Red Blood Structure and Function Flashcards
Describe the structure of RBCs(4)
→Mammalian RBCs are biconcave disc-shaped.
→ 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(reticuloendothelial system) 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.
What are proportions of the components of RBCs?
o 50% Proteins
o 40% Lipids
o 10% Carbohydrates
What is the primary function of RBCs and how does it achieve this?(4)
• Primary function of RBC is transport of respiratory gases to and from the tissues
- • rbc traverse the microvascular system without mechanical damage and retain a shape which facilitates gaseous exchange.
- the red cell membrane should be extremely tough yet highly flexible
- Lacks mitochondria so it won’t use O2 molecules it carries
Describe the three layers of lipid bilayer if RBCs
o An outer hydrophilic portion composed of glycolipids, glycoproteins, and
proteins
o A central hydrophobic layer containing proteins, cholesterol and phospholipids
o An inner hydrophilic layer of mesh-like cytoskeletal proteins to support lipid bilayer
What are the lipid components if the red cell membrane?
Phospholipids – 60%
Cholesterol - 30%
Sphingolipids – 10%
Describe the structure of the membrane (4)
o Asymmetric phospholipid distribution.
o Unesterified free cholesterol between.
o Uncharged phospholipids of outer layer : (Phosphatidyl choline and Sphingomyelin)
o Charged phospholipids of inner layer: Phosphatidyl ethanolamine , Phosphatidyl serine
Describe the cholesterol in the lipid membrane (3)
- Membrane cholesterol exists in free equilibrium with plasma cholesterol
- Membrane cholesterol is unesterified and lies between the two layers of the lipid bilayer
- The concentration of cholesterol in the membrane is an important determinant of membrane surface area and fluidity
What does increases in membrane cholesterol result in?(3)
- Increase in membrane cholesterol leads to an increased surface area and decreased deformability.
- RBCs with increased cholesterol appear distorted resulting in acanthocytosis
- ▪ An increase in cholesterol and phospholipid is a cause of target cells
What are the two major integral membrane proteins and what do they do?
A. Glycophorins: A, B, and C- are rich in sialic acid, which gives the red blood cells a very hydrophilic-charged coat. This enables them to circulate without adhering to other cells or vessel walls
B. Band 3: anion transporter, ion transport and maintenance of protein-protein interactions
What are other integral proteins?
Na+/K+ ATPase, Aquaporin 1, surface receptors, e.g. TfR
What is the role of glycophorins?(2)
the major integral membrane proteins, accounting for location of RBC antigens.
They impart –ve charge to cell, reducing interaction with other cells/endothelium
Name 4 peripheral proteins
Spectrin, Ankyrin, Protein 4.1 and Actin
What are peripheral proteins?(2)
Limited to cytoplasmic surface of membrane and forms the RBC cytoskeleton.
• Cytoskeleton acts as tough framework to support bilayer
Describe the structure of spectrin
- The most abundant peripheral protein
* Composed of alpha & beta chains
What is the role of spectrin?(4)
• Very important in RBC membrane integrity
- binds with other peripheral proteins to form the cytoskeletal network of microfilaments
- Controls biconcave shape and deformability of cell
- If denatured red cell becomes spherical, loses flexibility
What does ankyrin do?
• primarily anchors lipid bilayer to membrane skeleton, via interaction with spectrin and Band 3
What does Protein 4. 1 do?(2)
- may link the cytoskeleton to the membrane by means of its associations with glycophorin
- stabilises interaction of spectrin with actin
What does actin do?
o responsible for contraction and relaxation of membrane
What are sulphydrl and what do they require to work?
essential for the maintenance of their tertiary structure and therefore the structural integrity of the red cell.
These sulphydryl groups require NADPH generated by the pentose phosphate pathway to protect them from oxygen radicals.
How are carbohydrates attached to proteins and lipids?
glycosylation.
