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Hemotology Chapter 5
The Erythrocyte
56
Biology
Graduate
10/09/2012

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Term
Stages of erythrocyte maturation
Definition
hematopoietic stem cell (HSC) --> common myeloid precursor cell (CMP) --> colony forming unit (CFU-EMk) --> burst forming unit (BFU-E) --> colony forming unit (CFU-E)
Term
reticulocyte
Definition
cell lacking a nucleus
Term
maturation process of reticulocyte
Definition
After cell extrudes nucleus it has an odd shape so it is remodeled to eliminate excess membrane and acquire biconcave disc shape. It is alive for 2-3 days and spends half of that time in the bone marrow and half in the peripheral blood
Term
Normal Range for reticulocytes
Definition
percentage in peripheral blood is 0.5-2.5%
Term
Erythropoietin (EPO)
Definition
major cytokine for terminal RBC production
Term
function of EPO
Definition
Levels increase when hemoglobin levels drop, secreted in response to cellular hypoxia, constant when hemoglobin levels are normal
Term
origin of production of EPO
Definition
Renal cortical cells
Term
EPO effects on bone marrow
Definition
stimulates the production of RBC from stem cells, allows for more oxygen to be delivered to tissues
Term
erythrocyte membrane functions
Definition
maintain deformability (biconcave shape), elastic extension capability (resume to normal state after being stretched) and permeability (permeable to water and anions, impermeable to cations)
Term
Energy Substrate of the erythrocyte
Definition
ATP
Term
Extravascular erythrocyte destruction
Definition
hemoglobin is broken down in macrophages (spleen, liver and BM) into (1) iron (2) heme and (3) globin. Iron and globin are recycled and heme is catabolized by the macrophages
Term
Hemoglobin catabolism
Definition
Porphyrin ring is cleaved which releases CO (expired) and biliverdin.
Biliverdin is reduced to bilirubin released and bound to albumin, carried to liver and excreted in bile or later in urine
Term
Average dimensions of an erythrocyte
Definition
8 um in diameter, 2 um thick at the edges, 1 um thick in the middle (biconcave)
Term
life span of an erythrocyte
Definition
120 days
Term
function of 2,3-BPG
Definition
produced in the Rapoport-Leubering Shunt via one ATP molecule and is bound by hemoglobin
Term
relationship of 2,3-BPG and erythrocyte
Definition
when hemoglobin binds 2,3-BPG it has a decreased affinity for oxygen and oxygen is released in the tissues
Term
Regulation of Erythrocyte production
Definition
increase in EPO occurs when (1) oxygen delivery to the tissues is impaired (2) low intracellar oxygen
Term
membrane deformability
Definition
due to biconcave shape, stabilizes the viscosity of internal contents of the erythrocyte
Term
membrane permeability
Definition
freely permeable to water and ions, impearmable to cations. Osmotic equilibrium maintained by low permeability to cations, cation pumps and membrane pumps
Term
Mechanisms to regulate permeability to cations
Definition
maintained internally which is different than in the plasma via cation pumps in the membrane (1) Na+/K+ pump and Ca2+ pump
Term
mechanisms to regulate permeability to anions
Definition
the permeability to anions is maintained by the continual uptake of K+
Term
mechanisms to regulate permeability to glucose
Definition
passive glucose transporter
Term
mechanisms to regulate permeability to water
Definition
osmosis
Term
four pathways of erythrocyte metabolism
Definition
(1) glycolysis (2) hexose-monophosphate shunt(3) methemoglobin reductase pathway and (4) rapoport leubering shunt
Term
glycolytic pathway
Definition
erythrocyte obtains energy in the form of ATP from glucose breakdown
Term
Hexose Monophosphate Shunt (HMS)
Definition
maintains reduced glutathione (GSH) which keeps hemoglobin in its reduced funtional state
Term
Methemoglobin Reductase Pathway
Definition
maintains heme iron in the reduced state by reducing MetHemoglobin back to hemoglobin after oxygen dissociates
Term
Rapoport- Leubering Shunt
Definition
allows for production of 2,3-BPG
Term
Key intermediates of the glycolytic pathway
Definition
glucose is metabolized to lactate or pyruvate (recycled), the cell gains 2 ATPs (maintains shape, flexibility, membrane integrity and normal cation levels)
