Disorders of Absorption¶
Chapter 336 | Part 10: Disorders of the Gastrointestinal System · Part 10 – Gastrointestinal Disorders · Chapter 336
Key Clinical Points¶
- Diarrhea is defined as stool volume >200 mL or weight >200 g in 24 hours; steatorrhea is fat excretion >7% of dietary fat.
- Lipid absorption involves three phases: Digestive (lipolysis and micelle formation), Absorptive (mucosal uptake and re-esterification), and Postabsorptive (chylomicron formation and lymphatic delivery).
- Celiac disease is characterized by villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes; diagnosis requires TTG-IgA serology and biopsy.
- Small-intestinal bacterial overgrowth (SIBO) is diagnosed via duodenal aspirate (gold standard) or breath hydrogen testing; treated with rifaximin or metronidazole.
- Bile acid diarrhea results from limited ileal disease/resection and responds to cholestyramine; fatty acid diarrhea results from extensive ileal disease and responds to a low-fat diet.
- Ménétrier's disease is a protein-losing gastropathy with large gastric folds, treated with cetuximab (EGFR inhibitor) as first-line therapy.
- Lactose intolerance is the most common brush border disaccharidase deficiency; diagnosis via lactose-exclusion diet or breath hydrogen test (peak >20 ppm above baseline).
- Refractory celiac disease is defined as persistent villous atrophy and symptoms after 1 year of strict gluten-free diet; Type 2 is associated with T-cell lymphoma.
- Abetalipoproteinemia results in absent β-lipoproteins, failure to form chylomicrons, acanthocytes, and neurologic symptoms.
- Malabsorption can lead to specific clinical manifestations: tetany/paresthesia (Ca/Mg deficiency), night blindness/xerophthalmia (Vit A deficiency), and anemia (Iron, Folate, or B12 deficiency).
DEFINITION & OVERVIEW¶
• Diarrhea: Most common symptom of absorption disorders. Defined as an increase in stool number/frequency or a change in consistency. Objective measure: Volume >200 mL or weight >200 g in 24 hours. • Steatorrhea: Defined as fat excretion >7% of dietary fat. Characterized by large, bulky, and malodorous stools. • Osmotic vs. Secretory Diarrhea: Osmotic: Caused by unabsorbed nutrients (e.g., lactose) drawing fluid into the lumen; typically precipitated by eating and resolves with fasting. Secretory: Driven by enterotoxins (e.g., bacterial enterotoxigenic E. coli); continues even during fasting.
EPIDEMIOLOGY¶
• Celiac Disease: Global prevalence: 1.4%. US Seroprevalence: 0.2% (non-Hispanic black), 0.3% (Hispanic), and 1.0% (white). Risk in first-degree relatives: 10–15%. Genetics: HLA-DQ2 and DQ8 are necessary but not sufficient for development. • Lactose Intolerance: Very common worldwide; considered the genetic wild-type. Most common brush border disaccharidase deficiency.
ETIOLOGY & PATHOPHYYSOLOGY¶
• Luminal Phase of Digestion: Starts in mouth (mastication, lipase secretion) → stomach (acid, lipase, pepsin) → small-bowel (pancreatic enzymes: amylase, lipases, carboxypeptidase, trypsin). Bile Acids: Required for lipid/fat-soluble vitamin absorption; enterohepatic circulation involves synthesis in liver, secretion into intestine, and Na-dependent reabsorption in the ileum. Luminal Deficiencies: Caused by hepatobiliary disease, intestinal ileal resection, Crohn's disease, or small-bowel bacterial overgrowth (SIBO). • Mucosal Phase of Digestion and Absorption: Mediated by enterocytic brush border enzymes (peptidases, hydrolases). Enterokinase: Essential for converting pancreatic trypsinogen to trypsin. Lipid Processing: Long-chain fatty acids → re-esterified to triglycerides → packaged into chylomicrons with apolipoproteins → enter lymphatics. • Postabsorptive Phase: Involves chylomicron formation and exit via lymphatics. Motility Factors: Diabetes may damage the enteric nervous system; scleroderma affects intestinal smooth muscle.
