Malabsorption and Maldigestion

Malabsorption involves many disorders in which there is an inability of the gut to absorb nutrients from dietary intake, potentially including water and/or electrolytes. A closely related term, maldigestion is the inability to break down large molecules of food into their smaller constituents. Malabsorption and maldigestion can affect macronutrients (fats, proteins, and carbohydrates), micronutrients (vitamins and minerals), or both. These disorders present with weight loss, diarrhea, weakness, and fatigue. There are many causes, and the goal of management is to reduce symptoms, with specific treatments aimed at the underlying cause.

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Overview

Definition

Maldigestion refers to the inability to break down large molecules of food in the intestinal lumen into their smaller components. 
Malabsorption refers to the inability to transport nutrients across the intestinal mucosa into blood circulation. The term “malabsorption,” however, is often used to refer to both of these processes since food that is not digested properly will not be absorbed properly either.

Classification

Global malabsorption:

  • Results from diseases associated with either widespread mucosal involvement or a reduced absorptive surface
  • Multiple nutrients are inadequately absorbed.
  • Example: in celiac disease (CD) 

Selective malabsorption:

  • Results from diseases that interfere with the absorption of a single nutrient or a limited array of nutrients 
  • Example: In pernicious anemia, there is impaired absorption of vitamin B12.

Epidemiology

  • Exact prevalence is unknown due to multiple etiologies.
  • Prevalence in specific subgroups:
    • Patients with severe chronic pancreatitis: as high as 85%
    • Infants with cystic fibrosis (CF): 85%
    • HIV/AIDS: 26%–45%
    • Pancreatic cancer: 50%–100%

Etiology

Malabsorption has many causes from various mechanisms.

  • Abnormal motility due to:
    • Diabetic gastroparesis
    • Systemic sclerosis
    • Thyroid dysfunction
  • Abnormal milieu due to:
    • Small intestinal bacterial overgrowth
    • Zollinger-Ellison syndrome (ZES) (hypersecretion of gastric acid resulting in low pH)
  • Maldigestion due to:
    • Biliary obstruction and/or cholestasis
    • Bile salt deficiency
      • Hepatic cirrhosis
      • Primary biliary cirrhosis
      • Bacterial overgrowth (certain bacteria can deconjugate the bile salts, rendering them ineffective)
    • Pancreatic diseases:
      • Exocrine pancreatic insufficiency
      • CF
      • Chronic pancreatitis
      • Pancreatic cancer 
    • Disaccharidase deficiencies:
      • Lactase deficiency (resulting in lactose intolerance)
      • Sucrase deficiency
  • Abnormal GI epithelial:
    • Acutely abnormal epithelium
      • Acute intestinal infections such as Giardia
      • Alcohol ingestion
    • Chronically abnormal epithelium
      • CD
      • Inflammatory bowel disease (IBD): Crohn disease and ulcerative colitis 
      • Intestinal ischemia
      • Radiation enteritis
      • Whipple disease
  • Infiltrative disease: can affect both motility and absorptive ability
    • Lymphoma
    • Sarcoidosis
    • Amyloidosis
    • Systemic sclerosis
  • Postsurgical alterations of the GI tract:
    • Vitamin malabsorption after bariatric surgery/gastric resection
    • Bile acid malabsorption after intestinal resection, including surgeries performed for:
      • Malignancy
      • Volvulus
      • Ischemic bowel
      • Crohn enteritis

Pathophysiology

Factors required for effective absorption

  • Appropriate mechanical mixing
  • Normal enzyme synthesis, secretion, and activity
  • Mucosal integrity
  • Normal blood supply
  • Intestinal mobility
  • Balanced microbial flora
Table: Normal versus abnormal digestion and absorption of macronutrients
Type of nutrientNormal processAbnormal process
Fats
  • Lipases from the pancreas break down long-chain triglycerides into fatty acids and monoglycerides →
    • Combine with bile acids and phospholipids to form micelles
    • Micelles are absorbed in the proximal jejunum.
    • Bile salts remain in the intestinal lumen and are reabsorbed in the terminal ileum.
  • Medium-chain triglycerides are absorbed directly.
  • Absorbed fatty acids are combined with protein, cholesterol, and phospholipids to form chylomicrons, which are transported by the lymphatic system.
  • Fat-soluble vitamins (A, D, E, and K) are absorbed in the chylomicrons with fat.
  • Deficiency in lipases prevents effective breakdown of fats.
  • Most commonly due to pancreatic insufficiency
  • Results in:
    • Steatorrhea
    • Deficiencies of fat-soluble vitamins
    • Diarrhea (unabsorbed bile salts stimulate water secretion in the colon)
Proteins
  • Pepsin in the stomach starts digestion of proteins.
  • Pancreatic proteases and enterokinase from the brush border convert them to oligopeptides.
  • Amino acids, di- and tri-peptides are absorbed via specialized transporters.
  • Deficiency can result in muscle atrophy and edema.
Carbohydrates
  • Salivary and pancreatic amylase begin carbohydrate digestion.
  • Other enzymes in the microvilli brush border (including disaccharidases) break down carbohydrates into monosaccharides.
  • Absorbed via passive or active transport
  • Remaining carbohydrates are fermented by bacteria in the colon.
  • Most commonly due to deficiency in disaccharidases (e.g., lactase)
  • Colonic bacteria ferment unabsorbed carbohydrates into gases and fatty acids.
  • Results in flatulence, bloating, and diarrhea

Clinical Presentation

Malabsorption should be suspected in a patient with chronic diarrhea, unexplained weight loss, and/or unexplained nutrient deficiencies.

