Diarrhea, Pseudomembrane Colitis, Irritable Bowel Syndrome

Diarrhea

The passage of abnormally frequent stools with increased fluidity, volume, or both, due to impaired intestinal absorption and/or increased intestinal secretion. Diarrhea is often defined more precisely as stool weight exceeding 200–250 g per day, or more than 3 loose or watery stools per day.

Duration-Based Classification:

• Acute diarrhea: < 14 days (often infectious)
• Persistent diarrhea: 14–30 days
• Chronic diarrhea: > 4 weeks (often inflammatory, :, or functional)

Diarrheal Diseases by Etiology

• Viral gastroenteritis (viral diarrheal diseases)
  • Rotavirus enteritis
  • Adenovirus enteritis
• Bacterial gastroenteritis (bacterial diarrheal diseases)
  • Campylobacter enteritis ( cause: Campylobacter jejuni )
  • Salmonella enteritis ( causative agent: Salmonella enteritidis , S. typhimurium )
  • Typhoid fever ( causative agent: Salmonella typhi )
  • Paratyphoid fever ( causative agent: Salmonella paratyphi )
  • Shigellosis ( cause: Shigella dysenteriae, flexneri, boydii, sonnei )
  • Cholera ( causative agent: Vibrio cholerae )
  • Infections caused by Escherichia coli
• Gastrointestinal parasitosis
  • protozoa : Toxoplasmosis ( causative agent: Toxoplasma gondii ), Toxocariasis ( Toxocara canis/cati ), Giardiasis ( Giardia lamblia ), Amoebiasis ( Entamoeba histolytica ), Cryptosporidiosis ( Cryptosporidium parvum )
  • nematodes : Ascariasis ( caused by: Ascaris lumbricoides or baby roundworm ), Trichuriasis ( Trichuris trichiura or human whipworm ), Trichinella spiralis , Enterobiosis ( Enterobius vermicularis ), Strongyloides stercoralis , Ancylostoma duodenale , Necator americanes , Dracunculus medinensis ,…
  • cestodes : Taeniasis ( causes: Taenia solium , Taenia saginata or the defenseless tapeworm ), Diphyllobothrium latum , ( Hymenolepis nana or the children's tapeworm ), Echinococcus granulosus ,…
• Enterotoxicosis – caused by enterotoxins .
• Drug-induced diarrhea

Patophysiology

• Changes in the intestinal mucosa (impaired resorption, digestion, secretion and motility) lead to excessive losses of water and electrolytes, mainly sodium and potassium, metabolic acidosis and subsequent dehydration.
• Two main pathophysiological mechanisms: osmotic and secretory diarrhea.

• Viruses directly damage intestinal villi and enterocyte brush border enzymes.
• The pathogenesis of rotavirus diarrhea combines osmotic and secretory diarrhea. Osmotic diarrhea causes villous destruction (cell lysis), NSP4-induced glucose malabsorption (SGLT-1 inhibition) and inflammation (NK-κB, IL-8). Secretory diarrhea arises from cell proliferation in the crypts (compensatory proliferation of secretory cells), NSP4-enterotoxin (increased intracellular calcium, chloride secretion), vascular ischemia (impaired microcirculation) and inflammation.
• Enteroinvasive bacteria ( Salmonella spp., Shigella spp., Campylobacter jejuni, enteroinvasive E. coli ) are the cause of ulcerations and inflammatory infiltration of the intestinal mucosa.
• Some bacteria (enterotoxigenic E. coli, staphylococcal enterotoxin) stimulate active secretion of ions and water into the intestinal lumen with their toxins (c-AMP, c-GMP).
• Non-invasive bacteria and parasites adhere to the mucosa and cause inflammatory infiltration.

Laboratory finding

• Acute diarrhea with weight loss below 5% with good oral fluid intake can only be treated on an outpatient basis without laboratory tests.
• In case of loss of over 5%, epidemic diarrhea and bloody stools, we indicate a thorough examination
• manifestations of hemoconcentration – increased Hb and hematocrit
• determination of sodium , potassium and chloride , osmolality , ABR
• picture of severe toxic enteritis – metabolic acidosis (mainly due to losses of bicarbonates through stool)
• oliguria occurs , often with proteinuria , serum urea and creatinine increase
• hyperglycemia occurs in hypernatremic dehydration (we do not treat this with insulin because there would be a risk of brain edema )

Diagnosis

• medical history (change in diet, epidemic occurrence, administration of antibiotics and other medications)
• information when evaluating stool :
  • secretory diarrhea (most often infectious) – watery, thin, often with fever
  • carbohydrate malabsorption – foamy, sour smelling, pH drop below 6
  • chronic nutritional disorders – bulky, oily, putrid smelling
  • colitis (often infections – Salmonella , Shigella , Yersinia, Campylobacter ) – mucus-bloody
• right at the beginning we must send the stool for microbiological examination (it must not be too thin, we do not need to cultivate pathogenic organisms in watery stools)
• stool smear – the presence of polymorphonuclear cells indicates a bacterial infection
• In chronic disorders, stool examination is positive for fats, carbohydrates, reducing substances, trypsin, proteins
• to rule out cystic fibrosis , we will examine chlorides in sweat
• Serology is not relevant for acute diarrhea, but is important for recurrent and chronic diarrhea.

