Materiały źródłowe

• #1 Diarrhea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/928598-overview

  Diarrhea is the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. The augmented water content in the stools (above the normal value of approximately 10 mL/kg/d in the infant and young child, or 200 g/d in the teenager and adult) is due to an imbalance in the physiology of the small and large intestinal processes involved in the absorption of ions, organic substrates, and thus water. […] Such a derangement can be the result of either an osmotic force that acts in the lumen to drive water into the gut or the result of an active secretory state induced in the enterocytes. In the former case, diarrhea is osmolar in nature, as is observed after the ingestion of nonabsorbable sugars such as lactulose or lactose in lactose malabsorbers. Instead, in the typical active secretory state, enhanced anion secretion (mostly by the crypt cell compartment) is best exemplified by enterotoxin-induced diarrhea.

• #2 Four variants of the pathogenesis of diarrhea and its therapy – Parfenov – Terapevticheskii arkhiv

  https://ter-arkhiv.ru/0040-3660/article/view/31858

  Diarrhea is a symptom of many diseases; its pathogenesis is associated with four main mechanisms: water and electrolyte secretion into the intestinal lumen, osmolarity of the chyme, exudation, and impaired intestinal motility. […] The clinical manifestations, diagnosis, and therapy of bowel diseases are discussed in terms of the pathogenesis of diarrhea.

• #3 Pathophysiology of Diarrhea and Its Clinical Implications | Abdominal Key

  https://abdominalkey.com/pathophysiology-of-diarrhea-and-its-clinical-implications/

  In the gastrointestinal tract, ionic balance, fluid absorption, and secretion are vital to maintain homeostasis allowing for the maintenance of a membrane potential, adequate nutrient intake, normal gut motility, protection against microbes, and epithelial cell viability. […] Different pathophysiological mechanisms causing diarrhea, mainly secretory, osmotic, inflammatory, altered intestinal transit and loss of functional absorptive area, have been elucidated. […] In certain pathophysiologic states, the finely tuned ionic-fluid exchange becomes dysfunctional as a result of the failure of compensatory pro-absorptive/antisecretory mechanisms. The excessive secretion of sodium and chloride ions followed by the release of a large amount of water into the colonic lumen results in diarrhea. […] The mechanisms in this type of diarrhea include activation of intracellular mediators such as cAMP, cGMP, and intracellular calcium, which stimulate active chloride secretion from crypt cells and inhibit neutral coupled sodium chloride absorption.

• #4 Pathophysiology of Diarrhea

  https://vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/diarrhea.html

  Diarrhea is an increase in the volume of stool or frequency of defecation. […] There are numerous causes of diarrhea, but in almost all cases, this disorder is a manifestation of one of the four basic mechanisms described below. […] A distinguishing feature of osmotic diarrhea is that it stops after the patient is fasted or stops consuming the poorly absorbed solute. […] Diarrhea occurs when secretion of water into the intestinal lumen exceeds absorption. […] Many millions of people have died of the secretory diarrhea associated with cholera. […] Exposure to toxins from several other types of bacteria induce the same series of steps and massive secretory diarrhea that is often lethal unless the person or animal is aggressively treated to maintain hydration. […] Disruption of the epithelium of the intestine due to microbial or viral pathogens is a very common cause of diarrhea in all species. […] The immune response to inflammatory conditions in the bowel contributes substantively to development of diarrhea. […] Disorders in motility than accelerate transit time could decrease absorption, resulting in diarrhea even if the absorptive process per se was proceeding properly.

• #5 GI Intervention: Approach to Diagnosis & Therapy of the Patient With Acute Diarrhea | Today’s Veterinary Practice

  https://todaysveterinarypractice.com/gastroenterology/gi-intervention-approach-to-diagnosis-and-therapy-of-the-patient-with-acute-diarrhea/

  Stimulation of crypt enterocytes results in secretion of large volumes of fluid that exceeds the absorptive ability of the intestine. This occurs most commonly with infectious diseases, such as enteropathogenic Escherichia coli and salmonellosis, but is also a mechanism of diarrhea related to inflammatory bowel disease (IBD). […] Increased permeability of the intestinal mucosa causes loss of fluids, electrolytes, proteins, and blood into the intestinal lumen. It commonly accompanies erosive, ulcerative, neoplastic (intestinal lymphoma), and inflammatory processes, such as IBD and hookworm infection. […] Deranged motility is often secondary to disorders that cause diarrhea. Decreased segmental contractions result in transport of ingesta at a rate too fast for normal digestion and absorption.

• #6 Pathophysiology of Diarrhea and Its Clinical Implications | Abdominal Key

  https://abdominalkey.com/pathophysiology-of-diarrhea-and-its-clinical-implications/

  In the gastrointestinal tract, ionic balance, fluid absorption, and secretion are vital to maintain homeostasis allowing for the maintenance of a membrane potential, adequate nutrient intake, normal gut motility, protection against microbes, and epithelial cell viability. […] Different pathophysiological mechanisms causing diarrhea, mainly secretory, osmotic, inflammatory, altered intestinal transit and loss of functional absorptive area, have been elucidated. […] In certain pathophysiologic states, the finely tuned ionic-fluid exchange becomes dysfunctional as a result of the failure of compensatory pro-absorptive/antisecretory mechanisms. The excessive secretion of sodium and chloride ions followed by the release of a large amount of water into the colonic lumen results in diarrhea. […] The mechanisms in this type of diarrhea include activation of intracellular mediators such as cAMP, cGMP, and intracellular calcium, which stimulate active chloride secretion from crypt cells and inhibit neutral coupled sodium chloride absorption.

• #7 Mechanisms of infectious diarrhea | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/ncpgasthep1264

  Infectious diarrhea is a global health problem and can be classified, based on the pathogenesis and clinical presentation, as noninflammatory diarrhea or inflammatory diarrhea. […] Enterotoxigenic Escherichia coli and Vibrio cholerae infections cause ADP ribosylation of Gs protein, whereas heat-stable enterotoxin-producing E. coli stimulate cGMP production; both E. coli and V. cholerae increase chloride secretion by crypt cells to produce watery diarrhea. […] Cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators; invasive organisms, which can also secrete cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction and activate cytokines and inflammatory mediators.

• #8

  https://journals.lww.com/eurojgh/fulltext/2006/10000/pathogenesis_of_diarrhea_in_the_adult__diagnostic.3.aspx

  Studies of how certain microbes can induce diarrhea at the molecular level has contributed greatly to our understanding of the mechanisms of ion transport and fluid exchange in the gut. […] A variety of bacterial pathogens can induce secretory diarrhea and inflammatory diarrhea. […] It is clear that diverse pathogens utilize different mechanisms to cause intestinal disease, which include alteration in ion transport, disruption of tight junctions, and acute inflammatory responses. […] The heat-labile and cholera enterotoxins produced by E. coli and V. cholerae, respectively, increase the level of intracellular second messengers (e.g. cAMP and cGMP), which then activate the lumenal CFTR, resulting in the overstimulation of the secretory pathway. […] Cholera toxin and several other toxins produced by V. cholerae increase the permeability of tight junctions and stimulate Ca2+-dependent secretion.

• #9 Diarrhea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/928598-overview

  In osmotic diarrhea, stool output is proportional to the intake of the unabsorbable substrate and is usually not massive; diarrheal stools promptly regress with discontinuation of the offending nutrient, and the stool ion gap is high, exceeding 100 mOsm/kg. […] In secretory diarrhea, the epithelial cells ion transport processes are turned into a state of active secretion. The most common cause of acute-onset secretory diarrhea is a bacterial infection of the gut. Several mechanisms may be at work. After colonization, enteric pathogens may adhere to or invade the epithelium; they may produce enterotoxins (exotoxins that elicit secretion by increasing an intracellular second messenger) or cytotoxins. They may also trigger release of cytokines attracting inflammatory cells, which, in turn, contribute to the activated secretion by inducing the release of agents such as prostaglandins or platelet-activating factor. Features of secretory diarrhea include a high purging rate, a lack of response to fasting, and a normal stool ion gap (ie, 100 mOsm/kg or less), indicating that nutrient absorption is intact.

