RBC CHaPTER 3 Flashcards
OUTER LEAFLET lipids
PC sphingomyelin
inner leaflet lipids
Phos Iniositol, Ethanolamine, and serine
Flippase
maintains leaflet distributionof lipids. In senescent cells PS shifts to outer leaflet marking for destruction
Heinz Body
Deoxygenized nonfunctional hemoglobin bound to band 3.
Spectrin Ratio
horizontal interactions. More tetramers : dimers means more stability.
Ankyrin and Protein 4.2
attach spectrin to Band 3
Protein 4.1
attach spetrin to glycophorin C
Damaged RBCs
give off microvessicles leading to a spherocyte
Echninocytes
Spikey, expansion of outer leaflet
LCAT
esterifies cholesterol, preventing it from becoming part of the reb blood cell membrane. Only unesterified cholesterol in membrane. Leads to acanthocyte
Stomatocyte
expansion of inner leaflet.
Acive transport of calcium
out of cell. Too much Ca2+ causes crosslinking.
Glycolytic Pathway
glucose produces ATP.
Methhemoglobin reductase
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.
erythroblast
morphological distinguishable RBC in marrow with a nucleus
reticulocyte
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.
Reticulocyte stain
Nucleus gone, but remaining blue from RNA and mitochondria.
Siderocytes
reticulocyte or beyond contain iron granules identifiable by Prussian Blue.
Sideroblast
blast with iron deposits
shift or stress reticulocytes
released early.
EPO effects
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
esterified cholesterol
(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).
stomatocyte
expansion inner leaflet
zeta potential
comes from glycophorin extracellular domain glycosylation, repulses RBCs.
band 3
anion exchange protein Cl - HCO3- exchange. Binds Denatured hemoglobin greater than regular.
ankyrin
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.
Kindle Edition.
actin
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
cyanosis
(a bluish discoloration of the skin due to an increased concentration of deoxyhemoglobin in the blood).
epo function
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)
hypocis hif1
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
JAK stat
RBC destruction
accumulation of PS on outer membrane, decreased ATP production and glucose accumulation especially in the spleen leads to osmotic fragility due to decreased cation pump action, oxidized membrane proteins decrease deromability, IGG accumulates on membrane all triggering splenic macrophages.
