USMLE Prep 4

DNA polymerase that functions chiefly to replace RNA primers with DNA segments

DNA pol I

Removal of RNA primers & their replacement with DNA is accompanished by

DNA polymerase I = only bacterial DNA polymerase with 5' to 3' exonuclease activity

The suprascaular nerve innervates the supraspinatus & infraspinatus, which function to

abduct & laterally rotate the arm

Abnormalities in FGF receptor result in

congenital short-limbed dwarfism = achondroplasia

Fever, rash, & acute renal failure (elevated creatinine, oliguria) occuring within few weeks of starting beta-lactam antibiotic suggests

drug-induced acute interstitial nephritis (AIN) = affects *renal interstitium* - increased levels of eosinophils & IgE serum & eosinophilia (detected by Hansel or Wright stain) - type IV HS reaction = edema & leukocyte infiltration

HBV replication sequence

dsDNA --> +RNA template --> ds DNA progeny - replicates via reverse transcriptase

Response of Cushing syndrome caused by pituitary adenoma to dexamethasone

elevated ACTH levels suppressed by high-dose, but not low-dose, dexamethasone

Most common cause of coronary sinus dilation evident on echocardiography

elevated right-sided heart pressure secondary to *pulmonary hypertension*

Improved survival when used to treat HFrEF

enalapril

Bronchial epithelium & glands derived from

endoderm

Obstruction at foramen of Magendie & Luschka would cause

enlargement of all 4 ventricles

gamma-hemolytic / no hemolysis catalase-negative organisms include

enterococci non-enterococci (S bovis)

Insulin-like growth factors (IGF-I & IGF-II) decreases collagen degradation by inhibiting

enzyme matrix metalloproteinase-13 (MMP-13) - net effect of IGF-1 on bone = anabolic

epinephrine vs NE

epi = all 4 receptors NE = alpha, alpha2, beta1

Major characteristics of Streptococcus pneumoniae

gram-positive alpha-hemolytic optochin sensitive *bile-soluble* diplococci

cryoglobulins, cold-preciptable serum proteins that contain Igs, are most commonly associated with

hepatitis C virus infection

dilated pupils, yawning, piloerection, lacrimation, hyperactive bowel sounds. History of reacreation drugs.

heroin withdrawal - peaks 24-48 hours

Vancomycin-induced red man syndrom mediated by

histamine release - via non-IgE-mediated mast cell degranulation

Preformed antibodies against graft ABO antigens cause

hyperacute graft rejection - transplanted organ becomes mottled immediately after blood vessel anastomosis - intense inflammatory response seen within hours - screen ABO blood group!

Intimal tear in Stanford type A aortic dissection (involving ascending aorta) usually originates where?

in sinotubular junction

Absolute refractory period due to

inactivation of sodium channel

Effect of mannitol on plasma osmolality & plasma ADH

increased plasma osmolality --> increases plasma ADH

Ghon complex, fibrous focus in lower lobe of lung, occurs during....

initial infection M tuberculosis - ipsilateral hilar adenopathy

scopolamine effect on digoxin

interferes with increased PR interval on ECG

bumetanide class

loop diuretic

foramen rotundum transmits

maxillary division of trigeminal nerve (CN V2) --> to pterygopalatine fossa --> courses through inferior orbital fissure --> appears on face as infraorbital foramen as infraorbital nerve

*Bronchial cartilages*, smooth muscles, CT all derived from

mesoderm

Accumulation of cerebroside sulfate in

metachromatic leukodystrophy - deficiency of arylsulfatase A - progressive demyelination = ataxia, peripheral neuropathy, seizures, hypotonia

Earliest manifestation of diabetic nephropathy

moderately increased *albuminuria* (urine albumin levels <300 mg/day)* - screening for early-stage diabetic nephropathy best achieved through use of albumin-specific urine dipsticks

cutaneous neurofibromas if neurofibromatosis type I (von Recklinghausean disease) are derived from

neural crest cells - schwann cells = cutaneous neurofibromas

Rhinovirus - sense =

positive sense, single stranded - naked/nonenveloped

Infections caused by Schistosoma, Clonorchis sinensis, & Paragonimus wetermani treated with

praziquantel

codons for: proline lysine

proline: CCU, CCA, CCG, CCC lysine: AAA, AAG normal structure of B-chain of insulin = pro-lys lispro variant of insuline = lys-pro

Mechanism of amphetamines

promotes *release* of NE - cocaine = inhibits reuptake

RNA with most extensive secondary structure

rRNA

Responsible for vast majority of renal acid excretion in chronic acidotic states?

renal ammoniagenesis - renal tubular epithelial cells metablize *glutamine* to glutamate --> ammonium excreted in urine & bicabonate absorbed in blood

What is increased in COPD?

residual volume *functional residual capacity (FRC)* total lung capacity

nissl substance in neurons corresponds to

rough endoplasmic reticulum

Glycine is derived from

serine - derived from 3-phosphoglycerate, which can be produced from glucose

myocardial stunning

within *60 seconds* - ischemia less than 30 minutes --> restoration of blood flow = reversible contractile dysfunction (myocardial stunning) --> contractility gradually returns to normal over next few hours to days - after 30 minutes of total ischemia = ischemic injury becomes irreversible

cevimeline can be used for

xerostomia

Derivatives of first pharyngela arch

trigeminal nerve mandible maxilla zygoma incus malleus Treacher-Collins - can disrupt 1st & 2nd pharyngeal arches = hypoplasia of mandibular & zygomatic bones

Ascending aorta develops from

truncus arteriosus - also gives rise to pulmonary trunk - portion of aortic arch develops from fourth branchial / pharyngela arch

branch of common peroneal nerve. provides sensory innervation to posterolateral leg.

lateral sural cutaneous nerve

CN IX is derived from what pharyngeal arch?

Third

23-year-old woman with broken nose comes to ED accompanied by boyfriend. With boyfriend present, she explains that she tripped & fell in bathroom, hitting her face on the countertop. When asked privately if she feels unsafe with her boyfriend, the patient says, "No, everything is fine. He just gets a little crazy now & then when he has too much to drink." When questioned further about how she sustained her broken nose, she says, "He pushed me & I fell, but I'm sure it won't happen again." What is the most appropriate response to the patient?

*"Do you have a safe place to go in an emergency?"* Intimal partner violence (IPV) - best initial approach = gentle, supportive, open-ended inquiry & identification of emergency safety plans - should not counsel patient in directive way - assess immediate & future safety - should be offered opportunity to speak with hospital or community-based domestic violence advocate & provided info regarding shelters

37-year-old man returns to physician because of persistent pain in his dominant hands resulting from tenosynovitis of abductor pollicis longus. He is upset because he is no longer able to play tennis & softball, which he used to do regularly. He has been treated unsuccessfully over the past 7 months with ice, exercise, immobilization, physical therapy, & 2 corticosteroid injections. He says, "You are just shuttling me around through all these worthless treatments!" What is the most appropriate resonse?

*"It has really been very frustrating to get so little help from everything we've tried."*

Physician working on a rehabilitation unit discovers that a patient is experiencing an acute allergic reaction to a med. The physician calls for nursing assistance. When the nurse arrives, the physician instructs the nurse to administer "25 mg of diphenhydramine IV push." What responses from the nurse ensures a lower risk of communication errors?"

*"Preparing 25 mg of diphenhydramine for IV push."* Closed-loop communication - individual (sender) transmitting message to another individual (receiver), who then repeats message back to sender --> sender typically will confirm message by saying "yes"

Study is conducted to assess effect of beta-blocker therapy in patients with acute MI. Study found that 20 patients out of 90 who took a beta-blocker during the week prior to to developing MI had a major arrhythmia event during hospitalization. The study also determined that 30 patients out of 70 who did not take any beta-blocker developed a major arrhythmia. What was the odds ratio of developing major arrhythmia in patients who took beta-blockers compared to those who did not take beta-blockers

*(20 x 40) / (70 x 30)* Odds ratio = probability of event happening / probability of event not happening - odds of developing major arrhythmia in exposed group = 20/70 - odds of developing major arrhythmia in unexposed group = 30/40

D-A-S-E-V-R. At physiologic pH (7.4), this hexapeptide will contain a net charge of what?

*-1* - N-terminal aspartate = positive charge on its N-terminal amino gropu & negative chrge on carboxyl group - Glutamate contains negative charge on carboxyl group of its side chain - C-terminal arginine contains negative charge on its C-terminal carboxyl group & positive charge on its side chain Overall charges = +2 & -3 = -1

The table shows survival of patients who had an operation for a particular form of cancer: Interval(years) ~ No. of pts. ~ No. of pts. ~ % of pts. Surviving this interval 0-1 300 115 62 1-2 185 37 80 2-3 148 24 84 3-4 124 18 85 4-5 106 25 76 If a patient survives 2 yrs after the operation, which of the following is the probability of surviving at least 4 years?

*0.84 x 0.85* probability of surviving first year= 100% or 1, second year is 100% too or 1, third year = 0.84 and the fourth year= 0.85 then the probability for surviving at least 4 years= 1X 1X 0.84X0.85

What is the median number of episodes of urinary tract infections for children (n=100) in the sample shown in the graph? they gave u a chart of 100 children stating that 25 children 0 had uti, 30 children 1 had uti, 10 children 2 had uti, 35 children 3 had uti.

*1* 25 children =0 episodes ,so don't include them 30 children = 1 episode, so write 30 one time = 30 10 children = 2 episodes, so write 10 two times = 10, 10 35 children = 3 episodes, so write 35 three times = 35,35,35 now arrange them all in ascending order: 10, 10, 30, 30, 35, 35, 35 MEDIAN: EXCLUDE REPEATING ONES AND ARRANGE AS 10, 30, 35 MIDDLE VALUE = 30 BAR WITH 30 IN GRAPH SHOWS 1 EPISODE

Consider reaction catalyzed by fumarase: fumarate + H2O --> malate When measured in absence of fumarase, the deltaG for this reaction is 0 kcal/mol (neglecting any terms associated with H2O). The equilibrium constant for this reaction would therefore be what?

*1.0* For -RTlnKeq to be equal to 0, the lnKeq must be 0 --> Keq = 1 (natural log of 1 = 0)

Cystic fibrosis disease incidence is 1.2500 among whites. What is the approximate carrier frequency of this mendelian trait in this population?

*1/25* q^2 = 1/2500 q = 1/50 QR: carrier frequency = 2pq --> 2q = 2 x 1/50 = 0.04

Urine: Inulin = 200 mg/dL Glucose = 0 Potassium = 50 mEq/L Uric acid = 15 mg/dL PAH = 100 mg/mL Serum: Inulin = 2 mg/dL Glucose = 80 mg/dL Potassium = 5 mEq/L Uric acid = 3 mg/dL PAH = 0.2 mg/mL Assuming a hematocrit of 50% and a urine flow of 1 mL/min, what is the best estimate of this patient's renal blood flow?

*1000 mL/min* RPF = PAH clearance = (urine [PAH] x urine flow rate / plasma [PAH] RBF = (PAH clearance) / (1 - hematocrit) = [(100 x 1) / 0.2] / (1 - 0.5) = 500 / 0.5 = 1000 mL/min

15-year-old girl has virilizing adrenal hyperplasia. Increased serum concentrations of 11-deoxycorticosterone have resulted in hypernatremia, hypokalemia, & hypervolemia. Serum ACTH concentration is increased but serum aldosterone concentration is decreased. Administration of dexamethasone normalizes ACTH, 11-deoxycorticosterone, aldosterone, & androgen concentrations. What labeled enzyme is most likely to be defective in this patient?

*11beta-hydroxylase* - decreased aldosterone - increased 11-deoxycorticosterone = increased BP - XX: virtilization - decreased cortisol - increased sex hormones - increased BP - decreased K - decreased renin activity

An enzyme catalyzing the reaction E + A --> EA --> E + P was mixed with 4 mM substrate (compound A). The initial rate of product formation was 25% of Vmax. The Km for the enzyme is what?

*12 mM* 1/4Vmax = (Vmax x 4)/(Km + 4) (Km + 4) = (Vmax x 4)/(1/4Vmax) Km + 4 = 16 Km = 12 mM

Young woman (5'3" tall, 1.6 meters) who has a sedentary job & does not exercise consulted a physician about her weight, which was 110 lbs (50 kg). A dietary history indicates that she eats approximately 100 g of cabs, 20 g of protein, & 40 g of fat daily. What is the woman's approximate daily energy expenditure in calories (kcal) per day at this weight?

*1560* kcal Daily energy expenditure (DEE) = BMR + activity = amount of energy required each day Her weight = 110 lb/2.2 = 50 kg BMR = 24 kcal/kg = 50 kg x 24 = 1200 kcal/day She is sedentary = needs only 360 additional kcal (30% of her BMR) She needs 1200 + 360 = 1560 kcal each day

Young woman (5'3" tall, 1.6 meters) who has a sedentary job & does not exercise consulted a physician about her weight, which was 110 lbs (50 kg). A dietary history indicates that she eats approximately 100 g of carbs, 20 g of protein, & 40 g of fat daily. What is the woman's BMI?

*19.5* BMI = weight (kg) / square of height of individual (m) = (50) / (1.6)^2 = 19.5 BMI ranges - underweight = less than 18.5 - pre-obesity = 25-30 - class I obesity = 30-35 - class II obesity = 35-40

13-year-old girl brought to ED by her father after he found her in a semicomatose state with an empty bottle of antihistamine beside her bed. Plasma diphenhydramine measured hourly for 6 hours are shown. Time Plasma Drug Concentration (ng/mL) 1PM 240 2PM 202 3PM 170 4PM 143 5PM 120 6PM 101 Approximately how long after the first measurement (in hours) will it take for this patient's plasma concentration to drop below 10 ng/mL?

*20* 240/2 = 120 --> t1/2 = 4 hours 100 --> 50 --> 25 --> 12.5 --> 6.5% (4 t1/2) 240 x 0.065 = 15.6% --> must be at least 5 t/12 5 t1/2s x 4 hours = *20 hours*

Acetate + 2 O2 --> 2 CO2 + 2H2O = -243 NADH + H+ + 1/2 O2 --> NAD+ + H2O = -53 FADH2 + 1/2 O2 --> FAD + H2O = -41 GTP --> GDP + Pi = -8 ATP --> ADP + Pi = -8 What percentage of energy available from oxidation of acetate is converted to ATP?

*30%* 10 ATP (7.5 from NADH, 1.5 from FADH2, 1 from GTP) produced by TCA cycle (10 x 8 kcal = 80 kcal) Percentage of total energy available from oxidation of acetate that is converted to ATP = 80/243 = 33%

A 42 yr old man needs a kidney allograft. His lymphocytes are examined by the mixed lymphocyte reaction with killed stimulator cells from himself and from each of 5 prospective donors. A donor with which of the following thymidine incorporation value (cpm) will be most compatible (the pt has a thymidine incorporation value of 425/cpm)

*312* In Mixed Lymphocyte Reaction, lymphocytes from the donor and recipient are mixed and allowed to react. If they are compatible, there will not be stimulation and the lymphocyte may not proliferate; some lymphocytes will degenerate, and the count will reduce; if they are not compatible, the donor lymphocyte will be stimulated and will start to proliferate with a increased count. You can see the only count that is smaller than the host is 312. EASY answer: *the least amount of thymidine incorporation is always less harmful to host.*

50-year-old male with a "pot belly" & a strong fam history of heart attacks is going to their physician for advice on how to lose weight. He weights 220 lbs (100 kg) & is about 6 feet tall (1.85 m). His lifestyle can be best described as sedentary. How many kcal/day would the patient need to maintain this weight?

*3120* Daily energy expenditure (DEE) = BMR + physical activity factor = 24 kcal/kg/day x 100 kg = 2400 calories per day Sedentary = 30% of BMR = 720 calories per day Overall daily needs = 2400 + 720 calories per day = 3120 calories per day

70-year-old man being treated with new antifungal drug for fungal sepsis. The drug is actively secreted by kidney & has volume of distribution of 35 L & a clearance of 690 mL/min. The half-life of the drug (in min) is closest to what?

*35* t1/2 = (0.7)(35,000) / (690) = 35 min

25-yera-old man has respiratory frequency of 10/min, a tidal volume of 550 mL, & a dead space of 150 mL. What is the alveolar ventilation (in L/min)?

*4* Alveolar ventilation (VA) = (VT-VD) x RR = (0.550 L - .150 L) x 10/min = 4 L/min Minute Ventilation = VT x RR

Infant born to 26-year-old woman. Birth weight & length are at 10th & 15th percentiles. Protruding tongue, excessive skin at nape of neck, & upslanting fissures. Startle reflex is symmetric & weak. Cardiac auscultations = harsh, III/VI systolic murmur heard best over lower left sternal border. Patient has normal external female genitalia. Review of maternal medical records shows part history of 2 spontaneous abortions in last 3 years. Echo confirms VSD. What karyotypes is most likely found?

*46, XX, t(14;21)* Down Syndrome - most commonly caused by random meiotic nondisjunction - protruding tongue - excessive skin at nape of neck - birth weight & length often below average - hypotonia - weak startle (Moro) reflex Translocated Down syndrome - less common - inherited from unaffected parent with balanced translocation - fusion of 2 long arms (14q & 21q) & fusion of 2 short arms (14p & 21p)

When does Ventricular Free Wall Rupture typically occur?

*5-14 days after acute MI* - when coagulative necrosis, neutrophil & macrophage infiltration, & enzymatic lysis of CT have substantially weakened area of infarcted myocardium - ruptures appear as slit-like tear in infarcted myocardium - leads to hemopericardium & cardiac tamponande; profound shock

If fertilization and implantation occurred in a cycle, when would the beta-hCG level first be detectable in serum?

*8 days after fertilization* - beta-hCG = most sensitive method of detecting pregnancy - urine pregnancy test = 14 days

Acetate + 2 O2 --> 2 CO2 + 2H2O = -243 NADH + H+ + 1/2 O2 --> NAD+ + H2O = -53 FADH2 + 1/2 O2 --> FAD + H2O = -41 GTP --> GDP + Pi = -8 ATP --> ADP + Pi = -8 Of the total energy available from the oxidation of acetate, what percentage is transferred via TCA cycle to NADH, FADH2, & GTP?

*86%* TCA Cycle: each turn = 3 NADH 1 FADH2 1 GTP Each NADH = 53 kcal/mol --> 3 NADH = 159 kcal/mol FADH2 = 41 kcal/mol GTP = 8 kcal/mol Energy captured = 159 + 41 + 8 = 208 kcal/mol Total energy = 243 kcal/mol Fraction of energy captured = 208/243 = 86%

56-year-old female comes to ED because of chest pain & shortness of breath. You use test X to rule out possibility of pulmonary embolus. Her result is negative. Test X has specificity of 80% and a sensitivity of 90% when tested in 100 subjects with pulmonary embolus & 100 subjects without pulmonary embolus. Assume that this patient's pretest probability for having pulmonary embolus is equivalent to disease prevalence in the study population. What is the probability that this patient truly does not have pulmonary embolus?

*89%* Negative Predictive value (NPV) of test X = d/[c+d] = true negatives/total negative tests = 80/(10 + 80) = 89% = inversely proportional to prevalence of disease NPV decreases as prevalence of disease increases

10-year-old boy, small for his age in both height & weight with calculated, projected adult height of less than 5 feet, is photophobic, & develops a "butterfly" rash over his nose & cheeks if exposed to sun. He has a high-pitched voice, large nose, prominent ears, & has had multiple pneumonias in his childhood. An exam of fibroblasts from this patient demonstrated an increases sister chromatid exchange rate during mitosis as compared to cells from a normal child. The defective enzymatic activity in this child can be traced to what activities?

*A helicase* Bloom's syndrome - defective helicase

Experimental drug has been added to eukaryotic cell, & while the drug was designed to interfere with membrane transport process, the investigators found that in cells treated with the drug the lysosomes quickly turn into inclusion bodies. None of the material directed to the lysosomes for removal was being digested in the lysosome, & remained intact inside the organelle. An analysis of lysosomal contents in drug-treated cells indicated that the full complement of lysosomal enzymes were present in the organelle. Assuming that the drug is targeting just one protein, what proteins is most likely the target?

*A proton-translocating ATPase in the lysosomal membrane* Lysosome - contains single membrane that contains proton-translocating ATPase - if intravesicular pH cannot be lowered, digestive enzymes will be inactive = no digestion will take place

Know drugs that prolong QT interval

*ABCDE*: Anti*A*rrhythmics (class IA, III) Anti*B*iotics (macrolides) Anti*C*ychotics (haloperidol) Anti*D*epressants (TCAs - *amitriptyline* Anti*E*metics (ondansetron)

23-year-old man was diagnosed as HIV positive 3 years ago. He has been on a variety of anti-HIV drugs since then, including AZT, along with some dideoxy compounds & HIV protease inhibitors. He recently developed muscle weakness, to the point where he had difficulty walking. This complication has come about due to what?

*AZT inhibition of mitochondrial DNA polymerase* AZT = DNA chain terminator with greatest affinity for viral reverse transciptase - mitochondrial DNA polymerase also recognizes & utilizes AZT as substrate --> interferes with mitochondrial DNA replication & mitochondrial division

What is the most likely cause of elevated calcium level in a patient with sarcoidosis?

*Activated macrophages* Sarcoidosis - systemic & respiratory symptoms, pulmonary infiltrates, lymphadenopathy, noncaseating granulomas - *1-alpha-hydroxylase expression in activated macrophages in lung & lymph nodes --> PTH-independent production of 1,25-dihydroxyvitamin D --> increased intestinal absorption of calcium & subsequent hypercalcemia*

45-year-old man presents with blood in his stool. Workup reveals a stage 3 (Dukes 3) colon carcinoma, with multiple polyps within the colon. A fam history reveals that his father & grandfather both had colon cancer in their fifth decade of life. A potential initiating activating event in the development of this tumor is

*Activity of beta-catenin activity* Hereditary colon cancer / Adenomatous polyposis coli - fourth or fifth decade of life - defective protein = APC = regulates beta-catenin activity - loss of APC = inappropriately activated beta-catenin --> can stimulate expression of myc & cyclin D1 = promotes cell growth

39-year-old man comes to clinic with month-long history of fever, fatigue, joint pain, & urticarial skin rash. He did not seek attention immediately as he hoped his symptoms would resolve. Patient is generally improving but still very easily fatigued. Past medical history is unremarkable & patient takes no regular meds, although he has not seen a physician since early childhood. He is not married & has a history of multiple heterosexual partners. Patient recently stopped smoking, drinks alcohol socially & does not use illicit drugs. Physical exam is notable for moderately enlarged & tender liver. No jaundice is seen. Lab studies show significant elevations in serum ALT & AST. What is the most likely diagnosis in this patient?

*Acute hepatitis B* Acute hepatitis B - system, skin, & joint symptoms - hepatomegaly - elevated transaminase levels - may develop serum-sickness-like syndrome = joint pain, lymphadenopathy, pruritic urticarial vasculitis rash - RUQ pain may be present = DNA virus with incubation period of 30-180 days TRANSMISSION - sexually, parenterally, vertically = *B*aby-making, *B*lood, *B*irthing

19-year-old woman comes to the emergency department because of right lower abdominal pain for 10 hours. Her temperature is 39°C (102.2°F). Abdominal examination shows rebound tenderness of the right lower quadrant. She is admitted to the hospital, and an emergency exploratory operation is done. A photograph of the removed appendix is shown. Which of the following best describes the process involved in her condition? (pic of appendix shown)

*Acute inflammation* Acute Appendicitis - most common cause of acute abdomen - periumbilical pain, fever, nausea - RLQ pain eventually - rupture in peritonitis = guarding & rebound tenderness - periappendiceal abscess = common complication

55-year-old woman comes to physician because of persistent cough & recent, unintentional weight loss. She has never smoked & has no history of exposure to industrial pollutants. Physical exam reveals decreased breath sounds & dullness to percussion at left lung base. Imaging studies show irregular mass in lower lobe of her left lung & a left-side pleural effusion. A diagnostic thoracocentesis is performed & the aspirated fluid is sent for cytological evaluation. If a malignancy is diagnosed, it is most likely to be what type?

*Adenocarcinoma* - most common type overall - most frequently in women & nonsmokers - forms glandular or papillary structures

Treatment of Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency is target at directly suppressing what hormones?

*Adrenocorticotropic hormone* - defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol --> impairs cortisol synthesis - decrased cortisol sensed by hypothalamus = increase in ACTH secretion by anterior pituitary Treatment: low doses of exogenous corticosteroids to suppress ACTH secretion

45-year-old man referred to endocrinology for newly diagnosed diabetes mellitus. A week ago, his primary care physician noted an elevated fasting serum glucose level. The endocrinologist discussed the diff't treatment options available, including oral & injectable meds. He recommends treatment with a med that alters glucose metabolism within liver by increasing concentration of fructose 2,6-bisphosphate within hepatocytes. What conversions will be inhibited by high intracellular concentrations of this metabolite?

*Alanine --> glucose* Fructose-2,6-bisphosphate - controls balance between gluconeogenesis & glycolysis via inverse regulation of PFK-1 & fructose 1,6-bisphosphatase - activates PFK-1 = main regulatory enzyme in glycolysis --> converts fructose 6-phosphate to fructose 1,6-bisphosphate - interconversion of fructose-6-phosphate & fructose 2,6-bisphosphate achieved by bifunctional enzyme complex PFK-2 (increases fructose 2,6-bisphosphate levels) & fructose 2,6-bisphosphatase (decreases fructose 2,6-bisphosphate levels) Insulin - activates PFK-2 --> increased fructose 2,6-bisphosphate levels & augmented glycolysis - *high fructose 2,6-bisphosphate inhibits gluconeogenesis --> decreased conversion of alanine & other gluconeogenesis substrates to glucose*

32-year-old male is on a weight maintenance diet, so he doesn't want to lose or gain any weight. What amino acid must be present in the diet so the patient does not go into negative nitrogen balance?

*Alanine* - can be synthesized from pyruvate via transamination, which can be derived from glucose - the major gluconeogenic amino acid - 50% of amino acid released into blood from muscle are alanine & glutamine - alanine released by muscle is also produced by glucose-alanine cycle = involves transport of glucose from liver to muscle & return of carbon atoms to liver as alanine

27-year-old male became lost while hiking in Yosemite Nat'l Park. He was found eight days later. He had nothing to eat & only water to drink before being rescued. What lab tests should be run on the patient to determin eif her is suffering from overall protein malnutrition?

*Albumin* - standard for assessing overall protein malnutrition - made by liver & found in blood - non-specific carrier of FAs & other hydrophobic 'cules - when AAs become limiting, liver reduces levels of protein synthesis

52-year-old man with alcoholism comes to physician for follow-up exam. He has HT, type 2 diabetes mellitus, osteoarthritis, & dyslipidemia. Current meds include metformis, glyburide, metoprolol, & sildenafil. Three months ago, he began to follow a diet recommended by American Heat Association because of increased serum LDL-cholesterol concentration. He has been adherent with this new regimen. His BP is 135/85 mmHg. Physical exam shows spider angiomata on the face. Fasting studies show a serum LDL-cholesterol concentration of 148 mg/dL. The physician is considering prescribing pravastain. This drug should be used with caution because of adverse effects associated with what conditions?

*Alcoholism* Since statins are *hepatotoxic*, they should be used with caution in pts with liver disease and alcoholics This patient has "spider angiomata" (cirrhotic liver)

6-month-old boy brought to ED by his mother because of recent onset of vomiting, irritability, & jaundice. The infant was born at term & had been healthy until onset of these symptoms. All vaccinations are up-to-date. He had been breast-fed exclusively until 1 week ago, when cereals & fruit juices were introduced into his diet. Further evaluation reveals hepatomegaly & abnormal liver function tests. What enzymes is most likely to be deficient in this patient?

*Aldolase B* Hereditary Fructose Intolerance - vomting, hypoglycemia 20-30 minutes after fructose ingestion - hypoglycemia via intracelular accumulation of fructose-1-phosphate --> inhibits gluconeogenesis & glycogenolysis

52-year-old woman comes to the physician because of pain in her right knee. The knee is red, warm, & swollen. Serum uric acid concentration is 11.4 mg/dL. Joint fluid aspirate shows negatively birefringent crystals. Indomethacin therapy is started & she begins a purine-restricted diet. One week later, her 24-hour urinary acid excretion is 800 mg/day (N = 300-600 mg/day). What drugs is most appropriate to decrease the serum uric acid concentration in this patient?

*Allopurinol* - used prophylactically to treat chronic, tophaceous gout because it reduces size of established tophi - acute gout treated with nonsalicylate NSAIDs, indomethacin, or with colichicine - chronic gout is treated with uricosuric agent probenecid or sulfinpyrazone, which increases elimination of uric acid, or febuxostat or allopurinol, which inhibits uric acid production

Many human genes encode more than one polypeptide sequence. What mechanisms accounts for the production of more than one protein by one human gene in many cases?

*Alternative splicing of transcript* THIS IS EUKARYOTIC - *P*rokaryotes do *P*olycistronic - *Humans do alternative splicing* = why we have introns & extrons

Bronchoalveolar lavage fluid obtained from 34-year-old healthy volunteer contains elastase. This enzyme is most likely derived from what cells?

*Alveolar macrophages* Elastase - neutral protease - contained in macrophage lysosomes & in azurophilic (primary) granules of neutrophils - inhibited by serum alpha1 antitrypsin & macrophage elastase - excess = centriacinar & panacinar emphysema

Eukryotic signs peptide located at when terminus?

*Amino terminus*

35-year-old man brought to ED after ingesting unknown quantity of his antidepressant medicine. He is comatose & having intermittent seizures. ECG shows sinus tachycardia with 2:1 AV block & prolonged QRS duration . What drugs is most likely cause of these findings?

*Amitriptyline* - can induce seizures - can prolong QT interval = antidepressants

45-year-old woman comes to physician because of increasingly severe episodic pain in her muscles and joints since undergoing a divorce 6 months ago. She says, "I've been struggling with these symptoms for over 10 years, but they have just gotten worse since I've been on my own." She also has had problems sleeping during this period. Physical exam shows no swelling, tenderness, or joint effusion; however, symmetric tender points are elicited upon palpation of the lateral aspects of the neck muscles, shoulders, & inner thighs. Lab studies show erythrocyte sedimentation rate of 10 mm/h. What is the most appropriate pharmacotherapy for this patient?

*Amitriptyline* Fibromyalgia - women 20-50 - chronic, widespread musculoskeletal pain - tender points - stiffness - paresthesias - poor sleep - fatigue - cognitive disturbance (fibro fog) Treatment - exercise, antidepressants (TCAs, SNRIs), anticonvulsants

An infant with an inherited defect in ornithine transcarbamoylase is most likely to have an increased plasma concentration of what?

*Ammonia* Ornithine transcarbamylase deficiency - kidney stones - COLA - cysteine, ornithine, lysine, arginine

The precipitating event in the cows brain which leads to Mad Cow Disease is what biochemically?

*An altered secondary & tertiary structure for an existing brain protein*

Pharmaceutical researcher is studying target protein involved in signal transduction & cellular response to TSH. The protein is isolated & purified form thyroid follicular cells. Further analysis reveals that the protein contains multiple alpha-helical regions. Each of these regions is composed of 20 amino acid residues consisting primarily of valine, alanine, & isoleucine. This particular region of the protein most likely performs what functions?

*Anchoring to the cell membrane* G protein-coupled receptors - 3 major domains = extracellular (ligand binding), transmembrane domain, intracellular domain (coupled with heterotrimeric G proteins Transmembrane domain = nonpolar, hydrophobic AAs (alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, glycine) - arranged in alpha-helical fashion --> project hydrophobic R groups outwardly, anchoring transmembrane region of protein to hydrophobic core of phospholipid bilayer

18-year-old man has an appendectomy. Two weeks later, the abdominal incision has healed well & has a pink, shiny, granular appearance. What findings is most likely on exam of tissue obtained from the healing area?

*Angiogenesis* Phases of wound healing: Inflammatory = up to 3 days after wound = clot formation, increased vessel permeability & neutrophil migration into tissue; macrophages clear debris 2 days later *Proliferative* = *day 3 - weeks after wound* = deposition of granulation tissue & type III collagen, *angiogenesis*, epithelial cell proliferation, dissolution of clot, wound contraction - delayed wound healing in vitamin C & copper deficiencies Remodeling = type III collagen replcaed by type I collagen, increased tensile strength of tissue - delayed wound healing in zinc deficiency

Patient has CHF. Levels of what substances in RAAS system will be higher in pulmonary vein compared to pulmonary artery in the patient?

*Angiotensin II* Ang I converted to Ang II, primary within small pulmonary vessels by endothelial-bound Ang-converting enzyme --> Ang II = potent vasoconstrictor of systemic circulation = increased BP / increased afterload --> worsens cardiac output

Urge incontinence, or overactive bladder syndrome, is caused by uninhibited bladder contractions (detrusor instability). It results in a sense of urgency accompanied by an involuntary loss of urine. If behavioral therapy alone is unsuccessful, pharmacologic therapy with what receptor can help improve symptoms?

*Antagonism of muscarinic cholinergic receptors* Oxybutynin, Solifenacin, Tolterodine - antagonizes M3 on smooth muscle cells in bladder --> decreases production of IP3 & release of calcium --> smooth muscle relaxation

46-year-old patient comes to his doctor's office & complains of chest pain & headache. His CT scan reveals a tumor located just superior to the root of the right lung. Blood flow in what veins is most likely blocked by this tumor?

*Arch of the azygos vein* Azygos vein - arches over root of right lung --> empties into SVC

A 74 old man unable to repeat phrases and name objects after having a left sided stroke. Although reading comprehension is preserved, he has difficulty reading aloud and writing. His speech is fluent and his comprehension is normal . which is the following structures is most likely damaged?

*Arcuate fasciculus*

What is the best determinant of oral bioavailability via graph?

*Area under oral curve divided by area under IV curve* Bioavailability = fraction of administered drug that reaches systemic circulation in chemically unchanged form = always less than 1 = (AUC oral x dose IV) / (AUC IV x dose oral) IV: F = 1 Oral, IM, inhalation, topical = F < 100%

67-year-old male presents to your office with history of progressive dyspnea. He cannot tolerate moderate exertion & sleeps in a half-sitting position due to orthopnea. He has also noticed some swelling of his ankles. He does not smoke or consume alcohol. His past med history is significant for hypercholesterolemia & recurrent chest pain. What do you expect to be increased in this patient?

*Arteriolar resistance* Left-sided CHF - dyspnea on exertion, orthopnea (dyspnea while lying flat), & paroxysmal nocturnal dyspnea (waking from sleep gasping from air) - most common cause of RHF = LHF Decreased cardiac output --> RAAS --> increased sympathetic output = increased arterial resistance (afterload) = exacerbates heart failure

Several months to years after ischemic brain infarction, the necrotic area appears as a cystic cavity surrounded by a wall composed of dense fibers formed by

*astrocytes* / astrocytic processes / glial scar

65-year old man found to have iron deficiency anemia. He has no cough, abdominal pain, melena, change in bowel habits but reports anorexia & a 5-kg (11-lb) weight loss in past 2 months. Cardiopulmonary & abdominal exams are unremarkable. Rectal exam shows guaiac-positive brown stool. A 3-cm mass is found on colonoscopy. Biopsy shows pleomorphic cells with large, dark nuclei forming irregular, crowded glands, some of which contain mucus. Imaging studies reveal multiple mass lesions in the liver & lungs. This patient's neoplasm most likely originated from what locations?

*Ascending colon* / Right-sided colon cancer - large, bulky masses that protrude into colonic lumen - more likely to bleed

55-year-old woman with advanced metastatic breast cancer develops dyspnea & tachycardia. An echocardiogram confirms presence of pericardial effusion. During morning rounds, the medical attending informs the patient that a pericardiocentesis is needed. The attending is then called to the ED to assist with urgent case. On his way out, he asks the intern to obtain informed consent for the procedure. The intern obtains appropriate consent forms describing the procedure. She has never performed or observed a pericardiocentesis but remembers reading about it in a book last year. What is the most appropriate course of action by the intern?

*Ask the supervising resident to assist in obtaining informed consent for the pericardiocentesis* - ideally, informed consent should be obtained by person performing procedure - at minimum, provider taking consent should have thorough understanding of procedure & be able to answer patient's questions

52-year-old Caucasian male presents to your office complaining of periodic substernal chest pain that is precipitated by fast walking, especially uphill & against the wind. The pain remits following 5 minutes of rest. The patient has a history of HT & smokes one pack of cigarettes per day. His BP is 140/80 mmHg & his pulse rate is 80 beats per minute. His lungs are clear to auscultation, & no heart murmurs are heard. There is no peripheral edema. What is the most likely pathogenetic mechanism of this patient's condition?

*Atherosclerotic plaque obstructing 80% of the coronary artery lumen, no thrombus* Stable/Chronic Angina - deeply, poorly localized chest or arm discomfort (angina) - reproducibly associated with physical exertion or emotional stress - relieved within 5 minutes by rest &/or sublingual nitroglycerin

35-year-old woman is brought to ED after having a stroke. Evaluation shows intermittently decreased left ventricular filling. What best explains her condition?

*Atrial myxoma with systemic embolization* - 75% of myxomas occurin left atrium

67-year-old man brought to ED by his son after syncopal episode. Son was helping his father clean out his garage when his father complained of dizziness. As his son was helping him into a chair, the patient lost consciousness. He woke up spontaneously about a minute later without any disorientation or confusion. An ECG demonstrates bradycardia with regular rhythm & narrow QRS complexes. What locations is most likely responsible for pacing his patient's ventricles?

*Atrioventricular node* = 45-55 beats/min Third degree/complete heart block - SA node impulses cause atrial contraction while impulses generated by AV node cause ventricular contraction - atrial & ventricles depolarize independently of each other = AV dissociation - QRS complexes narrow since ventricular depolarization normal

45-year-old man with acute inferior wall infarct has hypotension secondary to sinus bradycardia. What drugs is most appropriate for this patient?

