Download PDF

Diarrhea and Constipation¶

Part 2: Cardinal Manifestations and Presentation of Diseases · Part 2 – Cardinal Manifestations & Presentation · Chapter 49

Key Clinical Points¶

Diarrhea is defined as the passage of abnormally liquid or unformed stools at an increased frequency; for adults on a typical Western diet, stool weight >200 g/d is considered diarrheal.
Acute diarrhea is defined as lasting ≤ 4 weeks; most cases are mild and self-limited, often not requiring diagnostic or pharmacologic intervention.
Fluid and electrolyte replacement is the cornerstone of management for all forms of acute diarrhea.
Stool microbiology is indicated for high-risk features: profuse diarrhea with dehydration, overtly bloody stools, fever ≥38.5°C (≥101°F), duration >48 h without improvement, recent antibiotic use, new community outbreaks, severe abdominal pain in patients >50 years, and elderly (≥70 years) or immunocompromised patients.
Secretory diarrheas are characterized by large volumes of watery stool that persist with fasting and show no fecal osmotic gap.
Rifaximin is suitable for uncomplicated traveler's diarrhea but not for invasive disease.
Constipation is common in developed countries, rarely associated with mortality, and often leads to self-medication.
The colon has a large capacity and can recover up to 4x the usual volume (0.8 L/d) if flow permits reabsorption.
Rectal distention causes transient relaxation of the internal anal sphincter via intrinsic and reflex sympathetic innervation.
Specific pathogens have distinct clinical markers: Yersinia may mimic appendicitis; E. coli O157:H1 is associated with HUS; several pathogens (Salmonella, Campylobacter, Shigella, Yersinia) can lead to Reactive Arthritis or Reiter's syndrome.

1. DEFINITION & OVERVIEW¶

• Diarrhea: passage of abnormally liquid or unformed stools at an increased frequency • Weight Threshold: For adults on a typical Western diet, stool weight >200 g/d is considered diarrheal. • Acute Diarrhea: Defined as duration ≤ 4 weeks. • Pseudodiarrhea: Frequent passage of small volumes of stool; often associated with rectal urgency, tenesmus, or a feeling of incomplete evacuation (common in IBS or proctitis). • Fecal Incontinence: Involuntary discharge of rectal contents; caused by neuromuscular disorders or structural anorectal problems. • Overflow Diarrhea: May occur in nursing home patients due to fecal impaction (detectable via rectal exam). • Constipation: altered bowel habits, typically infrequent bowel movements, straining, or passage of hard stools.

2. EPIDEMIOLOGY¶

• Prevalence: Chronic diarrhea (5.0%) and chronic constipation (8.8%) are common; women are affected 1.5x more often than men. • Impact: Acute infectious diarrhea is a leading cause of death in children under age 5 globally. • Risk Groups for Infectious Diarrhea: ◦ Travelers: Up to 40% of U.S. tourists to endemic regions (Latin America, Africa, Asia) develop traveler's diarrhea (common agents: E. coli [enterotoxigenic/enteroaggregative], Campylobacter, Shigella, Aeromonas, norovirus, Coronavirus, Salmonella). ◦ Immunodeficient Persons: Includes primary (IgA deficiency, CGD) and secondary (AIDS, senescence, pharmacologic suppression) states; often results in severe/prolonged illness. In AIDS patients, pathogens may include Mycobacterium, CMV, adenovirus, HSV, Cryptosporidium, Isospora belli, microsporidia, and Blastocystis hominis. ◦ Daycare Attendees: High risk for Shigella, Giardia, Cryptosporidium, and rotavirus. ◦ Institutionalized Patients: Common site for nosocomial infections, most commonly C. difficile.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

3.1 Normal Physiology¶

• Table 49-1 (Normal Gastrointestinal Motility): ◦ Stomach/Small Bowel: Synchronized MMC in fasting; accommodation, trituration, mixing, transit. ◦ Ileal Reservoir: Empties boluses. ◦ Colon: Irregular mixing, fermentation, absorption, transit. ◦ Cecum, ascending, transverse: reservoirs. ◦ Descending: conduit. ◦ Sigmoid/rectum: volitional reservoir. • Fluid Dynamics: ◦ Daily intake ≈ 9 L; ~1 L reaches colon; stool excretion ≈ 0.2 L/d. ◦ Colonic Capacity: Can recover up to 4x the usual volume (0.8 L/d) if flow permits reabsorption. • Ion Transport (Fig 49-1): ◦ Jejunum: Na^+ entry via SGLT1, NKCC1; Cl^- via ClC-2; K^+ exit via specific channels. ◦ Distal Colon: Na^+ enters via ENaC; Cl^- secretion via CFTR and ClC-2. • Motility: ◦ Migrating Motor Complex (MMC): 'Intestinal housekeeper' during fasting; 4 min duration, every 60–90 min. ◦ Propulsive Contractions: Occur during defecation to move contents forward. • Defecation Mechanics (Fig 49-2): ◦ Puborectalis Muscle: Forms a sling; must relax to straighten the anorectal angle from ~90° to ~130° during defecation.

