What is the definition of constipation?
- Variable, but:
1. Infrequent BM: <2/wk for 12 months
2. Infrequent BM: <3/wk for 12 mos w/straining, feeling of incomplete evacuation, hard stool at least 25% of time
What are the 3 patterns of colonic contractions?
- Motor func depends on contraction of CIRCULAR layer of smooth muscle:
1. Short duration stationary motor contractions: short areas of colon (focal); mix fecal material and extract water/electrolytes (15 sec)
2. Long duration: stationary or propagate short distances (orad or aboral direction); mixing and local propulsion (last up to a few mins)
3. Giant migrating complexes (MMC): propagate aborally over extended distances, causing mass mvmt of feces (1-2x/d) after water/electrolyte absorption-> may be precipitated by colonic distention
How does food intake affect colonic motility?
- Causes INC segmental activity via gastrocolic reflex, which may be mediated by CCK, which is responding to food in the stomach
- Response is proportional to the caloric content of a meal -> very heavy meal may induce exaggerated reflex
- Not the same food coming out; just that the entire body is connected
What hormones (4) influence colonic motility?
- CCK: INC frequency & amplitude of segmental contractions
1. PGF: stimulates longitudinal muscle contraction -> propagative
2. PGE: INH circular muscle contraction, so constipating
- Serotonin: mediates intestinal peristalsis & secretion in GI tract as well as modulation of pain perception
1. INC peristalsis
2. INC secretion
3. Modulates pain
What is the role of serotonin in the colon? Rxs?
- Serotonin (5-HT) is an important neurotransmitter in the brain-gut interaction
- Released by enterochromaffin cells: 80% of total body 5-HT in the GI tract
1. 5-HT3 receptor antagonists have offered some help in alleviating pain in IBS and functional dyspepsia
2. 5-HT4 receptor agonists have a pro-kinetic effect in humans
What are the differences b/t functional constipation and IBS-D?
- Both have symptoms >=3 mos, and onset >=6 mos prior to diagnosis
1. IBS-C predominant: starts with abdominal PAIN (have to have pain here; gets better with bowel movements)
2. Functional: NO pain, no alternating diarrhea
What is the epi of constipation?
- Prevalence: 12-19%
- More common in ppl with:
1. Little daily physical activity
2. Low income
3. Poor education
- In pts >65-y/o, esp. females
What is the non-drug-induced etiology of chronic constipation (table)?
- 1o colorectal disorder: less prevalent, and falls under idiopathic constipation (he would put IBS in here)
- 2o: something else going on that is causing the constipation
1. Rule out 2o causes and drugs first, then think about primary/IBS
- Neurogenic: peripheral or central
- Non-neurogenic: metabolic and myopathic
What are some drugs associated with constipation?
- Rule out 2o causes and drugs first, then think about primary/IBS
- Zofran (5-HT3 INH) given for nausea
What things might you think about when elderly person presents with constipation?
- ENDOCRINE/METABOLIC disease: DM, hypothyroid
- NEURO disease: autonomic neuropathy, cerebro-vascular disease, MS, Parkinson's, spinal cord injury
- PSYCH conditions: anxiety, depression
- STRUCTURAL ABNORMALITIES: anorectal conditions (fissures, hemorrhoids, rectal prolapse, rectocele), obstructive colonic lesions
- LIFESTYLE: dehydration, low cal diet, low fiber diet, immobility
- IATROGENIC: meds
What is the pediatric etiology of constipation?
- FUNCTIONAL: 95%
- ORGANIC: 5%
5. Endocrine CT disorder
6. Lead intoxication or botulism
What is the difference b/t pediatric func constipation and func fecal retention?
- Functional constipation: infants and pre-school
1. 2-wk duration of pebble-like, hard stools
- Functional fecal retention: common cause of chronic constipation
1. Fear and toilet refusal from infancy to 16-y/o
What are the important components in constipation diagnosis?
- Hx and PE; other medical conditions
- Evaluate current medication
- Rule out thyroid disorders or electrolytes problem
- Colonoscopy or barium enema (rarely done now)
- Colon transit of markers
- Anorectum manometry
What should you do with pts who present w/chronic constipation unresponsive to conservative tx?
