleep) are myoclonus

West Nile Virus infection...

meningitis, encephalitis, acute asymmetric flaccid paralysis... fever, rash headache, maculopapular rash. Passed by Culex mosquitos in summer/fall, esp warm climates Often if the patient has concurrent parkinsonian features as well that helps diagnosis.

Edwards p/w

micrognathia, low set ears, prominent occiput, heart defects, clenched hands w/ overlapping fingers, limited hip abduction, renal defects, rocker-bottom feet. Increases w/ maternal age >= 35.

How do antipsychotics cause dystonia?

motor neuron hyperactivity. Persistent myocyte stimulation causes a substance to be released from SR. Calcium binds to Troponin C. Ryanodine R is the channel that releases Ca2+ from SR. Ca2+-ATPase pump takes Ca2+ back up. In resting, tropomyosin covers myosin binding sites on actin filaments. Binding of Ca2+ to troponin C causes conformational change and pushes tropomyosin off of the myosin binding sites of actin. Myosin is the thick filaments.

What types of viruses need different machinery to replicate inside of a host cell?

negative sense RNA viruses need RNA dep RNA polymerase ds RNA need specific viral RNA polymerase in their virion Only the ss RNA positive sense can replicate just based off of the host's proteins

Presentation of cystathione beta synthease deficiency

new swelling in right leg, hx of lens dislocation and intellectual disability... DVT in one leg and caved-in appearance of chest wall.

RBC w/ spherocytosis...

no central pallor, and high MCHC... ankyrin, band 3 or spectrin protein mutations... or acquired from autoimmune hemolytic anemia.

What do you see in stool sample of a noninflammatory, watery diarrhea

no fecal leukocytes, no red cells, mucus w/ sloughed epithelial cells w/ dysentery or inflammatory diarrhea... see PMNs w/ or w/o red cells w/ enteric fever.. penetration and dissemination basically only salmonella typhi... see mononuclear leukocytes

Main side effect of ethambutol

optic neuropathy

When you have a patient on exogenous corticosteroids and they run into an acute adrenal insufficiency.. use a higher stress dose of corticosteroids to jumpstart them.

or you'll get hypotension/shock

Presentation of hyperacute rejection

organ becomes cyanotic and mottled right after anastomosis of donor and recipient blood vessles. Perfusion ceases immediately. Ischemic necrosis of glomeruli and renal cortex --> little/no urine. This is antibody mediated TYpe2HSN> Preformed IgG are the culprit. usually anti-ABO or anti-HLA antibodies.

What medications are associated w/ Raynaud's phenomenon?

p/w cold extremities amphetamines, ergotamine, chemo agents

Presentation of hydronephrosis

pain, lower extremity edema, palpable kidneys or bladder.

Pregnant woman comes down w/ knee and foot pain then aborts child....She works as an elementary school teacher

parvovirus... especially because it had hydrops fetalis.. aka fetal HF... so pleural effusions, ascites, pulmonary hypoplasia.

Diagnosis of tetanus

patient hx and physical Get immunization status. Boost every 10 years. There is no toxin assay

What does S viridans look like in IE presentation?

patient w/ MV prolapse, goes into dental procedure, then has gram pos bacteria that synthesis dextrans from sucrose... adheres to fibrin and platelets.

What does mx bx of dermatomyositis show?

perimysial infiltrates, perifascicular atrophy, patchy necrosis Can be caused by many underlying cancers.

Juvenile Myoclonic Epilepsy

periodic, sudden-onset, jerking mvmts of both arms.. Early in morning, soon after waking and aggravated by sleep deprivation. Idiopathic generazlied epilepsy that may be familial. No LOC. Can develop Gen TC or Absence Seizures.

antibodies in Poly/dermatomyositis

poly => anti-Jo-1 is anti histidyl tRNA synthetase... ANA, Muscle enzymes... endomyseal is polymyositis`

Collagenous colitis

presents w/ frequent diarrhea in older women (supepithelial collagen band thickening) ~acute appendicits = dense infiltrate/NP/necrosis ~Pseudomemranosu colitis = mucopurulent exudates of fibrin/bacteria/NPs

Type 1 osteogensis imperfecta

problem w/ osteoid genesis by osteoblasts.

Examples of passive aggressiveness....

procrastination, forgetfulness, purposeful inefficiency, sarcasm, denial of being angry while showing angry-passive behavior.

Presentation of HTN encephalopathy

progressive HA, n, v with nonfocal neurologic symptoms (confusion)

Histology of choriocarcinoma

proliferation of cytotrophoblasts and syncytiotrophoblasts can spread to lungs and cause alveolar hemorrhage/B/L infiltate, along w/ sustained uterine bleeding.

How do PBC and PSC usually present?

prolonged pruritis and fatigue... Eventually acholic stools and malabsorption of ADEK...

Non-lactose fermenting gram negative rod for UTI

pseudomonas, esp in catheter patients Enterobacter = Lactose-Fermenting, GNR Enterococcus Faecalis = Gram positive.

Scaphoid fracture

risk of avascular necrosis... because necrosis of proximal pole of scaphoid... These fx from falls on outstretched hand w/ wrist hyperextension... Anatomical snuffbox pain. Blood to the proximal pole proceeds ina retrograde manner and can be easily interrupted by a fracture. Leads to avascular necrosis and nonunion.

Menetrier Disease histo

rugal hypertrophy in stomach w/ parietal cell atrophy and decreased acid secretion

What do you use to examine the different vaginal pathologies?

saline microscopy aka wet mount... in Trichomonas will get an elevated pH.. NOT KOH that is for the whiff test of bacterial vaginosis.

Differences b/w primary ciliary dyskinesia and CF

same presentation dynein arm defect vs CFTR gene Situses inversus and infertility due to immotile spermatozoa, also normal growth versus pancreatic insuff, infertility due to absent vas deferens, failure to thrive. PDK can be dx w/ low nasal nitric oxide levels

Tooth bleeding primary or secondary sign...

secondary sign.. coag factor pathway also intramuscular hemorrhage, hemarthrosis, long bleeding time post surgery.

Healthy bone marrow

should be 1:1 of fat and hematopoietic elements. Most cases of Aplastic Anemia are aquired from direct toxic insult OR T-cell response leading to apoptosis of pluripotent stem cells. Drug exposures (benzene/chemo), carbamazepine, viral infections NO SPLENOMEGALY ~Fanconi Anemia is an inherited cause of AA that p/w short stature and absent thumbs and associated w/ increased risk of myelodysplastic syndromes/AML ~Myelodysplastic SYndrome is a defect in stem cell maturation that leads to ineffective differentiation of cell lines and pancytopenia. BM would be hypercellular w/ abnormally differentiated cells.

Sedentary smoker w/ diabetes and bad diet, what is best for reducing mortality?

smoking cessation #1 aspiring therapy #2 smoking w/ diabetes --> higher risk MI, hyperChol, poor glycemic control, ESrD. Smoking also increases chance of developing diabetes

Describe the murmur of hypertrophic cardiomyopathy

soft crescendo-decrescendo systolic murmur at the apex and left sternal border while supine that is more pronounced when standing up. Left ventricular outflow obstruction that worsens w/ decreased LV volume so don't use nitrates. Don't use any vasodilators (DHP CCBs, Nitros, ACE inhibitors) (decreased afterload means lower LV volumes) Don't use diuretics Use instead, negative inotropic agents (beta blockers) nonDHP ccbs, disopyramide.

Features of drug seeking

specific med request by name, running out of meds, pain out of proportion to physical exam... Lost or stolen meds from other providers as well. Determine first what the patient is currently on with a prescription record.

Subclavian Steal Syndrome

stenosis of subclavian proximal to origin of vertebral artery, causes retrograde flow of vertebral artery ipsilateral... Atherosclerosis causes this, also Takayasu arteritis and complications from heart surgery. Most are asymptomatic, when symptoms occur = arm ischemia in affected extremity or vertebrobasilar insufficiency (dizziness, diplopia, drop attacks) difference in >15mmHg of systolic pressure between arms is indicative. Doppler U/S for diagnosis *on opposite side, it would be brachiocephalic artery stenosis to cause this same syndrome. ~Coronary-Subclavian Steal syndrome occurs in patients w/ prior coronary artery bypass using internal mammary artery (IMA). Similarly, blood flow to IMA can reverse and steal flow from coronary ciculation durign increased upper extremity demand. p/w coronary ischemia

4 main types of intracellular receptors?

steroid, transcription factor R, thyroid hormone, fat soluble vitamin R

What drives pain in peripheral neuropathy? in sjogren's syndrome

substance P

Absence seizures

sudden impairment in consciousness, preserved muscle ton, unresponsive, short duration <20s, simple automatisms, easily provoked by hyperventilation Dx = EEG w/ 3Hz spike-wave discharge

Solar Lentigines

sun exposed areas... ephelides are caused by increased melanin production by melanocytes, whereas solar lentigo is caused by increased proliferation of melanocytes themselves. Both are hyperpigmented and flat, although solar lentigines are often larger and occur in adults.

What does exogenous T3 do to TSH

suppress rapidly

Active TB vs. Latent TB

symptoms, along w/ positive cultures of blood sputum means active T lymphocytes are the cells that secrete IFN gamma

How does Pheo stain?

synaptophysin, chromogranin, neuron specific enolase (granules w/ catecholamines) Highly vascular tumor w/ spindle-shaped/polygonal cells. intermittent 5 Ps symptoms

A-a gradient diseases affect on CO2

the hypoxemia etc. would impair alveolar ventilation --> increasing PaCO2 and decreasing PaO2 even w/ hyperventilation. PaO2 of 54 w/ PaCO2 of 26 ==> alveolar hyperventilation

Coccidioides on microscopy

thick walled spherules w/ packed endospores.

How does smoking mess w/ alpha1 antitrypsin?

through oxidation of a crucial methionine residue... AAT smokers get dyspnea at age 36 vs 51 as nonsmokers. It is panacinar and they also get liver cirrhosis.

What is the test for celiac disease?

tissue Transglutaminase... p/w diarrhea, weight loss, abdominal pain. maybe maybe maybe p/w constipation.

what is another name for tissue thromboplastin?

tissue factor... will see in DIC post fetal demise, if patient bleeding from gums, vagina, IV sites, catheter An abruption that leads to fetal demise is the most common cause of DIC in pregnancy

What type of proteins are made by HOX genes?

transcription factors.

EBV effect on B cells... leads to

transformation or immortalization... EBV-encoded oncogenes activate proliferative and anti-apoptotic pathways within the cell... Can still secrete immunoglobulins. Detect heterophile IgM antibodies to daignose... These react w/ sheep or horse erythrocytes.. sheep = paun bunnell... Highly specific 100%

What two factors predispose to testicular torsion?

trauma or a congenitally-horizontal positioning of the testes (bell clapper deformity)

What is serotonin made from AA wise

tryptophan

Calcium regulation

two hormones play a big role PTH = minute-to-minute concentrations Calcitriol = over longer term PTH from chief cells 1) increases bone resorption (Ca/P) 2) renal Ca reabsorption (reduces P reabsorption) 3) increased formation of 1,25-dihydroxycholecalciferol (upregulating 1alpha hydroxylase) increases intestinal calcium/phosphate absorption Symptomatic hypoparathyroidism = muscle cramps, paresthesias in fingers and lips, muscle strength and DTRs nromal but twitching of lower facial muscles on percussion of zygomatic arch.

Presentation of Crigler Najjar

type 1 is an autosomal recessive disorder of bilirubin metabolism caused by genetic lack of UGT enyme needed to catalyze bile glucuronidation When not correctly processed by liver, unconjugated hyperbilirubinemia develops... 20-25 in infants but can rise to even 50 Binds tightly to albumin. Cannot be filtered by glomerulus and is not excreted in the urine. Instead, the UnconjBili is gradually deposited into various tissues, including the brain. Leading to kernicterus p/w lethargy, muscle ridigidity, seizures

Patient w/ hypotension, fever, bloody diarrhea and tachycardia w/ untreated ulcerative colitis

worry about toxic megacolon.. need a KUB in the ER... Transmural inflammation causes release of inflammatory mediators, bacterial products, NO, cause colonic smooth muscle paralysis... Rapid colonic distension thins wall an makes it likely to perforate. Free air can be seen in the setting of rupture (abdominal guarding/rebound tenderness

In renal hypersensitivity interstitial nephritis

you will have eosinophilia in the tubules/urine, but will also have peripherally Also will be exposure to an offending drug.

Most common causes of SCID

#1 x-linked #2 adeonsine deaminase deficiency... adenosine accumulating is toxic to both T and B lymphocytes. Tx is BMTransplant, retroviral attempts have been promising though. Infect hematopoietic stem cells w/ genetic code for adenosine deaminase resulting in production of this enzyme by all daughter cells of that stem cell

What are the two functions of the spleen?

1) Destroy aged and abnormal erythrocytes and serve as the emergency storage of blood cells and platelets that can be delivered into the circulation when needed. 2) Clear circulating bacteria that become lodged in the cords. Esp in white pulp initiating active immune response. Half of body's total immunoglobulins are produced by the splenic B lymphocytes. ~Liver is primary source of complement production.

Most important two factors in treating hypovolemic shock?

1) Eliminating source of bleeding 2) Rapid infusion of blood products and crystalloid solutions (normal saline)... Intravascular volume and ventricular preload can icnrease. This preload stretches the myocardium (increases end-diastolic sarcomere length, leading to increase in SV and CO) (FrankStarling)

What is the life cycle of Strongyloides Stercoralis?

1) Filariform Larva penetrate skin and migrate to lungs 2) Filaform larva enter alveoli and travel to pharynx where they are swallowed and carried to small intestine 3) molt into adults that lay eggs w/in the intestinal mucosa 4) Eggs hatch into noninfectious rhabditiform larvae excreted into the stool (diagnosis) 5) rhaditiform larve in large intestine molt into filariform larva that reinfect the host by burrowing into alveoli 6) rhabditiform larva form adults that reproduce and lay eggs that hatch into more rhabditiform larva 7) non-infective rhabditiform larve molt into infectious filariform larva that can infect new people when leaving stool is stepped on

Ischemia-reperfusion induced damage occurs through 3 mechanisms?

1) oxygen free radical generation by parenchymal cells, endothelial cells, leukocytes 2) severe irreversible mitochondrial damage (permeability) 3) inflammation, attracts circulating neutrophils that cause injury 4) activation of complement CK leakes from brain, sk muscle and heart ~glutathione peroxidase actually protects from free radical injury ~mitochondrial vacuolization reduces cellular capacity for ATP generation associated w/ irreversible injury. CK not release from this though. ~Nuclear shrinkage, fragmentation, dissolution --> irreversible.

What are two enzymes fibrates change?

1) primary goal... they upregulate lipoprotein lipase leading to increased oxidation of fatty acids! yayy!! However, 2) Inhibit cholesterol 7-alpha hydroxylase --> rate limiting step of bile acid synthesis --> leads to gall stones.

3 ways to manage cyanide toxicity

1) sodium nitrite = methemoglboin formation, combines w/ cyanide to form cyanomethemoglobin 2) sodium thiosulfate = sulfur donor to promote hepatic rhodanese-mediated conversion of cyanide to thiocyanate, excreted in urine 3) hydroxocobalamin = cobalt moiety binds cyanide ions and forms cyanocobalamin, excreted in urine. Cyanide is a potent mitochondrial toxin that binds Fe3+ in cytochrome c oxidase inhibitng ETC leads to lactic acidosis and bright red venous blood,along w/ AMS, seizures, CV collapse. More likely in higher, longer doses w/ bad renal system.

Rib cage anatomy

1-7 true ribs 8-12 false costal cartilages connect ribs to sternum Top of sternum is jugular notch, then manubrium, then angle ridge, then body and xiphoid process at bottom.. ribs 11-12 floating (not connected to costal cartilages/sternum) Injury at right 8-11, likely liver injury, if either side rib 12, likely kidney if left 8-10 think spleen.

Causes of renal artery stenosis?

#1 is 70% patients have atheromatous obstruction at original of the renal artery. More in males and patients w/ DM. Ischemic kidney leads to rise in renin --> HTN... Stenosis may also cause renal atrophy due to oxygen/nutrient deprivation... Atrophic kidney will show crowded glomeruli, tubulointerstitial atrophy/fibrosis and focal inflammation. Congenital Renal Hypoplasia = failure of kidneys to develop to normal size... Involvement is usually unilateral. Don't usually cause secondary HTN

Autism DSM-5

-Multiple persistent deficits in social communication & interactions currently or by history involving = social-emotional reciprocity, nonverbal communication, developing OR maintaining OR understanding relationships -Restricted, repetitive patterns of behavior currently or by history = repetitive motor mvmts, insistence on sameness/inflexibility, fixated intrerests of abnormal intensity or focus, adverse responses to sensory input -early developmental period and cause impairment -not better explained by intellectual disability. More common in boys, usually age 2. ~Selective mutism is failure to speak in specific situations (like school) despite speaking elsewhere.

If gene A is frequency of 0.2 in a population and gene B is 0.3.. what is the expected frequency if there is no linkage disequilibrium?

0.3*0.2 for haplotypes w poth p*q... so 0.06.. but if the observed frequency of them together is 0.2... due to linkage disequilibrium because of the close proximity of the two genes.

Test is correct for 95% of disease negative patients... what is probability that in 8 patients without disease confirmed will be negative? what about one positive and 7 negatives what about 8 positives?

0.95^8 1-0.95^8 0.05^8 Must add to zero 1-0.05^8 is probability of at least one sample being negative

What is power?

1 - beta... not eta... beta is the probability of committing a type 2error. When researchers fail to reject a null hypothesis when it is truly false.

MEN1 vs 2A vs. 2B

1 = primary HPTH, pituitary tumors, pancreatic tumors 2A = medullary thyroid cancer, pheo, parathyoid hyperplasia 2B = medullary thyroid cancer, pheo, mucosal neuromas/marfanoid habitus

Goals of current AlzD therapies?

1) Enhanced cholinergic NT 2) neuroprotection via antioxidants..alpha tocopherol (vitamin E) 3) NMDA R Antagonsim... Memantine

Wound Healing

1) Inflammatory... fibrin clot of hemostasis.. Cytokines from activates platelets and damaged cells -> NP 1 day and MP 2-3 days 2) Proliferative... 3-5 days fibroblasts and endothelial vascular cells proliferate to form connective tissue and blood vessels... Around this time, epithelial cells proliferate at dermal edges and secrete BM material 3) Maturation phase... Scar formation... second week after injury.. Active fibroblasts secrete collagen, elastin, CT matrix TGFBeta and PDGF are big for 3rd phase. TGFBeta usually decreases at the end of healing to limit collagenous scar tissue... Hypertrophic or disfugirng scars may be caused by persistently elevated TGFbeta... leading to fibroblasts overactivation and proliferation. or duet o increased TGFbeta receptorexpression.

What is seen in DMD?

1) ambulation difficulties = clumsy, slow, waddling 2) Gower sign = progressive weakness and use of hands to support/stand 3) calf pseudohypertrophy = calf muscles hypertrophy initially in response to proximal muscle weakness and are later replaced by fat/connective tissue 4) Asymmetric weakening of the paraspinal muscles --> kyphoscoliosis Wheelchair bound by age 12

Chronic angina pectoris

1) deep poorly localized chest/arm discomfort 2) reproducability w/ physical exertion/emotional stress 3) relieved w/in 5 minutes of rest or nitro >75% of CSA

Requirements for hospice....

1) focus on quality not cure 2) symptoms control (esp pain/depression) 3) interdisciplinary team (spiritual, bereavements as well as medical/nursing) 4) services provided at home, assisted living, dedicated facility 5) prognosis of <=6 months

What 5 steps to prevent central catheter infections

1) hand hygeine sanitizer or soap/water 2) barrier precautions (mask/gown/sheet) 3) chlorhexidine antiseptic at site before 4) subclavian/IVJ 5) removal when no longer needed

Where is NADPH used in the cells?

1) high oxidative stress (RBCs) regenerates glutathione 2) Organs like liver/adrenal for reductive biosynthesis of cholesterol, fatty acid, steroids and cytochrome P450 metabolism 3) Phagocytic cells w/ a respiratory burst via NADPH oxidase

EMTALA requirements

1) hospitals provide medical exam screening to anyone who comes in ED 2) if individual has emergency condition, must treat and stabilize 3) must not transfer individual until stabilized

4 options for omphalomesenteric duct (vitelline)

1)persistent vitelline duct (fisutal b/w body and ileum) meconium discharge at birth 2) Meckel Diverticulum.. 3) vitelline sinus (partial closure, patent open at umbilicus 4) Vitelline duct cyst... peripheral portion of vitelline duct obliterates, central part remains.

Criteria for premature ejaculation...

1-2% of men... <1 minute of penetration most of the time for >6 month

What are the two components of deoxygenated blood that mix w/ pulmonary vein?

1. Bronchial arteries (bronchi and bronchioles) dual supply to lungs... Azygos/HemiAzygos take some, but most via pulmonary veins 2. Small cardiac Thebesian veins that drain into the LAtrium and ventricle also contribute to shunting. Drops O2 from 104 to 100 mmHg

What are the three phases of gastric acid secretion?

1. Cephalic 2. Gastric 3. Intestinal Cepahlic... mediated by cholinergic and vagal mechanisms, triggered by thought, sight, smell, taste of food.. Gastric... presence of gastrin (stimulates hitstamine; therefore, indirectly acid secretion) and the chemical stimulus of food and distension of stomach Intestinal... protein-containing food enters the duodenal, minor role Intestine actually downregulates gastric acid secretion after a meal... Ileum and Colon release peptide YY, which binds receptors ont he endocrine, histamine containign cells (ECLs) enterochromaffin-like... Binding counteracts cephalic/gastric phases of acid secretion by inhibiting gastrin-stimulating histamin release from ECLs... Somatostatin and PGs also inhibit gastrin release. *what is receptive relaxation? -allows gastric fundus to dilate in anticipation of food passing through thep harynx and esophagus. *what is post prandial alkaline tide? increase in plasma HCO3- and decrease in plasma Cl- secondary to surge of acid int he gastric lumen...

Symptoms of MMyeloma

1. Fatigability (anemia, normocytic normochromic) 2. Constipation (hypercalcemia) 3. Bone pain (back/ribs from osteoclast activating factor of myeloma cells) 4. Elevated serum protein 5. Renal failure

How does lung volume affect resistance?

1. Increased lung volume.. alveolar expansion and lenghwise stretching of interstitial alveolar blood vessels... Increases their length and reduces diameter increasing alveolar resistance 2. Decreased causes extra-alveolar arteries and veins to become narrowed due to decreased radial traction from adjacent tissues and compression from positive intrathoracic pressure... The point of lowest resistance is near FRC.

What is the track of pain temp by neuron?

1. dorsal root ganglia 2. dorsal horn 3. axons of second order neurons decussate in ventral white commissure and ascend in the contralateral lateral funiculus 4. Third order neurons in the ventral posteriolateral nucleus of the thalamus 5. Fourth order neurons in the primary somatosensory cortex in the parietal lobe

Turner's Syndrome why is it genetics? what is missing?

10 year old girl super low heigh, no breast buds/axillary hair, low harilne, short/wide neck, broad chest, widely spaced nipples Due to meiotic NONDJ Missing X loses SHOX gene for long bone growth. So all have short stature.

PHN affects?

10% of patients after Herpes Zoster, but >70% of patients >70 years old)

Normal CSF volume and pressure

125-150 mL and 50-180 mmH2O Non-communicating hydrocephalus can occur after a aqueductal stenosis, Arnold Chiari or Dandy Walker can all cause this Communicating means ther is no obstruction of CSF flow. Due to dysfunction/obliteration of subarachnoid villi... Meningeal infections due this or subarachnoid/IV hemorrhage. All venitriculi are symmetrically enlarged.

How high a temp to autoclaves needa hit?

134C or 273 F to desroy spores as well. Like Bacillus and Clostridium.

DRESS

2-8 weeks post drug exposure... phenytoin, carbamazepine, allopurinol, sulfonamides, antibiotics... Likely involves drug-induced herpes virus reactivation followed by clonal expansion of T cells that cross react w/ the drug... Fever, generalized LAD, facial edema, morbiliform skin rash w/ eosinophilia... Liver kidney and lugn all affected. Elevated serum alanine transaminase.

If your parents are heterozygous and your mate is homozygous, what is the probability of child getting auto rec disorder?

2/3 chances you inherited the allele (assuming youd know if auto rec homozygous), then 1/2 chance if you have it of passing to offspring! so 2/3 * 1/2 = 2/6 = 1/3

RNA interference...

20-30 base pair RNA sequences induce post-translational gene silencing... two types 1) small interfering RNA 2) microRNA -human genome has these. Each one capable of repressing hundreds of target genes. Even a few problems w this ---> serious problems within the cell. siRNA are introduced by pathogens or drugs. after being transcribed... miRNA undergoes processing in the nucleus to form a ds precurose that is exported into the cytoplasm. There precursor is cleaved into a short RTNA helix by ribonuclease protein, dicer. The individual strands are then separated and incorporated into RISC (RNA-induced silencing complex)... This multiprotein complex uses its associated miRNA as a template to bind complementary sequences on target mRNAs... Exact match --> degradation... partial match --> repression.

What percentage of those w/ chronic hepatitis develop cirrhosis?

20-50%

HL age distribution

20s and 60s.... it is bimodal.

DiGeorge/Velocardiofacial Syndrome

22q11.2 deletion Conotruncal cardiac defects (Tof Fallot, Truncus Arteriosus, Interrupted Aortic Arch) Abnormal facies Thymic hypoplasia/aplasia Craniofacial deformities (cleft palate) Hypocalcemia and parathyroidism Due to defective neural crest migration in 3rd/4th pharyngeal pouches...

What causes conjugate vaccines to work better than polysaccharide ones?

23-poly pneumovax protects against a wide range of serotypes, but antibody level declines over 5 years. It is not immunogenic in children <2 bc their humoral antibody response is immature. So this one for 2-64 and >65 13-valent conugated to diphtheria protein boosts immune response through T cell recruitment; allows for memory T cells and longer lasting antibody levels.. Therefore, strongly immunogenic in infancy. PCV13 for immunocompromised patients and adults >65.

What percentage of SAH patients have a vasospasm w/o nimodipine?

25% if caused by ruptured intracranial aneurysm. Symptoms manifest no earlier than 3 days after and most frequently 7-8 days after.

Short structure of the lac operon

3 genes = regulatory (i), promotoer (p), operator (o) 3 structural genes z = beta galactosidase = hydrolysis of lactose to glucose/galactose y = permease = transmembrane enzyme that increases permeability of cell to lactose a = beta galactoside transacetylase, transfers acetyl groupw and is unnecessary really... In the presence of low glucose high lactose, all three genes rise synchronously. It is a "polycistronic mRNA".. most prokaryotics like this, most eukaryotics not!

Embryonic kidney development...

3 sets of nephric systems.. 1) pronephros 2) meso nephros 3) meta nephros 1) cephalic of nephrogenic cord, forms then regresses 2) meso --> male wolffian ducts SEED... in females meso regresses and becomes Gartner's duct 3) metanephros = true kidney begins w/ metanephric diverticulum (ureteric bud). This penetrates into the sacral intermediate mesoderm to induce the formation of metanephric mesoderm. Reciprocal exchange b/ wureteric bud and metanephric blastema drives differentiation. Ureteric bud = collecting system of kidney (collecting tubules and ducts and calyces and pelvis and ureters Metanephric blastema = glomeruli, bowman's proximal tubule, loop of Henle and DCTs Kidneys migrate in cephalad direction during fetal development, forming new vascular connections w/ the aorta as they travel. Some of these vestigial vessels may persist as accessory renal arteries.

PCOS

30 year old woman with infertility issues... Early menarche w/ oligomenorrhagia. Also acne and hair growth on upper lip and chin P/W 1) Androgen Excess: Hirsutism, acne, androgenic alopecia, maybe axillary/pubic hair loss due to adrenal androgen deficiency. 2) Ovarian Dysfx = menstrual irregularity, polycystic ovaries 3) Insulin Resistance = acanthosis nigricans, glucose intolerance/diabetes, MESA 4) Obesity Tx = weight loss, Combo of OCPs, Metformin Happens due to increased levels of 3beta hydroxysteroid DHD, 17alpha hydroxylase, 17,20 lyase... Results in anovulatory cycles. There is decreased progesterone secretion. Leads to long-term risk because of this of endometrial hyperplasia and adenocarcinoma.

DCGs cause

3rd and fourth pharyngeal pouch failure of neural crest cells to migrate there.... Leading to parathyroid and thymic hypoplasia.. w/o thymis, look for viral, fungal, protozoal infection Also will have conotruncal cardiac anomalies from failure of neural crest cell migration If 1st and 2nd pharyngeal pouches involved can have hypertelorism, short palpebral fissures, micrognathia, bifid uvula and cleft palate

Where is the origin of a thymoma?

3rd pharyngeal pouch, as are the inferior parathyroid glands... The thymus is NOT the thyroid you dummy

What are normal levels of homocysteine?

4-14.. higher can cause clots due to endothelial damage. MTHFR deficiency is the most common genetic cause of hyperhomocysteinemia.

History of someone w/ PBC???

45 year old woman w/ a long history of pruritis and fatigue who has pale stools and xanthelasma. Lymphocytes and granulomas clog the bile ducts... causing scarring... Hepatocytes secrete bile to canaliculi which drain to interlobular bile ducts, but these have cholestasis and reflux. Can get dark urine... Fat sol vita deficiencies.. Reduced biliary cholesterol excretion can promote the hypercholesterolemia and xanthelasma. Cholesterol under eye lids.

How common is brown adipose tissue?

5% of body mass in neonates. Neonates need it bc immature nervous system, high body surface area/volume ratio, decreased ability to shiver for heat production. Look like one intracytoplasmic fat droplet for white adipose tissue, brown has several small intracytoplasmic vacuoles. More mitochondria. Higher O2 requirement and has more capillaries as well. Uncoupling of ETC and phosphorylation generates heat. Protons pumped out return to matrix via mitochondrial membrane protein, thermogenin (uncoupling protein). Lots found on kidney and adrenal glands.

How often is sexual dysfunction a side effect of anti-depressants?

50% of the time SSRIs... decreased libido, decreased arousal, anorgasmia in women, increased ejaculatory latency in men. Buproprion usually used for hypersomnia/low energy depression (less weight gain caused by it too) ContraI in bullemic, anorexic and seizure patients

Cleft Lip and Palates

5th and 6th week of development Unilateral Cleft lip alone due to failure of fusion of maxillary prominence and intermaxillary segment. First pharyngeal arch splits into the upper maxillary prominence and lower mandibular prominence. Fusion fo the 2 medial nasal prominence forms the midline intermaxillary segment. This will become the philthrum of upper lip, 4 medial maxillary teeth, and primary palate L and R maxillary prominences fuse w/ the midline intermaxillary segment to form the upper lip and primary palate. If one of the maxillary prominences fails to fuse w/ intermaxillary segment, a unilateral clef lip results... If both maxillary prominences fail to fuse, with the intermaxillary segment, bilateral cleft lip results. ~Failure of medial nasal prominences to fuse --> holoprosencephaly ~During weeks 7-8, maxillary prominences give rise to palantine shleves. The thin sheets of tissue that comprise the palantine shelves grow medilaly and fuse into the secondary palate. Fusion of 2nd palate w/ posterior aspect of primary palate forms complete palate. Failure of any of these can lead to clef palate. Either can occur in isolation but more likely together ~Pierre-Robin sequence, hypoplasia of mandibular prominence --> micrognathia --> posterior tongue --> cleft palate

When do children realize finality of death?

6 years old.

What is normal liver span?

6-12 cm

What is the rule for standard deviations???

68, 95, 99.7%

Which mole has more chromsomes?

69 for partial... XXX,XXY,XYY 2 sperm fertilize it and a normal ovum. gestational trophoblast disease... complete mole p/w pelvic pain and vaginal bleeding. Uterus larger than expected and beta-hCG markedly elevated due to trophoblastic hyperplasia. RF = maternal age, prior molar pregnancy, prior miscarriage, infertility. Complete results from fertilization of ovum w/ inactivated maternal chromsomes, either by one 23X that duplicates sperm or two sperm one x one y. ONLY paternal DNA... A zygote w/o X would not survive. Less common is the XY one. ~Partial moles have fetal tissue and mixed hydropic villi.

How many NT long is tRNA?

75-90

When does development of external genitalia occur?

8-15 weeks

Predisposing factors for Membranous Nephropathy

85% idiopathic Other 15% = 1. Systemic = DM, solid tumors (lung, colon), immunologic disorders (lupus) 2. Drugs = gold, penicillamine, NSAIDs 3. Infx = HepC, HepB, Malaria, Syphillis

How is EBV transmitted what is the R it binds?

90% oropharyngeal secretions... binds CD21... EBV envelope gp350 binds this... CD21 is aka CR2 is aka the cellular receptor for C3d complement protein. ~HIV binds CCR5 and CXCR4 via gp120 ~Parvo attaches to human erythroid cells via blood group P antigen (globoside) expressed by mature erythrocytes, erythroid progenitors, megakaryocytes, placenta, fetal liver and heart... ~Adenovirus has hexon and penton capsomeres on its surface... Rodlike structures (fibers) that project from penton base capsomeres and rseponsible for absorption into host cells. ~CMV just needs contact w/ GAG chains on host cell surface proteoglycans for entry.

Delusional Disorder

>=1 delusions for >=1 months Other psych symptoms absent, ability to function apart from this delusion, and behavior not obviously bizzare or odd... Subtypes are erotomanic (someone in love w/ them), grandiose (they have great talents), jealous, persercutory (believe they are being spied on, poisoned, harrassed) and somatic (believing bodily functions/sensations abnormal) Not schizo bc no other symptoms psychotic Not personality because not suspicious paranoid narcisitic and not pervasive across a broad range of situations. Not all over life, about instead very specific things. Tx = antipsychotics and CBT ~Brief Psychotic Disorder = >=1 psychotic symptom for >1 day but <1 month. Sudden onset w/ full return to premorbid functioning. ~Schizophreniform is >=2 of delusions, hallucinations, disorganized speech, grossly disorganized, or catatonic behavior and negative symptoms

Bipolar Disorder

>=1 week of irritable mood & increased energy/activity >=3 of the following... -distractability, impulsivity/risky behavior, grandiosity, flight of ideas, increased activity/psychomotor agitation, decreased need for sleep, talkativeness/pressured speech (DIGFAST) -impaired psychosocial function -psychotic features -may need hospitalization w/ psychotic features means there are delusions/hallucinations Depressive episodes not required for bipolar diagnosis ~In psychotic disorders, mood symptoms are not a prominent feature ~Delusional is >=1 delusions in absence of other psychotic symptoms. Functioning may be normal other than the delusion

Criteria for Schizophrenia

>=2 symptoms for >1 month or less if treated w/ at least one of >=1 month of the following -deulsions, hallucinations, disorganized speech maybe, grossly disorganized or catatonic behavior negative symptoms -continuous signs of disturbance, including prodromal or residual symptoms for >=6 months Significant decline in functioning *one of three for >=1 month during a period of 6 months, with prodromal or residual symptoms occurring the rest of the time ~Brief Psychotic Disorder is >=1 day but <1 month w/ full return to premorbid level of functioning. Schizophreniform is >1 month and <6 month of symptoms. ~Schizoaffective is major depressive or manic episode concurrent w/ active-phase of schizophrenia. Deulsions or hallucinations occur in absence of mood symptoms for >=2 weeks at some point in the illness.

How do you diagnose MM by BM bx?

A BM sample w/ >30% plasma cells is MM Usually catch at 70 years old. -normocytic, normochromic anemia IL1 secretion and IL6 as well --> osteoclasts and bone resorption (osteopenia) punched out lesions/bone pain Hypercalcemia Infection risk Also monocloncal immunoglobulin --> bence jone proteins Hyperimmunoglobulinemia leads to rouleaux formations on peripheral blood smearE Eventually renal failure due to infiltration of kidney w/ plasma cells, deposition of amloid, mets calcifications, inflammation by MPs and giant cells esp.

Progressive Supranuclear Palsy

A form of parkinsonism from neurodegeneration of midbrain and frontal subcortical white matter... P/w progressive gait dysfx, falls, executive function loss, vertical gaze palsy... Abnormally phosphorylated tau proteins on biopsy.

What is Naegleria fowleri?

A free-living, protozoan parasite that causes rapid meningoencephalitis with a high mortality rate. N fowleri is found in fresh water and transmission through nasal inhalation during recreational activities. After spread through cribiform plate --> encephalitis, smell/taste abnormalities... Then inflammation of frontal/temporal/brainstem/meninges

What antiHTN causes oligohydramnios and why?

ACE.. from low angiotensin 2 can result in fetal renal maldevelopment, leads to reduced diuresis and oligohydramnios. Can also lead to impaired cranial vascularization and development of the skull bones (hypocalvaria)

What drugs improve survival in systolic HF?

ACEi/ARBs Aldosterone antags Carvedilol!!... decreases myocardial work and oxygen demand and slows ventricular rate and reduces contractility... Lowers peripheral vascular resistance by decreasing renin and endothelin.

Kid w/ only problems during writing, gets distracted, fidgets, etc., performance below for age...

ADHD needs at least 2 settings... has to be in reading, or math as well as writing or in the home setting

Acute Rejection in Heart Transplant

ALMOST ALWAYS cell mediated acute rejection (2/5 hearts have this happen) RARELY humoral rejection of donated heart (diagnose by immunofluorescence) 1-4 weeks most common acute Will have dense infiltrate of lymphcoytes... T cell host sensitization against graft foreign MHC. ~initiation of new drug therapy can cause myocardial eosinophilia (HSN myocarditis) ~patchy ischemic heart in transplant might be from resuscitation of donor or transport of heart from donor ~scanty inflammatory reaction and interstitial fibrosis = chronic rejection

How is APML classified special?

AML M3 in the French-American-British (FAB) classification of leukemia

What is the difference b/w autonomic neuropathy and vasovagal syncope?

AN.. DM caused VV.. concomitant w/drawal of sympathetic efferent activity and enhanced parasympathetic activity (results in bradycardia, vasodilation, orthostatic hypotension)

How does drug induced lupus present?

ANA and anti histone antibodies... low grade fever, joint pains, erythematous rash on face/trunk

Determining significant differences b/ w means of several independent groups. >=3 groups

ANOVA...Null hypothesis is same mean... Alternative is different means. Chi squared is to evaluate the association between 2 categorical variables... qualitative and qualitative.

What problem protein is going on with xeroderma pigmentosum?

AP endonuclease is messed up, therefore nucleotide excision repair... Leads to photosensitivity, poikiloderma, hyperpigmentation all of sun exposed areas, also SCC... Thymine dimers are repaired by a UV specific endonuclease... ~3' --> 5' exonuclease is useful for proofreading in DNA mismatch repair

What is the sequence of mutations in colonic polyps?

APC inactivation, methylation abnormalities, COX2 overexpression, KRAs activation, DCC inactivation, p53 inactivation -> carcinoma

Crescendo-Decrescendo murmur in elderly systolic

AStenosis... Esp if >70 yeras old... Due to degenerative calcification of aortic valve leaflets... Calcific AS is caused by chronic hemodynmaic stress or atherosclerotic inflammation --> leads to progressive aortic valve leaflet thickening, calcification and stenosis. Longer and later peaking murmur is more severe AS... brief early is less severe... Intensity of murmur does not correlate w/ severity though.

Muscle Contraction, what is the role of ATP?

ATP binds sarcomere and causes myosin head detachment from the actin filament. W/O ATP muscle fixed in a contracted state 1) ATP on sarcomere, myosin detached 2) ATP hydrolysis, myosin cross-brdige-ADP-phosphate-complex... Tropomysoin prevents crosslinking between actin and myosin 3) calcium comes in, Ca2+ binds troponin and removes tropomyosin; allows myosin cross-bridge-ADP-phosphate complex to bind actin 4) ADP-phosphate complex is released after myosin crossbridge binds actin 5) New ATP comes in and detaches myosin from actin etc.

What is the most common cause of intracranial hemorrhage in children?

AV malformation

Pathogenesis of pre-eclampsia

Abnormal placentation... placental hypoxia and ischemia --> release of anti-angiogenic factors into maternal circulation... Causes endothelial injury. Damage to endothelium increases permeability resulting in proteinuria. Dysregulation of vascular tone --> BP --> end organ damage (headaches, visual changes, abdominal pain) ~It takes years to develop AAV nicking on fundoscopy of chronic HTN...

How to treat absence seizures / gen ton-clon activity?

Absence are momentary lapses in consciousness that have a 3Hz spike-wave-pattern on EEG... Young w/ typical absence don't usually develop new seizures types... But if older 10-12, assc w/ gen ton clonic OR myoclonic seizures One seizure -> no tx, multiple seizures --> braod spectrum like valproate. Ethosuximide perferred for just isolated absence.

What activates the adrenal medulla?

Ach preganglionic sympathetic neurons and then it secretes 80% epi 20% norepi into the blood stream

What state of Rb is activated?

Active (hypophosphorylated) and Inactive (hyperphosphorylated)... Active when cells are resting in Go... if you want to divide, phosphorylate it. ~Normal tissues have high p27 and cancer have low p27, it stops cell cycle.

How does residual volume of lungs change with aging?

Actually decrease in volume w/ aging due to destruction of alveolar walls.

How does MR change afterload?

Actually decreases it because the incompetent mitral valve serves as a low resistance regurgitant pathway Will eventually lead to eccentric hypertrophy due to chronic volume overload. Eventually cause contractile dysfunction.

Progression of antipsychotic typical induced EPS

Acute Dystonia (min-hours) Akathisia within days Parkinsons within weeks Tardive Dyskinesias w/in months-years ADAPT -manage w/ M1 antagonist (benztropine or trihexyphenidyl) OR benzos OR beta blockers

Evolution of H pylori

Acute infection at the antrum (primary) overtime moves to body... Acute infection --> NPs, chronic lymphocytes/lymphoid follicles/plasma cells. Antral involvement increase gastrin production and gastric acid secretion leads to duodenal ulcers... Body and fundus though leads to atrophic gastritis (loss of G cells and decreased gastric acid w/ longstanding infection)... Less likely for ulcers more likely for gastric adenocarcinoma... Fe def anemia and MALT..

Acalculous cholecystitis...

Acute inflammation of the gall bladder w/o gall stones... occurs in critically ill patients (sepsis, trauma, immunosuppression) and is associated w/ high mortality. Arises from gallbladder stasis and ischemia which injure gallbladder wall. Fever, RUQ pain, + murphy's, leukocytosis, and mild LVTs... Jaundice and palpable RUQ mass possible. Dx w/ U/S that shows acute cholecystitis (edematous/enlarged gall bladder w/ no gall stones)

What amino acid assists w/ secretion of acid in acute ischemic colitis?

Acute ischemic colitis in setting of Afib, likely embolic disease... Ischemic bowel then undergoes anaerobic metabolism, causing lactate accumulation in the blood that leads to an anion gap metabolic acidosis. Acidosis stimulates renal ammoniagenesis by which renal epithelial cells use glutamine from the blood to change to glutamate (create NH3) and then furter the alpha ketoglutarate (another NH3) and then to glucose, which loses a CO2 to give off H+ to the renal tubule fluid and an HCO3 to head back into the blood and increase pH. Under normal condition,s half of total amount of acid secreted in the urine is ammonium and remainable is titratable acids, particularly inorganic phosphate.

Acyclovir vs Gangiclovir in HSV/HSV2/VZV vs. EBV/CMV

Acyclovir works in the first 3. Enters the HSV_infected host cell, it is phosphorylated to acyclovir monophosphate via virally-encoded thymidine kinase. THis is the rate limiting step of activation. THis is then phosphorylated by cellular enzymes into active triphosphate form which impairs viral DNA polymerase-mediated replication of HSV. EBV/CMV do not produce the same TK as the other two so cannot convert acyclovir to its ative form. At VERY HIGH concentrations, somethign else does this. so kinda susceptible. Mutations in DNA polymerase may lead to acyclovir resistance,.

What anti viral drug for HSV causes nephrotoxicity?

Acyclovir!! 5-10% of patients who get the drug IV... Excreted via glomerular filtration and tubular secretion... When concentration in collecting duct exceeds solubility, crystallization and renal tubular damage occur... mostly, toxic complication is transient and prevented w/ adequate hydration. and reduced rate of injection. ~Use pretreatment w/ prednisone for radiocontrast induced allergic reactions ~Allopurinol pretreatment for lymphoma/leukemia

Compare colonic manifestations of various diseases

Adenocarcinoma = protuberant mass = dysplastic mucosal cells w/ gland formation CMV = multiple ulcers and mucosal erosions, Cytomegalic cells w/ inclusion bodies (OWLs) Cryptosporidium = Nonulcerative inflammation, Basophilic clusters seen on surface of intestinal mucosal cells Entamoeba histolytica = Numerous discrete flask-shaped ulcerated lesions, trophozoites containing RBCs Kaposi's Sarcoma = Reddish/violet, flat maculopapular lesions and hemorrhagic nodules, spindle-shaped tumor cells w/ small vessel proliferation Ulcerative colitis = contiguous areas of erythemaous friable, granular mucosa w/ possible pseudopolyps, inflammatory infiltrate w/ mucosa and submucosa crypt abscesses

Which female reproductive endometrial disorder shows hypertrophy?

Adenomyosis

Difference b/w adenomyosis and endometriosis?

Adenomyosis means enlarged uterus ~PCOS irregular menses ~Endometrial Hyperplasia = increased E gland/Stroma ratio w/ excess estrogen (irregular menses ) ~Endometriosis... nulliparity, early menarche, prolonged menses all RF... mutliparity, extended lactation, late menarche decrease risk Ectopic endometriujm reponds to hormonal influences.. Bleeding and shedding leads to blood colletions and hemoloysis and inflammation --> adhesions Adhesiosn interfere w/ ovulation and FT fujnction... resulting in infertility... If ureterosacral ligament involved --> fixed/retroverted uterus... Infiltration of posterior cul-de-sac can result in painful intercourse and tender posterior fornix

What is adjustment disorder w/ depressed mood vs normal sadness?

Adjustment disorder w/ depressed mood = onset w/in 3 months of stressor... marked distress and or functional impairment Normal sadness... not excessive or out of proportion

What is responsible for corneal reflex?

Afferent V1 and efferent VII

What arrhythmia should be worried about in severe aortic stenosis?

Afib (10%)... AS already have reduced CO due to obstruction, which ca be exacerbated w/ loss of atrial contraction... This contraction is esp important for patients w/ LV hypertrophy like theses. They are dependent on the contraction for filling... W/o contraction, preload can decrease to severe hypotension... Loss of atrick kick can mean increased pumonary venous pressure due to build up of blood in left atrium --> acute pulmonary edema...

Diference b/w Somatic Symptom Disorder and Conversion Disorder

After a stressful incident, acute onset, normal neuro exam, negative workout are suggestive of convesion disorder. It is a somatic symptom disorder w voluntary motor and sensory function deficits that are incompatible w/ any recgonized neurologic condition and cannot be explained medically/mental disorder otherwise. Weakness, paralysis, gait disturbance, blindness, diplopia, aphonia, anesthesia, seizures. Internal inconsistency at examination can demonstrate incompatibility. Belle indefference (incongruous lack of concern about symptoms) is also an indication. Somatic symptom disorder is characterized by excessive and persistent healthy anxiety and preoccupation w multiple somatic symptoms... Do not have loss of function w/ any illness. Acuteness and incompatibile neuro exam make conversion more liekly.

How do common clinical disinfectants work?

Alcohols (isopropanol/ethanol) = disrupt cell membranes/denature proteins Chlorhexidine = disrupts cell membranes and coagulates cytoplasm ^not sporicidal H2O2 = produces free radicals that oxidize cellular components Iodine = halogenation of proteins/nucleic acids ^sporicidal Alcohols require water for maximal activity and work best at 60-90% concentration. They are bactericidal, tuberculoidal, fungicidal, virucdial but not bacterial spores.

Nieman Pick what is the deficiency? also other deficient enzymes w/ key features

All AR except Fabry Sphingolipidoses Fabry.. alpha galactosidase.. globotriaosylceramide builds up, angiokeratomas, peripheral neurop, glomerulopathy T-Sachs.. beta-hexosaminidase A... Ganglioside builds up.... macular cerry red spot, progressive neurodegen Gaucher... Beta glucocerebrosidase.. glucocerebroside... HSM, pancytopenia, bone pain NPick... sphingomyelinase... sphingomyelin.. macular cherry red spot, progress neurodeg, HSM Krabbe.. .galactocerebrosidase... galactocerebroside and psychosine... progressive neurodeg, peripheral neurop, optic atropy Metachromatic Leuko dystrophy... Arylsulfatase A.. cerebroside sulfate.. progressive neurode, peripehral neurop ^^^Askenazi Jewish have the founder effect, loss of genetic variability with a group that historically conceiveing w/in their own communit... BLoom, Tay Sachs, Neimena PIck , Gaucher!!! Hurler's has dystosis multiplexus.. mucopolysaccharidosis w/ enlarged skull, abnormally shaped ribs, and vertebrae)

What side effect can be seen w/ SSRIs?

All anti-depressants carry risk of inducing mania... Mother's hx of mood swings suggests bipolar disorder so patient at increased risk... in this scenario, once they become manic, stop the antidepressant and start a mood stabilizer... Bipolar 1 at higher risk of this side effect than Bipolar 2

What are the 3 factors that increase gastric acid secretion?

All bind at parietal cell and induce K+/H+ ATPase to increase activity (can be blocked by PPI w/o their interaction) 1. Vagus nerve... ACh at M3R 2. Vagus N hits G cell via GRP and G cell secretes gastrin to hit CCKB R 3. Gastrin hits ECL cell and ECL cell releases histamine to hit H2R.

Effects of Dobutamine

All mediated by increase in cAMP 1) cardiac muscle... If Na+ channel activation for positive chronotropy 2) cardiac muscle... Ca2+ activation leads to positive chronotropy and also actin-myosin-troponin interaction for positive inotropy 3) smooth muscle.. cAMP dep K --> augmented Ca2+ uptake by SR --> vasodilation Overall decreases LV filling pressures (improve pulmonary congestion), increases CO, contractility, and heart rate Overall increases myocardial O2 consumption. Don't use in decompensated HF routinely. W/ cadiogenic shock it is outweight benefit.

Contact precautions

All patients needs gloves and occasional gowns Suspected Cdiff require contact precautions... handwashing w/ soap and water, gown for any patient contact and nonsterile gloves changed after contact.... Certain pathogens sent by droplets in air for limited periods need simple facemask when w/in 6-10 feet. Gowns and gloves not required. .. .>5 micron particles Airborne precautions, isolated room w/ neg pressure... and a N95 mask... for microns <5 particles TB, VZV *sterile gloves for minor procedures/surgery but not normal contact

Alpha 1 and Alpha 2 effects

Alpha 1 = sm m contraction, mydriasis, increased internal urethral sphincter tone and prostate contraction = also have a reflexive decrease in HR. Inhibits pacemaker activity of the SA node and slows conduction of AV node and decreaes contractility of myocardium Alpha 2 = CNS mediated decr BP, decr IOP, decr lipolysis, decr presynaptic norepi, increased platelet aggregation

Fabry Disease

Alpha-Galactosidase A deficiency --> acumulation of globotriaosylceramide P/W neuropathic pain, angiokeratomas andtelangiectasias... will get CV and renal disase(from buildup of Gb3 in glomerulus an ddistal tubule --> proteinuria and polyuria) Angiokeratomas are dark, red, non-blanching macules and papules that occur in clusters over buttocks, groin, umbilicus

What second messengers do the adrenergic receptors use???

Alpha1 = IP3 (increased) increased vasoconstriction, urethral constriction, pupillary dilation (radial muscle contraction) Alpha2 decr cAMP betas both increased cAMP Norepi hits alpha1, alpha2, beta1 little bit of beta2

What are the common protein misfolding neurologic disorders?

Alzheimer's = ApoE polymorphisms... which lead to altered lipid binding, inhibited neurite growth, and accumulation of amyloid-beta that aggregates. Creutzfeldt-Jakob... due to prions, which are contagious small misfolded proteins that cause other normal proteins to misfold, resulting in aggregates that are difficult to degrade. PKU...

What drugs need thyroid function tests before?

Amiodarone and Lithium

Drug that prolongs QT but low risk of Torsades...

Amiodarone... weird. Very little risk though. Due to homogenous effect of ventricular repolarization.

Diagnosing erythroblastosis fetalis from amniotic fluid??

Amniotic fluid bilirubin levels. ~NTD in infants via AFP

How does DM cause amyloid deposition?

Amyloid polypeptide (amylin) is partially responsible for beta cell dysfunction.... Stored in insulin secretory granules and is co-secreted w/ insulin from pancreatic beta cells... Deposits are universally seen in pancreatic islets of patients w/ T2DM. Both TD1m and T2 have strong genetic predisposition.

Where does Ang2 R Blocker work?

Angiotensin 2 stimulates type 1 ang2 receptors on vascular smooth muscle and adrenal cortex to secrete aldosterone. In ACE inhibitors, bradykinin is thought to increase PG production, which induces coughing due to bronchial irritiation.

Compartments of Leg and Nerves

Anterior = Deep peroneal w/ anterior tibial a.v. Lateral = Superficial peroneal n. Deep Posterior Compartment = Peroneal a.v. and Tibial n. w/ posterior tibial a.v..... posterior tibial a./v. borders on the superficial posterior compartment. Fascia is inelastic and limits outward expansion of muscles... If pressure in compartment increases, Q is compromised, ischemia... Acute Compartment Syndrome due to long-bone fractures, crush injury, thermal injury or bleeding/vascular disorders... Fasciotomy is the treatment... TO prevent dissablement.

Where does S aureus colonize?

Anterior Nares, NOT the oropharynx 50% of staph are MRSA... CAP or HAP... in general population 25% of population has nasal colonization Esp increased risk following surgery, periotneal dialysis, hemodialysis

What is damaged in Korsakoff Syndrome?

Anterior and Dorsomedial Thalamic Nuclei. Leads to memory loss and confabulation. When unsure of a fact, these patients fill in a fabricated story they believe to be true.

How do you specifically diagnose Rheumatoid Arthritis?

Anti-cyclic citrullinated peptides... tissue inflammation --> arginine residues in proteins such as vimentin to be converted to citrulline through cirtullination. This alters shape of these proteins, causing them to be neoantigens and generate an immune response. In Rh A this immune response is exagerated. Anti CCP really only in RA and measured w/ ELISA to various CCPs ~Rheumatoid factor not useful, present in 10% of healthy individuals ~antiphospholipid antibodies in SLE and antiphospholipid antibody syndrome

What is associated w/ candida vulvovaginitis?

Antibiotic use, high estrogen, systemic corticosteroids, uncontroleld DM, immunosuppression. Antibiotic use is most common, due to reduction of lactobacilli population (gram positive)..

Process of Western BLotting

Antibodies to specific prion protein added to a filter. Next a marker protein that combines w/ antibody-protein complex is sued to determine test positive Pts w/ HIV do this too for gp24, gp 41 and gp120/160, if 2/3 are positive --> positive ELISA patient's serum is tested directly; whereas western blotting uses electrophoresis first Northern for mRNA Souther for DNA Microarray has hybridization of many probes at once. cDNA is analyzed w/ fluorescent tag and placed on a gene chip containing complementary sequences for a large number of genes. SW blotting is for DNA-binding proteins.

Anti-Coagulants post ACS

Antithrombin can inhibit both Factor Xa in the coag cascade and thrombin. Both unfractionated heparin and LMWH contain a pentasaccharide sequence that binds to antithrombin and causes a change that increases its ability to inactivate factor Xa... However heparin must bind both antithrombin and thrombin together to form a tiernary complex to inactivate thrombin Only unfractionated heparin (Not LMWH) has a pentasaccahride chain long enough >18 units to bind both antithrombin and thrombin. As a result, unfractionated heparin has equal activity against factor Xa and thrombin... While MWH has greater actiivity against Factor Xa than thrombin. ~Enoxaparin is a LMW heparin that has fever of the required long saccharide units to bind thrombin and less antithrombic activity ~Fondaparinux is a synthetic pentasaccharide fator Xa inhibitor. None of the long units bind thrombin.

Specific Phobias treatments

Anxiety about a specific object/situation for > 6 months... Fear of flying, heights, animals, injections, blood -will be avoiding and it is common ~10% of population -usually develops in childhood often after traumatic events 1st line cognitive behavioral therapy short acting benzos acutely... Beta blocker is useful for performance anxiety like social anxiety disorder, but not indicated for specific phobia.

Pancytopenia w/o splenomegaly

Aplastic Anemia!! Has normochromic normocytic anemia, TCP, neutropenia... Profound reticulocytopenia... Nl cell lines on peripheral smear. Hypocellular bone marrow w/ fat cells and marrow stroma.. dry tap. Peripheral smear would pick up any blastic leukemias

Vomiting when just starting chemo, where in brain affected?

Area postremia (Chemoreceptor trigger zone) lies at the dorsal surface of medullaand caudal end of 4th ventricle. Receives blood from fenestrated vessels (outside BBB)

Treatment of ER positive tumors

Aromataze inhibitors are helpful. Aromatase is a P450 superfamily and expressed in ovariant tissue. Gonadotropin dependent. In postmeno state, follicular atresia leads to reduced numbers of granuloas cells and decreased ovariant estrogen synthesis; however, ovaries and adrenal glands to continue to produce androgens in big qualities. Extraovarian aromatases Estrogen main thing driving ER pos tumor growth Anastrozole, Letrozole, Exemestane all reduce synthesis of estrogen from androgens. These aromatase inhibitors decrease the synthesis of estrogen from androgens. Less effective in premeno women.

Mild is known but why does severe efferent constriction cause decr GFR?

As RPF decreases, slower capillary flow allows more time for filtration of plasma across the glomerular membrane.. Increases concentration of non-filterable plasma proteins int he capillaries, elevating oncotic pressure... As RPF decreases w/ increasing efferent constriction, the increased capillary oncotic pressure overall decreases GFR.

Amyloid Precursor Protein

Associated w/ Alzheimer's and it is on chromsome 21... Transmembrane protein found throughout the body... APP is processed in 1-2 pathways by proteolytic enzymes... Alpha and gamma secretase pathway is normal, no amyloidogenic proteins Beta secretase and gamma secretase leads to Abeta peptide which aggregates as amyloid plaques that are insoluble and neurotoxic. Therefore, down's syndrome have higher risk of AlzhDiz

How does methacholine challenge work?

Asthma needs FEV1/FVC <= 70% but b/w exacerbations, this is nromal... Bronchoprovocation testing can be useful in diagnosis but has normal spirometry values usually... Methacholine is an inhaled muscarinic cholinergic agonist that induces bronchoconstriction... Given increasing doses followed by serial spirometry... Hyperresponsiveness in patients w/ asthma. Can do the opposite for obstruction w/ bronchodilator = levalbuterol... Reversal of airflow obstruction after therapy suggests diagnsois of asthma. While irreversible obstruction suggests COPD/bronchiolitis.

Which two pediatric tumors affect cerebellum?

Astrocytomas and Medulloblastomas. Medullos are PNETs (Primitive Neuroectodermal Tumors)... sheets of deeply basophilic nuclei. Lots of mitoses as well. Pilocytic astrocytoma is the most common brain neoplasm of childhood. These have astrocytes and rosenthal fibers. Low grade tujmors. Ependymomas are the third most common in children --> arise in walls of ventriculi and can hamper CSF flow -> hydrocephlaus.. form rosettes.

Arches

At embryonic development, head, neck, upper thorax develop from a set of arches known as pharyngeal arches. Each is associated w/ a cranial nerve and an aortic arch... 1st pharyngeal arch is associated w/ the 1st aortic arch and the trigeminal nerve... etc.

Where do we usually find meningiomas in the brain?

At the falcine, parasagittal, or lateral convexities of the brain. Seizure can occur due to compression of the cerebral cortex... Often p/w HA, n, v from increased ICP... worsens during recumbency or sleep.

Immunodeficiency DDX

Ataxia-Telangiectasia = ataxia, telang, sinopulmonary Chediak-Higashi = oculocutaneous albinism, pyogenics, neuro dysfx CGD = severe bacterial/fungal, granulomas DiG = congenital Heart Diz, abnormal facies, hypocalcemia SCID = bacteiral, viral infx, chornic diarrhea, Mucocutaneous candidiasis Wisckott-Aldrich = recurrent infections worsen w/ age, easy bleeding, eczema

How does ACE in change creatinine?

Atherosclerosis means low renal perfusion (RAS, hypovolemia, CHF) lower GFR meaning he was in a high renin state. Many patients, 30% experience a rise in serum creatinine (2-5 days of starting ACE)... Patients w/ B/L RAS can experience a precipitous fall in GFR and acute renal failure when starting ACE... All due to efferent arteriolar dilation and lower intraglomerular pressure decreasing GFR in the setting of previously reduced renal perfusion.

In atropine toxicity what are the treatment options?

Atropine is an anticholinergic med administered prior to bronchoscopy to decrease respiratory mucus secretions and promote bronchodilation... Inhibit muscarinic Ach R competitively both central and peripheral... (delirium, coma, resp failure if overdosed)... Elderly at high risk. Want to reverse w/ tertiary amines NOT quarternary amines so use PHYSOSTIGMINE... galantamine, donepezil, rivastigmine.. lipophilic cholinesterase inhibitors used to increase concentration of Ach at the cleft.

Medical Collateral Ligament injury

Attaches proximally to the medial epigondyle of the femur and resists forces that push the knee medially.. Tiwsting injury or blow to the lateral knee while the foot is planted can cause a valgus stress injury.. Knee extended by placing one hand on the lateral thigh and pressing inward while the other hand is place on the medial aspect of the ankle and pushed outward. Laxity of th eknee and/or medial joint widening indicates MCL injury.

What is the main cause of Immune thrombocytopenic purpura?

Autoimmune destruction of platelets and is often associated w/ viral infections. Platelet abnormalities leads to microhemorrhages (petechia and mucosal bleeding (epistaxis) Leukocytoclastic vasculitis is associated w/ antibx use (penicillin/cephalosporins) or viral hepatitis infection; however, develop nonblanching petechiae or palpable purpura w/o bleeding

How do you ppx for MAC <50 cells in HIV?

Azithromycin How do you ppx Histo = itraconazole in Ohio/Mississippi river valley areas when CD4 <150 toxo <100 Trimethoprim-sulfa Pneumocystis CD4 <200 along w/ oropharyngeal candidiasis = trimethoprim sulfa MAC p/w fever, weight loss, diarrhea in HIV positive patient.. Elevated Alk Phos, Lactate DHD levels, HSM, anemia all common w/ MAC... Spreads via reticuloendothelial system. Grows at high temperatures.

Which anti fungals affect P450?

Azoles... all do ... when we use azoles, drugs metabolized by P450 have increased toxicity. Warfarin, Cyclosporine, Tacrolimus, Oral Hypoglycemics Cytochrome oxidase inducers (rifampin, phenytoin, carbamazepine, Phenobarbital) all increase azole metaoblism lowering azole concentration in serum

The story of the B cell

B cell precursors proliferate and mature in bone marrow... Then leave the BM and migrate to lymphoid organs and peripheral tissues where they are exposed to antigens.. On first exposure, new antigen, a clone of B cells becomes activated... Some differentiate into short lived plasma cell and release IgM through a T cell independent response Most mature B cells though, migrate to lymphoid follicles located in lymph node cortex to undergo germinal centers. A portion of these activated B cells form long-lived memory cells that remain dormant in lymph node until next encounter with the same antigen, but majority transform into antibody-secreting plasma cells. Isotype switching (IgM to others) occurs in germinal centers late in primary response... providing activated B cells the ability to produce antigen-specific antibodies of differing isotypes... Heavy chain constant reigons are isotype specific and distinguish the 5 GAMED... While variable regions are antigen specific... Light chains are antigen specific and do not determine the isotype... Isotype switching first required CD40 on activated B cell to bind CD40L on (CD154) activatedT cell.. Afterwards the isotype switching and genetic rearrangement of heavy chain constant regions occurs... THis is mediated by cytokines... IgG response or IgA response at mucosa from here on out. ~~VDJ heavy and VJ light chains occurs via DNA rearrangement... After undergoing immunoglobulin rearrangement, each B cell makes antibodies of a single specificity. High variety... Recombo here occurs during B cell maturation w/in the bone marrow. Affinity maturation occurs in germinal centers w/ somatic hypermutation.

Where do type A and B dissections originate?

B from left subclavian A from the sinotubular junction... These two areas are though to be predominantly affected due to increases inr ate of rise of pressure (dp/dT) and in shearing forces in patients w/ HTN.

If megaloblastic and give folate then develop neuro symptoms

B12 deficiency.

What cofactor is used to pass around amines?

B6 for transamination B7 for carboxylase B9 for nucleic acid synthesis B2/B3 for DHD

When is imprinting relevant?

Basically Angelman versus Prader-Willi... Paternally inhertied deletion in 15 is PW Angelman is maternally inherited deletion in 15 as well, same part

What determines most susceptible vascular regions for atherosclerosis?

Bends and branch points that encourage turbulent flow, which disrupts vascular wall integrity and leads to endothelial cell dysfunction. Also leads to decreased shear stress on vascular walls and prolonged endothelial contact w/ cholesterol particles AAA and Coronary arteries most susceptible. ~internal thoracic arteries = internal mammary arteries (good for bypass grafts)

What causes Macrosomia in babies w/ parents w/ diabetes during gestation?

Beta cell hyperplasia transplacental glucose transfer tot he fetus --> fetal insulin production --> beta cell hyperplasia/hyperinsulinism, babies born w/ increased fat deposition/growth. Loss of glucose transfer at birth --> hypoglycemia --> neuro injury.

How does anomalous pulmonary venous return work?

Blood from pulmonary (oxygenated) and systemic (deoxygenated) flow into the right atrium Need R-> L shunting to live ha This is different from transposition of great arteries (which results from linear rather than spiral development of the aorticopulmonary septum)

Cortisol effect on glucose

Blood glucose maintained by glucagon primarily, also epinephrine... also cortisol and growth hormone in prolonged fasting. Cortisol R are w/in the cytoplasm... when cortisol binds to the carboxy terminal portion causes release of the Heat Shock Proteins and receptor dimerization. Activated homodimers transported to the nucleus where they control gene expression by binding hormone-responsive DNA elements. Increase tx of enzymes involved in GNG and lipolysis/proteinlysis.

ALL in child what is more common if p/w dysphagia, dyspnea, stridor?

Both p/w fever, fatigue, pallor, petechiae, bleeding T ALL is more likely to be a large anterior mediastinal mass --> compress great vessels --> SVC Syndrome... Compress esophagus for dysphagia, also trachea for dyspnea/stridor... B iHC = 10, 19, 20... T is 2,3,4,5,7,8 B is 75% of ALLs...

What do Nef and Tat do for HIV?

Both viral genes. Tat is for viral replication. Nef decreases expression of MHC class 1 proteins on surface of infected cells.

Where is COMT found?

Brain and Liver

What is phytanic acid?

Branched chain fatty acid

What are some drugs to assist in fertilization of patients ?

Bromocriptine = Dopamine R agonist that inhibits pituitary prolactin secretion. Can restore fertility in women w/ hyperprolactinemia Clomiphene citrate = good for women w/ ovulatory failure who are normogonadotropic, normoprolactinemia and euthyroid... basically blocks feedback inhibition of estrogen on the hypothalamus enhancing release of pituitary gonadotropins. Pulsatile GnRH = If pituitary and ovaries are intact, then pulsatile GnRH can be used in patients with overactive hypothalamic GnRH secretion, hypogonadism = Hypogonadotropic, Hypogonadal anovulation. hCG = triggers ovulatory cascade in an oocyte donor when her follicles are deemed mature.

What grows germ tubes at 37 degrees?

C albicans.

How to differentiate levels of the spinal cord?

C has gracile and cuneate fasculus dorsally w/ no hole C1 mostly oval shaped cord w/ lots of white matter small gray matter C7 more gray matter T has hole and has intermediolateral cell column (preganglionic sympathetics) L has hole and gracile fascilulus no intermediolateral cell column L1 and L2 both have lateral interomediolateral cell colmuns too S has no gracile fasciculus and is just generally larger, but comparison w/ L is hard,

Difference b/w HTN arteriolar sclerosis & Charcot-Brouchard aneurysm?

C-B usually leads to an aneurysm.. They are caused by chronic HTN and involve the small penetrating arterioles that cause lacunar strokes. These however, lead to intraparenchymal hemorrhage within deep brain structures, appears acutely as a relatively large hyperdensity on CT scan (wound't be normal on CT) Lacunar infarcts are due to HTN arteriolosclerosis... Hit the basal ganglia, pons, subcortical white matter (corona radiata and internal capsule)... Lipohyalinosis and microatheroam are the big two terms used to represent this. Diabetes and Smoking also cause this.

