Approximately half of the world's population suffers from diarrhea at least once a year. Hence, besides influenza infections, diarrhea belongs to the most common illness symptoms. The causes of diarrhea are varied and range from infections with bacteria to tumor diseases. It is important to distinguish between acute, usually not requiring treatment, and chronic, or longer lasting, diarrhea, which can lead to death due to water and electrolyte loss, especially in weakened patients and children.
Are you more of a visual learner? Check out our online video lectures and start your pathology course now for free!

diarhhoe

Image: “All Ready to Go” by Anne Worner. License: CC BY-SA 2.0


Definition

Diarrhea is defined as a stool frequency of more than 3 stools per day, which have a high water content of over 75 % and an increased stool weight, about 250 g. The acute diarrhea usually lasts two to three days, and the reason is infections or intoxication. Prolonged diarrhea is chronic and can be caused by food intolerance, inflammatory bowel disease or tumors.

Classification

Classification according to the emergence of diarrhea

Diarrhea form Pathomechanism Possible Causes
Secretory diarroea The mucosa of the intestine releases active water or electrolytes from where water follows osmotically Chronic inflammatory bowel disease, food poisoning, intake of laxatives
Osmotic diarrhea Unabsorbed, osmotically active molecules, such as food ingredients or medicines pull water into the intestinal lumen Lactose intolerance, celiac disease, laxatives, sorbitol
Exudative diarrhea Inflammations of the intestinal mucosa lead to the accumulation of stool with mucus and blood Chronic inflammatory bowel diseases, bacterial / parasitic infections, colon Ca
Hypermotile diarrhea An increased intestinal motility leads to a reduced transit time of the stool, such that not enough water can be withdrawn Irritable bowel syndrome, hyperthyroidism, diabetic polyneuropathy
Steatorrhea Decreased amount of enzymes and bile acids leads to insufficient digestion and absorption of fats Exocrine pancreatic insufficiency, condition after cholecystectomy

Etiology

Food poisoning as a cause of diarrhea

Foodstuff can have a toxic effect on the human body for various reasons. The most common triggers of food poisoning are caused by toxins produced by bacteria, but even heavy metals such as lead or toxic chemicals can be present in the food and lead to poisoning with symptoms such as diarrhea.

Food poisoning with bacterial toxins

soft serve can be the cause of diarhhoea

soft serve can be the cause of diarrhea

The disease occurs due to the intake of bacterial toxins, the multiplication of bacteria itself is no trigger. In Germany, in most cases there is a contamination of food with staphylococcus aureus. One reason can be a lack of hand hygiene in the preparation of food. The bacteria are indeed killed by cooking, but not the enterotoxins they release. A very rapid onset of symptoms, about 30 minutes to 2 hours after eating, and an equally short duration of diarrhea symptoms are characteristic. Classically, several people are affected at the same time. Even bacillus and clostridia species can form enterotoxins and cause similar symptoms.

Other food poisonings

Other triggers of food intoxication include toxic metals such as arsenic, lead, zinc and antimony. Even fungal toxins such as muscarinic (fly agaric) and amatoxin (amanita phalloides) lead to diarrhea, amongst other symptoms. Saxitoxins, which can be accumulated in steamed mussels and oysters, lead to a disease pattern that is called paralytic shellfish poisoning which results in nausea with vomiting and diarrhea with abdominal cramps.

Food Borne Infections

In food borne infections, pathogenic germs are absorbed by the food, and the microorganisms multiply in the intestine. Even these often produce toxins, which is why there can be no clear separation of the food poisoning here.

Salmonellosis

Etiology of salmonellosis

The salmonella enteritis is caused by the consumption of contaminated drinking water or infectious food as result of insufficient hygiene. The pathogen is salmonella enteritidis, however out of the more than 2,600 known salmonella serotypes, another 30 pathogens are gastroenteritis pathogens. In 2004, a new subspecies called salmonella choleraesuis was discovered, which is very resistant against antibiotics and more frequently results in the death of patients.

