Constipation pathophysiology
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Constipation Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Constipation On the Web |
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American Roentgen Ray Society Images of Constipation |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]
Overview
About 1.5 liter fluid is entered the colon from small intestine every day. Colon has to excrete out only 200-400 mL stool. The defecation process is consisted of three important stages, include filling of the rectum, feeling the rectum filled, 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 disturbed 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 main microscopic histopathological finding in melanosis coli is brown granular pigment in lamina propria.
Pathophysiology
Colonic Function
- Water absorption
- About 1.5 liter fluid is entered the colon from small intestine every day. Colon has to excrete out only 200-400 mL stool.
- Colon absorbed water and transit the stool into rectum to store and then expel. The amount of water that is absorbed in rectum is depend of the state of hydration.[1]
- Both sodium and chloride are the key elements in reabsorbing water in colon. The more time stool remained in colon, the drier it can become.[2]
- Motility
- There are two kinds of gross motility in colon, include:[1]
- Repetitive non-propulsive contractions: The main type of contraction in mixing and absorption of contents
- High-amplitude propagated contractions (HAPCs): Large coordinated contraction in charge of pushing the stool forward. Increased forms are seen in the morning and after drinking or eating.
- Normal colonic transition is about 20-72 hours.[3]
- HAPCs are decreased mainly in constipation, maybe as the main pathophysiology.[4]
- On molecular basis, the main movements of the gut (peristalsis) are regulated through serotonin (5-hydroxytriptamine [5HT]). 5HT is released from enterochromaffin cells in case 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 ones. 5HT4 is to drive 5HT effect on the gut and 5HT3 is in charge of bowel sensation.[5]
- There are two kinds of gross motility in colon, include:[1]
Defecation
- The defecation process is consisted of three important stages, include:[6]
- Filling of the rectum
- Feeling the rectum filled
- Relaxation of pelvic floor muscles in a coordinated fashion
- Anal sphincters and puborectalis muscle are anatomical contributors to normal fecal consistency.
- Resting anal sphincter tone is caused by both non-voluntary internal (70%) and voluntary external (30%) anal sphincters tone.
- Rectoanal inhibitory reflex (RAIR) is consisted of relaxing the internal anal sphincter in response to rectal distention due to gas or stool. RAIR is completely regulated inside the gut and not controlled by peripheral or central nervous system. Hirschsprung's disease is completely ruled out by presence of RAIR.[2]
- When stool entered 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 that defecation is desired, the puborectalis muscle is voluntarily relaxed and external sphincter is opened, therefore defecation would be occurred with valsalva maneuver.[7]
Pathogenesis
- Primary constipation is caused by anorectal and colonic problems, while secondary constipation is caused by organic and metabolic diseases or medications.
Primary constipation
- Primary constipation is considered when the secondary causes of constipation became ruled out. Without any certain causes or alarm signs, empiric therapy with dietary fibers and laxatives are 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 in constipation. The procedure is consisted of ingestion of marker-contained capsule and taking abdominal X-ray after 120 h (5 days).[8]
- After counting and locating the markers, remaining more than 20% of markers within the colon 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]
- Most of the times patients experience normal transit time and stool frequency. Most of the times 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 the followings for ≥ 3 months and onset of ≥ 6 months before 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, which mostly involve young women.[12]
- The more severe form, called "colonic inertia", is the condition in which eating and prokinetics do not lead to increase motor activity and HAPCs.[13]
- It is postulated that slow-transit constipation is due to decreased number of interstitial cells of Cajal (ICC) and alteration of myenteric plexus neurons which secret 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 of patients with defecation disorder.
- Patients with defecation disorder often have problems even with 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]
- Most of the functional defecation disorders are due to dyssynergia. Dyssynergia is an acquired condition due to disorganized toilet habits, pain during defecation, obstetrics and back injuries.[17]
- The main pathogenesis in dyssynergia is lack of coordination among abdominal, rectoanal, and pelvic floor muscles contractions during defecation process.[17]
- Normal-transit constipation
Secondary constipation
- Most of medications can lead to constipation as a side effect. Therefore, a detailed drug history is needed in every patients with constipation.[18][19][20][21][22]
| Group | Drug | Alternatives |
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| Antihypertensives | Clonidine | |
| Calcium channel blockers | ||
| Ganglionic blockers | ||
| Antidepressants | Tricyclic antidepressants | |
| Cation-containing drugs | Oral iron supplementation |
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| Aluminum-containing drugs | Sucralfate | |
| Antacids | ||
| Analgesics | Opiates |
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| Cannabinoids | ||
| Anti-Parkinson |
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| Antiepileptic | ||
| Antipsychotic | ||
| Antihistamines |
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| Antispasmodics | ||
| Vinca alkaloids | ||
- Diseases that disturbed the nervous system may lead to constipation, such as diabetes mellitus, autonomic neuropathy, Chagas' disease, and Hirschsprung's disease.
- Both hyperglycemia and hypoglycemia can lead to bowel movement disturbance and constipation.[23]
Genetics
- Genetic studies showed the role of genetics in childhood constipation due to various pathogenesis.