Presentation of child w/ hereditary angioedema

C1 esterase inhibitor deficiency... autosomal dominant... causes episodes of painless, non-pitting, well-circumscribed edema... Face, neck, lips, tongue especially but internal organs can be affected... Tracheobronchial tree can cause respiratory obstruction and be fatal. Angioedema of GI tract --> abdominal pain, vomiting, diarrhea. Normally C1 esterease inhibitor suppresses activation of C1 compllement and rest of complement... It also inactivates Kallikrein which changes kininogen to bradykinin. Bradykinin and C3a/C5a mediate angioedema w/ vasodilation/permeability. Levels of C4, the substrate for C1 esterase are low. Kallikreine also works to convert plasminogen to plasmin

Child with puffy hips and swollen tongue, there is mild audible stridor no wheezing, what do you think??

C1EsteraseDeficiency!!!! If there is associated pruritis and urticaria, then you think mast cell activation (type 1 HSN reaction IgE OR opioid direct mast cell activation) Mechanism of C1 Esterase Def symptoms is excess bradykinin... ACE inhibitors can also cause this.

What two host defense molcls help w/ phagocytosis?

C3b and IgG Mannose binding lectin and C-reactive protein can also opsonize cells.

What are the two promoters, how far upstream, are they responsible for enhancement or initiation of transcription?

CAAT -75, TATA -25, initiation... Hogness Box = TATA... binding sites for transcription factors and RNA pol 2

What is a cell marker for monocytes?

CD14. Good for epithelioid MPs.

What helps differentiate sarcoidosis from organizing cryptogenic pneumonia, from lymphocytic interstitial pneumonitis?

CD4/CD8 ratio of bronchoalveolar lavage fluid... If >2:1 then sarcoidosis.

Anticholinergic (TCA overdose) toxicity versus Botulism toxicity

CMAP action potential is normal in TCA anticholinergic.. bc it produces muscarinic not nicotinic blockade... Botulism produces both nicotinic (diplopia, dysphagia) and muscarinic (dry mouth) blockades.. Inhibits acetylcholine release, preventing muscle contraction... Decrease in CMAP... High rate, repetitive nerve stimulation improves the deficit as the rapid depol increases calcium concentration in the preshnaptic nerve terminal helping to mobilize some Ach vesicles. Often 12-36 hours from ingestion get diplopia, dysphagia, dysphonia

How does calmodulin work?

Calmodulin helps bind free Ca2+ in all cells except skeletal and cardiac muscles... It basically works in cells w/o troponin for excitation-contraction coupling, esp in smooth muscle cells (which lack troponin)

What are some bacteria that invade gut mucosa?

Campylobacter, EHEC, Yersinia, Shigella, Salmonella

Migratory Thrombophlebitis, whatcha worried about?

Cancer... Hypercoagulability is a common paraneoplastic syndrome in visceral adenocarcinomas, esp of pancreas, colon, lung... Develops bc ACs produce thromboplastin-like substance capable of causing chronic intravascular coagulations that disseminate and migrate Known as Trousseau Syndrome. ~abnormal hemorrhage all over, maybe celiac sprue from bad Vit K absorption

How do antineoplastic proteasome inhibitors work?

Cancers can upregulate the proteasome to degrade pro-apoptotic proteins too quick.... BAX/BAK both would kill the cancer cell if not suppressed by Bcl2 family proteins Also in Bcl2 family is BAD, which forms a heterodimer w/ Bcl2 to free up BAX/BAD and cause apoptosis... Carfilozomib and Bortezomib promote BAD/BAX/BAK degradation Inhibit at the G2-M phase

Difference b/w capillary and cavernous hemaniomas

Capillary ones are small, superficial whereas cavernous are large and deeper.

What are neurophysins?

Carrier proteins for oxytocin and vasopressin from paraVentricular and supraOptic nuclei respectively.. They act as chaperone molcls as they are shuttled toward nerve terminals. Neurophysin 2 is for vasopressin.

What is aconitase?

Catalyzes conversion of citrate to isocitrate in the CAC

Where do GABA, serotonin, norepi, Ach, dopamine come from in brain?

Caudate, Raphe Nuclei, Locus Ceruleus, Nucleus Basalis of Meynert, substantia nigra

Lisinopril phsyio effects

Cause a hyperkalemia and bump in creatinine initially

What is carbon tetrachloride bad for?

Causes free radical injury... CCl4 is oxidized by P450 in liver... Results in formation of free radicals and raeacts w/ structural lipids of the memranes. Result is lipid degradation and H2O2 formation. Lipid peroxidation overall. Peroxides go on to form new radicals continuing a vicious circle. Will see CCl4 injury as ER swelling, destroyed mitrochondria, increased permeability of cell membranes.

As secretin and flow rate increase, how does this affected pancreatic secretions

Causes increased HCO3 secreted and decreased Cl secreted as flow rate increases. Na+ identical to plasma.

What determines response to leprosy?

Cel mediated immunity, Th1 positive + lepromin skin test is tuberculoid leprosy neg lepromin skin test, Th2 humoral response, higher bacterial load = lepromatous leprosy. Innate inability to recognize and mount a cellular immune response. More numerous, serious, disseminated.

What are three main causes of hyperkalemia?

Cell Lysis (rhabdomyolysis, tumor lysis syndrome), metabolic acidosis (intracellular to extracellular K+ shifts), abnormalities w/ renal excretion

What immune response takes down histo?

Cell-mediated (granulomas) ... it will spread to hilar/mediastinal lymph nodes bc tries to escape MP destruction.

What do NK cells destroy?

Cells infected by viruses

What is the difference in central and peripheral DI?

Central has low ADH and large volumes of dilute urine Peripheral has high ADH actually

How does ataxia telangiectasia present?

Cerebellar Ataxia, Telangiectasias (blanching nests of distended capillaries), increased risk of sinopulmonary infections... Also predisposed to hematologic malignancies and immune deficiecy of cell and humoral dysfx. IgA deficiency specifically Auto Rec condition due to mutation in ATM gene (ataxia telangiectasia mutated gene) is responsible for DNA break repair... Hypersensitive to XRays causing multiple chromosomal breaks.

Patient w/ endocarditis develops FNDs?

Cerebral Septic Emboli... unilateral paralysis often.

Horner's is an involvement of what in the spinal cord?

Cervical sympathetic ganglia!!!! Can happen anywhere along the sympathetic pathway to the eye... First order in the hypothalamus... axons decend through brainstem to C8-T2 (cilispinal center of Budge) at the spinal cord.. Here they synapse on second order neurons found in the intermediolateral cell column... These exit through spinal cord through anterior nerve roots and white communicating rami to reach third order neurons in the superior cervical ganglion.. Here fibers travel along carotid arteries to face/head.

Papillary Thyroid Cancer

Characterized by branching papillary structures w/ concentric calcifications (psamomma bodies). Tall cell variant has folilcular hyperplasia lined w/ tall epi cells... P/W nodular enlargement not pain/tenderness.

Sputum culture shows granule containing cells and crystalloid bodies?

Charcot-Leyden crystals... duhH! contain eosinophil membrane protein IN young patient if paroxysmal breathlessness w/o aspirin, infx, inhaled irratants, stress, exercise --> extrinsic allergic asthma.

Nursemaid's elbow?

Child comes to ER w/ refusal to move upper extremity... It is elbow extended and forearm pronated... any motion produces pain. Most likely nursemaid's elbow w/ annular ligament being displaced under the capitulum of the lateral epicondyle. Most often 1-4 years old. Sharp pull ont he hand while forearm is pronated and elbow extended. By age 5 annular ligament strong an unlikely. Reduction can be accomplished by fully supinating the forearm followed by fully flexing the elbow. A ruptured biceps tendon would actually present w/ a palpable mass in the upper arm.

Moderate PDA presentation

Childhood/Adolescence w/ lower extremity claudication, BP discrepancy, and delayed/diminished femoral pulses... Continuous murmurs/pulsatile intercostal collaterals can also develop secondary to this Congenital Aortic Coarct occurs in 10% of Turner's Syndrom patients.

Where is chloride content highest in RBCs? venous or arterial?

Chloride higher in venous blood. Chloride shift. Bicarbonate ions diffuse out of RBC into the plasma.

What is on Thayer-Martin medium?

Chocolate sheep blood agar infused with Vanc, Nystatin, Colistin, TMP Vacn pos Colistin/TMP for gram neg Nystatin for yeast

When will oxalate be high in the urine?

Chocolate, nuts, spinach all have high oxalate. Low calcium diets and intestinal malabsorption cause hyperoxaluria (as they bouth cause less calcium to bind oxalate in the gut.

Which GI lipid drug decreases LDL but increases TG?

Cholesytramine, Colestipol, Colesvelam (bile acid binding resins)

How to sample fetal DNA?

Chorionic villus sampling

What are the three gross specimen findings of Chron's?

Chron's p/w relapsing/remitting abdominal pain, diarrhea w/ or w/o blood, weight loss... 20% only colon, 80% ileum as well. CD is transmural w/ full thickness inflammation along w/ segmental. Creeping Fat - mesenteric fat wraps around the bowel. Cobblestoning (skip lesions w/ normal bowel) (elevated islands of healthy tissue are sparated from serpigionus damaged tissue) Thickening = all layers have inflammation --> hypertrophy of muscularis mucosa and fibrosis. Transmural inflammation leads to abscesses, strictures, fistulas. ~Amoebic Dysentery also has hematochezia, abdominal pain and uclerations, but ulcers are flask-shaped and smaller ~Collagenous colitis can cause chronic water diarrhea (>5-10 episodes a day).. but it is commonly in middle aged women and no bleeding/ulcerations/abdominal pain ~GVHost Diz of GI = abd pain/ulcerations but severe diarrhea >10L a day ~UColitis, obvious differences PLUS also forms pseuodpolyps (areas of granulation tissue that appear polyp like due to surrounding ulcerations)

Presentation of abdominal pain, chronic diarrhea, recent weight loss. Calcifications in epigastric area.

Chronic Pancreatitis.. Alcohol-induced secretion of protein-rich fluid can precipitate w/in the pancreatic ducts forming plugs that can calcify -->

What two diseases does Cladribine treat?

Cladribine --> hair cell leukemia and Langerhans Cell Histiocytosis Hairy Cell Leukemia.. patients p/w massive splenomegaly and pancytopenia TRAP+ (tartrate-resistant acid phosphatase) Another drug for HCL is pentostatin Langerhans Cell Histiocytosis -collective group of dendritic cell disorders... -in a child, p/w lytic bone lesions and skin rash or recurrent otitis media w/ a mass of mastoid bone -cells are functionally immature and don't stimulate T cells via antigen presentation. -cells are S-100 and CD1a positive. Birbeck Granules are characteristic

Operant conditioning versus classical conditioning

Classical is unlearned stimulus w/ unvoluntary response... Operant has punishment/reinforcement for a voluntary response and known link.

What is all included in Turner's Syndrome?

Coarctation of Aorta (5%) Bicuspid Aortic Valve (1/4) Streak Ovaries Amenorrhea and Infertility Horseshoe Kidney Cubitus valgus, broad chest, webbed neck, low hairline, short stature Premature Ovarian Failure --> high LH/FSH levels

How does Hep B virus help Hep D virus????

Coating of viral particles... Initial polypeptide assembly of HDV is designated Hepatitis D antigen... Very show, circular ssRNA... Replicatiion defective as it must be coated by external coat HepB sAg of HBV to penetrate the hepatocyte.

How are granulomas causing cavitations?

Collections of activated leukocytes releasing proteases, NO, ROS to contain the infection...

What are cholesteatomas?

Collections of squamous debris that form a round, pearly mass behind the tympanic membrane in the middle ear. They can occur congenitally or develop from infection/trauma/surgery. Primary are a result of chronci negative pressure in the middle ear causing retraction pockets int he TM that become cystic; as the squamous cell deris accumulates, it is formed. Secondary occur after squamous epithelium migrates to or is implanted in the middle ear. Cholesteatomas most commonl cause painless otorrhea. They can also produce lytic enzymes and are often discovered when they erode through the auditory ossicles causing conductive hearing loss. Can cause facial nerve paralysis of it gets big enough.

What is the term for fungus getting into TB cavities?

Colonization Invasion would be cough, hemoptysis, pleuritic chest pain, fever, extrapulmonary involvement.

Antihistamines drug action

Commonly described as H1 antagonists... but actually they are inverse agonists that stabilize the receptor in the inactive state. H1 R are on the vascular endothelium and bronchial smooth muscle where they mediate vascular permeability and bronchoconstriction, as well as CNS for alertness. 1st gen cross BBB and cause sedation. 2nd gen more specific to H1 and less BBB.

What mediates transfusion reaction immediate?

Complement mediated cell lysis from antibodies attaching. along w/ IgM and IgG attachment have NK/EOsinophil, NP and MP reactions

What happens in SMA Syndrome?

Compression of the tranvserse section of the duodenum (distally) via the SMA Narrowing of the aortomesenteric angle can occur w/ any condition that causes diminished mesenteric fat, including low body weight, recent weight loss, severe burns, prolonged bed rest. Can also occur w/ pronounced lordosis or after surgical correction of scoliosis bc procedure lengthens the spine decreasing mobility of SMA This whole thing will also compress the left renal vein as well.

Bacteria treated w/ antbx then put in isotonic solution what happens then hypotonic?

Conforms to spherule arrangement then ruptures... because the penicillin disrupts wall formation and causes sensitivity to osmotic lysis.

Baby with severely growing head circumference??

Congenital Hydrocephalus Causes = 1) Congenital Obstruction (aqueductal stenosis OR chiari malformation OR dandy walker syndrome) 2) Acquired Obstruction (congenital infection [CMV, toxo, meningitis, posthemorrhagic (intraventricular)) P/W macrocephaly, bulging fontanelle, poor feeding, DDelay, spasticity and hyperreflexia Tx is VP Shunt

What is Lissencephaly?

Congenital absence of gyri.. Severe mental retardation and seizures... Brain has smooth surface.

How does IBS present? Ulcerative Colitis?

Constipation alternating w/ diarrhea. Recurrent grossly bloody stool w/ abdominal discomfort and low grade fever... RF for colon cancer. Rectosigmoid cancer can cause hematochezia, but fever uncommon. Rectal Adenocarcinoma causes tenesmus (painful/ineffectual straining w/ defectation) and small caliber stool.

How does a PDA murmur present?

Continuous murmur w/ inspiratory splitting of S2 (left sternal border), maximum intensity as S2 Cyanotic CHD and premies are most at risk

Neonatal abstinence Syndrome

Crying, tremors, tachypnea, sneezing, diarrhea... hypotonia, seizures, vomiting, sweating Tx w/ opioids morphine/methadone. Gradually increase until symptoms controlled then wean off.

What is the antidote for serotonin syndrome?

Cryoheptadine, first gen histamine antagonist w/ nonspecific 5-HT1 and 5-HTR antagonist properties

What are the three features of celiac's histology?

Crypt hyperplasia, villous atrophy w/ intraepithelial lymphocyte infiltration, can know youre in the duodenum by the Brunner glands below the villi. p/w 6-24 months old leads to malabsorption symptoms. Also delayed puberty short stature and anemia if in adults. Screen w/ IgA anti-endomysial and anti-tissue transglutaminase antibodies... dx w/ biopsy.

What do you stain w/ mucicarmine?

Cryptococcus neoformans... Methenamine silver stain can identify them too Round cells w/ narrow based buds... Polysaccharide capsule is clear... ujnstained w/ india ink and stains red w/ mucicarmine.

Most common cause of homocystinuria

Cystathione synthase deficiency... can't make cysteine from homocysteine; therefore, need cysteine in theri diet... Leads to hypermethioninemia... Homocystinuria leads to hypercoaguability and thromboembolic occlusion and early ACS... Also get ectopia lentis (ocular lens displacement) and intellectual disability.

Whaat converts homocysteine to cysteine?

Cystathione synthase uses serine w/ vitamin B6 to make cystathione then cystathionase uses B6 to make cysteine.

What enzyme performs imprinting?

DNA methyltransferase with the help of S-adenosyl-methionine. CpG islands especiallyare silencing.

Muscle weakness, hypoglycemia, hepatomegaly, hypotonia, and short chains of glycogen... think

Debranching enzyme deficiency... aka Cori Disease Type 1 = von Gierke... HM, steatosis, lactic acidosis, fasting hypoglycemia, hyperuricemia and hyperlipidemia Type 2 = Pompe... normal glucose levels, severe CMEGALY, glycogen accumulation in lysosomes TYpe 3 = Cori = Hepatomegaly, ketotic hypoglycemia, hypotonia, weakness, abnormal glycogen w/ very short outer chains Type 5 = McArdle.. muscle phosphorylase deficiency, weakness and fatigue w/ exercise, no increase in blood lactate w/ exercise.

How does posturing work w/ brain stem damage?

Decerebrate (extensor) and Decorticate (flexor) posturings are determined based on whether the damage is above or below the red nucleus (midbrain tegmentum, pons) Below will causes Decerebrate (extensor) because of loss of excitation to upper limb flexors (via rubrospinal tract) and extensor predominance due to unopposed vestibulospinal tract output. If above the red nucleus is decorticate (flexor), due to loss of descending inhibition from the red nucleus and hyperactivity of upper limb flexors.

Why does influenza predispose to secondary infection?

Decreased cell size of epithelium and loss of cilia. Influenza surface protein neuraminidase also cleaves sialic acid off host glycoproteins, leading to more free sugar in respiratory tract. Suspect in pt w/ influenza who has worsening fever and productive cough, SOB, pleuritc cx px... S pneumo, S aureus, H flu are most common.

What is the biological mechanism behind Alzheimer's

Decreased choline acetyltransferase activity in the nucleus basalis of Meynert.

Urine of someone in DKA

Decreased pH decreased HCO3 and increased H2PO4

HOW DOES leptin work?

Decreases production of neuropeptide Y, a potent appetite stimulant, in the arcuate nucleus of the hypothalamus Stimulates production of POMC in the arcuate nucleus. Alpha-MSH is produced by cleavage of POMC and inhibits food intake. Usually mechanism in physiology is elevation in leptin chronically from enlarged fat stores --> leptin desensitization.

Norovirus or Rotavirus in childcare diarrhea outbreak?

Defs Noro... Rota has decreased due to vaccination. Esp if diarrhea watery w/o blodo/mucus bc lack of small bowel inflammation. can also get vomiting, fever, headache, malaise. Incubation is 1-2 days.

What drug do you give w/ carbapenems for them to work?

Dehydropeptidase I inhibitor = cilastatin... ... in the Kidney (except Meropenem)

What are the hyperintense lesions on T2-weighted MRI in MS?

Demyelinated plaques... HLA DRB1 predisposes

Repeated corticosteroid use on skin?

Dermal atrophy... Anti inflammation so no intraepidermal vesicles, superficial hyperkeratoses, epidermal hyperplasia, chronic inflammation (normal dermatitis eczematous).. instead have decreased ECM/GAGs w/ atrophy of CT of dermis w/ drying/cracking/tightening skin. maybe telangiectasias, mild trauma atrophic striae as well

What do NK cells do?

Destruction of cells w/ decreased or absent MHC class 1 proteins on the surface. Often virus-infected or tumor cells. Derived from lymphoid stem cells and comprise 10% of all circulating lymphocytes. Large w/ cytoplasmic granules containing perforins which produce holes in target cells then granzymes that induce apoptosis. 1. Do not express CD4, CD8, CD3. 2. Do express CD16 or CD56 3. Do not require thymus maturation and are present in athymic patients 4. Have no antigen-specific activities, do not require exposure to antigen for activation and do not possess antigen memory ability 5. Are activated by IFN gamma and IL-12

Gender in kids

Develop understanding of gender by age 3-4 and sense of permanency around 5-6. Normal for them to explore world by engaging in activities associated w/ the opposite gender. Gender dysphoria is a prolonged and intense feeling that a person's gender does not match one's assigned birth sex. More like puberty time. Increased risk of psych illness depression/anxiety

What is the underlying pathology behind ToF?

Deviation of the Infundibular Septum 1) VSD 2) Overriding aorta over RV and LV 3) RV outflow tract obstruction (extent determines severity) 4) RV Hypertrophy --> can lead to an impulse *harsh systolic murmur over mid-left upper sternal border Squatting increases SVR leading to increased blood flow to lungs and decreased right to left shunting via the VSD

What should you use w/ Ceftriaxone when treating S pneumo meningitis?

Dexamethasone to reduce levels of inflammatory cytokines to the LOS blebs. Inflammation driven by bacterial subcapsular components. leading to loosening of BBB tight junctions and vasogenic edema/elevated ICP and recruitment of leukocytes. Want to pretreat w/ dexa. Limits seizures and FNDs and death. N meningitidis and H flu DONT benefit from this pre treatment. They have less inflammation.

Pregnant woman birthing premie child < 34 weeks what improves the baby's survival?

Dexamethasone!!! This is the terminal saccular stage of development Until 33 weeks L:S is usually 1:1.. need >1.9 for mature lungs... Betamethasone, dexamethasone ahve effect of increased surfactant production and acceleration of maturation of type 2 pneumocytes... Adminstered to patients at risk of preterm labor (preterm rupture of membranes) ~MgSO4 decreases risk of premie cerebral palsy... ~Nifedipine is a CCB that results in myometrial relaxation by inhibition of MLCK phosphorylation... Terbutaline is a beta sympathomimetic that increases cAMP in myometrial cells... Both relax smooth muscle and inhibit preterm labor.

How to prevent doxycycline induced CMOP?

Dexrazoxane... chelating agent thoguht to block formation of iron-associated free radicals and inhibit anthracycline-topo2 complexes in healthy cardiomyocytes.

Fructose and Galactose disorders

Dietary fructose from fruits, veggies, table sugar, honey, processed foods... It is absorbed rapidly in bowel via GLUT5... Initially needs fructokinase, Aldolase B and triokinase.. Phosphorylated to F1P by hepatic fructokinase... F1P by aldolase B makes DHAP and glyceraldehyde... G is then phosphorylated to GA3P to enter glycolysis (done by triose kinase) DHAP converted to GA3P by triose phosphate isomerase. Aldolase B deficiency is life threatening hereditary fructose intolerance... presents when fructose enters diet... Vomiting, hypoglycemia 20-30 min after ingestion... Hypoglycemia is from intracellular accumulation of F1P and depletion of inorganic phosphate.. leading to inhibitiong of glycogenolysis and GNG... Failure to thrive, jaundice, hepatomegaly... Leads to liver/renal failure... Galactose1P UDP def = classic galactosemia.. vomiting, feeding intolerance, neonatal jaundice, hepatomegaly.. Soon after breastfeeding is when this begins... Galactokinase deficiency is a more benign disorder of galactose metabolism --> neonatal cataracts Fructokinase deficiency results in essential fructosuria, benign. Means freely excreted fructose in urine.

Drug that can provoke Prinzmetal Angina

Dihydroergotamine.. useful for acute migraine headache... Can induce vasospastic angina bc constricts vasc sm m via stimulation of both alpha adrenergic and serotonin receptors... Triptans, Cocaine/Amphetamines, Smoking are all also triggers.

Two tests for CGD

Dihydrorhodamine flow cytometry (DHR)... assesses the production of superoxide radicals by measuring conversion of DHr to rhodamine... A green compound that can be detected, if deficient in NADPH oxidase, will exhibit decreased fluorescence. NBT or nitroblue tetrazolium testing involves adding NBT to a sample of patients neutrophils. Properly functioning neutrophils produce ROS that can reduce the yellow NBT to dark blue formazan that precipitates w/in cells.

Varicose Veins, tell me more tell me more

Dilated, tortuous veins involving superficial venous drainage of the leg. Increased intra-luminal pressure or loss of vessel wall strength can lead to venous dilation and failure of venous valves. Back flow of blood that results exacerbates venous HTN and has vicious cycle of venous congestion most common in patients >50 years old and prolonged standing, obesity, pregnancy. Often familial. Complications = edema, stasis deramtitis, skin ulcerations, poor wound healing, infection. NOT PE

What is the initial step in the pathogenesis of infective endocarditis?

Disruption of normal endocardial surface... Most commonly areas of maximal turbulence in preexisting valvular leaflets... Atrial Surface of Incompetent AV valves OR the ventricular surface of incompetent semilunar valves... Fibrin and platelets serve as the foci for infection.

Genital Herpes and post herpetic neuralgia

Doesn't happen, that is VZV HSV2 is most common genital herpes... Causes inguinal LAD as well, along w/ fever, itchy painful vesicular genital rash. Rash w/ vesicles, ulcers, crusting. Sacral dorsal root ganglia become reactivated w/ recurrent genital lesions... Recurrence tends to be localized and less severe due to humoral immunity.

Inherited Disorders and their CV developmental defects

Downs = endocardial cushion defects (ostium primum atrial septal and regurgitant AV valves) DiGeorge = Tof Fallot, interrupted aortic arch Friedreich Ataxia = HCMOP Kartagener Syndrome = Situs inversus Marfan = Cystic medial necrosis (aortic dissection/aneurysm), MV prolapse Tuberous Sclerosis = valvular obstruction due to cardiac rhabdomyomas Turners = Aortic Coarctation, Biscuspid aortic valve

What is the PaCO2 target for patients w/ cerebral edema receiving hyperventilation?

Drop in PaCO2 helps w/ vasoconstriction decreasing ICP. Can cause local cerebral perusion decrease that can sometimes worsen neurologic injry... PaCO2 > 30 still If CSF maintains high ICP, then can displace CSF into the thecal sac (sheath of dura mater w/ CSF that surrounds the spinal cord)

What is the Smooth ER function?

Drug detoxification Lipid, phospholipid, steroid synthesis

What does high eosinophil count mean in the context of kidney problems?

Drug-Induced Interstitial Nephritis

Nmeunonic for pancreatitis drugs?

Drugs Causing A Violent Abdominal Distress Didanosine, Corticosteroids, Alcohol, Valproic Acid, Azathioprine, Diuretics (Furosemide, HCTZ)

Stress urinary incontinence w/ pregnancy mechanism

Due to increased intraabdominal pressure... Common in pregnancy... Increase in plasma volume rise in GFR (mediated by hormone relaxin), greater volume of urine yielded by this and leads to increased urinary frequency. From unchanged bladder volume from before and compression by fetus... Gravid uterus and maternal weight INCREASE intraabdominal pressure.. also pregnancy hormones decrease urethral tone and relax pelvic floor muscles (levator ani and coccygeus)... these normally function to maintain continence.

What can diabetics develop w/ xanthelasms?

Due to insulin resistance --> promotes increased VLDL, can get type IV or V HLD (increased VLDL, CM) and or secondary diabetic dyslipidemia w/ elevated LDL chol an dlow HDL chol. when testing patient for lipid disorders also test for daibetes. MP w/ vacuolated foamy cytoplasm containign cholesterol, phospholipids, TGs in xantehlasmsas

Patient w/ COPD started on supplemental O2 get encephalopathic/confused

Due to oxygen-induced hypercapnia... normally pulmonary vasoconstriction at poorly ventilated areas.. but high O2 leads to vasodilation of all of lung, even poorly ventilated areas. That way, can't push CO2 off, so end up decreasing affinity of hemoglobin for CO2 w/ oxygen but not blowing CO2 off, leads to increased blood pCO2 and decreased minute ventilation due to high O2. (o2 dominant receptors in COPD) All thanks to an increase in physiologic dead space. and reduction in total alveolar ventilation. V/Q mismatch.

What are the two most important factors for preventing catheter infections?

Duration of catheterization is most important... Use sterile techniques when inserting and remove when no longer needed.

Effect of solubility on the onset of gas anesthetics

During anesthetic induction w/ a gaseous agent, the partial pressure of the anesthetic rises in the blood until it reaches its partial pressure in inspired gas. At this point, no more anesthetic can dissolve and anesthetic is saturated... The speed at which blood becomes saturated depends on solubility. Highly soluble anesthetics dissolve easily in the blood, thus larger amounts must be absorbed before blood become saturated Blood solubility of an anesthetic is indicated by blood/gas partition coefficient... Higher blood solubility have larger blood/gas partitioning coefficients. N2O is poorly soluble, w/ B/G ~0.47. N2O blood partial pressure rises quickly and plateus, indicating total blood saturation.. .If higher solubility and higher blood/gas coeff then takes longer. Speed of induction is determined by rate at which brain tissues take up the agent, which is dependent on solubility of the anesthetic in blood. If an agent has poor blood solubility, the amount of gas needed to saturate blood is small and brain saturation occurs quickly. Conversely high soluble take more input and delayed saturation of CNS> Halothane is a highly soluble gas.

Fun fact about ApoB synthesis

During synthesis of ApoB-containing lipoproteins, microsomal transfer protein functions as a chaperone protein necessary for proper folding of ApoB and participates in transfer of lipids to newly formed CM and VLDL Loss of function mutation in the MTP gene. 1st year of life p/w foul-smelling stool and abdominal distension. Labs have low lipoproteins... ADEK... leads to RBCs w/ no essential fatty acids to be acanthocytes w/ thorny projections.

What adverse effect most worried about w/ beta-lactams?

Dyspnea, HypoTN, Tachycardia all suggest anaphylactic shock... Hypotension occurs in anaphyactic shock secondary to collapse of PVR, increase in permeability and leakage of capillary fluid. Stimulation of sm m tone of bronchial wall and increase in bronchial secretions --> dyspnea in anaphylaxis... Increase GI smooth muscle tone leads to vomiting, abdominal cramps, diarrhea Epi treats this by alpha1 counteracting dilation and increasing BP... Epi increases cardiac output too. Beta2 for bronchodilation. Don't use steroids bc not acute effects

How does Lesch-Nyhan present?

Dystonia, Choreoathetosis, self-mutilation, hyperuricemia all w/in first few years of life. Deficiency fo Hypoxanthine-Gunaine Phosphoribosyltransferase (HGPRT)... Deficiency means purine synthesis must compensate

How do you know the difference b/w E coli and Enterobacter?

E coli is indole positive because both are fast fermenters

What do E6 and E7 mess up in the cell?

E6 binds p53 leading to ubiquination and degradation so that the cell cannot halt growth to repair damaged DNA and trigger apoptosis E7 binds Rb and displaces bound transcription factors, promoting unregulated DNA replication and cyclin-mediated ell cycling.

What disease is tested for w/ heterophile antibodies and can cause lymphoma?

EBV... can also cause post-transplant lymphoproliferative disorder in allograft recipients It is Paul-Bunnel test in sheep antibodies It is Monospot test in horse antibodies Has a reactive lymphocyte

Difference b/w schizotypal and schizoid

Eccentric; odd thoughts, perceptions, behaviors vs. prefers to be a loner, detached, unemotional

what determines potency and binding affinity in a graph of effect and conc?

Efficacy is the intrinsic ability of a drug to elicit an effect. It is a measure of maximum ceiling of activity of a drug... Potency, though, dose of drug that is required to produce a given effect... Affected by affinity of the drug for its receptor and amount of drug that is able to reach the target tissue. Drugs that bind w/ higher affinity or are better able to gain access to target tissues have better potency. ED 50

How can infective endocarditis mess with the kidneys?

Elevated Cr and Proteinuria w/ hematuria.. It is a renal insufficiency due to a nephritic syndrome... Complicated by deposition of circulating immune complexes in the glomerular capillary wall - > GNephritis. Capillary wall thickening w/ subendo and subepi deposit formation. Hypercellularity may be seen in post strep GN or membranoprolif GN

Menstural Cycle on Progesterone for 10 days testing amenorrhea

Endometrial glands become more elaborate w/ more progesterone and the spiral arteries coil.. Exogenous intake for ~10 days matures the lining. When endometrium is no longer exposed (w/ withdrawal), PG production increases leading to vasoconstriction of the spiral arteries. Progesterone w/drawal also causes increased secretion of metalloproteases by endometrial stromal cells (to degrade ECM and also to cause apoptosis of endometrial epithelium) Overall is degeneration of functionalis layer.

What binds delta and mu- receptors?

Enkephalins, Endorphins, Dynorphins are all endogenous opioid peptides that are part of the body's naturall ocurring opioid system. These are released in response to noxious stimuli and bind to different receptors to allow physiologic modulation of pain. Mu, Delta, Kappa, N/OFQ R are all opioid receptors. Morhpine and Hydromorphine produce therapy by binding to mu receptors and modulating pain perception. Endogenous opiods play a large role in GI, endo, autonomic, emotional function. Beta endorphin is one endogenous opioid peptide that is derived from propiomelanocortin (POMC)... POMC also Goes through enzymatic cleave and modification to produce ACTH and MSH

Treatment for DVT during pregnancy

Enoxaparin or Dalteparin (LMWH) preferred bc long half life (4.5hours) and no lab monitoring... Renally cleared though don't use in reanl failure patients w/ Cr cl <30 Unfractionated hep (1-2 hours) is monitored w/ PTT and less useful... It may be used in those w/ renal insufficiency though... Used at 37 weeks and on too because can be discontinued at labor. Direct thrombin inhibitors, and warfarin not reccommended in pregoo. Clopidogrel/aspirin no role in acute VTE treatment.

What protozoan causes bloody diarrhea?

Entamoeba histolytica

What parasites cause enteritis?

Entamoeba histolytica (blood diarrhea w/ liver abscess).. giardia (protozoan non bloddy, frothy, putrid diarrhea), cryptosporidium (mass water diarrhea in HIV patients)

What organism has stacked brick intestinal adhesion?

Enteroaggregative e coli (EAEC)... Adhere to human jejunal, ileal, colonic mucosa and do not invade. Implicated in persistent diarrhea in infants in developing countries.

Difference b/w ergot and non-ergot

Ergot = bromocriptine, nonergot is pramipexole and ropinorole... ergot means derived from fungi.

What is the other name for Parvo?

Erythema Infectiosum... bright red rash on cheeks w/ circumoral pallor and fever... generalized reticular rash on arms/legs/trunk Acute arthropathy --> dults --> symmetric polyarthritis esp proximal IPs, MCPs, knee and ankles... Self-limited and non destructive.. Caused by immune complexes and usually happen when there is very little viremia. Very reduced infectivity here.

What cell uses glycolysis to produce no ATP?

Erythrocytes... 1,2BPG is converted to 2,3BPG (by bisphosphoglycerate mutase) bypassing the ATP generating step... Then 2,3BPG undergoes BPG phosphatase reaction to become 3-phosphoglycerate w/o generating ATP... 1,2BPG to2,3BPG is increased in hypoxia and chronic anemia. 2,3BPG serves to allosterically decrease hemoglobin's affinity for O2... Lower blood O2 concentrations means higher 2,3BPG levels w/in erythrocytes and release of O2.

How does extramedullary hematopoiesis present in the spleen/liver?

Erythroid precursor cells in clumps... EPO stimulated hyperplasic bone marrow invasion of other organs... Mostly chronic hemolytic anemias (like beta thalassemia) Thins bony cortex and impaired bone growth.. So many pathologic fractures.. Also get maxillary overgrowth and frontal bossing (chipmunk facies)

What causes hepatic steatosis in alcohol abuse?

Even if acute and short term a lot, due to decreased free fatty oxidation. TG accumulation w/in HC cytoplasm... Secondary to excess NADH production by the 2 major metabolism enzymes (alcohol dehydrogenase and Aldehyde DHD) Also impaired lipoprotein assembly and secreiton and an increase in peripheral fat catabolism. liver will show cytoplasmic vacuoles. In frozen section see lipids w/ oil red O or sudan black

What feature of hyperthyroidism is a beta blocker not going to fix?

Exophthalmos. This responds to glucorticoid therapy... Fibroblasts and adipocytes of orbit get TRAb and activated t cells. Fibroblasts secrete excess GAG elaeding to expansion of ground substance of retro-orbital tissues. Displaces eye forward.

Where is the mutation in Fragile X syndrome?

FMR1 gene, CGG repeats... Located on the long arm of chromosome X. When cells of affected individuals are cultured in folate-deficiency medium, area of increased repeats does not stain and appears broken. so fragile X. DDelay first, then macrocephaly, long narrow face, prominent jaw/chin/ears. Macroorchidism also.

When do VzV vesicles pop up?

Face, trunk limbs crusting w/in 6 days of onset... VZV vaccine is recommended to all children 12-18 years old

What is the most common thrombophilia?

Factor V Leiden 1-9% of population. Glu -> Arg near Protein C cleavage site for coag factor V. recurrent DVT, cerebral vein thrombosis, recurrent pregnany loss

Hypercoaguable state in a young patient, what is the most common cause?

Factor V leiden... not lupus or anything weird.. Inherited disorders are most common in patients < 50 w/ throboses of any obvious explanation for prothrombotic state. Plasma is resistant to normally antithrombotic effects of protein C, think factor V leiden... 2-15% of caucasians carry a specific factor V leiden mutation... 20% w/ abnormal venous thromboses have FVLeiden. ~Phospholipid antibody syndrome have prolonged aPTT... Lupus anticoagulants are the reason.

What is pulsus paradoxus?

Fall in systolic BP >= 10 mmHg on inspiration, JVD, tachycardia all point to cardiac tamponade. suspect Ctamponade on anyone w/ triad of muffled heart sounds, JVD, hypotension. During inspiration, pressure inpleural space and lung interstitium decreases increasing pulmonary vascular capacitance... This causes a fall in venous inflow to the heart... leads to a fall in venous inflow to the heart leading to decreased LV strok evolume and drop in systolic BP... this is exacerbated in tamponade due to extrinsic compression of ventricles... This acts to equalize left and right ventricular diastolic pressures allowing the septum to bulge into the left ventricle.. Further reduces stroke volume Conditions w/ PP constrictive pericarditis, COPD, asthma, PE ~Tension Pneumo... similar presentation, but absent breath sounds and hyperresonance to percussion on affected side ~Hemothorax... blunt or penetrating chest trauma could cause hemorrhagic hypotension, tachycardia/pnea. But absent breath sounds and dullness to percussion would be found.

What are the three causes of hernias?

Femoral = weakness of femoral canal Direct = weakness of transversus abdominus Indirect = Failure of processus vaginalis to close

What enzyme turns nonheme irone F3+ into Fe2+?

Ferrireductase in the gut lumen Also hepcidin inhibits transfer of iron from MPs that engulf RBCs and enterocytes that take up w/ DMT1 and secrete to blood w/ ferroportin1. Iron can choose to stay in enterocyte as ferritin bound, will eventually get excreted in stool as cells slough. All cells have transferrin receptors to take up circulating iron/transferrin complex when needed.

What two things cause polyhydramnios?

Fetal GI obstruction or anencephaly OR high fetal cardiac output (parvo, fetomaternal hemorrhage, alloimmunization) Basically impaired swallowing OR increased fetal urination *Maternal diabetes and multiple gestations cause mild polyhydramnios* Anencephaly is a NTDefect

Features of Kawasaki's disease....

Fever for >= 5 days + 4 of the following: 1) B/L non-exudative conjunctival injection (erythema) 2) cervical LAD > 1.5cm 3) Mucositis: erythema of palatine mucosa, fissured erythematous lips, strawberry tongue 4) extremity: edema of hands/feet, erythema of palms and soles, desquamation of fingertips 5) Rash: polymorphous ertyhematous on extremities that spreads to trunk Can lead to CA thrombosis or aneurysm

What are the many manifestations of lupus?

Fever, fatigue wt loss Symmetric, migratory arthritis Skin = butterfly rash/photosensitivity Serositis = Pleurisy, pericarditis, peritonitis Thromboemoblic = antiphospholipid/vasculitis Neuro = cognitive dysfx/seizures Labs = hemolytic anemia, TCP, leukopenia Hypocomplement ANA, AntidsDNA, anti-Smith Renal = proteinuria/ elevated creatinine. Basically normally a type 3 HSN, but can form antibodies against RBCs to become type 2... Autoimmune hemolysis formation of warm IgG antibodies. Spherocytosis, positive direct Coombs and extravascular hemolysis. SLE assc thrombocytopenia is also a thing... Antibodies against platelets.. Leukopenia can occur due to antibody mediated destruction on NPs, but less common.

What drug of CV actually inhibit rate limiting enzyme in bile acid synthesis and leads to more gall stones?

Fibrates = gemfibrozil... promotes gall stoens They inhibit cholesterol 7 alpha hydroxylase which leads to more cholesterol secretion

What drugs when used w/ statin cause myopathy ?

Fibrates >>>>> niacin and ezetimbe too though

Finasteride vs. Flutamide

Finasteride =>5alpha reductase inhibitors Flutamide = Androgen R binding inhibitor Use of long acting GnRH agonists as constant stimulation to treat prostate cancer (Leuprolide) can lead to rise in LH/T. As a result, antiandrogens are sometimes prescribed concurrently to limit tumor-stimulating effects Flutamide is a competitive T R inhibitor...

What is a common side effect w/ lisinopril regarding CV system?

First dose Hypotension and reflex tachycardia as well. Most likely to occur in patients w/ already high renin activity (such as those w/ volume depletion from other diuretic use or HF) Initiation of ACE leads to abrupt removal of vasoconstrictive effects of Ang2, resulting in decreased PVR and drop in BP. Start at low doses and titrate upward.

Schizophrenia vs. Schizoaffective vs. Atypical Depre/Bipolar w/ psych

First figure out if mania aligns only w/ mood symptoms... if does Depr/Bipolar w/ psych.. if not, then one of the schizos.... If there are significant mood symptoms of mania or depression, then schizoaffective (schizophrenia lacks these)... also schizoaffective needs a history of at least one 2 week episode w/o significant mood disturbance. Basically mania + hallucinations or delusions.

Major motions of hip and muscles responsible...

Flexion = iliopsoas, rectus femoris, tensor fascia lata Extension = gluteus maximus, semitendinosus, semimembranosus, biceps femoris (long head) Abduction = gluteus medius/minimus Adduction = adductor brevis, longus, magnus

Equation for reduced flow from change in resistance?

Flow = P1-P2 * r^4 all divided by viscosity*L If flow decreases by 16 times, then radius decreases by 2 times

Bursa knee pain

Fluid-filled synovial sac that serves to alleviate the pressure/friction at bony prominences and ligamentous attachments throughout the body... Bursae are vulnerable to injury from acute trauma or chronic repetitive pressure and also may become inflamed due to infection (septic bursitis), crystalline arthropathy, or autoimmune conditions.. Point tenderness is typical. Often swelling or erythema if a superficial bursa. Activate ROM is decreased or painful but passive ROM is normal (less pressur eon bursa) Repetitive anterior knee trauma from kneeling has features of prepatellar bursitis... B/w patella and overlying skin (carpet layers, mechanics, plumber) Anserine bursitis... medial knee and well defined tenderness 4cm distal to the anteriomedial joint margin of the knee... obesity/overuse in athletes Popliteal (baker) cysts = gastrocnemius or semimambranous bursa.. Due to extrusion of synovial fluid from knee into bursa in patients w/ OA or inflammatory joint disease Suprapatellar bursa is anterior b/w femur and quads. Often direct blow to distal thigh or prolonged/reptitive quad acticity/running

How would you describe Meckel's Diverticulum?

Forms due to incomplete obliteration of the omphalomesenteric duct that connects the midgut lumen and yolk sac cavity... Variety of tissues found here (pancreatic, gastric, colonic, jejunal, duodenal, endometrial). Can produce acid --> ulceration and lower GI bleeding... Often p/w painless melena. Can also get inflammed --> p/w acute appendicitis. Ectopy (also called heterotopy) is a term that IDs microscopically and functionally normal cells/tissues found in an abnormal location due to embryonic maldevelopment. ~Metaplasia is replacement of one type of epithelum w/ another type not typical for location. Unlike ectopia, metaplasia occurs during adult life and is a phsyiologic compensatory response. Increases cancer risk in degrees. ~Dysplasia is a change such as pleomorphism increased size of nucleus, loss of cellular orientation, loss of original tissue characteristics. (sign of malignancy)

What factors determine ratio of regurgitant to forward flow in MV regurge?

Forward Flow --> pressure in aorta/SVR Backward Flow --> mitral valve orifice size during systole and degree of Left Atrial Compliance.

Para-Aminohippuric acid, what's that tubular fluid/plasma concentration look like???

Freely filitered at glomerulus into Bowman's space; however, majority is secreted by PT via carrier-mediated activated transport... Not reabsorbed at any portion of the nephron. At bowman's space, conc is similar to plasma, but just keeps rising because water leaves. At PT secreted and Water reabosrbed shoots up... Increases at desc limb w/ loss of more water, tubular fluid more dilute later but that's Na/K/Cl selective, not PAH selective.

What is the fastest monosaccharide to be digested?

Fructose 1 phosphate type pathways... After Fructose becomes F1P via fructokinase and then GAldehyde and DHAP via Aldolase B.... Glyceraldehyde leads via triokinase to GA3P BYPASSING PFK1 a major regulatory step. Therefore, fructose is metabolized by the liver faster.

What causes amenorrhea in an exercising girl?

Functional Hypothalamic Amenorrhea Excessive weight loss/strenuous exercise/chronic illnes/eating disorder --> decreased adipose tissue/fat reserves --> decreased leptin production both decrease GnRH decreasing LH/FSH decreasing estrogen from ovaries.

G6PD enzyme problem

G6PD --> 6-phosphogluconate antimalarials, sulfonamides, infection, fava beans causing oxidative stress. P/w hemoytic anemia

What is the mutation of sickle cell disease?

GAA --> GTA OR GAG --> GTG. Glu to Val at position 6 of beta globin chain. Missense mutation

Can't fall asleep because feeling on edge, muscles are tense and chronic worrying....

GAD so treat w/ SSRI or SNRI. The distress is causing the no sleep. Acute relief w/ alparazolam but these are second line therapy due to risk of dependence/tolerance. Also potential for rebound and withdrawal symptoms. Don't use any benzos in history of Substance Abuse Disorder.

What are Reed-Sternberg cells derived from?

Germinal Center, B lymphocytes (neoplastic)

Acute Serum Sickness

Get a drug, then come in 10 days later w/ joint pain and pruritic skin rash. Skin bx w/ fibrinoid necrosis and NP infiltration of small blood vessels. Immune complex w/ complement activation. Also usually p/w fever.. timeline is 7-14 days. LAD and proteinuria can also occur. Deposition of IgG and or IgM complement fixing antibodies leads to localized complement consumption... Chimeric monocloncal antibodies (rituximab, infliximab) or nonhuman immunoglobulins (venom antitoxins) or someitmes, penicillin, cefaclor, TMP-SMX) Serum sickness causes release of C5a at sites of complex deposition, this leads to marginalization and neutropenia as a result. Also can cause TCP from platelet consumption.

How does Rhabdo get into the body, also what does it do to the neck? What neuro symptoms?

Gets in via Nicotonic Ach R on muscles... causes severe, painful throat spasms w/ food.. has hallucinations/disorientation/fever/agitation Will have hydrophobia = severe avoidance of water.. and pharyngeal spasms w/ pupil dilation and hypersalivation. ~EBV gets in via CD21 aka CR2 ~Rhinovirus via ICAM1 aka CD54 ~CMV gets in via cellular integrins

How do glucocorticoids and levothyroxine effect bones?

Glucocorticoids (chronic or recurrent) is needed in patients w/ rheumatoid arthritis, increased risk of osteoporosis... They increase osteoclast activity by increasing differentiation and decreasing osteoblast activity and synthesis of bone matrix also inhibit intestinal calcium absorption Hyperthyroidism/over-replacement of thyroid in patients w/ hypothyroidism increases bone turnover --> osteoporosis. Under treatment is not associated w/ osteoporosis

How does glucose get into adipose cells.

Glucose almost always travels from higher conc outside cell to lowrer inside, but cannot simple diffuse across cell membrane, needs a carrier protein. Transport w/ carrier proteins requires a conformational change when substrate is transported, unlike channel proteins. GLUT proteins are stereoselective and preferentially catalyze the entrance of D-glucose rather than L-glucose. Glut4 is the insulin-sensitive transporter found in sk m and adipocytes. GLUT4 is stored in cytoplasmic vesicles until insulin says jump to the membrane.

What converts GA3P to 23 BPG?

Glyceraldehyde 3 phosphate dehydrogenase

What do high levels of prolactin suppress and why is that a worry for women w/ prolactinomas?

GnRH leading to reduced LH and FSH and leading to hypogonadism... Leads to oligo/amenorrhea, galactorrhea, decreased bone density men = infertility, decreased libido, impotence If nonfunctioning can have bitemporal hemianopsia, headache, hypopituitarianism.. Estrogen maintains bone mass... Low estrogen lead to increased inflammatory cytokines (esp IL1 and TNFalpha) increasing expression of RANKL and increasing osteoclast activity... Loss of estrogen overal leads to osteoporosis.

What are the three stages of genitalia development?

Gonadal... primordial germ cells originate near yolk sac and move to the genital ridge, forming primitive gonads consisting of germ cells, supporting cells and steroidogenic cells. Under SRY, male gonads secrete testosterone and MIF Ductal stage: male embryo, MIF causes PMN regression while MN duct develops into SEED... In female, T and MIF are not there, so PMN (mullerian) becomes uterine tubes, uterus, cervix, upper vagina from materanl estrogen. and MN regresses. Genital stage: genital tubercle develops, urogenital folds transform. Genital swellings (labioscrotals), urogenital sinus as well.

How do you treat Graves Disease?

Graves is weight loss, palpitations, tachycardia and significant ophthalmopathy (proptosis, diplopia)... Triggered by thyrotropin R antibodies which bind and activated TSH receptor... TSH R is also present on the fibroblasts, adipocytes and other cells... Graves opthalmopathy is caused by stimulation of orbital fibroblasts by thyrotropin receptor antibodies, leading to deposition of GAGs... accompanied by T cell activation and inflammatory infiltration... Pushes globe forward and EOM restriction along w/ diplopia Glucocorticoids decrease peripheral T4 to T3 conversion but their anti-inflammatory effects improve Graves Ophthalmopathy... They also can prevent worsening of ophthalmopathy induced by radioactive iodine treatment. Don't use antithyroid drugs in Graves' Beta blockers would improve lid lag of eyes (caused by any hyperthyroidism) but not the diplopia/proptosis.

Atrophy of hypothenar eminence w/ normal triceps reflex. Where is the injury?

Guyon's Canal

What bugs cause acute otitis media in children 6mo-2yrs?

H influenzae and S pneumo Strains of H flu that don't produce a capsule are referred to as nontypeable. These are part of normal upper respiratory tract flora but can also produce otitis media, sinusitis, bronchitis. Most acute otitis media from children are this way Vaccination against H flu is w/ protein-conjugated HiB vaccine, confers immunity for type B strain. Recommended in all children 2 months to prevent HiB bacteremia, pneumonia, epiglottitis, meningitis If no vaccine... Complement C3b binds the capsule polysaccharide but serum factor H is bound as well, which degrades C3b If antibodies, then they bind and protect C3b but also provide FcReceptors for degradation.

What unexpected symptoms come along w/ separation anxiety disorder?

HAs, Stomach Aches, Nausea, repeated nightmares involving separation >=4 weeks in children and >= 6 months in adults.

What is a scary side effect of loop diuretics?

HF and CKD presentation, start on loop diuretics first line... Inhibition of similar NaK2CL symporters in inner ear can cause ototoxicity = tinnitus, vertigo, hearing impairment, deafness. It happens in higher doses, w/ CKD, rapid IV... or when used w/ other ototoxins like AGs, salicylates, cisplastin. Symptoms are reversible but hearing impairment may be permanent.

How does HIV entry work?

HIV uses CD4 as the primary receptor and chemokine receptor CCR5 as a coreceptor. Both are bound by gp120. After this, HIV enters.

Risk Factors for Cervical Cancer

HPV 16,18,31,33 Hx of STDs Early onset Sexual Activity Multiple/High Risk Partners Immunosuppression OCPs Low SES Tobacco Use

How to treat acute delirium w/ psychosis in elderly?

Haloperidol used at low doses minimal side effects. Only use benzo in elderly for delirium due to alcohol or benzo withdrawal

Physicians who realize they're being studied alter their behavior, what effect?

Hawthorne Effect

How do hemoglobin types migrate on electrode?

HbA migrates toward positive electrode anode quickly (negative charge)... HbS has a nonpolar valine replaces a negative glutamate, so decreases negative charge causes it to move more slowly toward anode. HbC has a glutamate residue replaced by lysine (positive) in beta gloin chain... even less negative charge so even more slowly than HbS... both S and C are missense mutations.

How is heart located in mediastinum to stab injuries?

Heart lies behind the sternum, most anterior is RV... inferior portion of the heart is the ventricles, and connects w/ central diaphragm tendon... Posterior surface of heart is LAtrium ~Azygos lies right of midline and posterior mediastinum drains blood from posterior intercostal veins to SVC.

IL12 Deficiency

Helper T cells unable to differentiate into Th1... wihtout these, no IFN gamma for macrophage activation... Activated MPs necessary for delayed HSN rxns and cytotoxicity against intracellular organisms... These patients suffer from severe mycobacterial infections IFNgamma nd IL12 make native CD4 into Th1.. which secretes IFNgamma, IL2, lymphotoxin Beta and also uses IFNgamma to suppress TH2 cells TH2 cells induced by IL4 and secrete IL4,5,10,13 and suppress TH1 w/ IL4/10 TH1 is for cell-mediated response, activating MPs and cytotoxic T cells. TH2 for activating B cells and class switching

What does the humoral response of antibodies toward influenza jump against?

Hemagglutinin is generally most important for protection. These antibodies neutralize the virus and block its binding to host cells. Antibodies to neuramindase are not the main source of protection against infection although they are protective (decrease extent of shedding and invasion)

Which diseases causes heart, pancreas, liver, skin pigmentation?

Hemochromatosis NOT Wilson's Disease... High iron GI absorption causes an iron overload... DM is also a factor, impotence, arthropathy, cardiac dysfx/enlargement, hepatomegaly, abdominal pain, skin hyperpigmentation (esp sun-exposed aireas)... Bronze Diabetes. >50% transferrin saturation w/ elevated ferritin and serum iron.

Paroxysmal Nocturnal Hemoglobinuria

Hemolytic Anemia, Hypercoaguability, Pancytopenia Infxs and Surgeries trigger exacerations. Caused by mutation acquired... in a PIGA gene w/in a clonal population of multipotent hematopoietic stem cells. Gene involved in the synthesis of the GPI anchor (glycosylphosphatidyl anchor)... Necessary for attachment of several cell-surface proteins, including CD55 (decay-accelerating factor) and MAC inhibitor protein (CD59) Overall lack of GPI leads to complement mediated hemolysis. More often at night bc complement activity is increased during sleep due to low pH. Patients also get thrombotic complications, likely due to release of free HgB and prothrombotic factor from lysed RBCs and platelets PNH --> aplastic anemia and pancytopenia. Flow cytometry for diagnosis

Hep B versus Hep C in sexually active aptient w/ skin and joint symptoms

Hep B causes skin and joint symptoms, elevated transaminase levels... DNA HepB virus incubates over 30-180 days. Onset is nonspecific but get a serum sickness-like syndrome w/ lymphadenopathy as well... the pruritical urticarial vasculitis is also present. Non icteric hepatitis usually... If icteric then will have elevated bilirubin. Impaired hepatic synthetic function, as indicated by long PT means poor prognosis... Most important early marker is HBsAg...

Graft versus Host disease presentation from transplanted liver

Hep C person gets new liver, and then a week later has n/v/abdominal pain, bloody diarrhea and painful maculopapular rash all over neck, back extremities w/ palms and soles can happen esp after allogeneic bone marrow transplant. Often immunodeficient already, so donor T cells from graft survive and migrate to host tissues where they recognize host MHC antigens as foreign and become sensitized. Skin, liver, GI tract most affected... Early sign is the diffuse maculopapular rash including palms/soles that may desquamate. GI involvement always diarrhea. Donated liver wouldn't be significantly affected here.

Which Hep causes fulmanant hep in pregnant women?

Hep E... ununeveloped ss RNA virus (fecal-oral spread)

Gilbert's What is the deal?

Hepatic Metabolism occurs in 4 stages 1. Uptake from bloodstream 2. Storage w/in hepatocyte 3. Conjugation w/ glucuronic acid 4. Biliary Excretion Normally Serum Total Bili is 0.2-1, usually <0.2 of which is direct fraction. Elevated conjugated bilirubin --> hepatobiliary disease (conjugated bili will reflux back into plasma when bile is slowed. If elevated unconjugated, then usually due to increased formation of bilirubin (hemolysis or slowing in conjugation (Gilbert) This is a disorder of glucorindidation. Production of UDP glucuronyl transferases (enzymes that gluronidate) are reduced. 9% of Western country people are homozygous for this 30% hetero. No apparent liver disease w/ mild unconjugated hyperbilirubinemia provoked by triggers... 1) hemolysis 2) fasting 3) physical exertion 4) fever 5) stress 6) faituge Dubin-Johnson is conjugated chronic hyperbilirubinemia. Direct of at least 50% otherwise normal liver.

What are some things that cause Fanconi Syndrome? Lots

Hereditary Defects... Wilson's, tyrosinemia, glycogen storage disorder, cystinosis Ischemia MMyeloma Nephrotoxins = ifosfamide, cisplatin, tenofovir, expired tetracyclines, ead poisoning

In essential fructosuria, what compensates for metabolism of fructose?

Hexokinase... converts fructose to fructose 6 phosphate.. instead of F1P of fructokinase

Why use sublingual not oral isosorbide dinitrate?

High first-pass metabolism...

Why can you get infected so many times w/ Neisseria Gonorrhea?

High variability of microbial antigenic structure!! It does form IgA and IgG antibodies, the highly variable surface antigens (LOS, Opa proteins, Porins) limit effectiveness.

What is the effect of obstructive lung diseases on the lungs?

Higher TLC, RV and higher RV/TLC ratio... indicating air trapping. Airway resistance is smallest when lungs are inflated due to radial traction of pulmonary tissue, so COPD patients minimize resistance by being hyperinflated

Where is an injection that causes hip drop of right side when left foot is on the ground when walking? Where at?

Hits the gluteus medius, minimis so that they cannot contract, and this will happen if the injection happens at the superiomedial buttocks... want to give butt injections in the superiolateral buttocks. TO avoid the superior gluteal nerve. (L4-S1) Leaves pelvis through the greater sciatic foramen above the level of the piriformis. What should you target in these injections? Von HOchstetter triangle... Palms on greater trochanter, fingers splitting anterior superior iliac spine. Ventrogluteal injection ideal.

IBD/colitis-associated colon cancer vs sporadic cancer...

Hits yonger, has falt lesions (non polypoid) that are the origin of dysplasia, happens proximal > distal esp w/ CD, multifocal, mucinous or signet ring cells/poorly differentiated cells compared to rarely mucinous/well differentiated, also have early p53 late APC compared w/ early APC late p53. Up to 30% of IBD patients develop CRC. Risk proportional to severity and duration. Give regular colonscopies to IBD patients.

What makes up Guyon's canal and what makes it worse?

Hook of Hamate & Pisiform Bone... after passing here, the nerve divides into a superficial branch --> medial 1.5 digits and hypothenar eminance AND deep motor branch supplies intrinsic muscles of the hand Most commonly injured at the elbow (funny bone) or fx medial epicondyle or nerve compression (resting on a hard surface).. injury p/w sensation/paresthesia in that distribution. Severe cases = weak wrist flexion, adduction.. finger abduction/adduction.. flexion of the 4th/5th digits

Which lipase maintains ketones in times of starvation?

Hormone sensitive lipase. In adipose tissue catalyzes the mobilization of stored TGs into free fatty acids and glycerol. Activated in response to stress hormones. Which increase Gs to cAMP to PKA and phosphorylation of HSL. Inhibited by insulin.

What is in a lung hamartoma?

Hyaline cartilage, fat, smooth muscle, respiratory epithelium, calcifications. Usually p/ a solitary lung nodule, incidental on xray.

How is serotonin formed?

Hydroxylation and decarboxylation of tryptophan by tryptophan hydroylase.

Scurvy, where does defect impact the cell.....

Hydroxylation of Proline and Lysine at rough ER... prolyl hydroxylase and lysyl hydroxylase... Vitamin C is the cofactor. . Impaires triple helix stability and covalent cross link formation.

Which drugs can cause a megaloblastic anemia?

Hydroxyurea, Pheyntoin, Methotrexate, Sulfa Drugs

What does gastrinoma do to parietal cells?

Hyperplasia and enlargement of gastric folds... (trophic effect)

Serotonin Syndrome Presentation

Hyperthermia Autonomic Instability Rigidity Myoclonus/Tremors Encephalopathy Diaphoresis

What would cause systolic anterior motion of the mitral valve?

Hypertrophic CMOP.

How does urea blood and urea urine levels indicate disease?

Hyperuricemia and Hyperuricosuria caused by gout, Lesch-Nyhan, Tumor lysis Syndrome, Myeloproliferative disorders.... Hyperuricosuria w/ Normouricemia is due to high protein diet. Hyperuricosuria predisposes to calcium stone formation because the uric acid stone precipitates as a nidus for calcium deposit

Receiving blood what electrolyte abnormality can occur?

Hypocalcemia because of citrate anticoagulant that blood is stored with... It chelates calcium... >5-6L of blood this is more likely over 24 hours.

What is supine hypotension syndrome?

Hypotension, Pallor, Sweating, Nausea, Dizziness that occur when a pregnant woman lies supine. Left lateral decubitus and sitting/standing resolve. >20 weeks gestation and due to gravid uterus compression and obstructing the inferior vena cava. Reduced preload lowers CO... Can lead to loss of consciousness and even fetal demise.

How does initial PE affect blood gasses?

Hypoxemia ensues... this stimulates respiratory drive, however, hyperventilation cannot improve blood oxygenation.. .CO2 is only partially removed and increases in ventilation cause more CO2 to be extreted leading to hypocapnia... pH alkalotic, PaCO2 down, PaO2 down, acute HCO3 no change

Which drugs casue hypothyroidism?

I AM SUddenly Lethargic... Amiodarine Sulfonamides Lithium

Which factors recruit neutrophils?

IL8, C5a, LtB4 Pus is a thin, protein-rich fluid, known as liquor puris and dead leukocytes, mostly neutrophils. IL8 induces phagocytosis in neutrophils once they have arrived.

CFTR mutations...

If a mutation affects an axons, it will be detectable via mRNA sequencing.. complementary DNA cDNA is ds DNA that is synthesized from an mRNA template.. 28 base pair deletion means runs further on a gel electrophoresis... 28 change means frameshift, duh!!.

What immunoglobulin prevents infection by parasites?

IgA actually does... CD4 helper T cells help as well... Prevents binding of trophozoites and impairment of adherence to upper small bowel mucosa.

Don't give patients w/ IgA deficiency blood w/ IgA

IgE antibodies against IgA. fatal anaphylaxis.

Which antibody crosses the placenta?

IgG... IgM does not, and that is the antibody seen in ABO

What happens at the cellular level in megaloblastic anemias???

Impaired DNA synthesis... Pancreatic insufficiency is also associated w/ vitamin B12 deficiency as pancreatic enzymes normally cleave R factor from B12, allowing B12 to bind IF and be absorbed.

Why does liver appear black in Dubin-Johnson Syndrome?

Impaired excretion of epinephrine metabolites that accumulate w/in lysosomes... Usually high direct hyperbilirubinemia 2-5mg/dL but other routine tests are normal. ~Gillbert/Crigler-Najjar have high unconjugated (indirect) bilirubin

What is the first step for working up malabsorption?

Impaired intestinal absorption of nutrients... May p/w diarrhea and steatorrhea (bulky, foul smelling stools w/ visible oil droplets and greasy toilet ring)... More often patients though, have non specific symptoms like wt loss, fatigue, vague abdominal discomfort. Commonly due to: defects in pancreatic secretions (CF/Chronic pancreatitis) Mucosal Disorders (celiac, IBD) Bacterial Overgrowth (GI surgery, abnormal motility) Parasitic Diseases Lipids are the most complex digestive pathway. Fats are earliest and most severely affected in generalized malabsorption. Testing for fat is the most sensitive strategy for screening. Qualitative Assay of Stool w/ Sudan III stain can quickly ID unabsorbed fat and confirm this. (stool should normally have no unabsorbed fat)

Asympatomatic patient w/ Anti Hep A viral titers?

In children age < 6 yeras old, HAV is subclinical/silent 80%... anicteric bc no jaundice observed. Typically more severe disease in adults >70% symptomatic w/ jaundice... Some develop an aversion to smoking!!

How does Listeria effect pregnancy?

In patients w/ impaired cell-mediated immunity --> meningoencephalitis In pregnant women in 3rd trimester.. get flu-like symptoms and intrauterine infection leading to preterm labor and neonatal sepsis.

How does tertiary hyperparathyroidism present?

In primary, Ca elevated but does not suppress PTH due to autonomous gland function. In CKD, pTH release may become independent of Ca2+ due to chronic parathyroid stimulation.. PTH remains elevated despite VitD and Ca2+ supplementation.

Where does the lowest osmolarity occur in the presence of ADH?

In the beginning of the Distal Convoluted Tubule!! ~100... then gets more concentrated as it goes... can end as high as 1200 hits bottom of medulla in limb at 1200 as well Comes in PTubule as 300 and this absorption is isotonic ADH stimulates V2 Receptors on principal cells of collecitng ducts, activating cAMP dep G protein system to insert aquaporin 2 into the apical membrane. **Distal Convoluted Tubule is IMPERMEABLE to water ADH only works on the collecting duct

Where does transketolase work?

In the cytosol... Uses B1 to shuttle 2-carbon fragments b/w sugar molcls. `3-Hydroxy-3-methylglutaryl-CoA is HMGCoA lyase... it is mitochondrial OTC is mitochondrias Pyruvate Carboxylase is mitochondrial

Why is the CFTR channel impaired?

In the phe508 version... Normal CFTR allows Cl ions to move out of the cell when ATP binds CFTR has impaired ATP binding and blocks chloride ions, creating sticky mucus build up. Technically CFTR pore opens after binding of 2 ATP molecules. p/w chronic cough, recurrent pneumonias, pancreatic damage.

In the Ras-MAPK pathway, what are the two states of activity?

Inactive Ras is bound to GDP... G GTPases help it bind GTP then that activates RAF which activates MAP kinase kinase... but when it is becoming inactive, Ras burns GTP w/ G activating protein to become GDP... Ras is activated when a GF binds tyrosine kinase

What are the two categories of ADHD symptoms?

Inattentive = difficulty focusing, distractible, no listening to instructions, disorganized, forgetful, loses objects Hyperactive = fidgety, unable to sit still, driven by a motor, hyper talkative, interrupts, blurts out answers Before age of 12, 2 settings

What drug can prevent gynecomastia in men? what drugs cause it?

Increased estrogen/androgen ratio causes it.. leads to ductal epithelial hyperplasia and stroma fibrosis Increase E from cirrhosis/obesity Decreased T from CKD/hypogonadism Medications = A) decreased A = GnRH agonists, ketoconazole B) decreased DHT = 5alpha reductase inhibitors C) inhibited androgen R = spironolactone/bicalutamide Tx w/ tamoxifen Danazol is a synthetic steroid w/ androgenic and antiestrogenic effects. It may improve gynecomastia in patients w/ hypogonadism but can lead to rapid growth of prostate cancer and would not be appropriate.

How does hyperthyroidism affect response to catecholamines?

Increased sensitivity to catecholamines due to the thyroid hormone-mediated upregulation of beta-adrenergic receptors. esp on the heart.

What does methylphenidate do?

Increases availability of norepi and dopamine. Increase release of norepi and dopamine from vesicular storage sites and blocking norepi and dopamine reuptake at synpases in frontal cortex. Amphetamines work the same way.

How does being started on an ARB and HCTH change your blood levels of something you monitor to measure compliance?

Increases renin activity!! ARB means a feedback increase in serum renin. Also Diuretic induced hypovolemia leads to decreased renal blood flow which increases renin

Haldane effect

Increasing Pressure O2, increases the binding to hemoglobin, which kicks off CO2 and H+ in the lungs. In peripheral tissues, Bohr effect is high H+ adn CO2 promote binding to deoxyhemoglobin and release of O2.

Kid w/ right sided scrotal enlargement that is present since birth and imcreases when he cries or strains to pass a bowel movement. No pain

Indirect Inguinal Hernia Normally the processus vaginalis is obliterated as testicles descend from retroperitoneal and a spermatic cord connects tunica vaginalis and scrotum to area above; however, if patent processus vaginalis, then small intestine can pooch down to scrotum above testicles If opening is small, may just get fluid leakage --> hydrocele. If large enough, indirect inguinal hernia will develop. In indirect inguinal hernia, intestine is within spermatic cord In direct inguinal hernia, intestine is outside spermatic cord and has pushed through peritoneum

Ethanol is dangerous w/ APAP because

Induction of cytochrome P450 enzymes that activate APAP to be a hepatotoxic metabolite

NFKappaB intracellular

Inflammatory cytokines, bacterial product, mitogens all activate I kappa B kinase, which phosphorylates IkappaB... When phosphorylated, I kappa B is ubiquinated and removed for proteolytic destruction which releases NFkappaB and thi is now activated...