Different animals can be carriers of the salmonella pathogen, such as poultry, swine and reptiles; thus many foods such as eggs, meat, milk and mussels can be contaminated with salmonella. Even in case of an adequate hygiene by the slaughter staff, who is the chronic carrier of salmonella, salmonella enteritidis can be transferred to the meat. In countries with inadequate treatment of water, the feces of infected animals can contaminate the drinking water and thus serve as a source of infection.

Symptoms of salmonella enteritis

In most cases, infection occurs in the warm season, especially among children and the elderly people. It is a matter of invasive gastroenteritis. Typical symptoms of salmonella enteritis are vomiting and diarrhea after an incubation period of a few hours up to seven days. Patients also develop a spasmodic abdominal pain. The duration of the disease is generally only for a few days.

Diagnosis of Salmonellosis

Salmonella species growing on XLD agar

Image: “Salmonella species growing on XLD agar” by Nathan Reading. License: CC BY 2.0

Appropriate investigation material is stool and vomit. Onoz- and Xylose Lysine Desoxycholate Agar in the culture serve as differentiation media. The classification in subtypes is based on the O-antigens and is useful for epidemiological investigations.

Note: The MUCAP test is a quick test for salmonella diagnosis. Salmonella have a C8-esterase. A substrate is contained in the MUCAP reagent, which is cleaved by the C8-esterase and thus releases a fluorescent dye.

A salmonellosis disease is notifiable under the Infection Protection Act.

Treatment and prophylaxis of salmonellosis

There should be no antibiotic treatment, since this leads to an extension of the bacterial elimination. In only about 5 % of the patients it comes to systemic infection with fever and massive fluid loss, such that hospitalization becomes necessary. Ciproflaxin and ampicillin are then suitable for children.

A small percentage of the patients do not completely eliminate the salmonella, such that they are asymptomatic chronic carriers for a long time and receive a prohibition of employment on activities involving food handling.

The prophylactic measures include cooking of poultry meat and eggs, as well as the strict separation of cutlery and cutting boards which are used before and after cooking, in order to avoid cross-contamination.

Typhoid Fever

Etiology of typhoid

Salmonella typhi also usually spreads by unsanitary conditions during the preparation of food and beverages. Thus, it leads to infections among Europeans, especially in long-distance travel to Africa, Southeast Asia and Latin America.

Disease pattern of the typhoid fever

The course of the disease can be divided into three stages. The incubation period varies, with 10 days being average.

  1. Stadium incrementi during the 1st week after infection: It results in unspecific general symptoms like headache, fatigue, constipation and a staircase-shaped increase in fever.
  2. Stadium fastigii in the 2nd-3rd week of infection:
    roseola on a chest of a man with typhus

    Roseola on the chest of a man with typhus

    After approximately 8 days, a very high fever (up to 41 ° C) is reached, which persists. A relative bradycardia, leukopenia and splenomegaly are added to this. A reddish, spotty rash, the so-called roseola, with prominence on the upper body and abdomen is typical, so are disturbances of consciousness, which give the disease its name. One can often notice the typhoid tongue, which is characterized by a white-gray coating in the middle, with reddish tongue tip and edges.

    perforations of the ileum

    Image: “Perforation des Ileums mit typhoiden Läsionen” by Openi. License: CC BY 2.0

    By destroying the Peyer’s patches of the small intestine, it leads to pea soup diarrhea from the 14th disease day onwards. Other possible symptoms include meningitis, osteomyelitis and bowel perforation.

  3. Stadium decrementi with stepwise decreasing fever.
Note: In case of typhoid fever, there are many typical symptoms. These include infectious atypical bradycardia and leukopenia, roseola, typhoid tongue and pea soup diarrhoea.

 

Diagnosis of typhoid fever

The detection of a salmonella infection is dependent on the disease week. One week after infection, the detection in blood cultures can be carried out; an antibody screening of blood serum is possible in the second week. From the third week on, a culture from stool samples can succeed.

In addition, the typical leukopenia is found in the blood, often along with a lack of eosinophilic granulocytes.

Treatment of typhoid fever

The antibiotic treatment is carried out with ciprofloxacin or ceftriaxone of the 3rd generation such as cephalosporins.

As is the case of salmonellosis, some of the affected remain chronic carriers for up to one year, especially if they have not received antibiotics. The salmonella survive in the gall bladder and the bile ducts, favored by gallstones.

