Uworld: 5-28

Front 1

Hydroceles and _____ inguinal hernias are formed by a similar mechanism.

What is the mechanism?
How does it differ?

Back 1

Hydroceles and INDIRECT inguinal hernias

Both caused by incomplete obliteration of processus vaginalis.

Hydrocele occurs when there's a connection between scrotum and abdominal cavity that only allows leakage of fluid; whereas, a hernia occurs when the opening allows the protrusion of abdominal organs along the inguinal canal.

Front 2

What is effect modification?
Give an example.

Back 2

Effect modification occurs when effect of a main exposure of an outcome is modified by another variable.

Ex: Likelihood that asbestos exposure will result in lung cancer is significantly impacted by smoking status.

Note that is not a form of bias.

Front 3

What are the molecular effects of smoking marijuana?

Presentation?

Back 3

Marijuana is a cannabinoid (not an opiate!) that contains tetrahydrocannabinol (THC).

THC stimulates cannabinoid receptors (CB1 and CB2 receptors) with effects lasting 1-4 hours.

Presentation: tachycardia, conjunctival injection (redness of sclera).

Note that marijuana is metabolized in the liver and then distributed and stored in lipophilic tissues and slowly released.

Remains in the body for up to 30 days after use.

Front 4

34 year-old male
Pruritic skin rash after exposure to outdoor plants
Erythematous linear eruption with vesiculations

Diagnosis
Pathophys

Back 4

Poison ivy contact dermatitis; skin lesion is usually linear because plant drags along skin

This is a delayed type hypersensitivy (Type IV)

Two phases:
-Sensitization: creation of hapten-specific T cells. Cutaneous dendritic cells take up haptens, express them on MHC-I and MHC-II molecules, travel to LN-->interact w/CD4's and CD8's causing activation and clonal expansion

Elicitation (re-exposure) phase:
Hapten taken up by skin cells (langerhans cells, DC's, keratinocytes) that express MHC-I/II molecules

Activate the proliferated hapten-specific T-cells in dermis/epidermis.

CD8 T CELLS ARE MAIN EFFECTOR in allergic contact dermatitis

Front 5

56 year-old female
h/o gallstones
Cramping abdominal pain, abdominal distention, vomiting
X-ray reveals air in biliary tree

Diagnosis
Pathophys

Back 5

Gallstone ileus--large gallstone obstructs ILEOCECAL valve

Front 6

Normal bleeding time
Prolonged PT
Notmal PTT

Diagnosis (explain)

Back 6

Normal bleeding time means normal platelet function

Normal PTT means normal INTRINSIC pathway (Factors XI, IX, XII)

Prolonged PT means abnormal EXTRINSIC PW (Factor VII deficiency)

Front 7

What is the anticodon of the tRNA that would insert the last amino acid into this polypeptide chain?

Back 7

Remember that U goes with A in RNA.

Also remember the stop codons:
UAA
UAG
UGA

Front 8

Which CCBs have the strongest effect on heart rate?

Back 8

Verapamil>Diltiazem>Nifedipine

Front 9

Which CCBs have the strongest effect on peripheral vasculature?

Back 9

Nifedipine>Diltiazem>Nifedipine

Front 10

Drug for atrial fibrillation
Causes constipation and second degree AV block

Back 10

Verapamil (may also cause bradycardia)

Front 11

CCB
Causes peripheral edema
Reflex tachycardia

Back 11

Amlodipine (selective for vascular smooth muscle)-->reflex tachycardia

Front 12

When is Lidocaine used?

Back 12

Arrhythmias post-MI

Front 13

12 year0old male
Turbid plasma that forms creamy supernatant on standing
Plasma lipoprotein lipase activity is low

Diagnosis
Pathophys
Other symptoms

Back 13

Lipoprotein lipase deficiency resulting in increased concentrations of serum chylomicrons (body unable to clear dietary lipid loads due to defective hydrolysis of TGs in chylomicrons)

Pts present in childhood w/hyperlipidemia, pancreatitis (ABDOMINAL PAIN), eruptive skin (NOT TENDON) xanthomas and HSM.

