[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Megaloblastic anaemia (B12 or folate deficiency)

[Conditions](https://durgical.com/en/conditions/) · [Vitamins and minerals](https://durgical.com/en/conditions/)

# Megaloblastic anaemia (B12 or folate deficiency)

Anaemia with large red cells caused by lack of vitamin B12 or folate, which stops the bone marrow copying DNA properly.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Stomach](https://durgical.com/en/anatomy/stomach/)
- [Ileum](https://durgical.com/en/anatomy/ileum/)
- [Jejunum](https://durgical.com/en/anatomy/jejunum/)
- [Tongue](https://durgical.com/en/anatomy/tongue/)
- [Spinal cord](https://durgical.com/en/anatomy/spinal-cord/)

## In biochemistry

- [Methionine cycle and transsulfuration: Step 4 · Methionine synthase (MTR), B12-dependent](https://durgical.com/en/biochemistry/pathways/methionine-cycle-and-transsulfuration/#paso-4)
- [Lactate dehydrogenase (LDH) as a lab marker](https://durgical.com/en/biochemistry/topics/lactate-dehydrogenase-as-a-lab-marker/)
- [Histidine](https://durgical.com/en/biochemistry/molecules/histidine/)
- [Folate (vitamin B9)](https://durgical.com/en/biochemistry/molecules/folate/)
- [Cobalamin (vitamin B12)](https://durgical.com/en/biochemistry/topics/cobalamin/)

## Microorganisms that cause it

- [Dibothriocephalus latus](https://durgical.com/en/microbiology/dibothriocephalus-latus/)

## In immunology

- [Bone marrow and hematopoiesis of immune cells](https://durgical.com/en/immunology/bone-marrow-and-hematopoiesis-of-immune-cells/)
- [Neutrophil](https://durgical.com/en/immunology/neutrophil/)

## In histology

- [Blood cells on a smear: erythrocytes, leukocytes, platelets](https://durgical.com/en/histology/blood-cells-on-a-smear-erythrocytes-leukocytes-platelets/)
- [Hematopoiesis and bone marrow](https://durgical.com/en/histology/hematopoiesis-and-bone-marrow/)

## In embryology

- [Folic acid and neural tube defect prevention](https://durgical.com/en/embryology/folic-acid-and-neural-tube-defect-prevention/)

## In the clinical exam

- [Sensory examination: modalities and dermatomes](https://durgical.com/en/clinical-exam/sensory-examination-modalities-and-dermatomes/)
- [Romberg test](https://durgical.com/en/clinical-exam/romberg-test/)
- [Spinal cord syndromes: complete, Brown-Séquard, central, anterior](https://durgical.com/en/clinical-exam/spinal-cord-syndromes-complete-brown-sequard-central-anterior/)
- [Anemia syndrome](https://durgical.com/en/clinical-exam/anemia-syndrome/)

## In physiology

- [Anemia physiology and compensation](https://durgical.com/en/physiology/anemia-physiology-and-compensation/)
- [Erythropoiesis and erythropoietin](https://durgical.com/en/physiology/erythropoiesis-and-erythropoietin/)
- [Absorption of iron, calcium and vitamin B12](https://durgical.com/en/physiology/absorption-of-iron-calcium-and-vitamin-b12/)
- [Somatosensory pathways: dorsal column and anterolateral](https://durgical.com/en/physiology/somatosensory-pathways-dorsal-column-and-anterolateral/)

## Why it happens

- [Vitamin deficiencies: what each one does to tissue](https://durgical.com/en/general-pathology/vitamin-deficiencies-what-each-one-does-to-tissue/)
- [Alcohol: how it injures the liver, brain, heart and fetus](https://durgical.com/en/general-pathology/alcohol-how-it-injures-the-liver-brain-heart-and-fetus/)

## What it is

A macrocytic anaemia caused by defective DNA synthesis, almost always from vitamin B12 or folate deficiency. It affects every rapidly dividing cell: bone marrow, mucosa and fetus.

## Who gets it

Folate deficiency is seen with malnutrition, alcoholism and pregnancy; it fell where flour is fortified, as in Colombia. B12 deficiency is commoner in older adults, vegans, after gastric surgery and with long-term metformin.

## Causes

- B12 deficiency: pernicious anaemia, gastrectomy or bariatric surgery, ileal disease or resection, vegan diet, metformin, proton pump inhibitors, fish tapeworm
- Folate deficiency: poor diet, alcoholism, pregnancy, chronic haemolysis, coeliac disease
- Drugs that block DNA or folate: methotrexate, trimethoprim, phenytoin, hydroxyurea, zidovudine

## Risk factors

- Older age
- Alcoholism
- Pregnancy and breastfeeding
- Gastric or bowel surgery
- Diet without animal foods

## Pathophysiology

Without methylene-tetrahydrofolate, thymidylate synthase cannot make dTMP; uracil enters DNA and replication lags while the cytoplasm keeps maturing (nuclear-cytoplasmic asynchrony). Precursors grow without dividing (megaloblasts) and many die in the marrow (ineffective erythropoiesis): LDH and indirect bilirubin rise. In B12 deficiency, folate is trapped as 5-methyl-THF, and methylmalonic acid also builds up and damages myelin.

