Lecture 13 - Absorption of Iron

Question 1

What are the roles of iron in the human body?

Answer 1

• Oxygen transport and storage
• Electron transport chain
• Plethora of enzymes
• Cell cycle control

Question 2

Why is tight regulation of iron levels crucial?

Answer 2

• Prevent iron deficiency anaemia

- Hereditary haemochromatosis (absorbing too much iron)

Question 3

What types of dietary iron is there?

Answer 3

Inorganic (majority) and Haem

Question 4

Where is dietary iron processed and by what?

Answer 4

Processed and absorbed by the mucosal cells of the small intestine.

Question 5

How much dietary iron is absorbed?

Answer 5

1-2mg (<10% of consumed iron)

Question 6

How is iron absorption controlled?

Answer 6

Regulated by the basolateral surface of the duodenal enterocyte by control of iron export through ferroportin into plasma.

Question 7

How is iron taken up into the duodenal enterocyte?

Answer 7

Via DMT1 and is stored or exported during its lifespan of a few days.

Question 8

What is Dcytb?

Answer 8

A ferric reductase

Question 9

What is DMT1?

Answer 9

Divalent metal transporter responsible for ferrous uptake

Question 10

Why must iron be bound to another molecule in the body?

Answer 10

Iron is toxic on its own

Question 11

What is ferroportin?

Answer 11

The efflux protein, the one known iron exporter, acted on by marker regulator. It transports ferrous iron out of the cell, generally aided by ceruloplasmin and/or hephaestin, which oxidise iron to its ferric state so it can bind Ferritin in the extracellular medium

Question 12

What does ferritin do?

Answer 12

Stores iron and releases it when the body needs it

Question 13

What is hephaestin?

Answer 13

Ferroxidase

Question 14

What is transferrin?

Answer 14

Essential for iron binding in blood

Question 15

Describe non-enterocyte iron transport

Answer 15

Transferrin receptor mediated endocytosis involved both transferrin receptors DMT1 and the ferric reductase STEAP3.

Question 16

Describe Haem transport

Answer 16

The iron (III) storage form must be reduced to iron (II) in order to cross the plasma membrane. In the blood, iron (II) is reoxidised to iron (III) by ferroxidase II.

Question 17

What is HCRP1?

Answer 17

Haem import protein; a protein enabling transmembrane transport of haem molecules from alimentary tract lumen into enterocyte.

Question 18

What is HO1?

Answer 18

Is essential for haem catabolism to release free iron and biliverdin

Question 19

What is haemolytic anaemia?

Answer 19

A disorder in which red blood cells are destroyed faster than they can be made

Question 20

What does PCT (Porphyria Cutanea Tarda) present like?

Answer 20

• Vampire appearance.
• Presents clinically as a pathological sensitivity of skin exposed to light causing scarring, hair growth and disfiguration.

Question 21

Where are the major stores of iron?

Answer 21

Liver, spleen, and bone marrow.

Question 22

Where does iron absorption take place?

Answer 22

Small intestine

Question 23

How do the body iron levels communicate with the small bowel?

Answer 23

Hepcidin

Question 24

What is hepcidin?

Answer 24

• Master regulator of iron metabolism

- Produced in the liver with bactericidal properties

Question 25

How does cellular iron regulation through IRPs work?

Answer 25

Cellular iron homeostasis is accomplished by the coordinated regulated expression of the transferrin receptor and ferritin, which mediate iron uptake and storage, respectively. The mechanism is post-transcriptional and involves two cytoplasmic iron regulatory proteins, IRP1 and IRP2.

Question 26

What happens if hepcidin is elevated by inflammation/infection?

Answer 26

Causes reticulo-endothelial sequestration of iron. Results in anaemia despite adequate body iron levels.

Question 27

By what mechanism does inflammation cause anaemia?

Answer 27

Inflammation increases interleukin-6 production. the consequent increase in hepcidin blocks macrophage iron release as well as the intestinal absorption of iron, resulting in hypoferremia.

Question 28

How is obesity related to anaemia?

Answer 28

Obesity may disrupt iron homeostasis, resulting in iron deficiency anaemia. This association may be due to increased hepcidin levels mediated by chronic inflammation.

Question 29

What is important when determining type of anaemia?

Answer 29

Ferritin levels

Question 30

What is transferrin saturation?

Answer 30

The ratio of serum iron and total iron-binding capacity, multiplied by 100.

Question 31

What does the total iron-binding capacity measure?

Answer 31

The blood’s capacity to bind iron with transferrin.

Question 32

What are the symptoms of anaemia?

Answer 32

Headache, dizziness, fainting, muscle weakness, motility disorder, shortness of breath, nausea, anorexia, changed colour of stool, palpitations, rapid heart rate, chest pain, angina, increased susceptibility to infection, menorrhagia, amenorrhoea

Question 33

What happens when you can’t make hepcidin?

Answer 33

Hereditary haemochromatosis (absorbing lots of iron, causing damage)

Question 34

What is Haemochromatosis?

Answer 34

A hereditary disease characterised by improper dietary iron metabolism which causes the accumulation of iron in a number of body tissues.

Question 35

What can iron accumulation lead to?

Answer 35

End organ damage, most importantly in the liver and pancreas, manifesting as liver failure and diabetes mellitus respectively.

Question 36

What is meant by Fenton reactions?

Answer 36

Iron and hydrogen peroxide are capable of oxidising a wide range of substrates and causing biological damage. The reaction is complex and capable of generating both hydroxyl radicals and higher oxidation states of the iron.

Question 37

What can Fenton reactions lead to?

Answer 37

Production of free radical mediated oxidative stress, cellular damage (DA adducts) and eventually cellular death via apoptotic signalling

Question 38

What is coeliac disease?

Answer 38

An autoimmune disorder of the small bowel. Reaction to gliadin, a gluten protein found in wheat, barley and rye. “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 villous atrophy.

Question 39

What are the symptoms of Coeliac disease?

Answer 39

IDA, diarrhoea, weight loss, fatigue