Constipation - Sleisenger and Fordtran's Gastrointestinal and Liver Disease

Definition and Symptoms

• Hard stools
• Difficulty with defecation
• Sensation of incomplete evacuation
• Abdominal discomfort, bloating, excessive straining
• Sensation of anorectal blockage

Rome IV Criteria for Functional Constipation (Box 19.1)

• (a) Straining during >25% of defecations
• (b) Lumpy or hard stools (Bristol Types 1-2) during >25% of defecations
• (c) Sensation of incomplete evacuation during >25% of defecations
• (d) Sensation of anorectal obstruction/blockage during >25% of defecations
• (e) Manual maneuvers to facilitate defecation (e.g., digital evacuation, pelvic floor support) during >25% of defecations
• (f) Fewer than 3 spontaneous bowel movements per week

Bristol Stool Form Scale

Risk Factors (Box 19.2)

• Female sex (particularly young women for slow-transit constipation)
• Older age (constipation affects 3-31% of the population; prevalent in women, children, older adults)
• Sedentary lifestyle / immobility
• Low dietary fiber and fluid intake
• Medications (opioids, anticholinergics, calcium channel blockers, tricyclic antidepressants, iron supplements, antacids containing calcium/aluminum)
• Systemic illnesses: hypothyroidism, hypercalcemia, diabetes mellitus, Parkinson's disease, multiple sclerosis, spinal cord lesions
• Mechanical obstruction (colorectal cancer, strictures)
• Pelvic floor dysfunction

Classification of Functional Constipation (Table 19.1)

• 59% - Normal-transit constipation
• 25% - Defecatory disorder
• 13% - Slow-transit constipation
• 3% - Combined defecatory disorder + slow-transit constipation

1. Normal-Transit Constipation

• Stool travels at a normal rate through the colon
• Patients may have a perception of difficult defecation and hard stools despite normal colonic transit
• Features: incomplete evacuation, abdominal pain may be present
• Physiologic tests: Normal
• Often overlap with IBS-C; psychological distress, somatization, and visceral hypersensitivity may contribute

2. Slow-Transit Constipation

• Characterized by infrequent stools (≤1/week), lack of urge to defecate, poor response to fiber and laxatives, generalized symptoms (malaise, fatigue)
• More prevalent in young women
• Physiologic test results: Delay in colonic transit - retention of >20% of radiopaque markers in the colon 5 days after ingestion
• Pathophysiology: Reduced number of high-amplitude propagating contractions (HAPCs) in the colon; changes in enteric excitatory motor innervation of smooth muscle
• Histopathological changes in enteric nervous system (reduced interstitial cells of Cajal and neuropeptide Y-containing neurons described)

3. Defecatory Disorder (Rectal Evacuation Disorder / Dyssynergic Defecation / Pelvic Floor Dyssynergia)

• Features: frequent straining, incomplete evacuation, need for manual maneuvers to facilitate defecation
• Physiologic tests: Abnormal balloon expulsion or defecography; inappropriate muscle contraction on manometry/EMG
• The patient paradoxically contracts the puborectalis and external anal sphincter instead of relaxing during defecation
• Often diagnosed by anorectal manometry + balloon expulsion test

Diagnostic Tests

Tests for Structural Disease

• CT / MRI / Barium enema - assess width and length of colon, exclude obstructing lesion
• Colonoscopy - reserved for patients with alarm symptoms (rectal bleeding, recent change in bowel habits, weight loss, fever) or age ≥45-50 for colorectal cancer screening. Yield in absence of alarm symptoms is low (~5.5% polyps, no cancers found in 786 patients)
• Plain abdominal X-ray - can demonstrate fecal loading; used with radiopaque marker studies

Physiologic Testing (reserved for refractory cases)

1. Colonic Transit Time

• Radiopaque marker (Sitzmarks) study: Patient ingests 20-24 inert markers; abdominal X-rays taken at Day 3 (72 hr) and Day 5 (120 hr). Retention of >20% of markers at 120 hours = slow transit.
• Distribution pattern helps localize problem:
  • Markers scattered throughout the colon = slow-transit constipation (colonic dysmotility)
  • Markers concentrated in the rectosigmoid = defecatory disorder (outlet obstruction)
• Wireless motility capsule - newer non-radiation method to measure regional and whole-gut transit times and contractility

