Uworld: 5-31

Front 1

4 year-old male
Difficulty walking
Frequent respiratory infections
High rate of radiation-induced genetic mutations in cultured cells

Diagnosis
Pathophys

Back 1

Ataxia-telangiectasia (AR disorder)

Cerebellar atrophy leads to ataxia in first years of life

Oculocutaneous telangiectasia is another manifestations, but is usually delayed

Pts with ataxia-telangiectasia also have severe immunodeficiency with REPEATED sinopulmonary infections.

Risk of CANCER is elevated because of INEFFICIENT DNA REPAIR.

High rate of radiation-induced genetic mutation due to DNA hypersensitivity to ionizing radiation (UV).

Front 2

What causes proptosis in Graves' Disease?

Treatment?

Back 2

Infiltrative ophthalmopathy characterized by edema and infiltration of lymphocytes and macrophages into extraocular muscles and connective tissue. Eventually inflammation becomes fibrosis, which restricts extraocular movements, causing diplopia.

Treated with high dose glucocorticoids to inhibit inflammatory infiltration.

Remember that conventional antithyroid drugs do not improve ophthalmopathy.

Front 3

What Vitamin D reaction is catalyzed by exposure to sunlight?

Back 3

7-dehydrocholesterol-->Cholecalciferol

Front 4

Hemochromatosis:
Pathophys
Risks

Back 4

Mutation of HFE gene (AR inheritance)
HFE expressed on basolateral surface of intestinal epithelium
It binds to transferrin receptor to regulate endocytosis of transferrin/iron complex into cells
If individual has mutatn HFE tha tis unable to detect circulating iron levels, there will be unregulated expression of iron uptake proteins
This will lead to excessive amount of iron absorbed by the GI tract, causing an iron overload

Liver cirrhosis and HCC are complications

Front 5

Most common cause of asceptic meningitis.

Back 5

Enteroviruses: Coxsackie, echo, polio, entero--responsible for over 90% of cases

Front 6

Outline the steps of the MAP-kinase signaling cascade.

Back 6

Growth factor binds receptor tyrosine kinase
Receptor is AUTO-PHOSPHORYLATED
Leads to Ras activation (a G protein that when activated is bound to GTP)
Activated Ras activates kinase which active MAP kinase (MITOGEN-ACTIVATED PROTEIN)

Note that mutated (permanently activated) Ras is assocd w/devt of malignant tumors.

Front 7

45 year-old male
HIV positive
Bronchoscopy for cough, chest pain
Mucicarmine stain reveals budding yeast forms with thick capsules

Diagnosis

Back 7

Cryptococcus neoformans--commonly manifests as CRYPTOCOCCAL MENINGITIS

Front 8

7 year-old male
Stung by a bee and developed generalized urticaria that required hospitalization
Later developed a puffy face and now reports foamy urine
4.5 g protein/day lost in urine

Diagnosis
Pathophys
Treatment

Back 8

Facial edema with massive protein loss = Nephrotic syndrome--most common cause if minimal change disease (also called lipoid nephrosis)

May be a/w resp infections, immunization, or atopic disorders

Light microscopy will show normal glomeruli
Immunofluorescence will NOT reveal immunoglobulin or complement deposits

EM will show DIFFUSE EFFACEMENT of foot processes of podocytes ("fusion of foot processes)

Important feature is RAPID response to corticosteroid treatment

Front 9

79 year-old male
Visual abnormalities, nausea, anorexia
History of atrial fibrillation
Receives weight-adjusted dose of digoxin

Pathophys of symptoms

Back 9

Digoxin is renally cleared with a half-life of approximately 1.5 days in pts w/normal kidney fn.

As pts age, renal function decreases progressively. This decrease is often not accompanied by rise in serum Cr (since Cr is derived form muscle tissue and lean body mass also decreases with age)

Thus, all elderly patients should receive reduced doses of renally cleared medications to prevent toxicity.

Front 10

Label structures.

Back 10

Front 11

34 year-old male
Recently diagnosed membranous glomerulopathy
Develops sudden onset flank pain and gross hematuria
Left-sided varicocele
Urinarlysis reveals increased proteinuria

Pathophys

Back 11

Membranous glomerulopathy is a common cause of nephrotic syndrome in adults

Inc'd permeability of glomerular capillary wall in nephrotic syndrome causes proteins to be peed out

Loss of anticoagulant factors, esp. AT III is responsible for thrombotic and thromboembolic complications of nephrotic syndrome.