Classic manifestations of micronutrient malabsorption

  • Diarrhea
  • Steatorrhea (pale, foul-smelling, bulky stools with oil droplets in toilet)
  • Flatulence (often occurring within 90 minutes of carbohydrate ingestion)
  • Unintentional weight loss
  • Fatigue and weakness due to anemia
  • Abdominal distention
  • Developmental delay or skeletal deformities in children
  • Edema, ascites, and/or pleural effusions may be seen in severe protein-calorie malnutrition.

Presentations related to specific micronutrient deficiencies

  • Anemia: B12, folate, or iron deficiency 
  • Bleeding: vitamin K deficiency
  • Dermatitis: vitamin B, C, or zinc deficiency
  • Peripheral neuropathies: B1 or vitamin B12 deficiency, or, more rarely, vitamin E deficiencies
  • Osteoporosis: calcium and/or vitamin D deficiency
  • Scurvy: vitamin C deficiency
  • Beriberi: B1 deficiency
  • Wernicke-Korsakoff syndrome: B1 deficiency
  • Pellagra (photosensitive pigmented dermatitis, diarrhea, and dementia): niacin deficiency (vitamin B3)
  • Night blindness, xerophthalmia, and follicular hyperkeratosis: vitamin A deficiency
  • Retinopathy and neurological problems: vitamin E deficiency
Characteristic skin rash associated with pellagra Malabsorption

Characteristic skin rash associated with pellagra

Image: “This child has the skin rash associated with pellagra” by CDC. License: Public Domain

Diagnosis

Work-up should first determine whether the malabsorption is global or selective, and then attempt to determine the underlying etiology. This is achieved through a history and physical examination, laboratory testing, and, in some cases, imaging and endoscopy.

History and exam

The etiology can often be ascertained from the history.

Detailed history for symptoms as above, as well as:

  • Weight loss
  • Chronic intestinal disease
  • Intestinal resection
  • Bariatric surgery 
  • Pancreatic surgery
  • Risk factors for CD 
    • Type 1 diabetes mellitus
    • Family history of CD
  • Excessive alcohol consumption
  • Recurrent peptic ulcer disease

Physical examination for:

  • Dermatitis
  • Pallor
  • Cachexia
  • Jaundice
  • Peripheral neuropathy
  • Muscle wasting
  • Abdominal tenderness or bloating
  • Ecchymoses

Laboratory, imaging, and endoscopy

Lab tests and imaging should be ordered based on suspected diagnosis, and may include:

  • Stool testing for:
    • Fecal fat
    • Fecal elastase (helpful in identifying pancreatic insufficiency)
  • CBC for anemia, which may show microcytosis or macrocytosis
  • Serum iron and total iron binding capacity
  • Folate and vitamin B12 level
  • Vitamin B1 level, if history of gastric bypass surgery
  • 25-hydroxy vitamin D level
  • CMP for liver enzymes, calcium, and albumin
  • Prothrombin time (PT), which may be increased in vitamin K (fat-soluble) malabsorption
  • Serologic antibody assessment for CD:
    • Anti-tissue transglutaminase antibodies (tTG-IgA) 
    • Anti-endomysial antibodies (EMA-IgA)
  • Carbohydrate breath test, if suspecting small intestinal bacterial overgrowth
  • Imaging:
    • Helpful if suspecting chronic pancreatitis, gallbladder, or liver disease
    • Findings are generally nonspecific and insensitive.
    • Consider:
      • MRCP
      • Ultrasound
      • Abdominal CT
  • Endoscopy and/or colonoscopy 
    • If suspecting CD or Crohn disease after lab testing
    • Biopsies may help confirm diagnosis.

Management

  • Address and treat the underlying disease.
  • Administer supplementation of:
    • Fluid and electrolytes
      • IV supplementation may be required in severe cases.
      • Patients with severe diarrhea may require ongoing oral rehydration solutions.
    • Nutrients: Calorie and protein replenishment are indicated for malnourished patients.
    • Essential vitamins and minerals
      • Fat-soluble vitamins may be particularly challenging and should be monitored closely.
      • Calcium and magnesium are usually required in patients with fat malabsorption.
  • Improve quality of life by optimizing control of diarrhea; antidiarrheal agents include:
    • Loperamide (Imodium)
    • Diphenoxylate with atropine (Lomotil)
  • Dietary interventions:
    • Avoid more than 1 serving per day of caffeine-containing beverages.
    • Avoid full-strength sugar-sweetened beverages and fruit juices.
    • Avoid artificial sweeteners sorbitol and xylitol.
  • Monitor for recurrence.

