what converts NE to E
dopa stands for..
how does cortisol affect epinephrine secretion?
adrenal venous drainage cortex inwards. cortisol produced in fasiculata will travel into adrenal medulla –> increase expression of gene encoding PNMT.
epinephrine and NE to dihydroxymandelic acid
epinephrine to metanephrine. norepinephrine to normetanephrine
Rh- women are treated with what 28 wks into gestation & immediately after? why?
treat with IgG against Rh (D) antigen. RhoGAM. stops mother from mounting immune response to Rh+ baby. small amounts, so IgG does not travel transplacentally & hurt baby.
RhoGAM is.. goal of therapy?
IgG against Rh (D) antigen. prevent mom from EVER mounting an immune response to Rh factor. Abs cover fetal erythrocytes & mom will sequester in spleen.
what type of immune response is mounted when Rh- mom exposed to Rh antigen in baby? what happens in subsequent pregnancy?
after transplacental fetomaternal hemorrhage, mom will mount maternal Ab response, form memory B-lymphocytes. subsequent prengnancies, Rh+ fetus at risk for hemolytic disease of newborn (erythroblastosis fetalis). maternal IgG anti-Rh antibodies cross placenta, enter fetal circulation, massive hemolysis of fetal erythrocytes.
IgG or IgM in RhoGAM? why?
IgG! while IgM is good for promoting agglutination of foreign cells, this isn’t so useful bc of low concentration of fetal cells in maternal circulation. IgG does not cause significant transplacental fetal hemolysis bc so little given.
somatostatin decreases secretion of.. (5)
(1) secretin (2) CCK (3) glucagon (4) insulin (5) gastrin. insulin is inhibited far more than glucagon. net = hyperglycemia.
somatostatin inhibits secretion of both glucagon and insulin. which is inhibited more?
insulin inhibited more. net effect: HYPERGLYCEMIA
adjust secretions from stomach and pancreas (affects environment of duodenum). S cells in crypts of Lieberkuhn in duodenum. also helps regulate duodenal pH (increase bicarb secretion in duodenum and inhibit acid secretion from stomach)
octreotide and lanreotide
deltaF508 mutation causes… (2) problems in CFTR
(1) abnormal protein folding and (2) failure of glycosylation. = absent from exocrine ductal cells.
protein abnormality of Friedreich’s ataxia? important for which 2 things. at what level is this gene affected.
frataxin gene: codes for mitochondrial protein, important for (1) respiratory fxn and (2) iron homeostasis. GAA repeat disruptions TRANSCRIPTION
monoclonal Ab that irreversibly binds to & inhibits TNF-alpha
what enzyme is exclusively expressed in inflammatory cells?
xanthine oxidase inhibitor
APML is what type of AML?
what suggests good prognosis in ALL (children)?
presence of CD10 antigen (CALLA)
causes of low glucose, high insulin, high c-peptide?
excess sulfonylurea & meglitinide use (stimulates insulin secretion). note: somatostatinoma inhibits insulin far more than glucagon.
sulfonylurea & meglitinide?
differentiate factitious hypoglycemia (sulfonylurea/meglitinide use) from insulinoma
urine hypoglycemic agent screen
presentation of glucagonoma (3)
(1) hyperglycemia (2) anemia (3) necrolytic migratory erythema (raised erythematous rash affecting face, groin, and extremities.
pancreatic cholera, or VIPoma (non-beta cell pancreatic islet cell tumor) causes..
results in WDHA syndrome (watery diarrhea, hypokalemia, achlorhydria).
what epidemiological measure depends on prevalence?
positive predictive value INCREASES w/ increased prevalence. more common the disease, more likely a patient with a positive test will be a true positive. [NPV: inverse association w/ prevalence, as prevalence increases, NPV decreases
which epidemiological values are inherent to the test itself?
sensitivity and specificity.
provision of identical measurements on different occasions separated by short time interval (reproducible)
describe acid fast stain process:
- aniline dye (CARBOLFUCHSIN) – penetrate wall and bind MYCOLIC ACID 2. treat slide w/ hydrochloric acid & alcohol - will dissolve outer cell membranes of nontuberculous bacteria, but presence of mycolic acids prevents decoliarization
describe mycobacterial cell wall
encapsulated w/ mycolic acid – waxy, long-chain fatty acid, covalently bound to the sugars within the cell wall
what two bacteria stain + w/ acid fast carbolfuchsin stain?
nocardia (weakly acid fast) and mycobacteria
which two bacteria have mycolic acid in cell wall
nocardia and mycobacteria
which two saccharides combine w/ aminoacid chain to form peptidoglycan layer in gram negative and gram positives?
