Red Blood Cells Flashcards
What is the development of red blood cells called?
Erythropoiesis
Describe rough process of erythropoeisis
The common myeloid progenitor can give rise to a proerythroblast. This in turn gives rise to erythroblasts and then erythrocytes (red blood cells).
What is required for erythropoiesis?
Iron, Folate, Vitamin B12 and Erythropoietin
How is anaemia caused?
When there is low iron, folate or vitamin B12 levels. Low iron levels result in microcytic cells where cells are smaller than usual and low B12 or folate levels cause macrocytic cells, where cells grow but cannot divide.
What is the role of erythropoietin and how does it work?
Erythropoietin is a growth factor and glycoprotein that is synthesised mainly in the cortical interstitial cells of the kidney in response to hypoxia. In a hypoxic environment, erythropoietin is released from kidney which interacts with erythropoietin receptor on red cell progenitor membrane stimulating bone marrow activity. Increased bone marrow activity leads to increased red blood cell production.
Why is iron important? What can lack of iron cause?
Iron is an important co-factor for enzymes and proteins involved in energy metabolism, respiration, DNA synthesis and cell cycle+apoptosis. 2 major functions include:
- Oxygen transport in haemoglobin
- In mitochondrial proteins cytochromes a, b and c for production of ATP cytochrome P450 for hydroxylation reactions.
Iron deficiency can cause:
spoon shaped deficiency on nails – koilonycihia
Swelling of the tongue - glossitis
Inflammation of the corners of the mouth - angular stomatitis
Where and what type of iron is absorbed?
Iron is absorbed in the duodenum and two forms of iron are found in the diet: Haem iron which is ferrous Fe2+ and the best absorbed form of iron. This is mainly animal derived. Second is non-haem iron which is Fe3+ and mainly derived from plant based food. This requires action of reducing substances like ascorbic acid or vitamin C for absorption. Some foods like soya beans contain phytates which makes absorption difficult.
How is iron homeostasis carried out?
Excess iron is potentially toxic to heart and liver plus there is no physiological mechanism by which iron is excreted. Hence, iron absorption is tightly controlled and only 1-2mg per day absorbed.
Where is iron stored?
At any time, around 3mg present in transferrin in plasma. 300mg stored in bone marrow which is used to make red blood cells and these contain 2500mg of iron in body. Reticuloendothelial system breaks down these red blood cells at end of life (mainly splenic macrophages) and so contains around 500mg. This returns iron to transferrin.
300mg iron stored in myoglobin in muscle and 150g in enzymes. Loss of skin cells results in 1-2mg iron loss everyday.
Liver stores iron as ferritin which is released to bloodstream and taken up from bloodstream. Around 250mg stored here.
1-2mg absorbed from diet everyday in ileum.
How is iron usually absorbed from the duodenum?
- Iron is usually reduced to its ferrous (Fe2+) form by duodenal cytochrome b, before binding the divalent metal transporter 1 (DMT1) on the apical (luminal) membrane of the duodenal enterocyte.
- Iron taken up into the cell is either stored directly as ferritin (which may be lost when the enterocyte dies and is shed into the gut lumen) or oxidised to the ferric (Fe3+) form and transported to the plasma via ferroportin.
What is the effect of hepcidin on iron absorption and when is it released?
When iron stores (ferritin) are full, there is upregulation of hepcidin expression and iron absorption is limited. This binds and degrades ferroportin so iron cannot be absorbed into plasma. This prevents the efflux of iron from the enterocyte, so it is lost when the cell is shed into the gut lumen.
What different factors act on erythropoeisis regulation?
Erythropoeitin increases erythropoiesis. Presence of iron allows erythropoeisis to carry on. Hepcidin decreases erythropoiesis as iron availability, absorption and transport is decreased. Cytokines, interleukins and tumour necrosis factor, as well as mediating their effect via hepcidin, in their increase in inflammation, also directly reduce the production of erythropoietin.
