Diarrhea and Constipation

Question 1

What are some definitions of Diarrhea? What is the pathophys?

Answer 1

 Increased stool fluidity (frequent patient definition)
 Three or more stools per day
 Stool weight ≥ 200 gm per day

 Normally the gut absorbs most of the fluid it secretes
 The small and large intestine absorb 99% of oral intake and endogenous secretions: a total fluid load of 9 to 10 L daily.
 When infections, toxins or other noxious substances are present, secretion and motility are altered to expel the unwanted material, and diarrhea results.
 Water moves across the intestinal mucosa secondary to osmotic forces generated by the transport of solutes (electrolytes and nutrients).
 A decrease in absorption or increase in secretion lead to additional fluid within the lumen and diarrhea.

Question 2

What is osmotic diarrhea? What is secretory diarrhea? How can you determine which kind of diarrhea predominates?

Answer 2

 Osmotic diarrhea results from the malabsorption of ingested non-electrolytes. These substances retain fluid osmotically within the gut lumen, reducing water absorption.

 Secretory diarrhea (more common) results from either malabsorption (most commonly) or secretion of electrolytes. Many bacterial toxins interfere with ion
transport in the gut, inducing a secretory diarrhea.

 Rarely are the etiologies of diarrhea are purely osmotic or purely secretory, but determining which mechanism predominates can be useful.

Stool osmotic gap:

290 - 2 ([stool Na+] + [stool K+]) = stool osmotic gap

Gap < 50 secretory diarrhea

Gap >100 osmotic diarrhea

Question 3

What are some etiologies of osmotic diarrhea? What improves it?

Answer 3

 Results from ingestion of poorly absorbed items such as mannitol, sorbitol,magnesium, sulfate.

 Disaccharides cannot be absorbed without the appropriate disaccharidase

o Most common disaccharidase deficiency is lactase deficiency.

o Lactase is present on the brush border cells of the small intestine in young mammals, but disappears in adults.

 Osmotic diarrhea disappears with fasting, or with stopping ingestion of the inciting agent.

Question 4

What is the mechanism of secretory diarrhea? Describe some common causes?

Answer 4

 Mechanism is always:

o Net secretion of anions (chloride or bicarbonate) –or-
o Inhibition of net sodium absorption (more common)

 Common causes:
o Infection (enterotoxins- See Chapter 32)
o Neuroendocrine tumors that produce peptides that stimulate secretion by epithelial cells
o Endogenous neurotransmitters and other modulators
 Acetylcholine, serotonin, histamine, inflammatory cytokines
 Work by altering intracellular messengers (cAMP, calcium, etc.)
o Exogenous compounds such as drugs and poisons
o Epithelial injury or decreased absorptive surface area, resulting in abnormal absorption
 Viral gastroenteritis
 Celiac sprue
 Inflammatory bowel disease
 Intestinal resection
o “Intestinal hurry”
 Rapid transit
 Prevents adequate time for absorption
 The malabsorption of electrolytes also can produce a component of osmotic diarrhea
 Examples: diabetes mellitus, post-vagotomy diarrhea

Question 5

Compare and contrast acute and chronic diarrheas and their causes?

Answer 5

 Acute diarrheas (< 4 weeks) are usually caused by infection, and are usually self-limited and/or easily treated.

 Some pathogens can cause chronic diarrhea, even in immunocompetent patients.
Examples are Giardia lamblia or Yersinia species.

Question 6

What is the difference between the etiologies of large and small volume diarrheas?

Answer 6

 The recto-sigmoid region of the colon acts as a storage reservoir. When there is inflammation in this area, frequent, small-volume stools are the result.

 If this area is intact, and the source of inflammation is the right colon or small bowel, stools will be less frequent, but high volume.

 Simply, small, frequent, painful stools often result of inflammation in the distal GI tract, and painless large-volume, watery stools are often the result of right colon or small bowel disease.

Question 7

Describe the differences between watery and inflammatory diarrheas?

Answer 7

 Watery: implies a defect in water absorption, either secretory (increased electrolyte secretion or decreased electrolyte absorption ) or osmotic (ingestion of
poorly absorbed substance)

 Inflammatory: often associated with signs/symptoms of inflammation such as blood in stool, fever, cramping

Question 8

What is the differential diagnosis of acute diarrhea?

Answer 8

Acute Diarrhea

 Infection (bacteria, viruses, protozoa, parasites)

 Food poisoning

 Food allergies

 Medications

 Early onset of chronic diarrhea

Question 9

What is the differential diagnosis of chronic diarrhea?

