Malabsorption syndromes

• Malabsorption and Maldigestion Overview:
  • Definition: Malabsorption involves the failed absorption of nutrients (fats, carbohydrates, proteins, vitamins, minerals, trace elements) at any stage of the digestive process. Maldigestion refers to the impaired breakdown of nutrients within the intestinal lumen or at the brush border. Despite differences, “malabsorption” often encompasses both due to their interdependent nature.
  • Focus: Primarily on dysfunctions at the level of the small intestine, pancreas, or gallbladder impacting nutrient absorption.
• Pathophysiology:
  • Small Intestine: Central to absorption, with its extensive surface area provided by villi and microvilli, and spaces within the lumen.
  • Digestion and Absorption: Involves mechanical mixing, enzymatic digestion, mucosal integrity, adequate blood supply, proper intestinal motility, and balanced microbial flora.
  • Symptoms: Overlap significantly but commonly include diarrhea, steatorrhea, weight loss, developmental issues or skeletal deformities (children), and anemia.
• Etiology:
  • Nutrient Absorption Stages:
    1. Luminal Phase: Mechanical mixing, enzymatic digestion.
    2. Mucosal Phase: Nutrient uptake via the mucosal membrane.
    3. Postabsorptive Phase: Distribution via blood and lymphatics.
  • General Causes: Arise from defects at any digestion or absorption level, encompassing a wide range of disorders.

Detailed Etiology and Pathophysiology

Fat Malabsorption

• Mechanism: Digestion and absorption of fats are intricate processes that start with emulsification in the stomach and continue with the action of pancreatic enzymes and bile acids in the small intestine. Lipids are then absorbed in the form of micelles in the jejunum.
• Specific Causes:
  • Bile Acid Insufficiency: Due to liver disease, cholestasis, or bile duct obstruction, leading to poor emulsification and fat malabsorption.
  • Pancreatic Insufficiency: Conditions like chronic pancreatitis or cystic fibrosis reduce the secretion of lipase, crucial for lipid digestion.
  • Intestinal Diseases: Diseases such as Crohn’s and celiac disease damage the intestinal mucosa, impairing absorption. Surgical resection of the small intestine similarly reduces the absorptive surface.

Carbohydrate Malabsorption

• Digestion and Absorption: Requires enzymatic breakdown of polysaccharides into monosaccharides at the brush border of the small intestine. Malabsorption occurs when these enzymes are deficient or when the absorptive surface is compromised.
• Specific Causes:
  • Enzyme Deficiencies: Such as lactase deficiency leading to lactose intolerance, the most common form of carbohydrate malabsorption.
  • Mucosal Damage: Conditions like celiac disease disrupt the mucosal integrity, affecting the function of brush border enzymes.

Protein Malabsorption

• Mechanism: Proteins are initially denatured in the stomach by acid and pepsin, then further broken down by pancreatic proteases into amino acids and small peptides in the small intestine for absorption.
• Specific Causes:
  • Pancreatic Insufficiency: Results in inadequate secretion of proteolytic enzymes, common in chronic pancreatitis.
  • Intestinal Resections: Loss of absorptive mucosa impacts protein absorption.

History

• Key Symptoms: Ongoing or chronic diarrhea, unintentional weight loss despite normal intake, greasy and foul-smelling stools that float, flatulence, bloating, and borborygmi.
• Abdominal Pain: Less common but possible, varying in intensity and location.
• Detailed Inquiry: Includes symptom duration and timing, changes in pain or stool characteristics, known triggers, associated symptoms like changes in bowel habits, and appearance of stools (e.g., floating, pale, greasy stools, oil droplets).
• Comprehensive Review: Past medical and family history, focusing on systemic and gastrointestinal conditions, medication use, previous surgeries, radiation exposure, caustic substance ingestion, allergies, and social habits (smoking, alcohol, drug use).