NAM and NAG. N-acetylmuramic acid and N-acetylglucosamine
left main coronary covers..
anterior and left lateral surface
right dominant coronary circulation? left dominant?
85-90% have posterior descending artery (PDA) from RIGHT coronary. 10%, PDA from circumflex branch of left coronary.
which artery supplies the inferior surface of left ventrical (diaphragmatic surface of heart)
PDA (usu from right coronary)
LAD supplies (3)
(1) anterior 2/3rd of interventricular septum (2) anterior wall of left ventricle (diagonal branches) and (3) part of the anterior papillary muscle
left circumflex of left coronary supplies
lateral and posterior superior walls of the left ventricle
acute marginal branches
supply wall of right ventricle. can provide collateral circulation in patients w/ LAD occlusion
rule out test for asthma?
negative methacholine (assessment for bronchial hyperactivity)
1st part of the duodenum overlies… 2nd runs from… 3rd overlies… 4th..
1st part: 1st lumbar vertebrae.
2nd part: runs from L1-L3.
3rd: L3, abdominal aorta, and inferior vena cava, close to uncinate process of pancreas and SMA and vein.
4th: courses superiorly and to left of L2 and L3 vertebrae and becomes jejunum past ligament of treitz.
what is the only part of the duodenum that is NOT retroperitoneal
1st part of duodenum
when does duodenum become jejunum?
past ligament of Treitz.
common bile duct
common hepatic duct + cystic duct. courses inferiorly, posterior to pylorus and within the head of the pancreas to drain into the second part of duodenum
where does the portal vein form?
retroperitoneally, when splenic vein joins superior mesenteric vein.
arises from common hepatic artery, courses inferiorly, posterior to first part of duodenum. splits into anterior superior pancreaticoduodenal artery and right gastric epiploic
anterior branch of obturator innervates? posterior branch?
anterior: gracilis, pectineus, adductors lungus and brevis. posterior: obturator externus & adductor magnus
abductors of thigh (2)
tensor fascia lata and sartorius (superior gluteal and femoral n respectively)
thigh flexion muscles (4)
psoas, iliacus, tensor fascia lata, sartorius. psoas directly from lumbar plexus. iliacus by femoral n.
classic time for obturator n. injury?
pelvic surgery, esp lymph node dissection.
nicotinic acid, or niacin, causes flushing & warmth bc…
prostaglandins (aspirin inhbitsi t)
vancomycin-induced “red man syndrome” mediated by…
how does capsaicin affect pain? via?
reduces pain by decreasing the level of substance P
platelet activating factor
powerful phospholipid activator. produced by a number of cells: neutrophils, basophils, platelets, endotheilal cells. impt mediator of platelet aggregation.
head bobbing w/ carotid pulsations also known as..
bounding femoral and carotid pulses marked by distension & quick collapse known as..
bobbing: de Musset sign (see with aortic regurgitation). transfer of momentum from large left ventricular stroke volume to head and neck.
bounding: water hammer pulses
delayed, prolonged carotid pulses signifies..
pulsus parvus et tardus. aortic stenosis. can also see systolic vibrations, or carotid “shudder” thrill.
rx for excessive tPA / urokinase / streptokinase?
four phases of menstrual cycle?
menstrual, follicular, ovulatory, and luteal
follicle stimulating hormone (at the start of menstruation) does what 2 things?
