6/2 UWorld

Question 1

MOA and use of Infliximab

Answer 1

• TNF-a inhibitor
  
  • Recall: TNF-a is an acute phase reactant produced by activated macrophages to mediate inflammation by accelerating neutrophil migration, and facilitate lymphocyte proliferation; TNF-a is responsible for fever, anorexia, corticotropin releasing hormone, septic shot, and cachexia
• Mechanism of action:
  
  • Is a monoclonal antibody to TNF-a
• Uses:
  
  • Used for autoimmune conditions due to anti-inflammatory effect
  • Rheumatoid arthritis, psoriasis, ankylosing spondylitis

Question 2

MOA and use of Cyclosporine

Answer 2

• Immunosuppressant
  
  • Blocks lymphocyte activation and proliferation
• MOA:
  
  • Binds cyclophilin (protein within cytosol of T-cells)
  • Inhibits calcineurin (which stimulates IL-2) à prevention of IL-2 transcription
• Uses:
  
  • Transplant rejection
  • Psoriasis
  • Rheumatoid arthritis
• Toxicity
  
  • Nephrotoxicity

Question 3

MOA and use of Sirolumus

Answer 3

Aka Rapamycin

• Immunosuppressant
  
  • Blocks lymphocyte activation and proliferation
• MOA:
  
  • Binds FKBp12 à inhibition of mTOR
  • Prevents response to IL-2

Question 4

MOA and use of Etanercept

Answer 4

• TNF-a inhibitor
  
  • Recall: TNF-a is an acute phase reactant produced by activated macrophages to mediate inflammation by accelerating neutrophil migration, and facilitate lymphocyte proliferation; TNF-a is responsible for fever, anorexia, corticotropin releasing hormone, septic shot, and cachexia
• Mechanism of action:
  
  • Mimics TNF-a receptor (aka it intercepts TNF-a before it can reach its target)
• Uses:
  
  • Used for autoimmune conditions due to anti-inflammatory effect
  • Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriasis

Question 5

MOA and use of Tacrolimus

Answer 5

• Immunosuppressant
  
  • Blocks lymphocyte activation and proliferation
• MOA:
  
  • Binds FK506 binding protein
  • Inhibits calcineurin à prevention of IL-2 transcription
• Uses:
  
  • Transplant rejection prophylaxis
• Toxicity:
  
  • Nephrotoxicity

Question 6

MOA of Dacluzimab

Answer 6

• Immunosuppressant
  
  • Blocks lymphocyte activation and proliferation
• MOA:
  
  • Binds CD25 (IL-2 receptor) à preventing response to IL-2
• THINK: Da-clu = da claw = claw grabbing on to the receptor

Question 7

What is the defect and associated triad in Ataxia telangiectasia?

Answer 7

Defect in ATM gene - failure to repair DNA double strand breaks

Triad: ataxia, telangiectasia, IgA deficiency

Question 8

MOA and use of Paclitaxel

Answer 8

• 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 9

What biochemical process is often defective in patients with accumulation of misfolded proteins (e.g. Parkinson’s and Alzheimers)

Answer 9

Ubiquination - misfolded proteins unable to be marked for degradation

Question 10

What is the embryologic origin of the ureteric bud

Answer 10

Mesonephros:

• Forms temporary kidney during 1^st trimester
• Later contributes to male genital system – Wolffian ducts

Question 11

What structures are formed by the ureteric bud

Answer 11

• Caudal end of the mesonephros becomes the ureteric bud which gives risk to ureter, pelvises, calyces, collecting ducts

Question 12

What structures are formed by the metanephros

Answer 12

• Interaction with the ureteric bud (caudal portion of mesonephros) induces differentiation and formation of glomerulus, Bowman’s space, proximal tubule, loop of Henles, and distal convoluted tubule

Question 13

What is the cause behind higher insulin levels in oral glucose vs. IV glucose

Answer 13

Incretins (hormones produced bby gut mucosa) stimulate pancreatic insulin secretion in response to sugar-containing meals

This response occurs independent of blood glucose levels

Question 14

What is temporomandibular disorder (TMD)

Answer 14

o Characterized by constellation of symptoms:

§ Unilateral face pain that worsens with jaw movement

§ Headache

§ Ear discomfort

Question 15

What nerve may be involved in temporomandibular disorder (TMD)

Answer 15

• Mandibular nerve
  
  • Largest branch of trigeminal nerve, containing both motor and sensory components
  • Sensory:
    
    • Sensation to TMJ, mandibular teeth, flood of mouth, inside of cheeks, anterior tongue, skin of lower face
  • Motor:
    
    • Muscles of mastication (medial and laterl pterygoid, masseter, temporalis)
    • Muscle of floor of mouth (mylohyoid)
    • Tensor veli palatati
    • Tensor tympani of middle ear

Question 16

Rank these in order from fastest to slowest speed of conduction:

Atria, ventricles, AV node, purkinje fibers

Answer 16

• Purkinje > atria > ventricles > AV node
  
  • Purkinje fibers must travel fastest to ensure that ventricles contract in a bottom-up fashion (necessary for efficient propulsion of blood into the pulmonary artery and aorta)

Question 17

Rank the rate of the different pacemakers from fastest to slowest (SA node, Bundle of His, AV node)

Answer 17

• SA > AV > bundle of His/Purkinje/ventricles

Question 18

Describe the function of each of the 4 muscles of the rotator cuff

Answer 18

• (1) Supraspinatus
  
  • Suprascapular nerve
  • Abducts arm initially (before deltoid kicks in)
  • Most common rotator cuff injury
  • Assessed with “empty can” test
• (2) Infraspinatus
  
  • Suprascapular nerve
  • Laterally rotates arm
• (3) Teres minor
  
  • Axillary nerve
  • Adducts and laterally rotates arm
• (4) Subscapularis
  
  • Upper and lower subscapular nerves
  • Medially rotates and adducts arm

Question 19

What type of drug is Chlordiazapoxide

Answer 19

Benzodiazepine

Question 20

What are the complimentary amino acids (G, A, U, C)

Answer 20

G - C

A - U

Question 21

What are the stop codons

Answer 21

UGA, UAG, UAA

Question 22

What type of HSR is acute hemolytic transfusion reaction

Answer 22

Type II HSR

Anti-ABO antibodies in the recipient will bind to donor erythrocytes, leading to complement activation

Question 23

What type of HSR is hemolytic disease of the newborn

Answer 23

Type II

Question 24

What type of HSR are each of the following (also include time frames):

• Hyperacute transplant rejection
• Acute transplant rejection
• Chronic transplant rejection
• Graft-vs-host disease

Answer 24

• Hyperacute
  
  • Within minutes
  • Type II HSR (pre-existing antibodies)
• Acute
  
  • Weeks-months
  • Type IV HSR
  • Cellular and humoral:
    
    • Cellular – CD8+ T-cells against donor MHCs
    • Humoral – antibodies develop after transplant
• Chronic
  
  • Months-years
  • Type II and IV HSR
  • Cellular and humoral
    
    • Cellular – CD4+ T-cells respond to recipient APCs presenting donor peptides
• Graft-vs-host disease
  
  • Timing varies
  • Donor (foreign) bone marrow is transplanted into the patient, and then the donor cells begin to attack the host

Question 25

What is Kussmaul sign, and what disorder is it found in

Answer 25

Kussmaul sign = JVD with inspiration (instead of normal decreased JVD) Occurs in chronic constrictive pericarditis

Question 26

What is pulsus paradoxus and what disorder is it found in?

Answer 26

* Decrease in amplitude of systolic BP by \> 10 mm Hg during inspiration * Usually when you inspire this decreases intrathoracic pressure and causes the ventricular septum to deviate to the L, causing a smaller LV and a normal but slight decrease in BP * In pulsus paradoxus, there will be an exaggerated decrease in BP * Seen in cardiac tamponade, asthma, obstructive sleep apnea, pericarditis, croup * Occurs in cardiac tamponade \> constrictive pericarditis (vs. Kussmaul sign)

Question 27

What is struma ovarii

Answer 27

teratoma comprised of thyroid tissue, which can present with hyperthyroidism

Question 28

Describe the timeframe of twinning

Answer 28

* 0-4 days – dichorionic/diamniotic * 4-8 days – monochorionic/diamniotic * 8-12 days – monochorionic/monoamniotic * \>13 days – conjoined twins

Question 29

With what type of twins can twin-twin transfusion syndrome occur?

Answer 29

Occurs in monochorionic/diamniotic twins Arterio-venous anastamosis leads to shunting of blood Donor – anemic, pale, growth restricted Recipient – polycythemic, plethoric, overloaded, heart failure

Question 30

What presents with "snowstorm" appearance on US

Answer 30

Hydatidiform mole

Question 31

What is another term for endodermal sinus tumor, and what serum marker will be elevated

Answer 31

Yolk sac tumor Elevated AFP

Question 32

Presentation of placenta abruption

Answer 32

* Premature separation of placenta from uterine wall before delivery * Presentation: * Abrupt, painful bleeding in the 3^rd trimester (vs. placenta previa which is painless) * Possible DIC, maternal shock, fetal distress * Life threatening for mother and fetus

Question 33

Differentiate between placenta accreta/increta/percreta and describe general presentation

Answer 33

* Defective decidual later – placenta improperly implants into the myometrium * Presentation: * No separation of placenta after delivery * Postpartum bleeding * Types: * Placenta accreta – placenta attaches to myometrium without penetration * Placenta increta – placenta penetrates into myometrium * Placenta percreta – placent penetrates and perforates through the myometrium * Can attach to rectum or bladder

Question 34

Presentation of placenta previa

Answer 34

* Attachment of placenta to lower uterus over internal cervical os * Presentation: * Painless third trimester bleeding (vs. placenta abrupta which is painful) * Often requires C-section

Question 35

Diagnostic criteria of preeclampsia

Answer 35

HTN: BP \> 140/90 after 20th week of gestation Proteinuria Edema

Question 36

Histology of granulosa-theca cell tumor

Answer 36

* Call-Exner bodies * Granulosa cells arranged haphazardly around collections of eosinophilic fluid, resembling primordial follicles

Question 37

Histology of Sertoli-Leydig cell tumor

Answer 37

Reinke crystals

Question 38

What does HELLP syndrome stand for and what is the reasoning behind the symptoms

Answer 38

* Stands for: * H - Hemolysis (anemia) * EL - Elevated Liver enzymes (RUQ pain, jaundice) * LP - Low Platelets (bruising bleeding) * Preeclampsia + thrombotic microangiopathy * Hemolysis = thrombi causing schistocytes * Liver enzymes = lack of RBCs leads to infarction of liver tissue * Platelets = all used up in thrombi

Question 39

What is Meigs syndrome

Answer 39

Triad of: ovarian fibroma, ascites, pleural effusion

Question 40

Quad screen values in trisomy 21 (AFP, bhCG, estriol, inhibin A)

Answer 40

* Decreased alpha-fetoprotein * Increased b-hCG * Decreased estriol * Increased Inhibin A