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Chapter 336: Disorders of Absorption

Chapter 336 | Part 10: Disorders of the Gastrointestinal System

KEY CLINICAL POINTS

  • Malabsorption syndromes result from defects in nutrient digestion, absorption, or postabsorptive transport.
  • Diarrhea is the most common symptom of malabsorption, with steatorrhea (fatty stools) being a hallmark of lipid malabsorption.
  • Celiac disease is an autoimmune disorder triggered by gluten, characterized by villous atrophy and malabsorption.
  • Short-bowel syndrome occurs after extensive small intestine resection, leading to severe nutrient and fluid losses.
  • Bile acid malabsorption is a key mechanism in both celiac disease and tropical sprue, often treated with bile acid sequestrants.

1. DEFINITION & OVERVIEW

Malabsorption syndromes involve impaired digestion, absorption, or postabsorptive transport of nutrients. These disorders can affect any phase of nutrient processing, including luminal digestion, mucosal absorption, and postmucosal transport. Diarrhea, weight loss, and nutrient deficiencies are common manifestations. The pathophysiology varies from enzymatic deficiencies to structural abnormalities and lymphatic dysfunction.

Table 336-1: Classification of Malabsorption Syndromes

Category Causes
Inadequate Digestion Postgastrectomy, pancreatic insufficiency, chronic pancreatitis, cystic fibrosis
Inadequate Absorption Bacterial overgrowth, ileal resection, Crohn’s disease, celiac disease
Impaired Nutrient Delivery Lymphatic obstruction, intestinal pseudo-obstruction, radiation enteritis
Endocrine/Metabolic Disorders Diabetes mellitus, hypoparathyroidism, adrenal insufficiency

1.1 Nutrient Digestion and Absorption

Lipid digestion requires pancreatic lipase and bile acids to form micelles for absorption. Carbohydrates are broken down by disaccharidases (e.g., lactase, sucrase-isomaltase) into monosaccharides. Proteins are digested by pancreatic proteases into amino acids. Absorption occurs via specific transporters (e.g., SGLT1 for glucose, GLUT5 for fructose).

1.2 Postmucosal Transport

Absorbed nutrients enter the portal circulation or lymphatics. Lipids are packaged into chylomicrons for lymphatic transport. Defects in this phase, such as lymphatic obstruction, lead to protein-losing enteropathy and edema.

2. EPIDEMIOLOGY

Celiac disease has a global prevalence of 1.4%, with higher rates in first-degree relatives (10–15%). Tropical sprue is rare but more common in tropical regions, though its incidence has decreased with improved sanitation. Ménétrier’s disease is uncommon, with a male predominance. Short-bowel syndrome occurs after resection of >100 cm of small intestine, often due to Crohn’s disease, trauma, or ischemia.

3. ETIOLOGY & PATHOPHYSIOLOGY

Malabsorption arises from defects in digestion (e.g., pancreatic insufficiency), absorption (e.g., celiac disease), or postabsorptive transport (e.g., lymphatic obstruction). Bile acid malabsorption disrupts lipid emulsification. In celiac disease, gluten triggers immune-mediated villous atrophy. Tropical sprue involves bacterial overgrowth and folate deficiency. Short-bowel syndrome results from loss of absorptive surface area.

Table 336-2: Defects in Lipid Digestion and Absorption

Phase Defect Example Disease
Digestive Decreased lipase secretion Chronic pancreatitis
Micellar Reduced bile acid Biliary atresia
Absorptive Mucosal dysfunction Celiac disease
Postabsorptive Chylomicron formation Abetalipoproteinemia

3.1 Bile Acid Pathophysiology

Bile acids emulsify fats and are reabsorbed in the ileum via Na-dependent transport. Deficiency leads to steatorrhea and malabsorption. In celiac disease, bile acid spillage into the colon causes secretory diarrhea.

3.2 Lymphatic Dysfunction

Intestinal lymphangiectasia results from dilated lymphatics, leading to protein loss and hypoproteinemia. Lymphatic obstruction in short-bowel syndrome causes edema and protein-losing enteropathy.

4. CLINICAL FEATURES

Symptoms include diarrhea (osmotic or secretory), weight loss, steatorrhea, and nutrient deficiencies (e.g., anemia, osteoporosis). Celiac disease may present with isolated iron deficiency or systemic symptoms. Tropical sprue causes folate deficiency and macrocytic anemia. Short-bowel syndrome leads to severe dehydration and electrolyte imbalances.

