# Clinical Cases: Digestion and Absorption

## Case 1: Lactose Intolerance

### Patient Presentation
**Demographics:** 28-year-old Asian female

**Chief Complaint:** Abdominal bloating, cramping, and diarrhea after eating dairy products

**History of Present Illness:** The patient reports that over the past 2 years, she has noticed progressive intolerance to milk and dairy products. Within 30-60 minutes of consuming a glass of milk, she develops abdominal cramping, bloating, excessive gas, and watery diarrhea. Symptoms resolve within a few hours. She can tolerate small amounts of cheese and yogurt without symptoms. She has no weight loss, bloody stools, or nocturnal symptoms.

**Past Medical History:** None

**Family History:** Parents (originally from China) avoid milk due to similar symptoms

### Physical Examination
- **Vital Signs:** Normal
- **General:** Well-appearing female in no distress
- **Abdomen:** Soft, non-tender, non-distended, normal bowel sounds

### Workup and Results
- **Lactose Hydrogen Breath Test:** Baseline hydrogen 8 ppm; 2-hour post-lactose hydrogen 78 ppm (positive, >20 ppm rise indicates lactose malabsorption)
- **CBC, CMP:** Within normal limits
- **tTG-IgA:** Negative (rules out celiac disease)

![Lactose Breath Test](case_01_image.jpg)
*Hydrogen breath test demonstrating a significant rise in breath hydrogen concentration after lactose ingestion, consistent with lactose malabsorption due to lactase deficiency.*

**Image Source:** Clinical diagram adapted from educational materials

### Diagnosis
**Primary Lactose Intolerance (Adult-type Hypolactasia)**

### Clinical Correlation to Carbohydrate Digestion/Absorption
Lactose, the disaccharide in milk, must be cleaved by the brush border enzyme lactase into glucose and galactose for absorption. Lactase persistence (the ability to digest lactose in adulthood) evolved in populations with dairy traditions. Most of the world's population experiences lactase decline after weaning (the ancestral state). When undigested lactose reaches the colon, bacterial fermentation produces hydrogen (detected in breath), carbon dioxide, and short-chain fatty acids. The gas causes bloating and flatulence; the osmotic effect of unabsorbed lactose draws water into the lumen, causing diarrhea. Symptoms correlate with the dose of lactose consumed, which explains tolerance for aged cheeses (low lactose) and yogurt (bacterial lactase assists digestion).

### Treatment
- Lactose avoidance or reduction to tolerable amounts
- Lactase enzyme supplements taken with dairy products
- Lactose-free dairy alternatives
- Calcium and vitamin D supplementation if dairy elimination affects intake
- Reassurance that this is not a disease but a normal genetic variant

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## Case 2: Pernicious Anemia (Vitamin B12 Malabsorption)

### Patient Presentation
**Demographics:** 65-year-old female

**Chief Complaint:** Progressive fatigue, weakness, and numbness in feet for 6 months

**History of Present Illness:** The patient reports gradually worsening fatigue, shortness of breath on exertion, and generalized weakness. She has noticed tingling and numbness in both feet that has progressed to her ankles. She feels unsteady when walking, especially in the dark. Her tongue occasionally feels sore. She has had mild memory difficulties recently.

**Past Medical History:** Hashimoto's thyroiditis on levothyroxine, vitiligo

**Family History:** Mother had thyroid disease and "blood problems"

### Physical Examination
- **Vital Signs:** BP 118/72 mmHg, HR 98 bpm
- **General:** Pale female appearing older than stated age
- **HEENT:** Smooth, beefy-red tongue (glossitis); pale conjunctivae
- **Neurologic:** Decreased vibration and position sense in lower extremities; positive Romberg sign; hyperactive reflexes in knees with absent ankle reflexes
- **Skin:** Scattered vitiligo patches

### Workup and Results
- **CBC:** Hemoglobin 8.2 g/dL, MCV 118 fL (macrocytic), WBC 3.8 (low), platelets 130
- **Peripheral Smear:** Macro-ovalocytes, hypersegmented neutrophils (>5 lobes)
- **Vitamin B12:** 95 pg/mL (severely low, normal >200)
- **Methylmalonic Acid:** Elevated (confirms B12 deficiency)
- **Anti-Intrinsic Factor Antibodies:** Positive
- **Anti-Parietal Cell Antibodies:** Positive
- **Gastrin Level:** Elevated (hypergastrinemia from achlorhydria)

![Pernicious Anemia Blood Smear](case_02_image.jpg)
*Peripheral blood smear showing macro-ovalocytes and a hypersegmented neutrophil (>5 nuclear lobes), characteristic findings of megaloblastic anemia due to vitamin B12 deficiency.*

