Iron Flashcards
Biggest stores of iron are in which organs
liver
spleen
bone marrow
Iron travels in the blood bound to
transferrin (makes iron inert)
Iron is transported into enterocytes from the gut via
DMT1
Iron is sequestered and made inert in cells by which protein
ferritin (“ferrets” iron away)
Iron is exported from enterocytes via
ferroportin
How does transferrin-bound iron get into cells (non-enterocytes)
via the transferrin receptor which cells can regulate; this gets endocytosed and Fe is taken off the transferrin
The master regulator of iron metabolism in the body is
hepcidin
What does hepcidin do
regulates (blocks) release of iron from cells into the blood
does this by binding ferroportin causing its internalisation and degradation
Where is hepcidin made
liver
Under what conditions does the liver release hepcidin
when iron levels are HIGH in the blood
How does the liver sense high iron levels
via HFE, TfR2, (hemojevelin) HJV in hepatocytes
How does hepcidin block absorption of iron from the gut
by inhibiting ferroportin in enterocytes it stops iron transport through enterocytes
Under what conditions is hepcidin transcription switched on and what condition does this cause
infection and inflammation
> anaemia of chronic disease (ACD)
Why is hepcidin upregulated in inflammation
iron generates ROS so limiting ensures it doesn’t make inflammation any worse
- anaemia of chronic disease seen in RA patients
Why is hepcidin upregulated in infection
IL-6 upregulates hepcidin.
Hepcidin stops iron leaving macrophages, because bacteria need it. We lock it away so they don’t have access. However bacteria make sidorophores which scavenge iron so they can compete.
Anaemia is defined as
Low haemoglobin
Haemoglobin below a certain g/dL depending on gender
Why do obese people often present with anaemia of chronic disease
low grade inflammation is associated with obesity > hepcidin upregulated
How can we differentiate clinically between anaemia of chronic disease and iron deficiency anaemia?
1) Gold standard: Hepcidin level
- High- ACD
- Low - IDA (low hepcidin as trying to absorb as much iron as possible)
2) Serum ferritin.
Serum ferritin levels correlate with iron levels.
High serum ferrtiin means it’s probably ACD.
(not a perfect measure tho as its an acute phase protein)
Which disease results if a person doesn’t have hepcidin
Hereditary haemochromatosis - no hepcidin so iron overload in body; iron accumulates in body tissues
What is the result (to organs) of hereditary haemochromatosis?
Iron accumulation causes end organ damage, most importantly in the liver and pancreas. Iron produces free radicals which are toxic to cells.
Hepatic: liver fibrosis, cirrhsis, carcinoma
Extra hepatic: diabetes mellitus, arrhythmia.
What is the treatment for hereditary haemochromatosis?
phlebotomy - taking blood (you’re removing iron)
What is the cause of herediatry haemochromatosis
gene mutations in TFR2, HJV, HFE protein genes; these proteins sense high iron in the blood and trigger hepcidin release from the liver
The most common causes of iron deficiency anaemia
Menstrual blood loss is the commonest cause of IDA in pre-menopausal women
Blood loss from the gastrointestinal tract is the commonest cause in adult men +post-menopausal women - tumour, IBD, coaeliac disease
What can exacerbate iron deficiency anaemia
other diseases (it’s common in the developing world) - Malaria, HIV/AIDS, hookworm infestation, schistosomiasis, tuberculosis etc
Describe the pathophysiology of coeliac disease
An autoimmune disorder of the small bowel
Reaction to gliadin, a gluten protein found in wheat, barley
and rye. Termed ‘gluten sensitive enteropathy’
Upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein, and the immune system cross-reacts with the bowel tissue, causing an inflammatory reaction.
This causes Villus atrophy and crypt hyperplasia - crypts are elongated but villi are destroyed so flattened surface epithelium
Symtpoms of coeliac disease
IDA, diarrhoea, weight loss (or stunted growth in children), and fatigue
Investigation for coeliac disease
Test: anti-tissue transglutaminase Ab followed by Small bowel biospy
