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
Describe the role of hepcidin
Increased in iron overload
Induces internalisation and degredation of ferroportin
Decreased by high erythropoietic activity
Describe the signs and symptoms of iron deficiency
Normal symptoms of anaemia
Pica (unusual cravings for non-nutritive substances)
Cold hands and feet
Angular cheilitis
Glossy tongue with atrophy of lingual papillae
Koilonychia (spoon nails)
Describe causes and symptoms of folate deficiency
Causes: dietary deficiency, increased requirement (pregnancy, severe skin disease), disease of small intestine
Symptoms: reduced sense of taste, diarrhoea, numbness + tingling in feet and hands, muscle weakness
What is the treatment for folate and vitamin B12 deficiency?
Folate = oral folic acid
Vitamin B12 = pernicious anaemia: hydroxycobalamine intramuscular for life; other causes: oral cyanocobalamine (beware of hypokalaemia at the beginning of treating severe pernicious anaemia)
What is vitamin B12?
Water soluble vitamin
Essential co-factor for DNA synthesis
Required for normal erythropoiesis
Essential for normal function and development of nervous system
Produced by bacteria
Good sources: meat, fish, milk, eggs, cheese
Describe the causes & symptoms of vitamin B12 deficiency
Causes: dietary deficiency, lack of intrinsic factor, diseases of the ileum, chemical inactivation of B12
Symptoms: glossitis & mouth ulcers, diarrhoea, parasthesia, disturbed vision, irritability
What is pernicious anaemia?
Decreased/absent intrinsic factor causes progressive exhaustion of B12 reserves
Autoimmune disease
2 types of antibody: blocking Ab blocks binding B12 to IF, binding Ab prevents receptor mediated endocytosis
How is vitamin B12 absorbed?
B12 binds to haptocorrin in the stomach
This complex is digested by pancreatic proteases, releasing B12 which then binds intrinsic factor (IF)
IF-B12 complex binds to cubam receptor which mediates the receptor-mediated endocytosis into enterocytes
B12 exits via MDR1
Binds to transcobalamin in blood & transported around
Majority stored in liver (3-6 year requirement)
What affect can vitamin B12/folate deficiency have on the nervous system?
Folate deficiency = can cause neural tube defects
Vitamin B12 deficiency = associated with focal demyelination (results in reversible peripheral neuropathy)
Serious condition: subacute combined degeneration of the cord = degeneration of the posterior and lateral columns of the spinal cord
