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

Impaired breakdown of food in the intestinal lumen

• Exocrine pancreatic insufficiency; → lack of enzymes → reduced hydrolysis of carbohydrates, proteins, and lipids
• Following 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 (reversibly inhibits gastric and pancreatic lipase)

Malabsorption

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's disease)
• Lactose intolerance
• Small intestine resection (short bowel syndrome)
• Chronic mesenteric ischemia
• Radiation colitis
• Impaired intestinal lymphatic circulation
• Hormonally active tumors (gastrinoma, VIPoma, carcinoid tumors)
• Small intestinal bacterial overgrowth (SIBO; blind loop syndrome)

References:^[1][2][3][4]

General symptoms

• Global malabsorption
  • Diarrhea (most common), steatorrhea, abdominal distension, 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)

Fat-soluble vitamin deficiencies

Vitamins	Symptoms	Causes	Sources
Vitamin A	Night blindness Retinopathy Xerophthalmia Xeroderma	Fat malabsorption disorders: IBD, celiac disease, cystic fibrosis, pancreatic insufficiency, cholestasis, orlistat use	Liver, kidney, butter, egg yolks
Vitamin D	Osteomalacia and rickets Clinical features of hypocalcemia (e.g., tetany)	Lack of sun exposure Kidney or liver disease Inadequate intake, fat malabsorption	Vitamin D has very few natural food sources Cholecalciferol (previtamin D3): fish Ergocalciferol (previtamin D2): plants, fortified foods (e.g., milk, cereals, formula)
Vitamin E	Neuromuscular disorders (e.g., muscle weakness, demyelination of the posterior column and spinocerebellar tract) Hemolytic anemia	Insufficient intake, fat malabsorption	Meat, eggs, oils, leafy vegetables
Vitamin K	Increased bleeding tendency (e.g., petechiae, ecchymoses)	Liver failure Fat malabsorption	Green vegetables, broccoli, spinach

The fat cat is in the ADEK (pronounced “attic”)

Water-soluble vitamin deficiencies

Vitamins	Clinical features	Causes	Sources
Vitamin B1 (Thiamine)	Beriberi Dry beriberi: symmetrical peripheral neuropathy (sensory and motor), progressive muscle wasting and paralysis, confusion Wet beriberi: high-output cardiac failure (dilated cardiomyopathy), cardiomegaly, edema Infantile beriberi: cardiomegaly, tachycardia, cyanosis; aseptic meningitis with vomiting and seizures Wernicke-Korsakoff syndrome: confusion, ataxia, and nystagmus Leigh syndrome	Chronic alcohol consumption Malnutrition, starvation Diarrhea, prolonged vomiting Diuretics, dialysis Bariatric surgery	Yeast, pork, whole grain rice (unpolished), cereals, legumes
Vitamin B2 (Riboflavin)	Sore throat Cheilitis, glossitis, stomatitis Corneal vascularization Normocytic normochromic anemia Seborrheic dermatitis	Insufficient intake: vegan, lactose intolerance ↑ Demand: pregnancy, lactation	Meat, fish, eggs, milk, green vegetables, yeast
Vitamin B3 (Niacin)	Pellagra 4 D's: dermatitis, diarrhea, dementia, da big tongue (glossitis)! Characteristic dermatitis: symmetric, erythematous or hyperpigmented rash in sun-exposed skin areas, particularly around the neck in a broad collar distribution (Casal necklace) Diarrhea and vomiting Neurologic symptoms: dementia, anxiety, insomnia, encephalopathy	Insufficient intake Chronic alcohol consumption Conditions associated with deficient tryptophan (i.e., malignant carcinoid syndrome , Hartnup disease ) or ↓ vitamin B6 (see below)	Meat (liver), cereals, seeds, legumes
Vitamin B5 (Pantothenic acid)	Deficiency is rare Adrenal insufficiency Enteritis Alopecia Dermatitis May lead to distal paresthesias and dysesthesias (burning sensation of the feet)	Insufficient intake	Liver, kidney, egg yolks, broccoli, milk
Vitamin B6 (Pyridoxine)	Cheilosis, glossitis, stomatitis Sideroblastic anemia Irritability, seizures, peripheral neuropathy	Malnutrition Chronic alcohol consumption Chronic disease (e.g., chronic renal failure, chronic hepatitis) Drug interactions (especially isoniazid )	Meat, nuts, whole grains, vegetables
Vitamin B12 (Cobalamin)	Megaloblastic anemia: mostly asymptomatic; possibly symptoms of weakness and cardiopulmonary impairment Neurologic symptoms Subacute combined degeneration of the spinal cord: symmetrical paresthesias of the extremities, ataxia, weakness, spasticity Irritability, memory loss, dementia	Pernicious anemia Gastritis Gastrectomy, ileal resection Crohn's disease Tapeworm Diphyllobothrium latum	Meat and dairy products
Vitamin C (Ascorbic acid)	Scurvy: hemorrhage, hyperkeratosis, coiled hairs Gingivitis Arthralgia, swollen joints Impaired wound healing	Prolonged insufficient intake	Citrus fruits, strawberries, tomatoes, potatoes, cabbage, spinach
Folic acid (Folate)	Megaloblastic anemia: mostly asymptomatic; possibly symptoms of weakness and cardiopulmonary impairment Glossitis Most common vitamin deficiency in the US	Insufficient intake Chronic alcohol consumption ↑ Demand: pregnancy, lactation Drug interactions (e.g., methotrexate, sulfonamides, phenytoin)	Green leaves

Other deficiencies

• Protein: edema, cachexia
• Iron deficiency anemia or microcytic anemia
• Electrolytes: hypokalemia or hypocalcemia
• Zinc deficiency
  • Etiology
    • Inadequate dietary intake
    • Acrodermatitis enteropathica (congenital deficiency)
    • Crohn's disease, liver and renal disease
  • Clinical findings: immune dysfunction, impaired wound healing, hypogonadism, diarrhea, dermatitis, alopecia, abnormal taste and smell
  • Diagnosis: measurement of plasma zinc levels (< 60 μg/dL is considered pathological)
  • Treatment: oral zinc supplementation (1–2 mg/kg/day elemental zinc)

References:^{[1][2][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][9]}

• Blood tests: macrocytic and/or microcytic anemia; ↓ electrolytes, ↓ total protein, vitamin deficiencies
• Stool tests
  • Analysis of fecal fat over 72 hours > 7 g/24 h is considered pathological
  • Detection of pathogens
• D-xylose absorption test: assesses the absorptive function of the upper small intestine
  • Overnight fast → collection of urine for 5 hours following oral administration of 25 g xylose → if urine xylose levels < 4 g/5 h, diagnostic for malabsorptive disorders with damage to the intestinal mucosa (e.g., celiac disease, Whipple's disease)
  • Collection of a venous blood sample after one hour → levels < 20 mg/dL of serum D-xylose are pathological
• Hydrogen breath test: assess the intestinal absorption of individual carbohydrates
  • Lactulose breath test: determination of orocecal transit time (small intestine transit time)
  • 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

References:^[1][2][20]