• #10 Diarrhea – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/symptoms-of-gastrointestinal-disorders/diarrhea

  Diarrhea occurs when unabsorbable, water-soluble solutes remain in the bowel and retain water. Such solutes include polyethylene glycol, magnesium salts (hydroxide and sulfate), and sodium phosphate, which are used as laxatives. Osmotic diarrhea occurs with sugar intolerance (eg, lactose intolerance caused by lactase deficiency). Ingesting large amounts of hexitols (eg, sorbitol, mannitol, xylitol) or high fructose corn syrups, which are used as sugar substitutes in candy, gum, and fruit juices, causes osmotic diarrhea because hexitols are poorly absorbed. Lactulose, which is used as a laxative, causes diarrhea by a similar mechanism. Overingesting certain foodstuffs can cause osmotic diarrhea. […] Diarrhea occurs when the bowels secrete more electrolytes and water than they absorb. Causes of increased secretions include infections, unabsorbed fats, certain medications, and various intrinsic and extrinsic secretagogues.

• #11 Diarrhea – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/symptoms-of-gastrointestinal-disorders/diarrhea

  Diarrhea occurs when unabsorbable, water-soluble solutes remain in the bowel and retain water. Such solutes include polyethylene glycol, magnesium salts (hydroxide and sulfate), and sodium phosphate, which are used as laxatives. Osmotic diarrhea occurs with sugar intolerance (eg, lactose intolerance caused by lactase deficiency). Ingesting large amounts of hexitols (eg, sorbitol, mannitol, xylitol) or high fructose corn syrups, which are used as sugar substitutes in candy, gum, and fruit juices, causes osmotic diarrhea because hexitols are poorly absorbed. Lactulose, which is used as a laxative, causes diarrhea by a similar mechanism. Overingesting certain foodstuffs can cause osmotic diarrhea. […] Diarrhea occurs when the bowels secrete more electrolytes and water than they absorb. Causes of increased secretions include infections, unabsorbed fats, certain medications, and various intrinsic and extrinsic secretagogues.

• #12 Diarrhea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/928598-overview

  In osmotic diarrhea, stool output is proportional to the intake of the unabsorbable substrate and is usually not massive; diarrheal stools promptly regress with discontinuation of the offending nutrient, and the stool ion gap is high, exceeding 100 mOsm/kg. […] In secretory diarrhea, the epithelial cells ion transport processes are turned into a state of active secretion. The most common cause of acute-onset secretory diarrhea is a bacterial infection of the gut. Several mechanisms may be at work. After colonization, enteric pathogens may adhere to or invade the epithelium; they may produce enterotoxins (exotoxins that elicit secretion by increasing an intracellular second messenger) or cytotoxins. They may also trigger release of cytokines attracting inflammatory cells, which, in turn, contribute to the activated secretion by inducing the release of agents such as prostaglandins or platelet-activating factor. Features of secretory diarrhea include a high purging rate, a lack of response to fasting, and a normal stool ion gap (ie, 100 mOsm/kg or less), indicating that nutrient absorption is intact.

• #13 Diarrhea – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/symptoms-of-gastrointestinal-disorders/diarrhea

  Infections (eg, gastroenteritis) are the most common causes of secretory diarrhea. Infections combined with food poisoning are the most common causes of acute diarrhea. Most enterotoxins block sodium-potassium exchange, which is an important driving force for fluid absorption in the small bowel and colon. […] Rapid intestinal transit and diminished surface area impair fluid absorption and cause diarrhea. Common causes include small-bowel or large-bowel resection or bypass, gastric resection, and inflammatory bowel disease. Other causes include microscopic colitis and celiac disease. Hyperthyroidism may cause diarrhea due to rapid transit. […] The stool osmotic gap, which is calculated 290 2 (stool sodium + stool potassium), indicates whether diarrhea is secretory or osmotic. An osmotic gap 50 mEq/L indicates secretory diarrhea; a larger gap suggests osmotic diarrhea. Patients with osmotic diarrhea may have covert magnesium laxative ingestion or carbohydrate malabsorption.

• #14 Mechanisms of infectious diarrhea | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/ncpgasthep1264

  Infectious diarrhea is an important public health problem worldwide. Research has provided new insights into the mechanisms of diarrhea caused by various pathogens that are classified as noninflammatory, inflammatory or invasive. These three groups of organisms cause two diarrheal syndromesnoninflammatory diarrhea and inflammatory diarrhea. The noninflammatory diarrheas are caused by enterotoxin-producing organisms such as Vibrio cholerae and enterotoxigenic Escherichia coli, or by viruses that adhere to the mucosa and disrupt the absorptive and/or secretory processes of the enterocyte without causing acute inflammation or mucosal destruction. […] Inflammatory diarrhea is caused by two groups of organismscytotoxin-producing, noninvasive bacteria (e.g. enteroaggregative Escherichia coli, enterohemorrhagic Escherichia coli and Clostridium difficile), or by invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp., Entamoeba histolytica). The cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators. Invasive organisms, which can also produce cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction, involving the activation of cytokines and inflammatory mediators. Regardless of the underlying mechanism they use, these various types of pathogen have all successfully evolved to evade and modulate the host defense systems. The mechanisms by which the different pathogens invade the host and cause infectious diarrhea are the topic of this Review.

• #15 Mechanisms of infectious diarrhea | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/ncpgasthep1264

  Infectious diarrhea is an important public health problem worldwide. Research has provided new insights into the mechanisms of diarrhea caused by various pathogens that are classified as noninflammatory, inflammatory or invasive. These three groups of organisms cause two diarrheal syndromesnoninflammatory diarrhea and inflammatory diarrhea. The noninflammatory diarrheas are caused by enterotoxin-producing organisms such as Vibrio cholerae and enterotoxigenic Escherichia coli, or by viruses that adhere to the mucosa and disrupt the absorptive and/or secretory processes of the enterocyte without causing acute inflammation or mucosal destruction. […] Inflammatory diarrhea is caused by two groups of organismscytotoxin-producing, noninvasive bacteria (e.g. enteroaggregative Escherichia coli, enterohemorrhagic Escherichia coli and Clostridium difficile), or by invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp., Entamoeba histolytica). The cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators. Invasive organisms, which can also produce cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction, involving the activation of cytokines and inflammatory mediators. Regardless of the underlying mechanism they use, these various types of pathogen have all successfully evolved to evade and modulate the host defense systems. The mechanisms by which the different pathogens invade the host and cause infectious diarrhea are the topic of this Review.

• #16 Pathophysiology of Diarrhea and Its Clinical Implications | Abdominal Key

  https://abdominalkey.com/pathophysiology-of-diarrhea-and-its-clinical-implications/

  Loss of resorptive area, destruction of epithelial cells, leaky tight junctions, and release of inflammatory mediators and products from immune cells that stimulate fluid secretion all have been implicated in the pathogenesis of inflammatory diarrhea. […] Diarrhea can result from an increased intestinal motility leading to a reduced intestinal transit time and poor absorption of water and substrates. […] Diarrhea results when mucosal injury or resection is such that the absorptive capacity of the intestine is diminished or overwhelmed.

• #17 Antibiotic-Associated Diarrhea Beyond C. Difficile: A Scoping Review | Published in Journal of Brown Hospital Medicine

  https://bhm.scholasticahq.com/article/39745-antibiotic-associated-diarrhea-beyond-c-difficile-a-scoping-review

  The two main toxins of C. difficile, toxins A and B play a critical role in the pathophysiology of CDI. Both are enterotoxic and cytotoxic; however, traditionally toxin A is named enterotoxin A and toxin B is named cytotoxin B. […] Although C. difficile is implicated in most AAD cases, other causes of Non-C. difficile Pathogen-specific AAD should also be considered. […] The role of Candida spp. in AAD has been debated since the 1950s and continues to be controversial. […] Only 40% of AAD can be accounted for by the above causes leaving a majority of AAD cases without an etiology.

