Lecture 5 - Anaemias

Question 1

What is an anaemia?

Answer 1

The term anaemia refers to a reduction of haemoglobin or red blood cell concentration in the blood

Question 2

How are anaemias classified?

Answer 2

Anaemias with raised, normal and reduced red cell size (MCV) are termed macrocytic, normocytic and microcytic, respectively. Anaemias associated with a reduced haemoglobin concentration within red cells are termed hypochromic and those with a normal MCH are termed normochromic.

Microcytic and Hypochromic = Low MCV and MCH = Iron deficiency or Thalassaemia

Normocytic and Normochromic = Normal MCV and MCH = Blood loss, Chronic disease or haemolysis.

Macrocytic = MCV raised = Megaloblastic anaemia.

Question 3

What causes microcytic, hypochromic anaemias?

Answer 3

1. Iron deficiency
   
   2. Chronic disease
   3. Thalassaemias

Iron deficiency anaemia
Normally the iron content of the body remains within narrow limits. Small amounts are absorbed from the diet and very little is lost as iron is not excreted but is instead lost in desquamated cells.
Causes include: Bleeding from the gastrointestinal tract, menorrhagia, malabsorption, malnutrition etc.
Symptoms include: Fatigue and weakness
Iron deficiency causes hypochromic microcytic anaemia (Low MCV and MCH as well as serum ferratin)

Chronic disease anaemia
In chronic inflammatory disease you can see patients develop anaemia and this is primarily due to the cytokines IL1 and TNFalpha being produced. These can have a negative impact on erythropoiesis and so RBC are not replaced at the usual rate.
Malignancy (bone marrow) produces a microcytic hypochromic anaemia.
Anaemia of chronic disease does not respond to Fe therapy, you need to treat the underlying cause.
These causes cannot be treated with iron tablets instead need to treat cause.

Question 4

What causes megaloblastic anaemia?

Answer 4

Megaloblastic anaemias are characterised by delayed maturation of the nucleus of red cells in the bone marrow due to defective synthesis of DNA. Red cells either die in the marrow ore enter the blood stream as enlarged, misshapen cells.
In clinical practice megaloblastic anaemia is almost always caused by deficiency of vitamin B12 or folate.
Both folate and vitamin B12 are necessary for the synthesis of DNA. Folate is needed in its tetrahydrofolate form as a cofactor in DNA synthesis. Deficiency of B12 leads to impaired conversion of homocystine to methionine causing folate to be trapped in the methyl form.
Deficiency in either leads to reduced dTTP thus delayed DNA synthesis.
* Immature red cells have less than normal number of cell divisions
* Large cells with large amounts of cytoplasm
* Chromatin abnormal
Causes include:
* Pernicious anaemia - Autoantibodies to gastric parietal cells make intrinsic factor needed to combine with B12 before absorption
* Folate deficiency
○ Malabsorption
○ Increased demand
○ Dietary deficiency

Question 5

What are haemolytic anaemias

Answer 5

Haemolytic anaemias describes a group of anaemias all characterised by abnormal destruction of RBCs.
1. Inherited - Problems intrinsic to the RBC
2. Acquired - Autoimmune, alloimmune

Question 6

What causes inherited haemolytic anaemias?

Answer 6

Inherited haemolytic anaemias

Abnormalities of haemoglobin
* Haemoglobinopathies
Abnormalities of RBC membrane
* Hereditary spherocytosis
* Hereditary elliptocytosis
Abnormalities of RBC metabolism
* Glucose 6-phosphate dehydrogenase deficiency
* Pyruvate kinase (PK) deficiency.

Abnormalities of RBC membrane
* Hereditary spherocytosis - RBC membrane problem - defects in genes coding for spectrin and ankyrin. Small cells, heavy stain. - Large amounts of RBC breakdown - splenectomy potential treatment.
* Hereditary elliptocytosis - Issue with membrane in particular spectrin. Cells have elliptical shape due to lack of flexibility. - Dimers cant form tetramer, gaps in scaffold.

Abnormalities in RBC metabolism
* G6PD deficiency - cells not protected from oxidative stress - lysed red blood cells
* Pyruvate Kinase deficiency - Cells cannot make enough ATP and become rigid and pumps do not function normally

Question 7

What causes aquired haemolytic anaemia?

Answer 7

cquired haemolytic anaemia

Autoimmune haemolytic anaemias (AIHA)
Autoantibodies against red blood cell antigens
AIHA - agglutination of RBC in peripheral circulation -cyanosis.
Agglutination will occur depending on temp (can be warm or cold depending on autoantibody)
Coombs test - detection of antibodies on surface of RBC.

Alloimmune haemolytic anaemia
* ABO incompatible blood transfusion
* Haemolytic disease of the newborn
*Infections such as malaria