What interleukin correlates closely w/ severity of GCA?

Inflammatory infiltrate of GCA is lymphocytes (CD4 positive T cells) and MPs and multinucleated giant cells... Production of cytokines, esp IL6 closely correlates w/ disease severity... Tocilizumab is effective at treating GCA.. IL6 monoclonal antibody

What is a presentation of neurocysticercosis?

Ingestion of Taenia solium (pork tapeworm) eggs excreted in feces of human carriers. Common in C/S america, Africa, Asia... takes months-years and causes seizures, FNDs, intracranial HTN... Dx is CT/MRI of cysts and scolex... will have eosinophilia and increased ESR Tx w/ albendazole (fluid-filled larval cysts surrounding the invaginated scolex (head of tapeworm))

What is the optimal site for a femoral nerve block?

Inguinal crease at the lateral border of the femoral artery. This will also anesthetize the saphenous nerve.

How does Gabapentin work?

Inhibits downstream presynaptic VG calcium channels, which prevents fusion and release of NT vesicles

The different effects of TCAs

Inhibits reuptake of norepi and serotonin and used in treatment of depression. They also though, inhibit fast channel conduction, slowing myocardial depolarization and leading to cardiac arrhythmias, most common cause of death in these patients.

Where are catheters/central lines usually placed

Inserted into the neck of the internal jugular vein or chest subclavian vein and is advanced to SVC, which is embryologically derived from the common cardinal veins.

Insulin vs. NPH

Insulin peaks quicker, starts working in 30 minutes, peaks in 2-4 hours, done by 5-8 hours NPH peaks at 6 hours lasts 18 hours

Where is the AV node?

Interatrial septum near opening of coronary sinus and septal leaflet of tC valve

What are symptoms of hemorrhoids

Internal hemorrhoids... above dentinate line (columnar epithelium)... autonomic innvervation from inferior hypogastric plexus... only sensitvie to stretch External hemorrhoids, below dentate line covered by squamous and have somatic innervation by pudendal nerve. Branches of pudendal supply the perineum and external genitalia in males... sensitive to touch, temperature, pain... Asymptomatic usually but can become painful.

Postpartum hemorrhage due to uterine atony... Failure to contract and compress placental site blood vessels... RF = prolonged labor and twin gestation... Boggy uterus... what blood vessel do you ligate?

Internal iliac arteries... B/L ligation (suturing) should stop uterine blood flow... preventing need for hysterectomy.. Uterus has collateral w/ ovarian arteries, which maintain function after ligation. First line to stop bleeding is uterine massage, uterotonic medications. External iliac becomes femoral artery

How does kidney look in chronic analgesic nephropathy?

Interstitial inflammation, fibrosis, tubular atrophy, papillary necrosis/scarring and calcification. Happens if analgesics taking in large doses over extended periods of time.

Difference b/w PAH and inulin in the tubules?

Inulin is 100% freely filtered, then not messed with PAH is 100% freely filtered, then secreted maximally by the renal tubules so that all is gone by the end of the kidney, all that reaches the kidney is gone.

Who to supplement breastfed infants?

Iron if preterm/low birth weight Vit D if breastfeeding only, lack of sunlight, dark skin pigmentation Vit K given at delivery bc not in breastmilk either. 7-dehydrocholesterol --> VitD3/2 by UVB

What are the two main ribulose-5-p pathways?

Irreversible G6PD route Nonoxidative, reversible transaldolase and transketolase route.

Random Features of GCA

Ischemic Optic Neuropathy is the risk Causes the giant cells also, but also inflammation of the media w/ fragmentation of the internal elastic lamina jaw claudication is extreme jaw pain w/ chewing

What happens to Bicarb w/ DKA?

It actually buffers the excess ketoacids so bicarbonate level falls immediately. There will also be a compensatory respiraotry alkalsois which lowers CO2 partial pressure. Will be acidotic w/ low CO2 and low HCO3

What is neprilysin?

It is the metalloprotease that cleaves and inactivates BNP, glucagon, oxytocin, bradykinin... New drug inhibits this. This will promote natriuresis and decrease BP by vasodilation if inhibited. HF therapy targeted at 2 things 1) RAAS 2) Sympathetic stimulation.

Why use primaquine w/ chloroquine when treating malaria?

It prevents disease relapse Every 48 hour fever = Vivax/ovale or falciparum... all species share a similar life cycle. 1) innoculation w/ Anopheles mosquito 2) travel to liver to infect hepatocytes/replicate 3) lysis of infected hepatocytes releases merozoites into the bloodstream 4) Merozoites go on to infect erythrocytes and cause erythrocyte lysis to hit more... Vivax/Ovale cause latent hepatic infection (exo-erythrocytic cycle) in the form of hypnozoites, responsible for relapses... That is what primaquine kills. ~Retinopathy is an adverse effect of long term chloroquine use.

Presentation of babesiosis

Ixodes tick so NE US... p/w fever, fatigue, myalgias, headache, flulike symptoms... Labs = anemia, TCP, increased LFTs. Blood smear has intraerthrocytic pleomorphic ring forms and sometimes maltese crosses.

Treating syphillis you worry about what?

Jarish-Herxheimer reaction... fever, chills, HA, myalgias At antibiotic initiation, this spirochete infection (sypihllis, Lyme, leptospirosis as well) leads to systemic inflammatory response... Rapid lysis of spirochetes releases bacterial lipoproteins into the bloodstream and triggers a strong innate immunologic response. Most are self-limited and don't require intervention.

3 stages of nevus?

Junctional Nevus = in epidermis only Compound both Intradermal only dermis

What is ARPexposed?

Know the RR of risk factor, they ask what the attribution to the total disease burden of people w/ RF is actually due to RF??? impact of a risk factor.. ARPexposed = 100 * [risk in exposed - risk in unexposed]/risk exposed OR ARPexposed = 100* [RR-1]/RR where RR = risk in exposed/risk unexposed

Distinctions of LEMS from MG

LEMS have hypo/areflexia, autonomic symptoms, classic incremental response to repetitive nerve stimulation`

Tubular proteinuria

LMW proteins (beta-2-microglobulin and immunoglobulin light chains) are normally filtered by the glomerulus and reabsorbed at PT. This condition occurs when PT function is disrupted (for ex tubulointerstitial nephritis) Overflow proteinuria when one protein produced in excess so it is filtered (MMyeloma or rhabdomyolysis w/ myoglobin)..

What causes rise in FSH during menopause?

Lack of feedback from Inhibin.

What condition has defective GH receptors?

Laron dwarfism.... Can have GH gigantisism w/ normal TSH levels. Child w/ taller, oily skin, long limbs.

What are the major hypothalamic nuclei for food?

Lateral = hunger Ventromedial = satiety

What does subacute combined degeneration take out?

Lateral corticospinal tract (spastic paresis) and dorsal columns (vibration/proprioception) also causes megaloblastic anemia and pancytopenia if due to Vit B12 def (usually) Also takes out spinocerebellar tracts (ataxia) Can also get atrophic glossitis (shiny, smooth, erythematous tongue)

What do both the infraspinatus and teres minor do?

Lateral rotation

How to dx crypto w/o stain?

Latex agglutination test.

Difference b/w atypical legionella and mycoplasma pneumonia

Legionella = diarrhea, high fever, lobar infiltrate Myco is interstitial infiltrate

What is the best indicator of mitral stenosis (MS)?

Length of time between S2 (specifically the A2 component from aortic valve closure) and the opening snap.. OS occurs due to abrupt tensing of the valve leaflets as mitral valve reaches its maximum diameter during forceful opening.. AS MS worsens, LA pressures increase due to impaired mvmt of blood into the LV... Higher pressure causes the valve to open more forcefully; as a result A2-OS interval becomes shorter as LAP increases

When doing LP, you will traverse through the X ligamentum to reach the spinal canal?

Ligamentum flavum NOT the posterior longitudinal

33 year old man w/ 3 mo history of muscle weakness and cramping. Appear shortly after he begins exercising. CK is increased. After forearm muscles are exercised, venous blood obtained from antecubital vein shows lactate concentrations that do not increase compared to normal values.

Likely a deficiency is glycogen phosphorylase (because can't break down glycogen in response to exercise and raise lactic acid)

Patient 3week old boy w/ clear-straw colored discharged from umbilicus and erythema around it... Also has small redducible umbilical hernia...

Likely a persistent allantois remnant. Complete failure of obliteration of urachus = patent urachus... Failure to close distal part of urachus would have been urachal sinus (purulent umbilical discharge due to recurrent infection) and failure of central part would be a urachal cyst. ~LAD involves decreased expression of neutrophil cell-adhesion proteins, beta-2 integrins. Neutrophils are less adherent to vascular endothelium and fail to migrate toward infected sites. Delayed separation of the cord > 1 month.

What organ is not likely to be infarcted w/ embolus from LAtrium?

Liver (has both portal vein and hepatic artery to supply it. If hepatic artery occluded, portal venous supply and retrograde arterial flow from accessory vessels (inferior phrenic, adrenal intercostals) takes over for liver parenchyma. UNLESS the liver is transplanted, then biliary tree infarction and organ failure because the collateral supply is severed during transplanation

What causes gynecomastia in alcoholic patients and why is it there?

Liver cirrhosis --> gynecomastia... arises from hyperestrinism due to increased adrenal gland production of androstenedione w/ aromatization to estrone and eventual conversion to estradiol Estradiol induces SHBG production (primarily in the liver), but also uterus and testes... Leads to increased testosterone binding and a decreased free testosterone/estrogen ratio. Impaired estrogen metabolism by the liver also contributes Leads to spider angiomata, testicular atrophy w/ decreased body hair.

What defect do you expect w/ fibular neck fracture?

Loss of sensation to the dorsujm of the foot. Also eversion. Deep peroneal has dorsiflexion. Most common injured is the common peroneal nerve here.

Low Potency and High Potency anti-psychotics

Low = sedation (histamine block), anticholinergic, orthostatic hypotension (alpha1 block) High potency = acute dystonia, akathisia, parkinsonism Low = chlorpromazine, thioridazine High = haloperidol, fluphenazine

When do cells sickle?

Low O2, acidemia, dehydration... sickled cells can't pass through microvasculature. They impede blood flow --> microinfarcts. Organs where blood moves slowly (spleen/liver) are predisposed to low O2 and acidity... also organs with higher demand (brain/muscles/placenta) ~2,3 BPG binds the 2 beta globin chains and stabilizes the T deoxyhemoglobin form... This decreases O2s affinity to O2 and facilitates O2 release at the tissue level...

Patient w/ HTN, HCholesterolemia, w/ a TIA should be started on

Low dose aspirin... Good for BP control, statin therapy, prevent ischemic stroke... Irreversibly acetylates/inhibits the COX enzyme (predominanetly COX1), preventing platelet synthesis of TXA2 (impairs aggregation) GI bleeding risk bc... 1) inhibition of platelet aggregation 2) impairment of PG dependent GI mucosal protection... Increases w/ higher doses but icnreased 2-3 fold w/ low dose... PPIs can help reduce risk of upper GI bleeding int hese patients.

What is the difference b/w low and high grade tumors in function?

Low grades are morphologically similar and architecturally similar to normal cells in the tissue of origin. Moderate grade in the middle High grade lack most features of original tissue Anaplastic... complete lack of differentiation Analplastics have the following features: 1) loss of cell polarity w/ complete disruption of normal tissue architecture (coalesce into sheets/islands) 2) Complete Variation in size/shape of cells = pleomorphism 3) Disproportionately large nuclei (high N/C) that are often hyperchromatic (deep-staining) w/ abundant coarsely-clumped chroamtin and large nucleoli 4) Numerous mitotic figures 5) Giant, multinucleated tumor cells

How does RSV present

Lower Respiratory Tract disease (bronchiolitis, pneumonia) in infants. Older children and adults can develop in close quarters, but really peaks in winter months.

Which lobe does primary TB usually hit?

Lower lobe... passed via respiratory droplets Carries to ipsilateral hilar lymph nodes --> Ghon complex = combo of these and lower lobe. In 95% of patients CD4 cells control the infection by forming mature phagolyosomes to kill intracellular mycobacteria and differentiating into cells that wall of TB in granulomas.

What can celiac due to Calcium and P levels?

Lower vit D due to fat vitamin malA leads to decreases in both... also high PTH further decreases P

What genes code for epidermal growth factor receptors?

Lung ERBB1 Breast ERBB2 (HER2/neu) Ovarian Gastric Tumors

What words would you use to describe Burkitt Lymphoma??

MPs and apoptotic bodies in a sea of medium-sized lymphocytes It is a very aggressive, high grade lymphoma... Responds well to short-term, intensive high-dose chemo. Excellent prognosis if limited disease. *overexpression of n-myc in neuroblastoma

Where is elastase contained in MPs and NPs? What about other pro and anti proteinases

MPs lysosomes... Azurophilic (primary) granules of NPs... Protineases = elastase, Cathepsin G, MMPs Anti-Proteinases = Alpha1-Antitrypsin, Alpha2-Macroglobulin, TIMPs

What are the eye and heart manifestations of Marfan's Syndrome?

MV prolapse and lens displacement

Progression of GP160 in cell?

Made in T cell RER, heavily glycosylated at Golgi then cleaved and exported as GP120 and gp41. Envelope proteins that mediate attachment.

Depression w/ psychiatric symptoms versus shizoaffective?

Major depression that develops psychotic features during the depressive episode.. Delusions/hallucinations are commonly mood congruent w/ depressive themes, although mood incongruent psychotic symptoms can occur... The diagnosis is differentiated from psych disorders becase... Psych symptoms are ONLY present during the episode of major depression. Important to distinguish as depression w/ psych needs antidepressant, antipsychotic and possibly ECT. ~schizoaffective is differentiated from MDD w/ psych by presence of delusions/hallucinations >=2 weeks in the absence of a major mood episode.

What is the capsule of GABHS what is the major virulence factor?

Major virulence is protein M... it inhibits phagocytosis and activation of complement. M proteins are on the surface and are antigenic... Capsule is made of hyaluronate, which is ground substance of humans so can't have an antigenic response to that!!

What nerve is jacked up in external otitis?

Majority of external ear is C2,C3 from great auricula rnad lesser occipital and auriculotemporal (V3) Inside is auricular branch of vagus and branch of facial Posterior part of external auditory canal as well as concavity and posterior eminentia of concha is innervated by vagus nerve. Vasovagal syncope after stimulation of this nerve.

Wernicke's what is destroyeeeed

Mamillary Bodies... ... Part of the Papez Circuit, for limbic system, which helps control emotion/memory Fornix could also be damaged but less likely Lesion to corpus callosum = alexia w/o agraphia Inferior colliculus is part of auditory pathway

How does Takayasu Arthritis present?

Maybe granulomas... Affects aortic arch, some of its branches (coronary/renal) in 1/3... Predominantly in females <40 years old. If there are giant cells in the aorta, distinguished usually based on age!! May also have lower BP and pulses in UExtremeties compared to cold/numb lower extremities

Confidence interval for 95%from the mean...

Mean +/- 1.96* (SD/squareroot of n) Will give 68%, 95% and then 99% 99% would be 2.58 68% would be 1.00

CNS tumor staining for synaptophysin

Means it has a neuronal origin. Rare and less than 15 of tumors. Majority are glial, meningiomas, pituitary adenomas. Gliomas + for GFAP... astrocytomas, glioblastoma multiforme, oligodendrogliomas, ependymomas, peripheral neural sheath tumors.

4 year old boy w/ high fever, nasal discharge, cough for 3 days... Came from Mexico, unvaccinated... B/L conjunctival injection and small white spots w/ erythematous base on buccal mucosa

Measles... Koplik spots... Spares palms and soles rash causes primary measles pneumo Secondary bacterial infections Encephalitis in days, ADEM in weeks, SASPanEncephalitis in years

How do ovulation predictor kits work?

Measures urinary LH positive 24 hours before ovulation... Once oocyte is released from ovary, sperm may fertilize it for up to 24 hours. Morula at 3 days Blastocyst at day 4 Implants at day 6 blastocyst and outer cell mass (trophoblast) differentiates into cytotrophoblast and syncytiotrophoblast. SCT invade the endometrial tissue 6-7 days after fertiliation and starts secreting beta hCG. Serum Beta-hCG most sensitve method (<5IU/L)... urine needs 20IU/L usually 14 days out

Where is the mass in SVC syhndrome?

Mediastinum not superiorsulcus/pancoast... Leads to headahces, dizziness, confusion, cerebral edema, swelling of face/neck, dilated collateral veins in upper torso causes 1) lung cancer 2) NHL

What part of the airway has the highest resistance to airflow?

Medium sized bronchi... trachea higher than bronchioles and termianl bronchioles almost zero resistance. Upper respiratory tract (nasal, mouth, pharynx, larynx) accounts for ~1/2 of total airway resistance... The remained is split b/w the 23 generations of airway on the way down... Highly turbulent airflow is the reason for high medium sized bronchiole airway resistance. Drops in lower generations because summated cross sectional area massively increases as you go up, this slows veloity altering low resistance laminar airflow to predominant in airways <2mm in diameter.

BPPV vs. Meniere vs. Vestibular neuritis

Meneire = increased pressure/volume of endolymph... recurrent vertigo, ear fullness and pain, unilateral hearing loss and tinnitus BPPV = otoliths in semicirular canals... nausea, vertigo brief episodes brought upon by head movement... NO auditory/tinnitus symptoms Vestibular neuritis = inflammation of vestibular nerve (viral or postviral)... single episode that lasts days... severe vertigo!! NO hearing loss

3 exocrine secretion types

Merocrine... cells secrete via exocytosis... salivary/eccrine sweat/apocrine sweat Apocrine... secrete via membrane bound veiscles.. mammary glands Holocrine... cell lysis.. .sebaveous and meibomian

How do you know when tumor is mets or primary brain? how does glioblastoma look

Mets is multiple well-circumscribed masses at the junction of gray and white matter Glioblastoma happens in cerebral hemispheres and can extend across corpus callosum. Their mass effect can also cause a midline shift. They typically are soft, poorly defined, with areas of hemorrhage and necrosis. Patients usually die w/in a year

What are the M cells of the peyer patch?

Microfold cells.

What is a Leukocytoclastic Vasculitis?

Microscopic Polyangitis Microscopic Polyarteritis HSN Vasculitis... all have fibrinoid necrosis of small vessels (arterioles, capillaries, venules)...

Patient w/ fixed/dilated pupils, where is the injury in the brainstem?

Midbrain (will see loss of gray-white matter differentiation w/ anoxic brain injury) upper midbrain specifically... Normal pupillary response depends on optic nerve to transmit light to midgrain at level of superior colliculus, where it is recieed by pretectal nucleus, sends to EW nucleus which send via CN3 to ciliary ganglion and eye in case of light in, pupillary reflex, postganglionic fibers innervate sphincter pupillae and constrict pupil. Pons is doll's eyes reflex

Opioid intoxication affect on BP and HR?

Miosis, Bradycardia, Hypotension (due to histamine release). Decreased bowel sounds also common.

Drugs used for pregnancy termination

Misoprostol = PG E1 agonist Mifepristone = PG antagonist, GC antagonist Methotrexate = Folic acid antagonist. Mifep leads to necrosis of the uterine decidua and prevents 1st trimester pregnancy development. Miso is a cause of cervical softening and uterine contraction to expulsion pregnancy.

What beta lactam can be used on a patient w/ a true penicillin allergy?

Monobactams, more specifically, aztreonam -aztreonam specifically binds penicillin-binding protein 3 (words well w/ aminoglycosides) Esp useful in patients w/ renal insufficiency who can't receive aminoglycosides but resistant to pip tazo

Best treatment for bipolar disorder?

Mood stabilizers = lithium, valproate, and 2nd gen antipsychotic quetiapine. Lamotrigine as well, better for depression than mania. Don't use antidepressant monotherapy. Lithium --> DI, hypothyroid, tremor, ebstein anomaly Valproate --> hepatotox/ NTubeDef Carbamazepine --> aplastic anemia, SIADH, nTubeDef Lamotrigine --> benign rash and SJS

What to use for treatment of malaria in africa?

Most are chloroquine-resistant, so mefloquine can be used... Others are atovaquone-proguanil and artemisinins.

How do atrial myxomas present?

Most common primary tumor, often in the left atrium Lead to murmur mimicking mitral stenosis (mid diastolic rumble).. Obstruction leads to dyspnea, lightheadedness, or syncope... Obstructive symptoms influenced by position... Lying down alleviates the problem whereas sitting up makes it worse... Myxomas can produce cytokines that lead to constitutional symptoms like fever/weight loss Will have mucopolysaccharide stroma and abnormal blood vessels. Would see vegetations not a "mass" on echo for IE

What type of membrane we talking about on CMV?

Most viruses bud through the membrane of the host cell; however, herpesvirus (CMV included) bud through and acquire lipid bilayer envelope from the host cell nuclear membrane.

How does methadone reduce cravings?

Mu opioid receptor agonist... for chornic pain control and opioid withdrawal/maintenance... Long half life w/ sustained effects after chronic dosing and suppresses cravings/withdrawal symptoms for >= 24 hours... Good bioavailability from oral... Potent opioid agonist w/ high affinity for opioid receptor which blocks euophoric effects of other opioids and accounts for potent analgesic effects... Adverse = QT prolongation and respiratory depression

What neoplasm of pancreas has columnar mucinous epithelium?

Mucinous Cystic Neoplasms

What are the three saprophytic fungi?

Mucor, Rhizopus, Absidia.... transmitted by inhalation and cause mucormycosis. Mucormycosis hits paranasal sinuses, causes periorbital HA, purulent nasal discharge. Have nonseptate, 90 degrees angles.

What histology would you expect in VZV? What causes eosinophilic cytoplasmic inclusions and a rash?

Multinucleated giant cells w/ intranuclear inclusions Pox virus --> molloscum contagiosum.

Piriformis Syndrome

Muscle injury or hypertrophy can compress the sciatic nerve to cause sciatica-like symptoms in buttocks and nerve distribution)... Muscle can be tender w/ deep palpation or on stretching w/ adduction and internal rotation

Classic Nerve Injury Presentations

Musculocutaneous = loss of sensation of lateral forearm and paralysis of forearm flexors at the elbow Axillary dug Median = palmar sensory loss (majority of digits 1-3). Motor deficits in wrist flexion/abduction, flexion of 2nd and 3rd digits, flexion/opposition of the thumb. Radial Nerve = loss of sensation over posterior arm/forearm, dorsolateral hand, dorsal thumb. Wrist drop from lack of extensors.

Normal proteins of Lynch

MutS detects a mismatch on new strand,distinguished from parent strand by occasionalnicks in phosphodiester bonds, MutL homolog recruited and complex slides along DNA molecule until 1 of the daughter strand nicks is encountered. At this point. Exonuclease 1 loaded and activated by repair complex. Daughter degraded backward past initial mismatch point, leavinga gap of ssDNA that is stabilized by ssDNA binding protein. DNA pol fills in, DNA ligase 1 seals nicks.

Familial Amyloid Polyneuropathy

Mutation in TTR gene --> misfolding and ECT deposition of transthyretin protein (prealbumin), causes FAP or FA cardiomyopathy

How does MSH2 lead to cancer?

Mutation in this DNA mismatch repair enzyme leads to Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

What is histology of HTCMOP?

Myocyte hypertrophy w/ large transverse diameter of myocytes and haphazardly arranged myocyte bundles... Interstitial spaces are promiment, maybe fibrosis Major cause of sudden cardiac death under stressful situation in young healthy individuals... Sarcomere proteins are messed up, maybe thick or thin filaments... 50% are familial... Autosomal Dominant w/ variable expression

NO role in local coronary blood flow autoregulation

NO is the most important. Adenosine also super important... NO is created and released by endothelial cells in the coronary vasculature. Synthesized from arginine by eNOS and released in response to NT, platelet products, thrombin, histamine, bradykinin, endothelin. Also in response to pulsatile stretch and flow shear stress in coronary arteries. It is the major regulator of flow-mediated vasodilation in large arteries

Does raising HDL improve CV outcomes?

NOOOOO, only LDL and HMG_CoA Reductase inhibitors

Which common enteric pathogen can be transmitted from domestic animals to humans?

NOT GIARDIA, S aureus, Shigella, Bacillus, Vibrio Parahem ONLY campylo of these Initial watery diarrhea later bloody --> abdominal cramping, tenesmus, leukocytes in stool.

SOB w/ exercise and also jaundice....

NOT Gilbert... bc duh dude, gilbert doesn't cause SOB... it's gotta be something that combines, them, liver + lung think A1AT

In aortic regurge, what maintains CO?

NOT increased concentric hypertrophy, actually just increased stroke volume. LV dilation caused by increase in LV end diastolic volume --> eccentric hypertrophy (ventricular wall lenghtening due to addition of myocardial contractile fibers in series). Overtime, this is overwhelming from increased wall stress. Leads to LV failure.

1st line for acute gouty arthritis in ED

NSAIDS... then colchicine... then glucocorticoids (esp last if DM patient)

What pathogen can cause tenosynovitis and pharyngitis?

Neisseria gonorrhea.

Ampho B has what serious side effect that can cause PVCs?

Nephrotoxicity leading to hypokalemia and hypomagnesemia. due to increased permeability of distal tubule.

Co-morbidities w/ Down Syndrome

Neuro = disability, early AlzDis Cardio = AV SD, VSD, ASD GI = duodenal atresia, hirschsprung Endo = hypothryoid, DM1, obesity Heme = Acute leukemia Rheum = atlantoaxial instability *AD due to extra copy of amyloid precursor protein

What is the most important contributor to air-fluid levels in cavitations?

Neutrophils recruited from systemic circulation by chemokines and activated by microbial molecules and opsonizing factors. Activated NPs release cytotoxic granules (lysosomes) containing MPO and digestive enzymes. However, these also cause significant damage to parenchyma, causing liquifying necrosis of lung tissue and abscess

Shigella gimme some facts dawg

Never a component of normal bacterial gut flora See sheet I made Fecal Leukocytes and occult blood. Fecal cultures grow non-lactose fermenting, gram negative rod on MacConkey. Ferments glucose w/o gas, no generation of H2S when grown on triple sugar iron agar, cannot replicate at refrigeration temperatures. Non-Motile

What three pathways from NAD+?

Nicotinamide adenine dinucleotide+ 1. Tryptophan --> NAD+ via the kynurenine pathway 2. Niacin --> NAD+ 3. Nicotinamide --> NAD+ NAD+ can undergo redox rxns to become NADH (via ATP synthesis for ex) OR NAD+ can have ATP added to make NADP+ and undergo reactions to form NADPH (reductive biosynthesis) fatty acids.

What are nitrates metabolized to?

Nitric Oxide and S-nitrosothiols via mitochondrial aldehyde dehydrogenase w/in vascular smooth muscle cells. Eventually cGMP leads to dephosphorylation of myosin light chains and causes relaxation Nitrates work primarily on large veins, where smooth muscle relaxation leads to venodilation and increased venous capacitance... Preload is reduced. Leading to reduced LV end diastolic volume and left wall stress. Decreasing O2 demand.

Patient w/ HIV/AIDS and headaches that lead to major seizure, but no travel to S/C america

No Neurocysticercosis because no travel to S/C america... no TB if no travel to developing countries or jail/hospital time Most likely Toxo... Gives multiple lesions... Extensive pet exposure is not essential for diagnosis bc can be transmitted through contamineda foods.

Does porcelain gallbladder always present w/ a clinical syndrome?

No sometimes, just an incidental CT finding!! Calcification and thickened gall bladder wall Potential manifestation of chronic cholecystitis, often associated w/ multiple gallstones. Due to dystrophic intramural deposition of calcium salts in the setting of chronic inflammation. Grossly, a bluish, brittle, thick gall bladder wall w/ crunchy feel. Increases risk of adenocarcinoma of GB

Can line of best fit/aka r be >1?

No... that's the slope, not r.... !!!

What is the most common calcium presentation of someone with a stone?

Normocalcemia, hypercalciuria... 80% of all stones are calcium stones (calcium oxalate or phosphate).. Hypercalciruia is the most common risk factor. Mostly idiopathic (maybe increased GI absorption, increased mobilization from bone or decreased reabsorption renally)... If hypercalcemia w/ hypercalcuria... think HPTH, sarcoidosis, malignancy or chronic acidemia

What is the blot for RNA?

Northern blot... Southern forDNA... DNA-bound protein/transcription factor for SW blot

How do you get PID after treating a vaginal discharge infection?

Not enough antibiotics or not covering both gonorrhea and chlamydia... PID involves endometrium, fallopiant tubes, and/or peritoneal cavity (Fitz/Hugh/Curtis)... most common cause of tubal-factor infertility... Ectopic pregnancy can also occur. Co infetion is common so treat w/ ceftriaxone or 3rd gen cephalosporin WITH azithromycin or doxycycline. Long term infection caused scarring and adhesion formation ... leading to fallopian tube scarring, loss of ciliary action, subsequent infertility. ~congenital absence of vas deferens = low sperm volume and acidic pH of ejaculate sample.

What measure to case-control studies report?

ODDS RATIOS>... odds of exposure in cases/odds of exposure in controls Incidence measures like relative risk and relative rate can't be measured in case controls because they already have the disease. RR and RR are calculated in prospective and retrospective cohort studies where RF assessment occurs first and then exposed/unexposed groups are followed over time and assessed for disease.

What is the difference b/w selection and observer bias?

Observer bias... misclassify data due to preconceived expectations or prior knowledge concerning the study or participatns... Esp when outomes are subjective... Pathologists know about the study or may have access to records to see. Selection bias is inappropriate (nonrandom) selection methods or through selective attrition of study participants. Many drop out of trial due to side effects so side effects look less likely.

How do you test for essential fructosuria?

Often asymptomatic... Fructose is a reducing sugar and can be detected via copper reduction test. A urine dipstick goes for glucose oxidase will show negative for both glucose and galactose.

What is the most common point of entry of Enterococcus endocarditis?

Older males w/ a GU procedure (cystoscopy)... can be GI or OB procedures too.

As you age, how does it affect your lungs?

Older, means you have increasing residual volume and increasing functional residual capacity, but total lung capacity is unchanged. So, as you age, your expiratory reserve volume is decreasing, vital capacity is decreasing, inspiratory reserve volume is decreasing... All sloped upward >35 basically... decreases in compliance are due to rib calcification leading to stiffening and from thoracic curvature of osteoporosis/arthritis. Lung compliance increases w/ age due to loss of elastic recoil, more destruction of alveolar ducts than w/ COPD --> destruction of alveolar walls.

In the absence of ADH, where is the tubule permeable to water?

Only Proximal tubule and thin descending limb... Thick Asc, DCT, Collecting all impermeable

What glands are parietal cells in?

Oxyntic gland... destroyed by CD4 cells in autoimmune gastritis

How does Hep B infection work?

P/W fever and joint pain often... Atypical lymphocytes too.. similar to EBV/CMV The mature virion (Dane particle) consists of a hexagonal protein core (capsid) covered w/ a lipid bilayer neveloped w/ proteins/carbs... HBV genome is a partially ds DNA molecule w/in the capsule After the virion enter the cell, capsid is released into cytoplasm and viral genome enters nucleus.... Viral DNA is then repaired to form a fully ds circular minichromsome by the RNAdepDNA polymerase it carries. Replication of the genome occurs w/in a newly synthesized capside containing fully length viral mRNA transcript. RT has both RNA and DNA dep DNA polymerase activity acts on RNA emplate to create a ss DNA intermdiate that is then converted back into circular partially ds DNA... Mature capside is then enveloped by a portion of ER containing virally-coded proteins to fomr a complete virion.

What's the deal w/ pancreatic pseudocysts?

P/W male w/ severe epigastric abdominal pain and vomiting after binge drinking --> four weeks later a palpable mass that is cystic. Proteolytic enzymes may disrupt walls of the pancreatic ducts and cause leakage of pancreatic secretions into the peripancreatic space. This high pancreatic enzyme content induces inflammation and granulation tissue forms encapsulating the fluid collection --> pseudocyst In contrast to epithelial lining of true cysts, these are granulation tissue and fibrous lining. Takes about 4-6 weeks following an episode of acute pancreatitis. Usually on the lesser peritoneal sac, bordered by the stomach, duodenum, and transverse colon. They are closely adherent to nearby solid organs.

What causes DVT -> MCA stroke?

PFO, ASD, VSD

Child w/ eczematous rash, intellectual disability, gait abnormality, musty body odor...

PKU!! autosomal recessive inheritance

What is the site of highest K+ reabsorption in the kidney?

PT actually!! 2/3... another 1/4 is in the thick asc limb K+ regulation though happens at collecting duct, hypokalemia causes K+/H+ ATPases to absorb almost all K+ and then hyperkalemia lets it go through apical K+ channels. Very high intake of K+ can lead to more urinary K+ than actually plasma K+

Best way to monitor warfarin?

PT in the form of INR... INR is a raio of patients INR to a control... target 2-3.0

What are the three options for hypcalcemia of malignany?

PTHrP, Bone Mets, 1,25 (OH2) VIT D (form lymphoma/granulomas)

How would you describe the locus ceruleus location?

Paired pigmented brainstem nucleus in the posterior rostral pons near the lateral floor of the fourth ventricle. Functions as principle site for Norepi synthesis and sends all over. Mood control, arousal via RAS, sleep-wake cycles, cognitiion, autonomic function... B/L pontine hemorrhage typically p/w coma due to RAS disruption.

What pancreatic neoplasm has papillary projections?

Papillary variant of pancreatic adenocarcinoma

How does hypokalemia present?

Paresthesias and muscle weakness

Two days ago, red/flushed cheeks, now a stomach/back/extremeties erythematous rash that is lace-like... Had a fever/congestion/HA early in the week...

Parvo Rash coincides w/ increases in IgM and IgG Benign and happens after 1-2 week incubation

What is the path of the ulnar nerve?

Passes b/w hook of hamate and pisiform bone in a fibroosseous tunnel known as guyon's canal... wewakness of finer abduction/adduction and clawing of 4th/5th fingers

How would you describe a PDA?

Patent due to PGE2 from the placenta... Results when the ductus arteriosus fails to close after delivery. P/W L-> R shunt, wide pulse pressures and bounding pulses, metabolic acidosis, signs of CV strain (tachycardia/cardiomegaly/eisenmeigers) Indomethacin and ibuprofen inhibit PGE2 and could close it **more common in preterm infants.

DM and Thallassemia

Patient w/ poor glucose control can have low Hemoglobin A1c... with high Hemoglobin A2 Both higher glucose and longer exposure of red cells to glucose will increase hemoglobin A1C levels... Conditions that alter red blood cell survival time affect hemoglobin A1C levels... Patients w/ elevated hemoglobin A2 suggest beta thalassemia... HbA2 becomes elevated in beta thalassemia to compensate for beta globin chain underproduction, but resulting microcytic red cells are prone to hemolysis... Increase in red cell turnover leads to low HgbA1c levels.

What is the name for B3 deficiency, what 3 things are needed to make NAD+

Pellagra... dermatitis (sunexposed areas causes rough, scaly, thick skin), diarrhea (due to atrophy of columnar epithelium of GI tract), dementia (neuronal degeneration in brain spinal cord) Niacin made from Trp via the kynurenine pathway, nicotinic acid (niacin), and nicotinamide. ~Carotene is the precursor to vitamin A ~Arginine is the precursor to creatinine, urea, NO, ornithine

Anaerobic infections from aspiration pneumonia (4)

Peptostreptococcus, Bacteroides, Prevotella, Fusobacterium Can cause necrotizing lung masses.

Where does fibrinous pericarditis affect the heart?

Pericardial inflammation overlying the necrotic segment of myocardium 2-4 days after transmural MI. Reaction to transmural necrosis... Affects adjacent visceral and parietal pericardium. Post-MI pericarditis is short-lived and dissappears w/in 1-3 days of aspirin therapy.

What active MS plaque is most specific?

Periventricular inflammatory infiltrates. Autoreactive T lymphocytes and macrophages against myelin. Leads to Patchy demyelination (axons are spared... prolonged disease though --> neuron death)... Residual findings = hypertrophy and hyperplasia of glial scarring.

At weeks 27, what happens to amniotic fluid ratios?

Phosphatidylcholine begins to rise and sphingomyelin stays the same ~Phosphatidylglycerol is a component of surfactant (levels increase after 36 weeks getation)... in parallel w/ increased surfactant production.. .PPC also increases then (lecithin)

What does carcinoid heart disease cause?

Plaque like deposits of fibrous tissue on the endocardium leading to TC regurgitation and pulmonic valvulopathy and Right HF... Limited to right heart as these vasoactive products are inactivated at pulmonary vasculature. Can diagnose w/ 5-hydroxyindoleacetic acid measurements (5-HIAA).. end product of serotonin metabolism.

Androgenic Alopecia Genetics

Polygeneic inheritance... causes temporal and vertix level hair loss.. Male pattern baldness. Variable expressivity. Many factors, including chromosome 20 influence things. Epilepsy, Glaucoma, HTN, ischemic heat disease, schizophrenia, and type 2 DM all polygenic inheritance

What is milrinone?

Positive inotropy and vasodilation --> PDE3 enzyme inhibitor

What can cause bladder distension in a child?

Posterior URETHRAL valves.

Why do CCBs cause peripheral edema?

Preferential dilation of precapillary vessels (arteriolar dilation) which leads to increased capillary hydrostatic pressure and fluid extravasation into the interstitium. RAAS blockers cause postcapillary venodilation and can normalize the increased capillary hydrostatic pressure, reducing this risk in patients taking CCBs

What is the pathogenesis of acute pancreatitis?

Premature activation of trypsin inside the pancreatic acini. Either toxin or ischemia leads to acinar cell injury. Causes necrotizing pancreatitis (areas of parenchymal necrosis that can lead to secondary bacterial infection) 1) Ductal Obstruction = gall stone, tujmor, chronic alcohlism w/ concretions... ischemia --> acinar cell dysfunction 2) Direct Parenchymal injury = alcohol, iatrogenic, hyperTG --> acinar cell dysfunction

What indicates low infectivity in chronic Hep B infection?

Presence of HBe antibody.. if HBeAg present then high infectivity... Anti-HBc IgM is present during window phase when both HBsAG and anti-HBs are absent.

What do serpentine cords do?

Prevent macrophage-mediated destruction of TB... also forms a highly toxic crystalline monolayer on hydrophobic surface (oil/water) that helps drive formation fo caseating granulomas.

INO description

Previously had optic neuritis = loss of color vision, blurry vision and pain of eye movement Now, INO... slowed adduction of left eye w/ right lateral gaze but convergence shows normal B/L adduction. MS is a demyelinating disease leading to impaired saltatory conduction.. leads to conduction block at nodes of Ranvier. Over time, sodium channels eventually redistriute across naked axons and surviving oligodendrocytes partially remyelinate, allowing for some restoration. Loss of axons in MS only happens in chronic MS.

What are the stages of prevention?

Primary = preventing a disease from becoming established = health promotion (regular exercise, no smoking, weight loss) Secondary = detecting a disease before it causes symptoms = individual case finding (cervical cancer screening), community screening (BP screening at state fair) Tertiary = treating a disease to prevent progression/complications = disability limitation (Blood sugar and BP control in diabetes), rehab (PT after stroke)

Hypoketotic hypoglycemia differential

Primary Carinitine Def -muscle weakness/myopathy, cardiomyopathy, elevated muscle TGs MCAD D -hypoglycemia and hypoketotic hypoglycemia Both lead to decreased beta oxidation so decreased ketone bodies.

Kid w/ hypoketotic hypoglycemia after a period of fasting, whatcha think?

Primary Carnitine Deficiency - muscle weakness, CMOP, elevated muscle TGs OR Medium chain acyl CoA Dehydrogenase -hypoglycemia -hypoketotic hypoglycemia!! MCAD Fatty Acid -- > actyl CoA via Acyl CoA Synthase, etc. there's a pathway on it enters via carnitine and CAT1 = acyl-carnitine in cytoplasm Carnitine transporter brings in Acyl-carnitine to Carnitine and Acyl CoA via CAT2 THEN!! Acyl CoA --> trans-enoyl CoA via acyl CoA dehydrogenase making FADH2... eventually leads to acetyl CoA w/ ketones and TCA cycle Need this running in periods of fasting!! MCAD is th emost common. All the acyl-CoA dehydrogenase deficiencies present the same. Tx is supplying glucose a lot. Also screen newborns.

How does a gout drug affect the side effects of penicillins?

Probenecid inhibits organic anion transporter (OAT1/3) from secreting uric acid, penicillin, cephalosporins, methotrexate into the renal proximal tubule cell from the blood It also uses its main action at the URAT transporter that reabsorbs uric acid from the urine into the renal proximal tubule cell.

What are some ways the pancreas defends itself form pre-active enzymes?

Proenzymes are synthesized and secreted from the pancreas... Activated by trypsin in the duodenal lumen after trypsinogen is converted to active, trypsin... Duodenal enterokinase does this reaction... Trypsin also can activate other trypsinogen molecules; therefore, even small amounts of it can result in an activation cascade... 1. Serine Peptidase Inhibitor Kazal-type1 (SPINK1) is secreted by pancreatic acinar cells and functions as a trypsin inhibitor. It impedes the activity of trypsinogen molecules that become prematurely activated within the pancreas. 2. Trypsin also serves as its own inhibitor by cleaving active trypsin molecules at a second site rendering them inactive **HEREDITARY pancreatitis is a rare disorder that results from mutations of SPINK1 gene. Most commonly an abnormal trypsin that is not susceptible to cleavage.

What is arginase deficiency??

Progressive (years 1-3) development of spastic diplegia, abnormal movements, and growth delay in the setting of elevated arginine. Arginase is a urea cycle enzyme that produces urea and ornithine from arginine. Dx is based on elevated arginine levels. Tx is a low protein diet (devoid of arginine). Unlike other urea cycle disorders, these patients have little or no hyperammonemia.

What mediates the flushing and skin warmth after niacin administration?

Prostaglandins (particularly PGD2 and PGE2)... given 30-60 min before. ~vanc red man syndrome is histamine release non IgE mast cell degranulation

What is the main treatment for urea cycle disorders?

Protein restriction... need essential amino acids but not in excess.

How to RAS and BRAF do? Related to Cancer

Proto-Oncogenes that code for cytoplasmic signal transducer proteins, upregulate cellular proliferation and differentiation. Braf --> malignant melanomas Ras --> pancreatic cancer Both cause constitutive activation in cancerous forms

How does IgA present?

Prupuric rash (100%), abdominal pain colicky 85%, polyarthralgia 70%

Tx of psoriasis topical

Psoriasis is caused by Th1 and Th17 cells causes hyperkeratosis/parakeratosis and acanthosis... Cytokines mediate this and leads to eruptions on elbows, knees, lumbosacral region, and scalp. One treatment option is vitamin D analogs for toipcal treatment... Calcipotriene (calcipotriol), calcitriol, adn tacalcitol... all meds bind and activate vitamin D receptor, a nuclear transcription factor that causes inhibition of keratinocyte proliferation and differentiation, also shown to decrease T cell response. ~Ustekinumab also used in psoriasis treatment, but human monoclonal that targets IL12 and IL23. inhibits differentiation and activation of CD4 Th1 and Th17

What is the random new test for gram positives?

Pyrrolidonyl arylamidase (PYR)... GABHS is positive GBS is negative. Enterococci are positive... Streptococcus gallolytics (bovi) negative.. but both of these growin in bile but S bovi doesn't grow in NaCl while Enterococci does... Both are gamma hemolytic (non)

Which G protein activates PIP2 -> DAG and IP3

Q

What is the difference b/w colonic masses growth in colonic adenocarcinoma?

R sided colon cancers tend to grow as exophytic masses. No obstruction because ascending colon has a larger caliber lumen and stool in proximal colon is more liquid. R sided colon cancers tend to present w/ iron deficiency anemia (weight loss, fatigue, pallor) due to occult blood loss.... Anorexia and Malaise as well Smoking, Obesity, Lots of eating meat, and not much eating vegetables increases the risk L sided cancers tend to infiltrate the intestinal wall and encircle the lumen. They cause a change in bowel habits (constipation) and usually obstruction (abdominal pain, distension, nausea vomiting)

Reasons for very high renin output?

RAS esp b/L diffuse atherosclerosis can cause this

4 mechanical complications from acute MI

RV Failure right away = hypoTN, clear lungs, Kussmaul sign Papillary M rupture.. 3-5 days... acute severe pulmonary edema, severe M regurge IV septum... new murmur holosystolic, stepped up oxygen b/w r atrium and r pulmonary artery Free wall rupture... pericardial tamponade, JVD, distant heart sounds

Where getting stabbed would cause an injury w/ wrist extension?

Radial nerve at midshaft humerus

Difference b/w rate and rhythm control

Rate control uses AV nodal-blocking drugs (beta blockers, CCBs) to prevent rapid ventricular response... Rhythm control maintains sinus rhythm w/ anti arrhythmic drugs ~Ranolazine is an antianginal agent that works by inhibiting late phase of inward sodium channels in ischemic cardiac myocytes.

Main culprit of HepA infection in US?

Raw or steamed seafood. Can actually cause an aversion to smoking. Largely supportive treatment, lasts 3-6 weeks. Those going to high risk endemic areas, those w/ chronic liver disease or clotting factors disorders or MSM should be vaccinated. Also close contacts of those w/ HepA

Leukocyte Adhesion Deficiency

Recurrent bacterial infections, pneumonias, etc. w/ skin infections due to S aureus but drainage/culture show no purulence. Infections resolve w/ antbx... Lab shows deficiency of CD18 on surface of leukocytes. p/w delayed umbilical cord separation >= 21 days and marked pheripheral leukocytosis w/ neutrophilia CD18 necessary for formation of integrins...

What two receptors are in the vestibular nuclei??

Regulates motion sickness....M1 and H1 R.. BOTH ANTIHISTAMINES and Scopolamine are common for this, but they both have anti-cholinergic side effects

Which cells secrete EPO?

Renal Peritubular Cells

What supplies blood to proximal ureter?

Renal artery Distal ureter blood supply from superior vesical artery. In b/w can be anastomoses and afferent branches from internal iliac, aorta, gonaadal etc. In renal transplant... blood supply established by anastomosing donor renal artery with recipient's external iliac artery. Proximal 1/3 of donor ureter is preserved and used to establish continuity from the collecting system of the kidney's to recipient's bladder. Most distal segment of ureter susceptible to ischemia due to lack of anastomoses.. causes leakage of urine 5-10 days after transplant.

What is endomyocardial fibrosis?

Restrictive CMOP of thickening/fibrosis of apical endocardial surface. It is most common in tropical regions (Uganda).

What is likely cause of septic abortion?

Retained products of conception w/ pregnancy termination.. .fever, abdominal pain, uterine tenderness, foul-smelling vaginal discharge... Usually S aurues, GN bacilli or Group B strep. Long term complications can lead to adhesions -> PID and asherman syndrome

What muscles manipulate the scapula?

Rhomboids (retract) and levator scapulae muscles (elevate) both innervated by dorsal scapular nerve

Where is he SA node?

Right atrium near the SVC opening... AV noe is RAtrium near septum at inferior portion of RAtrium.

How does splenic laceration present?

Rigid abdomen, normal heart/lung sounds, tender abdomen, bruse on left lower chest wall w/ tenderness to palpation... Shoulderp ain = peritoneal inflammation = Kehr sign. Hypotension and tachycardia as well. Phrenic nerve irritation can also cause hiccups due to spasmodic diaphragmatic contraction pulling air against a closed larynx.

What secretin test result is expected from gastrinoma?

Rise after secretin... Also ulcers beyond duodenal bulb are characteristic. Gastrin excess causes parietal cell hyperplasia and stimulates gastric acid secretion --> peptic ulcers, heartburn, diarrhea.

Why do you avoid monotherapy of SSRIs in bipolar disorder?

Risk of Mania...

What is ovarian torsion?

Rotation of the IP ligament (infundibulopelvic aka suspensory ligament of the ovary) around itself Leads to edematous and ichemic ovary... Sudden onset unilateral pelvic pain and nausea maybe w/ vomiting and fever... Pelvic U/S to diagnose.

What does obturator nerve do?

Runs in the obturator canal... Only nerve in this canal... Supplies obturator externus muscle and divides into anterior/posterior branches that supply the rest of the thigh adductor muscles... Anterior division is sensation to medial thigh distal. Bladder Cancer invasion can cause compression, or pelvic trauma or surgery.

How do you treat hyperemesis gravidarum?

SEVERE vomiting and nausea from pregnancy leads to electrolyte loss... Promethazine

Drug with a large arteriovenous concentration gradient after inhalation, what does it mean?

SLOW ONSET OF ACTION Before gas anesthetics can reach the brain, they must move through air -> lungs -> blood -> brain... Anesthesia occurs when enough has reached the brain. AV conc gradient is difference b/w arterial and venous blood. If more soluble in peripheral tissues, then higher gradient. Means a lot of arteriolar delivered is taken up so low venous... As a result, saturation of blood requires further absorption of anesthetic in order to replace that which is absored in peripheral tissues... Since blood saturation is taking longer so brain saturation is slower onset. In contrast, anesthetics w/ low peripheral solubility will have small AV gradients as there is less peripheral tissue uptake. Less anesthetic is required to replace the amount absorbed in peripheral tissue so blood saturation occurs quickly Potency is determined by minimal alveolar concentration for 50% of patients to not realize they are being exposed to noxious stimuli. Potent anesthetics have low mAC. AV gradient influences rate of induction not anesthetic potency!!! Inhaled air is determined by partial pressure of anesthetic... When air partial pressure equilibrates the blood, tissues are said to be saturated Lungs (pulmonary ventilation rate) rate of rise of gas tension in alveoli is directly proportional to depth and rate of respiration Blood... Solubility... higher means more anesthetic must be absorbed by blood to work effectively Target organ.. solubility in peripheral tissues negatively affects brain saturation.

What is order of trigeminal exits?

SOF Foramen Rotundum Foramen Ovale

What two presentations of trochlear nerve palsy?

SOblique... so up close reading or walking downsrairs, vertical diplopia. Also can have vertically deviated eye (hypertropia)

How to deliver bad news?

SPIKES 1) Set the Stage: arrange a private, comfortable setting, introduce members of team to family/patient, maintain eye contact sit at same level, schedule appropriate time interval and minimze interruptions 2) Perception... open ended questions to assess perception of situation 3) Invitation... ask the info they'd like to know 4) Knowledge... Warn patient bad news is coming, speak in simple/straightfoward terms, stop and check for understanding, remain cognizant of cultural/educational/religious issues 5) Empathy.. express understanding and give support 6) Summary/Strategy... summarize and create follow-through plan, include end of life discussions if applicable

How to remember what specificity rule in or out?

SPPIN... specificity rules in = total negatives / (total negatives + false positives) SNNOUT... sensitivity rules in = total positives / (total positives + false negatives)

Osteomyelitis in a SCD patient....

Salmonella!!! Resistance to opsonization is huge w/ this organism... It has a special Vi antigen on its capsule (virulence) that protects from both opsonization and phagocytosis. Sickling --> necrosis and potential for mucosa breakdown and bacterial seeding. Also vaso-occlusive crises -- focal areas of bone necrosis w/in which bacteria can establish infections. *Normally vaso-occlusive pain crises if non infective give oxygen IV fluids and high dose narcotics ~Adhesion to collagen is the main virulence factor in S aureus for osteomyelitis

What are the cancers associated w/ Li Fraumeni Syndrome?

Sarcomas, Breast, Brain, Adrenal, Leukemia

Mnemonic for Sulfa Drugs

Scary Sulfa Pharm FACTS Sulfonamide antbx Sulfasalazine Probenecid Furosemide Acetazolamide Celecoxib Thiazides Sulfonylureas p/w fever, UTI, SJS, hemolytic anemia, TCP, Agranulo, AIN, urticaria...

When should trazadone be used w/ caution?

Scenarios at increased risk of priapism... Multiple myeloma or Sickle cell disease

How do calcinosis and sclerodactyly present?

Sclerodactyly presents early as non pitting edema of fingers and toes. Later become thickened and shiny. Calcinosis can be painful or asymptomatic. CREST includes reflux/regurgitation from esophageal dismotility anti-centromere.

When do you use cinacalcet?

Secondary Hyperparathyroidism for patients w/ CKD or on dialysis

Features of WIlson's... Kayser-Fleiscer Rings, Cirrhosis, and....

Seen on slit-lamp, rings are formed through granular deposition of copper w/in Descemet's membrane in the cornea. Due to reduced formation and secretion of ceruloplasmin and decreasing hepatic secretion of copper into biliary system. Copper is a pro-oxidant that eventually leaks out of hepati ctissue into circulation to deposit in basal ganglia as well as cornea... Tx = d-penicillamine

How does PAN present?

Segmental Transmural Necrotizing Inflammation of medium to small sized arteries... Necrotic tissue and deposits of immune complexes, complement, plasma porteins produce a smudgy eosinophilic deposit (fibrinoid necrosis) to give a pattern of immune complex vasculitis

Attrition bias is a form of what bias?

Selection bias (a test that most often refers to systematic differences b/w groups in terms of treatment response or prognosis)

What drugs cause coronary seal?

Selectively dilate coronary arteries when really the ones that needed dilating were already dilated. Adenosine and Dipyridamole Esp decreases circulation through any collaterals that have developed. That's why these are used in myocardial perfusion imaging studes to see where there are ischemic areas.

What two antibodies are specific for SLE also which is sensitive?

Sensitive = ANA... Specific is anti-dsDNA (only 60% w/ SLE have this) Also anti-snRNPs (anti-smith) 20-30%... Esp skin rash that's worse w/ sunlight and arthralgias

What neoplasm of pancreas has glycogen-rich cuboidal epithelium?

Serous pancreatic neoplasms

Presentation of Pertussis

Severe coughing spells w/ classic inspiratory whoop OR post-tussive emesis Gram negative coccobacillus Usually a clear CXR since no pulmonary consolidation and lymphocytosis will be present

What is case-fatility rate?

Severity of disease or condition... Proportion of reported cases of a specific disease/condition that are fatal w/in the population affected by the disease/condition over a period of time.

ANAL FISSURES?

Sharp pain and bright red rectal bleeding on defecation --> anal fissure... These are due to stretching of the mucosa and characterized by longitudinal tears in anal canal distal to the dentate line. Spasm of sphincter can contribute to the pain and create tension across the wound --> chronic fissure. Most are related to chronic constipation w/ high anal pressures and hard passage of stool... Also w/ frequent diarrhea or anal sexual intercourse. Pain may be so severe that they withhold bowel mvmts. Most are at the posterior midline of the anal verge. Due to poor perfusion of the posterior anal canal. Distal to the dentate line. Fissures should be midline. Anterior can occur due to mechanical stress or alignment of muscular fibers in external sphincter

Child that is 6 years old w/ high Tanner stage and height... what is the worry?

She will be short for age in precocious puberty unless she is treated... *precocious puberty in caucasian females, is secondary sex characteristics at age < 7 years old. diaphysis -> metaphysis -> epiphysea cartilage -> epiphysis... this cartilage is the growth plate for linear growth... Sex steroids initially increase linear growth but they also cause closure of this plate... Irreversible end of growth once they close. At end of puberty growth spurt, 90% of max height has been attained.

MyoTomes and Reflexes

Shoulder elevation = C4 Shoulder Abduction = C5 Elbow Flexion, Wrist Extension = C5,C6 Elbow Extension, Finger Extension = C7 Wrist Flexion, Finger FLexion = C8 Finger Abduction = T1 Reflexes = Biceps/Bradialis = C5,C6 Triceps = C7,C8

More info on diffuse gastric adenocarcinoma

Signet ring cells involve stomach wall due to loss of cell adhesion protein E-cadherin.. Plaque like appearance and ill-defined, often infiltrate large areas of the stomach causing a leather-bottle stomach (linitis plastica) Most important factors for survival rate for gastric adenocarcinomas (both) are depth of invasion through gastric wall and regional lymph node involvement. Mets often supraclavicular (virchow) or periumbilical (sister mary joseph)

Difference in curves b/w simple diffusion and carrier protein diffusion?

Simple can be exponential and reach 95% across almost immediately if a conc difference exists. Whereas, carrierp roteins have a finite number and require discrete amount of time to pass a single molcl/ion through the membrane... You can saturate carrier proteins. Tm is when carrier proteins are saturated.. Similar to Vmax. Diffusion = pressure difference, * SArea,*SOL and invesely related to thickness of membrane and the square root of molecular weight`

Patient w/ T1DM p/w hyperpigmentation, decreased Na and increased K?

Since already have T1DM, more likely to get Addison's from autoimmune adrenalitis that attacks all 3 layers of the adrenal cortex. ACTH administration will not increase serum cortisol. GCs increase insulin resistance so decreased adrenal cortex secretion means less insulin requirement for the patient. Will also have a non anion gap met acidosis. Type 4 RTA. Decreased H+ excretion caues this and leads to a compensatory increase in chloride retention, which occurs to maintain electrical neutrality of ECF...

Where does insulin exert its effects on the body?

Sk M, Adipose, Liver all increase glucose uptake Liver.. incr glycogen synthesis and decrease glycogeneolysis pancreas (alpha cells) decrease glucagon secretion all contribute to hyperglycemia (poluria/polydipsia, lethargy, polyphagia/anorexia) Adip tissue/liver all decrease lipolysis and decrease ketogenesis Muscle to increase protein synthesis

Why is TSH best to screen for hypothyroidism?

Small changes in thyroid hormone have large changes in TSH... As production slows, TSH increases rapidly to increase it.

Different terrible symptoms features

Somatic Symptom = excessive anxiety & preoccupation w/ => 1unexplained symptoms Illness Anxiety = fear of having a serious illness despite few or no symptoms and consistent negative evaluations Conversion Disorder = Neurologic symptom incompatible w/ any known neuro disease; often w/ acute onset assocaited w/ stress Factitious Disorder = intentional falsification or inducement of symptoms w/ goal to assume sick role Malignering = falsification or exaggeration of symptoms to obtain external incentives

Protection of GI tract from infx

Sphincter of Oddi prevents reflux of nonsterile duodenal contents Bile acids inhibit bacterial growth Biliary flow washes them away BIle secretory IgA stops adherence Ecoli, Klebsiella, Enterobacter and enterococci can still do it and lead to cholangitis though.

What ligament does the splenic vessels run in?

Splenorenal ligament

Progression of B anthracis

Starts as just myalgia, fever, malaise... progress to hemorrhagic mediastinitis, bloody pleural effusions, septic shock , death

What are the major side effects of the AntiHyperlipidemics?

Statins = Hepatotox/Muscle Tox Ezetimbe = Hepatotox if w/ statins BASeq = N/Bloat/Cramp... Impaired ADEK Niacin = Flushing, pruritis, hepatotox, hyperuricemia/gout Fibrates = Muscle tox and gall stones Fish Oil = Fishy taste

What is nonbacterial thrombotic endocarditis associated with?

Sterile, platelet rich thrombi on mitral valve leaflets... Most commonly associated w/ advanced malignancy as well as chronic inflammatory disorders = DIC/SLE/APantibodyS Endothelial injury caused by circulating cytokines triggers platelet deposition. They still have mononuclear cells. Most patients asymptomatic but can emoblize.

What does Turner's do to ovaries?

Streak/atrophic ovaries... amenorrhea, infertility, no secondary sex charactertistscs (short, high arched palate, tanner 1 breasts w/ wide nipples).

Androgenic Alopecia

Strong familial predisposition w/ polygenic inheritance... DHT for follicular hiar growth.. Starts at temples, then center point on back of head, then clearing in the front treat w/ 5 alpha reductase inhibitors.

How does facial nerve exit the skull?

Stylomastoid foramen and courses w/in the parotid gland, so parotid gland tumors can cause facial droop. Thyroid surgery is scary if you damage recurrent laryngeal nerve when cauterizing the inferior thyroid artery because can get vocal cord paralysis and respiratory distress esp if B/L.

Where do spider angiomata come from?

SubQ vascular lesions of a central arteriole surrounded by many smaller vessels that blanch on compression. Mostly trunk, face, upper limbs. Estrogen causes arteriolar dilation. Number and size correlate to severity of disease.

TELLLL me about the infectivity of shigella

Super acid stable S. dysenteriae (10) > S. flexneri (100) > S sonnei (500) in terms of infectivity and acid stability Also survives bacterostatic action of the bile Incubation period is 24-72 hours. Starts w/ watery diarrhea --> fever, abdominal pain, dysentery w/ bloody diarrhea, tenesmus (painful rectal spasm associated w/ urge to defectate but little passage of stool) Campylo (500) and Entamoeba (1-10) and Giardia (1-10) are very acid stable

How does leaving a tampon in cause toxic shock syndrome?

Superantigen TSS toxin superlinks MHC2 of MP or dendritic cell and TCR of T cell no matter the connecction. p/w fever, vom, diarrhea, muscle pains, erythroderma (macular rash looks like sunburn)... Progresses to severe hypotension, elevated Cr, elevated transaminases. Can eventually cause desquamation of palms/soles 1-2 weeks later. Also assc w/ nasal packing S aureus is responsible for most cases. Activates large numbers of T cells. Major release of IL2 from T cells and IL1 and TNFalpha from MPs.

How does the lymphatic system of extremities work?

Superficial that follows the veins = skin/subQ tissue and deep lymphatics that follow arteries = deep muscles/superficial vessels In lower extremities, superficial is divided into medial and lateral tracks... Medial track runs along the long saphenous vein up to the superficial inguinal lymph nodes (bypassing popliteal nodes) Up to SuperoMedial and SuperoLateral Lateral track communicates w/ popliteal and inguinal nodes, more likely to cause LAD of popliteal and inguinal area.

How do meatuses drain?

Superior meatus drains for sphenoidal/posterior ethmoidal Middle drains frontal/maxillary/anterior ethmoidal Inferior drains nasolacrimal duct

44 year old man comes to the physician bc of 2 mo history of abdominal pain and idarrhea. Pain is relieved after eating and by antacid use. Labs show gastrin concentration of500 (normal 50-100) and gastric acid secretionof 80 (normal 6-40) w/ secretin.

Surgical treatmnent is removal of the tumor

What are the epidemiology, Pathogenesis, and Clinical Findings of Tabes Dorsalis?

Susceptible are patients w/ HIV non adherent to treatment for example Syphillis in MSM and HIV patients... HIV positive patients get neurosyphillis more rapidly Pathogenesisi = spirochetes directly damage dorsal sensory roots and eventually dorsal columns... Causes 1) sensory ataxia 2) lancinating pains 3) neurogenic urinary incontinence 4) argyll-robertson pupil Sensory Ataxia = wide-based gait and positive romber's Lancinating Pains = sharp, stabbing pains that last minutes to hours

Another name for infundibulopelvic ligament and what it carries

Suspensory ligament of ovary (ovarian vessels) Trasverse Cervical Ligament = Cardinal Ligament as well... Cervix and lateral fornix to the vagina to pelvic walls lateral... uterine artery in here.

Pressure of L atrium is measured how?

Swan Ganz catheter in a branch of the pulmonary artery that is inflated w/ a balloon also known as pulmonary artery occlusion pressure Intrapleural pressure is measured w/ pleural manometry by placing a catheter in the pleural space during thoracentesis.

What catheters traverse the pulmonary artery?

Swan-Ganz catheters

Where are nicotinic R found?

Symp and Parasymp ganglia on sk muscle cells and at the NMJ

1st step when suspecting septic arthritis

Synovial Fluid analysis... diagnostic arthrocenteses... want crystal analysis, cell count, gram staina dn culture... also blood cultures if septic arthritis suspected.

What happens during the 2 week washout of MAO inhibitors to wait?

Synthesis of more Monoamine oxidase The MAO inhibitors irreversible by MAOa and b. This helps avoid serotonin syndrome because otherwise the serotonin would never get broken down in the cleft.

Loss of pain and temperature sensation in the hands... what is your first thought?

Syringomyelia if bilateral... that is because pain/temp fibers cross. Esp if dorsal column is okay. These syrinxes usually form in the cervical reigion, damaging the ventral white commissure and ventral horns. The affected region starts 1-2 levels below the lesion (first order axons ascend in zone of Lissauer before synapsing)

What do you test for before giving etancercept?

TB!!!! loss of TNFalpha promotes reactivation of latent TB. Don't treat in patients w/ atypical mycos or fungi infections either

Excessive bleeding placing the catheter on a dialysis patient?

THINK Renal dysfunction --> accumulation of uremic toxins --> impair platelet aggregation and adhesion.. results in qualitative platelet disorder, characterized by prolonged bleeding tie w/ normal platelet count, PT, aPTT... Improved w/ dialysis

What treatment is useful after prednisone, methotrexate fail in Rheumatoid arthritis?

TNF-alpha

The story of the T cell

T lymphocytes are initially produced in the bone marrow, but migrate to mature during the first trimester of gestation in the thymus. In the thymus, TCR gene rearrangement, positive selection, negative selection, and expression of EC membrane markers/co-stimulatory molcls occurs. Pro-T cells arrive at the thymus as "double negative" cells = indicating they lack CD4/CD8 and their differentiation in the subcapsular zone. Next, the process of TCR beta gene rearrangement occurs w/ simultaneous expression of both CD4 and CD8. Once in the thymic cortex, the alpha genes rearrange to produce a functional alpha=beta TCR. Positive and negative selection occur w/ cells that fail either of the following two tests 1) Positive... T cells expressing TCR that is able to bind self MHC are allowed to survive. Those expressing a TCR that is not specific for MHC are eliminated. This occurs after TCR DNA rearrangement and prior to negative selection. It occurs in the thymic cortical epithelial cells (expressing self MHC). Positive selection is responsible for T cell recognizing self as normal 2) Negative... T cells w/ TCRs that bind w/ high affinity to self antigen or self MHC class 1/2 are elminiated. Occurs in the thymic medulla and involves interaction of developing T cells w/ thymic medullary epithelial and dendritic cells. This serves to eliminate T cells that may be autoreactive against self antigen. Prevents autoimmunity. **Affinity maturation is enhancing the hypervariale reion antigen binding affinity after initial binding of an antigen to membrane-bound immunoglobulin on a naive B lymphocyte and subsequent migration of that B lymphocyte to a lymph node. W/in germinal center, B lymphocyte somatic hypermutates where DNA coding for immunoglobulin variable chain is mutated randomly at a high rate. THen sees how well it binds antigen. This selects for good binding. Does not occur in T cells. **TCR DNA rearragnement is complex 10^15 possible antigen bindign sites out there. Join V,D,j,C regions of TCR and processes of junctional flexibility, N and P region NT addition, alternative joining of genes and mutlipe peptides. Matur eRCR

What sequence does telomerase add and to what chromosome, also what is the protein technically called?

TTAGGG to 3' end of chromosomes... it is an RNA-dep DNA polymerase It is composed of two elements = telomerase reverse transcriptase (TERT) subunit and telomerase RNA component (TERC). TERC is built in RNA template

Difference b/w subacute combined degen and tabes dorsalis

Tabes doesn't involve the lateral corticospinal tract. SCD = myelin layer vacuolization and axonal degeneration.

What are the three erectile dysfunction drugs?

Tadalafil, Sildenafil, Vardenafil... Both these and nitrates work through cGMP... PDE is how cGMP is degraded... taken together can lead to profound hypotension.

Why give drugs via rectum?

Taken up by inferior and middle rectal veins to bypass first pass of liver.

How does chronic lung rejection affect things?

Takes out the small airways Hyperacute = NP infiltration/fibrinoid necrosis and thrombosis Acute = perivascular (small lung vessels) and submucosal lymphocytic infiltrate Chronic = submucosal of small airways... granulation, scarring, bronchiolitis obliterans. p/w slowly worsening dyspnea, obstructive pattern on FEV1

SERMs

Tamoxifene and Raloxifene -Comp inhibitor of estrogen binding, but w/ mixed agonist/antagonist properties Prevents cancer in high risk patients Tamoxifen = adjuvant tx of br cancer Raloxifene = postmenopausal osteoporosis Adv effects = hot flashes, venous thromboembolism, endometrial hyperplasia and carcinoma (for tamoxifen) Also decreases total/LDL cholesterol an dno change in HDL

Aortic Dissections...

Tear in aortic intima... Ascending aorta type A... descending type B... as the dissecting intramural hematoma travels along aortic wall it can compress major arterial branches... BP discrepancy b/w arms... can compromise brachiocephalic trunk of left arm HTN is the primary risk factor (medial hypertrophy of aortic vasa vasorum) reduced blood flow to media... Medial degeneration w/ loss of smooth muscle -> arotic enlargement and stiffness... Atherosclerosis is more a predisposition for aortic aneurysm than dissection.. Monckeberg Sclerosis is arteriolosclerosis by calcific deposits in medial layer of muscular arteries >50 years old leading to isolated systolci HTN due to arterial hardening. Takayasu and GCArteritis can cause aortitis w/ medial inflammation... Also Tertiary Syphillis aka obliterative endarteritis of vasa vasorum... Can lead to aneurysms > dissections.

