Iron metabolism + microcytic anaemias Flashcards
(34 cards)
what is microcytic anaemia
reduced rate of haemoglobin synthesis so erythrocytes smaller and paler (hypochromic) than normal
causes of microcytic anaemia (TAILS)
- thalassaemia reduced globin chain synthesis
- anaemia of chronic disease hepcidin results in functional iron deficiency so reduced haem synthesis
- iron deficiency reduced haem synthesis
- lead poisoning acquired defect that inhibits enzymes of haem synthesis
- sideroblastic anaemia inherited defect in haem synthesis
function of iron
oxygen carriers
- haemoglobin
- myoglobin
co-factor in many enzymes
- cytochromes in ETC
- catalase protecting against oxidative stress
- Krebs cycle enzymes
why is free iron toxic to cells
- catalyst in formation of free radicals from ROS
- complex regulatory systems to ensure safe absorption, transportation and utilisation of iron
- body has no mechanism for excreting iron
ferrous vs ferric iron
- ferrous iron Fe2+ is reduced form of iron
- ferric iron Fe3+ is oxidised form of iron
- haem iron (Fe2+) is more readily absorbed than non-haem iron (mixture of Fe2+ and Fe3+)
- ferric iron must be reduced to ferrous iron before being absorbed from diet
how much iron is needed in diet
10-15 mg/day
1-2mg lost from body each day from skin and GI mucosa
dietary sources of haem iron (Fe2+)
- liver
- kidney
- beef
- chicken
- duck
- pork chop
- salmon/tuna
dietary sources of non-haem iron (Fe2+ and Fe3+)
- fortified cereals
- raisins
- beans
- figs
- barley
- oats
- rice
- potatoes
where does iron absorption occur
- duodenum
- upper jejunum
factors affecting absorption of non-Haem iron from food
negative influence
- tannins(tea) and phytates(chapattis, pulses) bind non-haem iron, inhibiting absorption
- antacids(Gaviscon) inhibit reduction of ferric to ferrous iron
- fibre
positive influence
- vitamin C prevents formation of insoluble iron compounds and helps reduce ferric to ferrous iron
- citrate prevents formation of insoluble iron compounds
iron absorption and transport
- DMT1 on apical surface of enterocytes facilitates uptake of non-haem ferrous iron (Fe2+) from intestinal lumen
- ferric iron (Fe3+) in intestinal lumen is reduced to ferrous iron by reductase (DcytB) before uptake by DMT1
- haem iron readily absorbed by enterocytes via folate transporter
- inside enterocyte haem degraded by haem oxygenase to release ferrous iron to join cytoplasmic pool of Fe2+
- iron in the enterocytes can be stored as ferritin or transferred into bloodstream via ferroportin
- in blood hephaestin converts Fe2+ to Fe3+
- transferrin binds to ferric iron in blood to transport around body
- mostly transported to bone marrow for erythropoesis or taken up by macrophages in RES as storage pool
regulation of iron absorption
- depends on dietary factors, body iron stores and erythropoiesis
- dietary iron levels sensed by enterocytes
control mechanisms
- regulation of transporters e.g ferroportin
- regulation of receptors e.g transferrin receptor
- hepcidin and cytokines
- crosstalk between epithelial cells and other cells
how does hepcidin regulate iron absorption
- hepcidin directly binds to ferroportin resulting in its internalisation and degradation, preventing iron from leaving cell (enterocytes and macrophages)
- down regulates iron uptake by inhibiting transcription of DMT1 gene
hepcidin synthesis increased in iron overload and decreased by high erythropoietic activity
iron recycling
- only small fraction of total daily iron requirement gained from diet
- most from recycling old or damaged red blood cells engulfed by macrophages in RES
- mainly by splenic macrophages and liver Kupffer cells
- macrophages catabolise haem from RBC
- amino acids reused and iron exported to blood (transferrin) or returned to storage pool as ferritin
where is functional iron
- haemoglobin ~2000mg
- myoglobin ~300mg
- enzymes ~50mg
- transported iron (transferrin) ~3mg
iron storage
ferritin (soluble)
- globular protein-iron complex with hollow core
- pores allow iron to enter and be released
haemosiderin (insoluble)
- aggregates of clumped ferritin particles, denatured protein and lipid
- accumulates in macrophages particularly in liver, spleen and marrow
cellular iron uptake
- Fe3+ bound transferrin binds transferrin receptor and enters cytosol by receptor-mediated endocytosis
- Fe3+ within endosome released by acidic microenvironment and reduced to Fe2+
- Fe2+ transported to cytosol via DMT1
- in cytosol Fe2+ can be exported by ferroportin, stored as ferritin or taken up by mitochondria for use in cytochrome enzymes
cellular iron uptake
- Fe3+ bound transferrin binds transferrin receptor and enters cytosol by receptor-mediated endocytosis
- Fe3+ within endosome released by acidic microenvironment and reduced to Fe2+
- Fe2+ transported to cytosol via DMT1
- in cytosol Fe2+ can be exported by ferroportin, stored as ferritin or taken up by mitochondria for use in cytochrome enzymes
mechanism of anaemia of chronic disease
- inflammatory condition causes cytokines released by immune cells
- causes causes inhibition of erythropoietin production by kidney and increased production of hepcidin by liver
- hepcidin causes inhibition of ferroportin so decreased iron release from RES and absorption in gut
- plasma iron is reduced (functional iron deficiency) so inhibition of erythropoiesis in bone marrow
how is iron lost
- desquamation of epithelia
- menstrual bleeding
- sweat
- pregnancy
iron deficiency
- most common nutritional disorder worldwide
- accounts for half of anaemia cases
- clinician must always seek to find underlying cause of deficiency
- could be due to insufficient intake/poor absorption, physiological reasons (pregnancy) or pathological reasons (bleeding)
causes of iron deficiency
- insufficient iron in diet vegan/vegetarian, financial constraints, anorexia
- decreased absorption of iron vegan/vegetarian, gastrectomy, coeliac disease
- bleeding menstruation, GI due to chronic NSAID usage, renal, nose, lungs
- increased requirement pregnancy, growth spurts, lactation
- anaemia of chronic disease functional iron deficiency
groups at risk of iron deficiency anaemia
- infants during transition from milk to solid food
- children
- menstruating women
- geriatric age group
signs and symptoms of iron deficiency anaemia
physiological effects
- tiredness
- pallor
- reduced exercise tolerance
- cardiac - angina, palpitations, heart failure
- increased repsiratory rate
- headache, dizziness, light-headedness
pica - unsual craving for non-nutritive substances e.g dirt, ice
cold hands and feet
epithelial changes
- angular cheilitis (mouth)
- glossy tongue with atrophy of lingual papillae
- Plummer-Vinson syndrome (oesophagus)
- koilonychia (nails)
