6/13 UWorld

Question 1

Describe the pathophysiology of aortic aneurysm in syphilis

Answer 1

Tertiary syphilis begins with vaso vasorum endarteritis and obliteration, resulting in inflammation, ischemia, and weakening of the adventitia

Question 2

What are the compenents of crescents in rapidly progressive glomerulonephritis

Answer 2

Fibrin and macrophages

Question 3

What is the equation for number needed to treat?

Answer 3

1/ARR

• Absolute risk reduction (ARR)
  
  • Looking at how much a beneficial intervention (rather than a risk factor) will affect the risk of disease
    
    • Risk of those not receiving intervention minus risk of those receiving intervention
  • Equation:
    
    • ARR = [c/(c+d)] - [a/(a+b)]
    • THINK: ARR = NPV – PPV

Question 4

What is the equation for relative risk

Answer 4

• Probability of getting disease in exposed group vs. probability of getting disease in unexposed
  
  • Calculated from cohort studies
• Equation:
  
  • RR = [a/(a+b)] / [c/(c+d)]
• Remember that it is a ratio! Not subtraction

Question 5

Equation for odds ratio

Answer 5

• Odds that group with disease (case) was exposed to a risk factor vs. odds that group without disease (control) was exposed
  
  • Calculated from case-control studies
• Equation:
  
  • OR = [(a/c) / (b/d)] = ad/bc

Question 6

Equation for relative risk reduction

Answer 6

• The proportion of risk reduction attributable to the intervention as compared to a control
• Equation:
  
  • RRR = 1 – RR

Question 7

Equation for attributable risk

Answer 7

• Difference in risk among exposed and risk among unexposed
• Equation:
  
  • [a/(a+b)] – [c/(c+d)]
• Same as relative risk, but subtraction instead of division

Question 8

What pathogens cause ring enhancing lesions in the brain

Answer 8

Toxoplasmosis

CNS lymphoma

Question 9

Where are enhancers/silencers located in reference to the gene they are working on (upstream, downstream

Answer 9

Can be located upstream, downstream, close to, far from, or even within (in an intron) the gene they are regulating

Vs. promoters which must be upstream

Question 10

What type of HSR is hyperacute (minutes) transplant rejection

Answer 10

Type II HSR

Question 11

Reverse transcription polymerase chain reaction is used to detect levels of what in a sample?

Answer 11

mRNA

RT-PCR used the sample mRNA to produce complementary DNA that can be amplified by PCR

Because cDNA is complementary to mRNA, it contains exons and any untranslated regions

Question 12

Describe gram to calorie ratios for:

• Protein
• Carbohydrates
• Fat
• Ethanol

Answer 12

Protein = 4 cal/g

Carbs = 4 cal/g

Fat = 9 cal/g

Ethanol = 7 cal/g

Question 13

Does oxygenated blood from mother to fetus come from the umbilical artery or umbilical vein

Answer 13

Vein

Question 15

What disease presents with diffuse ST segment elevation in all EKG leads

Answer 15

Pericarditis

Question 16

Do first generation antipsychotics treat positive or negative sx of Schizoprenia

Answer 16

Positive

Question 18

What is the mechanism behind increased risk of TB in silicosis

Answer 18

Impaired phagolysosome formation

Question 19

Describe the presentation of neurofibromatosis type 1

Answer 19

• Neurocutaneous disorder characterized by café-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules (pigmented iris hamartomas)

Question 20

Describe presentation of neurofibromatosis type 2

Answer 20

• Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas
• Presentation:
  
  • Hearing loss, tinnitus, balance problems, hyperpigmented skin lesions, cataracts
• REMEMBER 2’s:
  
  • Chr 22
  • Bilateral hearing loss
  • NF Type 2
  • Cataracts

Question 21

Mode of transmission of Hepatitis A

Answer 21

Travel to endemic areas

Contaminated water supply

Shellfish

Question 22

Mode of transmission of Hepatitis C

Answer 22

Exposure to infected blood

Sexual (less likely than Hep B to be transmitted this way)

Question 23

What anti-arrhythmic drug prolongs the QT interval but is associated with lower risk of torsade de pointes than the other QT-prolonging agents

Answer 23

Amiodarone

Other QT prolonging agent = Class IA (Procainamide, Quinidine, Disopyramide)

Question 24

What is a classic XR finding in Bacillus anthracis

Answer 24

Mediastinal widening

Question 25

What is unique about the capsule of Bacillus anthracis

Answer 25

It contains a D-glutamate capsule (remember poly-D) instead of polysaccharide

Question 26

What is the mutation associated with Lynch syndrome

Answer 26

MSH2, MLH1 -- DNA mismatch repair Not associated with APC mutation - recall that Lynch syndrome is hereditary nonpolyposis colon cancer (HNPCC)

Question 27

Symptoms of Parkinson's

Answer 27

* TRAPS + mask-like facies * Tremor (resting) * Rigidity (cogwheel) * Akinesia (or bradykinesia) * Postural instability * Staggering gait

Question 28

What adverse effects are likely to persist after adding carbidopa to levodopa

Answer 28

Carbidopa decreases peripheral conversion and enhances central converson of L-DOPA to DA Will have more central side effects - anxiety and agitation

Question 29

What are the peripheral side effects of levadopa that are decreased with Carbidopa