*Atropine* - blocks effects of ACh - elevates sinus rate & AV nodal & SA conduction velocity - decreases refractory period - used to treat bradyarrhythmias that accompany MI

A previously healthy 42-year-old woman has a 6-week history of fatigue, light headedness and shortness of breath. Laboratory studies show: Hematocrit-----25% Hemoglobin-----8.3 g/dl Leukocyte count----10,000/mm3 Platelet count-------250,000/mm3 Reticulocyte count-----4% Total serum bilirubin----3mg/dl Direct serum bilirubin---0.3mg/dl Urine urobilinogen------2+ A peripheral blood smear shows microspherocytes. Which of the following is the most likely cause of the anemia?

*Autoimmune hemolysis* - reticulocyte count >3% = over-production - indirect hyperbilirubinemia with urine urobilinogen = extravascular hemolytic anemia - presence of spherocytes & normal WBC & platelet count - normal spleen

Patients with CD4+ counts <50 cells/uL should be administered with

*Azithromycin* - prevents Mycobacterium avium complex (MAC) - common opportunistic pathogen of HIV pathogens MAC - fever, weight loss, diarrhea - anemia, hepatosplenomegaly, elevated alkaline phosphatase & lactase dehydrogenase via widespread involvement of reticuloendothelial system - grows well at high temperatures - optimum growth at 41 C - *resistant o many typical antimycobacterial drugs --> disseminated infection treated with clarithromycin or azithromycin in combo with rifabutin or ethambutol*

68-year-old man experiences increasing urinary frequency & difficulty starting & stopping his flow of urine. Exam of tissue obtained on biopsy of the enlarged prostate confirms benign prostatic hyperplasia. What is the most likely complication of his basic disease state?

*Bacterial cystitis*

Cell line is infected with virus obtained from 45-year-old male. Analysis of the progency viruses demonstrates that the phospholipid composition of the viral particle surface is highly similar to that of the cell nuclear membrane. The patient is most likely infected with:

*Cytomegalovirus* Most enveloped nucleocapsid viruses acquire lipid bilayer envelope by budding through plasma membrane of host cell - exceptions = *herpesvirus* --> bud through & acquire envelope from host cell nuclear membrane

Transgenic mice generated that are incapable of expressing beta2-microglobulin. What components of host defense is most likely to be altered in these mice?

*Cytotoxic T lymphocytes*

33-year-old woman with 9-year history of ulcerative colitis visits her physician because she is concerned about her risk of colon cancer. Her concern is ppted by recent death of one of her close fam-friends from colon cancer. She says that she wants to "undergo all the tests for colon cancer." Review of her med history shows that she has no other co-morbid conditions & that she is currently under the care of a gastroenterologist who has kept her disease well-controlled with sulfasalazine. Compared to sporadic colorectal carcinoma, colorectal malignancy arising in this patient would most likely exhibits what features?

*Be multifocal in nature* CRC = most common type of malignancy in patients suffering from IBD, particularly UC Colitis-associated carcinoma - young patients - progresses from flat & non-polypoid dysplasia - mucinous &/or signet ring morphology - develop early p53 mutations & late APC gene mutations - distributed within proximal colon (especiall Crohn's or concurrent primary sclerosing cholangitis) - *multifocal in nature* Colorectal carcinoma in IB - usually 10 years after - pancolitis = highest risk of CRC

70-year-old man comes to physician because of a 2-year history of urinary hesitancy & frequency. He states that he wakes two to three times a night to void, & that during the past year he has had intermittent pain with urination. Physical exam shows no abnormalities. Results of urinalysis are within reference range. Ultrasonography of abdomen shows bilateral dilation of renal collecting system. What is the most likely diagnosis?

*Benign prostatic hyperplasia*

26-year-old man comes to ED due to chest pain, palpitations, shortness of breath, & sweating. He has been to ED twice in past month for similar symptoms. The patient has no other med problems. Fam history is not significant. BP is 140/90 mmHg, pulse is 96/min, & respirations are 20/min. ECG is normal. The patient is tremulous & says, "I feel like I'm going to die." What is the most appropriate next step in management?

*Benzodiazepine administration* - *rapid* relief of symptoms Panic disorder - recurrent episodes of chest pain, tachycardiac, shortness of breath, sweating, tremulousness in young, otherwise healthy patient with normal ECG - unexpected onset of intense anxiety - peak within minutes - somatic presentations common - fears of dying from heart attack may prompt patient to go to ED

55-year-old man develops shortness of breath. Exam shows a harsh systolic ejection murmur at the base that radiates to neck. ECG shows evidence of prominent left ventricular hypertrophy. What cardiac abnormalities is most likely?

*Bicuspid aortic valve* Increases risk & hastens aortic stenosis - crescendo-decrescendo systolic ejection murmur - LV > aortic pressure during systole - loudest at heart base - radiates to carotids

52-year-old postmenopausal woman comes to office for evaluation of several months of episodic abdominal discomfort & nausea, especially after a fatty meal. She has no past medical history & does not use tobacco, alcohol, or illicit drugs. Her BMI is 33 kg/m^2. Physical exam shows a soft, nontender abdomen with normal bowel sounds. Liver span is 8 cm. Murphy sign is negative. Abdominal x-ray reveals no calcifications, but abdominal ultrasound shows small, non-obstructing gallstone. The patient prefers nonoperative management. What would best treat this patient's condition?

*Bile acid supplement* Normall, bile acids & phospholipids solublize cholesterol to prevent stone formation Hydrophic bile acids = ursodeoxycholic acid - reduces cholesterol secretion & increases biliary bile acid concentration - promotes gallstone dissolution

45-year-old man comes to physician due to pain, swelling, & erythema affecting his right leg. He says that he suffered a minor cut to his leg a few days ago while cleaning his garage. Physical exam shows an indurated region surrounding a minor laceration that is draining a purulent exudate. He is diagnosed with cellulitis & started on the appropriate treatment. Gram stain of the exudate shows gram-positive cocci in clusters. The organism most likely responsible for this patient's infection synthesizes a protein as part of its peptidoglycan cell wall that does what?

*Binds the Fc portion of IgG* Staph aureus: Protein A - virulence factor that forms part of outer peptidoglycan layer of S aureus - binds with Fc portion of IgG Abs at complement-binding site = prevents complement activation = decreased C3b = impaired opsonization & phagocytosis

argatroban has what mechanism of action?

*Binds to thrombin active site* Direct thrombin inhibitors = hirudin, lepirudin, argatroban - don't require AT-III for action = drugs of choice for HIT (stop heparin!)

26-year-old man brought to ED by police after assaulting customers in a restaurant. He explains that he meant no harm & was trying to talk to people & touch them to "heal their pain." The patient says he has been up all night for the past week devising a global strategy to end world hunger. He hears a voice telling him that he is "God's true son" and will need to sacrifice his life. The patient has no psychiatric or medical history. Fam history is significant for postpartum psychosis in his mother. He drinks alcohol socially but does not use illicit drugs. Physical exam is normal. On mental status exam, the patient is disheveled & paces continuously. His mood is very irritable & his speech is loud, rapid, & difficulty to interrupt. What is the most likely diagnosis?

*Bipolar I disorder with psychotic features* Manic episodes - can occur with or without psychotic features (delusions, hallucinations) - delusions = mostly congruent (grandiose themes involving special talent & powers)

Recognize *chemoreceptor trigger zone*, located on dorsal surface of medulla at caudal end of fourth ventricle

*D* - region = area postrema - receives blood from fenestrated vessels (where there is no BBB) = allows it to sample chemicals circulating in blood - acute nause following chemo = stimulation of CZT

Km for fumarase is approximately 5 uM for fumarate. The fumarate concentration in mitochonodria is 2 mM. If the fumarate concentration dropped to 1mM, the reaction rate would change in what ways?

*Decrease slightly* v = (Vmax x 2000 uM)/(5 uM + 2000 uM) = 99.8% Vmax Drops to 1... v = (Vmax x 1000 uM)/(5 uM + 1000 uM) = 99.5% Vmax Very slight decrease in velocity when [S] reduced from 2 to 1

29-year-old woman comes to office due to depression. Since breaking up with her boyfriend last month, she has been extremely sad & has difficulty getting out of bed. She describes sleeping 16 hours a day, increased appetite, 10-lb (4.5-kg) weight gain, low energy, decreased concentration, & loss of interest in socializing with her friends or fam. The patient has had several similar episodes in the past. When asked to describe the last time she felt well, she mentions a period of several weeks last year when she felt uncharacteristically confident & optimistic, was successfully juggling 3 part-time jobs, & felt well rested & energetic despite sleeping only 3-4 hours a night. The patient drinks 2 or 3 glasses of wine on weekends but does not use tobacco or illicit drugs. What is the most likely diagnosis?

*Bipolar II disorder* - current major depressive episode (>2 weeks, depressed mood, low energy, hypersomnia, increased appetite, decreased concentration, loss of interest) - past history suggestive of hypomanic episodes = lesser degree of severity, absence of psychosis = noticeable change in behavior but often very productive despite requiring less sleep - not manic episodes

49-year-old man comes to office due to 4 months of cough & weight loss. His med history is otherwise unremarkable & he takes no meds. The patient is a farmer who lives in Mississippi. He does not use tobacco, alcohol, or illicit drugs. His temp is 37.9 C (100.2 F). Exam shows right lobe crackles. Chest x-ray reveals a pulmonary infiltrate in the right upper lobe. Bronchoscopy with transbronchial biopsy shows granulomatous inflammation. HIV testing is negative. What is most likely causing this patient's symptoms?

*Blastomyces dermatitidis* - dimorphic fungus - can cause pulmonary infectionsin immunocompetent people - endemic areas = states adjacent to & east of MS & Ohio river valleys - some overlap with Histoplasmosis - env't = mold form - via resp route --> lungs --> transforms into yeast form = thermal dimorphism - can mimic pneumonia - pulmonary = granuloma formation - extrapulmonary = skin, bone, genitourinary - broad-based budding - treatment = itraconazole

Mechanism of drug of choice for absence seizures

*Blocks T-type Ca2+ channels & decreases calcium current in thalamic neurons* ADRs - GI symptoms - drowsiness

35-year-old woman with primary pulmonary hypertension undergoes an uncomplicated right lung transplantation. One month later, her FEV1 is normal, & an exercise stress test shows no abnormalities. What is most likely to be increased in the transplanted lugn compared with the left lung?

*Blood flow* Pulmonary Hypertension - underlying pathophysiology = restricted flow through pulmonary vasculature with elevation in vascular resistance

37-year-old house painter fell from a ladder & fractured his left third rib & the structures with which it articulated. What structures would most likely be damaged?

*Body of the second thoracic vertebra* Third rib articulates with... - body of sternum - *bodies of second & third vertebra* - transverse process of third thoracic vertebra

65-year-old man comes to ED with sore on his right hands. He is in the wool business & has recently returned from a tour of wool-processing plants in several Asian countries. Physical exam shows ulcer with black eschar & significant surrounding edema. The toxin causing edema around this patient's ulcer has mechanism of action most similar to different toxin produced by what bacteria?

*Bordetella pertussis* - produce, in addition to pertussis toxin, an exotoxin called *adenylate toxin* = calmodulin -dependent adenylate cyclase --> phagocyte dysfunction & edema Bacillus anthracis = 2 main virulence factors - antiphagocytic poly-gamma-D-glutamic acid capsule - anthrax exotoxin = trimeric toxin = protective antigen, edema factor, lethal factor Protective antigen - translocates both edema & lethal factor into cytosol --> once inside cells, *edema factor* acts as calmodulin-dependent adenylate cyclase --> increases cAMP concentration

62-year-old man comes to physician because of intermittent groin pain. He is a construction worker & says that the pain is worse when lifting heavy loads & after a long day of working. Physical exam shows bulge above inguinal ligament. The bulge increases in size when he bears down. A groin ultrasound reveals that the mass originates medial to inferior epigastric vessels. This patient's condition is most likely caused by what?

*Breakdown of transversalis fascia* Direct inguinal hernias - protrude through Heseelbach's triangle (transversalis fascia = floor of triangle) - more common in elderly - only pass through superficial inguinal ring - covered by external spermatic fascia only

Four days after admission to the hospital with multiple fracture sustained in a motor vehicle collision, a 27-year-old man has sudden onset of shortness of breath. His respirations are 30/min. Doppler ultrasonography of the lower extremities shows deep venous thrombosis, & a spiral CT scan of the chest shows evidence of multiple subsegmental pulmonary emboli. Anticoagulant therapy is begun. One week later, a follow-up CT scan of the chest is done to evaluate atypical chest pain. Results show no abnormalities, & the pain was considered to be musculoskeletal. Collateral circulation from what best explains the lack of identifiable pulmonary parenchymal infarcts in this patient?

*Bronchial arteries* - arise from thoracic aorta - usually there is one artery for right lung & two for the left lung - supply oxygenated blood to nonrespiratory conducting tissues of lungs & visceral pleura - *anastomoses occur between capillaries of bronchial & pulmonary systems*

8-year-old boy has failure to thrive, alopecia totalis, localized scleroderma, small face & jaw, "beak" nose, wrinkled skin, & stiff joints. He is determined to have a single-point mutation in nuclear protein, which is a silent mutation in terms of primary structure of protein. How could such a mutation lead to a disease?

*By creating alternative splice site in gene* Hutchinson-Gilford progeria - premature aging disease - mutation in LMNA gene, which encodes lamin A, a nuclear protein - most common mutation = C1824T = normal cytosine at position 1,824 replaced by thymine

47-year-old man brought to ED after vein involved in high-speed motor vehicle collision. He was a restrained driver & rear-ended slow-moving car on highway. He complains of chest pain, abdominal pain, & difficulty breathing. The patient has a med history of HT, asthma, & type 2 diabetes mellitus. On arrival, his BP is 98/54 mmHg & pulse is 121/min. Thirty minutes later, he becomes unresponsive & his pulse is no longer detectable. ECG demonstrates sinus tachycardia. Despite extensive resuscitation efforts, the patient dies. An autopsy would most likely show an injury involving what areas of the thoracic aorta?

*C* Blunt aortic injury / Traumatic aortic rupture - most commonly caused by motor vehicle collisions - via sudden deceleration - injury most often occurs as *aortic isthmus* = tethered by ligamentum arteriosum = relatively fixed & immobile - majority of patients die before reaching hospital - may see *widened mediastinum* on chest x-ray

32-year-old woman comes to office due to progressive exertional dyspnea & easy fatigability. She immigrated to the US from India several years ago & reports a history of rheumatic fever during her childhood. Cardiac auscultation reveals a diastolic high-frequency sound & a rumbling diastolic murmur heard best in the left fifth intercostal space at the midclavicular line. Cardiac catheterization performed for hemodynamic evaluation, & the results are shown in tracing (flip to see). Timing of high-frequency sound heard during cardiac auscultation of this patient best corresponds to what letter?

*C* Mitral stenosis - diastolic murmur at cardiac apex - elevated pressure gradient between left atrial & left ventricular end-diastolic pressure - loud first heart sound - early diastolic high-frequency opening snap after S2 - low-pitched diastolic rumble

What best describes the mechanism of liver injury in a patient with Hepatitis B?

*CD8+ T lymphocytes response to viral antigens on cell surface resulting in hepatocyte damage* Hepatitis B = proliferative phase; integrative phase Proliferative phase - hepatocyte surface: viral HBsAg && HBcAg expressed in conjugation with MHC I --> activates CD8+ T cells --> destroy infected hepatocytes - virion itself does not have cytopathic effect

The opening of what types of ion channel is required for release of NT from a synaptic ending?

*Ca2+ channel* Synapsin I = protein associated with vesicle membrane --> binds to actin (cytoskeletal filament holding vesicles in place) Calcium = vital element in process of NT release - when Ca2+ channels are blocked, NT release is inhibited

An 8-year-old male is brought to the ER with a two day history of fever, abdominal pain & diarrhea. Careful history taking reveals that the patient's pet puppy had diarrhea one week ago. Aside from the present episode, the patient has no significant past medical history & all of his vaccinations are up-to-date. His stool is negative for ova & parasites. What is the most likely cause of this patient's symptoms?

*Campylobacter* - can be transmitted from domestic animals (cattle, sheep, dogs, chickens) to humans - contaminated food (undercooked poulty, unpasteurized milk) - corkscrew fashion - acute gastroenteritis in children & adults in industrialized countries - inflammatory diarrhea = initially water, later bloody

Drugs that can cause SIAD

*Carbamazepine*, Cyclophosphamide, SSRIs ADH - synthesized within magnocellular neurons found in supraoptic & paraventricular nuclei of hypothalamus - most magnocellular neurons produce either vasopressin or oxytocin --> translated --> packaged into vesicles --> travel via anterograde axonal transport to posterior pituitary --> terminate into Herring bodies

It has been determined in healthy volunteers that the chloride content of erythrocytes is much lower in arterial blood than in venous blood. The action of what is mostly responsible for the observed difference?

*Carbonic anhydrase* - hemoglobin carries 15% of CO2 as carbamate - CO2 produced by tissue respiration --> enters RBCs --> hydrates by carbonic anhydrase to form carbonic acid --> carbonic acid undergoes spontaneous conversion to HCO3- & H+ --> many bicarb ions diffuse out of RBC into plasma To maintain electrical neutrality, chloride ions diffuse into RBC to take their place = chloride shift = high RBC content in venous blood

34-year-old man comes to ED with fatigue & lightheadedness. The patient had an upper respiratory infection last week, & since then his energy level has been low with shortness of breath on mild exertion. Otherwise, his medical history is insignificant. He is a lifetime nonsmoker. The patient's temp is 37 C (98.6 F), BP is 80/60 mmHg, & pulse is 120/min & regular. His pulse becomes undetectable to palpation during inspiration. The lungs are clear to auscultation, but the jugular veins are distended. What is the most likely diagnosis?

*Cardiac tamponade* - hypotension, tachycardia, jugular venous distention with clear lungs, & pulsus paradoxus (loss of palpable pulse during inspiration) - most likely due to patient's recent viral illness = viral pericarditis with significant pericardial fluid accumulation - pulsus paradoxus = abnormal exaggerated decrease in systolic BP >10 mmHg on inspiration

It is estimated that for paraaminohippuric acid (PAH), the extraction ratio (arterial plasma PAH minus venous plasma PAH divided by arterial plasma PAH) is near 90% at arterial plasma concentrations lower than 20 mg/dL. Once the plasma concentration of PAH is increased above this level, the extraction ratio decreases progressively. What best explains the observed decrease in the PAH extraction ratio?

*Carrier transport is saturated* PAH - organic acid - filtered from blood in glomerulus - secreted by cells lining proximal tubule of nephron - calculated clearance of this acid can be used to estimate *RPF* - filtration of PAH is not a process that can be saturated - *secretion is a carrier enzyme-mediated process = able to be saturated* - *as blood concentration of PAH increases, secretion of PAH by proximal tubular epithelial cells increased - but only up to max value of 80 mg/min* - max secretion rate corresponds with transport maximum (TMAX) of secretion enzymes = secretion plateaus; any increases in urine PAH concentration due to increased filtration

Fungal cultures grow a species of Candida with a mutation in a gene encoding an enzyme responsible for synthesizing a fungal cell wall polysacharide. The organism is most likely to be resistant of what antifungal agents as a result of this mutation?

*Caspofungin* - most active against Candida species & Aspergillus Echinocandins - block glucan synthesis - suppress fungal cell wall synthesis

A new antibiotic has been developed which shows a strong affinity for attacking amino acids with a specific orientation in space. In order for it to work well in humans, the antibiotic must be effective against amino acids in what configurations?

*D-configuration* - amino acids in humans = L configuration (except glycine which is neither L nor D) - bacterial amino acids = either L or D configuration - antibiotic needs to be effective against bacterial proteins & not human proteins

Specific enzyme is responsible for removing short fragments of RNA that are base paired to DNA template. What enzymes is most likely deficient in this strain of E coli?

*DNA polymerase I*

48-year-old man comes to hospital after day of high-grade fever, progressive headache, & double vision. The patient has been having purulent nasal discharge and frontal headache for the past several days. He has a history of type 2 diabetes mellitus. His temp is 38.9 C (102 F), BP is 110/70 mmHg, & pulse is 94/min. Physical exam shows ptosis, mydriasis, mild proptosis, & loss of corneal reflex of the right eye. Visual acuity is normal in both eyes, but the patient is unable to move the right eye in any direction. There is decreased sensation in the right upper face. What structures is most likely involved in this patient's presentation?

*Cavernous sinus* Cavernous sinus thrombosis - via contiguous spread of infection from medial third of face, sinuses (ethmoidal or sphenoidal), or teeth - via valveless vanous system (via superior & inferior ophthalmic veins) - common pathogens = Staph aureus & strep - headache, fever, diplopia - ovular muscle paralysis via injury of CNs III, IV, VI - ophthalmic & maxillary branches of CN V = loss of both upper facial sensation & afferent limb of corneal reflex - proptosis (eye protrusion) & chemosis (conjunctival swelling) may also be evident due to impaired venous drainage through opthalmic veins

48-year-old man comes to office due to several hours of right knee pain. The patient has a history of peptic ulcer disease & gastroesophageal reflux disease. His right knee is swollen, erythematous, & tender. Arthocentesis is performed & synovial fluid analysis shows needle-shaped, negatively birefringent crystals with many neutrophils. The med given to this patient selectively binds to an interleukin-1 inducible enzyme that is highly expressed by inflammatory cells & undetectable in surrounding normal tissue. What is the most likely drug used in this patient's treatment?

*Celecoxib* - inflammation --> cells secrete cytokines (IL-1, TNF-alpha) --> causes COX-2 upregulation in inflamed tissue

75-year-old man brought to ED by paramedics following a high-speed motor vehicle accident. Several attempts made to resuscitate him but are unsuccessful. The patient had no significant past medical history & took no medications. He was known to be in good health & tolerant of moderate levels of physical activity. ECG findings at his last office visit showed no abnormalities. At autopsy, heavy calcifications of the aortic valve are seen. What most likely preceded the aortic valve changes observed in this patient?

*Cell necrosis* Dystrophic calicification - affecting aging aortic valve - hallmark of cell injury & death - occurs in all types of necrosis (coagulative, fat, caseous, liquefactive) - in setting of *normal calcium levels* - fine, gritty, white granules or clumps - hematoxylin & eosin staining = dark-purple, sharp-edged aggregates - deposits that develop lamellated outer layers = psammoma bodies Dystrophic calcification in aged or damaged cardiac valves = endothelial & fibroblast death secondary to chronic hemodynamic stress or atherosclerotic inflammation = often benign in elderly adults (aortic sclerosis)

55-year-old woman comes to physician because of 2-week history of intermittent heartburn. She has 20-year history of significant sensitivity to cold weather. She states that her hands turn white when they are exposed to cold. She also states that skin on her fingers has become tighter over past year. Physical exam shows tight, shiny, hyperpigmented skin of face & hands. Several subcutaneous calcifications are present in upper extremities. Joint mobility is normal. Renal & pulmonary function studies show no abnormalities. An autoimmune disorder is suspected. AutoAbs directed against what antigens demonstrate high degree of specificity for this patient's condition & suggest a benign course?

*Centromere* Scleroderma --> CREST is more benign(compared to diffuse)--> Anti-centromere

9-year-old girl brought to ED by her parents due to severe headache, lethargy, & vomiting. Her symptoms began a few weeks ago with mild intermittent headaches & fatigue & have progressively weakened. A CT scan of the brain reveals a mass lesion, enlarged lateral & third ventricles, & a normal-sized fourth ventricle. What is the most likely site of obstruction in this patient?

*Cerebral aqueduct* Noncommunicating/obstructive hydrocephalus - tumors, scarring/post-hemorrhage, infection, CNS malformation

4-year-old Caucasian male evaluated for recurrent skin & respiratory infections. He has light skin & silvery hair. Horizontal nystagmus is present on eye exam. Peripheral blood smear demonstrates giant cytoplasmic granules in neutrophils & monocytes. The patient most likely suffers from what disorders?

*Chediak-Higashi syndrome* - AR - immunodeficiency, albinism, neuro defects - nystagmus - defect in neutrophil phagosome lysosome fusion - abnormal giant lysosomal inclusions visible on light microscopy - most commonly Staph & Strep - oculocutaneous albinism

Pharmacologist discovers new fungal metabolite with unusual antimicrobial properties. It naturally concentrates in endosomes, lysosomes, & phagolysosomes of cells & directly kills microorganisms (Mycobacterium tuberculosis) that are normally resistant to degradation in phagolysosomes. The metabolite has the undesirable effect of increasing pH within phagolysosomes. What processes will be primarily affected?

*Class II MHC molecule peptide loading* MHC II - expresses APCs - Antigen loaded in acidified endosome Macrophages presented in M tuberculosis --> granuloma formation Metabolite increases pH within phagolysosome --> metabolite will affect MHC II only

A patient's chronic infection of HBV & HDV assists what with what life cycle aspect of the current infectious agent?

*Coating of viral particles* HDV = double-shelled particle that resembles Dange particle of HBV Hepatitis D antigen (HDAg) = replicative defective = must be coated by external coat HBsAg to penetrate hepatocyte

Von Willebrand factor normally binds what?

*Collagen* vWF - promotes platelet adhesion at sites of vascular injury by binding to & crosslinking platelet glycoproteins (GpIb) with *exposed collagen* underneath damaged endothelium - carrier protein for factor VIII --> increases its plasma half-life

Firefighter brought to ER from the scene of a fire complaining of headaches, weakness, confusion, & difficulty in breathing. His skin & mucous membranes appear very pink/red. The causative agent of these symptoms inhibits electron transport & oxidative phosphorylation by what mechanisms?

*Combining with cytochrome oxdiase* *CO/CN* = complex *4* inhibitors (*4* letters)

30-year-old woman comes to ED with sudden-onset abdominal pain & ascites. Lab studies show anemia, reticulocytosis, leukopenia, & thrombocytopenia. Flow cytometry of patient's peripheral blood cell using appropriate monoclonal Abs shows CD55 & CD59 deficiency. CT scan of the abdomen shows hepatic vein thrombosis. What is the most likely cause of this patient's anemia?

*Complement activation* Paroxysmal nocturnal hemoglobinuria (PNH) - hemolytic anemia, hypercoagulability (hepatic vein thrombosis), pancytopenia - via acquired mutation of PIGA gene - gene involved in synthesis of glycosylphosphatidylinositol (GPI) anchor = necessary for attachment of cell-surface proteins, including CD55 (decay-accelerating factor) & CD59 (MAC inhibitory protein) --> help inactivate complement & prevent membrane attack complex from forming on normal cells - absence of CD55 & CD59 = complement-mediated hemolysis = occurs more often at night because complement activity increased during sleep due to lower blood pH - thrombotic complications (Budd-Chiari syndrome) via release of free hemoglobin, etc - often associated with pancytopenia & aplastic anemia Flow cytometry = absence of GPI anchor & CD55 & CD59 defiency

Researchers conduct prospective study that demonstrates association between alcohol consumption & transitional bladder carcinoma, with a relative risk (RR) of 1.81 & a p-value of 0.03. They can divide study subjects into 2 groups, smokers & non-smokers, & again examine the association between alcohol consumption & bladder cancer: Smokers - RR = 0.95 - P-value = 0.87 Non-smokers - RR = 1.03 - P-value = 0.96 The discrepancy between the overall results & the stratified results is best explained by what?

*Confounding* - association with both exposure & outcome & affects measure of association between exposure & outcome = initially appears to be statistically significant association between the 2 on crude analysis - *once results are stratified by confounding variable, association disappears* This case... - initial crude analyses suggests alcohol use was associated with bladder carcinoma with RR of 1.81 & p-value <0.05 - smoking = confounder - stratified analysis = both smokers & non-smokers have RR ~ 1 with large p-values (>0.05) - RR of 1.81 found on crude analysis disappears = no true association between alcohol consumption & bladder cancer

2 most immediate physical symptoms of marijuana use

*Conjunctival injection* Tachycardia

22-year-old man bought to ED 1 hour after being involved in motor vehicle collision. Physical exam shows intra-abdominal injuries requiring operative repair. During operation, he receives 10 units of whole blood. Postoperatively, his serum calcium concentration is 4.5 mg/dL. What features of transfused whole blood best explains the decreased calcium concentration in this patient?

*Contains ion-chelating compounds* Blood transfusion risks - infection transmission (low) - transfusion reactions - iron overload (may lead to secondary hemochromatosis) - *hypocalcemia (citrate is a Ca2+ chelator) - hyperkalemia (RBCs may lyse in old blood units)

A study is done to determine the efficacy of fish oil in preventing progression of renal disease in patients with lgA nephropathy. 100 consecutive patients with newly diagnosed lgA nephropathy are entered into the study. The odd numbered patients are treated with fish oil and the even numbered patients are treated with olive oil, an inactive fatty acid. Over the next 5 years, all patients are followed for the development of end-stage renal disease. Results are shown: . #reaching end Stage Renal Disease Fish oil Group (n=50) 3 Olive oil Group (n=50) 17 The incidence of end stage renal disease in the fish oil group was significantly lower than in the Olive oil group (p<0.01). which of the following best describes the Study?

*Controlled trial* - Treatment group vs inactive (placebo) group.

62-year-old male has a reddish, rough patch white scales on the top of his ear. He does not get this treated, & 3 years later it has become an enlarged, raised lesion with a central ulcerated area that will not heal. What is the most likely causative factor for this malignancy?

*Creation of pyrimidine dimers* Actinic keratosis that developed into SCC - frequent exposure to UV light = pyrimidine dimers in DNA

28-year-old man with vague abdominal pain, low-grade fever, diarrhea treated with antibiotics without significant improvement in his symptoms. Several weeks after symptom onset, patient develops a skin lesion over abdomen. His temp is 37.8 C (100 F), BP is 120/70 mmHg, & pulse is 88/min. On physical exam, the abdomen is mildly distended & tender to palpation. Bowel contents appear to be draining to surface of skin in right lower abdominal quadrant. This patient most likely suffers from what conditions?

*Crohn disease* - prolonged diarrhea & abdominal pain - transmural inflammation - enteroenteric fistula or enterocutaneous fistula (between bowel & skin)

Excisional biopsy specimen shows basal cell carcinoma. What is the most appropriate treatment?

*Cryotherapy* For actinicic keratoses & low-risk basal cell or squamous cell skin cancers, treatment options = cryosurgery, electrodessication & curettage, topical therapy with fluorouracil or imiquimod, & surgical excision For high-risk skin cancers, traditional surgical excision or Mohs surgery preferred

Mechanism of fenofibrate

*Reduced hepatic VLDL production* Fibrates - activate peroxisome proliferator-activated receptor alpha (PPAR-alpha) --> decreased hepatic VLDL production & increased LPL activity - decrease triglycerides by 25-50% - increased HDL by 5-20%

In addition to blocking conversion of angiotensin I to angiotensin II, ACEIs also produce systemic vasodilation by what mechanism?

*Decreased bradykinin degradation* ACEI - increased renin - increased Ang I - decreased Ang II - decreased Aldosterone - increased bradykinin

Cause of decreased levels of ACh in Alzheimer disease

*Decreased choline acetyltransferase activity in nucleus basalis* Decreased ACh level - via deficiency of choline acetyltransferase - decline in ACh levels most notable in basal nucleus of Meynert (participates in memory & cognition)

In response to influenza virus, infected respiratory epithelial cells begin secreting increased quantities of interferons. The specific interferons secreted by these cells will most likely cause what changes?

*Decreased protein synthesis by infected cells* Type I interferons (alpha & beta) - synthesized by most human cells in response to viral infections - bind to type I interferon receptors on infected & neighboring cells (autocrine/paracrine signaling) = trasncription of antiviral enzymes capable of halting protein synthesis, such as RNase L (endonuclease that degrades all RNA in cell) & protein kinase R (inactivates eIF-2, inhibiting translation initiation) - induce MHC class I expression of all cells & stimulate activity of NK & cytotoxic cells --> increase proportion of virally infected cells that undergo apoptosis

Mechanism of action of first-line treatment for trigeminal neuralgia

*Decreases sodium current on multiple levels* Carbamazepine - inhibits sodium channels from recovering from inactivation ADR - bone marrow suppression --> anemia, agranulocytosis, thrombocytopenia - SIADH

46-year-old woman comes to physician with easy fatigability & exertional dyspnea. Cardiac auscultation reveals diminished first heart sound & an apical holosystolic murmur radiating to axilla. Diffuse pulmonary crackles heard bilaterally. There is no jugular venous pressure or peripheral edema. What would most likely increase ratio of forward flow volume to regurgitant flow volume in this patient?

*Decreasing left ventricular afterload* Mitral regurgitation with left-sided heart failure - amount of blood that flow forward determined in part by left ventricular afterload - decreased afterload = resistance to blood flow into aorta reduced = diverts blood flow away from left atrium & toward aorta = increased *forward-to-regurgitant volume ratio* - arterial vasodilator therapy reduces left ventricular afterload = reduced heart failure symptoms in patients with mitral regurgitation Nitrates - increased peripheral venous capacitance - reduced cardiac preload - decreased left ventricular end-diastolic volume & pressure - decreased systemic vascular resistance - decreased cardiac afterload

15-year-old boy brought to office by mother due to difficulty with movement. The patient enjoys playing high school basketball but had to leave the team this year due to his progressively worsening symptoms. On exam, he is found to have significant kyphoscoliosis & a high plantar arch. His older brother suffered from a neuro disorder & died of heart failure at age 25. This patient most likely has what neuropathologic findings?

*Degeneration of spinocerebellar tracts* Friedreich ataxia - AR - mutation of frataxin (FXN) gene --> codes for essential mitochondrial protein involved in iron-sulfur enzymes - increased GAA repeats Involved sites - spinocerebellar & lateral corticospinal tract degeneration = gait ataxia, spastic muscle weakness - dorsal columns & dorsal root ganglia = loss of position & vibration - kyphoscoliosis & foot abnormalities (pes cavus) - hypertrophic cardiomyopathy & CHF - diabetes mellitus in 10%

Individual with point mutation affecting gene responsible for neurophysin synthesis most likely to suffer from

*Diabetes insipidus* Neurophysins = carrier proteins for oxytocin & vasopressi, produced within paraventricular & supraoptic nuclei & released from posterior pituitary - produced within neuronal cell bodies of hypothalamic nuclei - bind oxytocin & vasopressin & act as chaperone 'cules as they are shuttled toward nerve terminals in posterior pituitary Neurophysin II - binding site for specific vasopressin = involved in transport & packaging of vasopressin via ER & Golgi apparatus into neurosecretory granules

76-year-old woman brought to ED by her son due to lethargy & confusion over past 2 days. The patient has persistent atrial fibrillation & CHF & is on multiple meds. Recently, she has had nausea & decreased appetite. Today, she had 3 episodes of vomiting. The patient also reports vision difficulties. Temp is 36.7 C (98 F) & BP is 133/80 mmHg. Lab results: Sodium = 140 mEq/L Potassium = 5.7 mEq/L Calcium = 9.3 mg/dL Creatinine = 1.2 mg/dL Glucose = 85 mg/dL ECG shows junctional escape rhythm at rate of 48/min with occasional ventricular premature beats. Increased blood level of what meds is most likely responsible for her symptoms?

*Digoxin* Digoxin toxicity - atrial fibrillation + CHF - increased vagal tone - nausea, abdominal pain, fatigue, dizziness, confusion, blurred vision, abnormal color perception - cardiac arrhythmias = bradycardia, junctional escape beats via increased AV nodal block - elevated potassium

37-year-old man dies suddenly. He has a history of fatigue, dyspnea, dependent edema, & decreased ejection fraction. At autopsy, the structure of the valves is normal, but all four chambers of the heart are enlarged. A mural thrombus is attached to the wall of the left atrium. Histologic exam of the heart shows hypertrophies & atrophied muscle cells. What is the most likely diagnosis?

*Dilated cardiomyopathy* "Atrophic & Hypertrophic" myocytes combination is characteristic of DCM Showing symptoms of CHF with decreased EF and blood backing up

Dilation & curettage of uterus in ectopic pregnancy would reveals what features?

*Dilated, coiled endometrial glands & edematous stroma* - decidualized endometrium - vascularized edematous stroma - changes occur in luteal phsase of menstrual cycle under influence of progesterone - absent chorionic villi (no embronic or trophoblastic tissue)

42-year-old man had experienced cramping & stiffness of muscles, coupled with severe muscle weakness in his left leg. Over time, the muscle weakness becomes more severe, & his speech has become slurred, & he has to use a wheelchair to get around. He developed swallowing difficulties, & upon diagnosis was told he had less than 2 years to liver. A family history indicated that the man's father had begun to experience mild muscle weakness before he died in a car accident. The man's symptoms can be best explained at the molecular level by what?

*Elevated levels of superoxide* ALS - most often due to inactivating mutation of SOD --> elevated superoxide --> loss of motor neuron activity

82-year-old man brought to ED after syncopal episode. He has no chest pain or dyspnea but has severe constipation of recent onset. He was hospitalized 2 weeks ago for atrial fibrillation with rapid ventricular response & was discharged home with oral meds after appropriate management. His past med history is also significant for HT & severe COPD requiring oxygen therapy. His BP is 105/60 mmHg & pulse is 50/min. Exam reveals bilateral decreased breath sounds & normal heart sounds. ECG shows new-onset second-degree AV block. What drugs is the most likely cause of his current condition?

*Diltiazem* Constipation + new-onset 2nd-degree AV block + syncope in setting of new med used for AF = due to CCB therapy - diltiazem & verapamil = nondihydropyridine CCBs used for HT, angina pectoria, & supraventricular arrhythmias - block L-type calcium channels

Inhibit platelet aggregation by inhibiting phosphodiesterase activity & increasing cAMP

*Dipyridamole, Cilostazol* - increase in pain-free walking distances in patients with peripheral artery disease

17-year-old boy involved in gang flight, & a stab wound severed the white rami communicantes at the level of his sixth thoracic vertebra. This injury would result in degeneration of nerve cell bodies in what structures?

*Dorsal root ganglion & lateral horn of spinal cord* White rami communicantes - preganglionic sympathetic GVE & GVA fibers, whose cell bodies are located in lateral horn of spinal cord & dorsal root ganglia

34-year-old woman comes to physician complaining of double vision. She first experienced difficulty focusing her eyes while at work yesterday. Upon waking up this morning, her symptoms had progressed to frank diplopia. Her past medical history is insignificant. A complete physical exam is performed, including a full neuro assessment. Shining light into her right eye causes constriction of her right pupil, but not the left pupil. Shining light into her left eye causes constriction of only her right pupil. What additional physical exam findings is likely to be found in this patient?

