6/19 UWorld

Question 1

Defect in Lynch syndrome

Answer 1

• Defect in DNA mismatch repair (MMR) – e.g. MSH2, MLH1

Question 2

Presentation of Neurofibromatosis type 1 vs type 2

Answer 2

• Neurofibromatosis type 1
  
  • Caused by mutation in NF1 gene on chromosome 17
    
    • This gene is responsible for control of cell division
  • Neurocutaneous disorder characterized by café-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules (pigmented iris hamartomas)
  • Neurofibromas consist of proliferation of Schwann cells, fibroblasts, and neurites
• Neurofibromatosis type 2
  
  • Due to mutation of NF2 gene on chromosome 22
  • 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 3

MOA and uses of Paclitaxel

Answer 3

• MOA:
  
  • Hyperstabilization of polymerized microtubules in M phase so that mitotic spindle cannot break down and anaphase cannot occur
• Uses:
  
  • Used to treat ovarian and breast carcinoma
  • Also prevents intimal hyperplasia, so can be used as coating in stent placement to prevent stent restenosis

Question 4

Tumors associated with VHL

Answer 4

• THINK: HIPA
  
  • Hemangioblastoma, Inreased risk for RCC, Pheochromocytoma, Angiomatosis

Question 5

Describe deficiency in Medium-chain acyl CoA dehydrogenase deficiency (MCAD)

Answer 5

• Deficient enzyme for beta-oxidation à decreased ability to breakdown fatty acids into acetyl-CoA à accumulation of fatty acyl carnitines in blood with hypoketotic hypoglycemia
• Presentation:
  
  • Vomiting, lethargy, seizures, coma, liver dysfunction
  • Can lead to sudden death in infants or children
• Treatment:
  
  • Avoid fasting

Question 6

Adult derivatices of pros, mes, and rhombencephalon

Answer 6

• Prosencephalon à forebrain
  
  • Telencephalon
    
    • Walls à cerebral hemisphere
    • Cavities à lateral ventricles
  • Diencephalon
    
    • Walls à thalamus, hypothalamus
    • Cavities à third ventricle
• Mesencephalon à midbrain
  
  • Mesencephalon
    
    • Walls à midbrain
    • Cavity à aqueduct
• Rhombencephalon à hindbrain
  
  • Metencephalon
    
    • Walls à pons, cerebellum
    • Cavity à upper 4^th ventricle
  • Myelencephalon
    
    • Walls à medulla
    • Cavity à lower 4^th ventricle

Question 7

What cardiomyopathy is associated with chronic, excessive alcohol intake?

Answer 7

dilated cardiomyopathy

Question 8

Describe chromosomes and hormone levels in Klinefelter syndrome (testosterone, estrogen, LH, FSH)

Answer 8

47, XXY

Atrophied/hyalinized seminiferous tubules -> decreased testosterone and inhibin B -> increased FSH and LH -> increased estrogen production

Question 9

Will you see an increase or a decrease in the following values in obstructive lung disease:

• Residual volume (RV)
• Functional residual capacity (FRC)
• Total lung capacity (TLC)
• FEV1
• FVC
• FEV1:FVC

Answer 9

Residual volume (RV) - increased

Functional residual capacity (FRC) - increased

Total lung capacity (TLC) - increased

FEV1 - decreased

FVC - decreased

FEV1:FVC - decreased (< 80%)

Question 10

Diagnostic criteria for chronic bronchitis

Answer 10

• Chronic productive cough for > 3 months per year for > 2 consecutive years

Question 11

Histology of chronic bronchitis

Answer 11

• Characterized by hyperplasia of mucus-secreting glands in bronchi
  
  • Reid index (thickness of mucosal gland layer to thickness or wall) > 50%

Question 12

What disease presents with “blue bloating” vs. “pink puffing”

Answer 12

Chronic bronchitis = blue bloater

Emphysema = pink puffer

Question 13

Which is worse in upper vs. lower lobes?

Panacinar vs. centriacinar emphysema

Answer 13

Centriacinar = upper lobes (think: smoke rises)

Panacinat = lower lobes

Question 14

Describe effects of A1ATD on liver

Answer 14

• A1ATD due to misfolding of mutated proteins
• Misfolded proteins accumulate in the endoplasmic reticulum of hepatocytes = liver cirrhosis

Question 15

Describe basic premise and causes of bronchiectasis

Answer 15

• Chronic infection of the bronchi causes permanent dilation of airways
• Causes:
  
  • Cystic fibrosis, Kartagener syndrome, necrotizing infection, allergic bronchopulmonary aspergillosis

Question 16

What are the effects of histamine?

Effects on vessels and airways?

