8: Iron in health and disease

Question 1

What process is iron essential for?

Answer 1

Oxygen transport by RBCs

Question 2

What part of respiration is iron essential for?

Answer 2

Cytochrome system (electron transport)

Question 3

What are the two forms of iron found in the body?

Answer 3

Ferrous iron (Fe2+)

Ferric iron (Fe3+)

Question 4

Iron is ___ in high concentrations - why?

Answer 4

toxic

produces free radicals - oxidative stress

Question 5

Where is most iron found in the body?

Answer 5

Within RBCs as haemoglobin

Question 6

Which cells, found in the bone marrow, contain a lot of iron?

Answer 6

Bone marrow macrophages

Question 7

Where is haem produced?

Answer 7

Cytosol of RBC precursors

Question 8

Which organ stores iron as ferritin?

Answer 8

Liver

Question 9

Where in the GI tract is iron absorbed?

Answer 9

Duodenum

Question 10

Which protein converts Fe3+ to Fe2+ in the duodenum?

Answer 10

Cytochrome B

Question 11

Which transport protein moves iron from the lumen of the duodenum into the enterocytes?

Answer 11

DMT-1

Question 12

Which proteins transport iron

a) into duodenal enterocytes
b) from the enterocytes to the circulation
c) through the circulation to the bone marrow?

Answer 12

a) DMT-1

b) Ferroportin

c) Transferrin

Question 13

Where does iron go to be stored if it isn’t transported directly to the bone marrow?

Answer 13

Liver

Question 14

Which organ detects iron levels and acts to decrease absorption if there is iron overload?

Answer 14

Liver

Question 15

Which protein, produced by the liver, decreases iron absorption?

Answer 15

Hepcidin

Question 16

In what forms is iron

a) found in red blood cells
b) transported in the circulation
c) stored in the liver?

Answer 16

a) Haemoglobin

b) Transferrin

c) Ferritin

Question 17

Does hepcidin’s effect on ferroportin cause an iron deficiency?

Answer 17

No

The iron is there but it can’t reach the circulation

Lack of iron availability

Question 18

How many iron ions can transferrin carry at once?

Answer 18

2

Question 19

How does transferrin know where to deliver iron ions?

Answer 19

Cells express transferrin receptors

Question 20

Which tissue is rich in transferrin receptors?

Answer 20

Bone marrow

Question 21

Which cells express transferrin receptors?

Answer 21

Bone marrow macrophages (bone marrow)

Hepatocytes (liver)

Question 22

What happens to transferrin saturation in

a) iron overload
b) iron deficiency?

Answer 22

a) Increases

b) Decreases

Question 23

Which measurement is mainly used to diagnose iron deficiency?

Answer 23

Serum ferritin

Question 24

What does serum ferritin increase in response to?

Answer 24

Iron overload

But also infection, malignancy etc. because it’s an acute phase protein

Question 25

What happens to serum ferritin in patients with inadequate iron intake?

Answer 25

Decreases

Reflecting exhaustion of iron stores

Question 26

What type of anaemia is caused by iron deficiency?

Answer 26

Microcytic hypochromic anaemia

Low Hb

Low serum ferritin

Question 27

What are three clinical signs of iron deficiency anaemia?

Answer 27

Pallor - skin, conjunctiva

Koilonychia - spoon nails

Angular stomatitis

Question 28

Why might a patient be iron deficient?

Answer 28

Inadequate iron intake

Bleeding

Malabsorption

Question 29

What is occult blood loss?

Answer 29

Bleeding which isn’t detected by the patient or the doctor

e.g GI bleeds - peptic ulcers, tumours

Question 30

What causes anaemia of chronic disease?

Answer 30

Inflammatory cytokines associated with chronic disease

Question 31

What is the mechanism of iron unavailability in anaemia of chronic disease?

Answer 31

Inflammation causes increased storage of iron as ferritin

So hepcidin inhibits transport of iron as transferrin

So loads of iron is stuck in enterocytes and can’t reach the circulation

Question 32

What is the most common cause of iron overload?

Answer 32

Haemochromatosis

Question 33

A mutation in which gene causes haemochromatosis?

Answer 33

HFE gene

Question 34

What causes

a) primary

b) secondary

haemochromatosis?

Answer 34

a) Inherited gene mutation

b) Iron overload due to repeated blood transfusion

Question 35

Which liver protein is deficient in haemochromatosis?

Answer 35

Hepcidin

So no negative feedback of iron absorption > iron overload

Question 36

Which organs are affected by iron deposition in haemochromatosis?

Answer 36

Liver - cirrhosis

Skin - bronze

Heart - cardiomyopathy –> arrhythmias

Joints - arthritis

Pancreas - “bronze diabetic”

Pit. gland –> amenorrhoea, testicular atrophy

Question 37

Why does iron deposition cause disease in haemochromatosis?

Answer 37

High levels of iron ions produce high volumes of toxic free radicals

Question 38

How is haemochromatosis treated?

Answer 38

Weekly phlebotomy

just take blood to drive more Hb production and exhaust iron stores

Question 39

What is a common complication of untreated haemochromatosis?

Answer 39

Cirrhosis

Which may cause hepatocellular carcinoma

Question 40

What is offered to the families of patients with haemochromatosis?

Answer 40

Screening for HFE gene mutations

Question 41

Why is haemochromatosis screening important?

Answer 41

Liver damage is often clinically silent

Question 42

What is an iatrogenic cause of iron overload?

Answer 42

Repeated blood transfusions

Question 43

___ erythropoiesis can cause iron overload.

Answer 43

Ineffective erythropoiesis

Question 44

Which conditions, requiring regular blood transfusions, may result in secondary iron overload?

Answer 44

Thalassaemia

Myelodysplasia

Question 45

How is iron overload secondary to blood transfusions avoided?

Answer 45

Iron chelating drugs

Question 46

How do iron chelating drugs work?

Answer 46

Bind to Fe, form solution and are excreted by kidneys

Question 47

How are iron chelators administed?

Answer 47

IM