Anaemia

Question 1

Define the term anaemia

Answer 1

A haemoglobin concentration lower than the normal range. Anaemia in itself is not a diagnosis but a manifestation of an underlying disease state and it is important to establish the cause 9f the anaemia

Question 2

What are the 3 types of anaemia and what are the causes

Answer 2

Anaemias are classified according to the effect the underlying condition has on the average size of red blood cells
- Macrocytic (large cells)
- Microcytic(small cells)
- Normocytic (average size cells)

Question 3

Why might anaemia develop

Answer 3

• Reduced or dysfunctional erythropoeisis
• Abnormal Haem synthesis
• Abnormal globin chain synthesis
• Abnormal structure
• Mechanical damage
• Abnormal metabolsim
• Excessive bleeding
• Increased removal by reticuloendothelial system

Question 4

What are the signs and symptoms of anaemia

Answer 4

Symptoms - Shortness of breath, Palpitations, Headaches, Claudication, Angina, Weakness and Lethargy, Confusion
Signs - Pallor, Tachycardia, Systolic flow murmur, Tachypnoea, Hypotension

Specific signs associated:
Koilonychia - Spoon shaped nails (Iron deficiency)
Angular stomatitis - Inflammation of corners of mouth (Iron deficiency)
Glossitis - Inflammation & depalpitation of tongue (Vitamin B12 deficiency)
Abnormal facial bone development (Thalassaemia)

Question 5

What is folate

Answer 5

Folate is synthesised in bacteria and plants. Its absorption is mainly from duodenum and jejunum where it converts to tetrahydrofolate (FH4) and acts as a store in the liver. Its metabolic role is to provide carbons for other reactions, and recipient reactions include synthesis of nucleotide bases required for DNA and RNA synthesis

Question 6

Why is folate deficiency linked with haematinic deficiency

Answer 6

Folate deficiency has a detrimental effect on DNA synthesis which shows in red cell production with megaloblastic anaemia. If the deficiency occurs in pregnancy, it can result in neural tube defects in the developing uterus. Symptoms are those related to anaemia

Question 7

How does iron deficiency link with anaemia

Answer 7

Anaemia develops if the supply of iron is inadequate for the requirements of haemoglobin synthesis.

Question 8

What is vitamin B12

Answer 8

Vitamin B12 is a water-soluble vitamin and is an essential cofactor for DNA synthesis (due to its role in folate metabolism). It is required for normal erythropoiesis (the production of red blood cells) and is essential for normal function and development of CNS.

Question 9

How does B12 deficiency cause anaemia

Answer 9

B12 binds to a glycoprotein called intrinsic factor. A deficiency in intrinsic factor results in pernicious anaemia from lack of B12 absorption.

Question 10

How is B12 and folate linked.

Answer 10

B12 is required for just 2 metabolic processes in the body. One of them is to transfer a methyl group from FH4 to homocysteine to form methionine. This has a consequence for folate metabolism since a lack of B12 will effectively trap folate in the stable methyl-fh4 preventing its use in other reactions such as synthesis of nucleotides required for DNA synthesis

Question 11

Describe the role and complications associated with haematinic replacement treatment

Question 12

Describe subacute combined degeneration

Answer 12

Vitamin B12 deficiency results in reversible peripheral neuropathy but also results in subacute combined degeneration of the cord which refers to the degeneration of the posterior and lateral columns of the spinal cord. Onset is gradual and patients initially present with weakness which progressively get worse

Question 13

List the different causes of microcytic anaemia

Answer 13

• Thalassaemia (reduced globin chain synthesis)
• Anaemia of chronic disease
• Iron deficiency
• Lead poisoning
• Sideroblastic anaemia

Question 14

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

Answer 14

Haem iron:
- Liver
- Kidney
- Beef
- Chicken
Non-Haem:
- Fortified cereals
- Raisins
- Beans
- Figs

Question 15

Give an overview of iron absorption

Answer 15

Occurs in the duodenum and upper jejunum. Depends on specific carrier proteins. DMT1 located on upper surface of enterocytes facilitate uptake of non-haem ferrous iron (Fe2+) from intestinal lumen Ferric iron (Fe3+) reduced to ferrous iron by DcytB before uptake by DMT1.
Once in the enterocyte, haem is degraded to release ferrous iron. Iron within enterocyte can either be stored as ferritin or transferred into the bloodstream by ferroportin.