(1) stimulates formation of dominant follicle and (2) trigger estrogen secretion.
describe hormone progression in menstruation
FSH triggers estrogen.. estrogen triggers luteal surge.. luteal surge triggers progesterone
two most immediate physical signs of marijuana use. other signs?
immediate: rapid heart rate and conjunctival injection. also see mild euphoria w/ laughing behaviour, slowed reflexes, dizziness, impaired coordination, short term memory loss
pharmacokinetics of marijuana
metabolized in the liver, then distributed and stored in lipophillic tissues & slowly released
up to how long can marijuana be detected in urine?
up to 30 days
physical sign seen w/ NMDA receptor antagonist (ketamine) use?
histology of terminal bronchioles
simple cuboidal (no longer pseudostratified ciliate columnar)
up until where is cilia present in respiratory tract?
cilia are present through respiratory bronchioles (not in alveolar ducts or alveoli themselves). LAST FEATURE TO DISAPPEAR as epithelium changes (makes sense, needs to be below mucous secretion)
histology transition from bronchi to small bronchioles?
bronchioles lack goblet cells, glands, and cartilage plates (w/submucosal mucosa and serous glands)
pseudostratified columnar ciliated epithelium w/ goblet cells and submucosal mucoserous glands and cartilage.
bronchioles, terminal bronchioles, and respiratory bronchioles lack..
lack goblet cells, glands, and cartilage. terminal bronchiole – cilated simple cuboidal. cilia persist until end of respiratory bronchiole.
3 class 1A antiarrythmic drugs; level of inhibition of phase 0 depolarization; & effect on length of AP.
disopyramide, procainamide, quinidine. intermediate phase 0 block, prolonged AP
3 class IB antiarrhythmic drugs; level of inhibition of phase 0 depolarization; & effect on length of AP
lidocaine, tocainide, mexiletine. weak inhibition of phase 0 block, shortened AP.
3 class IC antiarrhythmic drugs; level of inhibition of phase 0 depolarization; & effect on length of AP
moricizine, flecanide, and propafenone. strong inhibition of phase 0 block, no effect on AP.
lidocaine is highly selective for
class IB drug, selective for rapidly depolarizing cardiac myocytes. rapid binding & release.
2 anti-arrythmic effects of propanol
(1) slows conduction through AV node (2) prolongs phase 4 depolarization in cardiac PACEMAKER cells. no affect on ventricular myocyte AP
adenosines site of action, mechanism?
primarily acts on AV node; slows conduction and decreases automaticity by hyperpolarizing (K+ channels). does NOT modulate ventricular myocyte AP
when clinical suspicion of adrenal crisis (lack of adrenal gland secretions) immediate rx?
glucocorticoids (stress dose of hydrocortisone). no need for wait for biochemical confirmation. note: glucocortoids needed for vasopressors to have an effect!
clinical indications for epinephrine (3)
anaphylaxis, severe asthma, cardiac arrest. stimulates both alpha and beta, so not a potent vasoconstrictor
clinical indications for dopamine infusion
(1) shock and (2) refractory cardiac failure
serum antibodies to PLAR2 (phospholipase A2 receptor) – a transmembrane protein abundant on podocyte suggests…
glomerulonephritis. involved in idiopathic membranous nephropathy. (not in secondary membranous nephropathy)
minimal change disease is possibly due to..
abnormal T cell production of a glomerular permeability factor that affects glomerular capillary wall –> leads to fusion of foot processes and marked proteinuria.
Mixed cryoglobulinemia found in..
patients w/ hep C. results in renal disease due to IgM deposition in glomerulus –> basement membrane thickening and cellular proliferation.
renal disease in multiple myeloma?
deposition of light chains (cast nephropathy)
of those that test negative, how many are actually disease free?
will vary with pretest probability & negative predictive value.
pretest probability & prevalence directly affects..
negative predictive value.
(high probability of having disease, low NPV if negative. low probability of having disease, high NPV.
validity of a test measures..
appropriateness of test. does the test measure what its supposed to?
congenital QT prolongation (decreased outward K+) predisposes pts to..
syncopal episodes, possibility of sudden cardiac death w/ polymorphic ventricular tachycardia, including torsades de pointes.
insulin downstream signaling cascade
receptor tyrosine kinase. autophosphorylation allows for intxn w/ IRS-1/2 (insulin receptor substrate).
