Haemopoiesis, Erythropoiesis and Iron Flashcards
What area is the bone marrow limited to in adults?
Pelvis, sternum, skull, ribs, vertebrae
What does the reticuloendothelial system (RES) so and what are the main organs in the system?
Remove old and senescent blood cells
Spleen and liver
Which phagocytic cells are contained in the RES?
Monocytes Macrophages Kupffer cells Tissue histiocytes Microglial cells in CNS
What is the lifetime of red blood cells?
120 days
Different haemoglobin types in an adult and foetus
Adult: alpha and beta
Fetus: alpha and gamma
Control of erythropoesis
- Reduced pO2 detected in interstitial peritubular cells in kidney
- Increased production of erythropoietin (hormone)
- Erythropoietin stimulates maturation and release of red blood cells from marrow
- Haemoglobin rises
- pO2 rises
- Erythropoietin production falls
Ferritin and haemosiderin
Soluble protein that stores iron
Macrophage iron, insoluble
Where does most of the iron in our body come from?
Breakdown of red blood cells
Iron stored in liver cells
95% as ferritin
5% as haemosiderin
What does transferrin do?
Binds to ferrous iron (Fe2+) and transports iron across apical surface of duodenum and upper jejunum
Fe2+ inside the enterocyte can either be:
- Stored as ferritin
- Transported into blood stream
How do babies take up iron?
Have receptors called lactoferrin, which take up iron from milk
What is iron exported out of the cell by?
Ferroportin
How is iron taken into red blood cells (and other cells)?
Binding of iron transferrin complex to transferrin receptor (TfR)
What enhances and inhibits the absorption of iron?
Enhances - vitamin C, ascorbic acid
Inhibits - tea, calcium/potassium
Control mechanism of iron absorption
- Regulation of transporters
- Expression of receptors e.g. HFE and transferrin receptor
- Hepcidin and cytokines
- Crosstalk between epithelial and other cells like macrophages
Hepcidin
- Binds to ferroportin to prevent iron from leaving enterocyte and entering blood stream
- Secreted by the liver
- Hepcidin production is decreased by high erythropoietic activity
What is hepcidin regulated by?
HFE
Transferrin receptor
Inflammatory cytokines
Physiological effects of anaemia
- Tiredness
- Reduced oxygen carrying capacity
- Cardiac symptoms e.g. angina, palpitations, development of heart failure
Signs of anaemia
- Pallor
- Tachycardia
- Increased respiratory rate
- Epithelial changes
Iron deficiency sign: hypochromic
Low haemoglobin content
Iron deficiency sign: microcytic
Low mean cell volume
Iron deficiency sign: anisopoikilocytosis
Changes in size and shape
Signs of iron deficiency
- Hypochromic
- Microcytic
- Anisopoikilocytosis
- Low serum ferritin
- Low Reticulocyte Haemoglobin Content (CHR)
Test for iron deficiency
Ferritin (acute phase protein so increased with inflammation etc), CHR (also low in patients with thalasaemia)
Why is excess iron dangerous?
Fe2+ can produce highly reactive hydroxyl and lipid radicals
Haemochromocytosis causes:
Liver cirrhosis, diabetes mellitus, hypogonadism, cardiomyopathy, arthropathy and skin pigmentation
hereditory Haemochromocytosis
- Autosomal recessive
- Mutation HFE gene
- Normally HFE protein competes with transferrin for transferrin receptor
- Mutated HFE cannot bind
- Treat with venesection (regular removal of blood)
Which transporter protein facilitates the uptake of non-haem ferrous iron (Fe2+)?
Divalent metal transporter 1
What is ferric iron reduced to ferrous iron by?
Duodenal cytochrome B reductase (DcytB)
Organs most susceptible to damage in hemochromatosis
Liver, adrenal glands, heart, joints and pancreas
Anaemia of chronic disease caused by:
Chronic inflammatory conditions. Increased activity of macrophages reduce the lifespan of red blood cells and signalling through the erythropoietin receptor is blunted. Furthermore, the chronic release of cytokines such as IL-6 increase the production of hepcidin by the liver resulting in less iron absorption.
Why might alcoholics develop a folate deficiency?
Inadequate intake and damage to intestinal cells
