Week of March 16th Flashcards
What are characteristic lab features of polycythemia vera (PV) and what is the cause
- 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
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?
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
Describe the metabolism of methionine
- 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
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?
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
Infarcts involving the anterior portion of the medial pons produce which defects and injure which CN?
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
What is the presentation and characteristic histology seen in polymyositis
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
Describe cardiac conduction velocity from fastest to slowest
Mnemonic: “Park At Ventura Avenue”
Fastest –> Slowest = Purkinje –> Atrial Muscle –> Ventricular Muscle –> AV node
Describe perfusion vs. diffusion-limited equilibration of gases
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
What are the manifestations of systemic mastocytosis?
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
Describe the effect of an AV shunt on LV pressure-volume loop
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
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?
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
Under HIPPA, when can physicians disclose patient information to friends and family members?
- 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.
784
Describe the manifestations of CMV disease in immunocompotent and immunocompromised patients
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.
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?
“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
What are the symptoms and causes of serotonin syndrome? What AA is the precursor to serotonin?
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
What sunscreens protect you from UVA vs. UVB radiation?
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
What types of dose adjustments for other medications need to be considered when taking niacin?
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
Describe the MOA and AE of protease inhibior class of antiretroviral drugs (e.g. indinavir)
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
What medications increase the risk of cholesterol gallstones?
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
Sudden upward stretching on teh arm at the shoulder can damage what nerve(s)?
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
Which organ system would show a vascular bed where the arterial/arteriolar resistance increases as blood oxygen content decreases?
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
Where are most intracranial schwannomas located and what are they associated with?
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
What does chronic rejection in lung transplant cause?
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
Why do surgeons need to be careful when removing sublingual mass?
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.
763
What is the medication of choice for the treamtent of gestational diabets?
Insulin
Describe Lambert-Eaton Myasthenic Syndrome
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
What favors the diagnosis of a lung hamartoma
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
What are the 3 zones of the adrenal gland and what do they secrete?
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)
What is and how do you calculate the attributable risk percent in the exposed (ARPexposed)
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
1186
What kind of drug would cause a dose-dependent increase in cardiac contractility and dose-dependent decrease in systemic vascular resistance
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
Which property of skeletal muscle is responsible for its resistance to the effect of verapamil?
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
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?
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
What are the functions of the free ribosomes in cytoplasm vs. bound ribosomes to RER
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
What is the substance-induced pyschosis from Phencyclidine (PCP) appear like?
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
Descirbe how the Schilling test is used to differentiate between dietary deficiency of vitamin b12, pernicious anemia, and malabosprtion syndromes.
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
Describe the Pringle manuever
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
What is one reflex indicating hypocalcemia and the most common cause?
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
What are the most common congenital breast anomaly seen in women and men?
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
How do cutaneous neurofibromas appear?
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
What are the most commmon causes of congenital heart disease that result in cyanotic symptoms at birth and what embyological events underlie these conditions?
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
What is the MOA of the 4 main drugs used for treatment of Mycobacterium tuberculosis (MTB)
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
Do high or low levels of cholesterol, bile salts, and phosphatidylcholine promote gallstone formation?
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
Which amino acids should be restricted from an infants diet with Maple Syrup Urine Disease (MSUD)
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
What occurs to DNA after UV damage?
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
What enzyme is decreased in gentically predisposed gestational hyperglycemia?
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
What can nafcillin, methicillin, and oxacillin be used to treat?
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
What is the karyote of complete vs. partial mole
Partial mole will have a triploid karyote (69 XXX or XXY) vs. complete mole (46 XX or XY; parental origin)
792
What antiarrythmics demonstrate strong use-dependence vs. reverse use-dependence
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
What is the most common viral cause of an aplastic crises in patients with sickle cell anemia?
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
How do ARBs work?
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
Ototoxicity secondary to loop diuretics usually occurs with what?
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
What does ischemic injury in most organs vs. brain result in?
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
What is the major determinant of whether or not a coronary artery plaque will cause ischemic myocardial injury?
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
What is the distincitive morphologic changes seen with acute hepatitis caused by viral infection
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
Describe caudal regression syndrome
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
Where is the chemoreceptor trigger zone (CTZ)
Area postrema of dorsal medulla near fourth ventricle
1741
When is a result considered statistically signifcant?
**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
Explain free energy
- 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
How do brown pigment stones typically arise?
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
Crescents on light microscopy are diagnostic of what condition and what do they contain?
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
What prevents edema formation in cor pulmonale secondary to COPD
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
How does the toxin of C. tetani travel?
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.
1402
A positive VDRL and pleocytosis in CSF are diagnostic of what?
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
The traid of low hemoglobin, thrombocytopenia, and absent hematopoietic cells in bone marrow is consistent with what? What is a compensatory mechanism?
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
What is the defect in a patient with orotic aciduria? Supplementation with which substances would be of benefit?
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
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?
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
How do you avoid complications while performing a throacentesis?
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
An infant is dx with renal carnitine wasting and severe carnitine deficiency. The pt most likely also has deficeint synthesis of?
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
What is the triad of ataxia telangiectasia and what is the defect?
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
Describe the difference in mutations and sx between pemphigus vulgaris and bullous pemphigoid
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
What are the classic sx and histological findings of primary hyperparathyroidism
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
How does glucagon increase serum glucose?
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
What does hyperammonemia in hepatic encephalopathy result in?
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
How can you diagnose C. diphtheriae?
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
What is the most common cause of HIV retinintis
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
How can the clinical course of ATN be divided?
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
What drugs are associated with medication-induced body fat redistribution syndrome
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
If a pt has lymphoma that expresses CD20, how would you treat it?
Rituximab is a monoclonal antibody used in lymphoma immunotherapy that specifically targets the CD20 (B-cell marker) surface immunoglobulin.
1628
The genetic instability of HCV is attributed in large part to its RNA-dependent RNA-polymerase, which lacks what?
Lacks proofreading 3’–>5’ exonuclease activity in its RNA polymerase and its envelope glycoprotein contains a hypervariable region prone to frequent genetic mutation.
388