Uworld: 6-2

Front 1

Why is Entacapone given with levodopa/carbidopa?

Back 1

Entacapone is a COMT inhibitor and inhibits peripheral methylation.

This increases the quantity of levodopa entering the brain rather than being metabolized in the periphery.

Tolcapone also does this.

Front 2

Best place to harvest great saphenous vein for CABG.

Back 2

Just below the pubic tubercle

Note that the SMALL saphenous vein is found at the lateral aspect of the foot

Front 3

Why does squatting relieve symptoms of TOF?

Back 3

Squatting increases systemic vascular resistance and decreases right to left shunting, thus increasing pulmonary blood flow

Front 4

Testicular mass causing elevated hyperthyroidism:
Which mass does this and how?

Back 4

Teratomas (often found in testes and ovaries)

Structure of hCG is similar to TSH, LH, and FSH

because of this, hCG can bind TSH (although with much lower affinity than TSH)

Note that should use hCG as tumor marker for teratoma.

Front 5

Most common lung cancer in non-smokers

Back 5

adenocarcinoma

Front 6

Most drugs are eliminated through the _______.

Back 6

Kidney--regardless of biotransformation (metabolism to active form)

Drugs with high hepatic clearance tend to have high lipophilicity and high Vd.

Front 7

What does vitamin C do and where in the cell does this take place?

Back 7

Hydroxylation of proline (PROLINE!) and LYSINE residues

In ROUGH ER

Front 8

This is a jejunal biopsy.
What is this and how did it happen?

Back 8

Normal intestinal mucosa with clear ("FOAMY") cytoplasm, which is prominent on tips of villi

Occurs due to ACCUMULATION OF LIPIDS

Typical of ABETALIPOPROTEINEMIA--
apolipoprotein B coats chylomicrons.

Impaired synthesis of apoB results in an inability to transport lipids from intestine.

This results in decreased serum levels of all lipids. Lipids are essential components of cell membranes, and their deficiency causes RBCs with abnormal membranes and thorny projections (acanthocytes).

Lack of lipids in neuron membrane leads to multiple neurologic abnlts.

Front 9

What about the genetic makeup of DNA segment of interest is required in order to perform PCR?

Back 9

Need to know bases the flank the target DNA to be amplified.

While PCR doesn't require the sequence of the target DNA be known, flanking sequences must be known to make primers.

A thermostable DNA polymerase, deoxynucleotide triphosphates (to build new DNA strands) and target DNA template strand are also necessary.

Front 10

How do TNF-alpha, catecholamines, glucocorticoids, and glucagon result in insulin resistance?

Back 10

Aberrant serine and threonine residue phosphorylation (inhibits tyrosine phosphorylation by insulin. Also hinders downstream signaling, resulting in resistance to normal actions of insulin)

Intracellular FFAs also suspected of increasing serine kinase activity as well.

Front 11

Appendix biopsy

Back 11

Carcinoid tumor: easily recognizable as there is no variation in shape/size of tumor cells.

They grow in nests/sheets.

Their granules contain secretory products of tumor cells.

Most common location of intestinal carcinoids is ileum. Also frequently occur in appendix and rectum.

Front 12

Thiopental:
Drug Class

Back 12

Short-acting barbiturate used for induction of anesthesia; after equilibration with brain it rapidly redistributes into skeletal muscle and adipose tissue

Front 13

12 year-old male falls from a tree but catches himself on a branch with his right hand.

Later presents with right hand clumsiness.

What happened?

Back 13

Sudden upward stretching on arm at shoulder can damage LOWER TRUNK OF BRACHIAL PLEXUS; this trunk carries nerves from C8 to T1 that ultimately form median and ulnar nerves.

These nerves innervate all of the intrinsic muscles of the hand.

Front 14

What class of diuretic would be given to a patient with long-standing HTN, MI, crackles on lung auscultation, and edematous swelling of lower extremities.

Back 14

Loop diuretic!!!

Likely furosemide

Front 15

Blood test for monitoring:
Warfarin therapy
Heparin therapy

Back 15

Warfarin therapy monitored by measuring PT (INR)

Heparin therapy monitored by measuring PTT

Front 16

What does the PAS (periodic acid-Schiff) reaction stain?

