This module deals with
- Functions and composition of erythrocytes
- Shape, structure and size of erythrocytes
FUNCTIONS OF ERYTHROCYTES
- Transport hemoglobin which in turn carries oxygen from the lungs to the
- RBCs contain large quantity of carbonic anhydrase which catalyzes the reversible reaction between carbon dioxide and water. Thereby makes it possible for the water of the blood to transport enormous quantities of carbon dioxide from the tissues to the lungs in the form of
- Hemoglobin in the cells is an excellent acid base buffer. Therefore, the RBCs are responsible for most of the acid base buffering power of whole blood
SHAPE OF RBC
- The mammalian RBCs are usually non-nucleated and non-motile cells, biconcave circular disc with central pale spot. Its shape differs in various species of animals:
- Dog, Cow, Sheep: Markedly biconcave.
- Horse and cat: Shallow concaving,
- Goat: Very shallow or flat surfaced
- Camel and Deer: Elliptical and sickle
- Cold blooded animals (amphibians and birds): Elliptical and
Significance of biconcavity of RBCs
- It increase the surface area thus facilitating the exchange of oxygen and carbon dioxide carried by the
STRUCTURE OF RBC
- The cell membrane of RBC is made up of lipids (lecithin, cephalin and cholesterol) and glycoprotein encloses a spongy inner structure called the stroma.
- The RBC membrane protein, Spectrin forms the inner lining of the membrane, whereas the outer layer is formed by glycoproteins, have the blood group antigens. The cell membrane is highly permeable to lipid soluble substances, glucose, urea and
- Hemoglobin is deposited in the inter-spaces of the spongy stroma. The surface of mature erythrocyte is smooth, while the immature RBCs have relatively rough
SIZE OF RBC
- Average diameter of RBC ranges from 4.1 to 7.5 µm .
|Species||Size (µm )|
- Surface area‚ varies from 57-67m2/ kg body weight in It is lowest in goat (lesser diameter) and highest in man (greater diameters).
COMPOSITION OF ERYTHROCYTES
- Erythrocyte contains 62 – 72% water and 35% solids. Of the solids, 95% is contributed by Hb and the remaining 5% by cell and stromal protein, lipids, phospholipids, cholesterol, cholesterol esters, neutral fat and
Energy is required for RBCs to
- To maintain the shape and flexibility of the cell
- To preserve high K+, low Na+ and low Ca++ ions within the RBCs against the concentration gradient of these ions of
- To maintain iron in ferrous (Fe++) state (to reduce ferric to ferrous state, NADH and NADPH are required).
- To generate reduced glutathione (anti-oxidant); this helps to maintain the ferrous
- To generate 2,3 Diphospho glycerate (DPG) for O2
- Mitochondria are absent in mature erythrocytes. These cells derive their energy from glucose metabolism via anaerobic Embden- Meyerhoff (EM) pathway (90%) and oxidative pentose cycle (10%) which produce NADH and Kreb’s cycle is very much reduced in activity.
CONCENTRATION OF RBCs
- The concentration of RBC depends on various factors such as interspecies, intraspecies and diurnal variation, age, sex, environment, exercise, nutritional status, climate and altitude.
Concentration of RBC in domestic animals (millions/ mm3 of blood)
|Species||Concentration of RBC|
|Fowl||3.0 (2.8 – 3.2 )|
|Pig||6.5 (5.8- 8.0)|
ABNORMALITIES OF RBC CONCENTRATION
- This module deals with
- Abnormalities of RBC concentration
- Erythrocyte indices
ABNORMALITIES OF RBC CONCENTRATION
- It is otherwise known as It is a condition of increased number of RBCs in the circulation. It is of two types.
