Blood cell abnormalities

Question 1

How is Chronic myeloid leukaemia caused

Answer 1

chromosomal translocation between chromosome 9 and 22
Results in modified chromosomes - chromosome 22 now has BCR gene (its own) and ABL gene (from chromosome 9) which fuse to form BCR-ABL gene.
this codes for BCR-ABL protein which forms tyrosine kinase
This causes increase in cell division and myeloid cells divide too quickly and so buildup in the bone marrow and then the blood

Question 2

difference between myeloid and lymphocytic leukaemia

Answer 2

CML - cells divide too quickly

• caused by formation of philadelphia gene
• affects granulocytes (neutrophils, basophils, eosinophils)
• causes hepatosplenomegaly ( build up of myeloid cells in liver and spleen cause it to enlarge)
• blood smear shows increased granulocytes and monocytes

CLL - cells don’t die as they should

• causal mutation is unknown but results in interference with B cell receptors
• affects lymphocytes esp B cells
• causes lymphadenopathy (build up of premature B cells in lymph nodes cause them to enlarge)
• blood smear shows smudge cells (smudged premature B cells)

Question 3

what causes Chronic lymphocytic leukemia

Answer 3

Unknown mutation causes interference with B cell receptor
Activates tyrosine kinases
prevents maturation or cell death of CLL cells

Question 4

Diagnosis of CLL

Answer 4

Full blood count and blood film
use flow cytometry to analyse cell surface markers or genetic testing (cytogenic analysis) meg to look for philadelphia chromosome

Question 5

name 4 mechanisms by which anaemia can be caused

Answer 5

1. Reduced production of red cells by the bone marrow e.g. deficiency of iron, B12 or folate, leukaemia .
   
   2. Loss of blood from the body e.g. gastrointestinal bleeding, heavy menstrual bleeding.
   3. Reduced survival of red cells in the circulation (haemolysis) e.g. sickle cell disease, G6PD deficiency, hereditary spherocytosis.
   4. Increased pooling of red cells in an enlarged spleen e.g. splenic sequestration in a young child with sickle cell anaemia.

Question 6

What are the common causes of microcytosis?

Answer 6

Reduced synthesis of haemoglobin
This is caused by reduced synthesis of haem (iron deficiency anaemia or anaemia of chronic disease)
Or reduced synthesis of globin (thalassaemia)

Question 7

causes of iron deficiency

Answer 7

Increased loss (blood loss)
eg hookworm, menstruation (menorrhagia)

Increased requirements
(physiological) eg pregnancy, infancy

Insufficient uptake
eg dietary (veg diet)
Malabsorption (coeliac disease, H pylori gastritis)

Question 8

Stages of iron depletion

Answer 8

Iron depletion (storage iron reduced)

Iron deficiency (+ low serum iron and transferrin)

Iron deficiency anaemia (+low Hb and haematocrit)

Question 9

common causes of ACD (anaemia of chronic disease)

Answer 9

• Rheumatoid arthritis 
	• Autoimmune disease 
	• Malignancy 
	• Kidney disease 
Infections such as TB or HIV

Question 10

Laboratory clues of anaemia of chronic disease



Answer 10

• C-reactive protein is high (unlike iron deficiency)
• Erythrocyte sedimentation rate (ESR) is high (unlike iron deficiency)
• Ferritin is high
• Transferrin is low
Acute phase proteins increase

Question 11

when is an increased/decreased reticulocyte count seen?

Answer 11

Increased: haemolytic anaemia, recent blood loss, response to iron/vit B12/folic acid treatment
Decreased: reduced output of RBS from bone marrow

Question 12

causes of macrocytic aneamia

Answer 12

lack of vit B12/folic acid
use fo drugs interfering with DNA synthesis
liver disease and ethanol toxicity
recent major blood loss with adequate iron stores –> reticulocytes increased
haemolytic anaemia –> reticulocytes increased