Megaloblastic anemia

Key takeaways

Megaloblastic anemia belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Megaloblastic anemia to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Megaloblastic anemia from memory before moving on to harder problems.

Reference excerpt

Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis. Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias. The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency. Loss of micronutrients may also be a cause. Megaloblastic anemia which is not caused due to hypovitaminosis may be caused by antimetabolites that poison DNA production directly, such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim). The pathological state of megaloblastosis is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by hypersegmented neutrophils (defined as the presence of neutrophils with six or more lobes or the presence of more than 3% of neutrophils with at least five lobes). These hypersegmented neutrophils can be detected in the peripheral blood (using a diagnostic smear of a blood sample).

Causes Vitamin B12 deficiency: Achlorhydria-induced malabsorption Deficient intake (e.g. vegan diet) Pernicious anemia Gastrectomy Celiac disease Biological competition for vitamin B12 by diverticulosis, fistula, intestinal anastomosis, or infection by the marine parasite Diphyllobothrium latum (fish tapeworm) Selective vitamin B12 malabsorption (congenital—juvenile megaloblastic anemia 1—and drug-induced) Chronic pancreatitis Ileal resection and bypass Nitrous oxide anesthesia (usually requires repeated instances). Folate deficiency: Alcoholism Deficient intake Increased needs: pregnancy, infant, rapid cellular proliferation, and cirrhosis Malabsorption (congenital and drug-induced) Intestinal and jejunal resection (indirect) Deficient thiamine and factors (e.g., enzymes) responsible for abnormal folate metabolism. Tea and toast diet Inherited Pyrimidine Synthesis Disorders: Orotic aciduria Inherited DNA Synthesis Disorders Toxins and Drugs: Folic acid antagonists (methotrexate) Purine synthesis antagonists (6-mercaptopurine, azathioprine) Pyrimidine antagonists (cytarabine) Phenytoin Nitrous Oxide Erythroleukemia Inborn genetic mutations of the Methionine synthase gene Di Guglielmo's syndrome Congenital dyserythropoietic anemia Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause.

Pathophysiology There is a defect in DNA synthesis in the rapidly dividing cells and to a lesser extent, RNA and protein synthesis are also impaired. Therefore, unbalanced cell proliferation and impaired cell division occur as a result of arrested nuclear maturation so the cells show nuclear-cytoplasmic asynchrony. In the bone marrow, most megaloblasts are destroyed prior to entering the peripheral blood (intramedullary hemolysis). Some can escape the bone marrow (macrocytes) to peripheral blood but they are destroyed by the reticulo-endothelial system (extramedullary hemolysis).

Diagnosis Vitamin B12 deficiency is normally recognized by a low blood level of Vitamin B12, which can be treated by injections, supplementation, or dietary or lifestyle advice. It can result from a number of mechanisms, including those listed above. For determination of cause, further patient history, testing, and empirical therapy may be clinically indicated. A measurement of methylmalonic acid (methylmalonate) can provide an indirect method for partially differentiating Vitamin B12 and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. Direct measurement of blood cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B12 is one necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. Vitamin B12 deficiency is but one among the conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of which can be detected in the urine and blood. Due to the lack of available radioactive Vitamin B12, the Schilling test is now largely a historical artifact. The Schilling test was performed in the past to help determine the nature of the vitamin B12 deficiency. An advantage of the Schilling test was that it often included Vitamin B12 with intrinsic factor.

Blood findings The blood film can point towards vitamin deficiency:

Decreased red blood cell (RBC) count and hemoglobin levels Increased mean corpuscular volume (MCV, >100 fL) and mean corpuscular hemoglobin (MCH) Normal mean corpuscular hemoglobin concentration (MCHC, 32–36 g/dL) Decreased reticulocyte count due to destruction of fragile and abnormal megaloblastic erythroid precursor. The platelet count may be reduced. Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age. Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs). Macrocytes (larger than normal RBCs) are present. Ovalocytes (oval-shaped RBCs) are present. Howell-Jolly bodies (chromosomal remnant) also present. Blood chemistries will also show:

An increased lactic acid dehydrogenase (LDH) level. The isozyme is LDH-2 which is typical of the serum and hematopoietic cells. Increased homocysteine and methylmalonic acid in Vitamin B12 deficiency Increased homocysteine in folate deficiency Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty. Elevated homocysteine and normal methylmalonic acid indicate folate deficiency, while elevated homocysteine and elevated methylmalonic acid indicate vitamin B12 deficiency. Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia.

See also List of circulatory system conditions List of hematologic conditions

References

External links

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Illustrations

Worked examples

Example 1 — a first encounter with Megaloblastic anemia

Start with the simplest possible case. Write down what Megaloblastic anemia claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Megaloblastic anemia before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Megaloblastic anemia ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Megaloblastic anemia

In research: Megaloblastic anemia appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Megaloblastic anemia in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Megaloblastic anemia is common in secondary-school and first-year university syllabi. It links to neighbouring topics Hematopathology, Nutritional anemias, so understanding it makes those chapters shorter.
In everyday life: Look for Megaloblastic anemia outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Megaloblastic anemia in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Megaloblastic anemia means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
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Frequently asked questions

What is Megaloblastic anemia in simple terms?

Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen.

Why does Megaloblastic anemia matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Megaloblastic anemia?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Megaloblastic anemia.