1. Pathophysiology and mechanisms of diarrhea
Dr. Mamlook Elmagraby

2. Objectives of the lecture:
Upon completion of this lecture, students should be able to:
Understand the physiology of fluid in small intestine
Describe the pathophysiology and causes of various types of diarrhea ( Secretory, osmotic, Exudative, Motility-related )
Define acute diarrhea and enumerate its common causes
Define chronic diarrhea and enumerate its common causes

3. Physiology
8 to 9 L of fluid enters the small bowel in a 24-hour period All but 1 to 2 L is absorbed in the small intestine and then enters the colon Almost all of this fluid is absorbed as it travels through the colon, leaving less than 200 g/day of stool Disruption of the absorption of ions, solutes, water or increased secretion of electrolytes results in water accumulation in the lumen and diarrhea Diarrhea is defined as having three or more loose or liquid stools per day, or as having more stools than is normal for that person

4. Pathophysiology Of Diarrhea

5. Pathophysiology and mechanisms of diarrhea
Flow in the GI tract involve massive fluid secretion into and absorption from the GI lumen Subtle abnormalities in input or output at any levels can result in diarrhea Thus, an excessive osmotic load, increased secretion, or diminished fluid resorption may result in diarrhea The causes of diarrhea include inflammatory, osmotic, secretory, motility, and exudative diseases

6. Pathophysiology and mechanisms of diarrhea
Secretory diarrhea
Secretory diarrhea means that there is an increase in the active secretion
In this form of diarrhea, the intestinal cells secrete more water than they can absorb
This diarrhea results when secretagogues maintain elevated rates of fluid transport out of epithelial cells into the GI tract lumen
Either blood-borne or intraluminal secretagogues include:
Endogenous endocrine products (VIP)
Exotoxins (cholera)
GI luminal substances (bile acids)

7. Pathophysiology and mechanisms of diarrhea
 There is little to no structural damage
It continues even when there is no oral food intake
This form of diarrhea can be caused by:
Cholera toxin
Toxins secreted by Escherichia coli and Salmonella
Enteropathogenic viruses (Rotavirus)
Vasoactive intestinal polypeptide (VIP) and other polypeptides

8. Pathophysiology and mechanisms of diarrhea
Osmotic diarrhea
Intraluminal non-absorbable osmotically active substances draw fluids from the plasma into the jejunum through the highly permeable jejunal epithelium
Osmotic diarrhea occurs when too much water is drawn into the bowels
An excessive osmotic load may come about in three different ways:
by direct oral ingestion of excessive osmoles
by ingestion of a substrate that may be converted into excessive osmoles
enzyme deficiency in the setting of a particular diet

9. Pathophysiology and mechanisms of diarrhea
Osmotic diarrhea stops on its own as soon as the patient stops taking the substance that caused it Osmotic diarrhea stops when the patient fasts This diarrhea can be caused by osmotic laxatives Lactose found in milk products cannot be absorbed and remains in the intestine, acting as an osmotic stimulus Sorbitol (often found in sugar-free foods) are difficult for the body to absorb and, may lead to osmotic diarrhea

10. Pathophysiology and mechanisms of diarrhea
Exudative diarrhea
Exudative diarrhea develops in the course of diseases that damage the mucosa
Exudative diarrhea occurs with the presence of blood and pus in the stool
This form of diarrhea can be caused by:
Infections of the small and large intestine
Inflammatory bowel disease

11. Pathophysiology and mechanisms of diarrhea
Dysentery
Dysentery is a bloody diarrhea with pus and necrotic tissue debris, leukocytes, red blood cells
A smaller volume of feces that contains more formed elements than the watery diarrhea
Diarrhea is also associated with tenesmus and lower left quadrant pain
The blood is a trace of an invasion of bowel tissue
Dysentery is a symptom of Entamoeba histolytica, and Salmonella

12. Pathophysiology and mechanisms of diarrhea
Inflammatory diarrhea
Inflammatory diarrhea occurs when there is damage to the mucosal lining or brush border, which leads to:
A passive loss of protein-rich fluids
A decreased ability to absorb these lost fluids
Inflammatory diseases cause chronic diarrhea with exudative, secretory, or malabsorptive components
Inflammatory causes of chronic diarrhea might present with features that suggest malabsorption or rectal bleeding

