red cell physiology Flashcards
control of erythropoiesis
essential to maintain RBC level.
controlled by erythroprotein-polypeptide hormone. released by particular cells in kidney- in response to hypoxia [low oxygen].
increases the number of stem cells committed to erythropoiesis. recombinant erythroprotein (EPO) used clinically to treat anaemias associated by renal failure.
maturation of erythrocytes
immature RBC- nucleus extruded and taken up by bone marrow macrophages. mRNA in reticulocyte allows haemoglobin to still be synthesised. The reticulocyte may enter blood stream. retic count elevated when erythropoieses is increases: bleeding? heamolysis?
measurement of RBCs
lifespan 120 days.
incubate sample of blood with 51Cr, which binds to Hb. measure disappearance from blood and sited of RBC destruction detected by surface counting. useful for haemolytic anaemias- increased disappearance and increased radioactivity at sites of destruction: spleen in spherocytosis, liver in sickle cell anaemia.
degradation of RBCs
occurs in the reticuloendothelial system [mononuclear-phagocyte system] of spleen, liver and bone marrow. proteins degraded and recycled, iron retained in stores, porphyrin from haem converted to bilirubin in liver
structure of haemoglobin
RBC- 640 million molecules of Hb. 2 components- HAEM & GLOBIN.
tetrameric: 4 globin chains, each made of polypeptide with a haem prosthetic group.
Haem: Ferrous ion, Fe2+ at the centre of a protoporphyrin complex.
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 aplha2beta2 subunits. Fetal Hb contains aplha2gamma2
iron
from diet. ferrous iron (Fe2+). (Fe3+ reduced to Fe2+ by stomach acid] --> 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. iron recycled 90%
oxygen transport
1L of plasma- 3ml of O2. 1L of plasma- 195ml of O2.
FBCs carry O2 from lungs to tissues and return to CO2. ferrous [Fe2+] iron in haem binds to O2. 4 x O2’s per Hb.
Hb as an allosteric protein
the binding of 1 O2 enhances, by conformational change, the binding of another O2 to another haem in the same molecule
the bohr effect
acidity enhances the release of O2 from Hb. increasing CO2 at constant pH also lowers Hb’s oxygen affinity. therefore O2 is more readily given up to metabolically active tissues, which produce H+ and CO2
2,3-Diphosphoglycerate [DPG]
present in RBCs at same molar conc as Hb. reduces O2 affinity of Hb- without it little O2 would make it to tissues. DPB binds to deoxyhaemoglobin to shift equilibrium. reduces O2 binding. fetal Hb unable to bind to DPG- hence higher O2 affinity. DPG increased when arterial O2 reduced chronically, so O2 more readily liberated to tissues.
carboxyhaemoglobin
Hb has much higher affinity for carbon monoxide than oxygen- carboxyhaemoglobin. CO-Hb does not readily dissociate. tissue becomes starved of O2. e.g. in cigarette smoke.
methaemoglobinaemia
iron in Ferric (Fe3+) not ferrous state cannot carry O2. patient may be cyanosed, symptoms of anoxia. Hereditary lack of glucose-6-phosphate dehydrogenase, which keeps Hb in reduced state. may be caused by drugs
carbon dioxide transport
10% dissolved. 30% bound to Hb- combines to form carbaminohaemoglobin. 60% as HCO3-.
CO2 + H2O —> HCO3- + H+. catalysed by carbonic anhydrase in RBC.
Hb buffers H+.
HCO3- may leave cell, Cl- enters [chloride shift] to maintain change
respiratory reflex: chemoreceptor reflexes.
monitor the P co2, P o2, and pH in the blood at the aortic and carotid bodies] and the CSF [at the medulla oblongata.