TNF-alpha induces insulin resistance by…
aberrant phosphorylation of signaling molecules.
activation of serine kinases –> phosphorylate IRS, which inhibits IRS-1 tyrosine phosphorylation by insulin. also phosphorylates insulin receptor.
how do thiazolidinediones reduce blood sugar?
insulin sensitization, PPAR-gamma
pneumocystis jirovecci (opportunistic HIV infxn) risk factor? prophylaxis?
risk CD4+ <200cells/uL & oropharyngeal candidiasis.
toxoplasma gondi (opportunistic HIV infxn) risk factor? prophylaxis?
risk: CD4+ < 100cells/uL & positive toxoplasma IgG antibody.
mycobacterium avium complex (M avium & M intracellulare) opportunistic HIV infxn risk factor? prophylaxis?
risk: CD4+ < 50 cells/uL
histoplasma capsulatum (opportunistic HIV infxn) risk factor? prophylaxis?
risk: CD4+ count < 150 cells/uL; endemic area (ohio & mississippi river valley)
distinguishing MAC from extrapulmonary TB infxn?
both have nonspecific symptoms of fever, weight loss, and diarrhea in HIV + pt.
but, MAC: marked (1) anemia (2) hepatosplenomegaly and (3) elevated alkaline phosphatase & lactate dehydrogenase levels –> due to wirespread involvement of RES.
growth differences between M. tuberulosis and MAC?
MA grows will at high temperatures. optimum growth at 41 C
rx for MAC?
azithromycine, rifabutin, ethambutol
TMP-SMX prophylaxis in HIV+ patients for.. (2)
(1) pneumocystic jiroveci < 200 (2) toxoplasma gondii < 100
mucormycosis grows in..
proliferate in walls of blood vessels (in paranasal sinuses, etc) and cause necrosis of corresponding tissue
fungal paranasal sinus infxn due to.. (2)
(1) mucor or (2) invasive aspergeillosis. distinguish w/ light microscopy. mucor = 90. aspergillus = 45
pyruvate dehydrogenase deficiency rx?
ketogenic diet recommended (bc carbohydrates may aggravate resultant lactic acidosis). i.e. lysine and leucine
amino acid catabolism produces what 2 general intermediates?
removal of amino group forms (1) glucogenic, i.e. intermediates of citric acid cycle or pyruvate or (2) ketogenic, i.e. producing acetoacetate or it’s precursors.
some amino acids are both (phenylalanine, isoleucine, tryptophan)
which amino acids are both ketogenic and glucogenic?
phenylalanine, isoleucine, tryptophan
which amino acids are exclusively ketogenic?
leucine and lysine (would not increase lactic acid).
alanine into glycolysis?
non-essential, glucogenic amino acoid. transaminated –> pyuvate
serine into glycosis?
nonessential, pyruvate via serine hydratase
asparagine into glycolysis?
nonessential, catabolized to ASPARTATE (asparaginase).
aspartate transaminated w/ alpha-ketoglutarate into (1) glutamate (gluconeogenic) and (2) oxaloacetate (TCA intermediate)
mult. possible. form neonatal death to mild episodic symptoms in adulthood.
thyroid hormones are..
iodinated amino acids
along w/ iodide, what is taken up by NIS (Na+ I- symporter)? (3)
(1) perchlorate (2) pertechnetate (3) radioactive iodine
presentation of HbC disease?
usu asymptomatic w/ mild hemolytic anemia and splenomegaly
speed of hemoglobin movement during gel electrophoresis?
hemoglobin A (glutamate) > hemoglobin S (valine) > hemoglobin C (lysine)
which bodily fluids is HepB in?
detected in all except stool. usu transmitted in blood, but can be in semen, saliva, sweat, tears, breast milk, and pathologic effusions.
wide, fixed splitting of S2 that does not vary w/ respiration?