Question 16

Give an overview of iron transport and metabolism

Answer 16

Once in the blood, iron is bound by the transport protein transferrin and mostly transported to bone marrow for erythropoiesis or taken up by macrophages in the reticuloendothelial system as a storage pool

Question 17

Give an overview on iron storage

Answer 17

Iron is stored in two forms, ferritin and its insoluble derivative haemosiderin. Ferritin (a protein-iron complex) can be incorporated by phagolysosomes to form hemosiderin granules. All cells have the ability to sequester iron as either ferritin or haemosiderin

Question 18

Give an overview on iron uptake

Answer 18

1) Fe3+ bound to transferrin binds to transferrin receptors and enters the cytosol receptor-mediated endocytosis
2) Fe3+ within endosome released by acidic microenvironment and reduced to Fe2+
3) The Fe2+ transported to the cytosol via DMT1
4) Once in the cytosol, Fe2+ can be stored in ferritin exported by ferroportin (FPN1), or taken up by mitochondria for use in cytochrome enzymes

Question 19

Give an overview on iron metabolism

Answer 19

Free iron is very toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species. To overcome this toxicity complex regulatory systems have evolved to ensure safe absorption, transportation and utilisation of iron.
Ferric iron must be reduced to the ferrous form before it is absorbed

Question 20

Give an overview on iron recycling

Answer 20

On a daily basis, only a fraction of total iron requirement is gained from the diet. Most of the iron requirement is met from the recycling of old red blood cells taken up by macrophages in the reticuloendothelial system and returned to the storage pool

Question 21

Understand how iron deficiency leads to anaemia

Answer 21

Iron deficiency is a sign, (not symptom) of anaemia. Anaemia develops if the supply of iron is inadequate for the requirements of haemoglobin synthesis.
Iron deficiency is the most common nutrient deficiency worldwide and accounts for around half of all cases of anaemia.

Question 22

Describe how iron deficiency anaemia is diagnosed

Answer 22

Causes of iron deficiency:
- Insufficient iron in diet
- Malabsorption of iron
- Bleeding
- Increased requirement (pregnancy)
- Anaemia of chronic disease
Signs and symptoms:
- Physiological effects include tiredness, pallor, reduced exercise tolerance
- Pica (cravings for non-nutritive substances)
- Cold hands and feet
- Epithelial changes

Question 23

Appreciate how iron overload can occur

Answer 23

Excess iron uptake due to defect of HFE protein.
Excess iron can exceed binding capacity of transferrin. Excess iron ‘deposited in organs such as haemosiderin. Iron promotes free radical formation and organ damage.
Hydroxy and hydroperoxyl radicals can cause damage to cells:
- Lipid peroxidation
- Damage to proteins
- Damage to DNA

Question 24

Describe the aetiology and treatment of Hereditary Hemochromatosis

Answer 24

It is an autosomal recessive disease caused by excessive absorption of dietary iron. As there is no system for the excretion of excess iron, it accumulates in tissues and organs, disrupting normal function.
Most susceptible organs are liver, adrenal glands, heart joints, pancreas, which can cause a number of issues such as cirrhosis, heart failure etc.
Defective gene resides on chromosome 6 and codes for a protein called HFE. This interacts with transferrin receptor reducing affinity for iron-bound transferrin. Defects in HFE therefor cause greater cellular uptake of iron.
Treatment is therapeutic phlebotomy to remove excess iron.