3.2 Pathophysiology of Diarrhea¶

• Mechanism-based Classification (Table 49-3): ◦ Secretory: Exogenous stimulants, ethanol, drugs/toxins, endogenous laxatives (bile acids), infections, tumors (VIPoma, etc.), Addison's disease. ◦ Osmotic: Laxatives (Mg, PO3), disaccharide deficiencies, nonabsorbable carbs (sorbitol, mannitol), FODMAP intolerance. ◦ Steatorrheal: Maldigestion (pancreatic insufficiency, SIBO), malabsorption (celiac, Whipple's), obstruction. ◦ Inflammatory: IBD, colitis, immune-related diseases, infections, radiation, malignancy. ◦ Dysmotile: IBS, neuropathy, hyperthyroidism, postvagotomy. ◦ Factitial/Iatrogenic: Munchausen, eating disorders, surgery (cholecystectomy, bypass).

3.3 Pathobiology of Causative Agents¶

• Table 49-2 (Clinical Features by Pathogen Type): ◦ Preformed Toxins (B. cereus, S. aureus, C. perfringens): Incubation 1–8h; high vomiting (3–4+); low fever (0–1+); watery diarrhea. ◦ Enteroadherent (E. coli, Giardia, Cryptosporidium): Incubation 1–8d; low vomiting (0–1+); moderate pain/fever; mushy/watery diarrhea. ◦ Invasive (Minimal Inflammation) (Rotavirus, Norovirus): Incubation 1–3d or 12h–11d; high fever (3–4+); watery diarrhea. ◦ Invasive (Severe Inflammation) (Shigella, E. histolytica): Incubation 12h–8d; high fever (3–4+); bloody diarrhea.

4. CLINICAL FEATURES¶

4.1 Acute Diarrhea Features¶

• General Presentation: Often accompanied by vomiting, fever, and abdominal pain. • Pathogen-Specific Clues: ◦ Yersinia: Severe abdominal pain/tenderness mimicking acute appendicitis. ◦ E. coli O157:H1: Risk of Hemolytic-Uremic Syndrome (HUS). ◦ Salmonella, Campylobacter, Shigella, Yersinia: May lead to Reactive Arthritis or Reiter's syndrome. ◦ Yersiniosis: Potential for autoimmune thyroiditis, pericarditis, or glomerulonephritis. • Systemic Associations: Can be a symptom of viral hepatitis, listeriosis, legionellosis, or toxic shock syndrome.

4.2 Chronic Diarrhea Features¶

• Physical Exam (Table 49-4): ◦ Malabsorption/IBD signs: Anemia, arthritis, dermatitis herpetiformis, edema, clubbing. ◦ Autonomic/CV signs: Pupil changes, orthostasis, skin/hand changes. ◦ Local findings: Abdominal mass, tenderness, rectal mucosal abnormalities, altered anal sphincter function. ◦ Systemic markers: Erythema nodosum (UC), flushing (carcinoid), oral ulcers.

5. DIFFERENTIAL DIAGNOSIS¶

5.1 Acute Diarrhea Differential¶

• Pseudodiarrhea: Frequent passage of small volumes; often associated with rectal urgency, tenesmus, or incomplete evacuation. • Fecal Incontinence: Involuntary discharge due to neuromuscular disorders or structural anorectal problems. • Overflow Diarrhea: Due to fecal impaction (detectable via rectal exam).

5.2 Chronic Diarrhea Differential¶

• Secretory: Exogenous stimulants, ethanol, drugs/toxins, endogenous laxatives, infections, tumors. • Osmotic: Laxatives (Mg, PO3), disaccharide deficiencies, nonabsorbable carbs, FODMAP intolerance. • Steatorrheal: Maldigestion (pancreatic insufficiency, SIBO), malabsorption (celiac, Whipple's), obstruction. • Inflammatory: IBD, colitis, immune-related diseases, infections, radiation, malignancy. • Dysmotile: IBS, neuropathy, hyperthyroidism, postvagotomy. • Factitial/Iatrogenic: Munchausen, eating disorders, surgery (cholecystectomy, bypass).

