Uworld

Front 1

Acyclovir

Back 1

Anti-viral against herpes viruses

-acyclovir can cause crystalline nephropathy if adequate hydration is not also provided.

-when acyclovir concentration in collecting duct exceeds solubility, crystallization, crstalluria, and renal tubular damage may result

-in most cases, this toxic complication is transient and can be prevented/treated with adequate hydration and dosage adjustment (slowing rate of IV infusion)

Front 2

Atherosclerotic plaques and acute coronary syndrome (MI)

Back 2

-plaque rupture can produce an acute coronary syndrome via superimposed thrombosis and/or thromboembolism

-likelihood of plaque rupture (or other change) has more to do with plaque stability the plaque size.
-plaque stability depends on mechanical strength of overlying fibrous cap – weak fibrous cap increases probability of plaque rupture

Front 3

-Chronic inflammatory progression of an atheroma

Back 3

-during chronic inflammatory progression of an atheroma, the fibrous cap is continually being remodeled

-balance of collagen synthesis and degradation determines mechanical strength of cap.

-activated macrophages in the atheroma contribute to collagen degradation by secreting METALLOPROTEINASES

-high intraplaque activity of metalloproteinases predisposes plaque to rupture --> acute coronary syndrome, including myocardial infarction

Front 4

Mucormycosis

Back 4

-Mucormycosis strongly associated with DIABETIC KETOACIDOSIS

-Mucor, Absidia, and Rhizopus (RAM) species are saprophytic fungi present in environment
-transmitted by spore inhalation to cause mucormycosis

-Mucomycosis = opportunistic infection

-classic clinical picture is paranasal sinus involvement in a diabetic or immunosuppressed patient
-the fungi form broad non-septate hyphae that branch at RIGHT ANGLES

Front 5

Hyper-IgM syndrome

Back 5

Results from inability of B-lymphocytes to undergo isotope switching from IgM to other Ig isotopes such as IgD/G/E/A.

-results in lymphoid hyperplasia and recurrent sinopulmonary infections.

-usually due to genetic absence of the CD-40 ligand on T-lymphocytes,
or from a genetic deficiency in the enzymes responsible for the DNA modification that takes place during isotope switching.

Front 6

Conversion of glucose to sorbitol

Back 6

-during hyperglycemia, excess plasma glucose is converted to sorbitol by aldose reductase.

-sorbitol accumulates within some cells and attracts water into these tissues --> osmotic cellular injury.

-this mechanism is implicated in the pathophysiology of cataracts and peripheral neuropathy in diabetes.

Front 7

Lung zones – ventilation and perfusion

Back 7

-perfusion (bloodflow) is much higher in base of lung than in apex

-ventilation is slightly higher in the base than in the apex

-therefore, the ventilation/perfusion ratio is higher in the apex than in the base of the lung.

Front 8

Zone 1 of lung

Back 8

-does not occur in lung under normal physiologic conditions – when it is present, zone 1 is in apex

-alveolar pressure > arterial pressure > venous pressure --> vessels collapsed

-arterial pressure is low because heart must pump blood "uphill" against gravity

-since arterial pressure is lower than alveolar pressure, pulmonary capillaries are collapsed and there is no blood flow – i.e., zone 1 represents alveolar dead space.

-regions of zone 1 can form when there is lower than normal pulmonary arterial pressure (e.g., with hemorrhage), or higher than normal alveolar pressure (e.g., with positive pressure ventilation).

Front 9

Zone 2 of lung

Back 9

-Zone 2 found in higher areas of lung (closer to apex)

-arterial pressure > alveolar pressure > venous pressure

-since alveolar pressure is greater than venous pressure, the pulmonary capillaries are initially obstructed near the venous end of the capillary bed.
-however, as arterial pressure rises during systole, capillary pressure becomes high enough to overcome alveolar pressure.

-therefore, blood flows through zone 2 in a pulsatile fashion

Front 10

Zone 3 of lung

Back 10

-zone 3 found in lower areas of the lung

-arterial pressure > venous pressure > alveolar pressure.

-since arterial and venous pressures are both greater than alveolar pressure, blood flows continuously through the pulmonary capillaries.

-when a person lies supine, the differences in lung perfusion are negated, as gravity then affects the lung equally from apex to base.
-in supine individual, lung is ENTIRELY COMPSED OF ZONE 3 blood flow.

Front 11

V/Q ratio

Back 11

Although both ventilation and perfusion increase from apex to base, perfusion increases to greater degree

-thus, V/Q ratio progressively decreases from ~2.5 to ~0.6

Front 12

Superior laryngeal nerve

Back 12

-superior laryngeal nerve and recurrent laryngeal nerve are branches off vagus

-superior laryngeal nerve:
--internal branch: sensory innervation above vocal cords
--external branch: cricothyroid muscle

-recurrent laryngeal nerve
--innervates all laryngeal muscles except cricothyroid
--provides sensory innervation below the vocal cords

Front 13

Aortic rupture

Back 13

-aortic rupture most comely caused by motor vehicle accidents

-MVA with sudden deceleration can cause different rates of deceleration between heart (in fixed position and aorta.

-most common site of injury is the AORTIC ISTHMUS – the connection between the ascending and descending aorta, distal to where the left subclavian artery branches off the aorta

Front 14

Acetaminophen toxicity

Back 14

-can be effectively treated by sulfhydryl group supplementation

-N-acetyl cysteine provides the sulfhydryl groups
-NAC also acts as a glutathione substitute – binds toxic metabolite

Front 15

Acetaminophen toxicity cntd.

