Diarrhea can occur via four main mechanisms: 1) Osmotic diarrhea due to ingestion of poorly absorbed substances or malabsorption that leaves solutes in the intestines drawing water, 2) Secretory diarrhea when intestinal secretion exceeds absorption such as from cholera toxin dramatically increasing secretion, 3) Inflammatory and infectious diarrhea resulting from disruption of the intestinal epithelium by pathogens allowing substances to pass directly into the lumen, and 4) Diarrhea associated with deranged motility when accelerated transit time decreases absorption. Infectious diarrhea is a very common cause and can incorporate elements of the other mechanisms.

1. PATHOPHYSIOLOGY OF
DIARRHEA
OLUWASEUN O. OLAIYA
Department Medicine and Surgery,
UMTH

2. INTRODUCTION
O Diarrhea is an increase in the volume of stool or frequency of
defecation.
O One of the most common clinical signs of gastrointestinal
disease.
O Can also reflect primary disorders outside of the digestive
system.
O Certainly, disorders affecting intestine ability to handle water
and electrolytes.

3. Normal stool frequency ranges from
3times a day to 3 times a week,
O Acute diarrhea are those lasting less than 2-3 weeks or
rarely 6-8 weeks mostly due to infections, approximately
80%.
O Chronic diarrhea are thise lasting at least 4weeks and more
usually 6-8weeks or longer. They are of the categories;
Osmotic, Secretory and inflammation.

4. EPIDEMIOLOGY
O At least 2 million people in the world, mostly children, die
from the consequences of diarrhea each year.
O This is not primarily due to the diarrhea itself but t sequel;
electrolyte derangement.
O Parsistent diarrhea however requires urgent intervention and
management.

5. MECHANISM OF DIARRHEA
O There are numerous causes of diarrhea, in almost all cases, it
manifestation can be described by four basic mechanisms.
O More than one of the four mechanisms can be involved in the
pathogenesis of a given case.

6. Contd. (MECHANISM OF DIARRHEA)
O The mechanisms are;
1. Osmotic Diarrhea
2. Secretory Diarrhea
3. Inflammatory and Infectious Diarrhea
4. Diarrhea Associated with Deranged Motility

8. 1. Osmotic Diarrhea
O Absorption of water in the intestines is dependent on
adequate absorption of solutes. If excessive amounts of
solutes are retained in the intestinal lumen, water will not be
absorbed and diarrhea will result. Osmotic diarrhea typically
results from one of two situations:
O Ingestion of a poorly absorbed substrate: The offending
molecule is usually a carbohydrate or divalent ion. Common
examples include mannitol or sorbitol, epson salt (MgSO4)
and some antacids (MgOH2).

9. O Malabsorption: Inability to absorb certain carbohydrates is the
most common deficit in this category of diarrhea, but it can
result virtually any type of malabsorption.
O A common example of malabsorption, afflicting many adults
humans and pets is lactose intolerance resulting from a
deficiency in the brush border enzyme lactase. In such cases, a
moderate quantity of lactose is consumed (usually as milk), but
the intestinal epithelium is deficient in lactase, and lactose
cannot be effectively hydrolyzed into glucose and galactose for
absorption.

10. We’re Still on Osmotic diarrhea…
O The osmotically-active lactose is retained in the intestinal
lumen, where it "holds" water. To add insult to injury, the
unabsorbed lactose passes into the large intestine where it is
fermented by colonic bacteria, resulting in production of
excessive gas.
O A distinguishing feature of osmotic diarrhea is that it stops after
the patient is fasted or stops consuming the poorly absorbed
solute.

11. 2. SECRETORY DIARRHEA
O Large volumes of water are normally secreted into the small
intestinal lumen, but a large majority of this water is efficienty
absorbed before reaching the large intestine. Diarrhea occurs
when secretion of water into the intestinal lumen exceeds
absorption.
O Many millions of people have died of the secretory diarrhea
associated with cholera.

12. O The responsible organism, Vibrio cholerae, produces cholera
toxin, which strongly activates adenylyl cyclase, causing a
prolonged increase in intracellular concentration of cyclic AMP
within crypt enterocytes.
O This change results in prolonged opening of the chloride
channels that are instrumental in secretion of water from the
crypts, allowing uncontrolled secretion of water.
O Additionally, cholera toxin affects the enteric nervous system,
resulting in an independent stimulus of secretion.

13. Secretory diarrhea…..in view
O Exposure to toxins from several other types of bacteria (e.g.
E. coli heat-labile toxin) 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.
O In addition to bacterial toxins, a large number of other
agents can induce secretory diarrhea by turning on the
intestinal secretory machinery, including:

14. O some laxatives
O hormones secreted by certain types of tumors (e.g.
vasoactive intestinal peptide)
O a broad range of drugs (e.g. some types of asthma
medications, antidepressants, cardiac drugs)
O certain metals, organic toxins, and plant products (e.g.
arsenic, insecticides, mushroom toxins, caffeine)
O In most cases, secretory diarrheas will not resolve during a
2-3 day fast.

15. 3. INFLAMMATORY AND INFECTIOUS
DIARRHEA
O The epithelium of the digestive tube is protected from insult by a
number of mechanisms constituting the gastrointestinal barrier,
but like many barriers, it can be breached.
O Disruption of the epithelium of the intestine due to microbial or
viral pathogens is a very common cause of diarrhea in all species.
O Destruction of the epithelium results not only in exudation of
serum and blood into the lumen but often is associated with
widespread destruction of absorptive epithelium.
O In such cases, absorption of water occurs very inefficiently and
diarrhea results. Examples of pathogens frequently associated
with infectious diarrhea include:

16. Still discussing Inflammatory&Infectious
Diarrhea
O Bacteria: Salmonella, E. coli, Campylobacter
O Viruses: rotaviruses, coronaviruses, parvoviruses (canine and
feline), norovirus
O Protozoa: coccidia species, Cryptosporium, Giardia
O The immune response to inflammatory conditions in the bowel
contributes substantively to development of diarrhea.
O Activation of white blood cells leads them to secrete inflammatory
mediators and cytokines which can stimulate secretion, in effect
imposing a secretory component on top of an inflammatory
diarrhea.

18. O Reactive oxygen species from leukocytes can damage or kill
intestinal epithelial cells, which are replaced with immature
cells that typically are deficient in the brush border enyzmes
and transporters necessary for absorption of nutrients and
water.
O In this way, components of an osmotic (malabsorption)
diarrhea are added to the problem.

19. 4. DIARRHEA ASSOCIATED WITH
DERANGED MOTILITY
O In order for nutrients and water to be efficiently absorbed, the
intestinal contents must be adequately exposed to the mucosal
epithelium and retained long enough to allow absorption.
Disorders in motility than accelerate transit time could decrease
absorption, resulting in diarrhea even if the absorptive process per
se was proceeding properly.
O Alterations in intestinal motility (usually increased propulsion) are
observed in many types of diarrhea. What is not usally clear, and
very difficult to demonstrate, is whether primary alterations in
motility are actually the cause of diarrhea or simply an effect.

22. Anything more???
O Yes
O Consult your books for additional information
on diarrhea