Back 16

Polysaccharides of fungal cell wall, mucosubstances, bm's

Also GLYCOPROTEIN of actinomycete Tropheryma whippelii (Whipple disease--presents as diarrhea, but can also affect joints, hearts, etc.)

Front 17

Periodic acid-Schiff reaction used on sample of intestine

Back 17

PAS-->Whipple Disease

Front 18

65 year-old male
Fatigue, mild normocytic anemia, anorexia
Lost 10 pounds over last 2 months
Irregular mass on right lung field

What is causing the patient's symptoms?

Back 18

Patient has a lung neoplasm; body responds to neoplasm via macrophage release of TNF-alpha

This accounts for cachexia--anorexia, malaise, anemia, weight loss and generalized wasting due to underlying systemic dz

Front 19

Compare amount filtered with amount excreted for:
PAH
Inulin
Glucose
Sodium
Urea

Back 19

PAH: at low concentrations, completely secreted, always secreted more than filtered

Inulin: neither absorbed nor secreted, so amount filtered would = amount excreted

Glucose:
Completely reabsorbed at low filtered levels (so no excretion), but as filtered levels increase, will excrete more and more

Sodium:
Approximately 1% of sodium filtered is excreted, nearly 99% is reabsorbed!!

Urea:
About 40-50% of urea filtered is reabsorbed with some variable secretion; so you'd expect to see about 1/2 of urea filtered to be excreted

Front 20

46 year-old female
Persistent diarrhea, weight loss, abdominal pain
Not responding to antibiotics
Doesn't remit with fasting
Duodenal and jejunal ulcers

What hormone is elevated?

Back 20

Gastrin: neuroendocrine tumors most commonly in pacnreas/duodenum

Characterized by upper GI ulcerations (jejunal ulcers to be specific)

VIPomas present with hard to control diarrhea, metabolic acidosis, and hypokalemia

Front 21

Cells that detect hypoxia and cause release of erythropoietin.

Back 21

RENAL cortical cells (EPO release stimulates production of RBCs in BM)

Front 22

Why does parenteral nutrition increase risk of gallstones?

Back 22

No enteral stimulation-->no CCK release-->Biliary stasis

In those w/ileal resection, disturbance of enterohepatic bile acid circulation results in supersaturation of hepatic bile

Front 23

How do choriocarcinomas spread?

Back 23

Hematogenously; lungs most common site of distal spread

Highly sensitive to chemo

Front 24

Enzyme deficiency in orotic aciduria.

Back 24

Lack ornithine transcarbamoylase (enzyme that converts Carbamoyl phosphate and ornithine into citrulline)

Deficiency of this enzyme increase carbamoyl phosphate levels, which is converted to orotic acid.

Front 25

What is ferritin?

Back 25

Stored form of iron; excellent marker of iron stores

Decreased in cases of iron deficiency and elevated in cases of iron overload

It's also an acute phase reactant and may be elevated in pts w/infections or inflammatory dz

Front 26

What do transferrin levels monitor?

Back 26

transferrin =transporter of iron; when supply of iron is dec'd, transferrin saturation drops

Front 27

Gallbladder stone
5% cholesterol

Back 27

Black pigment stone--form when inc'd unconjugated bilirubin precipitates in bile as calcium bilirubinate

Elevated levels of unconjugated bilirubin primarily a/w chronic hemolysis (sickle cell, beta-thal, hereditary spherocytosis)

Front 28

What are the manifestations of MEN1/2A/2B?
Do not gloss this over.
Be specific.

Back 28

MEN1:
Parathyroid--HYPERCALCEMIA
Pancreatic (gastrin)
Pituitary adenoma (prolactin, ACTH)

MEN 2A:
Medullary thyroid (calcitonin)
Pheo (episodic HTN, and HA!!)
Parathy

MEN 2B:
Medullary thyroid (calcitonin)
Pheo
Marfanoid habitus/mucosal neuromas

Pheo needs to be excluded in all pts w/medullary thyroid cancer

Front 29

How does a dysplastic cell differ from carcinoma?

