GROUP 3 – 1A2

Liao, Christine Angela

Lim, Danielle Sabrina
Lopez, Marika
Mabalot, Claire
Malang, Mindy

BIOCHEMICAL ASPECTS OF DIARRHEA

1. What is diarrhea? What are the symptoms associated with diarrhea?

Diarrhea is defined as an increase in daily stool weight above 200 g with increased liquidity and
frequency of more than three times per day. Diarrhea classification can be based on four factors:
duration of the illness, mechanism, severity, and stool characteristics. Diarrhea lasting less than
4 weeks is defined as acute, and diarrhea persisting for more than 4 weeks is termed chronic
diarrhea. The major mechanisms of diarrhea are secretory, osmotic, and altered motility.
Diarrheal stools are those that take shape of the container, so they are often described as loose
or watery. Some people consider diarrhea as an increase in the number of stools, but stool
consistency is really the hallmark. Associated symptoms can include abdominal cramps fever,
nausea, vomiting, fatigue and urgency. Chronic diarrhea can be accompanied by weight loss,
malnutrition, abdominal pain or other symptoms of the underlying illness.

2. What are the common causes of acute diarrhea?

A number of diseases and conditions can cause diarrhea, including
Viruses. Viruses that can cause diarrhea include Norwalk virus, cytomegalovirus and viral
hepatitis. Rotavirus is a common cause of acute childhood diarrhea.
Bacteria and parasites. Contaminated food or water can transmit bacteria and parasites to your
body. Parasites such as Giardia lamblia and cryptosporidium can cause diarrhea.
Common bacterial causes of diarrhea include campylobacter, salmonella, shigella and
Escherichia coli. When traveling in developing countries, diarrhea caused by bacteria and
parasites is often called traveler's diarrhea. Clostridium difficile infection can occur, especially
after a course of antibiotics.
Medications. Many medications, such as antibiotics, can cause diarrhea. Antibiotics destroy both
good and bad bacteria, which can disturb the natural balance of bacteria in your intestines. Other
drugs that cause diarrhea are cancer drugs and antacids with magnesium.
3. What are the common causes of chronic diarrhea?
Chronic diarrhea is classified as fatty or malabsorption, inflammatory or most commonly watery.
Chronic bloody diarrhea may be due to inflammatory bowel disease (IBD), which is ulcerative
colitis or Crohn's disease. Other less common causes include ischemia of the gut, infections,
radiation therapy and colon cancer or polyps. Infections leading to chronic diarrhea are
uncommon, with the exception of parasites.
The two major causes of fatty or malabsorptive diarrhea are impaired digestion of fats due to low
pancreatic enzyme levels and impaired absorption of fats due to small bowel disease. These
conditions interfere with the normal processing of fats in the diet.
Parasitic intestinal infections such as giardiasis can cause chronic diarrhea. Diabetes mellitus
may be associated with diarrhea due to nerve damage and bacterial overgrowth; this occurs
mainly in patients with long-standing, poorly-controlled diabetes.
Case 1:
4. What are the sequence of metabolic changes observed in diarrhea and correlate these
to the clinical manifestations observed in the patient (e.g., gastrointestinal function and
motility, alteration in fluid volume, composition, acid base balance etc.)
METABOLIC CHANGES OBSERVED IN DIARRHEA
Diarrhea stool contains large amounts of sodium, chloride, potassium and bicarbonate. All effects
of diarrhea result from water loss and electrolytes from the body in liquid stool. Additional amounts
of water and electrolytes are lost when there is vomiting and fever. These losses can result to
dehydration, metabolic acidosis, and potassium depletion.
1. Three Types of Dehydration
a. Isotonic Dehydration
Most frequent type of dehydration caused by diarrhea. Basically, the net loss of water and sodium
is equal or proportional. It is manifested first by thirst, and subsequent decreased skin turgor,
tachycardia, dry mucous membrane, sunken eyes, lack of tears, sunken fontanel in infants and
oliguria.
b. Hypertonic (Hypernatremic) Dehydration
This reflects a net loss of water in excess of sodium (there is a deficit of water and sodium but the
deficit of water is greater). It usually results from ingestion of fluids that are hypertonic during the
course of diarrhea. The hypertonic fluid creates an osmotic gradient that causes a flow of water
from ECF to the intestine, leading to a decrease in ECF volume coupled with an increase in
sodium concentration in the ECF. Thirst will be severe and out of proportion to the apparent
degree of dehydration. The patient is irritable and seizures may occur.
c. Hypotonic (Hyponatremic) Dehydration
There is a net loss of sodium in excess of water (deficit of water and sodium but the deficit of
sodium is greater). It is usually caused by drinking large amounts of water or other hypotonic
fluids that contain very low concentrations of salt and other solutes. Water is absorbed from the
gut while the loss of NaCl continues. The patient is lethargic and there may be some seizures.
Dehydration is the most dangerous consequence of diarrhea because it can cause decreased
blood volume, cardiovascular collapse, and death if not treated promptly.
2. Base Deficit Acidosis (Metabolic Acidosis)
During diarrhea, a large amount of bicarbonate may be lost in the stool. This may be remedied
by the kidneys which can replace the lost bicarbonate. However, this may fail if renal function
deteriorates, as what happens when there is poor renal blood flow due to hypovolemia. It can also
result from excess production of lactic acid.
3. Potassium Depletion
Potassium is an ion that is present in the fecal matter. If there is excess loss of feces, there would
also be excess loss of potassium ions. This is a greater threat to those who are malnourished as
they already have depleted potassium levels even before diarrhea starts. Signs of hypokalemia
include: general muscle weakness, cardiac arrhythmias, and paralytic ileus.
5. Evaluate the nutritional status and state of hydration of the patient (use growth chart
and assessment of hydration table). Compute for the ideal weight for age of the patient.