Answer 29

* Nausea and vomiting due to chemoreceptor stimulation * à nauseated hostage * Cardiac arrhythmias * à arrhythmia rope tying up the female hostage * Orthostatic hypotension * à female hostage passed out

Question 30

Where is the SA node located

Answer 30

R atrium near the opening of the SVC

Question 31

Where is the AV node located

Answer 31

RA near the septal cusp of the tricuspid valve

Question 32

What disease is associated with anti-mitochondrial antibodies

Answer 32

Primary biliary cirrhosis

Question 33

What antibody is associated with polymyositis/dermatomyositis

Answer 33

Anti-jo-1 ANA

Question 34

Describe the role of Cyclin D in cell replication

Answer 34

o Cyclin D activates CDK4 (kinase complex) o This kinase complex will phosphorylate Rb protein o Phosphorylated Rb becomes unbound from transcription factor E2F, allowing cell to progress from G1 to S phase

Question 35

Describe function of RAS (as an oncogene or tumor suppressor) + associated cancers

Answer 35

* Oncogene = is a signal transducer (GTP-binding protein) * Ras is associated with growth factor receptors in an inactive GDP-bound state * Receptor binding causes GDP to be replaced with GTP, activating Ras * Activated Ras sends growth signals to the nucleus * Ras inactivates itself by cleaving GTP to GDP via GTPase protein * Mutated Ras inhibits the activity of GTPase, thus producing a prolonged activated state of Ras * Most common oncogene abnormality * Associated with: * o Pancreatic adenocarcinoma * o Cholangiocarcinoma

Question 36

Name the oncogene and the tumor suppressor associated with breast cancer

Answer 36

Oncogene = HER2 (EGFR) Tumor suppressor = BRCA1/2

Question 37

What cancer will be CA 19-9+

Answer 37

Pancreatic cancer

Question 38

What cancers will be CEA+

Answer 38

* CEA – carcinoembryonic antigen * § Colon cancer * § Pancreatic cancer

Question 39

What cancers will be AFP+

Answer 39

§ Hepatocellular carcinoma § Hepatoblastoma § Yolk sac tumor § Mixed germ cell tumor

Question 40

What cancers will be b-hCG+

Answer 40

§ Hydatidiform mole § Choriocarcinoma § Testicular cancer § Mixed germ cell tumor

Question 41

What cancers will be S-100+

Answer 41

* o S-100 – Neural crest marker * § Melanoma * § Schwannoma

Question 42

What cancers will be alkaline phosphatase+

Answer 42

§ Metastasis to bone § Biliary disease § Paget disease of the bone

Question 43

What tumors will have psammoma bodies

Answer 43

Papillary thyroid carcinoma Serous papillary cystadenocarcinoma of the ovary Mesothelioma Meningioma

Question 44

What tumors secrete erythropoietin

Answer 44

* Potentially Really High Hematocrit * Pheochromocytoma * Renal cell carcinoma * Hepatocellular carcinoma * Hemangioblastoma

Question 45

Describe the synthesis of the pyrimidine, thymidine

Answer 45

* Glutamine + CO2 + ATP converted to carbamoyl phosphate via carbamoly phosphate synthetase II * Carbomoyl phosphate converted to orotic acid * Orotic acid converted to UMP via UMP synthase * UMP to UDP * UDP to dUDP via ribonucleotide reductase * dUDP to dUMP * dUMP methylated to dTMP via thymidilate synthase * THF is what provides the carbon needed for methylation (THF to DHF) * Thymidylate synthase catalyzes the transfer of methyl group * DHF gets converted back to THF via dihydrofolate reductase * THF is then re-methylated to continue the cycle

Question 46

MOA of Methotrexate

Answer 46

* Folate analog that competitively and irreversibly binds to dihydrofolate reductase, preventing convserion of DHF into THF * Inhibition of DHF reductase leads to a build-up of DHF * This means you have no THF to create dTMP * Interferes with the synthesis of DNA, RNA, and other rapidly dividing cells * Rapidly dividing cells are the ones that are preferentially targeted * Most effective during S phase (when cells are undergoing synthesis of new DNA)

Question 47

How do you reverse the toxicity of methotrexate

Answer 47

* **_Leucovorin_** (folinic acid – reduced form of folate) * - lucky feline (cat statue) * Can be used to reverse the toxicity effects of MTX (“leucovorin rescue”) * Folinic acid does not require DHF reductase

Question 48

MOA of 5-Fluorouracil (5-FU)

Answer 48

5-FU is a cytotoxic pyrimidine analog 5-FU is metabolized by intracellular reaction to it’s active form FDuMP FDUMP forms a complex with THF and inhibits thymidylate synthase (conversion of dUMP to dTMP using carbon from THF) Inhibition of thymidylate synthase by 5-FU will lead to a build-up of dUMP

Question 49

MOA of hydroxyurea

Answer 49

* Recall: * The precursor of all pyramidine nucelotides is UMP, which is then phosphorylated to UDP * Ribonucleotide reductase will convert UDP to dUDP * dUDP can then be de-phosphorylated into dUMP * Hydroxyurea works by inhibiting ribonucleotide reductase so that UDP cannot be converted to dUDP, thus blocking the de novo synthesis of thymidine