Page 314 - Concise Pathology for Exam Preparation ( PDFDrive )
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12 Haematology 299
Causes of Vitamin B 12 Deficiency
• Decreased intake: Nutritional deficiency (vegans, breastfed infants of vegan mothers)
• Impaired absorption:
• Gastric causes: Pernicious anaemia, destruction of gastric mucosa or gastric bypass surgery
• Intestinal causes: Malabsorption due to enteritis, celiac disease or tropical sprue,
competition for vitamin B 12 in fish tapeworm (Diphyllobothriumlatum) infestation or
blind loop syndrome (bacterial overgrowth in diverticulae of bowel)
• Drug-induced malabsorption: Implicated drugs include PAS, colchicine, neomycin,
ethanol and KCL
• Chronic pancreatic disease: Lack of pancreatic proteases and inability to degrade
R proteins, which compete with IF
• Zollinger–Ellison syndrome: Impaired absorption due to low pH of intestinal con-
tents reaching ileum
• Haemodialysis: Cause unknown
Causes of Folate Deficiency
• Inadequate intake: Young persons on junk food diets, elderly and terminally ill people
• Inappropriate cooking methods: Polyglutamates are sensitive to heat; boiling, steam-
ing or frying the food destroys folate content
• Excess utilization: Pregnancy, haemolysis and tumours
• Alcoholism: Reduces serum folate levels are attributed to inadequate diet, excessive
urinary loss and interference with the enterohepatic circulation of folate by alcohol.
• Impaired absorption
• Celiac disease and tropical sprue
• Drugs that block dihydrofolate reductase (methotrexate and trimethoprim), block
conversion of polyglutamates to monoglutamates (phenytoin), decrease absorption
and increase metabolism (anticonvulsants) and decrease absorption and increase
urinary excretion (oral contraceptives)
• Complication of haematological illness: Increased demand due to rapid proliferation of
haematopoietic cells in haemolytic anaemia, PNH, myelofibrosis, sideroblastic anaemia,
leukaemia and multiple myeloma.
Causes of Nonmegaloblastic Macrocytic Anaemia
• Haemolytic and posthaemorrhagic anaemia: Result in accelerated erythropoiesis,
which leads to increased reticulocyte count, premature release of the bone marrow re-
ticulocytes and shortened time between all cell divisions/skipping of cell division, all of
which cause macrocytosis.
• Thin macrocytosis: Thin macrocytes typically have increased surface area to
volume ratio. Increased surface area is attributed to excessive lipid content which
in turn may be seen in:
g
h
h
• Hepatic disease (obstructive jaundice): Bile salt excretion n Bile salt in plasma n
Free cholesterol due to decreased esterification n Increased uptake of cholesterol by
RBCs n Increased membrane surface area
• Postsplenectomy state: During maturation of reticulocytes in spleen, there is loss of
lipids; in the absence of spleen, there is decreased loss and excessive accumulation of
lipids in the RBC membrane resulting in increased surface area.
• Myelodysplastic syndrome (MDS), eg
• Aplastic anaemia
• 5q-refractory anaemia syndrome
• Acquired sideroblastic anaemia
• Hereditary dyserythropoietic anaemia
• Miscellaneous
• Alcoholism
• Hypothyroidism
• Myelophthisic anaemia
Clinical Features of Vitamin B 12 Deficiency
• General signs and symptoms of anaemia: Weight loss, angular cheilosis, dermatitis,
osteomalacia, pallor, icterus (lemon tint), low-grade fever (in severe anaemia), mucocu-
taneous bleeding (with thrombocytopenia)
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