chronicdiarrhea.ppt

8/14/2019 CHRONICDIARRHEA.ppt

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CHRONIC DI RRHE


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CLINICAL SCENARIO

A 50-year-old woman reported multiple loose bowelmovements associated with mild, cramping abdominalpain. She had been well until 2 months earlier, when herbowel 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.


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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 diarrheabecause 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


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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 % SPECIF IC FOR FUNCTIONAL ETIOLOGY


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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 g 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), herheight was 5 ft (1.5 m), and her body-mass index (the

weight in kilograms divided by the square of the height inmeters) was 26.4.

She was afebrile, with a blood pressure of 102/67 mm Hgand 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.


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CLUES ?

Hypothyroidism ? Underlying graves disease

Levothyroxine ? How long and any change in doses?

Think about celiac dz. ? Why ?


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CASE CONTD:

The patient received a diagnosis of the irritable bowelsyndrome, and diphenoxylateatropine and belladonnaphenobarbital were prescribed.

She noted some improvement with this regimen (e.g.,the number of stools per day decreased from 10 to 7), butshe reported tenesmus, and her diarrhea became watery.

At a follow-up visit 1 month later, she was advised tocontinue these medications.

One month later, the patient's gynecologist referredher to a gastroenterologist for further recommendations onmanagement of the irritable bowel syndrome.

The patient's stool was again negative for occult blood.


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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, withtwo or more of the following:improvement with defecation,an onset associated with a change in the frequency of

bowel movements, oran 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 colorectalcancer, rectal bleeding, or anemia; these would warrant further

evaluation.

When measured, daily stool output is low, typically less than 400 g per 24hours.

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


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CLASSIFICATION

By volume (large vs. small),

By pathophysiology (secretory vs. osmotic),

By epidemiology,

By stool characteristicswatery vs. fatty vs. inflammatory.

For the clinician, these classification schemes are onlyuseful if they serve to focus the diagnostic and

management approaches toward patients. In this regard,no single scheme is perfect; the experienced physician usesall of these classi f ications to expedite patient care


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SECRETORY DIARRHEA

Laxative abuse

(nonosmotic laxatives)

Post-cholecystectomy (from bile salts) Congenital syndromes (chloridorrhea)

Bacterial toxins

Ileal bile acid malabsorption

Inflammatory bowel diseaseUlcerative colitis

Crohn's diseaseMicroscopic (lymphocytic) colitis Collagenous colitis

DiverticulitisVasculitis

Drugs and poisons

Disordered motility

Postvagotomy diarrheaPostsympathectomy diarrhea Diabetic autonomic neuropathy Hyperthyroidism

Irritable bowel syndrome

Neuroendocrine tumors

Gastrinoma

VIPomaSomatostatinomaMastocytosisCarcinoid syndromeMedullary carcinoma of

thyroid Neoplasia

Colon carcinomaLymphoma

Villous adenomaAddison's diseaseEpidemic secretory

(Brainerd) diarrheaIdiopathic secretorydiarrhea


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questioning clinical implication

Onset

Congenital Chloridorrhea, Na+ malabsorption

Abrupt Infections, idiopathic secretory diarrhea

Gradual Everything else

Family historyCongenital 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 historyInfectious diarrhea, chronic idiopathic secretory

diarrhea

Weight lossMalabsorption, pancreatic exocrine insufficiency,

neoplasm, anorexiaPrevious 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


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HISTORY

questioning clinical implication

Intravenous drug abuse, sexual

promiscuityAIDS

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


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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, f requent small-volume bowelmovements ensue.(< 350 ml)

If the source of the diarrhea is upstream in the right colon orsmall bowel and if the rectosigmoid reservoir is intact, bowel movements arefewer, 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 r ight colon or small bowelsource.

PROBLEM: it is difficult for patients to quantify volume


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Waterydiarrhea

- a defect primarily in water absorption due to increased electrolytesecretion or reduced electrolyte absorption-secretory diar rhea

-ingestion of a poorly absorbed substance-osmotic diarr hea).