Answer 16

• Increased nasal and bronchial mucus production
  
  • à dripping nose sap
• Pain and pruritus, vasodilation, increased vascular permeability (which causes hives)
  
  • à red sap dripping from vascular branch (permeability)
• Bronchoconstriction
  
  • à guy constricting lung branch
• Functions as a neurotransmitter in the brain, where it regulates sleep and arousal
  
  • à brain tree

Question 17

What are the 1st generation antihistamines

Answer 17

• 1^st generation H1-blockers
  
  • Are lipophilic and can cross the BBB
• Diphenhydramine** and **Dimenhydrinate
  
  • à dragonfly fairy
• Chorpheniramine
  
  • à color fairy
• Hydroxysine, Meclizine, Promethazine
  
  • à fairy cuisine

Question 18

What are the 2nd generation H1 blockers

Answer 18

• 2^nd generation H1-blockers:
  
  • Are less lipophilic and so do NOT cross the BBB (less central effects)
• Fexofenadine
  
  • à fox
• Cetirizine
  
  • à Satyr
• Loratidine
  
  • à rat

Question 19

What uses do 1st generation antihistamines have that 2nd generation do not?

Answer 19

• Treats vestibular nausea or motion sickness
  
  • à seasick fairy sailors in front of the brain tree
  • Only 1^st generation H1 blockers because they are lipophilic so can enter the CNS and act of the vestibular system and brainstem
  • Drowsiness (can be used to treat insomnia)
    
    • à guy sleeping
• Antagonize peripheral and central muscarinic receptors (e.g. pupillary dilation, dry mouth, urinary retention, constipation, exacerbation of glaucoma, and delirium)
  
  • à anti-muscarinic tea party
• Treat extrapyramidal side effects caused by antipsychotics (e.g. acute dystonia)
  
  • à falling “extra parking” cone
  • This is because the anti-muscarinic effects re-establish dopaminergic-cholinergic balance
• Antagonize serotonin receptors in the CNS stimulating appetite and weight gain
  
  • à cut smiley face cake
  • à stuffed fairy next to cake

Question 20

What are the two long-acting Beta-2 agonists (LABA) used for asthma

Answer 20

• Salmeterol and Formoterol
  
  • = Salute
  • = formation
  • = ROL call
• Used for prophylaxis of asthma

Question 21

MOA of Montelukast and Zafilukast

Answer 21

Direct inhibitors of leukotriene receptors (CysLT1)

Causes broncodilation

Used for persistent asthma, espcially aspirin-induced asthma

Question 22

What drugs are substrates of CYP-450

Answer 22

• Always Think When Outdoors:
  
  • A - Anti-epileptics
  • T - Theophylline (caffeine-like drug)
  • W - Warfarin
  • O - OCPs

Question 23

MOA of Omalizumab

Answer 23

• Mechanism of action
  
  • Recall:
    
    • Mast cell degranulation is important to the pathogenesis of asthma
      
      • à bee hive
    • Antigen binding to IgE on mast cells causes degranulation and release of inflammatory mediators (e.g histamine)
      
      • à IgE gun shooting hive
  • Is an anti-IgE monoclonal antibody directed against the Fc portion of IgE (part that attaches IgE to mast cell), preventing mast cell sensitization
    
    • à limo guy grabbing end of IgE gun
• Uses:
  
  • Adjunctive therapy for moderate-severe persistent asthma

Question 24

MOA of Cromolyn sodium

Answer 24

• Cromolyn sodium à Lynn’s bee control in bottom R of image
  
  • Mechanism of action:
    
    • Inhibits mast cell degranulation, preventing the release of histamine
      
      • à bee sedating smoke

Question 25

What is used for emergent treatment of acute asthma exacerbation

Answer 25

* **_Short-acting beta-2 agonists_** * à beta-2 tuba kid flying away * **_Systemic corticosteroids_** * à moon face balloon on kid flying away * Oral or IV administration * à ivy on wall behind moon balloon * **_Nebulized Ipratropium bromide_** (anticholinergic) * à cat-ipra-pillar balloon * **_Epinephrine_** * à EPIC!

Question 26

Will the following value be high or low in restrictive lung disease: * TLC * FEV1 * FVC * FEV1:FVC

Answer 26

Decreased TLC Decreased FEV1 and FVC, but FVC is decreased more FEV1:FVC ratio is increased (\> 80%)

Question 27

What disease presents with: * In children * Lytic bone lesions * Skin rash * Recurrent otitis media * Restrictive lung disease

Answer 27

Langerhans cell histiocytosis * Neoplastic proliferation of specialized dendritic cells (especially in skin) * Birbeck (“tennis racket”) granules seen on EM * S-100 (+) and CD1a (+)

Question 28

What type of HSR is hypersensitivity pneumonitis

Answer 28

Aka Pigeon breeder or Farmer’s lung Mixed type III/IV HSR to environmental antigen Presents with dyspnea, cough, chest tightness, and headache Restrictive lung disease

Question 29

What pneumoconiosis is caused by aerospace and manufacturing industries

Answer 29

Berylliosis

Question 30

What pneumoconiosis is associated with shipbuilding and roofing

Answer 30

Asbestos

Question 31

Which pneumoconioses causes increased risk of cancer?