*Drooping of the left eyelid* Pupillary light reflex - CN II = afferent - CN III = efferent - both are functional in this patient - lesion = left CN III CN III palsy - somatic components = inferior, superior, & medial rectus; inferior oblique; levator palpebrae muscles - ptosis via paralysis of levator palpebrae - unopposed CN VI & superior oblique = down-&-out gaze - fixed, dilated pupil & loss of accomodation

Mother with diabetes gives birth to baby who is diagnosed as having dextroposition of aorta & pulmonary trunk with cyanosis & shortness of breath. What structures is required to remain patent until surgical correction of the deformity?

*Ductus arteriosus* or VSD - shunts blood from pulmonary trunk to aorta = partially bypasses lungs = mixed blood reaches body tissues = cyanosis

Researchers studying GI pathophysiology are in process of analyzing hundreds of gastric mucosal biopsy specimens taken from patients who underwent endoscopy at a local tertiary care center. They notice that colonization of the gastric antrum with S-shaped, gram-negative bacteria is associated with decreased number of somatostatin-producing antral cells. Depletion of these cells from the gastric antrum is most likely to cause what?

*Duodenal ulceration* H pylori - noninvasive = attached to gastric mucosa or deep in mucus layer overlying gastric epithelium H pylori-associated antral gastritis - early manifestation Chronic antral inflammation - decreased number of somatostatin-producing cells (delta cells) - somatostatin inhibits gastrin release --> absent? = high gastrin levels act both directly (via cholecystokinin B receptors) & indirectly (via histamin release by enterochromaffin-like cells) = increased hydrogen ion secretion by parietal cells = gastric fluid with very low pH = duodenal ulceration & duodenal gastric metaplasia

Married 78-year-old man brought to ED after ingesting ten 15-mg temazepam tablets. After he is stabilized medically, he undergoes psychiatric evaluation. What is most important in assessing his risk for suicide?

*Early morning awakening with decreased appetite* - early morning awakening = sign of depression

3-year-old boy presents with 3 days of low-grade fever, joint pain, & a "lacy-"appearing rash on his arms & legs. His rash began on his face & he appeared to have "slapped cheeks." The chemical messengers that caused the symptoms (vasodilatation presenting clinically as a "rash") can be classified as what?

*Eicosanoid* Fifth disease - eicosanoids control cellular function in response injury (viral infection) --> vascular endothelial cells secrete prostaglandins that act on smooth muscle cells = vaodilation = reddish apperance of infected ind

A 27-year-old male became lost while hiking in Yosemite Nat'l Park. He was found eight days later. He had nothing to eat & only water to drink before being rescued. What is an essential nutrient he has not received over the last 8 days?

*Eicosapentaenoic acid* (EPA) - 20 carbon FA containing 5 double bonds - can be derived from essential FA found in fish oilds (linolenic acid) - precursor of eicosanoids (prostaglandins, leukotrienes, thromboxanes) - ingested from fish oils

Normal, quiet expiration is achieved by contraction of what structures?

*Elastic tissue in lungs & thoracic wall*

31-year-old woman has enlarged right ovary detected on pelvic exam & confirmed on endovaginal ultrasonography. At laparoscopy, an 8-cm cyst filled with thick brown material is removed. Histologic sections show that the cyst is lined by macrophages containing abundant hemosiderin. What is the most likely diagnosis?

*Endometrioma* - endometriosis (ectopic endometrium-like tissue) within ovary with cyst formation - presents with pelvic pain, dysmenorrhea, dyspareunia - symptoms vary with menstrual cycle - *chocolate cyst* = endometrioma filled with dark, reddish-brown blood - complex mass on ultrasound

31-year-old woman has had several episodes of retrosternal chest pain while at rest during the past 6 months. The most recent episode occurred while she was asleep & produced several minutes of ST segment elevation on a home cardiac monitor. She has no known cardiac risk factors. What events in a large epicardial artery is most likely responsible for the chest pain?

*Endothelial cell dysfunction* ST elevation in young person with history of retrosternal chest pain = Prinzmetal Angina - vasoconstriction via platelet thromboxane A2 or increase in endothelin (produced by cells in tunica intima of epicardial artery) = endothelial cells are dysfunctional

34-year-old man comes to physician reporting one week of inability to extend his right wrist & several of his fingers on the same hand. He first began having difficulty while trying to type his thesis for graduate school on his computer. He is right-handed & does no recall any trauma. He has a history of asthma that was diagnosed while he was in college. Physical exam demonstrates impaired dorsiflexion of right wrist with normal strength of left wrist. Lab studies show: Complete blood count Hemoglobin = 13 g/dL Platelets = 320,000/uL Leukocyte count: 14,000 cells/uL - Neutrophils = 50% - Eosinophils = 28% - Lymphocytes = 17% - Monocytes = 5% Serum Abs against neutrophil myeloperoxidase are positive. This patient most likely has what conditions?

*Eosinophilic granulomatosis with polyangiitis* / Churg-Strauss - late-onset asthma, rhinosinusitis, eosinophilia - mononeuritis multiplex of epineural vessels of peripheral nerves

68-year-old woman comes to ED due to acute vision disturbance. She had an episode of dimming of vision in left eyes that occurred abruptly & resolved spontaneously in 20 minutes. For the past several weeks, the patient has had a dull ache in the left side of her jaw while chewing the resolves when she stops eating. She has also had malaise & hip muscle aches over the last several months. The patient has a history of HT & hypothyroidism. On exam, her BP is 130/70 mmHd & pulse is 66/min. Neurologic exam, including CNs & motor & sensory functions, is unremarkable. Visual acuity, vidual fields, & appearance of oculi fundi are normal. What is the best initial test for this patient?

*Erythrocyte sedimentation rate* Jaw claudication + episode of amaurosis fugax = Giant cell/temporal arteritis - most common form of vasculitis in ppl of northern European descent - almost exlusively in patients >50 y/o - half of patients = polymyalgia rheumatic = achy pain in shoulder & hip girdles *Check C-reative protein (CRP) level or erythrocyte sedimentation rate (ESR)* = nonsepcific but highly sensitive - if elevated, check temporal artery biopsy

A 3-day-old newborn develops fever & a stiff neck. Exam of CSF shows numerous neutrophils & many gram-negative rods. What is the most likely causal organism?

*Eschirichia coli K1* WATCH OUT! - they could have group B strep there, but it wouldn't be correct because it is gram positive

Man with tuberculosis started on combo therapy with isoniazid, ethambutol, rifampin, pyrazinamide, & pyridoxine. One month later, he returns to office reporting blurring of vision. Exam shows bilateral central scotomas. What is most likely responsible for this patient's visual symptoms?

*Ethambutol* - optic neuropathy = decreased visual acuity, central scotoma, or color blindness = may be reversible with discontinuation of drug

60-year-old woman is undergoing surgical excision of a renal cell carcinoma thrombus that extends into right renal vein. During the procedure, the vena cava is temporarily occluded above the renal veins. Increased venous pressure is most likely to be noted in what veins during period of occlusion?

*External iliac* - obstruction of ligation of IVC = blood from lower limbs has to reach heart & bypass obstruction through anterior abdominal wall anastomosis - external iliac vein --> inferior epigastric vein --> internal thoracic vein --> brachiocephalic vein --> right atrium SIMPLE VERSION: IVC clamped distal to all structures except external iliac vein = pressure in others but this should fall

13-year-old boy brought to urology clinic for follow-up of undescended right testicle discovered during evaluation in newborn nursery. Physical exam during today's appointment shows absence fo palpable right testis in scrotal sac. However, a round mass is palpates superior to scrotum, medial to right mid-inguinal point. Orchiopexy, replacement & fixation of testis into scrotum, is recommended to fam. During this patient's procedure, the malpositioned testis will most likely be pulled through physiological opening in what structures?

*External oblique muscle aponeurosis* Cryptorchidism = affects 3% of males & is more common in preterm infants - surgical intervention orchiopexy (after 6 months) --> must be mobilized through superficial inguinal ring & stitched into place in scrotum - superficial & deep inguinal rings = physiologic openings in external abdominal oblique aponeurosis & transversais fascia

35-year-old man comes to office with progressively worsening fatigue associated with dark urine & back pain. Two days ago, patient ate some large, flat beans brought home by his wife after a business trip to Egypt. Physical exam shows jaundice & pallor. Lab results reveal a hemoglobin level of 8 g/dL. Further evaluation reveals deficiency of enzyme involved in conversion of glucose-6-phosphate to ribulose-5-phosphate. The substance generated during this conversion is necessary for what biochemical processes?

*Fatty acid synthesis* G6PD deficiency - G6PD catalyzes first step in PPP (*oxidative portion of which generates 2 'cules of NADPH while converting G6P to ribulose-5-phosphate PPP - main source of NADPH - active in cells experiencing high oxidative stress (RBCs) when NADPH used to regenerate reduced glutathione - active in organs such as liver & adrenal cortex that are involved in reductive biosynthesis (synthesis of FAs, cholesterol, steroids) & cytochrome P450 metabolism - phagocytic cells generating respiratory burst via NADPH

After a stressful week of exam a medical student sleeps for 15 hours, then rests in bed for an hour before getting up for the day. Under these conditions, what statement concerning the students' metabolic state would be correct?

*Fatty acids are being released from adipose triacylglycerol stores* Fasting - FAs released from adipose tissue & oxidized by other cells - liver glycogen not depleted until 30 hours of fasting After overnight fast - both glycogenolysis & gluconeogenesis by liver help maintain blood glucose

Most effective agents for treatment of hypertriglyceridemia

*Fibrates* = *fenofibrate*, gemfibrozil, bezafibrate - activate PPAR-alpha = increased lipoprotein lipase - risk of pancreatitis rises with increasing triglyceride levels above 1,000 mg/dL

Recognize that dang *Cirrhosis*

*Fibrosis & nodular parenchymal regeneration* - portal HT from increased resistance to hepatic blood flow in advanced cirrhosis --> gastroesophageal varices

Macrocyclic antibiotic that inhibits *RNA polymerase*. It is bacteriocidal against C difficile & is used primarily for recurrent CDI.

*Fidaxomicin* - oral - minimal systemic absorption = high fecal concentrations - narrow spectrum of activity - for recurrent C diff CDI - can be treated with oral metronidazole, vancomycin, or fidaxomicin

45-year-old an who was recently started on med for paroxysmal atrial fibrillation undergoes stress ECG testing. Patient exercises on treadmill for 9 minutes & reaches 98% of age-predicted max heart rate without chest pain or ST-segment changes. His pre-test resting QRS complex duration is 95 msec (normal = 80-120 msec) & corrected QT (QTc) interval duration is 410 msec (normal < 440 sec). ECG findings recorded at his maximally achieved heart rate show a QRS complex duratin of 125 msec & QTc interval duration of 400 msec. Based on the patient's test results, what meds is most likely being used to treat his atrial fibrillation?

*Flecainide* Class IC antiarrhythmic - treats supraventricular tachycardias such as those cause by atrial fibrillation - binds fast sodium channels responsible for phase 0 depolarization of cardiac myocytes --> blocks inward sodium current --> *prolongs QRS duration* - slowest of class 1 agents to dissociate from sodium channels = do so during diastole = *use-dependence*

26-year-old previously healthy man brought to ED following a motorbike accident. He is found to have a maxilofacial injury. His condition is stabilized, & surgical repair is performed. While recovering, the patient develops difficulty chewing food. On exam, the jaw deviates to the right side when the patient is instructed to open his mouth. The nerve has been injured in this patient exits the skull through what foramina?

*Foramen ovale* Third division of trigeminal nerve / V3 / mandibular nerve - sensory innervation to face - motor innervation to muscles of mastication = 3 muscles that close jaw (masseter, medial pterygoid, temporalis) & single muscle that opens jaw (lateral pterygoid) Unilateral injury to CN V3 - unopposed action of contralateral pterygoid muscles = deviation of mandible toward paralyzed side on opening mouth Foramen ovale - also contains lesser petrosal nerve, accessory meningeal artery, emissary veins

Elevated levels of what contributes to Type 2 Diabetes?

*Free fatty acids* T2DM - via insulin resistance & relative insulin deficiency = acanthosis nigricans = sign of insulin resistance Insulin resistance - adipose cells: hinders antilipolytic effects of insulin --> lipolysis = release o free fatty acids --> contributes to insulin resistance by impairing insulin-dependent glucose uptake & increasing hepatic gluconeogenesis

Patient undergoes amniocentesis during 18th week of pregnancy. Amniotic fluid analysis shows increased level of acetylocholinesterase. This patient's amniocentesis results most likely suggest failure of what processes?

*Fusion of edges of neural plate* Neural tube defects - failure of fusion of neural plate edges during 4th week of fetal dev't - fusion begins in cervical region --> proceeds toward cranial & caudal ends of neural tube If either neuropore does not fuse - opening persists between neural tube & amniotic cavity = allows leakage of AFP & AChE into amniotic fluid *Detection of AFP & AChE used for prenatal screening of NTDs*

Cleft lip results from failure of what intrauterine processes?

*Fusion of maxillary prominence & intermaxillary segment* - 5-6th week of embryonic dev't - first pharyngeal arch splits into upper maxillary prominence & lower mandibular prominence - fusion of 2 medial nasal prominences = intermaxillary segment

On a routine newborn exam, it is noted that the red reflex is absent in one eye. An MRI shows a tumor blocking the retina. Regulation at what phase of the cell cycle would be affected by the mutation that leads to this tumor?

*G1 to S* Hereditary retinoblastoma - via inherited mutation in rb gene Rb gene = tumor suppressor gene - helps regulate E2F fam of transcription factors Absence of rb gene product - transition to S phase is unregulated = occurs continuously = tumor growth

8-month-old girl brought to office for evaluation of irritability & regression of motor skills. Her birth was unremarkable & she appeared to develop normally, but she can no longer sit or roll over. Her parents have also noticed that she startles easily with loud noises. Head circumference measurement is consistent with macrocephaly. Bilateral fundoscopic evaluation shows bright red fovea centralis that is surrounded by a contrasting white macula. Peripheral vision is decreased. Abdominal exam is normal. Accumulation of what metabolites is most likely present in this patient's tissues?

*GM2 ganglioside* *TH*a *M2!* Tay-Sachs - AR - Ashkenazi Jews - beta-*H*exosaminidase A deficiency = accumulation of cell membrane glycolipid GM2 ganglioside within lysosomes - normal dev't in first few months of life --> progressive neuro deterioration as glycolipids accumulate in brain - macrocephaly, abnormal startle reflex with acoustic stimuli - cherry-red macula spot - usually die by age 2-5 years

57-year-old pathologist, who had often cut himself while performing autopsies, develops blurred vision, dementia, personality changes, & muscle twitching in a very short period of time. The protein that is leading to these behavioral changes is best described as:

*GPI-anchored membrane protein* Prion disease - prion protein adopts alternative conformation & ppts in neural tissue - normal prion protein = GPI-anchored protein

Two months after a kidney transplant, a 32-year-old man who is taking immunosuppressive drugs develops an infection with cytomegalovirus. What is the most appropriate therapy?

*Ganciclovir* = CMV, especially in immunocompromised patients - more active than acyclovir against CMV

42-year-old woman comes to office with persistent hyperlipidemia despite 6 months of maintaining healthy diet & exercising regularly. Although her past med history is significant for biliary colic secondary to gallstones, the patient has refused elective cholecystectomy. Her father died of a MI at age 54, & her mother has diabetes mellitus. The patient's temp is 36.1 C (97 F), BP is 122/79 mmHg, pulse is 78/min, & respirations are 14/min. Exam shows no abnormalities. Lab studies obtained 1 week ago show elevated serum triglycerides & LDL cholesterol levels. Drug therapy is discussed with the patient. Give this patient's preexisting gallbladder disease, what drugs should be avoided?

*Gemfibrozil* - upregulate lipoprotein lipase = increased oxidation of fatty acids (liver, muscles) = fibrate = inhibits rate-limiting enzyme in bile acid syntheses, cholesterol 7-alpha-hydroxylase --> decreased cholesterol solubility = gallstone formation - also monitor for myopathy = increased risk when used with statins

What is the most likely cause of the Fragile X syndrome / CCG trinucleotide repeats in gene located on X chromosome?

*Gene methylation* - inactivates FMR1 = prevents transcription Fragile X - most common inherited cause of intellectual disability - developemntal delay!, ADHD, autism spectrum disorder! - delayed language acquisition & poor social skills = ASD

PARENTS: MALE a II b a II d FEMALE b II b c II f OFFSPRING: FEMALE: AFFECTED WITH DISEASE b II b d II c MALE: AFFECTED WITH DISEASE b II b d II f FEMALE: UNAFFECTED a II b a II f Two children in a family have a disease characterized by mental retardation and mild dysmorphic features. The family was evaluated by standard karyotype and then by DNA microsatellite polymorphism studies for two autosomal markers. A pedigree is shown. Which of the following is the most likely cause of the congenital disorder?

*Genomic imprinting* Prader Willi - When the kids inherit the gene from the mother it become imprinted, so both copies from the mother are inactive, so when they inherit the mutant allele from the father, the disease become manifested, but when the third child inherit the normal allele from the father, he is normal - maternal imprinting = gene from mom silent & *P*aternal gene deleted/mutated

Previously healthy 24-year-old woman comes to ED because of diarrhea, nausea, flatulence, & bloating for the past 5 weeks. Bowel movements are accompanied by abdominal cramping. She has not traveled out of the US. Tympanic temp is 37 C (98.6 F). Bowel sounds are increased. Test of stool for occult blood is negative. What is the most likely causal organism?

*Giardia lamblia* FLATULENCE, FOUL SMELLING ARE CLASSIC FOR GIARDIA Most common cause of parasitic infectious diarrhea in the states! It is the most frequently identified cause of diarrheal outbreaks associated with drinking water in this country.

A 70 year old man has progression of his Parkinson's disease tremor that is unresponsive to medications. A stereotactic operation is scheduled. To alleviate the tremor, the needle should be placed in which of the following locations?

*Globus pallidus* Parkinson disease - degeneration of dopaminergic neurons in substantia nigra Sterotactic needle - ablates globus pallidus --> cortical excitation

An 8-year-old boy has had generalized edema for 2 months. Lab studies of serum show: Glucose = 89 mg/dL Creatinine = 0.9 mg/dL Urea nitrogen (BUN) = 11 mg/dL Albumin = 2.8 g/dL Urinalysis shows 4+ protein oval fat bodies. The most likely cause is a disorder involving what structures?

*Glomerular capillary loops* Minimal Change Disease - primary damage = glomerular basement membrane = loss of negative charge --> allows protein to be filtered freely in large amounts across GBM

65-year-old man reports multiple episodes of lightheadedness while buttoning a tight shirt collar. During 2 episodes, he passed out briefly but sustained no injuries. His BP was 70/40 mmHg & pulse was 45/min during one of the episodes. Past med history is signiicant for HT & diet-controlled diabetes mellitus. The patient is a lifetime nonsmoker & drinks alcohol on social occasions. On physical exam, his BP is 125/72 mmHg & pulse is 76/min without orthostatic changes. Stimulation of afferent sensory fibers in what nerves is most likely responsible for this patient's symptoms?

*Glossopharyngeal* Carotid sinus HS - triggered by pressure on carotid sinus by t-shirt collar Carotid sinus - dilation of internal carotid artery located just above bifurcation of common carotid artery - afferent limb arises from baroreceptors in carotid sinus --> travels to medullary centers via Hering nerve (branch of vagus nerve) Carotid sinus pressure or massage - stimulates baroreceptors --> increases firing rate from carotid sinus = increased parasympathetic output & withdrawal of sympathetic output to heart & peripheral vascuature --> decreased BP (via peripheral vasodilation) & decreased cardiac output (decreased contractility/stroke volume & heart rate)

27-year-old man brought to ED due to confusion. His roommate says he has been binge drinking for last 5 days & probably has had very little to eat. Patient's medical history is significant for alcohol-related seizures 1 year ago. He had been sober until 2 weeks ago, when he started drinking again. The patient's past med history is otherwise unremarkable. On exam, he responds to voice but does not follow commands. Fingerstick glucose is 35 mg/dL & urine is strongly positive for ketones. Suppression of what is the primary cause of this patient's hypoglycemia?

*Gluconeogenesis* Ethanol metabolism - reduces NAD+ to NADH --> inhibits all pathways requiring NAD+, including reactions requiring gluconeogenesis - lactate cannot beconverted to pyruvate --> instead rxn drive from pyruvate to lactate - excess NADH inhibits conversion of malate to OAA - puruvate & OAA = intermediates in gluconeogenesis --> conversion of these molecules to lactate & malate inhibits gluconeogenesis

Base excision repair is used to correct single-base DNA defects spontaneously or by exogenous chemicals. What is the order of this process?

*Glycosylase, endonuclease, lyase, polymerase, ligase* Base excision repair - excessive consumption of dietary nitrites can promote deamination of cytosine, adenine, guanine to form uracil, hypoxanthine, xanthine --> not removed? = carcinogenesis - begins with recognition of abnormal bases via glycosylases --> cleave altered DNA bases from parent DNA = empty sugar-phosphate site (AP site) --> endonuclease cleaves 5' end of AP site before lyase / phosphodiesterase enzyme completes extraction of AP site from DNA by removing remaining sugar-phosphate group --> DNA polymerase fills gap with correct sugar-phosphate base --> ligase

42-year-old weightlifter preparing for upcoming strength competition. After lifting series of progressively heavier weights, he decides to increase weight on exercise bar to 175 kg (385 lbs), the heaviest he has ever attempted. He is able to hold the weight over his head for several seconds. However, his arms suddenly & involuntarily give way & he drops the weight to the ground. What structures was most likely responsible for the sudden muscle relaxation?

*Golgi tendon organ* = sensory receptors located at junction of muscle & tendon innervated by group Ib sensory axons - connected in series with contracting extrafusal skeletal muscle fibers - sensitive to increases in muscle tension but insensitive to passive stretch When muscle exerts too much force, GTOs inhibit contraction of muscle = sudden muscle relaxation - prevents damage to musculoskeletal system

65-year-old male dies in hospital of overwhelming pulmonary infection. Autopsy shows right lower lung lobe that is pale, firm & airless. Histologically, the alveoli are filled with exudate containing the neutrophils, fibrin & some fragmented RBCs. This patient died during what phase of his disease?

*Gray hepatization* - lung lobe that is pale & firm macroscopically - microscopic = exudates with neutrophils, fibrin, fragmented RBCs

Vein that accompanies anterior interventricular artery

*Great cardiac vein* - begins at apex of heart & ascends along with IV branch of left coronary artery - turns to left to lie in coronary sulcus & continues as *coronary sinus*

24-yer-old med student received hepatitis B virus vaccination 2 years ago. What findings is most likely on serologic studies at this time?

*HBsAb*

A healthy 28-year-old single mother of three healthy children recently started employment as a secretary at a local corporation. She has a variety of health care plans from which to choose. What types of plans is most likely to have the lowest out-of-pocket cost for this patient and her family?

*Health maintenance organization* - cheaper - immunizations for kids provided - patients restricted (except in emergencies) to limited panel of providers who are in network - required to designate primary care physician - payment denied for any service that does not meet established, evidence-based guidelines - requires referral from primary care provider to see a specialist

78-year-old patient presents with advanced cancer in posterior mediastinum. The surgeons are in a dilemma as to how to manage the condition. What structures is most likely damaged?

*Hemiazygos vein* - ascends on left side of vertebral bodies behind thoracic aorta - receives 9th, 10th, & 11th posterior intercostal veins *Descending aorta*

64-year-old man comes to ED due to fever, anorexia, & nausea. He recently immigrated to US to live with his son. Several weeks ago, on routine testing, the patient was found to have positive purified protein derivative test. He had no respiratory symptoms, & a chest x-ray was unremarkable. A month ago, he started isoniazid therapy with pyridoxine supplementation. Currently, temp is 38.3 C (100.9 F). On physical exam, there is mild abdominal discomfort. Lab studies are pending. What is the most likely cause of this patient's current symptoms?

*Hepatocyte damage* Patient with latent TB (positive TB skin test, no symptoms, unremarkable chest x-ray) started on INH therapy & now has fever, anorexia, nausea INH = *hepatotoxic* = increased AST/SGOT, ALT/SGPT - first 4-6 months of treatment

The reason for variable expression in *mitochondrially* inherited diseasse

*Heteroplasmy* - presence of both normal & mutated mtDNA Ex. Mitochondrial myopathy - presence of lactic acidosis & ragged skeletal muscle fibers = variable clinical expressions in affected fam members

In patients with Essential Fructosuria, a patient may sometimes be able to metabolize fructose due to compensatory activity of what enzymes?

*Hexokinase* Fructokinase deficiency = asymptomatic = AR = dietary fructose excreted unchanged in urine = hexokinase takes over role of fructose metabolism --> converts dietary fructose into fructose-6-phosphate --> can be metabolized in glycolytic pathway or converted to glucose-6-phosphate or glucose-1-phosphate

58-year-old man with dyspnea & chronic exertional angina is evaluated for coronary revascularization. He has a history of HT, type 2 diabetes mellitus, & hypercholesterolemia. His BP is 130/80 mmHg & pulse is 72/min & regular. Cardiopulmonary exam is normal with exception of fourth heart sound. Echo reveals hypokinesia of anterior wall of left ventricle & a left ventricular ejection fraction (LVEF) of 35%. The patient undergoes coronary artery bypass grafting. Repeat echocardiogram 10 days after surgery shows that hypokinesia is no longer evident & LVEF has increased to 50%. What best explains the changes in the cardiac contractility & wall motion seen in this patient?

*Hibernating myocardium* / Myocardial hibernation - state of chronic myocardial ischemia - myocardial metabolism & function reduced to match concomitant reduction in coronary blood flow = prevents myocardial necrosis - decreased expression & disorganization of contractile & cytoskeletal proteins, altered adrenergic control, reduced calcium responsiveness --> decreased contractility & left ventricular systolic dysfunction *Coronary revascularization & subsequent restoration of blood flow to hibernation myocardium improves contractility & LV function*

Multiple members of an extended fam are diagnosed with specific autoimmune disease. In an attempt to identify a marker to assess the risk for this disease in other fam members, the expression of what should be identified in each fam member?

*Histocompatibility antigens* Histocompatibility = having same/similar alleles of set of genes of HLA - presence of specific anti-HLA Ab indicates presence of corresponding MHC protein

During differentiation of mammary gland alveolar cells in late pregnancy, the hormone that acts synergistically with estrogen is what?

*Human placental lactogen* - may have actions either on the development (mammogenesis) or the function (lactogenesis) of the mammary gland - stimulates DNA synthesis in mammary tissue

27-year-old woman goes to clinic for evaluation of worsening abdominal pain & diarrhea. For several months, she has had mild, intermittent abdominal pain that is often accompanied by watery diarrhea & low-grade fever. In the last week, the abdominal cramps have worsened & she has seen streaks of dark blood in her watery-brown stools. She has lost 4.5-kg (10 lb) in the past 2 months. She denies changes in diet or recent travel. Physical exam shows mucosal ulcers in her mouth & a small anal fissure. Endoscopic exam of the colon shows areas of mucosal ulceration with deep fissures. Microscopic exam of biopsies from diseased rea of bowel shows acute & chronic colitis with nocaseating granulomas. What sites in the GI tract is the most common location of this disease process?

*Ileum* Crohns

63-year-old man comes to office for evaluation of 3 months of increasing cough with occasional hemoptysis, night sweats, & unintentional weight loss. He recently migrated from South Africa, where he worked in the gold mines. The patient has a histoyr of silicosis diagnosed 10 years ago. Vital signs show low-grade fever. Exam reveals diffuse, fine crackles with right upper lobe predominance. Chest x-ray shows diffuse small nodules, hilar adenopathy with prominent calcifications, & a right upper lobe cavitary lesion. Sputum is sent for appropriate staining & culture. This patient's increased susceptibility to the current infection is best explained by what factors?

*Impaired macrophage function* Silicosis - calcification of rim of hilar nodes (eggshell calcificatino) & birefringent silica particles surrounded by fibrous tissue - increased risk of TB - *impairs macrophage effector arm of cell-mediated immunity* - macrophage phagolysosomes disrupted by internalized silica particles = release of particles & viable bacteria

34-year-old Native American woman recently diagnosed with acute leukemia tells the physician that she wants to go to a traditional healer for treatment instead of undergoing therapy. What responses by the physician is most appropriate?

*In addition to seeing a traditional healer, I would like you to consider undergoing chemotherapy*

What is a requirement for referring a patient for hospice care?

*Patient has prognosis of <6 months* Hospice care - for terminally ill patients - when aggressive, curative treatment no longer desired - large population = cancer patients - compassionate care that focuses on comfort & quality of life - multidisciplinary team

37-year-old woman brought to ED after developing sudden-onset arm weakness & difficulty speaking. She has no significant medical history but takes oral contraceptives. Exam shows decreased right upper extremity strength & expressive aphasia. Cardiac auscultation is normal. MRI of the brain reveals acute infarction in the left frontal lobe. Further evaluation to determine an etiology is performed. During echocardiogram, agitated normal saline is injected into a peripheral vein & bublles are seen passing into the left side of the heart. What is the most likely cause of the observed finding in this patient?

*Incomplete fusion of atrial septum primum & secundum* Cryptogenic stroke - evaluated with echocardiography with "bubble study" to identify right-to-left intracardiac shunts = injected agitated normal saline IV - shunt detection improved by having patient release sustained Valsalva maneuver = increased right atrial pressure - frequently associated with atrial septal abnormalities such as *patent foramen ovale* (PFO) & atrial septal defect (ASD)

Bicornuate uterus most commonly results from what abnormal processes?

*Incomplete fusion of paramesonephric (mullerian) ducts* - increased risk of complicated pregnancy, early pregnancy loss, malpresentation, prematurity

Liver enzyme glucokinase catalyzes phosphorylation of glucose to glucose-6-phosphate. The value of Km for glucose is about 7 mM. Blood glucose is 5 mM under fasting conditions and can rise in the liver to 20 mM after a high-carb meal. Therefore, if a person who is fasting eats a high-carb meal, the velocity of glucokinase reaction will change in what ways?

*Increase from less than 50% Vmax to more than 50% Vmax* Vmax = (5 x Vmax) / (7+5) = 42% Vmax = (20 x Vmax) / (20 + 7) = 74%

A young woman (5'3" tall, 1.6 m) who has a sedentary job & does not exercise consulted a physician about her weight, which was 110 lb (50 kg). A dietary history indicates that she eats approx. 100 g of carbs, 20 g of protein, & 40 g of fat daily. Based on the woman's current weight, diet, & sedentary lifestyle, the physician correctly concludes that she should undertake what?

*Increase her caloric intake* Caloric intake = 400 + 80 + 360 = 840 kcal/day Expenditure = (110 / 2.2) = 50 kg --> 50 kg x 24 = 1200 + 360 (1200 x 0.30 for sedentary person) = 1560 kcal/day Caloric intake less than Expenditure = she is losing weight --> she needs to increase her caloric intake She is probably in negative nitrogen balance because her protein intake is low - 0.8 g/kg/day = recommended

Lorazepam given. Administration of lorazapem most likely to have what electrophysiologic effects on neuron?

*Increased influx of Cl-* Benzos - facilitates GABAA action by increased frequency of Cl- channel opening - decreased REM sleep

What will be found in *skin lesion* of patient whose intradermal injection of heat-killed Mycobacterium leprae causes dev't of large indurate nodule?

*Increased interleukin-2 & interferon-gamma in skin lesions* - strong CD4+ TH1 cell-mediated immune response - tuberculoid leprosy other spectrum: - lepromatous leprosy = test negative via weak TH1 cell-mediated immune response

54-year-old man with history of hepatitis C infection brought to ED by his wife after several episodes of vomiting bright red blood. He is admitted to hospital & appropriate treatment is initiated. During morning round the next day, patient is disoriented & cannot identify month or his current location. Physical exam shows significant abdominal distention & gynecomastia. Repetitive flicking motions of hands are seen when patient is asked to outstretch his arms & dorsiflex his wrists. What events is the most likely precipitant of this patient's altered mental status?

*Increased load of nitrogenous substance absorbed by gut* Hepatic encephalopathy - ppted by his recent GI bleeding - increased ammonia & other neurotoxins in circulation --> increased inhibitory neurotransmission & impaired excitatory NT release - lowering of blood ammonia is typically accomplished with oral admin of disaccharide (lactulose) --> acidification of colonic contents

32yo man brought to ED 20 min after having a generalized tonic-clonic seizure. 24hr Hx of fever, headache, intolerance to light. He's alert, temp 40C/104F, 140 pulse, fast respirations, 90/55bp. No focal neuro findings. IV fluids are given, and there is persistent bleeding around the IV site. Lab PT normal PTT normal Increased Fibrin degradation products and D-Dimer Which of the following changes is mos likely in the blood coag process of this patient?

*Increased plasmin generation* DIC - increased fibrin degradation products - decreased fibrinogen levels - PT & PTT just haven risen yet because it's too early Plasminogen --> Plasmin --> Fibrinolysis = cleavage of fibrin mesh; destruction of coagulation factors

During an investigational study, a newly synthesized drug (Drug X) is found to selectively block effects of inhibin. A researcher administers Drug X to an experimental animal. What is most likely to occur?

*Increased serum follicle-stimulating hormone concentration* - Sertoli cells (non-germ cells) secrete inhibin B --> inhibit FSH - FSH stimulates release of inhibin B from Sertoli cells in Seminferous tubules of testicles - defective FSH receptors --> prevents spermatogenesis = decreased inhibin B levels

Patient who has flank pain, hematuria, elevated lactate dehydrogenase (cell necrosis), & a kidney lesion on CT likely has renal infarction. The most common cause of renal infarction is systemic *thromboembolism* (from left atrium or ventricle). Systemic thromboembolism commonly occurs with

*atrial fibrillation* - irregular heart contractions can lead to clot formation

53-year-old man comes to physician with progressive exertional dyspnea. He has smoked 2 packs of cigarettes per day for 35 years. Physical exam shows increased anteroposterior diameter of his chest. Auscultation reveals decrased breath sounds & scattered wheezes throughout his lungs. Exam of his extremities is unremarkable. An echocardiogram shows moderate dilation of the right ventricle & increased central venous pressure. The absence of peripheral edema in this patient is best explained by what mechanisms?

*Increased tissue lymphatic drainage* COPD - via chronic bronchitis/emphysema - right ventricular dilation & elevated central venous pressure = cor pulmonale secondary to COPD --> rise in capillary hydrostatic pressure, net plasma filtration, interstitial fluid pressure *As interstitial fluid pressure increases, so does lymphatic drainage = can compensate for moderate CVP elevations & prevent dev't of clinically apparent edema*

During an experiment 500mg of both drug x and y are simultaneously administered iv , the serum concentration of both drug s after bolus administration is 5 mg and 2.5mg respectively.Assuming no drug interactions .which of the finding regarding the drug y is compared with drug x?

*Increased volume of distribution* The higher the Vd the lower the plasma concentration and vise versa. ex. quinidine higher Vd displaces digoxin. Vd = amount of drug in body /plasma drug concentration - so plasma drug conc and volume of distribution are inversely proportional

In patients with Tetralogy of Fallot, what mechanism during squatting relieves the patient's symptoms?

*Increasing systemic vascular resistance* - forces higher proportion of right ventricular output to enter pulmonary circulation & oxygenate pulmonary capillary beds = increased arterial oxygen concentration = relieves Tet spell ToF - pulmonic stenosis & overriding aorta = low ratio of systemic vascular resistance (SVR) to pulmonary vascular resistance (PVR) - low SVR:PVR ratio = deoxygenated right ventricular output takes low-resistance route to systemic circulation = acute hypoxemia (Tet spell)

Recognize Diffuse Gastric Adenocarcinoma/Cancer

*Infiltrative growth within stomach wall* Signet-ring carcinoma = cells that do not form glands - signet ring - diffuse involvement of stomach wall via loss of *E-cadherin* - plaquelike appearance - ill-defined - often infiltrate areas of stomach wall = "leather-bottle stomach" = *linitis plastica*

21-year-old man comes to ED due to abdominal pain, nausea, & vomiting. Patient strted having dull periumbilical pain several hours ago, but the pain is now more severe & localized to the right lower abdominal quadrant. His temp is 38.3 C (101 F), BP is 132/84 mmHg, pulse is 102/min, & respirations are 12/min. The patient keeps his hips flexed & there is max tenderness one-third of distance from anterior superior iliac spine to umbilicus in right lower abdomen. Bowel sounds are decreased. Lab studies show leukocyte count of 16,000/mm^3. What is the most likely cause of the change in the quality of pain in this patient?

*Inflammation of the parietal peritoneum* Appendicitis - can cause both visceral (dull, non-localized) & somatic (severe, well-localized) abdominal pain Visceral abdominal pain - via luminal distention & stretching of smooth muscle - carried by general visceral *afferent* fibers of autonomic nervous system - pain occurs in midline region - poorly localized - dull, constant, or cramping quality - afferent pain fibers for appendix, proximal colon, & overlying visceral peritoneum cross through superior mesenteric plexus & enter spinal cord at T10 to produce vague, referred pain at umbilicus Somatic pain - via irritation of parietal peritoneum - well localized, more severe, worsened with deep inspiration or pushing on abdominal wall

46-year-old man comes to ED with chest pain that began 30 minutes ago. He describes pain as a tight, squeezing sensation that radiates to the left arm. He also has increased sweating & nausea. The patient's ECG shows multiple-lead ST-segment elevation, & cardiac troponin levels are high. He has no known history of cardiac disease. He has a history of alcohol & cocaine abuse. As the patient finishes undergoing emergency cardiac catheterization, the physician is approached by a distraught woman who says she is his wife & asks about his condition. She says, "I am so worried; please tell me if my husband is okay." What is the most appropriate course of action?

*Inform the woman that the patient is stable, but that she will have to wait until he can give permission to share any details.* HIPAA - protects patient privacy - requires patient's explicit consents to share med info - when patient is incapacitated or not present, basic info can be shared in physician's professional judgement if in patient's best interest

How to fibrates contribute to formation of cholesterol gallstones?

