Macrocytic anaemia Flashcards
What are the causes of increased MCV with anaemia?
Megaloblastic anaemia (nucleus takes longer time to mature and cytoplasm grows bigger)
Haemolysis
Liver disease (postulated that liver cannot metabolize phospholipid in blood and they are deposited on cell membrane)
Bone marrow failure
- Primary: bone marrow filled with fat (e.g. aplastic anaemia)
- Secondary: bone marrow infiltration (e.g. leukemia, lymphoma, malignancy)
What are the causes of increased MCV without anaemia?
- Alcoholism
- Medications (e.g. zidovudine)
- Liver
- Early megaloblastic
- Early bone marrow disorder
What is a megaloblast?
- large immature, nucleated RBC due to defective DNA synthesis
- these cells are about twice the size of normal cells and often have twisted nuclei.
What are the causes of vitamin B12 deficiency?
Decreased Intake: Dietary deficiency occurs in strict vegans.
Decreased absorption due to problems in the stomach:
- Hypochlorhydria (reduced gastric acid) in the elderly or following gastric surgery can impair the release of Vitamin B12 from food.
- Total gastrectomy: The gastric parietal cells that synthesize intrinsic factor are removed.
- Pernicious anemia: Autoimmune destruction of gastric parietal cells leads to IF deficiency, hypochlorhydria and decreased pepsin production.
- Atrophic gastritis: Stomach secretes less hydrochloric acid and pepsin (that are required to release vitamin B12 from food) and less IF.
Decreased absorption due to problems in the upper small intestine:
- Pancreatic insufficiency
Usurpation of luminal cobalamin:
- Bacteria: Dysmotility syndromes or hypogammaglobulinemia leads to bacterial over-growth in the intestinal lumen. These bacteria consume Vit B12 and less is available for absorption.
- Fish tapeworm: colonizes the small intestine and consumes Vit B12
Decreased absorption due to problems in the terminal ileum:
- Crohn’s disease: most commonly affects the terminal ileum where the IF-vitamin B12. Crohn’s patients often have small bowel bacterial overgrowth syndrome, which could lead to bacteria consuming luminal vitamin B12.
- Ileal resection
- Autoantibodies against IF (also pernicious anaemia): These autoantibodies may prevent IF from binding to cobalamin and/or these autoantibodies may prevent the IF-cobalamin complex from binding to IF receptors in the terminal ileal mucosa
What are the causes of folate deficiency?
Dietary Deficiency: Edentulous elderly and psychiatric patients are particularly susceptible to folate deficiency.
Overutilization: Pregnant and lactating women (particularly in developing countries) may utilize more folate, leading to deficiency.
Celiac disease (gluten-sensitive enteropathy): autoimmune disease of the small bowel. The changes in the bowel cause malabsorption - make it less able to absorb nutrients, minerals and vitamins.
Drugs (e.g. Phenytoin sodium, MTX): Phenytoin sodium is a commonly used anti-epileptic medication.
What are the clinical manifestations of folate / vitamin B12 deficiency?
General: Weakness, shortness of breath, pallor, tachycardia.
GI tract:
- Glossitis (Smooth sore tongue with atrophy of papillae
- Hyperpigmented: blackened tongue)
- Nausea, epigastric pain, loss of appetite
Skin: hyperpigmented macular lesions.
What are the neurological manifestations of vitamin B12 deficiency?
Peripheral nerves: glove and stocking paresthesia
Spinal cord: subacute combined degeneration
- Posterior column: loss of fine touch, decreased vibration sense, decreased propioception (positive Rhomberg’s), gait abnormalities, ataxia
- Corticospinal tract: spastic paraperesis and a positive Babinski sign. 50% of patients have absent ankle reflexes with relative hyperreflexia at the knees
Cerebrum: dementia
Visual: optic atrophy
Autonomic neuropathy: sexual dysfunction, bladder and bowel incontinence
Pernicious anaemia is the most common cause of Vitamin B12 deficiency in developed countries. About 0.025% of the population in developed countries have pernicious anemia above the age of 40, but usually disease starts around 60+ years of age.
It is an autoimmune disease associated with _________/____________ leading to Vitamin B12 deficiency.
Anti-gastric parietal cells:
- Destroys gastric parietal cells leading to __________. <1% of Vitamin B12 absorbed.
- Presents with autoimmune gastritis affecting the fundus, with plasma cell and lymphoid infiltration.
- The parietal and chief cells are replaced by mucin-secreting cells.
- There is _______&____________
- The histological abnormality can be improved by corticosteroid therapy, which supports an autoimmune basis for the disease.
Anti-IF autoantibodies: These autoantibodies may prevent IF from binding to Vitamin B12 and/or these autoantibodies may prevent the IF-Vitamin B12 complex from binding to IF receptors in the terminal ileal mucosa.
anti-gastric parietal cell autoantibodies or anti-intrinsic factor autoantibodies;
IF deficiency
achlorhydria and absent secretion of intrinsic factor.
What are the investigations found in Vitamin/ B12 deficiency?
Peripheral blood smear
- Macrocytes (enlarged RBCs): fully hemoglobinized RBCs that result from omitted cell divisions during erythropoiesis.
- Hypersegmented neutrophils:
Full Blood Count (FBC): Decreased Hb, increased MCV.
Bone Marrow Aspirate: Enlarged RBC precursors (megaloblasts) due to omitted cell divisions during erythropoiesis.
Homocysteine and methylmalonyl CoA levels
- Vitamin B12 deficiency,: increased homocysteine, increased methylmalonyl coA
- Folate deficiency: increased homocysteine, normal methylmalonyl coA
Specific Tests for pernicious anaemia:
- Anti-parietal antibodies
- Auto-IF antibodies
- MRI: Examine CNS
- OGD: look for gastric atrophy
What is the treatment for vitamin B12/ folate deficiency?
If vitamin B12 + folate deficiency occurs simultaneously, replace vitamin B12 first to avoid neurological damage.
Vitamin B12 (hydroxycobalamine)
- Parenteral: Intensive therapy (1000 μg I.M to a total of 5–6 mg over the course of 3 weeks
- Maintenance: 1000 μg i.m. per 3 months OR Oral Vitamin B12 (2mg/day)
Folate
- Folate supplements will rapidly normalize folate levels in patient with only folate def
- ** Prophylactic folic acid should be recommended for all women planning a pregnancy to reduce neural tube defects