Pathophysiological Defects in Steatorrhea (Table 336-2)¶
• Lipolysis failure: Decreased lipase secretion (e.g., Chronic pancreatitis). • Micelle formation failure: Decreased intraduodenal bile acids. • Chylomicron formation failure: Absent β-lipoproteins (e.g., Abetalipoproteinemia). • Delivery failure: Abnormal lymphatics (e.g., Intestinal lymphangiectasia).
Histological Findings of Mucosal Disorders (Table 336-6/7)¶
• Agammaglobulinemia: No plasma cells; flat mucosa. • Abetalipoproteinemia: Normal villi; epithelial cells vacuolated with fat postprandially. • Celiac disease: Short or absent villi; mononuclear infiltrate; crypt hypertrophy. • Bacterial overgrowth: Patchy damage to villi; lymphocyte infiltration. • Folate/Vitamin B12 deficiency: Short villi; decreased mitosis in crypts; megalocytosis. • Zollinger-Ellison syndrome: Mucosal ulceration and erosion from acid.
CLINICAL FEATURES¶
• Steatorrhea & Osmotic Diarrhea: Steatorrhea: Large, bulky, malodorous stools. Osmotic Diarrhea: Triggered by eating; resolves with fasting (e.g., lactose intolerance). • Celiac Disease: Range: Asymptomatic to severe malabsorption. Common symptoms: Diarrhea, weight loss, growth failure in children. Additional signs: Bloating, irregular bowel habits, migraine headaches, ataxia. Atypical presentations: Isolated iron-deficiency anemia, osteoporosis, abnormal liver enzymes. • Lactose Intolerance: Symptoms: Diarrhea, abdominal pain, gassiness, bloating. Mechanism: Unabsorbed lactose acts as osmotic agent → colonic bacteria ferment lactose into H_2, CO_2, and methane. • Clinical Manifestations of Malabsorption (Table 336-5): Weight loss/malnutrition: Anorexia, malabsorption. Flatus: Bacterial fermentation of unabsorbed carbohydrates. Abdominal pain: Bowel distension or inflammation, pancreatitis. Tetany, paresthesia: Calcium and magnesium malabsorption. Azotemia, hypotension: Fluid and electrolyte depletion. Anemia: Impaired absorption of iron, folate, vitamin B12. Night blindness/xerophthalmia: Vitamin A malabsorption. Dermatitis: Deficiency of vitamin A, zinc, and essential fatty acids.
DIFFERENTIAL DIAGNOSIS¶
• Bile Acid vs. Fatty Acid Diarrhea (Table 336-4): Bile Acid Diarrhea: → Limited extent of ileal disease. → Reduced fecal bile acid excretion. → Normal bile acid pool size. → No or mild steatorrhea. → Responds to cholestyramine. Faty Acid Diarrhea: → Extensive ileal disease. → Increased fecal bile acid excretion. → Reduced bile acid pool size. → Steatorrhea >20 g. → Responds to low-fat diet. • SIBO vs. Celiac Disease: SIBO: → Deconjugation of bile acids → luminal bile acid deficiency → malabsorptive diarrhea with steatorrhea. → Potential for B12 deficiency (macrocytic anemia) and elevated serum folate. → Associated with some IBS patients. Celiac: → Primary focus on proximal small intestine; can be localized to duodenum or involve entire jejunum.
DIAGNOSTIC APPROACH¶
- Celiac Disease Diagnosis: Step 1: Serum antibody testing → primary choice is tissue transglutaminase IgA (TTG-IgA). Step 2: Measure serum IgA levels → if IgA deficient, use IgG-based tests (TTG-IgG or DGP-IgG). Step 3: Endoscopy with small-intestinal biopsy → confirm via histology (villous blunting, crypt hypertrophy, increased intraepithelial lymphocytes; Marsh classification).
- Lactose Intolerance Diagnosis: Step 1: Lactose-exclusion diet → assess for resolution of symptoms. Step 2: If ambiguous, perform Lactose-tolerance test or Breath hydrogen test. → Breath hydrogen: peak >20 ppm above baseline.
- SIBO Diagnosis: Step 1: Duodenal aspirate for bacterial titers (gold standard). Step 2: Breath hydrogen testing (lactulose or glucose) → interpret carefully for false positives.
