Haematopoiesis Erythropoiesis & Iron Flashcards
What is the function of bone marrow?
RBCs, WBCs, platelets prod here
What hormones control haematopoiesis?
Lymphocytes = ILs, TNFα. Granulocytes = G-CSF. Megakaryocytes = TPO. Erythroid = EPO.
What is the reticuloendothelial system?
Network in blood/tissues that is part of the immune system that consists of phagocytic cells = in the spleen can dispose of damaged RBCs
What is the role of a RBC?
Carry Hb, maintain iron in ferrous state, generate ATP, maintain osmotic equilibrium, flexible/large surface area means good gas exchange
Describe Hb
Tetramer of 2 pairs of globin chains,
gene on chromosome 11 + 16,
carry O2/CO2,
protects haem from oxidation
What are the stages of Hb breakdown?
Hb = bilirubin = conjugated with glucuronic acid in liver = enter bile = small intestine = bacterial proteases break off urobilinogen = portal vein to liver = blood to kidney = excreted in urine
What controls erythropoiesis?
Reduced pO2 detected by interstitial peritubular cells in kidney = increased prod of EPO = stim RBC release from bone marrow
What 2 metabolic pathways do RBCs use?
Glycolysis,
pentose phosphate pathway
Discuss the role of iron in the blood?
Transport/stores oxygen,
integral part of many enzymes,
body has no mechanism of excreting iron,
~80% from recycling
Outline the difference between available iron and stored iron
Stored = ferritin, haemosiderin.
Available = Hb, Mb, tissue iron, transported iron (on transferrin)
Where is the majority of stored iron found?
95% found in hepatocytes as ferritin
Why is a haem source of iron better than a non-haem source?
Haem source = in ferrous form.
Non-haem source = has to go through additional step to become ferrous
What vitamin increases the absorption of iron?
Vit c = ascorbic acid
How is iron absorption regulated?
Iron levels sensed by villi of enterocytes.
Control mechanism = reg of transporters, expression of HFE/transferrin receptors, hepcidin and cytokines
What is the central regulator of iron met and how does it function?
Hepcidin = secreted by liver/kidneys - increased in iron overload
degrades ferroportin (protein involved in moving iron out of cells) = prevents iron release from macrophage + iron absorb from gut
How does iron def present on a blood film and in blood parameters?
Hypochromic, microcytic, anisopoikilocytosis, low serum ferritin, low reticulocyte Hb content (CHR)
What tests should be ordered when testing for iron def?
1) ferritin (do bear in mind it’s an acute phase protein),
2) CHR: reticulocyte Hb content (remains low during inflam)
How is iron def treated?
Diet, oral iron, IM iron, IV,
transfusion (only in severe anaemia)
Why is excess iron dangerous?
Haemochromatosis = autosomal recessive, excess iron deposited in tissues = end organ damage.
Reduced Fe (Fe2+) can prod highly reactive hydroxyl and lipid radicals = damage lipid membrane, nucleic acid, protein
What is the pathophysiology of haemochromatosis?
autosomal recessive,
mutated HFE = believes transferrin is high (iron carrier) = increased intestinal release of iron as if there is iron def = excess deposition in tissues = first stored as ferritin then haemosiderin (toxic) = end organ damage.
What is ferritin?
Intracellular protein that stores iron
What is transferrin?
Iron-binding blood plasma glycoprotein that controls the level of free iron in fluids
What is pO2?
(partial pressure of oxygen) reflects the amount of oxygen gas dissolved in the blood
What is the primary source of ATP prod in RBCs?
Glycolysis
Defect in genes coding for which protein cause hereditary spherocytosis?
Spectrin, ankyrin, band 3 protein, protein 4.2
Roughly when does the switch from fetal to adult Hb occur?
3-6 months of age
Iron is absorbed in which part of the GI tract?
Duodenum and jejunum
Which transporter facilitates the uptake of ferrous iron from the intestinal lumen into enterocytes?
DMT1 = divalent metal transporter
What food product has adverse affects on iron availability?
Tea = tannins
How is iron excretion controlled?
There is no pathway for iron excretion, only absorbtion and mobilisation