Renal vein thrombosis can be a manifestation of hypercoagulable state.

Sudden onset abdominal or flank pain and gross hematuria due to renal vein thrombosis on left side-->obstruction in male patients impedes venous flow from left testis, and results in left-sided varicocele

Front 12

What congenital aortic morphology results in accelerated onset of calcific stenosis?

Back 12

Congenital bicuspid aortic valve

Front 13

Which drug class prolongs Thrombin Time?

Back 13

Drugs that directly inhibit thrombin (which is Factor II btw): argatroban, dabigatran

Front 14

Describe the change induced by stimulation (cAMP/DAG/IP3 levels) of adrenergic receptors by Norepinephrine.

Include the clinical effect seen.

Back 14

Remember: NE is an adrenergic agonist that affects predominantly alpha, and beta-1, little influence on beta-2

alpha-1: inc'd IP3, peripheral vasoconstriction

alpha-2: dec'd cAMP, dec'd release of NE, insulin

beta-1: inc'd cAMP, inc'd contractility

beta-2: inc'd cAMP, bronchodilation, vasodilation***

Note that NE's direct effect on heart rate (positive chronotropic) is counteracted by an indirect, baroreceptor-mediated reflex bradycardia that occurs following increase in peripheral resistance. Result is heart rate remains unchanged or even decreases.

Front 15

Retinoblastoma:
Hypo vs Hyperphosphorylation
Associated cancers

Back 15

Hypophosphorylated = active (does not allow G1-->S progression)
Hyperphosphorylated = inactive

Hyperphosphorylating mutations linked to retinioblastoma and osteosarcoma

Front 16

What vitamin is useful in treating measles?

Back 16

Vitamin A--also reduces time to recovery from pneumonia, diarrhea

Front 17

Burr cells are a sign of ______.

Back 17

Mechanical trauma to RBCs

Front 18

12 year-old male

Back 18

Pilocytic astrocytoma--low grade neoplasm arising from astroycytes

(can also develop in cerebral hemispheres)

Neoplasm is cystic with tumor nodule; solid mass = white, cystic component = dark gray

Will see pilocytic astrocytes and Rosenthal fibers on microscopic examination

Front 19

12 year-old male

Back 19

Medulloblastoma (2nd most common brain tumor of childhood)

Malignant, poor prognosis

Located exclusively in cerebellum

Medulloblastoma only has SOLID component, no cystic (fluid-filled) component. So appears light grey.

Front 20

Why doesn't an infection with neisseria gonorrhoeae result in long lasting umminty?

Back 20

Bacteria modifies outer membrane proteins via antigenic variation

Ab's generated during one infection will only be specific for that single antigenic episode

Also recall that repeated Neisseria infections can be caused by terminal complement deficiencies leading to inability to form MAC

Front 21

21 year-old male
Bilateral lens opacities
Urinary excretion of large amounts of galactose

Diagnosis
Pathophys of Syx

Back 21

Bilateral cataracts but otherwise asyx-->galactokinase deficiency

Results in elevation of galactose
Excess galactose converted to GLACTITOL by ALDOSE REDUCTASE
and to galactonic acid by galactose oxidase

Excess galactitol in cells responsible for cataracts

Front 22

47 year-old
Homeless alcoholic
Fevers, night sweats, weight loss, productive cough
CXR reveals cavitary lesion in right middle lobe with air fluid levels

Cause

Back 22

CXR lesion consistent with lung abscess, usually due to aspiration pneumonia--fusobacterium, peptostreptococcus, bacteroides

Also note it's in the right lobe; more likely to aspirate into right lung

Front 23

Why would a patient with COPD exhibit decreased cerebral vascular resistance?

Back 23

Patient is likely hypercapnic (elevated pCO2); most potent cerebral vasodilator

Front 24

What bleed values are abnormal for vWD?

Back 24

Deficiency of vWF causes a functional Factor VIII and platelet deficiency

Thus will have prolonged bleed time (influenced by changes to PLT fn) and prolonged PTT (sensitive to Factor VIII changes)

Front 25

Why can eukaryotic DNA be replicated at a much faster rate than prokaryotic DNA?

Back 25

Eukaryotic DNA has multiple origins of replication

Prokaryotes have 1 origin; also don't have introns (FYI)

Front 26

M. tuberculosis expresses decreased activity of intracellular catalase-peroxidase

Why would those pose a challenge to treatment?