• #18 Infectious diarrhea

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3035144/

  The pathogenic process of C. difficile infection starts with initial colonization followed by the production of two distinct exotoxins, Toxin A and B (TcdA and TcdB), as well as an additional toxin called binary toxin (CDT) which is found in some hypervirulent strains of C. difficile. […] The C. difficile toxins initiate an extensive inflammatory cascade that causes increased damage to host tissues resulting in fluid exudation. […] The overall picture of E. histolytica infection depends both on parasite components, including cysteine proteases, amoebapores, serotonin and PGE2 as well as the host inflammatory response with no single component providing a complete answer.

• #19 Pathophysiology of Diarrhea and Its Clinical Implications | Abdominal Key

  https://abdominalkey.com/pathophysiology-of-diarrhea-and-its-clinical-implications/

  Loss of resorptive area, destruction of epithelial cells, leaky tight junctions, and release of inflammatory mediators and products from immune cells that stimulate fluid secretion all have been implicated in the pathogenesis of inflammatory diarrhea. […] Diarrhea can result from an increased intestinal motility leading to a reduced intestinal transit time and poor absorption of water and substrates. […] Diarrhea results when mucosal injury or resection is such that the absorptive capacity of the intestine is diminished or overwhelmed.

• #20 GI Intervention: Approach to Diagnosis & Therapy of the Patient With Acute Diarrhea | Today’s Veterinary Practice

  https://todaysveterinarypractice.com/gastroenterology/gi-intervention-approach-to-diagnosis-and-therapy-of-the-patient-with-acute-diarrhea/

  Stimulation of crypt enterocytes results in secretion of large volumes of fluid that exceeds the absorptive ability of the intestine. This occurs most commonly with infectious diseases, such as enteropathogenic Escherichia coli and salmonellosis, but is also a mechanism of diarrhea related to inflammatory bowel disease (IBD). […] Increased permeability of the intestinal mucosa causes loss of fluids, electrolytes, proteins, and blood into the intestinal lumen. It commonly accompanies erosive, ulcerative, neoplastic (intestinal lymphoma), and inflammatory processes, such as IBD and hookworm infection. […] Deranged motility is often secondary to disorders that cause diarrhea. Decreased segmental contractions result in transport of ingesta at a rate too fast for normal digestion and absorption.

• #21 Pathophysiology of Diarrhea

  https://vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/diarrhea.html

  Diarrhea is an increase in the volume of stool or frequency of defecation. […] There are numerous causes of diarrhea, but in almost all cases, this disorder is a manifestation of one of the four basic mechanisms described below. […] A distinguishing feature of osmotic diarrhea is that it stops after the patient is fasted or stops consuming the poorly absorbed solute. […] Diarrhea occurs when secretion of water into the intestinal lumen exceeds absorption. […] Many millions of people have died of the secretory diarrhea associated with cholera. […] Exposure to toxins from several other types of bacteria induce the same series of steps and massive secretory diarrhea that is often lethal unless the person or animal is aggressively treated to maintain hydration. […] Disruption of the epithelium of the intestine due to microbial or viral pathogens is a very common cause of diarrhea in all species. […] The immune response to inflammatory conditions in the bowel contributes substantively to development of diarrhea. […] Disorders in motility than accelerate transit time could decrease absorption, resulting in diarrhea even if the absorptive process per se was proceeding properly.

• #22 Diarrhea – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/symptoms-of-gastrointestinal-disorders/diarrhea

  Infections (eg, gastroenteritis) are the most common causes of secretory diarrhea. Infections combined with food poisoning are the most common causes of acute diarrhea. Most enterotoxins block sodium-potassium exchange, which is an important driving force for fluid absorption in the small bowel and colon. […] Rapid intestinal transit and diminished surface area impair fluid absorption and cause diarrhea. Common causes include small-bowel or large-bowel resection or bypass, gastric resection, and inflammatory bowel disease. Other causes include microscopic colitis and celiac disease. Hyperthyroidism may cause diarrhea due to rapid transit. […] The stool osmotic gap, which is calculated 290 2 (stool sodium + stool potassium), indicates whether diarrhea is secretory or osmotic. An osmotic gap 50 mEq/L indicates secretory diarrhea; a larger gap suggests osmotic diarrhea. Patients with osmotic diarrhea may have covert magnesium laxative ingestion or carbohydrate malabsorption.

• #23 Pathophysiology of Diarrhea and Its Clinical Implications | Abdominal Key

  https://abdominalkey.com/pathophysiology-of-diarrhea-and-its-clinical-implications/

  Loss of resorptive area, destruction of epithelial cells, leaky tight junctions, and release of inflammatory mediators and products from immune cells that stimulate fluid secretion all have been implicated in the pathogenesis of inflammatory diarrhea. […] Diarrhea can result from an increased intestinal motility leading to a reduced intestinal transit time and poor absorption of water and substrates. […] Diarrhea results when mucosal injury or resection is such that the absorptive capacity of the intestine is diminished or overwhelmed.

• #24 Diarrhea – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/symptoms-of-gastrointestinal-disorders/diarrhea

  Infections (eg, gastroenteritis) are the most common causes of secretory diarrhea. Infections combined with food poisoning are the most common causes of acute diarrhea. Most enterotoxins block sodium-potassium exchange, which is an important driving force for fluid absorption in the small bowel and colon. […] Rapid intestinal transit and diminished surface area impair fluid absorption and cause diarrhea. Common causes include small-bowel or large-bowel resection or bypass, gastric resection, and inflammatory bowel disease. Other causes include microscopic colitis and celiac disease. Hyperthyroidism may cause diarrhea due to rapid transit. […] The stool osmotic gap, which is calculated 290 2 (stool sodium + stool potassium), indicates whether diarrhea is secretory or osmotic. An osmotic gap 50 mEq/L indicates secretory diarrhea; a larger gap suggests osmotic diarrhea. Patients with osmotic diarrhea may have covert magnesium laxative ingestion or carbohydrate malabsorption.

• #25 Diarrhea in Neonatal Ruminants – Digestive System – MSD Veterinary Manual

  https://www.msdvetmanual.com/digestive-system/intestinal-diseases-in-ruminants/diarrhea-in-neonatal-ruminants

  Diarrhea in neonatal ruminants is usually associated with disease of the small intestine and can be caused by hypersecretion or malabsorption. […] Hypersecretory diarrhea develops when an abnormal amount of fluid is secreted into the gut, exceeding the resorptive capacity of the mucosa. In malabsorptive diarrhea, the capacity of the mucosa to absorb fluid and nutrients is impaired to the extent that it cannot keep up with the normal influx of ingested and secreted fluids. This is usually the result of villous atrophy, in which the loss of mature enterocytes at the tips of the villi results both in a decrease in villous height (with a consequent decrease in the surface area for absorption) and in loss of the brush border digestive enzymes. The extent and distribution of villous atrophy varies with different pathogens and can explain variation in the severity of clinical disease.

• #26 Mechanisms of infectious diarrhea | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/ncpgasthep1264

  Infectious diarrhea is an important public health problem worldwide. Research has provided new insights into the mechanisms of diarrhea caused by various pathogens that are classified as noninflammatory, inflammatory or invasive. These three groups of organisms cause two diarrheal syndromesnoninflammatory diarrhea and inflammatory diarrhea. The noninflammatory diarrheas are caused by enterotoxin-producing organisms such as Vibrio cholerae and enterotoxigenic Escherichia coli, or by viruses that adhere to the mucosa and disrupt the absorptive and/or secretory processes of the enterocyte without causing acute inflammation or mucosal destruction. […] Inflammatory diarrhea is caused by two groups of organismscytotoxin-producing, noninvasive bacteria (e.g. enteroaggregative Escherichia coli, enterohemorrhagic Escherichia coli and Clostridium difficile), or by invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp., Entamoeba histolytica). The cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators. Invasive organisms, which can also produce cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction, involving the activation of cytokines and inflammatory mediators. Regardless of the underlying mechanism they use, these various types of pathogen have all successfully evolved to evade and modulate the host defense systems. The mechanisms by which the different pathogens invade the host and cause infectious diarrhea are the topic of this Review.