*Inhibit cholesterol 7alpha-hydroxylase* = rate-limiting step in synthesis of bile acids - reduced bile acid production = decreased cholesterol solubility in bile Fibrates - upregulate lipoprotein lipase = increased oxidation of FAs

Person diagnosed with group A streptococcal bacteremia. One of the body's major defenses in this type of disease is for eosinophils to phagocytize bacteria. Once internalized, the bacteria are destroyed by fusing the phagosome with a particular intracellular organelle. What would destroy the activity of that organelle such that the bacteria would not be incapacitated?

*Inhibiting a proton-translocating ATPase* Phagosomes fuse with lysosome - digestive enzymes have pH optimum of 5.5 = maintained within lysosome through actions of proton pump (*proton-translocating ATPase activity*)

Mechanism of itraconazole

*cell membrane sterol synthesis reduced by inhibition of C14 lanosterol demethylase* - inhibits fungal sterol (ergosterol) synthesis by inhibiting cytochrome P-450 enzyme that converts lanosterol to ergosterol

50-year-old man comes to physician because of fever, muscle pain, sore throat, & nonproductive cough for 7 days. He has two episodes of similar symptoms during the past year. He has smoked 2 packs of cigarettes daily for 30 years. His temp is 38.9 C (102 F). Rhonchi & crackles are heard on auscultation of the chest. Chest x-rays shows consolidation of the right lower lobe. What mechanisms is the most likely cause of these clinical findings?

*Injury to mucociliary escalator* Legionella pneumophila? The cilia are continually beating, pushing mucus up and out into the throat. The mucociliary escalator is a major barrier against infection. Microorganisms hoping to infect the respiratory tract are caught in the sticky mucus and moved up by the mucociliary escalator. Note how our purple invader has been trapped in the mucus and is being pushed upward towards the throat. Smoking seems to paralyze the cilia of the mucociliary escalator.

21-year-old patient being evaluated for major depressive disorder. During the interview, he admits to having several episodes in the past of feeling "on top of the world," able to function very well with only 4 hours of sleep per night, maxing out his credit cards, & "indiscriminate" sexual encounters with multiple partners. The elemental med most commonly used to treat this patient's disorder will lead to accumulation of what compounds?

*Inositol phosphate* Lithium for bipolar disorder - interrupts PI cycle - blocks action of inositol monophosphatases --> converts inositiol phosphate to free inositol

Evaluation of a section from what location is most appropriate to evaluate a patient's atrioventriculr node?

*Interatrial septum near attachment of septal cusp of tricuspid valve* AV node - lies in septal wall of right atrium - superior & medial to opening of coronary sinus in right atrium - supplied by AV nodal artery, which usually arises from right coronary artery - innervated by autonomic nerve fibers

Gives off upper six anterior intercostal arteries

*Internal thoracic artery*

27-year-old med student coughed on by patient who suffers form active pulmonary tuberculosis infection. The student has never been exposed to M tuberculosis before. What would most likely happen during first week after exposure?

*Intracellular bacterial proliferation* Mycobacteria - phagocytosed by alveolar macrophages --> sulfatide virulence factor expressed by M tuberculosis allows for intracellular bacterial proliferation --> eventually kills macrophage = cellular lysis

21-day-old boy brought to office by his mother because of palpable swelling in child's neck. He continues to feed well but appears comfortable only when held sideways. He is at 50th percentile for height, weight, & head circumference. The child favors looking toward right & cries when his head is turned to the left. There is firm swelling on left side of his neck that does not move when the child swallows. The remainder of exam is unremarkable. What conditions was most likely present prenatally?

*Intrauterine malposition* Congenital torticollis - typically develops by 2-4 weeks old - via birth trauma (breech delivery) or malposition of head in utero (via fetal macrosomia or oligohydramnioa) = SCM injury & fibrosis clinically... - head tilted toward affected side with chin pointed away from contracture - soft-tissue mass may be palpable in inferior one-third of affected SCM - resolve with conservative therapy & stretching exercises

Substance is identified that specifically & completely inhibits glucose transport in proximal renal tubules. In a healthy volunteer receiving this substance, glucose clearance will best approximate clearance of what substance?

*Inulin* Agent that inhibits proximal tubule glucose reabsorption ... - causes all filtered glucose to be excreted --> glucose clearance = GFR - Inulin also freely filtered at glomerulus & is neither reabsorbed nor secreted by renal tubules

Most common cause of type 1 diabetes mellitus

*Islet leukocytic infiltration* - autoimmune insulitis with progressive beta cell loss

52-year-old man being evaluated in ED for abdominal pain associated with watery diarrhea. His symptoms have been progressive over last month. He says he is depressed & often has difficulty remembering things. The patient has a 20-year history of alcohol abuse. On exam, he appears disheveled. A pigmented scaly skin rash is present in malar distribution of his face, neck, & back of his hands. The rash has been present for several months & worsen on exposure to sunlight. It is determined that the patient's symptoms are secondary to lack of a specific nutrient. Activity of what enzymes is most likely decreased in the patient as a result of this deficiency?

*Isocitrate dehydrogenase* Pellagra - photosensitive dermatitis, diarrhea, dementia - via B3 / niacin deficiency - in malnourished populations Niacin - precursor for NAD & NADP = cofactors for many dehydrogenase & reductase enzymes NAD = cofactor for - isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase

23-year-old man comes to the office with chest discomfort that usually occurs during exercise, such as when jogging or climbing stairs. The symptoms go away 5 to 10 minutes after he stops. The patient has not had syncope but mentions some shortness of breath that accompanies the chest pain. Fam history includes an uncle who died suddenly at age of 35 years. BP is 122/70 mmHg & pulse is 70/min & regular. Apical impulse is strong & sustained. He has a soft crescendo-decrescendo systolic murmur at the apex & left sternal border while supine that becomes quite pronounced when he stands up. What meds should be avoided while treating this patient's condition?

*Isosorbid dinitrate* Hypertrophic cardiomyopathy - dynamic left ventricular outflow tract (LVOT) obstruction that worsens with decreased left ventricular volume Avoid: Vasodilators = dihydropyridine CCBs, nitroglycermin, ACE inhibitors - decrease systemic vascular resistance = decreased afterload & lower LV volumes Diuretics - decrease LV venous filling (preload) = greater outflow obstruction

What is the major disadvantage of naloxone as a treatment for opioid overdose?

*It has a shorter duration of action than most opioids* Naloxone - relative short duration of action of 1-2 hours - used to diagnose opioid dependence & to treat acute opioid overdose - multiple doses may need to be administered

7-year-old boy with a two-day history of colicky abdominal pain now develops bloody stools. His mother states that his urine also appeared red today. Physical exam reveals palpable skin lesions on his buttocks. What additional findings is most consistent with this patent's condition?

*Joint pain* Henoch-Schonlein purpura (HSP) - most common small vessel vasculitis in children - affects boys 2-10 y/o - often preceded by viral or streptococcal upper resp infections - Ag from infection stimulates production of IgA Abs --> IgA immune complexes deposit n vessel walls - increased risk of intussusception; GI pain

46-year-old man comes to physician complaining of intermittent, bloody diarrhea & abdominal pain for past month. He has lost 12 lbs (5.5 kg) during period. He was diagnosed with HIV five years ago, but has been noncompliant with his antiretroviral meds. Lab results show CD4 count of 50 cells/uL & viral load of 650,000 copies/mL. Colonoscopy reveals multiple hemorrhagic polypoidal lesions. Biopsy of these lesions reveals spindle cells with surrounding blood vessel proliferation. What is the most likely cause of this patient's diarrhea?

*Kaposi's sarcoma* - via HHV-8 - extracutaneous spread of KS to lungs & GI tract is common Endoscopy results vary - reddish/violet flat maculopapular lesions to raised hemorrhagic nodules or polypoid masses Biopsy - spindle cells with cytologic atypia, blood vessel proliferation, extravasated red blood cells with hemosiderin deposition

An apparently healthy 6-year-old boy is enrolled in a research study designed to assess amino acid absorptive capacity of intestine. As part of the investigation, he is administered an oral solution containing free amino acids. Blood samples are then obtained at 15 minute intervals for the next 2 hours. The boy is found to have significantly decreased intestinal absorption of lysine, arginine, ornithine, & cysteine as compared to the other study participants. If his condition is left untreated, what complications is this patient at greatest risk of developing?

*Kidney stones* Dibasic amino acids = COAL = *C*ysteine, *O*rnithine, *L*ysine, *A*rginine - share common transporter in intestinal lumen & kidneys Cystinuria - defective transporter = impaired renal & intestinal absorption - AR - *recurrent nephrolithiasis = only clinical manifestation* - urinalysis = pathogomonic hexagonal cystine crystals

Km and Vmax in allosteric activator

*Km decreases & Vmax stays the same* - shifts curve left

44-year-old man brought to ED by his wife because of confusion that began a few hours ago. Earlier in the day, he complained of severe headache & nausea. On physical exam, his temp is 38.3 C (101 F) & nuchal rigidity is present. Lumbar puncture & CSF exam show: Opening pressure = 300 mm H2O Glucose = 20 mg/dL Protein = 200 mg/dL RBCs = 4 cells/uL Leukocytes = 760 cells/uL Neutrophils = 90% Lymphocytes = 10% Gram stain of the CSF would most likely reveal what?

*Lance-shaped, Gram positive cocci in pairs* Strep pneumoniae = most common cause of bacterial meningitis in adults of all ages!!!

A case control study is performed to determine the association between brain tumors and cell phone use.The results show an odds ratio of 4.3( 95 % confidence interval 0.9-8.2) for an association between brain tumors and cell phone use.Assume that a 99 % confidence interval was computed rather than the 95 % confidence interval.Which of the following statements best describes the size of the 99% confidence interval compared to the 95 % confidence interval ?

*Larger* You're increasing the confidence interval from 95% to 99%. In other words, you're widening the range of values in which you expect the value to fall within. Example: I take any given value, such as "4.3." I would be 10% sure (or, confident) that it fell between 4 and 5. I would be 25% sure that it would fall between 3 and 6. I would be 50% sure that it fell between 2 and 8. I would be 99% sure that it fell between 1 and 15. Those are just examples to show that as you increase the RANGE of values, you can be more confident that a SPECIFIC value falls within that range.

20-year-old man evaluated in clinic for right arm weakness & numbness. He is a competitive baseball pitcher & says that he played a lot more innings than usual last week because his team made the playoffs. Since then, the patient has had difficulty using the right arm, particularly when lifting objects. He has no known history of head, neck, or upper extremity trauma. On physical exam, there is diminished strength on right elbow flexion & an absent biceps reflex. This patient is most likely to have sensory loss over what areas?

*Lateral forearm* MC nerve injury - commonly occurs in should dislocation/trauma & strenuous upper extremity activity / baseball pitching - derived from C5-C7 from lateral cord - innervates forearm flexors (biceps brachii, brachialis) & coracobrachialis (flexes & adducts arm) --> remaining fibers become lateral cutaneous nerve of forearm = sensory innervation to skin of lateral forearm

Where to listen to the mitral valve?

*Left fifth intercostal space at midclavicular line* - also aspirate pericardial fluid at left fifth intercostal space

47-year-old man comes to ED because of 2-hour history of vomiting bright red blood. He has 20-year history of alcoholism. Physical exam shows jaundice & scleral icterus. Endoscopy shows esophageal bleeding from mucosa. The most likely cause of bleeding is an indirect shunting of portal blood to SVC via what veins?

*Left gastric vein* Esophageal varices are extremely dilated sub-mucosal veins in the lower esophagus. They are most often a consequence of portal hypertension, commonly due to cirrhosis; patients with esophageal varices have a strong tendency to develop bleeding. The majority of blood from the esophagus is drained via the esophageal veins, which carry deoxygenated blood from the esophagus to the azygos vein, which in turn drains directly into the superior vena cava. These veins have no part in the development of esophageal varices. The remaining blood from the esophagus is drained into the superficial veins lining the esophageal mucosa, which drain into the coronary vein (left gastric vein), which in turn drains directly into the portal vein. These superficial veins (normally only approximately 1mm in diameter) become distended up to 1-2 cm in diameter in association with portal hypertension.

52-year-old man brought to ED for hematemesis that began 1 hour earlier. He has regularly consumed large amounts of alcohol for the last 20 years and has been hospitalized numerous times due to ethanol intoxication. Physical exam shows jaundice & scleral icterus. Exam of his abdomen reveals palpable spleen & moderate ascites. Endoscopy shows bleeding esophageal varices. This patient's bleeding most likely resulted from chronic shunting of portal blood to systemic circulation via what veins?

*Left gastric*

In SLE, one specific antibody targets proteins complexed with small nuclear ribonucleic acid. These protein-ribonucleic acid complexes are most likely involved in what cellular functions?

*Removal of introns from RNA transcripts* SLE - malara rash, photosensitivity, Raynaud, fatigue Anti-Smith Abs = highly specific - normally complexes with snRNA in cytoplasm = snRNPs RNA pol II - synthesizes both mRNA & *snRNA* (combines with specific proteins to form snRNPs)

What embryonic arterial structure is most likely responsible for the origin of the patent ductus arteriosus?

*Left sixth aortic arch* - both ductus arteriosus & pulmonary arteries

37-year-old man brought to ED complaining of severe chest pain. His angiogram reveals thromboses of both brachiocephalic veins just before entering the superior vena cava. This condition would most likely cause a dilation of what veins?

*Left superior intercostal* - formed by second, third, & fourth posterior intercostal veins --> drains into left brachiocephalic vein

Major determinant of forward-to-regurgitant flow ratio in patients with mitral regurgitation

*Left ventricular afterload* - decreasing afterload = increased forward flow while reducing regurgitant flow

Diagnosis of multiple sclerosis made. What neuronal properties is most likely to decrease as a direct result of demyelination?

*Length constant* = space constant = measure of how far along an axon an electrical impuluse can propagate = distance at which the originating potential decreases to 37% of its original amplitude Myelination increases length constant & decreases time constant = improve axonal conduction speed

What tissue of the eye relies almost solely on anaerobic metabolism instead of the TCA/electron transport cycle?

*Lens*

60-year-old woman admitted to hospital with pulmonary embolism. Treatment with enoxaparin begun. The patient says, "That's not the heparin my other doctor gave me. Why am I getting this newfangled stuff?" Compared with heparin, what best explains the appropriateness of enoxaparin for this patient?

*Less monitoring required* Low-molecular-weight heparins (daltepain, enoxaparin) - *generally no coagulation monitoring required* - renal clearnce - less reliable dosing in very obese patients - less experience treating PE with hemodynamic instability - expensive;

72-year-old man comes to primary clinic with 6-month history of back & bilateral thigh pain provoked by walking. He normally can walk only 2-3 blocks before having to stop due to pain. However, when he is out walking with his grandchild, leaning on the stroller seems to provide pain relief. The patient also notices an occasional tingling sensation in his lower extremities. He has no prior trauma or history of rheumatologic disorders. On physical exam, muscular strength is normal & sensory findings are unremarkable. Peripheral pulses are full & symmetric. Thickening of what ligaments is most likely contributing to this patient's current presentation?

*Ligamentum flavum* - strong elastic ligament supporting posterior aspect of spinal canal Spinal stenosis - abnormal narrowing of spinal canal in lumbar region - lower extremity pain, numbness/paresthesia, weakness - onset of pain with walking = neurogenic claudication - symptoms are posture-dependent - extension of lumbar spine (standing, walking upright) further narrows spinal cord --> worsens symptoms - lumbar flexion (walking uphill, leaning on stroller/shopping cart) relieves pain - degenerative arthritis of spinal = most common cause of spinal stenosis (patients >age 60) Intervertebral disc degenerates & begins to protrude --> loss in disc height --> load on posterior aspect of spinal column = facet joint osteophytes & hypertrophy of ligamentum flavum

52-year-old woman comes to ED due to recurrent right lower extremity swelling, pain, & erythema. Her medical history includes type 2 diabetes mellitus, HT, & depression. Her meds include metformin, lisinopril, paroxetine, & multivitamin. The patient is diagnosed with cellulitis, admitted to hospital, & started on antibiotics. She is continued on her home meds. Three days later, the patient becomes agitated & delirious with severe abdominal cramps & diarrhea. Her temp is 39.2 C (102.6 F), BP is 180/100 mmHg, & heart rate is 120/min & regular. On exam, she is diaphoretic, tremulousness, & her pupils are dilated. Bilateral hyperreflexia & ankle clonus are present. The patient begins to have seizures. What antibiotics was she most likely given to treat the cellulitis?

*Linezolid* - used to treat infections caused by Gram-positive bacteria, especially VRE & MRSA - *has MAOI activity* = can ppt serotonin syndrome when used with SSRI (paroxetine) Serotonin syndrome - triad: autonomic instability, altered mental status, neuromuscular hyperactivity + GI symptoms & diaphoresis

In a population, the frequency of the HLA-A locus allele (A*01) is 0.20 and the frequency of the HLA-B locus allele (B*08) is 0.20. In the same population, the frequency of the haplotype A*01, B*08 is 0.16. What term best explains the population characteristics of the observed frequency of the A*01, B*08 haplotype?

*Linkage disequilibrium* - tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance - measured in population, not in a family, & often varies in diff't populations

Patient diagnosed with pure sensory stroke & received appropriate treatment. Her symptoms improved & she returned home to liver with her daughter after a few weeks of physical rehabilitation. Five years later, the patient dies of large MI. On autopsy, there are two 5- to 6-mm cavities in the deep structures of her brain filled with clear fluid. What processes was most likely responsible for the patient's brain findings?

*Lipohyalinosis with small vessel occlusion* - predisposes to small-vessel occlusion & infarction of CNS tissue with liquefactive necrosis & formation of fluid-filled cavity Lacunar infarct - lipohyalinosis & microatheromas = primary causes - via leakage of plasma proteins through damaged endothelium = hyaline thickening of vascular wall, collagenous sclerosis, accumulation of mural foamy macrophages with intimal layer of penetrating artery near origin off parent vessel

Consider a normal 25 year old man, about 70 kg in weight, who has been shipwrecked on a desert island, with no food available, but plenty of fresh water. The shipwrecked man will have most of his fuel stored as triacylglycerol instead of protein in muscle due to triacylglycerol stores containing what as compared to protein stores?

*More calories & less water* Adipose tissues = more calories (kcal) & less water than muscle protein - triacylglycerol stored in adipose tissue = 9kcal/g - adipose tissues = 15% water Contrast: muscle protein = 4 kcal/g = 80% water

What properties of skeletal muscle is responsible for its resistance to verapamil?

*Little dependence on extracellular calcium influx* In cardiac & smooth muscle cells... - influx of extracellular calcium --> activates sarcoplasmic RyR channels --> induces release of additional calcium from sarcoplasmic reticulum (calcium-induced calcium release) --> released calcium binds to troponin (cardiac muscle) or calmodulin (smooth muscle) = actin & myosin interact & cause muscle contraction L-type calcium channels in skeletal muscle - directly interact with RyR calcium channels --> release calcium from SR --> mechanical coupling between receptors = sarcoplasmic calcium release occurs without significant influx of calcium across plasma membrane - not dependent on extracellular calcium influx! Verapamil = nondihydropyridine CCB - acts on *blocking L-type calcium channels* = prevents initial calcium influx into cardiac mycoytes & vascular smooth muscle cells

Consider a normal 25 year old man, about 70 kg in weight, who has been shipwrecked on a desert island, with no food available, but plenty of fresh water. The fuel store least likely to provide a significant calories to the man is what?

*Liver glycogen* = fewest available calories = 320 calories Average (70-kg) man fuel composition: Adipose = 15 kg of fat Muscle protein = 6 kg Muscle glycogen = 0.15 kg Liver glycogen = 0.08 kg

Patient diagnosed with GAD & initiated on low dose of SSRI. She returns to office a week later & reports worsening of her anxiety symptoms. She also has difficulty falling asleep at night & is not able to concentrate at her work as a 911 emergency dispatch operator. What med is most appropriate for short-term control of her symptoms without causing excessive daytime fatigue & impaired judgment?

*Lorazepam* SSRIs = first-line therapy for both GAD & panic disorder = must be taken 4 weeks before any noticeable therapeutic effect occurs = initial activating effects can lead to increased agitation & anxiety during this period *Temporary course of benzos is sometimes used during SSRI initiation if there is significant increase in anxiety-related symptoms* Benzos - treatment of anxiety, insomnia, acute seizures, alcohol withdrawal Since patient's increased anxiety is causing insomnia, prescribing a benzo would be beneficial; works in mission-critical position = minimzation of undesirable daytime effects = priority = short- or *intermediate-acting benzo* = *lorazepam* Intermediate-acting benzos: Alprazolam, Clonazepam, Estazolam, Lorazepam, Oxazepam, Temazepam

44-year-old man with stab wound was brought to ED, & a physician found that the patient was suffering from laceration of right phrenic nerve. What has likely occurred?

*Loss of sensation in fibrous pericardium & mediastinal pleura* Phrenic nerve innervates... - pericardium - mediastinal & diaphragmatic (central part) pleura & diaphragm (inspiration) - contains GSE, GSA, GVE fibers

33-year-old patient suffering from sudden occlusion at origin of descending (thoracic) aorta. This condition would most likely decrease blood flow in what intercostal arteries?

*Lower six posterior* Posterior intercostal arteries - first two = branches of highest (superior) intercostal artery of costocervical trunk - remaining nine = branches of thoracic aorta

45-year-old woman comes to physician because of 6-month history of mouth ulcers, thickening of skin, & throbbing pain in her hands when exposed to cold. She also has had 1-month history of severe headaches & difficulty swallowing. Physical exam shows small red lesions around mouth & generalized muscle weakness. Lab studies show high titer of anti-Scl 70 (anti-topoisomerase I) Ab. A biopsy specimen of skin shows thinning of epidermis, hyalinization & obliteration of aterioles, & dermal thickening. These dermatologic changes are caused primarily by release of chemokines from what inflammatory cell types?

*Lymphocytes* T lymphocytes --> release cytokines that lead to collagen synthesis from fibroblasts

24-year-old woman with 2-year history of AIDS & a 4-month history of tuberculosis come to physician for follow-up exam. Current meds include antiretroviral therapy & antituberculosis therapy. Her vital signs are within normal limits. Physical exam shows no abnormalities except for muscular wasting. Results of a PPD skin test are nonreactive. The presence of what conditions in this patient is the most likely cause of the PPD skin test results?

*Lymphocytopenia* type IV hypersensitivity reaction is not working - this reaction is mediated by T lymphocytes (especially Helper CD4 cells ), and these cells are destroyed by HIV virus --> hence lymphocytopenia

8-month-old boy evaluated for dev'tal delay, failure to thrive, & episodic seizures. Physical exam shows ophthalmoplegia & hypotonia. Lab studies reveal elevated serum lactate level. Further histochemical studies show severely reduced pyruvate dehydrogenase enzyme activity in both freshly isolated peripheral blood lymphocytes & cultured fibroblasts. Increasing what substances in his diet is most likely to help this patient generate energy without further elevating lactate levels?

*Lysine*, Leucine = ketogenic diet = high-fat, low carb diet with moderate levels of protein Pyruvate dehydrogenase deficiency - presents in infancy with lactic acidosis & neuro defects - pyruvate dehydrogenase usually generates acetyl-CoA from pyruvate = links glycolysis & TCA cycle - buildup of pyruvate = shunted to lactate dehydrogenase = lactic acidosis

Proton gradient across membranes are essential for functions of what organelles?

*Lysosomes & mitochondria* - lysosomes = acidify intracellular milieu --> lysosomal hydrolases at their pH optima (5.5)

Crohn disease is associated with mutations in

*NOD2* = encodes intracellular microbial receptor --> decreased activity of NF-kappaB = reduced cytokine production

Common side effects of nondihydropyridine calcium channels blocks (*diltiazem*, verapamil)

*constipation* bradycardia *atrioventricular conduction block* (negative chronotropic effect) worsening of heart failure in patients with reduced left ventricular function (negative inotropic effect)

35-year-old woman comes to office due to insomnia & fatigue over past month. She has felt increasingly depressed, irritable, & hopeless since being let go from her job. The week prior to her last menstrual period was particularly difficult, & she stayed in bed most of the day. The patient has lost 3.6 kg (8 lb) and has felt unmotivated & unable to concentrate on looking for new work. Her other medical problems include hypothyroidism & migraine headaches. The patient drinks 1 or 2 glasses of wine several times a week & smokes marijuana once a month. Her meds include levothyroxine & naproxen. Physical exam is normal. Her TSH level is 0.9 uU/mL. What is the most likely diagnosis?

*Major depressive disorder* - depressed mood, low energy, loss of interest, insomni, weight loss, poor concentration - present most of day, almost sever day for >2 weeks - appetite, sleep, & motor activity increased or decreased - *untreated hypothyroidism is a known major medical cause of depression* (however, this patient's normal TSH level = hypothyroidism is well controlled with levothyroxine)

Newborn is born with hypoplastic mandible. What structure is also likely to be affected?

*Malleus* Treacher Collins syndrome - neural crest dysfunction --> mandibular hypoplasia, facial abnormalities - 1st & 2nd arches 1st arch cartilage: *M*axillary process --> *M*axilla, zygo*M*atic bone *M*andibular process --> *M*eckel cartilage --> *M*andible, *M*alleus & incus, spheno*M*andibular ligament

Research scientist studying metabolic pathways that contribute to obesity feeds experimental animals a high-carb, high-protein diet for a prolonged period. A sample of liver tissue is then obtained from the animals, and the activity of various enzymes involved in FA metabolism is measured & recorded. It is determined that beta-oxidation of FAs is inhibited within these cells as a result of the diet. An increase in what substances is most likely responsible for the observed effect?

*Malonyl CoA* - inhibits carnitine acyltransferase --> prevents transfer of acyl groups into mitochondria - high citrate = upregulation of actyl-coa carboxylase --> catalyzes conversion of acetyl-CoA to malonyl-CoA in rate-limiting step of de novo FA synthesis

36-year-old man has shortness of breath, hematuria, & oliguria. BUN & creatinine concentrations are increased. Anti neutrophilic cytoplasmic antibody assay is strongly positive. X-ray of chest shows multiple nodular infiltrates in lungs. Exam of urinary sediments is most likely to show what?

*Many red cell casts and erythrocytes* Rapidly Progressive (Crescentic) Glomerulonephritis - 90% = p- or c-ANCA

Thoracic surgeon removed right middle lobar (secondary) bronchus along with lung tissue from a 57-year-old heavy smoker with lung cancer. What bronchopulmonary segments must contain cancerous tissue?

*Medial & Lateral* Right middle lobar (secondary) bronchus - leads to medial & lateral bronchopulmonary segments

45-year-old man with long history of severe RA being treated aggressively with gold salts. Gins weight and has progressive ankle swelling. Has generalized edema. Serum creatinine concentration is 1. Urinalysis show 4+ protein, numerous hyaline casts, & oval fat bodies, but no red cell casts. Urinary protein excretion is 8.4 g/24 h. EM shows glomerular capillary loop obtained on biopsy. What is the most likely diagnosis?

*Membranous nephropathy* - can be secondary to: NSAIDs, penicillamine, gold, infections, HBV, HCV, syphilis, SLE, solid tumors = spike & dome

45-year-old man comes to ED due to 2 weeks of chest pain & cough. He has history of advanced HIV and has taken his antiretroviral meds inconsistently over the past few months. Temp is 38.1 C (100.6 F). Crackles are heard on pulmonary exam. CD4 cell count is 98/mm^3. Chest x-ray reveals nodules & hilar lymphadenopathy. Bronchoscopy is performed. Mucicarmine staining of patient's bronchoalveolar fluid shows budding yeast forms with thick capsules. Symptomatic infection with the organism causing this patient's condition most commonly manifests as

*Menigoencephalitis* Cryptococcus neoformans - budding yeasts with thick capsules - soil & pigeon droppings - India ink stain

24-year-old man comes to ED complaining of abdominal pain, vomiting, & severe watery diarrhea. He recently returned from camping trip & admits to eating wild mushrooms that he collected in the woods. His past medical history is insignificant & he takes no meds. He does not use illicit drugs. On physical exam, he is ill-appearing & jaundiced. His liver edge is soft, tender, & palpable 4 cm below the right costal margin. Lab tests are significant for elevated levels of alanine aminotransferases, aspartate aminotransferases, & bilirubin. Synthesis of what is most likely to be directly inhibited by the responsible toxin?

*Messenger RNA* Amatoxins - in poisonous mushrooms (Amanita phalloides / death cap) - absorption by GI tract --> transported to liver via portal circulation = active transport by organic anion transporting polypeptide (OATP) & sodium taurocholate co-transporter (NTCP) concentrates toxin within liver cells = amatoxins bind DNA-dependent RNA polyperase II --> halts mRNA synthesis = apoptosis - symptoms within 6-24 hours after ingestion = abdominal pain, vomiting, diarrhea - severe = acute hepatitis, renal failure - urine testing!

Recognize *normal-pressure hydrocephalus*

- decreased CSF resorption - can be secondary to *prior brain trauma or subarachnoid hemorrhage* - progressive symptoms - gait difficulties = magnetic gait - cognitive disturbances - urinary incontinence = late

Oocyte most likely arrested in what stages of meiosis immediately prior to fertilization?

*Metaphase of meiosis II* Female gametogenesis begins in utero at 4 weeks gestation when primordial germ cells migrate from yolk sac region into developing gonadal region --> differentiate into oogonia --> multiply by mitosis before beginning meiosis I --> now called primary oocytes --> cells arrest in prophase of meiosis I & remain there until ovulation = chromosome pairs arranged in tetrad during this phase = genetic recombination --> Telophase I = last phase of miosis I --> yields secondary oocytes & polar bodies --> *secondary oocyte begins miosis II (polar body degenerates) buthalts in metaphase II* --> secondary oocyte remains frozen in metaphase II until fertilization occurs

A 72 year old woman comes to the physician because of an 8-month history of burning chest pain & a bitter taste in her mouth; both symptoms occur at night when she lies down. The pain does not radiate & is not associated with shortness of breath. Physical examination shows no abnormalities. Which of the following is most likely to be associated with her symptoms?

*Metaplasia of esophageal epithelium* Vasospasm is very very rare for GERD. When you look @ metaplasia of esophagus, 5-15% of patients have symptoms of GERD Has been occurring for 8 months, meaning its chronic and very likely metaplasia Period of symptoms very important!

20-year-old woman comes to physician for exam prior to participating on college varsity volleyball team. She has a 1-month history of mild facial acne. Physical exam shows no other abnormalities. Treatment with a topical agent is begun. Three weeks later, she returns to the physician because of leg swelling & weight gain. Physical exam shows severe facial acne & acne on the chest & back. There is 2+ pitting edema of the lower extremities. Lab studies show a mildly increased serum direct bilirubin concentration & serum transaminase activities. The most likely cause of her condition is self-administration of what substances?

*Methandrostenolone* / Metandienone - orally-effecive anabolic steroid - popular among bodybuilders Has mildly androgenic side effects - oily, greasy skin - acne - additional body/facial hair - baldness

45-year-old woman comes to office for follow-up arthritis. For last year, she has had fatigue, weight loss, progressive joint pain in hands associated with prolonged morning stiffness. Past med history includes hypothyroidism, for which she takes levothyroxine. Patient does not use tobacco or alcohol. Exam shows doughy swelling involving multiple metacarpophalangeal joints in both hands. Following initial dianostic testing, multidrug treatment regimen is started. Soon after treatment begins, she develops painful mouth ulcers & nausea. Liver function tests show new aspartate transaminase & alanine transaminase elevations. What meds is most likely resonsible for adverse effects seen in this patient?

*Methotrexate* - folate antimetabolite - halts purine & pyrimidine synthesis via competitive inhibition of dihydrofolate reductase Toxicities - to tissues with rapid cellular turnover - oral & GI mucosa = ulcerations - hair follicles = alopecia - bone marrow = pancytopenia - hepatotoxicity - pulmonary fibrosis - middle-aged woman + polyarthritis + morning stiffness + systemic symptoms = RA

Treatment of cancer with 5-fluorouracil is effective because it prevents what?

*Methyl group transfer to dUMP to for dTMP* 5-fluorouracil - pyrimidine analod bioactivated to 5-dUMP --> covalently complexes with thymidylate synthase & folice acid - capecitabine = prodrug with similar activity - inhibits thymidiylate synthase --> decreased dTMP --> decreased DNA synthesis

19-year-old man came to ED, & his angiogram exhibited that he was bleeding from the vein that is accompanied by the posterior interventricular vein. What vein is most likely ruptured?

*Middle cardiac vein* - ascends in posterior interventricular groove - accompanied by interventricular branch of right coronary artery

72-year-old Caucasian woman comes to ED after several hours of severe back pain. Patient developed pain after experiencing sudden bump while driving over pothole. She has no previous history of back pain or major trauma. She has a long history of COPD with exacerbations requiring glucocorticoid use in past, though she has been stable since she quit smoking 5 years ago. The patient drinks 1 glass of wine daily. Her BMI is 18.4 kg/m^2. On exam, she has point tenderness over T10 vertebra. The neuro exam is unremarkable. X-ray of the spine reveals T10 compression fracture. What area on a PTH vs. Serum calcium graph would represent this patient's most likely metabolic state?

*Middle/Normal* In primary osteoporosis (osteoporosis not due to underlying medical disorder), serum calcium, phosphate, & PTH levels are typically in normal range

30-year-old woman who takes ibuprofen for arthritis has a marked increase in menstrual cramping after starting a drug to prevent peptic ulcer. What drugs most likely cause this adverse effect?

*Misoprostol* - can worsen menstrual cramping due to uterus contraction

51-year-old man has holosystolic murmur that is loudest over apical impulse & radiates to axillae. What is the most likely diagnosis?

*Mitral insufficiency* / regurgitation - holosystolic, high-pitched "blowing murmur" - loudest at apex & radiates toward axilla - often due to ischemic heart disease (post-MI), MVP, LV dilatation

38-year-old woman is being evaluated for shortness of breath. Patient has had poor exercise tolerance for the last month that she initially attributed to deconditioning. Over the last several weeks, her symptoms have gotten progressively worse & she currently feels short of breath even during mild exertion. The patient has no fam history of heart disease. As part of her evaluation, she undergoes right & left heart catheterization. The following date are obtained: Left ventricular end-diastolic pressure = 10 mmHg (normal = 3-12 mmHg) Left ventricular peak systolic pressure = 110 mmHg (normal = 100-140 mmHg) Pulmonary capillary wedge pressure = 36 mmHg (normal < 12 mmHg) What is the most likely cause of this patient's symptoms?

*Mitral stenosis* - increased LA pressure = reflected as elevated PCWP during pulmonary artery cath - left ventricular filling may be normal = increased pressure gradient between LA & LV during diastole

In hypertrophic cardiomyopathy, the patient's symptoms are most likely explained by left ventricular outflow obstruction created by what structures?

*Mitral valve leaflet & interventricular septum* HCM - AD - asymmetric ventricular septal hypertrophy - variable, dynamic left ventricular outflow tract (LVOT) obstruction - systolic anterior motion of mitral valve toward interventricular septum = eccentric mitral regurgitation & exacerbates LVOT obstruction - harsh crescendo-decrescendo systolic murmur at apex & left lower sternal border

46-year-ole woman comes for follow-up after episode of alcoholic pancreatitis. She was hospitalized 4 weeks ago for abdominal pain & also underwent treatment with benzos for alcohol withdrawal. The patient once drank 3 L of boxed wine daily but has been abstinent since discharge. She is motivated to remain abstinent but requests med to reduce her craving for alcohol. A med with what mechanisms of action would be most effective in this patient?

*Mu-opioid receptor blockade* Meds used to treat alcohol dependence - oral IM depot naltrexone - disulfiram - acamprosate Naltrexone - blocks mu-opioid receptor - can be initiated while individual is still drinking - blocks rewarding & reinforcing effects of alcohol - reduces craving for alcohol

15-year-old girl brought in for evaluation of amenorrhea. She has never menstruated, but her mother had menarche at age 14. The patient has no other medical problems or allergies. She takes no meds & does not use tobacco, alcohol, or drugs. She is not sexually active. Her height is 175 cm (5 ft 8 in), weight is 65 kg (143 lb), & BMI is 21.2 kg/m^2. Exam shows fully developed secondary sexual characteristics. Pelvic ultrasound shows shortneed vaginal canal with rudimentary uterus. What is the most likely diagnosis in this patient?

*Mullerian syndrome* Mayer-Rokitansky-Hauser (MRKH) syndrome - variabl uterine dev't & no upper vagina (short vagina) - patient cannot menstruate - normal ovaries, which secrete estrogen normally & enable regular dev't of secondary sexual characteristics (breast, pubic hair) Up to 50% of patients with Mullerian defects have unilateral agenesis

39-year-old man brought to ER for suspected suicide attempt. He has blurred vision; very dry, hot, red skin; dry mouth; urinary retention; confusion; hallucinations; loss of balance; & tachycardia. EMTs found an empty bottle of amitriptyline in his apartment. The date on the bottle was just 1 week ago, yet all the pills were missing. The effects the man is experiencing is due to inhibition of what processes?

*Muscarinic acetylcholine receptor signaling*

6-month-old girl has not had any illnesses, although mother says girl has trouble latching when breast feeding. She can roll over when prone but cannot roll form supine position or sit unsupported. Infant was born vaginally after uncomplicated pregnancy. Vital signs are within normal limits. On physical exam, the girl has a head circumference above 97th percentile for her age & a full anterior fontanelle. Remainder of her physical exam is unremarkable. At birth, girl's head circumference was at 50th percentile. CT scan of head reveals significant dilation of lateral ventricles. If this condition is left uncorrected, what is the most likely complication that will be seen in this patient?

*Muscle hypertonicity* Congenital hydrocepalus - macrocephaly, poor feeding, *muscle hypertonicity*, hyperreflexia - hypertonicity & hyperreflexia via upper motor neuron injury via stretching of periventricular pyramidal tract - treatment = shunt via ventriculoperitoneal route

A 27-year-old male became los while hiking in Yosemite National Park. He was found eight days later. He had nothing to eat & only water to drink before being rescued. The man's brain would attempt to decrease consumption of glucose & increase consumption of ketones in order to protect breakdown (catablism) of what?