Prophylaxis of the typhoid disease

Particularly in tropical destinations, hygiene is the best protection against an infection. Thus, the consumption of insufficiently cooked foods and tap water should be avoided. In addition, the vaccination can be done with dead or non-pathogenic live vaccine, whereby it should be noted that an adequate protection is achieved in only about 60 % of the vaccinated people.

Yersiniosis

The yersiniosis is an infectious disease caused by the bacterium Yersinia enterocolitica or Y. pseudotuberculosis. The pathogen is spread worldwide (Y.pseudotuberculosis more in Eastern Europe), and animals such as pigs or cattle serve as a reservoir. Therefore, the infection can be carried out through contaminated meat, dairy products and drinking water.

Note: Yersinia can multiply even in the refrigerator at temperatures of 4 – 8 ° C.

 

Symptoms of yersiniosis

Depending on the age of onset, other symptoms occur after an infection with yersinia.

  • Yersinia gastroenteritis: Especially in infants. It results in self-limiting bloody diarrhea with exsiccosis.
  • Pseudoappendicitis

    Image: “Abdominal and pelvic enhanced CT revealed mucosal thickness of cecum (circle) and enlarged lesional lymph node (arrows). Left panel indicates transverse imaging and right panel indicates coronal imaging” (Pseudoappendizitis) by Openi. License: CC BY 2.0

    Pseudoappendicitis (lymphadenitis of intestinalis) or Morbus Maßhoff:
    In older children and adolescents it results in inflammation with concomitant swelling of the mesenteric lymph nodes. Typically results in a lymph node conglomerate around the vermiform appendix, such that at the hospital the misdiagnosed appendicitis is often detected with fever and abdominal pain and mass around the appendix in the sonography.

  • Enterocolitis: The enterocolitis caused by yersinia is an invasive gastroenteritis. The bacterial cells migrate through the mucosa of the intestine and result in inflammation in the Peyer’s patches. The hereby resulting diarrhea continues 10-14 days and is accompanied by colicky abdominal pain.

After weeks to months following an enteral infection with yersinia, a common result are inflammatory late-onset diseases, such as the reactive arthritis, pyomyositis and persistent ileitis (Pseudo-crohn). These late effects are very frequently associated with the HLA type B27.

Diagnostics of the yersinia infection

The aim should be the direct detection of yersinia from blood culture, stool or infected lymph nodes. The so-called CIN breeding ground (Cefsulodin Irgasan-Novobiocin Agar) serves as the selective agar on which porthole-shaped red colonies grow after 1-2 days.

A namely obligation to notify the authorities exists during the detection of an acute infection with yersinia.

Treatment of yersiniosis

Usually only a symptomatic treatment for rehydration takes place. Severe gastroenteritis and systemic infections are treated with a combination of ciprofloxacin and ceftriaxone.

Note: Y. enterocolitica forms β-lactamases, such that (amino-) penicillins are not effective.

Shigellosis

The shigellosis, or bacterial dysentery, is a fecal-oral transmitted dysentery, which mainly affects the colon.

Etiology of the bacterial dysentery

Several shigella species come into question as pathogens. They are divided into groups from A to D.

Group Species Distribution Symptoms
A S.dysenteriae Tropics Serious disease patterns by formation of endo- and ectotoxin, lethality of 60%
B S.flexneri Worldwide Mild progressive form, since no ectotoxin is observed
C S.bodyii Middle East, North Africa Mild course
D S.sonnei Central Europe Summer diarrhea in children, no exotoxin, approximately 80 % of the shigellosis cases

The only reservoir for pathogens is the human body, such that the fecal-oral transmission occurs via contaminated food and drinking water.

Symptoms of the shigella dysentery

Diarrhea occurs after an incubation period of 2 – 10 days. In the mild progressive form this is referred to as white dysentery and in severe, bloody progressive form as red dysentery. Characteristically, the diarrhea is accompanied by abdominal pain and tenesmus with defecation. Even loss of appetite, fever and consequences of electrolyte loss are common. Gastrointestinal bleeding and intestinal perforation may occur as complications.

