USMLE 3

During what phase of the ventricular action potential does NE influence influx of Ca2+?

*2* Phase 2 = plateau - Ca2+ influx through VG Ca2+ chanels balances K+ efflux - Ca2+ influx triggers Ca2+ release from SR & myocyte contraction

Reduction means

subtract control rate = always use absolute value sign Tx rate - control rate / control rate aways divide last

Influenced by disease prevalence

Positive & negative predictive values

Characterized by recurrent episodes of early ejaculation accompanied by sense of lack of control.

Premature ejaculation - ejaculation within one minute of penetration, most of the time for at least 6 months - treatment = SSRISs

Circadian rhythm maintained by what nucleus in the hypothalamus?

supra*chiasmatic* nucleus (SCN)

If there is a reason to suspect abuse or neglect of an elderly patient...

the elderly patient should be interviewed alone - avoid intimidation by possible abusers

Postexposure prophylaxis for Rabies

wound cleaning + immunization with killed/*inactivated* vaccine & rabies immunoglobulin

A 61-year-old man has a 3-month history of dull, aching pain on the left side of his chest. What is the most appropriate next step in evaluation of this patient?

*Ask him for additional detail about his chest pain*

NSAID that *irreversibly* inhibits *COX-1 & COX-2* via acetylation

*Aspirin* (acetylsalicylic acid) - other NSAIDs (diclofenac, ibuprofen, indomethacin) *reversibly* inhibits COX-1 & COX-2

A 3-week-old infant has milk intolerance due to defect in enzymes that digest lactose. This enzyme is located at what sites in enterocytes?

*At apical surfaces* Lactase deficiency - lactase functions on brush border to digest lactose (in human & cow milk) into glucose & galactose

The vertebral angiogram show is from a 40-year-old man. The abnormality is marked "X." What clinical findings is most likely present? (labeled artery is the superior cerebellar artery).

*Ataxic limb movement*

A 54-year-old man is hospitalized after a planned abdominal surgery. One of his physicians administers a new drug whose mechanism of action you don't know. Shortly after administration of the drug the patient develops flushing, diaphoresis & nausea. His BP is 100/70 mmHg & heart rate is 55/min. His pupils are constricted but reactive to light. This medication is most likely given for what conditions?

*Atonic bladder* Cholinergic agonists - increased GI tract SM to produce nausea, vomiting, abdominal cramps, diarrhea - decreased heart rate, cardiac conduction & contractility - bradycardia, hypotension - increase secretion, excessive sweating, salivation & lacrimation Bethanechol - stimulates peristalsis in postoperative ileus treats non-obstructive urinary retention (atonic bladder)

A couple seeks genetic counseling following the recent diagnosis of cystic fibrosis in their youngest child. Their two older children are healthy and have normal sweat chloride test results. What is the likelihood that each of the unaffected children is a carrier of cystic fibrosis

2/3

2nd pharyngeal arch is associated with

2nd aortic arch facial nerve Gives rise to muscles of facial expression some ear & hyoid-associated structures

Describe movement of Na+ & K+ during one cycle of Na+-K+ pump (ATPase) in neurons.

3 Na out 2 K in

Metabolism of protein or carbs

4 calories (Cal) per gram or protein or carb

AA derivative of Nitric oxide

Arginine

Opens into the duodenum via minor papilla & is responsible for draining majority of pancreas

Dominant dorsal duct (of Santorini)

Provide motor innervation to the rhomboids (retract scapula) & levator scapulae muscles (elevate scapula)

Dorsal scapular nerve

Factor that prolongs disease duration and therefore, increases disease prevalence.

Improved quality of care. - ex. affected patients with diabetes survive longer

Most common mutation in patients with CF

Phe508 - *hyponatremia* via excessive salt wasting

Potential side effect of bupropion therapy, especially when med is given at higher doses

Seizures

Typically presents with fever, abdominal pain, uterine tenderness, &/or foul-smelling discharge after pregnancy termination. Common offending pathogens include *Staphylococcus aureus* & Escherichia coli via seeding of uterine cavity during instrumentation.

Septic abortion

Non-absorbable phosphate-binding polymer that decreases absorption of phosphate in GI tract.

Sevelamer - used to treat hyperphosphatemia in dialysis patients

Gram-negative, nonlactose-fermenting, *nonmotile*, rod-shaped bacterium

Shigella - hemorrhagic diarrheal disease

Medial medullary syndrome is an ischemic stroke syndrome caused by occlusion of the

anterior spinal artery - contralateral hemiparesis via damage to lateral corticospinal tract - contralateral hemisensory loss via dorsal column medial lemniscal pathway - ipsilateral tongue paralysis via hypoglossal nucleus

Highly specific for SLE

anti-*dsDNA*

Reinfection with HAV would be associated with presence of

anti-HAV IgM antibodies

In follicular lymphoma, there is overexpression of

antiapoptotic BCL2 - t(14;18) translocation

Nitric oxide is synthesized from

arginine & oxygen - by endothelial cells - causes vascular smooth muscle by relaxation by guanylate cyclase-mediated cGMP second messenger system

Claudication (intermittent muscle pain reproducibly caused by exercise & relieved by brief period of rest) almost always caused by

atherosclerosis of larger arteries

Features of eczematous dermatitis after chronic topical administration

atrophy/thinning of dermis - loss of dermal collagen, drying, cracking, &/or tightening of skin, telangiectasias, ecchymoses = *dermal atrophy*

Response to the loss of a loved one

bereavement - may *resemble* a major depressive episode

Constitutive expression of structural genes of lac operon occurs with mutations that impair

binding of repressor protein (Lac I) to its regulatory sequence in *operator* region

Located on *chromosome 8*. Associated with Burkitt lymphoma & diffuse large B cell lymphoma.

c-MYC

Mutation associated with Burkitt's lymphoma

c-Myc oncogene overexpression = t(8;14)

Recognize RBC casts & associations

can be way redder & thicker than this = *postinfectious glomerulonephritis*, glomerulonephritis, malignant HT (210/120)

ACE Inhibitors act on what part of the nephron

efferent arteriole (dilation) --> increased serum creatinine - reduce angiotensin II levels

A imbalance of estrogen & progesterone places patient with PCOS at long-term risk for

endometrial hyperplasia & adenocarcinoma

Asymptomatic patient with history of inborn error of sugar metabolism most likely has

essential fructosuria - benign, AR - defective *fructokinase* - fructose = reducing sugar = can be detected by copper reduction test - negative glucose oxidase test

Major muscles used when sitting up from supine position include

external abdominal oblique rectus abdominis hip flexors - *psoas major* - iliacus

Anemia in lead poisoning results from inhibition of what enzymes?

ferrochelatase *delta-aminolevulinic acid (ALA) dehydratase*

The first pharyngeal arch is associated with

first aortic arch trigeminal nerve

First sign of uncal herniation is a

fixed and dilated pupil on side of lesion - ipsilateral paralysis of oculomotor muscles & contralateral homonymous hemianopsia with macular sparing

Fourth pharyngeal arch associated with

fourth aortic arch superior laryngeal branch of vagus nerve many of the muscles of the pharynx & soft palate few laryngeal muscles

Coenzyme for number of important dehydrogenase enzymes, including transketolase, alpha-ketoglutarate dehydrogenase, & pyruvate dehyrogenase

Thiamine (vitamin B1)

Used in Acute Intermittent Porphyria (AIP) management

glucose & hemin - inhibit ALA synthase AIP - via accumulation of ALA & PBG - via inherited PBG deaminase deficiency combined with ALA synthase induction (meds, alcohol, low-calorie diet)

DNase is produced by what streptococcus?

group A streptococcus - degrades DNA in pus to facilitate spread of organism

Causes defects in platelet adhesion & coagulation (due to associated factor VIII deficiency). PTT may be abnormal or prolonged based on level of factor VIII deficiency, & platelet aggregation to ristocetin will be abnormal.

Von Willebrand disease

Haptoglobin *decreases* in any form of

hemolytic anemia

Most common adverse effect of fibrinolytic therapy

hemorrhage - signs of ICH = decreased consciousness, asymmetric pupils, irregular breathing

Branches off the inferior mesenteric artery to supply the transverse & descending colon

left colic artery

Of all the major vascular beds, what arteries are most susceptible to atherosclerosis?

lower abdominal aorta *coronary arteries*

Patients with familial chylomicronemia syndrome present in childhood with

marked triglyceridemia, recurrent *acute pancreatitis*, lipemia retinalis (milky-appearing retinal vasculature), eruptive xanhomas - AR - lipoprotein lipase (LPL) deficiency

BM splitting is seen on light microscopy using silver or periodic acid-Schiff stains in

membranoproliferative glomerulonephritis (MPGN)

Venous components of internal hemorrhoids drains into

middle & superior rectal veins --> communicate with internal iliac & *inferior mesenteric veins*

How to calculate *conditional probability*

multiple "patients surviving this interval" after the year they already survive

In neuroblastoma, there is overexpression of

n-Myc

Described pseudomonas aeruginosa

nonlactose-fermenting *oxidase-positive* *motile* gram-negative rod - malignant otitis externa (MOE) = in eldery diabetic patients = granulation tissue in ear canal

Where should thoracentesis be performed?

above: 8th rib in midclavicular line 10th rib along midaxillary line 12th rib along posterior scapular or paravertebral line - needle inserted lower = increased risk of penetrating abdominal structures

Rate-limiting enzyme that catalyzes first step in FA synthesis

acetyl-CoA carboxylase

Defects in porphobilinogen result in

acute intermittent prophyria (AIP) - acute attacks of abdominal pain - neuropsychiatric symptoms - red or brown urine

Patient with ST elevations in leads I & aVL most likely has an

acute lateral MI due to occlusion of *left circumflex artery*

Odds ratio

ad/bc

Limbs of gag reflex

afferent = CN IX efferent = CN X

What leads to the closure of the PDA?

after delivery... - separation of infant from placenta - rapid drop in pulmonary vascular resistance

Abnormalities of genes responsible for DNA mismatch repair found in patients with

nonpolyposis colorectal cancer & colorectal cancer (HNPCC, or Lynch Syndrome) - greater incidence of colorectal cancer, endometrial, & ovarian cancer

Clinical manifestations of Primary Ciliary Dyskinesia

situs inversus, chronic sinusitis, *bronchiectasis*, infertility = AR - dynein, assembly protein affected = AKA: Kartagener syndrome

A 50-year-old man with anginal pain takes nitroglycerin. The pain is rapidly relieved because of

stimulation of cyclic GMP formation

Safe location for intragluteal injections

superolateral gluteal region, although the anterolateral gluteal region is preferred

Leydig cells, which are analogous to female theca cells, produce

testosterone - in response to LH

Third pharyngeal arch is associated with

third aortic arch glossopharyngeal nerve part of hyoid bone stylopharyngeus muscle

2 groups. 1 group starts out getting intervention. Other group does not get intervention. Switch halfway through experiment

Crossover Design - everyone acts as their own control - have a *washout period*

Recognize *Disopyramide* action potential

Double Quarter Pounder - intermediate inhibition of phase 0 depolarization - prolonged effect on length of action potential Class I - block sodium channels

Phenomenon in which allele of one gene affects phenotypic expression of alleles in another gene

Epistasis

Caused by DNA methylation, an epigenetic process in which genes can be silenced by attaching methyk groups to cytosine residues in the DNA 'cule.

Genomic *imprinting* - offspring's genes expressed in parent-specific manner

Key NTs involved in pathophysiology of ADHD

NE & DA - stimulant drugs (methylphenidate & amphetamineds) = first-line drug treatments for school-aged children with ADHD

Test's ability to identify presence of disease

Sensitivity

Accelerated coronary artery disease, *tendon xanthomas* (nodular lipid deposits in tendons), & *xanthelasmas* are seen in

familial hypercholesterolemia - defects in LDL receptor or its ligand, ApoB-100

Main adverse effects seen with nitrate therapy include

headaches & cutaneous flushing along with lightheadedness & hypotension due to systemic vasodilation

Right-angle branchin hyphae are characteristic of

mucormycosis = mold infection via Mucorales or Rhizopus species

Usually, who is the next of kin?

patient's spouse - children may sometimes have joint next-of-kin status depending on state laws

Slows progression of hemochromatosis in women

physiological iron loss through *menstruation* & pregnancy

Causes of *Right* shift in oxygen-Hb dissociation curve

*ACE BAT*s *right* handed *A*cid *C*O2 *E*xercise 2,3-*B*PG *A*ltitude *T*emperature Anemia - can cause lactic acidosis Hypoventilation - increased CO2 retention

Bladder functioning of patients with multiple sclerosis

*Bladder hypertonia* via urodynamic studies - develop spastic bladder few weeks after developing acute lesion of spinal cord - increased urinary frequency & urge incontinence

Mitochondrial enzyme that activates caspases & indirectly brings about cell death through intrinsic pathway apoptosis

*Cytochrome c*

Microtubular motor protein that participates in retrograde axonal transport (moving organelles toward nucleus). Establishes latent phase following primary HSV infection.

*Dynein*

What protein is most likely involved in the transport process leading to disease recurrence of Herpes?

*Kinesin* = *Anterograde* transport of virus = motor protein that moves intracellular cargo (organelles, viral particles) away from nucleus, down axon, & toward nerve terminal - powered by ATP hydrolysis - guided by microtubule filaments

Coinfection of a host cell by 2 viral strains, resulting in progeny virions that contain nucleocapsid proteins from one strain & the unchanged parental genome of the other strain.

*Phenotypic mixing* - no change in underlying viral genomes (no genetic exchange) = next generation of virions revert to their original, unmixed phenotypes

Neutralizes reactive oxygen species, preventing cell injury.

*superoxide dismutase*, glutathione peroxidase, catalase - antioxidants

Thymus and inferior parathyroid glands arise from

3rd pharyngeal pouch

Incidence rate

= # of new cases / # of people at risk - people with disease not calculated into equation

Right ventricular diastolic pressure

= similar to right atrial/central venous pressure = 1-6 mmHg

ARR =

AR (attributable risk) Tx rate - control rate

Drugs that affect phase 4 of the action potential, reducing the rate of spontaneous depolarization in cardiac pacemaker cells

Adenosine - interacts with A1 receptors on seruface of cardiac cells --> increases potassium conductance

Typically used to treat Listeria

Ampicillin

Most common cause of Candida vaginitis

Antibiotic use via *reduction of lactobacilli population* --> facilitates Candida overgrowth

Most prominent organisms isolated from intraabdominal infections

B. fragilis, E. coli - polymicrobial

Selection bias created by choosing hospitalized patients as control group.

Berkson's bias

Correspond to lateral limb leads on ECG

Leads *I & aVL*

Main toxin of C perfringens / gas gangrene

Lecithinase --> *Phospholipid splitting* - concentration correlates with its lethal & necrotic effects - has at least 12 toxins, of which phospholipase C is the most injurious

A 78-year-old man with syncope feels heaviness in his chest with exertion and breathlessness when lying down. A crescendo/decrescendo systolic murmur is heard best at the second right intercostal space with radiation to the carotid arteries. What measurements of left ventricular & aortic pressure is most likely to be found on cardiac catheterization? Left Ventricular = Aortic =

Left Ventricular = 150/80 Aortic = 100/50 Aortic stenosis - *LV >> aortic pressure during systole* - loudest at heart base --> radiates to carotids

Major site of erythropoietin production in fetus

Liver

Presents as palpable breast masses with orderly rows of cells organized in single file

Lobular breast tissue

More medial of the 2 bones that articulate with radius

Lunate - scaphoid = other (more lateral) bone

Mutations that cause hereditary nonpolyposis colorectal cancer (Lynch syndrome)

MLH1 & MSH2

Innervates tensor tympani in middle ear

Mandibular nerve of Trigeminal nerve - patients with Temperomandibular disorder (TMD) involving mandibular nerve = both jaw pain & otologic symptoms

One of the most modifiable risk factors for falls

Medication use - psychotropic drugs, including antipsychotics, antidepressants, benzos - CCBs, NSAIDs

Portion of broad ligament that connects fallopian tubes to pelvic sidewall.

Mesosalpinx - broad ligament = wide sheet of peritoneal tissue that encapsulates reproductive organs anteriorly & posteriorly

Associated with opening snap of mitral valve & a low pitch rumbling murmur throughout diastole.

Mitral stenosis

Medial band-like calcifications occur in

Monckeberg's medial calcific sclerosis / medial calcinosis - calcified deposits in muscular arteries - individuals above age 50

What is naproxen?

*NSAID* = *gastric ulcers!!!*

Aldosterone receptor antagonists (*spironolactone*, eplerenone) inhibit effects of aldosterone & reduce...

*secretion of K+ & H+ by collecting tubule*

inhaled-anesthetic hepatotoxicity lab values

- elevated serum aminotransferase levels - *prolonged prothrombin time* - leukocytosis - eosinophilia - fulminant hepatitis - nausea, fatigue, anorexia - history of a recent injury, like emergency cholecytectomy - icteric

Competitive antagonists change

ED50 - shift right

E. coli strains that cause neonatal meningitis synthesize

K-1 capsular antigens

Characterized by episodic, transient attacks of coronary vasospasms (at rest and at night), producing temporary transmural myocardial ischemia with ST-segment elevation.

Prinzmetal (Variant) Angina - possible triggers = cigarette smoking, cocaine/amphetamines, dihydroergotamine/triptans - treatment = tobacco/drug cessation & vasodilator therapy (nitrates, CCBs)

What does Haemophilus require to support growth?

X factor (hematin) & V factor (*NAD+) - growth on sheep agar can be achieved by cross-streaking medium with Staph aureus --> H influenza will grow around streaks of beta-hemolytic S aureus colonies because S aureus actively secrete V factor (NAD+) into medium & facilitate release of additional X factor (hematin) from beta-hemolysis-induced erythrocyte lysis = satellite phenomenon

Thin filaments, which are composed of actin, tropomyosin, & troponin, anchor at the

Z line

Useful both as treatment for HT & as medical treatment for BPH

alpha1 selective blockers - doxazosin, prazosin, terazosin

LAD primarily supplies anterior aspect of left ventricle & interventricular septum, which corresponds to

anterior chest leads (V1-V4) - proximal occlusion involves these leads - distal LAD spares septal leads (V1-V2)

Where does Isotype switching occurs?

germinal centers late in primary response

On auscultation, the best indicator of mitral stenosis severity is

length of time between S2 (A2 component, caused by aortical valve closure) & opening snap (OS) - OS via abrupt tensing of valve leaflets as mitral valve reaches its max diameter during forceful opening - current standard of diagnosis = mean transvalvular pressure gradients via 2-D Doppler echocardiography

First-line meds for bipolar maintenenace treatment

lithium anticonvulsant valproate second-gen antipsychotic quetiapine

The largest collection of neurons in the CNS that use NE as NT is found in

locus ceruleus

Na+/K+/2Cl- cotransporter in the thick ascending limb is the target of

loop diuretics (furosemide, ethacrynic acid)

A 35-year-old woman comes to the physician for an initial visit. She refuses to fill out a questionnaire form about personal data & her medical history, then sits silently in the waiting room with her fists clenched. When the physician greets her in the exam room, she says, "Let's get this over with." What questions is most likely to facilitate communication with the patient?

"I can see that you are upset. Please tell me what is bother you."

On exam, supraspinatus can be isolated with what test?

"empty-can" supraspinatus test - abduction of humerus in parallel to axis of scapula (30 degrees forward flexion) while in full internal rotation (thumbs pointed to floor) Supraspinatus musle = abduction of arm (initial 15 degrees) + stabilization of glenohumeral joint - tendon is vulnerable to injury via impingement between acromion & head of humerus - supraspinatus tendinopathy = most common cause of rotator cuff syndrome

Blood oxygen content

(oxygen-binding capacity x percentage saturation) + dissolved oxygen

A 45-year-old woman with rheumatoid arthritis calls the physician on a Saturday morning because she cannot turn the bathroom faucet due to pain and weakness in her hands & wrists. She is tearful & says, "My husband has already left for work and my hands are too weak to turn the water on. It hurts too much and now I can't even take a bath." What is the most appropriate response?

*"People with rheumatoid arthritis often feel that their independence has been lost because of their pain. Perhaps using a tool with a long handle would help."

RBF = 1 GFR = 0.1 Assuming a hematocrit of 0.50, what is the best estimate of the filtration fraction when the mean arterial pressure is 120 mmHg?

*0.2* - 20% = normal FF Filtration Fraction (FF) = GFR / *RPF* - RPF = RBF x (1 - Hematocrit) = 1 x (1 - 0.5) = 0.5 L/min Filtration Fraction = (0.1 L/min) / (0.5) = 0.2

A 22-year-old woman is participating in a study that measures renal function. Evaluation of serum and urine shows the following: Na+ (mEq/L) - serum = 140 - urine = 100 K+ (mEq/L) - serum = 4 - urine = 50 Glucose (mg/dL) - serum = 100 - urine = Creatinine (mg/dL) - serum = 1 - urine = 100 p-Aminohippuric acid (mg/mL) - serum = 0.1 - urine = 50 Assuming a urine flow of 1 mL/min, what best represents her filtration fraction?

*0.20* FF = GFR/RPF GFR = C Creatinine = (100 x 1) / 1 = 100 RPF = C PAH = (50 x 1) / 0.1 = 500 FF = 100/500 = 0.2 Normal FF = 20% anyways...

0-1 years - patients at beginning = 300 - patients who died = 115 - percent of patient surviving = 62 1-2 years - patients at beginning = 185 - patients who died = 37 - percent of patient surviving = 80 2-3 years - patients at beginning = 148 - patients who died = 24 - percent of patient surviving = 84 3-4 years - patients at beginning = 124 - patients who died = 18 - percent of patient surviving = 85 4-5 years - patients at beginning = 106 - patients who died = 25 - percent of patient surviving = 76 If a patient survives 2 years after the operation, what is the probability of surviving at least 4 years?

*0.84 x 0.85* survived 2 years --> multiply probability of surviving next 2 years = 2--> 3 & 3 --> 4

A healthy 31-year-old woman comes to the office because she and her husband desire a second child. The husband is infertile and the patient's son, who was conceived via donor insemination, was recently diagnosed with glycogen storage disease type II (Pompe disease). This rare AR disease is known to affect 1 in 40,000 of the general population. Genetic testing confirms that the patient is a carrier for the disease. What is the probability of the patient having a second affected child with a different sperm donor?

*1/400* P(affected child given carrier parents) x P(carrier mother) x P(carrier father) = *1/4 (child of 2 carriers of recessive condition has 1/4 chance of being affected) x 1 (patient must be carrier given her first son has Pompe) x (1/200 x 2q = 1/100) = 1/400* - q = 1/square root of 40,000 = 1/200 P(carrier father) = 2q = 2 x 1/200 = 1/100 - in general, carrier frequency = 2pq - for rare AR disorders, p = 1 - probability of being carrier = 2x frequency of mutant allele = 2q

Two experimental drugs, drug & drug Y, are being evaluated for treatment of CHF. Patients receiving drug X have a cardiac index of 2.5 L/m^2 with a 95% confidence interval of 1.5 to 3.5. Patients receiving drug Y have a cardiac index of 1.7 L/m^2 with a 95% confidence interval of 0.7 to 2.7. A test of the significance of difference shows a p-value of 0.1. What is the likelihood that the difference in mean cardiac index of patients receiving drug X & drug Y is due to chance?

*10%* Standard p value = 0.1 --> if you accept there is a difference - that difference is due to *chance* alone --> p value = 0.1 = 10% --> difference between the 2 drugs cardiac indexes can be by chance alone in 10% of cases 0.1 > 0.05 = no difference between the 2 drugs Question asks about likelihood of difference between 2 drugs = stating that there is a difference when none exists = type I error = chance of type I error is given by p value = 10%

In a clinical study, 100 subjects are examined for a particular genetic alteration hypothesized to be related to prostate cancer. The results are shown in the table: AA = 30 AB = 25 BB = 45 If A is one allele, & B is the other, what is the frequency of the B allele?

*115/200* B + B = 90 1 B of AB = 25 90 + 25 = 115/200 200 = 2 copies of 100 chromosomes of 100 people AR disease --> BB = homozygous recessive --> clinically appears in population --> AB = heterozygous = carrier

Under control conditions, flow through a blood vessel is 100 mL/min under a pressure gradient of 100 mmHg. The diameter of the vessel is increased twofold & the pressure gradient is maintained at 100 mmHg. What is the current flow?

*1600* Q (flow) = Pressure / R Resistance = inversely proportional to 4th of radius --> increase diameter by 2 fold = increase flow by 1600 Resistance = P / Q = 8n (viscosity) x length / pier^4 --> Q = P/R

A healthy 22-year-old man who weighs 70 kg (154.3 lb) volunteers for a phase I clinical trial investigating the properties of a newly developed antimicrobial agent. The drug is found to have a volume of distribution of 10 L & exhibits first-order elimination kinetics. The rate of drug clearance is calculated to be 7 L/hr. It is determined that repeating the second dose when 75% of the drug is eliminated will minimize toxicity while maintaining trough levels above the minimum inhibitory concentration. Based on these research findings, what is the most appropriate dosing interval for this drug?

*2 hours* t1/2 = (0.7 x Vd)/CL = (0.7 x 10L) / 7 L/hr = 1 hour Takes 2 half-life intervals to eliminate 75% of drug --> takes 2 hours to excrete 75% of drug 0 --> 0 1 --> 50% 2 --> 75% 3 --> 87.5%

During the first meiotic division of human oogenesis, nondisjunction occurs between a pair of homologous chromosomes. If fertilization occurs, what is the possible number of chromosomes contributed by the female pronucleus?

*22 or 24* - normal = 23 sister chromatids in secondary oocyte (1N, 2C) = 1+ & 1- to normal

A 46-year-old man is referred to a dietician for evaluation of his food intake. He has been trying to lose weight but has been unsuccessful. The patient is 172.7 cm (5 ft 8 in) tall & weighs 113 kg (250 lb). Analysis of his food intake shows that he is consuming 3600 Calories a day. The dietitian recommends increasing physical activity & implementing a dietary plan. In the first phase, the patient is advised to reduce his daily dietary intake to 3,000 Calories, with 30% coming from protein. How much protein per day will this patient consume on the new dietary plan?

*225 g* 3,000 x 0.30 --> 900 / 4 = 225 g/day of protein

A 50-year-old man who has had a MI was subsequently diagnosed as having familial hypercholesterolemia, an AD disorder. His son has not been tested for hypercholesterolemia. What is the probability that the patien't granddaughter, through his son, will have hypercholesterolemia?

*25%* - assume he's Hh, because if he was HH, he would've been dead a long time ago - 50% chance the father passed H to his son; 50% chance the son passed H to his daughter 50% x 50% = 25%

Mean glomerular capillary hydrostatic pressure = 45 mmHg Mean Bowman space hydrostatic pressure = 12 mmHg Mean glomerular capillary oncotic pressure = 23 mmHg Mean Bowman space oncotic pressure = 0 mmHg Coefficient of filtration = 3 (mL/min)/mmHg Renal blood flow = 200 mL/min Hematocrit = 40% What best represents the glomerular filtration rate (in mL/min) in this animal?

*30* GFR = Kf (PGC - PBS) - (pieGC - pieBS) = 3 (45 - 12) - (23 - 0) = 30

An experimental drug X is being tested for the treatment of stage IV solid tumor malignancies. Part of the drug company's evaluation process is to analyze survival data after 3 months of treatment. The results are given in the table below: Treated with drug X: Alive at 3 months = 20 Dead at 3 months = 60 Treated with placebo: Alive at 3 months = 38 Dead at 3 months = 38 What best represents the number needed to harm for drug X?

*4* 60 / 80 = 75% 38 / 76 = 50% 75% - 50% = 25% 1/0.25 = 4 because... *NNH = 1 / Attributable risk*

A hyperactive 6-year-old girl develops microcytic anemia, cerebral edema, & ataxia. Determination of what serum enzyme activities is most likely to confirm the diagnosis?

*5-Aminolevulinic acid (delta-ALA) dehydrogenase* Lead poisoning - inhibits delta aminolevulenic acid & derrochelatase --> microcytic anemia

Increase in activity of what enzymes is most likely to increase rate of metabolism of glucose-6-phosphate through glycolysis in liver?

*6-phosphofructo-1-kinase* Phosphofructosekinase-1 - rate-limiting step = Fructose-6-P --> Fructose-1,6-BP

A 37-year-old man presents to the ED complaining of fever, chills, & malaise. He has no significant past medical history but admits to using illicit intravenous drugs on a regular basis. He is febrile, tachycardia, & hypotensive. Auscultation of his heart reveals a murmur. A preliminary diagnosis of infective endocarditis is established. Blood cultures grow vancomycin-resistant enterococcus, & he is started on an intravenous antibiotic administered every six hours. The antibiotic follows first-order kinetics & has a volume of distribution of 70 L & a clearance of 0.5 L/min. How much should be administered every six hours to maintain a therapeutic steady-state plasma concentration of 4 mg/L?

*720 mg* Maintenance dose = Cpss x CL / B - IV = B of 1 MD = 4 mg/L x 0.5 L/min 6-hour intervals: 2 mg/min x 60 min/hour x 6 hours = *720 mg*

A 25-year-old woman is attempting to conceive. A urinary luteinizing hormone kit detects a gonadotropin surge on the first morning void of the 15th day of her menstrual cycle. How soon after this event would it be feasible to detect human chorionic gonadotropin in her serum?

*8 days later* hCG - detectable in blood 1 week after conception - on home test in urine 2 weeks after conception

At what lung would would total pulmonary vascular resistance be the lowest?

*9* = FRC

During contraction of striated muscle, the thick & thin filaments alter their relationship with each other and the sarcomere shortens. What bands is most likely to maintain a constant length during muscle contraction?

*A* Myosin releases bound ADP & Pi --> displacement of myosin on actin filament = power stroke --> contraction = shortening of H & I bands & between Z lines --> *A band remains same length* *A* band is *A*lways the same length

A 45-year-old woman has an acute coronary occlusion. Within secondary, the ischemic region shows mitochondrial swelling & depletion of glcyogen granules. What metabolic events is the most likely cause of these cellular changes?

*ATP depletion*

A 16-year-old boy is brought to the physician because he is much shorter than his peers. He is proportionally developed & otherwise healthy. An x-ray of the wrist is recommended to assess bone age. What radiographic findings will be an indication that his growth is complete?

*Absence of the epiphyseal cartilaginous plate* - as child grows, epiphyses become calcified & appear on x-rays, separated on x-rays by layer of invisible cartilage where most of growth is occurring - as sex steroid levels rise during puberty, bone maturation accelerates - remaining cartilaginous portions of epiphyses becomes thinner --> cartilaginous zones become obliterate --> closure of epiphyses --> no further lengthening of bones

Anti-fibrinolytic med used to treat excessive postoperative bleeding

*Aminocaproic acid*, Tranexamic acid

Impaired in communicating hydrocephalus (secondary to arachnoid scarring post-*meningitis*)

*Arachnoid granulations* - symmetrical enlargement of ventriculi - ex. tuberculosis meningitis

A 1-month-old, full-term boy is brought to the ED by his mother due to difficulty awakening him. The mother says that the infant was left alone for a few minutes this morning & rolled off a bed. Since then, he has been sleepy & less active than usual. Physical exam shows a lethargic boy with a large, full anterior fontanelle. Bilateral retinal hemorrhages are seen on funduscopic exam. What should be strongly suspected in this patient?

*Abusive head trauma* Shaken baby syndrome - tearing of bridging veins & subdural hemorrhages - may occur weeks to months = acute on chronic subdural hemorrhages - shjaking motion = retinal hemorrhages - posterior rib fractures - rolling over is not typical before age 4 months

Visual symptoms associated with Diphenhydramine most likely due to blockade of what mediators?

*Acetylcholine* First-generation antihistamines - impaired visual accommodation due to *anticholinergic (anti-muscarinic)* effects = chlorpheniramine, diphenhydramine

A 23-year-old woman comes to the physician with migratory joint pains involving her hands & knees. Physical exam shows bilateral tenderness in her wrists & proximal interphalangeal joints. There is also a malar skin rash & generalized lymphadenopathy. A urinalysis reveals proteinuria. Further evaluation shows that the patient's lymphocytes contain a mutated & functionally defective Fas gene product. What immunologic mechanisms is most likely impaired in this patient as a result of this molecular defect?

*Activation-induced T lymphocyte death* - Fas receptor initiates extrinsic pathway of apoptosis - mutation of Fas receptor or Fas ligand --> prevents apoptosis of autoreactive lymphocytes --> increased risk of autoimmune disorders such as SLE

A 61-year-old woman with a long history of poorly controlled HT suddenly has excruciating anterior upper sternal pain radiating to the neck & back. On admission to the ED, her BP is 210/110 mmHg. Fifteen minutes later, while laying down, it is 110/64 mmHg. Transesophageal echocardiography shows aortic insufficiency, a suggestion of a double lumen of the ascending aorta, & a pericardial effusion. She dies suddenly while awaiting an operation. What is the most likely cause of death?

*Acute hemipericardium* Aortic dissection

A previously healthy 8-year-old boy is brought to the ED due to vomiting & lethargy. The patient had been on an overnight hiking trip with his family. During the trip, the fam lost their food pack while canoeing. They had to hike back to the car. The child became weak & was carried the last mile. No one has eated for approximately 24 hours. On exam, he appears listless. Mild hepatomegaly is noted. Lab results are as follows: Glucose = 30 mg/dL Acetoacetate = not detected Aspartate aminotransferase = 341 U/L Alanine aminotransferase = 412 U/L The child begins seizing as the intravenous line is placed. What enyzmes is most likely deficient in this patient?

*Acyl-CoA dehydrogenase* Hypoketotic hypoglycemia - after period of fasting - defect in FA beta-oxidation in mitochondria --> most common enzymatic defect = *acyl-CoA dehydrogenase* deficiency - periods of fasting = cannot oxidize fatty acids for energy or produce ketone bodies --> *hypoketotic hypoglycemia* - affected patients may remain asymptomatic for long periods until they experience *significant fast* - FA oxidation disorders & carnitine deficiency have been added to newborn screening - treatment = prevention of catabolism --> avoid prolonged fasting; promptly supplying *glucose* during periods of illness

As the result of fall onto a hard surface, a 20-year-old woman sustains a fracture of the medial humeral epicondyle, & a nerve is injured. What action will be most affected by this nerve injury?

*Adduction of all digits*

A 56-year-old woman comes to the physician's office for her first health maintenance exam in the past 5 years. She has a 2 x 2.5-cm lesion 4 cm from the nipple in the outer upper quadrant of her left breast. The lesion is nontender & nonmobile & has ill-defined borders. There is no discharge on compression of the nipple. What is the most likely explanation for these findings?

*Adenocarcinoma* - non-tender = rules out lymph node & fibrocystic diseases - any palpable non-tender breast mass in woman over 50 = underlying malignancy = adenocarcinoma

Endothelial cells of postcapillary venules increase expression of intercellular adhesion molecule-1 (ICAM-1) in response to cytokines. The increased expression of ICAM-1 results directly in what neutrophil functions?

*Adherance* / tight binding - defective in leukocyte adhesion deficiency type 1 (decreased CD18 integrin subunit)

A 48-year-old man with advanced metastatic gastric cancer is admitted to the hospital because of severe abdominal pain. High doses of oral analgesics, including numerous opioids, NSAIDs, & tricyclic agents, have not been successful in managing the pain. Morphine administered by IV infusion successfully controls his pain, but the doses needed cause respiratory depression. He has repeatedly stated that he does not want cardiopulmonary resuscitation & that he wishes "to die with dignity without unnecessary pain." What is the most appropriate course of action?

*Administer lowest dose of morphine that relieves pain, even if it depresses respiration* - patient doesn't want pain while dying - patient's call is main call - patient can prescribe appropriate analgesics hat *coincidentally* shortnes patient's life

A 40-year-old woman has recurrent calcium-containing renal calculi. What strategies is most likely to decrease her risk for forming additional calculi?

