Uworld: 5-24

Front 1

2 day-old neonate
Persistent vomiting
Atresia of large small bowel
Apple peel appearance

Diagnosis
Pathophys

Back 1

Jejunal, ileal, and colonic atresia are not caused by abnormal fetal development (they are not congenital malformation)

They're results of diminished intestinal perfusion in utero, which leads to ischemia of a segment of bowel, with subsequent narroiwng or obliteration of the lumen.

If a major vessel is occluded (such as the SMA), the area of intestinal wall necrosis is large.

Front 2

Apple peel atresia in neonate

Back 2

Vascular blockage in utero leading to bowel ischemia

Front 3

Describe the process of T cell maturation.

Where does it occur?

Back 3

In Thymus, T-cell Receptor (TCR) gene rearrangement, positive selection, negative selection and expresison of ECM markers and co-stimulatory molecules occur

Pro-T cells are double negative (lack both CD4 and CD8)
Then acquire both CD4 and CD8 ("double positive" AKA immature T cells)
FInal step in maturation is los sof either CD4 or CD8

Front 4

Efficacy vs Potency

Back 4

Efficacy - intrinsic ability of a drug to elicit an effect (such as receptor activation or dilation of a vessel). It's measured by maximum ceiling of activity (Vmax).

Potency - drugs that bind receptors with a higher affinity or are able to better access target wtissues will have greater potency. Potency of different agents can be determined by dose of drug required to produce one-half (50%) of the maximum biological response (ED50).

Front 5

Compare drug efficacy and potency.

Back 5

A much lower dose of drug 2 is required to produce the same effect as seen with drug 3, so Drug 2 is more potent than drug 3 and has a lower ED50. TO achieve higher potency, binding of drug 2 to its receptors must be higher than that of drug 3.

Drug 1 has a higher potency than Drug 2 because at low biological activity, it can cause same effect with much lower concentrations of drug.

Drug 1 demonstrates the lowest efficacy (ceiling of biological effect) of the three drugs graphed.

Drug 2 has a lower ED50 (greater potency) than drug 3. Both have equal efficacy.

Front 6

What cranial nerves can be affected by intracranial schwannomas?

Back 6

CN VIII (duh)--hearing loss and difficulty balancing

CN VII--facial paralysis

CN V--loss of sensation around mouth/nose, loss of corneal reflex, paralysis of muscles of mastication

Front 7

3 ways to get Down Syndrome.

Back 7

1) Meiotic non-disjunction (Trisomy 21)--95% of cases
2) Unbalanced Robertsonian Translocation
3) Genetic mosaicism--parents have two cell lines--one with a normal genotype and one with trisomy 21

Front 8

______ disomy exists in a ______ hydatidiform mole.

Back 8

Paternal disomy exists in a complete mole.

Front 9

Beginning with endothelial cell injury, describe the pathogenesis of atherosclerotic plaques.

Back 9

Endothelial cell injury-->exposure of subendothelial collagen (endothelial cell denudation)
Promotes PLT adhesion, aggregation, release of factors that promote migration of smooth muscle cells from media into intima, as well as SMC proliferation

These factors must include PDGF and TGF-beta.

Front 10

How would a prolactinoma predispose a patient to osteoporosis?

Back 10

High levels of prolactin suppress GnRH secretion from the thypothalamus.

Leads to decreased estrogen levels.

Front 11

Phencyclidine abuse:
MOA
Presentation

Back 11

Hallucinogen that inhibits NMDA receptor

Presents as slurred speech, ataxia, nystagmus, HOSTILE AND AGGRESSIVE behavior--may be indistinguishable from schizophrenia

Front 12

Which anti-tb agents are used for extracellular tb? Intracellular? Why?

Back 12

Extracellular: INH (inhibits mycolic acid synthesis--important for Tb cell walls), Ethambutol (inhibits arabinosyl transferase--impt for cell wall synthesis), Rifampin (inhibits DNA-dependent RNA polymerase)


Intracellular: Pyrazinamide--requires an acidic environment (as is present within macrophage phagolysosomes) to exert effects.