Diagnostics of the shigellosis

At the beginning of the disease, one histologically observes catarrhal dysentery, an inflamed, swollen intestinal mucosa. In severe cases, the image changes into the pseudomembranous-necrotizing dysentery. The histological image then resembles a chronic inflammatory bowel disease.

The diagnosis is made on the basis of clinical symptoms and a rectum smear, since the shigella die in the stool sample after a short time.

Treatment of the shigella dysentery

The treatment should be symptomatic, which means balancing the water and electrolyte losses. In addition, a calculated antibiotic treatment can be started with a quinolone. Many shigella are however affected by an R-plasmid resistant to numerous antibiotics, such that a change of antibiotic treatment after antibiogram is meaningful.

Note: Motility inhibiting anti-diarrheals such as loperamide should be taken only for a short period in most bacterial diarrheal diseases, as although they help against diarrhea, they also prolong the excretion of pathogens.

Infection with Escherichia coli

E. coli

Image: “E.coli auf Endo-Agar” by LenkaM. License: CC BY-SA 1.0

The most well known bacterium in the world is responsible for about 160 million diarrheal diseases and 1 million cases of death yearly.

Infections with enteropathogenic E. coli

Enteropathogenic E.coli strains, short EPEC, are a common diarrheal pathogen in infants and young children in developing countries. Through the EPEC adhesion factor EAF, the bacteria bind to the epithelial cells of the small intestine and inject toxins in the enterocytes using a type III secretion system.

Infections with enterotoxigenic E. coli

The transmission of ETEC occurs in tropical countries through contaminated food and drinking water. For the attachment to the mucosa of the intestine these strains have specific fimbriae called colonization factors. The pathogenic effect is caused by one of the cholera toxins similar to the heat-labile enterotoxin and two heat-stable (up to 100°C) toxins. Guanylate cyclase is stimulated through the toxins, among other things, whereby the sodium absorption is inhibited, and more water is extracted from the intestine. It often results in massive watery diarrheas, which are self-limiting in the form of traveller’s diarrhea. In children, it can lead to life-threatening courses through dehydration.

Infections with enteroinvasive E. coli

The infection with EIEC resembles a shigella infection. The bacteria penetrate the epithelial cells of the colon and lead to a granulocytic inflammation with discharge of blood and mucus. Even EIEC strains have toxins, which additionally lead to water and electrolyte loss.

Infections with enterohemorrhagic E. coli

Enterohemorrhagic E. coli, the so-called EHEC, are Shiga toxin producing E. coli with additional pathogenicity. Even 10-100 bacteria are enough for food poisoning with EHEC. The infection occurs mainly via milk and raw meat, but can also occur during close contact from person to person.

The Vera toxin present in the EHEC bacteria is phage-encoded and like the Shiga toxin acts neurotoxic and necrotic. In addition, EHEC has a plasmid encoded hemolysin that triggers the hemorrhagic-uremic syndrome, short HUS. The hemolytic-uremic syndrome, which is also called the Gasser syndrome, is a microangiopathic hemolytic anemia with thrombocytopenia and acute renal failure caused by bacterial toxins. If only 2 of these symptoms are present, one speaks of incomplete enteropathic HUS. With diarrhea, it is about the typical HUS, which is common in children. The atypical HUS without diarrhea occurs more commonly in adults.

The detection of EHEC is achieved through the PCR. The treatment should be symptomatic with electrolytes and infusions and plasmapheresis. Loperamide and antibiotics are absolutely contraindicated as they do not act against the toxins and there are indications that HUS symptoms occur more frequently among antibiosis. Since 2009, there is a monoclonal antibody called eculizumab, which inhibits the complement system and reduces the mortality with atypical HUS.

The suspicion or evidence of an EHEC infection is notifiable under law if an HUS is present, two or more people are sick, or the sick person works in the food industry. The suspicion, the illness and death by a bacterial HUS is also notifiable under law.

Infections with enteroaggregative E. coli

Following the attachment to the intestinal epithelium by fimbriae, it results in a diarrhea of secretory type through enterotoxins. An increased mucus production is typical, which delays the elimination of the pathogen, such that the disease can drag on for weeks. In case of immunosuppressed patients, such as HIV patients, EAEC is the most frequent cause of bacterial enteritis.

