5.7.2015 UWorld Notes

Question 1

Treatment resistance by decreasing ergosterol incorporation into the cell membrane: Resistance to which agent?

Answer 1

Nystatin (creates pores in membrane allowing release of K+ and ions from fungal cells).

Question 2

DNA and RNA synthesis antibiotic

Answer 2

(Pyrimidines) Flucytosine (Inhibits RNA synthesis in fungal cells)

Question 3

Cell wall antibiotic

Answer 3

(Echinocandins) Caspofungin: Inhibit glucan synthesis (part of fungal cell wall)

Question 4

Cell membrane antibiotic

Answer 4

(Polyenes) Amphotericin B and Nystatin bind ergosterol.

(Triazoles) Azoles inhibit synthesis of ergosterol.

Question 5

Griseofulvin: MOA

Answer 5

INteracts with fungal cell mts inhibiting mitosis.

Question 6

Caspofungin: MOA

Answer 6

Blocks synthesis of glucan component of fungal cell wall.

Question 7

Cyclosporine: MOA

Answer 7

Immunosupressant used in transplant patients to prevent rejection. Decreases synthesis of IL2 inhibiting T cells.

Question 8

Lecithin-sphingomyelin ratio

Answer 8

Marker of fetal lung maturity
Early regulation of fetal surfactant=glucocorticoids (main), T3, T4, insulin, estrogens, prolactin, androgens, catecholamines.
Later in gestation: Maternal and fetal cortisol (Corticosteroids given to moms who are at risk of having baby with lung immaturity).

Question 9

Oxytocin role in pregnancy

Answer 9

Secreted by posterior pituitary and stimulates myometrial contraction in delivery.

Question 10

Air fluid level in pulmonary abscess (local suppurative collections in lung parenchyma and necrosis of surrounding tissue)

Answer 10

Lysosomal enzymes released by neutrophils and macrophages. Lysosomal enzymes serve to digest pathogens and tissue debris AND chemotactically summon additional neutrophils/macrophages. Can also destroy parenchyma.

Question 11

IFN gamma associated with

Answer 11

NO synthase release and development of granulomas and caseous necrosis

Question 12

Eosinophils have

Answer 12

Major basic protein which damages parasites and can cause lysis of epithelial cells.

Question 13

IL12 stimulates

Answer 13

natural killer cells to destroy and T helper cell secretion of IFN gamma

Question 14

Mast cells

Answer 14

cell surface receptor binds to Fc aspect of IgE Ab. Whn mast cell bound IgE recognized Ag, mast cells degranulate and release histamine and products of arachidonic acid oxidation.

Question 15

Congential torticollis

Answer 15

2-4 weeks of age, caused by birth trauma/malposition in utero. SCM injury and fibrosis.
PE: Head tilted toward affected side and chin away from contracture. Soft tissue mass palpable in inferior 1/3 of affected SCM.
Treat: Stretching/conservative

Question 16

Post streptococcal glomerulonephritis

Answer 16

Antecedent skin infection (hx of streptococcal infection: impetigo, cellulitis, pharyngitis) and acute hematuria and edema.
Most common form of acute nephritis in kids.
Ab form against Ag expressed by nephritogenic strains of group A beta hemolytic streptococci (strep pyogenes)
Ab and Ag combine to form immune complexes that are deposited along glomerular basement membrane (T3 hypersensitivity).

Question 17

Cardiomyocyte phases of contraction

Answer 17

Phase 4: Resting potiental. Determined by K+. Negative resting potential -90mV reduces risk of arrhythmias.
Phase 0: Rapid depolarization. AP onset when Na+ ions rush into cell.
Phase 1: Rapid repolarization: Rapid closure of Na+ channels
Phase 2: Plateau: Opening L-type dihydropyridine sensitive Ca2+ channels and closure of some K+ channels. Mem permeable to Ca2+
Phase 3: Late rapid repolarization: Closure of Ca2+ channels and opening of K+ channels.

Question 18

Which encapsulated bacteria whose polysacchardie capsuel components can be covalently bound to protein carriers and used as vaccine Ag?

