A 42-year-old man with a 10-year history of Crohn's disease presents with progressive weakness and cognitive slowing over 4 months. He reports chronic diarrhea and recent weight loss. Examination reveals glossitis, loss of vibration sense in both lower limbs, and a positive Lhermitte sign. Laboratory findings: hemoglobin 8.5 g/dL, MCV 105 fL, serum B12 95 pg/mL, serum folate 6.2 ng/mL (normal 5.4). Bone marrow shows megaloblastic erythropoiesis with giant metamyelocytes. What is the primary mechanism of anemia in this patient?

Question

A 42-year-old man with a 10-year history of Crohn's disease presents with progressive weakness and cognitive slowing over 4 months. He reports chronic diarrhea and recent weight loss. Examination reveals glossitis, loss of vibration sense in both lower limbs, and a positive Lhermitte sign. Laboratory findings: hemoglobin 8.5 g/dL, MCV 105 fL, serum B12 95 pg/mL, serum folate 6.2 ng/mL (normal >5.4). Bone marrow shows megaloblastic erythropoiesis with giant metamyelocytes. What is the primary mechanism of anemia in this patient?

Accepted Answer

C. Malabsorption of cobalamin in the terminal ileum due to Crohn's disease. ## Clinical Context: B12 Deficiency in Crohn's Disease

**Key Point:** Crohn's disease causes B12 deficiency primarily through **malabsorption in the terminal ileum**, where the intrinsic factor–B12 complex is absorbed. This is the most common mechanism of B12 deficiency in inflammatory bowel disease.

## Why Terminal Ileum Matters for B12 Absorption

| Step | Location | Function | Affected in Crohn's? |
|------|----------|----------|---------------------|
| B12 binding to intrinsic factor | Stomach | Gastric parietal cells secrete IF | No (stomach usually spared) |
| Transit through small bowel | Duodenum, jejunum | Passive transit | Possibly, if inflamed |
| **Absorption of IF–B12 complex** | **Terminal ileum** | **Specific receptor-mediated uptake** | **YES — primary site of Crohn's involvement** |
| Enterohepatic circulation | Ileum | Reabsorption of B12 from bile | Disrupted in Crohn's |

**High-Yield:** Crohn's disease **classically affects the terminal ileum** (ileitis). This is the site of B12 absorption, making malabsorption the primary mechanism — not intrinsic factor deficiency.

## Pathophysiology of B12 Deficiency in IBD

```mermaid
flowchart TD
  A[Crohn's disease]:::outcome --> B[Chronic inflammation of terminal ileum]:::action
  B --> C[Damage to ileal epithelium]:::action
  C --> D[Loss of IF-B12 receptor expression]:::action
  D --> E[Impaired B12 absorption]:::urgent
  E --> F[Serum B12 depletion]:::outcome
  F --> G[Megaloblastic anemia]:::outcome
  F --> H[Neurological manifestations]:::outcome
  H --> I[Subacute combined degeneration]:::urgent
```

## Clinical Features Supporting B12 Deficiency

1. **Neurological signs**: Loss of vibration sense, positive Lhermitte sign → posterior/lateral column disease (subacute combined degeneration)
2. **Megaloblastic anemia**: MCV 105 fL, bone marrow shows megaloblastic erythropoiesis with giant metamyelocytes
3. **Serum B12 frankly low**: 95 pg/mL (normal >200)
4. **Serum folate normal**: 6.2 ng/mL (>5.4) — rules out pure folate deficiency
5. **Crohn's disease with terminal ileal involvement**: Classic risk factor for B12 malabsorption

**Clinical Pearl:** In Crohn's disease, B12 deficiency is often **asymptomatic hematologically** but presents with **neurological symptoms first** (cognitive slowing, paresthesias, ataxia). This is because neurological damage accumulates silently and becomes apparent only when stores are severely depleted.

## Why NOT the Other Mechanisms

**Intrinsic factor deficiency** (pernicious anemia):
- Requires autoimmune destruction of gastric parietal cells
- Associated with atrophic gastritis, not Crohn's disease
- Stomach is **rarely involved** in Crohn's (usually terminal ileum)
- Would require positive intrinsic factor antibodies

**Folate deficiency**:
- Serum folate is **normal** (6.2 ng/mL)
- Folate deficiency causes megaloblastic anemia but NOT neurological manifestations
- Crohn's can cause folate malabsorption, but this patient's folate is replete

**Parietal cell autoimmunity**:
- Not associated with Crohn's disease
- Would cause pernicious anemia, not Crohn's-related B12 deficiency
- No mention of autoimmune markers

**Mnemonic: CROHN'S B12 — C.R.O.H.N.'S = Cobalamin Reabsorption Occurs Here; Necroinflammation Stops absorption**
- The terminal ileum is the **primary site of B12 absorption**
- Crohn's inflammation destroys this site → malabsorption

## Management

- **IM B12 injections** (parenteral route bypasses malabsorption)
- Oral B12 supplementation is ineffective in malabsorption
- High-dose oral B12 (1000–2000 μg daily) may work if some ileal function remains
- Treat underlying Crohn's disease (5-ASA, biologics) to reduce inflammation

[cite:Harrison 21e Ch 100; Robbins 10e Ch 14]

![Megaloblastic Anemia diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2619.webp)

Answer

A. Impaired intrinsic factor secretion due to gastric involvement

Answer

B. Autoimmune destruction of parietal cells

Answer

D. Nutritional folate deficiency from chronic diarrhea

Explanation

Clinical Context: B12 Deficiency in Crohn's Disease

Why Terminal Ileum Matters for B12 Absorption

Pathophysiology of B12 Deficiency in IBD

Clinical Features Supporting B12 Deficiency

Why NOT the Other Mechanisms

Management

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Step	Location	Function	Affected in Crohn's?
B12 binding to intrinsic factor	Stomach	Gastric parietal cells secrete IF	No (stomach usually spared)
Transit through small bowel	Duodenum, jejunum	Passive transit	Possibly, if inflamed
Absorption of IF–B12 complex	Terminal ileum	Specific receptor-mediated uptake	YES — primary site of Crohn's involvement
Enterohepatic circulation	Ileum	Reabsorption of B12 from bile	Disrupted in Crohn's