Iron metabolism and microcytic anaemia Flashcards
inflammatory
cytokines released like IL6 c ^hepciidin so v iron released from RES and v absorption of fe2+ because ferritin absorption reduced fe2+ for RBC also cytokines cause inhibition of EPO production kidney so inhibitor of eryhtopoiesis
histology
haemosidirin
on a blood film how do microcytic anaemia usually present and lab results
hypochromatic
microcytic
v MCV
treatment
diet oral supplest (b side effects make them sick) IM or IV (should see 20g/L rise in 3 weeks) only b transfusion if emergency
iron uses? and why is free iron dangerous?
- carries 02 in hb (RBC) and myoglobin (myocytes)
- cofacor for many enzymes
- eg. cytochromes (oxidative phosphorylation)
- Krebs cycle enzymes
- cytochrome p450 enzymes (detoxification)
- catalse
-free fe2+ dangerous b of Fenten cycle, toxic to cells
f affects
NEGATIVE INFLUENCE -tannins in tea -PHYTATES (CHAPPTIIE ) -fibre (bind to fe2+) - antacids (need acid to reduce fe3+ to fe2+) POSITIVE \ -vit c and citrate b give e needed for the conversion of fe3+ to fe2+
how is fe2+ stored
ferritin (soluble ) haemosiderin (insoluble ) aggregates and c denaturing of lipids and proteins , accumulate in macrophages particularly In liver spleen and marrow
tst
ferritin (usually in cells ) but some in b and is constant level and v in b = iron defiicny - but don’t rule out normal deficiency b cancer/infalmmatio/liver disease -chR IS MORE RELIABLE SO USE HIS except for thalasmea
state of existence of iron
where is iron absorbed?
how us iron excreted?
ferrous and ferric (not useful fe3+) - we use ferrous state
duodenum and upper jejenum
no mechanism for excretion
absorption of iron
- from diet into chyme ham readily absorbed -nonhaem ferrous and ferric, but can only absorb fe2+ so /fe3+ is converted to fe2+ via REDUC/tase enzyme and used vit c as cofactor moves using DMT1 into enterocytes (co transported b fe2+ eve in and H+ out) fe2+ joins liable pool where stored a FERRTINor transported out the cell VIA FERROPORTIN out of the enterocyte b cant travel it b as fe2+ must be converted into fe3+(oxidase ) via hephaestin does this -hepcindin inhibits ferroporin controlling the amount of iron absorbed in our diet
microcytic anaemia what is it and examples?
smaller RBC than normal due to reduced Hb synthesis tharn normal
<80fl
Thalassaemia
Anaemia of chronic disease
Iron defic.
Lead poisoning
Sideroblastic anaemia
hepcidin
peptide hormone made my liver inhibits iron absorbed b causing ferroportin to be interlined and degraded so less fe2+ removed from ferritin stores of entroecytes and macrophages - so fe2+ inmacropages stored and not released c anaemia b cant use fe2+
iron def st
ANGINA pica (craving to eat non nutrition food like dirt) cold hands nadfeet epithelialchange s|(b they need iron ) kol…
heredity haemochromatosis
HFE gene defect on chromes 6 autosomal reccsiesibe usually interacts with transferring receptor c v affinity for it to fe2+ so more stored than released and has negative influence on hepcidin production so fe2+ not lost - symptoms same as before but bronze skin colour treated with venesection to remove that blood
HOW IS REcycleing controlled
- ferroportin - receptor HFE -hepcidin and cytokines
Haem vs non-haem iron?
how do interchange from NH to H?
what prevents absorption of iron and what promotes it?
H = fe2+ (meat)
non-haem fe3+ (veg/beans)
reduction which occurs at low pH in the stomach (as a result of the prescence of acid) fe3+ + e = fe2+
oxidation occurs at a high pH ; fe2+ = fe3+ + e
- inhibits; tannins (tea), phylates (pulses and chapattis) (because they bind to non-haem iron so inhibiting it ) antacids
- promotes ; vitamin c and citrates prevent the formation of insoluble iron compounds and also reduced ferric into ferrous as it donates e
o b film?
microcytic v MCV vMCHC ^ platelet unknown reason ^WBC’’ v reticulocyte hypo chromic
tranfusion asscaued haemosodierosis
soem conditons like tjalaksedm really rely o b trasnfeusoion as with every 400ml transfusion there’s 200mg iron stored and this builds up overtime as haemosiderin free radicals - diabets in pacnera -hyerpgonas -joints -liver cirrhosis -grey skin colour d build up
at risk of groups
prgannt infant child geriatric
cellular iron intake
fe3+ bound to transferrin travel in the b bind to receptor mediated endocytosis fe3+ then put into endosome and released into the acidic micorenvironemtns and reduced to fe2+ fe2+ transported to cytosol via DMT1 stored or move out via ferroportin
iron recalling
most iron is recycled in our body instead of making it new only daily dietary requirement old RBC engulfed by macrophages via phagocyte mainly splenic macrophages but some kpufeer cells - macrophages metabolise the haem - aareused and iron exported to b via transferrin or returned to storage pool ferrtinin in macrophages HOW
excess iron
insoluble haemosidrie , fedangerous because free radical in Fenton reaction
how much iron needed daily?
§
10-15mg/day
what is sideroblastic and lead poisoning anaemias , and how lead differ from the other types of microcytic anaemias
- S = inherited x-linked genetic defect of the ALA synthase gene, involved in the haem synthesis pathway
- presentations is sideroblastic cells in blood film
- L= aquired defect wheere you inhibit the enzymes involved in the haem synthesis pathway