## Classification

- From vitamin B12 deficiency
- From folate deficiency
- From drugs or inborn defects of DNA synthesis

## Symptoms and signs

- Tiredness, pallor, breathlessness on exertion
- Red, smooth, sore [tongue](https://durgical.com/en/anatomy/tongue/) (glossitis), mouth ulcers
- Mild jaundice (lemon-yellow tint)
- In B12 deficiency: tingling hands and feet, poor balance, forgetfulness, mood change
- Diarrhoea, weight loss

## Red flags

- Neurological symptoms (they involve the [spinal cord](https://durgical.com/en/anatomy/spinal-cord/) and can become permanent)
- Pancytopenia with bleeding or infection
- Severe anaemia with angina or heart failure

## Diagnosis

**Clinical**
Anaemia with high MCV and glossitis; ask about diet, drugs, surgery, alcohol and look for neurological signs.

**Tests**
Blood count with high MCV, hypersegmented neutrophils, macro-ovalocytes, low reticulocytes; high LDH and indirect bilirubin. Serum B12 and folate; methylmalonic acid (high only in B12 deficiency) and homocysteine (high in both). Intrinsic factor antibodies if B12 is low.

**Imaging**
Not needed for diagnosis; upper GI endoscopy if atrophic gastritis or a gastric lesion is suspected.

## Treatment

**Medical**
Replace the missing vitamin: B12 (intramuscular or high-dose oral) or folic acid, after measuring both

**Medical**
Treat the cause: malabsorption, drugs, alcoholism, parasites

**Follow-up**
Monitor potassium in the first days and the reticulocyte response

**Lifestyle**
Diet with leafy greens and legumes (folate) or animal or fortified foods (B12)

## Drugs for this condition

- [Folic acid](https://durgical.com/en/pharmacology/folic-acid/)
- [Cyanocobalamin](https://durgical.com/en/pharmacology/cyanocobalamin/)
- [Hydroxocobalamin](https://durgical.com/en/pharmacology/hydroxocobalamin/)
- [Calcium folinate](https://durgical.com/en/pharmacology/calcium-folinate/)

## Complications

- Subacute combined degeneration of the spinal cord (B12)
- Neural tube defects in pregnancy (folate)
- Heart failure from anaemia
- Hypokalaemia when treatment starts

## Prognosis

The anaemia responds within weeks (reticulocytes rise within days); long-standing nerve damage may remain.

## Prevention

- Folic acid before and during pregnancy
- B12 for vegans, after bariatric surgery and for at-risk older adults
- Flour fortification

## Test yourself

Think of the answer, then tap the question to see it.

## Why are the cells large in megaloblastic anaemia?

DNA synthesis lags while the cytoplasm matures; precursors grow without dividing.

## Which test tells B12 from folate deficiency?

Methylmalonic acid: raised in B12 deficiency, normal in folate deficiency; homocysteine rises in both.

## Why is LDH raised in megaloblastic anaemia?

Ineffective erythropoiesis: many precursors die inside the bone marrow.

## Which blood film finding is typical?

Hypersegmented neutrophils (five or more lobes) and macro-ovalocytes.

## Why is B12 measured before giving folic acid?

Folic acid corrects the anaemia of B12 deficiency but does not stop its nerve damage.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/megaloblastic-anaemia/)

## Related conditions

- [Pernicious anaemia](https://durgical.com/en/conditions/pernicious-anaemia/)
- [Coeliac disease](https://durgical.com/en/conditions/coeliac-disease/)
- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)
- [Spina bifida (myelomeningocele)](https://durgical.com/en/conditions/spina-bifida/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Vitamin B12 deficiency anemia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000574.htm) (MedlinePlus, US National Library of Medicine, 2026); [Folate-deficiency anemia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000551.htm) (MedlinePlus, US National Library of Medicine, 2026); [Methylmalonic Acid (MMA) Test: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/methylmalonic-acid-mma-test/) (MedlinePlus, US National Library of Medicine, 2026); [Homocysteine Test: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/homocysteine-test/) (MedlinePlus, US National Library of Medicine, 2026); [RBC indices: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003648.htm) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Source: https://durgical.com/en/conditions/megaloblastic-anaemia/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/megaloblastic-anaemia/