*Administration of a thiazide diuretic* - urine calcium decreased with thiazides = enhanced calcium reabsorption

A 26-year-old previously man comes to the office with a 3-week history of shortness of breath, cough, & hemoptysis preceded by an upper respiratory tract infection. He has no fever, night sweats, or weight loss. His BP is 150/85 mmHg & pulse is 86/min & regular. Physical exam reveals bilateral inspiratory crackles & lower extremity edema. His creatinine is 4.1 mg/dL. Urinalysis shows proteinuria & hematuria with dysmorphic RBCs. Bilateral pulmonary infiltrates are seen on chest x-ray. He is also found to have an increased carbon monoxide diffusing capacity (DLCO) on pulmonary function testing. Antibodies directed against what is most likely to be associated with this patient's condition?

*Alpha 3 chain of type IV collagen* Goodpasture syndrome via Rapidly progressive glomerulonephritis - nephritic syndrome = HT, edema, acute renal failure, hematuria, proteinuria - alveolar hemorrhage = shortness of breath & hemoptysis with infiltrates on chest x-ray - Hb in alveolar = increased alveolar oxygen absorption & high carbon monoxide diffusing capacity (DLCO)

Patient homozygous for apolipoprotein E-4 allele likely to suffer from

*Alzheimer dementia* Early-onset Alzheimer disease associated with 3 gene mutations APP = chromosome 21 presenilin 1 presenilin 2

A 65-year-old man is brought to the ED with new-onset confusion, suprapubic discomfort, & lack of urine output. His past medical history is significant for benign prostatic hyperplasia, hypertension, hyperlipidemia, & type 2 diabetes mellitus complicated by neuropathy. The patient also has a history of chronic insomnia & has been treated with several meds with little benefit. He does not know his current meds. On exam, the patient is afebrile, confused, & oriented only to self. Suprapubic fullness is present, but abdominal exam is otherwise unremarkable. A urinary catheter is placed & immediately drains 1000 mL of urine. What meds most likely has contributed to this patien'ts current condition?

*Amitriptyline* TCAs - occasionally used for *insomnia* - strong anticholinergic properties --> confusion, constipation, acute urinary retention - elderly patients at increased risk for side effects via comorbid conditions (dementia, benign prostatic hyperplasia), decreased hepatic & renal clearance of meds - contraindicated in elderly patients

A 22-year-old college student who has been treated for anxiety & depressed mood for 6 weeks develops episodes in which she feels light-headed & almost faints. Pulse is 110/min, & BP is 110/70 mmHg while lying down & 85/60 mmHg while standing. Which of the following drugs is most likely to have caused the orthostatic hypotension?

*Amitriptyline* TCAs = Amitriptyline, Nortriptyline, Imipramine, Desipramine, Clomipramine, Doxepin, Amoxapine - sedation, *alpha1-blocking effects including postural hypotension*, & atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth) Tri-C's = *C*onvulsions, *C*oma, *C*ardiotoxicity (arrhythmia due to Na+ channel inhibition)

An obese 52-year-old woman comes to the physician because of vaginal bleeding. Her last menstrual period occurred 6 months ago. Biopsy shows endometrial hyperplasia. This endometrial stimulation is most likely due to peripheral aromatization of what hormones?

*Androstenedione* - source of estrogen (estrone) after menopause becomes peripheral conversion of androgens --> increased androgens = hirustism

Fetal anomalies that account for polyhydramnios

*Anencephaly*, Gastrointestinal obstruction (duodenal, esophageal, intestinal atresia) - excessive accumulation of amniotic fluid - increased abdominal circumference out of proportion to gestational age

A 22-year-old man who recently immigrated to the US comes to the physician for routine care. He has no current symptoms. He takes no meds and has no known allergies. Lab testing yields the following results: Anti-hepatitis A IgM = negative Anti-hepatitis A IgG = positive The patient's country of origin does not offer universal immunization against hepatitis A, & he says he has not been vaccinated against the virus. What do these lab findings most likely suggest?

*Anicteric viral infections as a toddler* Asymptomatic patient with IgG Abs against hepaitis A virus likely have prior infection with HAV - children < 6 = HAV infection often silent/subclinical = *anicteric* = no jaundice observed - self-limiting disease

A 26-year-old woman has a 3-week history of joint pain & a photosensitive rash on her face & other exposed parts of her body. What tests is most useful in confirming the diagnosis?

*Antibodies against native DNA (double-stranded DNA)* Systemic lupus erythematosus (SLE) - classic presentation = rash, joint pain, fever - most commonly in female of reproductive age & African-American descent ANA Abs= sensitive, not specific Anti-dsDNA Abs = specific, poor prognosis (renal disease)

The elevated eosinophils in a patient contribute to the host defense against schistotomiasis through what mechanism?

*Antibody-dependent cell-mediated cytotoxicity* (ADCC)

A female neonate has profound hypotonia. The only known complication of pregnancy was polyhydramnios. The mother has a lack of facial expression & weak muscles; she says she did not have any problems as a infant or child. What best explains the difference in presentations in the mother & child?

*Anticipation* Myotonic dystrophy - baby had polyhydramnios because any hypotonic baby has polyhydramnios (they don't swallow properly) - *inherited as AD --> manifests anticipation phenomenon because it's one of the trinucleotide repeat disorders*

*Hypersegmented neutrophils* associated with what antibodies?

*Antiparietal cell Abs in serum* = Pernicious anemia = Vitamin B12 (cobalamin deficiency) Also... - folate deficiency - orotic aciduria - diamond-blackfan anemia

A 48-year-old woman with a complex medical history comes to the clinic due to a change in her body habitus. She says her legs are "like sticks" while her "belly is getting bigger." The patient also feels increasingly fatigued but does not have excessive daytime somnolence. She has been homeless for much of the last 5 years but has been living in a residential care facility for the last 12 months. On physical exam, she is distractable and has an inappropriate affect but is cooperative. Neurologic & mental status exam is otherwise normal. There is loss of adipose tissue from the extremities & face, with a noticeable increase in abdominal girth. What types of medications is most likely to be responsible for this patient's symptoms?

*Antiretroviral medication* - patient has redistribution of fat from extremities to fat Med-induced body fat redistribution (lipatrophy/lipodystrophy) = common ADR of HAART - mainly stavudine & zidovudine - also associated with protease inhibitor use

A 44-year-old man who was recently diagnosed with idiopathic membranous nephropahy after developing edema comes to the office due to a sudden onset of left flank pain & gross hematuria. The patient has no other medical problems. He is taking furosemide & ramipril. BP is 135/85 mmHg & pulse is 88/min. On exam, there is left flank tenderness. The patient's edema has improved from the last visit. There is a left-sided varicocele that the patient has not noticed before. Urinalysis show increased proteinuria & new hematuria. Serum lactate dehydrogenase is elevated. Urinary loss of what substances most likely predisposed this patient to his acute condition?

*Antithrombin III* membranous nephropathy + flank pain + hematuria + left vacicocele = renal vein thrombosis (RVT) via nephrotic syndrome - *loss of anticoagulant factors, antithrombin III = hypercoagulabel state* --> RVT --> sudden-onset abdominal or flank pain & gross hematuria with elevated lactate dehydrogenase via renal infarction

Caused by L-dopa, regardless of whether carbidopa is added to levodopa treatment?

*Anxiety & agitation*

A 73-year-old man with a history of angina is undergoing cardiac catheterization via right femoral artery. As the pig-tail catheter is advanced into apex of left ventricle, what valves will be crossed?

*Aortic valve*

An experimental drug is administered to a human subject with moderately severe congestive heart failure. Within minutes of intravenous administration, there is a measurable decrease in cardiac preload & cardiac afterload, & an increase in glomerular filtration rate. The effects of the drug are most similar to those produced by ...

*Atrial natriuretic peptide* - released from atrial myocytes in response to increased blood volume & atrial pressure - acts via cGMP - causes vasodilation & decreased reabsorption at renal collectin tubule - dilates afferent renal arterioles & constricts efferent arterioles --> diuresis - contributes to "aldosterone escape" mechanism

Recognize AV block & what it's due to

*Atrioventricular conduction disease*

A 69-year-old man is brought to the ED with sudden onset palpitations & dyspnea. His past medical history is significant for HT & GERD. An ECG reveals a heart rate of 120 beats per minute with an irregular rhythm, narrow QRS complexes, & no P waves. What physiologic factors most likely determines the ventricular contraction rate in this patient?

*Atrioventricular node refractory period* Atrial fibrillation - rapid ventricular response - most common cardiac arrhythmia - absent P waves - irregularly irregular R-R intervals - narrow QRS complexes - aberrant electrical impulses arise within regions of heightened atrial excitability (pulmonary veins) *Ventricular response in AF dependent on transmission of abnormal atrial impulses through AV node* - each time AV node excited = enters refractory period during which additional atrial impulses cannot be transmitted to ventricles = majority of atrial impulses never reach ventricles - average ventricle rate in AF = 90-170 beats/min

A 6-year-old boy says his left ear hurts. His mother says that he has been tugging the ear. The external canal & tympanic membrane appear normal, but the tympanic membrane does not move when the pressure in the nasopharynx is increased. What is the most likely cause of these findings?

*Auditory tube obstruction* - normally close = helps prevent inadvertent contamination of middle ear space by normal secretions found in back of nose Patulous Eustachian tube = dysfunctional = always open - failure to regulate air pressure - sensations of popping, clicking, ear fullness, & occasionally moderate to severe ear pain - young children = "tickle in my ear"

Primary central nervous system lymphoma is typically composed of

*B-lymphocytes* - most commonly associated with HIV/AIDS - pathogenesis - EBV infection

Biopsy of the mass reveals abnormal cells with t(14;18) chromosomal translocation. This chromosomal change is most likely to cause what abnormalities in gene expression?

*Bcl2 overexpression* = *B*-*C*ell *L*ymphoma-2 - follicular lymphoma

A 55-year-old male is brought to the ED with chest pain that began while he was watching television. His past medical history is significant for HT, asthma, & diabetes. He smokes two packs of cigarettes daily & consumes alcohol occasionally. His BP is 160/100 mmHg & his heart rate is 100/min. After initial treatment in the ED, his chest pain disappears but he becomes short of breath. His BP is now 135/85 mmHg & his heart rate is 65/min. Physical exam reveals prolonged expirations & wheezes in the bilateral lung fields. Impairment of what processes depicted below is most likely responsible for the patient's continued shortness of breath?

*Beta-blocker interaction in adrenergic synapses* Beta blockers - decreased mortality in acute coronary syndrome (MI) - adverse effect of nonspecific beta-adrenergic blockade = difficulty breathing in patients with asthma of COPD

Enzyme likely to play role in pathogenesis of pigment stones.

*Beta-glucuronidase* - released by injured hepatocytes - bacteria hydrolyzes bilirubin glucuronides to unconjugated bilirubin Pigment gallstones = composed of calcium salts of *unconjugated bilirubin* - arise secondary to bacterial or helminthic infection of biliary tract - liver fluke Clonorchis sinensis = high prevalence in East Asian countries = common cause of pigment stones

A 34-year-old woman is evaluated for several months of moderate hearing loss. She has also noticed a disturbing ringing noise in her left ear. She has had no recent ear infections or cold symptoms. The patient does not use cotton ear swabs & has no history of head trauma. Her father has bilateral hearing loss attributed to old age. On physical exam, the auditory canals are patent & tympanic membranes appear grey with well-visualized light reflex. Hearing is diminished on the left side. Neuro exam shows left-sided facial numbness, an asymmetric smile, & decreased afferent & efferent corneal reflex in the left eye. This patient's condition suggests an intracranial mass located in what locations?

*Between cerebellum & lateral pons* Cerebellopontine angle with acoustic schwannoma - impaired CN VIII = sensorineural hearing loss & tinnitus (vestibular portion = vertigo, dysequilibrium, nystagmus) - impaired CN V = loss of facial sensation (loss of afferent limb of corneal reflex) & paralysis of muscles of mastication - associated with NF2

A 55-year-old man comes to the physician because of a 2-month history of intermittent, severe, sharp abdominal pain that occurs primarily after meals & lasts about 30 to 60 minutes. There is no fever, diarrhea, or weight loss. Physical exam shows no abnormalities. What is most likely responsible for these symptoms?

*Biliary colic* - no fever = no cholecystitis - meal = contraction of gallbladder against impacted stone in cystic duct --> when response of meal ended after 60 minutes, stone will slip back inside gallbladder - associated with nausea/vomiting & dull RUQ pain - neurohormonal activation (CCK after fatty meal) triggers contraction of gallbladder --> forces stones into cystic duct

A 25-year-old man is brought to the ED because of palpitations & anxiety. A friend says the patient was smoking "crack" earlier in the evening. Blood pressure is 180/110 mmHg & pulse is 120/min. ECG shows sinus tachycardia. What is the most likely cause of these findings?

*Block of NT uptake at presynaptic nerve terminal* Cocaine - blocks DAT, NET, SERT in CNS to inhibit uptake of DA into nerve terminal sin mesolimbic pathway - blockage of NET = increased sympathomimetic activity

Primary mechanism of action of SSRIs

*Blockade of serotonin transporter* - first-line antidepressants

Tolerance of B lymphocytes to self-antigens develops in what compartment?

*Bone marrow* B lymphocytes... - complete their entire formative period in the bone marrow - only cells that are selectively unresponsive (tolerant) to self-antigen are allowed to leave the BM

A newborn with phenylketonuria is started on a strict phenylalanine-restricted diet. What amino acids must be supplemented to avoid negative nitrogen balance?

*Tyrosine* - becomes essential

A 60-year-old man develops cirrhosis. He had multiple transfusions following severe trauma in 1985. He has no history of jaundice or hepatitis. Serologic tests & polymerase chain reactions on his blood will most likely show evidence of infection with what hepatitis virus?

*C* Transmission - blood (IVDU, *post-transfusion*)

A 4366-g (9 lb 10 oz) male newborn is delivered at term. The cephalic vaginal delivery was difficult & complicated by severe depression of the right shoulder. An MRI shows avulsion of a single root of the brachial plexus. The ventral ramus of what spinal nerves has most likely been injured?

*C5* Erb palsy / waiter's tip - traction or tear of upper trunk = C5-C6 roots - infants = lateral traction on neck during delivery - adults = trauma

Important neutrophil chemotactic agents

*C5a* IL-8 LTB4 kallikrein platelet-activating factor

A specific RNA consisting of 90 nucleotides is purified for further analysis. It is found to contain high amounts of chemically modified bases such as dihydrouridine, pseudouridine, & ribothymidine, & its secondary structure arises from base pairing within the chain. What is the most likely composition of the 3'-end of this molecule?

*CCA* - *C*an *C*arry *A*mino acids rRNA = non-coding RNA = 74-93 nucleotides - cloverlead - acceptor stem: CCA tail hangs off 3' end = AA cound to 3' terminal hydroxyl group - 3' CCA tail added to 3' end of tRNA as posttranscriptional modification in eukaryotes & most prokaryotes - D loop contains numerous dihydrouridine residues --> facilitates correct tRNA recognition by proper aminoacyl tRNA synthetase

The initial vaccines against Haemophilus influenza type B prepared with capsular polysaccharides were not very effective in children less than 2 years old. Subsequent vaccines have been greatly improved by the conjugation of the capsular polysaccharides to one of several proteins. Why does this conjugation improve immunogenicity?

*CD4+ T lymphocytes are activated* - vaccine contains type b capsular polysaccharide (polyribosylribitol phosphate) conjugated to diphtheria toxoid or other protein - given between 2 & 18 months of age

A 21-year-old man has the sudden onset of fever, sweating, cyanosis, tachycardia, tachypnea, unstable blood pressure, & muscle rigidity after administration of halothane & succinylcholine for appendectomy. An abnormality in what is the most likely cause of this reaction?

*Ca2+ releasing channels* Malignant hyperthermia - rare, life-threatening - *inhaled anesthetics or succinylcholine* induce fever & severe muscle contractions - susceptibility often inherited as autosomal dominant with variable penetrance - mutations in *voltage-sensitive ryanodine receptor = increased calcium release from sarcoplasmic reticulum* - treatment = dantrolene (ryanodine receptor antagonist)

Treatment of psoriasis initiated with medication that activates a nuclear transcription factor. What drugs was most likely prescribed?

*Calcipotriene* Topical vitamin D analogs frequently used for psoriasis - calcipotriene (calcipotriol), calcitriol, tacalcitol - bind to & activate vitamin D receptor = nuclear transcription factor that causes inhibition of keratinocyte proilferation & stimulation of keratinocyte differentiation - inhibit T cell proliferation & other inflammatory mediators

A 35-year-old man who takes street drugs intravenously develops fever, cough, & hemoptysis. X-ray film of chest shows bilateral infiltrates. Echocardiogram discloses a 1-cm mass that is attached to tricuspid valve. Blood culture grows yeast. The most likely causal organism is

*Candida albicans* - dimorphic - forms pseudohyphae & budding yeasts at 20 C, germ tubes at 37 C - endocarditis in IV drug users

First-line therapy for *trigeminal neuralgia*, repetitive, unilateral shooting pain in the distribution of CN V that lasts (typically) for < 1 minute

*Carbamazepine* - inhibits neuronal high-frequency firing by reducing ability of sodium channels to recover from inactivation - can cause aplastic anemia - P450 inducer Trigeminal neuralgia / Tic douloureux - stabbing / electrical shock - usually unilateral, repetitive - triggered by any stimulus to CN V = chewing, brushing teeth, shaving, washing affected area of face, swallowing, expsoure to hot or cold temperatures - may occur for several months

A 29-year-old woman comes to the hospital due to fever & skin rash. She returned from a trip to Brazil 10 days ago. Her symptoms started 5 days ago with a headache, retro-orbital pain, high-grade fever, & joint & muscle pains. She has also had an episode of epistaxis. Today, she noticed a skin rash all over her body. Exam shows a diffuse maculopapular rash & scattered petechiae. Lab study results show thrombocytopenia. Her boyfriend traveled to Brazil with her & is asymptomatic. What disease has a similar mode of transmission to that causing this patient's symptoms?

*Chikungunya fever* Dengue fever - via Aedes aegypti/mosquito - tropical & subtropical regions - acute febrile illness with headache, retro-orbital pain, joint & muscle pain - hemorrhage, thrombocytopenia, leukopenia, hemoconcentration - Aedes mosquito also transmits virus causing chikungunya - Areas may have had simultaneous outbreaks of both dengue & chikungunya

A 45-year-old man comes to the office with groin pain & swelling. About a month ago, he noticed a sore on his penis but did not seek medical attention because the ulcer was no painful & disappeared within a week. Several days ago, he began to experience painful swelling in his inguinal region, with inflammation of the overlying skin & eventual formation of several draining ulcers. He also has mild fever & malaise that began around the same time as his groin symptoms. The patient is a sailor. His other medical problems include well-controlled HT & hyperlipidemia. Cell scrapings from his lesions show cytoplasmic inclusion bodies. What is the most likely cause of this patient's condition?

*Chlamydia trachomatis* - small, gram-negative, obligate *intracellular* bacterium - serotypes A - C = ocular (trachoma) in children - serotypes D- K = urogenital (sexual) & inclusion conjunctivitis - L2 - L3 = *lymphogranuloma venereum* - *appearance of ulcer followed weeks later by swollen, painful, coalescing inguinal nodes (buboes)* that can develop stellate abscesses & rupture - *intracytoplasmic chlamydial inclusion bodies* - doxycycline recommended

The termination of the pathway that originates in the skin of the right hand & travels through the right cuneate nucleus to the left ventral posterolateral nucleus of the thalamus occurs at what labeled cortical area of the brain?

*D* VPL = Vibration, Pain, Pressure, Proprioception, Light touch, temperature = somatosensory cortex - let side = opposite

A 36-year-old man comes to the office due to chronic, mild dyspnea & fatigue. The patient also says that his mind seems "foggy" all the time & he is not able to think clearly. He has no significant past medical history & does not take any medication. He lives a sedentary lifestyle & has smoked a half-pack of cigarettes a day for 5 years. Blood pressure is 140/85 mmHg, pulse is 84/min, & respirations are 18/in. His BMI is 31 kg/m^2. Lung auscultation is unremarkable. Chest x-ray is normal. Arterial blood gas analysis shows partial pressure of oxygen is 60 mmHg & partial pressure of carbon dioxide is 54 mmHg. His estimated alveolar to arterial oxygen gradient is 10 mmHg. What best explains this patient's lab findings?

*Chronic hypoventilation* Obesity hypoventilation syndrome (OHS) - chronic fatigue, dyspnea, difficulty concentrating, increased partial pressure of carbon dioxide (PaCO2) - increased CO2 production due to increased mass & surface area, sleep-disordered breathing, reduced lung volumes & compliance - healthy individuals: A-a gradient = 5-15 mmHg - hypoxemia in normal A-a gradient = both alveolar & arterial partial pressure of oxygen (PO2) low - patient's normal A-a gradient (10 mmHg) = further evidence of OHS

A 36-year-old man comes to the office due to skin lesions on his palms. The patient has yellowish skin nodules over the palmar creases that have been increasing in size & number over the past several years. He also has small clusters of yellow papules on his elbows, knees, & buttocks. His father died of a myocardial infarction at age 56. Biopsy of his lesions shows accumulation of lipid-laden macrophages. Immunoblot analysis suggests a lack of ApoE3 & ApoE4 in his circulating lipoproteins. What is most likely impaired in this patient?

*Chylomicrons remnant uptake by liver cells* Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) - xanthomas - premature coronary & peripheral vascular disease - AR - primary defects = ApoE3 & ApoE4 = apolipoproteins found on triglyceride-rich lipoproteins (chylomicrons & VLDLs) responsible for binding hepatic apolipoprotein receptors

Bronchi are lined with pseudostratified epithelium. As the airways continue distally, the epithelium changes. What features is last to disappear as the epithelium changes along the respiratory tube?

*Cilia* - present through respiratory bronchioles but are not present in alveolr ducts or in alveoli themselves - function to propel mucus toward pharynx - persist up to end of respiratory bronchioles Bronchi = pseudostratified columnar ciliated epithelium with goblet cells & submucosal mucoserous glands & cartilage Bronchioles, terminal bronchioles, respiratory bronchioles - lack goblet cells, glands & cartilage

Target of timolol ophthalmic drops.

*Ciliary epithelium* - acetazolamide, carbonic anydrase inhibitor, also decreases aqueous humor secretion by ciliary epithelium

What antimicrobial agent is most likely to be administered orally for treatment of potentially serious systemic infections because of its predictable bioavailability?

*Ciproloxacin* - given *orally*

Activation of cytoxic T lymphocytes to eliminate virus-infected cells requires... Interaction of Antigenic Peptide with: Combined with Signaling from:

*Class I MHC* *Interleukin-2 (IL-2)* CD8+ T cells - directly kill virus-infected cells - delayed cell-mediated HS (type IV) - acute & chronic cellular organ rejection NK cells - use perforin & granzymes to induce apoptosis of virally infected cells & tumor cells - activity enhanced by IL-2, IL-12, IFN-alpha, IFN-beta - induced to kill when exposed to nonspecific activation signal on target cell &/or to an absence of MHC I on target cell surface

A 22-year-old Caucasian male presents to the ER complaining of severe headaches & vomiting. Soon after, he slips into a coma & dies. Autopsy shows a ruptured cerebral aneurysm with extensive intracranial hemorrhage. This patient's condition is most likely associated with

*Coarctation of aorta* - may be associated with congenital cardiac anomalies or with berry aneurysms of Circle of Willis Spontaneous intracranial hemorrhage - young adults = AV malformations, ruptured cerebral aneurysms, or abuse of sympathomimetic drugs such as cocaine

A 3-year-old study is planned to assess incidence & etiology of respiratory disease in 574 individuals greater than age 60. The study consists of two groups: one group cares for children under age of 5; the second group does not care for children. At the onset of respiratory symptoms, cultures & serologic studies will be performed. What best described this study design?

*Cohort* study - compares group with given exposure or risk factor to group without exposure - looks to see if exposure or risk factor is associated with later dev't of disease - "who will develop disease?"

A 55-year-old man comes to the physician's office because of a second episode of acute severe pain in his right big toe. Exam shows an erythematous, swollen, & exquisitely tender right first metatarsophalangeal joint. Administration of what drugs is the most appropriate initial therapy?

*Colchicine* - acute & prophylactic values = *Acute* gout drug = NSAIDs, Glucocorticoids, Colchicine

A 2-year-old boy has brittle depigmented hair, cerebral atrophy, delayed myelination, motor delay, & mental retardation. Lysyl oxidase is decreased. The function of what substances is most likely defective in this patient?

*Collagen* MENKES DISEASE!!! - X-linked recessive CT disease - via impaired *copper absorption* & transport due to defective *Menkes protein (ATP7A) - leads to *decreased activity of lysyl oxidase* (copper is a necessary cofactor) = *brittle, "kinky" hair, growth retardation, hypotonia

What is the unique function of the central aggregate of *gap junctions* in a freeze-fracture image?

*Communication*

A genetic element is found to contain several genes & to catalyze its own movement within & between chromosomes. Inverted 35-nucleotide repeats are present at the ends of this genetic element. This genetic element in hepatocytes is incapable of replicating independently. Based on this description, this genetic element is best categorized as ...

*Complex transposon* - able to carry genes - can contain insertion sequences as well at the ends = help with insertion

During a study of the components of regulatory proteins, an investigator will most likely find that zinc finger motifs facilitate what functions?

*DNA binding* Zinc fingers = transcription factor motif - "protein contains 30 AA structural motif with 4 cysteine residues coordinated to zinc atom" - structural motif

A 24-year-old man comes to the physician with painful blisters on the shaft of his penis. The lesion erupted 2 days ago. The patient has had 5 lifetime sexual partners & is currently sexually active with one female partner; he uses condoms inconsitently. Exam shows multiple vesicular lesions on the penis, & Tzank smear is positive for multinucleated giant cells. HIV testing is negative. The patient has had several similar episodes every year for the past 2 years but had been too embarrassed to seek treat until now. What would most likely have prevented recurrence of this patient's condition?

*Continuous daily valacyclovir* Genital herpes simplex (HSV) - within S2, S3, S4 dorsal root (sensory) ganglia - recurrence of genital HSV can be suppressed or minimized with daily oral valacyclovir (preferred as it is dosed once daily & has good B), acyclovir, or famciclovir

Rasburicase helps to protect normal organs by what mechanisms?

*Converting uric acid into more soluble metabolites* Risk of Tumor Lysis Syndrome can be reduced by - allopurinol (xanthine oxidase inhibitor) - rasburicase Rasburicase - recombinant version of urate oxidase (present in many mammals but not humans) - catalyzes conversion of uric acid to allantoin = 5-10 times more soluble than uric acid

A 23-year-old man comes to the ED complaining that he has food stuck in his throat. His symptoms started 2 hours ago after eating fish at a local seafood retaurant. He has tried coughing & swallowing multiple times in an attempt to clear the food, but has so far been unsuccessful. The patient denies any difficulty with breathing. He does not appear to be in any distress on physical exam. Laryngoscopy reveals a fish bone lodged in the left piriform recess. During an attempt to retrieve the fish bone, a nerve is injured deep to the mucosa overlying the recess. What is most likely to be impaired in this patient?

*Cough reflex* Piriform recesses - bounded medially by aryepiglottic folds & laterally by thyroid cartilage & thyrohyoid membrane - thin layer of mucosa overlying piriform recess = all that protects superficially coursing internal laryngeal nerve = branch of superior laryngeal nerve (CN X)

Insidious onset of abdominal pain, diarrhea, constitutional symptoms. Prone to developing fistulas/absesses as lesions affect entire thickness of abdominal wall. Perianal disease (skin tags, fissures) also common.

*Crohn disease*

Researchers are studying the relationship between essential HT & a common mutation in the structure of a sodium channel protein. A study population is randomly selected & blood samples are obtained for leukocyte genotyping. The prevalence of HT is determined based on mean BP measurements obtained using standardized ambulatory blood pressure monitoring conducted over 1 week. Based on the analysis results, the researchers conclude that the sodium channel structure mutation is associated with HT. What best describes the study design used by the investigators?

*Cross-sectional studies* - exposure & outcome measured simultanesouly at particular point in time (snapshot study)

A study is performed comparing the effect of tramadol to placebo for painful polyneuropathy. Fifty patients are randomized to 1 to 2 sequences: tramadol followed by placebo or placebo followed by tramadol. Each treatment is delivered for 4 weeks with an interim 1-week washout period. After each treatment period, patients use a 10-point numeric scale to rate pain, paresthesia, & tenderness. What best described this study design?

*Crossover study* - subjects randomly allocated to sequence of 2 or more treatments given consecutively - allows patients to serve as their own controls - *washout period* (no treatment) period = added between consecutive treatments --> allows effects of priod treatment to wear off

A 34-year-old industry worker experiences rapid-onset shortness of breath, dizziness, palpitations, & flushed skin after accidental exposure to chemical fumes. Exam by an occupational physician shows that the patient is tachypneic & has a reddish discoloration of the skin without cyanosis. The patient is immediately instructed to inhale amyl nitrite from the safety kit. The success of this antidote is dependent upon its ability to convert hemoglobin into a form with increased affinity for what substances?

*Cyanide* - dependent upon its ability to bind ferric iron (Fe3+) with high affinity --> inhibits cytochrome c oxidase in mitochondria Cyanide poisoning = reddish skin discoloration, tachypnea, headache, tachycardia, nausea/vomiting, confusion, weakness - lactic acidosis + narrowing of venous-arterial PO2 gradient - *adminster inhaled amyl nitrite* --> oxidizes ferrous irone (Fe2+) in Hb to ferric iron (Fe3+ = methemoglobin = incapable of carrying O2 but has high affinity for cyanide --> binds & sequesters cyanide in blood = frees it from cytochrome oxidase = limits its toxic effects - hydroxycobalamin, vitamin B12 precursor, & sodium thiosulfate also antidotes for cyanide poisoning

After several courses of treatment for non-Hodgkin's lymphoma, a 33-year-old man develops gross hematuria. What drugs is most likely to be responsible for this adverse effect?

*Cyclophosphamide* - severe adverse effects = cystitis & cardiomyopathy

Which of the following immunosuppressive agents acts in the lymphocyte by complexing to & inactivating the lymphocyte-specific phosphatase calcineurin?

*Cyclosporine* - Calcineurin inhibitor - binds Cyclophilin - Blocks T cell activation by preventing IL-2 transcription - use = psoriasis, RA - adverse effects = *nephrotoxicity*, HT, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism

A pharmaceutical researcher develops a therapy to treat a protein misfolding disorder. Specifically, a mutation in this disorder leads to abnormal protein folding and subsequent intracellular degradation of the protein before it can reach the cell membrane. With the new combination drug therapy, the first drug corrects the processing & trafficking of the protein, enabling it to reach the cell surface membrane. Once the protein has reached the cell surface, its function is enhanced by the second drug. This therapy is most likely to be helpful in what conditions?

*Cystic fibrosis* - caused by mutations in CFTR protein - F508 = most common CFTR gene mutation --> *abnormal protein folding* & failure of glycosylation --> CFTR protein then targeted for degradation by proteasome before reaching cell surface = absence from apical membrane of exocrine ductal epithelial cells Lumacaftot & Ivacaftor = CFTR-modulating meds that can potentially help patients with CF by restoring CFTR proteins to membrane - enhance protein function (chloride transport) at membrane - improve predicted FEV - decreases rates of pulmonary exacerbations

Recognize complement-binding site of antibody

*D* - IgG & IgM = capable of & essential for triggering classical complement pathway after binding C1 = classical pathway - C1 must bind Fc portions of 2 different Abs at specific C1 binding sites - *complement binding site of both IgG & IgM = located in Fc portion closer to hinge region*

What drug is a skeletal muscle relaxant that works by a direct action on excitation-contraction coupling rather than an effect on the CNS?

*Dantrolene* - prevents release of Ca2+ from sarcoplasmic reticulum of skeletal muscle by binding to ryanodine receptor - clinical use = malignant hyperthermia, neuroleptic malignant syndrome (toxicity of antipsychotic drugs)

A 68-year-old man with benign prostatic hypertrophy starts taking terazosin. What changes is most likely in second messenger levels in the cells affected by this treatment?

*Decrease in IP3* *HAV*e *1* *M*&*M* - Gq --> Phospholipase C --> DAG & IP3 alpha1 selective blocker = terazosine = decreased IP3

Rationale for ursodeoxycholic acid for cholesterol gallstones

*Decrease in concentration of bile acids*

A 20-year-old man ingests 1 L of water over 1 hour. What sets of changes is most likely at the end of the hour? - Plasma ADH (vasopressin) - Urine osmolality - Urine flow

*Decreased Plasma ADH (vasopressin)* *Decreased Urine osmolality* *Increased Urine flow*

A 65-year-old woman is brought to the ED because of lethargy & confusion for 24 hours. She did not fall or injure herself recently. Meds include amitriptyline (150 mg at bedtime) for major depressive disorder & diphenhydramine for the past week (50 mg 3 times daily) for a pruritic rash. Her pulse is 100/min & regular, & BP is 135/80 mmHg. Physical exam shows a palpable mass in the midline extending 5 cm upward from the pubic symphysis. Her serum urea nitrogen (BUN) concentration is 45 mg/dL, & serum creatinine concentration is 2.8 mg/dL. What best explains the lab results?

*Decreased ability to empty bladder* Patient on amitriptyline --> anticholinergic side effect = retention

The resistance of a precapillary arteriole is increased in a muscle vascular bed. What most likely occurs in response to this increase?

*Decreased capillary filtration rate* R1 --- R2 --- R3 Resistance increased in R1 --> decreased flow downstream = decreased filtration rate

A 10-year-old girl has acute facial swelling & difficulty breathing. An acquired deficiency of C1 esterase inhibitor is suspected. What findings in serum will best support this diagnosis?

*Decreased concentration of C4* C1 esterase inhibitor deficiency = hereditary angioedema via unregulated activation of kallikgrein --> increased bradykinin - *decreased C4 levels* - ACE inhibitors contraindicated

What best accounts for difference in drug concentration following rectal administration when compared to oral administration?

*Decreased drug deliver to liver*

A 57-year-old man with a history of alcoholic cirrhosis is brought to the ED due to altered mental status. Over the weekend, he ate a lot of smoked meats at a local barbecue competition. Since then, he has been sleeping most of the day & is confused & disoriented when awake. On exam, he had abdominal distention with shifting dullness. The patient answers correctly when asked for his name but does not know that he is in the hospital & says the years is "1997." When asked to extend his hands as if stopping traffic, the patient makes rhythmic flapping movements. He is started on rifaximin. What is the most likely mechanism of action of this drug when used to treat this patient's current condition?

*Decreased intraluminal ammonia production* Hepatic encephalopathy (HE) - neurologic complication of cirrhosis due in part to liver's *inability to convert ammonia (neurotoxin) to urea* - excess ammonia --> shunted past liver --> crosses BBB = altered mental status - asterixis = rhythmic flapping of dorsiflexed hands - primary source of degraded nitrogen products = intestinal bacteria - *excess dietary protein intake (large steak meal) = trigger* Rifaximin = nonabsorbable antibiotic that alters GI flora to decrease intestinal production & absorption of ammonia - generally used in addition to lactulose (catabolized by intestinal bacterial flora to short chain FAs --> lowers colonic pH --> increases conversion of ammonia to ammonium) - sometimes used for traveler's diarrhea (inhibits bacterial RNA synthesis)

A 34-year-old woman has recurrent throbbing headaches that occur several times a month and cause significant distress. They are accompanied by nausea & photophobia. She has had 5 ED visits for these headaches over the last 6 months. During office visits, her BP ranges from 140/90 mmHg to 150/95 mmHg. Neurologic exam is unremarkable. The patient is prescribed metoprolol & is advised that the med is expected to decreased the frequency of headaches & also lower BP in the long term. What best explains this med's effect on BP?

*Decreased level of circulating renin* Beta blockers - useful for treating HT patients with comorbid conditions such as migraine, essential tremor, angina pectoris/prior MI, & atrial fibrillation - *act to inhibit renin release* --> reduces conversion of angiotensinogen to angiotensin I & reduces levels of angiotensin II (potent vasoconstrictor) & aldosterone (decreasing renal sodium & water retention) lower BP via 2 mechanisms 1. reduces myocardial contractility & heart rate 2. decreases renin release by kidney

I newborns, what mechanism increases left atrial pressure above right atrial pressure?