Note: EPEC- Pediatrics, ETEC- Tropics, EIEC- like Shigellosis, EHEC-HUS, EAEC-AIDS.

Botulism

Botulism

Image: “Botulism” by Herbert L. Fred, MD, Hendrik A. van Dijk. License: CC BY 2.0

Clostridium botulinum is the producer of the most potent toxin in the world. Under anaerobic conditions, such as in animal carcasses or insufficiently heated canned food, this bacterium can multiply and produce botulinum toxin. Infants can become infected even by eating contaminated honey, as their intestinal flora has not yet fully developed.

After the intake of poison there is an inhibition of acetylcholine secretion at the neuromuscular junction. First, the eye muscles are paralyzed, then other facial and pharyngeal muscles. Even vomiting and diarrhea are typical before death due to suffocation or cardiac arrest. The treatment is done with an antiserum, which reduces the mortality from about 90 % to 10 %.

Clostridium difficile infections

Clostridium difficile is an obligate anaerobic spore former with ubiquitous occurrence. Approximately 80 % of the infants and < 5 % of the adults are infected. The infection usually occurs nosocomially (48 hours after hospital admission until 4 weeks after dismissal), fecal-oral route. The diarrhea is highly contagious, even indirectly via surfaces.

Risk factors for Clostridium difficile infection:

  • previous antibiotic therapy (in particular, Clindamycin, ampicillin and cephalosporins)
  • Hospitalization
  • Old age
  • Therapy with PPI and/or NSAIDs
  • GI underlying disease
  • Immunosuppression

Clinical symptoms are watery, greenish diarrhea with foul odor, lower abdominal pain, fever, leukocytosis and hypoalbuminemia.

For the disease definition, one or more of the following points must hold true:

  • Diarrhea/toxic megacolon with detection of C. difficile enterotoxin A and/or cytotoxin B or cultural evidence of toxin-producing C. difficile in the stool;
  • Pseudomembranous colitis in the endoscopy;

    Pseudomembranous colitis

    Image: “Pseudomembranous Colitis” by Bijhenry aus der deutschsprachigen Wikipedia. License: CC BY-SA 3.0

  • Histopathologic evidence of a C. difficile infection through endoscopy, colectomy or autopsy.

The toxin proof is the gold standard for the diagnosis, but it is seldom applied. As a routine, enzyme immunoassay (EIA) are mostly used.

Note: A fast sample transport is essential, as the toxin decomposes within 2 h at room temperature!

The treatment of Clostridium difficile-associated enterocolitis consists of the completion of the previous antibiotic therapy (if acceptable from a clinical perspective) and an additional antibiotic therapy in case of persistent/severe symptoms, old/critically ill patients or if the current antibiotic therapy needs to be continued. Suitable for this, in order to avoid the selection of vancomycin-resistant enterococci, are Metronidazole in uncomplicated courses and Vancomycin in severe courses, during pregnancy or in children below 10 years. The surgical treatment can be necessary for intestinal perforation or toxic megacolon.

In case of VA CDI, the prophylaxis of an infected patient should be strictly observed with isolation in single rooms for up to 48 hours after cessation of symptoms.

In severe cases, the local health authorities must be notified (e.g. ICU requiring/surgery requiring course, recurrent infection, death from CDI < 30d after diagnosis).

Cholera

Vibrio cholerae

Image: “Vibiro cholera Elektronenmikroskopie” by Openi. License: CC BY 2.0

The cholera, or bile diarrhea and vomiting, is caused due to an infection with Vibrio cholerae. The transmission usually occurs through contaminated water in poorer countries without adequate supplies of clean drinking water. Approximately 85 % of the infections proceed inapparently; the other 15 % are associated with typical symptoms.

rice water stool

Image: “Reiswasserstuhl” by F1jmm. License: CC BY-SA 3.0

After an incubation period of 2 – 3 days, it results in diarrhea and vomiting, whereby the diarrhea is interspersed with flakes of mucus and is therefore called rice water stool. Due to massive exsiccosis, it then results in subnormal temperature and a typical facial expression with a pointed nose, sunken cheeks and standing skin folds.