Degree of Dehydration
The World Health Organization organized degrees of dehydration in three scales:
1. Severe dehydration, patient has at least 2 of the following signs:
a. Lethargy/unconsciousness
b. Sunken eyes
c. Unable to drink or drink poorly
d. Skin pinch goes back very slowly (2 seconds or more)
2. Some dehydration, patient has at least 2 of the following signs:
a. Restlessness, irritability
b. Sunken eyes
c. Drinks eagerly, thirsty

3. No dehydration, if not enough signs to classify as some or severe dehydration

• The patient on Case 1, the patient can be classified with NO DEHYDRATION, since the
patient is alert, with good skin turgor, and adequate urine output, which are signs of adequate
hydration.
6. Determine the adequacy of the patient’s diet before and during diarrhea relate this to the
cycle of malnutrition and diarrhea.
7. What biochemical significance if any, can be given to the use of “am” with sugar in
diarrheic patients?
• Based on the case, at the onset of diarrhea the mother stopped breastfeeding and the
giving of solid foods and instead shifted to giving “am” with sugar. (King, et al, of cdc.gov in 2003)
has a research of different rehydrating solutions to give to children suffering from diarrhea, and
rice water ORS is one of them. They also explained that foods high in simple sugars (Mono-
saccharides) should be avoided because the osmotic load might worsen the diarrhea. Rice water
however, is riced boiled in water, which then suspends the starch of the rice in the water. Starch
is alpha 1-4 heterogeneous polysaccharide which has a lower osmotic load compared to simple
sugars. However, sugar is put in the solution to give glucose to the child, which will serve as an
energy source for the child. Those reasons explain why the child is alert and with adequate
hydration.
8. What are the advantages of breastfeeding, use of home fluids or oral rehydration
solutions and other nutritional support for the patient?
• Breast milk promotes sensory and cognitive development and protects the infant against
infectious and chronic diseases. Exclusive breastfeeding reduces infant mortality due to common
childhood illnesses such as diarrhea or pneumonia and helps for a quicker recovery during illness.
Infants with diarrhea should always continue to breast-feed. It is an important source of water and
nutrients and can decrease stool volume and the duration of illness.
• Although Home fluids is not as appropriate as that of oral rehydrating salt solution for
treating dehydration, other fluids such as soups, cereal gruels, cereal-salt solutions, or home-
made sugar-and-salt solutions may be more practical and nearly as effective for preventing
dehydration. Home fluids should be given to children to drink as soon as diarrhea starts, and
feeding should be continued. Such early home therapy can prevent many cases from becoming
dehydrated and it also facilitates continued feeding by restoring appetite. The source of glucose
may be a food starch, such as a cooked cereal, or sucrose. As a practical guide, the amount of
starch used should be such that the fluid is thick but can still be drunk easily (usually not more
than 80 g/litre). In relation with the case, the use of “am” with sugar is used as home fluid for the
baby.
• Oral Rehydration Therapy (ORT) is the cheap, simple and effective way to treat
dehydration caused by diarrhea. When diarrhea occurs, essential fluids and salts are lost from
the body and must be quickly replaced. ORT is the giving of fluid by mouth to prevent and/or
correct the dehydration that is a result of diarrhea. As soon as diarrhea begins, treatment using
home remedies to prevent dehydration must be started. An effective solution can be made using
ingredients found in almost every household. This includes fluids at home such as tea, soups,
rice water and fruit juices to prevent dehydration, and the use of Oral Rehydration Salts (ORS)
solution to treat dehydration.
Case 2:
9. Discuss the biochemical basis of diarrhea caused by cholera.
A person can get cholera by drinking water or eating food contaminated with the cholera
bacterium. In an epidemic, the source of the contamination is usually the feces of an infected
person that contaminates water and/or food. The disease can spread rapidly in areas with
inadequate treatment of sewage and drinking water. V. cholerae elaborates several toxins and
factors that play important roles in the organism’s virulence. Cholera toxin (CT) is primarily
responsible for the key features of cholera. Release of this toxin causes mucosal cells to
hypersecrete water and electrolytes into the lumen of the gastrointestinal tract. The result is
profuse, watery diarrhea, leading to dramatic fluid loss.
Cholera toxin (CT) is primarily responsible for the key features of cholera.
 5 B subunits: Binding subunits
 A subunits (A1 and A2): Enzymatic subunits