MANAGEMENT & TREATMENT¶
- Celiac Disease Treatment: Step 1: Strict gluten-free diet (primary treatment). Step 2: Calcium and Vitamin D supplementation. Step 3: Dietary counseling for hidden gluten/lactose. Step 4: Lactase supplementation (alternative for lactose management).
- SIBO Treatment: Step 1: Antibiotics (rifaximin or metronidazole). Step 2: Surgical correction of anatomical issues (blind loops, strictures, large diverticula).
- Ménétrier's Disease Treatment: Step 1: Cetuximab (EGFR inhibitor) as first-line therapy. Step 2: Partial or total gastrectomy for severe disease with persistent protein loss despite cetuximab.
- Other Management: → Scleroderma/motility disorders: nonabsorbable antibiotics (rifaximin, metronidazole, doxycycline, amoxicillin-clavulanic acid, or cephalosporins) for several weeks.
COMPLICATIONS & PROGNOSIS¶
• Refractory Celiac Disease: Defined as persistent villous atrophy and symptoms after 1 year of strict gluten-free diet. Type 2: Associated with T-cell lymphoma. • Small-Bowel Adenocarcinoma: Risk factor in patients with chronic inflammation (e.g., Crohn's disease).
KEY PEARLS & CLINICAL TRAPS¶
• Steatorrhea Threshold: >7% of dietary fat. • Bile Acid vs Fatty Acid Diarrhea: Key differentiator is response to cholestyramine (positive in bile acid, negative in fatty acid) and steatorrhea amount (>20 g in fatty acid). • Celiac Screening: TTG-IgA is the first step; always check IgA levels to rule out deficiency. • Ménétrier's Treatment: Cetuximab is the specific first-line targeted therapy. • Symptom Correlation: Tetany → Ca/Mg loss; Night blindness → Vit A loss; Macrocytic anemia → B12 loss.
Reference Tables¶
TABLE 336-1 Classification of Malabsorption Syndromes Inadequate digestion¶
Harrison's 22e, p.2541
| Inadequate digestion | |
|---|---|
| Postgastrectomya | |
| Deficiency or inactivation of pancreatic lipase | |
| Exocrine pancreatic insufficiency | |
| Chronic pancreatitis | |
| Pancreatic carcinoma | |
| Cystic fibrosis | |
| Pancreatic insufficiency—congenital or acquired | |
| Gastrinoma—acid inactivation of lipase | |
| Drugs—orlistat | |
| Reduced intraduodenal bile-acid concentration/impaired micelle formation | |
| Liver disease | |
| Parenchymal liver disease | |
| Cholestatic liver disease | |
| Bacterial overgrowth in small intestine: | |
| Anatomic stasis | Functional stasis |
| Afferent loop | Diabetesa |
| Stasis/blind | Sclerodermaa |
| Loop/strictures/fistulae | Intestinal pseudo-obstruction |
| Interrupted enterohepatic circulation of bile salts | |
| Ileal resection | |
| Crohn’s disease | |
| Drugs (binding or precipitating bile salts)—neomycin, cholestyramine, calcium carbonate |
|
| Impaired mucosal absorption/mucosal loss or defect | |
| Intestinal resection or bypassa | |
| Inflammation, infiltration, or infection: | |
| Crohn’s diseasea | Celiac disease |
| Amyloidosis | Collagenous sprue |
| Sclerodermaa | Whipple’s diseasea |
| Lymphomaa | Radiation enteritisa |
| Eosinophilic enteritis | Folate and vitamin B deficiency 12 |
| Mastocytosis | Infections—giardiasis |
| Tropical sprue | Graft versus host disease |
| Genetic disorders | |
| Disaccharidase deficiency | |
| Agammaglobulinemia | |
| Abetalipoproteinemia | |
| Hartnup’s disease | |
| Cystinuria | |
| Impaired nutrient delivery to and/or from intestine: | |
| Lymphatic obstruction | Circulatory disorders |
| Lymphomaa | Congestive heart failure |
