Red Cells 1 + 2

Question 1

How are the normal ranges for a FBC derived?

Answer 1

By looking at subjects without disease, plotting normal distribution of values. Using mean +/- 2 standard deviations, does exclude 5% of normals

Question 2

What is a pathphysiological or morphological approach to the assessment of anaemia?

Answer 2

Pathophysiological
A) bone marrow or B) red cell or C) loss/destruction
A = ?cellularity ?stroma ?nutrients
B = ?membrane ?Hb ?enzymes
C = ?blood loss ?haemolysis ?hypersplenism

Morphological 
A) hypochromic, microcytic or B) normochromic, normocytic or C) macrocyclic 
A = serum ferritin
B = reticulocyte count
C = b12/folate, bone marrow

Question 3

What are the symptoms of anaemia?

Answer 3

Tiredness
Pallor
Breathlessness 
Ankle swelling 
Dizziness 
Chest pain 

May relate to underlying

• evidence of bleeding
• symptoms of malabsorption
• jaundice
• splenomegaly/lymphadenopathy

Question 4

What are the appropriate investigations for iron deficiency anaemia?

Answer 4

Serum ferritin as iron is stored in cells as ferritin
Low = iron deficiency anaemia
Normal/high = thalassaemia, 2ndary anaemia

Question 5

What is the structure of haemoglobin and the basis of haemoglobinopathies and thalassaemias?

Answer 5

Haemoglobin has 2 alpha chains: one from mum and one from dad, and 2 beta chains. May also have gamma or delta chains.

Haemoglobinopathies: abnormalities of haemoglobin synthesis
Thalassaemias: reduced or absent globin chain production caused by mutations or deletions in either alpha or beta genes. Can be minor or major

Question 6

How is haemoglobin broken down to bilirubin and what is the value of direct and indirect bilirubin measurement.

Answer 6

Haemoglobin is broken down into globin and haem
Iron is then broken down off haem
Further broken down into biliverdin, then bilirubin which binds to albumin and at this point it is unconjugated

Direct bilirubin is a measurement of conjugated bilirubin whereas indirect bilirubin is a measurement of unconjugated bilirubin

Question 7

What is the principle and uses of the direct anti globulin test in assessing haemolysis?

Answer 7

Defects antibody or complement on red cell membrane
Reagent binds to the Ab (or complement) on red blood cells and causes agglutination in vitro
Implies immune basis for the haemolysis

Question 8

What are the causes of inherited anaemias?

Answer 8

Inherited anaemia can come in the form of defects in

• red cell membrane: eg hereditary spherocytosis where RBCs are spherical due to a defect in structural proteins meaning they are broken down faster by the re system
• enzymes: eg G6PD deficiency where the cells are vulnerable to oxidative damage and it is x linked
• haemoglobin: eg thalassaemia, sickle cell where there is reduced or absent globin chains or structurally abnormal globin chains

Question 9

What is reticulocyte count useful for?

Answer 9

If it is increased = acute blood loss, eg haemolysis which can be acquired (immune) or innate (not immune)
If it is decreased, normal = 2ndary anaemia