Faciliates CO2 transport and pH buffering via Hamberger effect
Site of production
From yolk sac (3-4 weeks gestation)
From liver and spleen (1-7 months gestation)
From marrow (birth onward)
Stimulus for production
EPO stimulates production
\(\downarrow\) Oxygen delivery \(\to\) Hypoxia-Inducible factor 2 in peritubular cells of kidney \(\to\) EPO release \(\to \ \uparrow\)haematopoiesis
Process of production
Takes 7 days
Pluripotent stem cell \(\xrightarrow{mitosis}\) myeloid stem cell \(\xrightarrow{mitosis}\) basophilic erythroblast (because all dna/ribosomes) \(\xrightarrow{mitosis}\) polychromatic erythroblast (because mixed RNA and Hb) \(\xrightarrow{mitosis}\) reticulocyte (ejects nucleus, retains RNA and ribosomes) \(\xrightarrow{maturation}\) reticulocyte (no RNA, only Hb)
Requires iron for haem, and B12 + folate for DNA formation
Breakdown of cells
Survive 120 days, 90% removed by phagocytosis in reticuloendothelial system of spleen and liver, 10% haemolyse intravascularly
(60 days in neonates)
Glutathione from NADPH (from hexose monophosphate shunt) maintains integrity (lost with age, G6PD deficiency)
Breakdown of haem
RBC phagocytosed
Hb broken down into haem and protein
Protein deaminated. Ammonia \(\xrightarrow{\text{urea cycle}}\) urea in liver. \(\alpha\)-keto acids \(\xrightarrow{liver}\) gluconeogenesis or fatty acid synthesis
Haem \(\xrightarrow{\text{haem oxygenase}}\) biliverdin and free ferrous ion
Ferrous ion \(\xrightarrow{transferrin}\) circulates to cells \(\to\) stored as ferritin
Biliverdin \(\xrightarrow{\text{biliverdin reductase}}\) unconjugated bilirubin (lipid soluble), circulates bound to albumin \(\to\) taken up by hepatocytes \(\xrightarrow{\text{UDP glucuronyltransferase}}\) conjugated bilirubin (water soluble)
Conjugated bilirubin actively transported into bile
Bacteria reduce it into urobilinogen; 10% is enterohepatically cycled and excreted in urine, 90% reduced again to stercobilin \(\to\) excreted in faeces