Chapter 2: Erythropoiesis and Anaemia Flashcards
What is the life span of an RBC?
120 days
What colour does haemoglobin stain?
pink
How does chromatin change as normoblasts develop?
condenses
How long does the reticulocyte circulate in the blood until it matures?
1-2days
How many mature red cells does on pronormoblast give rise to normally?
16
What cells of the kidney produce erythropoietin?
peritubular interstitial cells of the kidney
What is the stimulus for erythropoietin production?
oxygen tension in the tissues of the kidney
How does erythropoietin stimulate erythropoiesis?
increases number of progenitor cells committed to erythropoiesis by activating transcription factors eg GATA-2 involved in initiating erythroid differetiation in stem cells
What occurs with chronic increase in erythropoietin?
extension of eryhtropoiesis into fatty marrow and extramedullary sites
How many polypeptide chains does each molecule of haemoglobin have?
4
What are the three forms of Hb in adult blood?
HbA ; HbF and HbA2
What are the polypeptide chains in HbA?
2x alpha and 2x beta
What are the polypeptide chains in HbF?
2x alpha and 2xgamma
What are hte polypeptide chains found in HbA2?
2 x alpha and 2xdelta
Where does haem synthesis largely take place?
mitochondria
What are the main constituents of haem?
protoporphyrin and Fe2+
What happens to the haemoglobin moelcule when O2 is unloaded?
the beta chains are pulled apart, allowing 2,3 DPG to bind, resulting in a lower affinity for O2
What is methaemoglobinaemia?
circulating Hb has oxidised iron (3+) instead of Fe2+
What other name is the anaerobic glycolytic pathway known as?
Embden-Meyerhof pathway
What is the function of hte production of NADH in glycolysis?
needed by the enzyme methaemoglobin reductase to change ferric iron to ferrrous form
What is the function of the hexose monophosphate shunt?
production of NADPH
What is the function of NADPH?
links with glutathione which prevents oxidative stress to RBCs
What enzyme is required for the hexose monophosphate shunt?
glucose-6-phosphate dehydrogenase deficiency
What is the most abundant protein in the RBC cell membrane?
spectrin
What is anaemia defined as?
reduction in haemoglobin concentration of the blood below normal for age and sex
What would cause low reticulocyte count in anaemia?
marrow disease; deficiency of iron, B12 or folate; lack of erythropoietin (renal disease); reduced tissue O2 consumption; ineffective erythropoeisis; chronic inflammatory or malignant disease
What is seen in the blood if there is ineffective eryhropoiesis?
unconjugated bilirubin and LDH
What is macrocytic anaemia?
red cells are abnormally large
How are marcocytic anaemias divided?
megaloblastic and non-megaloblastic
What is seen in megaloblastic anaemias?
erythroblasts in the bone marrow show delayed maturation of the nucleus compared to the cytoplasm
What causes the asynchronous maturation of the nucleus in megaloblastic anaemia?
defective DNA synthesis
What is the usual cause of megaloblastic anaemia?
deficiency of vit B12 or folate
What is the name of the IF-B12 receptor in the terminal ileum?
cubilin
What is B12 mainly bound to in plasma?
haptocorrin
Where is haptocorrin synthesised?
granulocytes and macrophages
What protein delivers B12 to bone marrow and other tissues?
transcobalamin
What is the function of methyl B12?
methionine synthesis: methylation of homocysteine to methionine
What is the form of folate which circulates in plasma?
reduced monoglutamate form
What is the function of folate?
conversion of uridine to thymidine
Where is folate absorbed?
duodenum and jejunum
What is the form of folate as a coenzyme?
methyl-THF
What drugs inhibit folate reactions?
methotrexate; trimethoprim
What is achlorhydria?
absence of HCl
What antibodies are invovled in PA?
against gastric H/K ATPase and IF
What are the features of vit B12 neuropathy?
progressive symmetrical neuropathy affecting peripheral sensory nerves- mainly DCML; lower limbs more than upper limbs
What is the thought to be the cause of neuropathy with vit B12?
defective methylation of myelin
What causes the non-megaloblastic macrocytic anaemia?
increased lipid deposition on the red cell membrane or alterations of erythroblast maturation time in marrow
What is the most frequent cause of a riased MCV wtihout anaemia
alcohol