• #27 Pathophysiology of diarrhea | PPT

  https://www.slideshare.net/slideshow/pathophysiology-of-diarrhea/28129951

  1) The document discusses the pathophysiology of diarrhea including the 6 main mechanisms: secretory, osmotic, decreased motility, infection, decreased surface area, and mucosal invasion. […] 3) Mechanisms of Diarrhea 6 mechanisms explain pathophysiology of diarrhea More than 1 mechanism may present at the same time […] 10) Primary Mechanism Defect Decreased motility Defect in neuromuscular unit(s) […] 11) Primary Mechanism Defect Decreased Decreased surface area functional (osmotic, capacity motility) Mucosal invasion Inflammation, decreased colonic reabsorption, increased motility […] 12) Major Causes of Diarrheal Illnesses: Secretory Infectious: Diarrhea 1.Rotavirus 2.Caliciviruses 3.Enteric adenoviruses 4.Astroviruses Infectious: endotoxin mediated 1.Vibrio cholera 2.Escherichia coli 3.Bacillus cereus 4.Clostridium perfringens

• #28 Mechanisms of infectious diarrhea | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/ncpgasthep1264

  Infectious diarrhea is an important public health problem worldwide. Research has provided new insights into the mechanisms of diarrhea caused by various pathogens that are classified as noninflammatory, inflammatory or invasive. These three groups of organisms cause two diarrheal syndromesnoninflammatory diarrhea and inflammatory diarrhea. The noninflammatory diarrheas are caused by enterotoxin-producing organisms such as Vibrio cholerae and enterotoxigenic Escherichia coli, or by viruses that adhere to the mucosa and disrupt the absorptive and/or secretory processes of the enterocyte without causing acute inflammation or mucosal destruction. […] Inflammatory diarrhea is caused by two groups of organismscytotoxin-producing, noninvasive bacteria (e.g. enteroaggregative Escherichia coli, enterohemorrhagic Escherichia coli and Clostridium difficile), or by invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp., Entamoeba histolytica). The cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators. Invasive organisms, which can also produce cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction, involving the activation of cytokines and inflammatory mediators. Regardless of the underlying mechanism they use, these various types of pathogen have all successfully evolved to evade and modulate the host defense systems. The mechanisms by which the different pathogens invade the host and cause infectious diarrhea are the topic of this Review.

• #29 Pathophysiology of diarrhea | PPT

  https://www.slideshare.net/slideshow/pathophysiology-of-diarrhea/28129951

  19) Specific Causes of Infectious Diarrhea: VIRAL CAUSES: Rotavirus: Mostly during winter months Primary infection in infancy moderate to severe illness Reinfection in adolescent mild illness MOA: invade upper small intestine May extend throughout small intestine and colon villous damage, secondary transient disaccharide deficiency inflammation of lamina propria […] 23) Oral Rehydration Therapy: The cheapest way to treat diarrhea to prevent dehydration Adequate glucose-electrolyte solution WHO recommendation: ORT + guidance on appropriate feeding practices main strategy to achieve reduction in diarrhea related morbidity and mortality […] 26) Why reduced osmolarity ORS? Pharmacokinetics and therapeutics values Glucose facilitates absorption of sodium (hence water) on 1:1 molar basis in small intestine Sodium potassium are needed to replace body loss in diarrhea Citrate corrects acidosis that may occur as results of diarrhea and dehydration.

• #30 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20231211/Study-reveals-new-mechanism-by-which-rotavirus-induces-diarrhea.aspx

  Rotavirus causes gastroenteritis, a condition that includes diarrhea, deficient nutrient absorption and weight loss. Severe cases result in approximately 128,000 deaths annually in infants and children worldwide. […] in this new study researchers at Baylor College of Medicine report a new mechanism by which rotavirus induces diarrhea, interfering with the normal absorption of nutrients in the intestine. […] The study, published in Proceedings of the National Academy of Sciences, is the first to show that rotavirus-altered lipid metabolism in the intestine plays a role in the disease. Rotavirus infection leads to the degradation of DGAT1, an enzyme involved in normal lipid droplet formation in intestinal cells, which in turn reduces the production of key nutrient transporters and other proteins required for normal intestinal nutrient absorption, leading to diarrhea.

• #31 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20231211/Study-reveals-new-mechanism-by-which-rotavirus-induces-diarrhea.aspx

  „But we found a new mechanism by which rotavirus induces diarrhea. Like the children who have a genetic DGAT1 deficiency that causes diarrhea, when rotavirus degrades DGAT1 the result is reduced production of the enzymes that are involved in degrading the food we eat and disruption of the mechanisms that transport nutrients into cells, which leads to diarrhea,” Smith said. […] „It was very surprising that a rotavirus protein that until now was only known to be important for the virus to replicate, also plays a role in causing diarrhea, a major component of the disease.”

• #32

  https://www.jci.org/articles/view/18326

  Diarrhea resulting from overstimulation of the intestinal tracts secretory capacity can develop in pure form (e.g., cholera) or as a component of a more complex disease process (e.g., celiac disease, Crohn disease). […] A number of secretory stimuli can cause diarrhea. These include bacterial enterotoxins, hormones generated by endocrine neoplasms, dihydroxy bile acids, hydroxylated fatty acids, and inflammatory mediators. […] Enteric infection with enterotoxin-producing bacteria […] The sequence of events, summarized in Figure 5, seems to be as follows. The enterotoxins attach to endocrine (enterochromaffin) cells on the villus surface of the intestinal epithelium, causing an increase of cAMP or cGMP. […] Common bacterial causes of enteritis and/or colitis are Shigella, Salmonella, Yersinia, enteroinvasive E. coli, Aeromonas, and Campylobacter. […] Diarrhea accompanied by rectal incontinence is an occasional complication of long-standing, insulin-dependent diabetes. […] Inflammatory mediators such as prostaglandins stimulate colonic secretion, contributing to diarrhea.

• #33

  https://journals.lww.com/eurojgh/fulltext/2006/10000/pathogenesis_of_diarrhea_in_the_adult__diagnostic.3.aspx

  Studies of how certain microbes can induce diarrhea at the molecular level has contributed greatly to our understanding of the mechanisms of ion transport and fluid exchange in the gut. […] A variety of bacterial pathogens can induce secretory diarrhea and inflammatory diarrhea. […] It is clear that diverse pathogens utilize different mechanisms to cause intestinal disease, which include alteration in ion transport, disruption of tight junctions, and acute inflammatory responses. […] The heat-labile and cholera enterotoxins produced by E. coli and V. cholerae, respectively, increase the level of intracellular second messengers (e.g. cAMP and cGMP), which then activate the lumenal CFTR, resulting in the overstimulation of the secretory pathway. […] Cholera toxin and several other toxins produced by V. cholerae increase the permeability of tight junctions and stimulate Ca2+-dependent secretion.

• #34 How Salmonella Bacteria Cause Diarrhea In Their Host | ScienceDaily

  https://www.sciencedaily.com/releases/2009/09/090911205127.htm

  Salmonella bacteria are cunning when it comes to triggering diarrhoea in their host. Researchers have succeeded in explaining a molecular mechanism that enables the bacteria to activate their host cells non-specific immune response, thus making the host ill. A single virulence factor is sufficient to allow the bacteria to trigger disease. […] The bacteria inject the protein molecule into an intestinal epithelium cell, where it triggers a cascade of signals inside the cell. SopE tampers with two specific GTPases called Cdc42 and Rac1. […] However, Hardt and his research group have now shown that Cdc42 and Rac1 are also a part of the cells early warning system. This system is indispensable for a rapid, non-specific defence against disease pathogens. […] The perfidiousness of SopE is that the bacteria tamper with, of all things, a communication system which a cell cannot simply replace or switch off, because otherwise the non-specific immune response would fail to happen or the cells skeleton would be paralysed. […] Consequently diarrhoea is the lesser of the two evils.

• #35 E. coli – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/e-coli/symptoms-causes/syc-20372058

  Escherichia coli (E. coli) bacteria normally live in the intestines of healthy people and animals. Most types of E. coli are harmless or cause relatively brief diarrhea. But a few strains, such as E. coli O157:H7, can cause severe stomach cramps, bloody diarrhea and vomiting. […] Only a few strains of E. coli trigger diarrhea. The E. coli O157:H7 strain belongs to a group of E. coli that produces a powerful toxin that damages the lining of the small intestine. This can cause bloody diarrhea. You develop an E. coli infection when you ingest this strain of bacteria. […] Dr. Nipunie Rajapakse says E. coli bacteria can create some stomach-turning symptoms, like abdominal pain and nausea. But it can get even worse. […] „There’s a specific type of E. coli. It’s called O157:H7, which can cause bloody diarrhea and has been associated with a condition that can cause kidney damage, especially in young children.”

• #36 Clostridioides (formerly Clostridium) difficile–Induced Diarrhea – Infectious Diseases – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridioides-formerly-clostridium-difficile-induced-diarrhea

  Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. […] The organism secretes both an enterotoxin and a cytotoxin, typically referred to as toxins A and B. However, not all strains of C. difficile produce toxins, and some people are asymptomatic carriers of toxin-producing strains. The main effect of the toxin is on the colon, which secretes fluid and develops characteristic pseudomembranes discrete yellow-white plaques that are easily dislodged. […] Antibiotic-induced changes in gastrointestinal flora are the dominant predisposing factors. Although most antibiotics have been implicated, the following pose the highest risk: Cephalosporins (particularly 3rd-generation), Penicillins (particularly ampicillin and amoxicillin), Clindamycin, Fluoroquinolones.

• #37 Clostridioides (formerly Clostridium) difficile–Induced Diarrhea – Infectious Diseases – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridioides-formerly-clostridium-difficile-induced-diarrhea

  Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. […] The organism secretes both an enterotoxin and a cytotoxin, typically referred to as toxins A and B. However, not all strains of C. difficile produce toxins, and some people are asymptomatic carriers of toxin-producing strains. The main effect of the toxin is on the colon, which secretes fluid and develops characteristic pseudomembranes discrete yellow-white plaques that are easily dislodged. […] Antibiotic-induced changes in gastrointestinal flora are the dominant predisposing factors. Although most antibiotics have been implicated, the following pose the highest risk: Cephalosporins (particularly 3rd-generation), Penicillins (particularly ampicillin and amoxicillin), Clindamycin, Fluoroquinolones.

• #38 Post-Travel Diarrhea | Yellow Book | CDC

  https://www.cdc.gov/yellow-book/hcp/post-travel-evaluation/post-travel-diarrhea.html

  While individual bacterial infections rarely cause persistent symptoms, travelers infected with bacteria known to cause mucosal inflammation, such as Campylobacter spp., Shigella spp., or Salmonella spp., as well as diarrheagenic Escherichia coli, can experience persistent diarrhea, including cases where the organism may be resistant against antibiotics commonly used for empiric treatment of TD. […] Clostridioides difficile-associated diarrhea can occur after or during antibiotic use, including malaria chemoprophylaxis. The association between C. difficile and antimicrobial treatment is especially important to consider in patients with persistent TD that seems refractory to multiple courses of empiric antibiotic therapy. […] As a group, parasites are the pathogens most likely to be isolated from patients with persistent diarrhea. Most parasitic infections have a less acute onset of symptoms than those caused by bacteria or viruses, and the probability of a traveler having a parasitic infection increases with increasing duration of symptoms.

• #39 Infectious diarrhea

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3035144/

  The pathogenic process of C. difficile infection starts with initial colonization followed by the production of two distinct exotoxins, Toxin A and B (TcdA and TcdB), as well as an additional toxin called binary toxin (CDT) which is found in some hypervirulent strains of C. difficile. […] The C. difficile toxins initiate an extensive inflammatory cascade that causes increased damage to host tissues resulting in fluid exudation. […] The overall picture of E. histolytica infection depends both on parasite components, including cysteine proteases, amoebapores, serotonin and PGE2 as well as the host inflammatory response with no single component providing a complete answer.

• #40 Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine

  https://www.mdpi.com/1422-0067/25/3/1544

  Patients with BAD exhibit enhanced colonic transit, heightened intestinal or colonic mucosal permeability, and an altered composition of the stool microbiome associated with diminished conversion of primary to secondary bile acids. […] The Farnesoid X receptor (FXR) plays a crucial role in regulating bile acid metabolism. Under normal physiological conditions, bile acids are reabsorbed within the ileum and activate the FXR signaling pathway, thereby significantly promoting fibroblast growth factor 19 (FGF19) biosynthesis. […] Decreased secretion levels of FGF19 from ileal cells lead to attenuated suppression of CYP7A1 activity resulting in elevated endogenous production of bile acids. Consequently, inadequate absorption capacity for excessive amounts of these compounds within the small intestinal tract may contribute to diarrheal symptoms.

• #41 Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine

  https://www.mdpi.com/1422-0067/25/3/1544

  Activation of FXR modulates free fatty acid (FFA) oxidation and enhances triglyceride clearance. […] FGF19, synthesized by ileal enterocytes in response to bile acids binding to FXR, interacts with fibroblast growth factor receptor 4 (FGFR4) expressed on hepatocyte cell membranes. […] The pathogenesis of BAD involves disruptions in the bile acid pathways, resulting in excessive delivery of primary bile acids to the colon. Takeda G protein–coupled receptor 5 (TGR5), also known as G protein-coupled bile acid receptor 1 (GPBAR1), is expressed on enteric nerves and enterochromaffin cells, and its activation can regulate motility in the small intestine and colon. […] Patients with BAD exhibit increased intestinal permeability and an altered gut microbiome, characterized by significantly lower microbial diversity and a distinct stool bacterial composition compared to patients without BAD.

• #42 Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine

  https://www.mdpi.com/1422-0067/25/3/1544

  Patients with BAD exhibit enhanced colonic transit, heightened intestinal or colonic mucosal permeability, and an altered composition of the stool microbiome associated with diminished conversion of primary to secondary bile acids. […] The Farnesoid X receptor (FXR) plays a crucial role in regulating bile acid metabolism. Under normal physiological conditions, bile acids are reabsorbed within the ileum and activate the FXR signaling pathway, thereby significantly promoting fibroblast growth factor 19 (FGF19) biosynthesis. […] Decreased secretion levels of FGF19 from ileal cells lead to attenuated suppression of CYP7A1 activity resulting in elevated endogenous production of bile acids. Consequently, inadequate absorption capacity for excessive amounts of these compounds within the small intestinal tract may contribute to diarrheal symptoms.

• #43 Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine

  https://www.mdpi.com/1422-0067/25/3/1544

  Activation of FXR modulates free fatty acid (FFA) oxidation and enhances triglyceride clearance. […] FGF19, synthesized by ileal enterocytes in response to bile acids binding to FXR, interacts with fibroblast growth factor receptor 4 (FGFR4) expressed on hepatocyte cell membranes. […] The pathogenesis of BAD involves disruptions in the bile acid pathways, resulting in excessive delivery of primary bile acids to the colon. Takeda G protein–coupled receptor 5 (TGR5), also known as G protein-coupled bile acid receptor 1 (GPBAR1), is expressed on enteric nerves and enterochromaffin cells, and its activation can regulate motility in the small intestine and colon. […] Patients with BAD exhibit increased intestinal permeability and an altered gut microbiome, characterized by significantly lower microbial diversity and a distinct stool bacterial composition compared to patients without BAD.

• #44 Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine

  https://www.mdpi.com/1422-0067/25/3/1544

  Activation of FXR modulates free fatty acid (FFA) oxidation and enhances triglyceride clearance. […] FGF19, synthesized by ileal enterocytes in response to bile acids binding to FXR, interacts with fibroblast growth factor receptor 4 (FGFR4) expressed on hepatocyte cell membranes. […] The pathogenesis of BAD involves disruptions in the bile acid pathways, resulting in excessive delivery of primary bile acids to the colon. Takeda G protein–coupled receptor 5 (TGR5), also known as G protein-coupled bile acid receptor 1 (GPBAR1), is expressed on enteric nerves and enterochromaffin cells, and its activation can regulate motility in the small intestine and colon. […] Patients with BAD exhibit increased intestinal permeability and an altered gut microbiome, characterized by significantly lower microbial diversity and a distinct stool bacterial composition compared to patients without BAD.

• #45

  https://journals.lww.com/eurojgh/fulltext/2006/10000/pathogenesis_of_diarrhea_in_the_adult__diagnostic.3.aspx

  Several pathogens are known to cause chronic diarrhea. […] The inflamed mucosa of patients with ulcerative colitis is very leaky to all monovalent ions because mucosal inflammation down-regulates expression of the Cl/HCO3 exchanger, impairs the Na+/H+ exchanger, and is associated with pro-inflammatory-mediated decreases in expression of Na+ channel subunits. […] The resultant increase in intercellular permeability also contributes to the chronic diarrhea associated with this disease. […] Of particular interest to the field of inflammatory bowel disease is the ability of bile acids to interact with the colonic epithelial cells to cause secretory diarrhea. […] TDOC increases electrogenic Cl secretion into the proximal colonic lumen. […] The etiology of chronic diarrhea needs to be methodically ascertained, and may represent a diagnostic challenge for both gastroenterologists and primary care physicians.

• #46 Pathophysiology of Diarrhea and Its Clinical Implications | Abdominal Key

  https://abdominalkey.com/pathophysiology-of-diarrhea-and-its-clinical-implications/

  In the gastrointestinal tract, ionic balance, fluid absorption, and secretion are vital to maintain homeostasis allowing for the maintenance of a membrane potential, adequate nutrient intake, normal gut motility, protection against microbes, and epithelial cell viability. […] Different pathophysiological mechanisms causing diarrhea, mainly secretory, osmotic, inflammatory, altered intestinal transit and loss of functional absorptive area, have been elucidated. […] In certain pathophysiologic states, the finely tuned ionic-fluid exchange becomes dysfunctional as a result of the failure of compensatory pro-absorptive/antisecretory mechanisms. The excessive secretion of sodium and chloride ions followed by the release of a large amount of water into the colonic lumen results in diarrhea. […] The mechanisms in this type of diarrhea include activation of intracellular mediators such as cAMP, cGMP, and intracellular calcium, which stimulate active chloride secretion from crypt cells and inhibit neutral coupled sodium chloride absorption.

• #47

  https://www.jci.org/articles/view/107002

  Using a triple-lumen constant perfusion system, we have studied ileal electrolyte transport in a patient with congenital alkalosis with diarrhea and made the following observations. First, chloride cannot be transported against electrochemical gradients, but can be readily absorbed or secreted down electrochemical gradients. Second, chloride secretion down an electrochemical gradient can be increased by raising lumen bicarbonate concentration. Third, sodium absorption does occur against electrochemical gradients and is associated with hydrogen ion secretion. Fourth, electrical potential difference (PD) between lumen and blood is near zero when lumen sodium concentration is 140 mEq/liter. Fifth, a normal sodium diffusion potential is present. Sixth, potassium is transported passively in response to electrochemical gradients.

• #48 Diarrhea Starts with Inflammatory Signal, Ends with Pathogen Clearance

  https://www.genengnews.com/news/diarrhea-starts-with-inflammatory-signal-ends-with-pathogen-clearance/

  Diarrhea may serve as a host defense mechanism when it is driven by an immune mechanism in which interleukin-22 upregulates claudin-2 and promotes pathogen clearance. […] Diarrhea is a purge with a purpose, insists a team of scientists at Brigham and Women’s Hospital (BWH). In support of this assertion, the scientists point to a new finding—at diarrhea’s base there is an immune mechanism that causes paracellular loosening. This mechanism, the scientists add, appears to promote pathogen clearance and limit disease severity. […] Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. […] Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance.

• #49 Diarrhea Starts with Inflammatory Signal, Ends with Pathogen Clearance

  https://www.genengnews.com/news/diarrhea-starts-with-inflammatory-signal-ends-with-pathogen-clearance/

  Diarrhea may serve as a host defense mechanism when it is driven by an immune mechanism in which interleukin-22 upregulates claudin-2 and promotes pathogen clearance. […] Diarrhea is a purge with a purpose, insists a team of scientists at Brigham and Women’s Hospital (BWH). In support of this assertion, the scientists point to a new finding—at diarrhea’s base there is an immune mechanism that causes paracellular loosening. This mechanism, the scientists add, appears to promote pathogen clearance and limit disease severity. […] Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. […] Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance.

• #50 Diarrhea Starts with Inflammatory Signal, Ends with Pathogen Clearance

  https://www.genengnews.com/news/diarrhea-starts-with-inflammatory-signal-ends-with-pathogen-clearance/

  Diarrhea may serve as a host defense mechanism when it is driven by an immune mechanism in which interleukin-22 upregulates claudin-2 and promotes pathogen clearance. […] Diarrhea is a purge with a purpose, insists a team of scientists at Brigham and Women’s Hospital (BWH). In support of this assertion, the scientists point to a new finding—at diarrhea’s base there is an immune mechanism that causes paracellular loosening. This mechanism, the scientists add, appears to promote pathogen clearance and limit disease severity. […] Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. […] Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance.

• #51 Pathophysiology of Diarrhea

  https://vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/diarrhea.html

  Diarrhea is an increase in the volume of stool or frequency of defecation. […] There are numerous causes of diarrhea, but in almost all cases, this disorder is a manifestation of one of the four basic mechanisms described below. […] A distinguishing feature of osmotic diarrhea is that it stops after the patient is fasted or stops consuming the poorly absorbed solute. […] Diarrhea occurs when secretion of water into the intestinal lumen exceeds absorption. […] Many millions of people have died of the secretory diarrhea associated with cholera. […] Exposure to toxins from several other types of bacteria induce the same series of steps and massive secretory diarrhea that is often lethal unless the person or animal is aggressively treated to maintain hydration. […] Disruption of the epithelium of the intestine due to microbial or viral pathogens is a very common cause of diarrhea in all species. […] The immune response to inflammatory conditions in the bowel contributes substantively to development of diarrhea. […] Disorders in motility than accelerate transit time could decrease absorption, resulting in diarrhea even if the absorptive process per se was proceeding properly.

• #52

  https://www.jci.org/articles/view/18326

  Diarrhea resulting from overstimulation of the intestinal tracts secretory capacity can develop in pure form (e.g., cholera) or as a component of a more complex disease process (e.g., celiac disease, Crohn disease). […] A number of secretory stimuli can cause diarrhea. These include bacterial enterotoxins, hormones generated by endocrine neoplasms, dihydroxy bile acids, hydroxylated fatty acids, and inflammatory mediators. […] Enteric infection with enterotoxin-producing bacteria […] The sequence of events, summarized in Figure 5, seems to be as follows. The enterotoxins attach to endocrine (enterochromaffin) cells on the villus surface of the intestinal epithelium, causing an increase of cAMP or cGMP. […] Common bacterial causes of enteritis and/or colitis are Shigella, Salmonella, Yersinia, enteroinvasive E. coli, Aeromonas, and Campylobacter. […] Diarrhea accompanied by rectal incontinence is an occasional complication of long-standing, insulin-dependent diabetes. […] Inflammatory mediators such as prostaglandins stimulate colonic secretion, contributing to diarrhea.

• #53 Antibiotic-Associated Diarrhea Beyond C. Difficile: A Scoping Review | Published in Journal of Brown Hospital Medicine

  https://bhm.scholasticahq.com/article/39745-antibiotic-associated-diarrhea-beyond-c-difficile-a-scoping-review

  A common complication of antibiotic use is the development of diarrheal illness. The pathogenesis of antibiotic associated diarrhea (AAD) may be mediated through alteration of intestinal microbiota, overgrowth of opportunistic pathogens, and direct drug toxicity on the gut. […] The likely pathogenesis of AAD includes alteration of intestinal microbiota, direct drug toxicity on the gut and development of a superinfection by a pathogenic microbe. […] Although the role of C. difficile in the pathogenesis of AAD has been well studied, there are considerable gaps in our understanding of the pathogenesis of non-CDI AAD due to putative microbial etiologies including C. perfringens, S. aureus, K. oxytoca, and Candida species. Identifying the etiology and understanding the pathogenesis of AAD will help in improving healthcare and in reducing the economic burden.

