CARDIO- Red Blood Cell Production and Survival Flashcards
what is the sequence of events forming a blood cell
hemocytoblast proerythroblast early erythroblast (ribosome synthesis) late erythroblasts (Haemoglobin accumulation) normoblast (ejection of nucleus) reticulocyte erythrocyte
how is red cell production regulated
RBC number is inversely related to ambient O2 pressure
key regulator = erythropoietin
how does erythropoietin regulate regulate RBC production
stimulus (hypoxia) - kidneys / liver release erythropoietin - erythropoietin stimulates the bone marrow - enhanced erythropoietin increased RBC count - increased O2 carrying ability of blood = homeostasis
what does ferroportin do
helps absorption of iron from intestines into the blood
what does erythroferrone do
inhibits hepcidin
what sources is iron found in
meat, eggs, vegetables, dairy
how is iron absorbed / regulated
gastric secretions and ascorbic acid help to absorb
DMT-1 and ferroportin regulate
why is vitamin B12 / folic acid needed
essential for RBC maturation and DNA synthesis
needed for the formation of thymidine triphosphate
deficiency leads to failure of nuclear maturation
what are the causes of iron deficiency
poor diet- inadequate intake / malabsorption
increased demand - pregnancy, growth
chronic blood loss
malabsorption
what are the signs of iron deficiency
spoon nails
anaemia - microcytes, hypochromic (pale)
what are the causes of B12 deficiency
inadequate intake
absorption defect
IF deficiency
drugs - anticonvulsants (inhibit absorption)
what are the signs of B12/ folate deficiency
macrocytes - megaloblastic anaemia
hyper segmented neutrophils
what are the treatments for deficiencies
Iron - iron infusion / tablets
B12- hydroxocobalamin
folate - give folic acid
what are some other factors that affect nutrient levels
renal disease - ineffective erythropoiesis
reduced bone marrow erythroid cells
what is ATP used for in RBC
maintaining shape and deformability, regulates intracellular cation concentration via Na/K pumps
how does a G6PD deficiency affect red blood cell production and survival
G6PD deficiency = low NADPH and GSH
meaning there is acute haemolysis on exposure to oxidant stress; oxidative drugs or infections
what is hereditary spherocytosis
loss of membrane integrity, RBC become spherical
deficiency in the protein with vertical interactions between the membrane skeleton and lipid bilayer
what is hereditary elliptocytosis
mutations in the horizontal interactions (spectrin =, ankyrin, actin, protein 4.1 deficiency)
what are haemoglobinopathies
mutations or deletions leading to the abnormal synthesis of globin chain in sickle cell disease / reduce rate of synthesis in thalassaemia
what happens in sickle cell disease
point mutation in beta globin gene makes insoluble Hb when deoxygenated leading to polymerisation = sickle shaped cells
what happens in thalassaemia
beta - loss of beta-chain causes mild microcytic anaemia
loss of both causes thalassaemia major
excess alpha chain precipitates in erythroblasts causing haemolysis and ineffective erythropoiesis
alpha thalassaemia - can be loss of 1,2,3,4
outline hereditary forms out haemolytic anaemia`
intrinsic
intravascular
red cell membrane disorders - hereditary spherocytosis, elliptocytosis
red cell metabolism - G6PD / PK deficiency
haemoglobinopathies - sickle cell. thalassaemia
outline acquired forms out haemolytic anaemia
extrinsic
extravascular
immune - autoimmune (warm/ cold)
alloimmune - haemolytic transfusion reaction/ haemolytic disease of the new-born
non-immune - infection, red cell fragmentation, chemical agents, secondary (liver/kidneys), PNH
