About 1.5 liter fluid enters the colon from small intestine every day. Colon only excrete out 200-400 mL stool. The defecation process consist of three important stages, include filling of the rectum, sensation of rectum fullness, and relaxation of pelvic floor muscles in a coordinated fashion. Primary constipation is caused by anorectal and colonic problems, while secondary constipation is caused by organic and metabolic diseases or medications. Diseases that disturb the nervous system may lead to constipation, such as diabetes mellitus, autonomic neuropathy, Chagas’ disease, and Hirschsprung’s disease. Chronic use of the laxative may lead to melanosis coli, which is identified by hyperpigmentation and brownish discoloration of colonic mucosa. The primary histopathological finding in melanosis coli is brown granular pigment in lamina propria.

• Water absorption
  • About 1.5 liter fluid enters the colon from small intestine every day. Colon excrete out only 200-400 mL stool.
  • Colon absorb water and transit the stool into rectum to store and expel. The amount of water that is absorbed in rectum depends on the state of hydration.^[1]
  • Both sodium and chloride are the key elements in reabsorbing water from colon. The more time stool remains in the colon, the drier it becomes.^[2]
• Motility
  • There are two mechanism of gross motility in colon including:^[1]
    • Repetitive non-propulsive contractions: The primary type of contraction responsible for mixing and absorption of contents.
    • High-amplitude propagated contractions (HAPCs): Large coordinated contraction responsible for pushing the stool forward. Increases in the morning and after drinking and/or eating.
  • Normal colonic transit time is about 20-72 hours.^[3]
  • HAPCs are usually decreased in constipation and maybe the main pathophysiology of constipation.^[4]
  • On molecular basis, the primary movements of the gut (peristalsis) are regulated through serotonin (5-hydroxytriptamine [5HT]). 5HT is released from enterochromaffin cells when the bowel wall undergo traction (e.g., due to food or bolus). There are seven subtypes of the 5HT receptors, among which 5HT₄ and 5HT₃ are the most important for peristalsis. 5HT₄ drives 5HT effect on the gut and 5HT₃ is responsible for the bowel sensation.^[5]

• The defecation process consist of three important stages including:^[6]
  1. Filling of the rectum
  2. Sensation of rectum fullness
  3. Relaxation of pelvic floor muscles in a coordinated fashion
• Anal sphincters and puborectalis muscle are anatomical contributors of normal fecal consistency.
• Resting anal sphincter tone is due to both involuntary internal (70%) and voluntary external (30%) anal sphincters tone.
• Rectoanal inhibitory reflex (RAIR) consist of relaxing the internal anal sphincter in response to rectal distention due to flatus or stool. RAIR is completely regulated by the gut and is not controlled by peripheral or central nervous system. Presence of RAIR rules out Hirschsprung’s disease as a differential diagnosis.^[2]
• When stool enters in rectum, the internal sphincter is relaxed by reflex. If the defecation is inconvenient, the puborectalis muscle is contracted and external sphincter is closed. In case defecation is desired, the puborectalis muscle is voluntarily relaxed and external sphincter is opened. Therefore, defecation may be assisted with valsalva maneuver.^[7]

• Primary constipation is caused by anorectal and colonic problems, while secondary constipation is caused by organic and metabolic diseases or medications.

• Primary constipation is considered when the secondary causes of constipation are ruled out. Without any certain causes or alarm signs, empiric therapy with dietary fibers and laxatives is administered. If the laxative treatment is successful, there will be no need to additional work up.
• Colonic transit test is needed if further work up is necessary for constipation. The procedure consist of ingestion of marker-contained capsule and taking an abdominal X-ray after 120 h (5 days).^[8]
• After locating and counting the markers, if more than 20% of markers remains within the colon, it is defined as slow transit disease.
  • Normal-transit constipation
    • The most common form of constipation referred to clinicians is normal transit constipation, which is also known as functional constipation.^[9]
    • Majority of the patients experience normal transit time and stool frequency. Numerous patients meet the criteria for irritable bowel syndrome with constipation (IBS-C) or psychological disorders.^[10]
    • Rome III criteria for functional constipation is presence of two or more than two of the followings for ≥ 3 months and onset ≥ 6 months before the diagnosis:^[11]
      • < 3 defecation per week
      • Straining during defecation
      • Lumpy or hard stool
      • Sensation if incomplete emptying of rectum
      • Sensation of in anorectal obstruction
      • Manual evacuation need for defecation
    • Most of the patients are cured with dietary fibers, osmotic laxatives, or enterokinetics.
  • Slow-transit constipation
    • Slow-transit constipation is consisted of significant decreased number of defecations, less than once a week and the majority of times involve young women.^[12]
    • The more severe form, called “colonic inertia”, is the condition in which eating and prokinetics does not lead to increase in motor activity and HAPCs.^[13]
    • The slow-transit constipation is due to decreased number of interstitial cells of Cajal (ICC) and alteration of myenteric plexus neurons which secretes substance P.^[14][15]
    • Hypoganglionosis, inflammatory neuropathy, and leiomyopathy are other causes of slow-transit constipation.
  • Defecation disorder
    • Straining and spending long times in toilet are the main findings in patients with defecation disorder.
    • Patients with defecation disorder often have problems with both liquid and firm stools. Therefore, laxatives are not effective mostly.
    • Anorectal manometery and balloon expulsion test are the gold-standard tests for diagnosing functional defecation disorder.^[16]
    • The majority of the functional defecation disorders are due to dyssynergia. Dyssynergia is an acquired condition due to disorganized toilet habits, chronic pain during defecation, obstetrics and back injuries.^[17]
    • The primary defect in dyssynergia is lack of coordination among abdominal, rectoanal, and pelvic floor muscles contractions during defecation process.^[17]

• Most of medications can lead to constipation as a side effect. Therefore, a comprehensive history of medications is needed in every patients with constipation.^{[18][19][20][21][22]}

• Diseases that disturb the nervous system may lead to constipation, such as diabetes mellitus, autonomic neuropathy, Chagas’ disease, and Hirschsprung’s disease.
• Both hyperglycemia and hypoglycemia may lead to bowel movement disturbance and constipation.^[23]

• Genetic studies have shown the role of genetics in childhood constipation by various mechanisms.
• Genes involved in the pathogenesis of childhood constipation and related diseases are as following:^[24]

Associated conditions with constipation are included:

• Diabetes mellitus
• Hypothyroidism
• Systemic sclerosis
• Parkinson’s disease
• Depression
• Eating disorders
• Colon cancer
• External compression from malignant lesion
• Strictures: diverticular or postischemic
• Rectocele (if large)
• Postsurgical abnormalities
• Megacolon
• Anal fissure
• Hypercalcemia
• Hypokalemia
• Hypomagnesemia
• Uremia
• Heavy metal poisoning
• Myopathies
• Parkinson’s disease
• Spinal cord injury or tumor
• Cerebrovascular disease
• Depression
• Degenerative joint disease
• Autonomic neuropathy
• Cognitive impairment
• Immobility
• Cardiac disease

• On gross pathology, there is no finding related to constipation.

• On microscopic histopathological analysis, there is no finding related to constipation.
• Chronic use of the laxative may lead to melanosis coli, which is identified by hyperpigmentation and brownish discoloration of colonic mucosa.
• The primary histopathological finding in melanosis coli is brown granular pigment in lamina propria.