Back 29

Dysplasia = REVERSIBLE change of epithelial cells

Epithelial malignancies progress through sequence of:
Low-grade dysplasia (does not involve entire thickness of epithelium)
-->High grade dysplasia (aka Carcinoma in situ)
-->Invasive carcinoma

Once dysplastic cells have breached BM (as sen in invasive carcinoma) process is no longer reversible

Front 30

What materials comprise a hamartoma?

Back 30

Disorganized cartilage, fibrous, and adipose tissue

Front 31

45 year-old female
Exertional dyspnea and fatigue
Atrophic skin changes in hands, cold-induced digital vasospasm
Accentuated second heart sound over left sternal border
Pitting lower edema, hepatomegaly

What is going on? Why?

Back 31

Patient has CREST syndrome---accentuated pulmonary component of second heart sound suggests increase in PA pressure-->cor pulmonale and syx of right-sided heart failure such as dyspnea on exertion, lower extremity edema and hepatomegaly

Both scleroderma and CREST develop due to increased deposition of collagen in tissues ("intimal thickening of pulmonary arterioles")

Due to proliferation and accumulation of monoclonal T-cells in affected tissues that secrete a variety of cytokines, esp TGF-beta

Front 32

Measles vs Rubella:
Viral families
Differences in presentation

Back 32

Measles = rubeola; paramyxovirus
Rash (koplik spots)


Rubella: TOGAVIRUS; low-grade fever and skin rash that starts on face and spreads to trunk/extremities. Will also see postauricular and occipital LAD

Front 33

23 year-old heterosexual male
Hepatomegaly
h/o Unprotected sex
No illicit drugs

What serum marker would you expect to find?

Back 33

Serum HBsAg

Although this individual isn't high risk, his clinical presentation suggests acute hepatitis B infection contracted during an episode of unprotected sex.

HBV can be rspread through blood (Primary means), semen, saliva, sweat, tears, breast milk, pathologic effusions.

Front 34

20 year-old college student
Insomnia, headaches, agitation, dysphagia
h/o of exploring caves
No drugs or EtOH

Diagnosis
Treatment

Back 34

Patient has rabies encephalitis--common manifestations = nonspecific, flu-like prodrome (malaise, anorexia, mild fever, HA, nausea, vomiting)

Can also result in painful spasms with swallowing or inspiration (latter responsible for dysphagia)

Postexposure prophylaxis likely isn't effective at this point, but prophylactic vaccination for indivudals at high risk of exposure to rabies virus (veterinarians, animal handlers, cave explorers, lab workers)

Need to receive KILLED (INACTIVATED) vaccine--live vaccine doesn't exist for rabies

Front 35

What cell type is involved in the initial pathogenesis of atherosclerosis?

Back 35

Thought to begin with ENDOTHELIAL CELL INJURY

Results from HTN, HLD, toxins (including EtOH); results in endothelial cell dysfn and/or exposure of subendothelial collagen (endothelial cell denudation)

Denudation promotes platelet adhesion

GFs produced by monocytes and platelets stimulate smooth muscle cell migration into and proliferation in the intima.

At same time, inc'd endothelial cell permeability allows LDL cholesterol into intima, where it's phag'd by accumulating macrophages and smooth muscle myocytes to produce foam cells.

Repetitive endothelial injury results in chronic inflammatory state. Results in progression of fatty streak within intima (containing mainly lipid-laden foam cells).

Front 36

Megaloblastic anemia
Bilateral foot numbness
Difficulty walking

What is deficient?

Back 36

COBALAMIN
COBALAMIN
COBALAMIN

Front 37

Describe the enzyme kinetics in this diagram.

Back 37

This is a classic case of capacity-limited (saturable) enzyme kinetics.

At low doses (point 1), quantity of drug-glucuronide formed is directly proportional to dose administered. In other words, when more of drug administered, more drug-glucuronide produced.

Because a fixed proportion of drug, rather than a fixed amount of drug, is converted to metabolite, early portion of graph represents first-order kinetics.

Fist-order kinetics are represented graphically by a linear line with a positive slope, which indicates increase in drug dose leads to PROPORTIONAL INCREASE in metabolite conversion (point 1).

When metabolizing enzyme's active sites become saturated, drug-glucuronide concentration doesn't continue to change w/increasing doses of substrate drug. It has reached its maximum capacity (Vmax).