Physical Examination

• Abdominal Exam: In-depth examination to check for distention, tenderness, hyper/hypoactive bowel sounds, and other abnormalities.
• Systemic Signs: Look for indicators of nutritional deficiencies such as pallor (anemia), muscle wasting, abnormal reflexes, skeletal deformities, rashes, delayed growth (in children), poor wound healing, ecchymosis, decreased visual acuity, peripheral neuropathy, auditory disturbances, and cognitive impairments.

Differential Diagnosis

Overlapping Symptoms Among Malabsorption Syndromes

• Malabsorption syndromes often share common symptoms, making them differential diagnoses for each other.

Conditions Masquerading as Abdominal Pain

• Pericarditis, Myocardial Infarction, Pulmonary Infarction: These conditions can refer pain to the abdomen, complicating the differential diagnosis.

Specific Differential Diagnoses Based on Syndrome or Symptom

• Primary Intestinal Lymphangiectasia (Waldmann Disease): Differentiate from constrictive pericarditis, Crohn’s disease, Whipple disease, systemic sclerosis, intestinal tuberculosis, and sarcoidosis.
• Ongoing Diarrhea Early in Life:
  • Cystic Fibrosis: Considered due to its impact on the pancreas and gastrointestinal function.
  • Congenital Chloride Malabsorption: A rare disorder affecting electrolyte balance and causing diarrhea.
  • Congenital Glucose-Galactose Malabsorption: Characterized by severe diarrhea in response to the ingestion of glucose or galactose.
  • Pancreatic Insufficiency: Can result from conditions like cystic fibrosis, leading to malabsorption and diarrhea.
  • Cow’s Milk Protein Allergy (CMPA): Immune response to proteins in cow’s milk, presenting with gastrointestinal symptoms including diarrhea.

Management Strategies

General Evaluation for Malabsorption Syndromes:

• Indications for Evaluation:
  • Initiated when nonspecific symptoms such as unintentional weight loss, persistent diarrhea, or poor wound healing suggest malabsorption but lack specificity for a direct diagnosis.
• Laboratory Testing Overview:
  • Laboratory tests are adjunctive, aiding in diagnosis but not definitive on their own.
• Blood Tests Include:
  • Comprehensive Metabolic Panel: Checks for electrolyte imbalances, liver function, and kidney function to identify systemic effects of malabsorption.
  • Complete Blood Cell (CBC) Count: Important for identifying anemia which could suggest nutrient deficiencies (e.g., iron, folate, vitamin B12).
  • Serum Albumin: Low levels indicate chronic protein malnutrition.
  • Magnesium, Zinc, Phosphorous Levels: Assessed due to their importance in various bodily functions and potential deficiency in malabsorption.
  • Vitamin Levels: Specific vitamins (B12, folate, D) are tested to identify malabsorption of these crucial nutrients.
  • Iron Panel: Includes serum iron, total iron-binding capacity, and ferritin, crucial for diagnosing iron deficiency anemia.
• Fecal Tests (Especially for Suspected Fat Malabsorption):
  • Fecal Fat Test: A screening test; if positive or if clinical suspicion persists, a more detailed evaluation follows.
  • 72-hour Fecal Fat Excretion Test: Considered the gold standard for diagnosing steatorrhea, requiring patient adherence to collection instructions for accurate results.
  • Sudan III Stain: A sensitive spot test performed on a stool sample.
  • Acid Steatocrit: A simpler, quick method for estimating fecal fat.
  • Near-Infrared Reflectance Analysis (NIRA): Offers a fast alternative to the 72-hour fecal fat test and can also measure nitrogen and carbohydrates.

