2. CLINICAL SCENARIO
A 50-year-old woman reported multiple loose bowel
movements associated with mild, cramping abdominal
pain. She had been well until 2 months earlier, when her
bowel habits changed from one formed stool per day to
frequent loose stools (soft) of moderate volume.
The abdominal pain was variable in intensity and was
slightly relieved with defecation.
She had no recent dietary changes and no family history
of intestinal problems, and she had not traveled outside
the United States. She did
not have anorexia, weight loss, hematochezia, episodes of
constipation or abdominal bloating, fever, dyspnea,
nausea, vomiting, pruritus, or flushing.
3. DEFINITION
More than 200 gms ?
Increased volume ? Hard to quantify
Increased frequency ? Some individuals have increased fecal
weight due to fiber ingestion but do not complain of diarrhea
because their stool consistency is normal. Conversely, other
patients have normal stool weights but complain of diarrhea
because their stools are loose or watery
conceptually
ratio= water-holding capacity of insoluble solids/
total water present
Consensus statement by AGA= decrease in fecal consistency lasting for four or
more wks
4. ORGANIC VS FUNCTIONAL DIARRHEA
shorter duration of diarrhea (less than 3 months),
nocturnal diarrhea,
an abrupt onset of diarrhea,
weight loss of more than 11 lb (5.0 kg), and
stool weight of more than 400 g per day.
70 % SPECIFIC FOR FUNCTIONAL ETIOLOGY
5. CASE…
The patient had a history of Graves' disease, which had been
treated 8 years earlier with radioiodine, and she was receiving
oral levothyroxine at a dose of 88 µg per day.
She said that she did not used alcohol, tobacco, or illicit
drugs.
She appeared well. Her weight was 131 lb (59.4 kg), her
height was 5 ft (1.5 m), and her body-mass index (the
weight in kilograms divided by the square of the height
in meters) was 26.4.
She was afebrile, with a blood pressure of 102/67 mm Hg
and a heart rate of 89 beats per minute.
She had no lymphadenopathy.
The lung and cardiac examinations were normal.
Her abdomen was soft, with normal bowel sounds and no
tenderness or hepatosplenomegaly.
There were no rectal masses;
A stool specimen was negative for occult blood.
Skin and neurologic examinations were normal.
6. CLUES ?
Hypothyroidism ? Underlying graves disease
Levothyroxine ? How long and any change in doses?
Think about celiac dx. ? Why ?
7. CASE CONTD:
The patient received a diagnosis of the irritable bowel
syndrome, and diphenoxylate–atropine and belladonna–
phenobarbital were prescribed.
She noted some improvement with this regimen (e.g.,
the number of stools per day decreased from 10 to 7), but
she reported tenesmus, and her diarrhea became watery.
At a follow-up visit 1 month later, she was advised to
continue these medications.
One month later, the patient's gynecologist referred
her to a gastroenterologist for further recommendations
on management of the irritable bowel syndrome.
The patient's stool was again negative for occult
blood.
8. PAINFULL FUNCTIONAL DIARRHEA-
IRRITABLE BOWEL SYNDROME
The irritable bowel syndrome is characterized by recurrent abdominal pain or
discomfort that occurs at least 3 days per month for at least 3 months, with
two or more of the following:
improvement with defecation,
an onset associated with a change in the frequency of
bowel movements, or
an onset associated with a change in the form (appearance)
of stool.
ABSENCE of alarm characteristics such as weight loss,
nocturnal symptoms, a family history of colorectal
cancer, rectal bleeding, or anemia; these would warrant further
evaluation.
When measured, daily stool output is low, typically less than 400 g per 24 hours.
Consistency varies from loose to soft and rarely is water
Diarrhea does not wake patients from sleep.
Long Hx, extending back to adolescence
Labs are usually nl (hg, esr, albumin)
The irritable bowel syndrome should be a diagnosis of exclusion
9. CLUES
The new symptom of tenesmus is consistent with rectal inflammation and points
away from the diagnosis of the irritable bowel syndrome. A more likely cause of
her chronic diarrhea would be celiac disease, microscopic or collagenous colitis,
or IBD.
