Iron Deficiency and Anaemia of Chronic Disease

Question 1

Where is iron found?

Answer 1

Mainly in haemoglobin

Iron (specifically ferrous) is found in the haem part of the haemoglobin and its role is to hold onto the oxygen in the Hb

Question 2

What factors affect iron absorption?

Answer 2

20mg iron/day to replace lost red cells BUT we can recycle iron;

• Some iron is lost via; desquamated cells of the skin and gut, bleeding (menstruation).
• Men need ~1mg/day and women need 2mg/day
• The human diet provides ~12-15mg-iron/day as iron occurs in; meat and fish (haem iron), vegetables, whole grain cereal and chocolate
• Most iron eaten is NOT absorbed though as you can only absorb ferrous (Fe2+) and not ferric (Fe3+)
• Tea turns iron into the FERRIC form and can lead to chronic low levels of ferrous!
• Orange juice AIDS absorption of iron.

Factors affecting absorption include:

• Diet – increase in haem iron (ferrous iron)
• Intestine – acid in the duodenum
• Systemic – iron deficiency (anaemia/hypoxia, pregnancy)

Factors that increase iron absorption are:

• Iron deficiency
• Anaemia/hypoxia
• Pregnancy

Question 3

How does our gut cell alter iron absorption?

Answer 3

Iron freely transports into the cell but ferroportin facilitates transport of iron into the blood

• Hepcidin inhibits ferroportin

Hepcidin level regulation:

• Hepcidin has iron-responsive elements within their genes so iron is part of the complex that switches on Hepcidin transcription
• Ferroportin is found in: enterocytes of duodenum, macrophages of spleen, hepatocytes

in duodenum:
Iron from the diet is taken into the cell -> protein shell forms around it to form ferritin OR can bind to transferrin in the blood plasma

Question 4

What is the features of transferrin?

Answer 4

The transferrin is usually 20-40% saturated with iron

Transferrin levels, Total Iron Binding Capacity (TIBC) and Transferrin saturation can therefore usually be measured

TF cannot enter cells directly and binds with the TF-R and is internalised as a whole. As the pH drops, iron is released and transferrin receptors are recycled

The reason for TF being around is that iron is TOXIC and INSOLUBLE so TF fixes this

Question 5

Where is erythropoietin produced?

Answer 5

Produced in the kidneys

Production is increased in response to hypoxia and this triggers more RBC precursors to be released

The RBC precursors survive longer and will; survive, grow and differentiate

Question 6

What are the laboratory conditions of anaemia of chronic disease?

Answer 6

** The patient will NOT be showing classic causes of anaemia, e.g. bleeding, have any bone marrow infiltration or have an iron/B12 or folate deficiency - THERE IS NO OBVIOUS CAUSE

Laboratory signs:

• Higher levels of C-reactive protein – an acute phase protein (inflammation/infection)
• Higher Erythrocyte Sedimentation Rate (ESR) – rises in inflammation/infection
• An acute phase response and increases in: ferritin, Factor VIII, fibrinogen and IG

Question 7

What conditions are associated with ACD?

Answer 7

• Chronic infections – e.g. TB/HIV
• Chronic inflammation.
• Malignancy
• Misc. – e.g. cardiac failure

Question 8

Describe the pathogenesis of ACD?

Answer 8

mostly due to CYTOKINE release – e.g. TNF and IL

Cytokines prevent usual flow of iron from duodenum to red cells – block iron utilisation by red cells

Cytokines also; stop EPO increasing, stop iron flow out of cells, increase production of ferritin, increase death of RBCs -> make less RBCs, more RBCs die and less iron available

Question 9

What are causes of iron deficiency?

Answer 9

Major causes:
- Bleeding – e.g. menstrual or GI

Minor causes:

• Increased use – e.g. growth/pregnancy
• Dietary deficiency – e.g. vegetarian
• Malabsorption – e.g. coeliac

Question 10

When do you carry out full GI investigations?

Answer 10

iron deficiency in :

• Male
• Woman over 40, post-menopausal woman, woman with scanty menstrual loss.
• A full GI investigation is – upper GI endoscopy (oesophagus, stomach, duodenum), duodenal biopsy and colonoscopy.

** if nothing is found, do a small bowel meal and follow through

• ** Do nothing if:
• Menstruating woman <40 with heavy periods OR multiple pregnancies and NO GI symptoms

Question 11

What laboratory parameters do you look at to confirm a diagnosis of iron deficiency?

Answer 11

• MCV
• serum iron
• ferrritin (storage protein)
• transferrin (=total iron binding capacity [TIBC])
• transferrin saturation

Question 12

What are normal ranges for MCV and haemoglobin?

Answer 12

MCV: 80-100

Hb: 120-150 g/l

Question 13

What are causes of anaemia with low MCV?

Answer 13

1. iron deficiency
2. thalassaemia trait
3. anaemia of chronic disease (can be low or normal)

Question 14

What are the ferritin levels in iron deficiency and ACD?

Answer 14

ferritin

• low in IDA
• high in ACD

*ferritin can be normal despite iron deficiency (e.g due to other chronic disease like rheumatoid arthiritis with bleeding ulcer)

** raised CRP and ESR with normal ferritin = sign of underlying condition

Question 15

What are tranferrin levels and saturation in ID and ACD?

Answer 15

transferrin
ID: increases
ACD: normal/low

transferrin saturation
ID: LOW - more transferrin and less iron
ACD: NORMAL - iron AND transferrin have both gone down so saturation is normal

Question 16

What further investigations can you do when diagnosing IDA (after excluding thalassaemia trait and ACD)?

Answer 16

• Endoscopy and colonoscopy
• Duodenal biopsy
• Anti-helicobacter antibodies
• Anti-coeliac antibodies
• Other – abdominal ultrasound to look at kidneys, dipstick urine, pelvic US to exclude fibrosis

Question 17

What would the blood film of an iron deficient patient look like?

Answer 17

pale cells

pencil cells