Week of March 16th

Question 1

What are characteristic lab features of polycythemia vera (PV) and what is the cause

Answer 1

• Increased RBC mass, increased plasma volume, and low EPO.
• Majority have JAK2 V617F mutation, rendering hematopoietic stem cells more sensitive to growth factors such as EPO and thrombopoietin.
• Sx: thrombotic events (blood hyperviscosity), petic ulceration and pruritis (histmaine release from basophils), gouty arthritis (increased cell turnover). Plethoric, ruddy face and **splenomegaly. **

8559

Question 2

An autopsy of a 45 y/o man with recent extensive MI and cardiogenic shock shows bilateral wedge-shaped bands of necrosis over cerebral convexity. What causes these findings?

Answer 2

Profound systemic hypotesnion during cardiac arrest or shock universly diminishes blood supply to brain, casuing global cerebral ischemia (i.e. ischemic-hypoxic encephalopathy).

The most vulnerable areas are affected first: pyramidal cells of hippocampus and Purkinje cells of cerebellum. Necrosis of areas supplied by distal-most branches of anterior/middle/posterior arteries can occur (watershed infarction) and appears as bilateral wedge-shaped bands of necrosis over the cerebral convexity, a few centimeters lateral to the interhemispheric fissure.

23

Question 3

Describe the metabolism of methionine

Answer 3

• Conversion of methionine to S-adenosyl-methionine (SAM) by SAM synthetase. SAM has an activated methyl group that can be transferred to acceptor molecules forming methylated prducts.
• SAM –> S-adenosyl-homocysteine (after transfer of activated methyl group) –> adenosine + homocysteine.
  
  • ​Alternatively, homocysteine can be converted back to methionine by combining with 5-methyl-THF in a reaction requiring vitamin B12 (cobalamin) –> forms methionine and THF.
  • Vitamin B12 deficiency results in accumulation of 5-methyl-THF and decrease in THF. Present with megaloblastic anemia and homocystinemia as methionine re-synthesis is impaired.
• Conversion of homocysteine to cystathionine requires cystathionine synthetase (defect is MCC of homocystinuria - ectopia lenthis, mental retardation, marfanoid habitus, and osteoporosis), Vitamin B6 as cofactor, and serine.
• Cystathionine is then converted to cysteine in rxn catalyzed by cystathionase and vitamin B6

1333

Question 4

Biochemists identify a mutation affecting trypsinogen that disrupts a critcal site on the protein involved in inhibiting teh active trypsin moiety. Patients with this mutation would most likely suffer from what?

Answer 4

Trypsin can activate all of the proteolytic pancreatic enzymes, including its own zymogenic form, after it has been converted to trypsin by dudoenal enterokinase. Premature activation of trypsinogen before it reaches the duodenal lumen can result in autodigestion of the pancreatic tissue.

Multiple inhibitory mehcanisms exist to reduce premature activation of trypsinogen including serine peptide inhibitor kazal type 1 (SPINK1), which is secreted by pancreatic acinar cells and functions as a trypsin inhibitor, and trypsin can also serve as its own inhibitor. Gene mutations that render trypsin insensitive to cleavage inactivation cause hereditary pancreatitis.

433

Question 5

Infarcts involving the anterior portion of the medial pons produce which defects and injure which CN?

Answer 5

The trigeminal nerve (V) arises from the lateral aspect of the mid-pons at the level of the cerebellar peduncles.

Infarcts involving the anterior pons affect the CS tract (contralateral hemiparesis and Babinski) and corticobulbar tract (contralateral lower facial palsy and dysarthria). Becuase pontine nuclei and pontocerebellar fibers are located here, infarction also causes contralateral dysmetria and dysdiadochokinesia, resulting in syndrome of ataxic hemiparesis

2125

Question 6

What is the presentation and characteristic histology seen in polymyositis

Answer 6

Symmetric proximal muscle weakness of arms and legs. Increased CK in serum and anti-Jo-1 antibodies. Associated wtih increased risk of malignancy.

Muscle biopsy reveals inflammation, necrosis, regeneration and fibrosis of muscle fibers.

Preceding damage to myocytes with subsequent over-expression of MHC I proteins on the sarcolemma leads to infiltration with CD8+ T lymphocytes and mycote damage.

748

Question 7

Describe cardiac conduction velocity from fastest to slowest

Answer 7

Mnemonic: “Park At Ventura Avenue”

Fastest –> Slowest = Purkinje –> Atrial Muscle –> Ventricular Muscle –> AV node

Question 8

Describe perfusion vs. diffusion-limited equilibration of gases

Answer 8

Normal alveolar pO2 is 104mmHg, which lies betwen tracheal (150) and venous blood (40) pO2 concentrations. Likewise, normal alveolar pCO2 is 40mmHG, between its tracheal (0) and venous blood (45) concentration.

The equilibraion of O2 in a normal individual at rest is perfusion-limited. As venous blood flows through pulmonary capillaries, equilibration occurs with the alveolar gas. Under normal resting conditions, diffusion of both O2 and CO2 across alveolar membrane is quick, with venous blood only needing to traverse about 1/3 total capillary length in order to completely equilibrate.

Situations where O2 equilibration can become diffusion-limited include disease states such as emphysema and pulmonary fibrosis, and physiologically in states of very high pulmonary blood flow, such as excercise.

1522

Question 9

What are the manifestations of systemic mastocytosis?

Answer 9

Characterized by the abnormal proliferation of mast cells and increased histamine secretion. Histamine increases the production of gastric acid by parietal cells causing gastric hypersecretion –> inactivation of pancreatic and intestinal enzymes, causing diarrhea. Other GI Sx include n/v, abdominal cramps, gastric ulcerations. Histamine-mediated Sx include syncope, flushing, hypotesnion, tachycardia, and bronchospasm. Skin manifestions include **pruritus, urticaria, and dermatographism. **

306

Question 10

Describe the effect of an AV shunt on LV pressure-volume loop

Answer 10

AV fistula = abnormal communication between an artery and vein that bypasses the arterioles, the major source of resistance in the vascular ssytem. AV shunts allow blood under arterial pressure to directly enter venous system. High-volume AV shunts can eventually result in **high-output cardiac failure **

• Increase cardiac preload by increasing the rate and volume of blood flow back to heart, which is reflected by elongation of the diastolic filling segment and a higher end diastolic volume.
• Because AV shunts aallow blood to bypass the arterioles, TPR is reduced, thus decreasing afterload as well

1518

Question 11

How can you calculate the probability that a child of parents from two different populations with different mutant allele carrier frequencies will inherit and AR disease such as CF?

Answer 11

If either parent is a carrier, the probability that the child will inherit the mutant allele from that parent is 1/2. To inherit the CF disease, the child must independently inherit a mutant allele from both parents.

So if a mother has 1/30 probability of carrying mutant CFTR allele and father has 1/100, the probability that both events will occur to produce child with CF is the product of the probabilities of these independent events: (1/30 * 1/2) * (1/100 * 1/2) = 1/12,000

1791

Question 12

Under HIPPA, when can physicians disclose patient information to friends and family members?

Answer 12

• When the patietn gives explicit permission or does not object when given a reasonable opportunity.
• In an emergency situation, health care providers can also share medical information when it is in the patient’s best interest based on their professional judgement.

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Question 13

Describe the manifestations of CMV disease in immunocompotent and immunocompromised patients

Answer 13

Immunocompetent: rare, but affected individuals have systemic mononuleosis-like syndrome characterized by fever, malaise, myalgia, atypical lymphocytosis, and elevated liver transaminases. In contrast to EBV, heterophil antibodies are not usually present.

Immunocompromised: severe retinitis, pneumonia, esophagitis, colitis, and/or hepatitis.

Question 14

Patient presents with diffuse pruritic papulopustular rash that demonstrates oxidase-positive gram-negative rods that produce pigment on culture medium. What is the casue and source of patients infection?

Answer 14

“Hot tub folliculitis” is a superficial and self-limited P. aeruginosa infection of the hair follicles. The culture of a pustule will reveal gram-negative, oxidase positive, non-lactose fermenting, motile rods that produce pigment.

NOTE that many infections by P. aeruginosa often begin with exposure to water source or creation of a moist environment (i.e. swimmer’s ear, hot tub, burn wound)

974

Question 15

What are the symptoms and causes of serotonin syndrome? What AA is the precursor to serotonin?

Answer 15

Sx: neuromuscular excitation (hyperreflexia, clonus, rigidity, tremor), autonomic stimulation (hyperthermia, tachycardia, diaphoresis, vomitting/diarrhea), AMS (agitation, confusion).

Cause: SSRI in excess or in conjunction with other serotonergic agents such as MAOIs or triptans.

Tryptophan is precursor of serotonin, adn metabolism occurs via the enzymes tryptophan hydroxylase and AA decarboxylase

Tx: cyproheptadine (antihistamine with anti-serotonergic properties)

2088

Question 16

What sunscreens protect you from UVA vs. UVB radiation?

Answer 16

PABA esters: UVB radiation absorbers. UVB is the major cause of burns, histologic skin damage, UVR induced immunosuppresion, skin photo-aging, and photo carcinogenesis.

Avobenzone: absorbs UVAI and UVAII

Zinc Oxide: broad spectrum against UVB, UVAI, UVAII

Question 17

What types of dose adjustments for other medications need to be considered when taking niacin?

Answer 17

Niacin can potentiate the effects of some anti-hypertensive medications because of its vasodilatory effects (can cause postrual hypotesnion) and thus doses of these meds may need to be reduced.

Niacin also causes insulin resistance and oftentimes necessitates an increase in diabetes medications.

There is an increase in serum uric acid in some patients therefore patients with gout shoudl be cautious.

162

Question 18

Describe the MOA and AE of protease inhibior class of antiretroviral drugs (e.g. indinavir)

Answer 18

MOA: inhibit viral protease, an enzyme responsbile for the final step of replication of HIV virus within host cells (i.e. inhibit cleavage of polypeptide precursors into matural viral proteins)

AE: lipodystrophy (“buffalo hump” apperance with central obesity and peripheral wasting), hyperglycemia (increased insulin resistance and diabetes), P450 inhibition

819

Question 19

What medications increase the risk of cholesterol gallstones?

