Lecture 2 - Red blood cells Flashcards
RBCs: strengths in having no nucleus, mitochondria, or ribosomes
Efficient and stable – nothing unnecessary
Room for haemoglobin
Unattractive to infecting organisms
RBCs: weaknesses in having no nucleus, mitochondria, or ribosomes
No capacity for making mRNA – no new protein
No Mitochondria no TCA cycle – limits the capacity to generate ATP or reducing power - vulnerable
No translation of mRNA no protein synthesis
Difference between adult and foetal haemoglobin
Normal adult haemoglobin contains 2α and 2β protein chains
Foetal haemoglobin contains 2α and 2γ chains as the gamma form has a higher affinity for oxygen, can take oxygen from the mother
RBC flexibility
Can adopt a torpedo shape for smoother movement through vessels
Can pass through bends in vessels
Slicing damage - what can cause it, how does repair work, and can it be recognised in a blood spot
Damage by fibrin strands (formed by small clots) in the circulation caused by local - clotting activation in sepsis can also cause slicing of cells
Self-repair mechanisms can occur as the cytoskeleton reforms and seals the membrane, even using a vacuole if required
The results are recognisable signs in the blood that can be recognised down the microscope
Membrane loss damage: what happens, how is the RBC removed, and what is the issue with the damage?
Diffuse damage can lead to membrane loss, causing the cell to shrink to make up for the lost membrane
As shrinkage occurs and becomes a “spherocyte”, the RBC becomes rigid and is eventually destroyed in the spleen
This means that the very high surface area to volume slowly changes, decreasing the usefulness of the RBC
Hereditary spherocytosis: what is it, what is it caused by, what does it cause, and what physiological effects occur due to it?
The red cell membrane is unstable and is progressively lost
Caused by a defect of red cell membrane proteins (such as ankyrin or Band 3)
This causes spherocytes to form
More rapid breakdown of red cells - anaemia, mild jaundice, gall stones, enlarged spleen
How does porphyrin structure interact with iron?
Holds iron in a flat two-dimensional structure allowing two interaction sites to remain above and below the plane:
- One fixes the molecule to the globin protein
- One is available to bind oxygen
(Porphyrin - heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits)
What do the 4 chains in haemoglobin allow for?
Change between a tight (release) and relaxed (keep) structure to affect oxygen binding
What factors affect whether haemoglobin is relaxed or tight
- pH
- CO2
- Metabolic products
Why can Malaria thrive as it does?
Can survive in the usually inhospitable RBC environment where it is protected from the immune system and has a good energy supply (haemoglobin)
Four conditions that actually help fight against Malaria
- Haemoglobin S
- Beta thalassaemia
- Deficiency of glucose 6 phosphate dehydrogenase (G6PD)
- Haemoglobin C
G6PD: what is it, what does it cause and how does it help stay protected from Malaria?
Glucose 6 phosphate dehydrogenase - Red cell enzyme that generates reducing power (NADPH) that protects the haemoglobin from oxidative damage
Deficiency means that when oxidative stress is high, haemoglobin is damaged as the phosphate shunt can’t generate reducing power and the red damages and denatured to one side of the cell and consequently the cell is swiftly destroyed
It is believed that oxidative stress in red cells is high during malarial infection, so malarial-infected red cells are destroyed providing some protection.
Sickle cell disease: what causes it, what does it do, what is the result, and how is the life expectancy of sufferers?
Sickle cell disease arises because of a single gene mutation substituting one amino acid in the beta-haemoglobin chain
When deoxygenated sickle haemoglobin forms long chains that alter the red cell shape
Sickle cells are prematurely destroyed in the spleen
Heterozygotes are generally well and not affected by the mutation, homozygotes have a greatly reduced lifespan