Front 13

57 year-old man
Right-sided eye pain, ipsilateral headache
Reports severe nausea and seeing halos

Diagnosis
Treatment
Treatment MOA

Back 13

Acute close-angle glaucoma

Treat with acetazolamide (carbonic anhydrase inhibitor)--acts in PCT and enhances HCO3- and H2O excretion as well as inc'd urinary pH (potential for metabolic acidosis)

Front 14

What reactions are affected by biotin deficiencies?

Back 14

1) Inc'd pyruvate-->converted to lactic acid (LACTIC ACIDOSIS)

2) Build up of propionyl CoA and metabolized into surplus of odd-chain fatty acids (need biotin to synthesize succinyl Coa from amino acids such as valine)

3) Need biotin for Pyruvate-->Acetate

Front 15

What features of Grave Disease are not found in other causes of hyperthyroidism?

Back 15

Exophthalmos
Infiltrative dermopathy (PRETIBIAL MYXEDEMA--infiltrative accumuln of glycosaminoglycans in dermis. Results in non-pitting edema sometimes scaly in appearance, resembles an "orange peel")

Front 16

How can ether help identify viruses?

Back 16

Ether and other organic solvents dissolve the lipid bilayer that makes up the viral outer envelope.

Loss of infectivity after exposure to ether is characteristic of enveloped viruses.

Front 17

36 year-old male
Hemoptysis, HTN, hematuria
Alcohol-fixed neutrophils treated with patient's serum demonstrate indirect immunofluorescence (see image)

Diagnosis
Pathophys

Back 17

Image shows positive-cANCA (cytoplasmic antineutrophil cytoplasmic Ab)--seen in Wegener's (a necrotizing granulomatous vasculitis)

Syx: Hemotpysis, chronic sinusitis/mucosal ulceration, rapidly progressive (CRESCENTIC) GLOMERULONEPHRITIS

Front 18

Back 18

p-anca stain

Front 19

Back 19

c-anca stain

Front 20

False vs True Diverticula:
Differences
Examples

Back 20

False: only contain mucosa and submucosa. These layers herniate through defects in muscular layer. Ex: Zenker (upper esophageal) diverticula.

True: Consists of all parts of intestinal wall: contains mucosa, submucosa, muscularis. Often contains ectopic mucosa (gastric epithelium and pancreatic most common). Ex: Meckel's diveritculum

Front 21

34 year-old alcoholic
Vomiting, prolonged oliguria
Vacuolar degeneration and ballooning of proximal renal tubules
Oxalate crystals in tubular lumen

Diagnosis
Pathophys

Back 21

Patient likely ingested ethylene glycol which is widely-available and found in antifreeze, engine coolant, hydraulic brake fluids.

Metabolized to glycolic acid, which is TOXIC TO RENAL TUBULES. Damage manifests itself as ballooning and vacuolar degeneration (predom in PCTs).

Leads to actue renal failure due to precipitation of calcium oxalate crystals.

Will also see anion gap metabolic acidosis.

Front 22

Where is the primary site of potassium absorption? Secretion?

Back 22

Majority of potassium is absorbed in the proximal tubule.

Potassium regulation (secretion) occurs in collecting duct.

Front 23

18 year-old girl
Nausea, vomiting, abdominal pain, bloody diarrhea
Garlic odor breath
BP 90/60
Consumed insecticide

Type of poison
Treatment
Treatment MOA

Back 23

Arsenic Poisoning

Treat with Dimercaprol

Dimercaprol is a chelating agent that will displace arsenic ions from enzymes.

Front 24

CaN2EDTA:
Use

Back 24

Lead, Mercury poisoning

Front 25

Methylene Blue:
Use

Back 25

Treatment of methemoglobinemia (converts iron in heme from Fe3+ to Fe2+)

Front 26

Beginning in the marrow, outline the process of T cell maturation. Include selection processes and interactions required.