Answer 19

Pharmacotherapy with fibrates, octreotide, or **ceftriaxone. **

Estrogenic influence facilitates the biosynthesis of cholesterol by increasing hepatic HMG-CoA reductase activity. Suppresion of cholesterol 7-alpha-hydroxylase activity (by medications such as fibrates) reduces the conversion of cholesterol to bile acids, resulting in excess cholesterol secretion in bile.

67

Question 20

Sudden upward stretching on teh arm at the shoulder can damage what nerve(s)?

Answer 20

Damage the lower trunk of the brachial plexus. This trunk carries nerve from C8-T1 spinal levels that ultimately form the median and ulnar nerves. These nerve innervate all the intrinsic muscles of the hand –> **hand clumsiness or paralysis **

1829

Question 21

Which organ system would show a vascular bed where the arterial/arteriolar resistance increases as blood oxygen content decreases?

Answer 21

Pulmonary vascular bed is unique in that hypoxemia causes a vascoconstrictive response. Such hypoxic vasoconstriction occurs in the small muscular pulmonary arteries in order to divert blood away from underventilated regions of lung toward more well-ventilated areas.

1587

Question 22

Where are most intracranial schwannomas located and what are they associated with?

Answer 22

Most are found at the cerebellopontine angle and are attached to CN VIII. Schwannomas at this location are called acoustic neuromas. Tinnitus, vertigo, and hearing loss are the typical symptoms of an acoustic neuroma. Bilateral acoustic neuromas occur in NF2 which differs from NF-1 in that it causes fewer cutaneous manifestations and presents with CNS involvement.

1305

Question 23

What does chronic rejection in lung transplant cause?

Answer 23

Affects small aireays, causing bronchiolitis obliterans. Lymphocytic inflammation, necrosis, and fibrosis of the bronchiolar wall occur. Ultimately, there is occlusion of the bronchiolar lumen.

535

Question 24

Why do surgeons need to be careful when removing sublingual mass?

Answer 24

Failure of migration of the thyroid gland can cause a lignual thryoid. Surgeons must be careful when remvoing any mas along the thyroglossal duct’s usual path, as the mass could be the only thyroid tissue present. Clinical features of hypothyroidism in children include lethary, feeding problems, constipation, macroglossia, umbilical hernia, large fontanels, dry skin, hypothermia, and prolonged jaundice.

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Question 25

What is the medication of choice for the treamtent of gestational diabets?

Answer 25

Insulin

Question 26

Describe Lambert-Eaton Myasthenic Syndrome

Answer 26

Disorder of NMJ d/t **antibodies** that are direct agaisnt the **voltage-gated calclium channels** that participate in **ACh release. ** _Sx_: **proximal muscle weakness** in form of gait alteration, difficutly arising from chair/climbing stairs. CN involvment, partiruarly **oculobular** seen with diplopia, ptosis, dysarthria, and/or dysphagia. Often presents wtih autonomic Sx such as dry mouth or impotence. May have **small-cell lung cancer**. _Distinguish from MG_: LEMS have **hyporeflexia** or areflexia, **autonomic Sx**, and a classic **incremental response to repetitive stimulation** 1900

Question 27

What favors the diagnosis of a lung hamartoma

Answer 27

Asymptomatic (50-60y/o) **peripherally located well-defined coin lesion** with "popcorn calcifications." Hamartoma is an excessive growth of a tissue type native to organ of involvement. Lung hamartomas contain islands of mature **hyaline cartilage**, fat, smooth muscle and clefts lined by respiratory epithelium. 552

Question 28

What are the 3 zones of the adrenal gland and what do they secrete?

Answer 28

Seperated into an outer cortex and inner medulla. Outher cortex is futher divided into 3 zones * **glomerulosa** - secrete mineralocorticoid homrones (primarily aldosterone) * **fasciculata** - secrete glucocorticoid hormones (primarily cortisol) * **reticularis** - secrete small amounts of androgens **ACTH** is the major trophic hormone of the zona fasciculata and reticularis, where the zona glomerulosa is primarily regulated by angiotensin II. Prolonged ACTH stimulation causes **hyperplasia** of zona fasiculata and reticularis, resulting in excessive cortisol produciton (Cushing syndrome)

Question 29

What is and how do you calculate the attributable risk percent in the exposed (ARP_exposed)

Answer 29

Important measure of the impact of a risk factor. It represents the **excess risk in an exposed population** that can be explained by exposure to a particular risk factor. It is related to attributable risk (AR), which is simply the difference between risk in the exposed and unexposed. ARP_exposed = 100 X [(risk in exposed - unexposed)/risk in exposed] can also be written as **ARP_exposed = 100 X [RR-1)/RR]**, where RR = risk in exposed/risk in unexposed 1186

Question 30

What kind of drug would cause a dose-dependent increase in cardiac contractility and dose-dependent decrease in systemic vascular resistance

Answer 30

_Isoproteronal_ is an **agonist at both B1 and B2-adrenergic receptors** and has **little or no alpha-adrenergic agonist effects**. It increases cardiac contractility by acting on myocardial B1-adrenergic receptors. In lower doses it selectively binds to B2-receptors, causing relaxation of vascular smooth muscle. 1836

Question 31

Which property of skeletal muscle is responsible for its resistance to the effect of verapamil?

Answer 31

Skeletal muscle does NOT require an influx of extracellular calcium for excitation-contraction coupling, whereas cardiac and smooth muscle depend on extracellular calcium entering the cell via voltage-gated L-type calcium channels for excitation-contraction coupling. These voltage-gated calcium chanels are the target of verapamil and other CCBs. 144

Question 32

10 days after taking a monoclonal antibody, a patient develops joint pain adn pruritic skin rash. Skin biopsy shows scattered areas of fibrinoid necrosis and neutrophil infiltration involving small blood vessels. What is the diagnosis and what is the mechanism?

Answer 32

_Acute Serum Sickness_: tissue deposition of circulating immune complexes (**Type 3 HSR**). The most common sx include **fever, pruritic skin rash, and arthralgias** that begin **7-14 days** after exposure to an antigen. LAD and proteinuria may also occur. Histology shows **small vessel vasculitis with fibrinoid necrosis and intense neturophil infiltration**. Deposition of IgG and/or IgM complement-fixing antibodies results in localized consumption and hypocomplementemia (**decreased serum C3 and C4 complement levels**). Can occur following administration of **chimeric monoclonal antibodies** (e.g. rituximab and infliximab), **nonhuman immunoglobulins** (e.g. venom antitoxins), and certain nonprotein drugs (penicillin, cefaclor, and TMP-SMX) 741

Question 33

What are the functions of the free ribosomes in cytoplasm vs. bound ribosomes to RER

Answer 33

_Free_: synthesize proteins that are used in the cytosol and cellular organelles. _Bound_: synthesize secretory, membrane-bound, and lysosomal proteins. The _RER_ is responsible for subsequent protein modification, folding, and transfer; well-developed in protein-secreting cells (e.g. enzyme-secreting pancreatic cells) _SER_: lacks surface ribosomes and functions in lipid synthesis, carbohydrate metabolism, and detox of harmful substances. 757

Question 34

What is the substance-induced pyschosis from Phencyclidine (PCP) appear like?

Answer 34

Among drugs of abuse, PCP is most likely to induce violent behavior. In addition to belligerence, PCP is known to cuase loss of coordination, **nystagmus**, and **acute brain syndrome** (sx including disorientation, poor judgement, and memory loss). **Violence and subsequent trauma are the most common causes of death with PCP intoxication**. Other lethal side effects commonly associated with drug abuse include MI and stroke with cocaine and respiratory depression with opioids. 1165

Question 35

Descirbe how the Schilling test is used to differentiate between dietary deficiency of vitamin b12, pernicious anemia, and malabosprtion syndromes.

Answer 35

_PHASE 1_: oral radiolabeled vitamin b12 + IM non-radiolabeled b12; ensures excretion of the radiolabeled form by creating a state of excess b12 (if parenteral dose were not admin, all oral b12 would be taken up by tissues in case of dietary deficiency and little would be excreted in urine) * _High urinary excretion of radioactive cobalamin_: evidence of normal absorption of this vitamin and is diagnostic of **dietary b12 deficeincy ** * _Low urinary excretion_: poor absorption of vitamin d/t either lack of IF (pernicious anemia) or malabsorption syndrome. _PHASE 2_: radiolabeled b12 + intrinsic factor * _High urinary excretion_: occurs if was d/t **lack of intrinsic factor**, as it would have been corected during this stage of testing * _Low urinary excretion_: **intestinal malabsorption** d/t **pancreatic insufficiency, intestinal bacterial overgrowth,** or **ileal disease**. 938

Question 36

Describe the Pringle manuever

Answer 36

The **portal triad** (hepatic artery, portal vein, common bile duct) runs through the **hepatoduodenal ligament**. In the setting of traumatic liver injury with persistent bleeding, occlusion of this ligament can be performed to idetnify the source (i.e., Pringle manuever). If liver bleeding does not cease, it is likely there has been injury to **IVC** or **hepatic veins**. 10583

Question 37

What is one reflex indicating hypocalcemia and the most common cause?

Answer 37

**Hyperactive jaw jerk reflex** is a variant of Chvostek's sign (facial muscle contraction elicited by tapping the facial nerve just anterior to ear). This sort of neuromuscular hyperexcitability becomes clinically apparent with serum calcium \<7.0 mg/dL. The most common cause of outpatient hypocalcemia is **primary hypoparathyroidism**, which is often d/t prior **loss of parathyroid tissue during thyroidectomy**. 1656

Question 38

What are the most common congenital breast anomaly seen in women and men?

Answer 38

**Accessory nipples** (i.e., polythelia) which are due to failure of appropriate involution of the mammary ridge. Usually asymptomatic, though they may **swell or become tender** along with the other breast tissue before or during menses, and during pregnancy or lactation. 8904

Question 39

How do cutaneous neurofibromas appear?