Note that tendon xanthomas are assocd w/familial hypercholesterolmia (high LDL); not highTG.

Front 14

Wernicke Encephalopathy:
Pathophys

Back 14

Lack of thiamine means lack of TRANSKETOLASE, ALPHA-KETOGLUTARATE DH, and PYRUVATE DH activity

alphta-ketoglutarate-->succinyl-CoA requires Thiamine!

Of note, metabolism of EtOH by Alcohol DH and Aldehyde DH consumed NAD+ which further inhibits all pathways requiring NAD+ (Succinyl DH: Succinate-->Fumarate)

So alcoholics lack NAD+ and thiamine dependent reactions.

Front 15

Molecular pathway by which E. coli results in septic shock.

Back 15

ENDOTOXINS of outer membrane of Gram negative bacteria, composed of LIPOPOLYSACCHARIDE (LPS).

LPS released during destruction of bacterial cell wall.

LPS is heat stable and arranged into three regions: O antigen, core polysaccharide, and LIPID A.

LIPID A causes activation of macrophages and granulocytes, releasing IL-1, TNF-alpha, IFN.

LIPID A INDUCES SHOCK

Note that it is not actively secreted by bacteria (it is released during cell division and by bacteriolysis)

Front 16

56 year-old woman
Just returned from cruise
Fever, HA, cough
Abdominal pain, watery diarrhea
Smokes
CXR reveals left lower lobe consolidation

Diagnosis
Other symptoms

Back 16

Legionella-pneumonia (won't appear on gram stain bc it's intracellular)

Will see HYPONATREMIA

Front 17

Which drugs can treat both bipolar disorder and tonic-clonic seizures?

Back 17

Valproate
Carbamazepine

Valproate increases inhibitory effect of GABA in CNS.

Front 18

Gastrointestinal ulcers
Renal sontes
Psychiatric disorder

Diagnosis
Effects

Back 18

Bones stones, groans, and psychic moans-->PRIMARY HYPERPARATHYROIDISM

Will see SUBPERIOSTEAL THINNING

Front 19

Describe the molecular events of muscle contraction. Begin with calcium.

Back 19

Front 20

Inotropic vs Metabotropic Receptors:
General
Examples (be specific)

Back 20

Inotropic: ion channels that open directly upon ligand binding, ex: NICOTINIC cholinergic receptors (resulting in immediate Na and Ca2+ influx, and immediate K+ efflux)

Metabotropic: utilize second messengers to indirectly influence corresponding ion channels

Ex: alpha1, M1, M3 (muscarinic)-->IP3
beta1, beta2-->cAMP and Protein Kinase A

Front 21

Where is intussusception most likely to occur?

Back 21

Ileocecal valve (intermittent, severe, colicky abdominal pain, currant jelly stools, sometimes a palpable mass in RLQ)

Front 22

HBV vs HCV:
Histologic Appearance

Back 22

In HBV, hepatocellular cytoplasm fills with granular, eosinophilic substance (HBV surface Ag)--"ground glass"

In HVC, there are lymphoid aggregates within portal tracts (lots of blue spots!) and focal areas of macrovesicular steatosis

Front 23

Hepatocytes

Diagnosis

Back 23

HBV (ground glass appearance due to accumulation of HB Surface Ag 'granules' in cytoplasm)

Front 24

Hepatocytes

Diagnosis

Back 24

HCV (not lymphoid cells!)

Front 25

63 year-old male
Muscle weakness, cramping
Takes HCTZ

Pathophys

Back 25

Decrease in intravascular fluid volume stimulates aldosterone secretion-->increased excretion of K+ and H+ in urine

Thus a hypokalemic metabolic ALKALOSIS

Hypokalemia manifests w/muscle weakness and cramping

Front 26

Systolic pressure gradient between LV and aorta:

Diagnosis
Effects

Back 26

Aortic stenosis-->Dilated CM

Front 27

How does viral myocarditis result in dilated CM?

