1. red cell physiology Flashcards
what is erythropoiesis controlled by what happens what can EPO be used for clinically
erythropoietin- released by peritubular cells in kidney i response to low O2 levels increases number of stem cells committed to erythropoiesis EPO can treat anaemia, renal failure, abuse by athletes
maturation of RBC
the nuclei of immature RBC extruded and taken up by bone marrow macrophage mRNA in reticulocytes allows Hb to still be synthesised reticulocytes may enter blood stream elevated levels retic count may suggest bleeding
how do you measure lifespans of RBC and what can this be useful for
• incubate a sample of blood with 51Cr, which binds to Hb. •Measure disappearance from blood + sites of RBC destruction detected by surface counting. •Useful for haemolytic anaemias - increased disappearance + increased radioactivity at sites of destruction: • Spleen in spherocytosis- abnormal coating in membranes of RBC • Liver in sickle cell anaemia
where does degradation of RBC occur
reticuloendothial system (mononuclear-phagocyte system) of spleen, liver + bone marrow. • Proteins degraded and recycled, iron retained in stores, porphyrin from haem converted to bilirubin in liver.
how can diabetes/ pre diabetes be tested for?
HbA1C: average blood glucose levels- glycated haemoglobin form of Hb covalently bound to glucose. Measured to identify 3 month plasma glucose concentration as RBC life span is 3 months- how much glucose has been exposed to the RBC in the last 3 months
structure of hb
2 components HAEM & GLOBIN Tetrameric: 4 globin chains, each made of polypeptide with a haem prosthetic group Haem: Ferrous iron, Fe2+ at the centre of a protoporphyrin complex The Globin chains linked by non-covalent bonds
adult and fetal hb
Adult haemoglobin (Hb A) contains a2ß2 subunits Fetal Hb contains a2γ2
how is iron absorbed from diet?
Ferrous iron (Fe2+) (if Fe3+ reduced to Fe2+ by stomach acid) –ve effects of antacids, chelation by tetracycline Fe3+ produced by mucosal cells of duodenum. Binds to apoferritin to produce ferritin (stores) Release iron into blood to bind with transferrin (transport) Delivers iron to bone marrow (ferritin stores) Iron in Hb
what happens to iron?
Iron recycled - very efficient (90%) from breakdown of RBCs in liver and spleen Iron uptake in guts increased when iron deficient: erythroid regulator from bone marrow & an iron stores regulator
Oxygen transport
• RBCs carry O2 from lungs to tissues and return CO2 • Ferrous (Fe2+) iron in haem binds O2 • 4 O2s per Hb • Hb is an ALLOSTERIC PROTEIN: operative binding of O2
Oxygen dissociation curve shape
sigmoidal
The Bohr effect
- Acidity enhances the release of O2 from Hb
- Increasing CO2 at constant pH also lowers Hb’s O2 affinity
- Therefore, O2 is more readily given up to metabolically active tissues (which produce H+ and CO2).
2,3-Diphosphoglycerate (DPG)
fetal
when does it increase
- Present in RBCs at same molar conc as Hb
- Reduces O2 affinity of Hb - in its absence Hb would yield little O2 to tissues
- DPG binds to deoxyhaemoglobin to shift equilibrium. Reduces O2 binding
- Fetal Hb unable to bind DPG - hence higher O2 affinity
- DPG increased when arterial O2 reduced chronically (e.g. at altitude, severe COPD) so O2 more readily liberated to tissues
Carboxyhaemoglobin
- Hb has a much greater affinity for carbon monoxide than oxygen - carboxyhaemoglobin
- CO-Hb does not readily dissociate
- Tissue becomes starved of O2
- CO - cigarette smoke so smokers have higher levels of CO-Hb - contributes towards vascular diseases due to smoking
Methaemoglobinaemia
- Iron in Ferric (Fe3+) not ferrous state
- Cannot carry O2
- Patient may be
–Cyanosed
–symptoms of anoxia (dizziness, respiratory distress, tachycardia)
- Hereditary lack of glucose-6-phosphate dehydrogenase, which keeps Hb in reduced state check medication
- May be caused by drugs - e.g. antimalarials, sulphonamides through oxidant stress
