Macrolytic and haemolytic

Question 1

What is vitamin B12 also called, and why is it needed?

Answer 1

Vit. B12 = cobalamin

Needed for the synthesis of myeline + assists in DNA synthesis

Question 2

What are the symptoms of vitamin B12 deficiency?

Answer 2

Fatigue
Lethargy
Depression
Poor memory
Breathlessness
Headaches
Pale skin

Question 3

What type of anaemia is caused by B12 and folate (Vit B9) deficiency?

Answer 3

Macrolytic anaemia

Question 4

What can be measured that will indicate B12 deficiency?

Answer 4

Measure methylmalonic acid

Will increase when B12 is deficient

Question 5

What are the functions of B12?

Answer 5

• Methionine synthase uses B12 to transport a methyl group from 5-methyltetrahydrofolate –> homocysteine to become tetrahydrofolate (THF) and methionine

Question 6

What is the function of THF, how might it be obtained in the diet?

Answer 6

THF plays a role in DNA synthesis (therefore less efficient production of THF in cells with rapid turnover)

May be obtained through dietary folate

Question 7

Compare B12 and B9 in terms of how long they are stored and where they are absorbed.

Answer 7

B12:

• stored for 3 years
• absorbed in the terminal ileum

B9:

• stored for 4 months
• absorbed in the duodenum and jejunum

Question 8

Explain how B12/B9 deficiency can lead to anaemia S+S.

Answer 8

B12/B9 deficiency —> DNA synthesis impaired —> cells fail to divide —> overlarge red cells —> increased rate of destruction of red cells —> anaemia S+S

Question 9

Describe how vitamin B12 is absorbed.

Answer 9

• Intrinsic factor is released by parietal cells in the stomach mucosae
• B12 then binds to IF = IF-B12 complex (formed in the stomach)
• Then absorbed in the terminal ileum

Question 10

How might the blood count, blood film and biochemistry in B12 and B9 deficiency appear?

Answer 10

Blood count:

• reduced Hb
• high MCV
• reduced WBC + platelets

Blood film:

• oval macrophages
• hypersegmented
• neutrophils

Biochemistry:

• increased LDH
• increased bilirubin

Question 11

What are the potential causes of vitamin B12 deficiency?

Answer 11

1. Nutritional - unbalanced/unsupplemented diets
2. Malabsorption:
   - Gastric: pernicious anaemia, surgical gastrectomy
   - Intestinal: ileal disease (Crohn’s)

Question 12

What is pernicious anaemia and how common is it?

Answer 12

Autoimmune condition
Antibodies produced against parietal cells + IF
This leads to gastric atrophy, reduced acid secretion and reduced IF secretion

Occurs in ~1-2% of the population >60 y/o (more common in females)

Question 13

What are the clinical features of pernicious anaemia?

Answer 13

• Insidious: gradual onset, but fatal if left untreated
• Glossitis: inflammation of the tongue
• Mild jaundice
• Neurological symptoms (peripheral neuropathy, damage to sensory and motor tracts, dementia, optic atrophy)

*Macrocytic anaemia, hypersegmented neutrophils and reduced serum B12

Question 14

How is pernicious anaemia treated?

Answer 14

IM B12 injections every 3 months for life

Question 15

What are the potential causes of folate deficiency?

Answer 15

1. nutritional: old age, poverty, alcoholism
2. malabsorption: coeliac, crohn’s
3. pregnancy
4. others: anticonvulsants

Question 16

What causes haemolytic anaemias? Where are the 3 main sites of pathology?

Answer 16

Shortened survival of RBCs
3 sites of pathology:
1. Membrane: hereditary spherocytosis, oxidising agents, antibodies against RBC membrane
2. Haemoglobin: abnormal structure (sickle cell), imbalance in alpha:beta synth (thalassaemia)
3. Enzymes: G6PD deficiency, etc.

Question 17

How might someone with haemolytic anaemia present?

Answer 17

Pallor
Jaundice (increased levels of bilirubin)
Gallstones
Splenomegaly

Question 18

What is hereditary spherocytosis? What is the inheritance pattern? What would investigations of the blood show?

Answer 18

• defect in protein of the RBC cytoskeleton
• high fragility and more prone to degradation
• autosomal dominant
• chronic haemolytic anaemia
• reduced Hb, increased LDH, increased serum bilirubin

Question 19

What is G6PD deficiency? What is the inheritance pattern?

Answer 19

• Hb and other RBC proteins become oxidised over time due to high PO2
• prolongs life of RBC preventing/reversing oxidising Hb
  X-linked
• symptoms present when exposed to a trigger (food, bacteria, drugs etc.)

Question 20

What is autoimmune haemolytic anaemia (AIHA)? What type of antibodies are involved?

Answer 20

• IgG antibodies react with RBC membrane proteins
• Attaches to RBCs and label them for destruction
• removed by spleen = extravascular haemolysis
• usually idiopathic but can be caused by drugs, CT disease or blood transfusion

Question 21

Describe the procedure of the direct Coombs/antiglobulin test and why it is done.

Answer 21

• Check if there if antibody on a red cell
• Procedure:
  1. blood sample taken from pt with AIHA
  2. patient’s washed RBCs are incubated with antihuman antibodies
  3. +ve result: RB C agglutination (antihuman antibodies bind to human antibodies on RBCs)