B12 and folate deficiency: megaloblastic anaemia
How vitamin B12 and folate let dividing cells copy their DNA, why their lack makes large, immature blood cells, why B12 deficiency also damages nerves, and how the cause is traced to the stomach, the ileum or the diet.
By the end, you can
- Describe how vitamin B12 is absorbed with intrinsic factor and where this can fail.
- Explain how a lack of B12 or folate slows DNA synthesis and produces megaloblasts and macrocytes.
- Explain why ineffective red cell production causes mild jaundice and can lower all blood counts.
- Explain why B12 deficiency, but not folate deficiency, damages the spinal cord and nerves.
- Relate the symptoms and findings to the stage of the mechanism that causes them.
- Recognise the blood film, marrow and laboratory features of megaloblastic anaemia and its mimics, and explain how B12 and folate replacement act on the mechanism.
What it is
Megaloblastic anaemia is anaemia in which developing blood cells in the marrow are abnormally large (megaloblasts) because DNA synthesis is impaired while the rest of the cell keeps growing. Most cases are caused by deficiency of vitamin B12 (cobalamin) or folate. Pernicious anaemia is B12 deficiency caused by autoimmune loss of intrinsic factor.
2 types to tell apart
- Vitamin B12 deficiency
- Usually from poor absorption: pernicious anaemia, stomach or ileal surgery, ileal disease, long-term metformin or acid suppression; less often a vegan diet without supplements. Stores last years.
- Folate deficiency
- Usually from poor intake, alcohol misuse, increased need (pregnancy, haemolysis), malabsorption or drugs such as methotrexate. Stores last months.
US spelling: anaemia → anemia.
Normal function
Absorbing vitamin B12 and folate
Vitamin B12 comes from animal foods. Acid and pepsin in the release it from food proteins. Parietal cells in the secrete intrinsic factor, which binds B12 in the duodenum and carries it to the terminal ileum, the only place it is absorbed.
The liver stores several years’ worth of B12, so deficiency develops slowly. Folate, from leafy vegetables, fruit and fortified foods, is absorbed in the upper small intestine; stores last only a few months.
Both vitamins are needed by every dividing cell. Folate supplies one-carbon units to make thymidine, one of the four DNA building blocks; B12 is needed to recycle folate into its active form, and also for a separate reaction important for myelin.
Underlying change · Step 1 of 4
How deficiency develops
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 2 of 4
DNA synthesis slows while the cell grows
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 4
B12 and the nervous system
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 4 of 4
Symptoms and the path to a cause
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .