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Red blood cells.

Creation, function and destruction.

How much blood should a 70kg adult have and of what proportions? 5L blood volume of which 40% cells and 60% plasma.
How many times more numerous are RBC than WBC? x500- approximately 2.4x10^13.
How often do RBC need to replace? RBC need to replace 1% per day to make up for expected lifespan of 100 days.
What does the biconcave disc and no nucleus allow the RBC to have? Pliable, high surface area/volume.
What does the RBC contain inside it? Bag of haemoglobin and enzymes for glycolysis- unable to divide or make new proteins.
How does the RBC prevent oxidation? By maintaining membrane integrity.
What forms "blood islands"? Embryological stem cells form blood islands in the yolk sac.
What is the cell pathway in the foetus? Cells migrate to liver then spleen then bone marrow in foetus.
How does the distribution of bone marrow change as we grow? At birth bone marrow is widely distributed, retreating to axial skeleton by adulthood.
What are the growth factors associated with RBCs? Interleukin 3, erythropoietin, androgens and thyroxine.
What is in the stroma of bone marrow? Fibroblasts, macrophages, endothelium and fat cells.
What is a reticulocyte? An immature RBC.
What is reticulin? Remnants of mRNA left once the nucleus of a maturing RBC has been extruded. Removed by the spleen in 1-2 days.
What can reticulocyte numbers be used to measure? A useful measure of marrow response to anaemia or treatment.
What can be used to stain reticulocytes? New methylene blue on slide.
How much iron to adults have and where is most of it? 3000-5000mg of iron of which 2/3 is in haemoglobin.
Where is Fe++ transported to? Transported into duodenal enterocytes.
What regulates iron absorption and release? Hepcidin regulates iron absorption and release from macrophages- increased in inflammatory disease hence less available iron.
Is there a mechanism to excrete iron? No.
How can humans lose iron? Menstrual loss, minor trauma, GI, blood sampling and very small amounts in urine and skin shedding.
What is the function of transferrin? Glycoprotein found in the blood plasma, that is capable of binding iron and thus acts as a carrier of iron in the bloodstream.
What is the function of ferritin? An iron-protein complex that is one of the forms of which iron is stored in the tissues (insoluble).
What is the daily requirement of folic acid/folate? 0.1mg.
Where is folate absorbed? Upper small bowel.
Where is folate stored and how much is stored? In the liver (10-20mg).
What is folate and its function? B vitamin that is important in the synthesis of nucleic acids.
What is the daily requirement of B12/cobalamin? 1 microgram, all from animal derived products.
What produces the "intrinsic factor" and what does it do? Gastric parietal cells. It binds to B12.
Where is B12 absorbed? In the terminal ileum.
What is B12 transported on? Transcobalamin II via portal circulation to the liver.
Why do RBC need B12? Required in change from 5 methyl tetrahydrofolate (THF) to THF. Further change to 5,10 methelene THF which catalyses conversion of uridine to thymidine.
What is erythropoietin? A hormone secreted by certain cells in the kidney in response to a reduction in the amount of oxygen reaching the tissues.
What controls erythropoiesis? Erythropoietin increases the rate of RBC production (erythropoiesis) and is the mechanism which controls erythropoiesis.
What is the structure of erythropoietin? Glycosylated 165 amino acid protein- renal 90%, liver 10%.
What are the medical uses of erythropoietin? Useful recombinant drug for renal anaemia and myelodysplasia (increase drive to erythropoiesis).
What switches on production of erythropoietin? Tissue hypoxia or anaemia, high altitude and epo producing tumours e.g. renal.
What is hypoxia? Deficiency of oxygen in the tissues.
In terms of hormones, what happens at low oxygen levels in tissues? mRNA for epo is increased and epo is produced.
What is spherocytosis? The presence in the blood of abnormally shaped red cells.
What does haemoglobin need to form? 2 alpha (zeta in foetus) chains and 2 beta chains.
What chromosome codes for the alpha chains? Chromosome 16.
What chromosome codes for the beta chains? chromosome 11.
What is Thalassaemia? An inherited defect in globin chain production.
What causes sickle cells disease? One amino acid change in the beta chain.
Why do RBCs need enzymes? For a glycolytic pathway ending with lactate and pyruvate providing energy.
What is energy needed for in RBCs? Maintain membrane integrity, prevent oxidation of enzymes and Fe++ and to maintain gradients of K+ and Ca++.
What would cause a oxygen dissociation curve to shift to the right? Acidosis and increased temperature will cause a right shift and hence deliver more O2 to tissues.
What does 2,3 diphosphoglycerate do? An intermediate step in glycolysis produces a right shift of O2 dissociation curve hence more released in the tissues.
When is 2,3 DPG increased? Exercise, anaemia and high altitude.
What is myoglobin? An iron-containing protein found in muscle cells- acts as a store for O2 for immediate use. One haem unit, one globin chain.
What is the normal blood pH? 7.35-7.45.
Why is acidosis important for enzymes? They work optimally at physiological pH.
What happens to cell membranes in acidosis? They become leaky.
What happens to neurones in acidosis? Become less able to transmit in acidosis- hyperactive in alkalosis.
What is the bicarbonate buffer equation? CO2+H2O--->H2CO3---->(H+)+HCO3-
What happens to the buffer equation is there is a decrease in pH? A decrease in pH will drive the equation to the left.
What are the buffer equations catalysed by? Carbonic anhydrase.
What is the buffer capacity of haemoglobin? 30%.
In terms of H+ what happens to haemoglobin after it loses its oxygen? It combines with H+ and the low pH decreases haemoglobin affinity for O2.
What happens to the RBC as it ages? Membrane becomes more rigid. Loss of glycolytic enzymes. Neoantigents exposed on cell surface.
What happens to old RBCs? Some RBC lost from GI tract/into soft tissues/menstrual loss. Some RBC destroyed within body.
What "mops up" free haemoglobin? Haptoglobin- cleared by the liver. Any excess can appear in urine.
What happens to the globin once the RBC is destroyed? Globin chains broken into AAs.
What happens to the iron once the RBC is destroyed? Iron bound to transferrin and returned to macrophages.
What happens to the porphyrin ring once the RBC is destroyed? Becomes bilirubin- bound to albumin and "conjugated" to glucuronide and then excreted in the bile.
Created by: robertspedding



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