Content Reviewers:

Rishi Desai, MD, MPH

Contributors:
Ursula Florjanczyk, Tanner Marshall, MS, Evan Debevec-McKenney, Anca-Elena Stefan
The gastrointestinal system depends on the coordination of
the sympathetic and parasympathetic nervous systems, pacemaker cells and neurons within the
walls of the stomach and intestine, and the smooth muscle in the gastrointestinal walls. If any
part is disturbed, then it can lead to gastroparesis, which is delayed gastric emptying in the
absence of a mechanical obstruction.
Gastroparesis is usually idiopathic, but it’s associated with a number of diseases like diabetes
mellitus, hypothyroidism, neurological conditions like Parkinson’s disease, viral infections, or
even an autoimmune attack.
There are also iatrogenic causes like inadvertent vagal nerve damage during surgery, or can be
due to medications like opioids, alpha-2-adrenergic agonists like clonidine, tricyclic
antidepressants like amitriptyline, and anticholinergics like atropine.
Individuals with gastroparesis can have symptoms like nausea, vomiting, upper abdominal pain,
early satiety, bloating, and in severe cases, unintentional weight loss. On physical examination,
there’s usually epigastric distention or tenderness in the upper abdomen, but
without guarding or rigidity.
When gastroparesis is suspected, individuals should undergo an upper endoscopy to make sure
that there’s no mechanical obstruction.
Because an upper endoscopy may not always reveal a mechanical obstruction, after the upper
endoscopy, an abdominal CT or magnetic resonance enterography can be done to confirm that
there is no mechanical obstruction.
Now, to establish the diagnosis of gastroparesis, a scintigraphic gastric emptying test should be
done.
For this test, medications that affect the gastric motility should be stopped at least 48 hours
before the test is done. In addition, individuals with diabetes mellitus should have their glucose
blood levels measured before the test and if they are hyperglycemic, then this should be treated
before the test is done as well.
For the test to be accurate, glucose levels should be lower than 275 milligrams per deciliter. Then
the individual usually ingests a low-fat egg-white meal and a tasteless radioactive material,
usually Technetium, which shows up on the scintigraphy. Imaging is performed immediately
after the ingestion and then again at two, and four hours after ingestion.
Delayed gastric emptying is defined as the retention of more than 60% of the gastric content at
two hours and more than 10% of the gastric contents at four hours. Based on the values at four
hours, delayed gastric emptying is considered mild if 10-15% of the gastric content is retained,
moderate if 15-35% of the gastric content is retained, or severe if more than 35% of the gastric
content is retained.
Once the diagnosis of gastroparesis is established, it’s important to investigate the underlying
cause.
Lab tests include hemoglobin to check for anemia, especially if malignancy is suspected, fasting
plasma glucose, serum total protein, albumin to assess for malnutrition, in individuals that have
unintentional weight loss, TSH to check for hypothyroidism, and an antinuclear antibody or
ANA to search for an autoimmune disease.
In individuals with diabetes mellitus, HbA1C is also taken to assess glycemic control.
If the individual has a history of smoking, then ANNA-1 or anti-Hu antibodies are also obtained,
because gastroparesis may also appear as a paraneoplastic syndrome, particularly with lung
cancer.
Next, it’s important to differentiate a myopathic process- a disorder of the skeletal muscles- such
as scleroderma, from a neuropathic process- a disorder of the nervous system- like diabetes. That
can be done with gastroduodenal manometry which is where a pressure-sensitive tube is
endoscopically placed through the nose and into the small intestine for 1 or 2 hours.
The tube senses pressure from muscle contractions. With a myopathic process, the muscle
contractions are low-amplitude, whereas with a neuropathic process, the muscle contractions are
usually of normal amplitude.
Treatment of gastroparesis is generally based on dietary modifications and avoiding medications
that delay gastric emptying.
First of all, individuals with diabetes mellitus should try to maintain tight glycemic control,
because acute hyperglycemia can delay gastric emptying. These individuals should also avoid
incretin based-therapies like Pramlintide and glucagon like peptide-1 analogues because they can
delay gastric emptying as well.
Dietary modifications that can help are eating smaller, more frequent meals, up to 5 times per
day, that are low in fat and contain soluble fiber, like black beans or broccoli. That’s because
both fat and insoluble fibers such as oats delay gastric emptying. Carbonated drinks, alcohol, and
smoking should also be avoided for the same reason.
Individuals with mild gastroparesis are told to focus on good hydration and are often given
vitamin supplementation. If the individual is unable to tolerate solids, then vitamins are added to
liquid meals.
If dietary modifications aren’t enough to control the symptoms of gastroparesis, then medication
therapy is used.
Prokinetic medications, like metoclopramide is first-line therapy with gastroparesis, because it
improves gastric emptying by increasing antral contractions of the stomach and by decreasing
gastric fundus relaxation after a meal. If the individual doesn’t respond to metoclopramide, then
another prokinetic medication, domperidone, may be used.
Before and during treatment with domperidone, electrocardiograms must be done, because
domperidone increases the risk for cardiac arrhythmias.
If the individual doesn’t respond to prokinetic medications, then macrolide antibiotics, such
as erythromycin can be given because they induce high-amplitude gastric contractions that
increase gastric emptying.
It’s important to keep in mind that Erythromycin can induce tachyphylaxis - meaning that the
more it’s administered, the less effective it will be.
Now, another condition that causes symptoms similar to gastroparesis is cyclic vomiting
syndrome.
Cyclic vomiting syndrome is an idiopathic disorder where an individual has episodes of recurrent
vomiting alternating with periods of normal health.
The pattern of vomiting episodes is different for every individual, but in general vomiting begins
early in the morning and is accompanied by lethargy, abdominal pain, and anorexia.
In adults, the episodes of vomiting usually last up to 6 days, followed by a few months of normal
health. In children, vomiting episodes are more irregular and can happen every few weeks.
Cyclic vomiting syndrome is associated with migraine headaches, as well as autonomic disorders
like having an elevated sympathetic tone, endocrine disorders that cause overstimulation of
the hypothalamic-pituitary- adrenal axis, various food allergies, and is linked to chronic cannabis
use.
Cyclic vomiting syndrome is a diagnosis of exclusion, that requires excluding other causes of
vomiting, like toxic etiologies or bowel disorders.
Treatment includes supportive measures, like preventing dehydration with intravenous
fluids, antiemetics like dolasetron, and using sedatives like lorazepam.