Back 27

Patients with acute onset of heart failure in setting of recent viral infection should raise suspicion for dilated CM caused by viral myocarditis.

Caused by an autoimmune reaction to myocytes that have been altered by viral infection.

Leads to dilatation of myocardium in all four chambers and resultant decrease in contractility.

Front 28

___gut derivatives rotate around the SMA.

Back 28

Midgut (Duodenum, small intestine, ascending colon, proximal 2/3 transverse colon)

Front 29

___gut derivates rotate around the IMA.

Back 29

Hindgut (transverse colon, descending, sigmoid colon)

Front 30

2 day-old neonate
Persistent bilious vomiting
Cecum fixed to RUQ

Pathophys
Associated Risks

Back 30

Malrotation of midgut around SMA--entire midgut fixed to superior mesenteric artery

Leads to intestinal obstruction, hence, bilious vomiting , and midgut VOLVULUS with intestinal perforation and gangrene as possible sequelae.

Note that intestinal twisting leading to ischemia = Volvulus

Front 31

5 year-old male
Receiving treatment for allergic rhinitis
Presents with fever, flushed cheeks, dilated pupils

Explain presentation

Back 31

Likely receiving H1 receptor (histamin) antagonist such as diphenhydramine for allergic rhinitis (has anticholinergic effects)

Fever is a result of inhibition of eccrine sweat glands

Flushing is a result of compensatory cutaneous vasodilation (to cool off)

Dilated pupils a result of inhibition of pupillary constrictor and ciliary mm.

Front 32

Bipolar I vs Bipolar II

Back 32

Bipolar I: h/o at least 1 manic episode with or without major depressive episodes (SIGECAPS: Sleep disorder, loss of Interest [anhedonia], Guilt, Energy deficit, Concentration deficit, Appetite disorder, Psychomotor retardation/agitation, Suicidality--needs at least 5 of these for major depression)

Bipolar II: at least 1 major depressive episode and at least one hypomanic episode

Front 33

29 year-old women
4 year h/o fatigue, "not happy"
Negative anhedonia, guilt
Denies suicidal ideation

Diagnosis

Back 33

Dysthymic disorder (syx must last more than 2 years!)

Front 34

7 month-old male
Thrush
2 episodes otitis media
3 episodes bronchiolitis
Low serum gamma-globulin
CXR reveals absent thymic shadow

Diagnosis--explain reasoning

Back 34

Severe combined immonudeficiency:
Recurrent otitis media (bacterial)
Bronchiolitis (Viral)
Candidiasis

Suggests primary defect in both cell mediated (T cell) and humoral (B cell) immunity

Thymic hypoplasia common among infants w/combined T and B cell deficiencies

Hypogammaglobulinemia and recurrent bacterial infections suggest concomitant B cell deficiency

Together, this forms the diagnosis of SCID

Note: Less than 1% of pts with DiGeorge have complete absence of thymus. Also, lack of characteristic DiGeorge findings (Facial abnlts, hypoparathy, and cardiac defects) makes DiGeorge less likely in this presentation.

Front 35

Label and include effect of damage

Back 35

A - Brodmann area 8--frontal eye field. Damage-->eyes deviate to ipsilateral side

B - Broca's area--comprehension intact, but can't formulate motor commands

C - Precentral Gyrus (Primary Motor Cortex)--Damage-->dysarthria due to paresis of skeletal mm involved in mvmt of mouth, tongue, larynx

D - Postecentral gyrus (Primary Somatosensory Cortex)--sensation loss

E - Wernicke's area--word salad, lack comprehension

Front 36

35 year-old alcoholic
Severe abdominal pain, vomiting
Laparotomy reveals swollen and partially necrotic pancreas

Pathophys

Back 36

In acute pancreatitis, inflammation leads to acinar cell damage-->abnormal activation of trypsin inside acinar cells

Trypsin then activates other proteolytic enzymes and starts a self-sustaining (it can also activate trypsinogen) cycle of digestion of pancreatic tissues

Autodigestion (autolysis) of pancreas = acute necrotizing pancreatitis

Front 37

40 year-old female
Worsening fatigue
Normal vitals, no other medical problems
Labs show elevated alkaline phosphatase

What blood test should be ordered next and why?