Term
key intermediates of the hexose monophosphate shunt
Definition
generates NADH, maintains reduced glutathione (GSH)(protects cell from oxidative injury by reducing reactive oxygen species)
Term
key intermediates of the methemoglobin reductase pathway
Definition
maintains iron in ferrous, reduced state, methemoglobin (hemoglobin with iron in ferric state), MetHb reductase and NADH reduce ferric back to ferrous
Term
key intermediates of the rapoport-leubering shunt
Definition
BPG mutase catalyzes 1,3-BPG to 2,3-BPG
Term
Glycolytis Pathways relationship to erythrocyte survival
Definition
provides energy for erythrocyte to maintain cell membrane properties. If the membrane cannot maintain those properties the cell becomes sodium and calcium logged (pumps), potassium depleted, water logged and changes to a sphere and removed from circulation
Term
Hexose Monophosphate Shunts relationship to erythrocyte survival
Definition
necessary for mainting hemoglobin in the reduced funtional state, if hemoglobin is oxidized it denatures and precipitates as heinz bodies
Term
Heinz Bodies
Definition
denatured hemoglobin which attaches to the membrane (decreases flexibility) and is removed from the cell by the spleen
Term
Methemoglobin reductase pathways relationship tp erythrocyte survival
Definition
mantains iron in the ferrous state in hemoglobin, if this pathway does not work then methb builds up which limits the oxygen carry capacity of blood
Term
Rapoport-leubering shunts relationship to survival
Definition
allows for the production of 2,3-bpg which is bound by hemeglobin and allows hemoglobin to have a decreased affinity for oxygen and release it into the tissues
Term
Hemoglobin is labeled for destruction when...
Definition
phosphitidylserine (inner leaflet)is exposed on the outer leaflet of the membrane
Term
extra cellular destruction
Definition
most efficient pathway of old RBC removal via hemoglobin break down into iron, heme and globin. Iron and globin are recycled, heme is catabolized by macrophages
Term
intravascular destruction
Definition
hemoglobin is dissociated into dimers and bound to haptoglobin. this complex is carried to the liver and excreted
Term
Intravascular destruction hemolysis levels
Definition
present in: hemoglobinemia, hemoglobinuria, and hemosidrinuria,
Term
extravascular destruction hemolysis levels
Definition
present in: indirect bilirubin and urobilinogen
Term
increased EPO
Definition
stimulates erythropoiesis
Term
decreased EPO
Definition
stimulate erythrocyte destruction
Term
Spectrin
Definition
predominant skeletal protein exists as a heterodimer of two large chains, functions as a spring, coiled tetramers can extend reversibly when the membrane is stretched but cannot exceed their maximum extend length without rupturing
Term
Polychromatophilic erythrocyte
Definition
another name for the reticulocyte because of the bluish tinge with stains due to the residual RNA and mitochondria
Term
Peripheral Proteins
Definition
Found primarily on the cytoplasmic face of the erythrocyte membrane and include enzymes and structural proteins
Term
Normoblast
Definition
erythroblasts with normal maturation
Term
Integral Proteins
Definition
transport proteins and the glycophorins (GPA, GPB and GPC), which are made up of three domains: the cytoplasmic, the hydrophobic and the extracellular
Term
Hemosiderunuria
Definition
when tubular cells loaded with iron are sloughed off and excreted into the urine
Term
Hemosiderin
Definition
complexed iron storage proteins
Term
Hemopexin
Definition
glycoprotein, synthesized in the liver and combines with heme
Term
Haptoglobin
Definition
plasma glycoprotein, present in plasma, carries hemoglobin dimers to liver
Term
Erythroblasts
Definition
nucleated erythrocyte precursors in the bone marrow
Term
Bilirubin
Definition
biliveridin reduced, released from the macrophage, bound to the plasma albumin and carried to the liver
Term
Acanthocytes
Definition
an increase in erythrocyte membrane lipids due to a disproportionate increase in cholesterol results in acanthocytes, reduced survival as compared to normal RBCs
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