*Decreased pulmonary vascular resistance* - decreased resistance in pulmonary vasculature --> increased left atrial pressure --> decreased prostaglandins

MRL-lpr/lpr mutant mice are useful biomedical research models because of their increased susceptibility to autoimmune disease. These mice are characterized by a defect in the fas gene & a marked increase in T-lymphocyte accumulations as compared with wild-type animals. Based on these characteristics, what is the most likely cause of increased susceptibility of these mutants to autoimmune disease?

*Decreased responsiveness to clonal deletion signals in the thymix cortex* - Fas gene defective = no clonal deletion - no apoptosis would occur due to lack of Fas = no clonal deletion

A 32-year-old man is started on infliximab for treatment of refractory Crohn disease. Ten days later, he develops joint pain & a pruritic rash. Skin biopsy shows scattered areas of fibrinoid necrosis & neutrophil infiltration involving his small blood vessels. What is most likely to accompany this patient's condition?

*Decreased serum C3 level* Acute serum sickness - tissue deposition of circulating immune complexes (type III HS) - fever, pruritic skin rash, arthralgias 7-14 days after exposure to antigen - small vessel vasculitis with fibrinoid necrosis & eutrophil infiltration - hypocomplementemia = decreased serum C3 levels - can follow chimeric mAbs (rituximab & infliximab) or nonhuman Igs (venom antitoxins)

A 58-year-old man develops esophageal candidiasis 2 days after completing antibiotic therapy for sinusitis. An oral antifungal drug is initiated. Meds include glipizide for type 2 diabetes mellitus & warfarin because of previous cardiac valve replacement. Six days later, his candidiasis has improved, but his serum glucose concentration has decreased from 120 mg/dL to 80 mg/dL, & his prothrombin time has increased from 30 seconds (INR = 2.5) to 40 seconds (INR = 3.3). What mechanisms of action explains the antifungal activity of this drug?

*Decreasing synthesis of ergosterol* Azoles = liver dysfunction (inhibits cytochrome P450) - *inhibit fungal sterol (ergosterol) synthesis by inhibiting cytochrome P-450 enzymes* that converts lanosterol to ergosterol CYP450 Inhibitors: *SICKFACES.COM* *S*odium valproate *I*soniazid *C*imetidine *K*ETOCONAZOLE *E*rythromycin (macrolides) *S*ulfonamides *C*hloramphenicol *O*meprazole *M*etronidazole

A 62-year-old man develops numerous superficial blisters over the scalp, face, groin, & trunk. New lesions develop over areas subjected to minimal trauma. Biopsy of one of the lesions shows an intraepidermal blister with suprabasal acantholysis. Serologic studies are likely to show an autoantibody directed against ...

*Desmosomal proteins* Pemphigus vulgaris - autoimmune skin disorder with *IgG Ab against desmoglein* - flaccid *intraepidermal* bullae caused by *acantholysis* (separation of keratinocytes = "row of tombstones" - Type II HS rxn - reticular (net-like) pattern - *Nikolsky sign positive* (separation of epidermis upon manual stroking of skin)

Activation of T lymphocytes is initiated when processed antigen binds to T lymphocytes receptor on cell membrane, & phospholipase C is activated. This results in production of what components of signal transduction?

*Diacylglycerol*

Several clinical trials have suggested that retinoic acid can induce remission in patients with acute promyelocytic leukemia. Such remission is related to the ability of retinoic acid to promote what?

*Differentiation of leukemic cells* Vitamin A (retinol) - antioxidant - essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells) - prevents squamous metaplasia - used to treat measles & acute promyelocytic leukemia (APL)

A 35-year-old woman has had type 1 diabetes mellitus for 20 years & microalbuminuria for 3 years. What findings is most likely on exam of tissue obtained on renal biopsy?

*Diffuse glomerulosclerosis* Diabetic glomerulonephropathy - LM = mesangial expansion - GBM thickening, eosinophilic nodular *glomerulosclerosis* (Kimmelstiel Wilson lesions)

Ergot alkaloid used to treat acute migraine headache. *Can induce vasospastic angina as it constricts vascular smooth muscle* via stimulation of both alpha-adrenergic (partial agonist) & serotonergic receptors

*Dihydroergotamine*

What would accumulate in embryonic tissue if Methotrexate were sued for ectopic pregnancy?

*Dihydrofolate polyglutamate* & folic acid Methotrexate = folic acid antagonist - competitively inhibits dihydrofolate reductase, which catalyzes synthesis of tetrahydrofolate

What will result in increased renal plasma flow & increased glomerular filtration rate?

*Dilation of Afferent Arteriole* - decreases vessel resistance - increased GFR via increased glomerular capillary hydrostatic pressure

A 17-year-old girl with a history of depression is brought to the ED after attempting suicide. Her parents report that she consumed 2 bottles of insecticide after having an argument with her sister approximately 2 hours prior to presentation. The patient's symptoms include nausea, vomiting, abdominal pain, & copious watery diarrhea. She has a known history of self-cutting & suicidal ideations but no prior suicide attempts. Blood pressure is 86/42 mmHg & pulse is 120/min. Her breath has a faint garlic odor, & she has numerous healing linear scars on her forearms. What meds should be administered immediately?

*Dimercaprol* Arsenic - odorless, tasteless, easily absrobed after infestion or inhalation - toxicity can result from *exposure to pesticides/insecticides*, contaminated water, pressure-treated wood, metallurgy, mining, glass-making - binds to sulfhydryl groups --> impairs cellular resipration via inhibition of pyruvate dehydrogenase = abdominal pain, vomiting, severe watery diarrhea, delirium, hypotension from dehydration - QT prolongation --> torsades de pointes - *garlic odor* First-line chelating agent = *dimercaprol* (British Anti-Lewisite) --> increases urinary excretion of heavy metals - narrow therapeutic index - side effects = nephrotoxicity, HT, fever

An 80-year-old woman comes to the physician because of a 2-week history of mild constipation & occasional inability to completely empty the bladder. She takes over-the-counter medications frequently. Vital signs are normal. Evaluation shows bladder distention & mild confusion. What drugs is the most likely cause her symptoms?

*Diphenhydramine* sedation *antimuscarinic* - tachycardia - mydriasis - *decreased gastric motility* - agitation - hot, dry skin - dry mouth anti-alpha-adrenergic

A 23-year-old woman has skin bilstering that results from a point mutation in a single gene. Epidermal cells in these patients become fragile & rupture. What is the most likely effect of the genetic mutation?

*Disrupted assembly of keratin into intermediate filaments* Epidermolysis bullosa - inherited skin condition caused by point mutation in single gene = disruption of assembly of keratin into intermediate filaments in stratum basale of epidermis = subtype of blistering diseases

Restless leg syndrome is characterized by an uncomfortable sensation in the legs accompanied by an urge to move them. It is worse at rest when falling asleep. What is the preferred med for treatment?

*Dopamine agonists* - ropinirole, pramipexole - functional iron deficiency in CNS linked to dysfunction of dopaminergic pathways (iron-dopamine model) - iron deficiency common in RLS

Actions most likely to be severely impaired if nerve if injured at fibular neck

*Dorsiflexion of foot* Foot drop - inverted & plantarflexed at rest - loss of eversion & dorsiflexion - steppage gait Common peroneal nerve (L4-S2)

Bypasses liver to enter the IVC & RA. Used for umbilical vein catheter.

*Ductus Venosus* - blood entering fetus via umbilical vein is conducted via ductus venosus into IVC, bypassing hepatic circulation

Patient's statin therapy is discontinued, & he is started on a med that inhibits cholesterol absorption at the brush border of the small intestine. What drugs was most likely started on this patient?

*Ezetimibe* - for patients who cannot tolerate statins - prevents cholesterol absorption at small intestine brush border

A 43-year-old man reports occasional chest discomfort over the last 6 weeks. He thinks it is most likely musculoskeletal pain but is concerned due to fam history of heart disease. The patient has no medical problems and does not smoke cigarettes. He leads an active lifestyle & exercises every day. He undergoes treadmill exercise stress testing. Baseline blood pressure is 122/75 mmHg & pulse is 54/min. After 10 minutes of exercise, his blood pressure is 155/80 mmHg & pulse is 150/min. He has no chest pain & ECG shows no abnormalities. Compared to pretest conditions, what is the most significant factor limiting coronary blood supply during the test?

*Duration of diastole* - arterial blood supply to myocardium via right & left coronary arteries arising directly from aortic root - *myocardial perfusion* mainly during *diastole* - increased heart rate shorter time of ventricular relaxation (*duration of diastole*) --> time available for max coronary blood flow decreases & becomes major limiting factor for coronary blood supply to myocardium

A large multi-country study used population data from 14 countries located within similar latitudes to evaluate association between dietary habits, including vitamin D intake, & prevalence of multiple sclerosis. What best describes the design of this study?

*Ecological study* - unit of analysis = *populations* - useful to generate hypotheses but should not be used to make conclusions regarding individuals within these populations (ecological fallacy)

A 42-year-old woman, gravida 4, para 4, comes to the clinic due to heavy & painful menstrual bleeding over the past 3 months. Her last menstrual period was 4 weeks ago. Menarche was at age 10, & menstrual periods last for 3-5 days & occur every 30 days. She is sexually active with her husband & does not have pain with intercourse. The patient had a bilateral tubal ligation 3 years ago after the birth of her last child. She takes no medications & has no allergies. BMI is 24 kg/m^2. Vital signs are normal. On bimanual exam, the uterus is uniformly enlarged. Urine beta-hCG is negative. Biopsy shows secretory endometrium. What is the most likely cause of thei patient's symptoms?

*Endometrial tissue in the myometrium* Adenomyosis = endometrial glandular tissue in myometrium - common in middle-aged parous females - heavy menstrual bleeding - dysmenorrhea - uniformly enlarged uterus - can only be diagnosed definitely by microscopic exam of hysterectomy specimen

A 63-year-old man comes to the physician after noticing a reddish tinge to his urine for the last couple of days. During evaluation of his hematuria, an abdominal CT scan reveals a left-sided renal mass. Further workup also shows multiple pulmonary & bone nodules. CT-guided biopsy of a peripherally located lung nodule demonstrates renal cell carcinoma. High-dose IL-2 is started, & 4 weeks later there is a significant reduction in his tumor burden. What mechanisms was most likely responsible for regression of his malignancy?

*Enhanced activity of natural killer cells* IL-2 - produced by helper T cells - major growth factor for T lymphocytes - promotes growth of B cells - activates NK cells & monocytes *Increased activity of T cells & NK cells = responsible for IL-2's anti-tumor effects*

Bind activator proteins that facilitate bending of DNA. DNA bending allows activator proteins to interact with general transcription factors & RNA polymerase II at promoter, increasing the rate of transcription.

*Enhancer sequences*

Viral particles isolated from the nasal exudate of a 10-year-old male are shown to lose their infectivity once exposed to ether. It can be concluded that the viral particles are most likely

*Enveloped* - ether & other organic solvents can inactivate "enveloped" viruses - solvent-induced disruption of dissolution of envelope lipid = loss of viral infectivity

A 25-year-old woman with newly diagnosed seizures comes to the ED with fever & skin rash. She had her first seizure 6 weeks ago, & an MRI of the brain revealed no structural lesions. She was started on phenytoin 4 weeks ago. Her temp is 38.9 C (102 F). There is a diffuse confluent erythema involving 60% of the body, palpable generalized lymphadenopathy, & symmetrical swelling. What lab findings is most likely to be present in this patient?

*Eosinophilia* Drug reaction with eosinophilia & systemic symptoms (DRESS) syndrome - 2-8 weeks afte drug exposure - associated with anticonvulsants (phenytoin, carbamazepine), allopurinol, sulfonamides, antibiotics (minocyclic, vancomycin) - likely involves drug-induced herpesvirus reactivation followed by clonal expansion of T cells that cross-react with drug - fever, generalized lymphadenopathy, facial edema, difuse morbilliform skin rash - eosinophilia, atypical lymphocytosis, elevated serum alanine transaminase

A cell biologist is studying the role of ribonucleoproteins in normal cellular function. He prepares a cell extract using a specific cell type obtained from a 73-year-old man. Ribonucleoproteins are separated & purified from cell extract for structural & functional analyses. These cells are found to express higher amounts of a particular protein in comparison to other cell types. This protein has reverse transcriptase activity that functions to add TTAGGG repeats to the 3' end of chromosomes. What cell types was most likely studies in this experiment?

*Epidermal basal cells* - stem cells have long telomeres Telomerase = ribonucleoprotein that adds TTAGGG repeats to 3' end of chromosomes *telomere region) - similar to reverse transcriptase enzymes = synthesizes ssDNA using ss RNA as template (RNA-dependent DNA polymerase)

In a patient on atorvastatin, what may precipitate acute renal failure?

*Erythromycin*/Macrolides - inhibit stain metabolism by metabolizing CYP3A4 - increased incidence of statin-induced myopathy & rhabdomyolysis -- acute renal failure = possible sequela of rhabdomyolysis

A 32-year-old man has dysphagia & odynophagia after ingesting a drain cleaner containing sodium hydroxide pellets. What is the most likely associated finding 3 months later?

*Esophageal stricture* - associated with caustic ingestion & acid refluex Sodium hydroxide = alkali - early complication = gastric perforation - late complication = stricture

A 6-month-old boy is brought to the ER with poor feeding & irritability. Physical exam reveals diffuse skin erythema. You also notice that the epidermis easily comes off with gentle pressure. What is the most likely cause of this patient's symptoms?

*Exotoxin-mediated skin damage* Staphylococcal Scalded Skin Syndrome (SSSS) - produce exfoliatin exotoxin - Nikolsky's sign - epidermal necrolysis, fever, pain associated with skin rash - most common in infants & young children

Eukaryotic proteins that exist as a nonmembrane-associated, glycosylated, disulfide-linked dimer in the mature form are generally found in ...

*Extracellular space* - Fibronectin - IgA

A 36-year-old woman comes to the office due to firm, nontender swelling of her right cheek for the past 4 months. The patient has had no fever, runny nose, sore throat, or cough. She drinks a glass of wine with dinner on most nights but does not use tobacco. Physical exam shows fullness of the preauricular space on the right side. An MRI of the region identifies a 2.2-cm mass in the right parotid gland, & a follow-up needle biopsy shows the lesion to be neoplastic. If left untreated, this patient is most likely to develop what?

*Facial droop* Extracranial portion of CN VII - motor innervation to muscles of facial expression - courses within parotid gland = 5 terminal branches = temporal, zygomatic, buccal, mandivular, cervixal Parotid gland tumors - can compress ipsilateral facial nerve --> facial droop - malignant neoplasms mostly

A series of experiments is performed to determine the mechanism by which a pharmacologic agent traverses cell membranes & accumulates within target cells. The rate of transport depends on the concentration of the drug only. When the extracellular concentration of the agent exceeds 10 mM, no further increase in the rate of uptake is observed. Structurally similar compounds pass through cell membrane, but at a lower rate. Ouabain, an inhibitor of Na+/K+ ATPase, fails to inhibit transport. What is the most likely mechanism by which this agent enters the cells?

*Facilitated diffusion* Ouabain - inhibits by binding to K+ site - after reaching extracellular concentration of 10 nM, no more increase can occur = must be carrier mediated - concentration at which all carriers are saturated & can't increase concentration anymore

After a full course of immunization with a new vaccine consisting of a recombinant polypeptide, 10% of adults fail to make antibody to the polypeptide. The nonresponders have increased frequency of one HLA type. What is the most likely explanation for the failure of this group to respond to immunization?

*Failure of T lymphocytes to recognize the polypeptide*

A 64-year-old man comes to the physician's office for a health maintenance exam. He has been unable to sustain erections during intercourse or masturbation for the past month. He does have spontaneous nocturnal & morning erections He had a MI 2 months ago. What is the most likely explanation for his current erectile disorder?

*Fear of sudden death*

A 45-year-old woman has weakness in the anterior thigh & is unable to extend her leg at the knee. Flexion of the hip & knee is normal. Sensation is absent on the medial side of the leg. What nerves is most likely injured?

*Femoral* (L2-L4) - sensory = *anterior thigh, medial leg* - motor = quadriceps, iliopsoas, pectineus, sartorius - cause of injury = pelvic fracture - decreased thigh flexion & *leg extension*

A 43-year-old man comes to the ED with a 3-day history of persistent headaches. The patient has a past medical history of hypertension but has had poor follow-up. Blood pressure is 224/115 mmHg & pulse is 67/min. He appears mildly confused during the physical exam, but no focal neurologic deficits are noted. Fundoscopic exam shows bilateral papilledema. Serum creatinine is 1.4 mg/dL. The patient is started on an intravenous medication that causes arteriolar dilation, improves renal perfusion, & increases natriuresis. Repeat blood pressure an hour later is 182/92 mmHg with improvement of his symptoms. What agents is most likely being used in this patient?

*Fenoldopam* - short-acting, selective, peripheral *dopamine-1 receptor agonist* --> activates adenylyl cyclase & raises intracellular cyclic AMP = vasodilation of most arterial beds with decrease in systemic BP - renal vasodilation --> increased renal perfusion, diuresis, natriuresis - beneficial in patients with acute kidney injury - given IV

What substance most likely contribute the most to blood vessel dev't in a patient's tumor?

*Fibroblast growth factor* Angiogenesis drive by 2 substances: *VEGF* - increases endothelial cell motility & proliferation *FGF*-2 - endothelial cell proliferation, migration, differentiation - embryogenesis - wound repair

A 45-year-old woman comes to the clinic with a 3-month history of persistent shoulder & back pain & easy fatigability. She also has pain & stiffness in all her muscles that worsens in the morning & evening. She does not participate in any regular exercise because her pain is exacerbated with activity. She works as a computer programmer & reports some difficulty concentrating on her job. Past medical history is significant for depression & GERD, but she is not currently taking any meds. Physical exam shows normal range of motion & 5/5 muscle strength in both upper & lower extremities. Soft tissue tenderness is present at several locations bilaterally above & below the waist. What is the most likely diagnosis?

*Fibromyalgia* - widespread musculoskeletal pain in association with fatigue & neuropsychiatric disturbances (paresthesias, poor sleep, depression, difficulty concentrating) - most common in women 20-55 - tenderness at characteristic locations in soft tissues & at bony prominences - abnormal central processing of painful stimuli

Immunohistochemical analysis of melanoma indicates that the malignant cells have decreased integrin expression. These cells are likely to exhibit poor adhesion to what components of the extracellular matrix?

*Fibronectin* - large glycoproteins produced by fibroblasts & some epithelial cells - binds to integrins, matrix collagen, glycosaminoglycans = mediator of cell adhesion & migration - *correlates with malignant behavior in number of tumors, including melanoma* - integrins = fam of transmembrane protein receptors that interact with extracellular matrix by binding to collagen, fibronectin, laminin

A 7-year-old boy is brought to the ED after injuring his right knee in a bicycle accident. Physical exam shows a swollen right knee with abrasion of the overlying skin. Distal motor & sensory innervation is intact, & popliteal & pedal pulses are +2. No other significant trauma is noted. X-ray reveals a nondisplaced patellar fracture. The patient is referred to orthopedics & paced in a leg cylinder cast. On follow-up a week after cast placement, he has paresthesias & numbness at the dorsum of the right foot & weakness of dorsiflexion at the right ankle. What is the msot likely site of nerve compression in this patient?

*Fibular neck* - common peroneal nerve frequently injured via superficial location at neck of fibula Sciatic nerve branches into - common peroneal (fibular) nerve & tibilal nerve just proximal to popliteal fossa - after coursing around neck of fibula, common peroneal nerve divides into deep & superficial branches - deep peroneal nerve --> anterior compartment muscles of the leg --> dorsiflex foot & toes - superficial branch --> lateral compartment muscles --> evert the foot - superficial peroneal nerve also --> sensory branches to dorsum of foot & lateral shin

Acting bilaterally, the external oblique muscles produce what movement of the vertebral column?

*Flexion* External oblique - superficial muscle - lateral to rectus abdominis - originates from external surface of lower 8 ribs - inserts into anterior half of outer lip of iliac crest & aponeurosis of anterior wall = largest abdominal muscles Functions: - flexes trunk - posterior pelvic tilt - same side flexion - rotation of trunk to opposite side (during unilateral contraction)

A 2-year-old girl is brought to the ED 90 minutes after ingesting a drug from her mother's purse. On arrival, the child is sedated, respirations & BP are normal. What drugs is most likely to reverse the sedation?

*Flumazenil* = competitive antagonist at GABA benzo receptor Benzos - less risk of respiratory depression & coma than with barbs

A 4-cm bronchogenic cyst is an incidental finding at autopsy of a 55-year-old man. The cyst most likely arose from what embryologic structures?

*Foregut*

A 45-year-old homeless man is brought to the ED 1 hour after the sudden onset of blindness. He has alcoholism and drank approximately 2 liters of a substance he thought was ethanol. Physical exam shows sweet-smelling breath. Serum toxicology screening is positive for methanol. What substances is most likely to be the cause of blindness?

*Formic acid* - methanol metabolized to formic acid by alcohol dehydrogenase

Patient is started on alternate intravenous antiviral agent for ganciclovir-resistant CMV. She develops hypocalcemia & hypomagnesemia. What agents is the most likely cause of these side effects?

*Foscarnet* = pyrophosphate analog = sometimes used for ganciclovir-resistant CMV - can chelate calcium - foscarnet-induced renal wasting of magnesium --> hypomagnesemia - reduction in release of PTH = hypocalcemic state - both hypocalcemia & hypomagnesemia = seizures

A male neonate has a palpable midabdominal mass. Abdominal ultrasonography shows no kidneys in the normal anatomic position and a single U-shaped renal mass with two collecting systems near the aortic bifurcation. What embryologic events best explains this finding?

*Fusion of the metanephric masses* Horseshoe kidney - inferior poles of kidneys fuse abnormally - as they ascend from pelvis during fetal dev't --> get trapped under inferior mesenteric artery & remain low in abdomen - functions normally - associated with hydronephrosis, renal stones, infection, chromosomal aneuploidy syndromes

Molecules testing of cancer cells reveals a mutation in the KRAS gene that results in constitutive activation of Ras protein. Under normal circumstances, this protein is only active when bound to what substances?

*GTP* RAS genes - code for small G-proteins involved in signal transduction in Ras-MAPK pathway - 2 states = *inactive GDP-bound state* & *active GTP-bound state* - becomes activated when growth factor ligand binds receptor tyrosin kinase on cell membrane --> autophosphorylation of receptor --> GDP removal & GTP binding - activated Ras --> phosphorylation cascade = activation of mitogen-activated protein kinase (MAPK) --> enters nucleus = gene transcription

36-year-old woman with CMV who underwent kidney transplantation 2 months ago develops fever, malaise, myalgia, & leukopenia. Meds include prednisone & cyclosporine. Most appropriate treatment includes admin of what?

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

A 3-year-old girl is brought to her pediatrician for a well child checkup. She has met all of the appropriate dev'tal milestones. Her height corresponds to the 60th percentile. Osteoblasts near the growth plates of her long bones secrete matrix material, & when they become trapped in the ossified matrix, they become known as osteocytes. These osteocytes remain connected to each other by

*Gap junctions* Osteocytes - long intracanalicular processes that extend through ossified bone matrix - cytoplasmic processes send signals to & exchange nutrients & waste products with osteocytes within neighboring lamellae via gap junctions - can sense mechanical stresses & send signals to modulate activity os surface osteoblasts --> help regulate bony remodeling

A 2-year-old child has a hemorrhage in the lower GI tract. A Meckel's diverticulum is surgically resected. What kind of ectopic tissue is most likely to be present in the diverticulum?

*Gastric* Meckel diverticulum - true diverticulum - persistence of vitelline duct - may contain *ectopic acid-secreting gastric mucosa &/or pancreatic tissue* - most common congenital anomaly of GI tract

What metabolic conversion most likely contributes to exacerbated cataract formation in hyperglycemic states

*Glucose to sorbitol* Cataracts - via hyperglucemia via poorly controlled diabetes mellitus - retinal, endothelial, lens, renal mesangial, Schwann cells more vulnerable because they are unable to regulate glucose transport

A 20-year-old man is evaluated in the ED for weakness, malaise, and dark urine. The patient was treated for a bacterial skin infection several days ago. Physical exam shows scleral icterus. Lab results reveal anemia with an elevated reticulocyte count. Abnormal erythrocytes are seen on peripheral smear. What substrate flow pathway is most likely deficient in this patient?

*Glucose-6-phosphate --> 6-Phosphogluconate* - G6PD = rate-limiting enzyme of PPP --> catalyzes conversion of G6P to 6-phosphogluconolactone --> subsequently converted to 6-phosphogluconate Glucose-6-phosphate dehydrogenase deficiency - X-linked recessive disorder - episodic bouts of hemolysis when RBCs experience increased oxidative stress - oxidative damage to RBCs = hemoglobin denatures --> insoluble Heinz bodies that are removed in spleen = *bite cells* PPP - generates both NADPH & ribose-5-phosphate, a precursor for nucleotide synthesis - RBCs utilize reduced NADPH to maintain steady supply of glutathione --> neutralizes free radicals & protects cells against oxidative damage - only mechanism for RBCs to generate NADPH

A 34-year-old African-American man comes to the physician because of muscle aches & reddish brown urine for 12 hours. He began treatment with trimethoprim-sulfamethoxazole 1 day ago for otitis media. He is allergic to penicillin. A sample of blood after centrifugation shows red serum. A deficiency of what enzymes is the most likely cause of these adverse effects?

*Glucose-6-phosphate dehydrogenase* - X-linked recessive - most common human enzyme deficiency - more prevalent among African-Americans - increased malarial resistance - *decreased NADPH in RBCs --> hemolytic anemia due to poor RBC defense against oxidizing agents (fava beans, sulfonamides, primaquine, antituberculosis drugs)* - weakness, malaise, dark urine - sclera icterus - anemia with elevated reticulocyte count

A 54-year-old man with a history of cirrhosis is brought to the ED by his wife, who found him agitated & confused. She reports that he was nauseous & vomited bright red blood several times yesterday. His cirrhosis is secondary to chronic hepatitis C infection, & he has received treatment for esophageal varices in the past. Physical exam reveals abdominal distention, decreased liver span, & testicular atophy. A jerky, irregular flexion-extension tremor involving his hands is seen with wrist extension. What is most likely to be elevated in this patient' astrocytes?

*Glutamine* Hepatic encephalopathy - likely due to recent GI bleeding via increase in nitrogen absorption by gut - excess ammonia in blood --> crosses BBB = taken up by astrocytes = *increased glutamine production*

Vitamin B6 (pyridoxine) is required for the enzyme that catalyzes the rate-limiting step in heme synthesis. What step in the pathway involves B6?

*Glycine & succinyl-CoA --> Aminolevulinic acid* - via Aminolevulinate synthase = rate-limiting step - disease = sideroblastic anemia (X-linked)

A 59-year-old man comes to the ED because of fever & shaking chills for 24 hours. He completed a course of fluorouracil for a neoplasm 1 week ago. His temperature is 39 C (102.2 F), & BP is 85/60 mmHg. Physical exam shows no other abnormalities. His hematocrit is 30%, leukocyte count is 400/mm^3, & platelet count is 100,000/mm^3. What agents will most specifically complement antibiotic therapy in this patient?

*Granulocyte colony-stimulating factor* Febrile neutropenia post-chemotherapy - low WBC count --> fatal gram negative organism sepsis - management = blood culture followed by antibiotics --> give granulocyte colony stimulating factors to induce synthesis of neutrophils

What labeled region of the sarcomere contains only thick filaments and no thin filaments?

*H band* - portion of A bands that straddles M line - AHM - *completely disappears*

An unimmunized 10-month-old girl is brought to the ED because of temperatures to 40 C (104 F) & listlessness for 24 hours. Exam shows a stiff neck. Leukocyte count is 24,000/mm^3. Gram stain of CSF shows small pleomorphic gram-negative bacteria that require NAD & hemin for growth. A vaccine for what organisms would have prevented this infection?

*Haemophilus influenza* - chocolate agar with factor V (NAD) & X (hematin)

A 35-year-old man is admitted to the hospital after sustaining multiple injuries in a motor vehicle accident. He undergoes surgery for an open fracture of the tibia and a spiral fracture of the humerus. The tibial repair is successful, but the surgeon operates on the wrong arm. What procedures would be most effective in preventing a similar error?

*Have the nurse and surgeon verify the surgical site independently* According to Joint Commission's sentinel event statistics... - wrong-site surgery = most frequently reported serious adverse event - preoperative verification = important to decrease risk - mark operative site! - *independent verification* of patient, procedure, & site by 2 healthcare workers (nurse & physician) should be performed

Tendency of study subjects to change their behavior as a result of their awareness that they are being studied.

*Hawthorne effect* (observer effect)

Autopsy of a 21-year-old Caucasian male shows extensive atrophy of basal ganglia & increased brain copper content. The main mechanism of excess copper removal in the healthy human body is

*Hepatic excretion into bile* Wilson's disease - AR - toxic accumulation of copper within organ tissues Normally... - 60% of ingested copper (0.6 - 3 mg/day) absorbed in stomach & duodenum, loosely bound to circulating albumin --> transported to liver --> incorporated into alpha2-globulin to form ceruloplasm --> resecreted into plasma = 90-95% of circulating copper - normal total body copper = 50-150 mg - senescent ceruloplasmin & remainder of ingested, unabsorbed copper = secreted into bile & excreted into stool = primary route for copper elimination

What cells secrete substance that controls iron storage & release by other cells involved in iron homeostasis (hepcidin: acute phase reactant synthesized by liver that acts as central regulator of iron hemeostasis)

*Hepatic parenchymal cells* Hepcidin - acute phase reactant - synthesized by liver - acts as *central regulator of iron homeostasis* - influences body iron storage via interaction with *ferroportin*

A 43-year-old man brought to the ED has the following arterial blood gas readings: pH = 7.25 pCO2 = 70 mmHg HCO3- = 25 mEq/L The patient most likely suffers from what conditions?

*Heroin overdose* Hypoventilation = increase in pCO2 & decrease in serum pH (*respiratory acidosis*) *Acute* respiratory acidosis - low pH - high pCO2 - normal to mildly increased HCO3- because renal compensation requires at least 24 hours of persistent respiratory acidosis

An unimmunized 2-year-old girl is brought to the ED after having a generalized tonic-clonic seizure. She has had a fever & an upper respiratory tract infection for the past 4 days. A gram stain of CSF show numerous gram-negative coccobacilli. What vaccines would most likely have prevented this infection?

*Hib* - vaccine contains type b capsular polysaccharide (polyribosylribitol phosphate) conjugated to diphtheria toxoid or other protein - given between 2 & 18 months og age Haemophilus influenza - small gram negative (*coccobacilli*) rod - meningitis, febrile convulsions, otitis media, pneumonia

A 55-year-old man comes to the office for evaluatin of chronic muscle weakness. Over the past several months, the patient has had increasing difficulty walking up stairs & lately has noticed difficulty combing his hair & lifting objects overhead. His temperature is 98 F (36.6 C), BP is 125/80 mmHg, & pulse is 78/min. On exam, the patient has symmetric proximal muscle weakness & mild muscle tenderness. There is no skin rash. Muscle biopsy reveals an endomysial mononuclear infiltrate & patchy muscle fiber necrosis. An autoantibody directed against what antigens in most likely to be seen in this patient?

*Histidyl-tRNA synthetase* (anti-Jo-1) Antinuclear antibodies (ANA) Polymyositis - middle aged with insidious onset of symmetric proximal muscle weakness affecting upper & lower extremities - muscle enzyme (serum creatinine kinase, aldolase) levels elevated - endomysial mononuclear inflammatory infiltrate & patchy muscle fiber necrosis - paraneoplastic manifestations = adenocarinoma, etc

The majority of cellular proteins & RNA are synthesized throughout the cell cycle & are only interrupted briefly during M phase. Synthesis of what proteins occurs predominately in S phase of the cell cycle?

*Histones* DNA Synthesis = S phase

A 38-year-old man comes to the office due to pain in multiple joints. He has a 5-year history of lumnar pain & a 2-year history of bilateral knee pain. The patient works in construction & his pain is worst after a long day on his feet. He has taken ibuprofen intermittently, but the pain is no longer tolerable. The patient has a paternal aunt with osteoarthritis. Physical exam shows blue-black spots on his sclera & diffuse darkening of auricular helices. What is the most likely cause of this patient's arthritis?

*Homogentisic acid dioxygenase deficiency* Alkaptonuria - relatively benign childhood disorder - severe arthritis in adult life - AR - *deficiency of homogentisic acid dioxygenase*, which normally metabolizes homogentisic acid into maleylacetoacetate - accumulated homogentisic acid = pigment deposits in CT throughout body - adulthood = *blue-black deposits* become apparent in sclerae & ear cartilage - urine turns black when exposed to air due to oxidation of homogentisic acid

A 72-year-old woman is brought to the ED after lying on the floor in her home for the past 2 days. The patient's neighbor called polic after phone calls were not answered & no one opened the door. She was found awake on the bathroom floor lying in feces & urine. The patient says she fell & injured her right hip & was unable to get up to call for help. She did not eat or drink anything during that time. On exam, the patient appears dehydrated & has right hip tenderness. Lab studies show serum glucose of 72 mg/dL & positive urine ketones. Radiographs of the right hip show a right femoral neck fracture. Increased activity of what enzymes is most likely contributing to both serum & urine lab findings?

*Hormone-sensitive lipase* = enzyme in adipose tissue - catalyzes mobilization of stored triglycerides into FFAs & glycerol - activated in response to stress hormones (catecholamines, glucagon, ACTH) --> stimulate Gs protein-coupled receptors on adipocytes --> increased cAMP & activated PKA --> phosphorylates & activates HSL --> lipolysis - inhibited by release of insulin Triglyceride metabolism during fasting: = presence of ketones in urine & maintenance of fasting blood glucose in low-normal range despite prolonged fasting

A 42-year-old woman comes to the office due to several months of episodic shortness of breath & cough. The patient has a history of migraines & occasionally takes acetaminophen. She is a school teacher & does not use tobacco, alcohol, or illicit drugs. Her temperature is 36.1 C (97 F), blood pressure is 110/80 mmHg, & pulse is 84/min. Pulse oximetry shows 96% on room air. Lung exam & chest x-ray are normal. Spirometry shows FEV1 is 71% of predicted value. Sputum analysis shows predominant eosinophils. The patient's symptoms are most likely related to exposure to what?

*House dust mites* Intermittent respiratory symptoms (dyspnea, cough) in setting of normal chest x-ray, sputum eosinophils, reduced FEV1 (< 80% predicted) = *asthma* - common aeroallergens = *dust mites*, cockroaches, pet dander, mold, pollen

A 38-year-old man comes to the physician because of involuntary movements of the arms and legs for the past month & progressive facial twitching and grimacing over the past year. Neurologic exam shows athetoid & choreiform movements of the arms & legs, dystonic movements of the tongue, dysarthria, impairment in immediate & short-term memory, & dyscalculia. What is the most likely diagnosis?

*Huntington's disease* - choreoathetosis & dementia - manifests between age 20 & 50

A 40-year-old woman is brought to the ED due to involuntary movements, ataxia, & tremor. Her symptoms started gradually 2 weeks ago & have worsened acutely over the past 2 days. She is having difficulty walking & almost fell while getting up from a chair. The patient's medical problems include bipolar disorder & recently diagnosed HT. Her meds include a stable dose of lithium for many years for bipolar disorder & a new blood pressure med started 2 months ago for HT. Neurologic exam reveals a resting tremor & difficulty with balance. Resting ECG shows normal sinus rhythm & nonspecific T wave abnormalities. What agent is most likely being used to treat this patient's HT?