Back 37

Bone and liver are primary sources of alkaline phosphatase (although there are other sites)

To clarify the importance of a moderately elevated alk phos, the hepatic gamma-glutamyl transpeptidase (GGTP) should be evaluated

GGTP is an enzyme predominantly present in hepatocytes and biliary epithelia

GGTP not present to a significant extent in bone. So it's useful in determining whether an elevated alk phos is of hepatic or bony origin.

Front 38

Male Pattern Baldness (androgenetic alopecia):
Mode of Inheritance

Back 38

Polygenic (influenced by multiple genes); also presents with variable penetrance

Front 39

Describe the phases of atrial mycoyte action potential (in pacemaker cells).

Which drugs affect which phase? What are their effects?

Back 39

Phase 0 (upstroke): Opening of L-type (long lasting) dihydropuyridine-sensitive Ca2+ channels, slow influx of Ca2+ into cell

Phase 3 (repolarization): Opening of K+ channels, and efflux of K+; closure of L-type Ca2+ channels

Phase 4 (pacemaker potential): slow influx of Na+ at end of repolarization; slow K+ efflux as K+ channels continue to close

Once membrane ~-50, T-type (Transient) Ca2+ channels open allowing Ca2+ to enter cell and contribute to depolarization

Drugs:
Phase 4:
-NE facilitates opening of L-type Ca2+ channels and Na+ channels-->rapid depolarization

-Adenosine and ACh: also act on phase 4; reduce rates of spontaneous depol by activating K+ channels and prolonging K+ flow, also inhibit L-type Ca2+ channels

Front 40

Phentolamine:
Drug Class

Back 40

COMPETITIVE alpha adrenergic antagonist

REVERSIBLE!

Front 41

Phenozybenazmine:
Drug Class

Back 41

IRREVERSIBLE alpha-adrenergic antagonist (will lower Vmax!)

Front 42

Clostridium botulinum vs Clostridium tetani:
Specific effects of exotoxins
Presentaiton

Back 42

C. botulinum: botulinum toxin inhibits acetylcholine release-->FLACCID paralysis

C. tetani: Tetanospasmin causes inhibition of inhibitory interneurons in SC that regulate firing of primary motor neurons. These inhibitory interneurons use GABA and GLYCINE as their NTs, but tetanospasmin prevents release of these NTs.

Presents with SPASTIC paralysis, muscle spasms, HYPERreflexia

Front 43

Methadone:
Specific MOA
Use
AE

Back 43

Long-acting mu receptor agonist.

Because it's long acting, its sustained effects allow for continuous suppression of withdrawal syx in heroin dependent patients.

Causes AEs similar to other opioids: miosis, respiratory depression seen up to 24 hours after one dose

Front 44

Thiamine:
B vitamin number
Reactions that require it
Effects of deficiency

Back 44

B1

Required for:
Pyruvate DH (pyruvate-->Acetyl CoA)

a-ketoglutarate DH (enzyme of TCA)

Transketolase (enzyme of HMP shunt)

Thiamine deficiency results in dec'd glucose utilization, which is pronounced in CNS. AN increase in erthryocyte transketolase levels after thiamine infusion is diagnostic for thiamine deficiency.

Front 45

Enzymes required for conversion of Fructose 6-phosphate to Ribose.

Back 45

F6P-->Glyceraldehyde 3-phosphate via TRANSALDOLASE

Glyceraldehyde-3-phosphate-->Ribose-5-phosphate via TRANSKETOLASE

This occurs in the nonoxidative reactions of HMP shunt.

