Haematology Flashcards
What is erythropoietin?
A circulating glycoprotein that adjust the amount of red blood cells produced by the bone marrow by the process of erythropoiesis.
How is erythropoiesis controlled?
INCREASE by:
- Hypoxia
- Haemorrhage
DECREASED by:
- Increase MCV due to transfusion
How does erythropoietic control RBC formation?
Increases the number of stem cells in bone marrow that will be converted to RBC precursors and therefore matured erythrocytes.
Where is EPO produced?
- 85% in the kidneys - peritubular capillary bed by interstitial cells in the renal cortex
- 15% from the liver
- Small amount from pericytes in the brain too (think that the brain increases EPO due counteract the effect of any hypoxia)
The liver is unable to compensate where these is renal disease that affects EPO production from the kidney; hence anaemia develops.
How is EPO secretion regulated?
- The main stimulus for EPO production is hypoxia
- Alternate sources of stimuli include androgens and cobalt salts (COBALamin vitB12)
Recent evidence suggests that the mechanism for the oxygen sensor that stimulates EPO production in the kidney works as an on/off mechanism. DeoxyHb stimulates whilst oxyHb inhibits the mRNA transcription.
- Respiratory alkalosis that develops at high altitudes also stimulates EPO production
- Like renin, EPO is also directly stimulated by beta adrenoreceptors stimulated by sympathetic nerves directly on renal interstitial cells.
What is haemoglobin F (foetal)?
Similar to haemoglobin A but he beta chains are replaced by gamma chains.
It has a higher affinity for oxygen than HbA due to the fact that it does not as effectively bind 2,3 DPG.
What happens to HbF following birth?
At birth, HbF in normal term pregnancy is around 40% of circulating Hb. As the baby matures over the next year this is gradually replaced in normal individuals with HbA.
After 4 months it is roughly 10% of circulating Hb.
HbF has a lower p50 (pO2 required for 50% oxygen saturation) because it has less effective binding with 2,3 DPG, i.e it holds on to oxygen more effectively.
What is the rhesus antibody system?
The Rh group of antigens are another common group of antigens on RBCs. There are numberous rhesus antigens but the main ones are C, D, E.
D is the most antigenic and relevant in pregnancy.
If a Rh negative mother has a Rh positive baby, she can develop autoantibodies against the Rh positive baby following foteo-maternal transfusion at time of delivery. Following this, if she has another baby, the autoantibodies will cause haemolysis in the second pregnancy and cause complications such as haemorrhage, foetal hydrops, haemolytic disease of the newborn.
This complication can be prevented by the administration of anti-d-antibodies during the post-partum period to prevent subsequent babies from the risk of anti-Rh antibodies.
What is the ABO system?
Describes the different antigens (aka agglutinogens) present on RBC membranes. This divides the general population into 4 major groups:
- Type A - has A antigen
- Type B - has B antigen
- Type AB - has both A and B antigen
- Type O - have neither A nor B antigen
This is important because in infants, the immune system will quickly develop antibodies to antigens not present on their own blood cells. Hence Type A will have anti-B aggultinin antibodies and vice verse. Type AB will have no antibodies whilst O will have both A and B antibodies.
What is the mechanism of haemolytic transfusion reaction?
When blood is transfused into a person who has developed antibodies against the agglutinogens, it causes these RBCs that express the antigen to agglutinate (clump together) and haemolyse.
This is not only isolated to ABO incompatibility reactions and can occur with less common antibody-antigenic reactions.
What happens to platelets in repeat transfusion of blood?
- Repeated transfusion result in low levels of thrombocytes due to haemodilution
- Many packets of RBCs contain only non-functional platelets
- There may be a small chance of the transfusion of anti-platelet antibodies or alternately, the production of new-antibodies by the transfusion recipient
What are the anti-clotting mechanisms?
Blood clotting is a balance between reactions that prevent clots in blood vessels and reactions that break down clots that form or both.
- Thromboxane A2 - pro-platelet aggregation
- Prostacyclin - anti-platelet aggregation
- Antithrombin III which is facilitated by heparin, causes inhibition of clotting factors IX, X, XI, XII
PLASMIN opposes this and causes fibrinolysis., the breakdown of fibrin (Fibrin degradation products) also inhibit thrombin by themselves and by tissue-type plasminogen activator (tPA).
How does heparin work?
Heparin is a naturally occurring anticoagulant that acts by helping antithrombin III to inhibit clotting factors IX, X, XI, XII.
How does warfarin work?
Inhibits vitamin K which is the cofactor for the enzyme that catalyzes conversion of glutamic acid to clotting factors I, VII, IX, X, protein C and S.