6. INVESTIGATIONS & DIAGNOSIS¶

6.1 Diagnostic Algorithm¶

• Acute Diarrhea (Fig 49-3): 1. Initial Assessment: History and physical exam → Determine if likely noninfectious or likely infectious. 2. Severity Classification: • Mild: Unrestricted activities. • Moderate: Altered activities. • Severe: Incapacitated. 3. Risk Factor Check: Identify high-risk features (Fever ≥38.5°C, bloody stools, f WBCs, immunocompromised, or elderly ≥70 years). 4. Decision Point (High-Risk Features?): • No → (Mild) Fluid/Electrolyte replacement → Observe → Resolve OR Antidiarrheal agents → Resolves or Persists. • Yes → Stool microbiology studies. • Pathogen found: Yes → Select specific treatment. • Pathogen found: No → Empirical treatment + further evaluation. • Chronic Diarrhea (Fig 49-4): 1. Initial Screening: Exclude iatrogenic problems (medication, surgery). 2. Blood Check: • Yes → Colonoscopy + biopsy. • No → Proceed to malabsorption features. 3. Malabsorption Features: If present → Small bowel evaluation (imaging, biopsy, aspirate). 4. Functional Assessment: If symptoms include 'pain before BM, relieved by BM' or sense of incomplete evacuation → Suspect IBS; Consider functional diarrhea → Opioid Rx + follow-up. 5. Stool Fat Quantification: • >20 g/d → Full gut investigation. • 14–20 g/d → 48h stool bile acid (search for small bowel issues). • <10 g/d → Normal stool. • Constipation (Fig 49-5): 1. Initial Assessment: Clinical and basic lab tests (Blood, CXR, Abx-ray). 2. Mechanical Check: Exclude mechanical obstruction via colonoscopy. 3. Colonic Transit Test: • Result: Abnormal → Known disorder? • Yes → Specific treatment (Rx). • No → Anorectal Manometry and Balloon Expulsion. • Result: Normal → Rectoanal angle measurement, defecation proctography. • Result: [Inconclusive] → Appropriate Rx: Rehabilitation program, surgery, or other. • Result: Normal → Consider functional bowel disease.

6.2 Stool Studies¶

• Indications for Study: 1. Profuse diarrhea with dehydration. 2. Overtly bloody stools. 3. Fever ≥38.5°C (≥101°F). 4. Duration >48 h without improvement. 5. Recent antibiotic use. 6. New community outbreaks. 7. Severe abdominal pain in patients >50 years. 8. Elderly (≥70 years) or immunocompromised patients. • Methodology: 1. Culture-independent methods (DNA sequences) are preferred for speed and sensitivity. 2. Culture-based methods, direct microscopy, and immunoassays (C. difficile, rotavirus, Giardia, E. histolytica) used when multiplexing is unavailable or for outbreak detection.

7. MANAGEMENT & TREATMENT¶

7.1 Acute Diarrhea Treatment¶

Fluid and Electrolyte Replacement: Cornerstone of management for all cases.
Antidiarrheal Agents: Used in mild cases without high-risk features.
Empirical Antibiotics: • Traveler's Diarrhea: May reduce severity/duration; Rifaximin used for uncomplicated cases (not for invasive).
Specific Treatment: Initiated when a pathogen is identified via microbiology.

7.2 Chronic Diarrhea & Constipation Management¶

Chronic Diarrhea: • Secretory: Address underlying cause (e.g., stop offending drug, treat tumor). • Osmotic: Identify and remove nonabsorbable substances. • Steatorrheal: Treat maldigestion or malabsorption. • Inflammatory: Manage IBD or specific infections. • Functional: Opioid Rx for confirmed functional cases (e.g., IBS).
Constipation: • Mechanical/Obstruction: Surgical or medical intervention based on finding. • Motility Issues: Treatment for known disorders (e.g., opioid use, prokinetics). • Outlet Dysfunction: Rehabilitation programs or surgery if manometry indicates pelvic floor issues.

8. PROGNOSIS & COMPLICATIONS¶

• Mortality: Acute infectious diarrhea is a leading cause of death in children under age 5 globally. • Complications: - HUS (from E. coli O157:H1). - Reactive Arthritis/Reiter's syndrome (from Salmonella, Campylobacter, Shigella, Yersinia). - Autoimmune thyroiditis, pericarditis, or glomerulonephritis (from Yersiniosis).