Answer 39

Benign, soft, flesh-colored, or lightly pigmented skin nodules consisting of Schwann cells and neural fibroblasts. Applying pressure to some neurofibromas may cause them to retract into subcutaneous tissue (**"button-hole" sign**) 8904

Question 40

What are the most commmon causes of congenital heart disease that result in cyanotic symptoms at birth and what embyological events underlie these conditions?

Answer 40

**Tetrology of Fallot, transposition of the great vessels,** and **truncus arteriosus** are the 3 major cynaotic heart diseases that can be caused by **abnormal migration of neural crest cells through the primative truncus arteriosus and bulbus cordis **to become the aorta and pulmonary artery via aorticopulmonary septation. In TOF, mild pulm stenosis allows the VSF to act mainly as L-\>R shunt early in childhood resulting in infrequent cyanotic episodes. Progressive increase in pulm HTN (d/t increased right-sided heart flow) eventually leads to shunt reveresal with significant increase in cyanotic sx. **Squatting** improves cyanosis bc resulting increase in sytemic pressure reduces amount of R-\>L shutning thru VSD (decreasing amount of blood bypassing lungs) 1705

Question 41

What is the MOA of the 4 main drugs used for treatment of *Mycobacterium tuberculosis (MTB)*

Answer 41

_Rifampin_: inhibits mycobacterial DNA-dependent RNA-polymerase _Isoniazid_: inhibits synthesis of mycolic acid _Pyrazinamide (PZA)_: **works best at relatively acidic pHs**, as within pahgolysosomes. It is therefore most bactericidal to MTB organisms engulfed by macrophages. The other agents have better activity agaisnt extracellular MTB (including organisms in necrotic foci and/or tissue cavities) _Ethambutol_: inhibits mycobacterial cell wall synthesis by blocking arbinosyl transferase 1769

Question 42

Do high or low levels of cholesterol, bile salts, and phosphatidylcholine promote gallstone formation?

Answer 42

**Low cholesterol concentrations** reduce the likelihood of cholesterol precipitation and gallstone formation. **High levels of bile salts and phosphatidylcholine** increase cholesterol solubility and decrease risk of gallstones. 78

Question 43

Which amino acids should be restricted from an infants diet with Maple Syrup Urine Disease (MSUD)

Answer 43

MSUD is caused by a **defect in alpha-keto acid dehydrogenase**, leading to **inability to degrade branched chain AAs (leucine, isoleucine, and valine)** beyond their deaminated alpha-keto acid state. _Sx_ include **dystonia, poor feeding,** and **"maple syrup scent" of urine** within first few days of life. _Treatment_ is dietary restriction of branched-chain AAs. 1335

Question 44

What occurs to DNA after UV damage?

Answer 44

By forming an abnormal covalent bond between adjacent thymine residues, UV rays damage DNA through formation of thymine (pyrimidine) dimers. These are recognized by a specific **endonuclease** (lack of this enzyme results in Xeroderma Pigmentosum) which initiates the process of repair by **nicking the strand at the thymine dimer**. This action signals the removal and replacement of damaged DNA. 1477

Question 45

What enzyme is decreased in gentically predisposed gestational hyperglycemia?

Answer 45

**Glucokinase** is a glucose sensor within pancreatic beta cells. It is the first enzyme in the glycolytic pathway (instead of hexokinase) and converts glucose to G6P. Inactivating mutations result in mild hyperglycemia that can be exacerbated by pregnancy. 1010

Question 46

What can nafcillin, methicillin, and oxacillin be used to treat?

Answer 46

These are **penicillinase-resistant penicillins** that are **active against isolates of S. aureus and S. epidermidis** that are resistant to other penicillins. They are NOT effective against MRSA, however. Nafcillin is commonly used empirically to treat skin and soft tissue infections (e.g. folliculitis, abscesses) for which S. aureus is usual cause. 1951

Question 47

What is the karyote of complete vs. partial mole

Answer 47

Partial mole will have a triploid karyote (69 XXX or XXY) vs. complete mole (46 XX or XY; parental origin) 792

Question 48

What antiarrythmics demonstrate strong use-dependence vs. reverse use-dependence

Answer 48

_Class 1C_ are potent Na channel blockers that exhibit **strong use-dependence** (slowest of class 1 agents to dissociate from Na channel) by **prolonging the QRS duration to a greater extent at higher HRs** (i.e. sodium blocking effects intensify as HR increases d/t less time betwen APs for medication to dissociate from receptor). _Class III_ block repolarizing K+ current and demonstrate **reverse use-dependence** (the slower the HR, the more QTc interval prolonged) 8869

Question 49

What is the most common viral cause of an aplastic crises in patients with sickle cell anemia?

Answer 49

**Parvovirus B19** (non-enveloped, ssDNA virus). Destruction of the erythroid precursor cells by this virus diminishes the number of reticulocytes availble to replace the deformed and/or removed erythrocytes. 1496

Question 50

How do ARBs work?

Answer 50

Block AT-1 receptors and inhibit effects of ATII resulting in arterial vasodilation and decreaed aldosterone secretion. Interfere with negative feedback mechanisms resulting in increased renin, angiotensin I and II levels. 691

Question 51

Ototoxicity secondary to loop diuretics usually occurs with what?

Answer 51

Higher dosages, rapid IV admin, or when they are used in combo with other ototoxic agents (**aminoglycosides, salicylates, and cisplatin**). Hearing impairment is usually reversible but has been reported to be permanent in some cases. 685

Question 52

What does ischemic injury in most organs vs. brain result in?

Answer 52

Although lethal ischemic injury in most organs results in **coagulative necrosis**, in the brain such injury produces a focus of **liquefactive necrosis** within 10 days of infarction. The infarcted CNS tissue is eventually replaced with a cystic astroglial scar. 177

Question 53

What is the major determinant of whether or not a coronary artery plaque will cause ischemic myocardial injury?

Answer 53

**Rate at which it occludes the involved artery**. A slowly developing occlusion would allow for formation of collaterals that could prevent myocardial necrosis. A thin fibrous cap, a rich lipid core, and active inflammation in teh atheroma would all decrease plaque stability and thus potentially promote rapid coronary occlusion via superimposed thrombosis if plaque were to rupture. 39

Question 54

What is the distincitive morphologic changes seen with acute hepatitis caused by viral infection

Answer 54

Balloning degeneration, hepatocyte necrosis, and portal inflammation. Some changes are specific to the virus. In patients infected with HepB, the hepatocellular **cytoplasm becomes filled with spheres and tubules of HBsAg (hepatitis B surface antigen) and the cytoplasm takes on a finely granular, eosinophilic apperance ("ground glass")**. Livers infected with HepC commonly have lymphoid aggregates within portal tracts and focal areas of macrovesicular steatosis. 367

Question 55

Describe caudal regression syndrome

Answer 55

Patients are born with **agenesis of the sarum and occassionaly lumbar spine** and experience resultant flaccid paralysis of the legs, dorsiflexed contractures of the feet, and urinary incontinence. Can range in severity from isolated anal atresia to sirenomelia. Frequently related to **poorly controlled maternal diabetes**. 1684

Question 56

Where is the chemoreceptor trigger zone (CTZ)

Answer 56

Area postrema of dorsal medulla near fourth ventricle 1741

Question 57

When is a result considered statistically signifcant?

Answer 57

**If the 95% CI does not cross the null value, which corresponds to a p-value of \<0.05. ** If the RR = 1 (null value), then there is no association between exposure and disease. RR \>1 indicates that exposure is associated with increased risk of disease vs. \<1 means associated wtih decreased risk fo disease. 1274

Question 58

Explain free energy

Answer 58

* If the free energy of the products is lower than that of the substrates, the sign of **deltaG will be negative**, indicating that the reaction favors **product formation**. * If the free energy of the products is higher than that of the substrates, **deltaG will be positive** and the reaction favors **substrate formation**. 2119

Question 59

How do brown pigment stones typically arise?

Answer 59

Common in rural Asian populations within increased incidence in women and elderly. Arise secondary to **infection of the biliary tract** (with *E. coli, Ascaris lumbricoides*, or liver fluke *Opisthorchis sinensis*), which results in the release of **B-glucuronidase** by injured hepatocytes and bacteria. The presence of this enzyme contributes to the hydrolysis of bilirubin glucuronides and increases amount of unconjugated bilirubin in bile. 70

Question 60

Crescents on light microscopy are diagnostic of what condition and what do they contain?

Answer 60

Diagnostic of **RPGN**. Consist of glomerular parietal cells, monocytes, macrophages, as well as **abundant fibrin**. Crescents eventually become sclerotic, disrupting glomerular function and causing irreversible renal injury. 24

Question 61

What prevents edema formation in cor pulmonale secondary to COPD

Answer 61

Right HF increases CVP, which leads to a rise in capillary hydrostatic pressure, net plasma filtration, and interstital fluid pressure. As the interstital fluid pressure increases, so does **lymphatic drainage**, which can compensate for moderate CVP elevations and prevent the development of clinically apparent edema. Large CVP elevations can overwhelm lymphatic reabsorptive capacity, leading to development of overt edema. 1578

Question 62

How does the toxin of C. tetani travel?

Answer 62

Toxin-mediated disease that cuases uncontrolled muscle spasms including aw stiffness d/t spasmodic contractions of masster (**t****rismus**] and contraction of facial muscles producing smiling apperance (**risus sardonicus**) and respiratory failure. Toxin travels within the **motor neuron by retrograde transport into the spinal cord** where it causes inhibition of inhibitiory interneurons and unregulated firing of primary motor neurons. 1402

Question 63

A positive VDRL and pleocytosis in CSF are diagnostic of what?

Answer 63

**Neurosyphilis** (component of tertiary syphilis) so vulvar lesions would be **gummas** (NOT chancre of primary syphilis or condyloma lata of secondary syphilis). Gummas often begin as painless, indurated granulomatous lesions that progress to white-gray rubbery lesions and may ulcerate. They are most commonly cutaneous. 651

Question 64

The traid of low hemoglobin, thrombocytopenia, and absent hematopoietic cells in bone marrow is consistent with what? What is a compensatory mechanism?