- Physiological (secondary) polycythemia
- An increase in RBCs occurs as a compensatory measure (in high altitude of 14000 to 17000 feet to compensate low PO2). Whenever tissues becomehypoxic because of too little oxygen in the atmosphere, for example at high altitude or because of failure of delivery of oxygen in the tissues as in cardiac failure, then the blood forming organs automatically produce large quantities of extra RBCs i.e 30% above the
- Increased Hb requirement during heavy muscular exercise to meet increased oxygen demand. In sports animals (racehorse, hunting dogs) RBC elevation is a normal
- Increased environmental stress / temperature, the spleenic contraction, and increased RBC synthesis by the bone marrow cause increased number of RBCs into the
- Hemoconcentration due to water loss that occurs in vomiting, diarrhoea, prolonged high fever and burns also causes
- Pathological polycythemia
- Due to decreased O2 supply to the tissue, chronic carbon monoxidepoisoning, myeloid (bone marrow) cancer, pulmonary emphysema, repeated
- Polycythemia vera is the condition due to bone marrow cancer (myeloid leukemia). It occurs as a result of genetic aberration in the hemocytoblastic cell line that produces the blood cells.
- Reduction in the number of erythrocytes in the circulation is called as oligocythemia
- Physiological oligocythemia occurs due to hemodilution; RBC number per unit volume is reduced. Example: pregnancy.
- Pathological oligocythemia is also known as anaemia.
- Abnormal reduction in the number of the erythrocytes or the hemoglobin content in the blood or both.
- Excessive whole blood loss occurs in hemorrhage or by blood sucking parasites (Hookworms, ticks), increased destruction of RBCs by the reticuloendothelial
- Impaired RBC production and Hb synthesis, due to deficiency of Fe, Cu, Vitamin B12 and folic
- Disease caused by blood parasites, (babesiosis) or drugs like sulphanamides, antimalarial drugs and high doses of aspirin (analgesic)
Anemia due to defective blood formation:
- Aplastic anemia
- It occurs due to lack of functional bone marrow caused by excessive x-ray treatment or bone marrow cancer, certain industrial chemicals, drugs etc.
- Anemic anemia
- Megaloblastic anemia:
- It is due to deficiency of iron, folic acid, Vitamin B12 (extrinsic factor) andintrinsic factor of the gastric
- Microcytic and hypochromic anemia:
- It results due to deficiency of iron results in small sized, decreased number of RBCs and low Hb
- Macrocytic and hyperchromic anemia:
- Lack of extrinsic factor, the Vitamin B12 causes decreased number of RBCs,large sized RBCs and high Hb content because the erythroblasts cannot proliferate rapidly enough to form normal number of RBCs, the cells that are formed are mostly oversized, bizarre in shape and have a fragile membrane.
- Pernicious anemia:
- It occurs due to the deficiency of the intrinsic factor of the gastric mucosa that interferes with the Vitamin B12
- Megaloblastic anemia:
Anemia due to excessive blood loss or increased RBC destruction:
- Excessive blood loss due to accident, peptic ulcers
- Hemolytic anemia:
- Following acute destruction of RBCs (haemolysis) the number of RBCs is below normal, but the RBC size and Hb content are normal, known as normocytic and normochromic anemia.
- Blood parasites: babesiosis, theileriosis and trypanosomiasis;
- Chemicals: Copper, lead, nitrate and nitrite.
Anemia due to abnormal structure of RBC:
- In some hereditary diseases the defects are with the RBC membrane – e.g., sickle cell anemia, defects in the globin chain structure (thalassemia) or its synthesis or the deficiency of the enzymes of the RBCs energy system, the pyruvate kinase and glucose 6 phosphate dehydrogenase (G.6-PD).
- Sickle cell anemia:
- In this type of anemia the cells contain an abnormal type of hemoglobin called as Hb “S”. It is caused by abnormal composition of β chains of the hemoglobin.
- When this type of hemoglobin is exposed to low concentration of oxygen it precipitates into long crystals inside the erythrocytes. These crystals elongate the cell and it gives the appearance of sickle
- The precipitated hemoglobin also damages the cell membrane so that the cells become highly fragile leading to
- It is otherwise known as Cooley’s anemia or Mediterranean anemia. It occurs due to defect in the synthesis of α or β peptide chains to form hemoglobin or due to deficiency of enzymes of the RBC energy system, pyruvate kinase and G-6-PD thereby depressing the hemoglobin synthesis.
- Sickle cell anemia:
- These indices help in the diagnosis various types of anemia (microcytic vs. macrocytic or normocytic).
- Mean Corpuscular Volume (MCV):
- It expresses the average cell size of the erythrocyte.