Summary
Alright, as a quick recap, gastroparesis is a functional syndrome of delayed gastric emptying,
that causes symptoms like nausea, vomiting, abdominal pain, early satiety, and bloating.
An upper endoscopy, as well as an abdominal CT or an MRI are done to rule out a mechanical
obstruction. A scintigraphic gastric emptying test is done to confirm the diagnosis
of gastroparesis and after 4 hours it’s considered mild if 10-15% of the gastric content is in the
stomach, moderate if 15-35% is left, and severe if more than 35% is left.
To find the cause of gastroparesis, lab work includes: hemoglobin, fasting plasma glucose, serum
protein, albumin, TSH, ANA, HbA1c, ANNA-1 and anti-Hu.
A duodenal manometry may also be performed to differentiate a mipathic cause from a
neuropathic cause of gastroparesis.
Treatment includes dietary modifications, avoiding medication that decreases gastric emptying,
hydrations and nutrition and if the symptoms are not controlled with dietary modifications,
medications such as metoclopramide, domperidone, and erythromycin are used.
On the differential is cyclic vomiting syndrome which causes recurrent episodes of vomiting that
alternate with periods of normal health and is associated with migraine headaches and abdominal
pain.
CVS is a diagnosis of exclusion and treatment includes supportive measures like intravenous
fluids, antiemetics, and sedatives.
Content Reviewers:
Rishi Desai, MD, MPH
Contributors:
Ursula Florjanczyk, Kaitlyn Harper, Sam Gillespie, BSc, Anca-Elena Stefan
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.