Red Cell Physiology Flashcards
Erythropoiesis
The process of forming new red blood cells
Erythropoietin
(EPO)
polypeptide hormone
Released by peritubular cells in kidney as response to hypoxia, e.g.
- Anaemia
- Altitude
- COPD
Increases number of stem cells committed to erythropoiesis
Why might recombinant EPO be used clinically
Treating anaemias associated with renal failure
EPO is released by the kidney
Reticulocytes and what elevated levels indicate
Immature RBC; nucleus extruded and taken up by bone marrow macrophages
Has some dollops of mRNA as cell is still developing
Elevated reticulocyte counts indicates ongoing erythropoeisis
- bleeding
- haemolysis
Average RBC Life Span
120 Days
How is RBC lifespan measured (vaguely)
Blood sample is taken out and radioactively labelled then injected back; measure rate at which it takes radioactivity decreases at body (should be 120)
HbA1c
Glycated/Glycosylated Haemoglobin
Spleen in spherocytosis
Genetic Condition;
Abnormal proteins in RBC (spectrin) that breaks down more rapidly
Degradation of RBCs - Where does it occur and what happens to the proteins
Occurs in reticuloendothelial system (mononuclear-phagocyte system) of spleen, liver + bone marrow
Proteins degraded and recycled;
- iron in stores
- porphyrin (from haem) converted to bilirubin in liver
Bilirubin; what might elevated levels indicate
Yellowish pigment that is made during the normal breakdown of red blood cells
Elevated levels indicate liver disease or elevated RBC breakdown
**Bilirubin causes jaundice
Components of Hb
Ferrous Iron (Fe2+) prosthetic groups [Haem] 2 alpha, 2 beta globin polypeptides linked via non-covalent bonds
Haem at centre of protoporphyrin complex
Foetal Hb vs Adult Hb
Foetuses have Hb containing a2γ2 vs adult which has a2b2
Theres a significant switch at the early part of birth where the foetal Hb is replaced
Best form of iron to get from the diet
Fe2+
This is why eating meat doesn’t necessarily give high iron levels (Fe3+)
Iron from diet; drug interaction
Some drugs (like tetracycline) can cause chelation of iron and prevent its uptake (antacids have a similar effect)
How does iron from diet metabolise
Fe3+ from diet reduced to Fe2+ by syomach acid/is taken up as Fe2+ in the first place
Fe2+ is then converted to Fe3+ in the duodenal cells because god knows why
It is then made into ferritin
Iron is delivered to bone marrow by transferring and stored as ferritin
Incorporated as Hb
Ferritin
Blood protein that contains iron; used to measure the body’s iron stores
Iron recycling
Very efficient; 90% from breakdown of RBCs in liver/spleen
Iron uptake in guts increased when iron deficient; erythroid regulator from bone marrow & an iron stores regulator
Two common causes of anaemia
Gastrointestinal Bleeding
Menstruation
How is Hb allosteric
When first O2 binds, a conformational change that increases the affinity of another subunit to O2, followed by another comformational change in the same protein
4th O2 binds approx 300x more readily than 1st
Oxygen Dissociation Curve
y-axis is percentage saturation of oxygen
Think of x axis as concentration
Not a linear relationship between oxygen saturation and concentration
When first O2 binds, allosteric nature causes change in the molecule; a plateau is eventually caused as a result of maximum saturation (in lungs)
Venous blood is approx 80% saturated believe it or not
What happens during exertion in terms of the oxygen dissociation curve
Say you start running; your tissues have a low partial pressure of oxygen so they have a massive offloading as they go down the steep part of the curve
The cells have their partial pressure of O2 dropping (O2 is consumed due to respiration); dramatic decrease in saturation so the Hb has to give up its O2
Maternal vs Foetal Oxygen Dissociation
Foetus has much higher affinity so O2 diffuses from mother’s blood to foetal blood
Bohr Effect
Acidity enhances O2 release from Hb (CO2 increases blood acidity)
Increasing CO2 at constant pH also lowers Hb’s O2 affinity
Thus O2 is more readily given up to metabolically active tissues (which produce H+ and CO2)
(Right curve is the effect of CO2 released from muscles during exertion)
2,3-Diphosphoglycerate (DPG)
Present in RBCs at same molar conc as Hb
Reduces O2 affinity of Hb; in its absence, Hb would yield little O2 to tissue
DPG binds to deoxyhaemoglobin to shift equilibrium so that oxyhaemoglobin is more likely to readjust (le chateliers), reducing O2 Binding
DPG increased when arterial O2 reduced chronically (e.g. at altitude, severe COPD), so O2 more readily liberate to tissues
2,3 DPG in foetus
Foetal Hb does not bind DPG, hence higher O2 affinity
Carboxyhaemoglobin
Hb has much greater affinity for CO than O2; so if exposed
e.g. via smoking, CO binds irreversibly to Hb to form carboxyhaemoglobin
Tissue becomes starved of O2
CO - Smokers have high levels of CO-Hb
Methaemoglobinaemia
Iron in Ferric (Fe3+) not ferrous (Fe2+) state
Cannot carry O2
Patient may be cyanosed or anoxic
Caused by Hereditary lack of G6P Dehydrogenase which keeps Hb in reduced state
May be caused by drugs, e.g. antimalarials through oxidant stress
CO2 transport in blood - Cl shift
10% dissolved in plasma
30% bound to Hb (forming carbaminohaemoglobin)
60% as HCO3- (important in pH)
(don’t memorise)
Catalysed by carbonic anhydrase in RBC
CO2 + H2O –> HCO3- + H+
Hb buffers H+ to modulate pH
HCO3- may leave RBC , Cl- enters (Chloride shift) to maintain charge
