Macrocytic Megalobastic anaemia

Question 1

What is B12 deficiency anaemia

Answer 1

Anaemia (low levels of Hb in the blood) caused by B12 deficiency.

This is a macrocytic megaloblastic anaemia.

Question 2

Epidemiology of B12

Answer 2

• Found in meat + dairy - bad 4 vegans
• Vitamin B12 deficiency increases with age.
• Unlike folate, vitamin B12 stores last for years before deficiency develops.
• B12 deficiency most commonly due to pernicious anaemia
• Pernicious anaemia: relatively common amongst Northern Europeans, with a high prevalence in those aged 60-70 years old
• F>M

Question 3

Vitamin B12 pathophysiology

Answer 3

essential vitamin for DNA synthesis in cells undergoing rapid proliferation

Deficiency of Vitamin B12 affects rapidly dividing cells, such as those in the bone marrow. This can lead to pancytopenia. As compensation for anaemia, the bone marrow produces abnormal precursors of RBCs - macrocytic, megaloblastic RBCs

Question 4

B12 + Neuro

Answer 4

Keeps levels of methylmalonic acid low > high levels can lead to:
- Peripheral neuropathy
- Subacute degeneration of the cord
- Focal demyelination

Question 5

Causes of B12 deficiency

Answer 5

• Inadequate intake(e.g. strict vegetarians, vegans)
• Inadequate secretion of intrinsic factor(e.g. pernicious anaemia, gastrectomy)
• Malabsorption(e.g. Crohn’s, tropical sprue, patients who have had gastric bypass)
• Inadequate release of B12from food(e.g. gastritis, alcohol abuse

Question 6

What is pernicious anaemia

Answer 6

Pernicious anaemia (PA) refers to vitamin B12 deficiency as a result of autoimmune destruction of the gastric epithelium. This may be due to anti-parietal cell antibodies or anti-IF antibodies.

Question 7

What do patients with PA develop?

Answer 7

chronic gastric inflammation, which may lead to gastric atrophy. Over time, the basal secretion of IF is severely decreased leading to the development of vitamin B12 deficiency.

Question 8

S + S of b12

Answer 8

Signs: Pallor, confusion, ataxia
Symptoms: General anaemia stuff
+ CNS involvement= Depression, memory loss, personality change

Question 9

1st line investigations for B12

Answer 9

• Full blood count (FBC): raised MCV
• Blood film: megaloblastic anaemia +/- hypersegmented neutrophils
• Haematinics: look for iron, B12, folate deficiency
• Lactate dehydrogenase (LDH): may be elevated
• Liver function tests (LFTs)

Question 10

Management of B12

Answer 10

• Treatment of the underlying cause
• B12 supplementation e.g. oral cyanocobalamin; intramuscular hydroxocobalamin

Question 11

What is folate deficiency anaemia?

Answer 11

Anaemia (low levels of Hb in the blood) caused by folate (vitamin B9) deficiency. This is a type of macrocytic megaloblastic anaemia

Question 12

Epidemiology of Folate deficient anaemia

Answer 12

• In general, megaloblastic anaemia and folate deficiency are seen most commonly in countries where malnutrition is problematic.
• High-risk patient groups include: children, pregnant women and the elderly.

Question 13

RF of Folate

Answer 13

• Elderly
• Poverty
• Alcoholic
• Pregnant
• Crohn’s or coeliac disease

Question 14

What is Folate (vitamin B9) important for?

Answer 14

important molecule which acts as a cofactor in amino acid metabolism and DNA/RNA synthesis.

BM affected hard since most active for cell division - leads to pancytopenia

Response to anaemia - BM compensates and releases megaloblasts in blood leading to macrocytic megaloblastic anaemia

Question 15

Other folate pathology

Answer 15

• Other rapidly dividing cells, include mucosal epithelial cells of the tongue. These are affected, preventing healing. This leads to glossitis.
• Folate is also essential for foetal development - deficiency can result in neural tube defects e.g. spina bifida. So supplementation is essential during pregnancy!

Question 16

Causes of folate defiency

Answer 16

• Inadequate intake
• Malabsorption(e.g. coeliac disease, resection)
• Increased requirements(e.g. pregnancy, malignancy disease)
• Increased loss(e.g. Chronic liver disease)
• Other(e.g. anti-convulsants, alcohol abuse)

Question 17

S + S of folate

Answer 17

Sign - pallor
Symptom - fatigue, SOB, palpitations, headache

Question 18

Primary investigations for Folate

Answer 18

• FBC: high MCV
• Blood film: macrocytic, megaloblastic RBC
• Haematinics: search for iron, B12 and folate deficiencies
• Serum and red cell folate: low

Question 19

Management of folate

Answer 19

• Treat underlying cause e.g. stopping drugs or alcohol consumption
• Folic acid supplements: always give alongside B12, because replacement of folic acid in the presence of vitamin B12 deficiency may cause significant neurological disease.