2. Anorectal Manometry

• Resting and maximum squeeze pressures of anal sphincters
• Rectoanal inhibitory reflex (RAIR) - absence suggests Hirschsprung's disease
• Rectal sensation thresholds
• Ability of the anal sphincter to relax during straining (paradoxical contraction = dyssynergia)
• High resting anal pressure suggests anal fissure or anismus
• A meta-analysis of 79 studies found abnormal manometry in 48% of patients with chronic constipation

3. Balloon Expulsion Test

• Patient attempts to expel a 50-mL water-filled balloon from the rectum (performed sitting on a commode)
• Suggests defecatory disorder if patient cannot expel or has significant delay
• Normal values: 4-75 seconds (women <50 yr); 3-15 seconds (women ≥50 yr)
• Used in conjunction with anorectal manometry (sensitivity enhanced when combined)
• Abnormal in 43% of patients with chronic constipation (meta-analysis)

4. Defecography (Evacuation Proctography)

• Thickened barium instilled into rectum; fluoroscopy (videos/films) obtained while patient rests, defers, and strains to defecate
• Evaluates:
  • Rate and completeness of rectal emptying
  • Anorectal angle changes (normally should open >15° on straining)
  • Amount of perineal descent (abnormal: <1 cm or >4 cm)
  • Structural abnormalities: large rectocele, internal mucosal prolapse, intussusception
• MRI defecography - preferred when available; no radiation, better soft tissue detail, detects cystoceles and colpoceles; limited by difficulty performing in sitting position
• Abnormal in 37% of patients with chronic constipation (excessive perineal descent criterion)

5. Electromyography (EMG)

• Assesses puborectalis and external anal sphincter activity
• Paradoxical increase in puborectalis activity on straining = dyssynergic defecation
• Abnormal EMG in 44% of patients with chronic constipation (meta-analysis)

1. Impaired evacuation on balloon expulsion or defecography
2. Inappropriate contraction of pelvic floor muscles on manometry, imaging, or EMG
3. Inadequate propulsive forces on manometry or imaging

Management

Step 1 - Lifestyle and Dietary Measures (First-line)

• Increase dietary fiber to 20-35 g/day (gradually to avoid bloating)
• Adequate fluid intake
• Regular physical activity
• Establish a regular defecation schedule (utilize the gastrocolic reflex after meals)
• Biofeedback therapy shown to improve stool frequency and rectal evacuation in patients with pelvic floor dyssynergia and slow transit

Step 2 - Bulk-Forming Agents (Fiber Supplements)

Step 3 - Osmotic Laxatives

• Magnesium hydroxide (Milk of Magnesia) - produces bowel movement within 6 hours; risk of hypermagnesemia in renal failure
• Magnesium sulfate - potent, produces large-volume liquid stool; risk of volume shifts
• Sodium phosphate - use with caution; risk of acute phosphate nephropathy (contraindicated in renal impairment, elderly)

• Lactulose - disaccharide metabolized by colonic bacteria; causes gas, bloating, abdominal cramps; sweet taste may worsen nausea (relevant in palliative care)
• Sorbitol - less expensive, equally effective as lactulose
• Polyethylene glycol (PEG / MiraLax) - large molecular weight polymer; not absorbed or metabolized; increases stool water content; excellent safety profile with minimal electrolyte disturbance; well tolerated long-term; the preferred osmotic agent

Step 4 - Stimulant Laxatives (Table 19.3/19.4)

• Stimulant laxatives are effective for short-term use; long-term use may cause melanosis coli (harmless pigmentation) and historically was suspected to cause cathartic colon (largely refuted)
• In opioid-induced constipation: a bowel stimulant (not just a stool softener) is essential; transdermal fentanyl less constipating than oral morphine

