Bilal - Constipation/Megacolon

Question 1

What is the definition of constipation?

Answer 1

• Variable, but:
  1. Infrequent BM: <2/wk for 12 months

OR

2. Infrequent BM: <3/wk for 12 mos w/straining, feeling of incomplete evacuation, hard stool at least 25% of time

Question 2

What are the 3 patterns of colonic contractions?

Answer 2

• 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

Question 3

How does food intake affect colonic motility?

Answer 3

• 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

Question 4

What hormones (4) influence colonic motility?

Answer 4

• CCK: INC frequency & amplitude of segmental contractions
• Prostaglandins:
  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

Question 5

What is the role of serotonin in the colon? Rxs?

Answer 5

• 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

Question 6

What are the differences b/t functional constipation and IBS-D?

Answer 6

• 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

Question 7

What is the epi of constipation?

Answer 7

• 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

Question 8

What is the non-drug-induced etiology of chronic constipation (table)?

Answer 8

• 1^o colorectal disorder: less prevalent, and falls under idiopathic constipation (he would put IBS in here)
• 2^o: something else going on that is causing the constipation
  1. Rule out 2^o causes and drugs first, then think about primary/IBS
• Neurogenic: peripheral or central
• Non-neurogenic: metabolic and myopathic

Question 9

What are some drugs associated with constipation?

Answer 9

• Rule out 2^o causes and drugs first, then think about primary/IBS
• Zofran (5-HT3 INH) given for nausea

Question 10

What things might you think about when elderly person presents with constipation?

Answer 10

• 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

Question 11

What is the pediatric etiology of constipation?

Answer 11

• FUNCTIONAL: 95%
• ORGANIC: 5%
  1. Anatomic
  2. Metabolic
  3. Neuropathic
  4. Drugs
  5. Endocrine CT disorder
  6. Lead intoxication or botulism

Question 12

What is the difference b/t pediatric func constipation and func fecal retention?

Answer 12

• 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

Question 13

What are the important components in constipation diagnosis?

Answer 13

• 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

Question 14

What should you do with pts who present w/chronic constipation unresponsive to conservative tx?

Answer 14

• Rule out 2^o causes
• Do colonoscopy, if indicated
• Other test to rule out 1^o causes: transit, manometry

Question 15

Who should get lab data (colon complaints)?

Answer 15

• 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

Question 16

What technique was used to get these images? Difference b/t the 2?

Answer 16

• 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

Question 17

What imaging (and other) techniques can be emplyed in the evaluation of constipation?

Answer 17

• Plain films of the abdomen for diagnosis of:
  1. Megacolon
  2. Impaction
• Barium Enema
• Colon Transit Study *(sitzmark study)
• Defecography
• Manometry

Question 18

What are Sitzmarks? Potential results?

Answer 18

• 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)

Question 19

What is anorectal manometry? When is it useful?

Answer 19

• 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

Question 20

Who gets severe idiopathic chronic constipation? Complaints?

Answer 20

• Mostly women
• Complaints include:
  1. Infrequent defecation
  2. Excessive straining when defecating
  3. Or both

Question 21

What pelvic floor muscle is important in defecation?

Answer 21

• 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

Question 22

What is the difference b/t normal defection and pelvic floor dyssynergia?

Answer 22

• 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

Question 23

What is the etiology of severe idiopathic constipation?

Answer 23

• One study:
  1. Slow transit constipation: 11%
  2. Dyssynergic defecation: 13%
  3. Combo of the two: 5%
  4. IBS: 71%

Question 24

What are some of the txs for constipation?

Answer 24

• 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)

Question 25

How are fiber and laxatives used to tx constipation?

Answer 25

• 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

Question 26

Name 3 pharma therapies for constipation (not laxatives).

Answer 26

• 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

Question 27

What is Hirschsprung disease? Epi?

Answer 27

• 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

Question 28

What is the pathogenesis of Hirshsprung? Late consequences?

Answer 28

• 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
  2. Neurogenesis
  3. Receptor tyrosine kinase activity
• Rectum ALWAYS involved, and sigmoid in most cases; rarely the entire colon

Question 29

What is the clinical presentation of Hirschsprung’s?

Answer 29

• 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

Question 30

How is Hirschsprung’s diagnosed?

Answer 30

• 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)

Question 31

What is going on here?

Answer 31

• Abdominal radiograph (left) and contrast enema (right) showing dilated colon
• Hirschsprung’s

Question 32

What is the tx for Hirschsprung’s?

Answer 32

• Surgical resection of aganglionic segment of bowel
• Normal ganglionic bowel brought down and anastomosed to the anus
• Sphincter function is generally preserved

Question 33

What are 5 causes of acquired (toxic) megacolon?

Answer 33

• 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

Question 34

What is this?

Answer 34

• Toxic megacolon: can be fatal, and can be caused by the 2 attached images

Question 35

What are these?

Answer 35

• 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

Question 36

What are these?

Answer 36

• Chagas disease

Question 37

What is the general organization of the GI wall histo (image)?

Answer 37

Question 38

What is the difference b/t these 2 images? Disease? Biopsy method? Staining?

Answer 38

• 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

Question 39

What are these?

Answer 39

• 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