All cells can synthesize ribose from Fructose-6-phosphate using nonoxidative reactions.

Front 46

Serpentine, medusa head appearance

Back 46

Bacillus anthracis

Front 47

Bacillus anthracis:
Mode of infection
Appearance on CXR
Requirement for pathogenicity

Back 47

Pulmonary anthrax (woolsorters disease) is caused by inhalation of spores most commonly while working with goat hair or hides. Hemorrhagid mediastinitis evident as widened mediastinum on CXR.

Requires a capsule that contains D-glutamate instead of polysaccharide--this prevents phagocytosis by host

Front 48

45 year-old male
Periodic epigastric abdominal pain, fatigue
Mild hepatomegaly
CT shows pancreatic calcifications with no e/o gallstones

Hgb 9.0
MCV 115

Diagnosis
Pathophys

Back 48

Chronic pancreatitis due to ethanol abuse

Alcohol-assocd hepatic steatosis probable cause of hepatomegaly

Megaloblastic anemia stems from folic acid deficiency. Folic acid is required for synthesis of purine and pyrimidine bases.

Note: If answer reads "diminished thymidine synthesis", this means FAULTY DNA SYNTHESIS!!

Front 49

A-a equation

Back 49

PAO2 = 150 - PaCO2/0.8

A-a = PAO2 - PaO2

Front 50

3 year-old male
Mental retardation
Fair-skinned
Blond hair, blue eyes
Musty odor

Diagnosis
Pathophys

Back 50

PKU likely due to deficiency of phenylalanine hydroxylase

Pallor of substantia nigra, locus ceruleus, and vagal nucleus dorsalis would also point to this diagnosis.

Front 51

In the US, what is the most prominent form of esophageal cancer?

Back 51

Adenocarcinoma > Squamous Cell Carcinoma

Front 52

67 year-old male
h/o HTN, TIA treated one month ago
Presents with mouth ulcers, fever

Diagnosis
Pathophys

Back 52

Mouth ulcers and fever are characteristic of NEUTROPENIA which was likely caused by TICLOPIDINE

This is why ticlopidine is rarely used and CBC must be performed biweekly for first three months.

Front 53

Acetaminophen toxicity:
Treatment
Treatment MOA (specific)

Back 53

N-acetyl cysteine; works by two ways:

1) Acts as glutathione substitute and binds to toxic metabolites of acetaminophen

2) Provides SULFHYDRYL groups to enhance non-toxic sulfation elimination of acetaminophen (enhance elimination of non-toxic acetaminophen metabolites)

Front 54

Pulmonary embolism:
Long-term treatment (prevention of recurrence)
Specific Treatment MOA

Back 54

Warfarin: inhibits vitamin K-dependent CARBOXYLAITON OF GLUTAMIC ACID residues on Factors II, VII, IX, and X (also known as vitamin K dependent clotting factors)

Note that therapy of warfarin doses is monitored via PT time (standardized via international normalized ratio--INR)

Front 55

Cilostazol:
MOA
1 other drug with this MOA

Back 55

Agents that increase PLT cAMP will decrease platelet aggregation by preventing PLT shape change and granule release

Cilostazol and Dipyridamole decrease the activity of PLT PDE (enzyme responsible for breakdown of cAMP)

Cilostazol additionally acts as a direct ARTERIAL VASODILATOR.

Front 56

Hormone responsible for gallbladder contraction

Back 56

CCK (made in duodenum and jejunum in response to FAs and AAs)

Front 57

Arginase:
Reaction catalyzed

Back 57

Arginine-->Urea + Ornithine (important for getting rid of ammonia!!!)