Answer 64

**Aplastic anemia.** A compensatory **increase in circulating erythropoietin levels** would be expected in individuals with aplastic anemia and normal renal function. Most anemias promote increased secretion of erythropoietin by the interstial cells in renal cortex. 1861

Question 65

What is the defect in a patient with orotic aciduria? Supplementation with which substances would be of benefit?

Answer 65

**Impaired de novo pyrimidine synthesis.** The defective enzymes are orotate phosphoribosyl transferase and OMP decarboxylase, which catalyze the final conversion of orotate to UMP. Will present with **hypochromic megaloblastic anemia, neurologic abnormalities, growth retardation and excretion of orotic acid in the urine**. **Uridine supplementation** improves symptoms by inhibiting carbamoyl phosphate synthetase II. 2066

Question 66

Neonate with ambiguous genitalia and clitoromegaly. Elevated levesl of testosterone and androstenedione. Mother experienced facial hair growth and voice deepending during preganncy. What enzyme is deficient in newborn?

Answer 66

Aromatase converts androgens into estrogens (i.e. androstenedione to estrone and testosterone to estradiol) in the ovaries, testes, placenta, and other peripehral tissues. _Aromatase Deficeincy_: AR, early embryonal life with **high androgen** and **low estrogen** levels in female fetus. **Maternal virilization** (eg hirsutism) commonly occurs during preg d/t transfer of excess androgens into maternal circulation. Affected newborn girls will have **normal internal genitalia and ambiguous or male-type external genitalia. ** 955

Question 67

How do you avoid complications while performing a throacentesis?

Answer 67

Should be performed above the **7th rib in midclavicular line**, the **9th rib along maxillary line** and **11th rib along posterior scapular line**. If the needle is inserted higher, there is risk of **lung injury**. Insertion lower than these points increases risk of penetrating abdominal structures (e.g. **liver injury** if below 9th rib at mid-axillary line), and insertion on injerior margin of rib risks striking the subcostal neurovascular bundle. 844

Question 68

An infant is dx with renal carnitine wasting and severe carnitine deficiency. The pt most likely also has deficeint synthesis of?

Answer 68

**Acetoacetate** **Carnitine deficiency impairs fatty acid transport into mitochondria, restricting ketone body production (i.e. reduces ability of FAs to enter mitochondria for beta-oxidation).** To tx a fatty acyl-CoA from cytosol to mitochondria, the cell must first form the fatty acyl-carnitine intermediate (via carnitine acyltransferase I on outer surface of inner mitochondrial membrane). Once inside, carnitine acyltransferase II on inner surface of inner mitocohdnria membrane catalyzes regeneration of fatty acyl-CoA molecule and free carnitine. 1886

Question 69

What is the triad of ataxia telangiectasia and what is the defect?

Answer 69

_Triad_: **cerebellar ataxia**, **telangiectasia** (superficial blanching nests of distended capillaries), and **increased risk of sinopulmonary infections**. AR with defect in gene that codes for **ATM** which plays a role in **DNA break repair**. The immune deficiency manifests as an **IgA deficeincy** and predisposes to infections of upper and lower airways. 587

Question 70

Describe the difference in mutations and sx between pemphigus vulgaris and bullous pemphigoid

Answer 70

_Pemphigus Vulgaris_: autoantibodies directed against **desmosomal proteins** (desmogleins 3 and 1). Painful, **flaccid bullae** and erosions of the skin and mucosal membranes; commonly involving oral mucosa. Bullae spread laterally with pressure (Asboe-Hansen sign) and new bullae may form with gentle traction (Nikolsky sign). _Bullous Pemphigoid_: autoantibodies against **hemisdesmosomal proteins**. Bullae remain intact and mucosal involvement is uncommon. 2065

Question 71

What are the classic sx and histological findings of primary hyperparathyroidism

Answer 71

MC d/t **parathyroid adenoma**. Sx include bone pain, renal stones, GI distrubances (e.g. peptic ulcer disease), and psychiatric disorders (*"bone, stones, abdominal groans, with psychiatric overtoans"*). **Asymptomatic hypercalcemia** is also common. Most commonly involve cortical (compact) bone in appendicular skeleton (pectoral girdle, pelvic girdle, limbs). **Subperiosteal thinning** is a characteristic feature and appears radiologically as subperiosteal erosions in phalanges of hand, a granular **"salt-and-pepper" skull**, and **osteolytic cysts** in long bones (osteitis fibrosa cystica) 631

Question 72

How does glucagon increase serum glucose?

Answer 72

**Increased production of glucose from the liver!** Glucagon stimulates insulin secretion from the pancreas. However, patients with type 1 diabetes rarely have significant residual beta cells. Unlike epinephrine, glucagon has an insigificant effect on skeletal muscle cells and adipocytes. 849

Question 73

What does hyperammonemia in hepatic encephalopathy result in?

Answer 73

**Depletion of alpha-ketoglutarate**, causing inhibition of the Krebs cycle. Excess ammonia also depletes glutamate, and excitatory neurotransmitter, and causes accumulation of glutamine, resulting in astrocyte swelling and dysfunction. 8578

Question 74

How can you diagnose C. diphtheriae?

Answer 74

Gram +, catalase +, aerobic or facultatively anaerobic, club-shaped rods. Grow on **cysteine-tellurite agar** as dark black, slightly iridescent colonies. It can also be cultured in **Loffler's medium** where it will develop cytoplasmic metachromatic granules (visualizable after staining with an aniline dye such as **methylene blue**) 1095

Question 75

What is the most common cause of HIV retinintis

Answer 75

**CMV infection** (specifically when CD4 \<50). Will show inflammatory vascular sheathing and associated hemorrhage. Histologic examination would reveal full-thickness retinal necrosi sand edema, with eventual replcement by atrophic scar tissue. Best treated with **ganciclovir**. 1646

Question 76

How can the clinical course of ATN be divided?

Answer 76

_Initiation_: original insult (e.g. ischemia) _Maintenace (oliguric)_: low GFR, low/absent urine output. LM shows granular casts in tubular lumina, and flattening of tubular epithelial cells and tubular epithelial necrosis with denudation of tubular BM. _Recovery_: **re-epithelization of tubules**. Polyuria and gradual normalization of GFR, leading to complete resolution of renal function in majority of pts. 1053

Question 77

What drugs are associated with medication-induced body fat redistribution syndrome

Answer 77

Characterized by redistribution of body fat from the extremities to the abdominal viscera and subcutaneous adipose tissues of the thorax, posterior neck, and supraclavicular region. Medications include **HIV protease inhibitors** and **glucocroticoids**. 1673

Question 78

If a pt has lymphoma that expresses CD20, how would you treat it?

Answer 78

**Rituximab** is a monoclonal antibody used in lymphoma immunotherapy that specifically targets the CD20 (B-cell marker) surface immunoglobulin. 1628

Question 79

The genetic instability of HCV is attributed in large part to its RNA-dependent RNA-polymerase, which lacks what?

Answer 79

**Lacks proofreading 3'--\>5' exonuclease activity** in its RNA polymerase and its envelope glycoprotein contains a hypervariable region prone to frequent genetic mutation. 388

Question 80

What is the best long-term treatment choice for gout

Answer 80

**Allopurinol** (xanthine oxidase inhibitor) is the best long-term treatment choice for chronic tophaceous gout regardless of the urinary excretion of uric acid. In patients who excrete large amounts of uric acid, **uricosuric drugs (probenecid or sulfinpyrazone)** should be avoided to prevent uric acid nephrolithiasis. 861

Question 81

The light microscopy of intestinal mucosa would most likely show what in a patient with lactase deficiency?

Answer 81

Small bowel mucosa of patients with lactase deficiency is **normal** on histological examination. 134

Question 82

Compare and contrast Myasthenia Gravis and Lambert-Eaton Syndrome

Answer 82

Both are caused by poor signal transmission at the NMJ. _MG_: **antibodies against ACh receptors**. **Weakness worse at end of day or with exertion**; **extraocular muscles** are affected first (ptosis, diplopia). Associated with risk of **thymoma**. **Improvement or resolution of weakness with tensilon (edrophonium) test**. **Decremental response with nerve stimulation** _LES_: **antibodies against pre-synaptic calcium channels**. **Weakness improves during the day and with excercise**; **proximal muscle** weakness. Associated with **pre-existing malignancy**. **No clinical improvement with tensilon test**. **Incremental response with nerve stimulation. ** 1267

Question 83

What is Reye syndrome and what is the characteristic histological findings?

Answer 83

Occurs in children with febrile illness (frequently viral disease) treated with **salicylates** (aspirin). It consists of **hepatic failure** (*vomitting and hepatomegaly*, rarely jaundice; increased ALT, AST, ammonia, bilirubin, prolonged PT and PTT) and **encephalopathy** (*cerebral edema* d/t toxic effect of hyperammonemia on CNS) LM of a liver biopsy shows **microvesicular steatosis** (small fat vacuoles in cytoplasm of hepatocytes); **there is no necrosis or inflammation in the liver**. EM findings include swelling, a decreaed number of mitochondria and glycogen depletion. 881

Question 84

How do you calculate attack rate?

Answer 84

Attack rate is the ratio of the number of people who contract an illness divided by the number of people who are at risk of contracting that illness. 10443

Question 85

What is decreased in patients wtih cryptorchidism (undescended testes)

Answer 85

Seminiferous tubules become atrophic and hyalinized as a result of temperature-induced damage, resulting in a significantly **decreased sperm count** as well as **decreased inhibin levels**. Hormonal function of leydig cells is usually not impaired. Thus, secondary sexual characteristics and sexual performance are normal. Should be corrected surgically early in life to prevent damage to seminferous tubules and decrease risk of testicular cancer. 580

Question 86

Describe cricopharyngeal muscle dysfunction

Answer 86

Condition caused by **diminished relaxation of pharyngeal muscles durign swallowing**. More force is subsequently required to move the food bolus downward. The subsequently increased intraluminal pressure in the oropharynx causes the mucosa to herniate through the wall at a point of muscle weakness, forming a **Zenker diverticulum**. Patients (elderly) present with **oropharyngeal dysphagia, coughing, choking, and recurrent aspiration. ** 279

Question 87

Bilious vomitting after the first 24 hours of llife is a sign of what?