Aplastic Crisis presentation of Parvovirus

Teenager w/ SCA comes in after a few days of a low grade fever and now has dyspnea/signs of anemia with a LOW reticulocyte count... virus is ss DNA (only one).

VG Na+ toxins

Tetrodotoxin (puffer fish) and Saxitoxin (dinoflagellates in red tide) both bind to Na+ channels inhibiting Na+ influx and preventing action potential conduction Ciguatoxin (exotic fish, Moray eel), Batrachotoxin (SA frogs) both bind to Na+ channel keeping it open and causing persistent depolarization. p/w paresthesias, weakness, dizziness, nausea and history of fish consumption. Pufferfish specifically is a Japenese delicacy. Death from respiratory failure. Tx w/ supportive care and intestinal decontamination w/ gut lavage and charcoal.

What cells are activated in Sarcoidosis?

Th1 w/ IL2 and IFNgamma secreted.

What is the deal w/ beta thalassemia mutation

The Kozak sequence has the mutation... a Consensus sequence that helps start translation in eukaryotes. Eukaryotic translation initiation requires assembly for 60S and 40S ribosomes, mRNA, initiation factors, initiator tRNA w/ methionine and GTP. The 40S binds to the 5' cap of mRNA and scans for AUG methionine start codon. When this start codon is positioned near beginning of an mRNA and is surrounded by the Kozak consensus sequence, it serves as the initiator of translation Kozak consensus sequence is analogous the Shine-Dalgarno Sequence in E coli... (gcc)gccRccAUGG (R is either adenine or guanine)... Leads to microcytic hypochromic anemia w/ hemolysis in the BM from ineffective erythropoeisis when alpha chains precipitate. Normal erythrocytes have central pallor ~1/3 cell diameter. Patients w/ beta thalassemia have smears w/ increased central pallor and anisopoikilocytosis (variation in size/shape), target cells, teardrop cells, nucleated red cell precursors and basophilic stippling.

What do you need to know to study PCR of a target exon?

The flanking NT sequences for the design of RNA primers. Exact NT sequence does not need to be known.

How do eosinophils look and work

They are pink, often w/ bilobed nuclei, packed w/ granules of major basic protein (an anti-helminthic toxin) capable of damaging epithelial/endothelial cells. Esp in patients w/ allergies/asthma. Destroys outer membrane of helminths. NPs tend to have >3 multilobed nuclei and are pale. Basophils contain granules tht stain dark blue and are irregular sized, obscured nucleus as well. Granules of Basophils contain = heparin, histamin, SRS-A (slow-reacting substance of anaphylaxis = a mixture of leukotrienes)

How do you treat cholesterol gallstones?

They are the most common type of gallstone... Primarily made of cholesterol monohydrate crystals but can contain variable amounts of calcium salts, bilirubin and mucin... Bile acids and phospholipids solubilize cholesterol to prevent stone formation. Decreased of either though can lead to supersaturated cholesterol, allowing crystallization... Fat, Forty, Fertile, Female all risk factors Cholecystectomy is the preferred treatment for symptomatic gallstones. However medical therapy is an option if surgery refused or high risk... Hydrophilic bile acids like ursodeoxycholic acid reduces cholesterol secretion and increases biliary bile acid concentration... Improves cholesterol solubility and can promote gallstone dissolution. Good response in mild stones but high recurrents. ~Estrogen increases cholesterol secretion ~Progesterone decreased bile acid secretion ~Fibrates increase cholesterol content in the bile

If you have Chron's then develop easy bruising???

Think Bile Acid malabsorption --> fat malabsorption --> ADEK deficeincy --> 2,7,9,10 deficiencies!!!! Coag disorders = large hematome formation in deep tissues/joints after minor trauma OR prolonged bleeding after surgery. Chron's can also have anklylosing spondylitis and peripheral arthritis (low back pain and joint stiffness at night)... also have low grade fever, fatigue, malabosrption, weight loss.

Altered mental status from UTI in elderly?

Think E coli... bacteremia esp (UTIs are the most common cause of this). Some strains have adhesive fimbrae allowing them to contaminate teh urethra and ascending the urinary tract to UTI/pyelo gram neg sepsis or septic shock can ensue when fighting lipopolysaccharide/endotoxin... Sepsis = hypo/hyperthermia, tachycardia, tachypnea, leukocytosis, korgan dysfx due to poor blood flow. Metabolic lactic acidosis as well. Tx is IV fluids, atnbiotics, ventilation, oxygenation.

What if you have an HIV patient you are treating for toxo, but end up coming up negative w/ serology/PCR....

Think EBV -If there is a lack of response to toxo treatment after 1-3 weeks... Primary Central Nervous System Lymphoma (PCNSL) is the second most common cause of ring-enhancing lesiosn w/ mass effect in HIV... Usually PCNSL is just single lesions, but can also be mulitple It is a diffuse, large cell non Hodgkin Lymphoma of B cell origin (late complication of HIV)... EBV is almost always the cause Definitive Dx needs brain bx... although T cells are often atypical in EBV (due to left shift dawg), B cells are implicated

What is cystic medial necrosis correlated with/

Thoracic Aortic Aneurysm!! w/ an increased risk of aortic dissection.

Potassium levels in DKA

Total potassium deficit, decreased intracellular potassium, but normal or increased ECF potassium because insulin drives K+ into cells.

Which way do eyes deviate in a frontal eye field lesion?

Toward lesions, because these prefrontal cortex regions push eyes away.

What happens to osteoporosis bone?

Trabecular thinning w/ fewer interconnections... 2 major types of bone are trabecular (cancellous/spongy) and cortical... Trabecular is 15% of skeleton by weight but more active due to large surface area.. Estrogen loss at menopause mostly steals from trabecular bone, esp in dorsolumbar vertebral bodies... Leads to trabecular thinning and perforation w/ loss of interconnecting bridges. Cortical bone is lost later. Neck of femur has bone types and common for fracture. ~Hyperparathyroidism --> subperiosteal thinning and cystic degeneration = osteitis fibrosa cystica. ~Osteopetrosis leads to the persistence of primary spongiosa in the medullar cavity..

Transference versus Projection

Transference is shifting of emotions/desires associated w/ a person from the past onto another person in the present. Positive or negative. Projection involves misattributing one's own unacceptable feelings onto another person.

How does PAN vasculitis present?

Transmural inflammation of the arterial wall w/ fibrinoid necrosis

What are you slicing in the carpal tunnel surgery?

Transverse Carpal Ligament (flexor retinaculum) on the volar aspect... Attaches to the hamate and pisiform on the ulnar side and trapezium/scaphoid on tuberosity of radial side. Carpal tunnel has the flexor digitorum profundus tendons, flexor digitorum superificialis tendons, the flexor pollicis longus tendon and the median nerve. Compression in this tunnel is what causes carpal tunnel. ~Palmar Aponeurosis... spans flexor retinaculum at wrist helps w/ fibrous flexor sheaths ~Aponeurosis of flexor carpi ulnaris at elbow spans from olecranon to the medial epicondyl and forms roof of the cubtal tunnel.. Helps for ulnar nerve compression at elbow. ~Interosseous membrane is a thick connective tissue that runs b/w radius and ulna.

What compresses the median nerve? in CTS or more proximal????

Travels b/w flexor digitorum superficialis and flexor digitorum profundus before entering the wrist/hand w/in the flexor retinaculum... Supraondylar humerus fx or entrapment b/w the pronator teres is proximal... Sensory loss in median nerve distribution, weak OAF of thumb and flexion of 2/3 digits and wrist flexion/abduction... includes loss of sensation over thumb Patients w/ injury at the wrist usually have preserved flexion of 2nd/3rd digits and wrist w/ normal sensation over thena eminance as the branches responsible for these are more proximal.

What should be monitored on clozapine... when to use it?

Treatment-Resistant Schizo Agranulocytosis, Seizures, Myocarditis, MESA

Computerized systems are not universally available

Try to focus on getting physicians to write clear orders and avoid using trailing zeros to prevent errors in dosage. also want to educate them to not use abbreviations. Computers good for high risk of adverse event, med allergies, drug interactions, dosage limits.

What molecule is released w/ histamine in anaphylactic reactions?

Tryptase (relatively specific to mast cells) useful to support clinical diagnosis of anaphylaxis. What causes degranulation of mast cells and basophils? aggregation and cross linking of mast cell antibodies of IgE (FcepsilonRI receptors) Leads to activation of non-receptor tyrosine kinases -> cascade

What carries the main prognosticating factor in colon cancer?

Tumor expansion = stage... Differentiation is more of a grade problem.. Tumor is more important for prognosis... If confined to mucosa (A) 90+% 5 year survival If muscular layer, 70-80%, lymph node or meds C/D poor.

Most important muscle in valsalva?

Tx paroxysmal SVt w/ valsalva... or carotid sinus massage... Increase vagal tone increase refractory period of AV node and help prevent re-entrant circuit from conducting... Adenosine recommended if these fail Valsalva is a forcible exhale against a closed glottis... Take a full inhalation closing glottis and bear down w/o exhaling. Recuts muscles ar erecruited and cause increased intra-abdominal pressure and intra-thoracic pressure.

UMN and LMN signs

UMN = spastic paralysis, clasp-knife rigidity, hyperreflexia, babinski sign LMN = flaccid paralysis, hypotonia, hyporeflexia, muscle atrophy & fasciculations

What random component of cellular functioning is involved in MHC degradation?

Ubiquitin ligase!!! It has to degrade the proteins first so that they can be attached to HLAs

What is associated w/ Autoimmune hepatitis in the GI?

Ulcerative Colitis

What do aminosalicylic acid derivatives treat?

Ulcerative colitis

ZES presentation

Ulcers beyond duodenal bulb even in jejunum also refractor to PPIs also can get diarreha from acid damagin intestines... diagnose by measuring basal and secretin stimulated gastrin levels... Patients w/ ZES should undergo testing to exclude MEN1 ~Glucagonoma... rare alpha cell tumor p/w diabetes and raised erythemaous rash of the groin (necrolytic migratory erythema) ~Insulinoma... hihg insulin/C peptide and hypoglycemia ~Carcinoid = diarrhea, bronchospasm, flushing, RS heart disease... secrete serotonin OR bradykinin ~Somatostatinomas... p/w DM, cholelithiasis (inhib CK), diarrhea/steatorrhea (inhib pancreatic enzymes/bicarb), achlorhydia VIPomas = watery diarrhea, achlorhydia, hypokalemia

Unfract Hep vs. LMWH

Unfract Hep... pentasaccharide sequence binds antithrombin... can get Factor Xa or use the loop long to bring in thrombin and form ternary complex LMWH has same penta sequence and binding to antithrombin but factor Xa interaction is same but no long loop for thrombin

Heparin overdoseeee

Unfractionated heparin (UFH) and LMWHs are commonly used anticoagulants in the hospital setting.... Heparin increases the effect of naturally occurring anticoagulant antithrombin 3... aPTT is measured to monitor therapeutic effect of heparin. Protamine sulfate to reverse things... It is a peptide that binds to heparin forming a complex that has no anticoag activity... Doesn't completely reverse the anti-Xa activity of LMWH

Occlusion of unilateral ACA and B/L aca symptoms

Unilateral --> contralateral foot/leg symptoms. B/L ACA can get behavioral symptoms and urinary incontinence as well if the frontal micturition center is affected (medial frontal lobe/cingulate gyrus)

What causes dimpling in breast cancer?

Upper outer quadrants are the most common site of breast cancer and presents as an irregularly shaped mass, adherent breast mass.... Dimpling is an indication that the suspensory ligament of the breast (Cooper's ligament) has been infiltrated w/ cancer and causes shortening and fibrosis. (distorts breast contour). ~Direct invasion of dermis by rare type of cancer (inflammatory breast cancer) can cause skin changes of erythema, and invasion of lymphatic spaces by malignant cells leading to lymphedema w/ finely pitted appearance known as peau d'orange. ~Most common site of mets is the axillary lymph nodes. ~Lacteriferous sinuses lie under the nipple and are reservoirs from mammary alveoli during lactation. Nipple discharege and superficial nipple changes caused by these being invaded. (PAGET's)

Complication occurring after hysterectomy presents w/ fever and flank pain...

Ureteral injury... Pelvic portion of ureter passes along the pelvic brim and courses medially and anteriorly to the bifurcation of the common iliac arteries. THen passes along lateral pelvic sidewall posterior to ovarian vessels to dive under the uterine vessels. Runs anterolateral surface of the cervix at the level of the internal os to enter trigone of the bladder. 1) Ureteral Obstruction = Flank pain from distention of the ureter... 2) Transection Injury = localized leakage of urine as well as flank pain... If one ureter is working, patients are able to void/urinate.

What is the most common site of fetal hydronephrosis caused by obstruction?

Ureteropelvic junction... commonly fetal hydronephrosis is detected via ultrasound at second trimester. Usually transient or insignificant as the renal pelvis has a high compliance and can accomodate large volumes of urine. Most common cause of unilateral fetal hydronephrosis is a narrowing or kinking of the proximal ureter at the ureteropelvic junction (UPJ). Newborns can p/w palpable abdominal mass and enlarged kidney... UPJ is the last segment of the ureters to canalize. Failure of canalization through abnormaly development of circular musculature and/or collagen fibrils. ~Posterior urethral valves are the most common cause of B/L fetal hydronephrosis in boys... They are caused by obstructive, persistent urogenital membrane at junction of bladder and urethra. ~B/L hydronephrosis can also be cause by urethral strictures and bladder neck obstruction, along with neurogenic obstructive uropathy (spinal cord damae)

Patient w/ rubber, aromatic amine dyes, textiles, or leather exposure at work for years has hematuria... what do you think?

Urothelial transitional cell carcinoma. also suspected in smoers. Peaks in 7th/8th decasdes... WIll have multifocal sessile or papillary tumors.

What is Cilostazol?

Used in patients w/ PVD who also want dilation of arteries = symptomatic relief and inhibition of platelet aggregation Thrombin, Adenosine Deaminase, Thromboxane A2 activate platelets on cell surface receptors. Interference w/ post-receptor signaling can alter platelet function. cAMP activates cAMP-dep PK or PKA leading to inhibition of platelet aggregation. Increasing intra-platelet cAMP decreases aggregation by preventing platelet from changing shape and degranulating This drug inhibits platelet PDE It's also an arterial vasodilator. Overall decreases claudication. Also, start PAD patients on a graded exercise program, which improves symptoms

Second Trimester Quadruple Screen

Used to ID pregnancies at high risk for congenital defects... increased MSAFP (AFP).. open neural tube defects, ventral wall defects (omphalocele/gastroschisis), mutliple gestation... decrease is aneurploides (18/21) also measure estriol, beta-HCG, inhibin A in context of gestational age. AFP made in fetal liver, GI tract and yolk sac (early gestation)... increase w/ gestational age... Accurate dating is crucial for calculations of risk... Gestational age can be off due to irregular menses... Ovulation usually occurs 14 days after day of full menstrual flow in women w/ monthly cycles... WOmen w/ irregular periods ovulate less predictably and are prone to anovulatory menstrual cycles... U/S to know forsure. ~Smoking increased risk of fetal growth restriction... decreased estriol levels not AFP correlate w/ this and placental abnormalities.

How big are lacunar infarcts usually?

Usually 5-6mm, can be up to <15mm... Usually basal ganglia, posterior limb of IC, pons, cerebellum. Lipohyalinosis and Microatheromas are the cause... Lipohyalinosis is due to leakage of plasma proteins through damaged endothelium leads to hyaline thickening, collagenous sclerosis, accumulation of foamy MPs Microatheromas are atherosclerotic accumulation of lipid-laden MPs w/in intimal layer of penetrating artery.

Patellar fracture

Usually due to a direct blow to the anterior knee.. Or excessive force on the quad... Swelling, tenderness, inability to extend knee against gravity and a plapable gap in extensor mechanism. Actually bones won't move around, just problems w/ muscles.

How long is the incubation of HepB?

Usually long asymptomatic period of 6-8 weeks... followed by acute disease lasting several weeks to months. HbsAg becomes undetectable in 3-6 months unless chronic phase begins. AntiHBsAG IgG rises after acute disease has resolved (unless chronic phase begins). Exacerbation of HepB would involve a spike in antigen levels

V2 or V3

V3 is mandibular V2 is maxillary

Patient w/ CKD suspect PE what's the test?

VQ scan, don't want to use contrast for CT angiography you'd normally prefer

Which murmur is not usually detectable at birth?

VSD... a loud, blowing, holosystolic murmur at left sternal border w/ no symptoms... Audible at 4-10 days as pulmonary vascular resistance continues to decline permitting L-R shunting.. Most are insignificant and close spontaneously.. Moderate to large VSDs will p/w heart failure, failure to thrive, diaphoresis w/ feeding No murmur as RV pressures are similar to LV... Rarely close spontaneously and can lead to chronic pulm HTN/cyanosis and Eisenmenger Syndrome.

What two syndromes from SMA syndrome?

Varicocele bc left renal vein and also duodenal obstruction at transverse section. Pr in left vein is usually higher than right due to compression b/w aorta and SMA (Nutcracker effect).. Persistnet elevated L renal pressure can cause flank/abdominal pain w/ gross/microscopic hematuria... = left renal vein entrapment syndrome.

What mediates migraines in women?

Vasoactive neuropeptides like substance P and calcitonin-gene related peptide (CGRP) cause neurogenic inflammation due to vasodilation and plasma protein extravasation. -neuronal sensitization occurs too, where central nociceptive pathways become more sensitive to painful/nonpainful stimulation Triptans are serotonin agonists (5-HT1B adn 1D) counter migraines by inhibiting release of vasoactive peptides, promoting vasoconstriction and blocking pain pathways int he brainstem. They stimulate postsynaptic serotonin receptors.

what does muscarinic stimulation due to skin?

Vasodilation... Muscarine is a toxin found in some mushrooms and causes widespread muscarinic agonism. Leads to vasodilation w/ hypotension and low BP. And inadequate cerebral perfusion.

Nitrates affect on the heart physiology

Venodilators that increase peripheral venous capacitance... Reduce cardiac preload and LV end diastolic pressure/volume... THis is good for patients w/ acute pulmonary edema. Lower LVEDP leads to reduction in LV systolic wall stress and decrease in O2 demand, relieving angina. Although mostly vein, does have some arteriolar effects...

Wallenburg Syndrome presentation

Vertebral or PICA are affected. vertigo, nystagmus (vestibular nucleus damage) ipsilateral cerebellar signs (ataxia w/ tendency to fall toward lesion) due to injury of inferior cerebellar peduncle, loss of pain/temp in ipsilateral face and contralateral body (spinal trigeminal and spinothalamic) bulbar weakness (dysphagia, dysphonia) due to injury to nucleus ambiguus. Ipsilateral Horner's too Traumatic vascular dissection is a common cause of ischemic stroke in young healthy people. Often vertebral arteries at C2 in the cervicocephalic junction... P/w local head and neck pain and FND due to cerebral ischemia.

How do cancers of pelvis (prostate included) spread to the spine?

Vertebral venous plexus... communicates w/ prostatic venous plexus.

How does surfactant get into alveolar space?

Via lamellar bodies (organelles w/ parallel stacks of membrane lamellae) released via exocytosis into alveolar spaces where lamellar contents unravel and spread along the alvoelar lining... As it degrades, surfactant is recycled back into the same type 2 pneumocytes via endocytosis for reprocessing.

What are some examples of food poisoning and toxin formed after ingestion?

Vibrio, ETEC, EHEC, Shigella

WHy does appendicitis pain move?

Visceral abdominal pain is due to distension/stretching of smooth muscle and carried via visceral afferent fibers of autonomics. Has poor localization, dull, cramping quality. Whereas, Somatic pain is usually due to irritation of the parietal peritoneum and well localized/more severe. As appendix becomes more inflamed it irritates the parietal peritoneum and causes new pain at McBurney's point. 2/3 from umbilicus to anterior superior iliac spine. Has rebound tenderness.

What is the differences b/w Vit C and K def on blood tests?

Vit C has normal PT and increased PTT Vit K has both increased PT and PTT

Tocopherol, what is it?

Vitamin E... fat sol.. scavenger of free radicals... Deficiency --> ataxia, hyporeflexia, loss of sensation, hemolytic anemia

Biliary Atresia Presentation?

W/in first 2 months of life, progressive or complete obstruction of extrahepatic bile ducts... Destruction by immune or virus related... Infants can appear healthy at birth then get jaundice in first 2 months, along w/ dark urine and acholic (pale or clay colored) stools due to excessive renal excretion of bilirubin and lack of intestinal bile. Firm hepatomegaly due to inflammation... Labs have elevated direct bilirubin and gamma-glutamyl transferase. Liver bx reveals intrahepatic duct proliferation, portal tract edema, fibrosis... Urgen surgery needed or cirrhosis and death w/in first 2 years. ~Gilbert = inherited, benign, reduced glucuronyl transferase. asymptomatic except fasting, illness w/ mild hyperbilirubinemia and jaundice ~Breast milk Jaundice = indirect hyperbilirubinemia in first 2 weeks. Likely beta glucuronidase in breast milk that deconjugates bilirubin. Increased absorption increased enterohepatic circulation of bili... Urine/stool unaffected ~Hemolytic Disease of Newborn = results from Rh incompatibility. (Rh+ infant) or ABO incompatibility. Jaundice on first day due to indirect hyperbilirubinemia and a positive direct Coombs confirms antibody mediated lysis.

Someone w/ anxiety disorder gets an SSRI... still having problems

Well SSRIs take 4 weeks to be noticable... Durign this period, initial activating can cause agitation/anxiety... Benzos good fro this time frame.... Short, Intermediate, and Long acting based on half lives... Patients w/ anxiety causing insomnia need one. Minimization of undesirable day time side effects means confined to sleep!! not Long >24 hours and short < 6 hours... Short = Triazolam, Oxazepam, Midazolam Intermediate = Alprazolam, Lorazepam, Temazepam Long = Diazepam, Chlordiazepoxide, Flurazepam

Kidney stone in someone w/ Chron's

When terminal ileum is inflamed, bile acids are lost inf eces. Loss of bile acids causes impaired fat absorption. The excess lipids in the bowel lumen bind calcium ions and these soap complexes are excreted in the feces. In the healthy bowel, dietary calcium binds dietary oxalate producing insoluble calcium oxalate salts the promote oxalate excretion. In chrons, calcium binds lipids instead as a result oxalate absorption isn increased promoting enteric oxaluria/CaOxalate stones. ~Cystinuria... defect in amino acid transporter gene resulting in elevated urinary cystine concentrations. Cystine stones in childhood.

Calcium Oxalate Crystals... where do they suggest ethylene glycol poisoning?

When they are found in the tubular lumen... P/W ATN, proximal tubular cell ballooning and vacuolar degeneration... Ethylene glycol is rapidly absorbed from GI tract and metabolized to glycolic acid (toxic to renal tubules) and oxalic acid, which precipitates as calcium oxalate crystals... Brake fluids, engine coolants, automobile antifreeze. ethanol intoxication symptoms, ARenalF (oliguria, anorexia, flank pain) 24-72 hours later... High anion gap metabolic acidosis and osmolar gap seen.

16 year old boy w/ tremors and difficulty walking. Declining school performance, moodiness, impulsiveness, more sleeping, weight loss, poor appetite, tremor is intention tremor in hands. Unsteady, broad based gait

Wilson's... ATP7B gene. Imparied cellular transport of copper. Accumulates in liver, brain, eye. Excess copper causes injury by binding sulfhydryl groups. Liver injury can be asymptomatic w/ steatosis OR acute hepatitis. Basal ganglia cause the parkinsonism w/ cerebellar ataxia/tremor. D-penicillamine contains a free sulfhydryl group to chelate copper.

Presentation of Sheehan Syndrome

Woman 2 weeks post partum w/ no lactation and she has weight loss, feels fatigued/tired... Has symptoms of orthostatic hypotension from decreased cortisol so hypotension.... panhypopituitarianism. Due to ischemic necrosis... Estrogen-induced hyperplasia of lactotrophs causes hyperplasia of pituitary but blood supply doesn't increase concortidantly. VUlnerable to infarction in peripartum hemorrhage.

Work of breathing stuff

Work done against elastic resistance of the lung is increased when tidal volujme is increased, while work done against airflow resistance is increased when breathing frequency is increased... Respiratory frequency can x axis while work of breathing y and your body will seek the lowest work of breathing rate Normal people this is around 15 In Obstructive Lung diseases with high airflow resistance, patients breathe at a lower rate (slow, deep breaths) to minimize work of breathing In Restrictive Lung Diseases... work of breathing is minimized against stiff lungs when tidal volume is decreased and RR is increased so breath rapid and shallow.

What is the mutation causing disease in hemophilia A?

X linked disorder due to factor 8 deficieny.. Many mutations can cause it, including enhancer mutations. random but two promoter sequences in humans are TATA and CAAT. 25 upstream and 75 upstream respectively.

8 hours after a 4 hour half life drug is administered at X dose in a volume of distribution of Y liters, what is the serum drug concentration?

X/2 and then divided by 2... over Y

Hormones and P/W of Klinefelter's

XXY decr T, increased LH/FSH, estradiol P/W primary hypogonadism, increased long bone length, gynecomastia, learning/socialization difficulties. absent deep voice, beard, male-pattern pubic hair and a tall stature is expected *Gynecomastia is associated w/ risk of malignant transformation!!

Lipid laden macrophages on microscopy of eye lid what ya think?

Xanthelasma... Classically associated w/ hyperlipidemia... Chronic cholestatic processes result in hypercholesterolemia and formation of xanthelasmas.

If pulmonary HTN is fixed, can heart repair?

Yes can return to normal

What are the two peroxismal disorders?

Zellweger Syndrome = Defective peroxisomal biogenesis... p/w infancy craniofacial abnormalities (large anterior fontanelle, widened sutures), hepatomegaly, profound neuro deficits (hypotonia, seizures, DDelay) death within months :( X-linked Adrenoleukodystrophy... defective transport of VLCFAs into the peroxisomes... p/w childhood/adulthood w/ neuro deterioration and adrenal insufficiency.. these VLCFA accumulate in the CNS/Adrenals/Testes

What is the most common DNA-binding domain in humans?

Zinc finger... these motifs have histidine and cysteine linkages that determine DNA-binding specificity. Many transcription factors use multiple zinc-finger motifs to recognize the right domains. The zinc atom forms linakges w/ cysteine and histidien then forms a stable, finger-shaped structure w/ 2 antiparallel beta strands and an alpha helix... Steroids, thyroid hormone, and fat soluble vitamins R are usually zinc finger.

Where is enteropeptidase

a duodenal brush border enzyme. Enteropeptidase deficiency occurs when both protein and fat malabsorption as trypsin is required to activate enzymes for both protein and lipid digestion. P/w diarrhea, failure to thrive, edema (due to hypproteinemia)

How long does it take TZD to work and what are its effects?

a few days to a few weeks.. For significant reduction Effects = 1) increase fatty acid uptake 2) increase adiponectin 3) increase insulin sensitivity (of muscle/liver) 4) decrease TNFalpha production 5) decrease leptin production TZD binds PPARgamma, a transcriptional regulator of genes involved in glucose/lipid metabolism... causes a change that binds other cofactors --> like retinoid X receptor RXR...

Kinesin

a microtubule associated motor protein whose function is anterograde transport of intracellular vesicles and organelles toward the plus (rapidly growing) end of microtubules... Uses ATP energy to move along microtubules. Kinesin carries vesicles and organelles away from the cell body in axons. Targeted toxic insult to this protein would be expected to impair transport Microvilli contain actin thin filaments.

What is Oseltamivir?

a neuraminidase inhibitor. Newly synthesized virions adhere to the host cell surface and form viral aggregates. Also prevents viral penetration of mucus secretions that protect the respiratory epithelium.

How does duodenal atresia present?

abdominal distension and bilious emesis

Possible manifestations of Henoch-Schonlein purpura

abdominal pain, arthralgias, recent infx, purpura on buttocks/thigs, stool occult blood, hematuria, intussusceptions due to immune complex IgA vasculitis Tx is supportive unless there are complications

What causes hemorrhoids?

abnormal distension of the anal arteriovenous plexus, which normally forms the anal cushions important for maintaining fecal continence. Chronically increased venous pressure due to prolonged straining or breakdown of supporting tissue from age cause these canals to bulge into the anal canal. They can inflame, thrombose, prolapse. Treat w/ rubber band ligation which cuts off the blood supply to the lesions and causes them to degenerate. Internal hemorrhoids = internal mesenteric vein, to superior rectal, visceral innervation so no pain.

Leucovorin

aka folinic acid... useful for methotrexate overdose... enhances cytotoxic action of 5-FU and is used incombo for colorectal cancer often.

Acrochorda

aka sin tags... benign, pedunculated outgrowths of normal skin... Develop at places of frction.

what is a pain reliever w/ anti cholinergic effects?

amitryptilline

How does amyloid work in Alzheimer's Disease?

an insoluble, fibrillary protein that deposits int he ECF of tissues... Apple-green birefringence in tissues due to their beta-bleated sheet... Amyloid deposition can affect multiple organs... Plasma cell tumors = AL deposition Chronic diseases = AA deposition Alzheimer's Disease it is beta-amyloid deposition (from cleavage of amyloid precursor protein = a transmembrane glycoprotein)... Early in disease, senile (neuritic) plaques can be found in the medial temporal lobe = hippocampus, amydala, entorhinal cortex) composed of Abeta core w/ dystrophic neurits... Abeta depoisition occurs in the media/adventitia of cerebral vessels and may cause weakening --> hemorrhage.

If you damage IMA, why not ischemia?

anastomoses from SMA... specifically the marginal artery of Drummond... sometimes the arc of RIolan (not always there).. IMA at risk during Abdominal Aortic Aneurysm repair

Why is horseshoe kidney tough for repair of abdominal aorta?

anomalous origins of multiple renal arteries to each kidney

Primary cause and 4 symptoms of NMS?

antagonism of central dopaminergic systems. hyperthermia, severe lead pipe rigidity, autonomic instability, altered mental status Serotonin Syndrome, same but has clonus/shivering/hyperreflexia. as opposed to bradyreflexia and diffuse rigidity of NMS.. More n,v,d in serotonin syndrome too (hyperthermia also less severe)

What does niacin do to benefit a patient with hyperTG-emia?

antagonizes VLDL cholesterol secretion doesn't stimulate PPAR-alpha R

Treatment for digoxin toxicity?

anti-digoxin Fab, stabilizing K+, cardiac pacemaker and Mg2+

Goodpasture's

antibody against alpha 3 chain of type 4 collagen.. Antibody formation may be triggered by an antecedent viral respiratory infection. Leads to RPGN

Elder Abuse

ask questions like do you feel safe? Who prepares your meals? who handles your checkbook? make sure no neglect, malnutrition, bruises, inconsistent history, psych abuse, Prompt reporting if it is suspected. ~Home Safe Evaluations are to identify RF for falls Need physical exam and history privately w/ patient to report abuse.

3rd phase of Lyme disease

asymmetric arthritis (often knee) and subacute encephalopathy (early disseminated Lyme disease) = decreased memory, somnolence, mood changes

Huntington Disease genetics

auto dominant caused by increase in number of CAG trinucleotide repeats in the gene that code for the huntingtin protein. Expansion of proteins polyglutamine regions results in gain-of-function that leads to pathologic interaction w/ other proteins, like tx factors. It transcriptionally represses (silences) other genes. Abnromal huntingtin causes increased HDAC silencing genes necessary for neuronal survival. As a result, one treatment option is histone deacetylase inhibitors that upregulate survival genes.

Achondroplasia inheritance

autosomal dominant occurs as a sporadic mutation in 85% of cases then is inherited autosomal dominant fashion in 15%...

Avoids people due to HSN of rejection in social situations

avoidant personality disorder

How is the long thoracic nerve injured and how does it present?

axillary lymph node dissection leads to paralysis of serratus anterior and winging of scapula

Argatroban

binds thrombin active site

Treating MI w/ bradycardia

can give atropine... leads to mydriasis... narrows anterior chamber angle and diminishes outflow of aqeuous humor --> angle closure glaucoma in people w/ shallow anterior chambers or higher than normal IOP...

Catheter fungal infection

can hit the catheter.. candida... pseudohyphae w/ blastoconidia. Lipid emulsion in the parenteral nutrition is thought to promote this growth.

What causes coma in patient w/ Reye's syndrome?

cerebral edema not viral encephalitis

Give someone tPA for a StEMI, what are you most scared they develop? How does it present?

comatose, asymmetric pupils, irregular breathing... Intracerebral hemorrhage.

When to culture for give tx for GBS

culture at 35-37 weeks and give intrapartum.

c-ANCA what is it?

cytoplasmic-staining anti-neutrophil cytoplasmic antibodies.... hits neutrophils... not mitochondria antimitochondrial antibodies w/ PBC

What to free ribosomes synthesize?

cytosolic and steroid hormones and help w/ drug detoxification and ATP production enzymes.

a b c d how to calculate false positives from spec and sens

d/B+D = specificity If 0.9= specificity and b+d = 200 0.9=d/200 d = 180

What is the name of head bobbing w/ carotid pulses and what is the usual diagnosis?

de Musset sign.. A regurge... Due to transfer of momentum from large LV stroke volume to head and neck. Also get water-hammer pulses w/ wide pulse pressure ~AStenosis will have narrow pulse amplitude (pulsus parvus) w/ a delayed peak and slow upstroke (pulsus tardus) due to diminished stroke volume and prolonged ejection time. ~same w/ mitral stenosis due to decreased LV end diastolic volume and stroke volume (pulse pressure and amplitude)

Paget's Disease histo description

dense, hypovascular, mosaic pattern of lamellar bone w/ irregular, haphazardly oriented sections separated by prominent cement lines. Thought to be environmentally factors like RANK/osteoprotegerin resulitng in excessive RANK, nfkappaB activation. leading to increased osteoclast differentiation. End resul tis a thickened deformed bone weaker than normal... In early PDB, adjacent marrow spaces are replaced by highly vascular stromal tissue as a result of increased endothelial cell and fibroblast proliferation due to cytokines secreted by osteoclasts. Increased vascularity causes AV shunting leading to high output cardiac failure

When to know when reassortment happens versus recombination if progeny gets a phenotype from obvious combination genetics and passes to progeny

depends on if nonsegmented or segmented... If non-segmented ds DNA then recombination w/ crossing over... if segmented viruses, reassortment.

What are testes pulled through in orchiopexy?

descend normally at 8 weeks by passing from abdomen into the deep inguinal ring to enter inguinal canal. This is an opening of transversalis fascia bounded by transversus abdominis muscle and inferior epigastric vessels.. Testes pass anteromedially to exit canal via superficial inguinal ring. The teste in CC is in the inguinal canal (so passed the deep inguinal ring, and has to be brough through the superficial inguinal ring made of external oblique.

Which congestion medication causes constipation?

dextromethorphan

What is psoas sign?

due to a retrocecal appendix can irritate the iliopsoas group of hip flexors... Psoas sign is abdominal pain elicited by passive thigh extension, which causes friction.

Overflow incontinence symptoms

due to impaired detrussor contractility or bladder outlet obstruction... involuntary loss of urine, trouble starting stopping, nocturnal enuresis, daytime uncontrolled voiding w/o sensation of full bladder, increased postvoid residual volume. Pts can develop this if they have diabetes --> autonomic neuropathy of detrussor muscle innervation. Initially --> loss of autonomic afferent sensation... Efferent fibers to bladder causes incomplete emptying. Can develop recurrent UTIs and pelvic floor relaxation at night is the casue of nocturnal enuresis. ~~ BPH don't see until 50-60, urge incontinence (bladder irritation from large prostate) OR overflow (from obstruction) ~Loss of perineal sensation due to cauda equina

Repeated abortions and then live child born w/ anomalous organs....

due to unbalanced chromosomal rearrangement, NOT gonadal mosaicism.

In patient with PCOS, what would you expect from testosterone, fasting insulin and LH?

duh LH will be highhhhh, because that is the whole point of LH/FSH >2... so increased insulin (insulin resistance), increased testoterone, increased LH

Who is most at risk for B6 def w/ isoniazid?

elderly, alcoholics, kidney/liver dysfunction

how will a patient w/ one testicle affect hormone levels?

elevated FSH, normal LH, low inhibin B if undescended then orchiectomy orhiopexy is surgery that allows descent. Androgen levels are not affected due to compensation.

What do you need w/ elevated alk phos to make significant?

elevated GGT (to rule out bone and in liver)

What levels of TSH, T3 and T4 do you normally see w/ primary hypothyroidism?

elevated TSH, low T4, but T3 is often normal because it has a short half-life and fluctuate widely and produced in peripheral tissues.

how to describe giardia on microscopy?

ellipsoidal cysts w/ smooth, well-defined walls and 2+ nuceli, pear shaped flagellated trophozoites.

What is telomerase...

end of linear eukaryotic chromsomes... repeat DNA sequences, like GT rich repeats (TTAGGG) can't fully replicate the 3' end of lagging chromsomal strands, DNA pol can't... Once at maximal limit for proliferation ~60, shortened telomeres trigger growth arrest. TP53 activated and cell dies. RNA dep DNA polymerase = telomerase... has two molecules, human telomerase reverse transcriptase (TERT) and telomerase RNA (TR/TERC) Germ cells and some adult stem cells have this, but >90% of cancer cells have increased telomerase activity.

Why would pancreatic lipase improve CF kid?

enhancing macronutrient and vitamin absorption, supplement failure to thrive.

GAD

excessive chronic anxiety that is uncontrollable about multiple issues for >=6 months. Muscle tension, sleep distrubance, sweating, nausea... First line is CBT and SSRI orSNRIs

How does excessive exercise cause amenorrhea?

exercise excessive suppresses secretion of GnRH, leadin to decreased release of FSH and low estrogen levels. E decreases bone resorption so decrease E increases osteoporosis .

What portion of airflow is messed up in asthmatics?

expiraotry airflow resistance causes the decreased FEV1/FVC... Bronchial challenge testing w/ methacholine can rule out astham... BHR is the concentration of inhaled aerosolized bronchoconstrictive substance required to produce a 20% decline in FEV1. These tests would say maybe asthma but not rule in or out ~CXR w/ hyperinflation during an asthma attack (nromal between) ~Eosinophil counts (sputum eosinophilia would be better) ~serum IgE helps but meh.. but doesn't account for intrinsic asthma causes like pulmonary infections, aspirin, cold air, inhaled irritants, stress, exercise -skin tests same thing.

What causes NTDs

failure of fusion of neural plate edges during the 4th week of fetal development... Begins in cervical region and proceeds toward cranial and caudal ends (rostaral and caudal)... Failure of rostral --> anencephaly... failure of caudal --> spina bifida If opening persists can get AChE in amniotic fluid.

What syndrome does phenytoin cause if taken w/ pregnany?

fetal hydantoin long term --> hirsutism, gingival hyperplasia, coarse facial features.

What happens to a cryptorchidism testicle?

fibrosis, prominent Leydig, hypoplastic Sertoli

Which fingers does carpal tunnel p/w?

first 3.5 digit. Thenar atrophy w/ weakness of thumb abduction/opposition

What is nonmaleficience?

first, do no harm don't prescribe drugs if risks outweigh benefits!! even if they want it

What are two scenarios that can increase ventricular preload and LV end diastolic pressure?

fluid overload from CHF and Renal Failure OR infusion of IV fluids

Tretrodotoxin = potent neurotoxin

found in pufferfish, functions by blocking VG sodium channels in nerve membranes.

What causes retinal damage in neonate oxygen therapy?

free radicals... local hyperoxia in retina induces changes to upregulate proangiogenic factors (VEGF). Retinal vessel prolifeartion, and detachment may result --> blindness. Retrolental Fibroplasia or Retinopathy of Prematurity

How does secondary hemochromatosis present?

frontal bossing, HSM, jaundice w/ Kupffer cells containing coarse, yellowish-brown cytoplasmic granules with hemosiderin. Can differentiate from lipofuscin w/ a prussian blue stain. Lipofuscin is made of lipids and phospholipids Once deposited in cells, iron binds to apoferritin to form ferritin micelles. Hepcidin inhibits transport of iron to transferrin from hepatocytes and MPs that engulfed iron.

What are a couple random risk factors for gall stones?

gallbladder hypomobility = spinal cord injury or those w/ total parenteral nutrition

Mitochondrial Myopathy

genrealized tonic-clonic seizures, erratic jerking of arms/legs, intermittent weakness... Decreased sensation and broad-based gait Sk m bx shows ragged, red-appearing muscle fibers. brain and muscle most affected due to high metabolic rate. seizure and neuropathy from lactic acidosis.

Test for candida

germ tube test... distinguishes it from other candidas too. Inoculation of C albicans into serum at 37C for 3 hours leads to formation of true hyphae from the yeast.

Overdose on beta blockers, what do you give someone to revive?

glucagon... works by increasing cAMP in cardiac myocytes. Beta blocker to causes depressed myocardial contractility, bradycardia, varying AV block... Glucagon works via GCP to increase cAMP and increase intracellular calcium during muscle contraction, increasing HR/contractility

What is the most abundant AA in collagen?

glycine... it is small adn can fit into confined alpha chains

Enfuviritide inhibits entry of viral core into host cytoplasm

gp41 inhibitor

Describe dry AMD and wet AMD

gradual vision loss in one or both eyes, esp when driving/reading... Chronic oxidative damage to retinal pigment epithelium and choriocapillaris leading to subretinal inflammation w/ abnormal EC deposition. Leads to drusen deposits. Wet MD Progressive EC accumulation of dry MD leads to retinal hypoxia which stimulates VEGF to neovascularize. Appear as grayish discolorations in the macula w/ areas of adjacent hemorrhage. THis p/w acute vision loss and metamorphopsia (distortion of straight lines). Patients w/ either tx w/ antioxidant vitamins and zinc and smoking cessation.. Wet MD give VEGFinhibitors = bevacizumab, ranibizumab

Measurement that changes in the blood of patient w/ SCD?

haptoglobin

When using a large population screening test, what is the goal of the first test?

high sensitivity ensure not to miss cases. Esp important for life threatening disease.

Precipitating causes of digoxin arrhythmia from toxicity?

hypokalemia @treatments start, hypovolemia, renal failure. Tx toxicity w/ anti-digoxin antibody fragments.

What is volume of distribution?

hypothetical fluid into which the administered amount of drug would need to be uniformly distributed to produce the observed plasma concentration. Vd in Liters = amount of drug given (mg)/plasma concentration (mg/L) Average total body water is 41L... 14L is ECF... plasma is 3L. If a drug is large molecular weight, bound to plasma proteins or is hydrophilic/charged, then generally remains in plasma compartment. and Vd is 3-5L. More Vd if lipophilic or hydrophobic Drugs that avidly bind tissues exhibit the highest Vd, often much higher than total body water volume because they accumulate readily within cells.

Partial vs. Complete Hyatidiform Mole on pathology and IHC?

iHC... complete is p57 negative partial is p57 positive Complete... diffuse trophoblastic proliferation and edematous chorionic villi (bunch of grapes) no fetal tissue Partial.. some enlarged villi w/ focal trophoblastic proliferation, some fetal tissue Complete has such high beta HCG that it can cause complications... 1) Hyperemesis gravidarum 2) Pre-eclampsia 3) Hyperthyroidism 4) Theca-Lutein cysts Partial will actually have normal-high betaHCG, normal uterine size, crampy abdominal pain w/ vaginal bleeding

Lumbar Puncture landmarks....

iliac crests and push into L3/L4 or L4/L5 in lateral decubitus position

What would you see on bx of ectopic pregnancy endometrium?

immature chorionic villi at fallopian tube nbut not in terus

Chediak Higashi presentation

immunodef, albinism, neuro defects in children. Nystagmus and peripheral/cranial neuropathies are common Defect in neutrophil phagosome lysosome fusion. Causes abnormal giant lysosomal inclusions that are visible on light microscopy of a blood smear. Leads to pyogenic infections by staph/strep. Abnormal storage of melanin in melanocytes leads to oculocutaneous albinism.

What is significant about Burkholderia cepacia?

in CGD patients more likely to be infected bc it is catalase-positive. Patients w/ CGD are not at increased risk of parasitic or viral infections. CGD causes inactivating mutation in NADPH oxidase.. impairs respiratory burst and inhibits phagocytic intracellular killing Recurrent infections w/ catalse-positive bacteria and fungi Oftne lungs, skin lymph nodes, liver involved w/ diffuse granuloma formation Dx is measurement of NP superoxide production (DHR flow cyto *dihydrohodamine OR NBT testing *nitroblue tetrazolium)

What does passive leg raise do for murmurs, what about abrupt standing?

increase then decrease preload

What is most important for preventing wrong surgical site procedures?

independent verification by 2 healthcare workers. Use timeoutes before and after procedures

CMV retinitis findings

inflammatory vascular sheating and associated hemorrhage... Full thickness retinal necrosis and edema w/ replacement by atrophic scar tissue... Esp if CD4 < 50

What causes myocytes to swell in hypoxic conditions?

intracellular Ca2+ accumulation. (need ATP to pump out in two options)

Abdominal pain and blood diarrhea following surgery hypotension...

ischemic colitis... Main watershed areas 1) splenic flexure (SM and IMA border supply) and 2) rectosigmoid junction (sigmoid artery and superior rectal artery) p/w pale mucosa w/ petechial hemorrhage on colonoscopy

What is the most common cause of HF in developed countries?

ischemic heart disease

What is c-JUN

it is a DNA binding protein... C-Jun and C-Fos are nuclear transcription factors that bind DNA fvia a leucin zipper motif. Needs SW blotting technique to detect them. ssRNA or DNA fro N/S... ds DNA for SW

Patient w/ hematuria and moderate proteinuria...

it is a nephritic syndrome... Renal biopsy w/ linear deposits suggests glomerular basement membrane disease. IF deposits are composed of IgG and C3, targeting collagen type 4. Will get infiltration of monocytes and macrophages. Will also get pulmonary symptoms.

What is delta agent in context of hepatitis...

it is the hepatitis D virus.. replication defective RNA virus only capable of causing infection when encapsulation w/ HBsAG happens... Coinfection or superinfection only.

What is the TC?

it is the teniae coli... used as a surgical landmark in appendectomies Begins as a continuous layer of longitudinal muscle that surrounds the rectum just below the serosa... At the rectosigmoid junction, this layer condenses to form 3 distinct longitudinal bands. These travel outside of the entire colon before converging at the root of the vermiform appendix... The TC have a similar function as the outer layer of muscularis externa of GI tract... TColi run the length of the colon and contract lengthwise to form haustra, colonic sacculations causing colon's segmented apearance.

What joint is most often involved in pseudogout?

knee > 50%... MTP is in normal gout. blue when parallel and yellow when perpendicular to slow ray of the compensator.

What do parietal cells look like in microscopy?

light cytoplasm, dark nucleus.

How does HBV cause HCC?

liver mass w/ high AFP in someone w/ known HBV = HCC... HBV-cirrhosis first. Integration of viral DNA into cellular genome of the host is a trigger for neoplastic changes... Viral protein HBx activates synthesis of insulin-like growth factor 2 and receptors for IGF1 --> cell proliferation. HBV genes also suppress p53 tumor suppressor Also chronic inflammation plays a role as well

Different types of adenomas

long glands w/ finger like projections = villous... large and sessile w/ cauliflower/velvety projections Tubular adenomas are dysplastic colonic mucosal cells from tube-shaped glands and tend to be smaller/pedunculated. Mixture is tubulovillous. Adenomas can cause occult bleeding --> Fe Def Anemia... Larger can cause obstruction... Villous can make PGE2, which results in increased insulin and secretory diarrhea w/ mucinous stools... Mucin is potassium rich and excessive production can lead to hypoproteinemia and hypokalemia. ~Hamartomous are disorganized mucosa glands smooth muscle, CT. ~HYperplastic are well differentiated mucosal cells that form glands/crypts... Crypts may be large or irregular but are NOT associated w/ dysplasia.

MCD basement membrane changes

loss of glomerular basement membrane anions, loss selective of albuminuria... damaged podocytes w/ foot process effacement and fusion

What is found in DIC blood studies?

low fibrinogen, high d dimer, long PT long PTT

If 46, XY but no sertoli cells normal Leydig cells....

male and female inside (T males male inside, no MIH)... and male outside (DHT normal)

Malignant Nephrosclerosis

malignant HTH leads to decreased GFR leads to higher RAAS vigorous cycle.

All patients w/ major depression should be screened for what disorder to differentiate?

manic episodes to see if actually bioplar disorder. if someone had a rapid response to SSRI, could mean treatment induced mania... Don't misdiagnose bipolar patients in the depressed phase.

What body type is seen w/ MEN2B

marfarnoid habitus

What is the suppression defense mechanism?

mature defense mechanism in which an individual intentionally puts aside unpleasant thoughts or feelings to better cope w/ present reality. In contrast to repression, individual is aware of the emotion but decides not to attend to it. In repression, Unacceptable thoughts or feelings are blocked from enteric conscious awareness. Rationalization is maching excuses for unacceptable feelings or situations (a student explaining that her poor performance was trickiness on the exam) Reaction formation (transforming a thoguht or feeling into its opposite)

What supplies blood to ACL?

middle geniculate artery.. causes hemarthrosis

small circular DNA that resemble bacterial chromosomes

mitochondria

Explain how mtDNA works?

mitochondria have their own DNA, can have point mutations and deletions. mtDNA mutations are unique and exclusively inherited from the mother. Affect both males and females w/ equal frequency (100%), but variable degrees of severity based on heteroplasmy. Mitochondria are randomly distributed, so some get more damaged others more normal.

CEA good for...

monitoring for colorectal recurrence. Elevated in pancreatic, gastric, breast, IBD, COPD, cirrhosis, pancreatitis.. Also higher in smokers than nonsmokers. CEA associated w/ worse prognosis.

presentation of homocystinuria

most common inborn error of methionine metabolism... p/w 3-10 years old w/ ectopia lentis (dislocated lens)... half have intellectual disability. Other manifestations mafarnoid habitus (arachnodactyly, scoliosis, elongated limbs). High risk of thromboembolic occlusion. Tx = Vitamin B6 and restriction of methionine

What is the problem if fragile X syndrome?

most common inherited cause of intellectual disability. Macro-orchidism, dysmorphic face. Developmental delay, ADHD, autism. Delays in language/social skills. Caused by a mutation in the fragile X mental retardation gene 1 (FMR1) on long arm of chromosome X... Normally 5-55 CGG repeats. Can expand during meiosis... Full mutations is >200 repeats leading to FMR1 hypermethylation... Which inactivates FMR1, preventing transcription and production of fragile X mental retardation protein, impairing neural development. Southern blots can be used to measure the degree of methylation and determine number of repeats.

Cavernous Sinus Thrombosis presentation

most commonly due to contiguous spread of an infection from medial 1/3 of face, sinuses (ethmoidal or sphenoidal) or teeth... Can communicate retrograde via valveless venus system (Superior/Inferior Ophthalmic veins)... S aureus is most common, streptococci, Mucor, Rhizopus also p/w HA, fever, diplopia, 3,4,6 paralysis.. loss of upper facial sensation and afferent of cornea via CNV involvement. Can get proptosis and chemosis (conjunctival swelling) ICA and pComm both run in cavernous sinus. It sits above sphenoidal sinus. Pituitary gland in the middle of cavernous sinus.

Patient w/ a lacunar sensory stroke, AKI, and TCP w/ schistocytes

most definitely TTP w/ a deficiency in ADAMTS13 cleaving vWF... Uncleaved vWF result in diffuse microvascular thrombosis... TCP and MAHA occur as shearing occurs... PT and pTT normal so not coag cascade. DIC not because long PT and PTT needed

Is pseudomonas motile? also what ear infection in diabetics?

motile... it is nonlactose fermenting too. Think malignant otitis externa Progression can lead to osteomyelitis of the skull base and cranial nere damage.

Giving opioid agonist then in antagonizing pain

mu opioid analgesics like morphine can cause contraction of smooth muscle cells of sphincter of Oddi leading to spasm and increase in common bile duct pressures... Although uncommon, these pressures in gallbladder can also increase potentially leading to biliary colic. They also cause histamine release leading to vasodilation of BV/itching They cause constipation by slowing gut motility They decrease parietal acid secretion Metabolized by liver but no hepatotoxicity No direct effect on pancreatic acini

Tzanck smear

multinucleated giant cells scraped from oral mucosa... often HSV primary infection... Tzanck smears have now been replaced by PCR testing... Primary HSV1 p/w gingivostomatitis ages 6mo-5 years... fever, malaise, chills 1 week after. Painful vesicles appear and cover lips/gingiva. They organize into extensive ulcers... Resolve in 1-2 weeks... Pain of gingivo often results in dehydration which causes hospitalization.

Why would you get muscle weakness in primary hyperaldosteronism?

muscle weakness, cramps from hypokalemia in primary it is either due to B/L nodular hyperplasia OR aldosterone-producing adrenal adenoma (Conn syndrome) The increased aldosterone doesn't usually lead to hypernatremia or pedal edema because the increased IV volume leads to increased filtration and natiuresis just as well.

Drug that prolongs QRS w/ exercise

must have strong use dependence... flecainide is often used for afib and does this. no change in QT interva.

What is the origin of NF type 1 neurofibromas???

mutliple, raised, fleshy tumors <2cm... Made of schwann cells and derived from neural crest

Most common cause of seeding of IE after a dental procedure?

need predisposition w/ damaged heart valve, usually MVProlapse is most common. If untreated can cause embolic strokes (present like normal strokes ya know). Vegetations... Often S viridans.

Patient w/ MG comes in w/ symptoms

need to do edrophonium test to distinguish cholinergic crisis from myasthenic crisis. Cholinergic crisis causes excessive stimulation of skeletal muscles and results in muscle that is refractory to future impulses. Cholinergic crisis also p/w muscle weakness; however, bc the NM junction becomes insensitive to ACh, edrophonium yields no improvement in symptoms... Temporarily discontinue AChE inhbiitors

What is graft versus host disease?

often w/ BMT. Competent donor T cells transplanted into immunocompromised patient and attack recipient's organs. Most have a diffuse maculopapular eruption that begins w/ palms, soles, back, neck

Majority of overdose deaths in the US!!!

opioids... both prescription and heroin. unintentional overdoses often.

partial pressures of the gases w/ inspiration

pO2 is 160 in inspired air, goes to 150 when mixed w/ water vapor. pCO2 is normally 40 and then venous blood has it at 45mmHg usually only takes venous blood to hit 1/3 of total capillary length to diffuse all in and out. If complete equilibration occurs before venous blood exits the pulmonary capillary then equilibration is perfusion limited. Diffusion limited means it doesn't equilibrate by the end of the capillary. Diffusing capacity of CO2 is >20 times greater than O2.

New onset odynophagia

pain on swallowing in setting of chronic dyspepsia/reflux, probably an ulcer. GERD p/w Heartburn, regurgitation, dysphagia, cardiac-like chest pain, globus (sensation of lump in the throat) and odynophagia. Odynophagia usually means progression to erosive esophagitis and formation of an ulcer. Esophageal stricture can also occur and usually produces dysphagia to solid foods w/ obstruction. Barrett's p/w no symptoms until a malignant transformation has occured (weight loss and dysphagia) 3 common causes of infective esophagitis = candida, HSV, CMV esp in immunosuppressed/HIV/BMT

What toxicity is associated w/ vincristine?

peripheral neuropathy and the neurotox is a dose-limiting side effect... Inhibit microtubule polymerization after binding beta-tubulin. prevents a mitotic spindle, which makes chromsomes unable to align and spearate. this leads to failure of division and cell death.

Paranoid personality disorder

pervasive pattern of distrust and suspiciousness, beginning in early adulthood and occuring in many settings... -believes they are being exploited by others... interprets benign comments and events as threats, reacts angrily, bears grudges, questiosn loyalty of partner

What bone do you drop on the dorsal side of the carpal?

pisiform.. it is on the palmar side... What do you worry about w/ a lunate fracture? carpal tunnel

Breakdown of plaques of atherosclerosis

plaque exists then ruptures later... Plaque stability depends on mechanical strength of the fibrous cap: fibroatheroma are more unstable and vulnerable to rupture... Chronic inflammatory progression of an atheroma --> fibrous cap is continually being remodeled. The balance of collagen synthesis and degradation determines the mechanical strength of the cap. Thin cap fibroatheromas = large necrotic core w/ thin fibrous cap Activated MPs infiltrate and breakdown ECM (Collagen) by secreting metalloproteinases. Can destabilize the plaque and lead to rupture.

What makes H flu type b so scary?

polyribosylribitol phosphate (PRP) capsule... inhibits complement mediated phagocytosis

Presentation of MSUD

poor feeding, vomiting, lethargy, burnt sugar smell from diapers. leucine, valine, isoleucine branched watch out!!

Why gyri are somatosensory and hemineglect

postcentral is somatosensory.. non dominant Parietal association cortex can result in hemineglect

CN3 palsy w/ berry aneurysm presentation, think -->

posterior communicating artery. Circle of Willis branch points have berry aneurysms... with 85% being anterior circulation = Acomm, Pcomm, MCA>.. Chronic smoking and poor HTN are risk factors. Unruptured aneurysms usually asymptomatic w/ HA/cranial neuropathies maybe. CN3 courses b/w posterior cerebral and superior cerebellar arteries as it leaves midbrain.

rapid y descent and S4

restrictive CMOP!! or diastolic HF... Transthyretin = senile systemic amyloidosis in myocardial tissue... Monoclonal light chains = AL amyloidosis,, mutated transthyretin is familial ATTR amyloidosis.

Presentation of foot drop

right leg weakness/numbness, unable to evert, numbness over dorsum of foot and lateral shin, has to lift foot higher than left, right foot slaps to the ground Common peroneal is the most common injured leg nerve... Begins in proximal popliteal fossa, sciatica divides into tibial and CPN. Common peroneal courses laterally into the anterior compartment of leg, passes the head/neck of fibula... Blunt trauma to lateral leg, fibular neck fractures and external pressure from casting can injure. PED eversion = peroneus longus and peroneus brevis dorsiflexion = tibialis anterior m Also lose anterolateral leg and dorsum of foot sensation Foot drop w/ steppage gait is classic. Dorsiflexion (deep personeal) + sensaton/eversion (superficial peroneal)

Presentation of acute angle closure glaucoma?

right sided eye pain and ipsilateral headache. Severe nausea, sees halos around objects. Acetozolamide at the PT causes bicarbo urine. inhibits carbonic anhydrase in eyes, pancreas, GI, CNS, RBCs... Eyes, CA modulates HCO3 formation in aqueous humour... Inhibition will decrease HCO3 and aqueous humor formation; thus a number of CA inhibitors relieve IOPs in open and closed angle glaucoma... Side effect = somnolence, paresthesias, urine alkalinization... can rarely cause acidosis, dehydration, hypokalemia/natremia.

Two mechanisms to reduce oropharyngeal candidiasis?

rinsing the mouth and using a spacer... tube to the mouth from inhaler, facilitates proper dosage! Overall the candidiasis is because of poor inhalation technique which deposits the medication in oral mucous membranes.

Somatostatin

secreted many parts of body, from delta cells of pancreas though supress secretin, CCK, glucagon, insulin, gastrin --> gall stones and steatorrhea and hyper/hypoglycemia

Ovarian vein thrombosis

septic pelvic thromboembolism, a complication that can occur via vaginal/caesarian delivery. Patients w/ this p/w fever, localized abdominal pain one week after delivery. Due to venous stasis (ovarian venous dilation), hypercoaguability (hormones) and endothelial damage (intrapartum vascular injury), persistent fever no response to antibiotics.... Left ovary trains to left renal vein and right ovary drains directly into right IVC.

Elevated urinary 5-hydroxyindoleacetic acid

serotonin breakdown product... carcinoid tumors!!

Atypical presentation of PKU

severe intellectual disability, history of seizures, abnormal pallor of catecholaminergic brain nuclei on autopsy, also can get hypopigemntation of skin/eyes/hair... also will usually have musty body odor... -> PKU pale brain nuclei bc of lack of neuromelanin. (basically light bc no tyrosine so no tyrosinase. Large concentrations of phenylacetate and phenyllactate will be present.

Fenoldopam

short-acting, selective peripheral dopamine1-R agonist w/ little or no alpha/beta effects... activates adenylyl cyclase and raises intracellular cyclic AMP leading to vasodilation of most arterial beds w/ a decrease in systemic BP... Renal vasodilation is prominent and increases renal perfusion, diuresis, natriuresis. ~don't often use hydralazine bc of reflex tachycardia.

Boy w/ Congenital Heart Defect and clubbing of feet

since lower extremities and not cyanotic at birth.. due to unoxygenated blood being devliered to the left subclavian, leads to lower extremity clubbing

What is used to treat status epilepticus?

single seizure >5min... or multiple discrete w/ incomplete recovery of consciousness b/w... IV lorazepam that potentiates the effets of GABA. Initial choice due to rapid onset.. IV phenytoin is a long acting that is administered concurrently to prevent recurrence... No matter what given... Inhibits neuronal high freq firing in the cortex by reducing sodium channel recovery from inactivation.

Behavioral Treatments of insomnia

sleep hygeine = regular schedule, avoid naps, avoid caffeine after lunch, avoid alcohol/smoking, adjust bedroom to be quiet/dark/cook, exercise regularly but not before bedtime. stimulus control = bed only for sleep/sex, go to bed only when sleepy, leave bed when unable to sleep and go to another room, fixed wake time including weekends relaxation = muscle relaxation/abdominal breathing, mental focus on peaceful image Sleep Restriction = time in bed to hours when actually sleeping, increas time in bed by 15-30 minute increments.

What nerve is in the posterior triangle?

spinal accessory nerve... cutting it means loss of ability to abduct w/ trapezius.... if more proximal injury then expect SCM weakness

Signs and symptoms of tension pneumo

tachycardia, hypotension, tachypnea, hypoxemia, absence of breaths ounds.

INR standards

target is 2-3 if on anticoagulation... Bleeding is a common complication, esp if INR >3.0 Tx w/ fresh frozen plasma if life threatening. Vitamin K helps long-term.

How does insulin R work?

tetrameric structure w/ 2alpha and 2beta subunits. Alphas are ECellular binding for insulin... Beta have tyrosine kinase in them.. Leads to autophosphorylation of IR, phosphorylation of IR substrates 1 and 2. They go on to effect two pathways 1) PI3K to GLUT4 and glycogen/protein synthesis 2) RAS/MAPK to cell growth/DNA synthesis TNFalpha induces insulin resistant through activation of serine kinases, which phosphorylate serine residues on IR and IRS1 that inhibit tyrosine phosphorylation of IRS1 by IR and hinder downstream signaling. Kind of beat it to the punch. Phosphorylation of threonine has similar effects. Catecholamines, glucocorticoids, glucagon all induce insulin resistance by same mechanisms. ~Phosphatidylinositol is PIP2 not PI3K

Where does the gonadal artery stem from?

the abdominal aorta both R and L R travels in front of IVC and behind ileum L travels behind L colic and sigmoid arteries Anterior over ureter, run parallel to external iliac vessels and supply testes via the spermatic cord.

Where does the ulnar nerve most often cause injury?

the elbow... leads to loss of sensory loss over medial 1.5 digits of the hand and weakness of wrist flexion/adduction, finger abduction/adduction and flexion of 4/5 digits

When thinking about what artery supplies what portion of colon, think about....

the foregut, midgut, hindgut derivatives

What is the technical name for propylthiouracil and methimazole?

thioamides

Thromboangiitis obliterans (Buerger's Disease)

thrombosing vasculitis of medium-small sized arteries... typically tibial and radial arteries... Mostly heavy cigarretes smokers w/ onset before 35 years old

Craniopharyngiomas are

tumors arising from the remnants of Rathke's pouch.. anterior pituitary especially.. Posterior pituitary+ anteiror lie in the sella turcica at skull base.. Typically CPs have 3 parts... 1) solid... actual tumor cells 2) cystic... machinery oil liquid 3) calcification Any CP can p/w headaches, visual field defects, hypopituitarianism, growth retardation... Compression of pituitary stalk leads to hyperprolactinemia. Usually 5-10 years old.

Candida skin test

type 4 HSN reaction w/in 48-72 hours... Dendritic cells presented to CD4 T lymphocytes on MHC class II molecules.. THese Th1 lymphocytes release interferon gamma recruits MPs leading to monocytic infiltration of area where antigen is introduced.

Histology of a partial mole

usually 69, XXX or 69, XXY... contains maternal and paternal DNA w/ extra chromosome set of paternal origin... Evacuated tissue has some edematous villi w/ focal trophoblastic proliferation and some normal villi. ~Complete mole is enlarged uterus out of proportion, snow storm ultrasound, thecal lutein cysts, hyperthryoidism, hyperemesis and pre-eclampsia. 46, XX w/ only paternal. ~Trophoblastic tumor is a proliferation of intermediate trophoblasts... This is malignant andproduces human placental lactogen. ~Gestational choriocarcinoma will show diffusely anaplastic/necrotic trophoblasts w/ absent villi but vascular invasion.

Where is beta2 present that you don't expect?

uterus Also alpha1 is at the eye and causes mydriasis... contraction of pupillary dilator muscle

Describe oral thrush lesions

white plaques on the patient's oral mucosa are characteristic. That can be easily scraped off, revealing an erythematous mucosal surface underneath. KOH will show yeast and pseudohyphae. Denture weareres, diabetics, immunosuppressed, and pateints receiving steroids, antibiotics, chemo... In addition, diaper rash and candida vulvovaginitis. Vulvovaginal could be from partner to male mouth.

Presentation of Addison's

woman w/ other autoimmune disease (primary hypothyroidism) ends up w/ severe hypotension, abdominal pain, vomiting, weakness, fever, hypoglycemia.. fix w/ immediate hydrocortisone or dexamethasone. Often vasopressors are useless in adrenal insufficiency because glucocorticoids have a permissive effect on vasoconstriction. ~Not hypothyroid crisis, similar hypoglycemia and hypotension, but altered sensations/hypothermia/bradycardia/hypoventilation, also due to long half life of levothyroxine, missing 2 days of therapy isn't likely to cause these problems.

If you have hyperthyrodism, your thyroid will be big

yeah

What causes anencephaly

yes a NTD, but more specifically anterior neuropore failure to close

Basophilic stippling versus ringed sideroblasts

Basophilic Stippling is for LEAD Ringer Sideroblasts is for Iron... they are seen in the bone marrow but not in the peripheral blood smear. .. Can be seen in lead poisoning as well!! Lead poisoning RF = lead, batteries, ammunition, construction P/W GI Pain (abd/constipation/anorexia) Neuro (cognitive deficits, peripheral neurop) Anemia Labs = anemia, elevated lead, elevated protoporphyrin, basophilic stippling on peripheral smear. Lead inhibits the heme synthesis pathway (ALA D and ferrochelatase) causing a microcytic, hypochromic anemia. Basophilic stippling also seen in thalassemias and myelodysplastic syndrome *Lead poisoning scenarios 1) bluish pigmentation at the gum tooth line 2) wrist drop or foot drop from peripheral neurop

Stepwise process of atherosclerosis

Begins w/ endothelial cell injury. Chronic from HTN, HLD, smoking, DM are all risk factors for this cell injury. Such injury leads to endothelial cell dysfunction and exposure of SEC Results in monocyte and lymphocyte adhesion and migration into the intima, while exposure of SEC promotes platelet adhesion.. Growth factors by monocytes/platelets stimulate smooth muscle cell migration into the intima. At the same time, increased vascular permeability allows LDL cholesterol into the intima where it is phagocytosed by the accumulating MPs and SMCs to produce lipid-laden foam cells (fatty streak) While this is happening, continued release of cytokines and growth factors results in chronic inflammatory state w/ underlying intima. This promotes further deposition of LDL cholesterol w/in the intima and stimulates SMC proliferation w/ increased production of collagen/proteoglycans Necrosis of foam cells results in release of toxic oxidizied LDL into the ECM --> perpetuating injury. Lesion eventually organizes into a core of lipid debris surrounded by moncoytes/lymphocytes w/ fibrous cap w/ mixed SMCs (fibrofatty atheroma)

Two most common proteins mutated in HT Obstruction CMOP

Beta-myosin heavy chain & Myosin-binding protein C Sarcomere genes overall are the focus. These contratile proteins have problems.

How to adrenergic drugs effect renin?

Beta1 R are on the juxtaglomerular cells. So beta blocking drugs of beta1 like metoprolol act to inhibit renin release.

What beta blocker do you use in acute MI treatment?

Beta1 selective... Metoprolol.. A-BEAM -reduce short term mortality (symptoms/re-infarction), minimize infarct size improve long term survival. ContraI to beta blockers include bradycardia, hypotension, HF w/ pulm edema... Non-cardioselective beta blockers could trigger a bronchospasm in patients w/ underlying lung disease (asthma/COPD) so should be avoided.

