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 Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. 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 Carbohydrates Carbohydrates are one of the 3 macronutrients, along with fats and proteins, serving as a source of energy to the body. These biomolecules store energy in the form of glycogen and starch, and play a role in defining the cellular structure (e.g., cellulose). Basics of Carbohydrates), micronutrients (vitamins and minerals), or both. These disorders present with weight loss, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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 Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. 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 Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview, 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 Chronic pancreatitis Chronic pancreatitis is due to persistent inflammation, fibrosis, and irreversible cell damage to the pancreas, resulting in a loss of endocrine and exocrine gland function. The most common etiologies are alcohol abuse and pancreatic duct obstruction. Patients often present with recurrent epigastric abdominal pain, nausea, and features of malabsorption syndrome (diarrhea, steatorrhea, and weight loss). Chronic Pancreatitis: as high as 85%
    • Infants with cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. 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 Systemic sclerosis Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma
    • 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 Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
      • Primary biliary cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
      • Bacterial overgrowth (certain bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview 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 Lactose intolerance Lactose intolerance (LI) describes a constellation of symptoms due to lactase deficiency (LD), the enzyme located in the brush border of the absorptive cells in the small intestine. Lactose is the disaccharide present in milk and requires hydrolysis by lactase to break it down into its 2 absorbable constituents, glucose and galactose. Lactose intolerance typically presents with bloating, abdominal cramping, diarrhea, and flatulence. Lactose Intolerance)
      • Sucrase deficiency
  • Abnormal GI epithelial:
    • Acutely abnormal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium
      • Acute intestinal infections such as Giardia
      • Alcohol ingestion
    • Chronically abnormal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium
      • CD
      • Inflammatory bowel disease (IBD): Crohn disease and ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn's disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis 
      • Intestinal ischemia Intestinal ischemia Intestinal ischemia occurs when perfusion fails to meet the demands of the intestines, resulting in ischemic tissue injury that can be life-threatening if bowel necrosis and/or perforation occurs. Symptoms can range from mild indigestion or diarrhea to severe abdominal pain. Intestinal Ischemia
      • Radiation enteritis
      • Whipple disease
  • Infiltrative disease: can affect both motility and absorptive ability
    • Lymphoma
    • Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
    • Amyloidosis Amyloidosis Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). Amyloidosis
    • Systemic sclerosis Systemic sclerosis Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma
  • Postsurgical alterations of the GI tract:
    • Vitamin malabsorption after bariatric surgery Bariatric surgery Bariatric surgery refers to a group of invasive procedures used to surgically reduce the size of the stomach to produce early satiety, decrease food intake (restrictive type) and/or alter digestion, and artificially induce malabsorption of nutrients (malabsorptive type). The ultimate goal of bariatric surgery is drastic weight loss. Bariatric Surgery/gastric resection
    • Bile acid malabsorption after intestinal resection, including surgeries performed for:
      • Malignancy
      • Volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. 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 nutrient Normal process Abnormal process
Fats
  • Lipases from the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. 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 Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix)
Proteins
  • Pepsin in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. 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 Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema.
Carbohydrates
  • Salivary and pancreatic amylase begin carbohydrate digestion.
  • Other enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes in the microvilli brush border (including disaccharidases) break down carbohydrates Carbohydrates Carbohydrates are one of the 3 macronutrients, along with fats and proteins, serving as a source of energy to the body. These biomolecules store energy in the form of glycogen and starch, and play a role in defining the cellular structure (e.g., cellulose). Basics of Carbohydrates into monosaccharides.
  • Absorbed via passive or active transport
  • Remaining carbohydrates Carbohydrates Carbohydrates are one of the 3 macronutrients, along with fats and proteins, serving as a source of energy to the body. These biomolecules store energy in the form of glycogen and starch, and play a role in defining the cellular structure (e.g., cellulose). Basics of Carbohydrates are fermented by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview in the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix.
  • Most commonly due to deficiency in disaccharidases (e.g., lactase)
  • Colonic bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview ferment unabsorbed carbohydrates Carbohydrates Carbohydrates are one of the 3 macronutrients, along with fats and proteins, serving as a source of energy to the body. These biomolecules store energy in the form of glycogen and starch, and play a role in defining the cellular structure (e.g., cellulose). Basics of Carbohydrates into gases and fatty acids.
  • Results in flatulence, bloating, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea

Clinical Presentation

Malabsorption should be suspected in a patient with chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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 Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview
  • Abdominal distention
  • Developmental delay or skeletal deformities in children
  • Edema, ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, and/or pleural effusions may be seen in severe protein-calorie malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries.

