Macrocytic Anaemia Flashcards
Classification of Macrocytic Anaemia and Common Causes
1) Megaloblastic B12 or folate deficiency Cytotoxic Agents Anti-folate drugs, e.g. phenytoin Orotic Aciduria Fanconi anaemia
2) Non-Megaloblastic Hypothyroidism Liver disease Alcoholism Diamond-Blackfan anaemia Pregnancy
What is Megaloblastic Anaemia?
Megaloblastic anaemia occurs due to impaired DNA synthesis. This causes ineffective haematopoiesis.
Megaloblasts are cells in which nuclear maturation is delayed cf. cytoplasmic maturation,
Main causes: Vit. B12 or folate deficiency
Folate Physiology
Folate found in green veg., nuts, liver and yeast
Absorbed by duodenal enterocytes.
Folate is used as a coenzyme in THF- imp for DNA and RNA synthesis.
Folate is stored in the liver and stores last for up to 4 months.
Vit. B12 Physiology
Found in all foods of animal origin. Stores can last up to 4 yrs.
Cobalamin in food is bound to salivary haptocorrin. Acidic environment in stomach favours transfer of cobalamin to haptocorrin therefore more binds gastric haptocorrin.
Rise in pH in duodenum –> transfer of B12 to intrinsic factor (secreted from gastric parietal cells)
B12-IF complex is absorbed in ileum, from where B12 enters circulation.
Biochemistry of B12 and Folate
Essential for de novo purine biosynthesis and thiamine synthesis.
Folate Deficiency Causes
Decreased intake: infancy, poor diet or alcoholism
Impaired absorption: tropical sprue, coeliac disease
Increased req.: pregnancy, adolescence, haemolysis, malignancy, inflammatory disease, renal dialysis
What drugs can cause folate deficiency?
Phenytoin
MTX
Trimethoprim
Labs of Folate Deficiency Anaemia
Serum folate low, red cell folate low (more accurate)
Homocysteine raised, normal methylmalonic acid (MMA)
Decreased reticulocyte count
Treatment of Folate Deficiency Anaemia
Folate supplementation (4 months)
Always combine w. Vit B12 unless pt. known to be normal B12
Folate supplementation can exacerbate/precipitate subacute combined degernation of cord
Causes of B12 Deficiency
Malabsorption:
1) lack of IF- total gastrectomy, pernicious anaemia
2) Terminal Ileum disease: resection, Crohn’s disease, bacterial overgrowth, tropical sprue, tapeworms
Inadequate intake: vegan diet
Congenital metabolic errors
Function of B12
Essential for myeline stabilisation
Pernicious Anaemia
- Pathophysiology
- Assoc.
Autoimmune disorder where the gastric parietal cells are destroyed –> atrophic gastritis. This manifests as achlorydia and lack of IF.
Lack of IF = B12 cannot be absorbed from food.
Autoantibodies against parietal cells and/or IF often present.
Assoc.: autoimmune thyroiditis, vitiligo, T1DM, Addison’s, hypoparathyroidism
Increased risk of gastric cancer
Presentation of B12 Deficiency
Anaemia: fatigue, weakness, dyspnoea
Neuropsychiatric: irritability, depression, psychosis, dementia and cognitive decline
Signs of B12 deficiency
Lemon-tinge to skin (mild jaundice from haemolysis)
Scleral icterus
Glossitis, angular cheilosis
Neurological: paraesthesiae, peripheral neuropathy and subacute combined degeneration of the spinal cord
Manifestations of Subacute Combined Degeneration of the Spinal Cord
1) Dorsal Columns: decreased vibration and proprioception sensation; gait difficulties
2) CST: weakness, spasticity, hyperreflexia
3) SCT: gait difficulties, ataxia, decreased proprioception sensation