*Muscle protein* - goal to save muscle tissue (AAs used for gluconeogenesis) - brain in starvation mode utilizes ketone bodies

Bacteria isolated from lung tissue of 32-year-old Caucasian male fail to decolorize with hydrochloric acid & alcohol after staining carbolfuchsin. What cell wall components is most likely responsible for this staining phenomenon?

*Mycolic acid* Acid-fast stain - detection of Mycobacterium & Nocardia - smear first treated with aniline dye (carbolfuchsin) --> dye (red color) penetrates bacterial cell wall --> binds with mycolic acids --> slid treated with hydrochloric acid & alcohol --> presence of mycolic acids prevents decolorization of mycobacteria --> counterstain (methylene blue) applied = taken up by decolorized bacteria

Patient diagnosed with acute MI complicated by acute severe heart failure. He is started on dobutamine infusion & is taken for coronary catheterization. What is most likely to be increased due to medication used in this patient?

*Myocardial oxygen consumption* Dobutamine - beta-adrenergic agonist with predominant activity on beta1 - used for refractory heart failure associated with LV systolic dysfunction & cardiogenic shock increased cAMP... - positive inotropic effect = increased cardiac contractility = increased cardiac output & decreased LV filling pressure - weakly positive chronotropic effect = increased heart rate --> combined with positive inotropic effect = *increased myocardial oxygen consumption* - mild vasodilation

8-year-old boy evaluated for exercise intolerance. The patient experiences fatigue, muscle pain, & cramps during exercise as well as severe muscle stiffness following strenuous activity. Physical exam is unremarkable. A forearm ischemic exercise test is performed by applying BP cuff on patient's exercising forearm & sampling blood lactate several minutes after exercise. The patient's bloods samples show no rise in lactate levels. Biochemical analysis of muscle biopsy reveals absent lactate dehydrogenase activity. In this patient, strenuous exercise leads to inhibition of glycolysis in skeletal muscle due to intracellular depletion of what substances?

*NAD+* - when oxygen is depleted (in exercising muscle), pyruvate converted to lactate (anaerobic glycolysis) Anaerobic glycolysis - NAD+ regenerated from NADH when pyruvate is converted to lactate via dehydrogenase Lactate Dehydrogenase deficiency - glycolysis inhibited in strenuous exercising muscle as muscle cells cannot regenerate NAD+ - high-intensity physical activity = muscle breakdown, pain, fatigue because insufficient amounts of energy produced in exercising muscle

23-year-old man comes to physician at girlfriend's insistence. She complains that one night last week he fell asleep while they were talking & that he frequently snores. He says that he almost always falls asleep in the afternoon while reading or watching television & typically feels refreshed after a brief nap. When asked whether he experiences any other symptoms, the patient hesitantly reveals that he sometimes hears a voice call his name prior to falling asleep. He also reports uncharacteristic episodes of clumsiness in which he has suddenly dropped objects or fallen to his knees. Exam shows no abnormalities. What is the most likely diagnosis of this patient?

*Narcolepsy* - overwhelming urges to sleep - cataplexy = sudden loss of muscle tone in response to intense emotions - via depletion of hypocretin-secreting neurons in lateral hypothalamus involved in maintaining wakefulness - shortened sleep latency - enter REM almost immediately - low CSF levels of hypocretin-1 or shortened REM sleep lateceny on polysomnography - hypnagogic hallucinations - feel refreshed after naps

66-year-old man with non-ischemic cardiomyopathy has persistent shortness of breath despite being on maximal heart failure therapy. He has no lightheadedness or chest pain. BP is 133/72 mmHg & pulse is 76/min. The patient is treated with a novel med that inhibits the metalloprotease neprilysin. This medication promoted natriuresis & decreases BP by vasodilation. Inhibitors of the metalloprotease prevent degradation of what substances?

*Natriuretic peptides* Brain natriuretic peptide (BNP) - release in response to high atrial & ventricular filling pressures (myocardial stretch) - protects against deleterious myocardial remodeling & fibrosis that occurs in heart failure Neprilysin = metalloprotease that cleaves & inactivates endogenous peptides including natriuretic peptides (BNP), glucagon, oxytocin, bradykinin Inhibition of neprilysin = increased levels of endogenous natriuretic peptides --> promotes beneficial effects in heart failure

Previously 21-year-old man brought to ED by friends 30 minutes after sudden onset of right-sided chest pain & difficulty breathing while playing basketball. He appears in acute distress. He is 6 ft tall & weighs 143 lb; BMI is 19 kg/m^2. Temp is 37 C (98.6 F), pulse is 110/min, respirations are 32/min, & BP is 120/70 mmHg. Pulmonary exam shows hyperresonant sounds over right lateral portion of chest. Breath sounds are decreased. A mild pleural rub is heard. A chest x-ray shows sharp line running parallel to chest wall adjacent to radiolucent area without lung markings. What is the most appropriate next step in management?

*Needle aspiration* - need to inflate lung

Pharyngeal exudate sample from woman in 20-25-y/o group placed on selective medium containing vancomycin, colistin, nystatin & trimethoprim. This medium favors growth of what bacteria?

*Neisseria gonorrhoeae* - pharyngeal exudates growth both gram + & - Chocolate agar-based medium = Thayer-Martin medium - used to isolate Neisseria - vanc inhibits gram positive - colistin/polymyxin inhibits gram negative - nystatin inhibits yeast - trimethoprim inhibits Proteus

59-year-old man comes to ED with diplopia that started several hours ago. His past medical history is significant for long-standing diabetes with poor glycemic control, right-knee osteoarthritis, & peptic ulcer disease. Physical exam shows right-sided ptosis with right pupil in inferolateral position. Pupils are equal in size & reactive to light bilaterally. This patient's condition is most likely due to what etiologies?

*Nerve ischemia* Diabetic neuropathy: Diabetic CN III mononeuropathy - acute onset dilopia - down & out position via unopposed pull by CN IV & VI - ptosis via paralysis of levator plpebrae - via ischemic nerve damage = CN III = relative sparing of peripheral part - *pupillary size & reactivity is normal*

62-year-old woman evaluated for refractory nausea & vomiting. She was recently diagnosed with ovarian cancer & underwent total hysterectomy with bilateral salpingo-oophorectomy & pelvic lymph node dissection. The patient was started on highly emetogenic adjuvant chemo. Despite taking ondansetron around the clock, she continues to have nausea & vomiting. She has no abdominal pain or constipation. Vital signs are normal. Exam shows a well-healed abdominal scar. There is no tenderness of abnormal masses. Bowel sounds are normal. Additional therapy blocking what receptors would be most likely to be helpful in this patient?

*Neurokinin 1*

37-year-old woman has 3-year history of progressive dementia & writhing movements in all four extremities. Her father died of a similar illness. What structures is most likely to be involved?

*Neurons of the striatum* Huntingtons - caudate is part of striatum!!!

What cell count is increased with use of corticoisteroids?

*Neutrophils* - via demargination of neutrophils previously attached to vessel wall = increased infection risk!!! - decreased: lymphocytes, monocytes, basophils, eosinophils - high doses = corticosteroid-induced psychosis = confusion, hallucinations (hypoalbuminemia = risk factor)

75-year-old man brought to ED after he was found unresponsive at home. The patient has a history of poorly controlled HT. BP is 240/120 mmHg & pulse is 104/min. He has extensor posturing & pinpoint pupils. CT scan of head without contrast reveals acute pontine hemorrhage with associated mass effect. Patient died several hours later. Autopsy reveals disruption of all pigmented neurons in posterior pons at lateral floor of fourth ventricle. These neurons normally produce what?

*Norepinephrine* HT hemorrhage in pons at level of *locus ceruleus* = paired pigmented brainstem nucleus in posterior rostral pons near lateral floor of fourth ventricle = principle site of NE synthesis Bilateral pontine hemorrhage = coma via disruption of reticular activating system - total paralysis with extensor posturing via corticospinal & corticobulbar tract injury - pinpoint pupils via descending sympathetic damage

1-year-old boy is brought to the physician by his mother for a well-child exam. She says he has no interest in toilet training. He is at the 30th percentile for height & weight. He has a vocab of about 10 words & recently began walking on his own. His mother consumed alcohol "several times" during her first trimester of pregnancy. What best describes the dev't of this boy? Motor = Language =

*Normal* - cruises, takes first steps (by 12 months) *Normal* - 200 words by age 2 (2 zeroes), 2-word sentences

A 22-year-old woman participates in a clinical study of a putative protein hormone that is synthesized in the liver in response to a decrease in the blood platelet concentration. injection of the hormone causes an increase in platelet production. Which of the following is the most likely location of the receptor that accounts for the increase in platelet count??

*On the cell membrane of megakaryocytes* The hormone that injected is thrombopoietin. Thrombopoietin receptors are on the cell membrane of Megakaryocytes - receptor with Jak/Stat pathway.

23-year-old man comes to office due to dysuria & a small amount of urethral discharge. He has no med problems, takes no meds, & has no known allergies. Temp is 37.1 (98.8 F). On genitourinary exam, urethral discharge is present. Under microscope, discharge is neutrophil-rich with intracellular gram-negative diplococci. Single IM injection of ceftriaxone is administered. A week later, the patient returns to office because his symptoms have not improved. What is most likely to improve his condition?

*Oral azithromycin* Urethritis in young man most likely due to N gonorrhoeae or Chlamydia trachomatis = give both ceftriaxone for N gonorrhoeae & doxycycline or azithromycin for C trachomatis

2-year-old boy brought to ED with fever, vomiting, & sleepiness. He had several episodes of emesis this morning, & his mother was unable to wake him from his afternoon nap. The boy has had mild rhinorrhea & fever for the past 3 days. Since the newborn period, the parents say that the patient has had multiple illnesses characterized by vomiting & sleepiness. Prior lab testing revealed increased blood ammonia levels during these episodes & markedly increased orotic acid excretion in the urine. Physical exam shows a tachypneic boy who is unresponsive to all stimuli. What enzymes is most likely to be deficient in this patient?

*Ornithine transcarbamylase* - carbamoyl phosphate synthetase = rate-limiting enzyme in urea cycle OTC deficiency - most common urea cycle disorder - excess carbamoyl phosphate --> stimulates pyrimidine synthesis - orotic acid accumulates - hyperammonemia via impaired ammonia excretion = vomiting, confusion/coma, tachypnea

infantile osteopetrosis

*Osteoclasts*

Assume that there is a microRNA that participates in regulating expression of particular cyclin kinase inhibitor. How might an alteration in this microRNA lead to uncontrolled cell proliferation?

*Overexpression of microRNA, so its acts as an oncogene* microRNAs - reduce amount of protein product formed from target mRNA - overexpressed = eliminate production of cyclin kinase inhibitor = no brakes on cell cycle

50-year-old man with a "pot belly" and a strong fam history of heart attacks is going to their physician for advice on how to lose weight. He weighs 220 lbs (100 kg) & is about 6 feet tall (1.85 m). His lifestyle can be best described as sedentary. Into what categories does his BMI place him?

*Overweight (pre-obese)* BMI = 29 - < 18.5 = underweight - 18.5 - 24.9 = healthy - 25-30 = pre-obese - > 30 obese

67-year-old Caucasian male with past med history significant for severe, ongoing drug-resistant HT, dies of intracranial hemorrhage. At autopsy, the right kidney is significantly shrunken, thought the left kidney appears grossly normal. What mechanisms most likely explains the renal morphology in this patient?

*Oxygen & nutrient deprivation* Unilateral renal artery stenosis - cause of 2ndary HT in 2-5% of HT patients - kidney affected by stenosis may become atrophied due to oxygen & nutrient deprivation - most common cause of renal artery stenosis (70%) = obstruction by atheromatous plaque at origin of renal artery stenosis = more common in males & patients with diabetes mellitus --> incidence increases with age --> ischemic kidney secretes high levels of renin = HT --> stenosis may also cause renal atrophy due to oxygen & nutrient deprivation

Treatment for Enterobius vermicularis / Pinworms

*PAM has Pinworms!* Pyrantel pamoate Albendazole Mebendazole

Mitral stenosis leads to an increase in LA pressure that is reflected as elevated

*PCWP* during pulmonary artery catheterization - normally, PCWP closely reflect left atrial & left ventricular end-diastolic pressure (LVEDP) - left ventricular filling may be normal = increased pressure gradient between LA & LV during diastole

Scientist has developed a drug that, when added to eukaryotic cells, leads to elevated lactate levels. An analysis of mitochondrial contents also demonstrated elevated alpha-ketoglutarate levels in drug-treated cells. This drug may be interfering with a reaction that requires what vitamins?

*Pantothenate* - elevation of lactate & alphaketoglutarate in TCA cycle = defect in reactions that catalyze oxidative decarboxylations Pyruvate accumulates if pyruvate dehyrogenase defective - increased pyruvate --> increased lactate Five cofactors needed for oxidative decarboxylation reactions - NAD+ - FAD - lipoic acid - thiamine pyrophosphate - *coenzyme A (derived from pantothenic acid! ding ding ding!)* Drug is blocking conversion of pantothenic acid to coenzyme A

Part of lymph node not well developed in DiGeorge syndrome

*Paracortex region* - T cells & dendritic cells - dendritic cells present antigens that they collect from blood & lymph to aggregated T cells in this region DiGeorge = poorly developed via deficiency of mature T cells

56-year-old woman with squamous cell carcinoma of lung has had fatigue, weakness, right flank pain, anorexia, & constipation for 6 weeks. Exam shows hematuria. The most likely cause of these symptoms is secretion of what substances by the carcinoma?

*Parathyroid-related protein* Squamous cell carcinoma of lung - hilar mass arising from bronchus - cavitation - cigarettes - hypercalcemia (produces PTHrP)

37-year-old man comes to physician because of progressive heartburn over past 6 months. The symptoms are most severe after eating large or spicy meals & are partially relieved with antacid therapy. An endoscopic specimen of the lower esophagus shows esophagitis. The most likely cause of the esophageal changes is a substance secreted by what cell types?

*Parietal cells* - secrete acid/HCl in stomach

A 6 yr old boy with a congenital HIV infection and has been fatigued for 3 weeks. Lab studies show Hb 4.6; Hematocrit 14%; leukocyte count 6500/mm3; retic count 0.5% of red cells; platelet count 200,000/mm3 Then a bone marrow smear was shown. Which of the following is the most likely causal organism of the patient's anemia?

*Parvovirus B19* = important treatable cause of anemia in HIV-infected patients - has tropism for erythroid progenitors --> pure red cell aplasia (PRCA) - failure to produce neutralizing Abs to virus following B19 infection in immunodeficient ppl --> persistent viremia & chronic PRCA (B19-PRCA) - seroprevalence rates for B19 in unselected ppl with HIV infection = high - low reticulocyte count = hallmark of Fifth disease

Activity of what enzyme is most likely increased as a result of Lesh-Nyhan syndrome?

*Phosphoribosyl pyrophosphate amidotransferase* Lesch-Nyhan syndrome - X-linked recessive - dystonia, choreoathetosis, self-mutation, hyperuricemia within first few years of life - deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) = functions in purine salvage pathway to convert hypoxanthine back to inosine monophosphate & guanine back to guanosine monophosphate Purine synthesis - first step = formation of PRPP by PRPP synthetase = can be used by adenine phosphoribosyltransferase & HGPRT for purine salvage or be converted to phosphoribosylamine by PRPP amidotransferase in first committed step of de novo purine synthesis

Leads to insulin resistance

*Phosphorylation of serine & threonine residues of insulin receptor & insulin receptor substrate by serine kinase* - this type of phosphorylation can be induced by: TNF-alpha, catecholamines, glucocorticoids, glucagon

20-year-old man evaluated for recurrent episodes of jaundice. He was separated from his parents at a young age & is unaware of any fam medical history. The patient resided in several foster homes throughout his childhood but currently lives alone. His temp is 36.7 C (98 F), BP is 120/80 mmHg, & pulses is 72/min. Physical exam shows pallor, icterus, & mild splenomegaly. There is no lymphadenopathy or hepatomegaly. The remainder of the physical exam is normal. Lab test results are as follows: Hemoglobin = 9 g/L Platelets = 198,000/mm^3 Leukocytes = 6500/mm^3 Lactate dehydrogenase = Increased Total bilirubin = 3.4 mg/dL Direct bilirubin = 0.2 mg/dL Aspartate aminotransferase (AST) = 25 U/L Alanine aminotransferase (ALT) = 30 U/L Direct Coombs test = Negative When the patient's RBCs are incubated in a hypotonic solution with glycerol, hemoglobin is released. The control sample does not release hemoglobin. This patient is at greatest risk of developing what?

*Pigmented gallstones* Hereditary spherocytosis - anemia - elevated lactate dehydrogenase - indirect hyperbilirubinemia - increased osmotic fragility = diagnostic test for HS!!! - due to RBC membrane defect - present with hemolytic anemia, jaundice, splenomegaly - *pigmented gallstones = complication of any hemolytic anemia* - may also present with aplastic crises via parvovirus B19 infection

New biomarker has been identified that allows for early detection of invasive gastric carcinoma. It has sensitivity of 89% & a specificity of 85% when compared to endoscopy with multiple biopsies. The test is used in 2 groups: population in US, where 5 out of 100,000 ppl have gastric cancer, & a population in China, where 100 out of 100,000 people has been diagnosed with the disease. What is the most accurate statement concerning this new test?

*Positive predictive value of the test is higher in the Chinese population* PPV = proportion of ind.s with positive test results who actually have disease = depends on prevalence of disease in pop being tested - most common the disease in the pop = more likely it is that patient with positive test actually has disease

Contralateral hemianopia with macuar sparing associated with occlusion of what artery?

*Posterior cerebral* - supplies occipital lobe = contains striate or primary visual cortex

83-year-old man with typical coronary circulation has been suffering from embolism of circumflex branch of left coronary artery. This condition would result in ischemia of what areas of the heart?

*Posterior part of left ventricle* - potential mitral valve insufficiency

A 32-year-old woman receives a dose of warfarin orally for a large deep venous thrombus of the right leg. She is currently taking an oral contraceptive. Her prothrombin time is 12 sec (INR = 1). Two hours after admin of warfarin, her prothrombin time remains 12 sec (INR = 1). What best explains why this patient's prothrombin time did not change?

*Preexisting circulating coagulation factors have not been cleared* Warfarin - administered orally - 100% bioavailability - highly teratogenic & fetotoxic - t1/2 = 2.5 days - extensively (99%) bound to plasma albumin & can displace many other drugs from site - Clotting factors still synthesized but at reduced levels - Undercaboxylated & have greatly reduced biologic activity - Clotting factors produced before coumarin therapy decline in concentration as function of factor half-life = latency period of 36-48 hours before effects seen

Embryonic chondrogenesis requires formation of mesenchymal condensations at site of future cartilage. During this development step, cAMP concentrations in cells comprising condensation increase significantly. Treatment with a membrane-permeable form of cAMP (dibutyryl cAMP) allows individual mesenchymal cells to differentiate into chondrocytes without first forming these condensations. Inhibition of what enzymes would most directly inhibit dibutyryl cAMP-mediated induction of chondrogenesis from mesenchyme?

*Protein kinase A* Know CAMP messenger pathway

63-year-old man comes to the office for a follow-up exam for HT. At his last appointment, he revealed that he had increased his alcohol intake from 3 to 6 12-oz cans of beer a day due to stress at work. The physician advised him to seek help for his alcohol use as it oculd be causing his elevated BP & has many negative health risks. He now tells the physician, "I thought about what you said. I know my alcohol use has gotten out of hand and is affecting my health. My wife and daughter also say that I need to quit. Please give me the phone number of that treatment center you mentioned; I'm going to call & make an appointment." What best describes this patient's stage of behavioral change?

*Preparation* Behavioral changes = 5 stages 1. Precontemplation = denial of problem 2. Contemplation = acceptance of problem & thinking about change 3. Preparation = planning to make change in near future 4. Action = putting active changes into place 5. Maintenance = maintaining change over long term

34-year-old man comes to physician because of upper abdominal pain. He describes vague discomfort that mostly happens in afternoon & at night & is partially relieved by food. He also complains of sometimes feeling nauseated. He denies vomiting, black or bloody stools, & weight loss. He takes no prescription or over-the-counter med. His fam history is negative for cancer. After initial evaluation, upper GI endoscopy is performed & reveals a small ulcer with a clean base in the duodenal bulb. What sites for biopsy is most likely to demonstrate the infectious agent responsible for this patient's current condition?

*Prepyloric area* Duodenal ulcer via H pyloria - highest colonization density in prepyloric area of gastric antrum

42-year-old man comes to physician because of swelling & tenderness of his right elbow for 8 weeks. An x-ray of the right upper extremity shows a destructive lytic mass at the right distal radius. Open biopsy shows metastatic clear cell carcinoma compatible with primary renal cell carcinoma. What additional findings is most suggestive of hereditary renal cell carcinoma in this patient?

*Presence of tumors in both kidneys*

Patient is prescribed chloroquine & primaquine. The addition of primaquine to the treatment regimen is most likely to have what effects?

*Prevent disease relapse* - chloroquine effective in eradicating chloroquine-sensitive plasmodia from bloodstream but has no activity against latent hepatic infection by P vivax & P ovale Primaquine - completely eradicates hypnozoites - P vivax & P ovale eradicate intrahepatic stages (hypnozoites) of malarial species = responsible for relapses

34-year-old woman with history of recurrent UTIs comes to physician with dysuria & increased urinary frequency. Her urine culture grows colonies of Gram-negative bacteria. The bacteria are isolated & placed in growth-enhancing nutrient solution, where they undergo rapid cellular division. As they are actively dividing, the bacterial cells are lysed & their DNA is extracted & purified. Analysis of the partially replicated DNA fragments show presence of uracil. This finding is most likely mediated by what enzymes?

*Primase* = RNA polymerase - uracil found only in RNA

27-year-old woman has suprasellar craniopharyngioma, which leads to pressure-induced atrophy of posterior pituitary. What responses is most likely in the kidney?

*Production of a hypotonic urine* - decreased ADH --> decreased absorption of water = hypotonic urine

62-year-old woman comes to hospital with intermittent but progressive substernal chest pain over the last 36 hours. Medical history includes hypertension & hyperlipidemia, but the patient has been poorly compliant with her medication regimen & outpatient follow-up. She previously smoked a pack daily for 30 years but quit last year. Her BP is 130/75 mmHg & pulse is 73/min. ECG on admission shows normal sinus rhythm with a 2-mm segment elevation in leads V2-V5. The patient is treted with medical management. However, on the fifth day of hospitalization she dies suddenly, despite adequate resuscitation. What is the most likely cause of death in this patient?

*Profound hypotension* - via ruptured left ventricular free wall - anterior wall MI - first 5-14 days after large anterior transmural MI (from LAD occlusion) - leads to hemopericardium & cardiac tamponade - sudden onset of chest pain & profound hypotension & shock

An increase in the serum concentration of what hormone is the most conclusive sign that ovulation has occurred?

*Progesterone* - increased progesterone indicative of ovulation - can be used as form of contraception

23-year-old woman, gravida 1, para 0, comes to office for a routine prenatal care visit. She is at 35 weeks gestation & feels well. She reports regular fetal movement & no contractions, loss of fluid, or vaginal bleeding. Pregnancy to date has been uncomplicated. She signed up for a clinical trial investigating prolactin. At 34 weeks gestation, she had a serum prolactin level several times higher than what was recorded prior to pregnancy. What hormones prevents lactation in this patient?

*Progesterone* - promotes maternal breast growth & dev't during prenatal period - first trimester = secreted by corpus luteum = successful implantation - 2nd & 3rd trimesters = produced by placenta After delivery, precipitous drop in progesteron allows prolactin to stimulate lactation Prolactin - manufactored by stimulation by thyrotropin-releasing hormone - inhibited by progesterone

29-year-old man comes to office to follow up sarcoidosis. He was diagnosed a year ago after presenting with a dry cough & hypercalcemia, & was treated with oral glucocorticoid therapy. The patient has been off treatment for the last 6 months. He now reports a 6 -week history of headaches, fatigue, & visual disturbances. On exam, visual field testing reveals bitemporal defects. The exam is otherwise normal. Lab studies agains show mild hypercalcemia, but the remainder, including complete blood count, serum glucose, creatinine, & electrolytes, is within normal refernce ranges. MRI of the brain shows a soft tissue mass involving the hypothalamus & pituitary stalk. What pituitary hormones is likely to be elevated in this patient?

*Prolactin* - patient has sarcoidosis manifesting as hypercalcemia (via excess calcitriol) & mass effect symptoms - disruption of dopaminergic pathways (by infiltrating sarcoid lesion) in pituitary stalk = loss of normal inhibitor control & subsequent increase in prolacting

Mechanism behind why niacin causes flushing?

*Prostaglandins* (PGD2 & PGE2) - can be diminished by pretreatment with aspirin Niacin - treats hyperlipidemia - raises HDL

A 27-year-old male became lose while hiking in Yosemite National Park. He was found eight days later. He had nothing to eat & only water to drink before being rescued. What cell can only use glucose for energy needs?

*Red blood cell* - lacks mitochondria = can only use glucose for fuel

Infant born to 23-year-old female is diagnosed with inherited condition that results in impaired transport of ornithine from cytosol to mitochondria. Restriction of what substances in diet can improve this patient's condition?

*Protein* Ornithine transcabamylase deficiency - ornithine transport into mitochondria essential for urea formation ~ ornithine needed to combine carbamoyl phosphate within mitochondria to form citrulline in second step of urea cycle - ammonia generated from metabolism of alpha AAs Disorders of urea cycle = increased ammoni --> CSN dysfunction - treatment = balancing dietary protein intake & protein output - protein restriction = main form of therapy for urea cycle disorders

Urine sediment microscopy reveals muddy brown casts. What renal structures are most likely to demonstrate signs of ischemic injury in the patient?

*Proximal tubules* Acute tubular necrosis - via decreased renal perfusion via severe hypovolemia, shock, or surgery - increased serum creatinine & BUN - oliguria - affects *renal medulla* - *straight portion of proximal tubule & TAL of Henle's loop* especially susceptible to hypoxia = participate in ATP-consuming transport of ions

39-year-old paraplegic man with indwelling bladder catheter comes to ED complaining of 24 hours of rigors, nausea, & vomiting. His temp is 38.9 C (102 F). Physical exam shows suprapubic & costovertebral angle tenderness. Urinalysis shows 3+ leukocyte esterase & numerous WBCs. Urine & blood cultures grow non-lactose-fermenting Gram-negative rods. What pathogens is the most likely culprit?

*Pseudomonas aeruginosa* - opportunistic - non-lactose-fermenting - oxidase-positive

12-year-old girl dies from pneumonia. She had chronic malabsorption & multiple episodes of cough with copious sputum production & occasional hemoptysis. The appearance of the lung at autopsy is shown (flip to see similar pic). A culture of the lung at autopsy is most likely to grow what organism?

*Pseudomonoas aeruginosa* Complications - recurrent pulmonary infections (S aureus - early infancy; *P aeruginoa - adolescence*) - chronic bronchitis & *bronchiectaiss* --> reticulonodular pattern on CXR, opacification of sinuses - pancreatic insufficiency - *malabsorption with insufficiency* - fat-soluble vitamin deficiencies - biliary cirrhosis - liver disease - meconium in newborns (1st sign) - fertility issues - nasal polyps - clubbing of nails - small stature - hyponatremia via excessive salt wasting - vitamin K deficiency --> treat carboxylation of prothrombin

9-month-old girl brought to ED 30 minutes after she had a generalized tonic-clonic seizure. She has had failure to thrive & dev'al delay since birth. She is at 3rd percentile for length & weight. Physical exam shows microcephaly, tachypnea, & hypotonia. Lab studies show hypoglycemia, hyperalaninemia, & lactic acidosis. After IV glucose is administered, her serum glucose concentration returns to within reference range. This patient most likely has a deficiency of what enzyme activities?

*Pyruvate carboxylase* - pyruvate (3 C) --> OAA (4C) - requires biotin (B7), ATP - activated by acetyl-CoA - in mitochondria

College student with Neisseria meningitidis. Prophylaxis can give reddish discoloration of their urine or tears. The reason this drug is effective in killing bacteria is how?

*RNA synthesis is inhibited*

What would be increased in patients with Obstructive Lung Diseases?

*RV/TLC* RV = indicated by graph - heightened lung volume @ end of max expiration FRC TLC - asthma, chronic bronchitis, emphysema, bronchiectasis = air trapping & hyperinflamation of lungs

26-year-old woman being treated for glomerulonephritis, photosensitive skin rash, & arthralgias. Rapid plasma reagin (RPR) test is repeatedly positive in this patient despite negative Treponema pallidum enzyme immunoassay (TP-EIA) testing. Coagulation study results are as follows: Bleeding time = Normal Activated partial thromboplastin time = Prolonged Prothrombin time = Normal Platelets = 240,000/uL This patient is at greatest risk for what complications?

*Recurrent miscarriages* Glomerulonephritis + photosensitive skin rash + arthralgia in young women = SLE - prolonged aPTT & false positive RPR = presence of circulating *antiphospholipid Abs* aPTT - in vitro = prolongation - in vivo = hypercoagulable state - false-positive results on nontreponemal serologic syphilis tests (RPR & VDRL) by reacting with cardiolipin (dominant antigen in tests)

Previously healthy 51-year-old woman comes to physician because of a 9-kg (29-lb) weight loss over past 6 months. She has smoked 2 packs of cigarettes daily for 20 years. She takes no meds. Vital signs are normal. Physical exam shows no abnormalities. Lab studies show: Hemoglobin = 17 g/dL Hematocrit = 52% Leukocyte count = 5100/mm^3 Platelet count = 250,000/mm^3 Serum: BUN = 17 mg/dL Creatinine = 1 mg/dL Urine: RBC = 14/hpf WBC = 1/hpf What is the most likely diagnosis?

*Renal carcinoma* h/o of smoking & weight loss + hematuria = RCC

18-year-old man comes to office due to progressive skin rash over past year. He also has long-standing history of intermittent burning sensation in his palms & soles that is exacerbated by stress & fatigue. The burning sensation is particularly severe after exercise, during which the patient notes that he sweats minimally. Skin exam shows clusters of non-blanching, red papules in the gluteal, inguinal, & umbilical areas. Lab evaluation reveals an undetectable level of alpha-galactosidase A. What conditions is this patient at greatest risk for developing?

*Renal failure* - Gb3 buildup in glomerulus & distal tubule = proteinuria & polyuria --> can progress to renal failure in abscence of enzyme replacement therapy Fabry disease = X-linked recessive - alpha-galactosidase deficiency (breaks down globotriaosylceramide (Gb3) - Gb3 accumulation in vasular smooth muscle cells, glomerular/distal tubule cells, cardiac myocytes, dorsal root & autonomic ganglia = ADRs - earliest symptoms during adolescence = neuropathic pain & hypohidrosis (decreased sweating) - exacerbating factors = exercise, stress, fatigue - late adolescence = angiokeratomas (dark red, non-blanching macules & papules in clusters over buttocks, groin, umbilicus), telangiectasias on skin - early & mid-adulthood = cerebrovascular & cardiac diseases = most common causes of death

24-year-old African American woman comes to ED with fever, malaise, & intense pain over her right thigh. She has long history of frequent presentations to hospital with painful crises. Usually patient is admitted & treated with supplemental oxygen & IV narcotics. This episode of pain is very different as she is febrile 39.4 C (103 F) with exquisite tenderness over right thigh. There are no skin changes. An MRI of the right lower extremity is obtained, & antibiotics are promptly initiated based on abnormal imaging results. Blood cultures grow nonlactose-fermenting, oxidase-negative, motile organisms. What virulence mechanisms is most likely contributing to this patient's current presentation?

*Resistance to opsonization* Sickle cell disease - recurrent painful vaso-occlusive crises that respond well to oxygen, IV fluids, & high-dose narcotics - functional asplenia = increased risk for infection by encapsulated S pneumonia, Neisseria, Haemophiluls, Salmonella Salmonella osteomyelitis - fever + thigh pain + abnormal MRI + bacteria via nonlactose-fermenting, oxidase-negative organism - *capsule = Vi antigen = protects it from opsonization & phagocytosis*

23-year-old man brought to ED by his roomate due to progressive weakness & confusion. Roommate says that the patient has been "drinking water all of the time & using the bathroom constantly" since he got sick with a cold 2 days ago. Temp is 37.8 C (100 F), BP is 96/58 mmHg, & pulse is 112/min. Physical exam shows dru mucous membranes & his urine has a strong, fruity odor. Lab results are as follows: Serum chemistry Sodium = 134 mEq/L Potassium = 3.8 mEq/L Chloride = 100 mEq/L Bicarbonate = 12 mEq/L Creatinine = 1 mg/dL Glucose = 498 mg/dL pH = 7.27 PaCO2 = 40 mmHg Based on the current lab findings, what is most likely occurring in this patient?

*Respiratory failure* Diabetic ketoacidosis - probz ppted by viral infection - hyperglycemia & anion gap metabolic acidosis confirm diagnosis - usually develop compensatory respiratory alkalosis by hyperventilating (Kussmaul respirations) = helps mitigate acidemia by causing drop in PaCO2 - severe = may lead to: pulmonary edema, respiratory fatigue, decreased mental status --> hypoventilation & subsequent hypercarbic respiratory failure PaCO2 above expected compensatory range (Winter Formula = PaCO2 = [1.5 x HCO3-] + 8 +/- 2) = superimposed respiratory acidosis interfering with normal compensatory response Bicarb of 12 should be compensated in range of 24-28 - however, his PaCO2 = much higher than expected = mixed acid-base disturbance = metabolic & respiratory acidoses

A thoracentesis is performed to aspirate an abnormal accumulation of fluid in a 37-year-old patient with pleural effusion. A needle should be inserted at midaxillary line between what two ribs as to avoid puncturing the lung?

*Ribs 7 & 9* Thoracentesis - for aspiration of fluid in pleural cavity at or posterior to midaxillary line

62-year-old woman who is a heavy smoker has an advanced lung cancer that spread into her right third posterior intercostal space posterior to the midaxillary line. If cancer cells are carried in the venous drainage, they would travel first to what veins?

*Right superior intercostal vein* - formed by union of second, third, and fourth posterior intercostal veins - drains into azygos vein on right & brachiocephalic vein on left

Contains septomarginal trabecula

*Right ventricle* (C) Septomarginal Trabecula / Moderator Band - forms bridge between IV septum & base of anterior papillary muscle of anterior wall of right ventricle - prevents overdistention of ventricle - carries right limb (Purkinje fibers) of AV bundle from septum to sternocostal wall of ventricle

37-year-old man comes to physician because of severe back pain for 2 days. Pain radiates down buttock, posterior thigh, & posterolateral leg. He also has numbness on side of his left foot. On physical exam, sensation to pain is decreased over lateral side of left foot. Deep tendon reflexes are absent at left ankle, & there is weakness of dorsiflexion of left foot. Compression of what nerve roots is most likely cause of these findings?

*S1*

Human serum albumin, the most abundant blood protein, has multiple roles, including acting as a buffer to help maintain blood pH. Albumin can act as a buffer due to what?

*The protein contains many amino acid residues with different pKa values* - can donate & accept protons at various pH values - can act as buffers over broad pH spectrum

43-year-old woman comes to office due to acute back pain after dragging heavy box. The pain is located in her lower back & radiates down the right posterior thigh to the foot. The patient describes the pain as "shooting" and grades it 8/10 in intensity. She has no bowel or bladder symptoms. The patient has tried over-the-counter analgesics with limited symptomatic relief. Vital signs are within normal limits. On physical exam, straight leg raise testing is positive on the right. Right hip extension is weaker when compared to the left. Knee jerk reflexes are 2+ & bilaterally symmetric, but the right ankle jerk reflex is absent. What nerve root is most likely affected in this patient?

*S1* Sciatica - low back pain that radiates down leg - via compression of lumbosacral nerve roots Sciatic nerve - derived from L4-S3 nerve roots - compression most often via *L5 or S1* S1 radiculopathy - pain & sensory loss down posterior thigh & calf to lateral aspect of foot - weakness on thigh extension (denervation of gluteus maximus) - absent ankle jerk reflex

Radiologist examines posterior-anterior chest radiographs of a 27-year-old victim of a car accident. What structures forms the right border of the cardiovascular silhouette?

*SVC* Cardiac silhouette / Cardiac shadow - right border = SVC, right atrium, IVC - left border = aortic arch (aortic knob), pulmonary trunk, left auricle, left ventricle

Lies on right side of ascending aorta and arch of aorta

*SVC* (A)

Addition of norepinephrine to a solution bathing an isolated cardiac muscle leads to an inc amt of work done at a given load without changing the initial length of the muscle. The inc in the muscle's work done at its new steady state is the result of an increase in which of the following?

*Sarcoplasmic Calcium concentration while load is lifted* Isometric contraction of the papillary muscle in a solution (high calcium concentration ... remember cardiac muscle relies on extracellular calcium concentration unlike skeletal muscle....) When norepinephrine is added, it increases the intracellular calcium concentration ...to maintain the isometric contraction

Management of somatic symptoms disorder

*Schedule regular visits with same provider* - can monitor her condition & avoid unnecessary diagnostic testing & specialist referrals

Peripheral smear of person with DIC shows

*Schistocytes* / Fragmented Erythrocytes DIC - bleeding from venous puncture sites - associated with sepsis, acute pancreatitis, burn injury - decreased platelet count, fibrinogen, factor V & VIII levels, prolonged PT & pTT DIC via gram-negative sepsis - coagulation cascade activated by bacterial endotoxins --> widespread fibrin deposition & consumption of coagulation factors & platelets = bleeding --> excess fibrin strands = shearing forces on circulating erythrocytes = schistocytes

Myasthenia gravis patient is started on appropriate treatment & reports significant improvement of her symptoms. However, she now complains of abdominal cramping, nausea, sweating, & diarrhea. What agents can be used to effectively control these new symptoms?

*Scopolamine*, Hyoscyamine = selective muscarinic ACh receptor antagonist = reduces side effects of cholinesterase inhibitors in sites where ACh action is mediated by muscarinic receptors (such as gut) - treatment of MG = cholinesterase inhibitor (pyridostigmine), immunosuppressive agent, &/or thmectomy - pyridostigmine = GI side effects via excessive cholinergic stimulation of gut

Impairment of what defense mechanism would most likely predispose to Giardia lamblia?