Answer 87

**Intestinal obstruction below the second part of the duodenum**. Common causes include **intestinal stenosis and atresia. ** _Intestinal atresia_ distal to duodenum occurs due to vascular accidents in utero. If the SMA is obstructed, **"apple-peel" atresia** occurs. This manifests as blind-ending proximal jejunum with abscence of a long length of small bowel and dorsal mesentery. The terminal ileum distal to the atresia assumes a **spiral configuration around an ileocolic vessel.** 319

Question 88

A patients blood with hemophilia A (VIII deficeincy) or B (IX deficiency) will most likely clot after addition of what?

Answer 88

Bleeding after tooth extraction and a hx of hemarthrosis is suggestive of hemophilia. VIII and IX are necessary for activation of X, which catalyzes conversion of prothrombin (II) into thrombin. In abscence of VIII or IX, activation of X and subsequent conversion of prothrombin to thrombin doesnt occur. Administration of **thrombin** however will make up for the deficeincy and result in blood clotting. 941

Question 89

Anorexia, nausea, low-grade fever followed by bilirubinuria and RUQ tenderness suggest what?

Answer 89

Acute hepatitis, which is most commonly caused by **HepA virus** in young adults (endemic in India; tx by fecal oral route, outbreaks described in child care settings). Acute hepatitis due to most hepatotropic virsuses causes hepatocyte **ballooning degeneration** (hepatocyte swelling), mononuclear cell infiltrates, and Councilman boddies (eosinophilic apoptotic hepatocytes) 1863

Question 90

What vitamin deficiency results in the anemia associated with chronic alcoholism

Answer 90

**Folic acid deficiency**. It is a megaloblastic anemia that develops d/t decreased synthesis of purines and thymidine. The peripheral blood smear shows macrocytosis, ovalocytosis, and neutrophils with hypersegmented neutrophils. 873

Question 91

What are the developmental milestones of a 3 y/o

Answer 91

Play in parallel but not cooperatively (social), climb stairs with alterating feet and ride a tricycle by operting the pedals (gross motor), speak in simple 3-word sentences (language), and describe their age and gender (cognitivie). Toilet training often begins by this age. Should be able to reproduce a circle and use utensils (fine motor) 1781

Question 92

What causes gram-negative sepsis

Answer 92

Results from release of endotoxins which are found in outer membrane of gram-negative bacteria, which is composed of LPS. Caused by the release of LPS from bacterial cells during division or by bacteriolysis. _LPS is not actively secreted by bacteria_. **Lipid A is the toxic component of LPS**; it casues activation of macrophages leading to widespread release of IL-1 and TNF-alpha, which cause s/sx of septic shock: fever, hypotension, diarrhea, oliguria, vascular compromise, DIC 1141

Question 93

What are the exceptions to the normal sympathetic innervation of organs?

Answer 93

* Adrenal glands - directly innervated by preganglionic neurons using ACh * Sweat glands - innervated by a two neuron efferent system where both neurons use ACh 1359

Question 94

What muscles are responsible for sitting up from the supine position?

Answer 94

**External abdominal obliques, rectus abdominus, and hip flexors.** The **iliopsoas muscle** is the most important of the hip flexors and includes the **psoas major, psoas minor, and iliacus**; these muscles originate on plevis and spinal column, cross hip joint, and insert on the femur. The rectus femoris, sartorius, tensor fascia lata, and medial compartment of thigh also contribute to hip flexion. 7621

Question 95

Describe the changes in the log dose-response curve expected for the effect of reversible competitive vs. noncompetitive antagonists

Answer 95

_Reversible competitive antagonist added to a full agonist_: 1) **parallel shift to the right** in the log-dose response curve, illustrating an **increase in the ED50** and 2) no change in the maximum effect (Emax) _Noncompetitive_: **change Emax** (reduced number of receptors available for binding), causing **downward shift. ** Note: reversible competitive antagonists can be overcome by high concentrations of agonist vs. noncompetitive antagonists which are able to remain bound. 1708

Question 96

What did the HOPE trial demonstrate about ACE-I and when are these drugs contraindicated

Answer 96

ACE-I reduce BP and decrease risk of CV events (MI, stroke, death) in high risk patients with CV and PVD. Patients wtih artherosclerotic CV and PVD can develop renovascular disease, manifesting as **renal artery stenosis** in which patients depend on ACE mediated efferent arteriole constriction to maintain renal perfusion and GFR. Because ACE-I can induce ARF in patients with bilateral renal artery stenosis, they are considered contraindicated in these patients. 695

Question 97

Describe mitochondrial DNA (mtDNA)

Answer 97

Exists as small circular chromsome with a slightly different genetic code than that of nuclear DNA. mtDNA codes for 14 proteins and the ribosomal and transfer RNA needed for mitochondrial protein synthesis. Diseases arising from mutations in mtDNA are transmitted from the mother to all of her offspring. 1473

Question 98

Where are enhancers/repressors located?

Answer 98

**Variable locations:** may be located anywhere upstream, downstream, or even within the transcribed gene. In contrast, promoter regions are typically found 25-70 bases upstream from their associated genes. 2025

Question 99

Describe the different speed of hemoglobin movement during gel electrophoresis

Answer 99

**Hemoglobin A \> S \> C** Both HbS and HbC result from missense mutations. With HbS, nonpolar AA (valine) replaces negatively charged AA (glutamate) vs. HbC where glutamate residue is replced by positively charged lysine. These result in an overall decrease in negative charge for the hemoglobin molecule. 1470

Question 100

Impetigo can cause what secondary complication

Answer 100

Rheumatic fever and acute post-strep glomerulonephritis are late sequelae of GAS (S. pyogenes) infection. Post-strep glomerulonephritis (HTN, hematuria, nephritic range proteinuria, RBC cast in urine, facial edema, cola-colored urine) can follow EITHER a skin infection (impetigo) or an episode of pharyngitis, whereas rheumatic fever is associated only with strep throat. 725

Question 101

How do you calculate number needed to harm (NNH)?

Answer 101

The NNH represents the number of people who must be treated before an adverse event occurs. **NNH = 1 / Attributable risk ** Attributable risk can be calculated by subtracting the adverse event rate in placebo group from rate in treatment group. 1231

Question 102

Loss of cardiomyocte contractility occurs how long after onset of total ischemia?

Answer 102

The depletion of ATP in critical cellular areas and the accumulation of toxins (e.g. lactate) result in loss of contractility **within about 60s** of total myocardial ischemia. When ischemia lasts \<30m, restoration of blood flow leads to reversible contractile dysfunction (myocardial stunning), with contractility gradually returning to normal over next several hours to days. However, **\>30m of total ischemia, ischemic injury becomes irreversible. ** 42

Question 103

What is status epilepticus and what is the treatment

Answer 103

_SE_: recurrent or continuous generalized tonic-clonic seizures that last \>30 minutes without a return to consciousness **Benzos (lorazepam)** are first-line agents. **Phenytoin** (or fosphenytoin) is administered simultaneously to prevent the recurrence of seizures. Phenytoin inhibits neuronal high-frequency firing by reducing the ability of sodium channels to recover from inactivation. 353

Question 104

Continued use of opioids does not cause tolerance to what side effects?

Answer 104

Tolerance to opioid induced **constipation** and **miosis** does not readily occur. 1257

Question 105

What is the function of kinesin?

Answer 105

**Microtubule associated motor protein** whose function is anterograde transport of intracellular vesicles and organelles toward the plus (rapidly growing) end of MT by using energy from ATP. The plus end typically lie at sites distant from the nucleus; thus, in neurons, kinesin carries **vesicles and organelles away from cell body toward nerve terminal.** 1936

Question 106

A new drug has been developed that is found to be an effective sulfhydryl group donor. This drug would be effective in treatment of what type of overdose?

Answer 106

**Acetominophen toxicity:** sulfation and glucuronide conjugation in liver are saturated and excess NAPQI is formed by CYP450 enzymes. With depletion of glutathione, NAPQI is free to interact with the cells causing hepatocellular injury and centrilobular necrosis. **N-acetyl cysteine** provides the sulfhydrl groups and also acts as a glutathione substitute and binds to the toxic metabolite. 857

Question 107

What enzyme is responsible for the conversion of a bruise to a greenish color?

Answer 107

**Heme oxygenase** converts heme to biliverdin, a pigment that causes the greenish color to develop in bruises several days after an injury. 1456

Question 108

What disease is caused by absence of normal blue and fluorescent green pigmented produced by nitroblue tetrazolium test and dihydrorhodamine flow cytometry test, respectively

Answer 108

**Chronic granulomatous disease**: X-linked mutation affected **NADPH oxidase**, leading to an inability of neutrophils to form the oxidative burst necessary to kill organisms in their phagolysosomes. Patients develop **recurrent bacterial and fungal infections** (particularly pneumonia, skin and organ abscesses, suppurative adenitis, and osteomyelitis) 571

Question 109

What occurs within the germinal centers of lymph nodes?

Answer 109

The primary immune response to a new antigen initially results in plasma cells that produce only IgM. **Isotype switching later occurs in the germinal centers** of lymph nodes and requires interaction of the CD40 receptor on B cells with the CD40 expressed by activated T-cells. IgG is the main serum immunoglobulin of the secondary response. 1614

Question 110

What is considered a variant of normal in adult patient heart?