Also there is change in consistency: watery
10. CLASSIFICATION
By volume (large vs. small),
By pathophysiology (secretory vs. osmotic),
By epidemiology,
By stool characteristics
watery vs. fatty vs. inflammatory.
For the clinician, these classification schemes are only useful
if they serve to focus the diagnostic and management
approaches toward patients. In this regard, no single
scheme is perfect; the experienced physician uses all of
these classifications to expedite patient care
12. HISTORY
QUESTIONING CLINICAL
IMPLICATIONOnset
Congenital Chloridorrhea, Na+ malabsorption
Abrupt Infections, idiopathic secretory diarrhea
Gradual Everything else
Family history
Congenital absorptive defects, IBD, celiac disease,
multiple endocrine neoplasia
Dietary history
"Sugar-free" foods Sorbitol, mannitol ingestion
Raw milk Brainerd diarrhea
Exposure to potentially impure
water source
Chronic bacterial infections (eg, Aeromonas),
giardiasis, cryptosporidiosis, Brainerd diarrhea
Travel history
Infectious diarrhea, chronic idiopathic secretory
diarrhea
Weight loss
Malabsorption, pancreatic exocrine insufficiency,
neoplasm, anorexia
Previous therapeutic
interventions (drugs, radiation,
surgery, antibiotics)
Drug side effects, radiation enteritis, postsurgical
status, pseudomembranous colitis, post-
cholecystectomy diarrhea
Secondary gain from illness Laxative abuse
Systemic illness symptoms
Hyperthyroidism, diabetes, vasculitis tumors,
Whipple's disease, inflammatory bowel syndrome,
tuberculosis, mastocytosis
13. HISTORY
QUESTIONING CLINICAL
IMPLICATION
Intravenous drug abuse, sexual
promiscuity
AIDS
Immune problems AIDS, immunoglobulin deficiencies
Abdominal pain
Mesenteric vascular insufficiency, obstruction,
irritable bowel syndrome
Excessive flatus Carbohydrate malabsorption
Leakage of stool Fecal incontinence
Stool characteristics
Blood Malignancy, inflammatory bowel disease
Oil/food particles Malabsorption, maldigestion
White/tan color Celiac disease, absence of bile
Nocturnal diarrhea Organic etiology
14. Large-Volume Versus Small-Volume Stools
RATIONALE: that the normal rectosigmoid colon functions as a storage
reservoir.
When that reservoir capacity is compromised by inflammatory or
motility disorders involving the left colon, frequent small-volume bowel
movements ensue. (< 350 ml)
If the source of the diarrhea is upstream in the right colon or
small bowel and if the rectosigmoid reservoir is intact, bowel movements are
fewer, but larger.( 750 ml or more)
Thus, frequent, small, painful stools may point to a distal site of pathology,
whereas painless large-volume stools suggest a right colon or small bowel
source.
PROBLEM: it is difficult for patients to quantify volume
15. Watery diarrhea - a
defect primarily in water absorption due to increased electrolyte
secretion or reduced electrolyte absorption-secretory diarrhea
- ingestion of a poorly absorbed substance-osmotic diarrhea).
The essential characteristic of osmotic diarrhea is that it disappears with
fasting or cessation of ingestion of the offending substance. This
characteristic has been used clinically to differentiate osmotic diarrhea
from secretory diarrhea that typically continues with fasting
Inflammatory: diarrhea implies the presence of one of a limited number of
inflammatory or neoplastic diseases involving the gut.
Fatty diarrhea: implies defective absorption of fat in the small intestine.
Fatty diarrhea (steatorrhea) should be suspected in patients who report
greasy, floating, and malodorous stools and those who are at risk for fat
malabsorption, such as patients with chronic pancreatitis
17. Peripheral neuropathy and orthostatic hypotension
may be the only clues to a diagnosis of amyloidosis.
A thyroid nodule with cervical lymphadenopathy may
be the only lead to the presence of medullary
carcinoma of the thyroid.
Tremor and other systemic signs should lead to
consideration of hyperthyroidism
The perineal, anal, and rectal examinations are
important. Signs of incontinence include skin
changes from chronic irritation, gaping anus, and
weak sphincter tone.
Crohn's disease is associated with perianal skin tags,
ulcers, fissures, abscesses, fistulas, and stenoses.
Fecal impaction or masses might be noted.