Back 15

-in therapeutic doses, 90% of acetaminophen is metabolized in liver by sulfating and glucuronide conjugation

-remainder eliminated in liver via oxidation by cytochrome-P450 system, and by urinary excretion of un-metabolized drug

-metabolite of cytochrome-P450 oxidase pathway is called NAPQI
-NAPQI = toxic and highly reactive compound

-in therapeutic doses, small about of NAPQI generated – normally metabolized by hepatic glutathione into non-toxic compounds

-with acetaminophen TOXICITY, sulfating and glucuronide conjugation in liver are saturated –> excess NAPQI is formed by the cyt-P450 enzymes

-with depletion of glutathione, NAPQI is free to interact with the cells, causing hepatocellular injury and centrilobular necrosis

Front 16

-Hypoventilation

Back 16

-hypoventilation causes increase in arterial pCO2 and decrease in serum pH (respiratory acidosis)

-acute respiratory acidosis presents with low pH, high pCO2, and normal to mildly increased HCO3-

--bicarb not markedly elevated because renal compensation requires at least 24 hours of persistent reparatory acidosis.

-vs. chronic respiratory acidosis:
--low/normal pH, high pCO2, high HCO3- (greater than 30)

Front 17

Homocystinuria

Back 17

-Cysteine becomes an essential amino acid in patients with homocystinuria,

--because the defective enzyme cystathionine synthetase produces the substrate used by cystathionase for the endogenous production of cysteine.

-homocystInuria = condition with hyper coagulability and premature atherosclerosis

-also ectopia lentis (displaced ocular lens), osteoporosis, mental retardation

Front 18

Nitrites as antidotes

Back 18

Nitrites are oxidizing agents – effective in TREATMENT OF CYANIDE POISONING, due to ability to cause methemoglobinemia

-Methemoglobin contains ferric (Fe3+) rather than ferrous (Fe2+) -- like Ferris Beuller, plus his two friends

-Cyanide binds to ferric iron more avidly than to mitochondrial cytochrome enzymes, which saves these mitochondrial enzymes from cyanide's toxic effect

Front 19

Cyanide poisoning

Back 19

-antidote is nitrites

-presents as rapidly developing cutaneous flushing, tachypnea, headache, tachycarida, with n/v, confusion, and weakness

-can progress to respiratory distress and cardiac dysfunction

Front 20

X-linked recessive trait – inheritance by a female

Back 20

-Given phenotypically normal parents, the probability that a female sibling of a male affected by an X-linked recessive disease will give birth to an affected child is 1/8.

-Equals probability that sister is a carrier (=0.5) x probability that sister's offspring would inherit the carrier gene assuming she is a carrier (0.5) x
probability that sister will have a male child (0.5)

0.5 x 0.5 x 0.5 = 0.125 = 1/8

Front 21

Mucormycosis (again!)

Back 21

-findings of facial pain, headache, and black necrotic eschar (piece of dead tissue) in patient with diabetic ketoacidosis are highly suggestive of mucormycosis.

-Histologic examination of the affected tissue is necessary to confirm the diagnosis.

-these fungi (RAM – Rhizopus, Absidia, Mucor) show broad non-septate hyphae with right angle branching.

-Treatment consists of surgical debridement and amphotericin B

Front 22

Treatment of Wilson's disease

Back 22

-Pathogenesis of Wison's disease (hepatolenticular degeneration) involves excess of non-ceruloplasmin-bound serum copper
--leads to injurious accumulation of copper in liver, CNS lenticular nucleus, and cornea

-chelation therapy with PENICILLAMINE is indicated to remove excess loosely bound serum copper

Front 23

Shiga-like toxins

Back 23

-Shiga-like toxins (aka, Vero cytotoxins) are produced by EHEC – Eneterohemorrhagic E. coli

-these toxins are nearly identical to the Shiga toxin produced by Shigella dysenteriae

-toxins function to INHIBIT THE 60S RIBOSOMAL SUBUNIT in human cells, thereby blocking protein synthesis by preventing binding of tRNA

-This mechanism differs from that of diphtheria toxin and exotoxin A of Pseudomonas, as these toxins act on EF-2 (elongation factor 2), rather than the 60S subunit.

Front 24

Absolute risk reduction

Back 24

ARR = event rate control – Event rate treatment

Event rate = events/total subjects

for example, if ARR = 4%, and event rate control = 6%, then Event rate treatment = 2%

--> If events in control group = 24, we can find number of total people in control group
2% = 24/x --> x = 1200

Front 25

Clavulanic acid

Back 25

-Clavulanic acid, sulbactam, and tazobactam are beta-lactamase inhibitors

-administration of clavulanate with amoxicillin expands amoxicillin's spectrum of activity to include strains of beta-lactamase synthesizing bacteria that would be resistant to amoxicillin alone.

-i.e., adding clavulanic add to treatment regimen decreases amoicillin cleavage by bacterial cells

Front 26

Peptostreptococci and Fusobacteria in lung abscesses

Back 26

-Peptostreptococci and Fusobacteria are anaerobic bacteria that are normally found in oral cavity

-they cause lung abscesses associated with aspiration

-risk factors for such abscesses include: alcoholism, seizure disorder, CVA, and dementia

Front 27

Diabetic neuropathy

Back 27

-Neuropathy is frequent complication of diabetes mellitus

-caused by diabetic microangiopathy, aka, endoneural arteriole hyalinization, which leads to nerve ischemia


-another pathogenetic factor is the accumulation of sorbitol, which leads to osmotic nerve injury.

-this can manifest as symmetric peripheral neuropathy