13. Pathophysiology and mechanisms of diarrhea
Rectal bleeding is usually a manifestation of colonic or rectal ulcerations
The presence of an inflammatory cause of chronic diarrhea is suggested by the presence of mucus and blood in the stool, by concomitant abdominal pain
This form of diarrhea can be caused by:
IBD
microscopic colitis
collagenous colitis
Infections

14. Pathophysiology and mechanisms of diarrhea
Motility Disorders
Rapid transit delivers fluid secreted during digestion to the distal small bowel or colon:
This prevents reabsorption of normally secreted fluid in the small bowel
It overcomes the reabsorption capacity of the colon
Reduced motility leading to slow transit might result in bacterial overgrowth with bile acid deconjugation and steatorrhea
The prototype disease examples are IBS and diabetes mellitus

15. Acute Diarrhea

16. Acute Diarrhea
Acute diarrhea is defined as stool with increased water content, volume, or frequency that lasts less than 14 days Most cases of acute diarrhea are caused by viral or bacterial infections and are self-limited, resolving without specific therapy Acute diarrhea in Western countries is common The symptoms typically last approximately 48 hours and clear spontaneously Fever usually indicates an invasive organism (Salmonella , Shigella, Entamoeba histolytica , or C. difficile)

17. Acute Diarrhea
Clinical investigation is not needed and is not cost-effective in most cases  
Most of the deaths associated with acute diarrhea occur in elderly persons
Most cases of acute diarrhea are caused by viral infection
Viruses commonly causing acute infectious diarrhea include noroviruses, rotaviruses, and adenoviruses
Bacterial causes of acute infectious diarrhea include Salmonella, Shigella, E. coli , Clostridium difficile 

18. Acute Diarrhea
These are the likely causes of most severe cases of acute diarrhea Protozoa are infrequent causes of acute diarrhea Risk factors include food consumption or preparation involving raw or undercooked meats and dairy products or contaminated fruits and vegetables Acute traveler's diarrhea is most commonly caused by E. coli Noninfectious causes of acute diarrhea are less common (ischemic bowel disease, medications)

19. Chronic Diarrhea

20. Chronic Diarrhea
A decrease in stool consistency continuing for >4 wk
Chronic diarrhea may be divided into three basic categories:
Watery
Fatty (malabsorption)
Inflammatory (with blood and pus)
Watery diarrhea may be subdivided into osmotic, secretory, and functional (hypermotility) types
Secretory diarrhea can be distinguished by high stool volumes that continue despite fasting and occur at night
Persons with functional disorders have no diarrhea at night

21. Chronic Diarrhea Major Causes Irritable bowel syndrome (functional)
Irritable bowel syndrome (IBS) is the most common cause of functional diarrhea
IBS is a symptom complex of crampy abdominal pain accompanied by altered bowel habits, either with diarrhea or constipation
Symptoms such as nocturnal diarrhea, progressive pain, weight loss, or blood in the stool suggest another diagnosis
All laboratory test results are normal in patients with IBS

22. Chronic Diarrhea Inflammatory bowel disease (inflammatory)
IBD often involve blood and pus in the stool
Early cases are often confused with IBS, but symptoms progress
Malabsorptive diarrhea (fatty)
Malabsorptive diarrhea result from impaired nutrient absorption and impaired digestive function
Classic symptoms include abdominal distention with foul- smelling, large, floating, pale, fatty stools and weight loss

23. Chronic Diarrhea Chronic infections (inflammatory)
Most microbial gastrointestinal infections cause acute self- limited diarrhea
Others persist, resulting in inflammation (invasive bacteria and parasites) or occasionally malabsorption (giardiasis)
Bacterial causes include Campylobacter, C. difficile, Yersinia
Parasitic diarrhea may be caused by Cryptosporidium, Cyclospora, Entamoeba, Giardia

24. Chronic Diarrhea Drug-induced
Laxatives, antacids, proton pump inhibitors, and antineoplastic agents are medications that can lead to diarrhea
Diarrhea may be osmotic or secretory
Symptoms resolve when the offending agent is eliminated
Endocrine (secretory/hypermotility)
Endocrine causes of chronic secretory diarrhea include Addison disease, carcinoid tumors, gastrinoma
Hyperthyroidism increases motility