Megaloblastic Anemia: Pathophysiology, Causes, and Diagnosis

What is megaloblastic anemia characterized by?

Macrocytic anemia caused by defective nuclear maturation due to impaired DNA synthesis.

What abnormal cells are observed in megaloblastic anemia?

Large abnormal RBC precursors in bone marrow and macro-ovalocytes in peripheral blood.

What are Howell-Jolly bodies?

Nuclear remnants seen in red blood cells, often associated with megaloblastic anemia.

What biochemical deficiency leads to megaloblastic anemia?

A decrease in thymidine triphosphate (TTP) synthesis from uridine monophosphate (UMP).

What vitamins are primarily responsible for TTP synthesis?

Vitamin B12 and folic acid deficiencies.

What are common clinical presentations of megaloblastic anemia?

Mild to severe anemia, weakness, fatigue, shortness of breath, and lightheadedness.

What hematologic feature indicates ineffective erythropoiesis in megaloblastic anemia?

A decrease in reticulocyte count due to increased precursors in the marrow and decreased release into circulation.

What is the typical MCV range in megaloblastic anemia?

Generally greater than 100 fL and may be as high as 160 fL.

What is the significance of hypersegmented neutrophils in megaloblastic anemia?

They are a morphological feature seen early in the disease and indicate impaired DNA synthesis.

What does the bone marrow morphology show in megaloblastic anemia?

Hypercellularity with a high myeloid to erythroid (M:E) ratio and presence of megaloblasts.

What are the main causes of vitamin B12 deficiency?

Dietary deficiency, pernicious anemia, and malabsorption syndromes.

What is pernicious anemia?

A common cause of vitamin B12 deficiency due to a lack of intrinsic factor from atrophic gastritis.

What is the recommended daily intake of vitamin B12?

24 micrograms per day, with increased needs during pregnancy and growth.

How is vitamin B12 transported in the body?

It binds to intrinsic factor and transcobalamin II for absorption and transport to tissues.

What is the role of vitamin B12 in metabolism?

It is essential for the synthesis of methionine from homocysteine and conversion of methylmalonyl CoA to succinyl CoA.

What are the hematologic features of peripheral blood in megaloblastic anemia?

Pancytopenia, macrocytic normochromic RBCs, and increased RDW.

What is the reticulocyte production index (RPI) in megaloblastic anemia?

Typically less than 2, indicating ineffective erythropoiesis.

What are the laboratory findings associated with ineffective hematopoiesis in megaloblastic anemia?

Elevated LDH, increased indirect bilirubin, decreased haptoglobin, and increased serum iron and ferritin.

What is the significance of increased megakaryocytes in the bone marrow?

It indicates thrombopoiesis is affected, leading to thrombocytopenia in peripheral blood.

What are the morphological features of RBCs in megaloblastic anemia?

Macro-ovalocytes, schistocytes, teardrop cells, spherocytes, and target cells.

What is the effect of vitamin B12 deficiency on infants born to vegan mothers?

They may be severely megaloblastic with retarded growth and psychomotor development.

What are the two types of intrinsic factor antibodies found in pernicious anemia?

Blocking antibodies that prevent B12-IF complex formation and binding antibodies.

What is the relationship between vitamin B12 deficiency and autoimmune conditions?

Pernicious anemia is often associated with autoimmune atrophic gastritis.

What is the lifespan of macrocytes in megaloblastic anemia?

Shortened survival time of 27-75 days.

What are Cabot rings?

Inclusions that may be present in peripheral blood in cases of megaloblastic anemia.

What is the prevalence of pernicious anemia in different populations?

More common in people of Scandinavian, English, and Irish descent, particularly in women over 50.

What are lymphotoxic antibodies associated with in patients?

They show a decrease in suppressor T cells and an increase in the CD4:CD8 ratio.

What is a common treatment for patients with suspected autoimmune involvement in vitamin B12 deficiency?

Steroid treatment.

What is one cause of vitamin B12 deficiency related to surgery?

Gastrectomy, which removes intrinsic factor-producing cells.

What condition involves bacterial overgrowth in the small bowel leading to vitamin B12 deficiency?

Blind loop syndrome.

Which fish tapeworm competes for vitamin B12 and is common in Scandinavian countries?

Diphyllobothrium latum.

What are common clinical manifestations of vitamin B12 deficiency?

Symptoms of megaloblastic anemia, including loss of appetite, glossitis, weakness, and paresthesia.

What neurological problems are more common in pernicious anemia than other types of B12 deficiency?

Degeneration of peripheral nerves and spinal cord, leading to symptoms like 'pins and needles' sensation and incoordinate gait.

What severe symptoms can occur in advanced vitamin B12 deficiency?

Severe weakness, stiffness of limbs, memory impairment, and depression.

What is the daily requirement for folic acid in adults?

50 to 100 µg/day.

What are some dietary sources of folic acid?

Green leafy vegetables, fruits, dairy products, cereals, and animal foods like liver and kidney.

What is the main cause of folic acid deficiency?

Decreased dietary intake due to factors like poverty, old age, alcoholism, pregnancy, and chronic disease.

What are common causes of folate malabsorption?

Tropical sprue and gluten-sensitive enteropathy.

What drug is known to induce folate deficiency by inhibiting DNA synthesis?

Methotrexate.

What laboratory tests are commonly used to diagnose megaloblastic anemia?

Low hemoglobin, elevated MCV, peripheral smear morphology, and serum B12 and folate levels.

What test evaluates the absorption of vitamin B12 from the intestinal tract?

The Schilling test.

What is the initial sign of response to vitamin B12 therapy?

Increase in reticulocyte count.

What is the recommended treatment for vitamin B12 deficiency?

Lifelong vitamin therapy with cyanocobalamin or hydroxocobalamin.

What is the treatment for folic acid deficiency?

Oral folic acid at a dose of 1-5 mg/day for 2-3 weeks.

What are vitamin-independent megaloblastic changes?

Megaloblastic changes that do not respond to B12 and folate treatments.

What inherited disorder shows increased excretion of orotic acid in urine?

Orotic aciduria.

What is a common cause of macrocytic nonmegaloblastic anemias?

Chronic liver disease and alcoholism.

What effect does alcohol have on red blood cells?

It has a direct toxic effect, leading to macrocytosis.

What is the role of LDH and bilirubin in screening for alcoholism?

They are helpful screening tools for detecting macrocytic anemia associated with alcohol use.

What is the significance of macrocytosis in relation to alcoholism?

It is a valuable screening tool for early detection of alcoholism.

What is the consequence of methotrexate on folate metabolism?

It inhibits DNA synthesis, leading to folate deficiency.

What is the relationship between folate deficiency and leukemia?

There is an association between folate deficiency and the development of leukemia in high-risk patients.