PG class PPT for RBC Structure and its Function and Physiology

1. Good Morning

2. Red cell
Structure and Physiology,
Hemoglobin and Iron
metabolism
Dr Muthukumaravel 2nd year
DNB (Immunohematology and Transfusion Medicine)
Apollo Indraprastha, New Delhi
Dr Sourav Chowdhury 1st 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

7. 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

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

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

12. Erythropoiesis
 Process of development, differentiation and maturation of erythrocyte.

13. 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

14. Site of Haematopoiesis:

15. Erythropoesis and Haemoglobin
Primitive Phase
 2 – 8 weeks
Definitive Phase
 8th week onwards
Gower 1
Zeta-E
Gower 2
A-E
Portland
Ep-G
8 – 24
weeks
•HbF A-G
24 weeks
•HbF – 90%
•HbA – 10%
At Birth
•HbF – 70%
•HbA – 30%

16. At 1 year of age:
HbA - 95%
HbA2 – 1.5–3.5%
HbF - < 1%

17. 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

18. 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.

20. Mechanism of Action of Epo
EPO+EPO-R COMPLEX
Conformational
changes in EPO-Rs
Initiate the
Intracellular Signalling
Endocytosis of
Epo/Epo-R Complex

22. 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

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

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

25. 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).

26. 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

27. 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

28. Cytoskeleton

29. 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

30. 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

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

32. 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 Fe2+ ion at centre of each
pyrrole ring.
 Without iron ring – Porphyrin Ring.

34. 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.

35. Discrimination by RBC in O2 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.

36. Fate of Hemoglobin
Hb is digested
by Proteolytic
enzymes
Heme
Iron
Stored as
Ferritin
Iron
Containing
Enzyme
Porphyrin
Ring
Converted to
Bilirubin
Globin
Broken to
Amino acid
For Protein
production

37. Iron Metabolism
i. Dietary iron
ii. Ferric form
iii.Ferritin
iv. Haem-Fe

38. Role of Hepcidin

40. Thank You for listening
and
Have a Nice day