S4: introduction to anaemia, B12 + folate metabolism + megoblastic anaemia & iron metabolism + microcyctic anaemia Flashcards
Define anaemia and name the important causes of anaemias
Anaemia = a haemoglobin concentration lower than the normal range
Reduced/dysfunctional erythropoiesis
Defects in haemoglobin synthesis
Abnormal structure and mechanical damage
Defects in red cell metabolism
Excessive bleeding
Describe the signs and symptoms of anaemia
Signs = pallor, tachycardia, systolic flow murmur, tachypnoea & hypotension Symptoms = shortness of breath, palpitations, headaches, claudication, angina, weakness + lethargy & confusion
What is folate?
Synthesised in bacteria and plants
Taken up by liver which acts as a store (3-4 months requirement)
Required for synthesis of nucleotide bases needed for DNA & RNA synthesis
Describe the role and complications associated with haematinic replacement treatment
Pernicious anaemia: beware of hypokalaemia (due to increased K+ requirement as erythropoiesis increased back to its normal rate)
List the different causes of microcytic anaemia
T = thalassaemia A = anaemia of chronic disease I = iron deficiency L = lead poisoning S = sideroblastic anaemia
Give examples of good dietary sources of haem and non-haem iron
Haem iron is the best source
Haem iron = liver, kidney, beef steak, chicken, duck, pork chop
Non-haem iron = fortified cereals, raisins, beans, figs, barley, oats, rice, potatoes
How is iron absorbed in the body?
Haem iron = Fe2+, non-haem = Fe2+, Fe3+
Reductase converts Fe3+ into Fe2+ (vitamin C is electon donor)
Fe2+ enters enterocyte via DMT1
Haem enters via diffusion and then converted to Fe2+ by haem oxygenase
Ferritin is store of iron in the enterocyte
Ferroportin transports Fe2+ out of the cell into blood
Hephaestin oxidises Fe2+ into Fe3+
Describe the causes of iron deficiency
Insufficient iron in diet Malabsorption of iron Bleeding Increased requirement Anaemia of chronic disease
Describe how iron overload can occur
Excess iron can exceed binding capacity of transferrin
Deposited in organs as haemosiderin
Promotes free radical formation and organ damage
Describe the causes and treatment of Hereditary haemochromatosis
Autosomal recessive disease caused by mutation in HFE gene
Results in loss of negative influences on iron uptake and absorption
Treat with venesection (draw blood periodically from the patient)
Why is iron required?
Oxygen carriers: Hb in red cells & myoglobin in myocytes
Co-factor in many enzymes: cytochromes, krebs cycle enzymes, catalase
Free iron is potentially very toxic to cells (no mechanism for excreting iron)
How is iron transported in the blood?
Transferrin binds two molecules of Fe3+ and transports iron around the body
What are factors that affect iron uptake?
Negative influence: tannins, phytates (chapattis), fibre, antacids
Positive influence: vitamin C and citrate
How is iron stored?
Functional (available) iron eg. Hb, myoglobin, enzymes
Stored iron: ferritin (soluble) = globular protein with hollow core (pores allow iron to enter and be released) & haemosiderin (insoluble) eg. accumulates in macrophages in spleen, liver and marrow
How is iron taken into a cell?
Fe3+ bound transferrin binds transferrin receptor and enters the cytosol receptor mediated endocytosis
Fe3+ released and reduced to Fe2+ (endosome)
Fe2+ transported to the cytosol via DMT1
Fe2+ can be stored in ferritin, exported by ferroportin (FPN1) or taken up by mitochondria