*Secretory IgA production* - binds trophozoites & impairs adherence to upper small-bowel mucosa Giardia lamblia = intestinal flagellate = 2 forms: trophozoite (pathogenic stage), cyst (infective stage) = bilaterally, symmetric, pear-shaped organism with multiple flagella & 2 nuclei (owl's eyes appearance) - cysts = oval & contain up to 4 nuclei - transmitted by drinking contaminated water (campers, travelers to endemic areas) or via fecal-oral transmission (children in day care centers) - diagnosis via stool microscopy for ova & parasites - small-bowel biopsy = villus atrophy & crypt hyperplasia Major immune mechanism - CD4+ T helper cells & secretory IgA production Children with IgA deficiency, X-linked agammaglobulinemia, common variable immune deficiency = predisposed

26-year-old man comes to office due to 3-day-history of dysuria & urethral discharge. The symptoms developed about about 2 week after he had unprotected sexual intercourse with a new partner. His temp is 37.1 C (98.8 F). On physical exam, a mucoid discharge is expressed with gentle milking of the penis. Gram stain of the discharge reveals numerous neutrophils with intracellular diplococci. A sample of the discharge is placed on an antibiotic-containing medium, & bacterial colonies are cultured. What term best describes the medium?

*Selective* Neisseria gonorrhoeae - culture on Thayer-Martin VCN selective medium = contains vancomycin, colistin, nystatin, & trimethoprim

Woman treated with opioid analgesic & her knee pain decreases significantly. Soon after admin, however, the patient experiences new-onset upper abdominal pain that makes it difficult for her to lie still. Vital signs are normal. Her BMI is 34 kg/m^2. Physical exam shows tenderness over right upper abdominal quadrant. Adverse drug effect involving what structure is most likely responsible for this patient's current condition?

*Smooth muscle cells* Mu opioid analgesics, like morphine = contraction of smooth muscle cells in sphincter of Oddi = spasm = increase in common bile duct pressures - pressure in gallbladder = biliary colic (rare) - management = discontinue --> alternative agents = NSAIDs (ketorolac, diclofenac)

18-month old boy being evaluated for neuro regression. He had normal neonatal course & early dev't until age 5 months. Boy subsequently developed gradual regression of dev't milestones such as inability to sit with support, poor head control, & loss of social smile. His weight & height are below fifth percentile. On physical exam, he has enlarged liver & spleen, diminished deep tendon reflexes in all limbs, & hypotonia. Fundoscopic findings include cherry-red macular spot. This patient most likely has accumulation of what substrate?

*Sphingomyelin* Niemann-Pick - AR - Ashkenazi Jews - sphingomyelinase deficiency - sphingomyelin accumulation within lysosomes = enlarged, foamy, vacuolated on EM - lipid-laden foam cells accumulate in liver & spleen - progressive neuronal accumulation = hypotonia & neuro degeneration - death by age 3

67-year-old man with nonischemic cardiomyopathy & was recently hospitalized for acute decompensated heart failure. The patient's symptoms have improved with multidrug treatment, but he has persistent shortness of breath on mild exertion. He has a history of HT & hypercholesterolemia. BP is 115/70 mmHg & pulse is 66/min. There is a third heart sound on heart auscultation & mild lower extremity pitting edema. A recent echocardiogram showed a left ventricular ejection fraction of 30%. What diuretics would be most liekly improve survival if added to this patient'c current regimen?

*Spironolactone* Mineralocorticoid receptor antagonists = spironolactone, eplerenone = mineralocorticoid receptor antagonists = reduce morbidity & improve survival in patients with CHF & decreased ejection fraction - recommended in addition to standard heart failure therapy (ACE inhibitors & beta blockers) - should not be used in patients with hyperkalemia or renal failure

65-year-old man brought to ED after developing sudden-onset right-sided weakness & difficulty speaking He has a history of paroxysmal atrial fibrillation & has been taking warfarin for the past several years with a stable prothrombin time. His wife adds that he started taking new drug 2 weeks ago, but she does not remember its name. Physical exam shows right hemiplegia, right hemisensory loss, expressive aphasia, & right homonymous hemianopia. MRI of the head shows a left middle cerebral artery territory infarct. Transesophageal echocardiogram reveals a small thrombus in the left atrium. This patient most likely started taking what drugs recently?

*St. John's wort* - increased warfarin metabolism = decreased drug levels = inadequate anticoagulation Thromoembolic stroke - via dislodged left atrial thrombus via adverse drug interaction = inadequate anticoagulation

In addition to inhibiting acetylcholinesterase, what other drug mechanism would help stabilize myasthenia gravis?

*Stimulate apoptosis* Immunosuppressants - reduce autoAb production - activation of TNF receptor = activates apoptosis in cells = destruction

What is decreased in lactose intolerance?

*Stool pH* Lactose intolerance - fermentation of undigested lactose by gut bacteria --> increased short-chain fatty acids (acetate, butyrate, propionate) that acidifies stool (decreased stool pH) - hydrogen gas also produced = increased breath hydrogen content - high amounts of undigested lactose in bowel = elevated stool osmolality --> attracts excess water in bowel lumen = osmotic diarrhea

34-year-old HIV-positive man comes to ED with sudden-onset fever, chills, productive cough, & left-sided chest pain that worsens with deep breathing. His symptoms began 3 days ago. Physical exam shows bronchial breath sounds over left lower lung. His most recent CD4+ lymphocyte count measured 1 month ago was 800 cells/uL. What organisms is most likely responsible for this patient's symptoms?

*Streptococcus pneumoniae* - normal CDD4+ lymphocyte count for adults = 400-1400 cells/uL - in immunocompetent individuals, S pneumoniae = most common cause of community-acquired pneumoniae = 70% of cases

Transgenic mice generated that are incapable of expressing Bruton tyrosine kinase. These mice are at increased risk for severe infections caused by what microorganisms?

*Streptococcus pneumoniae* X-linked / Bruton agammaglobulinemia - recurrent infections especially after 6 months old (↓ maternal IgG) - Streptococcus pneumoniae, Hemophilus influenzae, Streptoccocus pyogenes, and Pseudomonas - increased susceptibility to encapsulated bacteria and blood-borne viruses due to opsonization defect

What should be biopsied in Hirschsprung disease?

*Submucosa of narrow part* - demonstrates absence of ganglionic cells - submucosal (Meissner) & myenteric (Auerbach) autonomic plexi are absent in affected segment of bowel - submucosa of narrowed area = most superficial layer where absence of ganglion cells can be seen

20-year-old college student brought to ED by his roommate. Patient is frightened and claims that campus police are following him and plotting to kill him. His roommate says that the patient seemed "totally normal" until the past few days, when he began staying up all night to prepare for final exams. The patient has no known med or psychiatric history. His BP is 150/95 mmHg & pulse is 110/min. On exam, he is pacing, sweating profusely, hypervigilant, & has mildly pressured speech. What is the most likely diagnosis?

*Substance-induced psychotic disorder* - misuse of stimulants by college students to enhance academic performance is prevlent - evidence = paranoia, restlesness, hypervigilance, tachycardia, HT, diaphoresis - transient paranoid psychosis - scenario of a student studying for exams

Damage to this structure may result in contralateral hemiballism, characterized by *wild, involuntary, large-amplitude, flinging movements of proximal limbs (arm &/or leg) on one side of body*

*Subthalamic nucleus* - modulation of basal ganglia output Damage to subthalamic nucleus = decreased excitation of globus pallidus internus --> reduced inhibition of thalamus = contralateral hemiballism - most commonly via lacunar stroke = consequence of long-standing HT & diabetes mellitus

75-year-old patient has been suffering from lung cancer located near cardiac notch, a deep indentation on the lung. What lobes is most likely to be excised?

*Superior lobe of the LEFT lung*

Inferior mesenteric artery ligated, diseased portion of aorta is dissected, & graft is placed from below renal arteries to bifurcation of aorta. Collateral circulation from what vessels is most likely responsible for preventing ischemia of the descending colon?

*Superior mesenteric artery* SMA & IMA = 2 main vessels supplying small & large intestines, which are connected by pair of anastomoses = *Marginal Artery of Drummond* & inconsistently present arc of Riolan (mesenteric meandering artery)

Man presents to ER after ingesting an insecticide. His respiration rate is very low. Info from the Poison Control Center indicates that this particular insecticide binds to & completely inhibits cytochrome c. Therefore, what would occur in this man's mitochondria?

*The rate of ATP synthesis would be approximately zero*

69-year-old man with progressive pain beneath high right scapula & in his right arm for last several months. He has taken over-the-counter analgesics, which provide short-term relief, but the pain has become more severe & awakens him at night. The pain is associated with numbness in his right forearm extending up to the tips of the fourth & fifth fingers. The patient has also had persistent nonproductive cough & lately has been coughing up streaks of blood. He has a history of HT, GERD, & osteoarthritis. He has smoked 2 packs of cigarettes daily for more than 40 years but recently cut down to 4 or 5 cigarettes a day. What is the most likely cause of this patient's symptoms?

*Superior sucus tumor* / Pancoast tumor - superior sulcus = groove formed by subclavian vessel - shoulder pain radiating toward axilla & scapula = most common presenting symptom = via involvement of lower brachial plexus - Horney syndrome - Upper extremity edema via compression of subclavian vessels - Spinal cord compression & paraplegia via tumor extension into intervertebral foramina Lung cance - extensive smoking history + hemoptysis & shoulder pain

A central line is placed to accecss a structure embryonically derived from the common cardinal veins. This structure is represented by what labels shown in a chest CT?

*Superior vena cava* = derived from common cardinal veins = identified to right of heart on CT, posterolateral to ascending aorta, anterior to right pulmonary artery, just below level of carina - all veins in developing embryo ultimately drain into sinus venosus --> drains into primitive atrium of developing heart - cardinal veins form constituents of systemic venous circulation Catheter - inserted into neck (internal jugular vein) or chest (subclavian vein) --> advanced until catheter tip enters SVC

87-year-old nursing home resident with history of dementia and stroke treated with IV fluids & antibiotics, with improvement in fever, leukocytosis, & hypotension. On the third day of hospitalization, temp is 36.7 C (98 F), BP is 122/78 mmHg, & pulse is 86/min. On exam, he is mildly lethargic & his voice is soft & breathy. Rhonchi are still heard over lower right lung. There is left-sided facial droop & hemiparesis from his previous stroke. Chest x-ray demonstrates dense air space opacities in superior region of right lower lobe. What is the most likely underlying etiology of this patient's hospitalization?

*Swallowing muscle dysfunction* Septic chock secondary to pneumonia - residual hemiparesis & evidence of vocal cord paralysis (soft, breathy voice) = aspiration pneumonia via inhalation of oral secretions - superior regions of lower lobes & posterior regions of upper lobes = most dependent locations in lungs of supine individuals Aspiration pneumonia - *classically results in right lower lobe abscess* - elderly patients with dementia or hemiparesis

When switching from MAO Inhibitors to SSRIs, what processes occur during the washout interval to allow sertraline therapy to be initiated safely?

*Synthesis of monoamine oxidase* Ex. Phenelzine irreversibly inhibits MAO = takes up to 2 weeks following discontinuation of drug before enzyme resynthesized to levels adequate for normal monoamine degradation

45-year-old man comes to office due to right ankle pain for the past 2 days. The patient was running downhill on a dirt trail when he twisted his ankle inward. Since then, he has had pain & swelling at the right ankle but is able to walk unassisted. The patient has no other med conditions & takes no chronic meds. On exam, there is bluish discoloration over the lateral aspect of the joint. He has max tenderness to palpation at the anterolateral aspect of the ankle joint. Forced inversion of the foot also increases the pain. What structures is most likely injured in this patient?

*Talofibular ligament* Ankle sprain - inversion of plantar-flexed foot - lateral ankle ligaments weaker & injured more than medial ligaments - most common ankle sprains = anterior talofibuar ligament

Infection by mumps virus in men result in decreased fertility because of viral damage to what structures?

*Testes*

5-day-old newborn has been cyanotic since birth & has a soft systolic murmur. An x-ray of the chest shows decreased pulmonary vascular markings indicating a decrease in pulmonary blood flow. What is the most likely diagnosis?

*Tetralogy of Fallot* - anterosuperior displacement of infundibular septum 1. Pulmonary infundibular stenosis = most important determinant for prognosis 2. RVH = RV lift 3. Overriding aorta 4. VSD *PROV*e Squatting = increased SVR, decreased right-to-left shunt, improves cyanosis

Approximately 87% of deaths resulting from lung cancer are directly related to cigarette smoking. What best represents this findings?

*The attributable risk is 87%*

Metformin is the standard first-line oral med for Type 2 diabetes. The use of the drug has the potential side effect of lactic acidosis. What explains why this lactic acid buildup is rarely seen clinically?

*The cardiac muscle cells utilize the lactate as fuel* Metformin - can increase glucose uptake by tissues --> increased lactate formation - blocks lactate uptake by liver - should discontinue metformin if severe loss of cardiac tissue from MI

4-year-old boy has had history of skin infections, pneumonia, nausea, vomiting, & abdominal pain. He has been on antibiotics prophylactically for the past year, but still contracts various sorts of infection, both bacterial & fungal. A physical exam demonstrated hepatosplenomegaly. The boy most likely has inherited a mutation that prevents what reactions?

*The formation of superoxide* CGD - defect of NADPH oxidase (responsible for respiratory burst in neutrophils & produces superoxide from oxygen & NADPH) - X-linked recessive mostly

An alcoholic presents with swelling & fissuring of the lips, cracking at the angles of the mouth, red eyes, & an oily, scaly rash of his scrotum. What cofactors of enzyme complexes would be most affected by this condition?

*The functioning of the FMN components of complex I* Vitamin B2 (riboflavin) deficiency / Ariboflavinosis - both FAD & FMN require vitamin B2

Lysosomal hydrolases targeted to lysosome by addition of a carb residue to the protein. An inability to add this carb lads to a disease in which lysosomal hydrolases are treated as secreted proteins, & are exported from the cell, rather than taken to the lysosomes. The secreted proteins will have what effects on the cells & proteins in the circulation?

*There will be no effect on the proteins & cells in the circulation* - cytosol & other cellular components have pH near 7.2 = protected from hydrolases - pH of blood is maintained between 7.2 & 7.4 = escaped lysosomal enzymes will have no activity at that pH = will not effect proteins & cells in circulation

Consider the section of the TCA cycle in which isocitrate is converted to fumarate. This segment of the TCA cycle can be best described as requiring what coenzyme?

*These reactions require a coenzyme synthesized in the human from niacin (nicotinamide)* Niacin/B3 = NAD: - *isocitrate dehydrogenase* - *alpha-ketoglutarate dehydrogeanse* - malate dehydrogenase

Two programs for the treatment of patients with newly detected hypercholesterolemia were tried in a community. Program A was used in one district of community ad Program B was used in another. After 4 years, 40% of 110 Patients on program A and 53% of 95% patients on program B had been successfully treated for hypercholesterolemia. The p value for difference was 0.3. Based on these data, the health officials decide not to change to program B in 1st district. Which of the following best explains the decision?

*They attributed the difference in success rates to chance alone* p value is more than 0.05 and also there is not much drastic or remarkable difference in the group B . therefore the difference could be attributed to chance and hence the null hypothesis stays...null hypothesis can only be rejected when p value is less than 0.05

4-day-old infant brought to ED with abnormal movements. Patient has had intermittent episodes of tonic posturing over past 3 hours as well as poor feeding, vomiting, irritability for past 2 days. Mother also reports that his diapers smell like "caramelizing sugar." There are no known med problems in the fam, but the child's maternal aunt died "sometime in the first year" of life from unknown causes. Exam shows lethargic infant with intermittent posturing episodes & increased generalized muscle tone. Lab studies of plasma & urine confirm the diagnosis. In addition to appropriate dietary restriction, supplementation with what may improve this infant's condition?

*Thiamine* MSUD - AR - brain swelling may lead to death Branched-chain alpha-ketoacid dehydrogenase = 5 cofactors: 1. Thiamine 2. Lipoate 3. Coenzyme A 4. FAD 5. NAD

During fourth through eight weeks of gestation, there are five pairs of aortic arches. These will ultimately develop into components of the greater arteries. What pairs of aortic arches develops into common carotid arteries?

*Third* *C*ommon *C*arotid artery & proximal part of internal *C*arotid artery (palpated along inner side of sternocleidomastoid muscle) *C* is *3*rd letter of alphabet

13-year-old boy brought to office due to right knee pain. He started having mild ache in lower part of the right knee several weeks ago that has gradually worsened & causes him to limp. The pain has significantly limited his participation in basketball practice. It is relieved by rest & can be reproduced when the patient straightens out the right knee while seating in a chair. Further evaluation reveals avulsion of secondary ossification center of tibia due to repetitive muscle contraction & traction on bone. What is the most likely insertion site of the involved muscle tendon?

*Tibial tuberosity* Osgood-Schlatter disease (OSD) - overuse injury of secondary ossification center (apophysis) of tibial tubercle - young adolescent athletes after recent growth spurt - pain & swelling at tibial tubercle, insertion point of patellar ligament Quadriceps muscle group - leg extension at knee - rectus femoris, vastus intermedius, vastus medialis, vastus lateralis - repetitive contraction / jumping = chronic avulsion = proximal patellar tendon separates from tibial tubercle

What cellular junctions block backflow of glucose from basal side of intestinal epithelium into lumen of gut?

*Tight junctions (zonulae occludentes)* - prevents paracellular movement of solutes - composed of claudins & occludins

In the TCA cycle, a role for thiamine pyrophosphate is what?

*To form a covalent intermediate with the alpha-carbon of alpha-ketoglutarate*

60-year-old Caucasian male diagnosed with exertional angina. His treatment regimen includes metoprolol, isosorbide dinitrate & aspirin. He takes isosorbide dinitrate early in the morning & against the afternoon, but he does not take an evening dose. Suh as pattern of drug administration is intended to decrease what?

*Tolerance development* - around-the-clock nitrate admin rapidly = dev't of tolerance to nitrates - nitrate-free interval must be provided every day in patients that are using daily long acting nitrates - nitrate-free period = timed to occur during night when patient is sleeping & cardiac work is least

During early dev't of the respiratory system, the laryngotracheal tube maintains communication with the primitive foregut. What embryonic structures is most likely responsible for partitioning these two embryonic structures?

*Tracheoesophageal septum* - formed by fusion of tracheoesophgeal folds in midline - divides foregut into ventral portion, laryngotracheal tube (primordium of larynx, trachea, bronchi, lungs), & dorsal portion (primordium of oropharynx & esophagus)

4-year-old boy displays failure to thrive, extreme sensitivity to sun, hearing loss, severe tooth decay, pigmentary retinopathy, & premature aging. An analysis of fibroblasts from boy demonstrated extensive DNA damage in cells trying to grow, but minimal damage in quiescent cells, which have a greatly reduced rate of transcription as compared to growing cells. This child most likely has a defect in what processes?

*Transcription-coupled DNA repair* Cockayne syndrome - defect in transcription-coupled DNA repair - via mutations in either ERCC6 or ERCC8 gene - protein products of both genes involved in repairing DNA of actively transcribed genes - key = amount of DNA damage in growing cells

Bacterial strain X is resistant to ampicillin & sensitive to kanamycin. Bacterial strain Y is resistant to kanamycin & sensitive to ampicillin. Bacterial strains X & Y are grown in mixed culture in medium without antibiotics, then the culture is plated on medium containing both ampicillin & kanamycin. Bacterial colonies grown on plates. In a second experiment, DNase is added to mixed culture medium. When this mixed culture is plated on medium containing both antibiotics, no colonies grow. Assuming that bacterial cells are impermeable to DNase, what processes best explains these observations?

*Transformation* - any DNA can be used - adding deoxyribonuclease to env't degrades DNA in medium --> no transformation seen DNase present... - transposons degraded = antibiotic resistance cannot be transmitted from resistant strain to non-resistant one

32-year-old female presents to office with severe nausea & recurrent bilious vomiting. Her symptoms initially began as postprandial epigastric pain & early satiety, but have progressed over the last 2 weeks. She works as an actress, & tells you that her symptoms only started when she "landed a role in a soap opera" and was inspired to lose 25 lbs. on a "crash diet." On physical exam, her abdomen is tender & slightly distended with high-pitched bowel sounds. Concerned about a small bowel obstruction, you admit the patient to the hospital. A laparotomy is performed, & it observed that the angle between her superior mesenteric artery & her aorta is significantly decreased. What structures is most likely to be obstructed by the artery?

*Transverse portion of duodenum* - transverse portion of duodenum lies horizontally at level of L3, between aorta & superior mesenteric artery SMA syndrome - SMA & aorta normally form 45 degree angle --> *less than 20 degrees = transverse portion of duodenum can get entrapped between SMA & aorta* = symptoms of partial small bowel obstruction - secondary to diminished mesenteric fat, pronounced lordosis, surgical correction of scoliosis

A 25 yr old woman comes to the physician because of increasingly sever pain of the right hip during the past week. She runs 5 miles daily and recently changed her route because of construction. she now runs on uneven ground rather than pavement. Range of motion of the hip is full. The pain is exacerbated by flexion and internal rotation of the hip and by direct palpation over the lateral aspect of the hip. which of the following structures is most likely Involved?

*Trochanteric bursa* - tenderness on lateral side

During skeletal muscle contraction, calcium is released from SR & binds...

*Troponin* C --> allows binding of actin to myosin

Evolution of a MI occurs in several stages. The final stage of the healing process begins 2 weeks after infarction & involves what type of collagen?

*Type I collagen* - similar to *Tendon* collagen - most abundant type - major organic component in bones - defects = osteogenesis imperfect

What conversion pathways would be deficient in a patient with alkaptonuria?

*Tyrosine to fumarate* Alkaptonuria - AR - disorder of tyrosine metabolism - homogentisic acid accumulates in body --> excreted in urine = black color of urine if allowed to site & undergo oxidation - retained homogentisic acid selectively binds collagen tin CT, tendons, cartilage --> ochronosis = blue-arthropathy = manifests during adulthood

Infant born to a 34-year-old female noted to have flaccid lower extremities & absent ankle reflexes bilaterally. X-ray studies reveal poorly developed lumbar spine & sacrum. Mother has a complex past medical history & blames herself for "not caring enough for my baby." What factors during her pregnancy is most likely related to the baby's condition?

*Uncontrolled diabetes* Caudal regression syndrome - rare = 1:60,000 births - born with agenesis of sacrum & occasionally lumbar spine = flaccid paralysis of legs, dorsiflexed contractures of feet, urinary incontinence - can range in severity = isolated anal atresia ~ sirenomelia

Supplementation with what substance would be most beneficial in a patient with orotic aciduria?

*Uridine* Hereditary orotic aciduria - AR disorder of de novo pyrimidine synthesis = physical & mental retardation, megaloblastic anemia, elevated urinary orotic acid - defect in UMP synthase

35-year-old man is evaluted for progressive fatigue & shortness of breath. Recently, he has noticed bilateral leg swelling & abdominal distention despite overall weight loss. He does not use tobacco, alcohol, or illicit drugs. Despite treatment, the patient dies several weeks later. Autopsy reveals significant endocardial thickening with dense fibrous deposits around the tricuspid & pulmonary valves as well as moderate pulmonary valve stenosis. The left-sided cardiac chambers and valves are normal. Measuring the levels of what substances would have helped in diagnosing this patient?

*Urinary-5-hydroxyindoleacetic acid* (5-HIAA) = end product of serotonin metabolism Carcinoid heart disease - endocardiacl thickening & fibrosis of tricuspid & pulmonary valves - excessive serotonin --> fibroblast growth & fibrogenesis - plaque-like deposits of fibrous tissue on endocardium = tricuspid regurgitation, pulmonic valvulopathy, right-sided heart failure (ascites, peripheral edema)

During inspection of the external auditory canal, a speculum is inserted into the meatus in close contact with its posterior wall, causing the patient to suddenly become lightheaded and faint. He recovers spontaneously within a few minutes with no residual confusion. What nerves was most likely irritated during the procedure?

*Vagus* - posterior part of external auditory canal - concavity & posterior eminentia of concha Vasovagal syncope - after stimulation of posterior external canal by otoscope speculum

cryptococcal meningitis diagnosed by India ink staining of CSF. The main treatment for this infection is

*amphotericin B* & flucytosine, followed by fluconazole

7-day-old neonate born to 28-year-old woman brought to office due to progressive lethargy, vomiting, & poor feeding. The mother reports an uneventful pregnancy & perinatal course. She exclusively breastfeeds infant & has no medical problems in any of her children. On exam, the infant is somnolent & dehydrated with decreased muscle tone. Lab studies reveal metabolic acidosis with an elevated anion gap, ketosis, & hypoglycemia. Further evaluation reveals markedly elevated propionic acid level due to defective conversion of propionyl-CoA to methylmalonyl-CoA. This patient is most likely unable to use what amino acids for energy production?

*Valine* - catabolism of *threonine, isoleucine, methionine, valine* (all essential AAs / TIM.V) along with *odd-chain FAs* = propionyl-CoA - propionyl-CoA converted to methylmalonyl-CoA in reaction catalyzed by biotin-dependent propionyl-CoA carboxylase - isomerization of methylmalonyl-CoA generates succinyl-CoA --> enters TCA cycle Propionic acidemia - AR organic acidemia - via congenital deficiency of propionyl-CoA carboxylase - severe metabolic acidosis - hypoglycemia & ketosis secondary to acidosis - present 1-2 weeks after birth = lethargy, poor feeding, vomiting, hypotonia - treatment = low-protein diet with minimal amounts of TIM.V

Potent inhibitor of mutated BRAF. Anti-tumor effects with improve survival & long-term outcomes in advanced stage V600E-positive melanoma patients.

*Vemurafenib*

Destruction of what area of the hypothalamus results in food-seeking behavior?

*Ventromedial nucleus* - mediates satiety - destruction = hyperphagia - monitors blood flucose - center of satiety

23-year-old woman being evaluated for recurrent episodes of urinary tract infection. She has had 5 episodes of cystitis & an episode of pyelonephritis over the past year. The symptoms tend to occur a few days following sexual intercourse. The patient has no other med problems & takes no meds. Her temp is 36.7 C (98 F), BP is 110/70 mmHg, respirations are 16/min, & pulse is 65/min. Abdominal and genitourinary exams are normal. What is the most likely predisposing factor for pyelonephritis in this patient?

*Vesicoureteral urine reflux* UTIs - via fecal flora - gram-negative rods - sexual intercourse facilitates bacterial ascent up relatively short urethra & into bladder - anatomic or functional vesicoureteral reflux almost always necessary for dev't of acute pyelonephritis

Protein becomes glycosylated before proteolytically cleaved into 2 smaller proteins in endoplasmic reticulum & Golgi apparatus. Based on this data, what best describes the function of these 2 newly formed HIV proteins?

*Virion attachment to target cells* Only the polyprotein product of env gene is glycosylated to become gp160 --> gp160 then proteolytically cleaved within ER & Goli apparatus to form gp120 & gp41 - gp120 mediates viral attachment by binding to CD4 receptor - gp41 anchors gp120 via noncovalent interaction = fusion process between viruses & target cells

45-year-old Caucasian woman suffers from inability to walk. Her spinal cord shows symmetric myelin layer vacuolization & axonal degeneration involving the posterior columns & the lateral corticospinal tracts. What is the most likely cause of this patient's condition?

*Vitamin B12 deficiency / subacute combined degeneration degeneration of: - dorsal columns of spinal cord = bilateral loss of position & vibration sensation - lateral corticospinal tracts = upper motor neuron signs - axonal degeneration of peripheral nerves

Compared with the contents of freshly secreted hepatic bile, the proportion of what is decreased in bile stored in the gallbladder?

*Water* - comparing intrahepatic bile to extrahepatic bile (stored in gallbladder) - while gallbladder is store in gallbladder, water is reabsorbed by gallbladder epithelial cells to make bile concentrated

32-year-old migrant ranch worker brought to ER with painful paroxysmal involuntary muscle contractions involving mainly the jaw, neck, & trunk. The causative substance has most likely traveled by what routes?

*Wound --> motor neuron axons --> spinal cord* Clostridium tetani - spores found in soil & may contaminate injured tissue - puncture from soil-contaminated objects - retrograde transport to spinal cord & medulla (organism itself does not travel but remains at local wound site)

2-year-old girl is brought to office due to concerns about her dev't. The girl says 40 words & does not string words together. She can jump, walk upstairs slowly, build a 6-block toward, & follow short commands. She feeds & helps to dress herself. The girl's mother says, "My daughter is such a happy child. She loves playing with the other kids at day care. She is affectionate & caring toward us & her dog. I don't know why she won't speak. Her sister was using sentences by age 2. Did I notice this too late?" What is the most appropriate response by the physician?

*Your child may have a language disorder & could benefit from further assessment."* Age 2 - should have vocab of 50-200 words & be able to use 2-word phrases Isolated language disorder - motor & social skills normal - most commonly delayed milestone - many children will catch up in preschool - child should have *hearing examination* as well as speech & language evaluation

What characteristics of thiopental, but not of propofol, best explains the difference between these two drugs?

*Zero-order metabolic elimination of thiopental* Thiopental = IV anesthetic = ultrashort-acting barbiturate that is most commonly applied in the "INDUCTION" phase of general anaesthesia - Recovery is "SLOWER" due to zero-order kinetics - highly lipophilic = readily diffuses across membranes --> quickly accumulates in tissues reciving high blood flow = rapid onset of action

With ulnar nerve injury, patients have weakness of what at the wrist?

*adduction*/flexion and - finger abduction/adduction - flexion of 4th/5th digits

40-year-old chronic alcoholic enters hospital because of a variety of symptoms, including loss of feeling in his hands & feet, nystagmus, & difficulty with his balance when walking. This patient would have difficulty catalyzing what reactions?

*alpha-Ketoglutarate dehydrogenase* Pyruvate dehydrogenase Transketolase (HMP shunt) Vitamin B1 deficiency/Beriberi - required for oxidative decarboxylation rxns alpha-ketoglutarate dehydrogenase requires - thiamine (thiamine pyrophosphate) - lipoic acid - CoASH - FAD - NAD+

67-year-old man develops HT in recovery room 1 hour after hip replacement. He has a history of angina pectoris. The most appropriate therapy to decrease his BP without causing reflex increase in heart rate is a drug that antagonizes what receptors?

*alpha-adrenergic & beta-adrenergic* Nonselective alpha- & beta-antagonists = carvedilol, labetalol = modified suffixes (-olol) - decreased heart rate & contractility = decreased oxygen consumption

Certain chromosomal abnormalities can result in rudimentary development of cerebral hemispheres. What labeled structures in the cross section of a normal brain stem is expected to be most underdeveloped as a result of such an anomaly?

*corticospinal tract* - cut section through medulla No cerebral cortex --> no upper motor neurons --> no corticospinal tract Holoprosencephaly ~ Trisomy 13 ~ Patau

Tetralogy of Fallot results from

*deviation of infundibular septum* Tetralogy of Fallot - cyanotic spells that improve with squatting - prominent right ventricular impulse, systolic murmur - abnormal neural crest cell migration --> anterior & cephalad deviation of indundibular septum during embryo dev't = malaligned VSD & overriding aorta - squatting increases peripheral systemic vascular resistance (afterload) & decreases degree of right-to-left shunting across VSD

ewing sarcoma typically arises in

*diaphysis* of long bones, especially femur - second most common malignant bone tumor in children after osteosarcoma - more frequently in older children (10-15 years)

Gastric acid is neutralized by bicarbonate from submucosal glands of

*duodenum (Brunner glands)* & from pancreatic duct secretions

When is blood in the coronary arteries maximal?

*during diastole* During diastole... - AV valves open - aortic & pulmonary valves close During systole... - AV valves close - aortic & pulmonary valves open

Gastric bypass surgery can cause small intestinal bacterial overgrowth (SIBO) due to excessive bacterial proliferation in blind-ended gastroduodenal segment. SIBO results in deficiency of most vitamins & iron but incraesed production of

*folic acid* & vitamin K - enteric bacteria can produce vitamins (K, folate) - decreased B12, A, D, E, iron

Patient who has ingested rodenticide requires immediate

*fresh frozen plasma* + vitamin K - most rodenticides contain brodifacoum = long-acting 4-hydroxycoumarin derivative

Bile salts formed via bile acid conjugation with what amino acids?

*glycine & taurine* - increases their solubility = aid in lipid digestion & absorption through formation of micelles

Most enveloped nucleocapsid viruses acquire their lipid bilayer envelope by budding through plasma membrane of host cell. Exception include

*herpesviruses*, like CMV - *bud through & acquire envelope from the host cell nuclear membrane*

What levels of low in CSF in patients with narcolepsy?

*hypocretin-1* Hypocretin-1 (orexin-A) & hypocretin-1 (orexin-B) - neuropeptides produced in lateral hypothalamus - promote wakefullness - inhibit REM sleep-related phenomena

Increased elastic recoil of interstitial lung disease (restrictive lung disease) results in

*increased radial traction* (outward pulling) on airways = increased expiratory flow rates when corrected for low lung volume

Guidelines for women who culture positive for GBS or in women who have had an infant affected by GBS in past

*intrapartum* antibiotic prophylaxis - penicillin = first-line

Intimal flap in type B aortic dissection (of descending aorta) usually starts near origin of

*left subclavian artery*

Run along & perfuse *lesser curvature* of stomach.

*left* & right gastric arteries - frequently penetrated by gastric ulcers = hemorrhage

What lab value is decreased in CML?

*leukocyte (neutrophil) alkaline phosphatase* Other clues - myelocytes > metamyelocytes = meylocytic bulge - basophilia - eosinophilia - confirmed by t(9;22) or BCR-ABL1 fusion gene or mRNA

hematogenous osteomyelitis is most common in children & usually affects what part of bones?

*metaphysis* of long bones - slower blood flow & capillary fenestrae

schistocytes / helmet cells seen in what conditions?

*microangiopathic hemolytic anemia* - DIC, TTP/HUS, HELLP syndrome, mechanical hemolysis (heart valve prosthesis)

Erosions are defined as mucosal defects that do not fully extend through

*muscularis mucosa* Acute erosive gastropathy - can cause upper GI hemorrhage that leads to melena - limited to mucosal layer

cancer patient on oxycodone + naloxone (on accident) = what effect?

*nausea, vomiting, rhinorrhea* - withdrawal = generally no life-threatening

Nondepolarizing neuromuscular blocking drugs, like *tubocurarine*, reversed with

*neostigmine* = must be given with *atropine* to prevent muscarinic effects like bradycardia edrophonium other cholinesterase inhibitors

What repair is abnormal in XP?

*nucleotide* excision repair

Familial retinoblastoma occurs as result of mutations of each of the two Rb genes (two hits). These patients have increased risk of secondary tumors, especially

*osteosarcoma* - later in life Retinblastomas = most common ocular tumor in childhood - presents with white pupillary reflex = leukocoria Familial retinoblastoma - germline mutation that affects Rb tumor suppressor gene on chromosome 13

grade II astrocytoma caused by impaired activity of what protein?

*p53* --> secondary glioblastomas

Sartorius is longest muscle in body and originates from anterior iliac spine & inserts into

*pes anserinus* of anteromedial tibia shaft Pes anserinus bursitis = runners = anteromedial knee pain

The majority of anal fissures occur where?

*posterior midline* of anal verge - via poor perfusion of posterior anal canal - mucosa sensitive to trauma & slows healing time

Recognize *nitroprusside's* effect on cardiac pressure-volume cycle

- decreases left ventricular preload & afterload = adequate cardiac output delivered at lower LB end diatolic pressure (LVEDP) - stroke volume maintained

Recognize *brain arteriovenous malformation*

- developmental vascular lesions - present at age 10-30 with intracranial hemorrhage, seizure, headache, focal neuro deficits

12-year-old boy admitted to hospital in ketoacidosis with blood glucose level of 700 mg/dL (normal fasting levels are between 80 and 100 mg/dL). The boy is shown to have no detectable C-peptide upon further testing. A potential reason for the elevated blood glucose is:

*reduced number of glucose transport molecules in muscle membrane* - GLUT4 transporter = facilitative diffusion Type 1 diabetes - boy is producing no insulin Insulin - stimulates translocation of GLUT4 transporters from internal vesicles to plasma membrane of muscle & fat cells

Most common cause of death in ALS

*respiratory complications* ALS - thin anterior roots - mild atrophy of precentral gyrus - loss of neuronsin anterior horn = LMN lesions - degeneration & atrophy of lateral corticospinal tracts = UMN lesion - mutation of copper-zinc superoxide dismutase (SOD1) - treatment = riluzole --> decreases glutamate release

A healthy 54 year male undergoes exercise stress test.during moderate phase of exercise,her pulse 140.resp 25. bp 130/90. which of the following is the relative proportion of coronary oxygen delivery during the rest and during exercise times? Rest: systolic vs diastolic Exercise: systolic vs diastolic

*rest = systolic < diastolic* *exercise = systolic < diastolic* The greater amount of oxygen delivered to the heart is under the diastolic Blood pooling in heart --> heart gets in during diastole, rather than systole

32-year-old nulligravid woman evaluted for infertility. Her last menstrual period occurred 6 months ago. Menarche occurred at age of 13 years; menses had occurred at regular 28-day intervals. Physical exam shows milky discharge from both breasts. If pharmacotherapy is indicated, the most appropriate treatment is a drug with what mechanism?