*Hydrochlorothiazide* = Thiazide - limits sodium reabsorption in distal tubule --> mild volume depletion --> stimulates proximal tubular sodium/lithium reabsorption = lithium toxicity Lithium - drug interactions = *thiazides*, NSAIDs, ACEIs, Tetracyclines, Metronidazole

Shadow develops suddenly across visual field of one eye. Patient has no recent headaches, double vision, vertigo, light sensitivity, or nausea. Pupils are equal & reactive to light. Visual field testing by confrontation reveals patchy loss of vision. A flame-shaped retinal hemorrhage in the affected eye is noted on fundoscopic exam. What is the most likely cause of his visual disturbance?

*Hypertension* Acute retinal hemorrhage = arrow = via severe, poorly controlled HT - painless, unilateral visual disturbances - severe HT in retinal precapillary arteriole = endothelial disruption, leakage of plasma into arteriolar wall, *fibrinoid necrosis* - necrotic vessels --> bleed into nerve fiber layers = dot- & flame-shaped hemorrhages

A 45-year-old man who is undergoing dialysis for chronic renal failure starts receiving erythropietin therapy. He has a history of type I diabetes mellitus, peripheral neuropathy, & well-controlled HT. Exacerbation of what is most likely to occur in this patient?

*Hypertension* Erythropoietin - exacerbates HT --> more cells in lumen of blood vessels --> turbidity & chaos

A 58-year-old man comes to the ED due to sudden right-sided weakness. He has no sensory loss, problems speaking/swallowing, or difficulty with balance. The patient was previously told that he has elevated BP, but he does not routinely follow up with his physician. His mother has coronary artery disease & his father died of stroke. He takes no meds. Exam shows intact cranial nerves & sensory function. The patient has decreased strength (3/5) on right side. Initial CT scan without contrast reveals no abnormalities. Four weeks later, repeat brain imaging reveals a 9-mm, fluid-filled cavitary lesion in the left internal capsule. This patient's condition is most likely cause by...

*Hypertensive arteriolar sclerosis* - pure motor hemiparesis & small cavitary lesion in internal capsule = lacunar infarct = primarily caused by chronic HT --> lipohyalinosis, microatheroma formation, hardening/thickening of vessel wall (*HT arteriolar sclerosis*) - in acute setting, CT imaging may not reveal expected hypodensity of ischemic stroke via small infarct size (< 15 mm) --> after several weeks = necrotic lesions turn into cavitary spaces filled with CSF & surrounded by scar tissue called lacunas

Which of the labeled areas in the electron micrograph of skeletal muscle almost disappears when the muscle is maximally contracted?

*I* band I band - almost completely disappears H band - completely disappears

Indicated for patients with deficiency of IL-12 receptor

*IFN-gamma* IL-12 --> stimulates differentiation of naive T-helper cells into TH1 subpopulation Deficiency - severe mycobacterial infections via inability to mount strong cell-mediate granulomatous immune response

A biopsy from a Crohn's patient demonstrates reduced inflammation in regions of previously active ileoclitis. An increase in what cytokines is most likely responsible for the observed changes?

*IL-10* - reduces production of pro-inflammatory TH1 cytokines (IL-2 & IFN-gamma) & MHC-II expression - inhibits dendritic cells & macrophages - protective effect in Crohn's disease - overproduction of pro-inflammatory cytokines leads to pathology such as that observed in inflammatory bowel diseases

Sensitized TH2 cell exposed to inhaled allergens can produce a substance that promotes B-lymphocyte class-switching to synthesize IgE. This substance is

*IL-4* - TH2 cells secrete IL-4 & other lymphokines to stimulate B-cell Ab production as part of humoral adaptive immunity - TH2 helper cells also release IL-13 which, together with IL-4, preferentially promotes B-cell IgE production

A 40-year-old woman comes to the office due to new-onset genital lesions. On exam, she is found to have several genital warts in her vaginal area. Other tests for sexually transmitted diseases are negative. The patient admits to having a brief extramarital affair while traveling for business. The following week, the physician receives a phone call from the patient's husband, who is not a patient in the practice. He knows his wife was recently seen & would like info regarding her health as he is concerned about his physical symptoms. What would be the most appropriate response by the physician?

*If your spouse is a patient here, she would have to provide a release of info* HIPAA - protects patient privacy & confidentiality - *physician can respond to fam member's request for info only if patient has specifically provided verbal or written authorization for release of info to fam member* - written release of info doc preferred to protect from misunderstanding

In a student lab session, a male student finds erythrocytes in his urine. This finding is confirmed by the hospital lab. He denies any history of renal problems or recent illness. Vital signs are within normal limits. Antistreptolysin O titer is less than 1:100. Microscopic exam of urine is unremarkable except for rare red cell casts. There is no proteinuria. The most likely diagnosis is

*IgA nephropathy* - presents as occasional hematuria withount any other problems - most common nephropathy in the world

A healthy 6-day-old baby girl is brought to the office for her first well baby checkup. This is the mother's second child. She was born full-term, with a birth weight of 4200 grams (9.3 lb.) & a length of 51 cm (20 in). APGAR scores were 8 at 1 minute and 9 at 5 minutes. She was recently discharged from the well baby nursery 3 days ago. The baby's blood type A negative while the mother is B negative. High circulating levels of anti-A Abs are found in the mother's blood. Hemolysis did not occur in the baby because these maternal Abs are most likely of what class?

*IgM* Erythroblastosis fetalis & Hemolytic disease of newborn (HDN) - caused by maternal anti-fetal erythrocyte Abs = causes type II (Ab-mediated) HS response - implicated maternal Abs = IgG subtype = only class that can cross placenta - *with maternal blood types A & B, isoimmunization does not occurs as naturally occurring Abs (anti-A & -B) are of IgM type = cannot cross placenta* - type O mothers have Abs predominantly of IgG type

6-year-old boy evaluated for recurrent infections & failure to thrive. He has been hospitalized for pneumococcal pneumonia twice & has had 5 episodes of otitis media, requiring placement of tympanosotomy tubes. The patient also has a history of prolonged diarrhea caused by Cryptosporidium parvum. Physical exam shows large tonsils, palpable lymph nodes, & hepatosplenomegaly. Further evaluation shows that the patient has defective signaling between CD4+ T cells & B lymphocytes. What immunoglobulins likely has the highest serum concentration in this patient?

*IgM* Hyperimmunoglobulin M syndrome - defect in class switching in B lymphocytes - defective CD40L on Th cells --> class switching defect - high IgM - low IgG, IgA, IgE - recurrent sinopulmonary, GI, & opportunistic infections (Pneumocystis, Cryptosporidium)

The cystic fibrosis transmembrane conductance regulator (CFTR) consists of a single peptide chain with transmembrane segments & extracellular & intracellular regions. What peptide segments of CFTR is most likely located in a transmembrane segment?

*Ile-Phe-Val-Leu-Ile-Trp-Cys-Leu* CF - due to defect in CFTR gene on chromosome 7, deletion of *Phe508* - look for sequence with Phe!!!

Where is the optical cannulation site for the femoral vein?

*Immediately medial to femoral artery* 1 cm below inguinal ligament Femoral vein catheter - in patients with unavailable preferred access sites (subclavian, jugular vein)

A 5-year-old boy with a history of recurrent ear infections receives his preschool booster immunization against diphtheria-tetanus-pertussis. He is participating in a community-sponsored study to determine the humoral immune response to tetanus toxoid (tt). His response is well below normal for age- & sex-matched children. Peripheral B lymphocyte count & T lymphocyte count & function are within reference range. The antibody he makes is positive in both the passive hemagglutination & complement-mediated lysis of tt-coated erythrocytes. His antibodies do not opsonize tt-coated latex particles for phagocytosis & do not directly precipitate tt efficiently. This child most likely has a defect in what processes?

*Immunoglobulin isotype switching* Hyper-IgM syndrome - defective signaling between CD4+ T cells & B cells - *X-linked recessive* - severe pyogenic infections early in life - opportunistic infections = Pneumocystis, *Cryptosporidium*, CMV - fail to make germinal centers - *isotype switching patient has normal B & T cells* - complement can be activated by opsonization does not take place = IgG absent; IgM present

A 55-year-old woman who is obese comes to the physician because of daytime drowsiness, early morning headaches, & swollen ankles. During the interview, she says, "My husband tells me I snore too loudly. He can't get any sleep because of it." Echo shows an enlarged right ventricle & poor right ventricular function. What is most likely responsible for the dev't of right ventricular failure in this patient?

*Increased pulmonary artery pressure* Obstructive sleep apnea - pulmonary HT

A bacterium harboring a 15,000-base pair (bp) plasmid that encodes resistance to tetracycline & ampicillin segregates mutants that lose resistance to either drug. Each independent mutant plasmid appears to increase in size by approximately 5200 bp. What molecular event best explains these findings?

*Insertion of a transposon* Transposition = segment of DNA (transposon) that can "jump" (excision & reintegration) from one location to another - can transfer genes from plasmid to chromosome - excision --> may include some flanking chromosomal DNA = can be incorporated into plasmid & be transferred to another bacterium (ex. vanA gene from vancomycin-resistant Enterococcus to S aureus)

A 35-year-old woman comes to the hospital due to sudden-onset numbness of the left arm & face. The patient has no weakness but has had several days of generalized headache, dyspnea on exertion, & easy fatigability. She has a history of well-controlled asthma. Temperature is 37.7 (99.8 F), blood pressure is 110/60 mmHg, & pulse is 80/min. Light touch sensation is decreased in the left upper extremity & the lower left face. Strength & reflexes are normal. Cardiopulmonary & abdominal exams are unremarkable. She has no skin rash. Lab results are as follows: Hemoglobin = 8.6 g/dL Platelets = 24,000/mm^3 Blood urea nitrogen = 32 mg/dL Creatinine = 1.9 mg/dL Prothrombin time & activated partial thromboplastin time are normal. Peripheral blood smear shows numerous schistocytes. Urinalysis is positive for hematuria & proteinuria. What is the most likely primary pathogenesis of this patient's current condition?

*Impaired cleavage of von Willebrand factor* Thrombotic thrombocytopenic purpura (TTP) - new-onset neuro symptoms, anemia, schistocytes, thrombocytopenia, acute kidney injury - left arm & lower facial sensory loss = pure sensory lacunar stroke - exertional dyspnea & easy fatigability = secondary to anemia - via *deficiency of ADAMTS13* = von Willebrad factor (vWF)-cleaving protease - *large uncleaved vWF multimers more prothormbotic --> diffuse microvascular thrombosis* - *thrombocytopenia & microangiopathic hemolytic anemia* with schistocyte formation

What is the most likely consequence of impaired synthesis of interleukin-1 (IL-1)?

*Impaired function of T lymphocytes* IL-1 - secrete by monocytes, macrophages, B cells, dendritic cells, endothelial cells Target cell/tissue of IL-1 - TH cells --> costimulate activation - B cells --> promotes maturation & clonal expansion - NK cells --> enhances activity - macrophages & neutrophils --> chemotactically attracts - hypothalamus --> fever

A 3-month-old infant is irritable, feeds poorly, & frequently vomits. His current weight is at the 45th percentile & his head circumference is at the 96th percentile. Fundoscopy reveals white-yellow chorioretinal lesions in both eyes. Head CT shows enlarged ventricles and scattered intracranial calcifications. What is the most likely cause of this patient's condition?

*In utero infection* Congenital toxoplasmosis = hydrocephalus, intracranial calcifications, & chorioretinitis - *fetus affected only if mom infected during 1st 6 months of pregnancy*

A 45-year-old man has a MI. A coronary stent restores blood flow, but reperfusion causes a paradoxical increase in damage. What is the most likely mechanism of the new myocardial damage?

*Increase in lipid peroxidation of membranes* Reperfusion injury - associated with generation of free radicals - leads to hypercontraction of myofibrils through increased free calcium influx

K & Vmax in Competitive Antagonist

*Increased K* - think *K*ompetitive Antagonist = increased *K* Vmax = no change

Renal compensatory response for Respiratory acidosis

*Increased NH4Cl excretion* - enhances H+ removal - acidifies urine

What process is most responsible for the development of gallstones in Crohn disease?

*Increased bile acid wasting* - mucosa of terminal ileum inflamed --> bile acids lost in feces --> lesser amount of bile acid present in bile --> ratio of cholesterol/bile acids increases

A 60-year-old man comes to the physician for a follow-up exam. He had a myocardial infarction of the right ventricle 3 weeks ago. Physical exam shows an accumulation of free fluid in the peritoneal space. What mechanism is the most likely cause of this finding?

*Increased capillary hydrostatic pressure* Right HF - increased pressure in venules with resultant back-pressure on capillaries --> increased hydrostatic pressure --> transudate in peritoneal cavity & all dependent areas of body, like feet & sacral region

A 37-year-old woman, gravida 3 para 1, at 28 weeks gestation comes to the office due to loss of urine with cough. She reports fetal movement & has had an uneventful pregnancy. Several years ago she had a spontaneous vaginal delivery of a 3.5-kg infant. The patient has had no medical problems or surgeries. Her prepregnancy BMI is 32 kg/m^2. She has gained appx 15.88 kg (35 lb) during this pregnancy. Urine culture is negative. What is the most likely mechanism for this patient's urinary incontinence?

*Increased intraabdominal pressure* Stress urinary incontinence - gravid uterus & maternal weight gain increase intraabdominal pressure - pregnancy hormone also decrease urethral tone & relax pelvic floor muscle (levator ani, coccygeus) - laughin, coughing, other exertions = additional increases in intraabdominal pressure --> exceeds pressure point that maintains closure of urethral valve

Relative to the normal values for parameters that govern capillary exchange, what is the most likely cause of the edema that results from use of a venous occlusive tourniquet?

*Increased mean capillary hydrostatic pressure* Capillary hydrostatic pressure (Pc) - drives fluid out of capillary

A 3-year-old boy is brought to the physician with jaundice and pallor. He was adopted and his fam history is unknown. Lab studies show anemia, reticulocytes, & increased indirect bilirubin. A peripheral blood smear shows RBCs without central pallor. This patient is most likely to have what additional findings?

*Increased mean corpuscular hemoglobin concentration* Hereditary spherocytosis - anemia, reticulocytes, increased indrect bilirubin = hemolytic anemia - *RBCs without central pallor (spherocytes)* - *red cell index most specific for spherocytosis = elevation in mean corpuscular homoglobin concentration (MCHC)*

A 58-year-old man comes to the physician because of blood in his urine. He had a nephrectomy 10 years ago because of injuries sustained in a motor vehicle collision. Evaluation shows renal cell carcinoma in his remaining kidney & pulmonary metastases. Interleukin-2 (IL-2) therapy is started. Three weeks later, CT scan confirms regression of the tumor. What most likely caused the regression?

*Increased natural killer cell activity* Interleukin-2 - secreted by all T cells - stimulates growth of helper, cytotoxic, & regulatory T cells, & *NK cells*

A 52-year-old man is found to have HT during a routine examination. A systolic bruit is heard over the left renal artery. Angiography shows a discrete 95% obstructive lesion within the left renal artery; the right renal artery is normal. The right kidney is 11 cm, and the left kidney is 8.5 cm. What describes the most likely response to treatment?

*Increased plasma renin activity following administration of an ACEI* Aldosterone = final product of RAAS --> negative feedback on renin - add ACEI --> negative feedback pathway will be interrupted = increased renin Renal artery stenosis = increased renin with accompanying secondary hyperaldosteronism

A 62-year-old man with a long history of HT comes to the physician for a routine physical exam. His BP is 150/90 mmHg & heart rate is 74/min & regular. Cardiac auscultation shows a presystolic sound that immediately precedes the first heart sound & is best heard during expiration when the patient is lying on his left side. Chest x-ray reveals extensive calcification around the mitral & aortic valves. What is the most likely explanation for the additional heart sound?

*Increased stiffness of the left ventricular wall* S4 - extensive left ventricular hypertrophy via long-standing HT - calcifications on x-ray = degenerative mitral annular & aortic valve calcifications associated with systemic HT - sign of diastolic dysfunction - sudden rise in end-diastolic ventricular pressure caused by atrial contraction against ventricle that has reached elastic limit - any condition that = reduced ventricular compliance - low-frequency late diastolic sound

A 63-year-old man comes to the ED due to dyspnea. Over the past several days, the patient has experienced progressively worsening shortness of breath while walking his dog around the block. In addition, he could not breathe while lying in bed last night & fell asleep only after moving to the recliner. The patient experienced an acute MI 2 years ago & has been noncompliant with his meds & follow-up appointments. His temperature is 36.7 C (98 F), BP is 122/74 mmHg, pulse is 94/min, & respirations are 22/min. Physical exam reveals bibasilar lung crackles, jugular venous distention, & bilateral pitting lower extremity edema. Chest x-ray shows cardiomegaly & pulmonary venous congestion. What is most likely contributing to this patient's symptoms?

*Increased sympathetic nervous system activity* Acute decompensated heart failure - reduced cardiac output & excessive ventricular filling pressures --> compensatory neurohumoral stimulation = mediated via *increased sympathetic nervous system activity*, stimulation of RAAS, & release of ADH

Functions by stimulating insulin release following oral consumption of glucose.

*Incretins* Hormones with incretin effects = *glucagon-like peptide-1 (GLP-1)* = gastric inhibitory peptide (glucose-dependent insulinotropic peptide, GIP) Incretin-stimulated insulin release = independent of increase in insulin secretion brought on by elevations in blood glucose level

An 85-year-old woman has a malignant neoplasm in the wall of the sigmoid colon. To what groups of lymph nodes is the neoplasm most likely to metastasize initially?

*Inferior mesenteric* - colon from splenic flexure to upper rectum

Designed to prevent propagation of DVT from legs to lung vasculature & are used in patients who have contraindications to anticoagulation.

*Inferior vena cava (IVC) filter* - remember: left side of image corresponds to patient's right side - IVC courses through abdomen & inferior thorax in location anterior to right half of vertebral bodies - renal veins join IVC at L1/L2 - common iliac veins merge to become IVC at L4

A 23-year-old man is brought to the ED after he was stabbed in the right upper quadrant of the abdomen. His blood pressure is 70/42 mmHg, pulse is 135/min, & respirations are 26/min; pulse oximetry shows oxygen saturation of 95% on room air. Physical exam shows a stab wound 2 cm inferior to right costal margin. The patient's abdomen is firm & distended. Focused assessment with sonography for trauma (FAS) is positive for blood in the right upper quadrant. He is taken for immediate laparotomy, & approximately 1 liter of blood is evacuated from the peritoneal cavity. Brisk, nonpulsatile bleeding is seen emanating from behind the liver. The surgeon occludes the hepatoduodenal ligament, but the patient continues to hemorrhage. What structures is the most likely source of this patient's bleeding?

*Inferior vena cava* - portal triad runs through hepatoduodenal ligament = hepatic artery, portal vein, common bile duct --> occlusion = Pringle maneuver --> if liver bleeding does not cease when portal triad is occluded, it is likely there has been injury to *inferior vena cava* or hepatic veins

A 29-year-old nulliparous woman comes to the ED with right-sided pelvic pain. The pain is sharp & came on suddenly while she was shoveling snow this morning. It is accompanied by nausea & is worse with movement. The patient's last menstrual period was 2 weeks ago. Her temperature is 37.8 C (100 F), blood pressure is 100/60 mmHg, & pulse is 92/min. Pelvic ultrasound reveals a normal-sized uterus & left ovary, & a right adnexal mass measuring 6 cm with no blood flow to the ovary. Urine beta-hCG is negative. The patient's condition most likely involves pathology in what structures?

*Infundibulopelvic ligament* / Suspensory ligament of the ovary - houses ovarian nerve plexus - how ovary is suspended posterolaterally to uterus - blood supply to ovary Ovarian torsion - rotation of ovary around IP ligament - main risk factor = presence of large ovarian mass (cyst, neoplasm) - occludes ovarian vessels & nerves - sudden-onset *unilateral pelvic pain* & nausea - sometimes vomiting & fever - pelvic ultrasound = first-line diagnostic test = decreased or no blood flow to ovary

Likely decreased in patients with inactive FSH receptors

*Inhibin B* FSH receptor defects - high FSH (no negative feedback from inhibin B) - normal LH & testosterone because FSH does not play role in either LH or testosterone feedback

A 27-year-old woman who is seropositive for HIV is taking two different reverse transcriptase inhibitors & a protease inhibitor. What best explains the beneficial action of the protease inhibitor in this combination?

*Inhibiting protein that permits DNA chain elongation* Protease inhibitors - prevent maturation of new viruses

Renal mechanism of action of hydrochlorothiazide

*Inhibits Na+-Cl- symporter* Thiazide diuretics - inhibit NaCl reabsorption in early DCT - decreased Ca2+ excretion = hydrochlorothiazide, chlorthalidone, metolazone

CAAT on DNA coding strand is responsible for what functions?

*Initiation of transcription* CAAT box = highly conserved (consensus) sequence that functions as *promoter of transcription* in *eukaryotic* genome = 70-80 bases upstream from transcription start site Hogness (TATA) box = second promoter region in eukaryotic genome = 25 bases upstream from transcription start site Both CAAT box & TATA box promote initiation of transcription by acting as binding sites for general *transcription factors & RNA polymerase II*

What component of the second-messenger cascade is directly responsible for release of intracellular stores of Ca2+?

*Inositol 1,4,5-triphosphate*

Binding specificity for extracellular matrix proteins, such as fibronectin & laminin, to cell membranes depends on what classes of proteins?

*Integrin* = membrane proteins that maintain integrity of basolateral membrane by binding to collagen & laminin in basement membrane

A 32-year-old man is recovering from extensive burns. Fibroblasts near the site of injury actively synthesize precursor mRNA to be used as templates for protein synthesis. After transcription, extensive processing of the precursor RNA occurs to form the finalized mRNA sequence. The finalized mRNA then exits the nucleus & undergoes translation by ribosome complexes before being degraded. What steps involving the processing & handling of mRNA occurs only within cytoplasm of cells?

*Interaction with P bodies* mRNA first transcribed from DNA = unprocessed form called pre-mRNA/heterogeneous nuclear mRNA (hnRNA) - processing steps (5'-capping, poly A tail addition, intron splicing) --> finalized mRNA can leave nucleus - *cytoplasmic P bodies play role in mRNA translation regulation & mRNA degradation*

A 25-year-old woman gravida 1, para 0, who is Rh-negative, delivers a full-term Rh-positive neonate. The mother is given prophylactic anti-Rho(D) immune globulin immediately post partum. During her second pregnancy 3 years later, she is screened each trimester for Rho(D) antibodies. An indirect antiglobulin test done during the third trimester indicates the presence of anti-Rho(D) antibodies in her serum. What is the most likely mechanism for the occurrence of these maternal antibodies?

*Intrauterine transplacental fetal-maternal hemorrhages during the second pregnancy* In the new pregnancy... - mother against at risk of becoming "actively immunized" against D-antigen if child is Rh+ - active immunization occurs only if mother's blood is exposed to fetal blood Exposure can occur either "during pregnancy" or "at birth" during pregnancy... - *intrauterine transplacental fetal-maternal hemorrhages* - invasive procedure (like amniocentesis or fetal blood sampling) Direct connection of infant's antigens with mother's blood = antibodies formation in mother's blood

A 72-year-old man is hospitalized for acute exacerbation of CHF. His other med problems include HT, coronary artery disease, peripheral vascular disease, hypercholesterolemia, prostate cancer, & mild neurocognitive disorder. The patient is stabilized medically & discharged home to live with this daughter, who has supervised his meds in the past. A week later, he is rehospitalized with recurrent heart failure exacerbation. The patient thinks he took his meds appropriately since being discharged, but a pill count shows that he did not take the majority of his prescribed drugs. The daughter is contacted & says she organizes his pills daily & explains what meds he needs to take before leaving for work. What interventions would likely have prevented this outcome?

*Involvement of a social worker in discharging planning* - patient's relapse & rehospitalization liekly due to poor med adherence = stems from cognitive impairment - during hospitalization, social worker can contact or meet with involved fam members & assess whether there any social factors affecting patient's ability to return home - speaking with daughter earlier may have allowed health care team to identify potential barrier to adherence (daughter's job) & develop alternate strategy Effective discharge planning requires collaboration of multiple disciplines (physician, nurse, social worker)

A 12-year-old boy is evaluated in the clinic due to excessive bleeding following a tooth extraction. The patient also develops large bruises after only minor injury but has had no major bleeding episodes in the past. His maternal uncle died from an intracranial hemorrhage. Lab testing reveals decreased coagulation factor VIII activity levels. A referral is made to a clinical geneticist, who suspects that the patient has a deletion mutation in the enhancer sequence of the factor VIII gene. This mutation has resulted in decreased transcription of factor VIII by RNA polymerase II. What is the most accurate statement regarding the abnormal genetic sequence in this patient?

*It can be located upstream, downstream, or within introns of the gene* - Hemophilia A can be caused by a variety of different mutations in factor VIII gene, including deletions in enhancer sequence - eukaryotic genes have associated promoter & enhancer sequences that mediate transcription - enhancer sequences bind activator proteins that facilitate bending of DNA --> allows activator proteins to interact with general transcription factors & RNA pol II at promoter --> increased rate of transcription Enhancers & silencers may be upstream, downstream, or within transcribed gene

A new aminoglycoside antibiotic is developed that is believed to be particularly effective against Pseudomonas. The volume of distribution of the drug is measured in a group of volunteers and is determined to be 4.5. This new drug is most likely to have what properties?

*It is highly charged* - average total body water = 41 L E xtracellular fluid volume = 14 L = 1/3 of total body water --> plasma volume = 3L Drugs that remain in plasma compartment with Vd low - large molecular weight - bound extensively to plasma proteins - highly charged (hydrophilic)

A 35-year-old woman comes to the physician because of intermittent tingling & numbness of her feet during the past 6 months. She has a 30-year history of type 1 diabetes mellitus. Sensation of joint position is decreased in the toes & ankles, & vibration sense is decreased in the feet. There are decreased ankle jerks bilaterally. Pathologic changes of what most likely occurred in this patient?

*Large-diameter axons of the distal portions of peripheral nerves* Decreased ankle jerk reflex - Ia muscle spindle afferent & Ib golgi tendon organs = largest diameter nerve fibers - slow conductors Diabetes mellitus - distal peripheral neuropathy --> sensations affects carried by heavily myelinated axons / large diameter axons

A prospective study evaluates the relationship between regular antioxidant use (vitamin C & vitamin E) & risk of stroke in men age 40-60. The results of the study were adjusted to account for confounding variables. According to the study results, the men who consumed antioxidants for at least 5 years have a stroke relative risk of 0.75 (p <0.01). In contrast, the men who consumed antioxidants for less than 5 years have a stroke relative risk of 0.95 (p = 0.45). What factors likely explains why the relative risk of stroke is lower with longer antioxidant use?

*Latent period* - p-value of 0.45 for second result = small reduction in risk is not statistically significant --> used of antioxidants < 5 years = no appreciable benefit on stroke risk reduction - stroke risk reduction through antioxidant use is associated with long latent period - at least 5 years of continuous exposure to antioxidants were required to reveal protective effect of exposure on outcome (stroke)

A 61-year-old man has had weakness of the left leg for 6 months. Exam shows increased muscle tone & reflexes in the left lower extremity, & an extensor plantar response on the left. What labeled sites on the spinal cord is most likely damaged?

*Left lateral corticospinal tract* - corticospinal is ipsilateral until decussation of them in medulla/pyramid - if there was a lesion above this area, then it would be contralateral

Increase in what is most likely to increase the plateau value of the expiratory flow rate?

*Lung volume*

A 47-year-old morbidly obese woman comes to the physician seeking advice regarding weight loss. She has tried diet & exercise a number of times without success. Her other medical problems include type 2 diabetes mellitus & obstructive sleep apnea. Her body mass index is 43 kg/m^2. After a discussion about available surgical options, she expresses interest in the adjustable gastric band, an inflatable silicone device that is placed around the cardiac part of the stomach. In order to encircle the stomach, the band must pass through what structures?

*Lesser omentum* = double layer of peritoneum that extends from liver to lesser curvature of stomach = 2 ligaments: hepatogastric (connects to lesser curvature of stomach); hepatoduodenal (connects duodenum) Adjustable gastric banding - type of restrictive bariatric surgery for obese patients - inflatable silicone device placed around gastric cardia - intended to slow passage of food - to encircle upper stomach, gastric band must pass through lesser omentum

A 52-year-old postmenopausal woman comes to the office due to leakage of a few urine drops with coughing & sneezing. She has no dysuria, urgency, or changes in urinary frequency. The patient has had 3 spontaneous vaginal deliveries. Physical exam is notable for a mild cystocele. The patient is advised to perform exercises to strengthen her pelvic floor as part of treatment for her symptoms. What structures is the most likely target of the exercise?

*Levator ani muscle* = iliococcygeus, pubococcygeus, puborectalis - hold bladder & urethra in appropriate anatomic position - injury = urethral hypermobility &/or pelvic organ prolapse (cystocele) Pelvic floor = levator ani muscle - forms U-shaped sling around pelvic viscera

A 49-year-old woman is brought to the ED with squeezing chest pain & profuse sweating for the last 2 hours. Past medical history includes diest-controlled type 2 diabetes mellitus. ECG reveals ST-segment elevation in leads I, aVL, & V1-V4. The patient is immediately taken to the cardiac catheterization lab where she is found to have complete occlusion of the LAD coronary artery. The blockage is immediately opened, but after the intervention, she experiences recurrent & sustained episodes of ventricular arrhythmia. She is treated with antiarrhythmic agents. One of the agents used in this patient preferentially binds to rapidly depolarizing and ischemic ventricular myocardial fibers & has minimal effect on normal ventricular myocardium. What agents was most likely used in this patient?

*Lidocaine* Ventricular arrhythmias = common in first 24-48 hours after MI - amiodarone = drug of choice - *lidocaine = second-line agent when amiodarone not readily available or effective in suppressing arrhythmia* Class IB = lidocaine, mexiletine - weakest sodium channel blockers (dissociate fastest) - negligible effect on QRS duration in normal cardiac tisues - predominantly bind to sodium channels in inactivated state - *highly efficacious in inhibiting ischemia-induced ventricular arrhythmias*

A 59-year-old female is brought to the ER with fever, skin flushing, & an altered level of consciousness. Her blood pressure is 50/20 mmHg, & her heart rate is 120/min. If blood cultures are positive for E. coli, what bacterial factors is most likely responsible for this patient's current condition?

*Lipid A* - induces shock by activation of macrophages & granulocytes --> synthesis of endogenous pyrogens, such as IL-1, prostaglandins, & inflammatory mediators: TNF-alpha & interferon Septic shock - via release of endotoxins into bloodstream (found in outer membrane of gram-negative bacteria) - LPS released during destruction of bacterial cell wall - LPS = O antigen, core polysaccharide, Lipid A

How could a case of rubella have been prevented?

*Live attenuated vaccine* - measles, mumps, rubella MYRICSS MMR Yellow fever Rotavirus Influenza (intranasal) Chickenpox (VZV) SMallpox Sabin polio virus

Recognize alveoli and what would affect them

*Lobar pneumonia* - intra-alveolar exudate --> consolidation - may involve entire lobe or lung - S pneumonia most commonly - attract neutrophils

A 24-year-old man has a 6-year history of heroin abuse. The patient's addiction has cost him most of savings. His boss has spoken to him about his erratic moods & inconsistent work performance, & he is now in danger of losing his job. The patient asks for help, saying, "I have tried so hard to do this on my own. My parents have spent a lot of money on counseling. It helps for a while, but then I go back to using. They are fed up and refuse to see me anymore. I don't want to use, but the craving is so strong." The physician refers the patient to a methadone treatment program & he experiences marked reduction in his cravings. What drug properties is helpful in treating this patient's condition?

*Long half-life* - most commonly used agonists in US = methadone & buprenorphine Methadone = *full* mu-opioid receptor agonist used for control of chronic pain & in opioid withdrawal & maintenance of addiction = *long half-life* with sustained effects after chronic dosing & *suppresses cravings* & *withdrawal* symptoms for >24 hours - good bioavailability (36-100%) = oral administration - adverse effects = QT interval prolongation & respiratory depression with lethality in overdose

An acute extensive bilateral lesion in the reticular formation of the tegmentum of the midbrain is most likely to result in

*Loss of consciousness* Reticular activating system (midbrain) - reduced levels of arousal & wakefulness (coma)

A 58-year-old man has had progressive weakness over the past 8 months. Exam shows weakness & muscle atrophy in the upper & lower extremities. Muscle stretch reflexes are decreased in the upper extremities & increased in the lower extremities. He has no sensory deficits. What findings is most likely?

*Loss of myelin in the lateral column white matter & loss of ventral horn motoneurons* Amyotrophic lateral sclerosis (ALS) - combined UMN & LMN deficits with no sensory or bowel/bladder deficits (via loss of cortical & spinal cord motor neurons) - asymmetric limb weakness (hands/feet), fasciculations, eventual atrophy

A 24-year-old woman comes to the office after discovering a new mole on her right leg. She is worried that it might be skin cancer as she has used tanning beds several times a years since age 18. Physical exam shows a 5-mm brown, oval macule on her anterior thigh with a homogenous coloration & discrete borders. The lesion appears darker than her other moles. A biopsy of the lesion shows normal-appearing nevus cells clustered in the epidermis, & she is diagnosed with a benign acquired melanocytic nevus. During histologic analysis, her epithelial cells are each found to contain a condensed body composed of heavily methylated DNA at the periphery of the nucleus. This region of DNA is most likely associated with what genetic findings?

*Low transcription activity* - lyonization converts inactive X chromosome into condensed *heterochromatin* = compact body at periphery of nucleus (*Barr body*) - heterochromatin = heavily methylated DNA (cytosine converted to methylcytosine) & deacetylated histones

A 14-year-old boy develops a pruritic vesicular rash on his face & hands 3 days after hiking in the woods. What are most likely to be involved in his illness?

*Lymphocytes, cytokines, macrophages* Type IV / Delayed-type HS - sensitized CD4+ helper *T cells* encounter antigen & release *cytokines* --> inflammation & *macrophage* activation

A 54-year-old Caucasian male is hospitalized with spiking fevers & productive cough. He was diagnosed with right lower lobe pneumonia one week ago & received a short course of oral antibiotics, but his condition has failed to improve since then. Chest X-rays shows a round density with an air-fluid level in the lower lobe of the right lung. What contributed most to the observed lung lesion in this patient?

*Lysosomal content release by macrophages* Pulmonary abscesses - local suppurative collection within lung parenchyma = necrosis of surrounding lung tissues - abscess cavity communicates with air passage --> air-containing cavity on chest radiograph - suppurative destruction of lung parenchyma secondary to release of lysosomal enzymes by neutrophils & macrophages

Vertebral osteomyelitis should be suspected in patients with new or worsening back pain, fever, & recent endocarditis or bacteremia (especially S aureus). What is preferred for diagnosis?

*MRI*

A 60-year-old woman has a serum calcium concentration of 7 mg/dL & a serum potassium concentration of 2.8 mEq/L. Her serum PTH concentration is decreased. The decreased PTH is most likely related to a severe depletion of what?

*Magnesium* - decreased magesium = increased PTH - severely decreased magnesium = decreased PTH - common causes of decreased Mg2+ = diarrhea, aminoglycosides, diuretics, alcohol abuse

What pancreatic structures is derived from the ventral pancreatic primordium?

*Main pancreatic duct* & Uncinate process

In patients with bronchial asthma, what eosinophil products is most likely to be responsible for damage to epithelium?

*Major basic protein*

A 57-year-old man has had a MI. Development of what sequelae of infarction is associated with decreased survival?

*Major depressive episode*

A 78-year-old man comes to the physician because of progressive swelling of the right side of his face and neck & his right upper extremity. His right jugular vein is engorged. What diagnoses is most likely to be confirmed on an x-ray of the chest?