Answer 18

Strep penumo, N. meningitidis, H. infleunzae.

Carrier proteins: Mutant nontoxic diphtheria toxin, Neisseria meningitis, outer membrane protein complex, and tetanus toxoid.

Question 19

Schizophreniform disorder duration?

Answer 19

> 1 mo and

Question 20

11B hydroxylase deficiency

Answer 20

2nd most common cause of congenital adrenal hyperplasia. Deficiency=adrenal gland prevented from synthesizing cortisol and aldosterone efficiently. This leads to increased production of adrenal androgens due to cortisol and aldosterone precursors being diverted to adrenal androgen biosynthesis.

11B hydroxylase deficiency=ambiguous genitalia

Impaired metabolism of 11 deoxycorticosterone allows weak mineralocorticoid to accumulate leading to development of low renin HTN and hypokalemia.

Question 21

17 alpha hydroxylase deficiency

Answer 21

Impaired sex steroid and cortisol synthesis and increased production of mineralocorticoids.
Females with normal genitalia. Males=undervirilized.
No puberty. HTN. Hypokalemia (mineralocorticoid excess).

Question 22

21 hydroxylase deficiency

Answer 22

Most common cause of CAH. Decreased glucocorticoid and mineralocorticoid synthesis and increases production of adrenal androgens.
Female infants have ambiguous genitals and develop hypotension and hyperkalemia (mineralocorticoid deficiency).

Question 23

5 alpha reductase deficiency

Answer 23

Ambiguous genitalia in males because testosterone can’t convert to DHT. Females are normal.

Question 24

Coagulase negative staphylococci (gram positive, catalase positive cocci).

Answer 24

Polysaccharide slime adhering to prosthetic devices. Infections in catheters or implants. Prosthetic valve endocarditis.

Most are methicillin resistant (and cephalosporins/pencillins resistant because of altered PBP). Ciprofloxacin also accompanies methicillin resistance.
Vancomycin should be used. Gentamicin or rifampin can be administered in cases of deep seated methicillin resistant CoNS or staphylococcal PVE. Nafcillin or oxacilin can be used if staphylococci are methicillin-susceptible.

Native valve endocarditis should be treated with nafcillin or oxacillin.

Question 25

Cannot feel pinprick in perianal area (no rapid contraction of anal sphincter). Nerve root?

Answer 25

S4

Question 26

Cauda equina syndrome

Answer 26

Low back pain radiating to one or both legs, saddle anesthesia, loss of anocutaneous reflex. Bowel and bladder dysfunction (S3-S5 roots), loss of ankle jerk reflex with plantar flexion weakness of foot.

Question 27

Carpal tunnel syndrome

Answer 27

Median nerve compression. Repetitive wrist movements, hypothyroidism, diabetes, mellitus, and RA

Question 28

Acute compartment syndrome

Answer 28

occurs when increased pressure within fascial compartment compromises blood circulation and tissue function in that space. Long bone fractures.

Question 29

Dupuytren’s contraction

Answer 29

Fibroproliferative disease of palmar fascia. Nodules. Fingers lose flexibility and result in contractures that draw fingers into flexion.

Question 30

Vancomycin binds to

Answer 30

D-alanyl-D-alanine in cell wall peptide precursors and prevents formation of peptidoglycan.

Resistance: Change in peptide precursor structures which alters binding site for D-alanyl-D-alanine to D-alanine-D-lactate.

Question 31

Cylcoserine inhibits incorporation of D-alanine into UDP oligopeptide during bacterial wall synthesis. Not used because

Answer 31

High level of ototoxicity.

Question 32

Tetracycline

Answer 32

Inhibitor of protein synthesis that binds to 30S subunit and inhibits binding of aminoacyl tRNAs. Mechanisms of tetracycline resistance=increased efflux or production of protein that allows translation to happen even when tetracycline is present.

Question 33

Amikacin

Answer 33

Aminoglycoside that inhibits 30s ribosomal unit preventing bacterial protein synthesis.
Resistance: Preventing amikacin from entering cell or bacterial enzymes that alter it and prevent it from working.

