description about RBC membrane and its structural peculiarities,how it differs from other cells of our body. How this specialized cell manage homeostasis and function in a well defined manner. This presentation will also help in understanding various RBC storage lesions ,an important aspect of blood banking.
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Rbc structure and metabolism
1. D R A K S H A Y A T O M A R
D E P A R T M E N T O F I M M U N O H E M A T O L O G Y A N D
B L O O D T R A N S F U S I O N
A F M C , P U N E
RBC STRUCTURE AND
METABOLISM
2. INTRODUCTION
RBCs are complex ,metabolically active cells using
glucose to make ATP and reducing equivalents to ensure
flexibility and O2 delivery
Life span – 120 days
Neither use O2 for extraction of energy nor synthesizes
protein
Proteomics has identified 2200 separate proteins in RBC
that are the product of 5% of all human genes
3. RBC MEMBRANE
Erythrocyte membrane that is normal in structure and
function is essential for survival of red cell
Accounts for the cell's antigenic characteristics
Maintains stability and normal discoid shape of cell
Preserve cell deformability
Retain selective permeability
4. RBC MEMBRANE
Semipermeable lipid bilayer supported by a meshlike
protein cytoskeleton
Proteins and phospholipids are organized
asymmeterically.
Biochemical composition includes 52% proteins,40%
lipids and 8% carbohydrate.
7. Asymmetric phospholipids distribution is maintained by:
–Differential rate of diffusion through membrane bilayer
of choline containing phospholipids (PC and SM diffuse
slowly)
–Charged phospholipids interaction with membrane
skeletal protein.
–Active transport of amino phospholipids (PC and PE)
from outer to inner layer.
8. This asymmetric phospholipid distribution among
the bilayer is the result of the function of several
energy-dependent and energy-
independent phospholipid transport proteins.
10. MEMBRANE PROTEINS
Integral proteins
–Embedded in membrane via hydrophobic
interactions with lipids.
Peripheral proteins
–Located on cytoplasmic surface of lipid bilayer,
constitute membrane skeleton.
–Anchored via integral proteins
–Responsible for membrane elasticity and stability.
12. BAND 3
•Functions:
–Anion transport
Exchanges bicarbonate for chloride
–Structural:
Linkage of lipid bilayer to underlying membrane
skeleton.
–Interaction with ankyrin and protein 4.2, secondarily
through binding to protein 4.1.
Important for prevention of surface loss.
15. GLYCOPHORINS
Human RBCs glycophorins are integral membrane
proteins rich in sialic acids that carry blood group
antigenic determinants and serve as ligands for
viruses and parasites
16. AQUAPORINS
Aquaporins selectively conduct water molecules in
and out of the cell, while preventing the passage
of ions and other solutes
Allow RBC to remain in osmotic equilibrium with
extracellular fluid.
20. SPECTRIN
Flexible, rod like molecule, 100nm length.
Responsible for biconcave shape of RBC
Two subunits:
–Alpha and beta, entwined to form dimers.
–Associate head to head to form tetramers
End-to-end association of these tetramers with short
actin filaments produces the hexagonal complexes
observed
21.
22. ACTIN
Short, uniform filaments 35nm in length
Length modulated by tropomyosin/tropomodulin
Spectrintail associated with actin filaments
Approx 6 spectrin ends interface with one actin
filament, stabilized by protein 4.1
23. ANKYRIN
Interacts with band 3 and spectrin to achieve linkage
between bilayer and skeleton.
Augmented by protein 4.2.
24. OTHER PERIPHERAL PROTEINS
Protein 4.1
–Stabilizes actin-spectrin interactions
Adducin
–Also stabilizes interaction of spectrin with actin.
–Influenced by calmodulin
(thus can promote spectrin-actin interactions as
regulated by intracellular Ca concentration)
25. CHARACTERISTICS OF RBCs
DEFORMABILITY :
It is controlled by ATP driven membrane
cytoskeleton.
Loss of ATP leads to decrease in phosphorylation of
spectrin.
Increase in deposition of membrane calcium.
Rigid cells are removed from the circulation.
26.
27. PERMEABILITY :
Permeability properties of the RBC membrane and
the active RBC cation transport prevent colloid
hemolysis and control the volume of RBC.
Freely permeable to water and anions; relatively
impermeable to cations.
When RBC are ATP depleted Ca and Na are allowed
to accumulate intracellularly and K and water are
lost.
28. METABOLIC PATHWAYS
Mainly anaerobic, RBC have to deliver not consume
O2.
No nucleus/No mitochondria.
RBC metabolism may be divided into anaerobic
glycolysis and 3 ancillary pathways
29. RBCs contain no mitochondria, so there is no
respiratory chain, no citric acid cycle, and no oxidation
of fatty acids or ketone bodies.
The RBC is highly dependent upon glucose as its
energy source.
Energy in the form of ATP is obtained ONLY from the
glycolytic breakdown of glucose with the production of
lactate (anaerobic glycolysis).
30. RBC METABOLISM
Glucose transport through RBC membrane:
Glucose is transported through RBC membrane
by facilitated diffusion through glucose transporters
(GLUT-1).
31. GLYCOLYSIS
Importance of glycolysis in red cells:
Energy production: It is the only
pathway that supplies the red cells
with ATP.
Reduction of methemoglobin:
Glycolysis provides NADH for
reduction of metHb by NADH-
cytob5 reductase
In red cells 2,3
bisphosphoglycerate binds to Hb,
decreasing its affinity for O2, and
helps its availability to tissues.
32. UTILIZATION OF ATP
Phosphorylation of sugars and proteins
ATPase driven ion pumps
Maintenance of membrane asymmetry
Maintenance of red cell shape and deformability
using ATP dependent cytoskeleton
33. METH Hb REDUCTASE PATHWAY
Maintains Iron in reduced state for effective
transport of O2
Protect SH group of Hb and membrane proteins
from oxidation
35. LEUBERING RAPOPORT SHUNT
Binding of 2,3 DPG to DeoxyHb stabilise the tense
state of Hb and favours release of O2
36. LEUBERING RAPOPORT SHUNT
Free 2,3 DPG also binds with Band 3 and causes
partial detachment of membrane from cytoskeleton
allowing lateral movement of membrane structure.
37. PENTOSE PHOSPHATE PATHWAY
Production of NADPH – ‘reducing power’
Glutathione is needed in reduced form for:
Elimination of peroxide
Protection of proteins SH groups
This shunt also provide ribose 5 phosphate needed for
PRPP ( substrate for adenine nucleotides reqd for
continuing ATP synthesis)
40. HEMOGLOBIN OXYGEN DISSOCIATION
Dissociation and binding of oxygen by hemoglobin
are not directly proportional to pO2.
Sigmoid-curve.
It permits a considerable amount of O2 to be
delivered to the tissues with a small drop in O2
tension.