Answer 9

Chronic Diarrhea

 Watery diarrhea

o Osmotic diarrhea

 Osmotic laxatives

 Carbohydrate malabsorption

o Secretory diarrhea

 Bacterial toxins

 Inflammatory bowel disease

 Diverticulitis

 Vasculitis

 Medications and toxins

 Stimulant laxative abuse

 Disordered gut motility

 Endocrinopathies (hyperthyroidism, neuroendocrine tumors)
 Neoplasia (colon cancer, lymphoma, villous adenoma)

o Inflammatory diarrhea

 Inflammatory bowel disease

 Infectious diseases

 Diverticulitis

 Neoplasia

 Ischemic colitis

o Fatty diarrhea

 Malabsorption

 Maldigestion

 Celiac sprue

 Short bowel syndrome after surgical resection

 See Chapter 15, pages 15-20

 Pancreatic exocrine insufficiency

 Lack of adequate luminal bile acids

Question 10

How is chronic diarrhea treated?

Answer 10

 Supportive Care- replacement of fluid and electrolyte deficits

 Oral rehydration solutions (if not vomiting) containing glucose or amino acids will accelerate sodium and fluid absorption

 Rehydration solutions do not decrease stool output, in fact, stool weight may increase

 Empiric therapy with antibiotics for acute infectious diarrhea, depending on prevalence of infectious agent, severity of illness, and suspected etiology.

Question 11

How do fiber supplements help diarrhea? Examples?

Answer 11

 Fiber supplements

o Alter stool consistency but do not reduce stool weight
o Can be helpful in fecal incontinence by bulkening stool
o Can help delay stool transit, increasing stool form
o Examples: psyllium, guar gum

Question 12

How do opiates help with diarrhea? What are some examples? Which is the preferred? WhY?

Answer 12

 Opiates

o Decrease intestinal motor activity, slowing colonic transit time

o Decrease fluid secretion

o Enhance fluid transport

o Ameliorate abdominal cramping

o Increase anal sphincter tone

o Examples loperamide, diphenoxylate, codeine, morphine, tincture of

opium

 Loperamide is particularly preferred.

 Loperamide does not cross the blood-brain barrier (reducing risk for habituation or other CNS side effects)

o Avoid opiates in patients with severe acute colitis.

Question 13

When are somatostatin analogs used?

Answer 13

 Somatostatin analogs (octreotide)

o Improves diarrhea in specific conditions such as carcinoid syndrome, other endocrinopathies, AIDS-associated diarrhea.

Question 14

Which adrenergic agonist is used? How does it help diarrhea? When can it be used? Side effects?

Answer 14

 Adrenergic agonist (clonidine)

o Affects motility and intestinal transport

o Potentially useful in diabetic patients with diarrhea

o Can cause hypotension, limiting its usefulness in some patients

Question 15

What does bismuth subsalicylate do?

Answer 15

 Bismuth subsalicylate

o Antisecretory agent with rare side effects

o Decreases stool frequency and improves form

o Has antimicrobial (bismuth) and antisecretory (salicylate) properties

Question 16

What do probiotics do? Examples?

Answer 16

 Probiotics

o Modify colonic flora

o May stimulate microenvironment immunity and speed recovery of traveler’s diarrhea or anti-biotic-associated diarrhea

o Examples include Lactobacillus, Bifantis, Saccarhomyces boulardii,

Question 17

What are some definitions for constipation?

Answer 17

 It is important to understand how patients define constipation (e.g., hard stool, straining, inability to have bowel movements)

 Traditional medical definition is 3 for fewer bowel movements per week, but reports of stool frequency do not correlate well with complaints of constipation.

 Rome III Criteria for functional constipation (2006):

o Must include ≥ 2 of the following:

 Straining

 Lumpy or hard stools

 Feeling of incomplete evacuation

 Use of manual maneuvers to facilitate defecation (digital

evacuation, support of pelvic floor)

 Less than 3 bowel movements per week

o Rarely have loose stools unless using a laxative

o Insufficient criteria for constipation-predominant irritable bowel syndrome

o Symptoms must be present for ≥ 3 months

Question 18

What are some risk factors for constipation?

Answer 18

 Female gender (clear reason unknown)

 Age (decreased food intake, reduced mobility, weakening of abdominal and pelvic wall muscles, chronic illness, medications)

 Ethnicity (non-whites vs. whites in North America)

 Lower socio-economic class and education level

 Low fiber diet (suggested by observational studies)

 Physical inactivity (suggested by observational studies)

 Medication use

o Opioids

o Diuretics

o Antidepressants

o Antihistamines

o Antispasmodics

o Anticonvulsants

o Aluminum antacids

o NSAIDS in the elderly

Question 19

Describe 3 types of constipation.

Answer 19

 Normal-transit constipation
o Incomplete evacuation
o Abdominal pain can be present but isn’t a prevailing feature
o Normal physiologic testing

 Slow-transit constipation
o Infrequent stools (e.g., less than once a week)
o Lack of urge to defecate
o Poor response to fiber and laxatives
o Associated with generalized symptoms such as malaise, fatigue
o More prevalent in young women
o Physiologic testing reveals delayed motility

 Defecatory disorders
o Frequent straining
o Incomplete evacuation
o Need for specific maneuvers, such as digital evacuation, to produce a bowel movement
o E.g., pelvic floor dysfunction, rectal prolapsed

Question 20

What are some possible causes of secondary constipation?