Question 34

Brown adipocytes

Answer 34

White tissue=one intracytoplasmic fat droplet
Brown tissue=Many fat vacuoles and more mitochondria. No ATP is synthesized and energy release is dissipated as heat (electron transport and phosphorylation are uncoupled). Thermogenin=uncoupling protein

Question 35

Human placental lactogen

Answer 35

Carb metabolism is shunted toward supplying glucose and aa to fetus while excess free FA, ketones, and glycerol provide energy to the mother. This is accomplished through placental hormones (HPL).

HPL secreted from syncytiotrophoblast. Increases maternal insulin resistance which decreases maternal glucose use and increases blood glucose levels allowing glucose to be shunted to fetus. Maternal lipolysis and proteolysis are increased by HPL.

Insulin resistance also results from placental production of GH, estrogens, progesterone, and glucocorticoids.

Question 36

HCG

Answer 36

Maintains corpus luteum which causes it to secrete progesterone. Progesteron promotes maintenance of secretory endometrium.

Question 37

Thiazolidinediones

Answer 37

exert glucose lowering effect by decreasing insulin resistance. Bind to peroxisome proliferator activated receptor gamma (PPAR-gamma) which is transcriptional regulation of genese in glucose and lipid metabolism: adiponectin, FA transport protein, insulin receptor substrate, GLUT4.

Causes FFA levels to decrease and decreases insulin resistance.

Question 38

APC tumor suppressor gene

Answer 38

Growth of small adenomatous polyps from normal colonic mucosa (tubular glands and villous components).

Question 39

DCC gene

Answer 39

Deleted in Colon Cancer

Final step of adenomatous polyps to adenocarcinoma

Question 40

K-ras protoncogene

Answer 40

Leads to unregulated cell proliferation. Size increase in adenomatous polyps.

Question 41

p53 tumor suppressor gene.

Answer 41

Promotes apoptosis of cells with damaged DNA and regulates cell cycle. Mutation triggers final step of adenoma to carcinoma sequence.

Question 42

MSH2 gene

Answer 42

DNA mismatch repair gene. Implicated in development of colorectal cancer. (Lynch syn).

Question 43

Recurrent calcium based nephrolithiasis. What is the treatment?

Answer 43

Thiazide diuretics (decreases urine calcium excretion/increases Ca reabsorption):

1. Inhibits Na/Ca cotransporter of DCT. Activates basolateral Na/Ca antiporter which pumps Na into cell in exchange for Ca.
2. Increases Na and H20 reabsorption in PT leading to passive Ca reabsorption.

Good for patients with nephrolithiasis secondary to hypercalciuria.

Question 44

Acetazolamide

Answer 44

CA inhibitor acts on PCT to cause bicarbonate wasting. Metabolic acidosis worsens hypercalciuria and causes release of Ca phosphate from bone.

Question 45

Loop diuretics (furosemide)

Answer 45

Block Na-K-2Cl cotransporter and increase urinary Ca excretion.

Question 46

Mannitol (osmotic diuretic)

Answer 46

Causes volume depletion and hypernatremia with prolonged use. No effect on calcium.

Question 47

Spironolactone

Answer 47

Mineralocorticoid receptor antagonist. Acts of cortical collecting duct increases Na excretoin and K reabsorption. No effect on Ca.

Question 48

Triamterene and amiloride are

Answer 48

K-sparing diuretics that inhibit Na reabsorption in collecting duct by blocking epithelial sodium channel (ENaC). Amiloride increases Ca reabsorption.

Question 49

Hep Delta Ag is replication defective because

Answer 49

must be coated by external coat antigen HBsAg of Hep B virus. After coated, hep D virus can penetrate hepatocyte, survive in cell, replicate viral RNA and translate genome into protein.

Question 50

Noturnal palpitations and head pounding with exertion.
Head bobbing
Heart murmur

Answer 50

Palpitation from forceful ventricular contractions ejecting large LV stroke volume. Head pounding due to high amplitude pulsations of IC arteries. Head bobbing sign of widened pulse pressure=wide pulse pressure caused by aortic regurgitation!

