The Red Blood Cell Structure and Function

Question 1

Describe the structure of RBCs.

Answer 1

Mammalian RBCs are biconcave disc-shaped. They have flexible membranes with a high surface-to-volume ratio. They are 8 microns in diameter but are able to deform and pass through capillaries or RES without fragmentation.
The RBC is unique amongst eukaryotic cells as it lacks a nucleus, mitochondria and ER, and its cytoplasm is essentially rich in haemoglobin.

Question 2

Describe the main function of the RBCs, and what helps it achieve it.

Answer 2

The primary function of RBCs is the transport of respiratory gases to and from the tissues. To achieve this:

• the RBC should be capable of transversing the microvascular system without mechanical damage, and retain its shape
• the red cell membrane should be extremely tough, yet highly flexible

Question 3

Describe the structure of the red blood cell membrane.

Answer 3

It is a semipermeable lipid bilayer with proteins scattered throughout.
It consists of:
- an outer hydrophilic portion composed of glycolipids, glycoproteins and proteins
- a central hydrophobic layer containing proteins, cholesterol and phospholipids
- an inner hydrophobic layer of mesh-like cytoskeletal proteins to support the lipid bilayer

Question 4

Describe the RBC membrane lipids.

Answer 4

RBC membrane lipids make up about 40% of the membrane.
There is an asymmetrical phospholipid distribution throughout the RBC membrane. There is unesterified free cholesterol between them.

There are two types of phospholipids:
UNCHARGED PHOSPHOLIPIDS IN THE OUTER LAYER
- Phosphatidylcholine (PC)
- Sphingomyelin (SM)

CHARGED PHOSPHOLIPIDS IN THE INNER LAYER

• Phosphatidyl Ethanolamine (PE)
• Phosphatidyl Serine (PS)

Question 5

Describe the membrane cholesterol.

Answer 5

Membrane cholesterol exists in free equilibrium with plasma cholesterol. An increase in free plasma cholesterol results in an accumulation of cholesterol in the RBC membrane.
RBCs with increased cholesterol levels appear distorted, resulting in acanthocytosis.

Question 6

Describe RBC membrane proteins (and it’s two categories).

Answer 6

RBC membrane proteins make up about 50% of the membrane. They are split into two categories: INTEGRAL MEMBRANE PROTEINS and PERIPHERAL PROTEINS.

INTEGRAL PROTEINS: they extend from the outer surface and transverse the entire membrane to the inner surface. Two major integral membrane proteins are Glycophorins (types we’ve identified are A, B and C) and Band 3 (an anion transporter). Examples of other integral membrane proteins:

• Na+/K+ ATPase
• Aquaporin 1
• surface receptors (eg. TfR)

PERIPHERAL PROTEINS: they’re limited to the cytoplasmic surface of the membrane and form the RBC cytoskeleton. Major peripheral proteins include:

• spectrin
• ankyrin
• protein 4.1
• actin

Question 7

Describe the function of the peripheral protein Spectrin.

Answer 7

Spectrin is the most abundant peripheral protein. It is composed of α and β chains.
It’s very important in RBC membrane integrity as it binds with other peripheral proteins to form the cytoskeletal network of microfilaments. It controls the biconcave shape and deformability of the cell.

Question 8

Describe the function of the peripheral protein Ankyrin.

Answer 8

It primarily anchors the lipid bilayer to the membrane skeleton via interaction between spectrin and Band 3.

Question 9

Describe the function of the peripheral protein Protein 4.1.

Answer 9

It may link the cytoskeleton to the membrane by means of its associations with glycophorin. It also stabilises the interaction of spectrin with actin.

Question 10

Describe the function of the peripheral protein Actin.

Answer 10

It is responsible for the contraction and relaxation of the membrane.

Question 11

What are the functions of the RBC membrane?

Answer 11

SHAPE:
provides the optimum surface area to volume ratio for respiratory exchange AND is essential to deformability

PROVIDES DEFORMABILITY, ELASTICITY:
allows for passage through microvessels (capillaries)

REGULATES INTRACELLULAR CATION CONCENTRATION

ACTS AS THE INTERFACE BETWEEN THE CELL AND ITS ENVIRONMENT VIA MEMBRANE SURFACE RECEPTORS

Question 12

What is the use of red cell metabolic pathways?

Answer 12

Metabolism provides energy required for:

• maintenance of cation pumps
• maintenance of Hb in its reduced state
• maintenance of reduced sulfhydryl groups in Hb and other proteins
• maintenance of RBC integrity and deformability

Question 13

List the key metabolic pathways.

Answer 13

• Glycolytic or Embden-Meyerhof Pathway
• Pentose Phosphate Pathway
• Methaemoglobin Reductase Pathway
• Luebering-Rapoport Shunt

Question 14

What does the Glycolytic or Embden-Meyerhof Pathway do?

Answer 14

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

Question 15

What does the Pentose Phosphate Pathway do?

Answer 15

RBCs need GSH to protect them from oxidative damage. The Pentose Phosphate Pathway provides the reducing power, NADPH. NADPH maintains glutathione in its reduced form (GSH).

Question 16

What does the Methaemoglobin Reductase Pathway do?

Answer 16

It maintains ion in its ferrous state (Fe2+). In the absence of this enzyme, methaemoglobin accumulates and cannot carry oxygen.

Question 17

What does the Luebering-Rapoport Shunt do?

Answer 17

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

Question 18

RBCs can withstand life without structural deterioration. What contributes to this?

Answer 18

• GEOMETRY OF CELL: SURFACE AREA TO VOLUME RATIO: facilitates deformation whilst maintaining constant surface area
• MEMBRANE DEFORMABILITY: spectrin molecules undergo reversible changes in conformation, some are uncoiled and extended, whilst others are compressed and folded
• CYTOPLASMIC VISCOSITY DETERMINED BY MCHC: as MCHC rises, viscosity rises exponentially