Red Blood Cell Structure and Function Flashcards
Describe the structure of red blood cells.
- Biconcave disc-shaped - maximises surface area to increase efficiency of oxygen absorption
- Flexible membranes with a high surface-to-volume ratio.
- 8 microns in diameter but are able to deform and pass through capillaries or reticuloendothelial system without fragmentation.
- Lacks a nucleus, mitochondria and ER
- Cytoplasm is rich in haemoglobin.
Describe the main function of the red blood cells, and how it is adapted to doing so.
- Transport of respiratory gases to and from tissues.
To achieve this:
- RBC should be capable of transversing the microvascular system without mechanical damage and retain its shape
- Red cell membrane should be extremely tough, yet highly flexible
- Strength and flexibility determined by interactions between membrane and cytoskeletal proteins
Describe the structure of the red blood cell membrane.
It is a semipermeable lipid bilayer with proteins scattered throughout.
- Outer hydrophilic portion composed of glycolipids, glycoproteins and proteins
- Central hydrophobic layer containing proteins, cholesterol and phospholipids
- Inner hydrophobic layer of mesh-like cytoskeletal proteins to support the lipid bilayer
- Structural properties are linked to membrane
Describe the membrane lipids and cholesterol present in red blood cell membranes
- Membrane lipids make up about 40% of the membrane.
- Asymmetrical phospholipid distribution throughout the RBC membrane - phospholipids on outer and inner layers differ
- Unesterified free cholesterol between uncharged phospholipids and charged phospholipids. Polar hydroxyl group found close to the hydrophilic phospholipid head.
- Important determinant of membrane surface area and fluidity
- Increase in membrane cholesterol leads to an increased surface area and decreased deformability
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) - important as macrophages will recognise and phagocytose cells that express PS at their outer layers. Kept within inner layer to prevent unwanted phagocytosis
- Membrane cholesterol exists in free equilibrium with plasma cholesterol.
- An increase in free plasma cholesterol results in an accumulation of cholesterol in the membrane.
- Blood cells with increased cholesterol levels appear distorted, resulting in acanthocytosis.
- Increase in cholesterol AND phospholipids causes target cells due to abnormally high surface area
Describe the membrane proteins present in red blood cell membranes.
The membrane proteins make up about 50% of the membrane. They are split into two categories: INTEGRAL MEMBRANE PROTEINS and PERIPHERAL PROTEINS.
INTEGRAL PROTEINS
- Extend from the outer surface and transverse the entire membrane to the inner surface.
- Two major integral membrane proteins are Glycophorins* (types currently known 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
- Limited to the cytoplasmic surface of the membrane and forms the cell’s cytoskeleton.
Major peripheral proteins include:
- spectrin
- ankyrin
- protein 4.1
- actin
Describe Spectrin, ankyrin, protein 4.1 and actin
SPECTRIN
- Most abundant peripheral protein.
- Composed of α and β chains.
- Very important in RBC membrane integrity as it binds with other peripheral proteins to form the cytoskeletal network of microfilaments.
- Controls the biconcave shape and deformability of the cell.
- Requires phosphorylation for interactions by kinases using ATP. Reduced ATP means reduced phosphorylation. This leads to reduced interactions with actin to give membrane its elastic properties, therefore reducing deformability.
- If denatured red cell becomes spherical, loses flexibility
ANKYRIN
- Anchors the lipid bilayer to the membrane skeleton via interaction between spectrin and Band 3.
PROTEIN 4.1
- May link the cytoskeleton to the membrane by means of its associations with glycophorin.
- Stabilises the interaction of spectrin with actin.
- Mutations in spectrin and protein 4.1 (cytoskeletal proteins) weaken the horizontal linkage, decrease the membrane mechanical stability, and are responsible for hereditary
elliptocytosis (HE)
ACTIN
- Responsible for the contraction and relaxation of the membrane.
What are the functions of the red blood cell membrane?