Back 26

T cells initially produced in BM; migrate to Thymus

Pro-T cells arrive as double negative cells in subcapsular zone

TCR rearrangement occurs to form double-positives

In thymic cortex: positive selection allows T cells expressing TCR able to bind self MHC to survive. Cells expressing a TCR unspecific for self MHC signaled for elimination by apoptosis. Requires THYMIC CORTICAL EPITHELIAL CELLS.
Positive selection responsible for dev't of T cell repertoire that can recognize self.

Negative selection: TCRs that bind w/high affinity to self Ag or self MHC eliminated by apoptosis. Requires THYMIC MEDULLARY EPITHELIAL and DENDRITIC CELLS. Serves to eliminate T cells that may be overly autoreactive against self-Ag.

Front 27

Aortic rupture due to MVA:
Most common site of rupture

Back 27

Aortic isthmus: where ascending aorta becomes descending (at branch of subclavian)

Front 28

Back 28

The answer is A.

Remember: Hgb A is composed of two alpha and two beta chains.

Myoglobin is a monomeric protein and the primary oxygen-carrying protein of skeletal and cardiac muscles. The beta-subunits of hemoglobin and myoglobin are identical. As are the alpha-subunits.

P50 of Hgb is ~26mmHg, P50 myoglobin ~1mmHg

Each globular subunit of Hgb assocd w/1 heme group so a single Hgb molecule is able to carry 4 heme groups.

HOWEVER, each myoglobin carries only 1 heme group. Additionally, after binding to one oxygen molecule, the affinity of other heme molecules for O2 increases (heme-heme interaction), accounting for sigmoidal shape of Hgb curve.

Myoglobin has a much higher affinity for oxygen and doesn't experience heme-heme interactions; therefore, its oxygen-dissocn curve is hyperbolic.

Front 29

Amphotericin B:
MOA
Toxicities and their MOA

Back 29

MOA: Binds ergosterol of fungal cell membranes, leading to fungal cell lysis. Relatively selective since has a higher affinity for ergosterol (in fungal membranes) than for cholesterol (in human cell membranes). However, it does bind cholesterol to a degree which explains its AEs:

1) Infusion-related reactions (fever, chills, hypotn). Prevent w/antihistamines and antipyretics.

2) Dose-dependent nephrotoxicity bc it decreases GFR.

3) Electrolyte abnlts (hypoMg, hypoK)

4) Anemia due to suppression of renal EPO synthesis

5) Thrombophlebitis at site of injection

Front 30

What accounts for the significant increase in nosocomial staphylococcal infections (bacteremia and sepsis) over the last 20 years?

Back 30

Intravascular devices

Front 31

23 year-old male
Urinalysis positive for reducing sugar, negative for glucose
PMH unremarkable
No specific diet

Diagnosis
Pathophys

Back 31

Essentil fructosuria--benign disorder resulting from a defect or deficiency in FRUCTOKINASE.

PLEASE NOTE: this differs from hereditary fructose intolerance and classic galactosemia in that these disorders will be SYMPTOMATIC (failure to thrive, hepatomegaly--due to inability to breakdown sugars, cirrhosis)

Front 32

Label and explain

Back 32

Front 33

Telomerase:
Function
Role in oncogenesis

Back 33

Telomerase is a reverse transcriptase enzyme (RNA-dependent DNA polymerase) that adds TTAGGGG repeats to 3' end of DNA strands.

Stem cells have very long telomeres and active telomerase, but with every division, length of telomeres shortens. Terminally differentiated adult somatic cells have very short telomeres. Thought to be a signal for programmed cell death.

Cancer cells up-regulate telomerase activity, preventing cellular death. They're considered immortal.

Front 34

This bacterial exotoxin inactivates 60S ribosomal subunit.

Back 34

Shiga toxin (of both shigella and EHEC)

Front 35

Cryptococcus:
Sources
Route of infection

Back 35

Present in soil/pigeon droppings

Yeast transmitted via respiratory route, with lungs as primary site of entry

Front 36

What are the molecular effects of multiple sclerosis?

Back 36

Loss of myelin sheaths
Depletion of oligodendrocytes
Oligoclonal bands of IgG in CSF

Will also see lipid laden macrophages containing products of myelin breakdown

Front 37

32 year-old male
h/o PCP pneumonia
Severe chest pain on swallowing
Endoscopy reveals hyperemia, ulcerations of esophageal mucosa

Differential

Back 37

Patient is likely HIV-infected, as Pneumocystis jiroveci affects exclusively immunocompromised individuals.