*stimulation of dopamine receptors* Dopamine agonists (bromocriptine) - inhibits prolactin secretion - can be used in treatment of prolactinoma

The velocity of the alcohol dehydrogenase reaction will be at half max velocity when

*the ethanol concentration is equal to the Km for ethanol* Michaelis-Menton equation: v = 1/2Vmax Solving for Km, [S] = Km

Mechanism of 2,3-*dinitrophenol*

*uncoupler* Uncoupling agents - increased permeability of membrane = decreased proton gradient & increased O2 consumption - ATP synthesis stops, but electron transport continues - produces heat - used illicitly for weight loss

High QRS voltage in precordial leads is a sign of

*ventricular hypertrophy* - most commonly results from prolonged untreated HT

Egophany

- "goat sound" - heard by auscultation - patient says "E" but sounds like "A" - underlying *consolidation* (pneumonia)

Recognize *posterior communicating artery*, which can cause oculmotor palsy

- CN III courses between osterior cerebral & superior cerebellar arteries as it exits midbrain in interpeduncular space = diplopia, ptosis, down & out deviation of ipsilateral eye

Multiple myeloma: - PTH = - Urinary calcium = - 1,25-dihydroxyvitamin D = - Parathyroid hormone-related protein =

- Decreased - Increased - Decreased - Normal MM: - hypercalcemia via osteolysis by tumor cells - elevated Ca2+ --> inhibits PTH --> increased urinary loss of Ca2+ = hypercalciuria - hypercalcemia + light chain cast nephropathy = renal failure = loss of 1-alpha-hydroxylase enzyme = suppression = low vitamin D - PTHrP occurs with squamous cell carcinoma of lung, head, neck = not involved in this

Recognize attachment site for *posterior cruciate ligament* on coronal MRI of knee from posterior aspect

- PCL attaches to posterior part of intercodylar area of tibia & anterolateral surface of medial condyl of femur - prevents posterior displacement of tibia relative to femur when knee is flexed = posterior drawer test

Terminal deoxynucleotidyl transferase (TdT)

- add nucleotides to V, D, & J regions of Ab gene for Ab diversity = marker of immature lymphocytes, both B- & T-cells - *positive in neoplastic cells in ALL* --> commonly affects children

Recognize *necrosis & vascular proliferation* of pseudopalisading necrosis of glioblastoma multiforme

- capillaries seen in periphery GBM = most common primary brain neoplasm in adults = 40-70 - within hemispheres / above tentorium - commonly in frontal & temporal lobe

Recognize *glioblastoma*

- cerebral hemispheres - causes midline shift - butterfly glioma - poor prognosis

Recognize decreasing amplitude of cyclic intrapleural pressure changes during deep, rapid breathing, like seen in patient with diseased *Neuromuscular Junction*

- diaphragmatic contraction = intrapleural pressure fall during inspiration - patient's diaphragmatic contractions becoming progressively weaker with repetition *Weakening of inspiratory diaphragmatic contractions...* - *via pathology involving NMJ, the skeletal muscle itself, or lung tissue &/or chest wall* - myasthenia gravis, restrictive lung or chest disease = normal diaphragm fatigues rapidly

Recognize *ureteral obstruction* via BPH, renal stones, severe cancer, injury to ureter, etc

- distention/dilation of renal pelvis & calyces

Recognize *pneumothorax*

- don't be confused by history of asthma or any of that bullshi - asymmetry on the L side - you can see the lung all crumpled up and can see its opaque outline

Recognize *mitral regurgitation* tracing during cardiac catheterization

- excessive rise in left atrial systolic pressure - elevation of peak v wave pressure

Recognize retroperitoneal hematoma in the right retroperitoneum lying anterior to psoas muscle

- fluid is isodense with muscle - displaces right kidney anteriorly Femoral nerve - descends through fibers of psoas major muscle --> emerges laterally between psoas & iliacus --> runs beneath inguinal ligament into thigh Femoral nerve mononeuropathy - via: pelvic fracture, compression from hematoma or abscess, stretch injury, ischemia - weakness of quadriceps group - weakened iliopsoas - difficulty with stairs - fall secondary to "knee buckling" - patellar reflex generally diminished - *sensory loss over anterior & medial thigh & medial leg* - caused by retroperitoneal hematoma = acute, severe pain in groin, lower abdomen, or back

Recognize an *anhydride*

- formed when carboxylic acid & phosphoric acid react --> release H2O

Recognize a *phosphate ester*

- formed when phosphoric acid reacts with an alcohol = releases water

Recognize *Crohn disease*

- full thickness inflammation with knife-like fissures - anywhere from mouth to anus

Recognize *activated CD8+ cytotoxic lymphocytes* / atypical lymphocytes of EBV

- function to destroy virally-infected B-lymphocytes

Recognize Dandy-Walker malformation

- hypoplasia/absence of cerebellar vermis + cystic dilation of fourth ventricle with posterior fossa enlargement - patients often present during infancy with dev't delay & *progressive skull enlargement* - cerebellar dysfunction = unsteadiness & impaired muscle coordination - non-communicating hydrocephalus may occur via atresia of foramina of Luschka & Magendie = elevated intracranial pressure (irritability, vomiting)

Recognize *mitral stenosis* tracing

- increased left atrial pressure during diastole via primary obstruction of left ventricular filling

Recognize BP and Heart rate of Norepinephrine on graph

- increases systolic & diastolic pressure via alpha1-mediated vasoconstriction --> increased mean arterial pressure --> reflex bradycardia Add prazosin... - mean BP in straight line - heart rate opposite

Recognize *babesiosis*, transmitted via Ixodes tick

- intraerythrocytic ring inclusions - northeastern US - outdoor exposure in summer - also a vector of Borrelia burgdorgeri / Lyme disease

Acanthocytes / Spur cells

- irregularly space surface projections - typical of *abetalipoproteinemia*

Recognize *radial nerve*

- largest branch of brachial plexus - branches from C5-T1 - extensor muscle of upper limb - vulnerable at humeral midshaft - damage = weakend *extension of wrist*

Recognize *Bacterial polysaccharide* / T cell independent response given to health 1-year-old being immunized

- lasts longer period (ex. 2 months) - T cell independent Ag metabolized slowly = why IgM response for longer period

Recognize *competitive inhibitor* on Lineweaver-Burk plot

- lines for inhibited reaction intersect on y-axis with those for uninhibited reaction

Recognize *aortic stenosis* tracing

- obstruction of blood flow from left ventricle to aorta during systole - left ventricular systolic pressure higher than aortic pressure

Recognize blood flow curve obtained from *left ventricular myocardium*

- region most prone to ischemia & myocardial infarction

Recognize *A*uer rods of *A*ML, which stain positive for *PEROXIDASE*

- several myeloblasts = abundan basophilic cytoplasm - nuclei often folded or bilobed - Auer rods = myeloid differentiation = found in abundance in AML M3 (acute promyelocytic leukemia) AML - immature cells of myeloid origin unable to differentiate & mature - anemia, thrombocytopenia, neutropenia via marrow replacement by leukemic cells

Recognize *aorta* (C)

- stenosis of ascending aorta = LVH - C = ascending aorta = where right & left coronary arteries arise from - B = right superior secondary (eparterial) bronchus = removed in cancer in apex of right lung by lobectomy - E = descending (thoracic) aorta = where right & left bronchial arteries arise from - D = left primary bronchus = crossed superiorly by arch of aorta & pulmonary artery

Recognize *papilledema*

- takes time - causes fullness of optic disk - visual acuity = 20/20 - pupillary reflexes are normal

Recognize increased elastic resistance associated with *pulmonary fibrosis*

- work done against elastic resistance of lung increased when tidal volume increased - patients with stiff lungs / increased elastic resistance = work of breathing minimized when respiratory rate high & total volume low - rapid & shallow breaths favored - pulmonary fibrosis, pulmonary edema, acute respiratory distress syndrome

4-year-old boy (pedigree shown) has clumsy gait for past year. Exam calf hypertrophy and proximal muscle weakness. Creatine kinase increased. Muscle biopsy shows loss of muscle tissue, regenerating muscles fibers and fibrosis. Maternal uncle had similar findings and died at 15 years. Patient's sister is pregnant. Ultrasound identifies male fetus. Probability fetus has disorder?

1/4

How many base pairs per turn in DNA?

10

Normal platelet count

150,000 - 450,000 - decreased in Wiscott-Aldrich syndrome = WATER = Wiskott-Aldrich: Thrombocytopenia, Eczema, Recurrent (pyogenic) infections

Recognize relative pattern of oxygen saturation in cardiac chambers & outflow tracts of patient with VSD

= *Holosystolic murmur over left sternal border* = abnormal increase in O2 saturation (SpO2) from right atrium to right ventricle = presence of *left-to-right shunt* = allows left ventricular blood to enter RV during systole

Arches that make up cartilaginous structures of larynx, including cricoid & thyroid cartilages

4th & 6th

CN X is derived from what arch?

4th & 6th

Patients with CGD / NADPH oxidase deficiency are at increased risk of developing

5 catalase-positive organisms: Staph aureus *Burkholderia cepacia* Serratia marcescens Nocardia Aspergillus

Recognize borrelia recurrentis, which is an example of antigenic variation

= *Variation of major surface protein antigen of organism* "man develops fever, muscle pain, headache 1 week after being bitten by several ticks while camping near Grand Canyon...fever remits...feels better in 7 days...2-4 days later, symptoms recur...Giemsa stain on peripheral blood smear"

Conversion rxns affected by CAH / 21-hydroxylase deficiency

= 17-hydroxyprogesterone --> 11-deoxycortisol in zona fasciculata = progesterone --> 11-deoxycorticosterone in zona glomerulosa 11-deoxycorticosterone = precursor of aldosterone 11-deoxycortisol = precursor of cortisol

Recognize *chronic arteriovenous shunt* on venous return curve graph

= increased cardiac output of increased sympathetic stimulation to heart - venous return curve shifted right via circulating blood volume increased through renal retention of fluids

macrosomia

= newborn significantly larger than average = birth weight of more than 8 pounds, 13 ounces (4,000 grams), regardless of gestational age

A 19-year-old man is brought to ED after hitting his head on pavement when he fell off his motorcycle. An MRI of his head shows a transection of the pituitary stalk. What patterns best describes the secretion of pituitary hormones in this patient? ACTH = ? FSH = ? Growth Hormone = ? Prolactin = ? TSH = ?

ACTH = decreased FSH = decreased Growth Hormone = decrased Prolactin = increased TSH = decreased Lack of dopamine inhibition = increased prolactin

Inheritance of Hereditary spherocytosis

AD

An RNA produced from a fragment of DNA has the sequence of AAUUGGCU. The sequence of the nontemplate strand in the DNA that gave rise to this sequence is what?

AATTGGCT

Have additional protective effect on remodeling that is independent of BP. Reduce mortality in patients with systolic HF & are therefore recommended in all such patients.

ACE inhibitors & ARBs - recommended in all patients with systolic heart failure - improve hemodynamics

loop structure (RNA) occurs between what base pairs?

AU GC - occurs in G2 - conservative

Blocker of GP IIb/IIIa receptor

Abciximab - used for unstable angina & acute coronary syndrome

A 25-year-old woman comes to the physician because of a 2-year history of intermittent, diffuse, cramping lower abdominal pain. The pain is usually associated with2 to 6 days of loose, watery stools, and is typically relieved with defecation. Between these episodes, her stools are normal. Her vital signs are within normal limits. Physical examination shows no abnormalities. Laboratory studies, including complete blood count, metabolic panel, and thyroid function tests show no abnormalities. A drug targeting which of the following mechanisms of action is most appropriate for this patient?

Accentuation of μ-opioid myenteric plexus receptor

Present as benign suprasellar tumors in children & appears as cord/nests of palisading squamous epithelium with internal areas of lamellar *"wet" keratin* under light microscopy

Adamantinomatous craniopharyngiomas

Able to cross cell membrane & function as vasodilator when coronary blood flow is insufficient to meet myocardial demand

Adenosine - after 30 minutes of total myocardial ischemia = half of cellular adenine loss = failure of cellular homeostasis inevitable & ischemic injury irreversible

Epidermal growth factor receptor inhibitors (erlotinib, getfitinib) used to treat

Advanced non-small cell lung cancer

Recognize where *pancreas* will be on CT

Alcohol + epigastric pain + steatorrhea = chronic pancreatitis with exocrine insufficiency --> fat malabsorption - 72=hour stool collection confirms Pancreas - head = in curve of duodenum & overlies L2 = portion behind SMA (uncinate process) - overlies L1 & L2 - makes contact posteriorly with aorta, left adrenal gland, left kidney, renal vessels - tail courses with splenorenal ligament alongside splenic vessels

Can be used as medical therapy in Conn's syndromey

Aldosterone antagonists = spironolactone, eplerenone

Pain along medial knee & well-defined tenderness approximately 4 cm distal to anteromedial joint margin of knee. Frequently results from obesity or overuse in athletes.

Anserine bursitis

Part of hypothalamus involved in temperature control through regulation of autonomic nervous system

Anterior & Posterior nuclei Anterior nuclei = cooling via inhibition of autonomic nervous system = vasodilation & stimulation of cholinergic input --> sweating - destruction hyperthemia Posterior nuclei = heat conservation = heat production via vasoconstriction & shivering - destruction = hypothermia

Veins that drain into right atrium

Anterior cardiac vein

Antibodies highly specific for systemic sclerosis

Antitopoisomerase I (Scl-70) Anticentromere Anti-RNA polymerase III

D-A-S-E-V-R. What is the C-terminal AA of the hexapeptide?

Arg - peptides written with N-terminal AA on left & C-terminal AA on right

Most common cause of intracranial hemorrhage in children

Arteriovenous malformations

Rare AR condition caused by mutations in BLM gene.

Bloom syndrome - gene encodes for DNA helicase --> dysfunction = growth retardation, facil anomalies (microcephaly), photosensitive rash, immunodeficiency / recurrent infections

Cell surface marker expressed on monocytes & macrophages. Serves as receptor for LPS.

CD14 - binding of LPS to receptor = activation of macrophage

Cell surface marker present on granulocytes. Also present on nearly all Reed-Sterneberg cells & is therefore a cytologic marker useful in diagnosis of Hodgkin lymphoma.

CD15

low-affinity Fc receptor found no surface of NK cells, neutrophils, & macrophages.

CD16

36 y/o woman brought to ED by her husband because of 3 day h/o fever and increasing confusion. she is awake but slow to respond. T: 38.4C. PE and neurologic no other abnormalities. Exam of the CSF obtained on lumbar puncture shows: Pressure opening: normal appearance: clear glucose: 65 mg/dl Protein total: 85 mg/dl leukocyte: 110 mm3 lymphocyte: 98 erythrocyte count: 3% A gram stain of CSF shows no bacteria. CT-Scan of the head: enhance lesion within temporal lobe. Which of the following test most appropriate to confirm the diagnosis? Diagnostic test = Virus =

CSF polymerase chain reaction herpes simplex

Results from deposition of calcium hydroxyapatite crystals in periarticular soft tissues (especially tendons). Rotator cuff tendons most commonly affected.

Calcific tendonitis

Levels increased in colon cancer. Cannot be used to diagnose colon cancer but is useful for detecting residual disease & *recurrence&

Carcinoembryonic antigen (CEA)

In patient in cardiogenic shock after suffering a left ventricular inferior wall MI, what are the following: Cardiac output = Pulmonary capillary wedge pressure = Central venous pressure =

Cardiac output = decreased Pulmonary capillary wedge pressure = decreased Central venous pressure = increased Right ventricular MI = hypotension, elevated jugular venous pressure, clear lung - left ventricular inferior wall MI via proximal right coronary artery occlusion - elevated right atrial & central venous pressures, reduced pulmonary capillary wedge pressure, reduced cardiac output

What best describes peptide hormones? Receptor location = Onset of action = Example =

Cell membrane Rapid Insulin

What class is procainamide?

Class IA antiarrhythmic - commonly associated with drug-induced lupus syndrome

What class is verapamil?

Class IV antiarrhythmic - most cardioselective of CCBs - postent negative inotrope - has been replaced as drug of choice for PSVT - ADR = gingival hyperplasia

Adequate coverage against both aerobic streptococci & anaerobes essential for successful treatment of lung abscesses. What would be a good antibiotic?

Clindamycin

Nonciliated cells found predominately in terminal portions of bronchioles. Secrete secretory protein (protects against airway inflammation & oxidative stress) & surfactant components (prvent bronchiolar collapse)

Club / Clara cells

The triad of signs & symptoms that is most often present in a patient shortly after taking overdose of heroin includes what?

Coma Miosis Cyanosis

Lobar pneumonia: pronounced dilatation of alveolar capillaries. Some exudate containing mostly bacteria may be present in alveolar spaces.

Congestion

Have the strongest and most predictable effects on the inflammatory component of asthma

Corticosteroids (ex. fluticasone)

Intracellular polyphosphate granules are characteristic of

Corynebacterium diphtheriae - granules within cytoplasm evident with methylene blue staining

CD8+ T cells important in combating intracellular intestinal pathogens like

Cryptosporidium parvum Toxoplasma gondii

Antihistamine with anti-serotonergic properties that can be used in treatment of serotonin syndrome

Cyproheptadine

Recognize diastolic heart failure via *Transthyretin deposition*

Decompensated CHF - exertional dyspnea, orthopnea, bibasilar crackles, elevated jugular venous pressure LV diastolic pressure-volume curve = reduced LV compliance = diastolic dysfunction is main contributing factor to patient's CHF - decreased compliance = increased LV end-diastolic (LVED) pressures - shift in pressure-volume curve that goes upward & to left - higher LV filling pressures transmitted back to pulmonary vasculature --> pulmonary edema - impaired right ventricular filling or neurohormonal activation from low cafrdiac output = peripheral edema & elevated jugular venous pressure Restrictive cardiomyopathy = idiopathic or infiltrative (amyloidosis, sarcoidosis, hemochromatosis) = heart failure with preserved ejection fraction Transthyretin (TTR) = protein tetramer produced in liver - acts as carrier of thyroxine & retinol - mutations = increased tendency to misfold = amyloid protein --> infiltrative cardiomyopathy

Activation of gene expression... Methylation of gene = Formation of polycystronic messages = Histone acetylation levels =

Decreased No Increased

Indicated for treatment of Loa loa (loiiasis) & Wucheria bancrofti

Diethylcarbamazine

*Reversible* change in epithelial cells

Dysplasia Epithelial malignancy progression: low-grade dysplasia --> high-grade dysplasia/carcinoma in situ --> invasive carcionma - breach BM = no longer reversible

Important cause of urinary tract infections. Gram-positive cocci in pairs & *chains.* When grown on blood agar, they do not cause hemolysis (*gamma-hemolytic*)

Enterococcus - pyrrolidonyl arylamidase (PYR) positivity - able to grow in bile in 6.5% sodium chloride - unable to convert nitrates to nitrites = negative result on urinalysis nitrite

Most common cause of viral meningitis in children

Enterovirus / Group B Cosackievirus

Present as paraventricular tumors (floor of fourth ventricle) & have characteristic *perivascular rosettes* under light microscopy

Ependymomas

Insulin-independent transporters

GLUT-1 - RBCs, BBB GLUT-2 - hepatocytes, pancreatic beta cells, basolateral renal tubules & SI mucose GLUT-3 - placental, neuronal glucose transport GLUT-5 - fructose transporter - spermatocytes, GI tract GLUT-1, 2, 3, 5 always present on plasma membrane, regardless of insulin

Only GLUT transporter responsive to insuline

GLUT-4 - expressed in skeletal muscle & adipocytes

What induction agent can cause adrenal cortex suppression?

Etomidate - inhibits 11-beta-hydroxylase

Selectively inhibits intestinal cholesterol absorption

Ezetimibe

patient has emphysema. FEV/FVC = Total lung capacity = Diffusing capcity for carbon monoxide =

FEV/FVC = decreased Total lung capacity = increased Diffusing capcity for carbon monoxide = decreased Obstructive!

When do ventricular arrhythmias / fibrillation typically occur after MI?

FIRST AID = first 24 hours after post-MI UWORLD = first 48-72 hours after MI

Causes angiokeratomas, peripheral neuropathy, & glomerulopathy that typically present in adulthood.

Fabry disease / globotriaosylceramide accumulation *Fabry*'s *Gal* on the *Side* - alpha-*Gal*acto*Sid*ase

Some Ig 'cules are attached to the surface of macrophages, neutrophils, & B lymphocytes. What is the cell attachment site for the Ig molecule?

Fc receptors (FcR) - bind specifically to Fc portion of IgG 'cules = essential for process of opsonization

What pharyngeal arch is associated with CN V?

First pharyngeal arch - maxilla, zygoma, mandible, incus, malleus - muscles of mastication (masseter, temporalis)

Recognize the effects of adding *Rotenone --> Oligomycin --> Dintrophenol* to solution

First upward slope would = Roten*one* - inhibits complex *one* = would not affect electrons transported to complex II Oligomycin - ATP synthase inhibitor - not ATP produced because ETC stops Dinitrophenol - uncoupler = increases rate of oxygen consumption If added CN or CO, all electron flow would stop

Inhibits synthesis of both DNA (replication) & RNA (protein synthesis) in fungal cells

Flucytosine - used agaisnt Cryptococcus in combo with amphotericin B

Contains middle meningeal artery, middle meningeal vein, & meningeal (recurrent) branch of CN V3, which supplies dura & contains sympathetic fibers

Foramen spinosum

Cytogenetic studies typically show a small gap near tip of long arm of X chromosome

Fragile X - earliest manifestation = dev'tal delay

43-year-old man prospecting for gold in Arizona becomes stuck in desert after his truck breaks down. He brought a large supply of water with him but only a few granola bars as food. After 3 days, he is able to flag down a passing vehicle & obtain transportation to nearest settlement. During this ordeal, his liver begins to synthesize large quantities of glucose from source molecules such as alanine, lactate, & glycerol. As part of this process, PEP is formed from OAA in a reaction that requires a specific nucleoside triphosphate as a cofactor. What reactions directly synthesizes this cofactor?

GTP synthesized by succinyl-CoA succinate in TCA

Greater splanchnic nerves contain

GVA & preganglionic sympathetic GVE fibers

Can reduce cholesterol solubility and promote gallstone formation by reducing bile acid synthesis.

Gemfibrozil - use in caution with patients with underlying gallbladder disease!

GP IIb/IIIa is either deficient or defective in patients with

Glanzmann thrombasthenia - AR - presents in childhood with mucocutaneous bleeding - *peripheral smear shows no platelet clumping!*

What metabolic patterns would be observed in a person after 1 week of starvation? Brain use of fuels = Liver glycogen content (% of normal) = Nitrogen balance = Gluconeogenesis =

Glucose & ketone bodies <5 Negative Activated After 3-5 days of starvation... - brain begins using ketone bodies, in addition to glucose, as a fuel source - glycogen stores in liver depleted (<5% of normal) during first 30 hours of fasting - inadequate protein diet = negative nitrogen abalance

Carbon dioxide produced by tissue metabolism carried in blood predominately in what forms?

HCO3- in *plasma* = 70%

tartrate resistant acid phosphatase (TRAP) stains positive for

Hairy cell leukemia - neoplastic cells = B-lymphocyte precursors = CD20+ - splenomegaly, fatigue, pancytopenia

The condensation reaction between succinyl-CoA & glycine is the rate-limiting reaction in the biosynthesis of what compounds?

Heme

Patients with deficiencies in lysosomal enzymes and cannot break down glycosaminoglycans (GAGs), resulting in mucopolysaccharidoses.

Hurler syndrome Hunter syndrome - soft tissue & skeletal disease

Well-tolerated antirheumatic drug used in mild RA & SLE. Most significant toxicity is irreversible retinopathy. Patients should have regular ophthalmologic exams

Hydroxychloroquine

Recognize *Nocardia asteroides*

Immunocompromised patient + fever, headache + ring-enhancing lesion (likely abscess) on brain MRI + respiratory symptoms with pulmonary nodules + sputum studies revealing branching gram-positive organisms - weakly staining gram-positive - catalase-positive - rod-shaped - found in soil & healthy gingiva - beaded branching filaments - typically affects lungs, brain, or skin - treatment = trimethoprim-sulfamethoxazole

Compared with values while at rest, what cardiopulmonary responses are most likely while she jogs at a steady rate? Expired Minute Ventilation = ? Cardiac Output = ? Arterial PO2 = ?

Increased Increased Unchanged Response to exercise... - increased CO2 production - increased O2 consumption - *increased ventilation rate to meet O2 demands* - V/Q ratio from apex to base becomes more uniform - increased pulmonary blood flow due to *increased cardiac output* - decreased pH during strenuous exercise - *No change in PaO2 & PaCO2*, but increase in venous CO2 content & decrease in venous O2 content

20-year-old woman has had progressive weakness, anorexia, intermittent vomiting, & a 6-kg (13.2 lb) weight loss over the past 6 months. She is thin, her BP is 88/60 mmHg, & there is diffuse brown darkening of the elbow creases & in an old appendectomy scar. What sets of lab findings is most likely in this patient? ACTH = Serum Cortisol = Aldosterone = Urine: Na+ = K+ =

Increased ACTH Decreased Serum Cortisol Decrased Aldosterone Increased Urine Na+ Decreased Urine K+ Addison's Primary Adrenal Insufficiency - loss of adrenal gland --> hypotension - hyperkalemia (opposite of urine value) - metabolic acidosis

Phenomenon in which brief repetitive episodes of MI, followed by reperfusion, protect myocardium from subsequent prolonged episodes of ischemia

Ischemic preconditioning

Drug that causes myobacteria to lose their acid-fastness

Isoniazid - isolates become less resistant to decolorization with acid-alcohol agent - decreased synthesis of mycolic acids

Used as antifungal prophylaxis for HIV+ individuals with CD4 counts < 150 cells/uL who live in areas endemic for Histoplasmosis

Itraconazole - can also be used for chemoprophylaxis against Coccidioides

Used to treat infections caused by Strongyloides stercoralis & Onchocerca volvulus

Ivermectin

Patients with damage to these roots have pain radiating down anterior thigh with weakness on hip flexion (via denervation of iliopsoas).

L2 or L3

Level of inferior mesenteric artery

L3 - blood supply to colon from splenic flexure to upper rectum (descending & sigmoid colon)

Compression of this root results in pain/paresthesia radiating down lateral thigh & calf to dorsal foot

L5 - weakness on foot dorsiflexion & inversion (denervation of tibialis anterior), foot eversion (peroneus), & toe extension (extensor digitorum brevis)

Inflammation of vestibular nerve that causes acute-onset vertigo, nausea, & vomiting. Usually occurs in single episode following viral syndrome

Labyrinthitis

Area of hypothalamus that signals hunger

Lateral nuclei - lesions = loss of appetite; adults = starvation, infants = failure to thrive If you zap your *lateral* area, you shrink *laterally*

57-year-old man brought to ED following generalized tonic-clonic seizure. His wife reports that he has no history of seizures. However, she says that he has been complaining of intermittent headaches, memory loss, & problems with his vision for the past 2 weeks. Brain imaging shows a solitary mass within the right temporal lobe. What visual field defects is most likely present in this patient?

Lesions in temporal lobe can disrupt Meyer's loop --> contralateral superior quadrantanopia Other temporal lobe lesions - aphasia (dominant hemisphere lesions) - memory deficits - seizures (complex partial & tonic-clonic) - hallucinations (auditory, olfactory, visual)

Most potent chemotactic eicosanoid that stimulates neutrophil migration sites of inflammation

Leukotriene B4 - C5a also recruits & activates neutrophils, monocytes, eosinophils, basophils; 5-HETE, IL-8

Examples of differential media

MacConkey Eosin Methylene Blue (EMB) agars - used to culture enteric organisms Fermenter of lactose = pink on MacConkey agar = black of EMB agar

Pargyline targets

MAO

Presence of prolactinoma in addition to parathyroidoma or gastrinoma is consistent with

MEN 1

Play an important role in osteoclast differentiation

Macrophage colony-stimulating factor & receptor for activated *nuclear factor kappa-B* ligand (RANK-L) - Paget = excessive osteoclastic bone resporption followed by increased bone formation by osteoblasts = high bone turnover in affected areas = disorganized new bone - normal osteoclasts = 2-5 nuclei (abnormally can have up to 100)

Carries sensation from majority of external auditory meatus, except for posterior wall (vagus)

Mandibular branch of trigeminal nerve

Most common malignant brain tumor of childhood

Medulloblastoma - arises in cerebellum mostly

tinnitus + vertigo + sensorineural hearing loss

Meniere disease = *Increased volume of endolymph inner ear* = endolymphatic hydrops = feeling of fullness

Calcifcation associated with hypercalcemia. Affects normal tissues & organs.

Metastatic calcification - calcium deposition in more alkaline tissues involved in acid excretion = kidneys, lungs, systemic arteries, gastric mucosa

Drugs known to cause acneiform eruptions

Methyltestosterone/Anabolic steroids Epidermal growth factors receptor inhibitors Lithium

Protects from tachycardia caused by minoxidil and other direct vasodilators

Metoprolol

ketamine mech

NMDA antagonist

First-line treatment for acute gouty arthritis

NSAIDs = *Cyclooxygenase inhibitor*

What class is Pilocarpine?

Nonselective muscarinic receptor agonist

Impairment of respiratory control centers in brainstem can result in decreased frequency &/or amplitude of involuntary respirations. Voluntary breathing unaffected.

Ondine's curse

Heberden nodes & Bouchard nodes seen in

Osteoarthritis - brief morning stiffness may be present

Used for prophylaxis & treatment of Pneumocystis jirovecii pneumonia in patients with HIV

Pentamidine - may also be used for African sleeping sickness & leishmaniasis

Recognize intense pink discoloration of a PAS reaction for Tropheryma whippelii, which is *GLYCOPROTEIN*

Periodic acid-Schiff (PAS) reaction - oxidizes C-C bonds --> aldehydes = magenta color upon reacting with fuchsin-sulforous acid Diastase - can be used in conjunction with PAS - demonstrates glycogen - found in skin, liver, parathyroid, & skeletal/cardiac muscle - digests glycogen to form maltose & glycose = easily washed from sections during processing = negative reaction Glycoprotein present in cell walls of gram-positive actinomycete Tropheryma whippelii = magenta via PAS = diastase-resistant

Non-specific alpha-1 & alpha-2 blocker with no beta-blocking effects that causes profound fall in diastolic pressure & reflex tachycardia

Phentolamine

milrinone mechanism

Phosphodiesterase 3 inhibitor

Toxic megacolon, a complication of ulcerative colitis. Preferred diagnostic imaging study.

Plain abdominal x-ray - abdominal pain/distention, bloody diarrhea, fever, signs of chock

Caused by swelling of gastrocnemius or semimembranous bursa. Often form due to extrusion of synovial fluid from knee joint into bursa in patients with osteoarthritis or inflammatory joint disease.

Popliteal/Baker cysts

Can present with bilateral hydronephrosis & calyceal dilation due to obstruction of urine flow in urethra. Result from malformation of Wolffian duct, so it only occur in males.

Posterior urethral valves

P vivax & P ovale have dormant liver forms (hypnozoites) that require what therapy?

Primaquine

Avoid this med in patient with Prinzmetals angina.

Propranolol - would block vasodilation - would treat with *CCB/verapamil* or nitroglycerin

Recognize *calcium pyrophosphate*

Pseudogout / Calcium pyrophosphate deposition disease (CPPD) - acute mono- or oligoarticular arthritis - knee joint involved in >50% of pseudogout cases - elevated WBC count with *neutrophilic predominance* - rhomboid-shaped calcium pyrophosphate crystals - birefingent under polarized light = color pattern opposite of that seen in gout = blue when aligned parallel & yellow when perpendicular to slow ray of compensator

Gene transcription begins when...

RNA polymerase II attaches to one of the promoter regions in a process that requires general transcription factors

Removes oxygen and are used to culture anaerobic organisms

Reducing media (thioglycolate broth)

Most serious long-term adverse effect related to chloroquine use

Retinopathy

Characterized by loss of speech and motor skills, deceleration of head growth, & stereotypical hand moveents after period of normal dev't. It affects mainly girls & is associated with mutations in the MECP2 gene.

Rett syndrome - normal dev't until age 5-18 months - loss of babbling & motor control - seizures, intellectual disability, autistic features (avoiding eye contact), breathing abnormalities - X-linked dominant

Potent toxin that inhibits protein synthesis by cleaving rRNA component of eukaryotic 60S subunit.

Ricin (castor oil plant Ricinus communis)

Most frequently used agent for chemoprophylaxis of meningococcal disease.

Rifampin

Produces narrow zone of beta-hemolysis that enhances when plated perpendicular to S aureus.

S agalactiae (group B strep_ - skin & soft-tissue infections & newborn sepsis & meningitis

Most common cause of septic arthritis, particularly in children & adults over age 50

S aureus - ex. via IV drug use

gram-positive cocci that is coagulase-negative, catalase-negative, & pyrrolidonyl arylamidase (PYR)-positive. Forms small colonies with wide zone of beta-hemolysis & is sensitive to bacitracin (widely replaced by PYR test)

S pyogenes - can be transmitted via wounds - spreads to deep layers of skin & fascia via production of hyaluronidase & other hyrolytic enzymes - M protein = major virulence factor --> allows bacteria to evade phagocytosis by preventing activation of alternate complement pahtway - secretes extracellular toxin = hemolysins O & S = cytotoxins that cause hemolysis & pyrogenic exotoxins = superantigens that result in tissue injury & septic shock - severe pain - hypotensive - aggressive surgical debridement

Hematopoietic growth factor likely to cause myalgias and fever

Sargramostim (GM-CSF)

*Verocay bodies* composed of eosinophilic cores (Antoni A pattern) characteristic of

Schwannomas - mostly benign

What pharyngeal arch is associated with CN VII?

Second pharyngeal arch - styloid process of temporal bone, lesser horn of hyoid, stapes - muscles of facial expression

30-year-old woman has had diarrhea & weight loss for several months. She also has diffuse bone pain & weakness. Initial lab evaluation reveals a vitamin abnormality & normal magnesium levels. Her diarrhea improves following adherence to a gluten-free diet. What changes were most likely present during the initial lab evaluation of this patient? Serum Ca = Serum phosphorous = Serum PTH =

Serum Ca = decreased Serum phosphorous = decreased Serum PTH = increased Celiac disease - defective mucosal absorption of vitamins & nutrients - diarrhea --> vitamin D deficiency via malabsorption Vitamin D deficiency - both calcium & phoshorous absorption from GI tract decreased - increased PTH --> liberation of calcium & phosphorous from bones --> decreased bone mineralization --> osteomalacia

Characterise Coxsackie virus

Single-stranded RNA Icosahedral No envelope ssRNA --> icos --> naked birds CHRP = Picorna = PERCH = polio, echo, rhino, cox, HAV

Vein accompanied by marginal artery

Small cardiac vein

Adhesion to collagen is main virulence factor of

Staph aureus in osteomyelitis - nonmotile - capable of fermenting some sugars (lactose, mannitol)

Produce IgA proteases that cause cleavage of IgA Abs, preventing them from interfering with bacterial adhesion to mucous membranes

Streptococcus pneumoniae Neisseria gonorrhoeae

Inhibit fusion of lysosomes to phagosomes, permitting mycobateria to persist as facultative intracellular organisms within phagocytes

Sulfatides - virulence factor

Injury to the radial nerve where is due to repetitive pronation/supination of forearm, direct trauma, or subluxation of radius?

Supinator canal - damage here via repetitive pronation/supination of forearm (frequent screwdriver use), direct trauma, dislocation of radius - weakness during finger & thumb extension (finger drop) without wrist drop or sensory deficits Radial nerve - after passing through supinator canal (between superficial & deep parts of supinator m) --> deep branch continues to wrist to become posterior interosseous nerve = innervates muscle involved in finger & thumb extension

Part of hypothalamus that projects axons into posterior pituitary gland (neurohypophysis), producing vasopressing (ADH) & oxytocin.

Supraoptic & Paraventricular nuclei

Characterized by abnormal proliferation of mast cells & increased histamine release. Histamine release causes *hypersecretion of gastric acid* by parietal cells in stomach

Systemic mastocytosis - hypotension, flushing, pruritus - diffuse itching after hot showers - mast cell proliferation associated with mutations in *KIT* receptor tyrosine kinase

Inhibits fungal enzyme squalene epoxidase, which ultimately results in decreased ergosterol synthesis

Terbinafine - accumulates in skin & nails - used to treat dermatophytosis

Diuretics associated with increased bone mineral density & are recommended for treatment of HT in patients at risk for osteoporosis.

Thiazide diuretics, like hydrochlorothiazide - increases calcium absorption in DCT

Goal of stimulus therapy

To dissociate bedroom from any stimulating activities that do not involve sleep (reading, television, eating) & the fear of not sleeping - ex. if unable to fall asleep within 20 minutes, leave bedroom & do a relaxing activity in another room until patient feels sleep again rather than lying in bed awake & becoming increasingly worried & frustrated

Single most preventable cause of death & disease in US

Tobacco use, especially smoking - substantially increases risk for macrovascular (MI, stroke) & microvascular (retinopathy, nephropathy) complications of diabetes mellitus - increases likelihood of developing diabetes

Increases replication of osteoblast precursors, leading to increased formation of mature osteoblasts.

Transforming growth factor beta - also increases collagen synthesis & decreases bone resorption by increasing osteoclastic apoptosis

Genetic disorder via abnormal dev't of first & second pharyngeal arches

Treacher-Collins syndrome - mandibular, maxillary, zygomatic bone hypoplasia - airway compromise, feeding difficulties - hearing loss via absent or abnormal ossicles

Most common initial finding of patient going through alcohol withdrawal (often in hospital setting)

Tremor / the "shakes"

Omphalocele associated with what chromosomal abnormality?

Trisomies 13 & 18

Myelomeningocele associated with what chromosomal abnormality?

Trisomy 18

In the resting state of skeletal muscle, this covers the myosin binding sites on actin filaments

Tropomyosin

Granulation tissues composed of what collagen?

Type III collagen (7 days following acute MI) --> eventully replaced by type I collagen as infarct matures

Nonsense mutations / premature stop codons

UAA UAG *UGA* Duchenne muscular dystrophy - caused by frameshift mutations (most common) or *nonsense* mutations in dystrophin gene --> truncated, defective protein

Carnitine is synthesized from lysine & methionine. What vitamin is essential for this synthesis?

Vitamin C

Vertebral anomalies in association with renal anomalies are suggestive of

VACTERL association: Vertebral, Anal atresia, Cardiac defects, Tracheoesophageal fistula, Renal defects, Limb defects - renal anomalies = atresia, dysplasia, duplications

Used both as an anticonvulsant & a mood stabilizer

Valproate - blocks voltage-gated sodium channels & enhances GABA synthesis & release - treats absence, myoclonic, & generalized tonic-clonic seizures - drug of choice for myoclonic seizures - used in acute mania & maintenance treatment of bipolar disorder

Succinate dehydrogenase requires what vitamin for its cofactor?

Vitamin B2 / riboflavin - component of *FAD* & FMN = cofactors in redox reactions in TCA cycle

Vitamin deficiency that is associated with increased susceptibility of neuronal & erythrocyte membranes to oxidative stress. Clinical manifestations include ataxia, impaired proprioception & vibratory sensation, & hemolytic anemia.

