April 2 - Heme/onc Flashcards
TGF beta function
1) inhibits inflammatory response by decreasing T cell proliferation and cytokine production
2) wound healing
Pure red cell aplasia
Autoantiboies or self-reactive T cells inhibit red cell precursors and progenitors. Associated with leukemias, thymomas, parvovirus B19 infection
Primary hemochromatosis
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
Uremic platelet dysfunction
Renal failure leads to accumulation of uremic toxins and impaired platelet aggregation and adhesion. Leads to increased bleeding time with normal platelet count
Integrins
Embedded in membrane. Connect to actin cytoskeleton intracellularly and to ECM (fibronectin, collagen, laminin) extraceullarly
RNA interference
SiRNA and microRMA can silence mRNA, preventing translation. MicroRNA forms dicer which plays a role in silencing the mRNA
Wiskott Aldrich inheritance
X linked
Paget’s disease vs inflammatory breast cancer
PAgets: eczematous nipple lesion
Inflammatory breast cancer: rouch orange peel like rash on breast, not just nipple, due to dermal lymphatic invasion. Also edema
Treatment of acute intermittent porphyria
Glucose and heme. Both inhibit ALA synthase which is the rate limiting step in heme synthesis
Ristocetin aggregation test
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
Iron homeostasis: hepcidin and HFE
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
Ganciclovir ADRs
Interfers with host DNA syntehsis mroe than acyclovir does and so can cause bone marrow suppression
Pyruvate kinase
Converts PEP to pyruvate
Splenic red pulp
Removes damaged RBCs from circulation.Hyperplasia in hemolytic anemia.
Pyruvate kinase deficiency
Can’t convert PEP to pyruvate, decreasing ATP in red cells. REsults in cellular swelling and hemolysis
Haldane effect and Bohr effect
Haldane effect: Increased O2 in alveoli increases H+ and CO2 offloading
Bohr effect: increased pCO2/decreased pH in peripheral tissues increases O2 offloading.
Auer rod staining
Stain for peroxidase
West Nile Virus vs enterovirus encephalitis
WNV associated with rash and flaccid paralysis. Aside from polio, enterovirus doesn’t tend to cause falccid paralysis
Pramipexole
Direct dopamine agonist
Cyproheptadine
Serotonin receptor antagonist used to treat severe serotonin syndrome
Cerebral amyloid angiopathy
Causes recurrent spontaneous lobar hemorrhages.
Charcot-bouchard aneurysms
Associated with HTN. Cause hemorrhage into deep brain structures
Loss of quarter of visual field
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
Ataxia telangiectasia
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)
Organophosphates
Irreversible cholinesterase inhibitors
Methylmalonic acidemia
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
BH4
Cofactor in production of tyrosine, dopa, serotonin. Def can cause PKU
Vit A toxicity
Dry skin, HSM, vision problems, pseudotumor cerebri
Restless leg syndrome treatment
dopamine agonist
Pyridoxine
Necessary as cofactor for transamination and decarboxylation of amino acids.
Also necessary for gluconeogenesis
Biotin
Cofactor for carboxylase enzymes.
mRNA processing
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
