Normal Erythropoiesis Flashcards
What are the properties of red blood cells?
Full of haemoglobin to carry oxygen
No nucleus or mitochondria
High surface area:volume ratio to allow gas exchange
Flexible to squeeze through capillaries
Why do red blood cells have no nucleus?
To allow more space for haemoglobin molecules and to make the cell more deformable
What are some issues caused by the adaptions of red blood cells?
High oncotic pressure and oxygen rich environment
Limited lifespan and can’t divide or replace damaged proteins
Can only produce energy by glycolysis
What are some features of the red blood cell membrane?
Complex structure = not just lipid bilayer
Protein spurs and anchors to make it flexible
What is required to allow red blood cells to keep water out?
Energy is needed to maintain specific ion concentrations
What maintains ion concentrations in red blood cells?
The sodium potassium pump = keeps water out but requires ATP
What is haemoglobin?
Tetrameric globular protein
What chains does adult haemoglobin consist of?
2 alpha and 2 beta chains
What does the heme group consist of?
Fe2+ in a flat porphyrin group = oxygen binds to Fe2+
How many heme groups are there per subgroup?
One heme per subgroup = 4 subgroups per haemoglobin molecule so 4O2 can bind
Where does red blood cell production occur?
In the bone marrow = result of HSC proliferation and differentiation
What regulates red blood cell production?
Erythropoietin
When is erythropoietin released by the kidneys?
When hypoxia is sensed by kidneys = releases erythropoietin to stimulate red blood cell production
Where does red blood cell destruction normally occur?
In the spleen
What is the average lifespan of a red blood cell?
120 days
What cells take up aged red blood cells?
Macrophages
What happens when red blood cells are destroyed?
Contents are recycled = globin chains recycled to amino acids
Heme group broken down to iron and bilirubin
What happens to the bilirubin produced by heme breakdown?
Taken to liver and conjugated then excreted in bile
What are the steps in the breakdown of heme?
Heme - porphyrin - biliverdin - bilirubin
What are reactive oxygen species?
Free radicals that have unpaired electrons (e.g hydrogen peroxide)
Why are reactive oxygen species an issue?
They interact with other molecules and damage their structures
What is the importance of glutathione?
Protect against hydrogen peroxide by reacting with it to form water and GSSG
How is glutathione replenished by the body?
Using NADPH
How is NADPH replenished?
Using the hexose monophosphate shunt
What is the rate limiting step in glutathione production?
G6PD
How is CO2 transported in the body?
10% dissolved in solution
30% bound directly to Hb as carbamino-Hb
60% as bicarbonate = red cells help in production
What is bicarbonate exchanged for in red blood cells?
Exchanged for chlorine = HCO3- exported by facilitated diffusion
How do red blood cells buffer the H+ produced by CO2?
Using deoxygenated haemoglobin
What effect does chlorine entering the red blood cell in exchange for HCO3- have on the cell?
Preserves potential and causes cell to swell
What shape is the oxygen-haemoglobin dissociation curve?
Sigmoidal
How does red blood cells show co-operative binding?
As one O2 binds it changes the shape of Hb = makes it easier for next O2 to bind to another subunit
Where on the oxygen-haemoglobin dissociation curve can venous pO2 be seen?
At the shoulder of the steep part of the curve = large reserve of spare capacity
What effect to molecules that interact with Hb have on the dissociation curve?
Shift it to the right = examples include H+, CO2 and 2,3-BPG
What does shifting the dissociation curve to the right do to oxygen delivery?
Increases the amount of oxygen being delivered
What does glycolysis produce?
2 molecules of pyruvate, 2 ATP and 2 NADH
