VETERINARY PHYSIOLOGY –I (VPB -111) Blood – Part 2 (VCI Syllabus)

VETERINARY PHYSIOLOGY –I (VPB -111) Blood Part 2 (VCI Syllabus) – VCI Physiology Syllabus – Metabolism and fate of R.B.C

1. Functions of RBC (erythrocytes)

• Transport hemoglobin (which carry oxygen)
• Transport CO2 (due to carbonic anhydrase)
• Regulate acid – base balance

2. RBC Metabolism

Energy is required for RBCs to

• To maintain the shape and flexibility of the cell membrane.
• To preserve high K⁺, low Na⁺ and low Ca⁺⁺ ions within the RBCs against the concentration gradient of these ions of plasma.
• 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 state.
• To generate 2,3 Diphospho glycerate (DPG) for O₂ dissociation.
• Mitochondria are absent in mature erythrocytes (most imp. point). These cells derive their energy from glucose metabolism via anaerobic Embden- Meyerhoff (EM) pathway (90%) and oxidative pentose cycle (10%) which produce NADH and NADPH. Kreb’s cycle is very much reduced in activity.

3. Composition of RBC 

• 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 vitamins.

4. Shape of RBCs (erythrocyte)

Erythrocytes are generally considered to be discocytes, with some degree of concavity. 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 erythrocytes.
• Camel and Deer: Elliptical and sickle shaped.
• Cold blooded animals (amphibians and birds): Elliptical and nucleated.

5. Significance of biconcavity of RBCs (Advantage of DISCOID shape of erythrocytes)

• the provision of a larger surface area to volume ratio,
• minimal diffusion distance, and
• greater osmotic swelling (water intake) possible without threatening the integrity of the membrane.

6. What is erythrocytic PLASTICITY?

• Erythrocytes are tolerant of shape changes as they circulate. Many variations are noted as they pass through the small lumen (duct) of capillaries or rebound from a collision with a vessel bifurcation (branch). This property of tolerance for shape change is known as plasticity.

7. Structure of RBC (erythrocytes)

• 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.
• 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 surface.
• Erythrocyte contains 62 – 72% water and 35% solids. Of the solids, 95% is contributed by Hb

8. Size of RBCs in different animals

• Average diameter of RBC ranges from 4.1 to 7.5µm. Among the domestic animals, dogs have erythrocytes with the largest diameter (7 μm), and sheep and goats have those with the smallest (4–4.5 μm).  It seems that this was an adaptive feature, because RBCs of the smallest size are found in greater numbers. Because the sheep and goat were commonly found in regions of high altitude, with lower oxygen concentrations, the available hemoglobin was placed in a greater number of smaller packages so that a greater surface area would be available for diffusion.

Surface area‚ varies from 57-67m² / kg body weight in mammals. It is lowest in goat (lesser diameter) and highest in man (greater diameters).

9. Concentration of RBCs in different domestic animals

• 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)

10. Erythrocytic Indices

There are three indices, and each relates to a value for a single RBC. Accordingly, the units are small and are shown for each as follows. These indices help in the diagnosis various types of anemia (microcytic vs. macrocytic or normocytic).

• Mean corpuscular volume (MCV) in femtoliters (fL); It expresses the average cell size of the erythrocyte.
• Mean corpuscular hemoglobin (MCH) in picograms (pg); It gives the average weight of Hb present in the erythrocytes.
• Mean corpuscular hemoglobin concentration (MCHC) in g/dL (deciliter) or g percent. It is the average percentage of the mean corpuscular volume that the Hb occupies.

Normal range of erythrocyte indices in domestic animals

11. Life span of erythrocytes (days)

12. 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 spleen.
• In the birds liver acts as an organ of destruction of erythrocytes.

13. 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 span.
• Two types of destruction of erythrocytes takes place,

Intravascular 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).

Extravascular hemolysis

• 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 nodes.
• 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 erythrocytes.
• 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 feces.
• 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 proteins.

Hemolysis caused by external agents like

• Blood parasites: Babesiosis, theileriosis, trypanosomiasis and sarcocystosis.
• Chemicals: Copper, lead, nitrate and nitrite poisoning.