Session 4 ILOs - Anaemia and Iron Metabolism

Question 1

Define the term anaemia and understand the important causes of microcytic, normocytic and macrocytic anaemias

Answer 1

Anaemia is a haemoglobin concentration lower than the normal range

Microcytic anaemia (decreased RBC size):
- Reduced haem synthesis (iron deficiency, lead poisoning, anaemia of chronic disease, sideroblastic anaemia)
- Reduced global chain synthesis (alpha-thalassaemia or beta-thalassaemia)
Causes: TAILS (thalassaemia, anaemia of chronic disease, iron deficiency, lead poisoning, sideroblastic anaemia)

Macrocytic anaemia (increased RBC size):
- Megaloblastic anaemias
- Macronormoblastic anaemias
- 'Stress' erythropoiesis 
Causes: Vit B12 deficiency, folate deficiency, myelodysplasia, liver disease and alcohol toxicity

Normocytic anaemia (normal RBC size):
- Mostly acquired e.g. as a result of disease = anaemia of chronic disease (ACD) or anaemia of inflammation
- Also can be congenital or can be a complication from a particular medication
Causes: primary bone marrow failure (aplastic anaemia), secondary bone marrow failure (e.g. ACD, uraemia, HIV)

Question 2

Outline signs and symptoms of anaemia

Answer 2

Symptoms:

• Shortness of breath
• Palpitations
• Headaches
• Claudication
• Weakness and lethargy

Signs:

• Pallor
• Tachycardia
• Hypotension
• Tachypnoea (rapid breathing)

Question 3

Outline the common clinical features and important underlying causes of haematinic deficiency (iron, folate or vitamin B12 deficiency)

Answer 3

Iron deficiency - most common nutritional disorder worldwide:
Clinical features: sign not a diagnosis, extreme fatigue, weakness, pale skin, fast heartbeat or shortness of breath
Underlying causes:
-  Dietary deficiency
- Malabsorption of iron
- Bleeding
- Increased requirement
- Anaemia of chronic disease

Folate deficiency:
Clinical features: diarrhoea, reduced sense of taste, depression, muscle weakness, paraesthesia in feet and hands
Underlying causes:
- Dietary deficiency
- Increased requirements
- Disease of duodenum or jejunum
- Drugs which inhibit dihydrofolate reductase
- Alcoholism
- Urinary loss of folate in liver disease and heart disease

Vit B12 deficiency:
Clinical features: Glossitis and mouth ulcers, diarrhoea, paraesthesia, disturbed vision and irritability
Underlying causes:
- Dietary deficiency
- Lack of intrinsic factor (pernicious anaemia)
- Diseases of the ileum
- Lack of transcobalamin
- Chemical inactivation of B12
- Parasitic infestation
- Some drugs can chelate intrinsic factor

Question 4

Describe the role and complications associated with haematinic replacement treatment (iron, folate, vit B12 deficiencies)

Answer 4

Treatments:

Iron deficiency:

• Dietary advice
• Oral iron supplements
• Intramusclar iron injections
• IV iron
• Blood transfusion (only if severe with imminent cardiac compromise)
• RISK is that excess iron can be deposited in organs as haemosiderin and iron promotes free radial formation and organ damage
• RISK of transfusion associated haemosiderosis or hereditary haemochromostosis

Folate deficiency = simple
- Oral folic acid

Vit B12 deficiency - pernicious anaemia:

• Intramuscular Hydroxocobalamin (not oral)
• RISK of hypokalaemia at the beginning of treatment due to increased K+ requirement as erythropoiesis increases back to normal rate

Vit B12 deficiency - other causes (not pernicious anaemia):

• Oral Hydroxocobalamin
• Note: blood transfusion in patients with severe B12 deficiency anaemia can cause high output cardiac failure

Question 5

List the different causes of microcytic anaemia

Answer 5

TAILS:

• Thalassaemia
• Anaemia of chronic disease
• Iron deficiency
• Lead poisoning
• Sideroblastic anaemia

Question 6

Give examples of good dietary sources of haem and non-haem iron

Answer 6

Haem iron sources:
- Liver meat
- Beef burger
- Chicken
etc.

Non-haem iron sources:
- Fortified cereals
- Beans
- Potatoes
- Rice
etc.

Question 7

Give an overview of iron absorption, transport, storage and uptake into tissues

Answer 7

Absorption:
- Dietary iron (haem Fe2+ or non-haem Fe2+ and Fe3+) is absorbed by DMT1 (vit C is a co-factor in Fe3+ reduction) into the enterocytes of the small intestine

Transport:

• First, Fe2+ needs to be converted to Fe3+
• Two Fe3+ can bind to transferrin which can transport iron around the body

Storage:

• Iron needs to be stored in the ferric form of Fe3+ bound to ferritin (soluble)
• Haemosiderin are aggregates of clumped ferritin (insoluble) which accumulate in macrophages mainly in liver, spleen and marrow

Uptake into tissues:

• Occurs by receptor mediated endocytosis
• Fe3+ bound with transferrin enters cell by receptor mediated endocytosis
• Fe3+ released by acidic environment in endosome and is reduced to Fe2+
• Fe2+ transported to cytosol via DMT1
• Once in the cytosol, Fe2+ can be stored in ferritin, exported by ferroportin or taken up by mitochondria

Question 8

Describe how iron deficiency anaemia is diagnosed

Answer 8

Iron deficiency anaemia is diagnosed by:

• Plasma ferritin (gives a definitive diagnosis)
• But, normal or increased plasma ferritin does not exclude iron deficiency!
• CHr (reticulocyte haemoglobin content) can test for functional iron deficiency

Question 9

Outline how iron overload can occur

Answer 9

Iron overload can occur by:

1. Transfussion associated haemosiderosis
   - Repeated blood transfusions cause gradual accumulation of iron
   - Iron chelating agents (e.g. desferrioxamine) can reduce this, but can’t prevent it
   - Accumulation of iron in liver, heart and endocrine organs
2. Hereditory haemochromatosis
   - Autosomal recessive disease from mutation in HFE gene
   - HFE proteins normally interacts with the transferrin receptor reducing the affinity for iron-bound transferrin
   - HFE also promotes hepcidin expression through signalling pathways in the liver
   - Too much iron enters the cells and accumulates in end organs
   - Treatment with venesection