Differential Diagnosis

  • CD: also known as celiac sprue or gluten enteropathy, CD is an autoimmune reaction to gliadin, which is a component of gluten. Patients typically present with diarrhea and symptoms related to malabsorption (steatorrhea, weight loss, and nutritional deficiencies). Patients are screened with serological antibody testing, and diagnosis is confirmed by small intestine biopsy. Treatment requires a lifelong gluten-free diet.
  • Whipple disease: a rare fat-malabsorption syndrome caused by the bacterium Tropheryma whipplei. Patients often present with 4 characteristic symptoms, including weight loss, diarrhea/steatorrhea, arthralgias, and abdominal pain; additional systemic manifestations are also possible. Whipple disease is diagnosed with biopsy and treated with antibiotics.
  • Tropical sprue: a chronic diarrheal disease that involves the small intestine and is characterized by malabsorption of nutrients, especially folic acid, vitamin B12, carbohydrates, and fat. While no single pathogen has been identified as the cause of tropical sprue, it is likely that persistent overgrowth of coliform bacteria (e.g., Klebsiella, Escherichia coli, and Enterobacter) in the small intestine eventually causes significant small bowel structural damage and chronic diarrhea.
  • Bile acid malabsorption: diarrhea related to excessive bile acids entering the colon in some patients following cholecystectomy may overcome the terminal ileum’s reabsorptive capacity. The increased bile acids in the colon that lead to diarrhea are treated very differently (with bile-acid binding resins such as cholestyramine or colestipol) than those with marked degrees of bile acid malabsorption resulting in steatorrhea. In patients with fat malabsorption and steatorrhea, therapy is indicated with exogenous conjugated bile acids.
  • Crohn disease: a chronic, recurrent inflammatory bowel disease that causes patchy transmural inflammation that can involve any part of the GI tract. The terminal ileum and proximal colon are usually affected. Crohn disease typically presents with intermittent, nonbloody diarrhea and crampy abdominal pain. Diagnosis is established via endoscopy with biopsy. Complications include malabsorption, malnutrition, intestinal obstruction or fistula, and an increased risk of colon cancer.
  • Small intestinal bacterial overgrowth: patients with small intestinal bacterial overgrowth present with nonspecific symptoms of bloating, flatulence, abdominal discomfort, or steatorrhea. The diagnosis of small intestinal bacterial overgrowth is established by a carbohydrate breath test and treatment is with appropriate antibiotics.
  • Exocrine pancreatic insufficiency: in this condition, there is severely decreased pancreatic enzyme production as a result of chronic pancreatitis, surgical resection, pancreatic duct obstruction, or CF. The diagnosis of exocrine pancreatic insufficiency should be suspected in patients with a significant history of surgery and symptoms of malabsorption.
  • Short bowel syndrome: a malabsorptive condition most commonly associated with extensive intestinal resection for etiologies such as Crohn disease, bowel obstruction, trauma, radiation therapy, or vascular insufficiency. The short length of bowel results in insufficient surface area for fluid and electrolyte absorption. The patient typically presents with diarrhea, electrolyte abnormalities, and dehydration. Management options include antimotility agents, antisecretory agents, and total parenteral nutrition for patients, who cannot maintain themselves with oral intake.
  • Protein-losing enteropathy: also presents with edema and hypoalbuminemia, with or without diarrhea. However, these manifestations are due to loss of protein from the alimentary canal and not malabsorption.

References

  1. Mason J. (2021). Approach to the adult patient with suspected malabsorption. UpToDate. Retrieved April 12, 2021, from https://www.uptodate.com/contents/approach-to-the-adult-patient-with-suspected-malabsorption
  2. Ruiz A. (2021). Overview of Malabsorption. Merck Manual Professional Version. Retrieved April 12, 2021, from https://www.merckmanuals.com/professional/gastrointestinal-disorders/malabsorption-syndromes/overview-of-malabsorption?query=malabsorption
  3. Zackria R and Lopez RA. (2021). Postcholecystectomy Syndrome. StatPearls. PubMed. Retrieved April 12, 2021, from  http://www.ncbi.nlm.nih.gov/books/NBK539902
  4. Hogenauer C, Hammer HF. Maldigestion and Malabsorption. In: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, (10th ed.), Feldman M, Friedman LS, Brandt LJ (Eds.), Saunders, Philadelphia, 2016, p. 1788.
  5. Vijayvargiya P, and Camilleri M. (2018). Current Practice in the Diagnosis of Bile Acid Diarrhea. Gastroenterology, 156 (5), pp. 1233–38. PubMed. Retrieved April 12, 2021, from https://pubmed.ncbi.nlm.nih.gov/30844373/
  6. Zuvarox T. (2021). Malabsorption Syndromes. StatPearls. Retrieved June 7, 2021 from https://www.statpearls.com/articlelibrary/viewarticle/24657/

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