*Mass in the upper lobe of the right lung* SVC syndrome - common presentation of lung cancer in upper lobes - Pancoast tumor or mediastinal mass - impairs blood drainage from head (facial plethora) & upper extremities - blanching after fingertip pressure - can raise intracranial pressure - increased risk of aneurysm/rupture of intracranial arteries

A 45-year-old man comes to the ED due to sudden-onset vomiting & severe upper abdominal pain that radiates to his back. The patient's total bilirubin is 0.9 mg/dL, aspartate aminotransferase (AST) is 98 U/L, alanine aminotransferase (ALT) is 32 U/L, & alkaline phosphatase is 98 U/L. Serum lipase is markedly increased. Abdominal ultrasound reveals a normal gallbladder & common bile duct. The diagnosis of acute pancreatitis is made, & a specific etiology is established. What additional lab findings is most specific for the underlying cause of this patient's pancreatitis?

*Mean corpuscular volume of 108 fL* Acute pancreatitis - likely related to alcohol abuse given his >2 AST:ALT ratio & absence of gallstones on abdominal ultrasound - even in absence of anemia, *macrocytosis*

A 3-year-old boy is brought to the ED by his parents after he develops acute abdominal pain & vomiting. Imaging studies reveal a foreign body lodged within his intestine causing a small bowel obstruction. Laparotomy is performed to remove the foreign body; during the procedure, an incidental abdominal cyst is discovered & removed. The cyst is connected by a fibrous band to the ileum & the umbilicus. What conditions is also caused by the same embryologic defect responsible for the patient's abdominal cyst?

*Meckel diverticulum* Omphalomesenteric/Vitelline duct - connects midgut lumen with yolk sac cavity early in embryonic life - normally obliterates during 7th week of embryonic dev't Persistent vitelline duct / vitelline fistula - via complete failure of vitelline duct to close - small connection between intestinal lumen & outside of body at umbilicus - meconium discharge from umbilicus after birth if fistula is present Meckel diverticulum - most common vitelline duct anomaly - via partial closure of vitelline duct - fibrous band may connect tip of Meckel diverticulum with umbilicus

A 17-year-old boy is brought to the office due to occasional blood in the urine. The first episode occurred year ago, about 3 days after a flulike illness, & resolved spontaneously. He had a similar episode about 6 months ago, which also seemed to resolve. He does not have any other medical problems & does not use tobacco or alcohol. There is no history of blood or kidney disorder in the fam. The physical exam shows a healthy appearing young male. His vital signs are normal. On lab evaluation, blood urea nitrogen level is 14 mg/dL, & creatinine is 0.8 mg/dL. Urinalyis are as follows: Specific gravity = 1.013 Protein = +2 Blood = trace Glucose = negative Ketones = negative Leukocyte esterase = negative Nitrites = negative WBCs = 1-2/hpf RBCs = 20-30/hpf A renal biopsy is performed. What findings is most likely to be seen on microscopic evaluation?

*Mesangial deposition of IgA* / Berger disease - most common cause of glomerulonephritis - older children & young adults - painless hematuria within 5-7 days of upper respiratory tract infection - PSGN develops within 1-3 weeks of streptococcal pharyngitis vs. 5 days of IgA nephropathy & reoccurence is rare

Reverse transcription polymerase chain reaction is used to diagnose chronic myelogenous leukemia in a patient. What is most likely to be detected by this test?

*Messenger RNA transcript containing BCR & ABL exons* RT-PCR - used to detect & quantify levels of mRNA in a sample - cDNA contains exons of a gene along with the 5' & 3' untranslated regions CML - BCR gene on chromosome 22 fuses with ABL gene on chromosome 9 = BCR-ABL fusion gene - BCR-ABL fusion protein = constitutively active tyrosine kinase --> accelerates cell division & increases genetic instability

When a cytogenetic abnormality is suspected in an infant with multiple congenital anomalies, chromosomes from circulating leukocytes are analyzed. These chromosomes are most condensed & easiest to evaluate in what states?

*Metaphase* - *Chromosome are in their most condensed form during metaphase when the sister chromatids are attached. This is the primary stage when cytogenetic analysis is performed*

DNA from E coli & Haemophilus influenzae is digested with restriction endonuclease EcoRI & the fragments separated by agarose gel electrophoresis. An exam of the gel shows that the DNA from H influenzae was cleaved into numerous smaller fragments while that from E coli was not. What best explains this difference?

*Methylation of E. coli* - methylate DNA --> inactivation = cannot be cut

a 16-year-old boy has a 1-week history of a pruritic rash that has been spreading across his feet. He usually wears gym shows but frequently walks without shoes. Physical exam shows erythema, a few tense vesicles & bullae with red bases, & mild scaling on the soles of the feet. The rash extends up the sides of the feete to the malleoli. The most appropriate therapy is topical application of what?

*Miconazole* - Athletes foot / Tenia pedia

A young couple has been unable to achieve a viable pregnancy. Semen analysis shows normal quality and quantity of sperm. The woman has regular menstrual cycles & takes no contraceptives. Biopsy of her nasal sinus mucosa shows epithelial cells with majority of cilia bent at half their length. The most likely functional cause for this couple's infertility is a deficiency in what?

*Migration of conceptus* Kartagener's syndrome - conceptus (baby) cannot travel down fallopian tubes because cilia are not motile - impaired migration of ova/conceptus to reach uterus

Two weeks after an upper respiratory illness, a 6-year-old boy develops periorbital & peripheral edema. Other physical findings are normal; BP is 110/60 mmHg. Lab values show: Serum Creatinine = 0.8 mg/dL Protein = 4 g/dL Antistreptolysin O titer = 80 Todd unites (N = 12-166) Urine Protein = 4+ Erythrocytes = rre What is the most likely diagnosis?

*Minimal Change Disease* - *nephrotic syndrome = > 3.5 g/day* - ASLO is only a confounding factor here - most common nephrotic syndrome *in children* - may be triggered by recent infection

A 94-year-old man has been taking ibuprofen for osteoarthritis for the past 5 years. Two years ago, he developed renal failure, & serum creatinine concentration increased from 1.2 to 2.0 mg/dL. He recently developed GI hemorrhage from a gastric ulcer. He wants to continue taking the ibuprofen. What drugs is most likely to decreased this patient's risk for ibuprofen-induced gastric ulceration?

*Misoprostol* - PGE1 analog - *increased production & secretion of gastric mucous barrier* - decreased acid production - *prevention of NSAID-induced peptic ulcers* (NSAIDs block PGE1 production) - also used off-label for induction of labor (ripens cervix)

Researchers analyzing eukaryotic genome structure & function perform an experiment to extract DNA from exocrine pancreatic cells. During the purification process, they isolate small circular DNA molecules that resemble a bacterial chromosome. Further analysis shows that these molecules code for proteins, transfer RNA, & ribosomal RNA. From what cellular structures did these DNA 'cules most likely originate?

*Mitochondria* mtDNA = most common non-nuclear DNA found in eukaryotic cells - resembles prokaryotic DNA - maternally derived = small circular chromosomes - codes for 14 proteins, ribosomal & transfer RNA needed for mitochondrial protein synthesis

A 17-year-old girl comes to the physician because of shortness of breath. A systolic murmur is heard best in the left fifth intercostal space in the midclavicular line. What valvular abnormalities is the most likely cause of the murmur?

*Mitral insufficiency* - mitral valve prolapse in young women

A 14-year-old girl is admitted to the hospital because of palpitations, an irregular pulse, migratory polyarthritis, & a low-grade fever. She had acute tonsillitis 3 weeks ago. Assays for antistreptococcal antibodies & C-reactive proteins are positive. Her 10-day stay in the hospital is uneventful, & her ECG changes have resolved. Prophylactic antistreptococcal therapy is used for prevention of what long-term sequelae?

*Mitral valve stenosis* = late lesion of Rheumatic fever - via group A beta-hemolytic streptococci

Tend to be resistant to outliers

*Modes*

A 44-year-old man comes to the office due to low mood, impaired concentration, increased sleep & appetite, feelings of heaviness in his arms & legs, & loss of energy. He is having difficulty at work as he is overly sensitive to criticism. Although his boss has told him not to worry, the patient is concerned that his job is in jeopardy due to poor performance. His symptoms started 8 months ago without any clear-cut precipitating event. The patient received adequate trials of 3 different antidepressants without improvement & has been off of meds for the past several weeks. His physician is now considering ECT. The patient declines ECT & asks to try another med. The physician then considers phenelzine. The presence of what additional symptoms would make this an appropriate med for this patient?

*Mood reactivity* *MAO* *T*akes *P*ride *I*n *S*hanghai *T*rancypromine, *P*henelzine, *I*socarboxazid, *S*elegiline - effective antidepressants - inhibit oxidative deamination of serotonin, NE, & dopamine - used in *atypical subtype of major depression* & treatment-resistant depression Atypical depression - *mood reactivity*, leaden paralysis, rejection sensitivity, reversed vegetative signs of increased sleep & appetite

Primary target of diphenoxylate

*Motility* Diphenoxylate - opioid anti-diarrheal agent - structurally related to meperidine - binds to *mu opiate receptors* in GI tract & *slows motility* - low doses --> relieve diarrhea without other significant opiate effects - higher doses = morphine-like euphoria & physical dependence - to discourage abuse, it is combined with atropine Loperamide = another low-potency opioid agonist used in symptomatic treatment of diarrhea

A 45-year-old woman comes to the office due to unitentional loss of 6.8 kg (15 lb) over the past 6 months. She used to enjoy dining with friends but has become concerned about lower abdominal pressure & feeling full very quickly. She also has epigastric pain but no dysphagia, regurgitation, vomiting, or diarrhea. Physical exam shows bilateral adnexal fullness. A pelvix ultrasound shows bilateral complex ovarian masses with solid & cystic components. Chest x-ray is normal. CT scan shows stomach wall thickening & ovarian masses. What is most likely to be seen on histologic evaluation of the ovaries?

*Mucin-secreting signet cells* - unintentional weight loss & early satiety = malignancy - epigastric pain & gastric thickening on CT scan + lower abdominal pressure & adnexal masses = gastric & ovarian involvement - ovaries = common site for metastases (primary GI tract cancer mostly) = *Krukenberg tumor* = primary gastric cancer that has metastasized to ovary = nests of *signet ring cells* = mucin displacing nucleus

Bacterial factor most important during pathogenesis of Shigella

*Mucosal invasion* - invades GI mucosa, particularly via M cells that overlie Peyer's patches - can induce apoptosis of host cell & spread to adjacent cells via protrusions created via *actin polymerization* Shigella - mainly kids - non-lactose fermenting - produce acid (not gas) - non-motile - do not produce H2S

A 12-year-old girl is admitted to the hospital because of marked shortness of breath, an erythematous rash, & painful, swollen hip & knee joints. Antistreptolysin O titer is abnormally high. X-ray film of the chest shows an enlarged heart. She develops intractable congestive heart failure & dies on the second hospital day. What cardiac abnormalities is most likely to be seen at autopsy?

*Myocardial edema with Aschoff bodies* - Aschoff bodies = nodules found in hearts of individuals with rheumatic fever = areas of inflammation of CT of heart Rheumatic fever - inflammatory disease following Group A streptococca linfection (such as strep throate or scarlet fever) - Ab cross-reactivity that can involve heart, joints, skin, & brain - typically develops 2-3 weeks after streptococcal infection - commonly appears in children between ages of 5 & 17

A 53-year-old woman comes to the physician for a routine check-up. She has no current complaints. Her past medical history is significant for osteoarthritis of the right knee. Her mother suffered from HT & was diagnosed with breast cancer at age 68, from which she died 4 years later. Her father had diabetes mellitus & died in a motor vehicle accident at age 56. The patient's blood pressure is 140/85 mmHg & heart rate is 80/min. Physical exam is normal. Lab testing is significant for a fasting blood glucose level of 140 mg/dL on more than 2 occasions. This patient is most likely to die from...

*Myocardial infarction* - diabetes mellitus = one of the strongest risk factors for coronary heart disease

As part of an experiment, radiolabeled ATP is injected into skeletal muscle. During muscle contraction, the labeled ATP is observed to attach to the sarcomere. This attachment causes immediate

*Myosin head detachment from the actin filament*

A 27-year-old man with alcoholism is found unresponsive after he drank large amounts of alcohol without eating any food over a 3-day period. His serum glucose concentration is 30 mg/dL. This lab finding is most likely due to increased hepatic concentrations of...

*NADH* Ethanol metabolism - increases NADH/NAD+ ratio in liver --> oxaloacetate --> malate = prevents gluconeogenesis --> fasting hypoglycemia

A 4-year-old girl is brought to the ED because of a 5-day history of fever, diffuse abdominal pain, nausea, vomiting, & diarrhea. Exam shows petechiae, hepatomegaly, & splenomegaly. Hemoglobin concentration is 8.7 g/dL & platelet count is 60,000/mm^3. A peripheral blood smear shows erythrocyte fragmentation. What renal findings is most likely to be associated with her condition?

*Narrowing of the capillary wall by fibrin deposition* Hemolytic uremic syndrome - after infection with EHEC - children < 10 y/o - deposition of fibrin in capillary walls = normal pathogenesis by which renal failure occurs in TTP & HUS

Cells from a pancreatic carcinoma express very small amounts of class I MHC molecules and are resistant to recognition & killing by CD8+ T lymphocytes isolated from the host individual. Substantial tumor cell lysis is observed when these cells are cultured in the presence of a mixed leukocyte population isolated from the peripheral blood of a normal (cancer-free) individual. What leukocytes in the blood of the normal individual are most likely responsible for the in vitro lysis of tumor cells?

*Natural killer cells* - inhibited by MHC I - if cell doesn't express much MHC I --> eaten by NK cells - activated by IL-2

A male neonate is born prematurely to 22-year-old primigravida & experiences severe respiratory distress. The distress resolves with treatment, & by two weeks of age, the patient has adequate respiratory function. Ophthalmoscopy later shows abnormal retinal vascularization that extendes into vireous. The retinal findings in this patient are most likely related to

*Neonatal oxygen supplementation* Respiratory distress in premature neonate - via pulmonary surfactant deficiency in hyaline membrane disease - treatment = supplemental oxygen at high concentrations, nasal continuous positive airway pressure, &/or mechanical ventilation with intratracheal surfactant --> ADR = retinal damage Temporary local hyperoxia in retina - up-regulation of VEGF upon return to room air ventilation - retinal vessel proliferation (neovascularization) & possible retinal detachment with blindness may result = *retinopathy of prematurity / retrolental fibroplasia*

A 31-year-old female with new-onset generalized tonic-clonic seizures has an intracranial mass detected on head CT scan. Biopsy of the mass reveals neoplastic cells that stain positive for synaptopysin & negative for glial fibrillary acid protein. These neoplastic cells most likely originate from the same precursor tissues as

*Neurons* Synaptophysin - transmembrane glycoprotein in presynaptic vesicles of neurons, neuroectodermal & neuroendocrine cells - immunoreactivity of CNS tumor for synaptophysin = neuronal origin = rare / less than 1% of CNS tumors

A 21-year-old man develops wristdrop after sustaining a complete fracture of the upper arm associated with extensive tissue damage. The fracture was reduced successfully, & the ends of vessels & damaged nerves were apposed & surgically rejoined. Despite physical therapy, the extensor muscles have a decreased volume & can contract only weakly. Wound healing & flexion are good The most likely cause of this condition is abnormal function of what?

*Neurotrophic input* - wound healing & flexion are good = intact circulation - wrist drop = radial nerve injury --> supplies extensor muscles - injured nerves were apposed & surgically apposed = complete recovery unlikely - despite therapy, extensor muscles have decreased-volume & can contract only weakly

Target of tubocurarine

*Nicotinic ACh receptor* - nondepolarizing neuromuscular blocking drug

A 23-year-old woman is scheduled to undergo surgical repair of an aortic malformation. A ganglionic blocking agent is administered before the procedure to decrease her BP. The hypotension is achieved by binding of the drug at what receptors?

*Nicotinic* Ganglion-blocking drugs = Trimethaphan & Mecamylamine - inhibit effect of ACh at nicotinic receptors by active competitively (nondepolarizing blockade) at both sympathetic & parasympathetic autonomic ganglia

What medications would be most effective for lowering a patient's BP without worsening his ECG abnormalities?

*Nifedipine* or other Dihydropyridines = act on vascular smooth muscle (arterial SM) = vasodilation with little or no effect on cardiac conduction or contractility

Auer rods indicate

Acute myelogenous leukemia

Structural RNA found within complexes containing both protein & RNA synthesized at what intracellular site?

*Nucleolus* = dense round structure = in direct contact with rest of nucleoplasm without intervening membrane - contains ribosomal DNA coding for 28S, 5.8S, & 18S ribosomal RNA (rRNA) components, as well as *newly transcribed rRNA* in association with *ribosomal protein* translated in cytoplasm from mRNA = synthesis & assembly of immature 60S & 40S ribosomal subunits exported from nucleus to fully mature in cytoplasm

A 5-year-old girl is brought to the office by her mother because she is concerned that her daughter "sunburns too easily." The mother says the patient's skin becomes red & scaly with only minimal sun exposure. She first noticed the problem when her daughter was 7 months old during a trip to the beach. The mother has since avoided exposing her child to excess sunlight, but finds it difficult now that the patient has begun kindergarten. Physical exam shows thin & hyperpigmented skin. She also has a few nevi on her hands that have been enlarging rapidly. This patient's disorder is most likely due to a primary defect involving what processes?

*Nucleotide excision repair* Xeroderma pigmentosum - AR - defective nucleotide excision repair of DNA damaged by UV light --> accumulation of abnormal pyrimidine nucleotides & other carcinogenic adducts - skin of affected ind = normal at birth but present during first year of life with severe sun sensitivity (erythema, scaling) - skin malignancies develops as early as 5-6

Which of the following techniques is most accurate in showing that two bacterial DNAs are identical?

*Nucleotide sequencing*

What immunosuppressive agents acts by selectively binding to the epsilon (Eepsilon) chain of the T lymphocyte antigen-receptor complex?

*OKT3 monoclonal antibody* / Muronomab - first mAb approved for clinical use in humans - murine monoclonal Ab IgG2a Ab that specifically reacts with T cell receptor-CD3 complex on surface of circulating human T cells - binds to glycoprotein on CD3 complex to activate circulating T cells = transient activation of T cells

A previously healthy 4-year-old girl is brought to the office because her parents noticed dark red blood on her toilet tissue. She has no abdominal pain or discomfort with stooling. Her temperature is 36.7 (98 F), BP is 100/40 mmHg, & pulse is 112/min. Physical exam shows a soft & nontender abdomen, & bowel sounds are present. Her Hb is 8 g/dL & platelet count is 215,000/mm^3. Coagulation profile is normal. Sequential imaging using 99mTc-pertechnetate scintigraphy demonstrates focal radiotracer accumulation in the right lower quadrant. What embryologic processes most likely failed in this patient?

*Obliteration of the omphalomesenteric (vitelline) duct* Meckel diverticulum - ileal outgrowth - via failed obliteration of vitelline / omphalomesenteric duct - *if symptomatic, most common manifestation = spontaneous but painless lower GI bleeding* - potential lead point for intussusception = colicky abdominal pain & currant jelly - rdioisotope 99mTc-pertechnetate has affinity for parietal cells of gastric mucosa --> increased in periumbilical/right lower quadrant (RLQ)

A 63-year-old man comes to the physician because of "poor sleep" and daytime drowsiness. A sleep lab study shows frequent decreases in arterial PO2 & simultaneous increases in arterial PCO2 during sleep. Monitors show chest wall & diaphragmatic motion during these episodes. What is the most likely diagnosis?

*Obstructive sleep apnea* - high pco2 only during apnic episodes or when chronic

Microbiologists are investigating sugar metabolism in mild-type & mutant strains of Escherichia coli. Both strains are found to grow viable colonies on lactose-containing media. Each strain is then cultured on a new growth medium containing only glucose. Representative colonies of each strain from the new media undergo Western blot processing using a fluorescently labeled probe specific for beta-galactosidase. Wild-type bacterial colonies are found to contain only trace quantities of beta-galactosidase. However, the mutant colonies express significant amounts of beta-galactosidase. Further analysis reveals that the variant strain contains a mutation that inhibits the binding of a certain protein to its regulatory sequence. In what locations did this mutation most likely occur?

*Operator locus* - lac Z gene codes for beta-galactosidase = hydrolysis of lactose to glucose & galactose - lac Y = permease = allows lactose to enter bacterium - lac p = binding site for RNA polymerase during initiation of transcription = lac I repressor protein = product of lac I gene = constitutively expressed - culturing E coli in media with glucose = reduced expression of lac operon, even when media contains lactose as well - lac operon positively regulated by binding of CAP to site slightly upstream from promoter region = when cAMP concentrations are high Lac operon regulated by 2 distinct mechanisms 1. negatively binding of repressor protein to operator locus 2. positively by cAMP-CAP binding upstream from promoter region *Mutations impairing binding of repressor protein to its binding site at operator region prevents repression of genes of lac operon in absence of lactose region* --> prevents repression of genes of lac operon in absence of lactose = increased transcription of genes of lac operon in lactose-deficient media

A 48-year-old man comes to his physician because his wife noticed that his right pupil is "small." Physical exam shows that the right pupil is constricted and does not react to light. His left pupil is normal. These findings are most likely due to a lesion involving what structures on the right?

*Optic tract* - pupillary light reflex involves direct pathway to midbrain from optic tract Optic tract lesions - correspond to visual field loss on left or right half of vertical midline = homonymous hemianopsia - lesion in left optic tract = right-sided homonymous hemianopsia - via stroke, congenital defects, tumors, infection, surgery - *pupillary light reflex* --> lack of equal consensual pupillary constriction to light stimulus, esepcially a Marcus Gunn pupil, indicates optic nerve damage, brainstem death, or *optic tract damage* in between

A 62-year-old woman comes to the physician with decreased vision. Over the last 6 weeks, she has had progressive difficulty with visualizing objects on her right side. She also has intermittent headaches that are worse in the morning. Her past medical history is significant for non-small lung carcinoma that was diagnosed 2 years ago & treated surgically. Physical exam shows right homonymous hemianopia. When light is shone in the left eye, both pupils constrict. However, when the light is immediately moved to the right eye, her pupils appear to dilate. This patient's symptoms are most likely due to a left-sided lesion involving what structure?

*Optic tract* - contains mixed optic nerve fibers from temporal part of ipsilateral retina (nasal visual field) & fibers from nasal part of contralateral retina (temporal visual field) - lesions = contralateral homonymous hemianopia Afferent limb of pupillary light reflex = retina, optic nerve, optic chiasm, optic tract fibers, pretectal nucleus in midbrain - Marcus Gunn pupil = lesions involving optic nerve, such as optic neuritis in MS

A 52-year-old man comes to the office for a painless mass in high right groin. He noticed the mass several weeks ago, & it has slowly enlarged. The patient has a history of HIV, for which he takes antiretroviral therapy. He has not had any new sexual partners recently. Temp is 37.1 C (98.8 F). On exam, several enlarged, hard lymph nodes are palpated in the right inguinal area inferior to the inguinal ligament. An excisional biopsy is performed, & histopathology shows malignant cells. The malignant cells found in this patient most likely originated from what sites?

*Orifice of the anal canal* Patient has palpable, firm *superficial inguinal lymph nodes* - drain most cutaneous lymph from umbilicus down, including external genitalia & anus (below dentate line) - scrotum vulva

A 57-year-old man receives a sintered titanium oxide implant during total hip arthroplasty following traumatic injury. During the first 6 weeks following injury, bone ingrowth aneals to the bone-metal interface in both the femur & acetabulum, thus securing the prosthesis in position. Type I collagen secretion in the first stage of matrix formation is mediated by what cell types?

*Osteoblasts* - builds bone by *secreting collagen* & catalyzing mineralization in alkaline env't via ALP - differentiates from mesenchymal stem cells in periosteum - osteoblastic activity measured by bone ALP, osteocalcin, propeptides of type I procollagen

An 18-year-old woman, gravida 1, para 1, comes to the physician for a routine postpartum exam. She says that she often has milk leakage even when she is not ready to breast-feed her 6-week-old son. She reports that this symptom is particularly severe whenever he begins to cry. The physician reassures her that this is an entirely normal response. This reaction is most likely psychogenic stimuli that promote secretion of what mediators?

*Oxytocin* - assists in milk letdown - also promotes uterine contractions

68-year-old man comes to the office or a follow-up appointment. He has a history of advanced melanoma that is unresectable & resistant to adjuvant regimens. The patient recently began receiving monoclonal antibody infusions that were approved for advanced melanoma management after encouraging clinical trial results were published. The monoclonal antibodies block a specific cell surface receptor found on T lymphocytes, facilitating destruction of cancer cells by T cells capable of recognizing tumor antigens. What cell surface receptors is most likely blocked by the treatment?

*PD-1* / Programmed death receptor-1 - expressed on surface of activated T cells - binds to ligand, programmed death ligand 1 (PD-L1) --> downregulates immune response against tumor cells primarily by inhibiting cytotoxic T cells (similar to CTLA-4) - many types of cancer cells evade immune system by increasing expression of PD-L1 - *monoclonal Abs against PD-1* have been developed that prevent binding of PD-1 to PD-L1 -- *blocks T cell inhibition* = restores cytotoxic response & *promotes apoptosis* of tumor cells

During normal micturition, pressure within the bladder increases in response to what changes?

*Parasympathetic outflow from the sacral spinal cord* Micturtion = PANS action - involves contraction of detrusor muscle --> increase in pressur in bladder --> drives urine out - relaxation of sphincter

A 4-year-old boy is brought to the hospital after several episodes of vomiting. The boy's mother reports that he was playing at a local park prior to onset of illness. While cleaning him after the first episode of emesis, she found several small brown mushrooms clenched in his hands & brought samples with her. The boy is otherwise healthy & takes no meds. He is intubated due to somnolence & admitted to the intensive care unit. Analysis of the mushroom samples determines that the main poison stimulates muscarinic receptors. What is the most likely direct effect of this poison?

*Peripheral vasodilation* Muscarine = toxin found in certain mushrooms - acts as muscarinic agonists in place of ACh - increased parasympathetic nervous system activity - M2 & M3 = most toxicities M3 - present on endothelial surface - synthesis of NO --> diffuses into vascular SM cells --> cGMP --> myosin light chain phosphatase --> dephosphorylates myosin --> prevents interaction of myosin head with actin = *smooth muscle relaxation & vasodilation*

Cultured fibroblasts taken from infants suffering from hypotonia & seizures show an impaired ability to oxidize very long chain fatty acids (VLCFA) & phytanic acid. The defect is most likely localized to

*Peroxisome* - very long chain FAs or FAs with branch points at odd #ed carbons cannot must be metabolized by special form of beta oxidation or by alpha oxidation (branched chain fatty acids such as phytanic acid) within peroxisomes - diseases --> neurologic defects from improper CNS myelination

A 67-year-old man admitted for right lower lobe pneumonia subsequently develops hypotension & lactic acidosis. He is started on a NE IV drip. A few hours later, the antecubital vein being used for the infusion blanches & the tissues surrounding the IV site become cold, hard, & pale. Local injection of the affected tissues with what agents is most likely to be of greatest benefit?

*Phentolamine* Blanching of vein into which NE is being infused together with induration & pallor of tissues surrounding IV site = NE extravasation --> NE leak = intense alpha1 receptor mediated vasoconstriction --> local tissue necrosis = can be prevented by infiltration (using syringe with fine hypodermic needle) throughout affected area with 10-15 cc of sodium chloride solution containing 5-10 mg of phentolamine mesylate, an alpha receptor blocker - antidote must be given within 12 hours of extravasation to be effective

A 72-year-old man comes to the ED because of a 2-hour episode of loss of vision in the left eye. He has never smoked. Lab studies show: Hb = 20 g/dL Hematocrit = 62% Leukocyte count = 14,200/mm^3 Differential = normal Mean corpuscular volume = 87.2 um^3 Platelet count = 375,000/mm^3 What is the most appropriate therapy?

*Phlebotemy* Polycythemia vera - increased RBCs - increased WBCs - increased platelets - JAK2 mutation - normal Hemoglobin = 13.5-17.5 (males) - normal hematocrit = 41-53% (males) - normal platelet count = 150,000 - 400,000 - normal mean corpuscular volume = 80-100 Isolated monocular vision loss = initial manifestation of polycythemia vera

In gout, hyperuricemia resulting from overproduction of urate is most likely to result from a lack of feedback inhibition by ADP or GDP at what enzyme?

*Phosphoribosylpyrophosphate synthetase*

A 45-year-old man who has five children comes to the physician to discuss a vasectomy and asks about what to expect. What is most likely to occur during the first 4 weeks following the procedure?

*Presence of viable sperm in ejaculate* Vasectomy - not 100% sterilization - pregnancy rate after vasectomy = 1/2000 pregnancy rate via recanalization - some viable sperm = post-surgery complication - during the first few months after vasectomy, patients have to use another contraceptive method

A 50-year-old man is brought to the ER after developing blurred vision while cutting several trees in his garden. His past medical history is insignificant and he is not taking any meds. He has no history of illicit drug use. His temperature is 38.9 C (102 F), BP is 100/70 mmHg, pulse is 120/min, & respirations are 22/min. Physical exam shows flushed skin & dry oral mucosa. Both pupils are dilated & non-reactive to light. What drugs can potentially reverse this patient's condition?

*Physostigmine* = cholinesterase inhibitor - can be used to treat atropine overdose Jimson Weed (Datura stramonium) poisoning = Gardener's mydriasis - produces toxins (belladonna alkaloids) that possess strong anticholinergic properties Blockade of visceral muscarinic receptors - tachycardia - cutaneous flushing - delayed gastric emptying, decreased intestinal motility, secretion - bronchodilation - urinary retention via detrusor relaxation & contraction of external urethral sphincter - decreased lacrimation, salivation, sweating - mydriasis & cyloplegia - hallucinations, agitation & delirium

A 30-year-old man is evaluated for 6 months of persistent pain in his right buttock & posterior thigh. He is a construction worker & has difficulty lifting heavy objects of climbing stairs. He has no history of back injury & no associated back pain. Pas medical history is unremarkable. The patient does not use tobacco & drinks only moderate quantities of alcohol. On exam, the patient develops pain with forced adduction of the flexed thigh & internal rotation of the extended thigh against resistance. Further evaluation reveals possible entrapment of the sciatic nerve in the greater sciatic foramen. What structures passes through the foramen & occupies most of its volume?

*Piriformis muscle* - originates on anterior aspect of sacrum & occupies most of space in greater sciatic foramen - inserts on greater trochanter of femur - externally rotates thigh when extended - abducts thigh when flexed - sciatic nerve crosses below - *muscle injury of hypertrophy can compress sciatic nerve = pain, tingling, numbness in buttocks = piriformis syndrome* --> muscle can be tender with deep palpation or on stretching with adduction & internal rotation

A 33-year-old woman, gravida 2, para 1, at term gives birth to a 4167-g (9 lb 3 oz) male newborn by a spontaneous 30-minute vaginal delivery. Shortly after delivery of the placenta, there is a brisk flow of blood from the uterus. Manual palpation of the uterine cavity shows a large fragment of retained placental material. A curettage shows a fibrous nodule of placental tissue that is firmly adherent to the uterine wall. What is the most likely cause of the bleeding in this patient?

*Placenta accreta* - defective decidual layer --> abnormal attachment & separation after delivery - placenta attaches to myometrium without penetrating it = most common type - often detected on ultrasound prior to delivery - no separation of placenta after delivery --> postpartum bleeding = can cause Sheehan syndrome

*Extended-spectrum beta-lactamases* can be produced by gram-negative bacteria, rendering cephalosporins & other beta-lactam antibiotics inactive. What feature is most likely to be found in this organism?

*Plasmid with drug resistance gene*

A 42-year-old man with pneumococcal pneumonia has acute fibrinous pleuritis. What proteolytic enzymes is required to eliminate the exudate & restore normal pleural anatomy?

*Plasmin* Plasminogen --> Plasmin via tPA --> fibrinolysis Fibrinolysis = cleavage of fibrin mesh = destruction of coagulation factors

A 40-year-old woman discovers a breast mass during self-exam. At a routine health maintenance exam 2 months ago, her physician had told her all findings were normal. After having a mammogram that is suspicious for breast cancer, the patient begins to wonder if her physician failed to noticed the lump during her exam 2 months ago. She is most likely to sue the physician under what circumstances?

*Poor communication between the patient and physician*

Clinicians are developing an enzyme-linked immunosorbent assay test for diagnosing RA. The test is designed to detect the presence of serum Abs against citrullinated proteins. Two test populations with a differeing prevalence of RA are selected. The clinicians plan to assess the test's performance in the 2 populations by comparing a number of diagnostic test parameters. The difference in disease prevalence is most likely to affect what parameters?

*Positive predictive value* (PPV) - probability that someone who tests positive on a binary diagnostic test actually has disease - as disease prevalence increases, PPV also increases due to higher proportion of true positive

A 10-year-old boy is brought to the office due to tea-colored urine that he first noticed yesterday after routine swim practice. BP is 130/80 mmHg. Physical exam is normal with exception of bilateral periorbital edema. Lab results are as follows: Serum Sodium = 140 mEq/L Potassium = 4 mEq/L Blood urea nitrogen = 14 mg/dL Creatinine = 1.4 mg/dL Creatinine kinase = 86 U/L Urinalysis Protein = trace Leukocyte esterase = negative Nitrites = negative WBCs = 1-2/hpf RBCs = many/hpf Casts = RBC casts What is the most likely diagnosis?

*Post-infectious glomerulonephritis* - children with gross hematuris, periorbital edema, HT - RBC casts - elevated creatinine (renal insufficiency), streptococcal Abs, & decreased C3 (glomerular complement deposition)

A 45-year-old woman says that her feet feel hot. The skin of her feet is pink, dry, & hot. Which of the fibers are most likely to be disrupted?

*Postganglionic sympathetic* - atropine-like effect in feet --> blockade of sweat glands supplied by ACh-releasing sympathetic fibers - when sympathetics are disrupted, parasympathetics take over

A 34-year-old woman comes to the physician's office because she has had a cough, fatigue, low-grade fever, mild dyspnea, & aching joints for the past month. Physiacl exam shows no abnormalities. X-ray film of the chest shows bilateral hilar adenopathy with mild diffuse parenchymal infiltrates. Exam of tissue obtained by transbronchial biopsy during bronchoscopy shows noncaseating granulomas. What is the most appropriate therapy?

*Prednisone* Sarcoidosis - treatment = steroids (if symptomatic)

A 52-year-old man comes to the physician with concerns about a "heart problem." He feels fine, but was told to see a physician after a heart murmur was detected during a wellness fair at work. Physical exam reveals a holosystolic murmur best heard at the apex of the heart that radiates to the axilla. The remainder of his physical exam is normal. What is the best indicator of the severity of this patient's problem?

*Presence of audible S3* Mitral Regurgitation - *holosystolic*, high-pitched "blowing murmur" - mitral = *loudest at apex --> radiates toward axilla* - *best indicator of severe MR with left ventricular volume overload = presence of S3 gallop*

A pharmaceutical company has developed a drug that prevents egress of Mg2+ from the N-methyl-D-aspartate (NMDA) receptor. What is the most likely effect of this drug in a patient with an acute stroke?

*Prevention of Ca2+ entry into the neuron & reduction of excitotoxin-mediated cell death* NMDA blockers = in trial for stroke - block calcium entry into neurons --> prevent cell death calcium entry would cause excitotoxic cell death --> if the company's product makes Mg2+ ion stain channel, calcium cannot entry through it to cause excitotoxic cell death

A 45-year-old man has had four episodes of involuntary twitching of the right foot. Following the last episodes, he had a tonic-clonic seizure. What structures on the left is the most likely origin of the sieuzre?

*Primary motor cortex* - partial seizure with sec generalization due to inv of primary motor cortex - foot twitch --> primary motor cortex --> reticular formation or thalamus --> generalized seizure

Viremia is an essential feature of what disorders?

*Primary varicella infection* Varicella infects respiratory tract --> replicates for 2 week incubation period --> generally followed by viremia - virus goes throughout body & rests in ganglion - when immune system is low, reactivation of virus occurs -- herpes zoster

A 44-year-old woman comes to the clinical after several "near collision" over the past month while driving at night. She also has generalize pruritus. The patient has not seen a physician for several years & has missed several scheduled appointments. She takes no meds. On physical exam, her skin is diffusely coarse & dry. What processes is most likely responsible for these findings?