Patient presents w/painful swallowing, which is characteristic of esophagitis.

3 main causes of HIV-associated esophagitis:
Candida
CMV
HSV

Front 38

Babesiosis:
Pathophys

Back 38

Transmitted by tick bite. Endemic in NE US w/influenza-like syx, HSM, anemia. Often affects asplenic pts.

Front 39

26 year-old male
h/o childhood dermatitis, asthma, hay fever
Applies corticosteroid to flexor areas
Areas remain free of lesions and scales

What would biopsy show?
How would this differ if he didn't use the steroid cream?

Back 39

Patient is being treated for atopic eczematous dermatitis.

Histologic findings of active eczema include:
-intraepidermal vesicles
-epidermal hyperkeratosis
-scales
epidermal hyperplasia (acanthosis)
-chronic inflammatory infiltrate within dermis

Corticosteroids decrease production of ECM collagen and glycosaminoglycans. Consequences include atrophy of dermis w/loss of dermal collagen, drying, cracking, and/or tightening of skin.

Telangiectasia, ecchymoses from mild trauma, and atrophic striae may also be found.

Front 40

Risk of rapid correction of chronic hyponatremia?
Presentation
Pathophys

Back 40

Osmotic demyelination of axons in central part of pons

Called central pontine myeloniolysis

Presents as quadriplegia due to demyelination of corticospinal tracts and pseudobulbar palsy.

Front 41

56 year-old male
HIV positive
Weight loss, fevers, weakness
HSM
Blood cultures reveal acid-fast bacteria that grow best at 41ºC

Diagnosis
Treatment

Back 41

Infection with Mycobacerium avium complex (MAC)

MAC can affect both immunocompetent and immunosuppressed hosts

Entry through respiratory route

Tx: Clarirthromycin or Azithromycin with any combination of rifabutin and/or ethambutol

Weekly prophylaxis w/azithromycin recommended for CD4<50

Front 42

22 year-old male
Severe HA, vomiting
Goes into coma and dies
Autopsy shows ruptured cerebral aneurysm with extensive intracranial hemorrhage

Diagnosis
Other symptoms

Back 42

Since there is no h/o head trauma, patient likely suffered spontaneous intracranial hemorrhage. Most common causes are arteriovenous malformations, ruptured cerebral aneurysms, or abuse of sympathomimetic drugs such as cocaine.

BERRY ANEURYSMS are particularly PRONE TO RUPTURE WITH AORTIC COARCTATION because of HTN in branches of aortic arch proximal to coarct. SAH is the result.

Front 43

66 year-old male
Recent diagnosis of lung cancer
Dizziness, dysarthria, limb ataxia
Autopsy shows extensive cerebellar Purkinje cell degeneration

Diagnosis
Pathophys

Back 43

Paraneoplastic syndrome from lung cancer--caused by substances produced from tumor cells that induce an autoimmune response, with Abs produced against tumor cells cross-reacting w/body's own healthy organs and tissues.

Paraneoplastic cerebellar degeneration is a type of paraneoplastic syndrome most commonly assocd w/cancer of lung, breast, ovary, uterus, and lymphoma.

Front 44

Orthopnea:
Pathophys

Back 44

Results from acute exacerbation of baseline pulmonary edema that occurs when cetnral venous, pulmonary venous, and cardiac filling pressures are increased by redistribution of blood that had been pooled in dependent veins back into central circulation.

Seen in LEFT HEART FAILURE

Front 45

ANP vs BNP:
Where is each secreted from?
When is each secreted?
Function?

Back 45

ANP secreted by atria, and in some cases, ventricles in response to volume overload. Also released in response to HYPERTROPHY.

BNP predominantly secreted by ventricles, also in response to volume overload.

These peptides facilitate natriuresis and diuresis.