- Rule out 2o causes
- Do colonoscopy, if indicated
- Other test to rule out 1o causes: transit, manometry
Who should get lab data (colon complaints)?
- Labs should be performed in pts w/rectal bleeding, weight loss of ≥10 pounds, a family hx of colon cancer or inflam bowel disease, anemia, or (+) fecal occult blood tests, as well as a person with short-term history of constipation
1. Complete blood cell count (CBC)
2. Serum glucose, creatinine, Ca2+
3. Thyroid-stimulating hormone (TSH)
- Looking for red flags for cancer or IBD (UC, Chron’s)
- REMEMBER: 60-y/o w/severe constipation for past 3 months -> more worried than person who comes in with chronic history of the same problem
What technique was used to get these images? Difference b/t the 2?
- LEFT: normal colon
- RIGHT: colonic malignancy
- Do NOT underestimate importance of colonoscopy in pts >50, esp. those with new-onset constipation
- 1/20 Americans have colon cancer after age 50
What imaging (and other) techniques can be emplyed in the evaluation of constipation?
- Plain films of the abdomen for diagnosis of:
- Barium Enema
- Colon Transit Study *(sitzmark study)
What are Sitzmarks? Potential results?
- Used after colonoscopy; different techniques
- Pt takes 1 capsule on day 0; check x-ray on day 5
1. If >80% of marker passed by day 5 (5 or fewer markers left), then colon transit normal
- Capsules contain 24 radiopaque ring markers
- ATTACHED IMAGES of potential results:
1. Normal colonic transit
2. Colonic inertia: delayed passage of marker through prox colon and no INC in motor activity after meals or with admin of laxatives (SLOW)
3. Outlet delay: markers move normally through colon, but stagnate in rectum (more common in pelvic floor dyssenergia; problem in defection process)
What is anorectal manometry? When is it useful?
- Pressure in rectum goes up, pressure in sphincter goes down in normal person
1. If pressure in sphincter area is high when pt is trying to defecate, this is abnormal
- Helpful, but in severe cases
Who gets severe idiopathic chronic constipation? Complaints?
- Mostly women
- Complaints include:
1. Infrequent defecation
2. Excessive straining when defecating
3. Or both
What pelvic floor muscle is important in defecation?
- Puborectalis: unique, “sling-like” muscle that wraps around the rectum
- In resting phase, in a contracted state, and keeps rectum angled where it meets the anus, working as a sphincter to prevent accidental leakage of stool
- When it relaxes, sphincter relaxes
What is the difference b/t normal defection and pelvic floor dyssynergia?
- NORMAL: relaxation of puborectalis and external anal sphincter muscles, together with INC intra-abdominal pressure and INH of colonic segmenting activity
- DYSSYNERGIC: ineffective defecation associated with a failure to relax, or inappropriate contraction of, the puborectalis and external anal sphincter muscles
1. Will see outlet delay on sitzmark study
What is the etiology of severe idiopathic constipation?
- One study:
1. Slow transit constipation: 11%
2. Dyssynergic defecation: 13%
3. Combo of the two: 5%
4. IBS: 71%
What are some of the txs for constipation?
- PT. EDUCATION: INC fluid and fiber intake -> do NOT underestimate importance of dietary changes
- LAXATIVES: over-the-counter
- OTHER PHARMA:
1. Lubiprostone: Cl- channel activator that INC secretion of electrolytes in the colon
2. 5HT4 agonists, Prucalopride
- DISIMPACTION: pts with a fecal impaction
- BIO-FEEDBACK for pelvic dysfunction
- SURGERY: sub-total colectomy with ileorectal anastomosis (can get ischemic colitis; will have a little diarrhea forever after this)
How are fiber and laxatives used to tx constipation?
- Fiber supplementation can improve symptoms
1. Usually combine fiber supplement w/ laxative or osmotic agent
- BULK-FORMING laxatives: methylcellulose (pill), calcium polycarbophil
- SURFACTANTS (stool softeners): docusate sodium
- OSMOTIC agents: polyethylene glycol (Golytely, Miralax), lactulose
1. Less side effects, and easier to tolerate
- STIMULANT laxatives: bisacodyl (diphenylmethane), senna (anthraquinones)
1. Can cause more pain, side effects
- SUPPOSITORIES: more rapid -> glycerin, bisacodyl
Name 3 pharma therapies for constipation (not laxatives).