So at Point 2, the kinetics change from first-order to zero-order (saturable) kinetics--a constant amount of drug is metabolized and eliminated per unit time regardless of concentration of dose or drug.

Front 38

Where are gene-associated enhancer sequences located (in relation to gene)?

Back 38

Variable locations; note that enhancers ≠ promoter regions (TATA, which is 25 base pairs upstream, and CAAT boxes, which is 70 base pairs upstream).

Enhancers increase rate of transcription initiation through protein binding and interactions with transcription factors bound to promoter sequences.

Repressor elements are similar to enhancer elements, but they decrease instead of enhance transcription rates.

Front 39

Curling vs Cushing Stomach Ulcer

Back 39

Curling--burns

Cushing--head trauma

Front 40

How does a stomach ulcer differ from a stomach erosion?

Back 40

An ulcer involves the muscularis mucosa

An erosion does not involve the muscularis mucosa (it's limited to the mucosa and submucosa)

Front 41

Hyperplastic polyp vs Hamatomatous polyp

Back 41

Hyperplastic polyps contain well-differentiated mucosal cell

Hamartomatous polyps consist of mucosal glands, smooth muscle, and connective tissue

Front 42

Which types of intestinal polyps are most likely to transform into adenocarcinoma (qualities!)

Back 42

adenomatous polyps!! Which contain dysplastic mucosal cells and can transform into adenocarcinoma

Risk of adenocarcinoma determined by:
-degree of dysplasia
-VILLOUS adenomas much more likely to undergo malignant transformation than tubular adenomas
-Size: adenomas >4cm have 40% risk of becoming malignant, those <1cm are most likely benign

Front 43

35 year-old patient with sickle cell goes into sepsis and dies.

What was the likely cause of his sepsis?

Back 43

At some point, patients with sickle cell disease become functionally asplenic. Asplenism puts patients at risk for infection by encapsulated organisms.

Strep pneumo is most likely cause
followed by H flu

Front 44

Sickle cell patient with osteomyelitis

Cause

Back 44

Salmonella

Front 45

Which diuretic increases longevity in patients with heart failure? Why?

Back 45

Sprionolactone (in addition to ACEI, digoxin, diuretic)

In CHF pts, activation of renin-angiotensin-aldosterone system leads to elevated aldosterone levels.
Aldosterone is known to cause ventricular remodeling leading to cardiac fibrosis.

Note that while Furosemide (a loop diuretic) is a potent diuretic, it's mainly used for treating pulmonary congestion and fluid retention in heart failure patients.

Front 46

Flutamide:
MOA

Back 46

Inhibits binding to testosterone receptors

Front 47

Describe cardiac tissue conduction velocity by region of the heart.

Back 47

Park at Ventura Avenue

(fastest) Purkinje > Atrial> Ventricular > AV node (slowest)

Front 48

Describe phases I vs II of Schilling test (Intrinsic factor, radiolabeled B12)

Back 48

Phase 1:
Oral radiolabeled B12 given with IM injection of non-radiolabeled B12
High urinary excretion of radioactive cobalamin during this step is e/o NORMAL ABSORPTION and dx of DIETARY B12 DEFICIENCY (need to give concomitant cobalamin during this step to create state of excess circulating B12, otherwise all of orally administered radioactive B12 would be taken up by tissues and little would be excreted in urine).

Low urinary excretion of radioactive cobalamin rules out dietary deficiency and is suggestive of poor absorption of vitamin. Can result from lack of intrinsic factor (pernicious anemia) or malabsorption syndrome.

Phase II:
Radiolabeled B12 administered with IF and urinary excretion measured.
If cause of impaired absorption is lack of IF, it will be corrected during this stage of testing and urinary excretion of radiolabeled B12 would increase.

Low excretion of radiolabeled cobalamin after administration of intrinsic factor suggests another cause of poor cobalamin absorption such as pancreatic insufficiency, intestinal bacterial overgrowth or ileal disease.

Front 49

How is Bosentan useful in primary idiopathic pulmonary hypertension?

