Week of March 16th Flashcards

1
Q

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

A
  • 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. **

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2
Q

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?

A

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.

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3
Q

Describe the metabolism of methionine

A
  • 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

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4
Q

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?

A

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.

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5
Q

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

A

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

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6
Q

What is the presentation and characteristic histology seen in polymyositis

A

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.

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7
Q

Describe cardiac conduction velocity from fastest to slowest

A

Mnemonic: “Park At Ventura Avenue”

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

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8
Q

Describe perfusion vs. diffusion-limited equilibration of gases

A

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.

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9
Q

What are the manifestations of systemic mastocytosis?

A

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. **

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10
Q

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

A

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

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11
Q

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?

A

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

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12
Q

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

A
  • 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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13
Q

Describe the manifestations of CMV disease in immunocompotent and immunocompromised patients

A

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.

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14
Q

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?

A

“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)

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15
Q

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

A

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)

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16
Q

What sunscreens protect you from UVA vs. UVB radiation?

A

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

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17
Q

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

A

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.

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18
Q

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

A

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

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19
Q

What medications increase the risk of cholesterol gallstones?

A

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.

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20
Q

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

A

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 **

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21
Q

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

A

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.

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22
Q

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

A

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.

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23
Q

What does chronic rejection in lung transplant cause?

A

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

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24
Q

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

A

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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25
Q

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

A

Insulin

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26
Q

Describe Lambert-Eaton Myasthenic Syndrome

A

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

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27
Q

What favors the diagnosis of a lung hamartoma

A

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.

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28
Q

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

A

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)

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29
Q

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

A

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.

ARPexposed = 100 X [(risk in exposed - unexposed)/risk in exposed] can also be written as

ARPexposed = 100 X [RR-1)/RR], where RR = risk in exposed/risk in unexposed

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30
Q

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

A

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.

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31
Q

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

A

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.

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32
Q

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?

A

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)

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33
Q

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

A

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.

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34
Q

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

A

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.

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35
Q

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

A

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.

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36
Q

Describe the Pringle manuever

A

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.

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37
Q

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

A

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.

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38
Q

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

A

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.

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39
Q

How do cutaneous neurofibromas appear?

A

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)

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40
Q

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

A

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)

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41
Q

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

A

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

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42
Q

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

A

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.

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43
Q

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

A

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.

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44
Q

What occurs to DNA after UV damage?

A

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.

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45
Q

What enzyme is decreased in gentically predisposed gestational hyperglycemia?

A

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.

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46
Q

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

A

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.

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47
Q

What is the karyote of complete vs. partial mole

A

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

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48
Q

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

A

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)

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49
Q

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

A

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.

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50
Q

How do ARBs work?

A

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.

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51
Q

Ototoxicity secondary to loop diuretics usually occurs with what?

A

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.

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52
Q

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

A

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.

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53
Q

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

A

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.

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54
Q

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

A

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.

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55
Q

Describe caudal regression syndrome

A

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.

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56
Q

Where is the chemoreceptor trigger zone (CTZ)

A

Area postrema of dorsal medulla near fourth ventricle

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57
Q

When is a result considered statistically signifcant?

A

**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.

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58
Q

Explain free energy

A
  • 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.

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59
Q

How do brown pigment stones typically arise?

A

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.

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60
Q

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

A

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.

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61
Q

What prevents edema formation in cor pulmonale secondary to COPD

A

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.

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62
Q

How does the toxin of C. tetani travel?

A

Toxin-mediated disease that cuases uncontrolled muscle spasms including aw stiffness d/t spasmodic contractions of masster (trismus] 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.

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63
Q

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

A

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.

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64
Q

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

A

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.

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65
Q

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

A

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

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66
Q

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?

A

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. **

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67
Q

How do you avoid complications while performing a throacentesis?

A

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.

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68
Q

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

A

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

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69
Q

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

A

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

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70
Q

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

A

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

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71
Q

What are the classic sx and histological findings of primary hyperparathyroidism

A

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

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72
Q

How does glucagon increase serum glucose?

A

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.

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73
Q

What does hyperammonemia in hepatic encephalopathy result in?

A

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.

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74
Q

How can you diagnose C. diphtheriae?

A

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

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75
Q

What is the most common cause of HIV retinintis

A

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.

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76
Q

How can the clinical course of ATN be divided?

A

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

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77
Q

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

A

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.

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78
Q

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

A

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

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79
Q

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

A

Lacks proofreading 3’–>5’ exonuclease activity in its RNA polymerase and its envelope glycoprotein contains a hypervariable region prone to frequent genetic mutation.

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80
Q

What is the best long-term treatment choice for gout

A

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

81
Q

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

A

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

134

82
Q

Compare and contrast Myasthenia Gravis and Lambert-Eaton Syndrome

A

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

83
Q

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

A

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

84
Q

How do you calculate attack rate?

A

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

85
Q

What is decreased in patients wtih cryptorchidism (undescended testes)

A

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

86
Q

Describe cricopharyngeal muscle dysfunction

A

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

87
Q

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

A

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

88
Q

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

A

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

89
Q

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

A

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

90
Q

What vitamin deficiency results in the anemia associated with chronic alcoholism

A

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

91
Q

What are the developmental milestones of a 3 y/o

A

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

92
Q

What causes gram-negative sepsis

A

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

93
Q

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

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

1359

94
Q

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

A

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

95
Q

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

A

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

96
Q

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

A

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

97
Q

Describe mitochondrial DNA (mtDNA)

A

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

98
Q

Where are enhancers/repressors located?

