Hema/Onco 1 Flashcards
What are the 2 major effects of carbon monoxide on O2 delivery?
> CO reduces number of available heme binding sites for O2 – inc. HBCO, dec. O2 carrying capacity, dec. O2 content of blood
Dec. tendency for O2 to unload in tissues – left shift of O2 dissociation curve, w/ a more pronounced shift as HBCO concentration increases (unlike in anemia)
Why does HbS have a more pronounced clinical manifestation than HbC?
HbS has a glutamate to valine substitution, and since Val is nonpolar (neutral), it initiates hydrophobic interactions, causing aggregation of hemoglobin. HbC has a glutamate to lysine substitution, and since Lys has a polar positive charge, there is no aggregation.
Positive selection vs. Negative selection of T cells
> Positive: T cells w/ a TCR that can bind to self-MHC are allowed to survive (thymic cortical epithelial cells).
Negative: after positive selection, eliminates T cells w/ TCRs that bind too strongly to self-Ags or self-MHCs (thymic medullary epithelial or dendritic cells)
What is the Kozak consensus sequence?
> (gcc)gccRccAUGG – R is Adenine or Guanine and is placed 3 positions upstream from AUG.
This sequence is required to initiate eukaryotic translation and precedes the start codon.
Describe the molecular shifts that occur when O2 is loaded onto and unloaded from Hgb.
[include HCO3, H+, Cl; Bohr-Haldane effect]
> In lungs, the loading of O2 drives release of H+ and CO2 from Hgb (oxygenated form) – along w/ O2, HCO3 shifts back into RBC in exchange for Cl; CA converts H+ and HCO3 to CO2 + H20.
In peripheral tissues, CO2 and H+ facilitate O2 unloading (deoxy form) – CO2 converted to HCO3 and H+; HCO3 shifts out in exchange for Cl, H+ stays in RBC.
How does Hepcidin regulate iron homeostasis?
Ferroportin transfers intracellular iron into the circulation. When hepcidin interacts w/ ferroportin, the ferroportin is degraded and there is dec. intestinal iron absorption and dec. release from macrophages.
What causes increase/decrease of hepcidin levels? How do hepcidin levels affect regulation of iron?
> Increase: High iron levels, inflammation – dec. iron absorption, no release from macrophages.
Decrease: hypoxia, inc. EPO – inc. iron absorption, stimulate iron release from macrophages.
Why do patients w/ massive blood transfusions (>5L of blood) experience paresthesias?
Prior to storage, whole blood and pRBCs are mixed w/ a citrate anticoagulant solution. Infused citrate can chelate serum calcium, causing hypocalcemia, w/c may result in paresthesias.
What type of immunodeficiency is seen in Wiskott-Aldrich syndrome?
WAS is a combined B cell and T cell disorder. Since there is no humoral response, patients are prone to infection by encapsulated organisms. A T cell defect will also make them susceptible to opportunistic infections (P. jirovecii, herpes virus).
What kind of mutation is seen in Follicular Lymphoma?
A t(14;18) translocation moves the Bcl-2 proto-oncogene near an Ig enhancer element on chromosome 14. The resultant overexpression allows for B cell immortality.
Acute intermittent porphyria attacks are caused by what enzyme deficiency?
AIP attacks result from accumulation of aminolevulinate and porphobilinogen due to inherited PBG deaminase deficiency combined w/ ALA synthase induction (from meds, alcohol, etc). PBG deaminase deficiency alone is generally not enough to develop AIP attacks.