Answer 110

The **foramen ovale is patent** in 30% of normal adults. Although it usually remains functionally closed, any abnormality increasing RA pressure above LA pressure can produce a R to L shunt across the PFO which may cause hypoxemia and paradoxical embolization. A PFO should be suspected in any patient who has evidence of DVT of the extremities and has developed a stroke. 202

Question 111

Describe a normal (bell-shaped) distribution

Answer 111

The SD is calculated such that **68% of all values lie within 1 SD from the mean.** The remaining 32% of values lie outside of 1 SD, with 16% of those above and 16% below 1 SD from the mean. In addition, **95% of all values are within 2 SD** from the mean and **99.7% are within 3 SDs. ** 1201

Question 112

What is heteroplasmy

Answer 112

The variable severity of mitochondrial diseases is explained by the random distribution of normal and mutated mitochondria betwen daughter cells during mitosis; as a result, some cells may have completely healthy mitochondria, while other cells contain mitochondria affected by the genetic mutation. 596

Question 113

What aspect of IL-2 (Aldesleukin) that is responsible for its anti-cancer effect

Answer 113

IL-2 is produced by helper T cells and stimulates the growth of CD4/8+ T cells and B cells. Also activates NK and monocytes. This increased activity of T cells and NK cells is responsible for its anti-cancer effect on metastatic melanoma and RCC. 8530

Question 114

What is the most common site of injury of traumatic aortic rupture (e.g. from MVA)

Answer 114

Aortic isthmus, which is tethered by the ligamentum arteriosum and is realitvely fixed and immobile compared to the adjacent descending aorta. 2130

Question 115

Frontotemporal Dementia (Pick's Disease): macro/microscopic, sx

Answer 115

50-60 y/o w degeneration of **frontal lobes** that eventually progresses to temporal. Pick bodies (cytoplasmic inclusions of microtuble-associated protein tau) Sx **early personality and behavioral changes** (e.g. social inapporiate) and **altered spech patterns** (e.g. paucity of speech, repeated phrases). Neurocognitive deficits occur later. 594

Question 116

What drugs used in treatment of peripheral neruopathy should not be used in patients with BPH?

Answer 116

**TCAs** (imipiramine, doxepin, amitriptyline, clomipramine) are commonly used for painful diabetic neuropathy; have strong anticholinergic properties and may cause urinary retention. 575

Question 117

What is first-line for patients with rheumatoid arthritis and what are SE of drug

Answer 117

**Methotrexate**. SE include **stomatitis** (**painful mouth ulcers**) and **hepatotoxicity** (hepatitis, fibrosis, cirrhosis). Others include myelosuppresion, increased risk opporutnitisic infections, B cell lymphomas, and pulmonary fibrosis. 718

Question 118

S/Sx of DKA and treatment

Answer 118

Occurs MC in pts with type 1 diabetes and presents with n/v, abd pain, volume depletion (hyptoension, tachycardia), and ketones and glucose in urine. **Regular insulin** administered as IV infusion is preferred for acute treatment. 600

Question 119

What is an important allosteric activator of gluconeogenesis?

Answer 119

**Acetyl-CoA** To convert pyruvate to phosphoenolpyruvate, pyruvate first undergoes biotin-dependent carboxylation to oxaloacetate in the mitochondria; this rxn is catylzed by *pyruvate carboxylase*, the activity of which is increased by acetyl-CoA. 1034

Question 120

What coenzymes are required for branched-chain alpha-ketoacid dehydrogenase?

Answer 120

Branched-cahin alpha-ketoacid dehydrogenase, simmilar to pyruvate and alpha-ketoglutarate dehydrogenase, requires several coenzymes: Thiamine pyrophosphate, Lipoate, Coenzyme A, FAD, NAD (mnemonic: Tender Loving Care For Nancy). Some patients with maple syrup urine disease improve with high-dose thiamine treatment (thiamine-responsive). 1336

Question 121

Deletions or additions of a number of base pairs which are not a multiple of three indicate what?

Answer 121

**Frameshift mutation** has occured. These alter the reading frame of the gentic code, resulting in the formation of non-functional proteins. 1412

Question 122

Which cholesterol medications increase risk for gallbladder formation?

Answer 122

Both **fibrates** (gemfibrozil) and **bile acid-binding resins** (cholestyramine) increase cholesterol excretion by the liver. Along with the reduction in serum LDL, there is an increased risk for gallstones. 164

Question 123

What are the acid-base abnormalities with DKA

Answer 123

Characterized by triad of polydipsia, polyuria, and a fruity odor to the breath and/or urine. Associated with a high anion gap metabolic acidosis that is typically accompanied by compensatory respiratory alkalosis --\> low pH, low serum bicarb, low PaCO2. 2014

Question 124

Where is the defect localized in conditions with impaired ability to oxidize very long chain fatty acids (VLCFA) and phytanic acid?

Answer 124

**Peroxisomal diseases** are rare inborn errors of metabolism where peroxisomes are either absent or nonfunctional. VLCFA or fatty acids with branch points at odd-numbered carbons can not undergo mitochondrial beta-oxidation; these FAs are mtabolized by a special form of beta oxidation (VLCFA) or alpha oxidation (branched chain FAs such as phytanic acid) within peroxisomes. These diseases commonly lead to neurologic defects from improper CNS myelination. 1120

Question 125

What is an oxidase-positive bug that is a common cause of UTIs in patients with indwelling bladder caths

Answer 125

Pseudomonas aeruginosa: oxidase-positive, non-lactose fermenting, gram-negative organism 1146

Question 126

The genetic abnormalitiy of hemochromatosis primarily affects which process?

Answer 126

hemachromatosis gene (HFE) encodes an HLA class I-like molecule that apperas to affect **iron absorption from the gastrointesinal tract ** 393

Question 127

Differentiate gastric erosions vs. ulcers

Answer 127

_Erosions_: mucosal defects that **do not fully extend through the muscularis mucosa**. Usually occur wtih **acute erosive gastropathy** d/t use of NSAIDs, surgical stress, head trauma (Cushing ulcer), burns (Curling ulcers), smoking, and EtOH; can cause upper GI hemorrhage that leads to melena. _Ulcers_: penetrate through the mucosal layer and **extend into submucosal layers**. 290

Question 128

A elderly women presents with an adnexal mass. What is the cancer and what is the marker?

Answer 128

Ovarian malignancy. CA-125.

Question 129

In a patient with bitemporal hemianopsia, what are the levels of GnRH, LH, and testosterone?

Answer 129

Suspect pituitary tumor. MC prolactinoma which inhibit the entire axis of GnRH-LH/FSH-sex hormones. Cause impotence in men and amenorrhea in women of reproductive age (hypogonadotropic amenorrhea) 213

Question 130

Which tests should you consider before initiation of metformin?

Answer 130

SE is GI upset and **lactic acidosis. **CI in patietns wtih renal failure (*check serum creatinine*), liver dysfunxtion, CHF, alcohlism, and sepsis due to risk of lactic acid accumulation. 607

Question 131

Colcichine most likely affects which cell structure?

Answer 131

**Cytoskeleton**. Binds to intracellular protein tubulin and inhibits its polymerization into microtubules, which disrupts membrane-dependent functions such as chemotaxis and pahgocytosis. SE: nausea, abdominal pain, diarrhea. 859

Question 132

Cause of high incidence of fulminant hepatitis in pregnant women

Answer 132

**Hepatitis E virus** is an **unenveloped**, ssRNA virus spread through the fecal-oral route. High mortality rate observed in infected pregnant women. 48

Question 133

Why is the pO2 in the LA lower than that in the pulmonary capillaries?

Answer 133

**Venous admixture! **Becuase deoxygenated blood originating from the bronchial arteries mixes with oxygenated blood in the pulmonary veins. The left/righ bronchial arteries arise from descending thoracic aorta and carry oxygenated blood to bronchi/bronchioles, and together with the pulm rtery, form dual supply to lungs. *The majority of blood supplied by the bronchial arteries is returned to the left heart in deoxygenated form via the pulm veins*. 1542

Question 134

Explain the steps in base excision repair

Answer 134

Used to correct defects in single bases induced spontaneously or by exogenous chemicals. In this process, **glycosylases** remove the defective base, and the corresponding sugar-phosphate is cleaved and removed by **endonuclease**, followed by the action of **lyase**. **DNA polymerase** then repalces the missing nucleotides and ligase reconnects the DNA strand. 1475

Question 135

What would result from damage to radial nerve?

Answer 135

Receives fibers from C5-C8 and T1. Because this nerve tracts within the radial groove on the humerus, it is vulnerable to injury should the humerus fracture. Damage results in **"wrist drop"** where wrist and fingers cannot be **extended**. 1930

Question 136

What is the most common cause of fetal hydronephrosis?

Answer 136

In normal fetal development, the ureters are fully canalized before the metanephros begins to produce urine (8-10w gestation). Inadequate recanalization of **ureteropelvic junction,** the junction between kidney and ureter, is the MCC. 837

Question 137

What are general features that aid in localizing a transverse spinal cord section

Answer 137

* More proximal levels have increasing amounts of white matter and more ovoid sections * Lower cervical and lumbosacral regions have large ventral horns * Thoracic and early lumbar sections (T1-L2) contain lateral grey matter horns 8635

Question 138

Describe the 2 ways that lac operon is regulated

Answer 138

Negatively by binding of the repressor protein to the operator locus and positively by cAMP-CAP binding upstream from the promoter region. Constitutive expression of the structural genes of the lac operon occurs with mutations that impair the bindign of the repressor protein (Lac I) to its regulatory sequence in the operator region. 1479

Question 139

What is the treatment/MOA for Chronic Hep C

Answer 139

**Interferon alpha + Ribavirin** _Ribavirin_: multifactorial and includes **interfering with the dupliation of viral genetic material**, inducing lethal hypermutation, inhibiting RNA polymerase and inosine monophosphate dehydrogenase (depleting GTP), causing defective 5'-cap formation on viral mRNA transcripts, and modulating a more effective immune response. 8455

Question 140

What drug reverses the anticoagulant effect of heparin?

Answer 140

**Protamine sulfate**. Heparin increases the effect of naturally occuring anticoagulant antithrombin III. Note: vitamin K is used for reversal of warfarin. Aminocaproic acid and tranexamic acid inhibit fibrinolysis.

Question 141

What serological markers would suggest resolved Hep B infection?

Answer 141

Moderate to high levels of **anti-HBc** (not anti-HBc IgM component is replced with an IgG component) and **anti-HBs** without detectable viral antigens. 380

Question 142

How can you increase the power of a study?

Answer 142

Power of study increases proportionally with the sample size. The large a sample, the greater the ability to detect a difference when one truely exists. 1303

Question 143

Contrast MOA of phenytoin with ethosuximide

Answer 143

* Phenytoin, carbamazepine, and valproic acid inhibit neuronal high-frequency firing by reducing the ability of Na+ channels to recover from inactivation. * Ethosuximide blocks T-type calcium channels in thalamic neurons causing hyperpolarization

Question 144

Who should informed consent be obtained by?