What reverses TCA OD???

Bicarbonate sodium... TCAs cause widening of QRS or ventricular arrhythmias. Bind fast sodium channels. cause inhibition of muscarinic Ach, histamine, alpha-1-adrenergic.

What is the cause of absent jejunum in baby w/ bilious vomiting?

Bilious emesis is obstruction below the 2nd part of duodenum... Midgut volvulus, intestinal stenosis, and atresia... Absence of jejunum and part of ileum means atresia... They are the result of of vascular occlusion in utero.. Diminished perfusion leads to ischemia of a segment of bowel, with subsequent narrowing OR obliteration. If the SMA for example is occluded, a major area is cut out. Proximal segment ends in a blind pouch followed by an area of absent small bowel and mesentery and finally a distal segment that assums a spiral configuration around an ileocolic vessel..

How does benzodiazepine work?

Binds allosterically to the GABA R (at GABAa) The presence of benzo binding w/ GABA increases the frequency of opening of chloride channels. GABA is the main inhibitory NT of the CNS Made from glutamate using glutamate decarboxylase... GABAaR has 5 subunits and a central chloride channel... Influx of chloride from increased freq opening causes neuronal hyperpolarization and inhibition of the action potential. Barbituates act at a separate alloesteric site and work by prolonging duration of channel opening at normal doses and at higher doses work as GABAa R agonists. ~Baclofen works through GABAb (sk m relaxant) *one mech of benzo tolerance is downregulation of GABAa R

Which drugs cause pill-induced esophagitis?

Bisphosphonates, Ferrous Sulfate, NSAIDs, Potassium Chloride, Tetracyclines

How can you differentiate black and brown stones of gall bladder???

Black Stones = due to chronic hemolysis (sickle cell, spherocytosis) -increased enterohepatic cycling of bilirubin (ileal disease) Brown Stones -biliary tract infx (E coli, liver fluke) --> release of microbial beta glucuronidases Both lead to increased unconjugated bilirubin --> calcium-bilirubinate precipitation Stones usually categorized as cholesterol, pigment or mixed stones... C 1) Cholesterol stones formed when ability of bile salts to solubilize cholesterol is overwhelmed by high concentrations of cholesterol in the bile. Usually yellow-gray and hard. 2) Pigmented stones are always unconjugated bilirubin (soft and dark) can be brown or black... *Beta Glucuronidase is released by injured hepatocytes and bacteria. Enzyme hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin.

How to block chemo vomiting?

Block Neurokinin1 at the area postrema, to decrease firing to the nucleus tractus solitaris. NK1R antagonists prevent substance P release... Aprepitant, Fosaprepitant.

Hep B vs HepC

Both increase risk of HCC... Active hepatitis infection causes chronic liver cell injury and regenerative hyperplasia.. icnreasing number of hepatocyte divisions. This increases the chance for genetic mutations that induce malignancy HBV infection risk of HCC remains elevated due to persistence of HBV DNA in the host genome. Leads to continued trnascription of oncogenic viral proteins, such as HBx protein. This protein disrupts cell-cycle by activating multiple growth-promoting genes and inactivating p53. HCV is an RNA virus that lacks reverse transcriptase therefore unable to integrate ALSO chronic hep B leads to accumulation of hepB surface antigen w/in infected hepatocytes... results in finely granular, diffusely homogenous, pale eosinophilic cytoplasm (ground-glass hepatocytes) Necrosis, steatosis, apoptosis, portal inflammation. Acidophil (councilman bodies) deeply eosinophilic globules in shrunken apoptotic hepatocytes

Difference on scan b/w medulloblastoma and pilocytic astrocytoma???

Both will hit kids... Pilocytic astrocytomas will be a well-circumscribed, heterogenous mass.. Both could be in the cerebellum, but PA is most common brain tumor in children. Also, PAs are low-grade gliomas p/w HA, cerebellar findings... GFAP positive harilike processes and classic Rosenthal fibers (eosinophilic intracytoplasmic inclusions) due to slow growing nature, the majority of these patients are treated just w/ surgical resection. Ependymomas are rare.. on ventricles, most commonly 4th --> hdyrocephalus and perivascular pseudorosettes GMultiofrme.. adults in cerebral hemispheres crossing CC.. pseudopallsidating pleomorphic cells w/ necrosis Medulloblastoma... most common malignant childhood brain cancer... ONLY in cerebellum; however, not cystic.. Solid lesion that can compress the 4th ventricle causing hydrocephalus. Small cells w/ hyperchromatic nuclei that form HOMER WRIGHT rosettes (groupsing surrounding a neutrophil) Oligodendroglimoas (adults, calcified) well circumscribed, often in the frontal lobe. Fried egg appearance and chickenwire capillaries.

What is the major exception to blood flow pulmonary equals blood flow systemic?

Bronchial Circuit -supplies oxygen and nutrients to the pulmonary parenchyma from the systemic circulation, drains mostly into the left atrium (however <5% of total blood) mean systemic arterial pressure 70-100 mean pulmonary arterial presure 14

Antibiotics and their pregnancy fetal effects (4)

*Amoxicillin is 1st line for Lyme disease in pregnant or possibly pregnant patient Tetracyclines = teeth staining Chloramphenicol = gray baby syndrome Trim/SMX = neural tube defects AGs = ototoxicity, vestibulotoxicity Tetras... localize in enamel and dentin of developing teeth causing enamel hypoplasia --> yellow, bray, brown staining of deciduous teeth... If near term, permanent can also be affected... So tetras contraindicated in patients < 8 years old and pregnant. Also in animals, tetras can cross placenta and get taken into bone disrupting skeletal system Gray baby = gray skin, vomiting, lethargy, CV collapse AGs = injury to CN8 w/ sensorineural hearing loss, vestibular instability, ataxia ACE = impair renal function --> fetal anuria and oligohydramnios Opioids = neonatal abstinence syndrome.. irritability, tremors, sweating, yawning, feeding difficulties.

Intrapleural pressures of the lungs

-5 mmH2O at FRC, and -7.5 during inspiration Traumatic injury that penetrates can make intrapleural pressure 0, equilibrates w/ the atmospheric pressure via entry of air into the intrapleural space, will cause a pneumothorax. and lung will collapse inward.

Xnathomas break down

1) Eruptive Xanthomas... TG and lipids increase 2) Tuberous and Tendinous X = Achilles and extensors of fingres 3) Plane X = linear lesions in skin folds assc w/ PBC 4) Xanthelasma = soft eyelid or periorbital plaques w/ no lipid abnormalities usually Benign MPs packed w/ finely vacuolated foamy cytoplasm... High chol, phospholipid and TGs... Also usually enclosed by inflammatory cells and fibrotic stroma... No inflammation in xanthelasmas.

Timeline of LGV

1) Painless, small, shallow genital ulcer containing infected cells. Painless nature helps distinguish LGV from other diseases. Later followed by 2) swollen, painful ,inguinal nodes (Buboes) that develop stellate abscesses and rupture if left untreated can cause fibrosis, lymphatic obstruction and anogenital strictures/fistulas. LGV has granulomatous and NP inflammation w/ intracytoplasmic chlamydia inclusion bodies. Tx w/ doxy

What is accomplished by CN IX?

1) Somatic motor to stylopharyngeus muscle (elevates larynx during swallow 2) ParaSymp: inferior salivatory nucleus -> CN IX -> otic ganglion -> travels w/ auriculotemporal nerve (CN V) -> parotid gland secretion 3) sensory -> tympanic membrane, eustachian tube, posterior 1/3 of tongue, tonsillar region, upper pharynx (afferent of gag), carotid body and carotid sinus 4) special taste --> posterior 1/3 ~salivary secretion of submandibular/sublingual glands --> parasymp originating in superior salivatory nucleus on facial nerve via chorda tympani and lingual nerves across submandibular ganglion.

Different types of opthalmic drugs and their effect (3 categories)

1) Trabecular Outflow = muscarinic agonists increase 2) Uveoscleral Outflow = PG agonists 3) Aq Humor Inflow = Beta blockers, Alpha2 agonists, CAIs (carbonic anhydrase) Presentation of open angle glaucoma... many falls from an African American lady decreased vision in peripheral fields , hx HTN/T2DM, elevated IOP. Glaucoma is due to blocked fluid flow out, and leads to elevated pressure which pushes on the sides of the optic nerve.. Open angle that is. Aq humor is produced by the epithelial cells of the ciliary body. Secreted into posterior eye chamber and transferred through pupil into anterior eye chambel.. Anterior chamber angle (iridocorneal angle) contains a trabecular meshwork through which aqueous humor diffuses into Schlemm's canal (scleral venous sinus) and into episcleral and conjunctival veins. Dx of glaucoma... increased IOP, abnl visual field tests esp of peripheral vision.. Increased cup to disc ratio due to loss of ganglion cell axons... >0.6 D/C is abnormal. Timolol and other nonsel beta blockers decrease secretion of aqueous humor by ciliary epithelium.

Most common cause of recurrent UTIs in women

1) bladder mucosa normally doesn't allow bacterial attachment 2) normal urine is bactericidal due to high urea content and osmolarity 3) urine flow washes the bacteria downstream... these can be overcome when bacterial virulence factors (fimbriae to facilitate attachment, capsule to resist phagocytosis) cystitsi Normal vesicoureteral junction does not allow retrograde urine flow... But an increase in bladder pressure or anatomic abnormality can allow some urine to return to the ureter. W/O vesicuoureteral reflux, the ascent of pathogens to the kidneys is VERY unlikely.

Triad of Wiskott Aldrich

1) immunodeficiency 2) eczema 3) TCP

How long after strep can acute fever strike?

1-8 months. Syndenham chorea is due to an autoimmune reaction involving anti-strep antibodies that cross react w/ basal ganglia. PSGN is only a risk 1-6 weeks out.

three types of erythrocytosis

1. Absolute vs. relative... Hgb/Hct not accurately descriptive of conditions... Direct measurement of RBC mass is necessary... Increased total RBC mass is erythrocytosis; normal is relative erythrocytosis... 2. Primary vs. Secondary... EPO levels.. low is myeloproliferative disorder... Chronic hypoxia from high altitutudes, smoking, COPD, neoplastic tissue secretion 3. Hypoxic vs other causes of secondary erythrocytosis: -SaO2 is clutch... if SaO2 <925 or PaO2 <65mmHg causes polycythemia...

Bad reactions of AmphoB

1. Acute infusion related rxns = fever, chills, rigors, hypotension. Right after infusion and prevented w/ premedication w/ antipyretics and antihistamines... 2. Dose dependent nephrotoxicity... Drug induced decrease in GFR... monitor renal function 3. Electrolyte abnormalities... hypoMg and HypoK can develop. 4. Anemia from renal EPO synthesis suppression.. esp in patients on zidovudine 5. Thrombophlebitis at site of injection

How to assess decision-making capacity in a patient?

1. Communicates a choice: patient able to clearly indicate preferred treatment option 2. understands information provided: understands condition and treatment options 3. Appreciates consequences: acknowledges having condition and likely consequences of treatment options, including no treatment 4. Rationale for decision: patient is able to weight risks and benefits and offer reasons for decision. ^principle of autonomy. *Dx of mild cognitive impairment does not automatically revoke decision making capacity.

What are the stages of lobar pneumonia?

1. Congestion (days 0-2).. increase in permeability, accumulation of erythrocytes and abundant proteinacious material. Cytokines. Leakage into alveolar air space 2. Red Hepatization (days 2-4) ... proteinacious fluid turns into fibrin strands, exudate of fibrin, NPs and RBCs... Liver-like... Red, firm, airless 3. Gray Hepatization.. (4-7)... RBC disintegration w/ increased leukocyte infiltration --> gray lung... NP leave and MP come in for repair 4. Resolution > 7 days... MP secrete digestive enzymes that liquify fibrinous exudate, which is reabsorbed expectorated or phagocytosed. Normal again by 3 weeks. ~Bronchopneumonia is infection of terminal bronchioles that results in patchy consolidation of a number of lobules ~Atypical = interstitial infiltrate. ~Asthma is hyperresponsiveness of the airways and smooth muscle inflammation

Treating patient w/ Diphtheriae who is decompensating, what is the first thing to do?

1. Diphtheriae antitoxin (IVIG passive immunization) 2. Penicillin or erythromycin 3. DPT vaccine Antitoxin inactivates all circulating toxin, but ineffective against toxin that has gained access to cardiac/neural cells... This is referred to as passive immunization. Pre-existing neutral antibodies... antibiotics kill the bacteria halting new exotoxin.

4 Regions of involvement in HSP

1. GI tract... severe abdominal pain.. the vasculitis increases risk of bowel edema, bloody diarrhea, hematemesis, and intussusception 2. Kidneys.. Berger disease 3. Skin = palpable purpura on buttock and lower extremities... Results from leukocytoclasts of cutaneous vessels 4. Joints = self limited migratory arthralgias and arthritis (ankle/knee joints)

What are the three phases of ATN? What's it look like on histology?

1. Initiation Phase... corresponds w/ original ischemic or toxic insult and lasts 36 hours. Only a slight decrease in urine output. 2. Maintenance phase, tubular damage is done and they will have oliguria, fluid overload, hyperkalemia, acidosis... Second phase is about 1-2 weeks. GFR is low. Histo will show loss of columnar epithelium, interstitial edema, epithelial cell vacuolization. **increased ECF = weight gain, edema, pulmonary vascular congestion ***hyperkalemia symptomatic if >6.0 (fatal arrhythmias) ****Retention of both hydrogen and anions --> anion gap MetA ***** decreased sodium and calcium and increased phosphate and magnesium *Urinalysis shows low urine OsM <350, high urine sodium >30, high FeNa >1, muddy casts 3. Recovery phase is re-epitheliazation of tubules.. GFR recovers quickly as casts/debris is scleared. Tubular cells recover slowly, leading to transient polyuria and loss of electrolytes. Most patients recover!! *vigorous diuresis > 3 L/day. Hypokalemia is the scariest complication P/W increasing serum creatinine and BUN, a normal BUN/creatinine ratio, and oliguria. Most affects renal medulla... and proximal tubule + thick asc limb of Henle.

How does inflammatory acne work?

1. Keratinization of hair follicle w/ formation of keratin plug that blocks release of sebum 2. Hypertrophy of sebaceous gland w/ excess sebum 3. Colonization w/ propionibacterium acnes 4. Bacterial hydrolysis of TGs in sebum --> inflammatory fatty acids

What are the three most important mt DNA syndromes

1. Leber Hereditary Optic Neuropathy --> B/L vision loss 2. Myoclonic Epilepsy w/ ragged red fibers --> myoclonic seizures and myopathy associated w/ exercise. Sk muscle bx shows irregularly shaped muscle fibers 3. Mitochondrial encephalomyopathy w/ lactic acidosis and stroke like episodes (MELAS) --> young w/ seizures that look like strokes and have residual neurological deficits. Has muscle weakness, elevated lactate post exercise and at rest.

Why use Zolpidem and hypnotic agents?

1. Less potential for tolerance/addiction 2. No anticonvulsants properties 3. No muscle relaxing effects rapid action (15 min after administration) metabolized by P450. Eliminiation half life is 3 hours in normal livers.

Features of Aortic Regurgitation on Pressure Tracings?

1. Loss of aortic dicrotic notch 2. Steep diastolic decline of aortic pressure 3. High-Peaking LV and Aortic Systolic Pressures (wide pulse pressure). AR heard best when leaning forward sitting up. Peak intensity is just after aortic valve closes when prssure gradient b/w aorta and LV is maximal. It is a decrescendo murmur.

Stages of Leukocyte entrance

1. Margination... 2. Rolling... Sialyl Lewis X or PSGL-1 to L selectin or E/P selectin 3. Activation... slow rolling, samples chemokines, ativates integrins by inducing signaling cascade 4. Tight adhesion and crawling.. CD18 beta 2 integrins (MAC-1 and LFA1) to ICAM1 on endothelial cells 5. transmigration... integrin attachment and adherence to platelet endothelial cell adhesion molecule 1 (PECAM-1) LAD1 is absence of CD18... reccurrent skin infections w/o pus, and delayed detachment of umbilical cord and poor wound healing... LAD2 less severe no delay in separation umbilical cord LAD3 severe w/ bleeding

Pathogenesis of idiopathic pulmonary artery HTN?

1. Muscularization of small arteries 2. Medial Hypertrophy and intimal hyperplasia 3. Intimal Fibrosis (onion skinning) 4. Formation of capillary tuft (plexiform) If inherited, BMPR2 inactivating mutation --> auto dominant --> variable penetrance... predisposition for smooth muscle proliferation. Second insult (ions, drugs, infx) activates the process of increase endothelin, decreased NO PGI2. Leading to vasoconstriction, sm muscle proliferation, fibrosis, increased resistance >= 25mmHg... (normal <20) w/ loud second heart sound at left upper sternal border... ECG w/ right axis deviation. p/w dyspnea/fatigue... accentuation of pulmonary S2 and can lead to cor pulmonale.

Five types of anti-fungals and their action

1. Polyenes = ergosterol binding in membrane 2. Triazoles = inhibit synth of ergosterol 3. Echinocandins = inhibit synthesis of glucan of cell wall 4. Pyrmidines = incorporate and inhibit RNA?DNA/protein synthesis 5. Griseofulvin = MTs Pores formed by nystatin/ampho B that are polyenes allow leakage of ions (especially K+) from the cells. THisdisruptio --> lysis... AmphoB active against systemic Candida, Aspergillus, Cryptococcus, Histo, Blasto, coccidio Nystatin = topically or for oral candidiasis (swish and swallow)

What are the 5 stages of behavioral change?

1. Precontemplation = not think about behavior modification 2. Contemplation = thinking about behavior modification 3. Preparation = planning behavior modification 4. Action = putting plan into actin 5. Maintenance = maintaining new behavior Asking for the number for therapy is preparation not action. Decided to take steps to manage is preparation not action. Action would be enters treatment and reduces drinking.

Micturition Reflex (urination) Regulation

1. Sacral Micturition Center... Parasymp S2-S4 level and responsible for bladder contraction... Travel from white matter w/in pelvic nerves and stimulate bladder wall 2. Pontine Micturition Center... Pontine reticular formation. Coordinates relaxation of external urethral sphincter w/ bladder contraction during voiding 3. Cerebral Cortex - inhibits the sacral mictrurition center!! NPH incr SCR volume places traction of cortical efferent/afferent fibers of corona radiata, which disrupts perventricular pathways that trnasmit impulses from cortex to sacral micturition center. Leads to urge incontinence. Bladder fills with urine and empties reflexively when full. The patient has no sensation of bladder fullness and no control over function. Voluntary relaxation remains intact.

Steps of collagen synthesis

1. Signal sequence of pre-pro-alpha chain to ER 2. signal sequence cleaved 3. hydroxylation of selected proline/lysin residues (need vitamin C), glycine the other AA present. = hydroxylysine and hydroxyproline now if hydroxylated. 4. Glycosylation of selected hydroxylysine residues (w/ galactose/glucose) 5. Assembly of pro-alpha-chains into procollagen triple helix inside the cell. This happens via disulfide bonds b/w C terminal regions. 6. Procollagen transferred to Golgi then excreted to ECF 7. Terminal propeptides cleaved by N/C procollagen peptidases to make tropocollagen 8. Collagen molcls sponanteously assemble to collagen fibrils 9. Covalen cross linking of collagen via lysyl oxidase *Ehlers-Danlos means defective collagen synthesis. a) procollagen peptidase deficiency is an option. Formaiton of soluble collagen that does not crosslink. Leads to hyperextensible skin, fragile tissue, easy bruising, poor wound healing. Fibroblasts, Osteoblasts, Chrondroblasts all synthesize collagen

Presentation of subacute sclerosing panencephalitis

10 year old immigrant boy w/ ataxia, myoclonus, visual problems and recent decline in school work. *this is w/in years, can also get acute disseminated encephalomyelitis w/in weeks. enveloped ss RNA virus in paramyxovirus family... Hemagglutin (cell surface adhesion) and matrix protien for assembly.. SSPE, form of measles w/ an absent matrix protein that prevents mature virion particles from forming. Virus continues to replicate intracellularly leading to persistent nonproductive infeciton that evades eradication... Accumulation of viral nucleocapsids w/in neurons/OligoDs results in intranuclea rinclusions and inflammation/demyelination/gliosis Patients have high measles antibody titers and oligoclonal bands on CSF...

Chronic severely pigmented gall stones

10-25% of gallstone cases... Most common in rural Asian populations. Arise from conditions that increase unconjugated bile, which promotes calcium bilirubinate precipitation... Black stones from sickle cell anemia, beta thalassemia, hereditary spherocytosis... and increased enterohepatic cycling of bilirubin (ileal disease) usually if these black ones, high numbers, small, spiculated, friable.. Calcium carbonates and phosphates so radio-opaque. ~Obesity, MESA< multiparity, OCP and rapid weight loss all risk factors for cholesterol gall stones. ~Brown stones are more from infection by E coli or liver fluke that release beta glucuronidases

what is considered a high grade cell?

1:1 N to C w/ prominent nucleoli

Arteries surrounding portions of duodenum

1st = Gastroduodenal posterior, Right gastroepiploic posterior as well 2nd = anterior superior pancreaticoduodenal 3rd = SMA 4th duodenum becomes jejunum past ligament of Treitz.

1st line and 2nd line drugs for gouty arthritis?

1st is NSAIDs... contraindicated in PUD history 2nd is colchicine and oral or intra-articular glucocorticoids Colchicine binds intracellular tubulin and inhibits polymerization into microtubules... This disrupts cytoskeletal dependent functiosn (chemotaxis/phagocytosis)... Administered at the beginning of a flare up and repeated later... PPx while initiating urate-lowering therapy (allopurinol)... N/Abdominal pain, diarrhea at higher doses. Avoid in elderly or those w/ renal dysfx.

How affective are statins??

20-50% reduction in cholesterol/LDL

What does zidovudine, an NRTI inhibit in viruses?

3-5 phosphodiester bond formation

What is elevated in urine w/ carcinoid also how do you know if mets or not?

5-HIAA is elevated... Get CT/MRI of abdomen and plevis... Will not have symptoms if local because liver cuts everything up, if mets to liver then will have symptoms... Can produce serotonin, bradykinin, PGs... One patients presents w/ reddening of skin, warmth, cramps and diarrhea along w/ purple, vascular lesions around the nose.

Alcohol Withdrawal Syndrome

6-24 hours... mild withdrawal... anxiety, insomnia, remors, diaphoresis, palpitations, GI upset, intact orientation 12-48 hours... single or multiple generalized tonic-clonic seizures 12-48 hours alcohol hallucinosis... visual, auditory, tactile hallucinations; intact orientation; stable vitals 48-96 hours.. Delirium tremens... confusion, agitation, fever, tachycardia, HTN, diaphoresis, hallucinations... Chronic ethanol use --> downregulation of GABA R. Alcohol weakly inhibits excitatory NMDA R in the brain as well... chronic exposure leads to upregulation of these receptors. Adaptive changes result in tolerance and symptoms of withdrawal on abrupt alcohol cessation. *Tremor or "the shakes" is the most common initial finding.

How high is prolactin in a prolactinoma?

>200 difference b/w discharge from intraductal papilloma and pituitary adenoma is menopause early onset??? Patient w/ reproductive age w/ amenorrhea.. pregnancy must be excluded... If elevated serum prolactin, MRI of brain. 1st line treatment for prolactinomas is dopamine agonists (bromocriptine).

When is iron a risk to the body?

>20g body iron, HFE patients develop triad of 1) micronodular cirrhosis, 2) DM, 3) skin pigmentation... Increased risk of HCC, HF, testicular atrophy/hypogonadism. HFE protein causes enterocytes and hepatocytes to detect falsely low iron levels. leads to accujmulating in body... DMT1 of enterocytes increases absorption.. Hepcidin is decreased in hepatocytes, which means increased ferroportin expression on basoLat of enterocytes. Increases iron in circulation

What does histo histology look like?

A bunch of small lil ovoid bodies w/in a macrophage... In non-immunocompromised --> self-limiting pulmonary disease. In immunocompromised --> systemic histoplasmosis that may be fatal. p/w cough, low grade fever, HSMegaly, weight loss. Dx w/ bone marrow aspirate. Causes hilar adenopathy... Oval or Round yeasts w/in Macrophages. Culture on Sabouraud agar and grows hyphae. Can dx by antigen in blood and urine. Serologic for anti-histo as well.

Enterococcus IE then nephrotoxicity and ototoxicity...

AGlycoside... which irreversibly binds to bacterial 30S and causes genetic code misreading along w/ impaired translocation. ototox = hearing loss/tinnitus

Androgen Insensitivity Syndrome & Mullerian Aplasia

AIS... 46 XY males who appear female due to androgen R defect... In contrast to MKH.. patients w/ AIS have Minimal Axillary or Pubic Hair... In addition they will have cryptochid testes and no uterus/ovaries Mullerian Aplasia = Mayer-Roktansky-Kuster-Hauser... Variable uterine development, no upper vagina. Cannot menstruate = primary amenorrhea. Normal ovaries and regular secondary sexual characteristics of female.

How does MHC class 2 work....

APCs only to CD4.. Phagocytosis/endocytosis to take them up... Degraded material by acidification after endosome/lysosome fusion or phagosome/lysososome fusion. MHC class 2 molcls are synthesized at same time at rough ER and routed to endosomes by Golgi... Each MHC class 2 has a peptide fragment called an invariant chain bound to its antigen binding site. THe peptide fragments acts to guide the MHC class 2 molcl during sorting in the Golgi and occupy binding site until molcl enters an acidified endosome where it can bind foreign protein... Fusion of vesicles containing MHC class 2 w/ acdificied phargolysosomes w/ foreign antigens leads to degradation of the invariant chain and loading of MHC class 2. These are then displaced on surface. Without acidification of lysosome, antigen processing in associated w/ MHC class 2 would not occur... MHC class 2 wouldn't bind antigen and wouldn't bind TCR

How can Rheumatoid affect muscles?

ARF is an immune-mediated GABHS infection (pharyngeal)... Most serious is pancarditis, also get fever/fatigue/anorexia/tachycardia/tachypnea/hypotension... MV regurge murmur (holosystolic) Bx of interstitial fibrosis w/ central lymphocytes and MPs and scattered multinucleated giant cells = Aschoff body... Interstitial Myocardial Granuloma. ARF-myocarditis. Aschoff bodies are replaced by fibrous scar tissue --> chronic mitral valve stenosis. ~anthracycline CMOP is a patchy fibrosis w/ vacuolization and lysis of myocytes

What findings are concerning for a ruptured ectopic pregnancy as opposed to safe one so far?

Abdominal Pain, Bloody Vaginal Discharge, Orthostatic HypoTension. RF is tubal scarring. N Gonorrhea or C trachomatis are major.

What is the underlying mechanism for Zencker Diverticulum?

Abnormal spasm or diminished relaxation of the cricopharyngeal muscles during swallowing... Results in early oropharngeal dysphagia w/ a feeling of food obstruction at neck w/ coughing/choking... Increased oropharyngeal intraluminal pressure leads to herniation of the pharyngeal mucosa through zone of muscle weakness (false diverticulum)... in posterior hypopharynx (Killian triangle) Patients develop halitosis/regurigation and pulmonary aspiration may lead to recurrent pneumonia. Usually 1. voluntary oral phase, back of mouth lifted food to posterior pharynx 2. pharyngeal phase w/ involuntary pharyngeal muscle contraction to propel food bolus to esophagus and 3. esophageal phase, food stretches walls of esophagus stimulating peristalsis just above distension and moving food downward through LES

Best way to diagnose acute cholecystitis?

Acute Cholecystitis is gallstone obstruction of the cystic duct in >90% of cases. Ingestion of fatty foods makes it contract against impacted stone --> colicky... damage by stone to gallbladder mucosa causes inflammation/PGs. As blood supply from inflammation is more compromised --> leads to secondary bacterial infection... Can lead to gangrene/perforation to peritonitis or abscess. U/S is the preferred initial imaging test. Nuclear medicine hepatobiliary scanning (cholescinitigraphy) is the best when U/S is inconclusive. Radiotracer is administered IV and taken up by hepatocytes and excreted into the bile. Images as it moves through biliary system are obtained. In patent cystic duct... it will concentrate and concentrate in gall bladder... in acute/chronic cholecystitis, radiotracer will be taken up by liver and excreted into common bile duct and proximal small bowel but no gall bladder visualized due to obstruction.

What side effect is going on w/ halogenated inhaled anesthetics?

Acute Hepatitis... Halothane, Enflurane, Isoflurane, Sevoflurane module neuronal ion channels leading to CNS depression... Metabolized by P450... converted to reactive intermediates taht can injury liver or lead to immune-mediated damage... 2days to 3 weeks after med exposure w/ fever, nausea, jaundice, tender hepatomegaly, and elevated AST/ALT and bilirubin levels... Liver bx is typically not necessary but will show centrilobular hepatic necrosis. Supportive tx

Triad of Fat Embolism please

Acute Neurologic Abnormalities, Hypoxemia, Petechial Rash esp in patient w/ severe long bone or pelvic fractures... 33% of patients w/ B/L femoral fratures. Usually w/in 24-72 hours after the injury but as long as 2 weeks. Traumatic event dislodges fat globules from bone marrow allowing them to travel through sinusoids to pulmonary microvessels.. Occlusion of these impairs gas exchange --> hypoxemia... FFA from fat can also cause toxic injury (ARDS)... Some fat globules escape via precapillary AV shunts that open to the brain --> neuro impairment and dermal capillaries... Petechiae

Pituitary apoplexy

Acute intrapituitary hemorrhage... Usually on pre-existing adenoma... p/w severe HA, bitemporal hemianopsia, opthalmoplegia, panhypopituitariansim Neuro shows enlargement and hemorrhage tx = glucocorticoid replacement (to prevent life threatening hypotension) and surical decompression

What is the timeline for acute rejection also how does rejection chronic manifest in lungs?

Acute is <6 months.. .chronic can be bronchiolitis obliterans w/ obstructive spirometry pattern. w/ airflow limitation. Lymphocytic inflammation and destruction of epithelium of small ariways... Fibirnopruluent exudate and granulation tissue are in the lumen of the bronchioli.

First stage of LV HF induced pulmonary problems?

Acute pulmonary edema , increased filtration of plasma water and electrolytes into the lung interstitium and alveoli... IT is a transudate. not an exudate NPs only come w/ exudate not transudate. Would see alveolar hemorrhage in a different scenario for HSN angiitis or granulomatosis w/ polyangitis (Wegener's) and lupus erythematous.

What hyperplasias in response to ectopic ACTH?

Adrenal hyperplasia of BOTH zona fasciculata and reticularis Initially, exces ACTH rapidly acts to increase adrenal blood flow and metabolic activity in both layers. ACTH stimulates transfer of cholesterol to inner mitochondrial membrane by steroidogenic acute regulatory protein (rate limiting step in steroid production). Increased pregnenolone increases cortisol synthesis Eventually upregulate RNA/protein synthesis -> proliferation

Dopamine as you dose it up

Adrenergic agonist. At lower doses, stimulate D1R in the renal vasculature and tubules... increase in renal blood flow, GFR, Na+ excretion Vasodilation of mesenteric, cerebral, coronary beds As dose increases you get Beta1 R in the heart increasing contractility, HR, systolic BP As you get higher yo get alpha1 w/ generalized vasoconstriction and decreased CO due to increased afterload. ~Epinephrine does not significantly increase renal blood flow even at lower doses, due to lack of D1 R stimulation Norepi is Beta1=alpha1 > Beta2 Epi is Beta1=Beta2>alpha1

Cheynes Stokes Breathing...

Adv CHF... cyclic breathing pattern in which apnea is followed by gradually increasing then decreasing tidal volumes until the next apneic period. Chronic hyperventilation w/ hypocapnia, which induces apnea in sleep when partial pressure of CO2 falls below apneic threshold... Apnea --> excessive build up of CO3 --> ventilation response... Cycle of apnea and hyperventilation is further perpetuated by a prolonged circulation time b/w lungs and brain.

What buils up w/ recurrent MTX use?

After enteric target cell, MTX undergoes polyglutamination, resulting in intracellular accumulation.. Similarly folate and recycled DHF are stored w/in cell via polyglutamination. Bc MTX inhbiits DHF reductase, folic acid and DHF polyglutamate accumulate in the cell. *Folinic acid is a reduced form of folic acid (leucorvin) and can be used to ocunter MTX toxicity... Rescues normal cells by competing w/ MTX for DHF reductase binding sites. Can reactivate DHF reductase and allow re-initiation of DNA synthesis. *PABA is a folic acid precursor in prokaryotes, sulfonamide antbx are chemical anaolgues of PABA (para-aminobenzoic acid) and inhibit DiHydroPteroate Syntheataese to prevent conversion of PABA to folic acid... Humans don't do this. Tymidylic acid is a NT that contribues to pyrimidine formation.

What is bronchiolitis?

Age <2 years old get a respiratory tract infection.. most commonly caused by respiratory syncytial virus... typically starts w/ rhinorrhea and congestion followed by cough, low grade fever and increased work of breathing. p/w tachypnea, retractions, and diffuse wheezes/cracles, hypoxemia Illness peaks at 3-5 days, symptoms last several weeks. Worse for younger and more premee infants NOT Pertussis bc lungs are usually clear to auscultation in this NOT parainfluenza virus, which causes croup OR laryngotracheobronchitis.. it is less common cause of bronchiolitis.

WHat does a pattern of elevated BPs mean in an older person?

Age-related rise in isolated systolic HTN... Often in patients > 60 years old, responsible for 70% of HTN cases in this population. SBP > 140 is a risk factor for stroke/CVD. Aging causes increased arterial stiffness, caused by endothelial dysfunction and change in ECM (decreased elastin increased collagen)... Decr compliance of aorta an dmajor peripheral arteries causes elevated systolic pressures. ISH can also result from an increase in CO due to severe aortic regurge or anemia/hyperthyroidism

What do influenza vaccines stop?

Annual vaccine necessary for A and B... all people > 6 years old... It induces neutralizing antibodies to hemagglutin antigen to stop entry of influenza virus into host cells... Stop hemagglutin from binding sialylate receptors on host cell membrane and entering via endocytosis.

What causes cachexia?

Anorexia, malaise, anemia, weight loss, generalized wasting... Likely manifestation in a lung neoplasm. TNF alpha is the cytokine responsible. aka Cachectin.. Causes appetite suppression in the hypothalamus. Increases metabolic rate. Produces fever (along w/ IL1) mediates septic shock and hepatic release of acute phase reactants (CRP and fibrinogen)

What are the treatments of eating disorders??

Anorexia... BMI < 18.5... intense fear of gaining weight, distorted vies = CBT, nutritional rehab, OLANZAPINE Bullimia = recurrent binge eating, followed by compensatory behavior, excessive worry about body shape/weight, normal body weight though.. 1st line CBT, nutritional rehab, fluoxetine/SSRI Binge Eating = recurrent episodes of binge eatin, no compensation.. CBT, Behavioral weight loss therapy, SSRI, Lisdexamfetamine or Topiramate

How do eosinophils work w/ IgE?

Antibody-dependent cell-mediated cytotoxicity 1) parasitic defense: proliferation and activation during parasitic infection is stimulated by IL-5 produced by TH2 and mast cells... When a parasite invades the mucosa or enters the blood stream, it is coated by IgG and IgE antibodies that bind Fc receptors located on eosinophil cell surface. This triggers eosinophil degranulation of cytotoxic proteins (major basic protein) and reactive oxygen intermediates. This is all antigen-dependent cell-mediated cytotoxicity. NPs, MPs, NK cells all use this. 2) Type 1 HSN reactions: eosinophils also make PGs, LKTs, Cytokines that contribute to the inflammation in late phase of type 1 HSN reactions.

Antihistamine causing blurry vision, how?

Anticholinergic effects of 1st gen antihistamines (chlorpheniramine, diphenhydramine) Relieve allergies by releasing histamine from mast cells... Rhinorrhea, itchy eyes/nose, urticaria.. However, they have prominent side effects due to blockade of other receptors (alpha, serotonin, cholinergic) Ciliary muscle attaches to the lens via zonular fibers... Contraction of the muscle reduces tension on the fibers allowing lens to become more spherical and increasing refractive power. Ciliary muscle is under Parasymp control from Edinger-Westphal nucleus/ciliary ganglion... Inhibition of this pathway by antimuscarinics will limit accomodation and cause blurry vision for close objects. Will also get mydriasis from decreased PS to pupillary sphincter.

Carbidopa and levodopa w/ side effects

Anxiety and agitation are central effects of dopamine and are caused by L-dopa, regardless of carbidopa involvement... Carbidopa inhibits peripheral conversion of levodopa making it more available to the brain... High dose combos can cause behavioral changes (anxiety, agitation, insomnia, confusion, delusions)... N/V are in 80% of patients on only levodopa. Stimulates emetic center in brainstem outside of BBB. Tachyarrhythmias, w/ Afib are attributed to peripheral formation fo catecholamines Postural hypotension and hot flashes are from levodopa to dopamine ^these can be decreased w/ carbidopa

What is scotoma??

Any visual defect surrounded by a relatively unimpaired field of vision. Scotomas occur due to pathologic processes that involve parts of the retina or optic nerve. If processes involve the entire optic nerve --> monocular blindness *Mac Degen is the most common cause of blindness in people over 50 years old in the US. Progressive loss of central vision due to deposition of fatty tissue (drusen) behind the retina and neovascularization of the retina (dry and then wet MD) *What casues binasal hemianopsia?? Pressure to lateral areas of optic chiasm, can be calcified carotid arteries.

How does open angle glaucoma cause problems?

Aqueous humour is secreted by epithelial cells of the ciliary body into the posterior eye chamber.. The fluid then flows through the pupil into the anterior chamber to the iridocorneal angle. Here it diffuses through a trabecular meshwork into Schlemm's Canal... and drains into episcleral/conjunctival veins... A small amoutn diffuses through ciliary muscle and adjacent sclera (uveoscleral pathway) Open angle glaucoma.. increased IOP due to increased secretion or decreased outflow of Aq humor... Causes progressive loss of ganglion cell axons, which may be visualized as a pale optic disc and enlarged cup Cup is smaller part inside of disc... Increased is cup: disc ratio > 0.6 P/W symptoms over decades w/ progressive loss of visual fields... Glaucoma is treated w/ agents that change amount of aq humor... Latanoprost is a PG use in tx. it is a prodrug applied and converted to active form by esterases in the cornea... PGs are preferred 1st line tx for glaucoma althoguh the exact mechanism is uncertain... They decrease collagen content in uveoscleral outflow and increase outflow of aqueous humour.. Cause pigmentation of iris and eyelashes. ~~ CA inhibitors like Dorzolamide decrease formation of HCO3 in the ciliary body, leading to decreased Na/Fluid transport and decreased production of aqueous humor... ~Alpha-2 adrenergic agonists (brimonide) inhibit production of aqueous humor due to vasoconstriction of ciliary body ~Beta blockers (timolol) decrease production of aqueous humor.

What embryo problem can lead to fibrous bands of cecum/R colon compressing the duodenum?

Around 6 weeks gestation, the midgut (Supplied by SMA) herniates through the umbilical ring in order to grow rapidly. During this process, the midgut rotates 90 degrees counterclockwise, following additional growht, the midgut returns at 8-10 weeks gestation and turns an additional 180 counterclockwise... THe gut is fixed to the posterior abdomen on a wide mesentery Incomplete rotation will result in midgut malrotation. The cecum will rest in the RUQ instead of RLQ. Ladd's bands (fibrous) connect retroperitoneum in the RLQ to the right colon/cecum by passing over 2nd part of duodenum, causing intestinal obstruction. p/w bilious emesis during first fe days of life... Also because mesenteric base narrowed, mesentery is vulnerable to twisting around SMA.. Twisting referred to as midgut volvulus comprises intestinal perfusion and may lead to life-threatening bowel necrosis.

What is the atypical cell in MONO?

CD8 lymphocyte... The virus itself infects CD21 of B cells. The reactive atypical lymphocytes here are seen on blood smear. They appear larger than normal lymphocytes w/ abundant cytoplasm, eccentrically-placed nucleus, cell membrane that appears conoform.

Neonate at 5 weeks or so that has a spontaneous intracranial hemorrhage???

CHECK IF breastfeeding... There are low VitK stores at birth (poor placental transfer, sterile gut, low content in breast milk), neonatal liver cannot use VitK efficiently P/W intracranial, GI, cutaneous, umbilical, surgical site bleeding... prevent w/ intramuscular vitamin K at birth... It is a fat soluble vitamin that is an essential cofactor for gamma-glutamyl carboxylase that carboxylates coagulation factors 2, 7, 9 , 10. Exclusive breastfeeding is a big risk factor. CF also a risk factor because malabsorption of fat-soluble vitamins.

transplant patient w/ pnuemo and intranuclear and intracytoplasmic inclusions....

CMV!! enveloped ds DNA virus w/ a halo (owl's eye).. the inclusions are viral particles.

Mnemonic for Atypical Antipsychotics

CROZAQ Clozapine Risperidone Olanzapine Ziprasidone Aripiprazole Quetiapine Also Lurasidone, Asenapine, Iloperidone and Paliperidone though :( CROZAPQILA

What can you use to tract SLE flare ups??

CRP (C-reactive protein)...

What are some common manifestations of sarcoidosis?

CXR shows hilar lymphadenopathy, ACE elevated, arthralgias, kin changes (30-50%). Subcutaneous nodules, erythematous plaques or macules are all possible. Liver biopsy shows changes in 75% of patients. Usually scattered granulomas. Usually affect the portal triads more than the lobular parenchyma!

Why are smooth muscle and skeletal muscle excitations different?

Calcium plays an important role in cardiac/smooth/sk muscle cell coupling. Myocyte depolarization --> L type calcium channels --> in cardiac and smooth muscle leads to extracellular calcium that activates sarcoplasmic RyR channels inducing SR released.. Calcium binds troponin in cardiac or calmodulin in smooth muscle allowing actin/myosin to interact for contraction Skeletal muscle directly interact w/ RyR calcium channels to release calcium from the SR. The mechanical coupling b/w receptors allows SR calcium to occur w/o significant influx of calcium across the PM... Verapamil blocks L type Ca2+ channels preventing initial calcium influx in cardiac/sm muscle cells... BC sk muscle is not dependent on EC calcium influx, CCBs do not affect sk muscle contractility

Young patient gets an infection then has frothy/foamy urine

Can be caused by bile salts or proteinuria in the urine... MCD is likely and this leads to isolated hypoalbuminemia that lowers plasma oncotic pressure --> pitting LE edema

Three esophagitis w/ HIV

Candida = patches of adherent, gray/white pseudomembranes on erythematous mucosa.. Yeast cells and pseudohyphae HSV1 = small vesicles -> punched out ulcers... Eosinophilic intranuclear inclusions (Cowdry Type A) in multinuclear squamous cells at ulcer margins CMV = linear ulcerations = intranuclear and cytoplasmic inclusions

What two cells fight off fungal infections?

Candidemia... A single-celled budding yeast w/ pseudohyphae, also has germ tubes (hyphal structures formed when the organism is grown in a nutritionally rich serum)... 1) T lymphocytes... Th cells... prevent superficial candida infections (oral/esophageal, cutaneous, candida vulvovaginitis) 2) Neutrophils... prevent hematogenous/disseminated (candidemia, endocarditis) (cancer w/ chemo especially)

Lighting related complications??

Cardiac = arrest/arrhythmias Neuro = Peripheral damage, seizures, confusion, respiratory arrest, autonomic dysfx Derm = Lichtenberg figures (pathognomonic), burns MSK = rhabdomyoysis, bone fx, compartment syndrome Other = cataracts, rupture tympanic membranes, curling ulcers **erythematous cutaneous marks in a fern-leaf pattern = Lichtenberg figures 25% fatality rate and 70% of survivors w/ copmlications. 2/3 of death happen w/in first hour of injury Most commonly arrhythmia or respiratory failure...

HOW DO ANTERIOR HORN CELLS RESPOND TO TRAUMA TOAXONS

Cell body rounding, peripheral displacement of nuclei and dispersion of Nissl substance to the periphery of cells. Wallerian Degeneration occur sin the segment of axons that has lost connection w/ the cel body... Deneration of axons and myelin distal to injury. 1) swelling an irregularity are noted in distal segment of axon 2) within a week, axon is destroyed and its fragments digested by Schwann cells/MPs 3) Similar degenerative changes occur in the segment of the axons that lies proximal to the injury. Degeneration of proximal segment extends to closes nodes of Ranvier. ^axon Neuronal body goes under these changes 1) cell body edema 2) swollen and rounded w/ nucleus displaced to periphery 3) Nissl substance becomes fine, granular, dispersed (central chromatolysis). Axonal reaction w/in 24048 hours after injury... Peak at 12 days after injury. These changes are for increased protein synthesis by cells to regenerate severed axon.

What are the three main components of gall stones?

Cholesterol, Bile Acids, Phosphatidylcholine Increased cholesterol, decreased BA, decreased PC means more likey to form. Want micelles to remain unsaturated w/ cholesterol. If supersaturated, leads to nucleation then to aggregation to crystals promoted by mucus, calcium, and hypomotility to cholesterol stones. What are the two mechanisms for clearing cholesterol excretion of free cholesterol in bile and actual bile acids themselves. Free cholesterol converted into cholic and chenodeoxycholic acids w/ 7alpha-hydroxylase... These are conjugated to either glycine or taurine (to improve solubility/emulsifying ability) Bile salts then secreted into bile canaliculi... Amphipathic bile salts and PPC (a phospholipid) render free cholesterol soluble...

Diverticulosis

Classify true vs false (Meckels) and also traction versus pulsion... Pulsion.. or increased luminal pressure created during straining bowel mvmts (chronic constipation). Increased pressure causes mucosa and submucosa to herniate through areas of focal weakness. Similar to Zenker formation. Most commonly Dlosis affects the sigmoid colon and seen >60 years old. Most are asymptomatic. Some have hematochezia due to disruption of arterioles. Can become inflamed and p/w abdominal pain, low grade fever, constipation/diarrhea. If formed in fetus, then true diverticula Traction diverticula are created by inflammation and therefore scarring of the gut wall, which results in pulling and outpouching of the gut wall (true diverticula). Disesophagus due to mediastinal lymphadenitits due to TB or fungal infection.

Breakdown clinical, macroscopic, microscopic, biochemical, genetic, molecular features of Huntington's

Clinical = chorea and dementia and aggressiveness/apathy/depression.. decreased memory/concentration/psychosis. Usually p/w purposeless choreiform mvmts of extremities but less commonly can p/w bradykinesia. Macro = Atrophy of Caudate, Atrophy of putamen and frontal lobes.. Leads to dilation of frontal horns of lateral ventricles Micro = Loss of neurons in the caudate and putamen.. Leads to gliosis and neuronal loss. Overall loss of GABA Biochemical = decrease in GABA, Ach, Substance P in the striatum (caudate and putamen) Auto dom inheritance of chromsoome 4 CAG trinucleotide repeats in the huntingtin gene Mollcls =N-methyl-D-aspartate receptors bind glutamate and cause neuronal death (NMDA-associated toxicity) p/w 35-45 years and 15-20 years live afterward. 100% penetrance.

How does CO bind to heme?

Competitively NOT irreversibly... leads to formation of carboxyhemoglobin If only 1 binds it means the other 3 have increased oxygen affinity and impeding delivery to tissues... CO can also bind heart myoglobin decreasing ability for heart to use O2 and decreases CO... Also binds cytochrome oxidase inhibiting aerobi metabolism and exacerbatin tissue hypoxia... Tx w/ hyperbaric O2 because it hastens CO dissociation

Why does polyol pathway cause cataracts?

Conversion of glucose to sorbitol. Then eventually fructose, but w/ a high level of sorbitol in diabetes, it happens faster than fructose can be made. Sorbitol increases osmotic pressure for influx of water leading to osmotic cell injury but also oxidative stress from depletion of NADPH leads to cataracts and retinopathy/pneuropathy/nephropathy. AGE is another mechanism of diabetes damage. AGE accumulate in BVs and facilitate deposition of LDL in blood vessel walls -> atherosclerosis and microangiopathic complications. Also AGE of lens proteins --> cataracts (less of an influence)

Where does 7 alpha hydroxylase play a role?

Converts cholesterol to bile acids and increases risk of cholesterol stones.

The relationship b/w creatinine and GFR is nonlinear...

Creatinine can be normal after a loss of 50% of kidney function... begin to rise when GFR <60ml/min... As small GFRs decrease creatinine jumps up exponentially

What binds tighter, T or DHT?

DHT forsure, much higher affinity for testosterone receptor and mediates majority of T effects, including development of male external genitalia and prostate enlargement. Patients w/ androgenetic alopecia have higher levels of 5alpha-reductase and a higher quantity of androgen R ~Ketoconazole two actions... decreases synthesis of testosterone in Leydig cells also inhibits steroid hormone production by adrenals. ~Anastrozol, Letrozol, Exemestane all useful for post meno women w/ breast cancer. Greatest source of estrogen is conversion of androstenedione from adrenal glands into estrone through aromatization in the liver/muscle/fat.

Xeroderma pigmentosum

DNA damaged by UV light can't be repaired by NT excision repair... normal skin at birth, but 1st year sun sensitivity (erythema/scaling), esp face... Later atrophy, telangiectasias, hypo/hyperpigmentation. Eventually skin malignancies around 5 years old.

Which DNA pol has 5'->3' exonuclease activity?

DNA pol 1... not 3 w/ 3'->5' instead

DNA replication in bacteria

DNA pols 1 and 3 involved. SSBPs bind both leading and lagging strand... DNA ligas acts on the lagging strand. DNA pol 1 and 3 have 3'-> 5' exonuclease proofreading ability and is done at both strands.

BPH vs. PACarcinoma on DRE and effects of BPH on kidney

DRE is rubbery for BPH DRE is nodular and firm for PAC Bladder Outlet Obstruction --> voiding problems (hesitancy, straining, weak urinary system) and impaired urinary storage (daytime frequency, urgency, nocturia)... Increased hydrostatic force needed to overcome the obstruction, causes hypertrohpy of bladder wall and dilation of ureters, renal pelvis and calyces. If left untreated, urinary reflux can lead to pressure-induced parenchymal atrophy w/ scarring and CKD

How does diastolic and systolic HF affect arteriolar resistance?

Decrease CO means hypoperfusion means increased sympathetic stimulation and increased constriction/resistance.. also activates RAAS. ~CO is decreased in both diastolic and systolic HF. Will mean decreased perfusion of kidneys to activate RAAS Venous oxygen content will be decreased

How does exercise effect resistance?

Decrease TPR shift up on that curve by affecting both venous return and CO... even though BP increases. This occurs due to substantial arteriolar vasodilation in active skeletal muscles, mediated by local release of adenosine, potassium ions, ATP, CO, lactate.

What lab values does hemolytic anemia w/ schistocytes from mechanical valve cause?

Decrease haptglobin increased LDH. Hatpglobin binds free Hgb and promotes its uptake by reticuloendothelial system.

Aging changes of the heart

Decrease in LV chamber size, predominantly through shortening of apex-to-base dimension accompanied by a leftward bowing of the lower IV septum. Aortic valve calcified, leading to aortic stenosis. >65 years old.

Chronic Aortic Regurge effects on the heart

Decrease in diastolic BP, LV undergoes eccentric hypertrophy to compensate for increase in LV end diastolic volume leads to increase SV/CO. Pulse pressure is proportional to stroke voume.. Will have palpitations, head bobbing (de Musset sign), abrupt distension and collapse of carotid arteries (Corrigan sign) and peripheral arteries (water hammer pulse), or pistol shot femoral pulses (traube sign) on auscultation

How does melatonin change w/ Alzheimer's?

Decrease w/ progression.

What causes osteoporosis in a prolactinoma?

Decreased GnRH so decreased estrogen will also cause vaginal dryness.

Normal signs of an aging heart

Decreased LV chamber size (apex-base), decreased chamber length causing a ventricular septum to become sigmoid, atrophy of the myocardium --> increased interstitial connective tissue and amyloid deposition. Accumulation of cytoplasmic granules w/ brownish pigment --> lipofuscin pigment.

What enzyme is responsible for the transition to lactic acidosis in ischemic conditions?

Decreased activity of PDH... under hypoxic conditions the accumulation of NADH inhibits PDH.. leading to pyruvate becoming lactate by LDH. this regenerates NAD+ allowing for some ATP by anaerobic glycolysis... W/ significant ischemia like seen in acute mesenteric ischemia, patients will hyperventilate to eliminate CO2 and induce respiratory alkalosis.

As someone ages, what do you worry about when giving drugs?

Decreased renal clearance... esp for drugs like digoxin As people age, renal function declines progressively... Not seen w/ a rise in creatinine because as people age, there is a drop in muscle tissue and lean body mass which drive creatinine. Reduce doses for elderly w/ normal creatinine.

How does carbamazepine work?

Decreases sodium current on multiple levels. Inhibits neuronal high frequency firing by reducing ability of sodium channels to recover from inactivation.

Why does COPD cause hypoxemia?

Decreases the diameter of conducting airways, preventing adequate flow and emphysema causes by dilating alveolar air spaces so that their is unsufficient contact b/w air and deoxygenated blood in capillaries. Smoking independently increases hypoxia by increasing concentration of carboxyhemoglobin in the blood.

Subluxation of radial head injury

Deep branch of radial nerve, during passage through supinator canal leading to weakness during finger and thumb extension

Difference in lymphatic drainage between penis/balls/etc.

Deep inguinal for glans penis and superficial nodes Superficial inguinal nodes for scrotum. They actually get all cutaneous from the umbilicus to the feet, and anus up to dentate line.. .Except testis, galns penis and posterior cutaneous portion of calf. Calf/glans penis = deep inguinal Testes = para-aortic Superficial inguinal drain into deep inguinal

What three pathologies contribute to lumbar spinal stenosis?

Degenerative arthritis is main cause in spine... Usually >60 years old.. Overtime intervertebral disc degenerates and begins to protrude, resulting in corresponding loss in disc height. This loss of height places load on posterior aspect of spinal column, leading to formation of facet joint osteophytes that impinge nerve roots and hypertrophy of ligamentum flavum.

Dengue Fever and Chikungunya Fever?

Dengue fever... travel to Brazil, Aedes aegypti mosquito (S/SE Asia, Carribean, Americas).. acute febrile illness w/ HA, retro-orbital pain, joint/muscle pain.. Also hemorrahge (petechia, purpura, epistaxis, melena), TCP, leukopenia, Hemoconcentration Chikungunya is a febrile illness w/ fluilike symptoms, polyarthralgias/arthritis, diffuse macular rash... Happen in similar areas. Use bed nets, window screens, insect spray

5 stages of grief in terminal illness

Denial = denies illness, severity, prognosis Anger = directly expressed or may be displaced onto others Bargaining = strike a bargain in return for surviving Depression = sad, detached, hopeless Acceptance = come to terms w/ death at peace Median prognosis for unresectable prostate cancer 8-12mo, 3-6 months for mets. Hope is a great mechanism to help patients cope w/ painful emotions and ordeal of treatment. 1) figure out if denial is interfering w/ medical care or relationships. 2) if not, then don't confront it, just validate and hope. Focus on short-term plans and giving meaning w/ participation.

Transient HSN reaction to a drug, what would expect on skin biopsy?

Dermal Edema IgE mediated degranulation of mast cells. Can also have HSN due to non-IgE mediated degranulation (opiates, radiocontrast, physical urticaria) or mast cell-independent mechanisms (aspirin, hereditary anioneurotic edema) Urticaria is due to increased permeability of microvasculature --> edema of superficial dermis. Deep dermis/SubQ tissue is angioedema. Overlying epidermis is normal on bx, w/ lymphatic channels being engorged w/ transudative fluid. ~Acantholysis is lack of cohesion b/w keratinocytes in the epidermis. Pemphigus especially ~Acanthosis.. diffuse increase in thickness of stratum spinosum (prickle cell layer) b/w granular and basal layer... Psoriasis, seborrheic dermatitis, acanthosis nigricans ~Dyskeratosis... abnormal, premature keratinization of individual keratinocytes. Strongly eosinophilic w/ small basophilic nuclear remnant... SCC especially ~Spongiosis.. .intercellular epidermal edema that histologically appears as an increase in the width of spaces b/w cells... Spongiotic dermaittis (eczema especiallY)

What do administer after someone ingests tons of insecticide?

Dimercaprol right away (british anti-lewisite) increases urinary excretion of heavy metals by forming stable, nontoxic soluble chelates. Displaces arsenic from sulfhydryl grups of enzymes. very narrow TI though and nephrotox/hyperTN/fever side effects. .... Arsenic binds sulfhydryl groups disrupts cellular respiratoin and GNG. Sepcifically PDH is messed up bad. Also pressure treated wood, contamined waer from walls Acute = garlic breath, vomiting, watery diarrhea, long QT Chronic = hypo/hyperpigmentation, hyperkeratosis, stocking glove neuropathy Also give DMSA (succimer)

What is the difference between abdominal aortic dissection and abdominal aortic aneurysm?

Dissection would involve an intimal tear... Aneurysm is just chronic transmural inflammation. AAA associated w/ Age >60, smoking, HTN, male, Fx Hx... leads to oxidative stress, vascular smooth muscle apoptosis, and chronic transmural inflammation. MPs release matrix metallorpoteinases and elastases that degrade ECM leading to weakening and expnasion of the aortic wall. Ischemia of tunica media may play a role in the infrarenal AAA.. intimal layer of atherosclerosis decreases diffusion for oxygen.

Erythema Multiforme vs. Varicella vs. HSV vs. SJS

EM... can get oral mucous membranes or tongue... erythematous, round papules w/ target lesions and red inflammatory zone w/ pale ring and halo... cell-mediated immune process w/ inflammatory infiltrate (CD8). Assc w/ HSC/mycoplasma and may be due to an immune response against antigens int he skin. SJS... erythematous macules w/ necrosis and skin sloughing... also fever/hypotension... may cause target lesions but assc w/ meds Varicella... fever w/ vesciular eruption in multiple areas trunk face abdomen and extremities. HIV... can give a rash! in trunk/face/palms/soles

What treats cyanide poisoning... Toxicity of cyanide is binding to ferric iron w/ high affinity inhibiting cytochrome c oxidase in the mitochondria... means something fails...

ETC... --> severe lactic acidosis and death as a result of only anaerobic metabolism... Cyanide poisoning presents w/ reddish skin discoloration, tachypnea headache tachycardia often w/ n/v/confusion and weakness. Can progress to seizures/CV collapse... Labs indicate severe lactic acidosis in conjunction w/a narrowing of the venous-arterial PO2 gradient, bc tissue can't extract O2. Inhaled amy nitrite oxidizes ferrous iron (Fe2+) to Fe3+ generating methemoglobin and carrying out cyanide... Hydroxycobalamin and sodium thiosulfate are also antidotes.

What is the difference between ecological study and cross-sectional study?

Ecological study, study population data... useful to generate hypotheses but should not be used for conclusiosn (ecological fallacy) Cross-sectional surveys are snapshots of individuals at a given point... This is individual data not population data.

Triad of Wiskott-Aldrich

Eczema, Recurrent Infections, TCP... Mutation on X chromsome present in males as x linked... SCID pyogenics esp bc no humoral immune repsonse and those w/ polysaccharide capsules forsure. Tx is HLA matched BMt... Infections worsen as maternal IgG and maternal Mucosal IgA derived from colostrum are degraded at ~6months

Pinworm in chidren

Enterobiasis is the most common helminthic infx in the US... Enterobius vermicularis... Adults live in human intestine, mostly cecum/appendix.. Female worm migrates out through rectum onto perianal skin to deposit eggs (mostly at night) larvae mature w/in 6 hours and can be ingested by the same individual or spread to other humans Inflammation to eggs --> perianal itching Abdominal pain, nausea, vomiting if there is a heavy worm burden. Dx w/ Scotch Tape Test - oval and asymmetrically flattened eggs w/ bean-shaped appearance. Tx w/ albendazole or second line pyrantel pamoate

Most common viral cause of meningitis?

Enteroviruses are most common Arboviruses HSV type 2... enteroviruses = coxsackie, echo, polio and are >90% of cases.

Ductal Carcinoma in Situ

Epithelial elements of breast tissue proliferate during lactation and include branching ducts (connect lobules to sinuses that drain to nipple) DCIS arises from breast ducts. Precursor to the most common type of breast cancer, invasive ductal carcinoma... Age and nulliparity are RFs and breastfeeding is protective. DCIS shows microcalcifications in asymptomatic patients w/ normal breast exams. Histo demonstrates ducts distended by plemorphic cells w/ prominent central necrosis w/o extension beyond basement membrane. Spread of these malignant cells to nipple through duct system --> paget's disease. ~Lobular breast carcinoma = palpable breast masses w/ orderly rows of cells in single file ~Phyllodes tumor from stroma --> mlaignancy w/ diffusely disordered hypercellular connective tissue w/ cellular atypia and leaf-like projections.

How does pregnancy lead to gallstones?

Estrogen increase in cholesterol synthesis and Progestrone gall bladder hypomotility. OCPs also do this. 5-12% of women get gall stones when pregnant. Progesterone decreases gall bladder secretions and slows emptying

What two enzymes cause disulfiram reaction after alcohol?

Ethanol --> acetaldehyde via alcohol dehydrogenase and acetaldehyde to acetic acid via acetaldehyde dehydrogenase 1. Fomepizole inhibits 2. Disulfiram inhibits. Metronidazole causes a similar rxn w/ alcohol p/w headache, abdominal cramps, nausea, flushing

Why does ethanol cause gall stones?

Ethanol induces secretion of high protein low fluid secretions from the pancreas that are likely to precipitate and plug causing obstruction of pancreatic ductules. Alcohol also causes spasms of the sphincter of Oddi and has direct toxic effects on the acinar cells. Passed out pancreatitis patient, when you rule out gall stones, if you see high MCV >108 suggests vitamin deficiencies and likely alcoholic pancreatitis.

What can delay onset of Hemochromatosis in women?

Excess absorption of storage in 0.5-1.0g a year and 20g is serious. Women present later because of protective blood loss from menstruation and pregnancy.

What causes contractures?

Excessive MMP activity and myofibroblast accumulation at wound edges.. this all happens w/ second intention.

Succinate DHD

FAD serves as a component of succinate DHD. Complex 2 participates in both ETC and TCA.. During TCA, succinate DHD converts succinate to fumarate and transfers electrons to coenzyme Q (ubiquinone via FAD)

When calculating the filtration fraction....

FF = GFR/RPF not Renal Blood Flow Renal plasma flow = Renal blood flow* (1-Hematocrit)

Cirrhosis patient w/ hepatic encephalopathy after a recent GI bleed, what is the mechanism?

Failure of liver to metabolize waste products such as ammonia. Normally produced in the GI tract as a result of enterocytic catabolism of glutamine and colonic catabolism of dietary protein... GI bleeding causes increased nitrogen delivery to the gut in the form of hemoglobin, which is then converted into ammonia and absorbed into the bloodstream... Enters liver through portal vein and detoxified to urea. In the setting of chronic liver failure, this upswing in ammonia is too much to handle, and accumulation of ammonia ensues. Alters amino acid transport to BBB, impaired NT metabolism, and decreassed cerebral glucose metabolism. Leads to increased inhibitor NT and impaired excitatory NT. Usually give lactulose. Acidification of coloinic contents and converts absorbable ammonia to ammonium nonabsorbable.

What causes duodenal atresia

Failure of migration of the ventral pancreatic bud. It should appear at the 5th week and jump behind the pancreas by week 8. Ventral --> uncinate process of the head and main pancreatic duct Dorsal --> tail, bod, remainder of head. Surrounds the second part of the duodenum.. lead to obstruction or chronic/acute pancreatitis, most patients are asymptomatic though.

Neurapraxia

Failure of nerve conduction due to blunt injury by enlargement of l atrium especially... usually in the vicinity as it loops behind the ligamentum arteriosum, underneatha nd around the aortic arch. MStenosis can cause L atrial dilatation sufficient to impinge on L Recurrent Largyneal nerve = Ortner Syndrome. Recurrent laryngeal innervates all muscles of the larynx except the cricothyroid muscle... paresis of vocal cord muscles --> hoarseness.

How can you induce ovulation in someone w/ PCOS?

Failure of ovulation is a large cause of PCOS infertility. Treatment includes Menotropin (human menopausal gonadotorphin) mimicing FSH and triggers formation of dominant ovarian follicle... Then, hCG in a surge... the alpha subunit mimics LH so LH surge induces ovulation.

Patient w/ lactic acidosis in septic shock, what is the cause?

Failure of oxidative phosphorylation (leading to buildup of NADH and shunting of pyruvate to lactate) Hepatic hypoperfusion and end organ hypoperfusion are the roots caues. If liver is underperfused as well --> it can't clear lactate. p/w anion-gap metabolic acidosis Causes of lactic acidosis Enhanced Metabolic Rate = seizures/exercise Reduced O2 = Cardio/Pulm failure, ischemia/infarction Diminished catabolism = hepatic failure/hypoperfusion Decreased O2 = cyanide poisoning Enzyme defects = glycogen storage diseases (von Gierke), mitochondrial myopathies.

Congenital Umbilical Hernia

Failure of the Closure of the Umbilical Ring causes this The ring closure depends on abdominal muscles... p/w soft, nontender bulge, protrudes w/ increased abdominal pressure, typically reducible Mgmt = observe for spontaneous closure... elective surgery at age 5. ~Gastroschisis has bowel w/ no covering membrane and the umbilical cord is medial ~Omphalocele has sac w/ multiple loops covered by amnion and umbilical cord is at apex. ~Umbilical Hernias are NOT inguinal hernias (due to failure of processus vaginalis obliteration if congenital)

What are two conditions that play with the baseline calcium concentration in someone?

Familial Hypocalciuric Hypercalcemia AND cinacalcet increased sensitivity (decreases baseline calcium) FHH is benign autosomal dominant disorder caused by defective CaSR in PTH gland... Linked to Gprotein

Patient w/ poor diet p/w microcytic anemia.. but they don't notice any blood, diagnosis?

Fe def anemia.. occult blood loss. This needs to be excluded. Esp in a patient post menopausal. Get iron studies and do endoscopy.

Abnl large uterus w/ problems defecating but no pain on defectation/w/ sex

Fibroids most common.. Uterine leiomyomas can be on the serosal surface of uterus in the back , can also be intramural or endometrium... Subserosal fibroids can push on the colon and cause bulk-related symptoms of pelvic pressure. Leads to constipation. Splinting to defectate helps (manual deflection of obstruction) Submucosa fibroids in the endometrium --> heavy menstrual bleeding Pelvic organ prolapse.. = p/w pelvic pressure (bulge or something is falling out of my vagina). Posterior vaginal wall prolapse can cause constipation, and splinting is common, but NOT uterine enlargement.

Different destructions of liver and their diagnosis

Fibrosis and nodular parenchymal regeneration = cirrhosis = HepB/C/alcohol/hemochromtosis/nonAlcFLiverdisease ~Dilation of sinusoids and perivenular hemorrhage = acute venous outflow obstruction (Budd-chiari)...less common cause of cirrhosis ~Granulomatous Destruction of bile ducts PBC (less common cause of cirrhosis) ~intrahepatic hydatid cysts w/ surrounding fibrosis raction = Echinococcus infection (rare in US) ~pigment accumulation in hepatocytes = Dubin-Johnson Syndrome

What is a tubulovillous adenomatous polyp?

Fibrovascular stalk w/ tubular glands and villous components. Lined by dysplastic columnar epithelial cells that are seen in all colonic adenomatous polyps. Mild dysplastic cells are elongated/hyperchromatic loww of mucin. Increasing in size/shape (pleomorphism) and nuclei enlargement (hyperchromatism are severe dysplasia.

Focal vs Generalized seizures and their treatments

Focal = Simple and Complex Simple = no LOC or postictal state, motor/sensory/autonomic/psych symptoms... Complex = LOS and Post-ictal... May have automatisms... ^Both tx w/ narrow spectrum.. carbamazepine, gabapentin, phenobarbital, phenytoin Generalized Tonic-Clonic Myoclonic = no LOS or postictal state, brief jerking mvmts Absence = brief LOC, no postictal All valproic acid, lamotrigine, levetiracetaum, topiramate for TC/M and then ethosuximide for Abs

How to dx osteomyelitis in kids?