*Prolonged biliary obstruction* Vitamin A deficiency - night blindness - hyperkeratosis Primary biliary cholangitis - middle-aged women + generaized pruritus + signs of vitamin A deficiency - common autoimmune disease characterized by destruction of small bile ducts in liver - generalized pruritus due to bile acid accumulation in skin

What best describes the therapeutic benefit of the structure analogy of octreotide as compared with native somatostatin

*Prolonged duration of action* = long-acting somatostatin analog

A 44-year-old man with a history of heavy alcohol consumption comes to the ED with a nosebleed after getting into a fight while intoxicated. Continuous local pressure is applied & his bleeding resolves within 30 minutes. A detailed physical exam is performed after the bleeding subsides & shows distended paraumbilical veins, ascites, & a flapping hand tremor on wrist extension. What lab findings would be most indicative of a poor prognosis for this patient?

*Prolonged prothrombin time* Alcoholic cirrhosis - liver's functional reserve = key determinant of prognosis in patient's with cirrhosis - *serum albumin levels & PT = better indicators of liver's biosynthetic function* - *hypoalbuminemia, elevated bilirubin levels, prolonged PT = signs of inadequate liver function* = poor prognosis in cirrhotic patients

A 75-year-old man who is being treated for atrial fibrillation has an adequately controlled ventricular response rate at rest. During exercise or stress, his heart rate increases to an unacceptable rate. What drugs is most likely to be effective in controlling the patient's ventricular response rate during activity or stress?

*Propranolol* beta-blockers (class II) clinical use - SVT, *ventricular rate control for atrial fibrillation*, atrial flutter

A 70-year-old man begins taking a drug to prevent angina pectoris. At his next visit, his pulse has decreased from 70/min to 60/min, & his BP has decreased from 130/90 mmHg to 110/70 mmHg. The drug most likely to be responsible for these changes is what?

*Propranolol* beta-blockers: applications - *angina pectoris*, MI, SVT, HT, HF, Glaucoma, Variceal bleeding adverse effects: - erectile dysfunction, *cardiovascular adverse effects (bradycardia, AV block, HF)*, CNS adverse effects (seizures, sedation, sleep alterations), dyslipidemia (metoprolol), asthma/COPD exacerbations

Group A Streptococci demonstrate significant resistance to phagocytic killing when placed in fresh human blood. This resistance can be most effectively overcome by adding Abs to what?

*Protein M* = major virulence factor for Streptococcus pyogenes - inhibits phagocytosis & activation of complement - cytotoxic for neutrophils in serum = mediator of bacterial attachment

The nucleotide sequence encoding four amino acids near the amino acid terminus of a 10-kd protein is 5'-ACT GAT TGC GTT-3'. This sequence is mutated by insertion of a single nucleotide (A) in the second codon & becomes 5'-ACT GAA TTG CGT-3'. What consequences of this mutation is most likely?

*Protein truncation* Frameshift mutation is likely to result in a premature stop codon - addition or deletion of a single or two nucleotides at a time can alter sequence downstream - eventually during translation, a stop codon is encountered prematurely that will lead to truncated protein which will be dysfunctional & eliminated by protein degradation machinery - ex. = cystic fibrosis

A 69-year-old man has been taking a dopamine agonist for 4 weeks for Parkinson disease. He has had some benefit from this treatment & decides on his own to increase his dosage. What adverse effects is most likely to result from this increase in dosage?

*Psychoses* Dopamine agonists - ergot = bromocriptine - non-ergot (preferred) = pramipexole, ropinirole

A 54-year-old man comes to the office due to daytime sleepiness and lack of energy. The symptoms began 6 months ago & have progressively worsened so that he feels "completely drained" by the end of the day. The patient's wife mentions that he snores loudly. His past medical history is unremarkable, although he has not seen a physician in over 10 years. The patient does not use tobacco or alcohol, & he works in the warehouse of an agricultural supply company. BMI is 34 kg/m^2. Physical exam shows a narrow oropharynx & a large neck circumference. The patient is at increased risk of developing ....

*Pulmonary HT* Obstructive sleep apnea (OSA) - obese man with loud snoring, daytime sleepiness, suggestive exam findings (thick neck, narrow airway) - each nocturnal episode of reduced ventilation --> transient hypercapnia & hypoxemia --> *reflexive systemic & pulmonary vasoconstriction*, endothelial dysfunction, abnormal venous rturn & cardiac output, sympathetic cardiac stimulation - prolonged, untreated = pulmonary HT & right heart failure - associated with systemic HT

A 24-year-old man is brought to the ED after being stabbed in the chest. Exam shows a stab wound in the fourth intercostal space on the left, immediately lateral to the sternum. What structures is most likely injured?

*Right ventricle* 4th Intercostal Space = location of tricuspid valve = right atrium - right ventricle

A 48-year-old man comes to the office due to right inguinal discomfort. The patient first noticed "bumps" in his groin when he was dressing in the morning. He does not know how long they have been present but thinks they are relatively new. The patient was treated for gonorrhea several years ago but has not other medical problems. He drinks alcohol occasionally but does not use tobacco or illicit drugs. His mother died of metastatic melanoma. Cardiopulmonary exam is normal. The abdomen is soft & nontender. The right inguinal lymph nodes are enlarged & tender, as are several nodes in the right popliteal area. The distribution of lymphadenopathy in this patient would most likely be seen in what conditions?

*Purulent laceration on the right lateral foot* Lymphatic system of extremities - superficial lymphatic vessels --> follow venous system - deep lymphatic vessels --> follows arterial system - lateral lesion --> communicates with popliteal & inguinal nodes = lymphadenopathy in both popliteal & inguinal areas

A 5-year-old boy with developmental delay is brought to the office due to difficulty "seeing the board" at school. Exam shows a boy with a tall, thin habitus with elongated limbs. Fundoscopy shows bilateral lens subluxation. Four years later, the patient dies suddenly of a massive cerebrovascular accident. Autopsy shows middle cerebral artery thrombosis & old renal infarcts. His parents wish to know if anything could have been done to have prevented his death. What would have been the most appropriate supplementation for this patient?

*Pyridoxine* Homocystinuria - most common inborn error of methionine metabolism - most patients present at age 3-10 with *ectopia lentis (dislocated lens)* - half of patients = *intellectual disability* - *Marfanoid habitus* at high risk for thromboembolic occlusions - AR deficiency of cystathionine beta-synthase = requires *pyridoxine (vitamin B6)*

The epidermal growth factor receptor & platelet-derived growth factor receptor are both classified as...

*Receptor tyrosine kinases* - Insulin, I*GF*-1, F*GF*, PD*GF*, E*GF* = MAP kinase pathway Think *G*rowth *F*actors

A virologist is researching acylovir-resistant herpes simplex virus (HSV). Viral DNA analysis reveals a mutation in the thymidine kinase gene, resulting in a mutated enzyme that does not phosphorylate acyclovir to its active form. In an experiment, a resistant HSV type 2 strain containing this mutation is cultured in a cell line, & the cell culture is coinfected with a nonresistant HSV type 1 strain. It is found that some of the type 1 virions acquire resistance to acyclovir, & subsequent progeny continue to be resistant. What mechanisms best explains the observed findings?

*Recombination* - exchange of info between 2 viruses that have *nonsegmented*, dsDNA genomes - exchange of genes between 2 chromosome via *crossing over* within homologous regions - occurs between 2 *dsDNA molecules*

A 10-year-old boy comes to the office for a first visit. His family recently came to the United States as political refugees. The patient's mother says that he has required several blood product transfusions due to anemia, but she does not have prior records available with her. On exam, the patient's temperature is 37.1 C (98.8 F). BMI is 21 kg/m^2. Exam is notable for conjunctival pallor & moderate splenomegaly. Lab results are as follows: Hemoglobin = 9.4 g/dL Platelets = 240,000/mm^3 Enzyme assays performed on circulating blood cells demonstrate low pyruvate kinase activity. What is the most likely cause of this patient's splenomegaly?

*Red pulp hyperplasia* Pyruvate kinase deficiency = insufficient ATP production --> disrupts gradient --> water & potassium loss, defective maintenance of membrane architecture (echinocyte formation), hemolysis - reticuloendothelial cells in splenic *red pulp* involved in removal of damaged RBCs --> increased activity in pyruvate kinase deficiency --> undergoes hyperplasia = splenomegaly

A 34-year-old man is admitted to the hospital with acute chest pain. An electrocardiogram is obtained in the ED & shows ST segment elevation in leads II, III, & avF. A sample of blood is taken from the patient. A new test is used to measure the plasma homocysteine level 3 times with this blood sample. The results are 11.2 umol/L, 13.5 umol/L, & 17.1 umol/L (lab reference range = 4-14 umol/L). These results suggest that concerns should be raised about what with the new test?

*Reliability* = reproducible = similar or very close results on repeat measurements - in this example, repeat measurements of same sample = markedly different results = not very reliable - coefficient of variation should be calculated for this test & compared to that of other tests measuring plasma homocysteine

A 16-year-old girl has generalized weakness and nocturnal leg cramps. She is not taking any medications. Lab studies show: Serum Na+ = 135 mEq/L Cl- = 108 mEq/L K+ = 2.8 mEq/L HCO3- = 21 mEq/L Urine pH = 7 What is the most likely diagnosis?

*Renal tubular acidosis* Type 1 / Distal Renal Tubular Acidosis - *urine pH > 5.5* - defect in ability of alpha intercalated cells to secrete H+ --> no new HCO3- --> metabolic acidosis - *hypokalemia* - increased risk for calcium phosphate kidney stones (increased pH, increased bone turnover) Usually... Acidosis --> Hyperkalemia Alkalosis --> Hypokalemia *If these patterns differ, think about RTA!!!*

A 60-year-old man comes to the physician's office because of confusion and inability to concentrate. Which of the following is the best way to assess his concentration?

*Repeating a digit sequence backward* Concentration & Attention - based on digital span & attention to your questions

Membrane is most permeable to potassium ions at what point?

*Repolarization* - via closure of Na+ channels & simultaneous opening of K+ channels = sharp decrease in membrane permeability to Na+ & significant increase in K+ permeance that exceeds that of resting membrane - K+ efflux --> returns membrane potential back to resting potential

What procedures is most likely to increase serum aldosterone concentrations in an experimental subject?

*Restriction of water intake* Aldosterone - primarily regulates ECF volume & Na+ content - responds to *low blood volume states* - responds to hyperkalemia by increased K+ excretion

A 3-month-old infant has a severe lower respiratory tract infection. A virus isolated from the respiratory tract causes dev't of multinucleated cells in tissue culture. What types of drug is most likely to be effective in resolving the infant's infection?

*Ribavirin* - treatment for RSV

Which of the following types of RNA 'cules present in a eukaryotic cell is the most abundant?

*Ribosomal RNA* RNA polymerase I makes *r*RNA (most numerous RNA, *r*ampant)

During thoracentesis, needle is inserted along upper border of 10th rib at right midaxillary line. What structures is most at risk of being injured as a result of the intervention?

*Right hepatic lobe*

In Scurvy, symptoms are most likely caused by hypoactivity of an enzyme found in what compartments?

*Rough endoplasmic reticulum* Vitamin C deficiency / Scurvy - impaired collagen formation - gingival swelling/bleeding - perifollicular hemorrhages & coiled (corkscrew) hairs Collagen synthesis - begins with transcription of collagen genes in nucleus - collagen alpha-chains synthesized by RER-bound ribosomes & directed into cisternae of RER --> proline & lysine residues post-translationally hydroxylated

Maintains anteflexion of uterus

*Round ligament* - runs from lower aspect of uterus through inguinal ring to labia majora - not connected to ovaries - during pregnancy, may experience intermittent sharp pain due to irritation from sudden movements of stretching round ligament

Heard best when patient is in left lateral decubitus position at *end expiration*

*S3*

A 50-year-old man has a 10-year history of poorly controlled HT. Vital signs are: Pulse = 96/min Respirations = 16/min BP: left arm = 226/120 mmHg right arm = 218/118 mmHg With the patient in the left lateral decubitus position, a late diastolic sound is heard best with the bell at the apex. What is the most likely explanation for this auscultatory finding?

*S4* - in *late* diastole (atrial kick) - best heard at apex with patient in left lateral decubitus position - high atrial pressure - associated with ventricular noncompliance (hypertrophy) - left atrium must push against stiff LV wall - considered abnormal, regardless of patient age

A 34-year-old man comes to the physician due to painful urination. Physical exam shows a watery penile discharge. Urethral swabs obtained from the patient are negative for gonococcal infection. He is treated appropriately & his symptoms resolve. Two weeks later, he develops acute conjunctivitis, right knee pain, & vesicular rash on his palms & soles. This patient's condition is most likely associated with what?

*Sacroiliitis* Reactive arthritis - classic triad = urethritis, conjunctivitis, mono- or oligoarticular arthritis - seronegative - males 20-40 mostly - associated with HLA-B27 - keratoderma blennorrhagicum = hyperkeratotic vesicles on palms & soles - circinate balanitis = serpiginous annular dermatitis of glands penis - axial involvement = sacroiliitis

A 19-year-old woman is brought to the ED after a motor vehicle collision. The patient's medical history includes celiac disease & 3 episodes of pneumonia. Her BP is 80/45 mmHg & pulse is 130/min. Physical exam reveals pallor, & ultrasound shows a splenic laceration. She receives a blood transfusion with O-negative packed RBCs. During transfusion, the patient develops facial swelling, generalized hives, & shortness of breath. What is the most likely diagnosis in this patient?

*Selective IgA deficiency* - most common primary immunodeficiency - some have have recurrent sinopulmonary & GI infections via absence of secretory IgA - concomitant autoimmune disorders (celiac disease) also common - normal IgG & IgM - nblood transfusion = anaphylaxis --> should wear medicla alert bracelets & receive blood products washed of residual plasma or from IgA-defienct donor

An 80-year-old woman dies shortly after admission to the hospital because of a 3-day history of progressively increasing shortness of breath. She had a history of heart failure. Exam of the lungs during autopsy shows alveolar damage with distended lymphatics, congested alveolar capillaries, & pink-staining homogenous proteinaceous hyaline material in alveoli. What is the most likely cause of these findings?

*Septic shock* - exudate (due to inflammation) --> hyaline membrane Acute respiratory distress syndrome (ARDs) - alveolar damage - 3 days after admission (respiratory failure within 1 week of alveolar insult) - hyaline pink staining material in alveoli

A 5-month-old boy is brought to the office by his parents who are concerned that he has developmental delay. He has 3 older siblings, & the parents report that his siblings were much more active & interactive at the boy's age. The fam has just moved to the US from South America & did not have consistent primary care previously. Physical exam shows that the boy is unable to roll from front to back or back to front & does not seem to recognize his parents. Comprehensive lab evaluation reveals impaired tetrahydrobiopterin synthesis. What is most likely deficient in this patient?

*Serotonin* - formed via hydroxylation & decarboxylation of tryptophan Tetrahydrobiopterin (BH4) = cofactor in synthesis of - *serotonin* - tyrosine - DOPA Phenylketonuria - henylalanine hydroxylase - less common = *BH4 deficiency* secondary to dihydropteridine reductase deficiency --> *low levels of serotonin & other NTs* - high phenylalanine + low serotonin = progressive neurologic deterioration - delay, hypotonia, dystonia, seizures - treatment = low phenylalanine diet, BH4 supplementation

A tube is placed to drain fluid via an incision at the 5th intercostal space in the midaxillary line. What muscles is most likely to be dissected during this procedure?

*Serratus anterior* - originates along 1st-8th ribs --> inserts along entire length of medial scapular border - divided into 3 parts = superior, intermediate, inferior - inferior = arm elevation - all 3 = respiration by lifting ribs Chest tube - through skin & subcutaneous fat into 4th or 5th intercostal space in anterior axillary or midaxillary line - traverses through serratus anterior muscle, intercostal (external, internal, innermost) muscles, & parietal pleura to reach pleural cavity

A 23-year-old man comes to the physician due to a 2-month history of fatigue, malaise, & abdominal discomfort. He is found to have tender hepatomegaly with elevated liver function tests. The patient has never been vaccinated against hepatitis. He has had no raw or uncooked foods recently & recalls no ill contacts. There is no history of blood transfusion. The patient is a graduate student who immigrated to the United States 2 years ago & has not traveled outside the country since. He smokes 2 packs of cigarettes a day & consumes 1 or 2 bottles of beer on weekends. The patient does not use illicit drugs. He has had several episodes of unprotected sex with different femal partners within the past year. What is most likely to be present in this patient?

*Serum HBsAg* Hepatitis B virus (HBV) - sexual transmission among heterosexual partners & among MSM & percutaneous - vertical transmission common in high-prevalence areas

Man who works in gravel pit. Multiple small nodules seen on x-ray, some are calcified, in upper lobes.

*Silicosis* - associated with foundries, sandblasting, mines - increased susceptibility to TB - affects *upper lobes* - eggshell calcification of hilar lymph nodes on CXR

Patients receiving parenteral nutrition (through central venous catheter) are at high risk for what yeast infection?

*candidemia* (Candida in bloodstream) - can colonize catheter --> lipid emulsion in parenteral nutrition solution promotes growth of some Candida species = *pseudohyphae with blastoconidia*

A 28-year-old man is brought to the ED after being lost in a remote wilderness area for 3 weeks. He consumes all of the food in his backpack 2 weeks ago & has had only wild berries & pond water since then. Intravenous feeding is begun. Blood samples obtained before IV feeding was begun show increased serum concentrations of ketone bodies & urea nitrogen (BUN); glucose concentration is within the reference range. Use of what best explains the maintenance of a normal glucose concentration in thie patient?

*Skeletal muscle protein* After day 3 - adipose stores (ketone bodies become main source of energy for brain) --> depleted = *vital protein degradation accelerates = organ failure & death* - amount of excess stores determines survival time

A 4-year-old girl has had increasing difficulty climbing stairs over the past 3 months. She has a normal identical twin sister & an 8-year-old brother with similar problems; he has been diagnosed with Duchenne's muscular dystrophy. What best explains the discordance in the identical twins?

*Skewed X inactivation* Duchenne - X-linked disorder typically due to frameshift or nonsense mutations --> truncated or absent dystrophin protein --> progressive myofiber damage

A 10-year-old boy is brought to the ED by his parents 1 hour after he fell down the steps in the middle of the night. His mother reports that he has a history of wandering around the house at night, but her never seems to recall it afterwards. During these episodes, he does not scream or appear frightened. He is otherwise healthy, & he takes no meds. Physical exam shows a 2-cm area of edema & ecchymosis over the forehead. Polysomnography is most likely to show an abnormality in which of the following stages of sleep?

*Slow-wave (delta* Stage N3 (25%) - deepest non-REM sleep (slow-wave sleep) - when *sleepwalking*, nigh terrors, & bedwetting occur - delta = lowest frequency, highest amplitude

A 64-year-old woman comes to the physician's office because of gradually worsening abdominal cramps, nausea, diarrhea, flushing of skin, & heart palpitations. Twenty-four hour urinary 5-hydroxyindoleacetic acid excretion is increased. The most likely cause of these findings is a neoplasm originating in what structure?

*Small intestine* Carcinoid syndrome - secretion of 5-HT - recurrent diarrhea, cutaneous flushing, asthmatic wheezing, right-sided valvular heart disease - *increased 5-hydroxyindoleacetic acid (5-HIAA)* in urine - niacine deficiency = *most common malignancy in small intestine*

A 2-day-old infant is dusky & irritable. He was born to a 22-year-old primigravida with sporadic prenatal care. Delivery was uncomplicated, & Apgar scores were 7 & 8 at 1 & 5 minutes, respectively. His temperature is 36.7 C (98 F), BP is 70/30 mmHg, pulse is 148/min, & respiratory rate is 68/min. Physical exam shows a cyanotic & irritable newborn with mild-to-moderate resipratory distress. Auscultation reveals a continuous, machine-like murmur appreciated between the scapulae. Serum lactate is elevated. Echocardiogram shows the aorta lying anterior, inferior, & to the right of the pulmonary artery. Failure of what embryological processes is most likely responsible for this patient's condition?

*Spiraling* Tranposition of great arteries (TGA) - linear dev't of aorticopulmonary septum in utero = *anteriorly positioned aorta* connected to right ventricle - 2 parallel circulations - incompatible with life unless there is another coexisting connection = patent formane ovale, septal defect, or *patent ductus arteriosus* = allows mixing - become cyanotic, tachypneic, & tachycardic as PDA (*machine-like murmur*) begins to close = ages 1-3 days - elevated lactate via anaerobic metabolism in presence of poorly oxygenated blood

Which of the following is vasularized by the artery of the foregut but is not itself a foregut derivative?

*Spleen* Foregut - Celiac artery - Vagus = parasympathetic innervation - T12/L1 Structures supplied = pharynx (vagus nerve only) & lower esophagus (celiac artery only) to proximal duodenum - liver, gallbladder, pancreas, *spleen (mesoderm)*

A 64-year-old man comes to the ED after an episode of hematemesis. He also reports dark stools & abdominal pain for the past several days. The patient has a history of chronic pancreatitis. Abdominal exam shows epigastric tenderness to palpation. Rectal exam is notable for black, guaiac-positive feces. Upper GI endoscopy reveals a bleeding spot within a cluster of enlarged tortuous veins in the gastric fundus. The rest of the stomach & esophagus appears normal. Increased pressure in what vascular structures is the most likely cause of this patient's condition?

*Splenic vein* Gastric varices can be seen with *splenic vein thrombosis* - via chronic pancreatitis, pancreatic cancer, abdominal tumors - splenic veins runs along posterior surface of pancreas = can develop blood clot from pancreatic inflammation - *short gastric veins* drain fundus of stomach into splenic vein - splenic vein thrombosis can increase pressure in short gastric veins = gastric varices only in fundus - rest of stomach & esophagus usually not affected

A 10-year-old boy is being evaluated because of poor growth, recurrent episodes of sinusitis, & a chronic cough. An x-ray of the chest shows evidence of bronchiectasis. A rare inherited disorder causing immotile, structurally abnormal cilia in the respiratory epithelium is diagnosed. This patient's impaired mucociliary clearance is most likely to predispose him to pulmonary infections with what infectious agents?

*Staphylococcus aureus* - most common infectious organisms affecting children with Kartagener syndrome / Primary ciliary dyskinesia = Haemophilus influenza & S aureus - all patients should have pneumococcal vaccine & yearly flu vaccine in addition to standard childhood immunizations

Which of the following contaminants will be removed from a fluid passed through a 0.45 u filter?

*Staphylococcus aureus* - size of viruses = 0.02 - 0.2 um - size of bacteria = 0.3 - 3 um - mycoplasma = less than 0.45 um - components of viruses & bacteria = much smaller - everything would pass through filter except staph aureus

Common pathogen in septic abortion

*Staphylococcus aureus* others = gram-negative bacilli (E coli) & group B strep - part of normal vaginal flora --> seed uterine cavity during instrumentation

A 54-year-old woman with type 2 diabetes mellitus well controlled with oral hypoglycemia agents comes to the physician because of a 2-week history of swelling in her left knee. She tells the physician that her knee is very stiff when she awakens in the morning & a bedtime. The pain & stiffness worsen with exertion. Low-dose ibuprofen results in incomplete relief. What best explains why a larger dose of ibuprofen is more appropriate?

*The anti-inflammatory dose is nearly twice the analgesic dose* - since it's inflammatory, higher dose of ibuprofen (more potent NSAID) is needed

In what compartment is *transketolase* active?

*cytosol* - glycolysis - FA synthesis - pentose phosphate pathway

A 35-year-old man comes to the physician because of a 2-week history of nasal congestion. He has used a topical decongestant every few hours since his symptoms began. He experienced relief for almost 1 week, but then his nasal congestion returned. The patient has a history of allergic rhinitis & has had episodes of rhinorrhea in the past, but none of them lasted longer than a few days. He denies fever, throat pain, headaches, cough, & lymph node enlargement. Aside from his allergic rhinitis, the patient has no other medical problems. Physical exam shows nasal mucosa that appears edematous & red with few areas of punctate bleeding. The remainder of the exam reveals no abnormalities. What is the most appropriate next step in the management of this patient?

*Stop the decongestant* Vasoconstriction via alpha-adrenergic agonist = prominent in vessels of nasal mucosa = effective decongestants - phenylephrine, xylometazoline, oxymetazoline Tachyphylaxis = rapidly declining effect after few days of use - via decreased production of endogenous NE from nerve terminals via negative feedback mechanism = relative vasodilation (removal of normal vasoconstrictive tone) & subsequent edema & congestion --> exacerbation of nasal congestion symptoms - rebound rhinorrhea - *use of adrenergic agonists should be stopped to allow restorationof normal NE feedback pathways*

A 35-year-old African-American man with sickle cell anemia is admitted to the hospital because of fever, chills, & malaise. His WBC count is 24,000/mm^3 with 15% bands, 80% neutrophils, & 5% lymphocytes. He quickly becomes hypotensive & dies, despite aggressive resuscitation. His blood cultures are most likely to grow what organisms?

*Streptococcus pneumonia* Septicemia --> fatal hypotension - usually gram-negative *but* sickle cell disease patients functionally asplenic = increased risk for encapsulated organisms (S pneumoniae mostly) - all asplenic patients should receive penicillin prophylaxis & pneumococcal vaccination

A 19-year-old college student develops hematuria & proteinuria. Approximately 3 weeks ago, he had superficial cellulitis of the right proximal thigh & buttocks. His condition is most likely to be secondary to infection with

*Streptococcus pyogenes (group A)* - superficial cellulitis/impetigo caused by group A beta hemolytic strep can cause immune mediated post streptococcal GN - usually about 2-3 weeks after infection

What modifications of an endogenous pharmacologically active peptide would be most likely to slow the metabolism of the peptide, thus decreasing its clearance & increasing its half-life?

*Substituting a D for an L amino acid* - proteolytic enzymes prefer L-configuration (natural), rather than D-configuration (unnatural) - peptidases quickly recognize L-configurated peptides = short half-life

A 78-year-old woman has a 2-month history of flailing movements of the limbs on one side. There is no family history of a similar movement disorder. What structures is most likely to be involved?

*Subthalamic nucleus* - lesion = *contralateral hemiballismus*

In a cohort study, 10,000 men who consume alcohol were compared with 10,000 men who do not consume alcohol. The results show that men who consume alcohol have an increased risk for cancer of the bladder tha is statistically significant at the 5% level. What is the most appropriate interpretation of this result?

*Such an effect would occur by chance in less than 5% of repeated samples of this size* - definition of p value = tests null hypothesis, normally set as 0.05

A 31-year-old man comes to the ED complaining of right-sided scrotal pain & swelling that has gradually worsened over the last 3 days. His temperature is 38.3 C (101 F). On physical exam, his right hemiscrotum is warm, tender, & erythematous. The cremasteric reflex is present. A scrotal ultrasound reveals a fluid collection consistent with a superficial scrotal abscess. What lymph node groups is most likely to be tender & swollen?

*Superficial inguinal* - leaves lymph drainage from scrotum

Which of the following initiates the molecular damage that occurs following transient ischemia & reperfusion of cardiac muscle?

*Superoxide anion* Formation of free radicals via superoxide --> result = peroxidation of lipids

Where does anterior pituitary gland originate from?

*Surface ectoderm*

A 61-year-old woman comes to the office with skin dimpling on the right breast. She first noticed the skin changes 3 months ago while on vacation, & she is concerned that they have not resolved. The patient does not use tobacco, alcohol, or illicit drugs & used sunscreen while on the beach. She exercises regularly & takes a daily multivitamin. Her last menstrual period was 8 years ago. Physical exam shows a prominent, nontender skin retraction without discoloration or swelling of the right breast. There is also a 6-cm irregular immobile firm mass in the right upper outer quadrant of the breast. The left breast appears normal. This patient's findings are likely due to malignant infiltration of what structures?

*Suspensory ligament* Invasive breast carcinoma - irregularly shaped adherent breast mass - upper outer quadrants of breast = most common site of breast cancer - overlying skin retractions (dimpling) signal involvement of *suspensory ligaments* of breast (Cooper ligament)

Most important virulence mechanism by which *coaulase-negative* Staphylococcus causes disease

*Synthesis of extracellular polysaccharide matrix* Staphylococcus epidermidis - associated with foreign bodies (ventriculoperitoneal shunts) - biofilms

A 17-year-old girl has had general malaise & progressive intermittent pain in the knees over the past 6 weeks. She has a history of mouth ulcers. She is using hydrocortisone cream to treat a rash on her cheeks. Lab studies show: Hemoglobin = 7.2 g/dL Hematocrit = 31% Leukocyte count = 21,000/mm^3 Platelet count = 37,000/mm^3 What is the most likely diagnosis?

*Systemic lupus erythematosus* *RASH OR PAIN* *R*ash (malar or discoid) *A*rthritis (nonerosive) *S*erositis *H*ematologic disorders (cytopenias) *O*ral/nasopharyngeal ulcers *R*enal disease *P*hotosensitivity *A*ntinuclear antibodies *I*mmunologic disorder (anti-dsDNA, anti-Sm, antiphospholipid) *N*eurologic disorders (seizures, psychosis)

Cells that mediate hypersensitivity reaction of Candida extract skin reaction

*T-lymphocytes* Delayed-type HS reaction (DTH) - contact dermatitis, granulomatous inflammation, tuberculin skin test - mediated by T-lymphocytes = 1-2 days following antigen exposure why you wait 48-72 hours for annual PPD test to be read!

A 45-year-old man develops a fever, a cough productive of rusty sputum, & chest pain. Sputum cultures are positive for Streptococcus pneumoniae. He is treated with antibiotics and recovers uneventfully. What cell types is most likely responsible for regeneration of the injured tissue?

*Type II pneumocytes* - proliferate during lung damage

What drugs for maintenance therapy in patients with moderate to severe asthma has positive cardiac inotropic effects, produces vasodilation, has diuretic action, & stimulates diaphragmatic contraction?

*Theophylline* - causes bronchodilation by inhibiting phosphodiesterase --> increased cAMP levels via decreased cAMP hydrolysis - usage limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity) - metabolized by cytochrome P-450 - blocks actions of adenosine

A 78-year-old man comes to the office due to a one-month history of progressive dyspnea, generalized weakness, fatigue, & palpitations. He also reports tingling & numbness in both lower limbs. His daughter, who is visiting from another state, adds that since his wife's death a year ago, the patient has not been taking care of himself. Blood pressure is 105/50 mmHg & pulse is 104/min. Cardiovascular exam shows a displaced apical impulse at the sixth intercostal space, a third heart sound, & high-volume, collapsing carotid pulses. Bilateral basal crackles, 2+ bilateral pedal edema, & mild hepatomegaly are also present. Neurologic exam shows decreased light touch & vibration sense in the feet, with decreased knee & ankle reflexes bilaterally. Lab evaluation shows normal blood counts. Deficiency of what nutrients is most likely responsible for this patient's symptoms?

*Thiamine* deficiency - infantile & adult berirberi Adult beriberi - symmetrical *peripheral neuropathy* of distal extremities, with resulting sensory & motor impairments - wet beriberi = additional cardiac involvement, high-output CHF, peripheral edema, tachycardia

A 64-year-old Caucasian male loses consciousness near the entrance of an ER. A physician rushes to the patient & palpates a strong pulse along the inner side of the sternocleidomastoid muscle. The vessel palpated by the doctor is a derivative of what aortic arch?

*Third* - common & proximal internal carotid arteries - common carotid artery = palpated by physician

In an animal experiment, mice proerythroblasts are cultured in 2 different growth media; the first medium is folate deficient, whereas the second (control) is supplemented with folic acid. Both media contain high concentrations of erythropoietin. Over 48 hours, cells in the control media proliferate & differentiate into reticulocytes, whereas in the folate-deficient media, cell proliferation is minimal with the majority of of cells undergoing apoptosis. In another experiment, a substance is added to the folate-deficient media, which prevents apoptosis & permits proliferation of the proerythroblasts. What is the most likely substance added to the growth medium?

*Thymidine* - all biochemical functions of folate require reduce *tetrahydrofolate* form of vitamin, which is synthesized by dihydrofolate reductase (rate-limiting step of folate metabolism) Experiment: - inhibition of thymidylate synthase via low folate conditions increases ratio of dUMP to dTMP = incorporation of uracil into DNA in place of thymidine --> excessive activation of DNA repair mechanisms = dsDNA breaks & apoptosis Folate deficiency - inhibits synthesis of nucleic acids, particularly formation of dTMP (*deoxythymidine monophosphate*) --> defective DNA synthesis that characteristically causes increased apoptosis of hemopoietic cells & megaloblastic anemia

A previously healthy 65-year-old man is brought to the ED because of severe chest pain for 1 hour. His pulse is 95/min, & BP is 160/110 mmHg. The lungs are clear to auscultation. An S4 gallop & a grade 2/6 systolic murmur are heard at the apex. An ECG shows 3 mm of ST-segment elevation in leads V2 through V6. The most appropriate treatment includes immediate administration of

*Tissue plasminogen activator* Thrombolytics - *Early MI*, early ischemic stroke, direct thrombolysis of severe PE

What mechanism most likely explains for a patient's rapid recovery from propofol?

*Tissue redistribution of drug* Propofol & other highly lipophilic drugs - readily diffuse across membranes --> quickly accumulate in tissue receiving high blood flow = rapid onset of action - subsequently redistributed to organs receiving less blood flow = short duration of action

Serious, possibly fatal, adverse effects of a new drug may first appear only after the drug is approved for marketing by the Food & Drug Administration. The failure to detect these effects is best explained by the used of what premarketing clinical trials?

*Too few subjects to detect rare events*

A 44-year-old homeless man with a history of alcohol abuse is brought to the hospital after being found unresponsive. His temperature is 35.6 C (96 F), BP is 90/60 mmHg, & pulse is 110/min. He is unresponsive only to pain & has dry mucus membranes. The patient is initially treated with IV fluids, & his mental status slowly improves but then he develops decreased urine output & flank pain. A renal biopsy is eventually performed, which reveals marked ballooning & vacuolar degeneration of proximal renal tubules; multiple oxalate crystals are observed in the tubular lumen. What is the most likely pathogenesis of this patient's renal failure?

*Toxic renal injury* - proximal tubular cell ballooning & vacuolar degeneration in patient with acute renal failure = acute tubular necrosis - presence of oxalate crystals in tubular lumen = ethylene glycol poisoning = may have been used as substitute to alcohol --> patient initially manifests with symptoms of ethanol intoxication --> signs of acute renal failure (oliguria, anorexia, flank pain) develop 24-72 hours after ingestion - high anion gap metabolic acidosis & osmolar gap typically seen

In Burkitt's lymphoma, the gene translocated in the lymphoid cells produce a protein that is most directly responsible for what functions?

*Transciption activation* Burkitt lymphoma - maxillary or mandibular masses in children - strongly associated with EBV - tingible body macrophages - starry sky appearance = *translocation between c-Myc oncogene on long arm of chromosome 8 & Ig heavy chain region on chromosome 14 [t(8;14)]* - product of c-Myc = nuclear phosphoprotein = *transcription activator*

What step of viral replication is most likely to be inhibited as a result of raltegravir

*Transcription of viral messenger RNA* Integrase inhibitors: RED = Ral, Elvi, Dolutegravir - inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase = increased creatinine kinase

A 50-year-old man who recently immigrated to the USA from Russia develops fever, swelling of the neck, & difficulty swallowing. His vaccination history is uncertain. Exam of the throat shows a gray membrane across the pharynx. The pathogen responsible for this infection most likely acquires its virulence through what genetic events?

*Transduction* - toxin in Corynebacterium is acquired via phage infection Bacterial toxins acquired during lysogeny = COBEDS - Cholera toxin - O Ag of Salmonella - Botulinum exotoxin - Erythrogenic exotoxins of S pyogenes - *Diphtheria toxin* - Shiga toxin

Creation of knockout mouse that has a deletion in the platelet endothelial cell adhesion molecule 1 (PECAM-1) gene. The protein product of this gene is mainly localized to specific areas on the endothelial cells. Absent expression of this gene will most likely affect what neutrophil functions?