Answer 144

Informed consent should be obtained by the physician performing the procedure as this person is best qualified to describe the procedure and its potential complications and provide responses to patient questions.

Question 145

Dx and histologic changes for a young adult experiencing episodic CNS dysfunction that partially or fully resolves

Answer 145

**Multiple Sclerosis** d/t **sclerotic plaque** formation throughout the white matter --\> **demyelination** which **impairs saltatory conduction** down the axon, resulting in conduction blockade and/or slowing of neuronal signal transmission. * **Demyelination with relative preservation of axons** * Accumulation of lipid-laden macrophages (containing the products of myelin breakdown) * Astrocytosis (proliferation in response to injury) * Infiltration by lymphcoytes and mononuclear cells 917

Question 146

What endometrial changes immediately proceed menstural bleeding?

Answer 146

Endometrial cells undergo **apoptosis** upon withdrawal of endocrine stimulation by progesterone. 299

Question 147

Man presents with bilateral breast enlargement, tall stature, little body hair, and tests are small/firm. Whats diagnosis?

Answer 147

**Klienfelter syndrome** (47,XXY) - causes male hypogonadism, reduced spermatogenesis and male infertility. Elongated body with abnormally long legs, small atrophic testes and penis, and abscent secondary male characteristics. Gynecomastia and mildly decreased IQ common. Lab: **elevation of plasma gonadotropins** (primarily **FSH**) and **estradiol**, with **reduction in testosterone**. 1055

Question 148

What is the first step in the pathogenesis of atherosclerosis?

Answer 148

Initiated by repetitive endothelial cell injury, which leads to a chronic inflammatory state in the underlying intima of large elastic arteries as well as large and medium-size muscular arteries. 442

Question 149

How does Staph promote growth of a gram-negative coccobacilli which otherwise would demonstrate little growth on sheep agar?

Answer 149

H. influenza requires X (hematin) and V (NAD+) factors for growth. When grown in presence of S. aureus, there is the "satellitle phenomenon" where H. influenza grows only near the beta-hemolytic S. aureus colonies becuase they produce the needed X and V factors. 963

Question 150

TNF-alpha upregulates what process to facilitate decreased insulin-mediated glucose uptake?

Answer 150

Aberant serine and threonine residue phosphorylation by serine kinase leads to insulin resistance. These aberrant phosphorylations can occur in the presence of TNF-alpha, catecholamines, glucocroticoids, and glucagon. 1326

Question 151

Man develops watery diarrhea with abdominal cramps and n/v during trip to Mexico that resolved in a few days without ABX treatment. Dx and MOA

Answer 151

Traveler's diarrhea d/t ETEC that produces heat labile (**LT**, **cholera-like**) and heat stable (ST) enterotoxins. LT activates adenylate cyclase leading to increased intracellular cAMP, and ST activates guanylate cyclase leading to increased intracellular cGMP. Both cause water and electrolyte loss and watery diarrhea. 1099

Question 152

Whats the overall MOA of penicillins and cephalosporins?

Answer 152

Irreversibly binding to **penicillin-binding proteins** such as **transpeptidases**, which function to cross-like peptidoglycan in bacterial cell wall. Inhibition leads to cell wall instability and bacteriolysis. A change in the structure of PBPs that prevents ABX binding is one mechanism of bacterial resistance.

Question 153

Imaging of lung bipsy reveals apical granulomas with central caseous necrosis. Surrounding the necortic areas are large cells with abundant pale cytoplasm. What surface marker is specific for these cells?

Answer 153

The caseating granulomas of TB almost always contain large epithelioid macrophages with pale pink granular cytoplasm and surface **CD14** at the periphery. CD14 is a surface marker of the monocyte-macrophage cell lineaage. 1598

Question 154

What mutation is seen in patients with **primary hemochromatosis** and what does this result in? What are these pts at increased risk of?

Answer 154

**HFE protein mutations**, which normally interacts with transferrin receptor to increase endocytosis of iron-transferrin complex. Mutations that inactivate HFE cause enterocytes and hepatocytes to detect falsely low iron levels * _Enterocytes_ increase apical expression of **DMT1**, icnreasing iron absorption from intestinal lumen * _Hepatocytes_ decrease hepcidin synthesis; **low hepcidin** results in increased ferroportin expression on basolateral surface of enterocytes which allows increased iron secretion into circulation --\> iron overload. Pts develop triad of **micronodular cirrhosis**, DM, and skin pigmentation. Increased risk for HCC, CHF, and testicular atrophy/hypogonadism. 395

Question 155

What is the MOA of pioglitazone?

Answer 155

Thiazolidinediones (TZDs) bind **PPAR-gamma**, which is a transcriptional regulator of genes involved in glucose and lipid metabolism. TZD increases levels of **adiponectin**, a cytokine secreted by fat tissue, which results in **decreased insulin resistance**. 605

Question 156

Clinical presentation of restlessness, agitation, and dysphagia (d/t painful spasms with swallowing/inspiration) progressing to coma 30-50 days following exposure to cave bats

Answer 156

**Rabies encephalitis**. CDC recommends prophylactic vaccination (**killed vaccine**) for individuals at high risk of exposure to rabies virus 1465

Question 157

Describe the structrual genes of HIV

Answer 157

In HIV replication cycle, polyprotein precursors are encdoded for by the sructural genes (*gag, pol*, and *env*). Only the *env gene* polyprotein product is glycoslyated to gp160 and proteolytically cleaved within the ER and golgi to form envelope glycoproteins gp120 and gp41 * **gp120**: mediates viral absorption by binding to CD4 receptor of susceptible cells * **gp41**: anchors gp120; mediates fusion process between viruses and target cells 1672

Question 158

Which cell types work to control pulmonary TB infection?

Answer 158

The TH1 response involves the activation of specific **CD4+ T lymphocytes **by APCs, followed by an IFNy and IL-2 mediated activation of **macrophages** and cytotoxic T lymphocytes. These cells work together to contain TB within a caseous granuloma, which offers the macrophages inside and opportunity to kill the remaining organisms if the necrotic area is small enough. 1218

Question 159

Describe the role of BNP and ANP

Answer 159

BNP is elevated in patients wtih CHF. It is released by the ventricles when they are stretched as they often are in CHF from systolic dysfunction. It acts along with ANP to cause **vasodilation (decreased preload) and diuresis**. Both ANP and BNP activate guanylase cyclase, which induces an **increase in intracellular cGMP.** They counteract endothelin, sympathetic effects, and angiotensin II. **Nesiritide** is a recombent form of BNP that can be used in patients with decompensated LV dysfunction leading to CHF. 157

Question 160

Whats the risk of giving both ganciclovir and zidovudine?

Answer 160

AE of ganciclovir include neutropenia, anemia, thrombocytopenia, and impaired renal function. Used to treat CMV and is commonly administerd to patients with HIV. Both ganciclovir and zidovudine can impair hematopoietic cell DNS synthesis --\> **increased incidence of neutropenia and anemia **

Question 161

Describe the "permissive" effects of cortisol

Answer 161

Increases vascular and bronchial smooth muscle reactivity to catecholamines. Althought cortisol itself doesnt have a direct effect on vascular reactivity, it AUGMENTS the vasoconstrictive effect of catecholamines (i.e. "permissive" because cortisol allows NE to achieve its full vasoconstrictive potential)

Question 162

What is the major cause of AAA and how does this condition start?

Answer 162

**Atherosclerosis**. Atheromas can progress to weaken the underlying media of aortic wall. **Intimal (fatty) streaks** are the earliest lesion and are composed of intimal lipid-filled foam cells, which are derived from macrophges and smooth muscle cells that have engulfed LDL lipoproteins. These complexes then insudate into the intima through an injured, leaky endothelium.

Question 163

What is a rare but very serious complication of antithyroid drugs (e.g. methimazole and propylthiouracil)

Answer 163

**Agranulocytosis**, which commonly presents with **sudden onset of fever and sore throat**. If it is suspected, the eliciting drug should be discontinued and a WBC count with differential obtained. 637

Question 164

Wide, fixed splitting of S2 that does not vary with respiration is a charcteristic ausculatory finding of what?

Answer 164

**ASD**: creates L-R shunt becuase of high pressur ein LA resulting in increased blood flow thru pulm artery. **Eisenmenger syndrome** is the switch to R-L d/t chronic pulmonary HTN; manifests as late-onset cyanosis with clubbing and polycythemia. Closure of ASD may be required to prevent irreversible **pulm vascular sclerosis. ** 201

Question 165

How does malignant hyperthermia present and how is it treated

Answer 165

Occurs d/t hypersensitivty of skeletal muscle to **inhalation anesthetics** (halothane) and muscle relaxent **succinylcholine**. Sx **fever and muscle rigidty** post-op + tachycardia, HTN, hyperkalemia, and myoglobinemia. Tx is **dantrolene** (muscle relaxant), which acts on ryanodine receptors and prevents further release of Ca into cyplasm of muscle fibers. 855

Question 166

What uses tyrosine kinase-associated receptors and the JAK/STAT signaling pathway?

Answer 166

Colony-stimulating factors, prolactin, GH, and cytokines 1720

Question 167

Describe the GPCR domains for glycoprotein hormones

Answer 167

3 domains: **extracellular** (responsible for ligand binding), **transmembrane** (consisting of alpha helices with hydrophobic AAs such as valine, alanine, isoleucine, methionine, and phenylalanine), and **intracellular** (coupled with G-proteins). 1383

Question 168

How does the high mutability of HIV-1 allow for evasion of host humoral and cellular immune responses and development of resistance to anti-retroviral drugs

Answer 168

**Pol gene mutations** are responsible for acquired resistance to HIV reverse transcriptase inhibitors and HIV protease inhibitors. **Env gene mutations** enable escape from host neutralizing antibodies. 1722

Question 169

What glycoprotein of HBV poorly correlates with viral replication and forms spheres/tubules

Answer 169

A component of HBV envelope, **HBsAg** is a noninfective glycoprotein that forms spheres and tubules 22mm in diameter. Infected hepatocytes may secrete enormous quanitites of HBsAg, often considerably exceeding teh amount of HBcAg produced. 387

Question 170

What is mitochondrial vacuolization a sign of?