Back 26

Isoniazid must be processed by mycobacterial catalase-peroxidase for drug to be activated within bacteria

Note: INH also requires a specific protein sequence in the enzyme target (necessary for mycolic acid)--genetic modification of the INH binding site could also result in resistance to INH

Front 27

Lab values associated with B12 deficiency (not quality of RBCs).

Back 27

MMA
Homocysteine

Front 28

What is the effect of B12 replacement in someone with B12 deficiency anemia secondary to atrophic gastritis (on level of bone marrow)?

Back 28

Immature erythrocytes released from BM into periphery

Peripheral count of reticulocytes will rise within one week

Anemia typically takes 6 weeks to correct.

Front 29

55 year-old male
Severe, throbbing, right-sided orbitofrontal headache
Diplopia
Anisocoria
Right pupil dilated and nonreactive to both light and accomodation
Right eye is down and out with ipsilateral ptosis

Location of aneurysm

Back 29

CN III palsy due to aneurysm arising from either posterior cerebral or superior cerebellar arteries.

Front 30

Label, include effects of aneurysms

Back 30

A) Basilar artery
B) R Posterior Cerebral Artery
C) L Posterior Cerebral Artery (would cause third nerve palsy on LEFT)
D) Superior Cerebellar Artery
E) Parapontine Perforating Artery (no clue)
F) Anterior Inferior Cerebellar Artery (Aneurysm can compress FACIAL and VESTIBULOCHOCHLEAR nerves)

Front 31

Most common cause of osteomyelitis in Sickle Cell.

Back 31

SALMONELLA
followed by E. coli

Front 32

HIV positive patient
Latex agglutination positive for soluble polysaccharide antigen

Back 32

Cryptococcus: a budding yeast!

Front 33

Why might an elderly patient with no relevant medical history experience B12 deficiency?

How would this affect delivery of supplements?

Back 33

Gastric atrophy (normal part of aging process) leads to achlorhydria, dec'd release of IF

Would require parenteral B12 administration

Front 34

Direct arteriolar vasodilators:
Examples
AEs (not CN tox)

Back 34

Reflex tachycardia
Edema

(often give in combination with sympatholytics and diuretics)

Front 35

Enveloped virus with partially double-stranded circular DNA
Packs its own RNA-dependent DNA polymerase

Back 35

Hepatitis B virus

Front 36

8 year-old male
Diagnosed with acute MI
Increased serum methionine

Diagnosis
What amino acid is likely essential?

Back 36

Homocysteinuria

Due to defective cystathionine synthetase involved in Homocysteine-->Cystathionine (precursor of cysteine)

This leads to build up of homocysteine which is shunted to methionine

But no cysteine formed!

Front 37

DVT:
Treatment
How does this change in pregnancy?

Back 37

Warfarin is best long-term anticoagulant used for tx of DVT, however, it is contraindicated in pregnancy bc it's teratogenic (causes fetal warfarin syndrome)

Use heparin in pregnancy

Note:
ASA on its own is not enough for DVT

tPA is not used for DVTs, it's reserved for STEMIs and ischemic stroke

Front 38

55 year-old female
Weight gain, easy fatigability
Delayed relaxation of knee, ankle reflexes
Skin is very dry and thick

Likely diagnosis
Best screening test

Back 38

Patient likely has primary hypothyroidism (dec'd release of TSH from hypothalamus)

Serum TSH is the single most important screening test in diagnosing primary hypothyroidism.

Although TSH is not elevated in pts w/cetnral hypothyroidism, central hypothyroidism is UNCOMMON.

(Central hypothyroidism = unresponsive pituitary)

Front 39

Diagnosis
Pathophys

Back 39

Patient's history is consistent with native valve bacterial endocarditis (NVBE) complicated by embolic cerebrovascular accident.

Arrow shows vegetation attached to prolapsed mitral valve leaflet (arrowhead).

Vegetation is most probably source for embolus that lodged in one of patient's intracranial arteries (likely Left MCA based on presentation).

In short, cause = MV prolapse (MV prolapse predisposes to infected vegetations on mitral leaflets)

Rheumatic valvular dz potential, but less likely in US.

