The Red Cell
The mature erythrocytes of the human peripheral blood are non – nucleated cells and lack the usual cell organelles . The normal human erythrocyte is a biconcave disc , 7.2 µm in diameter , and has a thickness of 2.4 μm at the periphery and 1 µm in the centre . The biconcave shape renders the red cells quite flexible so that they can pass through capillaries whose minimum diameter is 3.5 μm . More than 90 % of the weight of erythrocyte consist of haemoglobin . The life – span of red cells is 120 days .
NORMAL VALUES AND RED CELL INDICES .
Range of normal red cell count in health is 5.5 ± 1.0 × 10¹2 / L in men and 4.8 ± 1.0 × 10¹2 / L in women . The packed cell volume ( PCV ) or haematocrit is the volume of erythrocytes per litre of whole blood indicating the proportion of plasma and red cells and ranges 0.47 ± 0.07 L / L ( 40- 54 % ) in men and 0.42 ± 0.05 L / L ( 37-47 % ) in women . The haemoglobin content in health is 15.5 ± 2.5 g / dl ( 13 18 g / dl ) in men and 14.0 ± 2.5 g / dl ( 11.5-16.5 g / dl ) in women . Based on these normal values , a series of absolute values or red cell indices can be derived which have diagnostic importance .
RED CELL MEMBRANE .
The red cell membrane is a trilaminar structure having a bimolecular lipid layer interposed between two layers of proteins . The important proteins in red cell membrane are band 3 protein ( named on the basis of the order in which it migrates during electrophoresis ) , glycophorin and spectrin ; important lipids are glycolipids , phospholipids and cholesterol ; and carbohydrates form skeleton of erythrocytes having a lattice – like network which is attached to the internal surface of the membrane and is responsible for biconcave form of the erythrocytes .
A number of inherited disorders of the red cell membrane and cytoskeletal components produce abnormalities of the shape such as : spherocylosis (spherical shape from loss of part of the membrane ) , ovalocytosis ( oval shape from loss of elasticity of cytoskeleton ) , echinocytosis ( spiny processes from external surface due to metabolic abnormalities of red cells ) , and stomato cytosis ( bowl – shaped red cells from expansion of inner membrane on one side ) .
NUTRITIONAL REQUIREMENTS FOR ERYTHROPOIESIS .
New red cells are being produced each day for which the marrow requires certain essential sub stances . These substances are as under :
- Metals . Iron is essential for red cell production because it forms part of the haem molecule in haemo globin . Its deficiency leads to iron deficiency anaemia . Cobalt and manganese are certain other metals required for red cell production .
- Vitamins . Vitamin B₁2 and folate are essential for biosynthesis of nucleic acids . Deficiency of B₁ , or folate causes megaloblastic anaemia . Vitamin C ( ascorbic acid ) plays an indirect role by facilitating the iron turnover in the body . Vitamin B6 ( pyridoxine ) , vitamin E ( toco pherol ) and riboflavin are the other essential vitamins required in the synthesis of red cells .
- Amino acids . Amino acids comprise the globin component of haemoglobin . Severe amino acid defi ciency due to protein deprivation causes depressed red cell production .
- Hormones . As discussed above , erythropoietin plays a significant regulatory role in the erythropoietic activity . Besides erythropoietin , androgens and thyroxine also appear to be involved in the red cell production .
HAEMOGLOBIN . Haemoglobin consists of a basic protein , globin , and the iron – porphyrin complex , haem . The molecular weight of haemoglobin is 68,000 . Normal adult haemoglobin ( HbA ) constitutes 96-98 % of the total haemoglobin content and consists of four polypeptide chains , a B₂ . Small quantities of 2 other haemoglobins present in adults are : HbF containing a 2 globin chains comprising 0.5-0.8 % of total haemoglobin , and HbA₂ having a 8 chains and constituting 1.5-3.2 % of total haemoglobin . Most of the haemoglobin ( 65 % ) is synthesised by the nucleated red cell precursors in the marrow , while the remainder ( 35 % ) is synthesised at the reticulocyte stage .
