Erythropoiesis Flashcards
What engulfs old RBCs?
Phagocytic cells of the liver and spleen
What are globular haemoglobin proteins broken down into after RBC break down?
Amino acids which enter the blood stream Haem group (minus iron) is converted to bilirubin Bilirubin is transported to liver and secreted into bile
What happens to iron after RBC breakdown?
Finds to transferrin in the blood and is recycled
What is erythrocyte production regulated by?
Erythropoietin (EPO)
Where is EPO released from?
Kidney
What is the process from myeloid stem cell to mature erythrocyte?
Proerythroblast (derived from myeloid stem cells)
Polychromatic erythroblast (Hb in cytoplasm)
Orthochromatic erythroblast (Nucleus shrinks, full complement of Hb in cytoplasm)
Erythroblast excludes nucleus
Reticulocyte into circulation
Mature erythrocyte
What is the shape of RBCs described as?
Biconcave disc
What are the approximate sizes of RBCs?
8 (micro)m diameter
2 (micro)m thick at edge
1 (micro)m thick in centre
What % of blood is plasma?
55%
What % of blood is the buffy coat and what is its constituents?
1%
Platelets and WBCs
What is haematocrit?
% RBCs
What makes up packed cell volume?
Everything but plasma
What regulates RBC ion balance volume?
Sodium pump
How is ATP synthesised in RBCs?
Anaerobic glycolysis
What helps keep iron in Fe2+ state?
NADH from glycolysis
What is partly metabolised through a hexose monophosphate shunt, and what does this shunt do?
Glucose
Produces NADPH, required for maintenance of adequate levels of reduced glutathione
What is produced when PO2 is reduced?
2,3 biphosphoglycerate- releases O2 from Hb
What is glutathione?
Tripeptide, consisting of glutamate, cysteine and glycine
What does glutathione do?
Reduced glutathione (it’s normal state) combats oxidative stress
What are ROS?
Free radicals- highly reactive molecules with unpaired electrons
What does excessive free radicals or inadequate antioxidant defence mechanisms lead to?
Damage of cellular structures and enzymes
What does glutathione protect against?
Toxic effects of ROS
Also essential to detoxify hydrogen peroxide, the primary intermediate in oxidative damage
What can glucose 6-phosphate dehydrogenase insufficiency cause?
NADPH deficiency, leading to reduced glutathione, leading to cell damage
What 3 forms is CO2 produced by tissues carried to the lungs in?
Physically dissolved in solution (10%)
Bound to Hb-carbamino-haemoglobin (30%)
As bicarbonate ion (60%)
What is CO2 transport facilitated by?
Carbonic anhydrase
What happens in the Cl- shift?
Chloride/bicarb exchange- exports HCO3- (facilitated diffusion)
Cl- enters to preserve cell potential
What is the structure of Adult Hb?
4 globin sub units, each containing a single haem molecule
Haem group contains single Fe2+ ion
Each haem group can bind one O2 molecule
When fully saturated, how much O2 will 1g Hb bind?
1.34ml
What is required for Hb synthesis?
Synthesis of globin chains- 4 per molecule of Hb
Synthesis of porphyrin ring (haem group)
Insertion of iron into haem
What globin sub units make up adult and foetal Hb?
HbF- predominantly a2y2, in late gestation y expression falls, B expression rises
HbA- predominantly a2B2
Do allosteric interactions (e.g. O2 binding to Hb) follow Michaelis-Menten kinetics?
No
What does increasing substrate concentration in allosteric interactions result in?
Sigmoidal curve rather than hyperbola, indicating co-operative behavior
What is co-operativity in allosteric interactions?
The influence that the binding of a ligand to one site on the molecule has on the binding of ligand to a different functional site
Describe the Hb dissociation curve in terms of arterial and venous blood
Arterial- plateau phase sustains SaO2 >90% over wide range of inspired (blood) pO2
Venous- steep phase of curve favours O2 offloading to tissues
Does HbF have a higher affinity for O2 and 2,3 BPG than HbA?
Higher for O2, lower for 2,3 BPG
This facilitates the transfer of O2 from mother to foetus
