Modifiable factors: Non-Modifiable factors:

Consumption of contaminated sources like Male

water 30-years old

V. cholerae enters the stomach

shuts down protein production to conserve

energy and nutrients, and also to survive the
acidic environment.

propel through the mucous layer on V. cholerae is in the intestines uses its attach to the finger-like cellular
top of the epithelial cells lining flagella to move toward the intestinal walls projections, called villi, on the
the intestines
surface of the epithelial cells.

V. cholerae begin to multiply and produce

toxins.

The toxins from V. cholerae enter the

epithelial cells itself

Toxin produce cholera enterotoxin, also

enterotoxin acts locally and does not called choleragen
invade the intestinal wall

this causes the G-protein to

cholera enterotoxin enters the epithelial
becomes permanently
cells, it leads to the ADP-ribosylation of the
Neutrophil in stool (PAKICHECK activated and it keeps
Gs alpha subunit of G-protein.
KUNG MATAAS NEUTROPHIL activating adenylate cyclase.
HAHAH) overproduction of the intracellular
secondary messenger protein, cyclic
adenosine monophosphate, or cAMP.
 causes chloride channels on the cells to inhibiting the channels that let sodium
increase the secretion of chloride into the and chloride back into the cell.
 subsequent
lumen generalized body
ABG Test: Primary weakness
abnormally high levels of luminal sodium and metabolic acidosis adynamic
chloride disrupt the osmotic with concomitant precordium
balance between the intestines and respiratory alkalosis
surrounding tissue with adequate
oxygenation
Vomiting large volume of fluid depleted
LBM/Severe water, bicarbonate, and potassium rush into electrolytes and
produced in the upper
diarrhea the lumen of the intestines as a result. severe dehydration and depletion of water in the blood.
intestine overwhelms the
electrolytes
absorptive capacity of the
 Fecalysis: lower bowel resulting in
severe diarrhea CHOLERA
 Light yellow, mucoid, AKI secondary
RBC: 1-3, WBC: 8-10 hypovolemic shock with Sunken eyes to 1)
 Positive for Entamoeba a significant decrease in (+) superficial cutaneous infection, 2)
coli cyst blood pressure. rugosity on both hands decreased
and feet ECV
poor skin turgor
Cholera is a contagious infection caused by the bacteria Vibrio cholerae, which can in turn cause severe gastroenteritis and excessive watery diarrhea for several days.
V. cholerae is a gram-negative, curved bacteria which looks like little red or pink comma-shapes on a gram stain.
It’s positive for oxidase and grows in alkaline media.
It has pili and a single polar flagellum, kind of like a tail, at one end which it uses for movement through the gastrointestinal tract.
It’s a facultative anaerobe so that means it can undergo respiratory and fermentative metabolism.
Transmission of V. cholerae typically occurs through a fecal to oral route.
This includes consuming untreated sewage water, and anything that comes in contact with it, like raw or undercooked fish including shellfish; and improper hygiene, like a lack of hand
washing after a bowel movement.
Cholera tends to be more common in developing countries and places lacking advanced sanitation and sewage treatment facilities, with high rates in some locations in Africa and South America.
People who have low gastric acidity or have an O-blood type are particularly at risk for a severe infection.
Now, when V. cholerae enters the stomach it shuts down protein production to conserve energy and nutrients, and to survive the acidic environment.
But once V. cholerae is in the intestines, it uses its flagella to move toward the intestinal walls; propel through the mucous layer on top of the epithelial cells lining the intestines; and
attach to the finger-like cellular projections, called villi, on the surface of the epithelial cells.
There, V. cholerae can begin to multiply and produce toxins.
And though V. cholerae does not enter the epithelial cells itself, the toxins do and they can cause a lot of trouble.
Now, the exact toxins produced can depend on the strain of V. cholerae.
Some strains produce toxins that won’t cause any, or maybe just mild clinical symptoms.
But some strains produce cholera enterotoxin, also called choleragen, which is most often the cause significant clinical symptoms.
When cholera enterotoxin enters the epithelial cells, it leads to the ADP-ribosylation of the Gs alpha subunit of G-protein.
So, this causes the G-protein to becomes permanently activated and it keeps activating a membrane-bound protein called adenylate cyclase.
This protein in turn leads to an overproduction of the intracellular secondary messenger protein, cyclic adenosine monophosphate, or simply cAMP.
Increase in cAMP causes chloride channels on the cells to increase the secretion of chloride into the lumen while inhibiting the channels that let sodium and chloride back into the cell.
So, the abnormally high levels of luminal sodium and chloride disrupt the osmotic balance between the intestines and surrounding tissue; and water, bicarbonate, and potassium rush into
the lumen of the intestines as a result.
This can cause symptoms like vomiting and voluminous amounts of watery diarrhea containing extremely high concentrations of sodium, potassium, chloride, bicarbonate; as well as
high levels of live V. cholerae ready to infect another individual.
There could also be flecks of the mucous layer of the intestine which looks similar to rice in water.
Typically, there is no fever, pain or cramping.
And while the incubation time for V. cholerae can take hours, to 2-3 days; severe dehydration and depletion of electrolytes can happen within 4 to 12 hours of the first bout of diarrhea or
vomiting.
These imbalances can lead to symptoms like disorientation, dry mouth, swollen tongue, sunken eyes, cold clammy skin, or shriveled and dry hands and feet.
Other, even more severe, fatal complications can come from depleted electrolytes and water in the blood.
Like low levels of bicarbonate can cause metabolic acidosis with deep and labored breathing called Kussmaul breathing.
Or low levels of potassium can cause muscle dysfunction including leg cramps, weakness and abnormal heart rhythms.
And low chloride and sodium can cause headaches, poor balance, disorientation, seizures and coma.
Finally, severe dehydration can cause hypovolemic shock with a significant decrease in blood pressure.
Diagnosis is typically made by a stool sample growing V. cholerae on a thiosulfate-citrate-bile salts-sucrose agar.
But even before a definitive diagnosis can typically be made, the first line of treatment is to rapidly replace the lost water and electrolytes with rehydration salts either orally or intravenously.
In cases of mild to moderate diarrhea, this type of supportive therapy is enough of a treatment course and the diarrhea may resolve on its own in about 3 to 7 days.
But more extreme cases may require antibiotics. In this case, the stool culture can be helpful in deciding which antibiotics would be most effective against the infecting strain, and may
include tetracyclines, ciprofloxacin, ofloxacin, furazolidone, or trimethoprim-sulfamethoxazole.