Question 51

Colon adenocarcinoma found in…

Answer 51

rectosigmoid colon.
left sided tumors more likely to cause obstruction: altered bowel habits, constipation, abdominal distension, n/v.

Ascending colon is second most common location of colorectal carcinomas. Right sided=large masses that protrude into colonic lumen. More likely to bleed and cause iron deficiency anemia. Positive fecal occult blood test.

Question 52

Lancet shaped gram positive diplococci. Vaccine against this contains:

Answer 52

Outer polysaccharide covering
Streptococcus penumoniae
Conjugated vaccine=better T cell response
Polysaccharide unconjugated vaccine=less of T cell response

Question 53

Goodpasture

Answer 53

Anti-glomerular basement membrane disease. Immunofluorescence: Linear deposits of IgG and C3. Presence of crescents in damaged glomeruli on light microscopy.

Anti-GBM Ab cross react with pulmonary alveolar basement membrane causing pulmonary hemorrhages. Combo of renal failure and hemoptysis is typical clinical presentation of anti-GBM disease.

Question 54

Alport syndrome and glomerulonephritis type 1

Answer 54

Alport: Nephritis, deafness, and ocular problems.
MPGN: Granular deposits. You can see increased mesangial matrix.

Question 55

Membranous glomerulopathy

Answer 55

Uniform diffuse capillary wall thickening. Nephrotic syndrome (generalized edema, marked proteinuria, hypoalbuminemia, hyperlipidemia, lipiduria). Granular deposits of IgG and C3 along glomerular basement membrane.

Question 56

FSGS focal segmental glomerulosclerosis

Answer 56

IgM and C3 deposits in sclerotic areas of glomeruli.

Question 57

Minimal change disease

Answer 57

Normal glomeruli on light microscopy
In kids
Presents with nephrotic syndrome
No deposits on immunofluorescence

Question 58

HBV

Answer 58

Partial double stranded circular DNA molecule housed in capsid. After virion enters cell, capsid is released into virla genome and transferred in the nucleus. Viral DNA is repaired to form ds circular minichromosome that can be transcribed into mRNAs. Reverse transcriptase creates a ssDNA intermediate that is converted to circular partially dsDNA. Mature capsid is enveloped by part of ER containing virally coded proteins forming completed virion.

Question 59

Neutrophil count increases following glucocorticoid administration as a result of demargination of leukocytes attached to vessel wall. But eosinophils and basophils…
T and b cells?

Answer 59

Eosinophils and basophils decrease with glucocorticoid admin.
T cells reduced more than B cells.
Glucocorticoids also inhibit monocyte differentiation into macrophages decreasing rate of antigen presentation by macrophages to T lymphocytes.

Question 60

Amiodarone=Class III anti-arrhythmic agent used to suppress cardiac conduction abnormalities. Multiple side effects which are

Answer 60

thyroid dsyfunction, blue gray skin discolartion, drug related hepatitis, pulmonary fibrosis.

Cuases thyroid problems because it is 40% iodine by weight. EXCESSIVE IODINE. Need to test people for preexisting autoimmune thyroid disease before starting them on this. Amiodarone-induced hypothyroidism treated with levothyroxine and amiodarone is continued (prolactin can be increased in this condition because of decreased thyroid feedback).

Amiodarone also can induce excessive thyrotoxicosis via too much TH production.

Question 61

Nucleosome core composed of:

Answer 61

H2A, H2B, H3, H4

H1 bind segment of DNA that lies between nucleosomes and facilitates packaging of nucleosomes into more compact structures.

Question 62

Class I antiarrhythmic medication

Answer 62

Binds to and blocks activated and inactivated voltage gated sodium channels in cardiac pacemaker cells and myocytes.
Dissociation of drug from channel occurs during resting state. Conformational state distinct form inactivated state that occurs after repolarization.

Use dependence: Tissues become more susceptible to blockade due to more time in activated and inactivated states because they are in rapidly depolarizing tissue.