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 membrane through the surface receptors scattered across the membrane
What is the use of red cell metabolic pathways?
List all of these pathways
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
The pathways are
- Glycolytic or Embden-Meyerhof Pathway
- Pentose Phosphate Pathway
- Methaemoglobin Reductase Pathway
- Luebering-Rapoport Shunt
What do the following pathways do?
- Glycolytic or Embden-Meyerhof Pathway
- Pentose Phosphate Pathway
- Methaemoglobin Reductase Pathway
- Luebering-Rapoport Shunt
GLYCOLYTIC OR EMBDEN-MEYERHOF PATHWAY
- Generates most (i.e about 90-95%) of the energy needed by RBCs.
- Glucose is metabolised and generates two molecules of ATP.
- Involved in the maintenance of the RBC shape, flexibility and cation pumps e.g Na+/K+ pump to regulate intracellular cation concentrations
PENTOSE PHOSPHATE PATHWAY
- Red blood cells 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).
METHAEMOGLOBIN REDUCTASE PATHWAY
- Maintains ion in its ferrous state (Fe 2+).
- In the absence of this enzyme, methaemoglobin accumulates and cannot carry oxygen.
LUEBERING-RAPOPORT SHUNT
- Regulates oxygen release from Hb and delivery to tissues
- Permits for the accumulation of 2,3-DPG, which is essential for maintaining normal oxygen tension, regulating haemoglobin affinity.
RBCs can withstand life without structural deterioration. What contributes to this?
- 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
Outline the importance of phosphatidylserine during apoptosis?
- Normally expressed on inside layer of membrane
- Phosphatidyl serine expressed on outer layer when undergoing apoptosis
- When phosphatidyl serine is expressed on the outer layer, macrophages recognize and engulf it
What is the composition of lipids in the RBC membrane?
60% phospholipids
30% cholesterol
10% sphingolipids
What maintains the surface area in the RBC membrane?
Strong cohesion between bilayer and membrane skeleton
Describe the carbohydrates found on red blood cell membranes
- Carbohydrates found on external surface of red blood cells
- Carbohydrate groups attached to proteins and lipids in red blood cell by glycosylation
- Carbohydrates may contain 2-60 monosaccharides
- Can be branched or straight
- Distinguishing factor for human blood types.
Monosaccharides found on the erythrocyte membrane
- Galactose
- Mannose
- Fructose
- N-acetyl galactosamine
- Glucuronic acid
- Glucose
- Sialic acid
- N-acetyl glucosamine
- Blood group antigens found on the red blood cell membranes and determine the blood group
Red blood cell membrane protein antigens
- Rhesus, Duffy and Kidd
Red blood cell membrane carbohydrate antigens
- ABO, Lewis
- Some blood groups are combinations of proteins and glycolipids
Glycolipids
- Lipids with a carbohydrate attached by a glycosidic (covalent) bond
- Maintains the stability of the cell membrane and facilitates cellular recognition, which is crucial to the immune response and allows cells to connect to one another to form tissues
Briefly describe and outline how the following affect red blood cells.
- Microcytes
- Hypochromia
- Macrocytes
- Anisocytosis
- Poiliocytosis
- Hereditary spherocytosis
- Hereditary elliptocytosis
Microcyte
- Where most red blood cells are smaller than normal due to reduced haemoglobin
Hypochromia
- Less haemoglobin
Macrocyte
- Where most red blood cells are bigger than usual due to increased haemoglobin
Anisocytosis
- Size variation in red blood cells
Poikilocytosis
- Shape variation in red blood cells
Hereditary spherocytosis
- Defects and abnormalities in ankyrin, A or B spectrin, band 3 and protein 4.2
- The edges appear larger due to gathering of ahemoglobin round the outside with none in the middle
Hereditary elliptocytosis
- A or B spectrin mutation causing defective spectrin-dimers or spectrin-actin associations
- Cells appear longer and thinner