*Transmigration* - after crawling to endothelial cell periphery, neutrophils migrate out of vasculature by squeezing in between cells via integrin attachments & adherence to PECAM-1

A 48-year-old man with a long history of alcohol abuse has painless vomiting of large amounts of bright red blood. Heart rate is 110/min & BP is 80/0 mmHg. He dies despite rapid transfusion of packed erythrocytes. At autopsy, the source of the hemorrhage is found in the lower esophagus. A photograph of the site is shown. What mechanisms most likely cause the hemorrhage?

*Transmission of portal hypertension to esophageal veins* Esophageal varices - bleeding is much more severe - long history suggestive of portal HT - dilated submucosal veins in *lower* 1/3 of esophagus secondary to *portal hypertension* - common in cirrhotics - may be source of life-threatening hematemesis

Band most likely represent radiolabeled ceftriaxone that is bound to what?

*Transpeptidases* = one form of penicillin-binding protein that function to cross-link peptidoglycan in bacterial cell wall Penicillins & Cephalosporins - *irreversibly* bind penicillin-binding proteins

A 2-day-old male neonate is transferred to the neonatal intensive care unit because of tachypnea & intense cyanosis. There is a prominent lift & soft, systolic murmur is heard along the left sternal border. S1 is loud at the lower left sternum. X-ray film of the chest shows a normal heart size & pulmonary vascular pattern. Echocardiography shows the aorta lying anterior and to the right of the pulmonary artery. What is the most likely diagnosis?

*Transposition of the great vessels* - aorta leaves RV (anterior) & pulmonary trunk leaves LV (posterior) --> separation of systemic & pulmonary circulations

A 56-year-old Caucasian male presents to the ED with a 6-hour history of burning substernal pain. His medical history is unremarkable & he takes no meds. He smokes 2 packs of cigarettes every day & consumes alcohol occasionally. An ECG performed in the ED reveals ST segment elevation in leads I & V3-V6. During the next several hours, the patient develops progressive shortness of breath. He is unable to lie still in the bed & insists on sitting up. What histologic features is most likely to be newly present in this patient's lung tissue?

*Transudate accumulating in the alveolar lumen* MI involving anterior & lateral walls of left ventricle - dyspnea & orthopnea via MI-induced acute left ventricular failure --> rapid onset pulmonary venous HT & acute pulmonary edema Cardiogenic acute pulmonary edema = increased filtration of plasma water & electrolytes into lung interstitium & alveoli - fluid that accumulates = transudate (ultrafiltrate of plasma caused by hemodynamic changes)

A 37-year-old woman has a renal cell carcinoma confined within fascia of the right kidney. During nephrectomy using a posterolateral approach, what layer is normally incised?

*Transversalis fascia* - invests kidneys * adrenals - kidneys = retroperitoneal - divides into prerenal & retrorenal fascia

After sampling red wine & cheese, a 55-year-old man has a severe pounding headache. Pulse is 110/min, & BP is 230/145 mmHg. He is most likely taking which drug?

*Tranylcypromine* Serotonin syndrome with cheese & *MAO inhibitors* *MAO T*akes *P*ride *I*n *S*hanghai = *T*ranylcypromine, *P*henelzine, *I*socarboxazid, *S*elegiline - can also occurs if take migraine meds, triptans, together with antidepressants, SSRIs & SNRIS - others = meperidine (Demerol, painkiller) or dextromethorphan (cough med) - drugs of abuse, such as LSD, have also been associated with serotonin syndrome

A 37-year-old previously healthy man comes to the office for evaluation of enlarged lymph nodes. He has an 8-week history of progressively enlarging cervical lymph nodes associated with subjective fevers, fatigue, & drenching night sweats. After initial assessment, the patient undergoes excision biopsy of enlarged lymph nodes in the left posterior triangle of the neck. Two weeks later, during a follow-up visit, he describes difficulty with overhead activities such as combing his hair or placing dishes on overhead shelves. Exam shows a left shoulder droop with weakness of left arm abduction above the horizontal position. Other shoulder movements are normal, & there is no sensory loss. What muscles is most likely paralyzed in this patient?

*Trapezius* - elevates scapula, rotates it upward, stabilizes shoulder Spinal accessory nerve / CN XI - pure motor - innervation to sternocleidomastoid & trapezius - superficial course through posterior triangle = vulnerable to penetrating trauma & iatrogenic injury (from cervical node dissection) Trapezius weakness - drooping shoulder - impaired abduction of arm above horizontal - winging scapula

An examiner strokes a wisp of cotton across a patient' left cornea. There is no response. The examiner then strokes the cotton across the patient's right eye; both eyes blink. The most likely explanation of these findings is damage to what cranial nerves on the left?

*Trigeminal* Corneal reflex - afferent = V1 ophthalmic (nasociliary branch) - efferent = VII (temporal branch: orbicularis oculi)

A 35-year-old woman, gravida 1, para 0, at 12 weeks gestation comes to the office for evaluation of genital warts. She first noticed the warts last week & is concerned that it has persisted. The patient has occasional mild pruritus but no pain. She is currently sexually active with her boyfriend & engages in oral & vaginal intercourse. Exam shows several verrucous, skin-colored lesions over the labia majora. The patient asks whether the lesion could affect her future child. The virus involved in the patient's condition also has an affinity to infect what structures?

*True vocal cords* Condyloma acuminatum / anogenital warts - via HPV = small dsDNA virus - infects basal epithelial cells via small breaks in skin or mucosal surfaces = predilection for stratified squamous epithelium (anal canal, vagina, cervix) - *In respiratory tract, true vocal cords = only area covered with stratified squamous epithelium* = protective - infants acquire respiratory papillomatosis via passage through birth canal of mothers infected with virus

Relatively specific to mast cells & can be used as a marker for mast cell activation in anaphylaxis.

*Tryptase*

Actively dividing fibroblasts in culture are transferred from a 37 C incubator to a 0 C ice bath, & 10^-6 M colchicine is added to the culture medium. After 30 minutes, many cells have been arrested in mitosis. What cytoskeletal proteins is most likely to be involved?

*Tubulin* Drugs that act on microtubules - mebendazole (antihelminthic) - griseofulvin (antifungal) - colchicine (antigout) - vincristine/vinblastine (anticancer) - paclitaxel (anticancer)

Eight hundred motor vehicle collision occurred over 2 years in a city with a population of 600,000; 600 of these accidents were alcohol-related. During the same period, there were 400 fatalities due to motor vehicle collisions, of which 75% were alcohol-related. What best represents the 1-year incidence of alcohol motor vehicle fatalities in this community?

*Unable to determine from available info* - no way to determine 1 year incidence without appropriate breakdown of statistics by year - incorrect to take 2 year incidence & divide by 2 = cannot claim that incidence was identical in both years

A 36-year-old woman comes to the office due to frequent urination since an exacerbation of multiple sclerosis 2 months ago. Most of her symptoms, including dizziness, leg weakness, & numbness, have improved with corticosteroid treatment. However, she has continued difficulty holding urine, & on several occasions has passed a small amount of urine while trying to reach the bathroom. She has no urine leakage during coughing or sneezing. The patient has no other medical problems. Her abdomen is soft & nontender. Neurologic exam shows hyperreflexia & increased tone in the lower extremities. Her postvoid residual volume is low. Glucose, serum = 160 mg/dL Urinalysis Blood = negative Leukocyte esterase = negative Bacteria = none White blood cells = 3-4/HPF What is the most likey explanation for her urinary symptoms?

*Uninhibited bladder contraction* Urge incontinence - via detrusor overactivity --> sudden &/or frequent urge to urinate & empty bladder MS - regions in pons & cerebral cortex partially inhibit micturition reflex & also regulate contraction/relaxation of external urethral sphincter --> spinal cord lesions above sacral region = loss of higher center control of micturition --> detrusor hyperreflexia & urge incontinence - frequent urge to urinate & pass small amount of urine - disease progression --> bladder = atonic & dilated --> overflow incontinence

A 48-year-old woman comes to the office with a 6-month history of involuntary passage of a few drops of urine when sneezing or coughing. She has recently been leaking even more urine with minimal activity, which has been embarrassing and has caused her to limit her social activities. The patient has no weakness, numbness, or fecal incontinence. She has a history of HT & type 2 diabetes mellitus. She does not use tobacco, alcohol, or illicit drugs. She is married & has 4 children. Her supine BP is 126/82 mmHg & her upright BP is 120/80 mmHg. External genitalia exam shows leakage of a small amount of urine from the urethra when the patient is asked to cough Neurologic exam is within normal limits. What is the most likely cause of her condition?

*Urethral sphincter dysfunction* Stress incontinence - continence is maintained by urethral sphincters - incompetence of urethral sphincter (mainly EUS) = major factor causing incontinence - most common form of incontinence - typically presents after age 45 - via increased abdominal pressure - most common in women

An 18-year-old woman comes to the office for evaluation of acne. The patient is very upset about the acne scarring, which worsened since she started college. She has been very stressed by upcomin exams & feels "exhausted" due to lack of adequate sleep. The patient has been using benzoyl peroxide & tretinoin for the past year. She was also prescribed an oral antibiotic but stopped taking it several months ago due to lack of improvement. The patient is sexually active with her boyfriend & uses an intrauterine device for contraception. Her periods are regular and lasts 5 days. She takes no other meds & does not use tobacco, alcohol, or illicit drugs. Physical exam shows nodulocystic acne with scarring on the face, chin, & upper back. The patient is interested in isotretinoin treatment. What is the best next step in management of this patient?

*Urine beta-hCG* Isotretinoin synthetic 13-cis-isomer - treats severe acne associated with scarring - also used in patients who fail therapy with topical tretinoin/benzoyl peroxide, antibiotics = potent teratogen = contraindicated in pregnancy - negative pregnancy test required prior to prescribing Retinoids - inhibit follicular epidermal keratinization

How to prevent neonatal tetanus

*Vaccination of pregnant women* Neonatal tetanus - unhygienic deliveries or cord care - 5-7 days after birth - spasms & hypertonicity - transplacental IgG to fetus

During an experiment on the cough reflex in humans, a subject inhales air containing different amounts of particles that will impact & adhere to mucus primarily in the trachea. Blockade of what afferent pathways would most likely prevent this subject's reflex to initiate a cough?

*Vagal* - taste from supraglottic region - swallowing - soft palate elevation - midline uvula - talking - *cough reflex* - parasympathetics to thoracoabdominal viscera - monitoring aortic arch chemo- & baroreceptors

A 34-year-old woman comes to the office due to progressive exertional dyspnea for the past 6 months. She has no chest pain, lightheadedness, or syncope. Past medical history is unremarkable & the patient takes no medication. She does not use tobacco, alcohol, or illicit drugs. The patient's mother died of pulmonary arterial HT at age 32. BP is 125/74 mmHg & pulse is 75/min. BMI is 23 kg/m^2. Exam reveals clear breath sounds without wheezes or crackles & a loud second heart sound at left upper sternal border. Chest x-ray reveals clear lung fields. ECG shows right axis deviation. If this patient's condition is inherited, what is the most likely cause of her disease?

*Vascular smooth muscle proliferation* Hereditary Pulmonry Arterial Hypertension - via mutation in BMPR2 - AD - variable penetrance - dysfunctional endothelial & *smooth muscle cell proliferation* - increased pulmonary artery pressure --> dyspnea & fatigue - heard as *accentuation* of pulmonary component of P2 - can lead to cor pulmonale

An 18-month-old boy is brought to the physician's office for a follow-up cardiac exam. He has a palpable thrill & a harsh, grade 4/6 holosystolic murmur that radiates over the precordium & is heard best at the lower left sternal border. What is the most likely diagnosis?

*Ventricular septal defect* - holocystolic, harsh-sounding murmur - loudest at tricuspid area

A 64-year-old man with stable angina is being treated with atenolol & aspirin. He reports that over the last week, his symptoms have been worsening. His physician decides to add a new medication to his regimen. Several days later, he presents to the ER complaining of severe dizziness. On physical exam, his BP is 100/70 mmHg & his heart rate is 38 beats per minute. What meds were most likely administered?

*Verapamil* When used concomitantly, non-dihydropyridine-type calcium channel blocks (verapamil, diltiazem) & beta-blocking agents = additive negative effects on heart rate, AV node conduction, myocardial contractility - significant sinus bradycardia & hypotension

Intermediate filament expressed in mesenchymal cells.

*Vimentin* - secures organelles inside cytosol - resistance to mechanical stress

A 65-year-old woman with chronic constipation comes to the ED because of a 3-day history of abdominal pain. Abdominal exam shows distention with tenderness in the left lower quadrant. Sigmoidoscopy shows no tumors, but the scope cannot be inserted beyond 15 cm because of abrupt luminal narrowing. What is the most likely diagnosis?

*Volvulus of the sigmoid colon* Volvulus - twisting of portion around its mesentery - can lead to obstruction & infarction - midgut volvulus more common in infants & children - sigmoid volvulus more common in elderly = coffe bean sign on x-ray

Occurs after stroke of Middle Cerebral Artery

*Weakness of face & dysarthria* Contralateral paralysis & sensory loss - face & upper limb Aphasia if in dominant (usually left hemisphere)

Examination of the lungs at autopsy shows nodular areas of chronic pneumonitis with necrotizing arteritis & focal collections of epithelioid histiocytes. The most likely diagnosis is

*Wegener's granulomatosis* Triad: 1. focal *necrotizing vasculitis* 2. *necrotizing granulomas in lung & upper airway* 3. necrotizing glomerulonephritis

A 26-year-old woman has a Trichomonas vaginalis infection and begins metronidazole therapy. The patient should be advised to avoid what during therapy?

*Wine* Metronidazole - disulfiram-like reaction = severe flushing, tachycardia, hypotension with alcohol

A researcher develops 2 functional mRNA sequences composed of CUC & CUU trinucleotide repeats, respectively. He subsequently incubates these mRNAs in a solution containing functional ribosomes & tRNAs charged with appropriate amino acids. After several hours, it is found that both mRNA sequences produce polypeptide chains containing leucine repeats. This observed finding is due to what genetic principles?

*Wobble* - certain tRNAs can recognize multiple different codons coding for same amino acid - first 2 nucleotide positions on mRNA codon require traditional (Watson-Crick) base pairing with their complementary nucleotides on tRNA, whereas third "wobble" nucleotide position may undergo less stringent (nontraditional) base pairing - genetic code = degenerate = more than 1 codon can code for particular AA - ex. codons CUC & CUU both code for leucine

A 45-year-old man develops a fever after an abdominal operation. Blood cultures grow Staphylococcus aureus. What is the most likely site of infection from which the organism gained access to the blood stream?

*Wound* - post-op wounds are common sources of S aureus

From the values of deltaG0 give in the table, what compound in the overall metabolic pathway V --> W --> Y --> Z will accumulate in the largest amount at equilibrium?

*Y* Product W = 4.4 (4.0 + 0.4) Product Y = 9.1 (3.4 + 5.7) More deltaG (9.1) involved directing reaction toward "Y" = accumulates in largest amount

A 32-year-old man has had malaise, a low-grade fever, & a 4.5-kg (10-lb) weight loss over the past 3 months. He has unilateral cervical lymphadenopathy. Lab studies show: Hemoglobin = 11 g/dL Hematocrit = 33% Mean corpuscular volume = 80 um^3 Reticulocyte count = 0.5% Serum iron = 25 ug/dL Total iron-binding capacity = 150 ug/dL (N = 250-460) Exam of tissue obtained on biopsy of a lymph node shows Hodgkin's disease, nodular sclerosing type. The most likely cause of the anemia is

*abnormal utilization of iron* Anemia of chronic disease - associated with conditions such as rheumatoid arthritis, SLE, *neoplastic disorders*, & chronic kidney disease - *decreased iron, decreased TIBC, increased ferritin* = normocytic, but can become *microcytic*

Key intermediate in TCA cycle. Nitrogen transporter in metabolic actions.

*alpha-ketoglutarate* Hyperammoniemia = ammonia detoxified to glutamate via glutamate dehydrogenase --> depletes alpha-ketoglutarate

In the liver, alanine is transaminated by alanine aminotransferase to pyruvate with the amion group being transferred to

*alpha-ketoglutarate* - to form glutamate - almost all aminotransferase enzymes use alpha-ketoglutarate as amino acid group acceptor During catabolism of proteins, AAs are transferred to alphla-ketoglutarate to form glutamate --> glutamate processed in liver to form urea = primary disposal form of nitrogen in humans

A 78-year-old man has had urinary retention for the past week. He has been treated for the past 2 weeks with a drug for chronic neuropathic pain. The drug is most likely to be

*amitriptyline* TCA - major depression, *peripheral neuropathy*, chronic pain, migraine prophylaxis - *nocturnal enuresis*

Amino acids that contribute at least one nitrogen or carbon to the purine ring during the biosynthesis of purine nucleotides are

*aspartate, glycine, glutamine* GAG = Amino Acids necessary for purine synthesis: Glycine Aspartate Glutamine

A 25-year-old woman at 32 weeks' gestation begins taking a drug to delay the onset of preterm labor. After the first dose, she notices tremlousness in her hands. What types of receptors is most likely to be involved in this effect?

*beta2-adrenergic* Ritodrine, Terbutaline = beta 2 agonist used for control of premature labor - relax uterus - used to decrease contraction frequency in women during labor - *most common adverse effect of beta agonists = muscle tremor!!!*

In order to maintain blood flow through body, this in the pulmonary circulation must closely match the blood flow in the systemic circulation

*blood flow per minute*

An 85-year-old man is transferred to the hospital from a nursing home for altered mental status & fever. Upon arrival, the patient is admitted directly to the intensive care unit with a presumptive diagnosis of septic shock. Antibiotic therapy is initiated. The patient is unable to provide any history, but his caretakers state that he has been having non-specific symptoms, including fever, for the past few days. The patient has a history of cardiovascular disease, diverticulitis, & dementia. His blood pressure is 60/40 mmHg despite aggressive intravenous hydration. NE is administered in response to the patient's hypotension. What cellular changes occurs directly in response to NE therapy?

*cAMP increase in cardiac muscle cells* NE - adrenergic agonist - affects alpha & beta1 receptors alpha1 = increased IP3 --> peripheral vasoconstriction alpha2 = decreased cAMP --> decreased release of NE & insulin beta1 = increased cAMP --> increased contractility

migratory thrombophlebitis should raise suspicion for

*cancer* - hypercoagulability = visceral adenocarcinomas of pancreas, colon, lung - migratory superficial thrombophlebitis = trousseau syndrome

How to calculate interstitial fluid volume

Extracellular Fluid = Interstitial Fluid - Plasma Extracellular = mannitol or inulin Plasma = albumin

A 58-year-old man develops an acute coronary thrombosis with resultant myocardial infarction. The swelling of the myocardial cells bordering the infarct is most likely due to

*depletion of ATP* - due to occlusion, O2 cannot reach mitochondria --> oxidative phosphorylation cannot occur --> no ATP production --> Na/K pump cannot work anymore --> loss of cellular function + cell death

Abuts the left anterior surface of the vertebral column & lies *posterior* to the esophagus & the left atrium.

*descending aorta*

Abdominal pain, bloody vaginal discharge, orthostatic hypotension, & positive pregnancy test are highly concerning for

*ectopic pregnancy that may have ruptured* - prior infection with *Neisseria gonorrhoeae* & Chlamydia trachomatis = predisposing factors

COPD can cause hypoxia sufficient enough to stimulate *increased*

*erythropoietin* production by cortical cells of kidney

Splenic infarct crisis in Sickle Cell Patients characterized by...

*fibrosis & atrophy* - via repeated infraction - presents in adult patients

A 40-year-old female presented to the physician for evaluation of worsening fatigue. She has no other medical problems. She does not use tobacco, alcohol, or drugs. Vital signs are within normal limits. Physical exam is within normal limits. Lab evaluation shows an alkaline phosphatase level of 180 U/L. What should be checked next?

*gamma-glutamyl transpeptidase* - moderately elevated alkaline phosphatase of unclear etiology should be followed up with gamma-glutamyl transpeptidase

A 2-year-old boy ingests an unknown quantity of iron sulfate tablets that his mother was given for anemia following childbirth. The most likely consequence of this ingestion is

*gastric bleeding* Iron poisoning - cell death via peroxidation of membrane lipids - nausea, vomiting, *gastric bleeding*, lethargy, scarring leading to GI obstruction - treatment = chelation (IV deferoxamine, oral deferasirox) & dialysis

A 44-year-old man is hospitalized with multiple injuries following a motor vehicle accident. An arteriovenous shunt created by the injury would most likely result in what changes in the left ventricular pressure-volume loop?

*green* AV shunt - via formation of AV fistulas - allows blood under arterial pressure to directly enter venous system - increase cardiac preload by increasing rate & volume of blood flow back to heart = elongation of diastolic filling segment (bottom line) & higher end diastolic volume - total peripheral resistance reduce = decreased afterload - high-volume AV shunts can eventually result in high-output cardiac failure

What type of glands are sebaceous glands?

*holocrine* exocrine gland - release entire content of cells via cell lysis

Desmopressin can alleviate bleeding in von Willebrand disease via what mechanism?

*increase in endothelial protein release* von Willebrand disease (vWD) - AD - vWF is secreted by endothelial cells & circulates in multimers non-covalently attached to clotting factor VIII - increased bruisability & mucosal bleeding Desmopressin (DDAVP) - synthetic analog of vasopressin / ADH - increases vWF release from endothelial cells - raises factor VIII levels - used for treatment of mild hemophilia A

Sickle cell patient with megaloblastic anemia is due to

*increased folate acid requirement* - via increased erythrocyte turnover

Basic fibroblast growth factor is applied to an experimentally induced dermal wound. A histologic section is prepared 72 hours later. Compared with an untreated wound, the most likely alteration in this wound is

*increased number of blood vessels* FGF - *product of macrophages in MI* - *stimulates angiogenesis*

Effect of cimetidine on prothrombin time of warfarin

*increased* CYP450 inhibitors: *SICKFACES.COM* *S*odium valproate *I*soniazid *C*IMETIDINE *K*etoconazole *F*luconazole *A*cute alcohol abuse *C*hloramphenicol *E*rythromycin (macrolides) *S*ulfonamides *C*iprofloxacin *O*meprazole *M*etronidazole

A 56-year-old man who has colon cancer is being treated with 5-fluorouracil. What is the mechanism of the antineoplastic action of this drug?

*inhibiting thymidylate synthetase activity* 5-fluorouracil - pyrimidine analog bioactivated to 5-FdUMP --> covalently complexes with thymidylate synthase & folic acid - capecitabine = prodrug with similar activity complex inhibits thymidylate synthase --> decreased dTMP --> decreased DNA synthesis clinical use = colon cancer, pancreatic cancer, basal cell carcinoma (topical)

Mallory-Weiss syndrome, associated with longitudinal tears at gastroesophageal junction, is associated with

*intraabdominal pressure* - during retching & vomiting - can be asymptomatic or lead to GI hemorrhage that manifests as hematemesis = 10% of cases of upper GI hemorrhage

An outbreak of hepatitis in New Delhi was characterized by high incidence of fulminant hepatitis in pregnant women, who experience a mortality rate of 20%. The virus responsible for the outbreak...

*is an unenveloped RNA virus* HEV - unenveloped, ssRNA virus - fecal-oral route - young & middle-aged adults in Asian, sub-Saharan Africa, Mexico - 6 week incubation period - high mortality rate in infected pregnant women

The *left 12th rib* overlies the parietal pleura medially & what laterally?

*kidney* - distal tip of 12th rib can be displaced into the retroperitoneum when fractured, lacerating the left kidney

Pulmonary artery occlusion pressure is measured at the tip of the pulmonary artery catheter after an inflated balloon occludes blood flow through a pulmonary artery branch. It closely corresponds to

*left atrial & left ventricular end-diastolic pressure* - pulmonary artery catheter / PAC / Swan-Ganz / right heart catheter

A 23-year-old woman has prolonged episodes of wheezing, dyspnea, & anxiety that are relieved by beta-adrenergic agonists. The major mediatory of her condition is

*leukotrienes* - bronchoconstriction in asthma, especially LTC, D, E4

Four months after a cholecystectomy for removal of gallstones, a 43-year-old woman has recurrent episodes of biliary colic. After endoscopic sphincterotomy, the episodes of colic do not recur. What defects in the sphincter of Oddi best explains this patient's course?

*loss of enteric inhibitory motor innervation* - symptoms are due to "contraction" of Sphincter of Oddi - defect = defect in relaxation - inhibitory motor innervation will relax the SOD - *loss of inhibitor motor innervation = a defect in relaxation = contraction* (like in this patient)u

A 65-year-old man with inguinal adenopathy undergoes a lymph node biopsy. Light microscopy shows replacement of nodal tissue by cells that form well-defined, uniform glandular structures. The nuclei are relatively small & nucleoli are inconspicuous. An immunohistochemical stain for prostate-specific antigen is positive. These findings are most consistent with ...

*low-grade, high-stage neoplasm* Adenocarcinoma of prostate - low grade = well-defined glandular structure - high stage = lymph node invasion

Most common site of metastases from renal cell carcinoma

*lungs* - bone = next most common Clear cell carcinoma - most common subtype - large, rounded or polygonal cells with clear cytoplasm - classic triad = hematuria, flank pain, palpable mass in minority of patients - often detected incidentally at advanced stage

Blood supply to femoral head derives mainly from ascending cervical & reticular branches of

*medial circumflex artery* - vulnerable from fractures of femoral neck

HIV-associated dementia involved inflammatory activation of

*microglial cells* = microglial nodules

Main distinguishing characteristic of atypical depression

*mood reactivity* - can be treated with MAOIs, like *phenelzine* - patients both treatment resistant & with atypical features are good candidates for trial of MAOI

Primary cell lines increased in stable COPD

*neutrophils*, macrophages, CD8+ T lymphocytes - release enzymes & proteases such as neutrophil elastase that cause alveolar damage, reduced ciliary motion, & increased mucus secretion by globlet cells

Long-term use of PPIs, such as *omemprazole*, may be associated with increased risk of

*osteoporotic hip fractures* - insoluble calcium (calcium carbonate) requires acidic env't for proper absorption --> acid-suppressing meds interfere with this process = problematic in older adults

Most common underlying malignancies associated with Dermatomyositis

*ovarian*, lung, colorectal, & non-Hodgkin lymphoma

In the biosynthesis of glucose from pyruvate by the liver, the first intermediate formed from pyruvate is

*oxaloacetate* Pyruvate carboxylase (biotin): - oxaloacetate can replenish TCA cycle or be used in *gluconeogenesis*

Rats subjected to chronic inhalation exposure of formaldehyde develop nasal squamous cell carcinomas. Decreased activity of what genes is likely to be found on cytogenetic studies of the tumor cells?

*p53* - decreased activity of tumor suppressor gene --> neoplasms - acts during G1 - "molecular policeman"

At a given PO2, more O2 can be unloaded from hemoglobin when what is decreased in erythrocytes?

*pH* A decrease in all factors (including H+) causes left shift --> decreased O2 unloading --> renal hypoxia --> increased EPO synthesis --> compensatory erythrocytosis *L*ower = *L*eft

Unchanged in methemoglobinemia

*partial pressure of oxygen* in blood (amount of oxygen dissolved in plasma)

Major ADRs of amlodipine

*peripheral edema*, dizziness, lightheadedness, gingival hyperplasia, constipation Dihydropyridines - amlodipine, clevidipine, nicardipine, nifedipine, nimodipine - act on vascular SM

A 45-year-old man has nausea, vomiting, & abdominal pain. He has tachycardia, absent bowel sounds, & involuntary guarding & rebound tenderness of the abdomen. The most likely cause of these findings is

*peritonitis* - voluntary guarding = appendicitis - involuntary guarding = peritonitis - appendicitis can progress to peritonitis

A 49-year-old man has a 1-week history of shortness of breath without fever, chills, or cough. Breath sounds are decreased in the left lower lobe, & there is decreased vocal & tactile fremitus & dullness to percussion in this area. The most likely diagnosis is

*pleural effusion* = decreased breath sounds = dull percussion = decreased fremitus = excess accumulation of fluid between pleural layers --> restricted lung expansion during inspiration - can be treated with thoracentesis to remove/reduce fluid

Defects in uroporphyrinogen decarboxylase result in

*porphyria cutanea tarda (PCT)* - most common form of porphyria - chronic photosensitivity = blistering in areas of sun exposure & elevated levels of uroporphyrinogen in urine

Intraductal papilloma is caused by

*proliferation of papillary cells* in duct or cyst wall with *fibrovascular core* - may contain foci of atypia or ductal carcinoma in situ - bloody discharge via twisting og vascular stalk of papilloma in duct

Alveolitis with interstitial edema, inflammatory cell accumulation, & type II epithelial cell hypertrophy & hyperplasia is believed to be an early & central event in the pathogenesis of

*pulmonary fibrosis* Idiopathic pulmonary fibrosis - repeated cycles of lung injury & wound healing with increased collagen deposition - honeycomb lung appearance & digital clubbing

A 45-year-old woman who has acute diverticulitis develops severe hypotension, tachypnea, & tachycardia. She subsequently develops cyanosis & hypoxemia unresponsive to oxygen therapy. X-ray films of the chest show a diffuse alveolar infiltrate. Blood culture grows Escherichia coli. A major factor in the pathogenesis of this syndrome is

*release of oxygen free radicals from sequestered neutrophils* Patient ruptured diverticuli --> led to sepsis - bacteria was attacked by neutrophils in capillaries of lungs --> neutrophils release enzymes or oxygen free radicals (via NADPH oxidase) to kill bacteria --> also damage pulmonary capillaries = rupture of capillary = allows for blood to spill into alveoli

Vascular access during cardiac catheterization is typically obtained via either the *common femoral artery* or radial artery. Arterial puncture above the inguinal ligament increases the risk of

*retroperitoneal hemorrhage* - portio nof vessel lies directly inferior to peritoneum - bleeding in retroperitoneal space *cannot be controlled* with external compression = life-threatening - hemodynamic instability = hypotension, drop in hemoglobin, ipsilateral flank pain

A previously healthy 56-year-old man has the sudden onset of severe headaches that become worse in the afternoons. His blood pressure is 180/110 mmHg. Renal arteriogram shows 85% occlusion of the right renal artery. The lab finding that best predicts whether an operation that relieves the obstruction will reduce the blood pressure to normal is increased renin activity in the

*right renal vein vs left renal vein* right renal artery occluded --> decreased pressure in blood getting to right afferent arteriole & JGA --> JGA secretes more renin = HT left renal artery is fine, & patient has HT --> increased pressure getting to left afferent arteriole --> left JGA would secrete less renin *Changes are occurring in afferent arteriole = see changes in veins leaving glomeruli* - *by the time blood circulates through heart & back to arteries, renin equal in both left & right renal arteries* *Plasma renin activity measured usually in renal veins*

Girl who took overdose of theophylline reports nausea & headache. She should be carefully monitored for

*seizures & tachyarrhythmias* Methylxanthines - low does = mild cortical arousal & insomnia, like caffeine - seizures = major cause of morbidity - treatment = activated charcoal to reduce GI absorption - beta-blockers treat theophylline-induced cardiac tachyarrhythmias

During the second and third trimesters of pregnancy, women have increased levels of circulating glucocorticoids but have few of the catabolic responses associated with excess glucocorticoids. The most likely explanation of this finding is increased

*steroid-binding protein* - bind to hormone --> prevents hormone from acting on receptors - *there's also increased synthesis of steroid-binding proteins in pregnancy*

Cricothyrotomy passes through

*superficial cervical fascia*, pretracheal fascia, *cricothyroid membrane*

A 28-year-old man reports extremely familial thoughts (deja vu) just before he has a seizure. What labeled area in the diagram is the most likely site of the causal lesion?

*temporal lobe* Stimulation of superior temporal gyrus... = altered perceptions of sounds & auditory illusions & hallucinations = seem remarkably real, almost as if reexperiencing past event (deja vu)

In superior gluteal nerve injury, there is atrogenic injury during intramuscular injection to

*upper medial gluteal region* / superomedial quadrant of affected buttock Trendelenburg gait / gluteus medius gait - hip drops down as ipsilateral foot is lifted off ground - observed when there is injury to the contralateral superior gluteal nerve or to gluteus medium muscle - superior gluteal nerve derived from L4-S1 ventral rami --> leaves pelvis through greater sciatic foramen above level of piriformis

Patient who is taking probenecid is expected to have increased excretion of

*urate* Probenecid - uricosuric drug - increases uric acid excretion in urine - primarily used in treating gout & hyperuricemia - filtered at glomerulus - inhibits kidney's organic anion transporter (OAT)

Detrusor overactivity results in

*urge incontinence*

Compared with a person who follows a lacto-ovo vegetation diet, a person whose vegetarian diet does not permit intake of milk or eggs is most likely to have a deficiency of

*vitamin B12 (cyanocobalamin)*

A 32-year-old man has a fam history of bleeding. Partial thromboplastin & bleeding times are prolonged, aggreagation of platelets with ristocetin is absent, & factor VIII (antihemophilic factor) concentration is decreased. The most likely diagnosis is

*von Willebrand's disease* = prolonged bleeding after trauma, brushing teeth, dental procedures, menorrhagia - intrinsic pathway coagulation defect = decreased vWF --> *increased PTT* (*vWF acts to carry/protect factor VIII*) = autosomal domainant - *no platelet aggregation with ristocetin cofactor assay* - treatment = desmopressin --> releases vWF stored in endothelium

Recognize *koilocytes*

- Pap smear = koilocye = sign of HPV = immature squamous cell with dense irregularly staining cytoplasm & perinuclear clearing = halo - enlarged pyknotic nucleus where chromatin has condensed as part of apoptosis = raisinoid appearance - smoking = increased risk of HPV infection developing into intraepithelial neoplasia & cancer

Recognize putamen

- Wilson's disease can cause cystic degeneration of putamen as well as damage to other basal ganglia structure = medial to the insulin & *lateral to the globus pallidus*

A 73-year-old man is evaluated for exertional dyspnea. His exercise tolerance has decreased over the last year, & he can barely walk 2-3 blocks without stopping. The patient also reports occasional episodes of lightheadedness & palpitations. He has had no chest pain or syncope. He was diagnosed with HT in the past but does not taken any meds. Physical exam reveals a cardiac murmur. The patient is referred to a cardiologist for further evaluation. Cardiac catheterization is performed, & the findings are show in the image. What points most likely corresponds to the peak murmur intensity in this patient?

- absence of any aortic valve pathology = pressure in aorta similar to LV pressure during systole Aortic stenosis - abnormal pressure gradient between left ventricular & aortic pressure tracings during systole - intensity directly related to magnitude of left ventricle to aorta pressure gradient = systolic ejection-type, crescendo-decrescendo murmur - starts after first heart sound & typically ends before A2 component of 2nd heart sound

Recognize Seborrheic keratosis

- benign, tan or brown epidermal tumor - middle-aged or elderly ind.s - flat macules - wart-like lesions - greasy surface & well-demarcated border - stuck-on appearance - rapid onset = Leser-Trelat sign = undiagnosed internal malignancy

Recognize *right atrium* on chest x-ray

- consolidation involving the right middle lobe (acute lobar pneumonia) can obscure this - right middle lobe = immediately adjacent to right border of heart - on posteroanterior (PA) chest x-ray projections, right atrium = most of right side of cardiac silhouette

Constriction of afferent arterioles... - GFR = - RPF = - FF =

- decreased - decreased - unchanged

An asymptomatic 42-year-old man with essential hypertension is started on an angiotensin-converting enzyme inhibitor. What shows the most likely effect of treatment on circulating levels of aldosterone, renin, & bradykinin? - Aldosterone - Renin - Bradykinin

- decreased Aldosterone - increased Renin - increased Bradykinin - ACEI blocks synthesis of AII & Aldosterone - AI & renin increase because they are both before the block - bradykinin increase because ACE is inolved in kinase system --> cough, angioedema

A healthy 5-year-old man who resides at sea level takes a 45-minute ride in a cable car from near sea level to a skin resort (altitude 3050 m [10,000 ft]). What labeled points on the diagram best represents this patient 30 minutes after arrival at the resort?