Vitamin E deficiency

Noradrenergic receptor classes found in both presynaptic & postsynaptic terminals

alpha2

Stable-angina long-term management in patient with bronchospasm

amlodipine - CCB

Fixed, wide splitting of S2 occurs in patients with

atrial septal defects

methocarbamol

central muscle relaxant used to treat skeletal muscle spasms

This antiHT agent's side effect profile includes impaired glucose tolerance, hypokalemia, increased serum lipids, and increased renin secretion

chlorothiazide

NSAID-associated chronic renal injury is morphologically characterized by

chronic interstitial nephritis & papillary necrosis "bilateral shrunken & irregular kidneys with few papillary calcifications"

What class is Lidocaine

class IB antiarrhythmic - overdose = neuro symptoms - indicated for ventricular arrhythmias Lettuce, Mayo, Tomatoes

no evidence of peripheral congestion. some symptomology. LVEF below 40%

class II NYHA systolic heart failure

Formaldehyde & Glutaraldehydes work as disinfectants by

cross-linking DNA & proteins - most commonly used for sterilization of hospital instruments that cannot withstand autoclave temps

Foods high in vitamin B2 / riboflavin

dark green veggies, especially broccoli, meats, dairy

Lab values of HUS

decreased hemoglobin & haptoglobin increased serum lactate dehydrogenase *increased unconjugated bilirubin* bleeding time may be increased

How to determine Vmax from Lineweaver-Burk plot

determined by intercept of Y-axis = 1/Vmax ex. if intercept on Y axis = 0.1 --> Vmax = 10

How to determine Km from Lineweaver-Burk graph

determined from x intercept on graph ex. If intercept = -2 mM --> -1/Km --> Km = 0.5

Recognize epinephrine vs epinephrine + propranolol effects on BP & HR (graphs)

epinephrine = alpha1, beta1, bet2 - alpha1 = increased BP = predominates at high doses - beta2 = vasodilation = predominates at low doses - beta1 = increased heart rate & contractility = systolic BP Increased diastolic BP via - abolition of vasodilation of beta2 - enhanced alpha1 Heart rate failed to increase with epinephrine = beta1 of epinephrine blocked *Propranolol counteracts epinephrine's beta2-mediated vasodilation & beta1-mediated heart rate while leaving alpha1 (vasoconstriction) = increased diastolic BP

Presence of erythroid precursor cells in liver & spleen is indicative of

extramedullary hematopoiesis - erythropoietin-stimulated hyperplastic marrow cell invasion of extramedullary organs - most frequently caused by *chronic hemolytic anemia*, such as beta-thalassemia - things bony cortex - impairs bone growth - chipmunk facies

Derivatives of second pharyngeal arch

facial nerve *stapes* styloid process lesser horn ofhyoid Treacher-Collins - can disrupt 1st & 2nd pharyngeal arches = hypoplasia of mandibular & zygomatic bones

Second division of trigeminal nerve / V2/ maxillary nerve exits skull via

foramen rotundum

Earliest morphological change in diabetic nephropathy

glomerular basement thickening with resultant mesangial matrix expansion

A vegan has been eating low quality vegetable protein for many years, & is now exhibiting a negative nitrogen balance. This may be occurring due to a lack of what in their diet?

one essential amino acid (ex. *lysine*) Negative nitrogen balance - via diet deficient in one essential AA or a very diseased state

Obstruction at foramen of Monro would cause enlargement of

only affected lateral ventricle

Hallucinations of recently deceased relatives in children...

part of normal grief reaction

Values that can help identify cause of metabolic alkalosis

patient's volume status & measuring *urinary chloride* concentration - pH > 7.45 = alkalosis - vomiting/nasogastric suctioning & thiazide/loop diuretic use = volume & Cl- depletion = metabolic alkalosis that is saline-responsive - hyperaldosteronism = metabolic alkalosis that is saline-unresponsive

21-year-old man comes to physician complaining of repeated episodes of palpitations that start & stop abruptly. After completing careful workup, physician suspects that there is abnormal conduction pathway in this patient's heart that bypasses AV node. What part of patient's ECG is most likely affected during normal sinus rhythm?

shortened *PR interval* Recurrent temporary arrhythmias = accessory conduction pathway (bundle of Kent) - recurrent temporary tachyarrhythmias via AV re-entry circuit - accessory pathway pre-excites ventricles = shortened PR interval = <0.12 seconds with early upslope (delta wave) at start of each QRS

Distended duodenum on an upper GI series would be suggestive of

small-bowel obstruction (as seen with gallstone ileus)

Combine to form the Achilles tendon

soleus gastrocnemius - inserts on posterior calcaneus - acts in ankle flexion

First branch of trigeminal nerve / V1 passes through

superior orbital fissure

Thymine is found where as a result of post-transcriptional modification?

tRNA

Recognize *sacrococcygeal teratoma*, which is due to defect of *primordial germ cell migration*

teratomas = derivatives of all 3 germ layers = derive from primitive streak

Patient with right-sided pure hemisensory loss has likely suffered from

thalamic stroke - thalamic ventral posterior lateral nucleus receives input form: spinothalamic tract & dorsal columns - ventral posterior medial nucleus receives input from: trigeminal pathway

Maleficence

the act of committing harm or evil - ex. when considering whether an amniocentesis is worth it since there is chance it will harm baby

Anterior mediastinal masses

thymoma teratoma thyroid cancer terrible lymphoma terrible T's!!!

Patient with history of heavy menstrual periods (menorrhagia) since menarche & frequent nosebleeds (epistaxis) as a child further suggests what disease?

von Willebrand disease = iron deficiency anemia too - easy bleeding via skin & mucosal sites

Tay-Sachs disease is an AR disorder for which the carrier frequency in ind.s of Ashkenazi Jewish descent is about 1 in 30. On the basis of this carrier frequency, what is the best estimate that a child born to two parents, both of whom are of Ashkenazi Jewish descent, will be affected by Tay-Sachs disease?

*1 in 3600* 1/30 chance mom is carrier x 1/2 chance of passing it on x 1/30 chance dad is carrier x 1/2 chance of passing it on = 1/3600

A 65-year-old man comes to the physician because of shortness on exertion for 3 years. He has smoked 2 packs of cigarettes daily for 50 years. His arterial oxygen saturation is 84% (N = 95-98%). This patient's inability to maintain adequate tissue oxygenation will most likely lead to increased production of what what in his erythrocytes?

*2,3-Bisphosphoglycerate* Conditions of low tissue oxygen concentration such as high altitude (2,3-BPG levels are higher in those acclimated to high altitudes), airway obstruction, or congestive heart failure will tend to cause RBCs to generate more 2,3-BPG in their effort to generate energy by allowing more oxygen to be released in tissues deprived of oxygen. Ultimately, this mechanism increases oxygen release from RBCs under circumstances where it is needed most. This release is potentiated by the Bohr effect in tissues with high energetic demands.

*25-year-old woman comes for counseling prior to conception. Has seizure disorder on valproic acid. Fetus at greatest risk for drug-related adverse effect during which pregnancy stage?*

*3 to 8 weeks* Teratogens: Week 1-3 - "all-or-none": the embryo either dies or survives without any complications Week 3-8 (embryonic period) - most vulnerable time period due to organogenesis Week 8-38 - growth and function of organ/embryo is affected - decreased susceptibility due to organs already formed

*A large study of serum folate levels in a sample of women age 16-45 reveals that this parameter is normally distributed with a mean of 0.5 ng/mL. According to the study results, 95% of serum folate observations in these patients will lie approximately between what limits?

*4 to 6 ng/mL* Normal (Gaussian) distribution 68/95/99 rule - 68% of observations within 1 SD of mean = *95% of observations within 2 SDs of mean* - 99.7% within 3 SDs of mean

*62-year-old with angina pectoris is referred for cardiac catheterization. Patient worried about hospital-associated infection. Studies show 30% of patients require admission after procedure, and 2 percent of admitted patients acquire hospital infection. Patient's risk for infection overall?*

*6/1000* = 0.3 x 0.02

*To decrease risk for cv disease 24 yo man begins diet. 1.53 95 kg BMI 32, Intends to lose 16 kg by limiting caloric intake to 2000 cal. to maintain the recommended protein intake (56g day); a balanced decreased in carbs and fat is required (caloric radio of fat and carbs is 30:55). which best describes number of calories that should be provided by fat in this its diet each day?*

*630* 56 g into 4 (1 g protein = 4 cal) = 1776 calories 30:85 = required ratio between fat & leftover calories (1776) = 0.36585 0.36 x 1776 = around 630 (not really but...)

*19-year-old woman is admitted to the hospital for antibiotic treatment of meningococcal meningitis. She is stabilized. Three days later, her pulse is 120/min, and blood pressure is 60/30 mm Hg. Physical examination shows bilateral flank tenderness. Serum studies show a sodium concentration of128 mEq/L, potassium of 5.4 mEq/L, and bicarbonate of 20 mEq/L. Which of the following is the most appropriate next step to determine the cause of this patient's hypotension?*

*Adrenocorticotropic hormone stimulation test* = can use metyrapone stimulation test Adrenal insufficiency - inability of adrenal glands to generate enough glucocorticoids - weakness, fatigue, orthostatic hypotension, muscle aches, weight loss

A 68-year-old man comes to the physician because of a 1-month history of light-headedness and tightness in his chest with exertion. He adds that the pain is worse after arguing with his wife, and the symptoms resolve with rest. He has a past history of lower gastrointestinal bleeding; evaluation at that time was negative on upper endoscopy and colonoscopy. His temperature is 37°C (98.6°F), pulse is 85/min, respirations are 15/min, and blood pressure is 110/75 mm Hg. Physical examination shows no abnormalities. His hemoglobin concentration is 8.2 g/dL, and hematocrit is 24%. Test of the stool for occult blood is positive. An ECG shows no abnormalities. Repeat colonoscopy shows no abnormalities. Which of the following is the most likely cause of this patient's gastrointestinal symptoms?

*Angiodysplasia* - tourtuous dilation of vessels --> hematochezia - most often found in right-sided colon & cecum via high wall tension - more common in older patients - confirmed by angiography - common cause of otherwise unexplained GI bleeding & anemia - black, tarry stool (melena)

*67-year-old man who eight months ago dx with primary lung carcinoma involving adrenal glands, liver, and bone. Had 17.6-lb weight loss during 3 months. PE shows cachexia and significant muscle wasting. Intracellular components increased in patient's muscle cells?*

*Autophagic vacuoles*

*A 25-year-old man is admitted to the hospital because of severe crush injuries to the chest and extensive burns over 30% of his body surface area. Three hours later, he develops tachypnea and dyspnea. Arterial blood gas analysis on room air shows a decreased Po2 and Pco2. A chest x-ray shows bilateral interstitial and alveolar infiltrates. The patient is intubated and mechanically ventilated. Damage to which of the following is most likely to preclude restoration of normal tissue architecture and pulmonary function in this patient?*

*Basement membranes* - overall the integrity of basement membrane would direct type 2 pneumocytes to ensure a normal restoration

*64-year-old with non-Hodgkin lymphoma and 3-day history of abdominal pain and nausea. T 99.7F, HR 100, bp 130/80. Abdominal exam tenderness of flanks and lower quadrants. BUN 34 and creatinine 3.8. CT shows bilateral hydronephrosis and lymphadenopathy compressing ureters. Tx to improve renal function?*

*Bilateral stents in the ureters* = allows urine to flow from kidney to bladder Hydronephrosis - urine unable to drain from kidney to bladder - distention/dilation of renal pelvis - via urinary tract obstruction - dilation proximal to site of pathology - serum creatinine elevated if obstruction is bilateral of if patient has only one kidney - leads to compression & possible atrophy of renal cortex & medulla

*21-year-old woman with 10-days difficulty walking. Two years ago had loss of vision in left eye which improved. Neuro exam shows decreased visual acuity in left eye with pallor of optic disc. Has past-pointing on a finger-nose test. Broad-based gait. MRI shows brain lesions in white matter of cerebellum. Pathogenesis?*

*CD4+ T lymphocytes are activated by myelin basic protein* - myelin basic protein associated in synthesis of myelin in CNS - patient has MS = autoimmune demyelinating disease

*25-year-old man just returned from work as worker from Africa begins oral chloroquine therapy for malaria caused by Plasmodium vivax. His initial therapeutic response is good, but he develops recurrent parasitemia 2 months later. Which of the following best explains the recurrence ?*

*Chloroquine is ineffective on exoerythrocytic malaria tissue stages*

Patient unable to dorsiflex or evert ankle or extend toes. Ankle inversion is intact. Sensation is decrased over dorsum of foot. Deep tendon reflexes are normal. Injury to what structure is the most likely cause of this patient's foot symptoms?

*Common peroneal nerve* - branch of sciatic nerve - originates at superior aspect of popliteal fossa - divides into deep & superficial peroneal nerves - common injuries at lateral neck of fibula = compression = prolonged lying down during surgery, crossing legs, leg casts or proximal fibular fracture *PED* = *P*eroneal *E*verts & *D*orsiflexes - if injured = foot drop*PED*

*52-year-old female with a history of breast cancer who received 4week course of radiations 6 months ago comes for followup. Exam shows no cancer recurrence. rr 26/min. CT chest shows b/l atelectasis in upper lung fields. Primary pathophysiological cause?*

*Contraction (secondary to radiation)*

68-year-old man with a 10-month history of shortness of breath and swelling of his feet, family history of cardiovascular disease. He smoked 2 packs of cigarettes daily for 50 years. Pulse 80/min, rr 24/min, BP 150/80. PE: 3+pitting edema of lower extremities. Diffuse, scattered wheezes are heard bilaterally on auscultation of the chest. Grade 2/6 pansystolic mumur heard best at lower left sternal border, which increases on inspiration. Maximal impulse palpated in sub-xiphoid area. S1 and S2 sounds are distant. Liver span 14 cm. Diagnosis?

*Cor pulmonale* - isolated right HF due to pulmonary cause - consequence of pulmonary HT - subsequent right ventricular failure (jugular venous distention, edema, hepatomegaly) - tricuspid insufficiency = pansystolic murmur at lower left sternal border

A 70-year-old woman comes to the physician for a routine pelvic examination. During speculum examination of the vagina and cervix, the Valsalva maneuver causes a bulge of the anterior vaginal wall. Which of the following is the most likely cause of this finding?

*Cystocele* = anterior vaginal wall prolapse - rectocele = posterior vaginal wall prolapse

Hereditary breast cancer most commonly associated with mutations in BRCA1 & BRCA2. These tumor suppressor genes are involved in

*DNA repair* BRCA1 & 2 - mutation increases risk of breast, ovarian, pancreatic cancer - AD inheritance - affected women have 70-80% lifetime risk for breast cancer

83-year-old with arteriosclerosis undergoes repair of infrarenal abdominal aortic aneurysm. Graft extends just below the renal arteries to the bifurcation of the aorta. Which organ will lose primary blood supply and rely on collateral circulation?

*Descending colon*

2-month-old female with T 102F, vomiting, diarrhea, dehydration. Exam of stool shows viral particles with wheel-like shape. Properties of virus? Type of nucleic acid/envelop/capsid symmetry

*Double-stranded RNA / Segmented / No / Icosahedral* Rotavirus - DS lines - 10-12 segments (BOAR) - icosahedral (double) - type of Reovirus

55-year-old woman is treated with 500 mg of drug X three times daily for cancer pain. She is pain-free, but she develops nausea, vomiting, & diarrhea, requiring cessation of drug X. Drug Y is started at 20 mg twice daily. She is pain-free, her appetite improves, & she gains weight. What best describes the maximal efficacy of these drugs?

*Drug X & Y are equally efficacious* - Y is more potent (less dose required to achieve certain effect), but they have the same efficacy (they both have the same max effect, i.e. relieve pain) Patient is pain-free with both

*35-year-old woman pain in left leg 2 days. PE shows deep venous thrombosis. Labs: platelet 200,000, PT 12 (INR 1), PTT 37. Heparin started. Five days later, platelet 120,000. Reason for decreased platelets?*

*Drug-related antibodies* Heparin-induced Thrombocytopenia as ex. = development of IgG Abs against heparin-bound platelet 4 (PF4) - Ab-PF4 complex activates platelets --> thrombosis & thrombocytopenia

8-year-old girl is brought to the physician by her mother because of a 3 week history of poor feeding chronic diarrhea and pale foul smelling stools. Mother says the symptoms began with colicky abdominal pain following introduction of solid food to the infant's diet. History of gluten sensitivity. 60th percentile for length and 25th percentile for weight. Which cell is dysfunctional?

*Enterocytes* The immune response activates CD8-positive T-cells that destroy enterocytes in the small intestine leading to malabsorption - lack of villi and increased numbers of lymphocytes in the lamina propria. - crypt hyperplasia: to replace the loss of enterocytes in celiac disease, the number of actively dividing cells in the crypts increases.

Workbench wiped down with alcohol, successfully inactivates viruses with which characteristic?

*Enveloped virion*

2-year-old boy 2-day history of fever, sore throat, rash. T 101.7 F (38.7 C). Widespread, red, sandpaper-like rash on extremities. Purulent exudate over tonsils. Dx streptococcus pyogenes (group A) infection. Cause of skin findings?

*Erythrogenic toxin*

If initial imaging studies are equivocal, what diagnostic test results would be most specific for acute cholecystitis?

*Failed gallbladder visualization on radionuclide biliary scan* Acute cholecystitis = gallstone obstruction of cystic duct --> ingestion of fatty foods stimulates contraction of gallbladder against impacted stone = colicky pain Ultrasound = preferred initial imaging test for diagnosis of acute cholecystitis --> *nuclear hepatobiliary scanning (cholescintigraphy) = alternative means when ultrasonography is inconclusive* Hepatobiliary scan - radiotracer administered IV = preferentiay taken up by hepatocytes & excreted into bile --> image of tracer moves through hepatobiliary system & intestine = obtained for up to several hours after injection

*48-year-old man 2-month increasing abdominal girth and inability to achieve erection. Smoked 1 pack cigarettes for 20 years and drug 1 pint of liquor daily. Vitals normal. PE shows scleral icterus, spider angiomata, gynecomastia, ascites and prominent umbilical venous pattern. Tests small. Cause of gynecomastia?*

*Failure of liver to degrade estrogen*

*45-year-old man bmi 26, total cholesterol 200, HDL 50, triglycerides 550. Which drug to prescribe?*

*Fenofibrate* Fibric acid analogs = Fenofibrate, Gemfibrozil - stimulate PPARalpha - alters transcription of genes involved in triglyceride metabolism, including lipoprotein lipase & apolipoprotein CIII --> increases peripheral catabolism of VLDL & chylomicrons, especially triglycerides!!! - reduces hepatic synthesis of cholesterol

*19-year-old woman 2-day history of pain in left index finger. Injured it when catching a ball. PE shows erythema of left index finger. Unable to flex the distal phalanx when proximal interphalangeal joint metacarpophalangeal joints restratined. Xray normal. Injured structure?*

*Flexor digitorum profundus tendon* - insertion = base of distal phalynx of digits 2-5 - flexes distal phalanges at distal interphalangeal joints of medial four digits - assist with flexion of hand Innervation: - medial part = ulnar nerve (C8, T1) - lateral part = anterior interosseous branch of median nerve (C8, T1)

During DNA replication in eukaryotic cells, what occurs when topoisomerase I cleaves a phosphodiesterase bond in one DNA strand?

*Free rotation of the two sections of the DNA helix on either side of the nick* - creates single- or double-stranded break in helix to add or remove supercoils

When adipocyte triglycerides are mobilized, the nonfatty acid domain of this molecule can be used by the liver for gluconeogenesis. What enzymes initiates this process?

*Glycerol kinase* Glycerol taken up by liver --> glycerol kinase = phosphorylates glycerol to glycerol-3-P --> becomes DHAP through glycerol 3P dehydrogenase... then DHAP can continue for gluconeogenesis

*25-year-old woman with fatigue for 3 wks and intermittent fever for 7 days, had teeth cleaned a month ago, no abx for prophylaxis, and had rheumatic fever as child and endocarditis 4 y ago. PE shows 2/6 murmur, ultrasound shows abnormal mitral valve. Photo of growth from blood cultures shown (GP cocci in chains). Characteristic of causal organism?*

*Greening reaction on blood agar* Viridans group streptococci - gram positive, *alpha-hemolytic* - normal flora of oropharynx - causes dental caries - causes subacute bacterial endocarditis - resistant to optochin - makes dextrans --> bind to fibrin-platelet aggregates on damaged heart valves

Alteration of what influenza virus proteins is most likely to result in altered reactivity to neutralizing antibodies?

*Hemagglutinin*

*55-year-old man northern European descent with 2-month weakness, altered skin color, bilateral knee pain. Siblings have type 2 diabetes and cirrhosis. PE bronzed skin, hepatomegaly, arthritis. Increased saturation of transferrin and ferritin. Liver biopsy increased iron content and cirrhosis Greatest risk?*

*Hepatocellular carcinoma* Risk factors = chronic hepatitis = cirrhosis (alcohol, nonalcoholic fatty liver disease, *hemochromatosis*, Wilson disease, A1AT deficiency) - Aflatoxins derived from Aspergillus (induce p53 mutations)

What would the most likely reason be for using a high dose of oral nitrate?

*High first-pass metabolism* Isosorbide dinitrate = low bioavailability due to extensive first-pass hepatic metabolism prior to release in systemic circulation - chronic nitrate therapies = long-acting oral formulations = isosorbide dinitrate or mononitrate) = used to prevent recurrent anginal episodes in patients with chronic stable angina - absobed via GI tract

27-year-old primigravid woman at 18 weeks gestation comes to physician for routine prenatal examination. The uterus consistent in size with 18 week gestation. Ultrasonography shows a male fetus. The collecting system and pelvis of the left kidney is dilated and the renal cortex appears compressed. The left and right ureters are not dilated. The right kidney appears normal. Amniotic fluid volume is normal. Which causing renal finding in this fetus ?

*Incomplete recanalization of proximal ureter* Hydronephrosis = *most common cause of unilateral fetal hydronephrosis* = inadequate canalization of uteropelvic junction = distention/dilation of renal pelvices - dilation proximal to site of pathology - serum creatinine elevated if obstruction bilateral or if patient has only one kidney - *leads to compression & possible atrophy of renal cortex & medulla*

*21-year-old man loses 15% total blood volume 2 minute after motor vehicle collision. Finding most likely?*

*Increased sympathetic nerve traffic to sinoatrial node* Hypotension & Hemorrhage .... Decreased arterial pressure --> decreased stretch --> decreased afferent baroreceptor firing --> *increased efferent sympathetic firing* --> decreased efferent parasympathetic firing - vasoconstriction - increased HR - increased contractility - increased BP

*46-year-old woman with 1-week low-grade fever and joint pain. Has chronic headaches and takes ibuprofen several times. PE diffuse maculopapular rash. UA 2+ protein, 10-20 WBC and eosinophils. Renal biopsy would show what?*

*Inflammatory infiltrates in interstitium* Tubulointerstitial nephritis - reversible - pyuria, hematuria, fever, arthralgias - maculopapular rash

32-year-old woman comes for a routine health maintenance exam. She has had intermittent constipation & flatulence. She says that there has been increasing tension with her husband, & she is uncertain about the viability of her marriage. Exam shows an ecchymosis on the right upper arm. Pelvic exam shows vaginal abrasions & is difficult to perform because of the patient' discomfort. She describes her mood as occasionally sad with no persistent depressed mood. She is moderately anxious & has a dysphoric affect. She has no suicidal or homicidal ideation or plan. What is the most appropriate next step or plan?

*Informing patient about domestic violence shelters*

Sequence-specific cleavage of proteins plays role in what processes?

*Initiation of coagulation*

48yo man with possible hypertension. based on 20 measurements, his average diastolic pressure is 94mmHg, SD is 8mmHg. If only four measurements were made rather than 20, which of the following statements would best describe the width of the 95% CI with regard the mean blood pressure?

*Larger* - decreased sample size = increased confidence interval

*Full-term newborn in respiratory distress. Imaging shows abdominal contents in left pleural cavity. Maldevelopment of which structure led to diaphragm defect?*

*Left pleuroperitoneal membrane* Diaphragmatic hernia - abdominal structures enter thorax - may occur via congenital defect of pleuroperitoneal membrane or via trauma - commonly on left side via relative protectino of right hemidiaphragm by liver - most commonly *hiatal hernia* = stomach herniates upward through esophageal hiatus of diaphragm - sliding hiatal hernia = most common = gastroesophageal junction displaced upward = hourglass stomach - paraesophageal hernia = gastroesophageal junction normal = fundus protrudes into thorax

*50-year-old man with pulmonary embolus. Treated with intravenous heparin. 24 hours later, warfarin added. Day 2, partial thromboplastin time is 52 seconds (control 26 sec), and prothrombin time is 12 seconds (control 12.1 sec; INR = 1). Best explanation for normal prothrombin time and INR?*

*Long half-life of factor II (prothrombin)*

45-year-old woman with 4-month joint pain, muscles aches and fatigue. Had a renal calculus 6 months ago and had cholecystectomy 1 year ago. Appears fatigue, depressed, there is mucosal pallor. No masses palpated in neck. Labs: erythrocyte count 3 million, K+ 4, Cl- 106, Ca2+ 13, phosphorous 2.7, alk phos 125. Technetium-99m scan shows 1.2 cm nodule in neck. Mutation?

*MEN1* / Wermer's syndrome - pituitary, parathyroid gland, pancreas - hyperparathyroidism

23-year-old woman seeks genetic counseling because her brother has Duchenne muscular dystrophy (DMD). Her brother has a deletion in the DMD gene. Although her mother does not have the deletion, the woman is told that her risk for carrying the DMD gene is greater than the general population. What best explains this increased risk?

*Maternal germline mosaicism* When the mother was an embyro, right after the segregation of germlines and somatic lines, the germline got de novo mutation in one of the clones that lead to "Germline Mosaicism"( both normal and mutant germ cells). But since her somatic lines were normal and segregated from germlines ,they are not affected. *If parents and relatives do not have disease, suspect gonadal (or germline) mosaicism In genetic testing, we normally test blood or skin cells, and since she has no somatic mutation, the test come out to be normal. Since her germline got both normal and mutant gene, she would transfer to her offsprings either gene just like if she was a carrier for that mutation. Now the son happened to inherit that mutant gene, and the risk is higher than gen. population for her daughter to inherit the mutant gene and be a carrier because mother is showing mosaicism. In other words, mother is a carrier, but since it's only limited to germline cells, she does not show any mutant gene on genetic testing.

*24-year-old man with 3-day progressive numbness of both feet ascended to thighs. Last 24 hours, numbness and tingling of hands. PE ataxic gait. Deep tendon reflexes diminished in upper extremities and absent in knees and ankles. Vibration and joint position absent in fingertips and feet bilaterally. Mild weakness distal upper extremities ad moderate weakness of lower extremities. Structure involved?*

*Myelinated primary afferents* Type Ia sensory fiber / Primary afferent fibers = sensory nerve = component of muscle fiber's muscle spindle Pacinian corpuscles - vibration, pressure Ruffini corpuscles - joint angle change, pressure

A 17-month-old boy has a history of recurrent bacterial infections. Neutrophils stimulated with osponized bacteria show decreased production of O2-, H2O2, HOCl, & OH radical. What enzymes is most likely deficient?

*NADPH oxidase* CGD - patients can utilize H2O2 generated by invading organisms & convert it to ROS = increased risk for infection by catalase + species (S aureus, Aspergillus) capable of neutralizing their own H2O2, leaving phagocytes without ROS for fighting infections

What lab tests is most useful in differentiating Strep pneumo from alpha-hemolytic streptococci?

*Optochin (P disk) susceptibility* Strep pneumo - optochin sensitive

In Sickle Cell Anemia, hemoglobin would most likely aggregate upon what?

*Oxygen unloading* HbS anemia - Hb aggregates under anoxic conditions - sickling via low oxygen levels, increased acidity, or low blood volume (dehydration) - form fibrous strands that reduce RBC membrane flexibility & promote sickling

*69-year-ole woman brought to ED 1 hour after onset of crushing, substernal chest pain & nausea. Physical exam shows pallor & diaphoresis. An ECG & an evaluation of serum cardiac enzyme activity confirm diagnosis of a MI of the anterior wall. Activation of platelets & segmented neutrophils during thrombogenesis in this patient caused release of cytokines, including platelet-derived growth factor. The mitogenic signal provided by this cytokine to SM cells at sites of vascular injury in this patient is most likely to be inhibited by what intracellular enzymes?

*Phosphatase* Cytokines work through a Receptor Associated Kinase JAK/STAT pathway. Since they have to use a kinase to have their effect, the opposite would be a phosphatase that cleaves the phosphate and inactivates them.

After operation, 65-year-old patient has lung region that is underventilated but well perfused. Which increases?

*Physiologic shunt* = in disease states = portion of cardiac output goes through regular pulmonary vasculature but does not come into contact with alveolar air due to filling of alveolar spaces with fluid (pneumonia, drowning, pulmonary edema) - important diagnostic feature = arterial PO2 does not rise to normal level when patient is given 100% oxygen to breathe

*Investigator studying vancomycin-resistant strain of Enterococcus faecalis. Ten generations created. Culture inoculated and resulting bacterial colonies are screened for vancomycin resistance. Vancomycin-sensitive colonies observed at frequency of one per 100 cells. Mechanism of decreased vancomycin resistance?*

*Plasmid loss*

3-year-old boy with progressive fever and skin lesions during 24 hours. T 102.9 F, pulse 120, RR 20, bp 110/60. PE shows large, flaccid, bullous lesions over trunk and abdomen. Another finding in pt?

*Positive nares culture for toxin-producing Staphylococcus aureus*

*45 yr old man with SOB on exertion x 6 months, nosebleeds since adolescence, 2 pics: clubbing + hemorrhagic lesions in tongue, inhaled albuterol doesn't improve his symptoms. Cause of symptoms?*

*Pulmonary AV shunting* Pulmonary AV Fistula - dyspnea, cyanosis (via right-left shunt) - paradoxical emboli - high output congestive cardiac failure Osler-Weber-Rendu Syndrome / Hereditary Haemorrhagic Telangiectasis (HHT) - AD - multi-organ vascular dysplasia - multiple AVMs that lack intervening capillary network - telangiectasias = most common - recurrent epistaxis - telangiectasias of skin, oral cavity, conjunctivae - cerebral AVMs --> cerebral hemorrhage

*58-year-old woman with 6-month shortness of breath and chronic nonproductive cough. 2-year history difficulty swallowing, joint stiffness, diffuse tightening of skin on face, neck, shoulders, arms, fingers. Sensitivity to cold weather, turn white. Hx of esophageal reflux. Biopsy showed atrophy of epidermis and deposition of collagen throughout dermis with loss of dermal appendages. PE cutaneous ulceration, clawlike flexion deformity, decreased joint mobility. At risk for which pulmonary disorder?*

*Pulmonary hypertension* Systemic sclerosis / CREST - via damage to pulmonary arterioles - 2nd heart sound - signs of right-sided heart failure via cor pulmonale

*A study is conducted to compare the incidence of myocardial infarction in patients undergoing two different types of angioplasty or an operative procedure to manage single-vessel coronary artery disease. A total of 1000 patients are enrolled. Through a chance process, 500 are assigned to undergo the operative procedure, 250 are assigned to undergo one type of angioplasty, and 250 are assigned to undergo a second type of angioplasty. All patients are followed for 3 years to determine the incidence of myocardial infarction. Which of the following best describes this study design?*

*Randomized clinical trial* - ppl allocated ar random to receive one of several clinical interventions - one of these interventions = standard of comparison or control

*12-year-old boy with mother concerned about enlarged left breast and family history of breast cancer. Left breast is slightly larger than right, nipple mildly tender. Penis slightly enlarged and pubic hair curling and beginning to darken at base. Best next step?*

*Reassure the mother that physical findings are not uncommon for his age*

Markers of early response to oral treatment in children with severe iron-deficiency anemia

*Reticulocyte count* - immature RBCs - reflects erythroid proliferation

*A transcription factor that activates expression of HMG coA reductase is identified, this TF is initially synthetized as a large precursor protein, with 2 membrane spanning domains. The transcriptional domain is released by proteolysis when the membrane has a decreased cholesterol concentration. The precursor protein is most likely initially produced in which of the following labeled area on this labeled diagram of a hepatocyte?*

*Rough endoplasmic reticulum* - site of synthesis of secretory (exported) proteins & of N-llinked oligosaccharide addition to many proteins - free ribosomes = synthesis of cytosolic & organellar proteins

*35-year-old woman with infertile, receive injection of contrast material into cervix. On hysterosalpingogram, contrast material also seen in peritoneal cavity, which explain this finding?*

*Spillage of contrast which is normal*

In a study of 100 subjects with colonic polyposis, 20 develop colonic malignancies over a 10-year follow-up period. To estimate the relative risk of colonic polyposis for the dev't of colon cancer, what control groups would be best?

*Subjects with no evidence of colonic polyposis* This is a prospective cohort study, so the BEST CONTROL group would be the one with no exposer i. e. one with NO EXPOSURE of colonic polyposis. SO IT WILL BE LIKE THIS... RR of Colonic Cancer for Cohort study where the RISK fastor is colonic polyposis ( 2 groups -- one with exposure and the other without exposure) one group -- 100 with colonic polyposis other group -- subjects without colonic polyposis.

An investigator conducts a meta-analysis of three genome-wide association studies of Crohn Disease. The studies encompassed 3200 cases and 4800 controls, all of European descent. The initial studies identified 11 significant loci with odds ratios above 1.3 and 1.5; the combined meta-analysis identified an additional 21 loci with odd ratio of 1.1 to 1.3. It is estimated that the 32 loci identified explain about 10% of the variance in disease risk with 2 loci accounting for 2% of the variance. Previous studies of twins indicated a 50% heretability rate for Crohn's disease. Which of the following best explains these results?

*The identified loci account for a relatively small part of the variance*

*20-year-old woman with 2-week fever, shaking chills, headaches, fatigue, and joint and muscle pain. Spent summer workin as lifeguard in Long Island, New York. Has splenectomy for motor vehicle collision 6 years ago. T 102.4 F. Peripheral blood smear shows small intraerythrocytic rings. Polymerase chain reaction for Plasmodium is negative. Causal organism from bite of?*

*Tick* Babesia - fever & hemolytic anemia - northeastern US - Ixodes tick - blood smear - treatment = atovaqoune + azithromycin

4-year-old male with recurrent UTIs, left kidney found small and non functional; right is normal. Nephrectomy is done, and the picture shown (dilated ureter and renal calyx). Microscopic exam of kidney will show which?

*Tubular atrophy* Pediatric Ureteropelvic Junction Obstruction (PUJO)? - hydronephrosis & eventual atrophy

32-year-old man with X-linked recessive disease has deafness, hematuria and progressive renal failure. Protein abnormality?

*Type IV collagen* Alport syndrome "can't see, can't pee, can't hear a bee" - basket weave appearance on EM

17-year-old boy in septic shock unresponsive to ADH (vasopressin). Treat is discontinued, and high-dose dopamine in started. Which receptors are stimulated?

*alpha1-adrenoreceptors* Dopamine: D1 = D2 > beta > alpha Applications - unstable bradycardia, HF, shock - inotropic & chronotropic effects at lower doses due to beta effects - *vasoconstriction at high doses due to alpha effects*

Treatment for chloroquine-resistant malaria

*mefloquine* - other useful antimalarials = atovaquone-proguanil & artemisins - small rings = trophozoites

35-year-old woman with fever and sharp chest pain for 3 days. T 101.3F. Friction rub heard. All causes of secondary pericarditis ruled out. Cause of primary pericarditis?

*virus*

Girl has chronic cough with thick sputum, abdominal cramps in RLQ, and frequent resp infections. Clubbing of fingers, hyperresonance on chest percussion. Diffuse crackles and scattered wheezes. On xray - diffuse hyperinflation of the right upper lobe. She has a healthy brother. What's the likelihood he is a carrier for the condition?

2/3 Cystic Fibrosis = 2/3

Retrospective study of incidence and outcome of subarachnoid hemorrhage. Incidence is 15 per 100,000 people, mortality is 6 per 100,000 people. Incidence remains constant, case fatality rate?

40% = 0.00006 / 0.00015

During bacteriophage T7 infection of a single E coli cell, 1000 bacteriophages are released. One of these particles contains a fragment of the E. coli chromosome rather than the T7 chromosome. Will this phage be able to inject its DNA into an E coli cell, and if so, how many T7 particles will be produced by this cell? Able to inject DNA = ? # of T7 particles produced = ?

Able to inject DNA? = Yes # of T7 particles produced = 0 First one is "Virulent Phage"-----> Lysed and Multiplied - Bacteriophage T7 belongs to T series of bacteriophages - parts of bacterial chromosomal DNA may become packaged in phage capsid (but no T7 particles produced after injecting DNA) Second one is "Tranducin Phage"----->Just inject the DNA of first E.Coli that proceed with Homologus Recombination.Does not lyse or multiply

What molecules must interact to induce cell activation by the superantigen toxic shock syndrome toxin-1? Molecule 1 = Molecule 2 =

Molecule 1 = Class II MHC Molecule 2 = T-cell receptor S aureus: Toxic shock syndrome - Binds MHC II & TCR outside of antigen binding site to cause overwhelming release of IL-1, IL-2, IFN-gamma, & TNF-alpha --> shock

Antiparasitic drug used to treat Chagas disease (American trypanosomiasis) caused by T cruzi

Nifurtimox

Damage of this nerve results in difficulty with foot plantar flexion (via involv't of gastrocnemius & soleus) & decreased sensation over sole.

Tibial nerve

Study designed to test the effectiveness of a new drug in the treatment of endometriosis, 100 women randomly assigned to one of two groups. 48 of women receive new drug, 52 receive standard therapy. The primary purpose of this method of assigning patients to different groups is to create which of the following?

Two groups with similar underlying characteristics

Origin/gives rise to thyroid follicular cells & epitheial linings of GI tract, middle ear, lung, bladder, & most of urethr

endoderm also: - liver, pancreas, lungs (form from outpouchings of primitive gut tube)