When the Stomach Attacks Itself: The Pathophysiology of Pernicious Anemia in a 61-Year-Old Woman With Numb Feet and a Sore Tongue
[Student Name]
University of Phoenix
NSG/521: Advanced Pathophysiology
Week 4 Assignment
[Instructor Name]
[Date]
Composite patient written as a model document. No real patient is described.
A composite 61-year-old retired bank teller with treated Hashimoto thyroiditis told her nurse practitioner that she had been exhausted for months, that her tongue felt raw and that her feet had been tingling and numb for about six weeks. She had begun to feel unsteady in the dark. Examination showed a smooth, beefy red tongue, reduced vibration and position sense in both feet and a positive Romberg sign. Her hemoglobin was 9.2 g/dL with a mean corpuscular volume of 118 fL; the blood smear showed large oval red cells and neutrophils with six or more nuclear lobes. Serum vitamin B12 was 162 pg/mL, methylmalonic acid was elevated and antibodies to intrinsic factor were present. Her anemia and her numb feet were two consequences of one missing vitamin, and the vitamin was missing because her immune system had destroyed the cells that let her absorb it. This paper explains the pathophysiology of pernicious anemia as it applies to her.
The Autoimmune Cause
Pernicious anemia is the end stage of autoimmune gastritis. CD4-positive T cells target the hydrogen-potassium ATPase, the proton pump of gastric parietal cells in the body and fundus of the stomach, and autoantibodies against the pump and against intrinsic factor accompany the attack (Toh et al., 1997). Over years, parietal cells are destroyed and the gastric lining becomes atrophic. Because parietal cells make both acid and intrinsic factor, the stomach loses both.
Autoimmune conditions tend to cluster. The patient's Hashimoto thyroiditis is one of the conditions most often associated with autoimmune gastritis, along with type 1 diabetes and vitiligo, which is why a person with one autoimmune disease who develops unexplained anemia or neurologic symptoms should be evaluated for pernicious anemia.
Why Absorption Fails
Vitamin B12 absorption requires several steps. In the stomach, acid and pepsin release B12 from food proteins, and it binds a carrier called haptocorrin. In the duodenum, pancreatic enzymes free it again, and it binds intrinsic factor. The B12 and intrinsic factor complex travels to the terminal ileum, where it binds a specific receptor and is absorbed (Stabler, 2013).
In pernicious anemia, the loss of parietal cells means little intrinsic factor is produced, and antibodies against intrinsic factor block what remains, either by preventing B12 from binding or by preventing the complex from binding its ileal receptor. Without intrinsic factor, only about 1% of oral B12 is absorbed by passive diffusion. Because the liver stores several years' supply, deficiency develops slowly, which explains the patient's gradual onset.
First Enzyme Role: Anemia
Vitamin B12, as methylcobalamin, is the cofactor for methionine synthase, which transfers a methyl group from 5-methyltetrahydrofolate to homocysteine, producing methionine and regenerating tetrahydrofolate. Without B12, folate is trapped in its methylated form and cannot be used to make the thymidine needed for DNA synthesis, the so-called methyl-folate trap (Stabler, 2013). Homocysteine also accumulates.
Impaired DNA synthesis with normal RNA and protein synthesis causes nuclear-cytoplasmic asynchrony in rapidly dividing cells. In the bone marrow, red cell precursors grow large while their nuclei mature slowly, producing megaloblasts. Many die in the marrow, a process called ineffective erythropoiesis, and those released are large, oval macrocytes, explaining her mean corpuscular volume of 118 fL. Neutrophils develop hypersegmented nuclei. The same defect in the rapidly dividing cells of the tongue produces atrophic glossitis, the smooth red tongue she described.
Second Enzyme Role: Nerve Damage
Vitamin B12, as adenosylcobalamin, is also the cofactor for methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA in mitochondria. Without B12, methylmalonic acid accumulates, which is why her methylmalonic acid level was elevated, a more specific marker of deficiency than the B12 level alone. The accumulation, together with impaired methylation reactions in the nervous system, is associated with abnormal fatty acid synthesis and defective myelin (Stabler, 2013).
The result is demyelination, most characteristically in the dorsal columns and lateral corticospinal tracts of the spinal cord, called subacute combined degeneration. Damage to the dorsal columns explains her loss of vibration and position sense and her positive Romberg sign: without proprioceptive input, she depends on vision to stay upright and sways when her eyes are closed. Peripheral nerves are also affected, producing tingling and numbness in the feet. Neurologic damage can occur even when the anemia is mild, and it may become permanent if treatment is delayed.