ASD –> increased flow through pulmonary artery. biggest complication: irreversible pulmonary vascular sclerosis
for Eisenmenger syndrome to occur..
muscular pulmonary arteries develop laminated medial hypertrophy such that pulmonary VR goes above systemic VR. becomes right-to-left shunt.
reversal of flow due to CHRONIC PULMONARY HTN
irreversible concern with ASD?
chronic pulmonary HTN (resultant right ventricular hypertrophy and right atrial enlargement) are in response to pul HTN and are REVERSIBLE.
prevent recurrence with primary HSV infxn?
DAILY valacyclovir, acylovir, or famciclovir. reduce recurrences.
short course of acyclovir rx during first episode..
reduces duration of viral shedding, time for lesion healing, constitutional symptoms, and local pain. does NOT alter viral latency or recurrence. needs to be AFTER first episode?
immunoglobulin therapy used for what virus? in which situation?
combat varicella zoster in (1) immunocompromised (2) neonates whose mothers developed perinatal varicella infxn (3) prophylaxis in pregnant females exposed to varicella
how does ANP reduce blood pressure?
peripheral vasodilation, natriuresis, and diuresis.
ANP signaling mechanism?
binds to natriuretic peptide receptor A (NPR-A), activate guanylate cyclase forming cGMP.
3 tissue effects of ANP
(1) kidney: ANP (a) dilates afferent arteriole, increasing GFR and urinary excretion of Na+ and H20. also, (b) limits Na+ reabsorption in PCT and (c) inhibits renin secretion
(2) adrenal gland: ANP restricts aldosterone secretion (increased Na and H20 excretion)
(3) blood vessels: ANP (a) relaxes vascular smooth muscle in arterioles and venules –> vasodilation. (b) increases capillary permeability, leading to fluid extravasation into the interstitium and decrease in circulating blood volume.
what is expected on peripheral blood smear after B12 replacement therapy (in deficient situation)
effective erythropoesis begins immediately & immature erythrocytes are release.
(1) reticulocytes peak early: left shifted & take longer to mature.
(2) anemia takes ~8 wks to correct, due to slower rise in hemoglobin / mature erythrocyte
serum haptoglobin levels with B12-deficiency anemia?
usually low due to ineffective erythropoesis and enhanced peripheral destruction.
in chronic atrophic gastritis, which hormones are elevated
profound hypochlorydia (due to parietal cell loss –> increased GASTRIN.
urea cycle main goal
convert AMMONIA generated from metabolism of alpha-amino acids into UREA.
urea cycle overview
5 enzymatic steps, 2 in mitochondrial matrix. 3 in cytosol
OTC (ornithine transcarbamoylase) deficiency vs. NAGS (N-acetylglutamate synthase) deficiency
both result in hyperammoninemia. OTC –> elevated carbomoyl phosphate –> orotic acid elevation (pyrmidine synthesis pathway.
NAGS –> hyperammonia w/ elevated ornithine but normal enzyme in rest of urea cycle.
3 major causes of hepatocellular carcinoma
(1) hepatitis B or C (2) chronic alcoholism (3) consumption of food contaminants (i.e. aflatoxins)
distinguishing cirrhosis from hepatocellular carcinoma
difficult, overlap in clinical presentation: upper abdominal pain, malaise, fatigue, weight loss, sensation of abdominal fullness.
elevated serum-AFP levels present in 50-75% of HCC. can help distinguish.
note: hep C can also have elevated AFP, but continuous rise –> HCC
hepatic adenomas. demographic, presentation, association?
young, middle aged women. length history of oral contraceptive use. identified when compains or abdominal pain in epigastrum or RUQ, incidental imaging, or sudden collapse w/ rupture & intraabdominal bleeding
GABA is made by.. broken down by… what cofactor is needed for both?
synthesis: glutamate acid decarboxylase (GAD) from glutamate.
breakdown: transamination via GABA transaminase.
both need vitamin B6 (pyridoxal phosphate)
3 types of GABA receptors: where, structure of receptor, effect of stimulation
GABAa: brain, ion channel, Cl- influx
GABAb: brain, G-protein, K+ efflux, decreased Ca++ influx, inhibtion of adenylyl cyclase
GABAc: retina, ion channel, Cl- influx
zolpidem (ambien), zaleplon, esZopiclone
ZZZ’s sleep. activate BZI substype of GABA receptor. reversed by flumenazil. rx: insomnia.
zolpidem shares benzo site on GABAa
which 2 anti-epileptics reduce GABA catabolism
valproic acid and vigabatrin
GABAb mediates action via..