Focal radiotracer uptake w/ infection of long bone metaphysis 1. Bacterial seeding --> focal bone marrow cellulitis... 2. inflammation in confined space compromises blood flow --> necrosis 3. Infection forced through vascular channels into cortex and spreads along periosteum 4. Reactive bone = involucrum... Retained, necrotic bone = sequestrum... draining sinus will push infection out. Hematogenous osteomyelitis classically affects children. Because metaphysis has slow-flowing, sinusoidal vasculature conductive to microbe passage. .. When epiphyseal plates close decreases chance of hematogenous osteomyelitis

Beck's Triad

For Cardiac Tamponade JVD, hypotension, muffled heart sounds... Also pulsus paradoxus (large inspiratory increase in systolic BP >10 mmHg) Low Voltage QRS, water-bottle-shaped heart, clear lungs Inspiration causes an increase in systemic venous return, increasing RHVolume. Leds to Rv expansion into pericardial space normally w/ little impact on the heart, however in conditions that impair expansion into pericardial space, this increased RV volume leads to bowing of septum toward LV. Leads to decrease in LV end diastolic volume nad foward stroke volume. Constrictive Pericarditis can also cause pulsus paradoxus... BUT is caused by scarring and loss of elasticity of the normal pericardial sac... takes several weeks to months to develop and only rarely occurs after several episodes of recurrent pericarditis. Causes of Ctamponade = malignant, radiation, infx (viral/TB/HIV), hydralazine, isoniazid, CT diseases (SLE/RA)

What are Foscarnet, Sofosbuvir, Oseltamavir, Lamivudine, Saquinavir

Fosacrnet... treats CMV colitis... Pyrophosphate analog that does NOT require intracellular activation. It binds both DNA pol in herpesvirus and RT in HIV... Foscarnet must be administered IV. Also, treating ganciclovir resistant CMV infections... Can also treat acyclovir resistant herpesvirus infections. Ganciclovir and Acyclovir both need intracellular activation by virally encoded kinases. Lamivudine... NRTI, must be phosphorylated by intracellular kianses then inhibits HIV RT. Oseltamavir and Saquinavir... no intracellular activaiton but not used for CMV infection... Oseltamivir is a sialic acid analogue inhibitor of Influenza A and B neuraminidase... Saquinavir is a HIV protease inhibitor that prevents cleavage of polyprotein precurosrs. Sofosbuvir inhibits NS5B RNA dep RNA pol for HEPCInfx requires intracellular activation

How do the different physical exam findings of around the heart present?

Friction rub in patient with previosu viral illness a week ago who now has sharp mid chest pain that increases w/ deep inspirations and decreases when he sits up. Fibrinous or serofibrinous pericarditis is the most common variant leading to pericardial friction rub. Usually caused by MI, rheumatic fever, or uremia. Although viral infection can also do it Kussmaul's is a paradoxical increase in JVD w/ inspiration... Chronic constrictive pericarditis,w hich takes years to develop.. Also restrictive CMOP, right sided HF, tricuspid stenosis and tamponade. If acute an no Hypotension, then not tamponade and likely no Kussmaul's bc pericarditis Pulsus paradoxus... drop in systolic BP of 10mmHg during inspiration.. Exaggeration of normal response to inspiration.. in cor pulmonale, chronic constrictive pericarditis, cardiac tamponade. Pericardial knock is present in constrictve chronic pericarditis... Takes years -months to develop. Brief, high freq sound shortly after S2.

Acute Rheumatic Fever Pathogenesis and odder presentation

GAStrep antibodies molecular mimicry cross react w/ CNS antigens... Specifically GAS antigens, M protein and N-acetyl-beta-D-glucosamine attack myosin, a cardiac protein, and lysoganglioside a neuronal cell surface protein. Often have sudden changes of voice pitch/volume. Erythema marginatum p/w faintly erythematous circular lesions w/ central clearing on trunk/extremities.

What is the role of fluticasone in chronic airway asthma?

GCs have anti-inflammatory effects. They inhibit inflammatory mediators (cytokines, PGs, LKTs). They reduce leukocyte extravasation and induce apoptosis of existing cells. They also decrease amount of mucus produced by goblet cells, reducing obstruction.

Different Galactose metabolism problems

Galactosemia is from deficiency of enzymes of galactose metabolism... Lactose is broken down into glucose and galactose... Galactose --> Gal1P by galactokinase... if GAL kinase deficiency --> galactose build up leads to galactitol int he lens meaning cataracts... Excess also spills into the urine and tests positive for reducing substance... In contrast... Galactose-1-Phosphate Uridyl Transferase deficiency results in more serious forms of galactosemia. Accumulation of Gal-1-P a toxic metabolite to liver and kidney... Patients w/ GALT deficiency present early w/ vomiting, lethargy, failure to thrive... *galactosemia tested for in normal newborn screening.

Causes of acute pancreatitis

Gallstones and alcohlism are most common... SCD patients at risk for bilirubin gallstones. 1) Recent ERCP (cholangiopancreatography) 2) Drugs (azathioprine, sulfasalazine, furosemide, valproic acid) 3) Infections (mumps, Coxsackie, Mycoplasma) 4) HyperTG 5) Structural Abnormalities of duct or ampulla (strictures, cancer, pancreas divisum) OR (choledochal cyst, stenosis of sphincter of Oddi) 6) Surgery 7) Hypercalcemia >1000 TG leads to problems because FFA exceeds binding capacity of albumin and leads to direct injury to pancreatic acinar cells.

Sorbital on the lens, what normall happens to it in most cells via the Poyol pathway?

Glucose enters... aldose reductase turns NADPH into NADP+ to make sorbitol... Sorbitol converted to fructose via sorbitol DHD making NAD+ into NADH Cataracts will impair red reflex... Long term hyperglycemia will oversaturate the polyol pathway... If the process is slow, like in long standing hyperglycemia, sorbitol accumulates happens in LuRKS THis leads to osmotic and oxidative stress and contributes to diabetic retinopathy, neuropathy, nephropathy... Increased stress leads to hydropic lens fibers that degenerate --> lens opacification and cataracts *ald reductase also converts galactose into galactitol normally insignificant, but in galactosemia (G1P UDT def) increased galactitol results in congenital cataracts.

Patient w/ underlying hyperglycemia, probably caused by decreased activity in glucokinase

Glucose stimulates insulin secretion.... 1) glucose enters beta cell through GLUT2 2) glucose is metabolized by glucokinase to G6P 3) G6P glycolysis -> Krebs -> ATP 4) High ATP/ADP ratio w/in beta cells --> closes ATP sensitive potassium channels (Katp) 5) Depolarization of beta cells results in opening of VG calcium channels 6) High intracellular calcium releases insulin Glucokinase has a lower glucose affinity than other hexokinases... This allows it to function as a glucose sensor in beta cells by varying the rate of glucose entry into the glycolytic pathway based on blood glucose levels... Heterozygous mutations in this gene cause decreased beta cell metabolism of glucose, ATP and diminished insulin secretion Maturity-Onset Diabetes of the Young!!!! p/w mild, nonprogressive, hyperglycemia that worsens w/ pregnancy induced insulin resistance. Homozygous --> fetal growth retardation and hyperglycemia at birth

Factors to look for when diagnosing adenocarcinoma of stomach from intestine?

Goblet cells for Barrett's change... Acid reflux, lower esophagus

When lifting a heavy weight, what stops you from pushign too hard and causes you to drop weights?

Golgi Tendon Organ... sensory R at the juntion of muscle and tendon innervated by 1b sensory axons. Connected in series w/ contracting extrafusal skeletal muscle fibers... When a muscle actively contracts against resistance, the increase in tension is transmissted through the tendon activating the GTO in the process. In contrast, GTOs are relatively insensitive to changes in muscle length... Because lenghtening occurs when a musle is passively stretched this is muscle fibers not tendon. 1b sensory axons from GTOs send inhibitory interneurons in the spinal cord which synapse w/ alpha motor neurons that innervate that same muscle. Thus, GTO is a negative feedback system for muscle tension. When a muscle exerts too much force, GTOs inhibit contraction of the muscle --> sudden muscle relaxation. Prevents damage.

What type of disease and sydrome do anti-GBM antibodies cause?

Goodpasture... nephritic

What is activated in the inositol triphosphate type pathway?

Gq activates phospholipase C which breaks down Phosphatidyl bisphosphate into inositol triphosphate and diacylglycerol.. DAG stimulates PKC which phosphorylates downstream proteins... IP3 produces most of its effects by increasing intracellular calcium which also activates PKinaseC.

Presentation of PSGN on IF and EM

Granular deposits of IgG, IgM and C3 in the GBM... Supepithelial humps on EM Light micro will show hypercellular glomeruli due to NP/MP infiltration and mesangial and endothelial cell proliferation.

Patients p/w necrotizing inflammation w/ granulomas of lungs and kidneys...

Granulomatosis w/ Polyangitis

Presentation of Cryptococcal Meningoencephalitis

HA, Fever, Lethargy (2 weeks or so) -more severe in HIV patients LP shows low glucose, increased protein, leukocyte count particularly low in HIV patients!!! Transparent capsule on India Ink Staining!!! -Cryptococcal antigen in CSF Culture on Sabouraud agar Tx = AmphoB w/ Flucytosine Long term Tx is Fluconazole India Ink stains the background of the slide and allows the thick polysaccharide capsule of yeast to be visualize as a clear halo w/ a dark background..

Tyramine crisis presentation

HTN, blurry vision, HA, tachycardia, tremors, diaphoresis after eating aged cheeses, cured meats, draft beer. MAO inhibitors (tranylcypromine, phelezine) function by increasing monoamine levels and used in atypical/treatment resistant depressions.

How does Conn's present?

HTN, hypokalemia, met alkalosis, decreased plasma renin tx is surgical resection or eplerenone/spironolactone (choice).. eplerenone has fewer side effects... Gynecomastia 1% eplerenone, 9% spironolactone

Single most important RF for thoracic aortic dissection?

HTN... Atherosclerosis is a RF for aortic aneurysm not as much dissection, and more abdominal... tertiary syphillis weakes aortic wall and increases risk of ascending aortic aneurysms not as much dissections. Intimal tear and dissection from HTN.. Cystic medial degeneration from CT disease (esp in younger patients) is also a risk factor.

What type of receptor in PCV?

Ha, weakness, diaphoresis, aquagenic pruritis, facial plethora, splenomegaly... assc w/ PUD and gouty arthritis... Labs = increased RBC mass, thrombocytosis, leukocytosis, low EPO levels. EPO R has no intrinsic kinase activity, must interact w/ jaun kinase 2 (cytoplasmic TKinase) to initiate downstream signaling.

Half life elimination of drug per hour yahta yahta

Half life is the time required for plasma concentration of drug w/ first order elimination to decrease by 50%. It depends on drugs properties like lipid binding, protein binding, metabolomics. Half life of a drug after administration of a single dose is t1/2 = (0.7*volume distribution)/clearance At time zero, 100% of drug is present if IV. After 5 half lifes, drug is completely eliminated. Don't just make up your own divisions, use the equations. In two half lives, 75% of drug is gone.

Build up of neutral AA in a kid w/ gait instability, pruritic skin rash, irritability and loose stools???

Hartnup disease... inactivating mutations in neutral amino acid transporter... Results in impaired transport of neutral amino acids (like tryptophan) in the small intestine and PT of kidney.. TT is an essential amino acid and precursor for niacin, serotonin, melatonin. Conversion of tryptophan to niacin is responsble for the generation of up to half of the NAD+ (nicotinamide adenine dinucleotide)... Leads to niacin deficiency type presentation.. pellagra-like skin eruptions (red, rough rash w/ sun) and cerebellar ataxia.. Dx is confirmed by measuring the neutral AA in the urine (neutral aminoaciduria)... High protein diet w/ daily niacin or NAD supplementation will show improvement.

What part is variant in HepC for reinfection by same virus or new?

HepC RNA dep RNA pol has no 3-5 proofreading... Differ subtypes up to 30-35% in their envelope proteins!! High muation rate leads to development of distinct quasispecies w/inthe infeted individual stemming from that one infection... Hypervariable genomic regions fro envelop glycoproteins. As host has antibodies made, one strain dies off and a new one takes its place.

What are the important heme clotting drugs

Heparin hits Xa and IIa Warfarin hits VII, IX, X, II Factor Xa inhibitors are direct (rivaroxaban/apixaban oral both) or indirect (fondarparinux Direct thrombin inhibitors are argatroban, Bivalidurin, Dabigatran (oral)

Symptoms of HyperPTH vs HypoPTH

Hyper.... -osteoporosis, nephrolithiasis, polydipsia/polyruria, constipation, bone pain, muscle pain Hypo.... -tingling, numbness, trousseau & chovstek, muscle spasms, seizures

How to know when phenylketonuria is due to phenylalanine hydroxylase deficiency or Dihydropteridine reductase deficiency?

HyperPhe anemia and elevated prolactin!!! is DHPTR def In classic PKU, tyrosine supplementation allows for intact function to tyrosine hydroxylasee. However, in BH4 problems, low dopamine levels persist because next enzyme in the chain, tyrosine hydroxylase also can't work... Bh4 type is <2% of hyperphenylalanemia cases... Leads to progressive neuro deterioration. Normally dopamine from the tuberoinfundibular pathway inhibits prolactin. Decreased BH4 casues low dopamine causes high prolactin!

Options for types of response to transplants

Hyperacute = min-hours = gross mottling/cyanosis, preformed antibodies against graft in recipeint's circulation Acute = exposure to donor antigens induces humoral or cellular activatino of naive immune cells (<6mo) Chronic = chronic, low grade immune response refractory to immunosuppresants... vascular wall thickening and luminal narrowing, interstitial fibrosis and atrophy. Will have lymphocytic infiltrate in acute ~calcineurin inhibitors cause reduced renal blood flow and damage to renal endothelial and tubular cells --> arteriolar hyalinization and tubular vacuolization.

What electrolyte balances can thiazides cause?

Hypercalcemia, Hyperglycemia, Hypercholesterolemia, Hyperuricemia, Hyponatremia, Hypokalemia. Inhibits Na/Cl cotransporter

Mechanism impaired by scurvy, also skin finding of follicles

Hyperkeratotic follicles w/ corkscrew hairs... easy bruising but mainly a deficit in hydroxylation of proline and lysin residues during collagen synthesis.

Deficiencies in which R could cause bad TB dissemination?

IFN gamma receptor is one example... Scary if BCG vaccine given to these patients. MPs infected w/ mycobacteria produce IL12, which stimulates T cells and NK cells to produce IFNgamma. This binds to its R leading to receptor dimerization and activation of JAK1 and JAK2. Leads to nuclear signaling via STAT1 and tx of IFN gamma regulated genes which promote mycobacterial killing. Also enhances viral and parasitic resistance by increasing expression of MHC.

What do you think when you hear periodic, simultaneous, non-peristaltic contractions of large amplitude and duration in the esophagus?

IMPAIRED neural inhibition = Diffuse Esophageal Spasm... -normally stimulated contractions by food bolus... originate from site of distension and propel food donwards... In this disease, several segments of esophagus contract inappropriately at the same time, which appears as disorganized non-peristaltic contractions on esophageal manometry and corkscrew esophagus on barium swallow. Leads to S/L dysphagia, Cx Px, heartburn, food regurge... Likely to myenteric plexus is the culprit.

What is changed w/ patients w/ narcolepsy that can be measured?

IN CSF THERE IS ABSENT hypocretin-1 (orexin-A) and hypocretin-2 (orexin-B)... Narcolepsy w/ cataplexy specifically. There are produced in the neurons in the lateral hypothalamus. Function to promote wakefulness and inhibit REM sleep phenomenon. Normal people have normal levels of these two. To dx recurrent lapses into sleep/napping multiple times w/in the day >= 3 time weekly for >=3 months at least 1) cataplexy (conscoius brief episodes of sudden B/L loss of muslce ton precipitated by emotions) or spontaneous abnormal facial mvmts w/o emotional triggers 2) hypocretin1 deficiency 3) rapid eye mvmt latency <= 15 minutes

Which type of disease causes aplastic anemia?

IV hemolysis. LDH elevated in hemolytic anemia

Best way to prevent embolization of a DVT?

IVC filter... for patients w/ contraindications to anticoagulation.

Hepatitis histology and presentation?

IVDU w/ feer, jaundice, anorexia... DING DING DING all hepatotropic viruses that cause acute viral hepatitis present the same histologically... Liver biopsy typically shows panlobular lymphocytic infiltrates, ballooning hepatocytes, hepatocyte necrosis, hepatocyte apoptosis... Apoptotic hepatocytes --> round acidophillic bodies = Councilman Bodies or Apoptotic bodies.

What are the Tmax of PAH and glucose? What about inulin/creatinine or urea?

Idk, there is one though none for creat/urea Glucosuria begins at 200mg/dL.. this is the threshold of glucose, at this point some nephrons w/ lower Tms will (transport maximums) will begin to leak, but at 375 excess is totally unabsorbed.

Knee Tear

In MRI, sartorius muscle is medial, and it is the side muscle seen disconnected.... ACL and PCL are within the articular capsule of the knee joint and cross one another as each spans from the femure to the tibia. PCL starts at anterolateral surface of medial femoral condyle and inserts into the posterior intercondyl area of tibia.... At the level of the tibial plateau, the ACL is anterior and the PCL is posterior... PCL prevents posterior displacement of tibia relative to femur and its integrity can be tested w/ posterior drawer test (posterior displacement when anterior tibia has pressure in the flexed position) Often PCL torn in anterior proximal tibial injuries.

Pneumobilia, where is the gall stone likely causing obstruction?

In the ileum... due to long standing cholelithiasis often in elderly women typically a large gall stone >2.5cm. Forms a cholecystoenteric fistula to duodenum due to increased pressure and necrosis b/w these tissues. Narrowest portion of the intestine is the ileum, so stones are most likely to get trapped here. p/w abdominal distension, n/v/, high pitched bowel sounds (tinkling), tenderness dilated loops of bowel w/ air-fluid levels due to intestinal obstruction.

What causes MCD?

Inciting event like upper respiratory infection, immunization, insect bite. Systemic T cell dysfunction leads to production of glomerular permeability factor ( a cytokine that damages podocytes and decreases the anionic properties of glomerular basement membrane). Loss of negative charge leads to loss of albumin in the urine

What is a field defect in development?

Incomplete division of the forebrain yields holoprosencephaly. Cleavage of prosencephalon into telencephalon and diencephalon is essential and happens at 5 weeks. Failure of sleavage can result from mild midline defects (cleft lip/palate, ocular hypotelorism) or severe defects (single midline eye, primitive nasal structure/probosccis) HPE is caused by genetics (SHH, trisomy 13), environmental (maternal alcohol use). It is a developmental field defect, which is when an intitial embryonic disturbance yields to multiple malformations by disrupting the development of adjacent tissues/structures Association is when multiple anomalies w/o a known unifying cause occur together, than alone. VACTERL. Deformations are structural anomalies that occur due to extrinsic mechanical forces.

What effect do OCPs have or estrogen have on thyroid levels...

Increase TBG levels... increasing bound T4 and decreasing free T4.. increasing TRH and TSH increasing total T4 overall. TBG binds 70% of bound-thyroid hormone, while the other 30% bound by albumin and transthyretin... Only free fraction. More than 99% of circulating thyroid hormone is bound plasma proteins creating a large circulating reservoir of thyroid hormone.

What is the sequence of events for pulmonary HTN from left sided HF?

Increased Diastolic Filling pressures Increased LAP Pulmonary Venous Congestion from backup Increased pulmonary artery pressure Vasoconstriction --> endothelial damage and capillary leakage of serum proteins... decreased NO and increased endothelin.. remodeling occurs. Intimal thickening (collagen) and medial Hypertrophy (smooth muscle cell proliferation) w/ HF, although pulmonary artery pressures rise, pulmonary arterial flow will remain the same or decrease w/ HF

Early minor COPD why no pulmonary edema?

Increased interstitial fluid pressure leads to increased lymphatic drainage. Even though these patients have ANP being released, which inhibits RAAS... the decreased CO and renal hypoperfusion of cor pulmonale has a net retentive effect on Na/Water

What is spinal muscular atrophy?

Infant w/ delayed growth, weak, can't lift up head when prone, unable to roll on one side. Decreased DTRs Caused by mutations in the survival motor neuron (SMN1) gene, which encodes a protein involved in the assembly of small nuclear ribonucleoproteins (snRNPs) in lower motor neurons... Defective snRNP assembly impairs spliceosome function and degeneration of anterior horn cells in the SC non-coding RNAs are those that function but don't code for protein... A collection of snRNPs and other proteins on pre-mRNA are the spliceosome. Spliceosomes remove introns from pre-mRNA by lceaving at the 5' end of intron 1 (splice donor site) and joining that end to a branch point... Freed 3'OH of exon1 then forms a phosphodiester bond w/ 5' at the acceptor splice site of exon 2

Timeline of TB infection primary

Inhaled in lower lobe and replicates w/in the alveoli... MPs phagocytose the organism but are initially unable to eliminate due to cord factor that prevents phagolysosome fusion/acidification. This allows TB to replicate in an unchecked fashion in the phagosome of alveolar MPs for the first few weeks of the infection. After a few eeks, APCs in the draining lymphatic system display mycobacterial antigens and release IL12, which stimulates naive CD4 lymphocytes to differentiate into T helper type cells. TH1 cells release IFN gamma, which activates MPs causing the m to form fully acidified phagolysosomes, differentiate into epithelioid cells Cause caseating necrosis to limit proliferation.

MOA of terbinafine?

Inhibition of squalene epoxidase... It is an allylamine. ~AmphoB and nystatin are polyenes that bind ergosterol -Caspofungin is an echinocandin that blocks synthesis of Beta 1,3D glucan (candida/aspergillus) -Flucytosine is an antimetabolite antifungal transformed into 5-FU in fungal cell to inhibit protein synthesis by replacing uracil.

What type of reaction is an insect sting?

Initial exposure causes class switching from IgM to IgE, then these IgE bind high affinity FceiR receptors on mast cells and basophils.. Subsequent exposure causes cross linking and degranulation in a type 1 HSN rxn. Histamine causes wheel and flare reaction with edema, vasodilation, itching, redness... If systemic --> anaphylaxis w/ bronchoconstriction and massive fluid shifts.

Progression of color of brusies

Initially a purple/bluish color... Erythrocyte destruction releases iron-containing heme molecules, heme oxygenase degrades heme into billiverdin, CO and ferrous iron while consuming oxygen and electrons provided by NADH/NADHPH cytochrome P450 reductase. Biliverdin further reduced to yellow via billiverdin reductase. Which is transported to liver bound to albumin

What are the targets in MOA of the 7 main types of diabetes drug?

Insulin Secretagogues = SU/Megs = increase insulin secretion by inhibiting beta-cell KATP channels Biguanides = metformin = stimulate AMPK, decrease glucose production and insulin resistance TZDs = glitazones = actiavte PPAR gamma to decrease insulin resistance GLP1s = atide and glutide = increase glucose-dep insulin secretion, decrease glucagon secretion, delay gastric emptying DPP4 inhibitors = sitagliptin, saxagliptin = increase GLP-1 and GIP levels Alpha-Glucosidase inhibitors = Acarbose and Miglitol SGLT2 In = increase renal glucose excretion

What proteins connect cells to the ECM via adhesions?

Integrins connect to fibronectin which connects to collagen. Integrins connet to actin intracellularly. Differential expression of integrin subtypes affects adhesion properties and correlates w/ malignant behavior. Hyaluronic acid is a GAG that contributes to water retention in the ECM and determines stiffness of the matrix... Keratan sulfate is a GAG in the ECM that may play a role in maintaining type 1 collagen fibril organization in many tissues.

What gives elastin its elastic properties?

Interchain cross-links involving lysine Made of Gly, Ala, Val... many proline/lysine residues. Few are hydroxylated. Translation to tropoelastin then ECF to microfibrillar (fibrillin) scaffold conjugation... Then lysyl oxidase (w/ help of copper) will deaminate some of the lysine residues of torpoelastin facilitating formation of desmosine cross links w/ neighboring polypeptides. These account for rubber-like properties of elastin.

Most likely cause of nipple discharge (pathologic type)?

Intraductal papilloma.. can lead to blood or serous discharge.. No breast mass or skin chnges... The papillary cells have a fibrovascular core. and foci of atypia/DCIS. ~Paget's has exczematous discharge w/ malignant cells at nipple surface ~Fibrocystic change has small diffuse cysts w/ or w/o metaplasia and frequently cyclic breat pain w/o nipple discharge ~Fat necrosis has irregular breast mass w/o nipple discharge. Histo shows liquifactive necrosis of adipocytes w/ hemorrhage ~Fibroadenoma = small, firm, mobile breast masses that occur due to proliferation of stroma and ducts w/ stromal prolifeartion compressing the ducts to slits.

What is the function of transverse tubules?

Invaginations (T-tubules) of muscle cell membrane (sarcolemma) located in close proximity to terminal cisterns of SR... They are in cardiac/skeletal muscle (striated) and contain VG L type Calcium channels (DHP) adjacent to the ryanodine receptors on terminal cisterns. During contraction, T-tubles allow the depolarization impulse to rapidly propagate through the interior of the muscle fiber. This ensures calcium release from SR occurs uniformly in the fiber, allowing synchronized myofibril contraction in each muscle cell. 17 year old boy w/ proximal muscle weakness can't keep head up and sparse transverse tubules on muscle fiber biopsy indicates, limb girdle muscular dystrophy... due to mutated sarcolemma protein (caveolin) affecting the coupling of excitation/contraction... Decreased #s of functional t-tubules in affected muscle fibers leads to uncoordinated contraction --> weakness. ~Impaired relaxation after sustained contraction occurs in myotonic dystrophy due to trinucleotide repeat expnasion altering myotonin-protein kinase. This protein facilitates myosin head detachment from the actin filament to enable relaxation.

Bicuspid Aortic Valve

Involves when three cusps are not three. instead they are two. And the conjoined cusps have a "raphe" in between them Happens a lot in Turner's Syndrome... presentation... thick, webbed neck, short 4th metacarpal (ring finger), also a broad chest and short stature. and a Aortic Coarctation. You will hear a bicuspid aortic valve, w/ an early systolic, high-frequency click over right second interspace. As valve calcifies --> stenosis or regurge. More susceptible to infectious endocarditis.

How does intermittent claudication present?

Ischemic muscle pain, decreased peripheral pulses, cool, dry, shiny skin, gangrene, small deep ulcers, thick brittle nails, HAIR LOSS

What does phenylephrine and isoproterenol do for heart?

Iso is non sel Beta agonist.. so beta1 incr contract, beta2 decrease vascular resistance PhenylEph.. sympathomimetic pure alpha. Causes vasoconstriction w/ increase in SVR

What are the 4 options of spina bifida?

It happens when there is a posterior vertebral defect from problems w/ caudal neural tube... 1_ spina bifida occulta... tuft of hair or dimple 2. meningocele... meninges herniates through defect 3. Myelomeningocele... Spinal cord and meninges herniate through 4. Myeloschisis... myelomeningocele w/ no skin covering. Valproate or epilepsy can increase risk of NTDs greatly.. also use of methotrexate or TMP-SMX

How does JAK STAT pathway work?

It is a nonR tyrosine kinase... GH comes in binds, causes JAK to dimerize and phosphorylate each other, then they phosophyrlate STAT which dimerizes both phosphorylated and goes on to be a transcription factor. Tx Turner's w/ GH

Why does ACE increase bradykinin?

It is actually responsible for the breakdown of bradykinin!!

What is the disease w/ both sensorineural hearing loss and congenital long QT syndrome?

Jervell & Lange-Nielsen Syndrome... B/L hearing loss.. predisposes to syncope and Torsades Mutations in genes KCNQ1 OR KCNE1 that encode voltage-gated potassium channels. These subunits contribute to the slow-acting component of the outward-rectifying potassiuj current. Responsible for phase 3 repolarization. Brugada is auto dominant associated w/ cardiac sodium or L-type calcium channels = pseudo RBB, ST elevation in V1-V3 and increased risk of Vtach/Cardiac Death

How effective is clopidogrel alone at preventing CV events?

Just as effective as aspirin

What 3 things are associated w/ Primary Ciliar Dyskinesia?

Kartageners!!! 1) bronchiectasias (permanent abnormal airway enlargement) with chronic cough and chronic sinusitis 2) situs inversus (r/l positioning of organs off) 3) infertility (sperm flagella men) and immobility of fallopian tube cilia (women)

IHC stains for cancers

Keratin --> epithelial not endothelium Muscle tissue = actin, caldesmon, desmin Endothelium = CD34 and vWF can stain endothelium Glial --. GFAP

What organ can be chronically affected by PNH?

Kidney... mutated phosphatidyl glycan class A (PIGA) gene, helps make GPI anchor protein... Helps attach CD55 DAF adn CD69 MAC inhibitory protein to RBC, WBC, platelets... Leads to uncontrolled complement-mediated lysis.. p/w hemolytic anemia, jaundice (UNConjB), hemoglobinuria, thrombosis, pancytopenia from stem cell injury... Iron deposition in the kidney --> hemosiderosis and eventually combined w/ microvascular thrombosis to yield CKD

Boy w/ recurrent nosebleeds, where are you likely cauterizing?

Kiesselbach's plexu sin the nasal septum... Anterior nose bleeds^ most common.. . Septal branch of anterior ethmoidal Lateral nasal branch of sphenopalatine Septal branch of superior labial ^All of these synapse at the plexus To stop nose bleed, lean forward and pinch nasal alae. ~Posteriorolateral branches and choanae likely to be posterior nosebleeds.. More severe, can't treat w/ cautery.

Which proteins are in charge of anterograde and retrograde motion on microtubules in the neuron?

Kinesin anterograde from ganglion/body to skin Dynein retrograde transport of HSV virus back to cell body. These movements are powered by ATP hydrolysis ~Lamins are proteins that help form the fibrillar network that lines the inside of the nuclear envelope. Structurals upport and organizing hte genome to regulate gene transcription. ~Spectrin... cytoskeleton protein localed intracellularly along PM.. Distinct shape of RBCs... problems w/ it ankyrin or band3 protein --> spherocytosis

What helps bacteria proliferate in CSF to cause meningitis?

Lack of hujmoral copmonenets (complement and immunoglobulins) in patients w/ meningitis, get blood cultures, LP and empiric antibiotics

Where do atherosclerotic plaques most develop?

Large elastic arteries (aorta and carotid) and in large/medium arteries (coronary and popliteal)... Abdominal aorta is always most heavily involved. Coronary then Popliteal then Carotids then Circle of Willis

Vernet Syndrome

Lesions of jugular foramen... dysfunction in 9,10,11. Dysphagia, hoarseness, loss of gag reflex on ipsilateral side, deviation of uvula toward normal side.

What muscles are targeted w/ pelvic floor exercises to reduce stress incontinence?

Levator ani muscles = iliococcygeus, pubococcygeus, puborectalis... hold bladder and urethra in appropriate position. Injury to these muscles results in urethral hypermoblity and/or pelvic organ prolapse (cystocele) Hypermobility results in incomplete closure of urehtra/bladder neck against anterior vaginal wall --> stress UI... Involuntary urine loss w/ increased intra-abdominal pressure (cough, laughing, straining) 1st line is lifestyle... like increasing fiber. also kegel exercises.

Student has finals coming up, studying a ton, then someone gets delusional, w/ pressured speech, sweating, pacing, hypervigilance, and high pulse/BP.

Likely drug induced bc of HR/BP/sweating... Substance-induced psychotic disorder. Misuse of stimulants by college students to enhance academic performance is prevalent. Paranoia, restlessness, hypervigilance, tachycardia, hypertension and diaphoresis are due to this intoxication. Transient paranoid psychosis can develop in intoxication w/ all major stimulants... Amphetamines/methylphenidate... Substance-induced psych w/ stimulant intox is predominantly pscyhotic symptoms. Acuteness, lack of previous history, and timeline w/ exams also correlate.

What causes sepsis in E coli infection????

Lipid A of LPS... Lipid A is responsible for the toxic properties of LPS... LPS is a very long, heat-stable molcl arranged into three regions: O antigen, core polysaccharide and lipid A... Induce febrile response in hypothalamus via IL1 O antigen is used to classify them.

Death of 78 year old due to something non cardiac, biopsy heart and see yellowish-brown granules intracytoplasmic... what is it?

Lipid peroxidation... insoluble pigment made of lipid polymers and protein-complexed phospholipids... Lipofuscin is considered wear and tear of aging... Yellow-brown, finely granular perinuclear pigment is the product of free radical injury and lipid peroxidation.. Common in liver and heart of aging or malnourished patients.

What condition exacerbats S3 heart sound?

Listening at end expiration S3 is a sudden limitation of ventricular movement during passive ventricular filling. It can be a normal finding in healthy children and young adults... However, presence after 40 years old is abnormal and suggests Ventricular volume overload. Often heart in aortic/mitral regurgiation or systolic HF. Best heard S3 w/ bell over apex while patient is in left lateral decubitus. Listening at end expiration by decreaseing lung volume and bringing heart closer to chest wall. Amyl Nitrite inhalation would decrease sound because it causes vasodilation and decrease in venous return/BP.

What are the cephalo-sporin resistant organisms?

Listeria monocytogenes, Meth-Res Staph, Enterococci... all have resistant penicillin binding proteins Atypicals (mycoplasm, chlamydia), no cell wall. Listeria avoids phagocytosis and spreads intracellularly. Cell mediated immunity is required to clear ithis infection. Humoral responses don't play a role. Infants get this infection because of weak cell-mediated immunity.

What tissue works a lot harder under chronic glucocorticoid therapy?

Liver... increased gluconeogenesis and glycogenesis.. by upregulating PEP carboxykinase, G6Phosphatase, glycogen synthase. causes lipolysis, altered fat distribution, atrophy adrenals, bone osteoporosis, T cell apoptosis/suppression, atrophy of muscle, thinning stria of skin poor wound healing. Causes catabolism of muscle to provide substrates for liver... Adipose tissue gets central obesity and hypertrophy of the dorsocervical fat pad and increase in appetite/calorie intake.

What should you worry about intubating a Rheumatoid Arthritis patient?

Long standing Rh Arth involves the cervical spine causing joint destruction w/ vertebral misalignment (Subluxation)... The atlantoaxial joint is most often involved as the atlas (C1) has a high degree of mobility relative to the axis (C2 odontoid and body) Chronically this leads to neck pain, stiffness, neurologic findings (sensory loss and muscle weakness)... Endotracheal intubation can acutely worsen the subluxation --> compressing the spinal cord and/or vertebral arteries... Acute spinal cord injury leads to flaccid paralysis w/ decreased/absent reflexes below level due to spinal shock... Eventually becomes spastic in days-weeks.

Panic Attack vs. Pheo

Look at BP, look at HR Esp if young and otherwise healthy, w/ normal EKG think panic disorder... Usually panic attacks peak w/in minutes and somatic presentations are common. Benzos for rapid relief of symptoms and SSRI to take home.

How does aging affect the kidney?

Loss of nephron mass along w/ arteriolosclerosis, focal glomerulosclerosis, tubulointerstitial fibrosis. These processes are symmetric.

How does blasto usually present?

Lung infection or flu-like illness or pneumonia.. Can be disseminated in immunocompromised patients. It is a large yeast w/ a single, broad based bud Coccidioides immitis is spherules (round encapsulated structures containing many endospores) Cryptococcus neoformans is a round yeast w/ variable sizes and narrow based buds. Candida Albicans is small oval yeast w/ narrow based budding Histo is smaller and found intracellular w/in macrophages Rhizopus is a broad, ribbon-like hyphae w/ rare septations

What is subacute cerebellar degeneration?

Lung mass, cerebellar symptoms, 2 week decline... Small cell lung cancer, along w/ breast ovarian and uterine... Anti-YO, anti P/Q, anti-Hu antibodies Patients show worsening dizziness, limb/truncal ataxia, dysarthria, visual disturbances... Paraneoplastic cerebellar degeneration is due to an immune response that cross-reacts w/ purkinje neuron antigens... Antibodies not always detectable.

What is the X inactivation process called?

Lyonization... Heterochromatin has methylated DNA... and deacetylated histones..

Differences between mitral stenosis, restrictive CMOP, Tamponade, dilated cmop on causes of pulm HTN

M stenosis... high PCWP, nl LV endo diastolic and peak systolic pressure Dilated and Restrictive CMOP cause system congestion as well so increase in LVEDP and PCWP. CT leads to equilibration of average intracardiac diastolic pressures... LVEDP and PCWP both elevated.

2 most important factors for osteoclast differentiation....

M-CSF and RANKL... which stimulate the development of mature, multinucleated osteoclasts... Interaction of RANK-L w/ RANK is blocked by protogerin (decoy R).... Bone turnover is regulated by ratio of OPG to RANK-L... Estrogen maintains bone mass by inducing production of OPG by osteoblasts/stromal cells.

What problem predisposes to multiple Neisseria infections?

MAC complex deficiencies end-byproduct of antibody complement fixation. Forms a pore in bacterial cell membrane, leading to electrolyte disturbances, inflow of free water and eventual cell lysis... this meningitis p/w fever (high), chills, altered mentation and petechial skin rash from Neisseria-induced small vessel vasculitis (esp palms/soles) --> septic shock... Tx is IV ceftriaxone for >2 weeks. -if patients produce too much IgA they increase risk of Neisseria infection bc IgA attaches and blocks IgG and IgM that induce complement mediated lysis... IgA doesn't fix complement, it prevents from attaching to mucosal surfaces.

MEN 1 vs MEN 2 genetics

MEN1 codes forMEN1 syndromes... mutliple endocrine neoplasia type 1 w/ pituitary adenomas, primary HPTH, pancreatic neuroendocrine tumors MEN2 codes w/ RET.... Proto-oncogene... >95% of patients w/ medullary thyroid cancer have RET (not necessarily MEN2)... Codes for a membrane bound tyrosine kianse receptor in cell cycle regulation --> constitutive activation. Calcitonin secreting C cells (parafollicular cells) show nests or sheets of polyglonal/spindle shaped cells w/ EC amyloid deposition (full-length calcitonin). Often seen in MEN2s, although majority of cases are sporadic!!! Paraneoplastics w/ calcitonin -> diarrhea/flushing. Calcium is usually normal due to downregulation of calcitonin receptors.

Triad of cold pack, intermittent diplopia, speech problems, and difficulty chewing

MGravis... type 2 HSN. HSN Pneumonitis is type 3 HSN. Processed proteins by Langerhans cells transport to hapten-specific T cells. Continued hapten exposure sensitizes T cells producing inflammatory cytokines.

S aureus, diabetes patient who had bacteremia now has progressively worsening back pain

MRI myelogram is clutch.. Worried about vertebral osteomyelitis. Hematogenous spread to the spine, or direct invasion from neighboring tissue. Heme spread is most common as vertebra is rich and vascular marrow. Increasing age can cause nutrient arteries to develop a corkscrew anatomy, which allows bacteria to more easily penetrate the marrow cavity. *suspect this in new/worsening back pain, fever, and recent endocarditis OR bacteremia *also in new neuro findings along with fever w/ or w/o bck pain. 1) blood cultures 2) MRI of spine Only do CT myelogram if they have metallic implants (not necessarily pacemaker)... CT myelogram okay for spinal stenosis.

Properties of a neuron and how they are affected by MS...

MS takes out myelin... Speed of conduction down an axon depends on 2 constans... Length constant and time constant... vel = length/time Length constant... space constant aka... how far along an axon an electrical impulse can propagate w/o requiring active regeneration by ion channels... Based on relative resistance of conduction along the axons compared w/ resistance across the membrane... Myelin increases length constatn by reducing charge dissipiation across the membrane... THis allows electrical impusle from individual sodium channels to travel farther allowing more activation of distant channels. Demyelination decreases length constant and result in shorter impulse conduction Time constant is time it takes for membrnae potential to respond to a change in membrane permeability (sodium channel activation)... Based on membrane resistance and capacitance... Myelin decreases membrane capacitance (reduces amount of charge stored by the membrane) and increases resistance (reduces charge leakage through membrane) in axon segments b/w nodes. This reduces time constant and allows memrane potential to change faster... Demyelination increases time constant and results in slower changes in membrane voltage. Velocity = decrease length and increase time so much slower. Summation is the additive effects of multiple postsynaptic potentials on a taret neuron's membrane potential. Summation can occur in dendrites, cell body and axon hillcock but not in the axon. Temporal summation is combined effect of sequential impulses from the same neuron over time, whereas spatial is combined effect of simultaneous impulses from several different neurons.

Pathogenesis of Granulomas

Macrophage presents to secretes IL-12 and IL-6 to differentiate T lymphocyte to be Th1 and secrete IFN gamma which activates the MP Th1 makes IL17, IL-2, TNFalpha (w/ the TH-17) MP makes I-1 and TNF-alpha Epithelioid macrophages which make fuse together to form multinucleated giant cells (langerhans giant cells) Caseating = central necrosis is present w/ granular/cheesy appearance... TB, leprosy, syphillis, cat scratch disease (kills both MPs and bacteria) Noncaseating (autoinflammatory conditions)

What component of atherosclerotic plaque provides stimulation for cellular growth?

Macrophages and platelets (after adhesion) and dysfunctional endothelial cells supply PDGF for collagen synthesis and smooth muscle migration and proliferation... Platelets also release TGFbeta to chemotactic for SMCs and induce collagen production NPs and erythrocytes have no role in chronic inflammation

Deviation toward a side, w/ decreased breath sounds and hemithorax opacification

Makes me think of collapsed lung due to bronchial obstruction... Complete collapse is usually due to a main stem bronchus -central lung tumors in chronic smokers can do this.. As the air in the lung gets absorbed into the blood, lung loses volume and alveoli collapse.. Heart and esophagus may also shift. Loss of radiolucent air is the reason for the opacification.

What inhibits FA synthesis in well fed state?

Malonyl CoA... ATP is high and inhibits isocitrate DHD, leading to high citrate in mitochondria... Citrate transferred to cytosol via citrate shuttle and cleaved by ATP citrate lyase to form acetyl CoA... High citrate + insulin --> Acetyl CoA carboxylase upregulation... converts acetyl CoA to malonyl CoA... Normally FA synthesis combines malonyl CoA w/ acetyl CoA to create a 4 carbon molecule Carnitine is the molecule that brings in FA to be broken down and malonyl CoA inhibits carnitine acyltransferase. FA can't get into mitochondria for beta oxidation.

Pulmonary HTN causes

Mean Pulm A pressure (nl 8-20) Pulmonary Cap Wedge Pr (nl 6-12) Can be primary, or secondary to LHF, chronic lung hypoxia, chronic pulmonary thromboembolic disease... Primary is from proliferative vasculopathy of pulmonary arteriolar smooth muscle, in BMPR2 mutation or CT disease or HIV... Endothelin 1 is a potent vasoconstrictor that promotes smooth muscle cell proliferation and is found in high concentrations in patients w/ PAH.. Endothelin R antagonists (bosentan and ambrisentan) inhibit sm m proliferation and alleviate vasoconstriction to improve dyspnea. 3 main path 1) Proenthelin (endothelin-1 to endothelinR inhibited) 2) NO pathway... Nitrates and PDE inhibitors increase cGMP to improve vasodilation/decrease proliferation 3) Arachidonic Acid pathway -prostacyclin analogs increase cGMP and do the same as 2

histologies of CNS tumors

Meningioma = psammoma bodies (syncytial nests which may calcify and appear as round, eosinophilic laminar structures) Adamantinomatous Cranipharyngioma = suprasellar tumors in children as cords/nests of palisading squamous epithlium w/ internal areas of wet keratin Ependymoma = paraventricular tumors (floor of 4th ventricle) and have perivascular rosettes Glioblastoma = cerebral hemispheres and corpus callosum, hypercellular areas of atypical astrocytes bordering regions of necrosis Oligodendrogliomas = white matter of cerebral hemispheres, fried egg appearing tumor (round nuclei w/ cleared halo cytoplasm Schwannomas = can come from VIII CN at cerebellopontine angle. Spindle cells w/ pallisdagin nuclei arranged in V e rocay bodies (eosinophilic cores) Antoni A pattern.

What are the durations and associated symptoms for the most common three types of headache?

Migraine... 4-72 hours w /auras photophobia phonophobia nausea Cluster... 15 min to 90 min... sweating, facial flushing, nasal congestion, lacrimation, pupillary changes Tension... 30 min to 7 days.. muscle tenderness in H/N or shoulders

Inhaled anesthetic what best correlates w/ potency?

Minimal Alveolar Concentration Potency is the minumum concentration in the brain necessary to achieve an adequate level of anesthesia... Partial pressure in brain will eventually equal that in lungs... potency is inversely proportional to MAC... lower MAC more potent drug... MAC increases w/ patient age and depends on body temperature. Blood gas/coefficient gradient is a measurement of solubility of the anesthetic in the body tisues... This has to do w/ onset of action and saturation... High BG coefficient absorbed more by blood and have slower onset of action High AV conc gradient means the tissue is used more by the body tissues and has a slower onset of action. Increased time needed to become saturate. Arterial tension curve depends on solubility of the anesthetic in blood.. .Partial pressur ein blood rises more rapidly w/ less soluble anesthetics, producing a steeper curve.

Kid comes in a few weeks after an upper respiratory infection w/ severe proteinuria.

Minimal Change Disease... >3.5g/day in adults, >50mg/kg/day in kids.. Hypoalbuminemia (<3g), generalized edema, hyperlipidemia... 1. Increased glomerular capillary permeability to plasma proteins -> loss of protein in urine. 2. Large decrease in albumin causes a drop in intravascular oncotic pressure. 3. Fluid shifts in intravascular volume depletion so RAAS is activated. Leads to sodium and water retention. 4. Low intravascular oncotic pressure --> increased lipoprotein production in the liver.

How do opiates work w/ their receptors.

Morphine is an opiate analgesic.. used to treat severe chronic pain in patients w/ cancer. There are 3 main opiate receptor subtypes... mu, delta, kappa... All of these transmembrane receptors are coupled to inhibitor G proteins... Morphine and the other commonly used opiates hit the mu receptor (strongest analgesic effects) In the spine, opiates bind to mu receptors on primary afferent neurons, closing voltage gated calcium channels and reducing calcium influx... decreasing excitator NT release from the presynaptic terminal BUT they also bind to mu receptors on post-snyaptic membrane, which opens K+ channels and leads to membrane hyperpolarization due to potassium eflux.

What markers are expected from SCLC?

Most aggressive type of lung cancer... Rapid local invasion and distant spread. Most have mets at dx... Synthesize hormones or hormone-like substances.. like ADH... Small cell carcinoma is sensitive to chemo/readiation, 5 year survival is low. Small cell show neuroendocrine differentiation. Stain for neuroendocrine markers = neural cell adhesion molecule (NCAM aka CD56), neuron specific enolase, chromogranin, synaptophysin. Some express neurofilaments. Neurosecretory granules also in the cytoplasm. ~expression of EGFR, KRAS< mucin in non-small cell carinomas ~vimentin is found on sarcomas

Different variations of twins and their likelihood

Most common set of twins if M and F is two sperm and two egg -> dichorionic and diamniotic aka dizygotic twins Monozygotic twins arise from fertilization of a single oocyte and develop from 1 zygote... Same sex and identical in appearnce... Usually during the end of the first week giving rise to monochorionic and diamniotic embryos. Early separate (25% not 75%) can have two of each(days 0-4) Late Division (8-12 days) = 1 amniotic and 1 chorionic.. high fetal fatality due to umbilical cord entanglement. After 13 days conjoinedtwins.

Syrinx

Most commonly b/w C8 and T1 levels... Further expansion can produce lower extremity weakness and hyperreflexia by affecting the lateral corticospinal tract, when usually it just atkes out the spinothalamic tract.. Loss of position of vibration if hits dorsal columns... If extreme scoliosis can occur due to paresis of paravertebral muscles.

4 layers of meckels' diverticulum and normal appendix, 3 layers of zenker's and diverticulosis

Mucosa, Submucosa, Muscularis and serosa 2 more widely used, but mucosa, submucosa, serosa

When calculating Reid index, what are you measuring?

Mucous gland distance/ distance from epithelium inside to cartilage (not including cartilage) Normal = 0.4. As chronic bronchitis progresses, total broncihal wall thicknes increases.

Inheritance of spinda bifida?

Multifactorial Closer a relative is to the affected person, more likely to develop the trait, but many things go into the formation. folate deficiency + genetics + neural tube development genes. 1st degree relatives 2-5% of recurrence. Whereas autodom/rec is 50-25% Cleft lip/palate, DM, CAD, HTN all multifactorial

What med is useful for urge incontinence?

Muscarinic antagonists, specifically M3 (oxybutynin).. because they relax the detrussor muscle and decrease production of IP3 and release of calcium, leading to smooth muscle relaxation. Decreased bladder contractions means increased bladder cpaacity and decreased sense of urgency. Start at a low dose in elderly and titrate up (anti cholinergic)

What is the breakdown of cholinergic toxicity effects?

Muscarinics = DUMBBELS Diarrhea/Diaphoresis Urination Miosis Bronchospasm Bradycardia/rrhea Emesis Lacrimation Salivation/Sweating Nicotinic Effects = M weakness, paralysis, fasciculations ^not resolved w/ atropine. Organophosphate toxicity, a cholinesterase inhibitor.. Also can get seizures or coma if persists. Atropine is a competitive inhibitor of Ach at muscarinic receptors. Pralidoxime is needed (a cholinesterase reactivating agent, allowing for degradation of excess ACh and treats both Nic and Musc effects but won't penetrate CNS)

ADPKD and kidney diseases

Mutations in PKD1 or PKD2 tubular cell proliferation and fluid secretion... cysts at any point of nephron but <5% of nephrons affected... Microscopic cysts at birth that enlarge over decades... When larger can compress parenchya Frequently silent, 50% undiagnosed. Flank pain, hematuria, and HTN... Renal Failure over 10-20years w/ end stage occuring at age 70... Extrarenal manifestations = liver cysts and cerebral aneurysms (saccular) ~ ARPKD presents at birth or first year w/ B/L flank masses (cysts formed by dilated distal tubules and collecting ducts... Enlarged kidneys at birth ~Multicystic Kidney Dysplasia... presence of multiple cysts of varying size in kidney and absence of normal pelvocaliceal system... Ureteral or Ureteropelvic atresia, w/ affected kidney nonfunctional.. U/S is diagnostic ~Horshoe Kidney is fusion of kidneys at lower poles... isthmus of renal tissue is anterior to great vessels and detected U/S ~ARPKD/ BL Renal Agenesis can both cauase Potter's w/ oligohydramnios... Potters = pulmonary hypoplasia, flattened nose, recessed chin, low set ears, limb defects, CV abnormalities...

Given x/y had MI then arrhythmia taking beta blocker and g/v had MI then arrhythmia not taking beta blocker what is odds ratio? SLOW DOWN

NOT x/y over g/v... instead make table Beta blocker -> major arrhythmia x and no arrhythmia y-x No beta blocker -> g and no arrhythmia v-g then a/b / c/d = odds ratio.... a b top row c d bottom row OR SHORTCUT disease among exposed/disease among not exposed for 1 divided by same equation for two

CD8 mediated cell death

Necrosis (injury) and apoptosis (host organism in response to cell damage, aging, embryogenesis, lymphocyte development). Tumor cells die by apoptosis. 1. Initiation... intrinsic, mitochondria-mediated pathway or the extrinsic, receptor-initiated pathway... Cells damaged by UV light, heat, hypoxia, toxins, radiation --> intrinsic apoptosis signals = phosphatidylserine OR thrombospondin... on their PMs... Extrinsic apoptosis is mediated by TNF when boudn to TNFR1 or FasL when bound to Fas R 2. Control... intrinsic mediated by bcl-2 proteins.. Bak/Bax/Bim are pro-apoptotic while Bcl-x and Bcl-2 anti-apoptotic. Tip the balance b/w these two forces results in changes of inner mitochondrial membrane. Mitochondrial permeability transition and release of cytochrome c and other pro-apoptotic proteins into the cytoplasm. These activate caspases. In extrinsic response, binding of death ligand and death receptor allows for pro-caspases molcls to be brought in close proximity. 3. Destruction... both intrinsic and extrinsic converge here --> caspase activation. These are proteolytic enzymes. Contain cysteine and cleave aspartic acid residues (Cysteine-Aspartic-Acid-Proteases)... there are 11 total. Initiator caspases activate effect caspases.

What is lead time bias?

New screening criteria catches lung cancers 3 months before normal screening, but mortality doesn't change. Lead time bias should always be considered when doing screening tests. This is an apparent increase in survival time among patients undergoing screening when they actually have an unchanged prognosis. Disease was detected earlier, but overall length of time rom disease onset to death is the same. Need to follow patients longer than expected survival time and then to estimate and compare mortality rates among patients who have undergone additional screening. ~Length-Time bias is when subjects w/ a rapidly progressive form of a disease are less likely to be detected by screening compared to those w/ slowly progressing disease. The bias tends to overstate the beneficial effects of screening. ~Measurement bias and observer bias refer to misclassification of outcome/and or exposure (labeling disease as non-diseased) related to poor study design ~Rare disease assumption refers to the practice of approximating the odds ratio and relative risk when conducting a case-control study for rare diseases.

Which protein is inhibited by ezetimibe?

Niemann-Pick C1-like 1 transporter protein NPC1L1... transports dietary cholesterol from GI lumen into intestinal enterocytes. Total amount of dietary cholesterol reaching liver decreases, lowering intrahepatocyte cholesterol levels. To compensate liver increases LDLR expression to draw cholesterol out of circulation.

Presentation of Staphy Scaled Skin

Nikolsky's positive, exofliatin exotoxin... Causes epidermal necrolysis, fever, pain and diffuse skin rash... SSSS is the most common in infants/ young children and it is frequently not fatal unless lesions become secondarily infected. Exfoliative toxins show specificity in blistering certain components of skin and act as proteases to clleave desmoglein. Bullous impetigo is a more localized form of SSSS involving another exfoliatve toxin.

Pos and Neg factors of osteoporosis

Nonmodifiable = age, female, white/hispanic/asian, personal fx hx of fx Modifiable.. decrased exercise, low body weight, poor calcium/vitD, excessive alcohol/tobacco, premature menopause, glucocorticoids

Why does HbS sickle?

Nonpolar Hydrophobic residues in interior and charged on surface normally... In sickle, this is flipped... Forms a hydrophobic pocket on beta globin surface that interacts w/ nonpolar residue on another hemoglobin. Leads to polymerization and erythrocyte sickling... Problem not seen w/ charged HbC.

What are the LV parameters for Diastolic HF?

Normal LV ejection fraction >50%, and normal end-diastolic volume... but there are increased LV filling pressures... Basically conditions that decrease LV compliance = ischemia leading to impaired relaxation, wall stiffness from restrictive CMOP, long standing HTN leading to LV hypertrophy. Much higher end diastolic pressure 0determined by blood volume in LV cavity and compliance of LV. Reduced compliance --> increased LV end-diastolic pressures. Decompensation occurs when increased LV end diastolic pressure causes pulmonary edema/dyspnea

What is the normal progression of squamous cells in a strat squamous arrangement?

Normal organized progression from tall cells in the basal layer to flattened cells on the surface... Individual cells are often pleomorphic (differing size and shape) and also show abnormalities such as as abudnant mitoses or hyperchromatic nuclei.

How do anovulatory cycles present?

Normal periods, 20-40 years old, last 24-35 days w/ flow ranging from 4-6 days... Adolescents and almost menopausers at risk for anovulatory cycles... In the absence of ovulation, ovarian follicle does not degenerate and become a corpus luteum No progesterone means Estrogen remains high, causing endometrium to proliferate. Proliferative becomes disorganized and fragile w/ unstable venouscapillaries resulting in irregular periods of stromal breakdown and bleeding, along w/ more heavy periods.

What is the cause of acne in their 20s?

Normally acne is associated w/ pubertal androgen surge... If someone is an aspiring athlete, must consider the possibility of anabolic steroid use. aka methyltestosterone.. . 1) follicular epidermal hyperproliferation 2) excessive sebum 3) inflammation 4) P acnes... After conversion to DHT, androgens promote 1 and 2. EGFR inhibitors and lithium both cause this reaciton too. ~excessive perspiration exacerbates but does not cause acne

Giving low dose epi and a drug... the HR goes down and the SVR goes up....

Normally at low doses, Epi hits beta1=beta2> alpha... but if only getting alpha effects, then betas must be blocked by the drug... non-selectively so propranolol

How can women with Turner's have a baby?

Normally impossible due to ovarian failure (mostly)... however, supplemental estrogen/progesterone can prepare endometrium well In vitro vertilization with a donated ovum can also provide something for implantation. Success rates are around 60%. Must do a thorough renal, cardiac, thyroid examination before.

What is the precursor lesion to SCC in the lung, what condition is it similar to?

Normally would have pseudostrat ciliated columnar but get squamous metaplasia, esp from smoking... Similar to Barrett's This metaplasia means decreaesd ability to clear lungs, so increased risk of infections.. This whole thing is reversible on discontinuation of smoking but may progress to dysplasia/ SCC

OCD dx

Obsessions = recurrent, intrusive, anxiety provoking thoughts/urges/images Compulsions = response to obsesssions w/ repeated behaviors/mental acts, behaviors not connected w/ preventing feared event. TIme consujming > 1hour a day w/ significant distress/impairment. Tx w/ SSRI/CBT

How does medulloblastoma present?

Obstructive hydrocephalus symptoms... Posterior fossa.

Hemorrhage and the association by lobe

Occipital = homonymous hemianopsia Parietal = contralateral sensory loss Frontal = contralateral hemiparesis

What happens to the eyes during uncal herniation?

Oculomotor nerve palsy w/ fixed dilated pupil. (PS on outside of CN3) Expanded space occupying lesions of the temporal lobe often cause increased ICP and transtentorial herniation of the uncus. Will also have vesitbular-ocular reflexes lost, and decorticate then decerebrate posturing. Causes 1) ipsi CN3 2) ipsi PCA compression (contraL homonymous hemi) 3) compression of contraL cerebral peduncle so ipsi lateral hemiparesis 4) Brainstem hemorrhages for pons/medulla can cause autonomic problems

Which opioid can precipitate withdrawal??

Opioids bind G PCRs mimicking endogenous opioid peptides, long term activation on nociception-trasnmitting neruons is associated w/ increased pain sensitivity due to -increased turnover of inhibitor opioid R and decoupling of R from seocndary messengers -upregulation of NMDAR increasing dose requirement to provide same level of pain relief and pain from benign stimuli ( opioid-induced hyperalgesia).. opioid withdrawal can occur w/in 24-48 hours of acute cessation of opioid tolerant patients --> n/v/mylagias/dilated pupils/tachycardia Buprenorphine is a partial opioid agonist that has low intrinsic activity for opioid mu receptors... However, it bidns w/ high affinity and can prevent binding of toher meds. Acts as an antagonist in the rpesence of full opioid agonists... Can lead to withdrawal

First line treatment for chronic cancer pain??

Opioids... Tolerance to most side effects occurs. However, tolerance to miosis and constipation does not readily occur... Constipation is the most persistent and common side effect... Decreased secretions and gastric motility. Normal bowel function rarely resumes. Patients who require prolonged opioids should recieve prophylactic bowel regimen (fluids, fiber, laxatives) ~~Opioids produce mood, euphoria, pleasure in dopaminergic pathways of nucleus accumbens... Tolerance is rapid ~~Respiratory depression is the most serious, yet rare side effect... Depresses by reducing responsiveness of brainstem respiratory centers to increased levels of CO2. If you take opioids regularly this side effect is unlikely

Cat Scratch Disease

Oral cavity of cates and transferred via scratches/bites... Typically a primary inoculation --> vesicular -> erythematous to papular --> tender regional LAD (single lymph node)... Axillary LAD is super common Can also cause bacillary angiomatosis in immunocompromised patients... Red purple papular skin lesions w/ vascular proliferations... BA fatal if untreated.

What is the path of the brachial plexus?

Originates from C5-T1 and combine into 3 trunks. These pass b/w middle and anterior scalene muscles (scalene triangle) in the posterior neck. Interscalene nerve block is a regional anesthesia technique for procedures of shoulder/upper arm... Anesthetic into scalene triangle and affects brachial plexus roots/trunks... Can cause transient ipsilateral diaphragmatic paralysis (anesthetizing phrenic nerve) Dont do lung block in patients w/ chronic lung disease

Excessive facial hair growth treated topically with....

Ornithine decarboxylase is involved in DNA stabilization/repair... Inhibition --> decreased cell growth and increased apoptosis Eflornithine is a topical inhibitor to treat this.

What stain makes fat black for PE of fat?

Osmium tetroxide... respiratory distress, non focal neuro symptoms and TCP chest lesions... after long bone fractures... 1) release of mediators from platelets which adhere to and coat fat emboli resulting in TCP and 2) systemic activation of LPLipase and intravascular release of toxic levels of oleic acid Microvascular occlusion of cerebral white matter, brain stema nd spinal cord --> neuro manifestations

Breakdown the C diff toxins

P/w watery diarrhea, fulminant colitis aka toxic megacolon as well present in 2-3% of normal people, 70% of healthy infants... Clinda, FQs, penicillins, and cephalosporins can all induce it. Toxin A (enterotoxin) and Toxin B (cytotoxin)... Both inactivate Rho-regulatory proteins involved in signal transduction and actin cytoskeleton structure maintenance. Therefore, they disrupt intracellular tight junctions leading to cell rounding/retraction and paracellular intestinal fluid secretion.

Common drugs for acute intoxication and their features

PCP = phencyclidine = Hallucinogen = violent, amnesia, nystagmus (horiz or vert), ataxia LSD = hallucinogen = visual hallucinations, euphoria, panic, tachycardia/HTN = Lysergic acid diethylamide Cocaine = stimulant = cx px, seizures, mydriasis, agitation, tachy/HTN Methamphetamine = stimulant = violent, psychosis, diaphoresis, tachy/HTN, choreiform mvmts, tooth decay Marijauna = psychoactive = munchies, euphroia, dysphoria/panic, slow reflexes/time, dry mouth, CONJUNCTIVAL INJECTION Heroin = opioid = euphoria, depressed mental status, miosis, respiratory depression, constipation PCP is an NMDR antagonist leading to excessive release of excitatory NTs... inhibits reuptake of Norepi, dopamine, serotonin... Moderate amounts --> dissociative symptoms of detachment, withdrawal, higher leads to violence.

N-methyl-D-aspartate R antagonism... what drug and what's the clinical scenario?

PCP.. phencyclidine... disoriented, belligerent, jerky mvmts, visual hallucinations, agitation, sedation, HTN, tachycardic w/ vertical nystagmus primarily NMDAR antag, also inhibits reuptake of Norepi, Dopamine, Serotonin and sigma-opioid effects. Fatalities from related trauma. causes both horizontal and vertical nystagmus. Poor judgment, memory loss. NMDAR agonists... glutamate, aspartate, D-cycloserine.

Presentation of PCV versus Primary Myelofibrosis

PCV = pruritis, erythromelagia, splenomegaly, thrombosis, erythrocytosis Primary Myelofibrosis = severe fatigue, splenomegaly, hepatomegaly, anemia and BM fibrosis JAK2 works through STAT pathway... Both often have JAK2 resulting in constitutive action of tyrosine phosphorylation pathway... Ruxolitinib is a JAK2 inhibitor can be approved for treatment of primary myelofibrosis Janus kinase is the kinase associated w/ a tyrosine non-kinase receptor that still dimerizes.

What advanced monoclonal antibody treatment can mess up melanoma?

PD-1... programmed death receptor 1 expressed on surface of activated T cells... It binds its ligand, PD-L1 downregulating the immune response against tumor cells by inhibiting cytotoxic T cells... Many types of cancer cells evade immune system by expressing PDL1... Antibodies can prevent this binding and block T cell inhibition, restoring cytotoxic response and promoting apoptosis.

What 4 enzymes use thiamine?

PDH, alpha ketoglutarate DHD, branched chain alpha ketoacid DHD, transketolase of PPP. Diagnose w/ low erythrocyte transketolase activity but increased w/ addition of thiamine. = Wernicke's

What is needed for OAA to become PEP?

PEP carboxykianse... and GTP as cofactor... creates CO2.

What two pathologies cause the cryptogenic stroke found on bubble study?

PFO and ASD... PFO is failure of septum primum and secundum to fuse FOvale is used in fetal to shunt blood from the right side of heart to the left easily. 25% of adults have this patent... although birth -> breathing -> decr PVR usually pushes this whole closed and fibroes. Valsalva manuever could push a clot through!

What pathway has Akt in cancer?

PI3K/Akt/mTOR pathway PIP2 pathway w/ Tyrosine kinase receptor bound by growth factor leads to Akt activation (protein kinase B)... this is a serine/threonine specific protein kinase... Akt activates mtOR (mammalian target of rapamycin) which translocates to the nucleus to induce genes involved in cell survival, anti apoptosis, and angioegensis... mTOR is inhibited by PTEN (phosphatase and tensin homolog), tumor suppressor protein from PIP3. cancer increases mTOR decreases PTEN.

What parameter changes w/ number of participants/prevalence?

PPV and NPV PPV = true positives/(true positives + false positives) Populations w/ lower prevalence will have lower true positives and higher numbers of false positives so PPV decreases As prevalence increases PPV increases ~Positive and Negative likelihood raitios are how a particular positive or negative test result influences pretest probability of having a disease... Likelihood ratios >1 indicate that the test result is associated w/ the presence of disease; <1 mean test result is associated w/ absence of the disease... Based on sens and specificity

HIV patients, CD4 <200 and G6PD

PPx for Pneumocystis jiroveci pneumonia... TMP-SMX is DOC, but dapsone given if TMP-sMX allergy... Dapsone side effects = fever, rash, methemoglobinemia... Dapsone also puts oxidative stress on body, so G6PD should be checked before administration to prevent hemolytic anemia... G6PD factors 1. Infections 2. Drugs = dapsone, anti-malarials, sulfonamide antibiotics 3. DKA 4. Favism (fava beans) fatigue, jaundice, dark urine, high high reticulocyte count w/ red cell fragments, microspherocytes, bite cells.

Drug induced lupus from isoniazid use, what is the cause?

PREDILECTION FOR slow acetylators at the liver... Anti histone antibody present all actually drug induced lupuses are due to this fact. Drug lupus lacks cutaneous, neuro and renal complications Procainamide, Hydralazine, Isoniazid are metabolizide via phase 2 acetylation int he liver... Hepatic expression fo N-acetyltransferase is genetically dtermined... Patients slow predisposed Also predisposed to drug induced peripheral neuropathy

What do PS and Symp secrete at nerve terminals and what are the exceptions?

PS has Ach at Nicotinic then Ach at muscarinic Somatic has Ach at nicotinic Symp has ACH at nicotinic then NE at alpha/beta mostly Sometimes Ach at nicotinic then Ach at eccrine sweat glands OR just straight Ach at nicotinic of adrenal medulla

When is adenosine ideal?

PSVTs p/w suddenly comes on and focus of automaticity lies above ventricles (aorta or AV node)... palipitations, heart racing, BP normal but pulse super high.... drug leads to flushing, chest burning (from bronchospasm), and SOB, hypotension, high grade AV block.

How does Buerger's Disease work?

Patient will have distal lower extremity vascular insufficiency... Heavy smokers will develop immune HSN to tobacco. Most likely diagnosis is Buerger's Disease... a Vasculitis of medium and small-sized arteries... Mostly tibial/radial. Acute and chronic inflammation of the arterial walls, often w/ thrombosis of the lumen which undergoes recanalization.. The segmental thrombosing vasculitis often extends into contiguous veins and nerves (rare in other vasculitis).. Can eventually encase all three (arteries, veins and nerves in fibrous tissue) Don't know if it is due to HSN to tobacco or from endothelial cell toxicity from tobacco. Mostly seen in heavy smokers < 35 years old. More common in Israel, Japan, India than US/Eruope May p/w calf, foot, hand intermittent claudication, maybe superficial nodular phlebitis and cold sensitivity (Raynaud's). If severe distal pain, even at rest, nerves most likely involved... Eventually leads to gangrene of toes, feet, fingers. Tx is smoking cessation.

Problems w/ MGravis Treatment

Patients can get nausea, abdominal cramping, sweating, vomiting, diarrhea.. Selective Muscarinic Antagonists good to treat this muscarinic overstimulation are M3 blockers = Glycopyrrolate, Hyoscyamine, Propantheline...

Glutathione reductase activity presentation Pyruvate Kinase deficiency presentation Transketolase deficiency

Patients w/ riboflavin (B2) deficiency becuase its needed for FAD and NADPH... p/w normocytic anemia, cheilosis, stomatitis, glossitis congenital hemolytic anemia, impaired glycolytic ATP generation Transketolase is the enzyme that utilizes B1. Decreased in thiamine deficiency aka Wernicke-Korsakoff and beriberi

Who does primary spontaneous pneumothorax affect?

Patients w/o preexisting pulmonary disease. Occurs when a large change in alveolar or intrapleural pressure results in a break in the visceral pleura and subsequent trapping of air between the parietal and visceral spaces. Superficial alveoli in the apices experience greater pressure changes (due to weight of lungs pulling down), prediposing to blebs. They rupture spontaneously, esp in tall thin males <20 years old. Most important risk factor is smoking. Taller people also have more negative pressure in their lung apices. Compensatory hyperinflation = Normal lung parenchyma expands due to loss of adjacent lung volume. (segmental/lobar collapse OR removal surgery). collapse of adjacent lung tissue due to extrinsic compression by intrapleural air and does not result in parenchymal epxansion. Obstructive Hyperinflation = lung segment expands due to partial obstruction of the airway supplying it. (bronchogenic carcinoma)... On inspiration the airway expands, which allows mvmt of air into the segment... As the airway closes on expiration, air is trapped behind the obstruction.