Therapy

Most acute infectious gastroenteritis resolves spontaneously, therefore, in the vast majority of cases, antibiotic therapy is not indicated. Maintaining adequate hydration of the child is key. In case of reduced hydration, rapid oral replacement of water and electrolyte losses is important, possibly correction of metabolic acidosis, and subsequent maintenance of hydration and timely initiation of refeeding, which prevents further damage to the intestinal mucosa and thus the development of protracted gastroenteritis.

Rehydration

Oral (enteral) rehydration is the preferred treatment for dehydration, as it is as effective as intravenous rehydration but has fewer side effects and a shorter hospital stay.

Oral rehydration solutions (ORS):

• hypoosmolar, sodium content 60 mmol/l, composition according to ESPGHAN recommendations;
• e.g. Kulíšek®, Kulíšek forte®, HIPP ORS 200®, Vodníček Baby®, Vodníček Jahoda®, Enhydrol Banán® ;
• if the child is unable to drink the solution, it is administered via a nasogastric tube;
• The loss of fluids and ions is compensated for in a short period of time – depending on the degree of dehydration, 30–80 ml/kg within 4 hours.

Maintaining hydration:

• after correcting dehydration, the daily recommended volume of fluids is administered frequently and in small doses in the form of usual drinks (breast milk, infant formula, tea, mineral water, ...);
• hyperosmolar drinks such as juices or cola are not suitable;
• PRR is used to compensate for the accompanying fluid and ion losses due to diarrhea and vomiting – 10 ml PRR/kg and each stool, up to a maximum volume of 100–150 ml.

Recommended composition of glucose rehydration solution:

• 60 mmol/l Na, 20 mmol/l K, min. 25 mmol/l Cl, 10 mmol/l citrate, 74–111 mmol/l glc
• osmolality 200–250 mOsmol/l
• rice solution is similar – glucose is omitted and minerals are dissolved in the rice broth
• The rehydration solution is administered chilled to 4–8 °C by tea spoonfuls (5–10 ml of solution every 5–10 min or continuously via nasogastric tube)
• mild conditions (with a loss of up to 5%) can be treated on an outpatient basis (50–100 ml/kg is administered over 4 hours)
• moderately severe conditions require hospitalization
• in case of repeated vomiting or diarrhea, add the amount lost (according to weight, or calculate 50–100 ml per watery stool)
• after 4 hours we check hydration, if it has improved, we start timely re-alimentation
• during diarrhea, administer 10 ml of solution per kg and each watery stool
• It is fundamentally wrong to use juice or cola for rehydration – high osmolality and few ions

Drug treatment

Most acute gastroenteritis does not require medication. In the vast majority of cases, antibiotics are not indicated.

Indications for antibiotics:

• suspected or confirmed bacterial infection (esp. Salmonella enteritidis )
  • in infants under 3 months of age,
  • in premature children under 1 year of age,
  • in immunodeficient or immunosuppressed children,
  • with a current serious illness or malnutrition,
  • with signs of sepsis;
• severe campylobacter gastroenteritis ;
• severe Giardia lamblia infection ;
• infections with Vibrio cholerae , Shigella dysenteriae , Salmonella typhi , Entamoeba hystolytica , etc.

Antibiotic:

• the drug of choice is cotrimoxazole – for salmonella, shigella, yersinia, ETEC, EIEC – for about 7 days
  • For campylobacter we give erythromycin , for clostridium difficile we give vancomycin
  • Giardia and entamoeba are treated with metronidazole

Pharmacotherapy:

• antiemetics (for persistent vomiting): ondansetron;
• absorbency : smectite;
• drugs that reduce increased intestinal secretion in infectious acute gastroenteritis: racecadotril (does not affect intestinal motility);
• probiotics: strains Lactobacillus GG and Saccharomyces boulardii (according to ESPGHAN/ESPID recommendations).

Micronutrients, disinfectants, and motility-suppressing drugs are not indicated in developed countries.

Prevention: vaccination against rotavirus gastroenteritis

Pseudomembranous enterocolitis

Pseudomembranous enterocolitis (also referred to as CDAD – Clostridium difficile–associated diarrhea) is a serious, life-threatening complication in patients treated with broad-spectrum antibiotics. These antibiotics disrupt the normal intestinal microflora and lead to intestinal dysbiosis. From a pathogenetic perspective, toxins produced by Clostridium difficile play the central role.

Cause

The causative agent is the anaerobic Gram-positive rod Clostridium difficile, which can proliferate excessively after treatment with broad-spectrum antibiotics—especially clindamycin, cephalosporins, and aminopenicillins—and begins to produce enterotoxin A and cytotoxin B.

