Haem breakdown
- RBC – men (4.7-6.1 x1012/l), women (4.2-5.4 x1012/l)
- Erythrocytes (Er) are produced in the BM, then lose their nucleus but still contain RNA (reticulocytes)
- After 4th day they circulate in blood and after 120 days are phagocytosed and destroyed by spleen (extravascular hemolysis)
- Haemoglobin (Hb) broken into haem ring and globin protein; Fe removed and returned to bone marrow (BM) or iron storage pool
- Biliverdin is transformed to bilirubin (BR), and then circulates to the liver bound to albumin (UCB), which then is conjugated to glucuronic acid in hepatocytes and excreted in bile. Most BR is excreted in stool but small amount is absorbed in ileum and returns to liver via portal vein (this is the source of conjugated BR in plasma)
- Minority of Er go through intravascular hemolysis, the released Hb can have several fates
- Majority of Hb complexes with haptoglobin (PP), this complex is removed from circ by hepatocytes
- Excess Hb can also complex with hemopexin (PP)
Iron absorption, transport and storage
- Absorption
- Mostly in proximal SI (duodenum)
- Store regulator mechanism – control absorption of non-haem Fe from GIT (absorption is inversely proportional to Fe stores)
- Erythroid regulator mechanism – is driven by erythropoeisis (↑erythropoeisis increases Fe absorption)
- Dietary iron
- Haem iron – easily absorbed into mucosal cells as ferrous state (Fe2+) (meat)
- Non-haem iron – is in the ferric state Fe3+, absorbed less easily (vegetables, grains)
- Absorption inhibitors – iron chelators, egg proteins, cow’s milk, achlorhydria
- Absorption facilitators – human breast milk, ascorbic acid
- Iron requirement
- Fe is lost through cells lining the GIT, shed through superficial squamous cells and lost in sweat
- Obligatory iron loss – 1mg/day (men), 2mg/day (menstruating women)
- Increased Fe need – first 18 months of life, adolescent growth spurt, pregnancy (approx 750mg lost during average pregnancy)
- Iron transport
- Transported in plasma by transferrin (PP synth by liver). Each molecule can carry 2 Fe atoms
- Highest concentrations of CSR for iron-transferrin complex is on developing erythroblasts
- Iron storage
- Major sites – macrophages in BM and Kuppfer cells in liver
- 2 storage forms of Fe – ferritin (short- term storage), hemosiderin (long-term storage, not available for immediate use)
- Body iron content – 4g for adult male (smaller in women)
- Iron indices
Erythropoiesis
- Kidney dependent > response to hypoxia / anaemia > EPO (renal cortex)
- Extra medullary haematopoiesis (EPH) performed in liver and spleen when the BM cant supply the body’s demand for blood cells. Seen in many haematological disorders. Marked hepatosplenomegaly is indicative of chronic EMH. It may also be seen on X-ray as hair-on-end appearance.