Lactose Intolerance - MBBS University Exam Model Answers

Q1. Define lactose intolerance. What is its biochemical basis? (5 marks)

1. Normal digestion: Lactose (a disaccharide of glucose + galactose) is hydrolyzed by lactase (LPH) at the small intestinal brush border. The monosaccharides are then absorbed via SGLT1 (glucose/galactose) and GLUT2 (basolateral transport). Hydrolysis by lactase is the rate-limiting step.
2. Enzyme deficiency: When lactase activity is inadequate, unhydrolyzed lactose accumulates in the intestinal lumen:
   • Acts as an osmotically active solute - retains water isosmotically → osmotic diarrhea
   • Delivered to the colon, where colonic bacteria ferment it, producing:
     • Short-chain fatty acids (SCFAs)
     • H₂ (hydrogen gas) → exhaled in breath (basis of breath test)
     • CO₂ and methane (CH₄) → bloating and flatulence
   • SCFAs facilitate colonic reabsorption of fluid with Na⁺; when colonic capacity is exceeded, osmotic diarrhea results
3. Genetic basis: Lactase-phlorizin hydrolase is encoded by the LCT gene on chromosome 2q21-22. The C/T-13910 polymorphism in the MCM6 gene (upstream enhancer of LCT) determines persistence vs. non-persistence. The C/C-13910 genotype = hypolactasia (non-persistence). The T allele binds the transcription factor Oct-1 more strongly, maintaining lactase expression.

• Yamada's Textbook of Gastroenterology, 7th ed. | Goldman-Cecil Medicine | Basic Medical Biochemistry, 6th ed.

Q2. Classify lactase deficiency. (5 marks)

1. Primary (Adult-Onset) Lactase Deficiency / Adult Hypolactasia

• Most common form worldwide (affects ~75% of the global adult population)
• Lactase activity is high at birth, then progressively declines after weaning; by age 5-10 years, activity falls to ~10% of neonatal levels
• Autosomal recessive pattern - associated with C/C-13910 genotype
• Lactase non-persistence phenotype
• Commonest in Asians (100%), African Americans (81%), Native Americans (95%), Mediterranean populations (53-71%)
• Least common in Northern/Western Europeans (Danes 3%, Dutch 0%)

2. Congenital Lactase Deficiency

• Rare autosomal-recessive disorder
• Lactase activity is severely reduced or totally absent from birth
• Presents immediately when newborn is fed breast milk or lactose-containing formula
• Features: severe watery diarrhea, dehydration, weight loss, failure to thrive
• Most commonly described in Finland (first 5 mutations in LCT gene)
• Treatment: lactose-free diet → allows normal growth and development

3. Secondary (Acquired) Lactase Deficiency

• Due to injury to the intestinal brush border (epithelium), causing transient loss of lactase
• Reversible - recovers when the brush border regenerates
• Causes:
  • Viral gastroenteritis (most common secondary cause; lactose intolerance occurs in 50-70% post-gastroenteritis)
  • Celiac disease (gluten-free diet restores lactase)
  • Giardiasis (treat with metronidazole/tinidazole)
  • Tropical sprue
  • Small intestinal bacterial overgrowth (SIBO)
  • Crohn disease
• More severe in individuals with baseline low lactase activity
• Basic Medical Biochemistry, 6th ed. | Yamada's Textbook of Gastroenterology, 7th ed. | Goldman-Cecil Medicine

Q3. Describe the clinical features of lactose intolerance. (5 marks)

• Symptoms are dose-dependent (proportional to the amount of lactose consumed)
• No weight loss (distinguishes from malabsorption syndromes like celiac disease)
• Symptoms are relieved by eliminating dairy products
• High-fat dairy (full-fat milk, cheese) causes fewer symptoms than low-fat/skim milk because fat slows gastric emptying, allowing more time for residual lactase to act
• Foods with highest lactose: milk, ice cream, yogurt
• Yogurt is often tolerated because live yogurt bacteria contain endogenous β-galactosidase
• Costanzo Physiology, 7th ed. | Ganong's Review of Medical Physiology, 26th ed. | Goldman-Cecil Medicine

Q4. How is lactose intolerance diagnosed? Describe the Hydrogen Breath Test. (8 marks)

Diagnostic Methods:

• Consistent history of symptoms after dairy intake
• Resolution of symptoms on a 2-week lactose-free diet trial
• This alone is sufficient in most clinical settings

• Fast overnight (meal before 07:00 hrs, restrict wheat and fiber)
• Brush teeth/use mouthwash to minimize oral bacteria
• Measure baseline (fasting) breath H₂
• Administer 50 g lactose in 180 mL water (adults); 2 g/kg up to 50 g (children)
• Measure breath H₂ at 15, 30, 60, 90, and 120 minutes
• Positive (diagnostic): Rise of >20 ppm above fasting baseline at 2 hours

• Acidic colonic pH (inhibits H₂-producing bacteria)
• Methanogenic flora (convert H₂ to CH₄ instead)
• H₂-deficient colonic flora
• Recent antibiotic use