Other associated physical findings include
exophthalmos (hyperthyroidism),
aphthous ulcers (IBD and celiac disease),
lymphadenopathy (malignancy, infection or
Whipple's disease),
enlarged or tender thyroid (thyroiditis, medullary
carcinoma of the thyroid),
arthritis (IBD, Whipple's disease),
wheezing and right-sided heart murmurs
(carcinoid syndrome), and
clubbing (liver disease, IBD, laxative abuse,
malignancy).
PHYSICAL EXAMINATION
18. CASE:
Six months after the first visit to her physician, the patient consulted a general internist
while she awaited her appointment with a gastroenterologist.
Her diarrhea persisted, and occasional nausea, vomiting, fever, and chills had developed.
She had no weight loss but now reported that she was awakened during the night several
times each week by fecal incontinence or the need to defecate.
Tests of stool samples for ova and parasites, salmonella, shigella, and
campylobacter were negative.
Stool smears had no white cells or red cells.
Blood tests showed a white-cell count of 4100 per cubic millimeter, with
no leftward shift. The hematocrit was 35%, with a normal mean
corpuscular volume, and the platelet count was 310,000 per cubic
millimeter.
Liver-function tests were normal, including the serum albumin level
(4.3 g per deciliter).
A referral for an urgent evaluation by a gastroenterologist was made, and an appointment
was scheduled for the next month.
A few days later, the patient visited her endocrinologist for a regular follow-up of Graves'
disease. The free thyroxine level was normal, at 1.0 ng per deciliter, and the thyrotropin
level was low, at 0.12 µU per milliliter (normal range, 0.20 to 5.39). Her dose of
levothyroxine was reduced to 75 µg per day.
19. CLUES:
Absence of fecal leukocytes makes inflammatory diarrhea less likely,
although the sensitivity of this test is only 70% and specificity is 50%
The test for fecal lactoferrin has higher sensitivity.
Bacterial infections are rarely a cause of chronic diarrhea.
The sensitivity of tests of three fixed, concentrated stool specimens for ova
and parasites is up to 85%, although giardiasis, amebiasis, and
persistent infection with microsporidia, coccidia, or cryptosporidia
remain possibilities.
The low level of thyrotropin warrants a reduction in the dose of
levothyroxine, although the patient's increasingly severe symptoms
should not be attributed to overreplacement with levothyroxine.
20. CASE
The patient returned to her internist 1 month later. She noted a decrease in stool
frequency to six bowel movements per day and a 3-lb (1.4-kg) weight loss.
The serum sodium level was 139 mmol per liter; chloride, 103 mmol per liter;
potassium, 2.8 mmol per liter; bicarbonate, 21 mmol per liter; blood urea nitrogen,
10 mg per deciliter (3.6 mmol per liter); creatinine, 0.7 mg per deciliter (62 µmol per
liter); and glucose, 89 mg per deciliter (4.9 mmol per liter).
Oral potassium chloride at a dose of 40 mmol per day, pantoprazole at a dose of 40 mg
twice a day, and promethazine at a daily dose of 12.5 mg every 4 to 6 hours as
needed for symptom relief were prescribed, with reported benefit.
Several days later, she was evaluated by a gastroenterologist and an upper endoscopy
and colonoscopy were scheduled
A repeat measurement of potassium showed a level of 3.6 mmol per liter; the vitamin
B12 level was 463 pg per milliliter (342 pmol per liter) (normal range, 180 to 900 pg
per milliliter [133 to 665 pmol per liter]); free thyroxine, 1.1 ng per deciliter; and
thyrotropin, 0.35 µU per milliliter. Stool samples were negative for giardia.
21. CLUES AND DIFFERENTIAL
DXHypokalemia and acidosis
any chronic diarrhea
VIPoma
rectal villous adenoma inflammatory
bowel disease celiac
disease
neoplasm
microscopic colitis
Next step ??
22. CASE:
The patient returned 2 months later (9 months after her initial presentation)
for endoscopy and colonoscopy. She reported an additional 15-lb (6.8-kg)
weight loss, anorexia, increased nausea, and approximately eight bowel
movements per day.
Her colonoscopic examination was normal to the cecum; biopsies were not
performed.