Distinguishing Other Causes of B12 Deficiency
Pernicious anemia is only one cause of low B12, and the mechanism helps separate it from the others. Long-term metformin use and acid-suppressing drugs such as proton pump inhibitors reduce absorption but do not produce intrinsic factor antibodies. Surgery that removes the stomach or terminal ileum, and ileal disease such as Crohn disease, remove the sites of intrinsic factor production or absorption. Strict vegan diets lack B12 entirely, although deficiency takes years to appear. This patient took neither metformin nor acid suppressants, had no bowel surgery and ate a mixed diet, and her intrinsic factor antibodies pointed to the autoimmune cause. Establishing the cause matters because it decides whether B12 must be replaced for life and whether the stomach needs further evaluation.
Why Folate Alone Is Dangerous
Folic acid supplements can bypass the methyl-folate trap enough to restore DNA synthesis in marrow cells, so folate alone can correct the anemia of B12 deficiency. It does nothing for methylmalonyl-CoA mutase, however, so the neurologic damage continues, now hidden because the blood count looks better. This is why B12 deficiency must be ruled out before treating a macrocytic anemia with folate.
Other Consequences
Loss of gastric acid has additional effects. Iron absorption depends partly on acid to keep iron in its absorbable form, so iron deficiency often coexists with pernicious anemia and may appear after B12 treatment when new red cells consume iron stores. Chronic loss of acid also causes gastrin to rise, stimulating enterochromaffin-like cells and increasing the risk of gastric neuroendocrine tumors, and autoimmune gastritis carries an increased risk of gastric adenocarcinoma (Htut et al., 2021). Some guidelines suggest endoscopic evaluation after diagnosis for these reasons.
Diagnosis and Treatment
The diagnosis rests on evidence of B12 deficiency, a low B12 level supported by elevated methylmalonic acid and homocysteine, plus evidence of the autoimmune cause, antibodies to intrinsic factor, which are highly specific, or parietal cell antibodies, which are more sensitive but less specific (Htut et al., 2021). Treatment replaces B12 in a form that bypasses the absorption defect: intramuscular injections, often daily or several times weekly at first and then monthly for life, or high-dose oral B12, which relies on passive absorption. Because of her neurologic signs, the patient began injections. Her reticulocyte count rose within a week, confirming that the marrow could respond, and her iron stores were rechecked because of the risk of unmasked iron deficiency.
Conclusion
In this woman, an autoimmune attack on gastric parietal cells removed intrinsic factor and acid, making her unable to absorb vitamin B12. Once her liver stores were exhausted, B12 deficiency impaired DNA synthesis, producing megaloblastic anemia and glossitis, and disrupted myelin metabolism, damaging her spinal cord and peripheral nerves. The two enzyme roles of B12 explain why she had both blood and nerve findings, why methylmalonic acid confirms the diagnosis and why folate alone would have hidden a progressing neurologic injury.
References
Htut, T. W., Thein, K. Z., & Oo, T. H. (2021). Pernicious anemia: Pathophysiology and diagnostic difficulties. Journal of Evidence-Based Medicine, 14(2), 161-169. https://doi.org/10.1111/jebm.12435
Stabler, S. P. (2013). Vitamin B12 deficiency. New England Journal of Medicine, 368(2), 149-160. https://doi.org/10.1056/NEJMcp1113996
Toh, B. H., van Driel, I. R., & Gleeson, P. A. (1997). Pernicious anemia. New England Journal of Medicine, 337(20), 1441-1448. https://doi.org/10.1056/NEJM199711133372007
How this NSG 521 Week 4 example is structured
The University of Phoenix library guide for NSG/521 lists Week 4 as Endocrine and Hematology, with pernicious anemia among the research topics. The paper begins with the autoimmune cause, then follows vitamin B12 through absorption to its two enzyme roles, because each role explains a different set of findings: one produces the anemia, the other the neurologic damage. The final sections use the mechanism to explain diagnosis, treatment and a common error. Students search this week as NSG 521 Week 4, NSG521 Wk 4 or NSG/521 Wk 4; all three are the same assignment.
NSG/521 Week 4 questions, answered
What does NSG/521 Week 4 usually ask for?
The library guide for NSG/521 lists Week 4 as endocrine and hematology, with topics including diabetes, thyroid disease, iron deficiency anemia, pernicious anemia and folate deficiency. Many sections ask for a paper on the pathophysiology of one of these conditions applied to a patient.
Why does B12 deficiency cause nerve damage but folate deficiency usually does not?
Both vitamins are needed for DNA synthesis, which is why both cause megaloblastic anemia. Only B12 is also a cofactor for methylmalonyl-CoA mutase, and failure of that pathway contributes to abnormal myelin and nerve damage.
Is oral B12 enough for pernicious anemia?
High-dose oral B12 can be effective because a small fraction is absorbed by passive diffusion without intrinsic factor, but many clinicians start with injections, especially when neurologic symptoms are present. The choice depends on severity and the patient's ability to adhere.
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