April 2 - Heme/onc

Question 1

TGF beta function

Answer 1

1) inhibits inflammatory response by decreasing T cell proliferation and cytokine production
2) wound healing

Question 2

Pure red cell aplasia

Answer 2

Autoantiboies or self-reactive T cells inhibit red cell precursors and progenitors. Associated with leukemias, thymomas, parvovirus B19 infection

Question 3

Primary hemochromatosis

Answer 3

AR defect in HFE which regulates iron absorption at enterocyte. HFE normally increases endocytosis of iron transferring complex so can detect iron level and regulate it in enterocyte

Question 4

Uremic platelet dysfunction

Answer 4

Renal failure leads to accumulation of uremic toxins and impaired platelet aggregation and adhesion. Leads to increased bleeding time with normal platelet count

Question 5

Integrins

Answer 5

Embedded in membrane. Connect to actin cytoskeleton intracellularly and to ECM (fibronectin, collagen, laminin) extraceullarly

Question 6

RNA interference

Answer 6

SiRNA and microRMA can silence mRNA, preventing translation. MicroRNA forms dicer which plays a role in silencing the mRNA

Question 7

Wiskott Aldrich inheritance

Answer 7

X linked

Question 8

Paget’s disease vs inflammatory breast cancer

Answer 8

PAgets: eczematous nipple lesion
Inflammatory breast cancer: rouch orange peel like rash on breast, not just nipple, due to dermal lymphatic invasion. Also edema

Question 9

Treatment of acute intermittent porphyria

Answer 9

Glucose and heme. Both inhibit ALA synthase which is the rate limiting step in heme synthesis

Question 10

Ristocetin aggregation test

Answer 10

Measures vWF-dependent platelet aggregation by activating GP1b receptors on platelets that vWF binds to.

Used to distinguish vWF deficiency from GP1b defeciency (Bernard-Soulier syndrome). VWF def corrects with addition of normal plasma to patient’s platelets. Bernard soulier syndrome does not

Question 11

Iron homeostasis: hepcidin and HFE

Answer 11

Hepcidin is secreted by liver when there is high iron or inflammation (hepcidin an acute phase reactant. Removes ferroportin channels to decrease plasma iron by preventing releaes to circulation. Inhibits iron absorption in gut as there are ferroportin channels in the basolateral membrane of enterocytes. Excess iron in the enterocytes gets excreted in feces.

HFE regulates hepcidin production to regualte iron absorption. Mutated in hemochromatosis

Question 12

Ganciclovir ADRs

Answer 12

Interfers with host DNA syntehsis mroe than acyclovir does and so can cause bone marrow suppression

Question 13

Pyruvate kinase

Answer 13

Converts PEP to pyruvate

Question 14

Splenic red pulp

Answer 14

Removes damaged RBCs from circulation.Hyperplasia in hemolytic anemia.

Question 15

Pyruvate kinase deficiency

Answer 15

Can’t convert PEP to pyruvate, decreasing ATP in red cells. REsults in cellular swelling and hemolysis

Question 16

Haldane effect and Bohr effect

Answer 16

Haldane effect: Increased O2 in alveoli increases H+ and CO2 offloading

Bohr effect: increased pCO2/decreased pH in peripheral tissues increases O2 offloading.

Question 17

Auer rod staining

Answer 17

Stain for peroxidase

Question 18

West Nile Virus vs enterovirus encephalitis

Answer 18

WNV associated with rash and flaccid paralysis. Aside from polio, enterovirus doesn’t tend to cause falccid paralysis

Question 19

Pramipexole

Answer 19

Direct dopamine agonist

Question 20

Cyproheptadine

Answer 20

Serotonin receptor antagonist used to treat severe serotonin syndrome

Question 21

Cerebral amyloid angiopathy

Answer 21

Causes recurrent spontaneous lobar hemorrhages.

Question 22

Charcot-bouchard aneurysms

Answer 22

Associated with HTN. Cause hemorrhage into deep brain structures

Question 23

Loss of quarter of visual field

Answer 23

Damage to temporal lobe damages meyer’s loop (outer part) and causes “pie in the sky” defect

Damage to parietal lobe damages inner part of loop and causes “pie on the floor” defect

Question 24

Ataxia telangiectasia

Answer 24

Autosomal recessive mutaiton in ATM gene. Cerebellar atrophy occurs in first few years resulting in ataxia. Telangiectasias develop later on. Repeat sinopulm infections due to immunodef. Increased cancer risk due to decreased DNA repair (Can’t fix stress-induced dsDNA breaks)

Question 25

Organophosphates

Answer 25

Irreversible cholinesterase inhibitors

Question 26

Methylmalonic acidemia

Answer 26

Autosomal recessive deficiency of methylmalonyl coA mutase. Certain amino acids and odd chain fatty acids are converted to propionyl coA and then to methylmalonyl coA. Methylmalonyl coA is converted to succinyl coA which can enter TCA cycle by methylmalonyl mutase with B12 as cofactor.

Propionyl coA and MMA build up resulting in metabolic acidosis. Also get hypoglycemia and ketones and hyperammonemia

Question 27

BH4

Answer 27

Cofactor in production of tyrosine, dopa, serotonin. Def can cause PKU

Question 28

Vit A toxicity

Answer 28

Dry skin, HSM, vision problems, pseudotumor cerebri

Question 29

Restless leg syndrome treatment

Answer 29

dopamine agonist

Question 30

Pyridoxine

Answer 30

Necessary as cofactor for transamination and decarboxylation of amino acids.
Also necessary for gluconeogenesis

Question 31

Biotin

Answer 31

Cofactor for carboxylase enzymes.

Question 32

mRNA processing

Answer 32

5’ cap, 3’ polyA tail, slicing all occur in nucleus.

In cytoplasm, most gets translated by ribosomes, some interacts with P bodies that are involved with mRNA regulation and turnover