Front 40

Friedrich's ataxia:
Heart defect

Back 40

Hypertrophic CM

Front 41

Tuberous sclerosis:
Heart defect

Back 41

Valvular obstruction due to cardiac rhabdomyomas

Front 42

Turner's syndrome:
Heart defect

Back 42

Coarctation of the aorta

Front 43

Down syndrome:
Heart defect

Back 43

Endocardial cushion defects resulting in ATRIAL septal defects (endocardial cushions); may also have regurgitant AV valves

Front 44

45 year-old male
2 year history abdominal discomfort, greasy stools, weight loss
Treated for joint pain with ibuprofen
Intestinal biopsy shows multiple macrophages loaded with PAS-positive granules

Diagnosis
Significance of PAS-positive granules
Treatment (General)

Back 44

Whippled disease caused by the actinomycete, Tropheryma whippelli.

Proliferates in small intestine, joints, and CNS.

Appears as rod-shaped bacilli and PAS-positive granules (consist of LYSOSOMES and PARTIALLY DIGESTED BACTERIA)--this alone should clue you in on infection

Treat with Abx

Front 45

List tumor promoters (proto-oncogenes) and tumor suppressors (anti-oncogenes)

Back 45

Proto-oncogenes (tumor promoters); activating mutations lead to cancer:
ras
N-myc
ERB-B1/B2
TGFalpha
abl

Anti-oncogenes; deactivating mutations will lead to cancer:
BRCA-1/2
NF-1
APC, DCC, p53
RB
WT-1

Front 46

List three different types of necrosis and which tissues exhibit them.
Exclude caseous and enzymatic fat necrosis.

Back 46

Coagulative -- all organs except CNS following lethal ischemic injury

Liquefactive - CNS infarcts

Fibrinoid necrosis-- walls of BVs during immune complex vasculitis

Front 47

Essential fructosuria vs Hereditary fructose intolerance:
Presentation
Enzymes affected

Back 47

Essential fructosuria: Large amounts of fructose from diet excreted in urine; due to deficient fructokinase (BENIGN)

Fructose intolerance: aldolase deficiency,
results in vomiting, hypoglycemia after fructose ingestion

Front 48

6 month-old male
Recent onset vomiting, irritability, jaundice
Exclusively breast fed until one week ago
Began eating cereals and fruit juices
Exam reveals hepatomegaly and abnormal LFTs

Diagnosis
Pathophys

Back 48

Hereditary fructose intolerance due to deficiency in ALDOLASE B

Front 49

This bursitis arises in those who spend a lot of time on their knees, e.g., roofers, gardeners, prostitutes

Back 49

Prepatellar bursitis ("housemaid's knee")

Front 50

Korsakoff Syndrome:
What region of the brain is damaged?
Presentation

Back 50

MEDIAL DORSAL NUCLEUS of thalamus (m for memory!)

Damage due to alcoholism causes memory loss and confabulation (fill in gaps of a story when can't remember something)

Memory and learning impairment is usually permanent.

Front 51

Role of BRCA gene.

Back 51

DNA repair

Front 52

PSGN:
Glomerular light microscopy findings
Immunofluorescence findings (include deposits)

Back 52

LM findings will show diffuse HYPERCELLULAR glomeruli (filled with neutrophils, monocytes)

Immunofl is "starry sky" in appearance and will have deposits of IgG, IgM and C3 in GBM

Front 53

32 year-old female
History of amenorrhea
Presents with white nipple discharge
FMH significant for maternal breast cancer at 50

Diagnosis

Back 53

Prolactin-secreting pituitary adenoma

Note: if you were thinking nipple discharge due to breast cancer (as in intraductal papilloma), discharge would be bloody or serosanguinous

Front 54

What's the cut off for hyperpyrexia (in ºC)?
Treatment: immediate and general

Back 54

Anything above 40ºC is hyperpyrexia and may lead to permanent brain damage if left untreated.

Body needs to be cooled immediately using cold blankets, cold water enemas, application of cool saline bags, etc.

Rectal or oral administration of acetaminophen is the antipyretic of choice (in children)

Dec'd PGE2 will decrease the hypothalamic set point (temperature).

Front 55

What two regions of the intestine are most susceptible to ischemic damage during hypotension/low perfusion states?

Back 55

Splenic flexure
Distal sigmoid colon

Front 56

Breast biopsy:
What is it and why?

Back 56

Fibroadenoma--cellular/myxoid stroma encircling glandular and cystic spaces. Epithelium of fibroadenoma can be compressed by surrounding stroma (as seen in this patient).

This is mostly seen in women in their 20s or 30s.

Usually freely movable, palpable.