Presentations related to specific micronutrient deficiencies

  • Anemia: B12, folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12, 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 Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis: calcium and/or vitamin D deficiency
  • Scurvy: vitamin C deficiency
  • Beriberi: B1 deficiency
  • Wernicke- Korsakoff syndrome Korsakoff syndrome Korsakoff syndrome is a severe and late neuropsychiatric manifestation of Wernicke encephalopathy. Korsakoff syndrome presents with personality changes, anterograde and retrograde amnesia, and confabulation. Some of these changes are irreversible. Wernicke Encephalopathy and Korsakoff Syndrome: B1 deficiency
  • Pellagra (photosensitive pigmented dermatitis, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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 Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin rash associated with pellagra

Image: “This child has the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of 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 Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • Family history of CD
  • Excessive alcohol consumption
  • Recurrent peptic ulcer disease Peptic ulcer disease Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). 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 Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview, 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 Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of 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 Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins (tTG-IgA) 
    • Anti-endomysial antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins (EMA-IgA)
  • Carbohydrate breath test, if suspecting small intestinal bacterial overgrowth
  • Imaging:
    • Helpful if suspecting chronic pancreatitis Chronic pancreatitis Chronic pancreatitis is due to persistent inflammation, fibrosis, and irreversible cell damage to the pancreas, resulting in a loss of endocrine and exocrine gland function. The most common etiologies are alcohol abuse and pancreatic duct obstruction. Patients often present with recurrent epigastric abdominal pain, nausea, and features of malabsorption syndrome (diarrhea, steatorrhea, and weight loss). Chronic Pancreatitis, gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract, or liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. 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 Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
      • IV supplementation may be required in severe cases.
      • Patients with severe diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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 Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea; antidiarrheal agents Antidiarrheal agents Antidiarrheal agents include several drug classes, including opioid agonists, somatostatin analogues, adsorbents, and bile acid sequestrants. These medications mainly work through antimotility and/or antisecretory effects. 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 Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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 Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. 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 Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea/steatorrhea, arthralgias, and abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of 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 Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine and is characterized by malabsorption of nutrients, especially folic acid, vitamin B12, carbohydrates Carbohydrates Carbohydrates are one of the 3 macronutrients, along with fats and proteins, serving as a source of energy to the body. These biomolecules store energy in the form of glycogen and starch, and play a role in defining the cellular structure (e.g., cellulose). Basics of 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 Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview (e.g., Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella, Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli, and Enterobacter) in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine eventually causes significant small bowel structural damage and chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea.
  • Bile acid malabsorption: diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea related to excessive bile acids entering the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix in some patients following cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy: Approaches and Technique may overcome the terminal ileum’s reabsorptive capacity. The increased bile acids in the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix that lead to diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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 Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation that can involve any part of the GI tract. The terminal ileum and proximal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix are usually affected. Crohn disease typically presents with intermittent, nonbloody diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and crampy abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Diagnosis is established via endoscopy with biopsy. Complications include malabsorption, malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries, intestinal obstruction or fistula, and an increased risk of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix 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 Chronic pancreatitis Chronic pancreatitis is due to persistent inflammation, fibrosis, and irreversible cell damage to the pancreas, resulting in a loss of endocrine and exocrine gland function. The most common etiologies are alcohol abuse and pancreatic duct obstruction. Patients often present with recurrent epigastric abdominal pain, nausea, and features of malabsorption syndrome (diarrhea, steatorrhea, and weight loss). 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 Short bowel syndrome Short bowel syndrome is a malabsorptive condition most commonly associated with extensive intestinal resection for etiologies such as Crohn's disease, bowel obstruction, trauma, radiation therapy, and vascular insufficiency. The short length of bowel results in insufficient surface area for fluid and electrolyte absorption. 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 Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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 Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and hypoalbuminemia, with or without diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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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