More Specific Evaluation of Malabsorption Syndromes:

• Directed Evaluation Based on Clinical Suspicion:
  • If the initial evaluation and clinical context point towards a specific malabsorption syndrome, more targeted tests are pursued.
• Breath Tests:
  • Used for diagnosing carbohydrate malabsorption syndromes and SIBO, although not considered completely reliable for SIBO diagnosis.
• Jejunal Aspirate Culture:
  • The gold standard for diagnosing SIBO, confirming bacterial overgrowth in the small intestine.
• Imaging and Advanced Diagnostics:
  • Computed Tomography (CT): Utilized for identifying structural causes of malabsorption, such as pancreatitis.
  • Magnetic Resonance Cholangiopancreatography (MRCP): Helps diagnose exocrine pancreatic insufficiency by visualizing the bile ducts and pancreatic ducts.
  • Magnetic Resonance (MR) Elastography: A non-invasive technique to assess liver stiffness, aiding in the diagnosis of liver fibrosis or hepatic amyloidosis.
  • Endoscopic Retrograde Cholangiopancreatography (ERCP): Used when pancreatic insufficiency is suspected, especially following pancreatitis or in the presence of high fecal elastase levels.
• Endoscopy and Biopsy:
  • Indications: When visualization and tissue sampling are necessary for diagnosis, such as for Crohn’s disease (cobblestoning of the duodenal mucosa) or celiac disease (mucosal scalloping).
  • Colonoscopies and Biopsies: For diagnosing conditions like ulcerative colitis.
  • Acid-fast Stains: Differentiate between Tropheryma whipplei and Mycobacterium avium in biopsy samples.
• Example of Specific Condition Evaluation – Celiac Disease:
  • A child with symptoms worsened by cereal introduction, alongside diarrhea, growth delays, and abdominal discomfort. Consideration of celiac disease especially if there’s unexplained iron-deficiency anemia.
  • Diagnostic Tests: Duodenal or jejunal biopsy (showing blunted villi or increased intraepithelial lymphocytes), serologic studies (gliadin antibodies, tissue transglutaminase antibodies), and response to a gluten-free diet.
  • Dietary Trials: Eliminating specific foods or ingredients can diagnose and treat conditions like lactose or fructose intolerance.

Treatment and Management

• Nutritional Support: Dietary modifications to eliminate offending agents (e.g., gluten in celiac disease) and supplementation of deficient nutrients.
• Addressing Underlying Causes:
  • Enzyme Replacement Therapy: For pancreatic insufficiency.
  • Bile Acid Supplements: For bile acid malabsorption.
  • Antibiotics: For conditions like SIBO.
• Interprofessional Care: Essential for managing the multifaceted aspects of malabsorption, involving gastroenterologists, dietitians, and primary care providers.

Special Considerations

• Pediatric Patients: Malabsorption can significantly impact growth and development, requiring careful management and monitoring.
• Chronic Conditions: Long-term management strategies are crucial for chronic conditions like Crohn’s disease, including regular monitoring and adjustments in treatment to manage flare-ups.

Complications

The complications that can arise from malabsorption and maldigestion are as numerous as the points at which these processes can be interrupted, delayed, or absent. When a malabsorption syndrome is severe enough, poorly controlled, or of long enough duration, complications can include (not a comprehensive list):

• Gastrointestinal symptoms (e.g., chronic diarrhea, bloating, flatulence)
• Malnutrition
• Weight loss/poor weight gain
• Vitamin, mineral, trace element deficiencies (e.g., vitamin D, B12, iron, folate)
  • Osteomalacia/rickets disease, coagulopathy, visual impairment, skin changes
• Hematologic disorders
  • Anemia
  • Coagulopathy
• Visual impairment
• Dermatologic manifestations
• Musculoskeletal dysfunction:
  • Growth delay (in children)
  • Skeletal deformities (e.g., rickets)
  • Bone mineral density abnormalities (e.g., osteoporosis)
  • Cachexia
• Electrolyte disturbances
• Cardiovascular disease:
  • Cardiac arrhythmias
• Neurologic dysfunction:
  • Peripheral neuropathy
  • Ataxia [9]
• Endocrine dysfunction:
  • Parathyroid dysfunction
  • Chronic fatigue