Toxin A

Toxin A induces accumulation of fluid within the intestinal epithelium of the host. This involves the buildup of a thick, viscous fluid of blood origin. As a result, epithelial cells become dysfunctional and are no longer able to adequately regulate water transport due to the excessive amount of viscous fluid inside the cells. Toxin A is considered the probable cause of diarrhea, which is the first symptom of pseudomembranous enterocolitis. It also exhibits strong chemotactic activity toward polymorphonuclear leukocytes (PMNs) and is therefore responsible for the inflammatory response of the intestinal epithelium. Toxin A is toxic to most immune system cells because it disrupts cytoskeletal components.

Toxin B

Toxin B does not exhibit enterotoxic activity but kills intestinal epithelial cells. It is approximately 100–1000 times more toxic than toxin A.

Destruction of intestinal mucosal cells occurs only when both toxins are present simultaneously. Toxin A damages the surface structures of intestinal mucosal cells and at the same time neutralizes the potential protective effect of PMNs. This enables toxin B molecules to successfully attack epithelial cells. Toxin B kills intestinal epithelial cells only when their surface structures are already damaged and when water transport dysfunction is present. Extensive ulcerations then develop in the intestinal mucosa—necrotic lesions known as pseudomembranes. These consist of conglomerates of destroyed epithelial cells, dead PMNs, fibrin, and mucin, forming cauliflower-like, yellowish crusts that can be relatively easily detected by endoscopy.

CDAD may also be caused by other antibiotics. It can develop after 5–10 days of treatment, but also several days after the end of therapy. After beta-lactam antibiotics it occurs in up to 15% of patients, and after clindamycin in up to 25%. In most cases, the disease resolves after discontinuation of antibiotic therapy.

Clinical presentation

Signs of pseudomembranous enterocolitis include:

• severe inflammatory ulcerations of the intestinal mucosa, with mortality rates that may reach up to 45%;
• sudden onset of frequent watery diarrhea with dehydration;
• nausea, abdominal pain, often fever and leukocytosis;
• only mild elevation of C-reactive protein (CRP);
• foul-smelling stool containing mucus fragments and blood;
• in progressive cases, shock and death.

Diagnosis

Accurate diagnosis is based on two main criteria:

• Endoscopy – whitish or yellowish pseudomembranes in the colon with a tendency to coalesce (ulcers typical of bacillary or amoebic dysentery or ulcerative colitis are usually absent).
• Detection of clostridial toxin – performed using ELISA from a stool sample.

Polymerase chain reaction (PCR) is also used to increase diagnostic sensitivity.

Therapy

Basic management includes discontinuation of the current antibiotic therapy and oral administration of vancomycin (which acts only locally, as its bioavailability after oral administration is minimal). A newer selective therapy is provided by the macrolide antibiotic fidaxomicin; its main disadvantage is its high cost.

Oral metronidazole is no longer recommended due to globally decreasing sensitivity and insufficient concentrations of the drug in the distal segments of the colon.

In cases of severe colitis with intestinal paralysis, oral vancomycin is combined with intravenous metronidazole or tigecycline. In fulminant colitis, surgical treatment may be required (subtotal colectomy with terminal ileostomy).

Antimotility agents are not administered due to the risk of toxic megacolon; diarrhea represents the body’s attempt to eliminate the pathogen. The benefit of probiotics has not been proven in treatment. In cases of recurrence, fecal bacteriotherapy (fecal microbiota transplantation, FMT) is used successfully—administration of homogenized donor stool into the patient’s intestine via a nasogastric tube or enema.

Irritable Bowel Syndrome

Irriatble bowel syndrome is characterized as pain or discomfort that lasts for at least 12 weeks in the previous year and that:

1. they ease or disappear after defecation;
2. are associated with a change in the frequency and/or character of stools.

• The diagnosis of irritable bowel syndrome is further supported by feelings of urgency to defecate, a feeling of incomplete emptying, passage of mucus, bloating and distension of the abdomen; the symptoms usually do not awaken patients from sleep.
• The etiopathogenesis is the same as that of upper functional dyspepsia

Clinical picture

• Abdominal pain and discomfort, constipation, diarrhea, feeling of incomplete emptying.
• Alarming symptoms and risk factors are:

1. age over 50 years ( colorectal cancer ),
2. temperature,
3. weight loss,
4. blood or pus in the stool,
5. steatorhea,
6. dehydration .

Diagnostics

• By exclusion (in the differential diagnosis, primarily exclude colorectal cancer, diverticular disease of the colon, IBD (Inflammatory Bowel Disease ) , intestinal infections).
• History, physical examination, laboratory examination (as in upper dyspepsia) + stool examination ( OK , culture, parasitology), imaging techniques ( US ).
• Colonoscopy is not indicated, but it has a positive effect in terms of calming the cancer-phobic patient.

Treatment

1. If diarrhea predominates – a lactose-exclusion test, antidiarrheal drugs , and the addition of soluble fiber.
2. If constipation predominates - dietary measures (sufficient hydration, soluble fiber, defecation stereotypes), sometimes laxatives must be administered .
3. Painful symptomatology – spasmolytics (pinaverine…).

• The administration of antidiarrheals and laxatives should be carefully considered and possible adverse effects monitored.