- Genes involved in the pathogenesis of childhood constipation and related diseases are as following:[24]
| Group | Gene | OMIM/Chromosome | Syndrome | Other manifestations |
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| Autonomic nervous system | GFAP | 203450/17q21 | Alexander disease |
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| LMNB1 | 169500/5q23 | Cavitating leukodystrophy – autonomic failure |
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| PHOX2B | 209880/4p12 | Congenital central hypoventilation syndrome |
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| HSN2 | 201300/12p13 | Hereditary sensory and autonomic neuropathy type II and III |
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| IKBKAP | 223900/9q31 | |||
| MECP2 | 300005/Xq28 | MECP2 duplication |
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| - | - | Multiple sclerosis-anaemia |
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| SCN9A | 167400/2q24 | Paroxysmal extreme pain disorder |
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| TCF4 | 610954/18q21 | Pitt-Hopkins syndrome |
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| NRXN1 | 610954/2p16.3 | |||
| Innervation | ATRX | 301040/Xq13 | Alpha-thalassemia mental retardation syndrome |
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| RET | 162300/10q11 | MEN2B |
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| ZEB2 | 235730/2q22 | Mowat-Wilson syndrome |
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| HPSE2 | 236730/10q24 | Ochoa syndrome |
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| Muscular | - | 612198 | Abdominal wall hypoplasia |
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| - | 300270 | Adrenomyodystrophy |
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| COL4A5 | 308940/Xq22 | Alport syndrome with diffuse leiomyomatosis |
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| COL4A6 | ||||
| PTRF-CAVIN | 613327/17q21 | Congenital generalised lipodystrophy, type 4 |
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| DES | 601419/2q35 | Desmin-related myopathy |
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| SCN4A | 170500/17q23 | Hyperkalemic periodic paralysis (HYPP) |
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| ZNF9 | 160900/3q21 | Myotonic dystrophy |
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| DMPK | 602668/19q13 | |||
| - | 600096 | Puerto Rican infant hypotonia syndrome |
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| SMN1 | 253300/5q12 | Spinal muscular atrophy |
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| - | 244450 | Kaufman syndrome |
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| AXPC1 | 609033/1q31 | Posterior column ataxia with retinitis pigmentosa |
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| CBP | 180849/16p13 | Rubinstein-Taybi syndrome |
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| EP300 | 180849/22q13 | |||
| HUWE1 | 300706/Xp11 | Turner mental retardation syndrome |
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| UPF3B | 300676/Xq25 | X-linked syndromic mental retardation -14 |
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| Electrolyte disturbance | SLC12A3 | 263800/16q13 | Gitelman syndrome |
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| SLC6A8 | 300036/Xq28 | Creatinine transporter defect |
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| CASR | 239200/3q21 | Hyperparathyroidism – neonatal familial |
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| AVPR2 | 304800/Xq28 | Nephrogenic diabetes insipidus |
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| SPINK5 | 256500/5q32 | Netherton syndrome |
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| Malformation | HLXB9 | 176450/7q36 | Currarino syndrome |
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| MED12 | 305450/Xq13 | FG syndrome |
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| FLNA | 305450/Xq28 | |||
| SIX3 | 157170/2p21 | Holoprosencephaly |
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| VANGL1 | 600145/1p13 | Sacral defect with anterior meningocele |
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Associated Conditions
Associated conditions with constipation are included:
- Diabetes mellitus
- Hypothyroidism
- Systemic sclerosis
- Parkinson's disease
- Depression
- Eating disorders
- Multiple drugs use
- 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
Gross Pathology
- On gross pathology, there is no finding related to constipation.
Microscopic Pathology
- 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 main microscopic histopathological finding in melanosis coli is brown granular pigment in lamina propria.
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References
- ↑ 1.0 1.1 Sleisenger, Marvin (2010). Sleisenger and Fordtran's gastrointestinal and liver disease : pathophysiology, diagnosis, management. Philadelphia: Saunders/Elsevier. ISBN 9781437727678.
- ↑ 2.0 2.1 Andrews CN, Storr M (2011). "The pathophysiology of chronic constipation". Can J Gastroenterol. 25 Suppl B: 16B–21B. PMC 3206564. PMID 22114753.
- ↑ Southwell BR, Clarke MC, Sutcliffe J, Hutson JM (2009). "Colonic transit studies: normal values for adults and children with comparison of radiological and scintigraphic methods". Pediatr. Surg. Int. 25 (7): 559–72. doi:10.1007/s00383-009-2387-x. PMID 19488763.
- ↑ Dinning PG, Smith TK, Scott SM (2009). "Pathophysiology of colonic causes of chronic constipation". Neurogastroenterol. Motil. 21 Suppl 2: 20–30. doi:10.1111/j.1365-2982.2009.01401.x. PMC 2982774. PMID 19824935.
- ↑ Grundy D, Al-Chaer ED, Aziz Q, Collins SM, Ke M, Taché Y, Wood JD (2006). "Fundamentals of neurogastroenterology: basic science". Gastroenterology. 130 (5): 1391–411. doi:10.1053/j.gastro.2005.11.060. PMID 16678554.
