Malabsorption

Despite the distinct underlying pathological mechanisms of malabsorption and maldigestion, the term malabsorption is used to refer to both disorders in clinical practice. Malabsorption (e.g., celiac disease, lactose intolerance) describes a malfunction of the intestinal wall, resulting in the insufficient absorption of breakdown products. Maldigestion (e.g., exocrine pancreas insufficiency or cholestasis) is caused by an intraluminal disorder (insufficient secretion of pancreatic enzymes or bile), which prevents the adequate breakdown of food in the intestinal lumen. Both disorders can lead to malnourishment, which, in children, may manifest with delayed and inadequate physical development. Adults mainly present with chronic diarrhea, weight loss, and signs of malnutrition (e.g., iron deficiency anemia). Diagnostic tests assess the digestion of individual food components. Management focuses on the underlying disease; e.g., patients with celiac disease should adhere to a gluten-free diet.

Malabsorption disorders can be caused by either the insufficient absorption or digestion of nutrients. The condition can be further defined as global or partial.

• Global malabsorption: in diseases causing diffuse mucosal damage or a reduction of the absorptive surface (e.g., celiac disease)
• Partial malabsorption: caused by a localized absorption impairment, resulting in deficiencies of specific nutrients (e.g., vitamin B₁₂ deficiency in patients with diseases affecting the terminal ileum)

Maldigestion

Maldigestion is an impaired breakdown of food in the intestinal lumen.

Exocrine pancreatic insufficiency

• Definition: inability of the pancreas to produce enzymes necessary for digestion, including amylase, lipases, and proteases (e.g., trypsinogen, chymotrypsinogen, elastase)
• Etiology
  • Cystic fibrosis
  • Chronic pancreatitis
  • Obstruction (e.g., due to pancreatic cancer)
  • Shwachman-Diamond syndrome: rare autosomal recessive condition and second most common cause of exocrine pancreatic insufficiency in children (after cystic fibrosis)
• Pathophysiology: : lack of digestive enzymes → malabsorption of carbohydrates, proteins, fats, fat-soluble vitamins (A, D, E, K), and vitamin B₁₂
• Clinical features: steatorrhea, deficiency symptoms
• Diagnostics
  • ↓ Elastase in stool
  • ↓ Bicarbonate and ↓ pH in duodenum
  • Normal results in D-xylose absorption test

Other causes

• Gastric resection: lack of gastric acid → impaired breakdown of nutrients
• Bile acid deficiency: : e.g., cholestasis, bile acid malabsorption → incomplete emulsification of fats
• Medications: orlistat

Malabsorption

Malabsorption is an impaired absorption of digested food caused by alterations of the intestinal mucosa.

• Inflammatory bowel disease (e.g., Crohn's disease)
• Celiac disease (gluten-sensitive enteropathy)
• Infections (e.g., tropical sprue; , giardiasis, traveler's diarrhea, Whipple disease)
• Lactose intolerance
• Small intestine resection (short bowel syndrome)
  • Definition: a condition in which the small intestine is unable to adequately absorb nutrients, water, and electrolytes
  • Etiologies: surgical resection (e.g., for Crohn disease or trauma), congenital abnormalities
  • Complications: intestinal failure that requires intravenous supplementation
• Chronic mesenteric ischemia
• Radiation colitis
• Impaired intestinal lymphatic circulation
• Hormonally active tumors (gastrinoma, VIPoma, carcinoid tumors)
• Small intestinal bacterial overgrowth (SIBO; blind loop syndrome)
• HIV enteropathy

General symptoms

• Global malabsorption
  • Diarrhea (most common), steatorrhea, abdominal distention, flatulence
  • Weight loss, fatigue
  • Additional symptoms of specific deficiencies
• Partial (isolated) malabsorption: only symptoms specific to individual nutrient deficiencies (e.g., impaired cobalamin absorption with megaloblastic anemia)

Deficiencies

• Deficiency of fat-soluble vitamins: See “Vitamin A deficiency” and “Vitamin D deficiency” in “Osteomalacia and rickets”
• Deficiency of water-soluble vitamins: See symptoms of individual vitamin deficiencies in “Vitamins”.
• Other deficiencies
  • Zinc deficiency
  • Protein: edema, cachexia
  • Iron deficiency anemia or microcytic anemia
  • Electrolytes: hypokalemia or hypocalcemia

• Blood tests: macrocytic and/or microcytic anemia; ↓ electrolytes, ↓ total protein, vitamin deficiencies
• Stool tests
  • Analysis of fecal fat; over 72 hours (e.g., using Sudan stain)
  • Detection of pathogens
• D-xylose absorption test: assesses the absorptive function of the upper small intestine
  • Physiology
    • The intestinal absorption of D-xylose requires intact mucosa but no digestive enzymes.
    • Most of the absorbed D-xylose is eliminated by the kidneys without being metabolized, which is why insufficient intestinal absorption results in low urine xylose levels.
  • Method: The patient fasts overnight, then 25 g of D-xylose is administered orally. Then:
    • Urine is collected over 5 hours. Urine D-xylose levels < 4 g/5 h are considered pathological.
    • A venous blood sample is collected after one hour. Serum D-xylose levels < 20 mg/dL are considered pathological.
  • Interpretation
    • ↓ D-xylose levels (urine and blood) occur in malabsorptive disorders that involve damage to the intestinal mucosa (e.g., celiac disease, Whipple disease) and in cases of bacterial overgrowth.
    • Normal (elevated) D-xylose levels suggest a different cause of malabsorption.
• Hydrogen breath test: assess the intestinal absorption of individual carbohydrates
  • Lactulose breath test: determination of orocecal transit time (small intestine transit time) ^[1]
  • Glucose hydrogen breath test: if abnormal bacterial colonization of the small intestine is suspected
• Further testing (for underlying diseases): e.g., celiac disease or lactose intolerance

Differential diagnoses of malabsorption

Protein-losing enteropathy

• Definition: a condition characterized by massive loss of protein that can occur as a complication of several gastrointestinal disorders
• Etiology
  • Massive loss of protein caused by various gastrointestinal disorders
  • Erosive or ulcerative (e.g., Crohn's disease, clostridium difficile infection)
  • Increased intestinal permeability to proteins (e.g., celiac disease, bacterial overgrowth)
  • Impaired lymphatic circulation (e.g., intestinal lymphangiectasia, Whipple's disease)
• Clinical features: hypoalbuminemia with peripheral edema
  • In cases of systemic diseases, symptoms may be those of the underlying condition.
  • Further gastrointestinal symptoms may occur depending on the underlying disorder.
• Treatment: treatment of the underlying disease

The differential diagnoses listed here are not exhaustive.

• Symptomatic treatment
  • Oral supplementation of fluid, nutrients, and vitamins
  • Calorie and protein-enriched diet
  • IV nutrition in severe cases (e.g., following extensive intestinal resection)
• Causal treatment of the underlying disease