CholeraThis is subsequently followed by general body reactions such as dizziness and coma. The diagnosis can be done quickly through microscopy and stool culture. The definitive diagnosis is done with the help of antiserum. For rehydration the WHO-Oral Solution consisting of glucose, sodium chloride, sodium citrate and potassium chloride is recommended. In addition, there are several oral cholera vaccines, which are administered in different endemic areas.

Lambliasis

Giardia intestinalis

Image: “Giardia intestinalis” by CDC/Janice Haney Carr.

The lambliasis or giardiasis is an infection of the intestinal tract caused by the protozoan Giardia intestinalis. Typical symptoms of the Lamblia dysentery are diarrhea, flatulence and malnutrition in case of prolonged illness. The detection of trophozoites or cysts is done using microscopy of stool or from the biopsy of the intestinal tract. Even an antigen detection using ELISA or PCR is possible. The treatment is done with metronidazole. It is presumed that a resolved infection can cause lactose intolerance or other food intolerances with persistent gastrointestinal complaints.

The infection with Giardia is notifiable under law.

Life cycle of the parasite Giardia lamblia.

Life cycle of the parasite Giardia lamblia.

Amoebic Dysentery

Histopathologic image of amoebic dysetery found in endoscopic colonic biopsy

Image: “Histologische Aufnahme einer Amöbeninfektion im Darmgewebe“. License: CC BY-SA 3.0

Entamoeba histolytica passes as a cyst in the small intestine and as a four-core stage thereafter in the colon. There, the amoeba further lives in the form of trophozoites. They forms cysts, which are excreted in the stool (up to 50 million per day!). The minuta form of the Entamoeba histolytica causes self-limited diarrhea. The magna-form, on the other hand, penetrates the colonic mucosa and passes from there into the bloodstream. It, then, settles in the form of abscesses in all sorts of organs, including the intestines. Amoebic dysentery, therefore, results in raspberry jelly-like diarrhea with abdominal pain and exsiccosis. Even peritonitis and abscess rupture in the liver are common.

Note: Often the disease doesn’t break out until many years after the infection.

Popular Exam Questions about Diarrhea

The correct answers can be found below the references.

Bild: Von Jerad M Gardner, MD. Lizenz: CC BY-SA 3.0

Image: by Jerad M Gardner, MD. License: CC BY-SA 3.0

1. A 28-year-old woman introduces herself in your general medical practice because of diarrhea that has persisted for 3 weeks. She claims to have bought a dog from Greece 2 months prior, that sometimes has rancid grease-smelling, loose stools. Now she is experiencing similar diarrhea and has lost 5 kg of weight. You ask the young woman for the submission of a stool sample. In microscopy, you see the following:

It is most likely an infection with:

  1. Entamoeba histolytica
  2. Giardia intestinalis
  3. Enterotoxigenic E. coli
  4. Shigella dysenteriae
  5. Yersinia pseudotuberculosis

2. A 44-year-old otherwise healthy woman is accompanied by her husband to the emergency room because of diarrhea, disturbance of consciousness, dysarthria and petechiae on the lower legs. You diagnose acute renal failure with systolic blood pressures up to 210 mmHg. In the hemogram, thrombocytopenia and hemolysis is noticeable. In the blood smear you see fragmentocytes. You give a diagnosis of hemolytic uremic syndrome with thrombotic thrombocytopenic purpura. You assume an infection with EHEC as the cause. What is the appropriate treatment?

  1. Loperamide dose
  2. Antibiosis with ciprofloxacin
  3. Waiting
  4. Plasmapheresis
  5. Elotuzumab dose

3. At a birthday party where there was custard in the afternoon, 6 children suddenly fall ill with diarrhea in the evening. After 2 to 3 hours the symptoms cease as suddenly as they appeared. This is most likely a case of diarrhea caused by:

  1. Salmonella typhi
  2. Staphylococcus aureus toxin
  3. Shigella dysenteriae toxin
  4. Botulinum toxin
  5. Saxitoxin
Do you want to learn even more?
Start now with 500+ free video lectures
given by award-winning educators!
Yes, let's get started!
No, thanks!

Leave a Reply

Your email address will not be published. Required fields are marked *