- ↑ Bharucha AE (2006). "Pelvic floor: anatomy and function". Neurogastroenterol. Motil. 18 (7): 507–19. doi:10.1111/j.1365-2982.2006.00803.x. PMID 16771766.
- ↑ Rao SS (2010). "Advances in diagnostic assessment of fecal incontinence and dyssynergic defecation". Clin. Gastroenterol. Hepatol. 8 (11): 910–9. doi:10.1016/j.cgh.2010.06.004. PMC 2964406. PMID 20601142.
- ↑ Rao SS, Camilleri M, Hasler WL, Maurer AH, Parkman HP, Saad R, Scott MS, Simren M, Soffer E, Szarka L (2011). "Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies". Neurogastroenterol. Motil. 23 (1): 8–23. doi:10.1111/j.1365-2982.2010.01612.x. PMID 21138500.
- ↑ Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (2006). "Functional bowel disorders". Gastroenterology. 130 (5): 1480–91. doi:10.1053/j.gastro.2005.11.061. PMID 16678561.
- ↑ Ashraf W, Park F, Lof J, Quigley EM (1996). "An examination of the reliability of reported stool frequency in the diagnosis of idiopathic constipation". Am. J. Gastroenterol. 91 (1): 26–32. PMID 8561138.
- ↑ Cash BD, Chey WD (2005). "Review article: The role of serotonergic agents in the treatment of patients with primary chronic constipation". Aliment. Pharmacol. Ther. 22 (11–12): 1047–60. doi:10.1111/j.1365-2036.2005.02696.x. PMID 16305718.
- ↑ Preston DM, Lennard-Jones JE (1986). "Severe chronic constipation of young women: 'idiopathic slow transit constipation'". Gut. 27 (1): 41–8. PMC 1433176. PMID 3949236.
- ↑ Bassotti G, Roberto GD, Sediari L, Morelli A (2004). "Toward a definition of colonic inertia". World J. Gastroenterol. 10 (17): 2465–7. PMC 4572142. PMID 15300885.
- ↑ He CL, Burgart L, Wang L, Pemberton J, Young-Fadok T, Szurszewski J, Farrugia G (2000). "Decreased interstitial cell of cajal volume in patients with slow-transit constipation". Gastroenterology. 118 (1): 14–21. PMID 10611149.
- ↑ Tzavella K, Riepl RL, Klauser AG, Voderholzer WA, Schindlbeck NE, Müller-Lissner SA (1996). "Decreased substance P levels in rectal biopsies from patients with slow transit constipation". Eur J Gastroenterol Hepatol. 8 (12): 1207–11. PMID 8980942.
- ↑ Rao SS, Ozturk R, Laine L (2005). "Clinical utility of diagnostic tests for constipation in adults: a systematic review". Am. J. Gastroenterol. 100 (7): 1605–15. doi:10.1111/j.1572-0241.2005.41845.x. PMID 15984989.
- ↑ 17.0 17.1 Rao SS (2008). "Dyssynergic defecation and biofeedback therapy". Gastroenterol. Clin. North Am. 37 (3): 569–86, viii. doi:10.1016/j.gtc.2008.06.011. PMC 2575098. PMID 18793997.
- ↑ Fosnes GS, Lydersen S, Farup PG (2011). "Constipation and diarrhoea - common adverse drug reactions? A cross sectional study in the general population". BMC Clin Pharmacol. 11: 2. doi:10.1186/1472-6904-11-2. PMC 3049147. PMID 21332973.
- ↑ Simonson W, Han LF, Davidson HE (2011). "Hypertension treatment and outcomes in US nursing homes: results from the US National Nursing Home Survey". J Am Med Dir Assoc. 12 (1): 44–9. doi:10.1016/j.jamda.2010.02.009. PMID 21194659.
- ↑ Dolder C, Nelson M, Stump A (2010). "Pharmacological and clinical profile of newer antidepressants: implications for the treatment of elderly patients". Drugs Aging. 27 (8): 625–40. doi:10.2165/11537140-000000000-00000. PMID 20658791.
- ↑ Talley NJ, Jones M, Nuyts G, Dubois D (2003). "Risk factors for chronic constipation based on a general practice sample". Am. J. Gastroenterol. 98 (5): 1107–11. doi:10.1111/j.1572-0241.2003.07465.x. PMID 12809835.
- ↑ Rosti G, Gatti A, Costantini A, Sabato AF, Zucco F (2010). "Opioid-related bowel dysfunction: prevalence and identification of predictive factors in a large sample of Italian patients on chronic treatment". Eur Rev Med Pharmacol Sci. 14 (12): 1045–50. PMID 21375137.
- ↑ Takahashi T, Matsuda K, Kono T, Pappas TN (2003). "Inhibitory effects of hyperglycemia on neural activity of the vagus in rats". Intensive Care Med. 29 (2): 309–11. doi:10.1007/s00134-002-1580-3. PMID 12594591.
- ↑ Peeters B, Benninga MA, Hennekam RC (2011). "Childhood constipation; an overview of genetic studies and associated syndromes". Best Pract Res Clin Gastroenterol. 25 (1): 73–88. doi:10.1016/j.bpg.2010.12.005. PMID 21382580.