Answer 170

Irreversible cell injury, signifying that the involved mitochondria are permanently unable to generate ATP

Question 171

A testicular malignancy (particuarlly nonseminomatous germ cell tumors) can secrete what hormone that results in hyperthyroidism

Answer 171

**hCG**. The alpha subunits of hCG, TSH, LH and FSH are identical and beta subunits of hCG and TSH share significant sequence homology. Because of this, hCG can bind to TSH receptor and cause **paraneoplastic hyperthyroidism. **

Question 172

What protective mechanism suppresses pathogenic strains of C. difficile

Answer 172

**Intestinal biomass**: intestinal bacteria supress overgrowth of C. diff by competing for nutrients and adhesion sites within the gut. **ABXs** can alter intestinal balance leading to overgrowth of pathogenic strains. C. diff causes disease by releasing two toxins that damage the mucosal lining of the LI leading to diarrhea (Toxin A) and necrosis (Toxin B) with pseudomembranes.

Question 173

What are the two morphological variants of gastric adenocarcinoma?

Answer 173

_Intestinal type_: **solid mass** that projects into stomach lumen and is composd of **glandular-forming cuboidal or columnar cells** _Diffuse type (linitis plastica)_: **infiltrates stomach wall** and displays **signet-ring** pattern on LM.

Question 174

What is the most common abnormality predisposing to native valve bacterial endocarditis (NVBE)

Answer 174

Mitral valve prolapse, which predisposes to infected vegetations on mitral leaflets.

Question 175

What artery supplies the diaphragmatic surface of the heart?

Answer 175

The inferior wall of the LV forms most of the diaphragmatic surface of the heart. The **PDA** supplies this area, which is usually derived from the RCA. 1871

Question 176

Symmetric enlargement of ventricles is characteristic of what brain abnormality?

Answer 176

**Communicating hydrocephalus,** which usually occurs secdonary to dysfunction or obliteratio of subarachnoid vili. This dysfunction is usaully a sequelae of meningeal infection (including **TB meningitis**) or subarachnoid/intraventricular hemorrhage. 15

Question 177

What histiological feature is unique to the duodenum

Answer 177

**Brunner's glands** of the submucosa, which secrete alkaline mucus into ducts that empty into the crypts of Lieberkuhn. Peyers patches, in contrast, are lymphoid aggregates specifc to the ileum.

Question 178

What is the cause of hemolytic disease of the newborn (erythroblastosis fetalis)

Answer 178

Maternal sensitization to Rh antigens during a prior preganncy with Rh(D)+ fetus. In subsequent Rh(D)+ pregancies, **materal anti-Rh(D) IgG antibodies** cross placenta and cause fetal hemolysis. Sx anemia, jaundice, generalized edema (hydrops fetalis), **nucleated erythrocytes**, and **extramedullary hematopoesis** (hepatosplenomegaly)

Question 179

What acid base abnormality is suggestive of pulmonary embolism (PE)

Answer 179

Acute respiratory alkalosis: increased pH, reduced PaCO2 and PaO2 1981

Question 180

What is the cause of Dubin-Johnson syndrome and what is the presentation

Answer 180

Conjugated chronic hyperbilirubinemia that is not associated with hemolysis. Defect in hepatic excretion of bilirubin glucuronides across the canalicular membrane. Grossly the liver is black. Histological features are normal, though a dense pigment composed of epinephrine metablites within lysosomes can be seen. 101

Question 181

What defect leads to the development of methylmalonic acidemia

Answer 181

Catabolism of isoleucine, valine, threonine, methionine, cholesterol, and odd-chain fatty acids leads to formation of **propionic acid**, which is converted to **methylmalonic acid** by biotin-dependent carboxylation. **Isomerization** of methylmalonyl CoA forms **succinyl CoA,** which subsequently enters TCA. Defects in isomerization lead to development of methylmalonic acidemia. 1341

Question 182

How does atopic dermatitis (eczema) present and what is it associated with?

Answer 182

Seen in childhood; presents wtih intense pruritus and eryhtematous, weeping/crusted papules and plaques that occur in response to certain environmental antigens. It is associated with other atopic diseases such as allergic rhinitis and asthma. 876

Question 183

How does C. diff colitis damage intestinal mucosal cells

Answer 183

**Toxins A** (enterotoxin) and **B** (cytotoxin) **innactivate Rho-regulatory proteins** involved in signal transduction and **actin cytoskeletal structure** maintenace. As a result, the toxins cause **disruption of intracellular tight junctions** leading to cell rounding/retraction as well as increased (paracellular) intestinal fluid secretion. 1397

Question 184

Describe fxn of various apolipoproteins

Answer 184

A-I: LCAT activation (cholesterol esterification) B-48: chylomicron assembly and secretion by intestine B-100: LDL uptake by extrahepatic cells C-II: lipoprotein lipase activation E-3 and 4: VLDL and chylomicron remanant uptake by liver cells

Question 185

What is the cal per gram of protein and fat

Answer 185

Metabolism of 1g protein or carbohydrate produces **4 cal** of energy, while metabolism of 1g of fat produces **9 cal**. 755

Question 186

What are the virulence factors of Bacillus anthracis?

Answer 186

* Antiphagocytic poly-y-D-glutamic acid capsule * Anthrax exotoxin - composed of protective antigen (translocates edema and lethal factor into cytosol). Edema factor acts as a calmodulin-dependent AC that increases cAMP --\> fluid within and between cells, and suppression of neturophil and macrophage fxn. *Bordetella pertussis* produces adenylate cyclase exotoxin that is simmilar to edema factor. 1101

Question 187

What is the effect of adenosine and dipyridamole on myocardial ischemia d/t atherosclerotic lesions

Answer 187

Selective vasodilators of coronary vessels that can cause **coronary steal**, a phenomenon in which blood flow in ischemic areas is reduced due to arteriolar vasodilation in nonischemic areas. Can lead to hypoperfusion and worsening of existing ischemia. 952

Question 188

Primary amenorrhea in a patietn wtih fully developed secondary sexual characteristics suggests what?

Answer 188

Presence of an anatomic defect in genital tract such as Mullerian duct abnormalities (gives rise to fallopian tubes, uterus, cervix, and upper vagina). **Mullerian agenesis** can present with shortened vaginal canal and rudimentary uterus. 1809

Question 189

Severe intellectual disability, hx of seizures, and abnormal pallor of catecholaminergic brain nuclei are suggestive of what?

Answer 189

PKU: inability to convert phenylalanine into tyrosine which is catalyzed by phenylalanine hydroxylase and requires cofactor tetrahydrobiopterin (BH4). Also presents wtih mousy/musty body odor. 1483

Question 190

What are the CYP450 inhibitors vs. inducers

Answer 190

_Inducers_: "Guiness, Coronas, and PBRs induce chronic alcholism." Griseofulvin, Carbamazepine, Phenytoin, Barbs, Rifampin, St. John wort, chronic alcoholism _Inhibitors_: "CRACK AMIGOS." Cipro, Ritonavir, Amiodarone, Cimetidine, Ketoconazole, Acute alcohol use, Macrolides, Isoniazid, Grapefruit juice, Omeprazole, Sulfonamides.

Question 191

MOA of Raltegrair

Answer 191

**Integrase inhibitor** --\> dirsupts ability of HIV dsDNA to integrate into host cell's chromosomes, thus **preventing host cellular machinery from being used to synthesize HIV mRNA.** 8371

Question 192

What changes in LVEDP, LVEDV, and EF would be seen with heart failure

Answer 192

_Diastolic_: decrease in ventricular diastolic compliance but normal ventricular contractile performance. LVEDP must be increased in order to achieve a normal LVEDV and SV. Normal EF. _Systolic_: decrease in ventricular contractile performance (decreased EF) and requires an increase in both LVEDP and LVEDV to improve SV. 186

Question 193

What drug decreases adenomatous polyp formation?

Answer 193

Studies have linked increased activity of **COX-2** to some forms of colon adenocarcinoma and suggest **aspirin** use decreases polyp formation. 431

Question 194

Distinguish grade from stage

Answer 194

The extent of tumor expansion is characterized by the **stage** of a tumor. The degree of tumor differentation (from well-differentiated to anaplastic) is **grade**. Tumro stage is the most important criteria for determining prognosis.

Question 195

What specific organism would be resistant to agents that attack the peptidoglycan cell wall such as penicillins, cephalosporins, carbapenems and vanc

Answer 195

All organisms in the Mycoplasm genus (including Ureaplasma), as they lack peptidoglycan cell walls. Infections can be treated with anti-ribosomal agents like tetracycline and erythromycin.

Question 196

Recurrent lobar hemorrhages in an elderly patient most likley results from what?

Answer 196

**Cerebral amyloid angiopathy** which occurs when B-amyloid is deposited into arterial wlal, resulting in weakning and predisposition to rupture. **Reccurrent hemorrhagic stroke** is the most common presentation. Unlike cerebral hemorrhages cuased by HTN, amyloid-associated strokes are less severe and are usually located in cerebral hemispheres (l**obar strokes**) vs. HTN hemorrhagic strokes which are larger and tend to involve basal ganglia. 499

Question 197

What is the most important mechanism for Shigella to cause disease?

Answer 197

**Mucosal invasion is most important!** Invades M cells in Peyer's patches and can induce apoptosis of host cell and spread to adjacent cells via protrusions created through host-cell actin polymerization. Releases *shiga toxin* (AB exotoxin): A subunit inactivtes 60S RSU of host and prevents protein synthesis. Non-motile (in contrast to Salmonella), non-lactose fermenting organisms that produce acid (not gas, compared to E.coli). Does not produce H2S (in contrast to Salmonella). 1135

Question 198

What is the immediate treatment of rat poison?

Answer 198

Most rodenticides contain brodifacoum, a long acting 4-hydroxycoumarin derivative. Immediate treatment with **FFP** and **Vitamin K.**