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Diarrhea: Clinical
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Diarrhea: Clinical
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Anca-Elena Stefan, MD, Sam Gillespie, BSc

Diarrhea is defined as having more than 3 liquidy stools in 24 hours or having a stool
weight of over 200 grams per day, but nobody measures stool weight since that can get
messy - especially if you’re having diarrhea!

Diarrhea is also classified as acute if it lasts for less than 2 weeks, persistent if it lasts for
2 to 4 weeks, and chronic if it lasts for more than a month.

Diarrhea can also be classified as either inflammatory or non-inflammatory.

Inflammatory diarrhea causes inflammation of the gastrointestinal epithelium and this

usually happens with invasive pathogens or as a result of a chronic inflammatory bowel
disease, and usually there are systemic symptoms like fever.

In contrast, non-inflammatory diarrhea can be either secretory or osmotic, and neither

one usually causes systemic symptoms like fever.

With secretory diarrhea, there’s increased water and electrolyte secretion and decreased
absorption.

With osmotic diarrhea, some of the ingested nutrients aren’t fully absorbed, and they
remain in the intestinal lumen and pull in water through the process of osmosis!

Now, most cases of acute diarrhea are caused by pathogens, mostly viruses, but also
bacteria, protozoa, and parasites that mostly spread through fecal-oral transmission.

The minority of cases of acute diarrhea are due to non-infectious causes like stress,
medications, or a toxic ingestion.

Most people with acute diarrhea don’t need to come to the hospital, because symptoms
aren’t severe and resolve within 2 weeks. But in terms of figuring out the cause, it’s
helpful to ask the right questions - like playing Sherlock Holmes.

With infectious organisms, diarrhea is non-inflammatory and secretory, stools are watery
and usually associated with vomiting and this is mostly caused by viruses, such as
norovirus and rotavirus.

Watery diarrhea can also be related to the ingestion of contaminated food - food
poisoning - and in this case timing offers a clue. If diarrhea occurs within six hours of the
ingestion, then the culprit may be Staphylococcus aureus or Bacillus cereus, if diarrhea
occurs 8 to 16 hours after the ingestion, then the culprit may be Clostridium perfringens,
and if diarrhea occurs more than 16 hours after the ingestion, then the culprit may be
enterotoxigenic E. coli.

In contrast, when there’s inflammatory diarrhea, the stools are bloody and mucousy -
called dysentery- and other symptoms include severe abdominal pain and fever. This is
mostly caused by invasive pathogens like Salmonella, Shigella, Yersinia, Campylobacter,
and enteroinvasive E. coli - and these are sometimes shortened to SSYCE.

More specifically, exposure to contaminated foods - particularly animal products like

meat, dairy, and eggs has been associated with Salmonella infection, and drinking
contaminated water can lead to a Giardia infection.

If there was any recent antibiotic use, Clostridium difficile may be the culprit because it
can cause pseudomembranous colitis.

On the physical examination, the most important thing is to assess the degree of
dehydration, and based on the volume lost through stools and/or vomiting, dehydration
can be mild, moderate and severe.

Mild dehydration means that 5% of the total weight was lost and the individual may only
be thirsty.

Moderate dehydration means that 6 to 9% of the total weight was lost and in this case
the individual may have dry mucous membranes, sunken eyes, decreased urine output,
tachypnea, and tachycardia.

Finally, in severe dehydration, more than 10% of the body weight is lost and the
individual might have very dry mucous membranes, decreased skin turgor, cool limbs,
anuria, significant tachypnea and tachycardia, and in extreme cases hypotension and a
loss of consciousness.

Laboratory tests are not usually done in individuals with acute diarrhea, but in severe
cases where there are signs of moderate or severe dehydration - electrolytes, creatinine
and urea nitrogen should be taken in order to rule out renal dysfunction.

In some cases, a CBC can also be helpful. For example, thrombocytopenia and anemia is
suggestive for hemolytic-uremic syndrome which is often caused by E. coli O157 which
produces Shiga toxin. Another example, is that there can be a very elevated white blood
cell count in Clostridium difficile infections.

Finally, for individuals that are ill appearing, or in vulnerable populations like the elderly
or with comorbid conditions, or in fields that could cause a public health concern - like
daycare workers, a more thorough workup should be considered. That includes blood
cultures, fecal leukocytes or fecal lactoferin which helps differentiate inflammatory from
non-inflammatory diarrhea, stool cultures for SSYCE, C.diff toxin assays,
enterohemorrhagic E.coli Shiga toxin, and Entamoeba histolytica testing which is done by
sending three stool specimens that are collected on consecutive days, because ova and
parasite excretion can be intermittent. It’s also worth sending off testing for common
viruses like norovirus and rotavirus to make sure that it isn’t a severe viral gastroenteritis.

Treatment of acute infectious diarrhea is mainly about fluid repletion and dietary
adjustments.

Fluid repletion should be primarily done using oral rehydration solutions that are taken
orally or with a nasogastric tube, and in severe cases like individuals with severe
hypovolemia should be given intravenous fluids. One to two liters of isotonic crystalloids
are given initially to restore tissue perfusion and this is continued until the individual is
euvolemic.

Typically the diet should be focused on liquids and simple foods like juices, soups, bread,
and crackers. In addition, dairy products like milk and cheese should be avoided for a few
months, because acute infectious diarrhea often causes secondary lactose malabsorption.
Live culture yogurt is an exception because it contains live active bacteria that help break
down and digest the lactose in milk.

Empiric antibiotic treatment is given for individuals who are severely ill or have risk
factors for complications or if the onset of symptoms was travel-associated. Some
common regimens are azithromycin 500mg once daily for three days or fluoroquinolones
such as ciprofloxacin 500 mg twice daily for 3 to 5 days.