Back 49

This is what primary idiopathic pulmonary hypertension is:
Inherited form of primary pulmonary HTN due to dec'd apoptosis of endothelial and smooth muscle cells in pulmonary arterioles (example: 36 year-old woman with dyspnea and weakness with dec'd intraluminal diameter of small branches of pulmonary artery and medial hypertrophy; mother had similar syx and died at 42)

Bosentan is an enothelin-receptor antagonist. Endothelin is a potent vasoconstrictor and stimulant of endothelial proliferation.

Bosentan, by blocking endothelin, has been shown to decrease pulmonary arterial pressure and lessen progression of vascular and right ventricular hypertrophy.

Front 50

Aerosol flunisolide therapy:
How does it work (drug class)

Back 50

Inhaled glucocorticoid--beware of thrush

Front 51

48 year-old male
Small fibrotic focus in lower lobe of right lung
Calcified lymph node in right lung hilus

Back 51

M tuberculosis infection
A lower lung lesion (Ghon focus) accompanied by ipsilateral hilar adenopathy is described as a Ghon complex

Remember: immune response to M. tuberculosis if TH1 cell mediated, resulting in caseating necrosis where organisms are present.

Front 52

BM biopsy

Back 52

BM infilitrated by plasma cells; note characteristic appearance of plasma cells (basophilic cytoplasm, eccentric nucleus, clock face distribution of chromatin)

This is diagnostic of multiple myeloma

Expect to see:
Normocytic and normochromic anemia seceondary to BM infiltration and replacement by malignant plasma cells

-Secretion of IL-1 (osteoclast activating factor) and IL-6 to activate osteoclasts-->bone resorption (PUNCHED OUT LYTIC LESIONS ON X-RAY)

Hypercalcemia due to inc'd bone destruction

Produciton of monoclonal immunoglobulin by abnl plasma cells-->inc'd susceptibility to infection (presnce of M protein and monoclonal light chains--Bence-Jones protein in urine)

AL amyloid forms due to accumuln of monoclonal immunoglobulin light chains; apple-green birefringence (AL amyloidosis contributes to dev't of renal failure in multiple myeloma)

Renal failure develops due to infiltration of kidney by plasma cells, deposition of amyloid

Front 53

Punched out bone lesions
Apple green birefringence with Congo red stain

Back 53

Multiple myeloma

Front 54

Diagnosis
Cause

Back 54

Acanthosis nigricans

Benign causes: insulin resistance (inc'd insulin and insulin-like GFs stimulate epidermal and dermal prolifereation)--insulin resistant states include DM, acromegaly, obesity and others

Malignant acanthosis nigricans a/w underlying neoplasms, esp of GI/GU tract
Sudden appearance of this in middle-aged or elderly pts is suggestive of underlying malignancy, with GASTRIC ADENOCARCINOMA the most common cause of malignant acanthosis nigricans

Front 55

29 year-old female
Decreased vision and pain around her eyes, aggravated by eye movement
Intention tremor of left arm

What are the eye symptoms called?
What disease is this?

Back 55

Eye symptoms = optic neuritis (pain with ocular movements and dec'd vision)

Intention tremor = sign of cerebellar dysfn

Both of these are seen commonly in multiple sclerosis

Etiology remains unknown but is currently considered an AUTOIMMUNE DZ

Front 56

38 year-old female
Severe, right-sided facial pain
Like a knife stabbing my face
Instigated by meal or teeth brushing

Diagnosis
Treatment

Back 56

Trigeminal neuralgia--episodes of sudden and severe pain of CN V (particularly V2 and V3)--triggered by any stimulus to CN V, e.g., chewing, teeth brushing, shaving

Tx: Carbamazepine is drug of choice

Front 57

Phenytoin:
MOA

Back 57

Inhibits neuronal high-frequency firing by reducing ability of sodium channels to recover from inactivation

Front 58

Carbamazepine:
MOA

Back 58

Inhibits neuronal high-frequency firing by reducing ability of sodium channels to recover from activation

Front 59

Dermatologic name for a bruise by size

Back 59

<5mm: petechiae
5mm-1cm: purpura
1cm+: ecchymoses

Front 60

Why would a patient with sickle cell present with pancytopenia?

Back 60

Formation of autoantibodies against RBCs, WBCs, and platelets

This is a type II hypersensitivity rxn

Front 61

What spinal effects does B12 deficiency have?