Answer 31

Asbestos * Causes fibrosis of lung or pleura; cancer of lung or pleura (mesothelioma) * Lung carcinoma more common than mesothelioma

Question 32

Describe presentation of Berylliosis

Answer 32

Noncaseating granulomas in lung, hilar lymph nodes, and systemic organs Looks similar to sarcoidosis

Question 33

Which pneumoconioses is associated with increased risk for TB and why

Answer 33

Silicosis Silica impairs phagolysosome formation (increased risk for TB)

Question 34

Describe the pathogenesis behind acute respiratory distress syndrome (ARDS)

Answer 34

Due to diffuse damage to alveolar-capillary interface Caused by neutrophil activation inducing protease- and free radical-mediated damage of type I and type II pneumocytes Endothelial damage = increased capillary permeability = protein-rich leakage into alveoli = diffuse alveolar damage and noncardiogenic pulmonary edema Results in intra-alveolar hyaline membrane

Question 35

Causes of ARDS

Answer 35

Sepsis, Pancreatitis, Pneumonia, Aspiration, Uremia, Trauma, Amniotic fluid embolism, Shock, Infection

Question 37

What is the function of smooth ER, and where is a lot of it found

Answer 37

o Site of steroid synthesis and detoxification of drugs and poisons o A lot of smooth ER found in adrenal cortex and hepatocytes

Question 38

2 functions of Golgi apparatus

Answer 38

Post-translational protein modification Distribution center for proteins and lipids from ER to secretory vesicles, lysosomes, or plasma membrane

Question 39

Describe the amino acids that can be modified in the golgi apparatus

Answer 39

o Asparagine (modifies N-oligosaccharide) o Serine (adds O-oligosaccharide) o Threonine (adds O-oligosaccharide)

Question 40

How does Golgi apparatus mark a protein to be sent to lysosome

Answer 40

Adds mannose-6-phosphate to proteins destined for lysosomes

Question 41

What is I-cell diseaase

Answer 41

* o I-cell disease = deficiency in mannose phosphorylation * No mannose to target lysosomal proteins = proteins are secreted extracellularly instead of into lysosome * Corneal clouding, coarse facies, HSM, skeletal abnormalities, restricted joint movement, +/- intellectual disability * Death by age 8

Question 42

What are the 3 most imporant vesicular trafficking protiens

Answer 42

Coat protein I and II (COPI and COPII) Clathrin

Question 43

Describe the origin and destination of each of the trafficking protiens: COPI, COPII, Clathrin

Answer 43

* COPI * retrograde * from Golgi to rough ER * COPII * anterograde * from rough ER to golgi * Clathrin * from golgi to lysosomes * from cell membrane into cell

Question 44

What are the function of chaperones

Answer 44

Intracellular protein involve in facilitating and/or maintaining protein folding

Question 45

What is heat shock protein

Answer 45

A type of chaperone Heat shock protein (e.g. HSP60) are expressed at high temperatures in yeast to prevent protein denaturing/misfolding

Question 46

Which cyclin-CDK complexes assist in the progression from G1 to S phase

Answer 46

Cyclin D + CDK4 Cylcin E + CDK 2

Question 47

What are the exclusively ketogenic amino acids, and in what disorder are they important

Answer 47

Lysine and leucine Patients with pyruvate kinase deficiency should stick to a ketogenic diet in order to prevent the buildup of pyruvate

Question 48

What are the negatively charged amino acids

Answer 48

The acidic ones Aspartate and glutamate

Question 49

What are the positive charged amino acids (make up histone since they bind to neg. DNA)

Answer 49

Are the basic amino acids * THINK: His lies are basic * His = histidine, lies = lysine, are = arginine, basic * o Lysine * o Arginine * o Histidine * Arginine and lysine are within histones * THINK: the only + charged AA that sounds like histone is not in histones

Question 50

Can cholinesterase inhibitors be used to reverse the effects of depolarizing or non-depolarizing neuromuscular blockade

Answer 50

Non-depolarizing (e.g. Rocuronium) - MOA is competitive inhibition of ACh receptor, so increasing ACh will undo effects Depolarizing agents (e.g. Succinylcholine) are ACh agonist which cause contant depolarization so that the receptor cannot respond to subsequent impulses Can only be reversed by AChE inhibitors during phase 2