Recall some carbohydrates that can be found on the cell surface
o Galactose, Mannose, Fucose, N-acetylgalactosamine, Glucuronic acid, Glucose, Sialic acid, N-acetylglucosamine
Name some blood groups associated with specific membrane structures
Many antigens are proteins: e.g. Rhesus, Duffy, Kidd
Others are carbohydrates; e.g. ABO, Lewis
Others are combination of glycolipids and proteins
What are the functions of the cell membrane?
- Provides the optimum surface area to volume ratio for respiratory exchange
- deformability, elasticity allowing for passage through micro vessels (capillaries)
- Regulates intracellular cation concentration.
4.Acts as the interface between the cell and its environment via membrane surface receptors.
- Allows water and electrolytes to exchange via cation pumps.
- RBC controls volume and H2O content primarily through control of intracellular concentrations of Na+ and K+ via these cationic pumps which require ATP.
What is acanthocytes?
o RBCs with increased cholesterol appear distorted
What is hereditary spherocytosis?(4)
Ankyrin def or abnormalities
A or B spectrin def or abnormalities
Band 3 protein abnormalities
Protein 4.2 abnormalities
How does hereditary elliptocytosis arise?(3)
A or B spectrin mutation – defective spectrin dimer
A or B spectrin mutation – defective spectrin-ankyrin association
Protein 4.1 deficiency or abnormalities
How does the RBC withstand life without structural deterioration?
- Geometry of cell; surface area to volume ratio: facilitates deformation whilst maintaining constant surface area.
- Membrane deformability: Spectrin molecules undergo reversible change in conformation: some uncoiled and extended, others compressed and folded.
- Cytoplasmic viscosity determined by MCHC (mean cell hemoglobin concentration, as MCHC rises, viscosity rises exponentially.
What are the globin components of HbA, HbA2, and HbF, and what are their proportions?
HbA: • α2β2 ,96-98 %
Hb A2: • α2δ2, 1.5-3.2 %
HbF:• a2γ2
0.5-0.8 %
Describe the structure of haemoglobin(2)
• Hb is a tetramer of 4 globin (α2β2) chains each with own haem gp.
- Haem consists of protoporphyrin ring with Ferrous iron atom.
What is the difference between alpha and beta chain length?
• Alpha chain is 141 amino acids long; Beta chain is 146 amino acids
What is metabolism energy required for?(4)
Maintenance of cation pumps
Maintenance of RBC integrity and deformability
Maintenance of Hb in reduced state
Maintenance of reduced sulfhydryl groups in Hb and other proteins
What are the key metabolic pathways of RBCs?
- Glycolytic or Embden-Meyerhof Pathway
- Hexose Monophosphate Shunt
- Methaemoglobin reductase Pathway
- Luebering-Rapoport shunt
Describe the glycolytic pathway of RBCs(3)
Glucose is metabolized and generates two molecules of ATP (energy).
Generates 90- 95% of energy needed by RBC’s
Functions in the maintenance of RBC shape, flexibility and the cation pumps
Describe the pentose pathway of RBCs(3)
The pentose phosphate shunt provides the reducing power, NADPH
NADPH maintains glutathione in the reduced form (GSH)
RBC uses GSH to protect it from oxidative damage
Describe the methemoglobin reductase pathway for RBCs
Maintains iron in the ferrous (Fe++) state.
In the absence of this enzyme, methaemoglobin accumulates and it cannot carry oxygen
Describe the Lueberg-Rapoport shunt
Permits the accumulation of 2,3-DPG which is essential for maintaining normal oxygen tension, regulating haemoglobin affinity
- Luebering-Rapoport pathway is a biochemical pathway in mature erythrocytes involving the formation of 2,3-bisphosphoglycerate and which regulates oxygen release from haemoglobin and delivery to tissues.
2
how does membrane cholesterol exist within a RBC?
→Membrane cholesterol exists in free equilibrium with plasma cholesterol.
what determines the strength and flexibility of RBCs?
→ interactions between the membrane & cytoskeletal proteins
what maintains surface area in the RBC?
→ strong cohesion between bilayer and membrane skeleton