9. SPECIAL CONSIDERATIONS¶

9.1 Travelers¶

• Risk: Up to 40% of U.S. tourists to endemic regions (Latin America, Africa, Asia) develop traveler's diarrhea. • Pathogens: E. coli, Campylobacter, Shigella, Aeromonas, norovirus, Coronavirus, Salmonella, Giardia, Cyclospora. • Management: Rifaximin for uncomplicated cases; avoid in suspected invasive disease.

9.2 Immunocompromised¶

• Risk Groups: Primary (IgA deficiency, CGD) and secondary (AIDS, senescence, pharmacologic suppression). • Pathogens: Mycobacterium, CMV, adenovirus, HSV, Cryptosporidium, Isospora belli, microsporidia, Blastocystis hominen. • Special Cases: Hemochromatosis patients are prone to invasive infections with Vibrio and Yersinia.

10. KEY PEARLS & CLINICAL TRAPS¶

• Stool Study Triggers: Fever ≥38.5°C, bloody stools, f WBCs, immunocompromised status, or age ≥70 years. • Rifaximin: Specific for uncomplicated traveler's diarrhea; avoid in suspected invasive disease. • Colonic Reserve: The colon can handle up to 4x the normal volume (0.8 L/d) if transit is slow enough for reabsorption. • Defecation Mechanics: Rectal distension → relaxation of internal anal sphincter; puborectalis must relax to increase anorectal angle by ≥15° (from ~90° to ~130°). • Pathogen Differentiation: - Preformed toxins (e.g., Staph) → rapid onset, high vomiting. - Enterotoxins (e.g., Cholera) → 8–72h incubation, watery diarrhea. - Invasive (e.g., Shigella) → severe inflammation, bloody stools.

Reference Tables¶

TABLE 49-1 Normal Gastrointestinal Motility: Functions at Different Anatomic Levels Stomach and Small Bowel…¶

Harrison's 22e, p.303

Stomach and Small Bowel
Synchronized MMC in fasting
Accommodation, trituration, mixing, transit
Stomach ~3 h
Small bowel ~3 h
Ileal reservoir empties boluses
Colon: Irregular Mixing, Fermentation, Absorption, Transit
Cecum, ascending, transverse: reservoirs
Descending: conduit
Sigmoid/rectum: volitional reservoir

TABLE 49-2 Association Between Pathobiology of Causative Agents and Clinical Features in Acute Infectious Diarrhea…¶

Harrison's 22e, p.306

PATHOBIOLOGY/AGENTS	INCUBATION PERIOD	VOMITING	ABDOMINAL PAIN	FEVER	DIARRHEA
Toxin producers
Preformed toxin
Bacillus cereus, Staphylococcus aureus, Clostridium perfringens	1–8 h 8–24 h	3–4+	1–2+	0–1+	3–4+, watery
	8–72 h	2–4+	1–2+	0–1+
Enteroadherent
Enteropathogenic and enteroadherent E. coli, Giardia organisms, cryptosporidiosis, helminths	1–8 d	0–1+	1–3+	0–2+	1–2+, watery, mushy
	1–3 d 12–72 h	0–1+ 0–1+	3–4+ 3–4+	1–2+ 1–2+
Invasive organisms
Minimal inflammation
Rotavirus and norovirus	1–3 d	1–3+	2–3+	3–4+	1–3+, watery
	12 h–11 d	0–3+	2–4+	3–4+
Severe inflammation
Shigella species, enteroinvasive E. coli, Entamoeba histolytica	12 h–8 d	0–1+	3–4+	3–4+	1–2+, bloody
APPROACH TO THE PATIENT Acute Diarrhea
The decision to evaluate acute diarrhea depends on its severity and duration and on various host factors (Fig. 49-3). Most episodes of acute diarrhea are mild and self-limited and do not justify the cost and potential morbidity rate of diagnostic or pharmacologic inter- ventions. Indications for evaluation (stool microbiological studies) include profuse diarrhea with dehydration, overtly bloody stools, fever ≥38.5°C (≥101°F), duration >48 h without improvement, recent antibiotic use, new community outbreaks, associated severe abdominal pain in patients aged >50 years, and elderly (≥70 years) or immunocompromised patients. In some cases of moderately severe febrile diarrhea associated with fecal leukocytes (or increased fecal levels of the leukocyte proteins, such as calprotectin) or with overt blood, a diagnostic evaluation might be avoided in favor of an empirical antibiotic trial (see below). The cornerstone of diagnosis in those suspected of severe acute infectious diarrhea acquired domestically is microbiologic analysis of the stool. Workup for a microbiologic cause now starts with culture- independent methods. These methods, relying on the identification of unique DNA sequences, are more rapid, sensitive, specific, and cost-effective. The less sensitive culture-based methods for bacte- ria, direct inspection for ova and parasites, and immunoassays for certain bacterial toxins (C. difficile), viral antigens (rotavirus), and protozoal antigens (Giardia, E. histolytica) are now primarily used when multiplexed tests are not available or for outbreak detection that still relies on isolate cultures and should be done when an outbreak is suspected or in domestically acquired severe diarrhea. Alternatively, the aforementioned clinical and epidemiologic asso- ciations may assist in focusing the evaluation. If a particular patho- gen or set of possible pathogens is so implicated, either the whole panel of routine studies may not be necessary or, in some instances, special cultures may be appropriate, as for enterohemorrhagic and other types of E. coli, Vibrio species, and Yersinia. There is no indi- cation for serologic or endoscopic evaluation to exclude underlying intestinal diseases in the context of acute diarrhea.