| Lymphangiectasia | Constrictive pericarditis |
| Mesenteric artery atherosclerosis | |
| Vasculitis | |
| Endocrine and metabolic disorders | |
| Diabetesa | |
| Hypoparathyroidism | |
| Adrenal insufficiency | |
| Hyperthyroidism | |
| Carcinoid syndrome |
TABLE 336-2 Defects in Lipid Digestion and Absorption in Steatorrhea¶
Harrison's 22e, p.2541
| PHASE, PROCESS | PATHOPHYSIOLOGIC DEFECT |
DISEASE EXAMPLE |
|---|---|---|
| Digestive | ||
| Lipolysis formation | Decreased lipase secretion |
Chronic pancreatitis |
| Micelle formation | Decreased intraduodenal bile acids |
|
| Absorptive | ||
| Postabsorptive | ||
| Chylomicron formation | Absent β-lipoproteins | Abetalipoproteinemia |
| Delivery from intestine | Abnormal lymphatics | Intestinal lymphangiectasia |
TABLE 336-3 Defects in Enterohepatic Circulation of Bile Acids PROCESS Synthesis Biliary secretion Maintenance of…¶
Harrison's 22e, p.2543
| PROCESS | PATHOPHYSIOLOGIC DEFECT |
DISEASE EXAMPLE |
|---|---|---|
| Synthesis | Decreased hepatic function |
Cirrhosis |
| Altered canalicular function |
||
| Maintenance of conjugated bile acids |
Bacterial overgrowth | Jejunal diverticulosis |
| Abnormal ileal function |
TABLE 336-4 Comparison of Bile Acid and Fatty Acid Diarrhea Extent of ileal disease Ileal bile acid absorption Fecal…¶
Harrison's 22e, p.2543
| BILE-ACID DIARRHEA | FATTY ACID DIARRHEA | |
|---|---|---|
| Extent of ileal disease | Limited | Extensive |
| Reduced | ||
| Fecal bile acid excretion | Increased | Increased |
| Yes | ||
| Bile acid pool size | Normal | Reduced |
| Normal | ||
| Steatorrhea | None or mild | >20 g |
| Yes | ||
| Response to low fat diet | No | Yes |
TABLE 336-5 Pathophysiology of Clinical Manifestations of Malabsorption Disorders¶
Harrison's 22e, p.2549
| SYMPTOM OR SIGN | MECHANISM |
|---|---|
| Weight loss/malnutrition | Anorexia, malabsorption of nutrients |
| Flatus | Bacterial fermentation of unabsorbed carbohydrate |
| Abdominal pain | Bowel distention or inflammation, pancreatitis |
| Tetany, paresthesia | Calcium and magnesium malabsorption |
| Azotemia, hypotension | Fluid and electrolyte depletion |
| Anemia | Impaired absorption of iron, folate, vitamin B 12 |
| Night blindness/ xerophthalmia |
Vitamin A malabsorption |
| Dermatitis | Deficiency of vitamin A, zinc, and essential fatty acid |
TABLE 336-6 Diseases That Can Be Diagnosed by Small-Intestinal Mucosal Biopsies LESIONS Diffuse, Specific…¶
Harrison's 22e, p.2550
| LESIONS | PATHOLOGIC FINDINGS |
|---|---|
| Diffuse, Specific | |
| Agammaglobulinemia | No plasma cells; either normal or absent villi (“flat mucosa”) |
| Abetalipoproteinemia | Normal villi; epithelial cells vacuolated with fat postprandially |
| Patchy, Specific | |
| Diffuse, Nonspecific | |
| Celiac disease | Short or absent villi; mononuclear infiltrate; epithelial cell damage; hypertrophy of crypts |
| Tropical sprue | Similar to celiac disease |
| Bacterial overgrowth | Patchy damage to villi; lymphocyte infiltration |
| Folate deficiency | Short villi; decreased mitosis in crypts; megalocytosis |
| Vitamin B deficiency 12 |
Similar to folate deficiency |
| Radiation enteritis | Similar to folate deficiency |
| Zollinger-Ellison syndrome | Mucosal ulceration and erosion from acid |
| Protein-calorie malnutrition | Villous atrophy; secondary bacterial overgrowth |
| Drug-induced enteritis | Variable histology |