Front 46

8 year-old male
2 day h/o fever, abdominal pain, diarrhea
Stool negative for O&P
Patient's pet had diarrhea one week ago


Diagnosis

Back 46

Campylobacter jejuni

Front 47

What is the cause of Guillain-Barre?

Back 47

Campylobacter jejuni

Front 48

23 year-old female
Acute pancreatitis that resolves on fasting
PMH unremarkable
Denies alcohol use

Diagnosis
Cause

Back 48

Gallstones typically affect middle-aged and older patients unless there is a predisposing condition (young patient w/sickle cell for example)

This patient is unlikely to have gallstones and does not consume alcohol, so must be a less common cause:
-Recent ERCP (endoscopic retrograde chalongiopancreatography)
-HYPERTRIGLYCERIDEMIA (not hypercholesterolemia!!)

Front 49

77 year-old male
BP 170/70
Returns with bilateral ankles swelling and flushing

Diagnosis
What drug was given?

Back 49

Patient has isolated systolic HTN (common form of HTN)

Thiazide diuretics and dihydropyridine calcium antagonists are first-line treatment for isolated systolic HTN

Side effect profile most consistent with amlodipine

Front 50

Side effects of CCBs (dihydropyridine)

Back 50

Flushing
Ankle swelling

Front 51

t(9;22):
Diagnosis
Associated protein
Treatment

Back 51

CML
bcr-abl
Imatinib

Front 52

Atypical antipsychotics:
List them
How do they differ from typical antipsychotics?

Back 52

Antipsychotic ROCS!
Risperidone
Olanzapine
Clozapine
Quetiapine (Seroquel)

Atypicals can treat both positive and negative syx of schizophrenia

Front 53

How does Crohn's disease contribute to kidney stones?

Back 53

Wehn wall of terminal ileum is inflamed, most bile acids are lost with feces, which causes impaired fat absorption. Calcium then binds to lipids, making it unavailable for complexing with oxalate. The excess lipids are excreted with feces.

As a result, increased oxalate is absorbed, promoting formation of urinary stones.

Front 54

What key growth factors promote angiogenesis?

Back 54

VEGF
FGF (fibroblast growth factor)

Front 55

Which cytokines increase the expression of VEGF?

Back 55

IL-1, IFN-gamma

Front 56

35 year-old IVDU
Fever, jaundice, anorexia
Liver biopsy reveals mononuclear infiltrates, hepatocyte swelling, acidophilic bodies

What are the acidophilic bodies a result of?
What are these bodies called?

Back 56

Fever, jaundice, anorexia-->acute viral hepatitis

All of hepatotropic viruses that cause acute viral hepatitis produce the same histopathologic findings: hepatocyte necrosis and apoptosis

Acidophilic bodies = COUNCILMAN BODIES or APOPTOTIC BODIES

Front 57

A 34 year-old male receives a kidney transplant. His T-lymphocytes quickly recognize the foreign HLA molecules of the renal transplant cells.

Inhibition of what substance would reduce the proliferation and differentiation of these T lymphocytes?
How?

Back 57

Calcineurin--essential protein in activation of IL-2, whoch promotes growth and differentiation of T cells.

Immunosuppressants such as cyclosporine and tacrolimus work by inhibiting calcineurin activation.

Front 58

2 equations for cardiac output.

Back 58

CO = SV x HR

CO = O2 consumption/arteriovenous O2 difference

Front 59

Bronchi reveal thickened bronchial walls, neutrophilic infiltrates, mucous gland enlargement and patchy squamous metaplasia of bronchial mucosa.

Diagnosis
Cause

Back 59

Chronic bronchitis.

Cigarette smoking.

Front 60

Wide, fixed splitting of S2

Back 60

Atrial Septal defect

Front 61

What is Eisenmenger syndrome and what vessels are affected?

Back 61

ASD creases a LtoR shunt because of high pressure in LA. Increased flow through pulmonary artery, which may develop medial hypertrophy.

At this point, pressure builds and flow becomes Rto (presenting w/late cyanosis).

Eisenmenger syndrome = name for reversal of shunt flow.

Over time, pulmonary vascular sclerosis becomes irreversible.