Answer 20

 Mechanical obstruction

o Neoplasm

o Stricture

o Extrinsic compression

 Metabolic or endocrine disorders

o Diabetes mellitus

o Hypo/hyper thyroidism

o Hypokalemia

o Hypercalcemia

 Medications

 Neurologic or myopathic disorders

o Parkinson’s disease

o Multiple sclerosis

o Spinal cord injury

Question 21

What are some non-pharmacologic strategies that should be used to treat constipation?

Answer 21

 Reassurance

 Behavioral adjustments
o Set aside regular, unhurried time for defecation
o Respond to the urge to defecate
o Increase activity if sedentary lifestyle
o Avoid constipating drugs if possible

 Addressing confounding psychosocial issues

 Pelvic floor physical therapy if defecatory disorders are present

 Dietary changes
o Increased dietary fiber and fiber supplements can improve mild to moderate constipation.
o Fiber can cause increased bloating, flatulence.
o Instruct patients to increase fiber intake slowly, over weeks, to goal 20 to 25 gm per day.
o Commercially available fiber supplements
 Methylcellulose (Citrucel)
 Psyllium (Metamucil)
 Calcium polycarbophil (FiberCon)
 Guar gum (Benefiber)

Question 22

Describe 3 types of osmotic laxatives.

Answer 22

 Poorly absorbed ions

o Magnesium, sulfate, phosphate compounds
 Magnesium hydroxide
 Fleet phosphosoda
o Create a hyperosmolar environment in the lumen
o Caution use of magnesium and phosphate compounds in those with renal insufficiency

 Poorly absorbed sugars

o Lactulose
 Non-absorbable synthetic disaccharide (galactose + fructose)

 Since not absorbed in the small intestine, undergoes fermentation in colon by bacteria to short chain fatty acids, H2 and CO2

 Lowers stool pH

 Side effects include abdominal bloating and discomfort
o Sorbitol
 Used commercially as an artificial sweetener
 Very similar effects and side effects as lactulose, but cheaper

 Polyethylene glycol (PEG)

o Metabolically inert
o Binds to water molecules within the lumen, increasing intraluminal water
o Not metabolized by colonic bacteria
o PEG solutions with electrolytes are often use for colonoscopy preparations retention

Question 23

What do stimulant laxatives do? Describe two examples.

Answer 23

Stimulant Laxatives- stimulate intestinal motility and increase intestinal secretion. Begin working within hours and often cause abdominal cramping.

 Anthraquinones (e.g., casarca, senna, aloe)

o Inactive plant glycosides that pass through small intestine unchanged

o Hydrolyzed by bacterial glycosidases in the colon to their active metabolites

o Active metabolites increase transport of electrolytes into the lumen, and increase motility by stimulating the myenteric plexus.

o No clear evidence that long term use causes adverse effects, but is in question

 Bisacodyl

o A diphenylmethane compound

o Hydrolyzed by intestinal enzymes, acts both on the small and large bowel

o Effects similar to anthraquinones

o No evidence of adverse events with long term use

Question 24

Describe 2 stool softeners.

Answer 24

Stool Softeners

 Docusate sodium
o A detergent that stimulates fluid secretion by small and large bowel.

o Studies have shown it to be less effective than pysllium.

 Mineral oil
o Becomes emulsified into the stool, providing lubrication of the stool for passage

o Long-term use can cause malabsorption of fat-soluble vitamins, anal seepage

Question 25

Describe 3 types of enemas or suppositories.

Answer 25

 Phosphate enemas
o Cause distension and stimulation of rectum
o Cause superficial damage to rectal epithelium
o Can lead to hyperphosphatemia and hypocalcemia in those that can’t evacuate enemas quickly

 Saline or tap water enemas
o Distend the rectum and soften the feces
o Does not damage the rectal mucosa, and appears to be as effective as phosphate enemas

 Stimulant suppositories
o Glycerin- causes an osmotic effect
o Bisacodyl- stimulates enteric neurons

Question 26

Which chloride channel activator is used? How does it work?

Answer 26

Chloride Channel Activator

 Lubiprostone

o Activates the chloride 2 channel, increasing intestinal secretion and transit

Question 27

Which guanylate cyclase C agonist is used? How does it work?

Answer 27

Guanylate Cyclase C Agonist

 Linaclotide

o Peptide homologue of a heat-stable enterotoxin; activates guanylate cyclase C, leading to increase cGMP

Question 28

What are the prokinetic medications? How do they work?

Answer 28

Prokinetic Medications

 5HT4 agonists

 Increase contractility of the intestine

 Two previous agents removed from the market

 Continuing research is being done on other agents