Front 58

Black vs Brown Pigment Stones (in GB):
Etiology

Back 58

Black Pigment Stone: intravascular hemolysis

Brown Pigment Stones:
Biliary Tract Infection

Front 59

Biliary Sludge:
Cause

Back 59

Incomplete gallbladder emptying in response to CCK stimulation

Can result in acute cholecystitis

Risk factors include:
Pregnancy
Rapid weight loss
Prolonged use of parenteral nutrition or octreotide

Front 60

Dystrophin:
Role

Back 60

Note that this is the gene DELETED in Duchenne's

Dystrophin is muscle structural protein that allows for interaction of extracellular connective tissue with the intracellular contraction apparatus.

Front 61

Eggshell calcifications of hilar nodes

Back 61

Silicosis

Also presents w/birefringent particles surrounded by fibrous tissues on histologic exam

Front 62

Calcified pleural plaques with ferruginous bodies

Back 62

Asbestosis

Front 63

Describe the pathophysiology behind developing a brown pigment stone (GB).

Back 63

Brown pigment stones typically arise secondary to infection of biliary tract, which results in release of beta-GLUCURONIDASE by injured hepatocytes and bacteria (usually E.coli)

beta-glucoronidase contributes to hydrolysis of bilirubin glucuronides and increases the amount of unconjugated bilirubin in bile.

This significantly elevates the risk of developing more brown pigment stones.

Front 64

NT changes of HD.

Back 64

Low GABA
Low ACh

Front 65

7 year-old male
Low-grade fever, headache
Malaise
Slapped cheek appearance

Diagnosis
Site of viral replication

Back 65

Erythema infectiosum (fifth disease) due to Parvovirus B19

The virus is highly tropic for erythrocyte precursors and is found predominantly in the BONE MARROW.

Front 66

35 year-old male
Endocardial thickening due to dense fibrous deposits around tricuspid and pulmonary valves
Pulmonary valve stenosis

Diagnosis
Pathophys
Diagnostic lab value

Back 66

Fibrous intimal thickening with endocardial plaques limited to right heart = Carcinoid heart disease a/w carcinoid syndrome

Carcinoid syndrome procudes skin flushing, abdominal pain, n/v, diarrhea, due to produciton of SEROTONIN, kallikrein/bradykinin/histamine/PGs by carcinoid tumors

Degree of endocardial fibrosis correlates w/PLASMA levels of 5HT and URINARY excretion of serotonin metabolite 5-HYDROXYINDOLEACETIC acid

Note that carcinoid syndrome causing R-sided endocardial fibrosis may progress to pulmonic stenosis and/or restrictive cardiomyopathy.

Front 67

26 year-old female
Glutamine for arginine substitution near protein C cleavage site in Factor V gene product

Diagnosis
Complications

Back 67

Factor V Leiden mutation (normally Activated Protein C inactivates factors Va and VIIIa)

In FVL, Factor Va has reduced susceptibility to cleavage by APC and results in hypercoagulable state (predisopses to DVT and PE).

Front 68

21 year-old male
Impaired balance, difficulty speaking
Developed slowly over last few months
Elevated serum transaminases
Negative viral serologies

Diagnosis

Back 68

Wilson's Disease

Should perform slit lamp examination to check for Kayser-Fleischer rings

Note: Wilson's is an autosomal recessive disease due to mutation of gene ATP7B--hinder copper metabolism by reducing formation and secretin of ceruloplasmin and by decreasing secretion of copper into biliary system.

Front 69

Right-sided endocarditis:
Bacterial cause

Back 69

Staph AUREUS (not EPIDERMIDIS!!!)

likely an IVDU

Front 70

What drug class can decrease adenomatous polyp formation?

Back 70

COX-2 inhibitors

For unknown reasons, increased COX-2 activity has been associated with increased incidence of adenomas.

Front 71

44 year-old female
Dry skin
Night blindness

Back 71

Vitamin A deficiency

Could be due to biliary obstruction leading to cholestasis and fat soluble vitamin malabsorption

Front 72

Back 72

Very large nucleated cells (use red cell size for comparison) with scant cytoplasm-->blast cells-->leukemia likely

Auer rods (even if they're purple!!)--->AML