Synthesis of haem occurs largely in the mitochondria by a series of biochemical reactions. Coenzyme , pyridoxal – 6 – phosphate , derived from pyridoxine ( vitamin B6 ) is essential for the synthesis of amino levulinic acid ( ALA ) which is the first step in the biosynthesis of protoporphyrin . The reaction is stimulated by erythropoietin and inhibited by haem . Ultimately , protoporphyrin combines with iron supplied from circulating transferrin to form haem . Each molecule of haem combines with a globin chain synthesised by polyribosomes . A tetramer of 4 globin chains , each having its own haem group , constitutes the haemoglobin molecule.
RED CELL FUNCTIONS .
The essential function of the red cells is to carry oxygen from the lungs to the tissue and to transport carbon dioxide to the lungs . In order to perform these functions , the red cells have the ability to generate energy as ATP by anaerobic glycolytic pathway ( Embden – Meyerhof pathway ) . This pathway also generates reducing power as NADH and NADPH by the hexose monophosphate ( HMP ) shunt .
- Oxygen carrying . The normal adult haemoglobin , HbA , is an extremely efficient oxygen – carrier . The four units of tetramer of haemoglobin molecule take up oxygen in succession , which , in turn , results in stepwise rise in affinity of haemoglobin for oxygen . This is respon sible for the sigmoid shape of the oxygen dissociation curve .
The oxygen affinity of haemoglobin is expressed in term of P50 value which is the oxygen tension ( pO₂ ) at which 50 % of the haemoglobin is saturated with oxygen . Pulmonary capillaries have high pO₂ and , thus , there is virtual saturation of available oxygen – combining sites of haemoglobin . The tissue capillaries , however , have relatively low po , and , thus , part of haemoglobin is in deoxy state . The extent to which oxygen is released from haemoglobin at pO₂ , in tissue capillaries depends upon 3 factors the nature of globin chains , the pH , and the concentration of 2,3 – biphosphoglycerate ( 2,3 BPG ).
Normal adult haemoglobin ( HbA ) has lower affinity for oxygen than foetal haemoglobin and , therefore , releases greater amount of bound oxygen at pO₂ of tissue capillaries .
A fall in the pH ( acidic pH ) lowers affinity of oxyhaemoglobin for oxygen , so called the Bohr effect , thereby causing enhanced release of oxygen from erythrocytes at the lower pH in tissue capillaries .
A rise in red cell concentration of 2,3 – BPG , an inter mediate product of Embden – Meyerhof pathway , as occurs in anaemia and hypoxia , causes decreased affinity of HbA for oxygen . This , in turn , results in enhanced supply of oxygen to the tissue .
- CO₂ transport . Another important function of the red cells is the CO₂ transport . În the tissue capillaries , the pCO₂ is high so that CO₂ enters the erythrocytes where much of it is converted into bicarbonate ions which diffuse back into the plasma . In the pulmonary capillaries , the process is reversed and bicarbonate ions . are converted back into CO₂ . Some of the CO₂ produced by tissues is bound to deoxyhaemoglobin forming carbamino – haemoglobin . This compound dissociates in the pulmonary capillaries to release CO₂ .
RED CELL DESTRUCTION . Red cells have a mean life – span of 120 days , after which red cell metabolism gradually deteriorates as the enzymes are not replaced . The destroyed red cells are removed mainly by the macrophages of the reticuloendothelial ( RE ) system of the marrow , and to some extent by the macrophages in the liver and spleen. The breakdown of red cells liberates iron for recirculation via plasma trans ferrin to marrow normoblasts , and protoporphyrin which is broken down to bilirubin . Bilirubin circulates to the liver where it is conjugated to its diglucuronide which is excreted in the gut via bile and converted to stercobilinogen and stercobilin excreted in the faeces . Part of stercobilinogen and stercobilin is reabsorbed and excreted in the urine as urobilinogen and urobilin . A small fragment of protoporphyrin is converted to carbon monoxide and excreted in expired air from the lungs . Globin chains are broken down to amino acids and reused for protein synthesis in the body .