Oppositional defiant disorder

Pattern of angry/irritable mood, argumentative/defiant behavior, or vindictiveness for >= 6 months -argues w/ adults, defies authority figures, refuses to follow rules -deliberately annoys others -blames others for their own mistakes or misbehavior -easily annoyed, angered, resentful, vindictive -not due to another mental disorder ODD (home and school usually).. Must be excessive compared to age-appropriate norms... ~Conduct Disorder.. more severe and aggressive... Physical aggression and cruelty towards people/animals, destruction of property or stealing/deceit seen in conduct disorder. ODD may precede conduct disorder and increases risk of adult antisocial behavior, impulse control, sustance abuse, anxiety, depression ~Antisocial = disregard and violation of rights of others and is not for peolple <18 years old...

Lung cancer curve of mortality

Peaks 20-50 years after the peak of smoking 1955 - so 1980s peaked. Started to decrease after 2000 to a decline in tobacco use. Pancreatic cancer is #4 and follows breast cancer trends. Breast cancer is the most common non-skin cancer. Food refrigeration and food preservation and better sanitation have led to decreases in stomach cancer rates. Colon mortality decreased from surgical technique and chemo adjuvant.

Common antibiotic resistance mechanisms....

Pencillins = beta-lactamase, ESBL, mutated PBP, mutated porin protein Vanc = mutated peptidoglycan cell wall, impaired influx/efflux Quinolones = mutated DNA gyrase, impaired influx/efflux AGs = AG-modifying enzymes, mutated ribosomal subunit protein, mutated porin protein Tetras = impaired influx/efflus, inactivated enzyme Rifamycins = mutated RNA polymerase extended spectrum beta lactamase organisms need carbapemes. This gene is encoded on a plasmid. Can inactivate penicillins, cephalosporins, monobactams (aztreonam)

How to get out a baby quick who is decelling heart rate during delivery

Perineal body incision at posterior vaginal wall... Tendinous point of the perineum separates urogenital and anal triangles... This is an episiotomy to enlarge the vaginal outlet to facilitate delivery and reduce the risk of severe perineal lacerations... Midline episiotomy is a vertical incision from the posterior vaginal opening to the perineal body.... It transects vaginal lining and submucosal tissue but not the external anal sphincter or rectal mucosa. Improper repair --> pelvic organ prolapse or dyspareunia.

Why does longterm therapy on levo/carbidopa cause on-off period?

Periodic fluctuations in motor function can happen w/ reduced mobility for `4 hours... As PD progresses, therapeutic window becomes more narrow possibly due to natural/levodopa induced nigrostriatal degeneration... Small chanes in drug levels can result in motor fluctuations --> dyskinesias in mild elevations and reductions to bradykinesia... Medication and dosing are unpredictable of motor fluctuations later in disease.

Dissociative Disorders

Persistent, or recurrent experiences of 1/both = depersonalization (feelings of detachment from or outside of one's self) OR derealization (experiencing surroundings as unreal)... There is intact reality testing (not a psych disorder) ^Depersonalization and Derealization Disorder Inability to recall important personal info, usually of a traumatic/stressful nature -not explained by another disorder -gaps in autobiographical memory ^Dissociative Amnesia Marked discontinuity in identity and loss of personal agency w/ fragmentation into >= 2 distinct personality states -associated w/ severe trauma/abuse ^Dissociative Identity Disorder

Borderline Personality Disorder

Pervasive pattern of unstable relationships, self-image and affects and marked impulsivity w/ >5 of the following = -frantic efforts to avoid abandonment -unstable/intense interpersonal relationships -markedly/persistently unstable self-image -impulsivity in >=2 areas that are self-damaging -recurrent suicidal behaviors/threats/self mutilation -affective instability (mood reactivity) -chronic feelings of emptiness -inappropriate & intense anger -transient stress-related paranoida/dissociation 20% of psych inpatients

How does diphtheria get its toxin production?

Phage (tox gene)... this is lysogenization (process)

Pig infected by human and bird flu, they mix, create new flu that can attack either but can't propagate that feature to the next generation

Phenotype mixing!! no change in underlying viral genomes, so progeny will revert. ~Interference occurs when one virus inhibits replication/release of a second virus infecting the same cell... ~Reassortment would be genome mixing w/ 2 segmented viruses progeny would carry changes ~Recombination (exchange of genes b/w 2 chromosomes (dsDNA) by crossing over, progeny would keep ~Transformation is incorporation of viral genome into host cell

Guy comes in with repeated use of consistent decongestant and now his nose has punctate hemorrhages... stop using becuase the alpha adrenergic agonist could be causing tachyphylaxis.

Phenylephrine, XYlometazoline, Oxymetazoline for tx allergic rhinitis and common cold associated congestion. Rapidly decline in effect after a few days = tachyphylaxis. It occurs because of decreased production of endogenous norepi from the nerve terminals due to a negative feedback mechanism. Resulting in relative vasodilation and edema/congestion. This exacerbates nasal symptoms. Rebound rhinorrhea (rhinitis medicamentosa) use of topical decongestants for >= 3 days. Also is nitroglycerine has this phenomenon. The decrease in effect is explained by diminished release of NO from the target cells. Drug intervals of 8-10 hours should be maintained during use of nitros to prevent tachyphylaxis

Lung cancer nerve compression.

Phrenic nerve is C3-C5 and descends through neck and thorax to innervate the ipsilateral hemidiaphragm... Phrenic nerve irritation can cause dyspnea, hiccups, and referred pain tot he shoulder... (supraclavicular nerve C3/C4) Phrenic nerve palsyis associated w/ respiratory distress, dminished breath sounds and elevation of affected hemidiaphragm. (upward mvmt of affected diphragm is seen on inspiration w/ fluoroscopy) Horner's can happen from lung tumor SVC syndrome can happen Recurrent laryngeal nerve --> hoarseness Dysphagia from compressing esophagus Pleural effusions

Frontotemporal Dementia vs. Alzheimer's

Picks... 50-60s, frontal/temporal focus, initial neuronal loss in frontotemporal lobes and pick bodies present, causes personality/behavioral changes (apathy/socially inappropriate behavior) also alters speech patterns and causes repetitive phrases, 20-40% auto dominant Alzeimer's... mild-moderate brain atrophy, 60-70s, parietal/temporal loss of neurons first,a long w/ neurofibrillary tangles and amyloid plaques.. Impairs recent memory.. increased w/ Chromosome 21 APP gene, APOE4, presenillin 1 and presenillin2

What is the name of fungus causing hyper and hypopigmented skin lesions

Pityriasis versicolor... hypopigmented and hyperpigmented or erythematous macules or patches on the upper body... Caused by malassezia species yeasts and the infection is confined to stratum corneum of the skin... Common in hot/humid climates and due to tanning of adjacent skinmostly in healthy individuals w/ no underlying immunologic deficiencies. Dx w/ KOH showing spaghetti and meaballs. Hyphae have short, cigar-butt appearance. ~Intertrigo is a well-defined erythematous plaques w/ satellite vesicles or pustules in warm moist skin areas (axillae, groin, skin folds)... Candida species.

Ristocetin test for vWF

Platelets don't aggregate in response to risteocetin... When normal plasma added to soln of patients platelets and ristocetin, appropriate platelet aggregation occurs. vWF binds Gp1bR on platelet membrane adn mediates platelet aggregation and adhesion to SEC... vWF also is a carrier for factor 8 and prolongs half life Ristocetin activates GP1b R on platelets and makes them available for vWF binding. When vWF decreased, poor aggregation. Normal plasma contains vWF Will also present w/ prolonged bleeding due to factor 8 deficiency.. PTT will be prolonged or normal depending on extent. OCPs first line for menorrhagia due to vWF... Also treat w/ desmopressin ~Bernard-Soulier... GP1b def... TCP, enlarged platelets and mucocutaneous bleeding... Platelet aggregation w/ ristocetin will be abnormal... But vWF levels normal so addition of normal plasma will still mean abnormal test ~Glanzmann-Thrombasthenia... GP2b/3a def... mucocutaneous bleeding, platelet aggregation in response to ristocetin is nromal ~Hageman Def... Factor XII.. makes marked PTT prolongation w/o bleeding diathesis.

Visceral Pleura vs Parietal pleura in pleuritic chest pain

Pleuritic cx px is sharp, localized, severe pain exacerbated by coughing, breathing, changing position. Visceral pleura = covers all surfaces of the lung, including pulmonary fissures.. no pain fibers here Parietal pleura... covers outer boundary of pleural space and subdivided 1) Costal Pleura = thoracic wall (ribs, sternum, intercosal spaces, costal cartilages 2) Mediastinal Pleura = mediastinum 3)Diaphragmatic = covers surface of diaphragm 4) Cervical = extens w/ apices of lung into the neck Diaphragmatic and Mediastinal both have phrenic nerve. The rest of parietal pleura has innervation of pain via intercostal nerves and felt closer to source of pain.

Difference b/w Pneumococcal polysaccharide vac and Conjugate vacc

Pneujmo polysacc is 23 serotypes, T cell independent response, driven by B cell activation. Moderate antibody response Pneumo conjugate has 13 serotypes, involves attachment to inactivated diphtheriae toxin, allows conjugation to be displayed to T cells and have B lymphocyte activation. Higher antibody titers and memory cells.

Atopic Dermatitis: Poison Ivy

Poison Ivy Dermatitis... poison oak/sumac/ivy all make urushiol, a hapten... Get highly pruritic, erythematous rash w/ papules/vesicles/bullae. Rash most frequently forms as linear streaks as the patient walks. It's delayed type 4 HSN.. 1)sensitization... creates hapten-specific T cells takes 10-14 days. Cutaneous dendritic cells take up haptens and express them on MHC1/2 as hapten-conjugated peptides. These DCs travel to draining lymph nodes and interact w/ hapten sens CD4/CD8... causes activation/clonal expansion 2) elicitation phase... w/in 2-3 days of re-exposure --> hapten is taken up by skin and causes hapten-sensitized T cells in the dermis/epidermis to reac.

Difference b/w IM and oral vaccine for polio

Polio oral (live attenuated) increases duodenal IgA secreted for mucosal immunity... Peyers patches stimulate the response. They get plasma cells that secrete IgA dimers linked by a J chain... These IgA dimers bind immunoglobulin receptor (pIgR) on basolateral surface of intestinal epithelial cells and undergo transcytosis. As the IgA dimer is released into the intestinal lumen, a portion is still attached to the antibody (secretory component). Also live attenuated stronger immune response than killed Sabin = live attenuated oral

What is the major virulence factor of H flu?

Polyribosylribitol phosphate this is the polysaccharide capsule, made of this polymer. PRP capsule protects form phagocytosis and complement-mediated lysis by binding factor H, a circulating regulator protein that normally prevents complement deposition on host cells. HiB vaccine is composed of PRP conjugated to a protein toxoid. Trehalose Dimycolate is a cell wall component and major virulence factor of TB, protects it from being killed by MPs and stimulates granuloma formation.

Palpable spleen, esophageal varices and NO alcohol use/cirrhosis

Portal Vein Thrombosis... If hepatic vein thrombosis, would cause damage to liver... No ascites because no sinusoidal hypertension.

How to dissect urethral injuries

Posterior and Anterior Urethra Anterior is bulbous + penile segments outside of body/just above testicles and posterior segment is membranous segment and prostatic segment. *Membranous segment is most susceptible to injury because it is relatively unsupported. ... This injury esp if a pelvic injury occurs at the bulbomembranous junction. *Bulbous segment is injured in scenarios of perineum being struck forcefully.. straddle injury like falling on a crossbar or the top of a fence *Urethral segment injured in penetrating trauma or instrumentation.

Which drugs inhibit peripheral conversion of Thyroid hormone??

Propylthiouracil (PTU) and Beta Blockers and Ipodate (contrast agent)

What histology is associated w/ GBMultiforme?

Pseudopallisading necrosis w/ capillaries in periphery

B/L skin lesions over elbows w/ thin stratum granulosum and prominent parakeratotic stratum corneum w/ occacional foci of NP accumulation.

Psoriasis

RF for suicide

Psych disorders, hopelessness, never married/divroced/separated, living alone, elderly white man, unemployed, physical illness, Fx Hx, family discord, access to firearms, substance abuse/impulsivity Protective = social support/family connected, pregnancy, kparenthood, religion Access to firearms --> 3 times the risk of suicide completion w/ higher fatality rate.

Causes of ED

Psychogenic stressors, performance anxiety/depression, medications, vascular/neuro impairment, GU trauma (prostatectomy) Esp if it is an acute problem overnight. usually psychogenic. If physiologic, then intermittent before then became persistent. If psychogenic, will wake up from REM sleep w/ erections.

How does prostate cancer treatment affect testosterone and DHT levels?

Pt w/ nocturnal back pain, spinal tenderness, enlarged prostate... eh... Most are androgen dependent. Androgen deprivation therapy by surgical orchiectomy OR pharm suppression of testosterone via Leuprolide (GnRH) analog are both useful... Pulsatile GnRH causes a rise in LH/testosterone... However, continuous --> initial rise then a huge dip. Suppresses pituitary LH release and reduced T production at leydig cells...

How does C tetani take action?

Puncture wound, colonizes the site, then sends tetanospasmin retrograde axonal to CNS Here it cleaves SNARE protein which inhibits exocytosis of GABA and Glycine P/W muscle spasms, opisthotonus, sardonicus smile, lockjaw/trismus. Patients are irritable and develop smas to minor stimuli like loud noises Botulism is a flaccid paralysis

What is a rare form of marrow failure w/ severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis?

Pure Red Cell Aplasia (PRCA).. Inhibition of erythroid precursors and progenitors by IgG autoantibodies or cytotoxic T lymphocytes... Often associated w/ thymomas and lymphocytic leukemias. When a thymoma is present, removal can cure PRCA... Thus, all patients w/ PRCA should undergo a chest CT scan. Can also result from Parvo B19 virus... Attacks and destroys pro-erythroblasts... Recent parvo infection can be confirmed via the detection fo anti-B19 IgM antibodies in the serum.

What is the treatment for toxoplasma gondii?

Pyrimethamine AND sulfadiazine AND Leucovorin (folinic acid) if allergic to sulfas, then Pyrimethamine AND Clindamycin AND Leucovorin = Leucovorin prevents BM suppression and GI inflammation Toxo is an obligate intracellular protozoan worldwide! Cat is the definitive host, w/ humans being infected after ingesting food/water contaminated w/ cat feces (has oocysts) or undercooked meat (pseudocysts) Immunocompromised individuals --> encephalitis w/ multiple necrotizing brain lesions p/w fever, headache, altered mental status, and FNDs... Usually multiple ring enhancing lesions w/ edema.

What is biotin used for?

Pyruvate Carboxylase in GNG (pyr to OAA) Acetyl CoA Carboxylase (Acetyl CoA to malonyl CoA) FA Synthesis Propionyl CoA Carboxylase (Prop CoA to methylmalonic CoA) FA Oxidation poor diet, excessive raw egg white consumption (high levels of biotin-binding avidin in egg whites) and congenital disorders. Mental status changes, myalgias, anorexia, macular dermatitis/derm changes. Can also get a metabolic acidosis ~B1,B2,B3,B5 all necessary for pyruvate dehydrogenase -B6 cofactor for alanine transaminase

Meningococcal vaccine...

Quadrivalent = capsule against A,C,Y,W fused to diphtheroid toxin to allow MHC/APC response. T cells Serogroup B vaccine... Capsular polysaccharides can't be usedalone because of molecular mimicry. New recombinant form for high risk populations now.

How would an optic tract lesion cause an RAPD?

RAPD in pupil contralateral to the tract lesion as the nasal portion of the retina contributes more input to the pretectal nucleus than temporal portion of the retina.

Pressure ranges of different aspects of the heart

RAtrium.. 1-6... RV 2-30... Pulmonary artery 8-25... pulmonary artery wedge is 6-12[distal PA branches] Cardiac Cath is to get intracardiac pressures in patients w/ unexplained symptoms... Right-sided pressures are muc lower than those of left side... Balloon tipped pulmonary artery catheter is inserted into the subclavian or Internal jugular vein.. Enters SVC, waveform appears, balloon inflated and catheter advanced... Location of tip is determined by pressure readings SVC pressure = RA pressure, 1-6 Rise in pulmonary artery pressure from LA back pressure and pulmonary capillary resistance LV end diastolic pressure is 6-12 end systolic is 90-140

What is abnormal in patients w/ SCD trait?

RBC ct, reticulocyte ct, hemoglobin level allll are normal, but there is relative protection from malaria. .. NOT IMMUNE. Increased sickling in parasite infected cells and accelerated removal of these cells by splenic monocyte-MP system. Life expectancy is same for those w/ trait.

How to calculate Renal Blood Flow from PAH clearance??

RBF = PAH clearance / (1- HCT)

Triad of hematuria, flank pain, palpable abdominal mass

RCC, but really only p/w <10% of cases usually just fever, malaise, anorexia, weight loss. PCV and Hypercalcemia pssible from here.

RF and protective factors for epithelial ovarian cancer

RF = Fx Hx, Infertility, Nulliparity, PCOS, Endometriosis, BRCA1/2, Lynch, Postemenopatusal Hormone Therapy Protective = OCPs, Multiparity, Breastfeeding, Salpino-oophorectomy Things that reduce number of ovulations mean less repair needed at ovarian surface.

What is nontreponemal syphillis test?

RPR/VDRL... antibody to cardiolipin-cholesterol-lecithin antigen... low sensitivity for early infections... Treponemal is for treponemal antignes... greater sensitivity for early infections 2ndary sypillis... fever, arthralgias, diffuse LAD and widespread maculopapular rash --> Secondary Syphillis... oral lesions, condyloma latum, hepatitis

What organ has lowest blood flow during systole? How do you know not RV?

RV has much lower pressures, which allows blood flow... LV is lowest. Systolic reduction is greatest in the subendocardial myocadium (region most prone to ischemia/MI) In all other organs, blood flows continuously thoruhgout cardiac cycle w/ pressure gradient from the arterial to venous

Fractured mid humerus, what is in danger?

Radial nerve, deep brachial artery!! will p/w wrist drop (forearm extensors at the elbow).. C5-T1... and hand extensors. Also brachioradialis and supinator muscles. Cutaenous to dorsal hand, forearm and upper arm. DBA runs inferior to teres major then runs w/ radial nerve.

Patient w/ knee swelling a couple weeks after a GI bug... what do you think

Reactive Arthritis... duh... Has histocompatibility w/ antigen HLA-B27 p/w asymmetric arthritis of the large joints. = conjunctivitis, urethritis, keratoderma blennorrhagicum. Clinical manifestations are caused by immune complexes involving bacterial antigens

Insulin intracellular effects

Receptor autophosphorylation then PI3K pathway gets more GLUT4 along w/ glycogen/lipid/protein synthesis. Intrinsic TK --> insulin receptor substrate 1. Then this activates severeal pathways to induce insulin... PI3K promotes glycogen synthesis by activating protein phosphatase, which dephosphorylates glycogen synthase, leading to activation, and RAS/MAPKKinase gets cell growth DNA synthesis ~Phosphlipase C is part of the IP3/Ca2+ messenger system... Phospholipase C converts PIP2 to IP3/DAG.. ~PKA works on the glucagon/epinephrine side via activation of glycogen phosphorylase kinase to stimulate glycogen pbreakdown.

OSA peripheral

Recurrent episodes of airway collapse due to bulky tongue and crowded, narrow oropharynx Neuromuscular weakness is the origin and mechanism in OSA because this only happens in sleep. A time of muscle relaxation... Upper airway dilator muscles weakne during the transition from wake to sleep leading to airway narrowing and collapse. Stimulation of hypoglossal nerve using an implantable nerve stimulator causes the tongue to move slightly forward, increasing AP diameter of airway. ~lingual nerve arises from V3 supplies sensation to tongue.

During thyroid surgery, injure a nerve next to inferior thyroid artery, what is it?

Recurrent laryngeal nerve. Can also happen when injuring the thyrocervical trunk as well. U/L injury -> hoarseness B/L injury -> inspiratory stridor, respiratory distress due to focal cord paralysis. ~If superior thyroid artery think superior laryngeal nerve external branch. supplies cricothyroid muscle

X-linked agammaglobulinemia presentation?

Recurrent sinopulmonary, Giardia gastroenteritis, failure to thrive, low immunoglobulin... In this condition, a mutation in Bruton Tyrosine Kinase gene causes failure of bone marrow pre-B cells (CD19/CD20) to develop into mature circulating B lymphocytes CD19,20,21... XLA have low/absent B cells and pan-hypogammaglobulinemia Very increased risk of pyogenic infection (encapsulated) More susceptible to some viruses and giardia

How does varenicline help quit smoking?

Reduces nicotine withdrawal and prevents nicotine from binding and inducing reward response. Stimulates alpha4beta2 Nicotinic AchR in the CNS... partial agonist of this receptor that competes w/ full agonist nicotine. This limits downstream release of dopamine and reward pathways. Decreases cravings and reward effects

What studies most likely to have recall bias?

Retrospective studies such as case control studies. People w/ an adverse event are more likely to recall previous exposure to studied risk factors. Minimize w/ prospective studies. ~Detection Bias = a risk factor itself may lead to extensive diagnositc evaluation and increase probability that a disease is identified. ~Allocation bias = way patients are assigned to the treatment and control groups. Nonrandom possibly. Selection bias is different, when studied sample does not represent the general population because of nonrandom selection. ~Referral Bias = case and control populations differ due to admission or referral practices. For instance, asbestos as a RF for lung cancer conducted at a hospital specializing in asbestosis may select patients w/ lung cancer from respiratory department and a control group w/o lung cancer from other departments... Because hospital specializes in asbestosis, patients in respiratory are more likely to have history of this exposurel.

What type of antibodies come in the Rh prevention shot?

Rhesus groups are non-glycosylated, transmembrane proteins on the surface of RBCs. THe D antigen is the most immunogenic of the group and is present on erythrocytes of Rh positive people. Fetal RBCs can enter maternal circulation and elicit an IgG maternal antibody response --> memory B lymphcoytes (Rh alloimmunization). Leads to hemolytic disease of newborn Anti-Rh(D) immune globulin can be adminstered (polyclonal antibody product) consisting of IgG anti-D antibodies collected from pooled donor plasma. Given at 28 weeks at 28 weeks gestation and immediately postpartum. Basically these bind any that enter maternal circulation preventing their interaction w/ materanl immune system.

What do the main TB drugs do?

Rifampin = inhibits bacterial DNA-dep RNA polymerase... causes rash, red-orange body fluids, cytopenias, GI Isoniazid.. inhibits mycolic acid synthesis... causes neurotox (B6), hepatotox... resistance from decreased activity of bacterial catalase-peroxidase. Pyrazinamide (unclear MOA)... hepatotox/hyperuricemia Ethambutol... inhibits arabinosyl transferase (optic neuropathy)... resistance from increased activity of enzymes of cell wall synthesis. Streptomycin... AG family so high resistance... Only used now for tularemia, plaque, TB.. 16srRNA of bacterial 30S subunit, preventing protein synthesis... Resistance from modification in ribosomal binding sites.

Sequence of events in malignant hyperthermia

Ryanodine R is located on surface of SR of sk muscles and is a Cach. Releases small amounts of calcium in cytoplasm of muscle fiber during muscle contraction... Abnormaly Ryanodine R release large maounts of calcium after exposure to anasthetic... excess free Ca stimulates ATP dep reuptake by SR... Excessive consumption of ATP --> heat...loss of ATP leads to muscle damage... Rhabdomyolysis leads to release of K+, myoglobin, CK into circulation p/w tachycardia, HTN, hyperK+, myoglobinemia, fever, muscle rigidity... Tx w/ dantrolene a muscle relaxatn.

Food poisoning of cream <2 hours after eating

S aureus exotoxin formed prior to ingestion. Forms a heat-stable protein toxin called enterotoxin. causes nausea/vomiting/abdominal cramps. Usually innoculates food by food hadlers. Food sits at room temp for some time and S aureus multiplies. Usually hits < 6 hours. Bacillus cereus also has this clinical picture but contaminates more starchy foods like rice.

What are the biofilm producing organisms?

S epidermidis (prosthetics and IV catheters), Streptococcus mutans & sanguinis (dental plaques), Pseudomonas (CF pneumo and contract lenses), Viridans streptococci (endocarditis), Nontypable H flu (otitis media) Once bacteria have built up in numbers and amount of biofilm, will rupture in planktonic life cycle (dispersing seeds into bloodstream/surrounding area)

Two most likely sepsis results in SCAnemia patient... who does this gram positive cause sepsis?!

S pneumo and H flu... Lipoteichoic acid mainly, also peptidogloycans, bacterial products/exotoxins.

What does S viridans versus S epidermidis... realize the difference!!!

S viridans synthesizes dextrans from sucrose.

What indicates seriousness of MRegurge?

S3 gallop... Regurgant flow to atrium results in elevated pressure and blood volume in L atrium, which increases the amount of blood reenteric the LV during diastole... S3 occurs when Lv is unable to accomodate excess blood. S3 is sudden cessation of blood flow to LV during passive filling phase of diastole. Dilated Ventricle or More Blood S3. Normal in young adults but no in older. Absence of S3 can exclude severe chronic MR. ~S4 is a low frequency diastolic sound of atrial kick of ventricular diastole and it is blood colliding w/ stiff ventricular wall. Concnetric LV Hypertrophy or HTCMOP

The heart sound right after S2 = S3 or S4?

S3... due to rapid passive filling of ventricles in diastole... sudden cessation of filling as ventricle reaches its elastic limit... Age <40 and pregnant is normal.. Assc w/ systolic HF, mregurge, high output S4... atrial gallop just before S1.. Heard immediately after atrial contraction as blood is forced into a stiff ventricle. Healthy older adults... Younger adults/children abnormal.. Diastolic dysfx

Abdominal/pelvic trauma and then a retroperitoneal hematoma...

SAD PUCKER Suprarenal (adrenal), Aorta/IVC, Duodenum (2-4), Pancreas (head/body), ureters/bladder, colon (asc/desc), kidneys, esophagus, rectum (mid-distal) Pancreas most likely cause... malpositioned seat belts or sterring wheels in MVCs. Lifethreatening blood loss but mostly asymptomatic An intraperitoneal organ like liver, spleen, stomach, transverse colon would lead to a hemoperitoneum. Not retroperitoneal hematoma.

drugs causing photosensitivity?

SAT for Photo Sulfonamides Amiodarone Tetracyclines 5-FU

Esophageal cancer RFs

SCC = alcohol use, smoking, N-nitroso foods, esophageal disease underlying Adeno = Barrett's, GERD, obesity, tobacco N-nitroso is preserved or pickled vegetables.

What disease caues hypoxia-induced hemolysis?

SCD... Causes fibrosis and atrophy of the spleen. p/w scleral icterus, tenderness of back/long bones of thighs and anemia... Hemolytic anemia --> jaundice Vaso-occlusion by sickled RBCs causes hypoxia in many organs... Microvascular occlusion in spleen from trappled sickle cells in rigid splenic cords is autoinfarction... At risk of Salmonella typhi, Group B streptotoccous, Haemophilus, S pneumo, N meningitiids anything encapsulated Patients w/ SCD may get macrocytosis or megaloblastic anemia because they have a higher folic acid requirement. Extramedullary EPO can occur in SCD and lead to an elevated reticulocyte count. But if the Reticulocyte count is low, there is an inadequate response to anemia and lack of red blood cell formation... ***macrocytosis can occur in liver failure due to increase in circulating phospholipids and cholesterol that absorb onto erythrocytes, resulting in membrane expansion... Usually it is mild though <110.

Patient w/ pyelonephritis and low BP.... think...

SEPSIS... pulse 70/40 w/ pyelo Rapid onset respiratory failure think ARDS... B/L pulmonary infiltrates and hypoxemia in the absence of heart failure... Due to pulmonary trauma (contusions or inahled irritants) or sepsis/burns/pancreatitis... 3 Phases of ARDS 1. Exudative Phase.... -inflammatory cytokines TNF, IL1, IL6 activate pulmonary endothelium and recruit NPs to lung who release inflammatory mediators. Leads to increased capillary permeability and leakage of protein rich fluid into the alveolar space. Oragnizing of debri leads to formation of hyaline membranes. 2. Proliferative Phase... One-Two weeks later, endothelial cells, pneumocytes, fibroblasts proliferate in the attempts to repair damaged lung... collagen deposited and scarring occurs. Edema reabsorbs. 3. Fibrotic Phase... Excessive collagen deposition leads to irreversible pulmonary fibrosis and pulmonary HTN.

What should you check before giving canagliflozin?

SGLT2 inhibition --> significant urinary glucose loss... 2nd/3rd line to non-insulin regimens. SEff = UTIs and genital mycotic infections. Increased diuresis can lead to symptomatic hypotension... Avoided in moderate-severe renal impairment due to lack of efficacy and increased adverse effects.

How does finasteride affect the prostate?

SHRINKS IT... Terazosin and Tamsulosin are smooth muscle relaxants that work on dynamic component of bladder outlet obstruction. Work over days/weeks... Do not change prostate 5-alpha reductase inhibitors = finasteride/dutasteride... inhibit DHT.. work in 6-12 months Antimuscarinics are used to treat overactive bladder (Frequency, urgency, incontinence) they cause urinary retention and used in BPH only once another drug has addressed BOO>

Someone comes in w/ serious skin infx, you don't ask about home drugs they stay on them, what serious reaction could occur?

SSyndrome... increased serotonin effect on 5-HT1A and 5-HT2A receptors... methamphetamines can cause too... Linezolid treats infections by gram positive bacteria, particularly vancomycin resistance enterococcus and MRSA... Has MAO-i activity and can precipitate serotonin syndrome.

Triad of Reactive Arthritis after an STI, what is the cause?

Seronegative spondyloarthropathy (Rheum neg) most common in men 20-40 assc w/ HLA-B27.. manifest symptoms w/in 1-4 weeks of primary infection and can have palms/soles rash... Axial involvement w/ sacroillitis in 20% of cases. Can have hyperkeratoderma blennorrhagigum (hyperkeratotic vesicles on palms/soles) and circinate balanitis (serpiginous annular dermatitis of the glans penis) Due to chlamydia in GU or campylo, c diff, shigella, salmonella, yersinia

How does MV prolapse present?

Short late-systolic murmur at the cardiac apex w/ a midsystolic click.. Murmur disappears w/ squatting.... When you are standing MV prolapse regurigates a bit... When squatting.. there is delayed mV prolapse and tightening of chordae.. due to increased venous return 2nd to squatting. Click is the tensing of chordae tendinae.. Due to malalignment of the valve margins during systole... Maneuvers change LV volume and cavity size therefore, can change timing and intensity of the murmur.. Squatting from standing increased venous return and LV volume... Bringing valve leaflets intoa normal anatomic arrangement. Most commonly sporadic due to myxomatous degeneration (deterioration of connective tissue).. affecting MV leaflets and chordae tendinae.. Secondary is associated w/ CT disorders (Marfan, Ehler Danlos, OR Osteogenesis imperfecta).. Proliferation of spongiosa of the valve leaflets, fragmentation of elastin fibers w/ increase in mucopolysaccharide and collagen type 3.

Osler Weber Rendu Syndrome

Skin and mucosal telangiectasias as well as recurrent severe nosebleeds. (hereditary Hemorrhagic telangiectasias).. Auto dominant. Can involve GI and urinary tract as well. Can even occur in brain, liver, spleen rarely.. Rupture causes epistaxis, GI bleeding, hematuris.

Inserting a chest tube

Skin and subQ fat into 4/5th intercostal spacein the anterior axillary or midaxillary line. Tube traverses the serratus anterior muscle, intercostal muscles (external, internal, and innermost) and parietal pleura to reach pleural cavity. Inferior serratus anterior facilitates arm elevation by pulling lower end of scapular forward (scapular rotation)... All 3 muscles help ribs lift during respiration.

Biliary Sludge

Slow/incomplete emptying in response to CCK --> gallbladder hypomotility. Absorbs water from bile so conditions that lead to hypomobility actually dehydrate the bile. Promotes precipitation and sludge state. Can be asympto or lead to colic... Leads to acute cholecystitis or cholangitis. made of mucin, cholesterol crystals, calcium bilirubinate, other calcium salts... basically precursor to a stone RF = pregnancy, rapid weight loss, high spinal cord injuries, prolonged Pareneteral nutrition.

Piriform recess

Small cavities on either side of laryngeal orifice. Bounded medially by the aryepiglottic folds and laterally by the thyroid cartilage and thyrohyoid membrane. ... Normal swallowing, food is diverted by the epiglottis laterally through the piriform recess into esophagus... All that protects it though is a thin layer of mucosa... Superior Laryngeal nerve CNX pushes through here. Afferent for cough reflex. Foreign bodies can lodge here. Cough is afferent 10 efferent 10.

Who are OCPs contraindicated for?

Smokers and people over age of 35.. due to DVTs/clotting. Prior history of thromboembolic stroke/event Estrogen dependent tumor HYpertriglyceridemia Decompensated liver disease pregnant

How to screen for urinary cysteine?

Sodium Cyanide-Nitroprusside Test... Cyanide is added to urine converting cystine to cysteine. Nitroprusside is then added and reacts w/ the sulfhydryl group on free cysteine causing a red-purple discoloration. positive. Tx cysteine stones w/ urianry alkalinization w/ acetozolamide and also hydration. Cystinuria is an autorecessive disorder affecting high affinity sodium-independent dibasic AA transporters on the apical membrane of intestinal and proximal renal tubular epithelial cells.

What all can baclofen treat in MS?

Spasticity... agonist at GABA-B receptor.. good for monotherapy... Tizanidine can also be used.

What is another cause of varices in a patient w/o liver problems, but instead chronic pancreatitis?

Splenic Vein Thromosis... due to chronic pancreatitis, pancreatic cancer, abdominal tumors... Splenic vein runs along the posterior surface of the pancreas and can develop a blood clot from pancreatic inflammation... Short gastric veins drain the fundus ino the splenic vein. Splenic vein thrombosis can increase pressure in short gastric veins and cause gastric varices only in the fundus. Rest of the stomach/esophagus unaffected.... P/W upper GI bleed from fundus

Progression of C tetani

Spores in soil, contamined injured tissue, likely puncture wounds from soil-contamination. Low O2 tension and high nutrients --> germination... produce tetanospasmin. Bacterial cells lyse and toxin is released to gain access to motor neuron at axon terminal. Toxin travels up motor neuron retrograde to spinal cord and medulla. Organism stays put but toxin travels Unregulated motor neuron and tetany. Jaw stiffness (trismus), sustained contraction of facial muscles (risus sardonicus), spasmodic back/neck contraction = opisthotonus. Can lead to respiratory failure.

Regions of fungi

Sporothrix = gardening Coccidioides immitis = SW states, mold is present in soil Histo = Ohio/Miss River Valleys... soil, bird, bat droppings, caves, chicken coops Blasto = Ohio/Mis R and Great Lakes Region... found in soil ParaC = S/C America

What are the stepoffs of cell types as you move down the bronchi?

Starts w/ goblet cells, mucus, ciliated columnar, mucosal glands, cartilage Proximal Bronchioles = no cartilage Terminal Bronchioles = no goblet cells no mucus (serous fluid takes over) , club cells become present.. more simple cuboidal not ciliated columnar Respiratory Bronchioles = alveolar MPs present, rare cilia but still present No cilia in alveolar ducts or alveoli *wouldn't make sense for mucus to be below cilia that scoops it out.

Difference b/w Argyll Robinson pupil and optic neuritis

Still same accomodation but no reaction to light... but in AR there is no pain w/ eye movement or visual loss.

Epidermal Growth Factor Receptor and cancer treatment

Stimulates in a paracrine/autocrine fashion leading to downstream activation of KRAS... Membrane bound GTP-binding protein that stimulates cellular growth and proliferation. If KRAS constitutively active, then monoclonal antibodies like cetuximab or panitumumab that block EGFR are useless. These tumors are resistant.

Patient with amenorrhea, galactorrhea, fatigue, depressed mood, weight gain... 30 prolactin, 11 TSH, anti-TPO positive....

Stimulation of lactotrophs by thyrotropin releasing hormone. In patients w/ chronic hypothyroidism, compensatory increase in thyrotropin releasing hormone (TRH), leading to increased TSH Prolactin is regulated by primarily inhibitor effects of dopaminergic neurons from the hypothalamus.. However, lactotrophs can express TRH receptors and TRH stimulates synthesis of prolactin Elevated TRH levels in pituitary in patients w/ primary hypothyroidism can increase prolactin secretion leading to hyperpRO In premenopausal women --> galactorrhea Prolactin suppresses GnRH secretion from hypothalamus leading to reduced LH and hypogonadism/amenorrhea. Infertility, decreased libido, impotence (in men) ~~ Antidopaminergic drugs (antipsychotics and metoclopramide) can reduce inhibitor effect of dopamine on prolactin secretion and lead to hyperprolactinemia, but TSH has little effect on dopamine pathways.

Difference b/w diagnosis of Subacute granulomatous thyroiditis and hashimoto thyroiditis

Subacute granulomatous thyroiditis = ESR and CRP are elevated, decreased radioiodine uptake... infalmamtory infiltrate w/ MP and giant cells Hashiomotos = positive TPO antibody, variable radioiodine uptake.. .Lymphocytic infiltrate w/ germinal centers and eosinophilic epithelial cells = Hurthle cells. Painful vs Painless Viral vs Autoimmune SGT (Quervain), follows viral illness due to cross-reaction of immune response against viral proteins or tissue natigens.. P/w transient hyperthyroid phase... due to release of stored thyroid hormone... Low TSH levels suppress synthesis of new thyroid hormone. Self limited and resolves in < 6 weeks.

Patient can't keep hip tilted upward of opposite side when standing on one leg

Superior gluteal n. damage... Trendelenburg sign due to weakened gluteus medius. Often caused by pelvic trauma or iatrogenic damage during hip surgery or buttocks injections. Damage to this S Glut n. also takes out gluteus minimus and tensor fasciae latae muscles causing pelvis to sag toward the unaffected side when they stand on the affected leg (trendelenburg) and also when walking lean toward affected side (gluteus medius lurch) ~Inferior gluteal n. injury leads to gluteus maximus muscle problems... Problems for extension and external rotation of the thigh at the hip... causes difficulty rising from a seated position and climbing stairs. ~Obturator nerve injury causes impaired thigh adduction and medial thigh sensory loss ~Sciatic nerve injury (hits posterior compartment of thigh, hamstrings), divides into tibial and common fibular/peroneal there. All motor sensory to foot.

What separates orbit from sinuses

Superiorly by thick orbital plate of frontal bone and laterally by thick bone of the zygoma and greater/lesser sphenoid wings. Orbital floor is composed of a thin layer of bone that separates the orbit from the air filled maxillary sinus. Medial wall has thin ethmoid and lacrimal bones separating from ethmoid air cells. Blunt trauma to eye causes rapid decrease in pressure that typically does not rupture the globe but is transmitted posteriorly to the orbit... Medial and inferior walls and weakest most likely to rupture... Fx in imaging w/ fluid (blood) or henitation or orbit through sinuses.

How are peri-infarction pericarditis patients treated?

Supportive at first, if persistent, then aspirin in combo w/ colchicine

Side effectsof chloramphenicol....

Suppresses bacterial protein synthesis by binding 50S and inhibiting peptidyl transferase enzyme.. Dose related anemia, leukopenia and TCP reversible w/ w/drawal of medication. Also causes a dose-independent aplastic anemia (severe and fatal w/o BMT)

How do the main contraceptives work?

Systemic Progestins = combined hormonal/pill patch ring and progestin implant/injection... suppress GnRH and pituitary gonadotropin secretion --> inhibits ovulation Locally acting progestins = progestin-only pill/Levonorgestrel IUD --> thicken cervical mucus, impair sperm penetration.. thin uteruine lining and impair embryo implantation but so do combined. Women on these two continue to have ovulatory cycles. Copper IUD --> creats chronic cytotoxic inflammatory response in uterus, impairing sperm migration. From release copper ions. Toxic to sperm. O/P inhibit GnRH by feedback... LH spike is inhibited so ovulation is inhibited. ~clomiphene citrate... selective estrogen resceptor modulator that stimulates FSH/LH to stimulate follicular development in the ovaries...

How does fas/FasL work?

TNF receptor family... Fas receptors initiate extrinsic pathway of apoptosis through their death domain... Trimerize after binding FasL and allow death domains to forma d binding site for adaptor protein called fas-asscociated death domain (FADD)... FADD initiates 8 and 10 intiator caspases start cascade of activation of executioner caspases 3 and 6. Mutations in Fas/FasL lead to accumulation of autoreactive T cells and SLE/autoimmune diseases

What interluekins mediate septic shock???

TNFalpha most importnat... produced by activated MPs... IL1 and IL6 also. Hypotension, tachycardia, tachypnea, elevated or decreased body temp. 1) Early Sepsis... increased CO, peripheral vasodilation, warm extremities 2) Late Sepsis... SV decreases, CO decreases, distal hypoperfusion... cool and clammy w/ delayed cap refill, altered mental status, decreased urinary output.

Where does HPV infect in the throat?

TRUE vocal cords not false ones... types 6 and 11... Infects basal epithelial cells through small breaks in the skin... Hits True VC because the only area of the respiratory tract w/ strat squamous epithelium. Can give to children via passage through birth canal w/ HPV. Can lead to weak cry, hoarseness and stridor in baby.

Klinefelter's Presentation

Tall, sparse body hair, gynecomastia, intellectual disability, infertility, cryptorchidism, poor judgement/insight "eunuchoid body habitus"

What is leukocytoclastic vasculitis???

Teenager comes in week after sore throat that received treatment and has violaceous, raised, nonblanchable lesions over B/L lower extremities. This is a cutaneous small vessel vasculitis affects the skin typically due to drug exposure. Or Hep B/C exposure. Penicillins, cephalosporins, sulfonamides, phenytoin and allopurinol can cause it. Skin --> nonblanching palpable purpura in lower extremities. Skin lesions show inflamed small blood vessels w/ fibrinoid necorsis... Nps and fragmented neutrophilic nuclei... ~Erythema Nodosum shows panniculitis (inflam subQ fat) w/ painful, erythematous nodules in lower extremities. Histo widening of CT septate due to NP infiltration and fibrin exudation... also histiocyte/Giant cell infiltration w/ septal fibrosis. ~SubQ Rheumatoid Nodules are round, firm, nontender lesions that arise at pressure points in patients w/ advanced rheumatoid arthritis. Usually have a necrotic center w/ palisading MPs and lymphocytes

Where does H pylori colonize in duodenal ulcers?

The antrum... Leads to decreased somatostatin formation and increased gastric secretion... These stimulate parietal cells to produce excess acid. Leads to increased acid load emptying into proximal duodenum leading to duodenal ulcers. Bx antrum to confirm H pylori... Gastric ULCERS on the other hand are associated w/ colonization of gastric corpus or body. This etiology is not acid related, these have normal/reduced acid level... These are due to direct mucosal damage and chronic inflammation. Somatostatin Producing cells = Delta D cells.. within the pyloric gland next to gastrin cells... Parietal cells int he oxyntic gland w/ chief cells

What lab values in someone w/ Kilnefelter's?

They have testicular atrophy, B/L gynecomastia, cryptorchidism, sparse facial/body hair, intellectual disability, long legs High LH/FSH, low T, no sperm!!!... Progressive destruction and hyalinization of the seminiferous tubules cause testes to be small and firm... Serum inhibin levels are decreases as a result of Sertoli Cell damage. Leydig cells also usually damaged --> decreasing T Gonadotropin excess --> high estrogen levels --> gynecomastia azo-ospermia = infertile (those w/ mosaic variants though may have variable spermatogenesis)

What should aorta and LV do during systole?

They should be super similar, a difference of much higher LV pressure suggests aortic stenosis. and lower pressure after the valvular blockage

X-linked recessive problem that results in servere reactions to drugs

Think G6PD possibly

Patient comes in with high fever for 3-5 days then goes home then comes back w/ a maculopapular rash

Think HHV6, roseola infantum... Usually rash starts on trunk and spreads to face/extremities... ~Coxsackievirus A16 is a hand-foot-mouth disease in children.. P/W erythematous oropharyngeal ulcers and maculopapular or vesicular lesions on palms/soles ~Rubella and Measles are rashes that start on the face and spread to trunk/extremities. Also they have Forchheimer's spots on soft palate for rubella and measles has pathognomonic Koplik spots on buccal mucosa ~ParvoB19 causes erythema infectiosum.. flulike w/ slapped cheek rash and truncal reticular rash.. ~s pyogenes will have a scarlet fever, a diffuse sandpaper textured rash in skinfolds.

Newborn girl w/ jaundice, hepatomegaly, generalized edema. Low hemoglobin level and coombs positive. Peripheral blood smear w/ nucleated RBCs (extramedullary hematopoesis)

Think Hemolytic Disease of newborn w/ IgG against Rh(D)+ fetus. edema = hydrops fetalis from accumulation of interstitial fluid. Severe anemia stimulates liverspleen etc. to make RBCs Can have anemia/jaundice/kernicterus

26 year old woman w/ 2 spontaneous abortions gives birth to child w/ protruding tongue, palpebral fissures, VSD, excessive neck skin, decreased startle reflex

Think Robertsonian Translocation Down's Syndrome... 46, XX, t14;21 most likely. Most commonly, Down's syndrome yeilds 47, XX +21, but that is in older patients. This robertsonian is due to fusion of 2 long arms (14q and 21q) and fusion of two short arms w/ non esssential genetic material.

Waxing and waning lymph node enlargement painless chronic

Think follicular lymphoma... Most common indolent NHL in adults 2nd most common overall... t(14;18) translocation w/ bcl-2 overexpression. ~DLBCL is one rapidly enlarging node ~Burkitt is like a mass in jaw/face/abdomen that grows

Most common cause of postpartum hemorrhage?

Uterine atony, but uterus should respond to uterotonic agents... if doesn't then think other causes. If placenta was removed in pieces think placenta accreta... Morbidly adherent to myometrium.. Scar tissue from prior surgery can result in malformed absent decidual layer. Prevents normal separation after delivery. ~Signs of placental abruption = painful prolonged uterine contractions, tender abdomen, vaginal bleeding before dleivery.

V/Q throughout lung

V and Q are increased at the base, perfusion increase is far greater causing a high V/Q at the apex = 3

If doing combo insulin, what is the move?

Very Fast and Glargine... lol... Basal-Bolus... Regular insulin forms dimers due to hydrogen bonding b/w the C termini of the B chains... this allows it to form hexamers in the presence of zinc ions.. This causes a short dela in absorption of insulin following subQ injection... resulting in higher postprandial glucose levels and hypoglycemia afterward... Alteration of AA structure at the C terminal of insulin B chain can prevent polymerization and allow more rapid absorption aka aspart, lispro, glulisine. **Reversed lysine and proline residues at C terminal of B chain. ~Glargine is less soluble at physiologic pH, causing it to precipitate at injection site and be slowly released into circulation ~Detemir has a covalently bonded fatty acid, which promotes self-aggregation and reversible binding to albumin to allow slow, sustained release

Permisiveness

WHen one hormone allows another to exert its maximal effect. Cortisol and Norepi for example... Additive is when both work, A and B, but together they are A+B... Synergistic is A and B work but together they are even greater than A+B ~Tachyphylaxis... decreased drug responsiveness in a short period following one or more doses (rapid tolerance)

What is the mechanism of AIDS dementia?

WHen patients are non-compliant w/ HAART --> get hydrocephalus ex-vacuo from cortical atrophy, which allows Ventricle to expand maintaining normal CSF pressure. CSF fluid is in ventricular system and constantly secreted by the choroid plexus and absorbed by granulations of the arachnoid mater. ~NPH chronic reduction in CSF absorption at arachnoid villi, resulting in enlargement of ventricles out of proportion to overlying cortical atrophy. ~High Pressure Hydrocephalus... more acute impairment in CSF absorption (cerebral venous sinous thrombosis, meningitis, acute SAH) p/w mental status change, sseizure, HA, FNDs ~Noncommunicating Hydrocephalus is an obstruction of CSF flow b/w ventricles and subarachnoid space (aqueductal stenosis, Arnold Chiari malformation, tumors) all from elevated ICP too. Only ventricles proximal to obstruction are dilated. ~Pseudotumor cerebri is increased ICP (idiopathic intracranial HTN) w/o ventricular enlargement.

What's a great clinical predictor of insulin resistance?

Waist circumference. Visceral fat especially.. measurement of WC or waist-to-hip ratio is effective for this assessment. Moderate elevations in BMI useful for this assessment (25-35). >102cm or 40 inches in males OR >88cm or 35 inchest in females assc w/ higher risk of insulin resistance, diabetes, CAD ~insulin resistance increases TG and low HDL, but no effect on LDL ~ketones don't really rise w/T2DM

Most common side effect of TZDs?

Weight gain and edema... the increase in peripheral edema can decompensate underlying Heart Failure... Worse when given in combo w/ insulin. Weight gain is from increased fat storage and number of adipocyte in subQ tissue. Hepatotox risk for troglitazone (no longer available)... Pio and Rosiglitazone have no risk of hepatotoxicity

How does being an alcoholic and then getting megaloblastic anemia work?

Well as you would expect, poor diet, but it is also accelerated bc an alcoholic will get an anemia w/in a few weeks.

Grafting Coronary Arteries

When ALD alone is occluded by atherosclerosis... use left internal mammary thoracic artery (superior patency rates) When multiple coronaries/vessels other than LAD, great saphenous veins often used. G S V is longest in the body. Inferiorlateral to the pubic tubercle. Dives deep through the cribiform fascia from the saphenous opening to join femoral vein.

Can you have high indirect bilirubinemia w/o jaundice?

Yes... HUS in kids especially... will have no jaundice but low haptoglobin and hemoglobin with high indirect bilirubinemia.

What are the lesions of genitals of syphilis by stage?

You follow stage for naming.. Primary is chancre at innoculation site, 1-3 weeks post exposure resolves in 3-6 weeks. Secondary is condyloma lata, large gray wartlike growths in genital/perineal region Late is gummas, painless indurated granulomatous lesions that progress to white-gray rubbery lesions that may ulcerate. Diastolic murmur in this patient think ascending aortic aneurysm --> aortic valve insufficiency. *neurosyphillis = subacute meningoencephalitis, tabes dorsalis, common in any stage but most common late

If they get AAT presentation, usually homozygous for ?

Z allele, causing decreased secretion of AAT secondary to abnormal protein folding. Therefore, measure AAT level then do a confirmatory genetic test. Liver involvement is a greater concern for the beginning of live. Usually intrahepatocyte accumulation of AAT can progress to cirrhosis and HCC. Will see in periportal hepatocytes. Stain w/ PAS and resist digestion by diastase.

Most common congenital breast anomaly in women and men

accessory nipples aka polythelia, supernumerary nipples. Failure of involution of the mammary ridge... Asymptomatic... May swell or become tender similar to normal breast tissue before or during menses, pregnancy, lactation. Anywhere along the embryonic milk line b/w axilla and perineum, 50% B/L. Treatment is not needed... Identical histology to normal nipple. P/w Hyperpigmentation, epidermal thickening, pilosebaceous structure of Montgomery areolar tubercles, smooth muscle bundles (areola) and mammary glands/ducts.

What causes clear cells in clear cell carcinomas

accumulation of glycogen and lipid

Problem w/ beta thallasemia

actually mRNA formation problem not a heme synthesis problem. Dx w/ Hb A2 higher than 5% or so. Most comonly aberrant precursor mRA splicing or premature chain termination during mRNA translation.

How does N meningitidis and S pneumo colonize the meninges?

aerosolized droplets colonize nasopharynx... (fimbrae and pili)... usually asympatomatic carrier but in ~0.2%, bacteria penetrate epithelium into blood stream... Capsular polysaccharides help it survive and evade complement. Bacteria penetrate the cerebral capillary endothlieum or the choroid plexus to enter meninges.

Patient w/ pale/cold/blue vein and area from IV, what will help?

alpha1 R on the veins so, use an alpha1 R blocker to stop the vasoconstriction... Can lead to local tissue necrosis. Prevent by using a syringe w/ a fine hypodermic needle through the areas w/ 10-15cc of NaCl w/ 5-10mg Phentolamine mesylate... Give w/in 12 hours of extravasation.

How to differentiate b/w bone and liver alk phos?

also from placenta in pregnant women!! 1) electrophoresis and specific monoclonal antibodies 2) heat denaturation (bone specific alk phos is easily heat denatured)

Which drugs can cause neural tube defects?

anti-epileptics, methotrexate, trimethoprim (stuff focused on folic acid) Neuropores fail to fuse (4th week) leading to a persistent connection between the amniotic cavity and spinal canal. Assc w/ maternal diabetes and low folic acid intake before conception/during preggo. Increased Alpha-fetoprotein in amniotic fluid and materanl serum (except spina bifida occulta = normal AFP). Increased ACHE in amniotic fluid is a confirmatory test (It flows through CSF into defect and then amniotic fluid) Anencephaly... failure of rostral neuropore to close... no forebrain open calvarium... p/w polyhydramnios (no swallowing center in the brain) Spina Bifida Occulta... Failure of caudal neuropore to close.. no herniation.. Usualloy at lower vertebral levels. Dura is intact. Assc w/ tuft of hair or skin dimple at level of bony defect. **all baed lon folate deficiency --> decreased DNA methylation and Post-Translational Methylation of Cytoskeletal Proteins --> Decreased cell size, number, migration

What medication can mask hypoglycemia?

beta blockers... will only experience the sweating/hunger symptoms.... Brain needs glucose. GH, sympathetic stimulation, cortisol all work to stop hypoglycemia... Glucagon increases GLycogenolysis and GNG.. .EPi limits glucose use by insulin-sensitive tissues and also sitmulates hepatic glycogenolysis/GNG... There are 2 categories of hypoglycemia responses 1) Neurogenic.. sympathoadreanl activation via norepi/epi via adrenergics or cholinergics sympathetic release of Ach at muscarinic R causing sweating, hunger, paresthesias. = termulousness, palpitations, anxiety/arousal. 2) Neuroglycopenic = behavioral changes, confusion, visual problems, stupor, seizures. Beta blockers inhibit half the neurogenic response. Inhibits hepatic GNG as well and lipolysis (beta2). Therefore, for diabetics.... USE selective beta1 blockers and beta blockers w/ intrinsic sympathomimetic activity (pindolo, acebutolol)

Drugs induced in AIN

beta lactmas, sulfonamides, NSAIDs, rifampin, diuretics will see inflammatory cells in the interstitium and granuloma formation.

What chemical in sweet peas can cause cystic medial degeneration?

beta-aminopropionitrile causes inhibition of lysyl oxidase, needed for cross-linking elastin fibers and collagen fibers... Ingestion can cause a change in elasticity of the aorta that mimics myoxmaotus degeneration in Marfans

How does Fidaxomicin work?

binds sigma subunit of RNA polymerase and prevents Cdiff recurrence well... Less damaging to neighboring bacteria than vanc. It is a macrocyclic antibiotic (related to macrolides)

How does hepatic encephalopathy affect the brain?

bleeding from cirrhosis --> increased nitrogen in the gut --> increased circulatory ammonia due to failure of liver to metabolize them Astrocytes normally regulate neurotransmission by taking up glutamate present in synapse, preventing excessive neuronal excitation. Glutamine synthetase, glutamate undergoes a condensation reaction w/ ammonia to form glutamine. Glutamine is then release by astrocytes and taken up by neurons where it is converted back to glutamate for use as a NT. When excess ammonia is present, it crosses BBB and astrocytes still take it up, they increase glutamine production. Excess glutamine win astrocytes leads to increased intracellular osmolarity, causing astrocyte swelling and impaired glutamine release. Hyperammonemia consequently decreases amount of glutamine available for converstion to glutamate in eurons --> disrupting excitation.

What are common PT, PTT, bleeding times?

bleeding time = 2-7 min activated partial thromboplastin = 25-40s prothrombin time = 11-15 seconds

How is orotic acid produced?

block in urea cycle leads to overproduction of carbamoyl phosphate which is metabolized by di-hydro-orotate dehydrogenase to orotic acid. Excessive amounts are found in citrullinemia and OTC deficiency. These are also accompanied by hyperammonemia

What are the derivatives of neural crest cells migrating to intestinal wall?

both Auerbach/Myenteric and Meissner/Submucosal plexuses Neural crest cells migrate caudally, rectum is always last and is always involved in Hirschsprung disease. Fail to pass meconium w/in 48 hours of birth. Also obstruction, bilious vomiting and distension.

What is raloxifene good for?

both bone fx and breast cancer prevention. -does cause hot flashes and venous thromboembolism though... tamoxifen increases risk of Endometrial Hplasia/carcinoma

What lung values chang ew/ bronchitis vs. emphysema.

both have normal or decr FVC, low FEV1 lowFEV1/FVC TLC: Nl versus way increased FRC increased versus very increased Pulm compliance: normal versus increased Bronchodilator response: partial versus none DLCO: normal versus decreased

What is injected into patients w/ dystonia for temporary relief?

botulinum toxin type B into SCM for torticollis. Temporary because regeneration of nerve teminal occurs in 3 months. Can also be used to relax esophageal sphincter in esophageal achalasia.

What is the Cushing Triad?

bradycardia, HTN, decreased respirations

Amniotic Fluid Embolism

cardiogenic shock, hypoxemic respiratory failure, DIC, seizures, coma Pregnancy or shortly after delivery... Amniotic fluid has arachidonic acid metabolites and enters maternal circulationg through uterine trauma/cervical lacerations... Anaphylactoid reaction Can cause occlusion and vasospasm of the maternal pulmonary circulation... LWill find fetal squamous cells in the maternal pulmonary arteries.

Acute retinal hemorrhage

cause by HTN... gradual vision loss then an acute drop of a curtain... Painles, unilateral visual disturbance. Causes endothelial disruption and leakage of plasma into arteriolar wall and fibrinous necrosis. Necrotic blood vessels then can bleed into the nerve fiber layers. Causing dot/flame hemorrhages. Also copper or silver wiring, compression of veins /AV nicking and small, white foci of retinal ischemia = cotton wool spots.

What regions can we find pilocytic astroctyomas?

cerebellum, brainstem, hypothalamic region, optic pathways.. They are well differentiated neoplasms comprised of spindle cells w/ hair-like glial processes that are associated w/ microcysts. These cells are mixed w/ rosenthal fibers and granular eosinophilic bodies. Medulloblastoma is 2nd most common. Ependymomas are 10% of posterior fossa tumors in children.. NEUROBLASTOMAS are the most common extracranial solid tujmor in children. Undifferentiated, small round, blue cell tumors. A neuritic process called a neuropil is a pathognomonic feature of these neuroblastoma cells. NSE, chromogranin, synaptophysin, S100 all positive... More than 90% have elevated urinary levels of homovanillic acid and vanillylmandelic acid.. N-myc on chromosome 2 is a marker.

Where in spine is involved w/ rheumatoid arthritis?

cervical spine, subluxation/cord compression

What happens to contraction during total myocardial ischemia?

cessation of aerobic glycolysis and initiation of anaerobic glycolysis. Seoncds and results in inadequate production of ATP and accumulation of deleterious metabolites. Although ATP levels remian normal for first few minutes, ATP is rapidly depletes from areas of the cell w/ high metabolic damnd. Such as cytosol surrounding contraction fibers and electrolyte transport pumps. Loss of contractility w/in 60 seconds. ATP continues to fall as ischemia persists while lactate levels rise. Ischemia lasting <30 minutes is reversible. But resotration of blood flow, full myocardial contractiliyt no restored. Instead, prolonged dysfunction called myocardial stunning w/ contractility gradually returning. Under hypoxic conditions... ATP -> ADP -> AMP -> ADENOSINE... cross membrane and be vasodilator.

Features of NF1

chromosome 17, leads to 5 things 1) Cafe-au-lait spots.. .axillary or inguinal freckles or hyperpigmented lesions w/ smooth/irregular borders 2) Neurofibromas: short, sessile, pedunculated lesions that vary ins ize. Multiple throughout body 3) Eye: Optic Nerve Glioma that can cause visual loss. Lisch nodules are pigmented, asymptomatic hamartomas of the iris 4) Bony Abnormalities: sphenoid dysplasia, congenital pseudoarthrosis, scoliosis 5) Meningiomas, astrocytomas, etc.brain tumor

What's a use for nitrates also what are the main adverse sid effect (5) when do you NEVER USE THEM (3)?

chronic stable angina... Systemic vasodilaiton... Decr Myocardial O2 demand. Adv = HA (throbbing), cutaneous flushing, lightheadedness/hypotension, reflex tachycardia... AVOID in HYPERTROPHIC CMOP and RV INFARCTION and those on PDE inhibitors

Where are hyperdensities seen on CT brain of SAH?

cisterns/sulci, kind of all over bottom portion. Often circle of willis, with anterior communicating artery being most common. Berry Aneurysms assc w/ Ehlers Danlos and AD PCKD and AV malformations. Blood accumulates b/w arachnoid and pia mater. Lumbar will have xanthochromia.

What all is stopped from bleeding with the pringle maneuver?

clamping the hepatoduodenal ligament --> common bile duct, hepatic artery, hepatic portal vein and cystic artery. If this does not stop bleeding, then likely an injury to inferior vena cava OR hepatic veins

Procollagen peptidase where is it used?

cleaves terminal regions of pro-collagen molcls exocytosed by fibroblasts or smooth muscle cells making it into insoluble tropocollagen that aggregates to collagen fibrils. Prolyl Hydroxylase... responsible for the hydroxylation of proline on pro-collagen chains (needs vitamin C), needed to form triple helix.

Systemic Mastocytosis

clonal mast cell proliferation occurs in bone marrow, skin, other organs. Often this is associated w/ KIT mutation a Tyrosine Kinase... Prominent expression of mast cell tryptase... Excessive histamine release w/ degranulation of mast cells mediates many symptoms = syncope, flushing, hypotension, pruritis, urticaria... In addition, histamine leads to gastric acid secretion --> gastric ulceration... Excess acid inactivates pancreatic enzymes and intestinal enzymes --> diarrhea..

When working with adolescents, focu son

coaching to find close peers w/ complementary behavior medical practices. Positive family functioning, physician empathy, immediate benefits of treatment all increase adherence. Also role models and support. THis age really wants to fit in and they are rebelling/pushing limits. Prefrontal cortex does not fully develop until 3rd decade of life. SO can't weigh risks and benefits.

What is Laplace's Law?

collapsing pressure = 2(surface tension)/R Assuming a constant surface tension, a sphere w/ a smaller radius will have a higher collapsing pressure and collapse. Air will flow down its pressure gradient to the larger sphere. Surfactant counteracts this by decreasing surface tension as a sphere decreases in size. As it decreases in size it gets mroe concentrated and decreases ST greatly. As it grows larger, surfactant more spread out and less protected. Surfactant helps keep open smaller alveoli during expiration and assists in expansion during inspiration. It is mostly composed of DiPalmitoylPhosphatidylCholine (DPPC)

Bronchioalveolar carcinoma?

columnar, mucin-secreting cells that line the alveolar spaces w/o invading stroma/vessels... Located at periphery of lung. Preinvasive adenocarcinoma... W/ or W/o intracellular mucin... Will become invasive disease if not resected... P/w cough, SOB, hemoptysis. Also copious gray/watery sputum if mucinous form (bronchorrhea) CXR shows pneumonia like consolidation.

How to treat PCOS?

combo hormonal contraceptives, weight loss, metformin (for the increased risk of diabetes) Excessive male-pattern growth in a woman = hirsutism. 1) increased androgens (PCOS, Cushing's, O/Adrenal tumors) 2) increased conversion to DHT 3) higher sensitivity of hair follicles to DHT (idiopathic hirsutism) W/ excessive androgens, soft/non-pigmented villous hair --> coarse/pigmented terminal hair in face/chest/back. Virilization occurs w/ very high androgen levels and is clitoromegaly, increased muscularity, deepening of ovice. #1 cause hirsutism is PCOS... combo OCPs are first line. Suppress LH from pituitary decreasing androgen production. Also increase SHBG by liver (decreasing free T levels)

How do statins work lol?

competitive inhibition of HMG-CoA reductase, preventing conversion of HMG-CoA to mevaloinc acid. Decreased liver cholesterol synthesis leads to increased hepatic clearance of LDL from circulation by LDLR... After mediating endocytosis of LDL particles, LDLR are returned to cell surface for resuse and recycling. LDL is digested and used for metabolic purposes... LDLR recycling allows intrahepatic cholesterol to remain at normal levels while blood levels are low.

Warfarin-Induced Skin Necrosis...

complication of warfarin initiation.. due to transient hypercoaguable state.. can occur during the first few days of warfarin therapy Overall anticoag effect of warfarin is inhibit vitK dep gamma carboxylation of 2,7,9,10... Also decreases it for proteins C and S, which exert anticoagulant effect (through proteolysis and deactivation of factors V and VIII)... Protein C has a short half life, so its anticoagulant activity is reduced quickly when warfarin therapy is initiated... by 50% in the first day... 2,7,9,10 sitll high though, so pro-coagulant... Thrombosis and clots lead to skin necrosis... Heparin bridge is needed for warfarin initiation to avoid this.

Choanal atresia presentation?

congenital obstruction of the posterior nasal passages. Infants w/ B/L choanal atresia can p/w upper airway obstruction and cyanosis w/ feeding.. but not drooling... Inability to pass NG tube through the nares.

Triad of hydrocephalus, intracranial calcifications, chorioretinitis in newborn

congenital toxo... Chorioretinitis... inflammation of choroids and the retina and can leave cotton-like white/yellow scars on the retina visible on fundoscopy. HSM, rash, seizures, etc. Transmitted transplacentally. Mother must be infected the first 6 months of pregnancy.

Initial action of digoxin, is it to increase Ca2+ in or decrease Na+ out

decrease Na+ out

How does MM affect PTH, Ca2+, vitD, and PTHrP?

decrease PTH so decrease VitD, increased calcium from breaking up bone, normal PTHrP (non existent here)

Most common adverse effect of methylphenidate

decreased appettite, weight loss, insomnia.. encourage child to eat nutrient dense foods.

Levels of 21 hydroxylase deficiency

decreased cortisol, decreased aldosterone, increased ACTH, increased 17-hydroxyprogesterone p/w females w/ virilization + symptoms, males just symptoms symptoms = salt wasting, hyperkalemia, hyponatremia, metabolic acidosis, major hypovolemia/hypotension, vomiting. Also hypoglycemia from cortisol deficiency

Features of familial chlymicronemia =

defect in lipoprotein lipase, APOC2 either one... also elevated CM... also causes acute pancreatitis, lipemia retinalis, eruptive skin xanthomas, HSM versus Hyperchol which causes corneal arcus, tendon xanthomas, xanthelasmas, prematured CAD Fam dysbetalipo has also CAD/pVR and tuboeruptive/palmar xanthomas

Facial pain ,HA, nasal eschar w DKA and dry mucous mebranes in young patient

definitely mucormycosis w/ mucor or rhizopus. On bx fungi appear broad, ribbon-like nonseptate hyphae w/ right angle branching... Tissue invasion via blood vessels --> thrombosis. Differentiate from Aspergillus that is just invasive via septate narrow hyphae w/ sharp angle branching

Patients w/ CF and transepithelial potential difference

don't actually have increased Chloride secretion, just have increased sodium reuptake, heavily. So increased water coming back in. This is because like in the nose, not enough chloride is being secreted so Na+ wants to come back in. p/w chronic cough, recurrent sinusitis in young Caucasian patients In intestinal and respiratory epithelia, CFTR secretes chloride ions into lumen and inhibits opening of ENaC, which dereases sodium reabsorption. High lumenal salt retains water in lumen --> well-hydrated mucus... If a saline solution is applied to the nose, patients w/ CF have increased sodium absorption via ENaC and sodium is absorbed intracellularly but chloride left out to dry. The whole thing is reversed in sweat ducts, where CFTR reduces salt contetn of sweat by reabsorbing luminal chloride and stimulating ENaC to increase sodium absorption from the lumen into cells.

