Rbc Structure and Physiology

PG class PPT for RBC Structure and its Function and Physiology

1. Good Morning

2. Red cell S tructure and P hysiology , Hemoglobin and I ron metabolism Dr Muthukumaravel 2 nd year DNB (Immunohematology and Transfusion Medicine) Apollo Indraprastha, New Delhi Dr Sourav Chowdhury 1 st year DNB Immunohematology and Transfusion Medicine Apollo Indraprastha, New Delhi

3. Blood is the liquid connective tissue of the body. Actual blood volume is calculated according to “Weight” of the individual.

4. Blood volume: Male – 70 ml / kg body weight Female – 66 ml / kg body weight Neonates – 85 ml / kg body weight Pregnant women – 100 ml / kg body weight

5. Functions of Blood Transport of: Gases, nutrients, waste products Processed molecules Regulatory molecules Regulation of pH and osmosis Maintenance of body temperature Protection against foreign substances Clot formation

6. Haematopoiesis Formation of blood cellular components All cellular blood components are derived from haematopoietic stem cells Largely controlled by feedback mechanism ( Cytokines )

7. Transcription factor network for Erythrocyte: LRF- Leukaemia/Lymphoma Related factor SCL- Basic Helix loop helix factor miR - MicroRNA C-MYB- Proto- Onco gene

8. Erythropoiesis Process of development , differentiation and maturation of erythrocyte.

9. Metabolic Changes: Multipotent Stem cell Proerythroblast Early erythroblast Late erythroblast Normoblast Reticulocyte Erythrocyte Phase 1: ribosome synthesis Phase 2: hemoglobin accumulation Phase 3: ejection of nucleus Adenylate cyclase Metabolism ATPase activity Active to Passive TfR expression Iron uptake

10. Site of Haematopoiesis:

11. Erythropoesis and Haemoglobin Primitive Phase 2 – 8 weeks Definitive Phase 8 th week onwards

12. At 1 year of age:

13. Requirements For Erythropoiesis INTRACELLULAR FACTORS Haematopoietic and Erythroid specific transcription factors Receptors for haematopoietic growth factors Proteins - Hb , Membrane, Cytoskeleton Protein. EXTRACELLULAR FACTORS Haematopoietic growth factor Nutrients (Vitamins and Minerals) Stromal cells and Matrix support

14. Erythropoietin Erythropoietin (EPO), also known as hematopoietin or hemopoietin , is a glycoprotein cytokine secreted by the kidney that stimulates red blood cell production ( erythropoiesis ). Site of production: Interstitial fibroblasts in the kidney in close association with peritubular capillary and proximal convoluted tubule. Perisinusoidal cells in the liver.

15. Mechanism of Action of Epo EPO+EPO-R COMPLEX

16. Three basic components RBC Membrane Structure:  1. glycocalyx on the exterior, which is rich in carbohydrates;  2. lipid bilayer which contains many transmembrane proteins,  3.phospholipids and cholesterol layer

17. RBC Membrane CONSISTS OF: PROTEIN 44% LIPIDS 48% PHOSPHOLIPID 54% CHOLESTROL MOLECULES 46% CARBOHYDRATE 8%

18. Lipid Bilayer consists: Phospholipid 60%. Cholesterol 30%. Glycolipid 10%. Integral protein. Peripheral protein.

19. Integral Proteins: Names Definition Function Glycophorin Sialic acid rich glycoproteins imparts a negative charge to the cell, reducing interaction with other cells/endothelium Band 3 protein Anion Exchanger 1 Exchanges bicarbonate for chloride (chlorine shift).

20. Peripheral Proteins: Names Definition Function Spectrin Cytoskeletal protein on the intracellular side of the plasma membrane Responsible for biconcave shape of the RBC Actin Abundant protein of the cell membrane Plays role in protein to protein interaction Ankyrin Family of adapter protein Interacts with band3 protein and spectrin to achieve linkage between bilayer and skeleton Protein 4.1 A major structural protein Stabilises actin- spectrin interactions. Protein 4.2 ATP-binding protein Regulate the association of protein 3 with ankyrin Tropomyosin Heterodimeric protein Stabilizing the actin filaments

21. Cytoskeleton: Formed by structural protein Basic unit : hexagonal lattice with 6 spectrin molecules. Tail end: tetramers linked to actin and protein 4.1. Head end: ß spectrin linked to ankyrin

22. Cytoskeleton

23. Deformibility and Resiliency of Red cell: While RBC moves through Capillaries it deforms and it is the function of membrane and cytoskeleton to make it possible by, Tank-treading of its membrane Tumbling motion Stretching RBC is able to do such feat and maintain the blood flow Larger surface area:volume ratio Fluidic state of its membrane Interaction between its membrane phospholipids integral proteins and peripheral proteins

24. Defects in RBC Membrane: Hereditary Spherocytosis Ankyrin deficiency or abnormalities Α or β spectrin deficiency or abnormalities Band 3 protein abnormalities Palladin ( protein 4.2 ) abnormalities Hereditary Elliptocytosis Α or β spectrin mutation = defective spectrin dimer Α or β spectrin mutation = defective spectrin ankyrin association Protein 4.1 deficiency or abnormalities

25. Haemoglobin Iron-containing oxygen-transport metalloprotein . Two parts – Haem part and Globin part

26. Haemoglobin Globin Consists of 4 polypeptide chains: Two alpha chains each with 141 amino acid. Two beta chains with 146 amino acids. Haem Flat ring molecule with 4 pyrrole ring. Single Fe 2+ ion at centre of each pyrrole ring. Without iron ring – Porphyrin Ring.

27. Function of Haemoglobin Carbon dioxide is also carried by haemoglobin, it does not compete with oxygen for the iron-binding positions but is bound to the protein chains of the structure. The iron ion may be either in the Fe2+ or in the Fe3+ state. But Fe3+cannot bind oxygen. In binding, oxygen temporarily and reversibly oxidizes (Fe2+) to (Fe3+), thus iron must exist in the +2 oxidation state to bind oxygen.

28. Discrimination by RBC in O 2 transfer: The synergistic effects of hemoglobin, carbonic anhydrase and the band 3 protein make red blood cells the ideal vehicle for oxygen delivering to the tissues. As long as oxygen is supplied by these ideal vehicles, oxygen intoxication of the tissues is precluded. Band 3 protein mediates the "Chloride-Shift", i.e., the anion exchange of CI'/HCO3. Because of the Chloride-Shift, red blood cells are able to recognize metabolically active tissues and to supply the adequate amount of oxygen to the tissues.

29. Fate of Hemoglobin

30. Iron Metabolism Dietary iron Ferric form Ferritin Haem-Fe

31. Role of Hepcidin

32. Thank You for listening and Have a Nice day