Back 61

Degeneration of dorsal columns (ascending)

and degeneration of corticospinal tract (descending) pathways

Loss of position and vibration sensation, ataxia, spastic paresis are common manifestations

Front 62

What is the most common amino acid found in collagen?

Back 62

Glycine--Gly-X-Y-333 (found in at least every third amino acid position

Front 63

Brain biopsy
What happened and how long ago did it occur?

Back 63

Deeply eosinophilic neurons = "red neurons"--sign of irreversible neuronal injury

This is in response to inadequate blood supply to the brain, leading to ischemic stroke. These microscopic changes occur 12-24 hours after cessation of blood supply are are described as "red neurons".

Front 64

Fever, weight loss, muscle pain
Muscle biopsy shows transmural inflammation of arteries with fibrinoid necrosis

What is this and what disease is it associated with?

Back 64

Transmural inflammation of arterial wall with fibrinoid necrosis = POLYARTERITIS NODOSA

Inflammation can occur in any organ with exception of lung

Associated with HEPATITIS B INFECTION in 10 to 30% of cases

Front 65

What problem does a decreased angle between the aorta and SMA develops?

Back 65

Entrapment of the transverse portion of the duodenum between the SAM and aorta--causes partial intestinal obstruction (bilious vomiting!)

Front 66

40 year-old man with pain on defecation
Pain is sharp and severe, but subsides within minutes of passing bowel movement
He sees spots of bright red blood on toilet paper
Rectal exam reveals tear of anal mucosa

What are these tears called? Where are they mostly likely to occur?

Back 66

This is an anal fissure (a longitudinal tear in the mucosa of the distal anal canal)

Majority occur at POSTERIOR MIDLINE of ANAL VERGE

This is bc the posterior anaal canal is poorly perfused and makes its mucosa sensitive to trauma by hard fecal masses--anal fissures are a/w constipation and low-fiber diets

Front 67

HbA1c vs HbA2:
What does HbA1c measure?
When is HbA2 elevated?

Back 67

HbA1c is glycosylated hemoglobin A1 (HbA1 = alpha2beta2); in normal adults, HbA1 makes up about 97% of total hemoglobin, while HbA2 (alpha2delta2) makes up about 2.5% and fetal Hg makes up less than 1%

HbA2 is elevated in beta-thalassemia to compensate for decreased synthesis of HbA1 that results form beta-globin chain UNDERProduction

Note that in sickle cell, the HbS percentage is increased and the HbA21 levels are reduced. HbA2 percentage is normal.

Front 68

4 year-old male
Fever, bilateral conjunctivitis, bright red tongue
Skin on fingertips is sloughing

What disease is this?
What is this patient at risk of?

Back 68

Kawasaki disease is a vasculitis of medium-sized arteries that affects very young children. Presents with:
-STRAWBERRY TONGUE
-edema of hands, feet, palms, soles; desquamation of fingertips (periungal)
Generalized rash (beginning on extremities and moving to trunk)

Lethal Complication= CORONARY ARTERY ANEURSYM

Front 69

What disease is this?
What specific damage occurs?

Back 69

This is Wilson's Disease (Kayser-Fleischer rings)--rare, autosomal recessive disease

Copper accumulation will cause damage to hepatic tissue through generation of free radicals.

From there it will leak from hepatocytes into blood and deposit in cornea, basal ganglia.

Will results in BASAL GANGLIA ATROPHY.

Front 70

What is this?

Back 70

Hepatocellular carcinoma

Front 71

There are three types of Rapidly Progressive GN:
Type 1: Goodpasture's
Type 2: Immune-complex
Type 3: Pauci immune

List what you can about each.

Back 71

Type 1: Linear GBM deposits of IgG and C3; anti-GBM ab's cross-react w/pulmonary alveolar BM's, producing pulmonary hemorrhages (hemoptysis)

Type 2: Lumpy bumpy granular pattern; complication of poststreptococcal GN, SLE, IgA nepropathy, or Henoch-Schonlein purpura

Type 3: Pauci Immune--no immunoglobulin or complement deposits; associated with ANCA (C-Wegener's)