Iron Deficiency and Anaemia of Chronic Disease

Question 1

In what state is the iron in the haem group of haemoglobin?

Answer 1

Fe2+ (ferrous)

Question 2

How much iron do you need per day to maintain the production of red blood cells?

Answer 2

20 mg/day

Question 3

How can iron be lost under normal, non-pathological conditions?

Answer 3

Desquamation of cells in the skin and gut

Bleeding (menstruation is one of the largest causes of loss of iron from the body in women)

Question 4

How much iron does the human diet normally provide?

Answer 4

12-15 mg/day

Question 5

State some natural foods that are high in iron.

Answer 5

Meat and fish
Vegetables
Whole grain cereal
Chocolate

Question 6

Which form of iron cannot be absorbed?

Answer 6

Fe3+ (ferric)

Question 7

What effect does drinking tea have on iron absorption?

Answer 7

Cups of tea promotes the conversion of Fe2+ to Fe3+ so less absorbed

Question 8

Why do meat and fish eaters have an advantage over vegetarians in terms of iron absorption?

Answer 8

They will absorb iron in the haem form

haem iron= iron has already been incorporated into a haem group so easier for u to absorb

Question 9

State three systemic causes that increase iron absorption.

Answer 9

Iron deficiency
Anaemia/hypoxia
Pregnancy

Question 10

Which channel, on the basement membrane of intestinal epithelial cells, allows movement of iron into the circulation?

Answer 10

Ferroportin

Question 11

What is a key regulator of iron absorption that affects ferroportin?

Answer 11

Hepcidin

Question 12

How is the level of hepcidin affected?

Answer 12

There are certain proteins (such as hepcidin) that have iron-responsive elements in their genes
So iron is part of the complex that switches on hepcidin transcription

High iron - high hepcidin - low ferroportin- low absorption

Question 13

How is iron stored within cells?

Answer 13

In ferritin micelles

Question 14

What transports iron in the circulation?

Answer 14

Transferrin

Question 15

State three parameters that can be measured that involve transferrin?

Answer 15

Transferrin
Transferrin Saturation
Total Iron Binding Capacity (TIBC)

Question 16

What is the normal transferrin saturation?

Answer 16

20-40%

Question 17

Where is erythropoietin produced and what effect does it have?

Answer 17

Kidneys (stimulated by hypoxia)
Increase in red blood cell precursors
Red blood cell precursors will survive longer and the EPO will make them grow and differentiate to produce more progeny

Question 18

What is anaemia of chronic disease?

Answer 18

Anaemia that is seen in patients with chronic disease

Question 19

What typical signs of anaemia will ACD patients NOT have?

Answer 19

They will NOT be bleeding
They will NOT be iron deficient, B12 deficient or folate deficient
They will NOT have any bone marrow infiltration

Question 20

State some laboratory signs of being ill.

Answer 20

Raised Erythrocyte Sedimentation Rate (ESR, raised due to RBC clumping together due to increased blood fibrinogen levels)

Acute phase response:
Raised C-reactive protein (CRP, an acute phase protein involved in complement activation during inflammation)
Raised Ferritin (cells die in inflammation and leak ferritin)
Raised Factor VIII
Raised Fibrinogen
Raised Immunoglobulins

Question 21

State some causes of anaemia of chronic disease.

Answer 21

Chronic infections – e.g. TB/HIV
Chronic inflammation – e.g. SLE, rheumatoid arthritis
Malignancy
Miscellaneous (e.g. cardiac failure)

Question 22

What is the underlying cause of ACD?

Answer 22

ACD is due to the cytokine release that happens when someone is unwell
The cytokines
a. They stop erythropoietin from increasing
b. Stop iron flowing out of cells and hence the utilisation of iron by RBC
c. Increase production of ferritin ie stuck as ferritin, cannot be utilised
d.Increased death of red cells

Question 23

Give examples of cytokines involved in ACD.

Answer 23

TNF-alpha

Interleukins

Question 24

State four broad causes of iron deficiency.