- Mean Corpuscular Hemoglobin (MCH):
- It gives the average weight of Hb present in the
- Mean Corpuscular Hemoglobin Concentration (MCHC):
- It is the average percentage of the mean corpuscular volume that the Hb occupies.
NORMAL RANGE OF ERYTHROCYTE INDICES IN DOMESTIC ANIMALS
|Species||MCV (fl)||MCHC (%)||MCH (pg)|
|Dog||60-77 (70)||32-36 (34)||20-24|
|Cat||39-55 (45)||30-36 (33)||13-17|
|Cow||40-60 (52)||30-36 (33)||19|
|Sheep||23-48 (33)||31-38 (33)||10-14|
|Goat||15-30 (23)||35-42 (38)||8|
|Horse||34-58 (46)||31-37 (35)||18|
|Pig||50-68 (63)||30-34 (32)||16-20|
- This module deals with lifespan and fate of erythrocytes.
LIFE SPAN OF ERYTHROCYTES
- Life span of erythrocytes (days)
SITE OF DESTRUCTION OF ERYTHROCYTES
- In most of the domestic animals bone marrow functions as a chief site of destruction of erythrocytes, whereas in man it is the
- In the birds liver acts as an organ of destruction of erythrocytes.
FATE OF ERYTHROCYTES
- The erythrocytes have a remarkable capacity to change their shape when they pass through the capillaries but they become less deformable when they reach the end of their life
- Two types of destruction of erythrocytes takes place,
- Intravascular hemolysis
- Extravascular hemolysis
- About 10% of aged RBCs undergo intravascular hemolysis within the capillaries due to loss of compressibility of RBCs caused by increased membrane permeability and osmotic change.
- When this occurs the hemoglobin is released, which combine with haptoglobulin which is removed by the cells of the mononuclear phagocytic system (MPS).
- About 90% of the aged RBCs are directly destroyed by the mononuclear phagocytic system (MPS).
- The Hb and proteins are catabolised by the MPS cells. The MPS (also known as reticulo- endothelial system) includes the histiocyte or macrophages, stellate or Kupffer cells of the sinusoids of the liver, spleen, mononuclear cells of bone marrow and lymph
- The globin of the Hb is degraded to amino acids and is reutilized. Iron removed from the heme is stored in the MPS cells in the form of ferritin or hemosiderin and utilised for the synthesis of hemoglobin or enters the plasma and combine with apotransferrin to form transferrin. The transferrin enters the bone marrow to produce more
- The heme is converted to bile pigments, biliverdin (a green pigment) and then reduced to bilirubin (a yellow pigment). The free bilirubin enters the plasma, binds with albumin and transported to liver. In the liver bilirubin is conjugated with glucuronic acid, secreted in bile to enter intestine. Large intestinal bacteria reduce the bilirubin to urobilinogen, most of that are excreted in feces in the oxidised form of urobilin or stercobilin which impart colour to
- Part of the urobilinogen is reabsorbed into the enterohepatic circulation and reexcreted in bile. Some of the urobilinogen in the plasma enters the kidneys to be excreted in urine as urobilin.
- Globin protein portion of hemoglobin is broken down to amino acid and used in the formation of new hemoglobin or other
Hemolysis caused by external agents like
- Blood parasites: Babesiosis, theileriosis, trypanosomiasis and
- Chemicals: Copper, lead, nitrate and nitrite
- This module deals with
- Regulation of erythropoiesis
- It is the processes of formation of erythrocytes, leukocytes and platelets in the body. Formation of erythrocytes and leukocytes respectively are known as erythropoiesis and leukopoiesis.
- During embryonic state the blood islands of pander of the yolk sac functions as a site of hematopoiesis. The mesenchymal cells of the liver, spleen, bone marrow and lymph glands are the hemopoietic organs in early fetal
- The bone marrow is concerned with the production of erythrocytes, granulocytes and platelets during postnatal life, whereas the lymphocytes production occurs in the lymphoid tissues of lymph glands, Payer’s patches of intestine, spleen and
- The lymphoid tissues of the bone marrow and also the spleen are the sites of production for monocytes. In ruminants, hemolymph nodes (hemal) functions as spleen. It takes part in the erythropoiesis during the foetal period, while granulopoiesis, is more prevalent in postnatal life.