- LUBIPROSTONE: locally-acting Cl- channel activator that enhances chloride-rich intestinal fluid secretion
- MISOPROSTOL: PG analog that can stimulate colonic activity
- PRUCALOPRIDE: 5HT4 pro-kinetic agent
1. Available in Europe and Canada, but not in US
What is Hirschsprung disease? Epi?
- Congenital aganglionic megacolon: disorder characterized by obstipation from birth and colonic dilatation proximal to a spastic, non-relaxing and non-propulsive segment of distal bowel
- Obstipation: severe or complete constipation
- EPI: 1:5000-8000 live births and 4:1 M > F
1. 10% of cases in Down's
2. Most cases sporadic, but a few familial
What is the pathogenesis of Hirshsprung? Late consequences?
- Absence of ganglion cells in lg bowel (so bowel remains spastic) submucosa (Meissner) and muscle wall (Auerbach)
1. Func obstruction, so progressive dilatation and hypertrophy proximal to aganglionosis
- LATER: massive distention outruns hypertrophy, wall becomes thinned and ruptures
1. Mortality: superimposed enterocolitis w/fluid and electrolyte disturbances; perforation with peritonitis
- Heterogeneous defects in genes regulating:
1. Migration and survival of neuroblasts
3. Receptor tyrosine kinase activity
- Rectum ALWAYS involved, and sigmoid in most cases; rarely the entire colon
What is the clinical presentation of Hirschsprung's?
- Initial presentation: failure to pass meconium
1. Obstructive constipation, occasional passage of stool
2. Bouts of diarrhea, abdominal distention
- Spastic, and a lot of stool above it, so pressure above can sometimes cause leakage of stool via diarrhea; stops when pressure goes down, so they have constipation again
How is Hirschsprung's diagnosed?
- RECTAL BIOPSY: have to do this b/c gold standard for diagnosis -> dx if ganglion cells are absent
- Abdominal radiographs: massively dilated colonic segment
- Contrast enema
- Anorectal manometry: heightened pressure (see attached image)
What is going on here?
- Abdominal radiograph (left) and contrast enema (right) showing dilated colon
What is the tx for Hirschsprung's?
- Surgical resection of aganglionic segment of bowel
- Normal ganglionic bowel brought down and anastomosed to the anus
- Sphincter function is generally preserved
What are 5 causes of acquired (toxic) megacolon?
- C. diff pseudomembranous colitis: diarrhea initially, but colon may get overwhelmed, leading to constipation and loss of albumin (can even perforate)
1. If colitis is severe, the colon will resign
- Inflammatory bowel disease (IBD: UC or Crohn's)
- Obstruction: tumor or inflammatory stricture
1. Always rule this out when you see a massively dilated colon; may or may not see big mass -> may have to go in with a scope next
2. Pseudo-obstruction (adynamic colon): rare, elderly, after an infection
- Functional disorder associated with PSYCH disease and medication
- Chagas disease: trypanosomes invade bowel wall and destroy enteric plexus (inflam of the ganglia)
1. People coming in from South America
- NOTE: acquired megacolon is a rare, but fatal condition
What is this?
- Toxic megacolon: can be fatal, and can be caused by the 2 attached images
What are these?
- Chagas disease: infection of T. cruzi in myenteric plexus causing loss of ganglion cells in dilated portion of colon (attached)
- Live in thatched roofs
- Invade Meissner's plexus: submucosa
What are these?
- Chagas disease
What is the general organization of the GI wall histo (image)?
What is the difference b/t these 2 images? Disease? Biopsy method? Staining?
- Normal colon wall (left) vs. Hirschsprung's disease (congenital aganglionic megacolon; right)
- Has to be a rectal suction biopsy because you have to get deep enough
1. May have sibling diagnosed with this
- May do sequential biopsies up the colon, starting at the rectum to see where the ganglion cells start
- Can re-stain with CALRETININ to ensure there are no ganglion cells (ignore 4th image; just shows non-specific staining)
1. Box 3 is up-close image of 2
2. Usually, ganglion cells come in little clusters
What are these?
- Normal ganglion cells in the GI tract
- Ganglion cells: lots of cytoplasm and prominent nucleoli off to the side
- Usually, ganglion cells come in little clusters