The upper endoscopic examination was normal to the fourth portion of the
duodenum, with no evidence of pale, yellow, or shaggy mucosa, findings that
would be suggestive of Whipple's disease.
Two small-bowel biopsy specimens obtained from the fourth portion of the
duodenum showed mild chronic inflammation, with no evidence of giardia
and no villous flattening.
The serum gastrin level was normal, at 15 pg per milliliter, and
stool samples were negative for Clostridium difficile.
Repeat blood chemical tests were normal except for a potassium level of 2.5
mmol per liter. The dose of potassium chloride was increased to 80 mmol
per day; a follow-up potassium measurement 1 week later was 3.4 mmol per
liter.
A skin test for tuberculosis was positive.
23. CLUES
Ulcerative colitis, Celiac disease and colonic neoplasm
appear to be ruled out.
Positive PPD ? Intestinal TB
Hx. of drinking unpasteurized milk? an
unlikely diagnosis in the United States, especially in
an immunocompetent patient, and it would not
appear to account for this patient's persistent
hypokalemia.
increases concern regarding secretory diarrhea; stool
electrolyte levels should be evaluated
24. CASE
chest radiograph was normal.
One month later, the patient returned for a flexible
sigmoidoscopic examination to investigate the possibility
of collagenous colitis; biopsy specimens obtained during
this examination were normal.
The patient had now lost a total of 27 lb (12.2 kg).
A repeat potassium measurement showed a level of 2.9 mmol
per liter; the dose of potassium chloride was increased to
120 mmol per day.
The stool sodium level was 70 mmol per liter, and the stool
potassium level was 82 mmol per liter
25. CLUES
fecal osmotic gap
290–[(stool sodium level+stool potassium level)x2], is less than 50 mOsm,
a finding that is consistent with secretory diarrhea.
secretory diarrhea+ profound hypokalemia+weight loss = Highly suspicious for
neuroendocrine tumor
Testing VIPoma and
for medullary carcinoma of the thyroid, which may also cause chronic
secretory diarrhea.
A
carcinoid tumor and mastocytosis are other potential causes of this
presentation, but the patient does not report other typical symptoms such as
flushing.
Abuse of nonosmotic laxatives remains a possibility to be tested
by means of urine and stool screening, if the results of gastrointestinal peptide
hormone screening are unrevealing.
26. CASE
The serum calcitonin level was less than 1 pg per milliliter (normal range, 0 to 4).
The 5-hydroxyindoleacetic acid (5-HIAA) level in a 24-hour urine specimen was 4.4
mg (normal range, 0 to 6.0).
The VIP level was more than 400 pg per milliliter (normal value, <50).
27. elevated VIP level should be confirmed with repeat
testing, this result strongly supports a diagnosis of the
VIPoma syndrome.
VIPomas are rare VIP-secreting tumors that arise most
often in the tail of the pancreas and classically result
in watery diarrhea and hypokalemia, as well as
hypochlorhydria or achlorhydria.
Abdominal computed tomography (CT) or magnetic
resonance imaging should be performed to localize
the tumor and look for metastases.
Treatment with a long-acting somatostatin analogue
should be initiated to control the patient's diarrhea.
28. COMPLEX DIARRHEA
Most clinically significant diarrheas are complex;
rather than being produced by a single
pathophysiologic mechanism, they are due to
several. These may include the effects of
substances released by enteric endocrine cells,
cytokines released by local and remote
immunologically reactive cells, by the activity of
the enteric nervous system, and by peripherally
released peptides and hormones (paracrine,
immune, neural, and endocrine systems)
29. PINES
Further complicating the understanding of diarrhea is that certain mediators not only
affect epithelial or muscle function, but also each other.
For example, enteric nerves may stimulate mast cells and products so released from mast
cells (particularly histamine) may alter enteric neuron functions A single agonist—such
as prostaglandin—may have multiple, simultaneous effects on epithelial function,
muscle contraction, and the paracellular pathway, leading to effects on ion transport,
motility, and mucosal permeability
Thus, multiple modulators and multiple effectors contribute to the final clinical picture. A
full appreciation of the pathophysiology of diarrhea requires consideration of
paracrine, immune, neural, and endocrine modulators, a regulatory system that can be
abbreviated by the acronym “PINES”
