Flashcards in RBC CHaPTER 3 Deck (42):
OUTER LEAFLET lipids
inner leaflet lipids
Phos Iniositol, Ethanolamine, and serine
maintains leaflet distributionof lipids. In senescent cells PS shifts to outer leaflet marking for destruction
Deoxygenized nonfunctional hemoglobin bound to band 3.
horizontal interactions. More tetramers : dimers means more stability.
Ankyrin and Protein 4.2
attach spectrin to Band 3
attach spetrin to glycophorin C
give off microvessicles leading to a spherocyte
Spikey, expansion of outer leaflet
esterifies cholesterol, preventing it from becoming part of the reb blood cell membrane. Only unesterified cholesterol in membrane. Leads to acanthocyte
expansion of inner leaflet.
Acive transport of calcium
out of cell. Too much Ca2+ causes crosslinking.
glucose produces ATP.
protects hemoglobin from oxidation via NaDH and MHR.
Hexose monophosphate shunt
provides NADPH and GSH to reduce oxidants
Rppoport Leubering Pathway
Produces BPG o affect hemoglobin oxygen affinity
RBC progenator development
BUFE-> CFU E. BFU E responds to IL3 and GMCSF. CFU-E responds EPO.
morphological distinguishable RBC in marrow with a nucleus
pinched off nucleus
4 RBC blast stages
pronormoblast, basophillic normoblast, polychromatophillic normoblast, orthochromic normoblast
RBC development characteristics
decrease in N:C ration, initially nucleus is all of pronormoblast. Lacey to compact and darker. BLuish and basophillic to pink and acidophillic due to presence of hemoglobin.
Nucleus gone, but remaining blue from RNA and mitochondria.
reticulocyte or beyond contain iron granules identifiable by Prussian Blue.
blast with iron deposits
shift or stress reticulocytes
stimulates bfu and cfu to divide and mature. increases rate of hemoglobin and mRNA generation. decreasesnormoblast maturation time. increases rate of enuclation. stimulates shift reticulocytes.
Extravascular hemoglobin destruction pathway
Heme + globin -> biliverdin + CO + Fe -> billirubin > billirubin - Albumin -> to liver. Bilirubin diglucornide -> urobilinogen -> stoolor blood and kidney.
compare contrast cfu e bfu e
bfu e more quiescent higher prolifertive capacity, more responive to early acting cytokines IL 3 GMCSF, cfu e more responsive to EPO
normal reticulocyte concentration
.5-2% RBC in peripheral blood
(LCAT). Esterified plasma cholesterol cannot exchange with the red cell membrane. When LCAT is absent (congenital LCAT deficiency or hepatocellular disease), free plasma cholesterol increases, resulting in accumulation of cholesterol within erythrocyte membranes and RBC membrane surface area expansion. An excess of cell membrane due to proportional increases in cholesterol and phospholipids, maintaining the normal ratio, results in the formation of macrocodocytes (large target cells).
expansion inner leaflet
comes from glycophorin extracellular domain glycosylation, repulses RBCs.
anion exchange protein Cl - HCO3- exchange. Binds Denatured hemoglobin greater than regular.
is a large protein that serves as the high-affinity binding site for the attachment of spectrin to the inner membrane surface. Ankyrin binds spectrin near the region involved in dimer–tetramer associations. In turn, ankyrin is bound with high affinity to the cytoplasmic portion of band 3 (the anchor for the membrane skeleton). 15 Band 4.2 binds to ankyrin and band 3, strengthening their interaction and helping to bind the skeleton to the lipid bilayer at its major attachment point.
These short filaments are stabilized by their interactions with other proteins of the red cell skeleton including tropomodulin, adducin, tropomyosin, and band 4.9. Spectrin dimers bind to actin filaments near the tail end of the spectrin dimer. Band 4.1 interacts with spectrin and actin and with GPC in the overlying lipid bilayer. It serves to stabilize the otherwise weak interaction between spectrin and actin and is necessary for normal membrane stability. 8 This complex of spectrin, actin, tropomodulin, tropomyosin, adducin, band 4.9, and band 4.1 serves as the secondary attachment point for the red cell skeleton, binding to GPC of the membrane.
RBC ion concentration
very low sodium and calcium compared to plasma, higher potassium magnesium
(a bluish discoloration of the skin due to an increased concentration of deoxyhemoglobin in the blood).
Stimulates BFU-E and CFU-E to divide and mature Increases rate of mRNA and protein (hemoglobin) synthesis Decreases normoblast maturation time Increases rate of enucleation (extrusion of nucleus) Stimulates early release of bone marrow reticulocytes (shift reticulocytes)
hypoxia trggers HIF1 ginds to EPO promoter element
main EPO function
progenators which require high EPO die, but during hypoxia are rescued from apoptosis
EPO signaling cascade