If a specific pathogen is identified then it can be treated according to the antibiotic that it
is most susceptible to. But some bacteria, like enterohemorrhagic E. coli shouldn’t be
treated with antibiotics because the use of antibiotics increases the toxicity of E. coli’s
Shiga toxin.

Antimotility medications like loperamide can also be used in individuals with diarrhea to
help reduce the frequency of stools. But they should be avoided in individuals with
dysentary who aren’t on antibiotics, because they can prolong or worsen the disease
course.

In persistent diarrhea, the causes differ a bit, and parasitic organisms like Giardia,
Cryptosporidium, and Entamoeba histolytica, are more common - especially in individuals
who travel or who work in a daycare facility.

Giardia and Cryptosporidium cause non-inflammatory secretory diarrhea associated with

abdominal pain, whereas Entamoeba histolytica causes inflammatory diarrhea with
bloody stools, severe abdominal pain, and fever. In this situation, three ova and parasite
samples are sent for testing, and stool antigen testing may also be used to diagnose
specific parasitic infections.

Finally, there’s chronic diarrhea, and the causes vary a bit based on the socio-economic
status of the population.

In low-income countries, chronic diarrhea is mostly caused by infectious organisms such

as Giardia, whereas in high-income countries, chronic diarrhea is mostly caused by
inflammatory bowel disease, and malabsorption syndromes like celiac disease or lactose
intolerance.

If infections with the organisms causing acute diarrhea persist and become chronic in
spite of the treatment, then the individual may be immunocompromised and HIV testing
may be indicated.

A work up for chronic diarrhea typically includes a complete blood count, which is used
to identify anemia, and this is usually seen when there’s chronic disease or
gastrointestinal bleeding. A complete blood count can also identify an elevated white
blood cell count like in inflammatory conditions.

Erythrocyte sedimentation rate, or ESR, and C-reactive protein, or CRP, are also done,
and if they are elevated, then again that’s a sign of inflammation.

Also, a total protein and albumin must be done- because chronic diarrhea can lead to
malnutrition.

And finally, stool occult blood and antibody tests for HIV can be done.

If stools are watery, calculating the stool osmotic gap can help differentiate secretory
diarrhea from osmotic diarrhea.

The stool osmotic gap is determined by taking 290 milliosmoles per kilogram, which is
the constant of the stool osmolality, and subtracting the sum of stool sodium and stool
potassium multiplied by 2.

For example, let’s say that our specimen contains 50 millimoles per litre of sodium and
20 millimoles per litre of potassium. Here, the stool osmolar gap will be 290
milliosmoles per kilogram minus two times 50 plus 20. So 290 minus two times 70 or
290 minus 140, which is 150 milliosmoles per kilogram.

Now, if the stool osmotic gap is greater than 125 milliosmoles per kilogram, then it’s an
osmotic diarrhea which may be caused by malabsorption due to celiac disease, for
example.

Celiac disease may cause steatorrhoea-which is the presence of fat in the stool, weight
loss, abdominal pain, and skin rashes.

Lactose intolerance causes watery diarrhea and abdominal pain.

If the stool osmotic gap is less than 50 milliosmoles per kilogram, then it’s a secretory
diarrhea.

Chronic secretory diarrhea may be caused by a VIPoma which is a tumor that produces
vasoactive intestinal peptide that increases water and electrolyte secretion in the
intestinal lumen.

The diagnosis here is made by measuring the serum level of VIP, which can exceed 75
picograms per milliliter if there’s a VIPoma.

Another cause may be a carcinoid which is a neuroendocrine tumor that is usually located
in the gastrointestinal tract and secretes serotonin that leads to secretory diarrhea and
flushing.

There’s also Zollinger Ellison syndrome, which is a neuroendocrine tumor that secretes
gastrin and this can also be a cause of chronic secretory diarrhea.

On the other hand, inflammatory bowel disease causes inflammatory diarrhea with
bloody stools, fever, and weight loss.

Another lab test - stool calprotectin - which is released by neutrophils in the

gastrointestinal tract is a good marker for inflammatory bowel disease.

With inflammatory diarrhea, both upper and lower endoscopy procedures are usually
needed to assess the extent of mucosal damage.

Each specific cause of chronic diarrhea has a specific treatment, but general measures
that include fluid repletion and dietary adjustments are indicated and also symptomatic
treatment with loperamide can be tried to lower the stool frequency.

Summary
Alright, as a quick recap. Acute diarrhea is mostly caused by infectious organisms, and in
severe cases, laboratory tests such as a CBC, electrolytes, urea nitrogen, creatinine,
blood cultures and stool cultures are necessary.

Treatment of acute diarrhea relies on fluid repletion using oral rehydration solutions or
intravenous fluids if there’s severe hypovolemia. In some cases, empiric antibiotic therapy
with azithromycin or ciprofloxacin can be started.

With persistent diarrhea, the main cause is a parasitic infection.

And with chronic diarrhea, a full blood workup is done and this includes CBC, ESR, C
reactive protein, total protein and albumin, antibody test for HIV and stool occult blood.

With watery stools, the stool osmotic gap can be calculated.

In secretory diarrhea, the stool osmotic gap is lower than 50 millimoles per kilogram and
this can happen with VIPomas, Carcinoid tumors or Zollinger Ellison syndrome.

In osmotic diarrhea, the stool osmotic gap is greater than 125 millimoles per kilogram
and this can happens with malabsorption syndromes such as celiac disease and lactose
intolerance.

With inflammatory diarrhea, stool calprotectin is a marker of inflammation and in most

cases, an upper and lower endoscopy are needed.

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