- The mesenchymal cells of the yolk sac produce primitive stem cells, which give rise to the pleuripotent stem cells (colony forming units – CFU). These stem cells give rise to five different blast cells, viz.
- Proerythroblast to form RBC
- Myeloblast to form neutrophils, eosinophils and basophils
- Monoblast to form monocyte
- Lymphoblast to form lymphocyte
- Megakaryoblast to form platelets. Depending on the microenvironment, e., the location of the stem cells and the growth factors, the stem cells differentiate into progenitor cells of different blood cells (Committed Stem Cells-CSC). A CSC that produces erythrocytes is called colony-forming unit-erythrocyte (CFU-E). Similarly, CFU that produce granulocytes and monocytes are designated as CFU- GM.
- The stem cells continue to divide throughout the life of the animal and a part of the cells remains as pleuripotent stem cells and retained in the bone marrow to maintain supply of stem
- The pleuripotent stem cells differentiate to form the CSC. Several hemopoietic growth factors and differentiation factors stimulate the growth and differentiation of these stem cells into a particular progenitor
- Cytokinins are the growth factors that regulate the formation of blood cells. Two cytokinins that stimulate red cell and WBC formation are the colony stimulating factors and interleukins. Erythropoietin increases erythrocyte precursor formation.
- From stem cell, the formation of reticulocyte takes about 72 hours and conversion of reticulocyte to erythrocyte requires 48 hours. Thus RBC formation requires 5 days
- Under appropriate stimulation, CFU-E progenitor cells produce proerythroblast. Hb synthesis begins in polychromatophil erythroblast and maximum synthesis occurs in orthochromatic
- The metarubricyte ejects the nucleus to become the reticulocyte that contains some mitochondria, ribosomes and endoplasmic reticulum. In 1-2 days, they develop into erythrocytes and enter circulation.
REGULATION OF ERYTHROPOIESIS
- The level of oxygen in the tissue is the principle regulatory factor of erythropoietic activity of the bone marrow. The kidney cells, during hypoxia, releases erythrogenin (erythropoietin releasing factor) from the glomeruli, which in turn acts on erythropoietinogen, an µ2 globulin of plasma and converts it into free erythropoietin(hemopoietin). Kidney produces 90% of erythropoeitin and liver produces about 10%.
- Erythropoietin as a hormone stimulates hemopoietic stem cells of bone marrow to produce the committed stem cells-proerythroblast, thus initiates erythropoiesis. It stimulates,
- The proliferation of rubriblast by mitosis in the developing
- Accelerates maturation of the rubricytic
- Induces the release of reticulocytes into the circulation.
THE ROLE OF VITAMINS AND MINERALS IN ERYTHROPOIESIS
- Vitamin B12 and folic acid are essential for the maturation of erythrocytes. Vitamin B12 isrequired for DNA synthesis and folic acid for RNA synthesis. Macrocytic anemia is a very common in Vitamin B12 and folic acid
- Thiamine (B1), Pantothenic acid, Nicotinic acid, Vitamin E and pyridoxine (B6), riboflavin,biotin and ascorbic acid are essential for Deficiency of Vitamin
B6 causes microcytic hypochromic anaemia in pigs. Pantothenic acid deficiency results in deficiency of ALA synthatase in birds and animals. Normocytic anemia in swine and primates is due to Vitamin E deficiency.
- Minerals such as iron, copper and cobalt are essential for erythropoiesis. Iron acts as an integral part of Hb which is absolutely essential for Hb synthesis. Copper acts as a co-factor in ALA dehydrase in Hb synthesis. It is part of the enzyme ferroxidase which is necessary for oxidation of ferrous iron to ferric form and is necessary for the incorporation of iron into Hb. Copper deficiency is common in pigs, which may interfere with Fe absorption and utilization. In ruminants cobalt plays a key role for the synthesis of Vitamin B12 by the rumen bacteria which in turn is required for the normal production of erythrocytes.
- A low percentage (1 to 3%) of erythrocytes in circulation has a network of bluish threads within the cell and is called
- These cells are immature RBCs, which have entered into the circulation at times of need from blood forming
- In some diseases or due to excessive loss of blood or destruction of RBCs, the reticulocytic number increases in circulation. These cells have less or no O2 carrying capacity.