What is the definition of orthostatic hypotension?

drop in BP on standing from the supine position (>=20 systolic, >=10 diastolic).. Causes significant amount of blood 0.5-1L to pool into veins below the heart. 1. Decr venous return 2. Decr V filling and decr CO 3. Drop in BP so compensatory baroreceptor reflex 4. increased sympathetic tone to alpha1 PVR and myocardial HR/contractility Beta1 Other causes of orthostatic hypotension = hypovolemia (from hemorrhage), hyperglycemia, diuretics OR autonomic dysfunction (parkinson's and diabetes)

Dystrophic calcification of aortic valve

dystrophic calc is classic of cell injury and death... all types of necrosis cause this... normal calcium levels... fine, gritty, white granules/clumps... H/E dark-pruple. Can become psammoma bodies if lamellated Endothelial and fibroblast death secondary to hemodynamic stress or atherosclerotic inflammation --> release of cellular degradation product into valve --> thickening of valve leaflets/annulus... Often benign in older adults but eventually cause AS

Where does the mutation usually occur in somatic mosaicism...

early, like between morula and blastocyst, to where the cells within are all mixed, and they are spread throughough the body... Defined as mutliple, genetically different cell lines in the body. Esp from chromosomal nondisjunction and also mutations... Early the error, more cells affected. Somatic Mosaicism... disease manifestations to develop in affected individuals... 45,X/46,XX is most common. Mild Turner's. Germline... affects cells giving rise to gametes allowing genes to pass to the offspring. Chance of a child being affected depends on proportion of gametes w/ the mutation... No clinical manifestations in the parents.

Red Dead Neurons and timeline

eosinophilic cytoplasm, loss of nissl, pyknotic nuclei 12-24 hours 1-3 days NP 3-7 Microglia 1-2 weeks reactive gliosis and liquefactive necrosis (for 1 month), vascular proliferation too>2 weeks glial scar and cystic area surrounded by dense glial fibers (1 month)

Side effect of EPO stimulating agents

erythropoietin and darbepoitein alpha can be used to treat CKD, as GFR <30ml/min. Untreated anemia in CKD and dialysis patients can lead to cardiac dysfunction, fatigue, weakness, mental status changes... and ESAs improve anemia, avoiding need for blood transfusions. However, they are associated w/ thromboembolic events due to increased blood viscosity. Many patients also develop HTN, due to activation of EPOR on vascular endothelial/smooth muscle cells.

Transfusion and come down with double negative (separated by a week mono).. think CMV

fatigue, splenomegaly, atypical lymphocytosis, atypical lymphocytes... CMV can be acquired in transfusions via leukocyte laden blood products. If he were immunocompromised, id think differently though (other things like HHV6, HIV, Toxo, etc.)

Presentation of HSV

fever, headache, seizures, aphasia, mental status and behavior changes HSV-1 encaphlitis results from primary oropharyngeal infection that travels via the olfactory tract or reactivation of latent virus in the trigeminal ganglion. Edema/hemorrhage of inferior and medial temporal lobes is common. Temporal Lobe damage --> aphasia and personality changes (hypersexuality/aggression)

What are the lesions made of in pseudomembranous colitis?

fibrin and inflammatory cells and cellular debris... Risk factors = recent antbx, hospitalization, PPI

What does neutropenia put you at special risk of...

gram negative infections, like pseudomonas... Perivascular bacterial invasion of arteries and veins in dermis and subQ w/ release of exotoxins destroys human tissue --> necrosis and ulcerations from insufficient blood flow... Exotoxin A (protein synthesis inhibitor), elastase (degrades elastin of BV), and phospholipase C (degrades cellular membranes) and pyocyanin (ROS) Differentiate from DIC by platelet count and coag times

What's the deal w/ actinomycoses?

gram pos anaerobic bacteria... colonize mouth, colon, vagina and can be found in dental carries. Most often leads to cervicofacial abscesses --> systemic infection Pulmonary actinomycosis (relatively rare) develops most aspiration. Leads to lower lobe consolidation w/ air bronchograms. Patients w/ alcoholism at increased risk. Filamentous, branching patterns and characteristic sulfur granules formed from calcified mycelial fragments. Sulfur granules grossly appear yellow; hematoxylin and eosin staining gives them a basophilic appearance.

Biopsy of sporothrix tracking up arm shows...

granuloma w/ cigarrete bud yeast.. spreads up lymphatics forming subQ nodules

Congenital Diaphragmatic Hernia presentation

herniation of abdominal viscera through the thoracic cavity in congenital diaphragmatic hernia... Infants exhibit respiratory distress shortly after birth due to pulmonary hypoplasia... Results in scaphoid abdomen and bowel sounds in the chest.

Presentation of avascular necrosis

hip pain, decreased ROM, sickle cell disease, pain dully achy at rest as well as exacerbated w/ mvmt Can also be caused by glucocorticoids, vasculitis, radiaiton, alcohol abuse, traumatic fracture Wedge shaped necorsis, articular cartilage is viable but distorted Dead bony trabeculae have empty lacunae Necrosis of surrounding adipocytes

What is HER2 oncogene...

human epidermal growth factor receptor w/ tyrosine kinase activity in the intracellular domain... Plays a role in epithelial growth and inflammation... Epithelial cell carcinomas overexpress HER2 demosntrate increased proliferation and resistance to apoptosis.. Worse prognosis for breast cancers HER2+... Trastuzumab is used to treat these tumors.

Ganciclovir + TMP??

human host DNA synthesis inhibition to a greater extent than acyclovir in ganciclovir... Major adverse effects are neutropenia, anemia, TCP, impaired renal function... TMP-SMX also has inhibition of purine/pyrimidine synthesis also causes myelosuppression. Combing the two --> Bone marrow suppression... so does zidovudine which can be even more combined to cause myelosuppression.

Sequence of destruction of gall bladder in cholecystitis?

hydrolysis of lectihins to lysolecithins, disrupting mucus layer... Luminal epithelium is then exposed to detergent action of bile salts, resulting in chemical irritation and PG release... Inflammation of the mucosa and deeper tissues --> gallbladder hypomotility... Increasing distension and internal pressure results in ischemia... Bacteria E coli, klebsiella, enterococcus, enterobacter) invade and cause infection. Also susceptible to injury because cystic artery lacks collateral circulation.

How does PSGN present on bx?

hypercellular glomerulus. Hematuria, proteinuria, urine RBC casts are present w/ hypercellular glomeruli, think this. PSGN has anti strep antibodies (anti-streptolysin O, anti-DNase B, anti-cationic proteinase) and low C3 concentration. Cryoglobulins maybe. Hypercellularity is due to leukocyte infiltration w/ endothelial/mesangial proliferation. EM would have electron dense epithelial side of BM humps. Thesea re immune complexes. They have IgG and C3 w/ starry sky appearance on immunofluorescence.

SIADH from small cell presentation

hyponatremia w/ urine osmolality > 100mOsM/kg H2O... euvolemia appearing w/ creeping decrease in sodium.

Presentation of Waterhouse Friderichsen?

hyponatremia, hyperkalemia, hypoglycemia (due to cortisol deficiency) heralds onset of adrenal crisis. Low platelet count, petechial rash, abnl bleeding for DIC and sepsis

What is Dandy Walker?

hypoplasia/absence of cerebellar vermis and cystic dilation of 4th ventricle w/ posterior fossa enlargement Progressive skull enlargement... Cerebellar dysfx --> unsteadiness and impaired muscle coordination... Non communicating hydrocephalus may occur due to atresia of Luschka and Magendie foramina. Can also have associated agenesis of corpus callosum OR malformations of face/heart/limbs. ~Achiari 2 malformation is downward displacement of cerebellar vermis and tonsils below foramen magnum... often have spinal myelomeningocele. ~Hypoxic-Ischemic brain injury may occur w/ complicated deliveries... p/w altered consciousness and decreased spontaneous movements during neonatla period... Neuroimaging --> watershed necrosis of gray matter.

How does DI effect ICF and ECF volumes compared to hemorrhage?

iCF and ECF decrease in DI -head trauma due to hypothalamic/pituitary damage is possible... Decrease in vasopressin expression leads to excessive free water excretion leading to hyperosmotic volujme contraction.. Hyperosmotic volume contraction can occur in DI, dehydration, sweating Acute GI hemorrhage will cause loss of ECF volume w/ no effects on ICF ~adrenal insufficiency will cause loss of NaCl w/ ECF volume depletion, resulting in shifting free water into ICF so expansion ~Hypertonic saline will cause hypertonic volume expansion. Both volume and osmolarity of the ECF are increased. High OsM of ECF leads to shifting water from ICF to ECF. ~Primary polydipsia and SIADH both cause retention of free water in the body> leads to expanded ICF and decrease in OsM of both comparemntes. ECF expansion limited bc of compensatory secretion of Aldosterone and ANPs.

Where is a femoral vein catheter usually placed?

if subclavian and jugular vein (the preferred) are unavailable due to access or uncooperationor someting. The femoral vein is a major deep vein of the loewr extremity. Femoral nerve, femoral a, femoral v. great saphenous vein sartorius muscle, inguinal ligament, and thigh make the triangle Cannulation should occur 1cm below the inguinal ligament and 0.5-1cm medial to femoral artery pulsation

Different types of studies

in crossover, treatments are given then washout period then other option for treamtent. In this way, patients are their own controls -problem is effects of one treatment may carry over and alter response to next treatment, why you use washout period. ~Case-Control = select patients w/ a dsiease and without a disease (cases and controls) then determine their past exposure to >= 1 risk factors associated w/ disease ~Case series = descriptive study that tracks patients w/ a known condition to document natural history or response to treatment. ~Cross-Sectional study.. prevalence study.. Simultaneous measurement of exposure and outcome. Snapshot that uses surveys. Inexpensive and easy to perform. ~Prospective Cohort identifies 2 groups based on their exposure status to a risk factor. These 2 cohorts are followed overtime to assess development of disease. Sometimes ID exposure then look forward in chart, usually start and then track over time.

Vit A effects

individuals who consume 10 times the daily recommended allowance of Vit A are prone to hepatic injury/cirrhosis and acute toxicity Acute = n/vomiting/vertigo/blurred vision Chronic = alopecia, dry skin, Hepatotox/megaly, hyperlipidemia, HSM, visual problems,,, pseudotumor cerebri Teratogenic.. microcephaly, cardiac anomalies, fetal death early

Rectus abdominis muscle incised to make room for large baby... what is at risk?

inferior epigastric artery Transversus abdominus connects the xiphoid process to the pubic symphysis... Arcuate line is a horizontal line below the umbilicus that demarcates the lower limit of posterior rectus sheath. Above this, surrounded by anterior and posterior sheats; below muscle only coverd by anterior cheat... Superior and inferior epigastric arteries supply sup and inf portions of rectus abdominus muscle... Epi ascends posterior to recuts abdominus and enters lateral aspect at the arcuate line.. No supporting posterior sheath, trauma to inferior epigastric artery below the arcuate line can result in significant hemorrhage. C section involves midline vertical separation of rectus abdominus muscle. Horizontal may be considered when additional space necesary. Must ligate these arteries first though.

What initates appendicitis in the age groups

inflamed, hyperemic, edematous appendix... peaks in children 6-10. Caused by obstruction of appendicular lumen... Usually fecaliths. Hyperplastic lymphoid follicles, foreign bodie,s nematodes, carcinoids as well... Retained mucus causes the appendicular wall to distend and impair venous outflow... Results in hypoxia -> ischemia -> bacterial invasion -> inflammation -> necrosis -> peritonitis on rupture

X-linked agammaglobulinemia

intact T cell function (good response to candida induration) w/ very low immunoglobulin levels suggests XLA. Mutation in Bruton Tyrosine Kinase that causes failure of bone marrow pre-B cells to develop into mature B lymphocytes. Patients have very low or absent numbers of B lymphocytes. In this disease, germinal centers and primary lymphoid follicles do not form due to absence of B cells.

Most frequent bacterial cause of appendicitis?

intraabdominal abscess --> B fragilis... unique surface polysaccharides for this, also E coli, enterococci

When do brain AV malformations present?

intraparenchymal hemorrhage in children

Someone comes in with irregular rhythm, narrow QRS, no p waves... what determines rate of V contraction?

irregular rhythm and no p waves --> Afib... narrow QRS means still AV node though.. THis means continuous chaotic, atrial depolarizations.. HR <150 AF is initiated by aberrant electrical impulses that arise w/in regions of heightened atria excitability (most often the pulmonary veins)... Once triggered, AF leads to electical remodeling of the atria w/ development of shorter refractory periods and increased conductivity. This facilitates creation and persistence of multiple ectopi foci and re-entrant impulses w/in the atria and risk of chronicity of subsequent AF... S tach would still get P waves SVT wouln'dt be irregular Each time AV node excited it enters refractory period during which additional atrial impulses can't get through; majority of impulses never reach venitrlces.... Average ventricular rate in AF is 90-170.

How do cephalosporins function?

irreversible binding to PBPs... Transpeptidases are one form of PBP that function to cross-link peptidoglycan in the bacterial cell wall. Inhibition of transpeptidase leads to cell wall instability and bacteriolysis.

Stab wounds at different sites at the heart

know posterior, anterorior, lateral, also for xrays

How do vessels present in transposition of great arteries?

lack of spiraling... aorta is inferior, anterior, to the right of pulmonary artery 1. Ridges appear at opposite sides of truncal lumen 2. Ridges grow toward each other 3. Cells at ventricle base grow toward endocardial cushions form muscular part of IV septum 4. Spiraling of Aorticopulmonary septum results in pulmonary trunk anterior to aorta. TGA is due to linear rather than spiral development of aorticopulmonary septum in utero... Aorta will be connected to RV and pulm to LV... 2 parallel circulations. INcompatable w/ life so give PGE2 to keep the PDA alive. or keep PFO, septal defect... Normal initially but become cyanotic, tachypneic, tachycardic as PDA closes. Ages 1-3 days. Elevated lactate inthe blood --> anaerobic metabolism due to presence of poorly oxygenated blood. ~truncus arteriosus is failure of conotruncal septation, p/w cyanosis and respiratory distress, ech shows single large trunk w/ VSD. ~Membranous portion of the IV septum results from proliferation of endocardial cushiosn. Failure of this leads to VSD.

Damage caused by sudden upward jerking of the arm at the shoulder damages the....

lower trunk of brachial plexus... This carries C8 and T1 spinal leels... Together they innervate the intrisnic muscles ofthehand (lumbricals, interossei, thenar, hypothenar) Kumpke's palsy... weak lumbricals impairs flexionof metacarpopharalangeal joints and impaired extension of the interphalangeal joints. Relative sparing of extrinsic flexors and extensors leads to total claw hand deformity... Involvement of T1 proximal to sympathetic trunk may cause horner's

If doing PCR w/ RT, what are you checking for???

mRNA in a sample... if in RT-PCR you are looking for translocation, will see mRNA with exons of both fused. aka in CML... wil see mRNA w/ BCR-ABL fusion exons... also 9;22 abl;bcr presenttion of someone w/ AML = 3 mo fatigue, dyspnea, early satiety, abdominal discomfort, splenomegaly no LAD... w/ low hemoglobin, low platelets, high leukocytes

Side effects of MTX

mTX first line DMT for RA severe. Inhibits growth of rapidly dividing cells... leads to oral/GI ulces, alopecia, bone marrow tox, hepatotox and pulm fibrosis, ~Hydroxychloroquine for mild RA or SLE and causes irreversible retinopathy ~Minocycline tetracycline w/ weak Rheum Activity = photosensitivity dermatitis

What types of problems are people w/ Alzheimer's encountering?

memory loss, esp of recent events executive dysfx (planning/organizing) visuospatial impairment (getting lost in one's own neighborhood)... p/w neuritic (senile plaques) extracellular deposits often found on the medial temporal lobe (hippocampus/amygdala/entorhinal cortex) composed of Abeta core amyloid beta surrounded by dystrophin neurites. Abnormal accumulation of Abeta is toxic to neurons and is thought to occur secondary to impaired clearance and overproduction of amyloid precursor protein. Neurofibrillary tangles are found in neuronal cytoplasm and consist of aggregates of hyperphosphorylated tau protein, which normally mediates microtubule stabilization. ~Executive Dysfunction w/ vascular dementia and this would be caused by multiple lacunar infarcts.

Difference b/w methotrexate and 5-FU

methotrexate just works on the DHF reductase can be overcome w/ Leucovorin (N5-formyl-tetrahydrofolate) whereas 5-FU works on thymidylate synthase directly. *5-FU has reduced cytotoxic effect in cells that are deficient in THF.. It needs THF to form complexes w/ thymidylate synthase... For this reaosn, leucovorin can be utilized to potentiate toxicity by fluoropyrimidines (such as Fluorouracil)

What is a disease of old age that leads to hyperintense hearing?

middle ear cavity has 3 auditory ossicles (MIS) and 2 skeletal muscles (tensor tympani and stapedius)... Stapedius arises from the wall of the tympanic cavity and inserts on the neck of the stapes. It is innervated by the stapedius nerve (CN VII)... Functions to stabilize the stapes; paralysis --> due to injury or facial nerve lesion causes stapes to oscillate more widely --> hyperacusis... Patients complain of increased sensitivity to everyday sounds and will withdraw socially... Tx is sound therapy retraining using broadband white noise. Tensor Tympani arises from the cargilagenous portion of the auditory tube and adjoining part of sphenoid bone and inserts into the malleus. It functiosn to contract tympanic membrane medially increasing its tension and dampening sound transmission. Innervated by mandibular branch of V3. **ipsilateral hyperacusis is a common finding in Bell's palsy

Porphyria Cutanea Tarda (PCT)

most common disorder of porphyrin synthesis... Early porphyrin enzyme deficiencies cause abdominal pain, neuropsych symptoms w/o photosensitivity... Late steps (PBG conversion) derangements cause photosensitivity, which is thought to be due to accumulation of porphyrinogens that react w/ O2 on excitation by UV light. This disease is caused by uroporphyrinogen decarboxylase (UROD) deficiency which is either inherited or acquired (more commonly)... mainfesting in the presence of iron and susceptible factors (alcohol, smoking, halogenated hydrocarbons, hepC, hIV) Photosensitivity presents as a blister and vesicle on sun-exposed areas as well as edema, pruritis, pain, erythema... Deficiencies in coproporphyrinogen oxidase, protoporphyrinogen oxidase or ferrochelatase can also cause photosensitivity) ~ALA dehydratase & porphobilinogen deaminase deficiencies do not cause photosensitivity because they accumulate not porphyrinogens or porphyrins. PBG deaminase deficiency is seen in acute intermittent porphyria (abdominal pain and neuropsych symptoms) ~ALA synthase will decrease formation of all porphyrins. Leading to decreased heme synthesis and hypochromic/microcytic anemia. Pyridoxine phosphate deficiency works with ALAs def

Multiple Myeloma

neoplastic B lymphocytes mature into plasma cells that synthesize abnormal, large amounts of monoclonal immunoglobulin or immunoglobulin fragments.. MM is normochromic, normocytic anemia and weakness, lytical bone lesions (vertebral column causing back pain/path fractures), hypercalcemia and AL amyloidosis which lead to renal dysfunction. Erythrocyte rouleaux formations are classic on peripheral blood smear and bence-jones proteins in urine. SPEP shows M peak.

Homeless man found on the ground w/ silver staining organism in the broncheoalveolar lavage and oral thrush?

no he has impaired cellular immunity, could be AIDS.. silver staining for PCP.. an atypical fungal infection. Inhalation --> innoculation of alveolar space, not aspiration. Normal cell-mediated immunity clerance... Diffuse bilateral interstitial infiltrate also indicates this... Methenamine silver stain.

Why does HepC have hypervariable genomic regions?

no proofreading 3'-5' exonuclease activity 5' -> 3' activity is for DNA pol 1 to engage in nick translation, important for DNA repair and removal of RNA primers during replication.

Buspirone

non benzo anxiolytic in treatment of GAD... slow onset of action so not useful in acute anxiety... Typically takes 2 weeks, not effective in treating panic disorder... partial 5HT1aR... no muscle relaxant or anticonvulsant properties.

How does modafinil work?

non-amphetamine stimulant that enhances dopaminergic signaling.

What repairs does base excision repair fix?

non-bulky base alterations... depurination, alkylation, deamination, oxidation Dietary nitrites can promote deamination of cytosine, adenine, guanine to form uracil, hypoxanthine, xanthine respectively

What is CO poisoning versus Cyanide poisoning vs. blood loss on PaO2, SaO2, O2 content?

normal PaO2 for all CO has low SaO2, cyanide has normal SaO2 anemia has normal SaO2 O2 content decreased for anemia and CO poisoning, normal for cyanide poisoning.

How will intestinal mucosa look on bx of patient w/ lactase deficiency?

normal mucosa

In patient w/ severe cirrhosis, giving vit K will it help long PT?

not usually, honestly, because clotting factor synthesis is impaired, insufficient quantities of clotting factors to undergo VitK dependent carboxylation/activation Liver also synthesizes albumin --> ascites/peripheral edema Severe cirrhosis causes high output cardiac failure due to chronic splanchnic vasodilation and development of intrahepatic AV shunts. Also associated w/ TCP due to decreased TPO

How does infusing dopamine effect parkinson's?

nothing bc doesn't cross tight junctions of BBB L-DOPA has low lipid solubility as well, but able to enter brain due to its high affinity for large neutral amino acid transporter

How do you know shaken baby syndrome

now known as abuse head trauma... due to vigorous shaking... Causes tearing of bridging veins and subdural hemorrhages. Because AHT may occur repeatedly over weeks-months can have acute or chronic hemorrhages. Causes retinal hemorrhages = ruptured congested retinal veins. And can have posterior rib fractures.

How does a pinealoma present?

obstructive hydrocephalus from aqueductal stenosis (papilledema, HA, vomiting, blurry vision) and dorsal midbrain parinaud syndrome due to compression of pretectal region of midbrain. Limitation of upward gaze w/ a down prefereance, B/L eyelid retraction = collier sign (sclera visible above the superior corneal limbus), light-near dissociation (pupils that react to accomodation but not to light) Most common is a germinoma, midline malignant tumor thought to arise from embryonic germ cells. Often can present w/ central precocious puberty and diabetes insipidus.

Presentation of imperforate hymen

obstructive lesion caused by incomplete degeneration of central portion of fibrous tissue band connecting the walls of the vagina. At birth, vaginal secretions stimulated by the mother's estrogen can cause mucocolpos (accumulation of mucus in the vaginal canal), which may manifest as bulging introitus... If this remains undiagnosed, mucus is reabsorbed and the child will be asymptomatic until mencharce... Then p/w primary amenorrhea w/ cyclic abdominal/pelvic pain due to accumulation of mesntrual blood in the vagina and uterus (hematocolpos)... Pressure from blood causes defecation pain and back pain... Secondary sex development is noromal Exma shows vaginal bulge/mass palpated anterior to the rectum. ~Kallmann Syndrome is due to impaired synthesis of gonadotropin RH by the hypothalamus. Primary amenorrhea w/ absent secndary sex characterists and olfactory sensory defect.

What are the additional features of FMR1 gene deletion you expect?

obviously prominent forehead, long narrow face, and chin, large testes... but also hyperlaxity of joints in the hand and speech motor delay and anxiety/ADHD/autism

Psoas muscle

originates at anterior surface of transverse processes and lateral surface of vertebral bodies at T12-L5. Inferiorly the psoas combines w/ iliacus to form iliopsoas muscle --> hip flexion... Intraabdominal or more distal infections can spread to these muscles and cause abdominal pain, fever, weight loss... RF = HIV, IVDU, diabetes, prior abscess ~Erector spinae muscles are along the posterior side of spine at the same level of vertebrae really, run longitudinally alogn the entire spinous processes and cause B/L contraction of spine extension.

What are some side effects of mannitol?

osmotic diuretic used in management of cerebral edema and increased ICP... Mannitol works by increasing plasma or tubular fluid osmolality causing water to move from interstitial space into the vascular bed. In kidneys, osmotic diuretics primarily work in the proximal tubule an dloop of Henle to produce diuresis. Overaggressive treatment can cause pulmonary edema, excessive volume depletion, hypernatremia in certain patients. Due to increase in hydrostatic pressure. Cautiously used in patients w/ CHF and pre-existing pulmonary edema.

Lab findings for PSGN

p/w gross hematuria, edema, HTN Decreased C3, maybe C4 too increased creatinine increased anti-DNase B and increased AntiHelicase AHase Increased ASO and Increased anti-NAD (from pharyngitis specifically)

Rheumatoid Arthritis

pain, swelling, morning stiffness in multiple joints = PIP, CMP, MTP, NO INVOLVEMENT of dip fever, weight loss, anemia cervical spine involvement = subluxation/cord compression Labs = positive for rheumatoid factor IgM which is Fc portion of human IgG and also for anti-CCP... anti-cyclic citrullinated pepdie... ESR and CRP correlate w/ disease activity XRAY = soft tissue swelling, joint space narrowing, bony erosions... *Swan neck, ulnar deviation, rheumatoid nodules (firm, nontender, subQ at pressure points like elbows and forearms) ~anti-centromere antibodies = CREST syndrome

How does Coxsackie virus present? A type

painful vesicles in the oropharynx and on hands (palms/dorsal fingers), feet OR herpangina... fever w/ posterior pharyngeal vesicles w/o a rash

Oral involvement of ulcers w/ ulcers showing flaccid bullae/erosions

pemphigus vulgaris any mucosal site but oral is most common... Often bullae are weak and rupture before presentation (only erosions remaining)... Bullae spread laterally when pressure is applied = asboe-hansen sign and new blisters may form wtih gentle traction/rubbing (nikolsky sign) tombstoning and intraepitheilial cleavage... antibodies against desmogleins.

S pneumo major virulence factor...

polysaccharide capsule... prevents phagocytosis... Capsule swells and appears as a halo around the blue stained bacterial cells when specific anti-capsular antibodies and methylene blue dye are added = Quellung reaction... Infection elicits anti-capsule antibody production. and lasting immunity against that particular strain. But there are like >90 different variations of this, so eep. Other virulence factor is IgA protease, adhesins (adhesion to epithelial cells), and pneumolysin (cytotoxin taht causes pores in cell membrane and lysis)

Presentation fo ulcer induced gastroduodenal rupture

posterior duodenum --> epigastric pain, unstable vitals, hematemesis in setting of dyspepsia. Duodenal bulb is 5cm starts at pylorus and extends to insertion of the gall bladder. liver/gall bladder anterior to bulb, portal vein, common biliary duct and gastroduodenal lie posterior. Common hepatic artery is superior to duodenal bulb. Inferior PD A --> lower duodenum and head of pancreas What does the short gastric come off of and supply? comes off of splenic arteries supplies the upper portion of great curvature/fundus

What lobes must susceptible in supine individuals to pneumonia?

posterior regions of upper lobes and superior regions of lower lobes. anaerobic bacteria (peptostreptococcus, bacteroides, prevotella, fusobacterium) *soft, breathy voice suggests vocal cord paralysis, poor swallowing function

Body dysmorphic disorder

preoccupation w/ >= 1 perceived physical deficit, defects are not observable or appear slight to others, repetitive behavior or mental acts in response to preoccupation, significant distress/impairment, specific insight Mgmt = antidepressants (SSRIs) cognitive behavioral therapy Recognized under OCD category

Difference in histology b/w secretory and proliferative phase endometrium?

proliferative.. < 1:1 gland:stroma ratio, with straight glands that have small lumens... uniform... In secretory, squiggly tubular lumens, edema everywhere, bigger stromal volume, dilated and coiled and wide lumens. Normal menstrual cycle is 28 days +/- 7 days

Conduct Disorder

psych disorder of children and adolescents patterns that violate major societal norms and rights of others. Bullying physical fights, using weapons, torturing animals, breaking into houses, ssex. Middle childhood to adolescence and is more common in boys. Greater risk of developing antisocial personality disorder as adults. (can't be diagnosed until 18) ~ODD is toward authority figures. ~kleptomania... tension/anxiety lead to theft.

Which artery spared by PAN?

pulmonary normally segmental, transmural, necrotizing inflammation of med-small arteries. Rare bronchial artery invovlement, but usually just elsewhere. 1/3 of patients have livedo retciularish (purplish netwrok pattern lace) and palpable purpura

What layer is hypertrophied in congenital pyloric stenosis?

pylroic muscularis mucosae

What is the main mechanism of Wernicke's

pyruvate DHD, alpha-ketoglutarate DHD, and transketolase don't work.. Due to thiamine def... Metabolism of ethanol by alcohol DHD and aldehyde DHD consujmes NAD+ and increases NADH/NAD RATIO... THIS MEANS ENTIRE CAC is inhibited. However, in Wernicke's thiamine dep enzymes are especially affected, aka alpha-ketoglutarate in CAC>

Why is isoniazid monotherapy a no go?

rapid emergence of antibiotic resistance in TB... 1) decrease in bacterial expression of catalase-peroxidase enzyme needed for isoniazid actiation 2) modification of protein target binding site for isoniazid

How does scabies spread?

rapidly spreading, pruritic rash w/ erythematous papules and excoriations on extremities... Sarcoptes scabiei mite, burrows into skin and spreads person-person... Flexor surfaces of writst, lateral fingers, finger webs.. .Worse at night due to delayed type 4 HSN to mite, mite feces mite eggs...

Bloom Syndrome

rare auto rece disoder caused by mutations in the BLM gene. Encodes DNA helicase... responsible for unwinding the double helix during DNA replication Helicase dysfunction results in chromosomal instability, growth retardation, facial anomalies, photosensitive rash and immunodeficiency.

What do ras, erb-b2, and n-myc do in cancer?

ras... proto-oncogene encodes for protein that participates in MAPK. Overexpression leads to increased sensitivity of cells to mitogenic stimuli... in many cancers ERb-b2.. TK activity to epidermal growth factor receptor... Over expression is associated w/ breast/ovarian/gastric cancers, etc. not squamous cell N-myc neuroblastoma

What is in Hesselbach's triangle and what lies immediately laterally to femoral hernias in women?

rectos abdominus, inferior epigastric vessels and inguinal ligament... The femoral vein and even further than that femoral artery. Occur mostly on the right. Just lateral to pubic tubercle and lacunar ligament and just medial to femoral a/v. Femoral hernias more likely to strangulate a few hours after incarceration and incarcerate (can't reduce)

Presentation of Downs Syndrome at birth

risk if >= 35 years old.. bc risk of nondisjunction from oxidative stress, depletion of mature oocytes, shortening of oocyte telomeres. flat face, epicanthal folds, upslanting palpebral fissures, protruding tongue, small ears, VSD/ASD/AV defect in 50% of patients... Causes by meiotic nondisjunction in 95%, doubled 21 in one gamete... other 5% Robertsonian translocation (break near centromeres of two chromsomes (14 and 21 for example) and transfer of genetic material between... Leads to fetus w/ 46 chromosomes but 3 copies of 21. ~Edwards 18 is 2nd most common anueploidy nondisjunction, then Patau 13

If a study has too high of a p value and concludes no difference, then later a meta analysis sees difference, what is the problem with study?

sample size. This is a type 2 error (beta).. related to how much power a study has to detect a difference exists... Power = 1- beta... Type 1 error is falsely conclude there is a difference ~Berkson's bias = selection bias that can be created by selecting hospitalized patients as the control group. ~If RR between studies are the same, there is not likely a flaw in study design.

Nodes for a proximal rectum mass

sample the pararectal (inferior mesenteric) and internal iliac distal to dentate line --> inguinal nodes Bowel wall nodes (epicolic) inner bowel margins (paracolic) mesenteric vessels (intermediate nodes) and origin of S/IMA (principal nodes) Sentinel lymph nodes (first 1-4 draining a segment) are site of mets. In colon cancer... KRAS is activated and APC is inactivated... Rb is inactivated, tp53 is inactivated

What is the placeholder for schizophrenia before 6 months

schizophreniform... 66% go on to have schizophrenia... 1month > to < 6months Have to rule out medical/substance-induced etiologies.

Complications of lung cancer invading superior sulcus (groove formed by subclavian vessels

shoulder pain (most common), often lower brachial plexus involvement. Paresthesias/weakness/atrophy Horner's Upper extremity edema from subclavian congestion Spinal Cord Compression/paraplegia if it gets into intervertebral foramina.

Acanthosis nigricans

sign of insulin resistance Insulin resistance in adipose cells hinders the antilipolytic effects of insulin leading to release of FFAs. In turn, chronically elevated FFA levels contribute to insulin resistance by impairing insulin-dependent glucose uptake and increasing hepatic GNG.

How would you describe staining of H influenzae?

small, pleomorphic, gram negative coccobacillus requiring both factor X (hematin) and factor V (NAD+) to grow. Since these are in erythrocytes, optimal concentratiosn are present only in lysed blood agar (chocolate agar). Growth on regular need supplementation by impregnated disks. Localted infections of Hib can happen in undervaccinated patients. Hib has a polyribosylribitol phosphate polysaccharide capsule. It invades everywhere, can cause septic arthritis.

How does staining for acid fast work?

smear is treated w/ carbolfuchsin (aniline dye)... Red dye penetrates bacterial cell wall to bind mycolic acids. Then treated w/ HCl acid and alcohol... Dissolves outer cell membranes and non TB bacteria. Counterstain like methylene blue is applied to see bacteria... Nocardia is a gram positive w/ mycolic acid in cell wall. Less than mycobacteria tho so weakly acid fast

Ectopic ACTH tumor presentation

smoker w/ fatigue weakness, weight loss, skin darkening in sun-exposed areas, ecchymoses, proximal muscel weakness and lung mass. ACTH causes hyperpigmentation becuase of alpha-MSH in the pro-opiomelanocortin and direct stimulation of MC2R Receptor on melanocytes by ACTH... Weight loss is more common w/ Cushingoid central obesity ACTH secreting usually lung, but can also be from bronchial or pancreatic carcinoid... ACTH not inhibited ectopically by high dose dexamethasone

How do you diagnose floppy baby ?

stool bacterial toxin... Constipation before paralysis. Milk weakness reduced feeding and lethargy also. Some can have weakned suckleing or swallowing or gag reflex. Infant botulism from spores whereas adults from toxin. Based on ELISA and PCR

Where does permeability to water begin in tubule?

stops at thin asc limb and is not possible at early DCT, but at late DCT is ADH dependent fluid filtered into Bowman's Capsule is isotonic. PCT has water reabsorption passive.. tubular fluid is isotonic. Renal medulla takes over for the desc/asc limbs, interstitiujm is hypertonic (higher OsM than plasma)

What are the drugs that influence conversion of plasminogen to plasmin???

streptokinase (non-fibrin-specific), tPA, reteplase, tenecteplase (these three are fibrin specific), urokinase all increase this conversion aminocaproic acid inhibits this Plasmin can hit fibrinogen, cause 1) fibrinogen degradation products OR plasmin can hit the fibrin clot cause 2) fibrin split products (d-dimers) Fibrin-specific are better because non-systemic activation and decreased risk of bleeding. Most effective w/in 6 hours of MI. Contraindications to fibrinolytics = hemorrhagic stroke, ischemic stroke w/in 1 year, active internal bleeding, BP >180/110, suspected dissecting aneurysm. Can end up w/ a reperfusion arrhythmia (benign, not associated w/ increased mortality)... Accelerated idioventricular rhythmi s a common one.

Flank pain radiating to the groin w/ a ballotable flank mass w/in a week of pelvic surgery...

suggests ureteric obstruction. Ureter is near pelvic vessels... Courses anterior to illliac vessels (pelvic node resection for uterus/cervix) and just posterior to uterine artery near fornix of vagina.. Vulnerable during pelvic surgery of hysterectomy and pelvic LAD... Unintential ureteral ligation causes obstruction w/ hydronephrosis and flank pain due to distention of ureter. Urine output and serum creatinine remain w/in normal limits w/ unilateral obstruction bc contralateral kidney takes over.

Test for psoas major in appendicitis or psoas abcess?

supine, right knee flexed and externally rotated. Resists extension of leg and thigh at the hip arises from transverse processes and lateral aspects of the 12thT-5L vertebrae... Courses down pelvic brim anterior to the hip joint capsule and deep to the inguinal ligament into the lesser trochanter of the femur. Iliacus and Psoas muscles are major hip flexors Hematogenous/Lymph seeding or continguous spread. RF = DM, IVDU, HIV, immunosuppression fever, back/flank pain, inguinal mass, difficulty walking... Pain exacerbated by stretching/extending psoas.

Rotator Cuff Syndrome most common injury

supraspinatus tendon.. .prone to repeated impingement and trauma b/w the humeral head and the acromion... esp in abduction... Originates in supraspinous fossa of acromion and inserts on superior portion of head of humerus... can cause calcification and thickening and pain

What embryonic layers forms anterior pituitary?

surface ectoderm Gastrulation into 3 germ layers at week 3. Thickened epiblast cell layer appears at caudal end of embryo and grows cranially.. Epiblast cells then undergo an epithelial-to-mesenchymal transition, causing them to lose their cell-cell adhesion properties. This allows them to migrate downward through the primitive streak to form mesoderm and endoderm layers... Remaining epiblast --> ectoderm. About 2 days after gastrulation, some epiblast cells migrate cranially through the primitive node to form midline cellular cord = notocord. Induces overlying ectoderm to differentiate into the neuroectoderm and nerual plate. Neural plate --> neural tube and neural crest cells. Remainder of ectoderm becomes surface ectoderm.

Partner abuse

suspect in nonadherence to visits and many ER visits, inconsistent explanation of injuries, location of injuries, overally intrusive partern, discomfort w/ undressing, fearful/tearful/evasive Interview ensure privacy ( make partner leave), be nonjudgemental, open, ask about emergency planning, and there is no pressure to leave partner OR to disclose/report Offered to speak w/ a hospital or community-based domestic violence advocate regarding shelters.

DMARDs

swelling, pain, morning stiffness of multiple joints for >6 weeks = RhA Foundation of management is disease-modifying antirheumatic drugs (DMARDs).. alleviate pain and reduce long-term joint destruction and disability 1st line... methotrexate, sulfasalazine, hydroxychloroquine, minocycline, TNFalpha inhibitors These drugs take weeks to work... so systemic/intra-articular glucocorticoids OR NSAIDs are for immediate relief during transition. GCs inhibit phospholipase A2 so fewer PGs/LKTs also depress immune system by inhibiting cytokines, adhesion proteins to reduce leukocyte recruitment/activation, also toxic to lymphocytes.

Schwannomas... tumors of peripheral nerves that arise from Schwann cells...

they appear as biphasic w/ highly cellularized areas (antoni A) intermixed w/ mixoid low cellular regions (Antoni B)... A are composed of spindle cells (elongated w/ regular, oval nuclei) that form pallisading patterns w/ interspersed nuclear-free zones = Verocay bodies. S100+ due to their neural crest cell origin. Schwannomas can occur anywhere along the cranial vault or spinal canal. Most common is the site of the cerebellopontine angle (CN VIII) = tinnitus, hearing loss, vertigo. ~Glioblastoma = pseudopallisading necrosis and abundant neovascularization and hemorrhage. Frontotemporal white matter and grows along white matter tracts across corpus callosum. ~Meningiomas are arranged in lobules or whorls. ~Optic Glioma is often associated w/ NF1. Immature astrocytes w/ microcystic degeneration of Rosenthal fibers (intractyoplasmic eosinohpilci bundles)

What nodes to the left coli, sigmoid, and superior rectal arteries drain ?

they are all branches of IMA drain into IMA nodes... get descending and sigmoid colon and upper rectum

How are 3 branched chain AA broken down into and what is the cofactor?

thiamine Valine isoleucine go by branched-chain alpha-ketoacid DHD into propionyl CoA to methylmalonyl CoA to succinyl CoA to TCA Whereas leucine goes same enzyme to acetyl CoA to TCA Branched chain alpha ketoacid DHD needs 5 cofactors... Tender Loving Care for Nancy Thamine, Lipoic Acid, CoA, FAD, NAD MSUrine Disease p/w neurotoxicity of seizures/irritability/lethargy/poor feeding, also a isoleucine metaoblite --> sweet odor in urine.

What is the histology of chronic bronchitis?

thickened bronchial walls, neutrophilic/lymphocytic infiltrates, increased mucus glands and patchy squamous metaplasia

What to look for on CT scan of constrictive pericarditis?

thickening and calcification of pericardium normally 1-2mm thick but can become 4-20 in this condition. rapid y descent that becomes both deeper and steeper during inspiration is indicative.

How would you describe clubbing what causes it?

thickening of distal phalanges, hypoxia... flattening of nail folds, shininess of nail and distal portion of finger... Lungs = Lung cancer, TB, CF, bronchiectasias, Pulm HTN, empyeme, basicall hypoxia Heart = 5Ts or bacterial endocarditis Other = IBD, hyperthyroid, malabsorption In R-> l due to failure of platelet precursors to fragment completely into platelet w/in pulmonary circulation... Increase in peripheral megakaryocytes/platelet clumps.. Increased PDGF/VEGF in fingers/toes... Elevated levels of PGE2 in clubbing.

Child p/w dark blood on stool....

think Meckel's first... usually painless lower bleeding if Meckel's is symptomatic... Can also be a lead point for intussusception w/ colicky abdominal pain and currant jelly/strawberry jam stool Ectopic gastric mucosa secretes acid and creates local ulceration/bleeding... 99mTc-pertechnetate has an affinity for parietal cells of the gastric mucosa... A pertechnetate scan can indicate increased uptake in the RLQ being Meckel's.

Postprandial epigastric pain w/ food aversion/weight loss and a normal upper GI series in the setting of generalized atherosclerosis....

think chronic mesenteric ischemia... Bowel suffers from diminished blood supply... Analogous to stable cardiac angina

Patient can't evert or dorsiflex...

think common peroneal nerve... Sciatic nerve comes down and splits into common peroneal nerve and tibial nerve (back)... common peroneal nerve crosses to anterior side... splits into deep peroneal and superficial peroneal nerve Common peroneal is susceptible to injury at the lateral neck of the fibula caused by compression (prolonge dlying w/ surgery, crossing legs, leg casts) or proximal fibular fracutre Patients p/w foot drop bc tibialis anterior and toe extension inhibited... Superficial peroneal provides foot eversion and sensory loss over lateral leg/dorsolateral foot. ~Femoralnerve (hip flexion and knee extension weakness ~Sciatic nerve = sensory loss and weakness of lower leg muscles (hamstrings) ~Tibial nerve (larger of two sciatic nerve branches) inversion and plantarflexion compression at fibular neck from a cast can cause foot drop with impaired sensation over dosral foot

Immigrant child w/ sore throat and fever

think diphtheria (corynebacterium) AB exotoxin that inhibits protein synthesis by ADP ribosylation of EF2... p/w cervical LAD, pharyngeal exudates/coalescing pseudomembranes, sore throat, fever... Can cause suffocation, Myocarditis, HF/HBlock, Neuro toxicity

Started on isoniazid, month later abdominal pain

think hepatotoxicity... 15% of patients get mild hepatic dysfunction... Transient increases in ALT/AST... First 4-6 months of treatment, most return to normal w/ continued INH therapy... low fever, anorexia, nausea In <1% of cases, frank hepatitis (w/ jaundice) can occur. --. severe liver dysfunction/death. Don't worry about INH peripheral neuropathy if supplemental pyrodixine is also given.

SCLC w/ headache, weakness, altered mental status, seizures

think hyponatremia from SIADH... Causes subclinical hypovolemia (apparent euvolemia) .. Mild increase in ECFcauses increasein natriuresis selectively... Normal ECF volume w/ low low plasma osmolality. Volume overload features not seen.

Family moves to impoverished area of two and son has neuro regression

think lead toxicity that is inhibiting ALA dehydratase and ferrochelatase... In heme biosynthesis --> anemia... Because protoporphyrin IX cannot combine w/ Fe2+ to form heme it incorporates zinc, leading to elevated zinc protoporphyrin. ALA is also increased. Esp possible in houses before 1978. Children have incomplete BBB so especially susceptible.

Blotchy red muscle fibers on Gomori trichrome stain

think mitochondrial myopathy... Abnormal mitochondria accumulate under the sarcolemma of muscle fibers... The fibers have an irregular shape and size on cross section. Mitochondrial myopathies are also known as red ragged fiber diseases.. 1) Myoclonic Epilepsy w/ ragged red fibers (MERRF).. 2) Leber Optic Neuropathy (blindness) 3) Mitochondrial Encephalopathy w/ Stroke-Like EPisodes and Lactic Acidosis (MELAS). Maternal inheritance bc mutation in mito

What if you biopsy bone and see multinucleated giant cells, w/ over 100 cells...

think paget's Receptor activator of nuclear factor kappaB ligand... IS RANKL... Low OPG/RANK-L ratio means increased osteoclast formation and activity --> multinuclear osteoclast bad Osteoprotegerin competitively binds RANK-L and prevent sits binding to RANK on osteoclasts. M-CSF is also important for osteoclast differentiation. Normal osteoclasts have 2-5 nuclei, not 100. OPG loss of function mutation causes decrease binding to RANKL and inhibition of the survival. ~FGFs help differentiation of osteoblast precursors. ~IGF1 decreases collagen degradation by inhibiting MMP13 and helps build bone. ~TGFBeta increases formation of osteoblast precursors

Patient w/ autoimmune conditions, very low pH, and megaloblastic anemia...what gastrin, gastric pH, parietal cell mass would you expect?

think pernicious anemia high gastrin, high pH, low parietal cell mass CD4+ mediated immune response against parietal cells in body and fundus... (autoantibodies are different, useful for dx but not pathogenesis)

Muscle bx shows overexpression of MHC1 on sarcolemma w/ CD8 infiltration w/ patchy necrosis and regneration and fibrosis of muscle fibers.. will also have macrophages with the CD8 lymphocytes

think polymyositis Associated w/ interstitial lung disease and myocarditis will have elevated CK/aldolase (muscle enzymes)... ANA, anti-Jo-1

Patient has sickle cell trait and comes in with hematuria gross

think renal papillary necrosis... Esp if abrupt onset... 1) sickel cell disease or trait (obstruction of small kidney vessels -> ischemia) 2) analgesic nephropathy.. NSAIDs inhibit renal blood flow decreasing PG synthesis vasoconstricting afferent -> ischemia 3) DM --> vascular wall changes -. vasculopathy and hypoperfusion ischemia 4) pyelonephritis and UT obstruction lead to edeamtous interstitiaum w/ compressed medullar vasculature -> ischemia... will have sloughed papillae 9tissue fleks) and dark or bloody urine w/ colicky flank pain.

What's the deal with the toxin in traveler's diarrhea?

this is the organism EColi (ETEC), gram neg motile enteric rod... normally colonize the GI tract.. Watery diarrhea w/ abdominal cramping, n/v/low fever... Causes diarrhea in infants and travelers in developing countries w/ poor sanitation Disease requires colonization (usually small intestine via pilli adhesion) and elaboration of the heat labile (LT) and or heat stable enterotoxins (plasmid encoded) the LT (heat labile) enterotoxin, similar to cholera toxin, increases intracellular cAMP in gut mucosal cells by activating the stimulatory Gs... ST enterotoxin is not inactivated by heat (likely due to small molecular size) , causes increased cGMP in host cell cytoplasm via guanylate cyclase on host gut mucosal cells... Both of these cause decreased reabsorption and increased secretion of Na/Water/Elytes resulting in watery diarrhea.

What type of aneurysm risk is conferred w/ GCA?

thoracic aorta aneurysms... NOT berry aneurysms Especially affects the temporal artery.. bx shows scattered granulomatous inflammation, centered on media w/ intimal thickening, elastic lamina fragmentation, giant cell formation... w/o distinct granulomas...

Process that is defective in a patient w/ familial Parkinson's?

ubiquination Proteasome process all together. Impairment of this system is also implicated in Alzheimer's Disease. Failure to degrade abnormal proteins causes misfolding, aggregation, obstruction and death. Parkin, PINK1, DJ-1 genes encode for a protein copmlex that promotes degradation of proteins... Each is associated w/ autosomal recessive early onset parkinsons <50 years old.

Restless leg syndrome

unpleasant sensations in the legs, onset w/ inactivity or at night, relief w/ movement Idiopathic, iron deficiency anemia, uremia, diabetes all cause it tx avoid alcohol/sleep deprivation and dopamine agonists like pramipexole.

In central DI, when you give desmopressin, what is something random you are decreasing clearance of?

urea!! Cortical collecting duct is impermeable to urea, but vasopressin activates urea transportesr in the medullary collecting duct, increasing urea reabsorption and decreasing urea clearance. Passive reabsorption of urea into medullary interstitium in the presence of ADH significantly increases the medullary osmotic gradient, allowing more concentrated urine. 100% filtered, 50% R at PCT in cortex 75% from 25% entering at the loop, impermeable at the thickAsc to medullary collecting duct, then eventually only 20-50% excreted, rest enters medulla.

25 year old man p/w severe abdominal pain, nausea, vomiting for 1 hour. Pain starts in left flank and radiates to groin. Pulse is 100, BP 150/100. Physical exam shows left flank tenderness and left lower quadrant tenderness in abdomen. Bowel sounds are hypoactive. Stool occult blood negative.

ureteral calculus NOT torsion of testes

Uterus in pregnancy (even ectopic)

uterine specimen would reveal decidualized endometrium only, consistent w/ dilated, coiled endometrial glands and vascularized edematous stroma (changes w/ progesterone) Embryonic and trophoblastic tissue would be present if actually in the uterus as well

Cavernous Hemangiomas, consequences for pathology

vascular malformations (sporadic or familial) that most commonly occur with the brain parenchyma, above the cerebellar tentorium... They consist of clusters of dilated, thin-walled capillaries w/ little or no interventing nervous tissue. They often have seizures and may develop progressive FNDs due to mass effect leading to interruption of microcirculation... These lesions have a tendency to bleed, contributing to cortical/subcoritcal irritation or hemorrhagic stroke... They appear hyperdense/bright mass on contrast CT.

What is the peroxisomes function?

very long (beta oxidation) and branched-chain (alpha oxidation) fatty acid degradation, along w/ hydrogen peroxide degradation

What is the major determinant of viral tropism?

viral surface glycoproteins being able to bind complementary to host plasmalemma receptors... In enveloped viruses, capsid isn't involved, and it is at least this is the glycoproteins. ie hemaggluttin of influenza A...

Newborn w/ IV hemorrhage...

vitamin K deficiency... p/w increased intracranial pressure (altered, enlarging head, bulging fontanel, downward driven eyes) Germinal matrix not a factor for full term infants, starts dissappearing at week 28.

What causes fishy odor of Whiff test?

volatilization of amines produced by G vaginalis

Proper handwashing =

washing all surfaces of the hands and fingers w/ soap and water for at least 15 seconds, drying w/ disposable towel then using towel to turn off faucet.

Make sure you are in the right units

watch out for seconds and minutes

Tx of PCOS

weight loss to reverse insulin resistance and may restore ovary function... OCPs if they don't want to become pregnant. Minimzes endometrial proliferation and reduces androgenic symptoms For those who want to become pregnant give them clomiphene, a SERM that prevents negative feedback on hypothalamus and pituitary by estrogen.

Ankle sprain

what causes lateral ankle sprains?? Inversion of a plantar flexed foot... 3 ligaments stabilize lateral and 3 medial. Lateral are weaker and more often injured than medial... . Most commonly only the anterior talofibular ligament... pain and ecchymosis at anterolateral aspect of ankle... other can be induced by stronger forces = calcaneofibular and posterior talofibular Medial ligaments = tibionavicular, anterior tibiotalar, posterior tibiotalar, tibiocalcaneal.

?Why is arterial O2 a bit lower than alveolar O2

when it enters sytemic circulation, drops due to addition of bronchial circulation, intrapulmonary AV anastomoses and Thebesian veins of the heart. Calculate A-a gradients!!!

HIV dementia, what is the finding?

young patient w/ dementia and big HIV infection... cognitive decline mediated when CD4 <200... usually attn/working memory problems, executive dysfunction, slow info processing. Inflammatory activation of microglial cells. HIV infected monocytes initially cross the BBB to become perivascular macrophages. Microglial cells group to make nodules around small areas of necrosis and may fuse into MNGcells. Damage from inflammatory cytokine release by MPs/MGs

How long does cell mediated response to tuberculosis take to form?

~8 weeks or less but not less than 3... can often have a negative initial tuberculin skin test. Most patients w/ primary TB have negative CXR after months a Ranke complex can be seen.

What is the normal CD4 count range for adults?

400-1400.

What are the histology of common liver pathologies?

APAP overdose = centrilobular necrosis Alcoholic Hep = HC swelling/necrosis, Mallory Bodies, NP infiltration, fibrosis B-Chiari = severe centrilobular congestion and necrosis Hemochromatosis = iron hemosiderin w/ noninflammatory necrosis w/ fibrosis Reye... acute post infectious disorder of encephalopathy/liver disease.. most common in children... leads to panlobular microvesicular steatosis.

What is the progression of sporadic colorectal carcinoma?

APC/beta-catenin pathway is classic. 1. APC tumor suppressor gene mutation (cell growth/adhesion). also in pts w/ FAP... 2. Methylation abnormalities and Cox2 overexpression in hyperproliferative epithelium Later, K-rAS, DCC, p53 occur. KRAS= unregulated cell proliferation DCC = avoidance of apoptosis ^ usually in larger adenomas >1cm or carcinomas. p53 regulates cell cycle (common in carcinomas, rare in adenomas) MLH1 and MSH2 cause Lynch Syndrome = Hereditary nonPolyposis colorectal cancer 1. Progression from normal mucosa to small adenomatous polyp (adenoma)... APC mutation 2. Increase in size... KRAS proto-oncogene facilitates this. Leading to Uncontrolled cell Proliferation. Normally KRAS encodes a G protein like protein that regulates cell cycle by stimulating and inhibiting as necessary. Will lead to constitutive activation. 3. Malignant transformation = p53

What is the process of bile acid usage in the intestines?

Bile acids are produced in the liver and excreted with bile into the duodenum. There, they emulsify fat droplets to form water-soluble micelles that allow pancreatic lipase to efficiently hydrolyze TGs into fatty acids and monoglycerides. In the jejunu, micelles come in contact w/ gut epithelium, which facilitates passive absorption of fatty acids and cholesterol across brush border of enterocytes. Bile acids are ionized and can't pass^ They get reabsorbed in the terminal ileum Ratio of Cholesterol/Bile Acid predicts gall stones.

What do the following do? C3a, IL-4, IL-5, LktC4, PAF

C3a = anaphylatoxin split form C3... it stimulates mast cell histamine release IL-4 differentiates CD4 into Th2 (aids in humoral immunity against extracellular pathogens). Also stimulates B cell growth and isotype switching to IgE IL-5 promotes growth/differentiation of eosinophils and basophils and stimulates class switching to IgA LktC4 = along w/ D4/E4 vasoconstriction, increased vascular permeability, mucous hypersecretion, bronchospasm

What liver mass can cause death from operation?

Echinococcus granulosus (most common cause of hyatid cysts)... often middle east, south america, africa, china, mediterranean... or SW USA... From Sheep and Dog exposure Asymptomatic initial infection... leads to cyst and RUQ pain w/ Hepatomegaly. Lungs and muscles can be involved. Unilocular if E granulosus Multilocular if E multilocularis Larvae implant w/in capillaries, triggering inflammatory reaction (monocytes/eosinophils)... Larae encyst. Eggshell calcification and encapuslated. has fluid w/ budding cells that become daughter cells. Outer capsule is thick and fibrous. Albendazole and surgery are choice for symptomatic patients. Spilling of cyst can lead to anaphylactic shock. Manipulate w/ caution.

What is the mechanism behind Mallory-Weiss tears?

Esophagogastric-squamocolumnar junction. These are due to rapid increase of intraabdmoinal and intraluminal gastric pressure during retching/vomiting. Coughing, hiccuping, abdominal trauma as well... Hiatal Hernias are found in ~1/2 of the patients w/ M-W syndrome. Commonly this M-W syndrome is assc w/ alcoholism. p/w asymptomatic OR GI hemorrhage as hematemesis. About 10% of upper GI bleeds are from M-W syndrome. Almost never life-threatening.

What are the 6 major GI hormones.. including actions and secretion site

Gastrin = Gastric H+ secretion... G cells of gastric antrum & duodenum Somatostatin = decrease secretion of other GI hormones... D cells of pancreatic islets & gut mucosa Cholecystokinin = increase pancreatic enzyme/HCO3- secretion... I cells of small intestine Secretin = increase pancreatic HCO3- secretion and decrease Gastric H+ secretion.... S cells (small intestine) -stimulus is when lots of gastric acid hits the duodenum (begins as pH goes below 5 and rises dramatically as it goes below 3) -no effect on acinar pancreatic cells GIP = increase insulin release decrease gastric H+ secretion... K cells of small intestine Motilin = increase gi motilit... M cells (small intestine)

What genetic phenomenon explains PraderWilli and Angelman Syndrome?

Genetic Imprinting (selective inactivation of either maternal or paternal)

What disease is resembled by PBC?

Graft versus Host disease PBC is a chronic autoimmune liver disease --> destroys small and mid-sized intrahepatic bile ducts w/ resulting cholestasis. -common in middle aged women and associated with autoimmune disorders -p/w fatigue, itching, hepatomegaly -alk phos will be elevated and AMA positive in most cases -bx = lymphocytic inflammation and destruction o fintrahepatic bile ducts w/ necrosis/microndular regeneration fo perioportal tissues. Granulomas too. PBC all happens inside the liver because small and mid sized ducts. GVHD occurs in immunocompromised patients when allogeneic bone marrow or other lymphocytic rich tissues (liver/blood). Donor T cells migrate into host tissues, recognize MHC antigens as foreign. Skin/liver/GI most affected. Liver is often heralded by a rise in Alk Phos... along w/ lymphocytic infiltration and destruction of small intrahepatic bile ducts.

What is the progression of TB?

Infects lower lung in the Ghon focus, caseates a granulomas, then spreads to lymph nodes forming a Ghon Complex, then has 3 options 1) Latent Infection =dormant bacteria walls itself off --> Leads to secondary TB w/ apex, hemoptysis, night sweats, cough, extensive calcification (hits apex due to high O2 and low lymphatics) (is cavitary and caseuous here w/ liquifactive necrosis) --> eventually leads to miliary TB and liver spread 2) Resolution = Bacterial is cleared and scar formation 3) Progressive Primary =Failed immune response results in progressive lung consolidation and necrosis --> leads to miliary TB

Explain Adjustable Gastric Banding

Inflatable, silicone device placed around the gastric cardia... Slows the passage of food and increases satiety and limits amount of food that can be consumed. The band must pass through the lesser omentum, made of the hepatoduodenal and hepatogastric ligaments. B/w these 2 layers of lesser omentum, close to the right sided fere margin, sit the hepatic artery, common bile duct, portal vein, lymphatics and hepatic plexus... R and L gastric arteries are also here (near where lesser omentum attaches to the stomach)

How does Q Fever present?

Inhalation of bacteria from air w/ animal waste. Acute and Chronic stages. Acute febrile >10 days, fatigue, myalgias. Severe headaches often retroorbital and assc w/ photophobia. Often have pnuemonia w/ lobar consolidation. Leukocyte count is often normal. WIll get increased liver enzymes and TCP. Chronic is fatal if not treated. Is infective endocarditis in patients w/ valvular disease.

MGravis v LEaton

MG worse at end of day, EOM esp Risk of thymoma Tensilon test helps Decremental response in nerve stimulations tudies LE improves during day, weakness of proximal muscles Pre-existing malignancy No clinical improvement w/ tensilon Incremental response to nerve conduction studies

Differences b/w Class 1 and Class2 MHC

MHC class 1 = heavy chain and beta2, all nucleated cells, CD8, gets viruses/tumors/antigens of cytoplasm, causes apoptosis of presenting cell MHC class 2 = alpha and beta polypeptide chains, APCs (including B cells, MPs, Dendritic cells, Langerhans cells), CD4 Mostly gets bacterial, when antigens are phagocytosed and digested win lysosomes, where they bind MHC2 Antigen presentation leads to activation of Th cells which stimulate humoral and cell-mediated immune responses

Where does the spinal cord terminate?

L2 w/ the conus medullaris conus Medullaris Syndrome... flaccid paralysis of bladder/rectum, impotence, saddle anesthesias (S3-S5), mild weakness of leg muscle... caused by disk herniation, tumor, spinal fractures Cauda Equina on the other hand... usually a massive rupture of IV disk that compresses 2 or more spine roots of cauda equina. Trauma or space occupying lesion can cause. Provide sensory and motor to most of lower extermities, pelvic floor and sphincters. P/W low back pain radiating to one or both legs, saddle anesthesias, loss of anocutaneous reflex, bowel/bladder dysfx (S3-S5), loss of ankle jerk.

How are coal dust cleared?

Larger particles in the trachea, bronchi, proximal bronchioles via MC escalator.. Finest particles <2um reach respiratory bronchioles and alveoli where they are phagocytosed. MP engulfs then is activated for pulmonary inflammation. PDGF and ILGF are released stimulating fibroblasts to proliferate and release collagen.

What are the four places that optic tract fibers project?

Lateral Geniculate Nucleus, Superior Colliculus (reflex gaze), pretectal area (light reflex), suprachiasmatic nucleus (circadian rhythms)

What does the thoracodorsal nerve innervate?

Latissimus dorsi muscle... shoulder extension, adduction, internal rotation

What CSF infection can immunosuppressed patients get from contaminated food and flagellated motility? How is it transmitted to neonates?

Listeria monocytogenes Can be transmitted transplacentally OR via vaginal contact during delivery causing neonatal meningitis

What is a risk factor for developing calcium oxalate stones?

Lower urinary citrate!!! This often occurs in the setting of chronic metabolic acidosis (distal RTA or chronic diarrhea) due to enhanced renal citrate reabsorption. due to an imbalance of the factors that facilitate and prevent stone formation. Increased urinary concentrations of calcium (hypercalciuria), oxalate (hyperoxaluria), and uric acid (hyperuricosuria) promote sal crystallization wherease increased urinary citrate and high fluid intake prevent this. Citrate is an anti-calcium oxalate stone former. Citrate binds free calcium preventing stone formation. Often give patients w/ this problem potassium citrate to prevent recurrent stones. **Higher calcium dietary actually reduces likelihood of calciumoxalate stones bc calcium intestine precipitates w/ oxalate there to form stones that get pooped out

Which protease inhibits ANP?

Neprilysin ( a metalloprotease )... It also inactivates bradykinin, glucagon, enkephalins, and natriuretic peptides... ANP is secreted due to systolic volume expansion. ANP lowers BP through peripheral vasodilation, natriuresis, and diuresis ANP binds natriuretic peptide receptor on cell membranes and activates guanylate cyclase... increased cGMP leads to three things 1) Kidney... dilates afferent arterioles, incr GCR/urinary excretion of Na/H2O. Also limits sodium reabsorption (in PT and inner medullary collecting duct) and inhibits renin 2) Adrenal Gland... restricts aldosterone secretion, leading to increase in Na/Water excretion 3) BV... Relaxes vascular sm muscle so vasodilation, also increases capillary permeability so more fluid in interstitium.

What type of virus in influenza? How is it human and swine flu?

Orthomyxovirus... humans, birds, swine... possess surface proteins hemagglutinin (HA) and neuraminidase (NA) These HA/NA are virulence factors but also targets for the immune system by antibodies. When 2 distinct strains infect the same cell. Avian coinfection w/ human influenza A and animal influenza A --> can package these together and create a novel strain to which humans are susceptible but have no immunologic resistance. This is antigenic shift and is responsible for pandemics/epidemics. Term phenotype mixing is similar but can't be sustained for the next generation. In contrast, antigenic drift is point mutations in HA/NA genes that slightly differ products. Complementation occurs when 2 different strains of a mutant organism are able to produce wild-type offspring. Typically both parents have homozygous mutations in different genes of the same metabolic pathway allowing the corssing to bypass both metabolic blockades and display wild-type phenotype.

What increases the risk of cholangiocarcinoma?

PSC, fibropolycystic disease, chronic infection w/ Opsithorchis sinensis (liver fluke)

What are the steps for analyzing an acid base question???

Page 561+ A-a If acidotic... CO2 >44mmHg... then use A-a if normal = obesity hypoventilation, high altitude, NM disorders *A-a normal is 5-15 If A-a high = R-L shunt, edema, lung disease, PE If acidotic and CO2 <44mmHg, check HCO3-... if HCO3- <20 then check anion gap Na - Cl - HCO3 If 8-12 then normal so HARDASS If >12 then MUDPILES If alkalemic.... check if PCO2 <36 then respiratory... so Hysteria, Hypoxemia, Salicylates, Tumor, PE (Check A-a) If HCO3- > 28 then think loop diuretics, vomiting, antacid use, hyperaldosteronism

What type of inflammation is observed on bx of dermatomyositis

Perifascicular

What space does the axillary nerve branch through in the shoulder, what nerve roots make it up?

Quadrangular Space... C5-C6 Bound above by teres minor, below by teres major, medially by long head of triceps. Supplies deltoid and teres minor muscles. Most often an anterior dislocation or proximal humeral fx causes injury... Upper lateral loss of sensation and weakness of shoulder abduction

How does obesity present in terms of lung diseases if inducing hypoxemia?

Restrictive lung disease presentation.. It alters the ability of the lungs and chest wall to stretch. Causes microatelectasias. Obese patients typically have increased respiratory rates w/ reduced tidal volumes (rapid-shallow breathing) Reduction in expiratory reserve volume is the biggest indicator. Minimal effect on RV, but FVC is reduced. Can also reduce FEV1 and TLC

What type of histology is expected from Hepatitis A?

Spotty Necrosis w/ ballooning degenerating (hepatocyte swelling w/ wispy/clear cytoplasm), Councilman Bodies (eosinophilic apoptotic hepatocytes), and mononuclear cell infiltrates p/w fever, malaise, anorexia, n/v, RUQ pain... After several days, jaundice, pruritis, dark-colored urine (from increased conjugated bilirubin), acholic stool (lacks bilirubin pigment) Self limited.

How do you distinguish the three major types of urinary incontinence?

Stress = coughing, lifting, sneezing *due to decreased urethral sphincter tone and urethral hypermobility Urge = sudden, overwhelming urge to urinate *detrussory hyperactivity Overflow = incomplete emptying & persistent involuntary dribbling *impaired detrussor contractility and bladder outlet obstruction

How does the Circadian Rhythm work?

Suprachiasmatic nucleus recieves input from special photosensitive ganglion cells in the retina via the retinohypothalamic tract... SCN processes this and sends info to other nuclei and pineal gland to modulate temperature and cortisol, and melatonin. Cortisol peaks in morning low at night... Melatonin opposite. It is easier to lengthen the natural sleep/ wake cycle than to shorten it so eastward travel takes longer to recover from than westward.

What is the difference b/w ventral and lateral spinothalamic tract?

Ventral carries light tough/pressure Lateral carries pain/temperature

What are the main locations of the CFTR protein?

biliary tree, airways, intestines, sweat and pancreatic ducts works on both chloride and sodium When eccrine sweat first produced, it is isotonic w/ ECF, then as it travels through the eccrine duct to skin surface, chloride is reabsorbed via CFTR and sodium, therefore water flow. RF for hyponatremia in CF is breast/formula feeding prior to introduction fo sodum-rich foods;also high temperatures; therefore need salt supplementation

Break down the lac operon

consists of a regulatory gene (lac l) promoter gene (lac p), operator region (lac o) and three structural genes lacZ for beta galactosidase -- which turns lactose into glucose and galactose lacY gene for permease, allows lactose to enter the bacteria Lac p region is the binding site for RNA polymerase during initiation of transcription, Lac I repressor protein is the product of lac l gene and is constitutively expressed (binds operator region lac o) In presence of lactose, if glucose levels are high adenylate cyclase inactivated to not make more cAMP which normally activates catabolite activator protein (CAP) helping promoter binding.

Problem w/ left cerebellar hemisphere, where do you expect clinical symptoms?

left side, ipsilateral... dysdiadochokinesia, limb dysmetria, and intention tremor Sends fibers via the lateral corticospinal tract and rubrospinal tract. Vermis modulates axial/truncal posture via connections w/ medial descending motor systems... lesions here would lead to truncal ataxia = wide based, unsteady gait. Vertigo/Nystagmus from disruption to the inferior vermis and flocculonodular lobe.

What are three main causes of hypoMg?

loop diuretics/meds, alcohol use, uncontrolled DM w/ polyuria

Patients on longterm Levodopa --> problems

motor fluctuations and dyskinesia.. often >5 years after starting therapy. basically better mobility on the drug worse parkinson's off the drug. Dyskinesias develop when on the drug --> involuntary mvmts Nigrostriatal degeneration in Parkinsons --> excessive exctation of the GP internus by the Subthalamic nucleus, causes excessive inhibition of thalamus --> then reduced activity to cortex. Medically intractable PKD may benefit from high frequency DBS of the globus pallidus internus or subthalamic nucleus. Inhibits firing of these nuclei leading to thalamo-cortical dis inhibition.

Injury to radial nerve at axilla

typically fracture of the neck of humerus weakness of forearm, hand, finger extension (wrist drop, no triceps reflex) w/ sensory loss over posterior arm, forearm and dorsolateral hand. Injury at the midshaft humerus (radial groove) usually causes weakness of hand/finger extensor muscles w/ sparing of triceps brachii and sensory loss of posterior forearm/dorsolateral hand