Answer 24

Bleeding
Increased use (e.g. growth, pregnancy)
Dietary deficiency (e.g. vegetarian)
Malabsorption (e.g. Coeliac disease)

Question 25

In what 4 groups of patients do you perform full GI investigations given the fact that they are iron deficient but have a good diet and excluded from coeliac disease?

Answer 25

``` Male Women over 40 Post-menopausal women Women with scanty menstrual loss slide 31 for explanations Summary: Male OR any female who has reached/about to reach menopause or does not really bleed much normally ```

Question 26

State some other investigations that can be performed.

Answer 26

Antibodies for coeliac disease | Check for urinary blood loss

Question 27

State three causes of a low MCV.

Answer 27

Iron deficiency Anaemia of chronic disease Thalassemia trait

Question 28

How would you confirm thalassemia trait?

Answer 28

Haemoglobin electrophoresis

Question 29

How does serum iron help distinguish between the three causes of microcytic anaemia?

Answer 29

Iron deficiency – LOW serum iron ACD – LOW serum iron Thalassemia trait - NORMAL serum iron so it rules out thalassemia trait

Question 30

Describe the difference in ferritin levels in iron deficiency and anaemia of chronic disease.

Answer 30

Iron deficiency – LOW ACD – HIGH (ferritin is an acute phase protein and so will rise in eg chronic infections or inflammation. Also because cytokines in ACD promote ferritin production)

Question 31

Why is ferritin not always reliable? What should you do instead in these scenarios?

Answer 31

Some people may have a anaemia of chronic disease and be iron deficient due to bleeding e.g. rheumatoid arthritis and a bleeding ulcer. Bleeding reduces ferritin stores but cytokines from ACD blocks iron transport out of the cell and so ferritin may build up. This means that the amount of ferritin that leaks into the blood may seem normal) You need to check the signs of infection/inflammation such as ESR and CRP to see if there is an underlying condition causing a rise in acute phase proteins

Question 32

Describe the difference in transferrin in iron deficiency and ACD.

Answer 32

Iron deficiency – HIGH | ACD – LOW/NORMAL

Question 33

Describe the difference in transferrin saturation in iron deficiency and ACD.

Answer 33

Iron deficiency – LOW | ACD – NORMAL

Question 34

What is the diagnosis of a man of any age with a low ferritin?

Answer 34

Iron deficiency | He needs upper and lower GI endoscopies to look for the source of the bleeding

Question 35

State what you’d expect the following parameters to be in iron deficiency: a. Hb b. MCV c. Serum Iron d. Ferritin e. Transferrin f. Transferrin Saturation

Answer 35

a. Hb - LOW b. MCV - LOW c. Serum Iron - LOW d. Ferritin - LOW e. Transferrin - HIGH f. Transferrin Saturation - LOW

Question 36

State what you’d expect the following parameters to be in anaemia of chronic disease: a. Hb b. MCV c. Serum Iron d. Ferritin e. Transferrin f. Transferrin Saturation

Answer 36

a. Hb - LOW b. MCV - LOW/NORMAL c. Serum Iron - LOW d. Ferritin - HIGH/NORMAL e. Transferrin - LOW/NORMAL f. Transferrin Saturation - NORMAL

Question 37

State what you’d expect the following parameters to be in thalassemia trait: a. Hb b. MCV c. Serum Iron d. Ferritin e. Transferrin f. Transferrin Saturation

Answer 37

a. Hb - LOW b. MCV - LOW c. Serum Iron - NORMAL d. Ferritin - NORMAL e. Transferrin - NORMAL f. Transferrin Saturation - NORMAL

Question 38

what is acute phase reaction

Answer 38

The acute phase response is a complex systemic early-defense system activated by trauma, infection, stress, neoplasia, and inflammation. Although nonspecific, it serves as a core of the innate immune response involving physical and molecular barriers and responses that serve to prevent infection, clear potential pathogens, initiate inflammatory processes, and contribute to resolution and the healing process. Acute phase proteins are an integral part of the acute phase response.