Why are vitamin B12 and folate required?
One of the important requirements of Vitamin B12 and Folate is for the synthesis of thymidine, one of the pyrimidine bases in DNA. The consequences of B12 and folate deficiency overlap, with both inhibiting DNA synthesis. Deficiencies of Vitamin B12 and Folate affect all rapidly dividing cells. In particular this manifests in the bone marrow where cells are able to grow but unable to divide normally, a process known as megaloblastic erythropoiesis. Also affects cells of epithelial surfaces of mouth and gut and gonads.
What are sources of vitamin B12?
Vitamin B12 is found exclusively in food of animal origin, apart from in fortified cereals.
Examples: Meat, Liver & kidney, Fish, Oysters & clams, Eggs, Milk & cheese and Fortified cereals.
What are sources of folate?
Green leafy vegetables, Cauliflower, Brussels sprouts, Liver & kidney, Whole grain cereals, Yeast, Fruit. Western diet usually rich in these.
How is vitamin B12 absorbed?
- B12 is cleaved from food proteins by hydrochloric acid in the stomach and then binds to proteins known as haptocorrins. Bound B12 passes to the duodenum, where it is cleaved from the haptocorrin and binds to the glycoprotein intrinsic factor (IF).
- IF is essential for B12 absorption: it is highly resistant to digestion by gut enzymes and transports B12 to the ileum, where B12-IF complex is absorbed.
- Once in the circulation, B12 is bound to the transport protein transcobalamin.
What can vitamin B12 deficiency result from?
- inadequate intake e.g. veganism
- lack of acid in stomach (achlorhydria) - can be caused by a partial gastrectomy
- inadequate secretion of IF: pernicious anaemia (an autoimmune disorder)
- Malabsorption e.g. coeliac disease
What is the RDA, total body stores and absorption location of folic acid? When do requirements increase?
10 micrograms is RDA. About 10mg stored in body which should last 3 months. Absorbed in small intestine and requirements increases during pregnancy or in disease states where there is increased red blood cell production such as sickle cell anaemia.
How is a red blood cell broken down?
The erythrocyte circulates for 120 days and is ultimately destroyed by the phagocytic cells of the spleen (macrophages). When acted on by reticuloendothelial macrophages, iron is released from the haem ring, and bound to transferrin, returns to the bone marrow to produce more red blood cells. Rest of haem molecule broken down to form bilirubin which is excreted in bile. Globin part is broken down to amino acids.
What is haemopoeisis?
The formation and development of blood cells
What is the common origin of blood cells?
Blood cells of all types originate in the bone marrow.
They are derived from pluripotent haemopoietic stem cells (HSCs) throughout life. The HSCs give rise to lymphoid stem cells and myeloid stem cells, from which red cells (erythrocytes), granulocytes, monocytes and platelets are derived.
Describe intravascular life span of: erythrocytes, neutrophils, monocytes, eosinophils, lymphocytes and platelets.
E: 120 days N: 7-10 hours M: Several days Eo: Little shorter than N L: Very variable P: 10 days
What are the 2 essential characteristics of HSCs?
- Self-renew - some daughter cells remain as HSCs so pool of HSCs not depleted.
- Differentiate to mature progeny - other daughter cells follow a differentiation pathway and are committed to cell type so can’t divide.
How does site of haemopoeisis change through life?
Haematopoeitic stem cells arise from the mesoderm during first 3 weeks of gestation. Primitive red blood cells, together with platelet precursors and macrophages, are initially formed in the vasculature of the extra embryonic yolk sac, before the liver takes over between six and eight weeks of gestation, as the main site of haemopoiesis. Liver then takes over between 6-8 weeks of gestation and is the main source up to birth. Following birth, the bone marrow is the sole site of haemopoiesis in healthy individuals and in children, this takes place in all bones. In adults, restricted to pelvis, femur and sternum.
