Red cells haemorrhage and intro to anaemia Flashcards
basic structure and function of RBC’s
discoid, 7microm diameter
No nucleus or RNA
Shape allows: flexibility (can go through capillaries half their diameter) and increased area for gas exchange
RBC function
Carry Hb
Allows gas exchange: carry oxygen form lung to tissues, carry CO2 tissues to lungs
How is the RBC’s unique shape and deformability created? what can go wrong?
Determined by membrane (lipid bipolar layer) and cytoskeletal proteins (spectrin, actin, ankyrin)
Inherited abnormalities of said membrane proteins = shortened lifespan of red cells.. cell hemolysis (can’t pass through the filter membrane in the spleen so easily so are taken out of the circulation quicker)
Hereditary spherocytosis
How does the RBC get energy?
No nuclei or mitochondria, but needs energy source to keep Hb in reduced state and maintain osmotic equilibrium
glycolytic pathways produce ATP - maintains osmotic equilibrium
HMP shunt produces NADPH - keeps Hb reduced
- Inherited defects in enzyme pathways
- GGDP deficiency, increased red cell hemolysis and turnover
Haemoglobin carriage
2 alpha and 2 beta chains then haem group
Small amounts of HbF and HbA2
defective production of global chains = thalassemia
Deficiency of iron - reduced production of haem = low Hb
Erythroid unit development
From myeloid multi lineage progenitor
- Erythroid burst forming unit earliest (BFU-E), respond to IL-3, GM-CSF and HIGH levels of EPO
- Erythroid colony forming units (CFU-E), more EPO receptors, respond LOW doses EPO
Morphological stages
pronormoblast
Normoblast - early intermediate and late stages of development
Reticulocyte
Erythrocyte
Kinetics of erythropoiesis
1 promormoblast –> 16 RBC’s
7-10 days, reticulocyte maturation 2 days
4 cell cycles/ divisions
Erythroid changes with differentiation
Progressive increase in haemoglobin
Chromatin clumping
Extrude nucleus
Loss of RNA
Significance of reticulocytes in the blood?
normally 1-2% of red cells, increased in blood loss hemolysis, low in cases of bone marrow failure
Crticial requirements for red cell production
iron
folate
vitamin B12
Regulation of erythrocytes
av RBC lifespan 120 days ERYTHROPOIETIN regulates - glycoprotein - Produced in the kidney - Production of EPO in response to low oxygen tensions
Effects of EPO
Acts through specific EPO receptor to increase RBC production stimulation of BFU-E and CFU-E inc hemoglobin synthysis Inc RBC maturation time Ince reticulocyte release Inc hemoglobin therefore inc Ox delivery
new methods in doping testing
compare ratio of mature: immature RBC’s if nigh numbers of mature not accompanied by high numbers of immature, suggests RBC’s artificially introduced by transfusion, else must demonstrate through hemaotcrit + haemoglobin results over time
EPO clinical implications
Renal failure patients, low Hb Clinical use of recombinant EPO - anaemia of renal failure - other anemias - potential for abuse - sport