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PathoPhysiology of Diarrhea

Diarrhea is an increase in the volume of stool or frequency of defecation. It is the


reversal of the normal net absorptive status of water and electrolyte absorption to
secretion. The increase of 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.
For many people, diarrhea represents an occasional inconvenience or
annoyance, yet at least 2 million people in the world, mostly children, die from the
consequences of diarrhea each year.

Chronic vs Acute Diarrhea

Diarrhea is characterized by loose, watery stools or a frequent need to have a bowel


movement. It usually lasts a few days and often disappears without any treatment.
Diarrhea can be acute or chronic.

Acute Diarrhea Chronic Diarrhea

 Lasts 2-3 days  Lasts at least 4 weeks


 May be due to bacterial or viral  Usually due to intestinal disease or
infection, or via food poisoning disorder
 Fairly common

A condition known as traveler’s diarrhea happens when you have diarrhea after being
exposed to bacteria or parasites while on vacation in a developing nation.

Pathophysiology and mechanisms of diarrhea

Normally, absorption is quantitatively greater than secretion in the intestines.


Therefore, either a decrease in absorption or an increase in secretion can lead to
diarrhea. When infectious agents, toxins, or other noxious substances are present
within the gut, fluid secretion and motility are stimulated to expel the unwanted material,
producing diarrhea.
There are four major mechanisms of diarrhea:
(1) the presence in the gut lumen of unusual amounts of poorly absorbable, osmotically
active solutes (osmotic diarrhea);
(2) intestinal ion secretion or inhibition of normal active ion absorption (secretory
diarrhea);
(3) exudation of mucus, blood, and protein from sites of inflammation: and
(4) deranged intestinal motility.

Types of diarrhea

intestinal epithelial cells actively secreting


Secretory diarrhea water and electrolytes due to
secretagogue (substance that promotes
secretion)
Osmotic diarrhea Ingested solutes poorly absorbed
Disruption of the epithelium of the
Inflammatory and Infectious Diarrhea intestine due to microbial or viral
pathogens

Decreased surface area/ Deranged Decreased solute absorption, decreased


Motility transit time

Motility disorders

Motility-Related Diarrhea Motility disorders cause diarrhea by either accelerating


gastrointestinal transit or by slowing transit, thereby predisposing to small intestinal
bacterial overgrowth (SIBO). Motility related diarrhea can be either secretory or osmotic.

Secretory Diarrhea

Secretory diarrhea occurs when the bowel mucosa secretes excessive amounts
of fluid into the gut lumen, either due to activation of a pathway by a toxin, or due to
inherent abnormalities in the enterocytes.

 Vibrio cholera (organism of interest) produces cholera toxin which strongly


activates adenylyl cyclase, causing a prolonged increase in intracellular
concentration of cyclic AMP within crypt enterocytes. The sudden change results
in prolonged opening of the chloride channels that are instrumental in secretion
of water from the crypts, allowing uncontrolled secretion of water.
Note: You have the option to not mind these (a, b, c), I just placed it here
kasi I don’t know the functions of these enzymes. 
a. adenylyl cyclase- enzyme with a key regulatory role.
b. cyclic AMP- Cyclic AMP is a second messenger in the cellular
action of a wide variety of hormones and other extracellular
regulatory molecules. It activates cyclic AMP-dependent protein
kinase (PKA), which in turn phosphorylates and thereby regulates
key proteins that participate in physiological responses.
c. crypt enterocytes- where glucose and amino acids are embedded
and transported throughout the intestine.

In addition to bacterial toxins, some agents that can induce secretory diarrhea by
turning on the intestinal secretory machine include:

a. laxatives
b. hormones secreted by certain types of tumors (e.g. vasoactive intestinal peptide)
c. a broad range of drugs (e.g. some types of asthma medications, antidepressants,
cardiac drugs)
d. certain metals, organic toxins, and plant products (e.g. arsenic, insecticides,
mushroom toxins, caffeine)

In most cases, secretory diarrheas will not resolve during a 2-3 day fast.

Osmotic Diarrhea

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:

 Ingestion of a poorly absorbed substrate: The offending molecule is usually a


carbohydrate or divalent ion.
o Common examples include mannitol or sorbitol, epson salt (MgSO4) and
some antacids (MgOH2).
 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 lactose intolerance- this results from a deficiency in the brush border
enzyme lactase where:
a. moderate consumption of lactose (milk) is not effectively
hydrolyzed into glucose or galactose for absorption.
b. The osmotically active lactose retains in the intestinal lumen and
“holds” water.
c. The unabsorbed lactose then passes in the large intestine where it
is fermented by colonic bacteria that results in the production of
excessive gasses.

Osmotic Diarrhea’s notable feature is it stops after the patient fasts or stops his/her
consumption of the poorly absorbed solutes.

Inflammatory and Infectious Diarrhea

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.
Disruption of the epithelium of the intestine due to microbial or viral pathogens is
a very common cause of diarrhea in all species. 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. In such cases, absorption of water
occurs very inefficiently and diarrhea results. Examples of pathogens frequently
associated with infectious diarrhea include:

 Bacteria: Salmonella, E. coli, Campylobacter


 Viruses: rotaviruses, coronaviruses, parvoviruses (canine and feline), norovirus
 Protozoa: coccidia species, Cryptosporium, Giardia

The immune response to inflammatory conditions in the bowel contributes


substantively to development of diarrhea. 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. 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.

Decreased surface area

Rapid transit prevents adequate time for absorption, diarrhea results despite
intact mucosal absorptive capacity. Intestinal hurry has been linked to abnormal enteric
nervous system function. Many endocrine diarrheas, such as those due to peptide-
secreting tumors or hyperthyroidism, may lead to diarrhea not only by effects on
intestinal electrolyte transport but also by accelerating intestinal motility. Conversely,
slow intestinal transit may lead to a secretory diarrhea by promoting bacterial
overgrowth in the small intestine. Excess bacteria in the small intestine disrupt digestion
and may alter electrolyte transport.
References:

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

http://www.bioline.org.br/request?ms04013

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

https://www.paediatricsandchildhealthjournal.co.uk/article/S1751-7222(12)00087-
X/abstract

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