Megaloblastic Anaemia PDF

# Megaloblastic Anaemia ## Definition and Characteristics - **Overview of Megaloblastic Anaemia:** A type of anaemia caused by impaired DNA synthesis during red blood cell (RBC) production. - **Role of Folate and Vitamin B12:** - Results from deficiencies in vitamin B12 or folic acid, or distur...

# Megaloblastic Anaemia ## Definition and Characteristics - **Overview of Megaloblastic Anaemia:** A type of anaemia caused by impaired DNA synthesis during red blood cell (RBC) production. - **Role of Folate and Vitamin B12:** - Results from deficiencies in vitamin B12 or folic acid, or disturbances in folic acid metabolism. - Key characteristics include: - High mean corpuscular volume (MCV) greater than 110 fL. - Low hemoglobin (Hb) and RBC count. - Decreased white blood cells (WBC) and platelets. - Folate is a crucial substrate in DNA synthesis, while vitamin B12 acts as a co-factor in the conversion of homocysteine to methionine. - This biochemical reaction produces tetrahydrofolate, which is essential for synthesizing thymidine monophosphate for DNA incorporation. - Deficiencies in either vitamin lead to elevated plasma homocysteine levels and impaired DNA synthesis, resulting in nucleocytoplasmic asynchrony. ## Pathophysiology of Megaloblastic Anaemia - **Cellular Changes and Effects:** - All proliferating cells exhibit megaloblastosis, affecting various tissues including the buccal mucosa, tongue, and gastrointestinal tract. - Cells arrested in development die within the bone marrow, leading to hypercellular marrow and ineffective erythropoiesis. - Hemolysis within the bone marrow raises bilirubin and lactate dehydrogenase (LDH) levels, but iron stores are typically elevated. - **Morphological Features:** - Mature RBCs are large and oval, sometimes containing nuclear remnants, while immature precursors appear as giant metamyelocytes with large nuclei. - Mature neutrophils may show hypersegmentation, with six or more nuclear lobes. - Severe cases may present with pancytopenia in peripheral blood. - **Neurological Implications:** - Vitamin B12 deficiency, unlike folate deficiency, can lead to neurological diseases in up to 40% of cases in developing countries. - Pathological findings include focal demyelination in the spinal cord, peripheral nerves, optic nerves, and cerebrum. - Common neurological manifestations include sensory neuropathy, peripheral paraesthesia, and ataxia. ## Clinical Features of Megaloblastic Anaemia - **Symptoms:** - Common symptoms include malaise (90%), breathlessness (50%), and paraesthesia (80%). - Other symptoms may include: - A sore mouth (20%). - Weight loss. - Impotence. - Poor memory. - Depression. - Personality changes. - Hallucinations. - Visual disturbances. - **Signs:** - Physical examination may reveal: - A smooth tongue. - Angular cheilosis. - Vitiligo. - Skin pigmentation changes. - Heart failure. - Pyrexia - **Differentiation of Anemia Types:** - These signs reflect the systemic effects of megaloblastic anaemia on the body. - Megaloblastic anaemia is characterized by impaired DNA synthesis and nucleocytoplasmic asynchrony, with megaloblastic bone marrow and hypersegmented neutrophils. - Non-megaloblastic macrocytic anemia results from red cell membrane abnormalities and presents with large round RBCs and normal neutrophils. ## Vitamin B12 Absorption and Deficiency - **Absorption Mechanism:** - The average diet contains 5-30 µg of vitamin B12, primarily from animal sources. - Daily requirement is about 1 µg, with absorption involving gastric enzymes and intrinsic factor produced by gastric parietal cells. - The B12-intrinsic factor complex is absorbed in the terminal ileum, where it binds to transcobalamin II for transport to tissues. - **Causes of Vitamin B12 Deficiency:** - **Dietary Deficiency:** Primarily affects strict vegans. - **Gastric Pathology:** Conditions like hypochlorhydria in the elderly or total gastrectomy lead to deficiency. - **Pernicious Anaemia:** An autoimmune disorder causing intrinsic factor deficiency, leading to poor B12 absorption. - **Small Bowel Pathology:** Conditions affecting the terminal ileum or bacterial overgrowth can impair absorption. - **Anti-intrinsic factor antibodies** are diagnostic for pernicious anaemia. - **Anti-parietal cell antibodies** are present in many cases but are not definitive. - **Investigative Approaches:** - The Schilling test, though less common now, measures B12 absorption and helps differentiate causes of deficiency. ## Folate Absorption and Deficiency - **Absorption Mechanism:** - Folates are sourced from plants and bacteria, with rich sources including vegetables, fruits, and animal proteins. - The average western diet exceeds the minimum daily intake, but cooking can destroy folate content. - Total body folate stores are small, leading to rapid deficiency under inadequate intake. - **Causes of Folate Deficiency:** - **Poor Intake:** Particularly in the elderly or those with psychiatric conditions. - **Malabsorption:** Conditions like Coeliac disease or small bowel surgery can lead to deficiency. - **Increased Demand:** Situations such as pregnancy or hemolysis increase folate requirements. - **Diagnostic Considerations:** - Drug Interactions: Certain medications can interfere with folate metabolism. - Serum folate levels can be misleading due to dietary intake fluctuations; red cell folate levels provide a more accurate assessment of folate stores. - A single folate-rich meal can normalize serum levels in true deficiency cases. ## Management of Megaloblastic Anaemia - **Initial Treatment Protocol:** - In severe cases, treatment should start with both folic acid and vitamin B12 before test results are available to prevent worsening neurological symptoms. - Transfusion may be considered in cases of angina or heart failure. - **Treatment of Vitamin B12 Deficiency:** - For uncomplicated deficiency, hydroxocobalamin 1000 µg IM is administered for six doses, followed by maintenance therapy every three months. - In cases with neurological involvement, higher doses may be required until stabilization. - **Treatment of Folate Deficiency:** - Oral folic acid (5 mg daily for three weeks) is effective, with maintenance therapy of 5 mg weekly - Prophylactic folic acid is recommended during pregnancy to reduce neural tube defect risks and in chronic hematological diseases.