1
Q

describe the structure of RBCs

A

β†’Mammalian RBCs are biconcave disc-shaped.

β†’ have flexible membranes with a high surface-to-volume ratio.

β†’They are 8 microns in diameter but are able to deform and pass through capillaries or RES without fragmentation.

β†’The RBC is unique amongst eukaryotic cells as it lacks a nucleus, mitochondria and ER, and its cytoplasm is essentially rich in haemoglobin.

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2
Q

what is the function of red blood cells and what are the requirements for this ?

A

β†’ transport of respiratory gases to and from the tissues.

β†’ RBC should be capable of transversing the microvascular system without mechanical damage, and retain its shape

β†’the red cell membrane should be extremely tough, yet highly flexible

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3
Q

describe the structure of the red blood cell membrane and what it consists of

A

β†’semipermeable lipid bilayer with proteins scattered throughout.

It consists of
β†’an outer hydrophilic portion composed of glycolipids, glycoproteins and proteins

β†’ a central hydrophobic layer containing proteins, cholesterol and phospholipids

β†’an inner hydrophobic layer of mesh-like cytoskeletal proteins to support the lipid bilayer

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4
Q

how much by % do RBC membrane lipids make up?

and describe the distribution of RBC membrane lipids

A

β†’RBC membrane lipids make up about 40% of the membrane.

β†’There is an asymmetrical phospholipid distribution throughout the RBC membrane.

β†’ unesterified free cholesterol between the phospholipids

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5
Q

what are the types of phospholipids in the RBC membrane and where are they found?

A

UNCHARGED PHOSPHOLIPIDS IN THE OUTER LAYER β†’phosphatidylcholine (PC)
β†’sphingomyelin (SM)

CHARGED PHOSPHOLIPIDS IN THE INNER LAYER β†’phosphatidyl ethanolamine (PE)
β†’ phosphatidyl serine (PS)

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6
Q

how does membrane cholesterol exist within a RBC?

A

β†’Membrane cholesterol exists in free equilibrium with plasma cholesterol.

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7
Q

what does an increase in free plasma cholesterol mean?

A

β†’An increase in free plasma cholesterol results in an accumulation of cholesterol in the RBC membrane.

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8
Q

what % of the membrane do RBC membrane proteins make up?

A

50%

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9
Q

what are the two categories of RBC membrane proteins?

A

β†’integral membrane proteins and peripheral membrane proteins

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10
Q

describe integral membrane proteins and give examples

A

β†’extend from the outer surface and traverse the entire membrane to the inner surface.

β†’Two major integral membrane proteins are Glycophorins (types we’ve identified are A, B and C) and Band 3 (an anion transporter).

β†’other integral membrane proteins:
β†’ Na+/K+ ATPase
β†’Aquaporin 1
β†’surface receptors (eg. TfR)

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11
Q

describe peripheral membrane proteins and give examples

A

β†’limited to the cytoplasmic surface of the membrane and form the RBC cytoskeleton.

Major peripheral proteins include: 
β†’ spectrin 
β†’ankyrin 
β†’protein 4.1 
β†’actin
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12
Q

what are the functions and properties of spectrin?

A

β†’Spectrin is the most abundant peripheral protein.

β†’composed of Ξ± and Ξ² chains

β†’ important in RBC membrane integrity as it binds with other peripheral proteins to form the cytoskeletal network of microfilaments.

β†’It controls the biconcave shape and deformability of the cell.

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13
Q

what is the function of ankyrin?

A

β†’anchors the lipid bilayer to the membrane skeleton via interaction between spectrin and Band 3.

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14
Q

what is the function of protein 4.1?

A

β†’links the cytoskeleton to the membrane by means of its associations with glycophorin.

β†’It also stabilizes the interaction of spectrin with actin.

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15
Q

what is the function of actin?

A

β†’responsible for the contraction and relaxation of the membrane.

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16
Q

what are the functions of the RBC membrane?

A

β†’shape : provides the optimum surface area to volume ratio for respiratory exchange

β†’provides deformability and elasticity : allows for passage through microvessels (capillaries)

β†’regulates intracellular cation concentration

17
Q

what are red cell metabolic pathways for?

A

Metabolism provides energy required for:
β†’maintenance of cation pumps
β†’maintenance of Hb in its reduced state
β†’maintenance of reduced sulfhydryl groups in Hb and other proteins
β†’maintenance of RBC integrity and deformability

18
Q

what are the key metabolic pathways in RBCs?

A

β†’Glycolytic or Embden-Meyerhof Pathway
β†’ Pentose Phosphate Pathway
β†’Methaemoglobin Reductase Pathway
β†’ Luebering-Rapoport Shunt

19
Q

what does the glycolytic or Embden-Meyerhof pathway do?

A

β†’It generates 90-95% of the energy needed by RBCs.
β†’In it, glucose is metabolised and generates two molecules of ATP.
β†’It functions in the maintenance of the RBC shape, flexibility and cation pumps.

20
Q

what does the pentose phosphate pathway do?

A

β†’RBCs need GSH to protect them from oxidative damage.

β†’The pentose phosphate Pathway provides the reducing power, NADPH.

β†’NADPH maintains glutathione in its reduced form (GSH).

21
Q

what is the methaemoglobin reductase pathway for?

A

β†’It maintains ion in its ferrous state (Fe2+).

β†’In the absence of this enzyme, methaemoglobin accumulates and cannot carry oxygen.

22
Q

what does the Luebering-Rapoport shunt do?

A

β†’permits for the accumulation of 2,3-DPG, which is essential for maintaining normal oxygen tension, regulating haemoglobin affinity.

23
Q

what are the methods RBCs use to avoid structural deterioration?

A

β†’geometry of cell & surface area to volume ratio facilitates deformation whilst maintaining constant surface area

β†’membrane deformability
spectrin molecules undergo reversible changes in conformation, some are uncoiled and extended, whilst others are compressed and folded

β†’cytoplasmic viscosity determined by MCHC :
as MCHC rises, viscosity rises exponentially

24
Q

what determines the strength and flexibility of RBCs?

A

β†’ interactions between the membrane & cytoskeletal proteins

25
Q

what two effects does an increase in cholesterol have on RBCs?

A

β†’RBCs with increased cholesterol levels appear distorted resulting in acanthocytosis.

β†’ cause of target cells

26
Q

what maintains surface area in the RBC?

A

β†’ strong cohesion between bilayer and membrane skeleton

27
Q

what is the structure of haemoglobin?

A

β†’ globular haemoprotein
β†’ contain haem as a tightly bound prosthetic group
β†’ complex of protoporphyrin IX and ferrous iron (Fe 2+)
β†’ iron held at the center of the haem molecule by bonds to the 4 nitrogen of porphyrin
β†’ 2 alpha and 2 beta globin chains