Class 1 antiarrhythmics: Na channel binding strength is 1C>1A>1B. 1C has blocking effects that accumulate over multiple cardiac cycles. Tachycardia causes sodium channel blockade which slows conduction speed and stops the “bad rhythm”

Class 1B: Lidocaine, mexiletine, and tocainide. Bind less avidly to Na channels than other class 1 antiarrhythmics. Dissociation from channels occurs rapidly. Minimal cumulative effect over multiple cycles. These drugs are more selective for ischemic myocardium because reduced resting membrane potential delays Na channel transition from inactivated to resting state.

Amiodarone is Class 3 antiarrhythmic medicine. Block potassium channels and prolong phase 3 repolarization.

Disopyramide, quinidine and procainamide are class 1A drugs. They have intermediate dissociation speed.

Propafenone and flecainide are class 1C and have slow dissociation speed.

Propranolol is class 2 antiarrhythmic drug. Causes chronotropy and inotropy via B1 blockage.

Verapamil is calcium channel blocker. Class IV antiarrhthmic drug. Diltiazem is another drug.

Question 63

Which cells contain lots of SER?

Answer 63

All steroid producing cells (adrenals, gonads, liver). ACTh stimulates cells in adrenal cortex to produce glucocorticoids and also mineralocortocids and androgens.

SER=enzymes for steroid and phospholipid biosynthesis

Question 64

Mullerian aplasia

Answer 64

Vaginal agenesisi; no upper vagina; variable uterine development; primary amenorrhea; normal ovaries; regular develop of secondary sex characteristics; 50% have urologic anomaly (unilateral renal agenesis).

Patients with androgen insensitivity syndrome have minimal axillary/pubic hair due to androgen resistance. No uterus or ovaries. 46, XY.

Kallman syndrome: Decreased synthesis of GnRH. Females rarely affected–those with this condition present with primary amenorrhea, no secondary sex characteristics, olfactory sensory defect.

Klinefelter: 47 XXY. Males. Tall stature, poor secondary sex characteristics, atrophic testes, infertility.

Turner: Primary amenorrhea, short stature, webbed neck, shielded chest, streaked ovaries. No secondary sex characteristics.

Question 65

Lightheadedness when standing=orthostatic hypotension. What does standing up cause in heart?

Answer 65

Increase venous return
Decreased ventricular filling and drop in CO and BP
Drop in Bp->baroreceptor reflex->increased symp. and decreased parasym. activity
Increased symp. tone raises peripheral vascular resistance through alpha1 adrenoreceptors of peripheral vasculature. Increase in venous return and cardiac output.

Question 66

Cardiac tamponade

Answer 66

Elevated JVD (elevation of central venous pressure in SVC). along with hypotension and tachycardia, this indicates cardiac tamponade or tension pneumothorax. No hx of chest trauma and no abnormal lung auscultation=pnumothorax unlikely.

Cardiac tamponade due to serous viral pericarditis and acute pericardial effusion.

Beck’s triad: hypotension, distended neck veins, distant/muffled heart sounds on auscultation and tachycardia. Indicative of tamponade.

Pulsus paradoxus: Drop in systolic blood pressure of >10 mmHg on inspiration is non specific sign but suggestive of tamponade when coupled with hypotension, tachycardia, JVD.

MI would produce similar symptoms: hypotension, tachycardia, weak pulses, JVP but would also be pulmonary edema on auscultation.

Question 67

What can utilize ketone bodies as energy source?

Answer 67

Brain, kidneys, cardiac muscle, and skeletal muscle.

Erythrocytes cannot use ketone bodies bc they don’t have mitochondria. Liver cannot use ketone bodies for energy because lacks enzyme succinyl coA acetoacetate which is required to convert acetoacetate to acetoacetyl coA

Question 68

Acute rheumatic fever

Answer 68

Clinical manifestations: Acute migratory polyarthritis and pancarditis (weak heart sounds, tachycardia, pericardial friction rubs, arrhythmias).
Myocarditis may produce cardiac dilation that can cause mitral regurgitation and heart failure.

Chronic rheumatic heart disease=fibrosis of valve leaflets and mitral stenosis.