iron Flashcards
What is the Fenton reaction?
Ferrous iron plus hydrogen peroxide produces damaging, highly reactive hydroxyl radicals plus ferric iron
What are the two storage forms of iron?
Ferritin and haemosiderin
Main site of absorption of iron
Duodenum and proximal jejunum
Main storage site of surplus iron
Hepatocytes
Most iron in the body is found in…
Erythrocytes and macrophages
Main role of hepcidin
Regulator of iron absorption and macrophage iron release
Where is hepcidin synthesized?
Hepatocytes
In what forms does hepcidin circulate?
Free, and bound to alpha-2 macroglobulin
What is ferroportin?
The main exporter of iron from within cells to the blood stream
How does hepcidin regulate iron release/absorption?
By binding to ferroportin, which causes its internalisation and degradation
Where is ferroportin found?
On the basolateral surface of jejunal enterocytes and on macrophages
What is the role of hephaestin and ceruloplasmin in iron metabolism?
They are multicopper oxidases that catalyse the oxidation of Fe 2+ to Fe 3+ for loading onto transferrin. Hephaestin does this from enterocytes and ceruloplasmin does this from macrophages and hepatocytes.
The erythroid progenitor cells uptakes which form of iron:
a) hepcidin bound
b) ferroportin bound
c) transferrin bound
d) hephaestin bound
c) transferrin bound
Where does heme synthesis occur?
In the mitochondria of the erythroid progenitor cell
How many subtypes of hereditary haemochromatosis are there?
6
What is the classical hereditary haemochromatosis phenotype? How many of the subtypes have this classical phenotype?
Normal Hb
Increased ferritin and transferrin saturation
Tissue iron overload
5/6 of the subtypes have this classical phenotype
What is the most common genotype for hereditary haemochromatosis?
Homozygous C282Y (cysteine to tyrosine at position 282) mutation of the HFE gene on chromosome 6
Briefly describe the pathogenesis of hereditary haemochromatosis.
Insufficient hepcidin cause increased ferroportin causes excessive iron absorption which exceeds the needs of the body. Deposition of Fe in parenchymal organs eg liver and pancreas
Benefits of early diagnosis and therapy for hereditary haemochromatosis
Prevent the development of tissue damage
Reduce morbidity and mortality
Provide long-term survival similar to the general population
Improve mental wellbeing
Therapy for hereditary haemochromatosis
Phlebotomy - 1 unit (500mL) blood/week until serum ferritin 50-100 ug/L
How is therapeutic phlebotomy for hereditary haemochromatosis monitored?
Measure serum ferritin every 10-12 phlebotomies (approx 3 monthly) until target of 50-100 ug/L is reached. May need to monitor more closely when approaching target to ensure iron deficiency does not develop.
Carrier frequency of HFE gene mutation?
1 in 10
Prevalence of hereditary haemochromatosis (HFE gene C282Y homozygotes) in a Caucasian population?
1 in 200
Second most common mutation of HFE gene after C282Y? What kind of disease is this gene mutation associated with?
H63D (his63asp). H63D homozygotes and C282Y/H63D compound heterozygotes are not considered disease-associated genotypes and rarely get clinically significant iron overload