The essential characteristic of osmotic diarrhea is that it disappears withfasting or cessation of ingestion of the offending substance. Thischaracteristic 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 numberof inflammatory or neoplastic diseases involving the gut.

Fattydiarrhea: implies defective absorption of fat in the small intestine.Fatty diarrhea (steatorrhea) should be suspected in patients who reportgreasy, floating, and malodorous stools and those who are at risk for fatmalabsorption, such as patients with chronic pancreatitis


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PHYSICAL EXAMINATION

PHYSICAL EXAMINATION


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PHYSICAL EXAMINATION Peripheral neuropathy and orthostatic hypotension

may be the only clues to a diagnosis of amyloidosis.

A thyroid nodule with cervical lymphadenopathymay 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 areimportant. Signs of incontinence include skinchanges from chronic irritation, gaping anus, andweak sphincter tone.

Crohn's disease is associated with perianal skintags, ulcers, fissures, abscesses, fistulas, andstenoses.

Fecal impaction or masses might be noted.

Other associated physical findings includeexophthalmos (hyperthyroidism),

aphthous ulcers (IBD and celiac disease),lymphadenopathy (malignancy, infection orWhipple's disease),enlarged or tender thyroid (thyroiditis, medullarycarcinoma of the thyroid),arthritis (IBD, Whipple's disease),wheezing and right-sided heart murmurs(carcinoid syndrome), andclubbing (liver disease, IBD, laxative abuse, malignancy).


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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 chi l ls had developed.

She had no weight loss but now reported that she was awakened during the night severaltimes each week by fecal incontinence or the need to defecate.

Tests of stool samples for ova and parasites, salmonella, shigella, andcampylobacter were negative.

Stool smears had no white cells or red cells.Blood tests showed a white-cell count of 4100 per cubic millimeter, withno leftward shift. The hematocrit was 35%, with a normal meancorpuscular volume, and the platelet count was 310,000 per cubicmillimeter.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 anappointment was scheduled for the next month.

A few days later, the patient visited her endocrinologist for a regular follow-up ofGraves' disease. The free thyroxine level was normal, at 1.0 ng per deciliter, and the

thyrotropin level was low, at 0.12 U per milliliter (normal range, 0.20 to 5.39). Herdose of levothyroxine was reduced to 75 g per day.


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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 forova and parasites is up to 85%, although giardiasis, amebiasis, andpersistent infection with microsporidia, coccidia, or cryptosporidia

remain possibilities.

The low level of thyrotropin warrants a reduction in the dose oflevothyroxine, although the patient's increasingly severe symptomsshould not be attributed to overreplacement with levothyroxine.


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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 mol perliter); 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 40mg twice a day, and promethazine at a daily dose of 12.5 mg every 4 to 6 hours asneeded for symptom relief were prescribed, with reported benefit.

Several days later, she was evaluated by a gastroenterologist and an upperendoscopy and colonoscopy were scheduled

A repeat measurement of potassium showed a level of 3.6 mmol per liter; thevitamin B12 level was 463 pg per milliliter (342 pmol per liter) (normal range, 180 to900 pg per milliliter [133 to 665 pmol per liter]); free thyroxine, 1.1 ng per deciliter;and thyrotropin, 0.35 U per milliliter. Stool samples were negative for giardia.


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CLUES AND DIFFERENTIAL DX

Hypokalemia and acidosis

any chronic diarrhea

VIPoma

rectal villous adenomainflammatory bowel disease

celiac disease

neoplasm

microscopic colitis

Next step ??


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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 bowelmovements per day.

Her colonoscopic examination was normal to the cecum; biopsies were notperformed.

The upper endoscopic examination was normal to the fourth portion of theduodenum, with no evidence of pale, yellow, or shaggy mucosa, findings thatwould be suggestive of Whipple's disease.

Two small-bowel biopsy specimens obtained from the fourth portion of theduodenum showed mild chronic inflammation, with no evidence of giardiaand no villous flattening.

The serum gastrin level was normal, at 15 pg per milliliter, and

stool samples were negative for Clostridium dif f icile.