Step 5 - Stool Softeners / Emollients

• Docusate sodium - anionic surfactant; reduces surface tension of stool, allowing water to penetrate
• Evidence of efficacy is limited; generally not adequate as monotherapy for significant constipation
• In palliative care, often ineffective due to multifactorial nature of constipation

Step 6 - Newer Secretagogues (for chronic/refractory constipation)

Lubiprostone

• Bicyclic fatty acid (prostaglandin E1 derivative); activates type 2 chloride channels (ClC-2) in intestinal epithelium
• Increases intestinal fluid secretion and transit
• FDA-approved: 24 mcg twice daily for chronic idiopathic constipation in adults; 8 mcg twice daily for IBS-C (women ≥18 yr)
• Most common side effect: nausea (nauseating, especially on empty stomach)

Linaclotide

• 14-amino acid peptide; activates guanylate cyclase C (GC-C) receptor on luminal surface of intestinal epithelium
• Increases intracellular cGMP → increased chloride and bicarbonate secretion into intestinal lumen → increased stool water content; also reduces afferent nerve firing (visceral analgesia)
• FDA-approved: 145 mcg once daily (chronic constipation); 290 mcg once daily (IBS-C)
• Phase 3 trials: 20% responders vs. 5% placebo (≥3 CSBM/week for ≥9/12 weeks)
• Diarrhea most common adverse effect (~4% discontinuation)
• Contraindicated in children <6 years (deaths in juvenile mice); not recommended ages 6-18

Plecanatide

• GC-C agonist; mechanistically similar to linaclotide
• FDA-approved: 3 mg once daily
• Phase 3 trials: ~20% responders vs. ~11% placebo
• Diarrhea in 5.1%; discontinuation in 2.7%

Step 7 - Serotonergic Agents (5-HT4 Agonists)

• Prucalopride - highly selective 5-HT4 agonist; accelerates colonic transit; effective for chronic constipation; FDA-approved (2018); available outside the USA for longer
• Tegaserod - partial 5-HT4 agonist; withdrawn from US market (2007) due to cardiovascular safety concerns; limited availability
• Cisapride - withdrawn due to potentially lethal cardiac dysrhythmias (QT prolongation)

Step 8 - Peripheral Opioid Antagonists (for opioid-induced constipation)

• Methylnaltrexone - quaternary ammonium compound; does not cross the blood-brain barrier; antagonizes peripheral opioid receptors without reversing central analgesia
• Naloxegol - PEGylated naloxone; oral; peripherally acting
• Alvimopan - peripherally acting; used postoperatively

Step 9 - Biofeedback Therapy

• Treatment of choice for dyssynergic defecation / pelvic floor dyssynergia
• Shown to improve stool frequency and rectal evacuation in adults with pelvic floor dyssynergy
• Accelerates colonic transit in this subset
• No benefit demonstrated in constipated children
• Mode of action: extrinsic autonomic efferent pathways mediate the response

Step 10 - Surgical Options (rare, for refractory cases)

• Subtotal colectomy with ileorectal anastomosis - for severe, medically refractory slow-transit constipation confirmed by colonic transit studies; only after defecatory disorder has been excluded
• Surgery carries risk of diarrhea, incontinence, and small bowel obstruction

Special Populations

Opioid-Induced Constipation (Palliative Care - Table 132.5)

• Most patients on opioids experience constipation
• Transdermal fentanyl less constipating than oral morphine
• Stimulant laxative (not just softener) is required
• Bulk-forming agents often worsen constipation in palliative patients (poor oral intake)
• Osmotic agents (lactulose, sorbitol): many patients dislike sweet taste, may exacerbate nausea
• PEG: generally well tolerated

Neurologic Disease

• Parkinson's disease: slow transit, reduced postprandial colonic activity, paradoxical anal sphincter contraction; dopamine-deficient enteric neurons contribute; botulinum toxin injection into puborectalis may help outlet dysfunction
• Multiple sclerosis: constipation in 43-51%; multifactorial (reduced colonic motor activity, immobility, medications)
• Spinal cord lesions above sacral segments: upper motor neuron pattern; delayed rectosigmoid transit; abolished rectal sensation; require bowel management programs with stimulant suppositories, digital stimulation