Gprotein !! :(
most common type of malignancy in patients suffering from inflammatory bowel disease, particularly ulcerative colitis?
colitis-associated carcinoma vs. sporadic colorectal carcinoma
colitis-associated: (1) younger, (2) progress from flat & nonpolypoid dysplasia (3) histologically appear mucinous and/or have signet ring morphology (4) develop EARLY p53 and LATE APC [opposite of sporadic] (5) be distributed within the proximal colon (esp w/ crohn’s or primary sclerosing cholangitis) 6. be multifocal in nature
colitis-associated usu HIGHER GRADE & more likely to be anaplastic
what type of carcinoma is associated with 1st p53 mutation and then APC
colitis-associated colorectal carcinoma
alpha-1 antitrypsin is..
serum protein that inhibits several diff proteolytic enzymes (most important neutrophil elastase) and reduces inflammation
alpha-1 antitrypsin results in..
panacinar emphysema and liver disease (hepatomegaly, hepatosplenomegaly, cholestasis, elevation of hepatocellular enzymes)
can be asymptomatic until end-stage liver disease.
most severe consequence: cirrhosis and hepatocellular carcinoma
diagnosis of alpha-1 antitrypsin deficiency should be suspected in..
all patients w/ premature onset (<50 of chronic bronchitis, emphysema, or dyspnea) as well as nonsmokers w/ COPD.
history of neonatal hepatitis w/ cholestasis should heighten suspiscion
fever, jaundice, and anorexia in an IV drug user?
acute viral hepatitis
histopathologic findings w/ hepatotropic viruses
panlobular lymphocytic infiltrates, ballooning hepatocytes, hepatocyte necrosis, hepatocyte apoptosis.
apoptotic hepatocytes form round acidophilic bodies = COUNCILMAN bodies, or apoptotic bodies
Kupffer cells phagocytize hepatocellular debris. may appear hypertrophied & laden w/ lipfuscin pigmen in biospy specimen.
hepatocytes accumulate hemosiderin pigment in hemochromatosis.
apoptotic hepatocytes = round acidophilic bodies
liquefactive necrosis classically occurs..
in CNS infarcts – dead tissue digested and removed by autolytic mechanisms. also occurs in suppurative bacterial infxn –> degradation via heterolytic mechanisms
inflammation and necrosis of arterial walls in vasculitis. immune complex, complement, and plasma proteins form fibrin-like eosinophilic deposits
verapamil often used for
rate control in atrial fibrillation w/ rapid ventricular response (bc blocks calcium channels in AV node).
2nd line: digoxin
contraindication to the use of non-selective beta-blockers (i.e. propanol) for atrial fibrillation?
severe COPD and asthma
most common side effect of amlodipine
lidocaine is mainly used for what cardiac problem
ventricular arrythmia, esp after an acute MI
most frequent adverse reaction to verapamil
constipation and gingival hyperplasia. also bradycardia & heart blocks
cardioselective & vascular selectivity of 3 calcium channel blockers
verapamil – most cardiac.
nifedipine – most vascular.
diltiazem – between
clinical features of melanoma (ABCDEs)
- A: asymmetry: when bisected, the 2 sides are not identical
- B: border irregularities: uneven edges, pigment fading off
- C: colour variegation: variable mixtures of brown, tan, black & red
- D: > or = 6mm
- E: lesion changing in size, shape, or colour; new lesion
melanoma commonly metastasizes to..
brain, GI, bone, liver, and lungs
melanocytes are of what embryological origin
neural crest cells
mesoderm gives rise to..
dermis, bones, muscles, blood vessels, visceral tissue
epidermis & its appendages, mammary glands (modified sweat glands), lens of eye, adenohypophysis.
most common metastatic tumors to brain are
lung, renal, and melanoma