TABLE 49-3 Major Causes of Chronic Diarrhea According to Predominant Pathophysiologic Mechanism Secretory Causes¶

Harrison's 22e, p.308

Secretory Causes
Exogenous stimulant laxatives
Chronic ethanol ingestion
Other drugs and toxins
Endogenous laxatives (dihydroxy bile acids)
Idiopathic secretory diarrhea or bile acid diarrhea
Certain bacterial infections
Bowel resection, disease, or fistula (↓ absorption)
Partial bowel obstruction or fecal impaction
Hormone-producing tumors (carcinoid, VIPoma, medullary cancer of thyroid,
mastocytosis, gastrinoma, colorectal villous adenoma)
Addison’s disease
Congenital electrolyte absorption defects
Osmotic Causes
Osmotic laxatives (Mg2+, PO−3, SO−2)
4 4
Lactase and other disaccharide deficiencies
Nonabsorbable carbohydrates (fructose, sorbitol, lactulose, polyethylene
glycol)
Wheat and FODMAP intolerance
Steatorrheal Causes
Intraluminal maldigestion (pancreatic exocrine insufficiency, bacterial
overgrowth, bariatric surgery, liver disease)
Mucosal malabsorption (celiac disease, Whipple’s disease, infections,
abetalipoproteinemia, ischemia, drug-induced enteropathy)
Postmucosal obstruction (1° or 2° lymphatic obstruction), amyloidosis
Inflammatory Causes
Idiopathic inflammatory bowel disease (Crohn’s, chronic ulcerative colitis)
Lymphocytic and collagenous colitis
Immune-related mucosal disease (1° or 2° immunodeficiencies, food allergy,
eosinophilic gastroenteritis, C1-esterase inhibitor deficiency, graft-versus-
host disease)
Infections (invasive bacteria, viruses, and parasites, Brainerd diarrhea)
Radiation injury
Gastrointestinal malignancies
Dysmotile Causes
Irritable bowel syndrome (including postinfectious IBS)
Visceral neuromyopathies
Hyperthyroidism
Drugs (prokinetic agents) and poisons
Postvagotomy
Factitial Causes
Munchausen
Eating disorders
Iatrogenic Causes
Cholecystectomy
Ileal resection
Bariatric surgery
Vagotomy, fundoplication

TABLE 49-4 Physical Examination in Patients with Chronic Diarrhea 1. Are there general features to suggest…¶

Harrison's 22e, p.311

1. Are there general features to suggest malabsorption or inflammatory bowel
  disease (IBD) such as anemia, arthritis, dermatitis herpetiformis, edema, or
  clubbing?
  2. Are there features to suggest underlying autonomic neuropathy or collagen-
  vascular disease in the pupils, orthostasis, skin, hands, or joints?
  3. Is there an abdominal mass or tenderness?
  4. Are there any abnormalities of rectal mucosa, rectal defects, or altered anal
  sphincter functions?
  5. Are there any mucocutaneous manifestations of systemic disease such as
  dermatitis herpetiformis (celiac disease), erythema nodosum (ulcerative
  colitis), flushing (carcinoid), or oral ulcers for IBD or celiac disease?

TABLE 49-5 Causes of Constipation in Adults¶

Harrison's 22e, p.312

TYPES OF CONSTIPATION AND CAUSES	EXAMPLES
Recent Onset
Colonic obstruction	Neoplasm; stricture: ischemic, diverticular, inflammatory
Medications
Chronic
Medications	Ca2+ blockers, antidepressants
Disorders of rectal evacuation	Pelvic floor dysfunction; anismus; descending perineum syndrome; rectal mucosal prolapse; rectocele
Psychiatric disorders	Depression, eating disorders, drugs
Generalized muscle disease	Progressive systemic sclerosis