Summary
So, to recap: Cholera is a contagious, severe gastroenteritis caused by the gram-negative Vibrio cholerae bacteria.
It’s route of transmission is fecal to oral through consumption of contaminated sources like water and shellfish.
Some strains produce cholera enterotoxin at the surface of intestinal epithelial cells which leads to the over-activation of cAMP by permanently activating Gs alpha.
Patients most often present with voluminous “rice-water” diarrhea that quickly leads to dehydration and electrolyte imbalances that can be fatal if not rapidly treated with rehydration salts.

Pathophysiology (MEDSCAPE)
V cholerae is a comma-shaped, gram-negative aerobic or facultatively anaerobic bacillus that varies in size from 1-3 µm in length by 0.5-0.8 µm in diameter. Its antigenic structure consists of
a flagellar H antigen and a somatic O antigen. The differentiation of the latter allows for separation into pathogenic and nonpathogenic strains. Although more than 200 serogroups of V
cholerae have been identified, V cholerae O1 and V cholerae O139 are the principal ones associated with epidemic cholera.

Currently, the El Tor biotype of V cholerae O1 is the predominant cholera pathogen. Organisms in both the classical and the El Tor biotypes are subdivided into serotypes according to the
structure of the O antigen, as follows:
 Serotype Inaba - O antigens A and C
 Serotype Ogawa - O antigens A and B
 Serotype Hikojima - O antigens A, B, and C

The clinical and epidemiologic features of disease caused by V cholerae O139 are indistinguishable from those of disease caused by O1 strains. Both serogroups cause clinical disease by
producing an enterotoxin that promotes the secretion of fluid and electrolytes into the lumen of the small intestine.

To reach the small intestine, however, the organism has to negotiate the normal defense mechanisms of the GI tract. Because the organism is not acid-resistant, it depends on its large
inoculum size to withstand gastric acidity.

The infectious dose of V cholerae required to cause clinical disease varies by the mode of administration. If V cholerae is ingested with water, the infectious dose is 103 -106 organisms. When
ingested with food, fewer organisms (102 -104) are required to produce disease.

The use of antacids, histamine receptor blockers, and proton pump inhibitors increases the risk of cholera infection and predisposes patients to more severe disease as a result of reduced
gastric acidity. The same applies to patients with chronic gastritis secondary to Helicobacter pylori infection or those who have undergone a gastrectomy.

V cholerae O1 and V cholerae O139 cause clinical disease by producing an enterotoxin that promotes the secretion of fluid and electrolytes into the lumen of the small intestine.
The enterotoxin is a protein molecule composed of 5 B subunits and 2 A subunits. The B subunits are responsible for binding to a ganglioside (monosialosyl ganglioside, GM1) receptor
located on the surface of the cells that line the intestinal mucosa.

The A1 subunit of cholera toxin activates adenylate cyclase to cause a net increase in cyclic adenosine monophosphate (cAMP). The increased cAMP then carries on the
downstream effects. cAMP blocks the absorption of sodium and chloride by the microvilli and promotes the secretion of chloride and water by the crypt cells.[3, 4] The result is
watery diarrhea with electrolyte concentrations isotonic to those of plasma.

Fluid loss originates in the duodenum and upper jejunum; the ileum is less affected. The colon is usually in a state of absorption because it is relatively insensitive to the toxin.
However, the large volume of fluid produced in the upper intestine overwhelms the absorptive capacity of the lower bowel, resulting in severe diarrhea. Unless the lost fluid and
electrolytes are replaced adequately, the infected person may develop shock from profound dehydration and acidosis from loss of bicarbonate.

The enterotoxin acts locally and does not invade the intestinal wall. As a result, few neutrophils are found in the stool.

The O139 Bengal strain of V cholerae has a very similar pathogenic mechanism except that it produces a novel O139 lipopolysaccharide (LPS) and an immunologically related O-antigen
capsule. These 2 features enhance its virulence and increase its resistance to human serum in vitro and occasional development of O139 bacteremia.