**Image Source:** Wikimedia Commons, CC BY-SA 3.0

### Diagnosis
**Pernicious Anemia with Subacute Combined Degeneration of the Spinal Cord**

### Clinical Correlation to Vitamin B12 Absorption Physiology
Vitamin B12 absorption requires a complex pathway. Dietary B12 is released from food proteins by gastric acid and pepsin, then binds R-proteins in the stomach. In the duodenum, pancreatic proteases digest R-proteins, and B12 transfers to intrinsic factor (IF), secreted by gastric parietal cells. The IF-B12 complex travels to the terminal ileum, where specific receptors (cubilin) internalize it. In pernicious anemia, autoimmune destruction of parietal cells eliminates both acid secretion (needed to release B12 from food) and intrinsic factor (essential for ileal absorption). The resulting deficiency affects rapidly dividing cells (causing megaloblastic anemia) and causes demyelination in the spinal cord (subacute combined degeneration affecting posterior and lateral columns).

### Treatment
- Intramuscular vitamin B12 injections (1000 mcg daily for 1 week, then weekly for 1 month, then monthly for life)
- Alternative: high-dose oral B12 (1-2 mg daily) - some absorption occurs passively without IF
- Monitor for hypokalemia during treatment (rapid cell production consumes potassium)
- Neurologic deficits may be partially reversible with early treatment
- Surveillance for gastric carcinoid tumors and gastric cancer (increased risk in autoimmune gastritis)

---

## Case 3: Hemochromatosis (Iron Overload)

### Patient Presentation
**Demographics:** 52-year-old male of Northern European descent

**Chief Complaint:** Fatigue, joint pain, and elevated liver enzymes

**History of Present Illness:** The patient was found to have elevated liver enzymes (AST 68, ALT 82) on routine bloodwork. He reports progressive fatigue for 2 years and joint pain, particularly in the second and third metacarpophalangeal joints bilaterally. He has also noticed decreased libido. His wife comments that his skin has become "bronzed" despite limited sun exposure.

**Past Medical History:** Recently diagnosed with type 2 diabetes (6 months ago), atypical for his body habitus

**Family History:** Father died of liver disease at age 58; brother has "iron problems"

### Physical Examination
- **Vital Signs:** Normal
- **General:** Bronze/slate-gray skin discoloration
- **Abdomen:** Hepatomegaly (liver palpable 4 cm below costal margin), non-tender
- **Musculoskeletal:** Tenderness and bony swelling of 2nd and 3rd MCP joints bilaterally
- **Genitourinary:** Testicular atrophy

### Workup and Results
- **Iron Studies:** Serum iron 285 mcg/dL, TIBC 290 mcg/dL, transferrin saturation 98% (markedly elevated), ferritin 2,850 ng/mL
- **Liver Function:** AST 68, ALT 82, ALP normal, albumin 3.4
- **HFE Gene Testing:** Homozygous for C282Y mutation
- **Liver MRI:** Hepatic iron overload (signal loss on T2-weighted images)

![Hemochromatosis Liver](case_03_image.jpg)
*Prussian blue staining of liver biopsy showing extensive blue-staining iron deposits within hepatocytes, characteristic of hereditary hemochromatosis.*

**Image Source:** Wikimedia Commons, Public Domain

### Diagnosis
**Hereditary Hemochromatosis (HFE-related)**

### Clinical Correlation to Iron Absorption Physiology
Iron absorption is tightly regulated because humans have no mechanism for iron excretion. Dietary non-heme iron is reduced by DcytB at the brush border and transported into enterocytes by DMT1. Iron can be stored in ferritin within the enterocyte (lost when the cell sloughs) or exported across the basolateral membrane via ferroportin. Hepcidin, produced by the liver, is the master regulator - it binds ferroportin and causes its degradation, blocking iron export. In HFE-related hemochromatosis, the C282Y mutation impairs hepcidin signaling, resulting in inappropriately low hepcidin levels. Without adequate hepcidin, ferroportin activity is unchecked, and iron absorption continues regardless of body stores. Iron accumulates in the liver (cirrhosis), pancreas (diabetes), heart (cardiomyopathy), pituitary (hypogonadism), joints (arthropathy), and skin (bronze discoloration).

### Treatment
- Therapeutic phlebotomy: weekly removal of 500 mL blood (containing ~250 mg iron) until ferritin <50 ng/mL
- Maintenance phlebotomy every 2-4 months to keep ferritin 50-100 ng/mL
- Avoid vitamin C supplements (enhances iron absorption)
- Avoid excessive alcohol (worsens liver disease)
- Screen first-degree relatives with HFE genetic testing
- Diabetes and hypogonadism may not resolve but can be managed
- Liver transplantation for end-stage liver disease