A

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

99
Q

Describe the different speed of hemoglobin movement during gel electrophoresis

A

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

100
Q

Impetigo can cause what secondary complication

A

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

101
Q

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

A

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

102
Q

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

A

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

103
Q

What is status epilepticus and what is the treatment

A

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

104
Q

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

A

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

1257

105
Q

What is the function of kinesin?

A

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

106
Q

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?

A

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

107
Q

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

A

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

1456

108
Q

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

A

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

109
Q

What occurs within the germinal centers of lymph nodes?

A

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

110
Q

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

A

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

111
Q

Describe a normal (bell-shaped) distribution

A

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

112
Q

What is heteroplasmy

A

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

113
Q

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

A

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

114
Q

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

A

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

2130

115
Q

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

A

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

116
Q

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

A

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

575

117
Q

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

A

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

118
Q

S/Sx of DKA and treatment

A

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

119
Q

What is an important allosteric activator of gluconeogenesis?

A

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

120
Q

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

A

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

121
Q

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

A

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

1412

122
Q

Which cholesterol medications increase risk for gallbladder formation?

A

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

123
Q

What are the acid-base abnormalities with DKA

A

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

124
Q

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

A

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

125
Q

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

A

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

1146

126
Q

The genetic abnormalitiy of hemochromatosis primarily affects which process?

A

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

393

127
Q

Differentiate gastric erosions vs. ulcers

A

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

128
Q

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

A

Ovarian malignancy. CA-125.

129
Q

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

A

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

130
Q

Which tests should you consider before initiation of metformin?

A

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

131
Q

Colcichine most likely affects which cell structure?

A

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

132
Q

Cause of high incidence of fulminant hepatitis in pregnant women

A

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

48

133
Q

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

A

**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

134
Q

Explain the steps in base excision repair

A

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

135
Q

What would result from damage to radial nerve?

A

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

136
Q

What is the most common cause of fetal hydronephrosis?

A

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

137
Q

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

A
  • 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

138
Q

Describe the 2 ways that lac operon is regulated

A

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

139
Q

What is the treatment/MOA for Chronic Hep C

A

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

140
Q

What drug reverses the anticoagulant effect of heparin?

A

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.

141
Q

What serological markers would suggest resolved Hep B infection?

A

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

142
Q

How can you increase the power of a study?

A

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

143
Q

Contrast MOA of phenytoin with ethosuximide

A
  • 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
144
Q

Who should informed consent be obtained by?

A

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.

145
Q

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

A

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

146
Q

What endometrial changes immediately proceed menstural bleeding?

A

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

299

147
Q

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

A

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

148
Q

What is the first step in the pathogenesis of atherosclerosis?

A

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

149
Q

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

A

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

150
Q

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

A

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

151
Q

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

A

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

152
Q

Whats the overall MOA of penicillins and cephalosporins?

A

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.

153
Q

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?

A

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

154
Q

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

A

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

155
Q

What is the MOA of pioglitazone?

A

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

156
Q

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

A

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

1465

157
Q

Describe the structrual genes of HIV

A

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

158
Q

Which cell types work to control pulmonary TB infection?

A

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

159
Q

Describe the role of BNP and ANP

A

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

160
Q

Whats the risk of giving both ganciclovir and zidovudine?

A

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 **

161
Q

Describe the “permissive” effects of cortisol

A

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)

162
Q

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

A

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.

163
Q

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

A

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

164
Q

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

A

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

165
Q

How does malignant hyperthermia present and how is it treated

A

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

166
Q

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

A

Colony-stimulating factors, prolactin, GH, and cytokines

1720

167
Q

Describe the GPCR domains for glycoprotein hormones

A

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

168
Q

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

A

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

169
Q

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

A

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

170
Q

What is mitochondrial vacuolization a sign of?

A

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

171
Q

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

A

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. **

172
Q

What protective mechanism suppresses pathogenic strains of C. difficile

A

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.

173
Q

What are the two morphological variants of gastric adenocarcinoma?

A

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.

174
Q

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

A

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

175
Q

What artery supplies the diaphragmatic surface of the heart?

A

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

176
Q

Symmetric enlargement of ventricles is characteristic of what brain abnormality?

A

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

177
Q

What histiological feature is unique to the duodenum

A

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.

178
Q

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

A

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)

179
Q

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

A

Acute respiratory alkalosis: increased pH, reduced PaCO2 and PaO2

1981

180
Q

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

A

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

181
Q

What defect leads to the development of methylmalonic acidemia

A

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

182
Q

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

A

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

183
Q

How does C. diff colitis damage intestinal mucosal cells

A

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

184
Q

Describe fxn of various apolipoproteins

A

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

185
Q

What is the cal per gram of protein and fat

A

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

755

186
Q

What are the virulence factors of Bacillus anthracis?

A
  • 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

187
Q

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

A

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

188
Q

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

A

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

189
Q

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

A

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

190
Q

What are the CYP450 inhibitors vs. inducers

A

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.

191
Q

MOA of Raltegrair

A

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

192
Q

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

A

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

193
Q

What drug decreases adenomatous polyp formation?

A

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

194
Q

Distinguish grade from stage

A

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.

195
Q

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

A

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.

196
Q

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

A

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 (lobar strokes) vs. HTN hemorrhagic strokes which are larger and tend to involve basal ganglia. 499

197
Q

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

A

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

198
Q

What is the immediate treatment of rat poison?

A

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