• #54 Antibiotic-Associated Diarrhea – Harvard Health

  https://www.health.harvard.edu/a_to_z/antibiotic-associated-diarrhea-a-to-z

  In healthy people, many different species of bacteria live inside the bowel. Many are harmless or even helpful to the body, but a few have the potential to be aggressive troublemakers. Under normal circumstances, the „bad” bacteria are far outnumbered. So, the bowel’s natural ecological balance keeps them under control. […] This can change dramatically when a person begins treatment with an antibiotic. This is because antibiotics can kill large numbers of the bowel’s normal bacteria, altering the delicate balance among the various species. […] One type of bacteria in particular, a species called Clostridium difficile (C. difficile), can overgrow inside the bowel, producing irritating chemicals that damage the bowel wall and trigger bowel inflammation, called colitis. This can cause abdominal pain, cramps, diarrhea, and fever. In some cases, high-volume, diarrhea is so frequent that the person develops dehydration (very low levels of body water).

• #55 Antibiotic-Associated Diarrhea – Harvard Health

  https://www.health.harvard.edu/a_to_z/antibiotic-associated-diarrhea-a-to-z

  In healthy people, many different species of bacteria live inside the bowel. Many are harmless or even helpful to the body, but a few have the potential to be aggressive troublemakers. Under normal circumstances, the „bad” bacteria are far outnumbered. So, the bowel’s natural ecological balance keeps them under control. […] This can change dramatically when a person begins treatment with an antibiotic. This is because antibiotics can kill large numbers of the bowel’s normal bacteria, altering the delicate balance among the various species. […] One type of bacteria in particular, a species called Clostridium difficile (C. difficile), can overgrow inside the bowel, producing irritating chemicals that damage the bowel wall and trigger bowel inflammation, called colitis. This can cause abdominal pain, cramps, diarrhea, and fever. In some cases, high-volume, diarrhea is so frequent that the person develops dehydration (very low levels of body water).

• #56 Antibiotic-Associated Diarrhea – Harvard Health

  https://www.health.harvard.edu/a_to_z/antibiotic-associated-diarrhea-a-to-z

  In healthy people, many different species of bacteria live inside the bowel. Many are harmless or even helpful to the body, but a few have the potential to be aggressive troublemakers. Under normal circumstances, the „bad” bacteria are far outnumbered. So, the bowel’s natural ecological balance keeps them under control. […] This can change dramatically when a person begins treatment with an antibiotic. This is because antibiotics can kill large numbers of the bowel’s normal bacteria, altering the delicate balance among the various species. […] One type of bacteria in particular, a species called Clostridium difficile (C. difficile), can overgrow inside the bowel, producing irritating chemicals that damage the bowel wall and trigger bowel inflammation, called colitis. This can cause abdominal pain, cramps, diarrhea, and fever. In some cases, high-volume, diarrhea is so frequent that the person develops dehydration (very low levels of body water).

• #57 Antibiotic-Associated Diarrhea Beyond C. Difficile: A Scoping Review | Published in Journal of Brown Hospital Medicine

  https://bhm.scholasticahq.com/article/39745-antibiotic-associated-diarrhea-beyond-c-difficile-a-scoping-review

  A common complication of antibiotic use is the development of diarrheal illness. The pathogenesis of antibiotic associated diarrhea (AAD) may be mediated through alteration of intestinal microbiota, overgrowth of opportunistic pathogens, and direct drug toxicity on the gut. […] The likely pathogenesis of AAD includes alteration of intestinal microbiota, direct drug toxicity on the gut and development of a superinfection by a pathogenic microbe. […] Although the role of C. difficile in the pathogenesis of AAD has been well studied, there are considerable gaps in our understanding of the pathogenesis of non-CDI AAD due to putative microbial etiologies including C. perfringens, S. aureus, K. oxytoca, and Candida species. Identifying the etiology and understanding the pathogenesis of AAD will help in improving healthcare and in reducing the economic burden.

• #58 Travelers’ Diarrhea | Yellow Book | CDC

  https://www.cdc.gov/yellow-book/hcp/preparing-international-travelers/travelers-diarrhea.html

  An acute (less than 2 weeks) bout of TD can lead to persistent enteric symptoms, even in the absence of continued infection. This presentation is commonly referred to as post-infectious irritable bowel syndrome. […] Prophylactic antibiotics afford no protection against nonbacterial pathogens and can remove normally protective microflora from the bowel, increasing the risk for acquisition of resistant bacterial pathogens. […] Antibiotics are effective in reducing the duration of diarrhea by approximately 12 days in cases caused by bacterial pathogens susceptible to the antibiotic prescribed. However, concerns about the adverse consequences of using antibiotics to treat TD remain.

• #59 Post-Travel Diarrhea | Yellow Book | CDC

  https://www.cdc.gov/yellow-book/hcp/post-travel-evaluation/post-travel-diarrhea.html

  In some cases, persistent symptoms relate to chronic underlying GI disease or to a susceptibility unmasked by the enteric infection. Most prominent among these is celiac disease, a systemic disease manifesting primarily with small bowel changes. […] In some patients who present with persistent GI symptoms, healthcare professionals will not find a specific cause. After an acute diarrheal infection, patients might experience a temporary enteropathy characterized by villous atrophy, decreased absorptive surface area, and disaccharidase deficiencies, which can lead to osmotic diarrhea, particularly after consuming large amounts of fructose, lactose, sorbitol, or sucrose.

• #60 Post-Travel Diarrhea | Yellow Book | CDC

  https://www.cdc.gov/yellow-book/hcp/post-travel-evaluation/post-travel-diarrhea.html

  In some cases, persistent symptoms relate to chronic underlying GI disease or to a susceptibility unmasked by the enteric infection. Most prominent among these is celiac disease, a systemic disease manifesting primarily with small bowel changes. […] In some patients who present with persistent GI symptoms, healthcare professionals will not find a specific cause. After an acute diarrheal infection, patients might experience a temporary enteropathy characterized by villous atrophy, decreased absorptive surface area, and disaccharidase deficiencies, which can lead to osmotic diarrhea, particularly after consuming large amounts of fructose, lactose, sorbitol, or sucrose.

• #61 What Is Diarrhea & Your Digestive System | IMODIUM®

  https://www.imodium.com/diarrhea-treatment/what-is-diarrhea

  Diarrhea is considered the event of passing watery, loose stools 3 or more times in a day. […] When the cells in your small intestine or colon are irritated, the relaxed and regular movement of your intestines can become overactive. Essential salts and fluids, as well as nutrients from the food that you eat, end up being passed through the colon too quickly. With less fluid being absorbed by the body, the result is loose or watery stools, which is more commonly known as diarrhea. […] Persistent or chronic diarrhea can lead to malnutrition, abdominal pain, and weight loss. Some of the signs you should look out for are sudden weight loss, blood in the stools or sleepless nights due to constant restroom visits. Malabsorption syndromes in which food cannot be digested and absorbed are common causes of chronic diarrhea. Some other prevalent causes include inflammatory bowel disease (Crohn disease and ulcerative colitis) and irritable bowel syndrome (IBS). […] IMODIUM helps restore the guts natural rhythm, enabling it to start absorbing fluids, salts, and nutrients as it normally would.

• #62 GI Intervention: Approach to Diagnosis & Therapy of the Patient With Acute Diarrhea | Today’s Veterinary Practice

  https://todaysveterinarypractice.com/gastroenterology/gi-intervention-approach-to-diagnosis-and-therapy-of-the-patient-with-acute-diarrhea/

  There is mounting evidence that changes in microbial populations play an important role in pathogenesis of acute and chronic enteropathies of dogs. In a recent study, dogs with acute diarrhea, especially those with acute hemorrhagic diarrhea, had the most profound alterations in their fecal microbiome compared to healthy dogs, and observed changes differed between acute and chronic disease states. […] Hemorrhagic gastroenteritis (HGE) is a diarrheal syndrome of unknown etiology that has a predilection for small breed dogs; it has not been reported in cats. Speculation regarding pathogenesis includes type-1 hypersensitivity reaction to food components, CPE, and C difficile toxins A/B.