• Small intestinal bacterial overgrowth (SIBO) - produces early H₂ rise within first 30 minutes

• Give 50 g oral lactose → measure blood glucose over 2 hours
• Normal: Rise in blood glucose >1.1 mmol/L (>20 mg/dL) for capillary; >1.4 mmol/L (>25 mg/dL) for venous plasma - excludes lactase deficiency
• Abnormal (positive for deficiency): Flat curve (glucose does not rise) because lactose is not digested/absorbed

• Direct measurement of disaccharidase (lactase) activity from second portion of duodenum
• Gold standard for definitive diagnosis but invasive; rarely done in routine practice

• PCR/pyrosequencing for C/T-13910 polymorphism in MCM6 gene
• Commercially available; good for identifying primary hypolactasia
• Limitation: Cannot predict the amount of lactose a patient can tolerate; limited clinical utility
• Tietz Textbook of Laboratory Medicine, 7th ed. | Yamada's Textbook of Gastroenterology | Symptom to Diagnosis, 4th ed.

Q5. Discuss the management of lactose intolerance. (5 marks)

1. Dietary Modification (First-line)

• Reduce or eliminate lactose intake - avoid milk, ice cream, cream
• Distribute lactose intake throughout the day (small amounts better tolerated)
• Most adults can tolerate up to 12 g lactose/day without significant symptoms
• Fermented/matured dairy products (aged cheese, yogurt with live cultures) are better tolerated:
  • Yogurt: live bacteria have endogenous β-galactosidase → pre-digest lactose
  • Aged hard cheeses have very low residual lactose
• Consume dairy with other foods (slows gastric emptying, reduces symptoms)
• Full-fat milk preferred over skim milk (fat delays gastric emptying)

2. Lactase Enzyme Supplementation

• Oral lactase tablets (e.g., Lactaid®, Dairy-ease®) taken with lactose-containing meals
• Useful for patients with chronic symptoms who do not wish to avoid dairy entirely
• Provides exogenous β-galactosidase to hydrolyze dietary lactose
• Limitation: Gastric acid can inactivate some preparations; not a panacea for all patients

3. Lactose-Reduced / Lactose-Free Products

• Pre-treated milk with added microbial lactase

4. Probiotics

• Organisms such as Lactobacillus, Bifidobacterium, Saccharomyces containing β-galactosidase
• May help through colonic flora adaptation (selection of lactose-fermenting species)

5. Treat Underlying Cause (for Secondary Lactase Deficiency)

• Celiac disease → gluten-free diet
• Giardiasis → metronidazole or tinidazole
• Tropical sprue → oxytetracycline
• Post-gastroenteritis: Lactase activity will recover spontaneously as brush border regenerates; advise dairy-free diet for 2 weeks after gastroenteritis

6. Calcium/Nutritional Supplementation

• Patients avoiding dairy need alternative calcium sources (fortified foods, supplements) to prevent osteoporosis
• Yamada's Textbook of Gastroenterology, 7th ed. | Symptom to Diagnosis, 4th ed. | Ganong's Review of Medical Physiology

Q6. Differentiate Lactase Persistence vs. Non-persistence. (Short note, 3 marks)

Q7. A 22-year-old student complains of bloating, flatulence, and diarrhea every time she drinks milk. She has no symptoms when she avoids dairy for 2 weeks. How would you manage this patient? (Clinical scenario)

• Characteristic symptoms after dairy intake
• Complete resolution on 2-week lactose-free diet trial

1. Dietary: Reduce or eliminate lactose-containing foods (milk, ice cream). Substitute with lactose-free milk or fermented dairy (yogurt, aged cheese)
2. Enzyme supplements: Lactase tablets (Lactaid®) taken with dairy-containing meals
3. Other brush border enzymes are normal - only lactose needs to be restricted; no other dietary changes required
4. Calcium supplementation if dairy is fully eliminated
5. Reassurance: Not life-threatening; no further investigation needed if symptoms fully resolve

• Costanzo Physiology, 7th ed. (BOX 8.2)

Quick Revision Points (for MCQ/Viva)

• Lactase is a brush border disaccharidase of the small intestine
• Lactase hydrolyzes lactose → glucose + galactose
• Transport: SGLT1 (brush border, Na⁺-dependent) → GLUT2 (basolateral)
• Commonest cause worldwide: adult-type hypolactasia (primary)
• Gene: LCT gene, chromosome 2q21-22; regulated by MCM6 enhancer (C/T-13910)
• Symptoms: osmotic diarrhea + gas (H₂, CO₂, CH₄)
• Best non-invasive test: Lactose Hydrogen Breath Test (50 g lactose; >20 ppm rise = positive)
• Gold standard (invasive): Jejunal biopsy with disaccharidase assay
• Treatment: dietary restriction + lactase supplements
• Yogurt is tolerated due to bacterial β-galactosidase
• Post-gastroenteritis lactose intolerance: reversible (brush border regenerates)
• Secondary causes: celiac disease, giardiasis, SIBO, viral gastroenteritis