Iron

Question 1

Biggest stores of iron are in which organs

Answer 1

liver
spleen
bone marrow

Question 2

Iron travels in the blood bound to

Answer 2

transferrin (makes iron inert)

Question 3

Iron is transported into enterocytes from the gut via

Answer 3

DMT1

Question 4

Iron is sequestered and made inert in cells by which protein

Answer 4

ferritin (“ferrets” iron away)

Question 5

Iron is exported from enterocytes via

Answer 5

ferroportin

Question 6

How does transferrin-bound iron get into cells (non-enterocytes)

Answer 6

via the transferrin receptor which cells can regulate; this gets endocytosed and Fe is taken off the transferrin

Question 7

The master regulator of iron metabolism in the body is

Answer 7

hepcidin

Question 8

What does hepcidin do

Answer 8

regulates (blocks) release of iron from cells into the blood

does this by binding ferroportin causing its internalisation and degradation

Question 9

Where is hepcidin made

Answer 9

liver

Question 10

Under what conditions does the liver release hepcidin

Answer 10

when iron levels are HIGH in the blood

Question 11

How does the liver sense high iron levels

Answer 11

via HFE, TfR2, (hemojevelin) HJV in hepatocytes

Question 12

How does hepcidin block absorption of iron from the gut

Answer 12

by inhibiting ferroportin in enterocytes it stops iron transport through enterocytes

Question 13

Under what conditions is hepcidin transcription switched on and what condition does this cause

Answer 13

infection and inflammation

> anaemia of chronic disease (ACD)

Question 14

Why is hepcidin upregulated in inflammation

Answer 14

iron generates ROS so limiting ensures it doesn’t make inflammation any worse

• anaemia of chronic disease seen in RA patients

Question 15

Why is hepcidin upregulated in infection

Answer 15

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.

Question 16

Anaemia is defined as

Answer 16

Low haemoglobin

Haemoglobin below a certain g/dL depending on gender

Question 17

Why do obese people often present with anaemia of chronic disease

Answer 17

low grade inflammation is associated with obesity > hepcidin upregulated

Question 18

How can we differentiate clinically between anaemia of chronic disease and iron deficiency anaemia?

Answer 18

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)

Question 19

Which disease results if a person doesn’t have hepcidin

Answer 19

Hereditary haemochromatosis - no hepcidin so iron overload in body; iron accumulates in body tissues

Question 20

What is the result (to organs) of hereditary haemochromatosis?

Answer 20

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.

Question 21

What is the treatment for hereditary haemochromatosis?

Answer 21

phlebotomy - taking blood (you’re removing iron)

Question 22

What is the cause of herediatry haemochromatosis

Answer 22

gene mutations in TFR2, HJV, HFE protein genes; these proteins sense high iron in the blood and trigger hepcidin release from the liver

Question 23

The most common causes of iron deficiency anaemia

Answer 23

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

Question 24

What can exacerbate iron deficiency anaemia

Answer 24

other diseases (it’s common in the developing world) - Malaria, HIV/AIDS, hookworm infestation, schistosomiasis, tuberculosis etc

Question 25

Describe the pathophysiology of coeliac disease

Answer 25

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

Question 26

Symtpoms of coeliac disease

Answer 26

IDA, diarrhoea, weight loss (or stunted growth in children), and fatigue

Question 27

Investigation for coeliac disease

Answer 27

Test: anti-tissue transglutaminase Ab followed by Small bowel biospy