• #63 On the Pathogenesis of Post-Transplant Diarrhea in Kidney Transplant Recipients. – ATC Abstracts

  https://atcmeetingabstracts.com/abstract/on-the-pathogenesis-of-post-transplant-diarrhea-in-kidney-transplant-recipients/

  On the Pathogenesis of Post-Transplant Diarrhea in Kidney Transplant Recipients. […] Post-transplant diarrhea is a frequent complication after kidney transplantation but its etiology is unknown in the majority of cases; herein, we investigated whether post-transplant diarrhea is associated with gut microbial dysbiosis. […] Shannon diversity index was significantly lower in the Diarrhea Cohort than the No Diarrhea Cohort (mean 3.00.7 vs. 3.60.5, P0.001, Wilcoxon rank sum test). At the genus level, 13 commensal genera were significantly lower in the Diarrhea Cohort than the No Diarrhea Cohort (q value0.15, Benjamini-Hochberg correction). […] Our identification of lower abundance of commensal bacteria and associated impaired metabolism represent plausible pathways for post-transplant diarrhea, which supports future studies targeting the gut microbiota to prevent and/or treat post-transplant diarrhea.

• #64 Diarrhea: Causes, treatment, and symptoms

  https://www.medicalnewstoday.com/articles/158634

  Two potentially serious complications of diarrhea are dehydration (in cases of severe and frequent diarrhea) and malabsorption (in cases of chronic diarrhea). […] Diarrhea can also indicate a wide range of underlying chronic conditions. Diagnosis and treatment can help prevent further problems. […] Most cases of diarrhea resolve without treatment, and a doctor will often be able to diagnose the problem without the use of tests. […] However, in more severe cases, a stool test may be necessary especially if the symptoms persist for longer than a week. […] If a person has chronic or persistent diarrhea, the doctor will order tests according to the suspected cause. […] Diarrhea is a common problem with many potential causes.

• #65 Pathophysiology of diarrhea | PPT

  https://www.slideshare.net/slideshow/pathophysiology-of-diarrhea/28129951

  19) Specific Causes of Infectious Diarrhea: VIRAL CAUSES: Rotavirus: Mostly during winter months Primary infection in infancy moderate to severe illness Reinfection in adolescent mild illness MOA: invade upper small intestine May extend throughout small intestine and colon villous damage, secondary transient disaccharide deficiency inflammation of lamina propria […] 23) Oral Rehydration Therapy: The cheapest way to treat diarrhea to prevent dehydration Adequate glucose-electrolyte solution WHO recommendation: ORT + guidance on appropriate feeding practices main strategy to achieve reduction in diarrhea related morbidity and mortality […] 26) Why reduced osmolarity ORS? Pharmacokinetics and therapeutics values Glucose facilitates absorption of sodium (hence water) on 1:1 molar basis in small intestine Sodium potassium are needed to replace body loss in diarrhea Citrate corrects acidosis that may occur as results of diarrhea and dehydration.

• #66 What Is Diarrhea & Your Digestive System | IMODIUM®

  https://www.imodium.com/diarrhea-treatment/what-is-diarrhea

  Diarrhea is considered the event of passing watery, loose stools 3 or more times in a day. […] When the cells in your small intestine or colon are irritated, the relaxed and regular movement of your intestines can become overactive. Essential salts and fluids, as well as nutrients from the food that you eat, end up being passed through the colon too quickly. With less fluid being absorbed by the body, the result is loose or watery stools, which is more commonly known as diarrhea. […] Persistent or chronic diarrhea can lead to malnutrition, abdominal pain, and weight loss. Some of the signs you should look out for are sudden weight loss, blood in the stools or sleepless nights due to constant restroom visits. Malabsorption syndromes in which food cannot be digested and absorbed are common causes of chronic diarrhea. Some other prevalent causes include inflammatory bowel disease (Crohn disease and ulcerative colitis) and irritable bowel syndrome (IBS). […] IMODIUM helps restore the guts natural rhythm, enabling it to start absorbing fluids, salts, and nutrients as it normally would.

• #67 Clostridioides (formerly Clostridium) difficile–Induced Diarrhea – Infectious Diseases – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridioides-formerly-clostridium-difficile-induced-diarrhea

  C. difficile induced colitis may also follow use of certain antineoplastic medications. […] Toxic megacolon, which rarely develops, is somewhat more likely after use of antimotility medications. Limited tissue dissemination occurs very rarely, as do sepsis and acute abdomen. […] Symptoms of C. difficile induced diarrhea typically begin 5 to 10 days after starting antibiotics but may occur on the first day or up to 2 months later. […] Glutamate dehydrogenase (GDH) antigen is produced by all C. difficile strains. […] A nucleic acid amplification test (NAAT) using PCR to test for the toxin gene is very sensitive for toxigenic strains but cannot tell whether they are actively producing toxin. […] If possibly causative antibiotics are being used, they should be stopped as soon as possible, or patients should be switched to an antibiotic regimen less likely to cause C. difficile induced diarrhea.

• #68 Clostridioides (formerly Clostridium) difficile–Induced Diarrhea – Infectious Diseases – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridioides-formerly-clostridium-difficile-induced-diarrhea

  Antibiotic therapy can cause intestinal overgrowth of toxin-secreting C. difficile, resulting in a pseudomembranous colitis that can be severe and difficult to cure. […] Diagnose using a stool assay for C. difficile antigen and toxin and sometimes PCR testing for the toxin gene. […] Treat with oral fidaxomicin or vancomycin. […] Recurrence is common; re-treat with antibiotics, and consider fecal transplantation or bezlotoxumab for refractory recurrences.

• #69 The Pathogenesis of Infectious Diarrhea | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4613-1789-0_19

  During the past decade much has been learned about the events that convert a peaceful state of coexistence between microbes and the gut into a diarrheal illness. […] Research into the pathogenesis of infectious diarrhea has been concerned with several aspects of the problemthe events leading to colonization of the intestine by pathogens and their attachment to or invasion of the intestinal wall, the mechanisms by which intestinal water and solute transport is distorted, leading to diarrhea, and finally, the factors that regulate shedding of offending organisms and repair of the damaged intestine. […] The effective application of new basic pathophysiology concepts to the care of patients with diarrhea has been widely publicized. […] Treatment programs based on modern concepts of diarrhea pathogenesis have led to a dramatic reduction in mortality and morbidity in many Third-World countries. […] Perhaps because of a lesser level of concern over the problem, physicians in developed countries have been relatively slow to take up these rational approaches to treatment.

• #70 Why we get diarrhea | ScienceDaily

  https://www.sciencedaily.com/releases/2017/06/170614121040.htm

  Investigators explore the immune mechanism that drives diarrhea, concluding that it plays a critical role in pathogen clearance in the early stages of infection. […] The hypothesis that diarrhea clears intestinal pathogens has been debated for centuries. […] We sought to define the role of diarrhea and to see if preventing it might actually delay pathogen clearance and prolong disease. […] They conclude that diarrhea is critical to enteric pathogen clearance, and that IL-22 may play a key role in host defense.

• #71 Diarrhea Starts with Inflammatory Signal, Ends with Pathogen Clearance

  https://www.genengnews.com/news/diarrhea-starts-with-inflammatory-signal-ends-with-pathogen-clearance/

  Diarrhea may serve as a host defense mechanism when it is driven by an immune mechanism in which interleukin-22 upregulates claudin-2 and promotes pathogen clearance. […] Diarrhea is a purge with a purpose, insists a team of scientists at Brigham and Women’s Hospital (BWH). In support of this assertion, the scientists point to a new finding—at diarrhea’s base there is an immune mechanism that causes paracellular loosening. This mechanism, the scientists add, appears to promote pathogen clearance and limit disease severity. […] Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. […] Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance.

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