1. In the small intestine, the toxin attaches by means of the B subunits, binding to ganglioside
receptor present in the cell membrane of mucosal cells.
2. The A subunit then dissociates, and the A1 peptide passes across the inner aspect of the
plasma membrane. It catalyzes the ADP ribosylation (using NAD+ as donor) of the GS
regulatory protein, which inhibits the GTPase activity and fixes it in its active form. Thus
adenylate cyclase becomes chronically activated.
3. This result in an elevation of cAMP, which is thought to activate a protein kinase that
phosphorylates one or more membrane protein involved in active transport.
4. The consequence of this chain of events is that absorption of NaCl into the intestinal cells
is blocked and active secretion of Cl is stimulated.
5. Luminal chloride causes secretion of bicarbonate and sodium, with obligate water, leading
to massive diarrhea with rice watery stool.

10. What are the clinical manifestations of this type of diarrhea?

Symptoms of cholera can begin as soon as a few hours or as long as five days after infection.
Cholera infection is often mild or without symptoms but can sometimes be severe. Approximately
one in ten (10%) infected persons will have severe disease characterized by profuse watery
diarrhea accompanied by vomiting, which can quickly lead to dehydration and shock.
Signs and symptoms of dehydration include:
1. Watery diarrhea (sometimes in large volumes)
2. Rice-water stools
3. Fishy odor to stools.
4. Vomiting.
5. Rapid heart rate.
6. Loss of skin elasticity
7. Dry mucous membranes (dry mouth)
8. Low blood pressure.

11. Is the treatment given to the patient adequate? Discuss the proper management for
diarrhea caused by Cholera.
Cholera can be simply and successfully treated by immediate replacement of the fluid and salts
lost through diarrhea. Patients can be treated with oral rehydration solution (ORS), a prepackaged
mixture of sugar and salts to be mixed with 1 liter of water and drunk in large amounts. This
solution is used throughout the world to treat diarrhea. Severe cases also require intravenous
fluid replacement. With prompt appropriate rehydration, less than 1% of cholera patients die.
Treatment of cholera according to CDC:
1. Oral or intravenous hydration is the mainstay of cholera treatment.
2. In conjunction with hydration, treatment with antibiotics is recommended for severely ill
patients. It is particularly recommended for patients who are severely or moderately dehydrated
and continue to pass a large volume of stool during rehydration treatment. Antibiotic treatment is
also recommended for all patients who are hospitalized.
3. Antibiotic choices should be informed by local antibiotic susceptibility patterns. In most
countries, Doxycycline is recommended as first-line treatment for adults, while azithromycin is
recommended as first-line treatment for children and pregnant women.
4. None of the guidelines recommend antibiotics as prophylaxis for cholera prevention, and
all emphasize that antibiotics should be used in conjunction with aggressive hydration.

References:
■ https://www.cdc.gov/cholera/general/index.html
■ https://www.medicinenet.com/cholera/article.htm
■ https://www.cdc.gov/cholera/treatment/antibiotic-treatment.html
■ http://patients.gi.org/topics/diarrhea-acute-and-chronic/
■ http://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease
■ http://rehydrate.org/diarrhoea/tmsdd/2med.htm
■ http://www.rehydrate.org/dd/su37.htm
■ Integrated Management of Childhood Illness (IMCI) by Rouena S. Villarama
■ IMCI chart booklet
■ Strasinger, Susan King, and Di Lorenzo Marjorie Schaub. Urinalysis and Body Fluids. F.A.
Davis Company, 2014.
■ Kumar, V., Abbas, A. K., & Aster, J. C. (2015). Robbins and Cotran pathologic basis of
disease (Ninth edition.)
■ Blanca Ochoa, MD and Christina M. Surawicz, MD, MACG, University of Washington
School of Medicine, Seattle, WA – Published October 2002. Updated April 2007. Updated
December 2012.
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