Repeat blood chemical tests were normal except for a potassium level of 2.5mmol per liter. The dose of potassium chloride was increased to 80 mmolper day; a follow-up potassium measurement 1 week later was 3.4 mmol perliter.

A skin test for tuberculosis was positive.


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CLUES

Ulcerative colitis, Celiac disease and colonic neoplasm

appear to be ruled out.

Positive PPD ? Intestinal TBHx. 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'spersistent hypokalemia.

increases concern regarding secretory diarrhea; stool

electrolyte levels should be evaluated


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CASE

chest radiograph was normal.

One month later, the patient returned for a flexiblesigmoidoscopic examination to investigate the possibility of

collagenous colitis; biopsy specimens obtained during thisexamination were normal.

The patient had now lost a total of 27 lb (12.2 kg).

A repeat potassium measurement showed a level of 2.9mmol per liter; the dose of potassium chloride wasincreased to 120 mmol per day.

The stool sodium level was 70 mmol per liter, and the stoolpotassium level was 82 mmol per liter


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CLUES

fecal osmotic gap290[(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 forneuroendocrine tumor

TestingVIPoma and for medullary carcinoma of the thyroid, which may also

cause chronic secretory diarrhea.

A carcinoid tumor and mastocytosis are other potential causes ofthis 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 peptidehormone screening are unrevealing.


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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 permilliliter (normal value,


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elevated VIP level should be confirmed with repeat testing,this result strongly supports a diagnosis of the VIPomasyndrome.

VIPomas are rare VIP-secreting tumors that arise most

often in the tail of the pancreas and classically result inwatery diarrhea and hypokalemia, as well ashypochlorhydria or achlorhydria.

Abdominal computed tomography (CT) or magneticresonance 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.


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COMPLEX DIARRHEA

Most clinically significant diarrheas are complex;rather than being produced by a singlepathophysiologic mechanism, they are due to

several. These may include the effects ofsubstances released by enteric endocrine cells,cytokines released by local and remoteimmunologically reactive cells, by the activity of

the enteric nervous system, and by peripherallyreleased peptides and hormones (paracrine,immune, neural, and endocrine systems)

PINES


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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 agonistsuch as prostaglandinmay 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 ofparacrine, immune, neural, and endocrine modulators, a regulatory system that can beabbreviated by the acronym PINES

SECRETORY DIARRHEA


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SECRETORY DIARRHEA Laxative abuse (nonosmotic

laxatives)

Post-cholecystectomy (from bile salts)

Congenital syndromes (chloridorrhea)

Bacterial toxins

Ileal bile acid malabsorption

Inflammatory bowel diseaseUlcerative colitisCrohn's diseaseMicroscopic (lymphocytic) colitis

Collagenous colitis Diverticulitis Vasculitis

Drugs and poisons

Disordered motility

Postvagotomy diarrheaPostsympathectomy diarrheaDiabetic autonomic neuropathy

HyperthyroidismIrritable bowel syndrome

Neuroendocrine tumorsGastrinomaVIPoma

SomatostatinomaMastocytosisCarcinoid syndromeMedullary carcinoma of thyroid

NeoplasiaColon carcinomaLymphomaVillous adenomaAddison's disease

Epidemic secretory (Brainerd) diarrheaI diopathic secretory diarrhea


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OSMOTIC DIARRHEA


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INFLAMMATORY DIARRHEA

Inflammatory bowel disease

Ulcerative colitis Crohn'sdisease DiverticulitisUlcerative jejunoileitis

Infectious diseases Pseudomembranous colitis Invasive bacterial infections

Tuberculosis,yersinosis,othersUlcerating viral infections

CytomegalovirusHerpes simplexAmebiasis/other invasive parasites

Ischemic colitis

Radiation colitis

NeoplasiaColon cancerLymphoma


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FATTY DIARRHEA

Fatty diarrhea

Malabsorption syndromes Mucosal diseases

Short bowel syndrome Postresection diarrhea Small bowel bacterial

overgrowthMesenteric ischemia

MaldigestionPancreatic exocrineinsufficiencyInadequate luminal bileacid


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chronicdiarrhea.ppt

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