Table 336-5: Pathophysiology of Clinical Manifestations

Symptom Mechanism
Weight loss/malnutrition Anorexia, malabsorption of nutrients
Diarrhea Impaired absorption of water/electrolytes
Flatus Bacterial fermentation of unabsorbed carbohydrates
Anemia Iron/folate/vitamin B12 deficiency
Osteoporosis Vitamin D/calcium malabsorption

4.1 Nutrient Deficiencies

Fat-soluble vitamins (A, D, E, K) deficiency is common in steatorrhea. Vitamin B12 deficiency occurs in ileal disease. Iron deficiency may present with glossitis or anemia.

4.2 Gastrointestinal Symptoms

Diarrhea is often watery or fatty. Bloating, flatulence, and abdominal pain are common. In celiac disease, steatorrhea and weight loss are prominent.

5. DIFFERENTIAL DIAGNOSIS

Differential diagnoses include infectious causes (e.g., Giardia, C. difficile), inflammatory bowel disease, pancreatic insufficiency, and drug-induced enteropathy. In celiac disease, differentiate from nonceliac gluten sensitivity and lactose intolerance. In tropical sprue, exclude other malabsorption syndromes.

6. INVESTIGATIONS & DIAGNOSIS

Diagnostic tests include stool analysis (osmotic gap, Sudan III for fat, elastase), serum vitamin levels, and imaging (barium follow-through, MRI enterography). Small-bowel biopsy is critical for celiac disease, tropical sprue, and lymphatic disorders. Serologic tests (e.g., TTG-IgA) are first-line for celiac disease.

Table 336-6: Diseases Diagnosed by Small-Intestinal Biopsy

Lesion Type Pathologic Findings
Diffuse, Specific Agammaglobulinemia: No plasma cells; flat mucosa
Patchy, Specific Intestinal lymphoma: Malignant cells in lamina propria
Diffuse, Nonspecific Celiac disease: Short/absent villi; mononuclear infiltrate

6.1 Stool Analysis

Spot stool for Sudan III staining (fat), 72-h fecal fat collection, and osmotic gap calculation (290 – 2*(Na+ + K+)).

6.2 Imaging and Biopsy

Barium follow-through, MRI/CT enterography, and endoscopic biopsy for mucosal evaluation. Biopsy findings include villous atrophy in celiac disease, PAS-positive macrophages in Whipple’s disease.

7. MANAGEMENT & TREATMENT

Treatment depends on the underlying cause. Celiac disease requires a strict gluten-free diet. Short-bowel syndrome is managed with teduglutide, parenteral nutrition, and dietary adjustments. Bile acid sequestrants (e.g., cholestyramine) treat bile acid malabsorption. Antibiotics address bacterial overgrowth in tropical sprue.

7.1 Celiac Disease

Strict gluten-free diet. Lifelong adherence is critical. Nutritional supplementation for deficiencies (iron, B12, folic acid).

7.2 Short-Bowel Syndrome

Teduglutide (GLP-2 analog) to enhance adaptation. Parenteral nutrition initially. Low-fat, high-protein diet with medium-chain triglycerides.

8. PROGNOSIS & COMPLICATIONS

Celiac disease complications include refractory disease, lymphoma, and malnutrition. Tropical sprue may lead to chronic folate deficiency and neurological deficits. Short-bowel syndrome risks include osteoporosis, protein-losing enteropathy, and sepsis. Untreated malabsorption can result in cachexia and cachexia-related mortality.

9. SPECIAL CONSIDERATIONS

Pregnancy: Celiac disease requires strict gluten-free diet to prevent fetal complications. Pediatrics: Nutritional supplementation is critical in children with celiac disease or tropical sprue. Elderly: Increased risk of osteoporosis from vitamin D deficiency. Special populations: Ménétrier’s disease may progress to malignancy; monitoring is essential.

10. KEY POINTS & CLINICAL PEARLS

  1. Diarrhea in malabsorption is often osmotic or secretory, with steatorrhea indicating lipid malabsorption. 2. Celiac disease is diagnosed by serology (TTG-IgA) and biopsy. 3. Bile acid sequestrants are first-line for bile acid malabsorption. 4. Short-bowel syndrome requires multidisciplinary management with diet, medications, and possibly surgery. 5. Nutritional supplementation is critical to prevent deficiencies in all malabsorption syndromes.