- decreased atmosphere oxygen (PO2) --> decreased PaO2 --> increased ventilation --> decreased PaCO2 --> respiratory alkalosis --> altitude sickness - increased 2,3-BPG --> binds Hb = Hb releases more O2 - increased renal excretion of HCO3- = compensates for respiratory alkalosis - chronic hypoxic pulmonary vasoconstriction --> pulmonary HT & RVH

Recognize ecthyma gangrenosum caused by *Pseudomonas aeruginosa*

- febrile neutropenia & sepsis - increased susceptibility with gram-negative organisms, like Pseudomonas = strong association with ecthyma gangrenosum - skin patches = necrosis & ulceration via insufficient blood flow - contributing virulence factors = exotoxin A (protein synthesis inhibition), elastase, phospholipase C (degrades cellular membranes), pyocyanin (generates reactive oxygen species)

Recognize Aspergillus fumigatus

- fungal rhinosinusitis - fungal hyphae branching at acute angles with septations - grows on decaying veggies - leukemia & lymphoma = strong risk factors

Recognize MRI of structure within *Middle Cranial Fossa*

- houses temporal lobes of brain & pituitary gland

Recognize Acanthosis nigricans

- hyperpigmented, velvety plaques - axilla or neck - associated with diabetes mellitus, obesity, visceral malignancy, endocrinopathy

Constriction of efferent arterioles.... - GFR = - RPF = - FF =

- increased - decreased - increased

Recognize *Adenocarcinoma* of colon

- occult blood in stool - barium studies of transverse colon = intraluminal mass

Presentation of CMV esophagitis

- odynophagia = pain with swallowing - dysphagia = difficulty swallowing = can be accompanied by fever or burning chest pain = *linear & shallow ulcerations* in lower esophagus - tissue biopsy = enlarged cells with basophilic or eosinophilic intranuclear inclusion bodies - can occur in transplant patients

Recognize *airway resistance along bronchial tree*

- upper respiraotry tract (nasal passages, mouth, pharynx, larynx) = half of total airway resistance - remainder derives from lower respiratory tract = begins at trachea & consists of 23 generations of airways - resistance within trachea & mainstem bronchi = relatively high --> increases in medium-sized bronchi because of high turbulent airflow --> resistance is max between bronchial generations 2-5 --> drops in subsequent generations (small bronchi, bronchioles) because summated cross-sectional area massively increases - low-resistance laminar airflow predominates in airways <2 mm in diameter

Normal respiratory quotient

0.8 = ratio of CO2 to O2 across alveolar membrane - used to estimate metabolic rate

5'-ACG-CUA-CCA-UUG-UAA-CAA-GUU-AGC-UAG-3' Which tRNA anticodon is responsible for adding the last amino acid to the truncated polypeptide during protein translation?

5'-CAA-3' Stop codons: *UAG* *UAA* UGA *Codon just prior to first stop codon will be last codon to add amino acid* --> 5'-UUG-3' = last codon to add amino acid to truncated protein --> will be carried by 5'-CAA-3' anticodon

Metabolism of ethanol

7 Cal per gram

First step in synthesis of bile acids

7-alpha-hydroxylase = cholesterol --> 7-alpha-hydroxylcholesterol = lower ratio of cholesterol to bile acids = lower risk of cholesterol stones

5' end of all mRNA is capped with

7-methylguanosine residue via unique 5' to 5' linkage - occurs in nucleus as RNA is being transcribed - methylated cap protects mRNA from degradation by cellular exonucleases --> allows it to exit nucleus

Metabolism of fat

9 Cal per gram of fat

Recognize immunofluorescent rapidly progressive glomerulonephritis

= *crescent formation* light microscopy Nephritic syndrome - HT, hematuria (RBCs in urine), moderate proteinuria - linear deposits of Ig along glomerular BM = IgG, C3 - anti-GBM Abs target collagen type IV

Recognize hypercellular glomerulus typical of poststreptococcal glomerulonephritis (PSGN)

= *decreased serum C3 level* - elevated anti-streptolysin O, anti-DNase B, anti-cationic proteinase - cryoglobulins may be present

Recognize primary somatosensory cortex

= all somatic sensory modalities (touch, temp/pain, vibration/proprioception) of contralateral body

Recognize *left gaze with internuclear ophthalmoplegia*

= disorder of conjugate horizontal gaze via damage to MLF Conjugate horizontal eye movement - activated by frontal eye field in cerebral cortex --> projects to contralateral paramedian pontine reticular formation --> sends efferents to ipsilateral CN VI nucleus at level of *facial colliculus in dorsal pons* - subsequently, CN VI nucleus projects to ipsilateral lateral rectus muscle (abducts eye) & contralateral medial rectus subnucleus of CN III (adducts eye) via MLF Unilateral MLF lesion - can be via lacunar stroke in pontine artery distribution - lesion in right dorsal pons --> disrupts MLF = impaired adduction of ipsilateral (right) eye during conjugate horizontal gaze - convergence & pupillary light reflex preserved

Recognize Hydrocephalus ex-vacuo CT

= hydrocephalus caused by central neuronal volume loss - patients with neurodegenerative diseases (*AIDS* dementia) - significant cortical atrophy --> allows ventricles to expand while maintaining normal CSF pressure

Positive straight leg test

= pain elicited in supine patient when leg is held straight while raised off examining table = sign of sciatic nerve root (L4-S3) irritation = more sensitive for intervertebral disc herniation causing sciatica

Cardiac Output equations

= stroke volume x heart rate = *rate of oxygen consumption* / ateriovenous oxygen content difference

*0.95^8* Each of the 8 blood sample results = *independent event* = one patient's result has no impact on another's - 95% probability of correctly testing negative & 5% probability of incorrectly testing positive - chance of all 8 tests testing negative = *multiply probability* of each test returning negative result = 0.95^8

A research lab develops a new serologic test for detecting prostate cancer. The new assay is compared to transrectal ultrasound-guided prostate biopsy to determine sensitivity & specificity parameters. It is found that the test result is negative in 95% of patients who do not have the disease. If the new assay is used on 8 blood samples taken from patients without prostate cancer, what is the probability of all 8 test results coming back negative?

Deficiency that causes glycogen storage disease type II (Pompe disease).

Acid alpha-glucosidase / Acid maltase - cardiomyopathy, muscle weakness, hypotonia

Life-threatening disorder caused by the inability to metabolize fructose-1-phosphate

Aldolase B deficiency - acutely symptomatic after ingesting fructose-containing foods --> eventually develop liver failure - treatment = eliminate dietary fructose

Anti-CD52 humanized mAb used for chronic lymphocytic leukemia

Alemtuzumab A*lym*tuzumab - chronic *lym*phocytic leukemia - initiates direct cytotoxic effect via complement fixation & Ab-dependent, cell-mediated cytotoxicity

Drug that results in decreased uterine contractions & mydriasis affects what receptors?

Alpha & Beta-adrenergic agonists alpha1 - q - increased vascular smooth muscle contraction - *increased pupillary dilator muscle contraction = mydriasis* - increased intestinal & bladder sphincter muscle contraction - ex. ophthalmic preparation of phenylephrine (selective alpha-adrenergic agonist) dilates pupil before ophthalmoscopic exam beta2 - uterine relaxation (tocolysis) --> defers premature labor - ex. ritodrine, terbutaline

Recognize hippocampus on MRI

Alzheimer's = atrophy in temporoparietal lobes & hippocampus!

Frequently seen on peripheral blood smear of lead poisoning

Basophilic stippling - inhibition of erythrocyte 5' nucleotidase by lead --> ribosome aggregation via inability to degrade RNA = nonspecific = seen also in thalassemias & myelodysplastic syndrome

Treatment of choice for specific phobia

Behavioral therapy

Coenzyme for *carboxylation* enzymes

Biotin

Recognize *mixing of deoxygenated blood* effect on partial pressure of oxygen

Blood in pulmonary arteries comes from systemic venous system & is normally deoxygenative --> blood moves through pulmonary capillaries --> becomes more oxygenated until equilibrates with alveolar pO2 (104 mmHg) = curve's upward deflection & plateau Blood in left atrium & ventricle has slightly lower pO2 (100 mmHg) than blood in pulmonary capillaries via *mixing of deoxygenated blood* with oxygenative blood from pulmonary veins = downward deflection sources of deoxygenated blood: - bronchial circulation - small cardiac (thebesian) veins --> drain into left atrium & ventricle

Characterized by unstable relationships, impulsivity, mood lability, & self-harm

Borderline personality disorder

Symptoms similar to those seen in SVC syndrome but on only onse side of body

Brachiocephalic vein obstruction - obstructed right brachiocephalic (innominate) vein - right brachiocephalic veinformed by union of right subclavian vein & right internal jugular vein - *right brachiocephalic vein also drains right lymphatic duct, which drains lymph from right upper extremity, right face & neck, right hemithorax, & right upper quadrant of abdomen*

Neutrophils become firmly attached to endothelium via binding of

CD 18 beta 2 integrins (Mac-1 & LFA-1) to intercellular adhesion molecule-1 (ICAM-1) on endothelial cells

Most common cause of *congenital bilaeral absence of vas deferens (CBAVD)*

CFTR gene mutation - CBAVD = azoospermia & infertility but normal levels of FSH, LH, & testosterone - *elevated sweat chloride levels*

Anticonvulsants that are also used as mood stabilizers

Carbamazepine & Lamotrigine - carbamazepine --> aplastic anemia - lamotrigine --> rash, Stevens-Johnson syndrome

Treatment of choice for extended-spectrum beta-lactamase (ESBL)-producing organisms

Carbapenems

Tracks patients with known condition to document history or response to treatment.

Case series - qualifying study

Odds of exposure to certain characteristic is compared between affected individuals & unaffected individuals who serve as controls

Case-control study - looks to see if odds of prior exposure or risk factor differs by disease state

Most commonly due to atherosclerosis, cardioembolic disease, or vasculitis (giant cell arteritis). Causes acute monocular vision loss. Exam reveals cherry red spot at macula due to diffuse retinal ischemia.

Central retinal artery occlusion

Tolerance acquired within fetal thymus during negative selection.

Central tolerance

Multiple & deep ulcers. Base may have gray to yellow exudate.

Chancroid - Haemophilus ducreyi - gram-negative bacteria via sexual contact - painful - ragged border - associated with grey exudate - clumping pattern of bacteria on Gram stain - higher prevalence in sub-Saharan Africa (like Botswana - South Africa), Latin America, Asia

Location of WT-1 tumor suppressor gene.

Chromosome 11

Location of RB tumor suppressor gene (anti-oncogene).

Chromosome 13 --> retinoblastoma & osteosarcoma

Location of NF-1.

Chromosome 17

Lecithinase (toxin A) is produced by

Clostridium perfringens - hydrolyzes lecithin in cell membranes = cell lysis & gas gangrene

Necessary cofactor for methionine synthase, the enzyme that transfers methyl group from 5-methyltetrahydrofolate to homocysteine, forming methionine & regenerating tetrahydrofolate

Cobalamin

People with common exposure. Will they develop disease

Cohort --> prospective --> retrospective = exposed in past --> what happened to those people

Individuals are followed over time to determine incidence of disease of interest

Cohort studies - compares group with given exposure or risk factor to a group without exposure - looks to see if exposure or risk factor is associated with later dev't of disease

Multinucleated giant cells & large pinkish-purple *intranuclear* (not intracytoplasmic) inclusions.

Cowdry type A bodies of Herpes simplex virus type 2

Evaluates exposures & outcomes of interest in individuals at given point in time (snapshot).

Cross-sectional surveys/studies - frequency of disease & frequency of risk-related factors are assess in present - what is happening?

Recognize leukocytoclastic vasculitis

Cutaneous small vessel vasculitis - affects skin - via drug or pathogen (hepatitis B or C) - drugs = *penicillins*, cephalosporins, sulfonamides, phenytoin, allopurinol - *nonblanching palpable purpura* - lower extremities - markedly inflamed small blood vessels with fibrinoid necrosis - first 24 ours = neutrophils

Inhibits incorporation of D-alanine into UDP-MUrNAc-oligopeptide during bacterial cell wall synthesis

Cycloserin - high level of ototoxicity

Used to treat psoriasis. Inhibits NFAT (nuclear factor of activated T cells) from entering nucleus & modulating transcription activity.

Cyclosporine - impairs IL-2

People with disease of interest (cases) & people without disease (controls) asked about previous exposure to variable being studied (ex. acetaminophen use)

Exposure odds ratio

Typically identified by biopsy after mammography screening shows microcalcifications in asymptomatic patients with normal breast exam

DCIS - *ducts* distended by pleomorphic cells with prominent central necrosis without extension beyond ductal BM

E coli that does *not* ferment sorbitol on sorbitol-containing MacConkey agar & does not produce glucuronidase.

EHEC )157:H7 - inactivates ribosomal subunits (Shiga-liek toxin) - does not invade intestinal mucosa

Examples of food poisoning resulting from exotoxin *after ingestion* of contaminated food

ETEC & Vibrio cholera --> watery diarrhea EHEC & Shigella --> inflammatory diarrhea

Produce toxins that increase intracellular cyclic GMP, leading to watery diarrhea & electrolyte loss

ETEC (ST) & Yersinia enterocolitica (Y enterocolitica enterotoxin)

Topical ornithine decarboxylase inhibitor used to decrease rate of facial hair growth

Eflornithine

CT disorder that classically involves genetic mutation of type V collagen. Leads to joint hypermotility & skin hyperelasticity & fragility. Due to defective collagen production. Wound healing is impaired.

Ehlers-Danlos

Noncompetitive antagonists change

Emax - shift down

Acts as agonist at motilin receptors in stomach & duodenum, contributing to drug's GI side effects.

Erythromycin

Lactose-fermenting, indole-positive gram-negative rods

Escherichia coli - most common etiology of UTIs among elderly women - indole positive = ability to convert tryptophan to indole --> distinguishes from Enterobacter cloacae (another lactose-fermenting gram-negative rod)

An 82-year-old man develops mild shortness of breath 3 months after beginning therapy that includes bleomycin for a localized squamous cell tumor & mouth. What pulmonary function test results are most likely to be observed in this patient? FEV/FVC = Diffusing Capacity = Total Lung Volume =

FEV/FVC = No change (or increased) Diffusing Capacity = decreased Total Lung Volume = decreased

A 22-year-old woman is brought to the ED because of shortness of breath & wheezing for 6 hours. Her symptoms began shorly after visiting her friend who has cats. She has a history of similar symptoms after exposure to cats. On arrivals, she speaks in short sentences. Her respirations are 32/min. What sets of results is most likely on pulmonary function testing? FEV:FVC = Residual Volume =

FEV:FVC = decreased Residual Volume = increased Obstructive Lung Diseases - Chronic Bronchitis - Emphysema - Asthma - *increased RV*, increased FRC - decreased FEV, decreased FVC --> decreased FEV/FVC ratio - V/Q mismatch

AR condition caused by mutations in genes responsible for repair of interstrand DN crosslinks. Most common inherited cause of aplastic anemia & presents with short stature, absent thumbs, & increased malignancy risk.

Fanconia anemia

Case Fatality Rate

Fatal Case / Total Number of People with Disease

Activate peroxisome proliferator-activated receptor-alpha transcription factors, which leads to stimulation of lipoprotein lipase activity & a decrease in triglyceride levels

Fibrates

Which aortic arch is obliterated in fetal dev't?

Fifth pharyngeal & aortic arches?

Inhibits both DNA (replication) & RNA (protein synthesis) in fungal cells. Mainly used as synergistic agent with amphotericin B.

Flucytosine

Axillary nerve involves what cause of injury?

Fractured *surgical neck of humerus*

Produced in stomach & regulates food intake. Levels increase in fasting states & fall after eating.

Ghrelin

Treatments for hepatic encephalopathy

Lactulose - increases conversion of ammonia to ammonium Rifaximin - decreases intraluminal ammonia production

Overexpressivity of this suggests more aggressive breast tumor

HER2 - typically responds to trastuzumab

p < 0.05 means

Ha is correct - reject Ho = H1 is correct

Pharynx --> lymphatics --> meninges This is the mechanism of spread of

Haemophilus influenzae meningitis

Are isotype-speciic & distinguish 5 isotypes

Heavy chains

Rare disorder that results from mutations involving trypsinogen or SPINK1 gene

Hereditary *pancreatitis* --> abnormal trypsin = not susceptible to inactivating cleavage by trypsin

Recognize graph for *noise-induced hearing loss*

High-frequency hearing loss due to chronic noise exposure - trauma to stereciliated hari cells of *organ of Corti* - shearing forces against tectorial membrane - high-frequency hearing lost first - both air & bone conduction affected

p > 0.05 means

Ho is correct

Presently the first-line med for treatment of essential HT in general population

Hydrochlorothiazide

What cellular adaptations is most likely in the epidermis of affected skin in this patient?

Hyper*plasia* Psoriasis - acanthosis with parakeratotic scaling (nuclei still in stratus corneum) - munro abscesses - increased stratum spinosum - decrased stratum granulosum - auspitz sign = pinpoint bleeding spots from exposure of dermal papillae when scales scraped off

Secreted by macrophages to stimulate helper T-cells

IL-1

Stimulates growth & differentiation of bone marrow stem cells & is produced by T-helper cells.

IL-3

A penetrating wound to the back to the immediate right of the vertebral bodies would strike the

IVC - passes through right side of central tendon of diaphragm at level T8

If blood samples are collected from 25 healthy volunteers instead of 100, what best expresses the expected impact on the standard error & 95% confidence interval about the mean?

Increased standard error Decreased width of 95% confidence interval *CI = x +/- Z (SE)*

Produced by liver in response to stimulation by growth hormone. Functionas mitogen & as inhibitor of apoptosis.

Insulin-like growth factor-1

Acquired skin infection involving upper natal cleft of buttocks.

Intergluteal pilonidal disease

Structurally similar to pyridoxine (vitamin B6). Antibiotic increases urinary excretion of pyridoxine - often causes frank deficiency of vitamin B6. Leads to defective synthesis of NTs like GABA. ADR = *peripheral neuropathy*

Isoniazid = *vitamin deficiency*

Glycosaminoglycan in extracellular matrix that plays role in maintaining type I collagen fibril organization in number of tissues (cornea)

Keratan sulfate

Second part of duodenum is at what level?

L2

Abdominal aorta bifurcates at what level?

L4

Characterized by presence of multiple cysts of varying size in the kidney & the *absence of a normal pelvocaliceal system.* Condition is associated with ureteral or ureteropelvic atresia, with the affected kidney essentially rendered nonfunctional. Abdominal ultrasound of the fetus or newborn is diagnostic.

Multicystic kidney dysplasia

Trehalose dimycolate is a cell wall component & major virulence factor of

Mycobacterium tuberculosis - protects M tuberculosis from being killed by macrophages & stimulates granuloma formation

Found in neutrophils. Converts hydrogen peroxide to hypochlorous acid, a bactericidal compound that also causes oxidative damage to host cells.

Myeloperoxidase

Scientists studying the principles behind oxygen-hemoglobin dissociation have discovered a way to successfully separate Hb tetramers into individual alpha & beta subunits. During an experiment, a solution is created that contains only monomeric beta-hemoglobin subunits under physiologic conditions. If measured, the oxygen dissociation curve of the dissolved beta subunits will most likely resemble what lines / curve?

Myoglobin = much higher affinity for oxygen than hemoglobin = monomeric protein - only found in bloodstream after muscle injury - partial pressure of oxygen at which 50% of myoglobin 'cules are oxygen satruated (P50) = 1 mmHg = much lower than P50 of hemoglobin (26 mmHg) - secondary & tertiary structures of myoglobin & hemoglobin beta subunit are almost identical (alpha-subunits are also very similar to myoglobin)

Expression if amplified in neuroblastoma

N-myc proto-oncogene

Catalyzes reduction of molecular oxygen to superoxide free radicals, aiding bacterial destruction by phagocytic cells.

NADPH oxidase

Mechanism of PCP

NMDA *antagonism* = substance-induced psychosis - dissociative symptoms - agitation, hallucinations, violent behavior - trauma due to combative behavior - horizontal & vertical nystagmus

Where does the posterior pituitary gland originate from?

Neural tube - brain & spinal cord - pineal gland - retina

Primary cells responsible for intense inflammatory response seen in patients with gout

Neutrophils - NSAIDs = first-line therapy - patients with contraindications to NSAIDs = colchicine

Property of S saphrocyticus that allows it to be differentiated from other coagulase-negative Staphylococci

Novobiocin resistance

Tolerance that develops by means of T-cell anergy, which is the functional inactivation of T-cells that are reactive to self-antigens

Peripheral tolerance

NNT

Number Needed to Treat = 1/ARR

Gives rise to the artery of ligamentum teres, which supplies a minor portion of the femoral head. Important in children because it supplies region of femoral head proximal to epiphyseal growth plate.

Obturator artery

Surgical technique used to distinguish source of right upper quadrant bleeding.

Occlusion of portal triad (Pringle maneuver) - if hepatic bleeding persists after occlusion of portal triad, *inferior vena cava* or hepatic veins are likely injured

Anti-IgE Ab. Inhibits IgE binding to mast cells, preventing mast cell degranulation. Used in some patients with severe persistent asthma to lower IgE levels & improve allergen-induced bronchial constriction.

Omalizumab

Blocks binding of RANK-L to RANK & reduces formation of osteoclasts

Osteoprotegerin

Methylparaben is a derivative of

PABA (para-aminobenzoic acid) - *p-Aminobenzoic acid esters*

Inactivation of LDL-receptor degradation, increasing amount of LDL removed from bloodstream.

PCSK9 inhibitors - Alirocumab, Evolocumab

A 40-year-old man with end-stage renal disease due to type 1 diabetes mellitus is hospitalized for initiation of hemodialysis. A tunneled dialysis catheter is inserted into the right internal jugular vein. Before he is able to undergo dialysis treatment, the patient develops bleeding around the catheter exit site that is difficult to control. He has not been treated recently with anticoagulants. Further exam of this patient would most likely show what lab results? PT = Activate partial thromboplastin time = Platelet count = Bleeding time =

PT = Normal aPTT = Normal Platelet count = Normal Bleeding time = Prolonged Excessive bleeding + renal dysfunction = accumulation of uremix toxins in circulation - qualitative platelet disorder = prolonged bleeding time - uremic bleeding can be improved with dialysis

Recognize opening of parotid gland duct

Parotitis - swelling of cheek for weeks - elevation with small opening in area on exam of oral mucosa

Continuous murmur with *inspiratory splitting of S2*. Heard best at left infraclavicular area.

Patent ductus arteriosus - congenital rubella - prematurity - cyanotic congenital heart disease

Metabolic bone disease due to chronic kidney disease (CKD) Phosphate Parathyroid hormone Calcitriol

Phosphate = increased Parathyroid hormone = increased Calcitriol = decreased CKD - decreases GFR --> decreases filtered phosphate load --> elevated serum phosphate levels --> reduces serum free calcium concentrations & stimulates osteocytes & osteoclasts to release fibroblast growth factor-23 (FGF-23) = decreases proximal tubule phosphate reabsorption --> reduces calcitriole synthesis - long-term elevation in PTH (secondary hyperparathyroidism) can lead to friable bones & osteitis fibrosa

Recognize curve 1 - phosphatidylcholine; curve 2 - sphingomyelin in amniotic fluid of pregnant woman

Phosphatidylcholine / lecithin = component of pulmonary surfactant Sphingomyelin = common membrane phospholipid Amniotic fluid lecithin/sphingomyelin ratio = commonly used measure of fetal lung maturity - amniotic fluid concentration of lecithin equals sphingomyelin until middle of third trimester --> type II pneumocytes begin secreting surfactant --> *lecithin concentration increases sharply while sphingomyelin level remains unchanged* By 35 weeks gestation, L/S ratio averages 2:1 or higher = lung maturity

Catalyzes major rate-limiting step in glycolysis by converting fructose-6-phosphate to fructose-1,6-bisphosphate

Phosphofructokinase-1

Interconverts glucose-6-phosphate and glucose-1-phosphate. Links glycogenolysis, glycogenesis, & glycolysis

Phosphoglucomutase

Capsule component & major virulence factor for Haemophilus influenza type b (Hib)

Polyribosylribitol phosphate (PRP) - epiglottitis - fever, stridor, dyspnea

Typically located 25 or 75 bases upstream from their associated genes & function to initiate transcription

Promoter regions

Decrease intraocular pressure by increasing outflow of aqueous humor

Prostaglandin F2alpha - latanoprost, travoprost Cholinomimetics - pilocarpine, carbachol

Vitamin involved in the following reaction: glutamate + oxaloacetate --> aspartate + alpha-ketoglutarate

Pyridoxine / Vitamin B6

A healthy 34-year-old coal mine worker is trapped underground following partial collapse of an access shaft. Rescue efforts are directed toward clearing the obstructed tunnel, but it takes 2 days to reach him. While being taken to the surface, the miner tells rescuers that he feels dizzy & weak. He had an emergency supply of water but has not eaten anything for over 30 hours. Fingerstick blood glucose concentration is 78 mg/dL. What biochemical reaction is most likely responsible for maintaining this patient's current blood glucose levels?

Pyruvate --> oxaloacetate - pyruvate carboxylase *Oxaloacetate --> phosphoenolpyruvate* - Phosphoenolpyruvate carboxykinase Fructose-1,6-bisphosphate --> fructose-6-phosphate - fructose-1,6-bisphosphatase Glucose-6-phosphate --> glucose - Glucose-6-phosphatase 1st 12-18 hours of fasting = glycogenolysis --> once hepatic glycogen stores become depleted, *gluconeogenesis* becomes major process to keep glucose within normal range

In what reactions is biotin (vitamin B7) used as a cofactor?

Pyruvate carboxylase: *pyruvate to oxaloacetate* (gluconeogenesis) Acetyl-CoA carboxylase: acetyl-CoA to malonyl-CoA (FA synthesis) Propionyl-CoA carboxylase: propionyl-CoA to methylmalonyl-CoA (FA oxidation) = carboxylase enzymes = CO2 carrier Deficiency an occur via - poor diet - excessive raw egg white consumption (high levels of biotin-binding avidin in egg whites) = dermatologic chnages = metabolic acidosis

Enzyme involved in Hepatitis B: dsDNA --> ssRNA

RNA polymerase II

Directly compares >2 treatments. Usually subjects are randomly assigned to experience a specific exposure (mediation) or not exposure (placebo) & are followed to assess for outcome of interest (disease)

Randomized clinical trial

Universal enhancers of CYP45 pathway

Rifampin Phenobarbital *Phenytoin* - concurrent use of warfarin with these meds = decreased efficacy of warfarin - *patient's INR subtherapeutic comapared to her target INR range*

Occlusion of this artery is most likely to cause inducible ischemia of the inferior surface of the heart

Right coronary artery

Coagulase-*negative* staphylococci. Ubiquitous skin contaminant.

S *epidermidis* - most common cause of endocarditis in patients with prosthetic valves & septic arthritis in patients with prosthetic valves

Staphylococcus that ferments mannitol

S aureus

Type of staphylococcus resistant to novobiocin

S saprophyticus - UTIs in sexually active young women

Recognize Abducens Nerve

SO4 *LR6* R3

Loss of sensation at the medial aspect of the leg would result from a lesion of what nerve?

Saphenous nerve - largest pure sensory branch of femoral nerve

Opens into the major papilla & dunctions to drain the inferior/posterior portion of the head & uncinate process.

Small ventral duct (of Wirsung)

In the diagram of a blood vessel, what is the principal site of nitric oxide action in producing vasodilation?

Smooth Muscle

B cereus characteristically contaminates what foods?

Starchy foods such as rice (reheated fried rice)

Know steps regulated by fructose-26,-bisphosphate

Step*s* going from Glucose 6-phosphate --> Pyruvate

Mature defense mechanism that involves channeling unacceptable impulse into acceptable form of behavior (intense hostility & anger redirected by choosing boxing as sport)

Sublimation

Genetic analysis identifies a specific mutation in the NR5A/SF-1 gene that results in selective impairment in Sertoli cell function in a newborn boy who is found to have a micropenis at birth. Remainder of hypothalamic-pituitary-gonadal axis is unaffected. When he is 16 y/o, serum hormone levels are obtained. What patterns of blood hormone levels are most likely to be seen? Testosterone = Inhibin = FSH = LH =

Testosterone = Normal Inhibin = Decreased FSH = Increased LH = Normal Sertoli cells (non-germ cells) - secrete inhibin B --> inhibit FSH

Test'a ability to measure what it is supposed to measure

Validity (accuracy)

Toxins that result in increased intracellular cyclic AMP in intestinal mucosal cells, which leads to decreased absorption & increased secretion of sodium, chloride, & water

Toxins produced by: Bordetella pertussis (adenylate cyclase toxin) ETEC (LT) Campylobacter jejuni (C jejuni enterotoxin) Vibrio cholerase (choleragen toxin)

Most lateral of the distal carpal bones & articulates with first metacarpal.

Trapezium - the thumb swings on trapezium

Holosystolic murmur that *increases with intensity during inspiration* (Carvallo sign).

Tricuspid regurgitation

Articular cartilage is made of

Type II collagen

Human mAb used in psoriasis that targets IL-12 & IL-23. Inhibits differentiation & activation of CD4+ TH1 & TH17 cells.

Ustekinumab (Stelara)

Loss of this support contributes to uterine prolapse into vagina.

Uterosacral ligaments - connects posterior aspect of uterus to anterior portion of sacrum - hold uterus in anteverted or retroverted position

Short PR interval, slurred initial upstroke of QRS complex (delta wave), & widening of QRS complex. Due to accessory pathway that bypasses AV node & directly connects atria & ventricles.

Wolf-Parkinson-White (WPW) syndrome

Recognize 100% Specificity

Y = 100% Specificity - X = 100% Sensiticity - middle line = Most Accurate

Of the second-generation antipsychotics, this is most often noted for causing prolonged QT interval

Ziprasidone

Primary mechanism underlying giant cell arteritis

cell-mediated immunity - production of cytokines, especially *interleukin-6* Giant cell/temporal arteritis - inflammatory infiltrate in affected vessels = lymphocytes (CD4-positive T cells) & macrpohages - IL-6 correlates with severity of disease - monoclonal Ab against IL-6 (tocilizumab) = effective in treating GCA

Most cases of sporadic colorectal carcinoma arise via

classic adenoma-to-carcinoma sequence (*APC*/beta-catenin pathway) later ... KRAS, DCC, p53

Left-sided colon cancers tend to infiltrate the intestinal wall & encircle the lumen, causing

constipation & symptoms of intestinal obstruction

The right lateral geniculate nucleus is located in the thalamus & relays visual info to ipsilateral primary visual cortex. Damage to this structure would result in

contralateral homonymous hemianopsia

Unilateral infarction of primary visual cortex in occipital lobe via posterior cerebral artery occlusion results in

contralateral homonymous hemianopsia with macular sparing - macula receives collateral circulation from middle cerebral artery

Treatment of NMS caused by risperidone

dantrolene = *inhibition of calcium ion release from sarcoplasmic reticulum of skeletal muscle* --> reduces muscle rigidity/contraction by antagonizing ryanodine receptors --> inhibits calcium ion release from SR of skeletal muscle

Mutations that impair binding of cAMP-CAP to its regulatory site upstream from promoter will...

decrease transcription of lac operon - cAMP-CAP = positive regulator

Registers low-frequency sound

distal cochlea - apex near helicotrema (wide & flexible)

Relative means

divide control rate = last Tx rate / control rate

Secretin, the hormone that produces bicarbonate, is produced by the

duodenum - S cells

Irreversible retinal damage can occur with long-term use of

hydroxychloroquine

Metabolic effects of *chlorthalidone*

hyponatremia - inhibition of Na+/Cl- co-transporters in distal convoluted tubule hypokalemia - compensatory rise in renin & aldosterone hypercalcemia - increased reabsorption in distal tubule hyperglycemia *hypercholesterolemia* - decreased insulin secretion & increased insulin resistance hyperuricemia

Number Needed means

iNverse ARR to treat or harm Tx rate - control rate --> 1/ARR

Action of Vasoactive intestinal polypeptide on sphinecter of oddi

increased *relaxation* of intestinal smooth muscle & *sphincters*

Indicates biliary injury

increased alkaline phosphatase & gamma-glutamyl transpeptidase

Lymph from upper third of rectum drains to

inferior mesenteric lymph nodes - colon from splenic flexure to upper rectum - sigmoid colon

Venous components of external hemorrhoids drains into

inferior rectal vein --> internal pudendal vein --> communicates with internal iliac vein

Sertoli cells, which are analogous to female granulosa cells, produce

inhibin - in response to FSH - suppresses FSH production - facilitate spermatogenesis within seminiferous tubules

Mechanism of the most common death of TCA overdose

inhibit fast sodium channel conduction --> slows myocardial depolarization --> cardiac arrhythmias

Kozak consensus sequence plays major role in

initiation of eukaryotic translation process

Recognize *pancreatic pseudocyst*

inner walls of lesion lined with *fibrous & granulation tissue* Pseudocyst = complication of acute pancreatitis - most common location = lesser peritoneal sac

Lymph from prostate drains primarily into

internal iliac lymph nodes - lower rectum --> anal canal - bladder - vagina (middle third) - cervix - prostate

Lymph from inferior portion of bladder drains to

internal iliac nodes - lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), cervix, prostate

Lymph from prostate drains to

internal iliac nodes - lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), cervix, prostate

Can provide *rapid*, temporary relief of symptoms in Rheumatoid arthritis patients starting on DMARDs

intraarticular glucocorticoids (*prednisone*)

Right-sided colon cancer usually grow as exophytic masses & present with occult bleeding & symptoms of

iron deficiency anemia = initial symptoms of weight loss & progressive fatigue

Decreased activity of hepatic N-acetyltransferase results in diminished ability to metabolize drugs such as

isoniazid & sulfonamides --> increased likelikhood of toxicity

Patient with chronic, progressive loss of peripheral vision has typical features of

open-angle glaucoma

Impairment of detrusor contractions from sacral lesion or autonomic neuropathies will result in

overflow incontinence

The dorsal pancreatic bud forms the

pancreatic tail, body, *most of the head*, small accessory pancreatic duct

Fourth aortic arch gives rise to

part of true aortic arch subclavian arteries

IGN-gamma production is responsible for

phagolysosome formation inducible nitric oxide synthase release development of granulomas & caseous necrosis

First aortic arch is associated with

portion of maxillary artery - arch regresses almost completely

Antimitochondrial antibodies are seen in patients with

primary biliary cirrhosis - cholestatic symptoms (pruritus, jaundice, steatorrhea) & abnormal hepatic enzyme levels

Forms the anterior (sternal) surface of the heart & the majority of its inferior border

right ventricle

Sciatic foramen is divided into greater & lesser sciatic foramina by

sacrospinous ligament

Calcium binding to troponin C ...

shifts tropomyosin away from myosin binding site on actin

Recognize *Intussusception*

this = portion of intestine open with necrotic segment in lumen - "collapses telescope" - impaired venous return from invaginated segment of bowel --> ischemia & subsequent necrosis of intestinal wall - most typical location = ileocolic junction - most common in children younger than 2 y/o - colicky, intermittent abdominal pain, nausea, vomiting, currant jelly stools - tubular mass may be palpable in lower right abdominal quadrant - barium enema = diagnostic & therapeutic

Major muscle involved in foot inversion

tibialis posterior (innervated by tibial nerve)

DNA-binding proteins include

transcription facotrs (Myc, CREB) steroid receptors (cortisol, aldosterone, *progesterone*) thyroid hormone receptor fat-soluble vitamin receptors - vitamin D, retinoic acid DNA transcription & replication proteins

Most vulnerable to injury during a hysterectomy

ureters

Cancers of pelvis, including prostate, spread to lumbosacral spine via the

vertebral venous plexus --> communicates with number of venous networks, including the *prostatic venous plexus*