29 - Diseases of the Colon and Rectum Flashcards
1
Q
Colon & Rectum - Development
A
First trimester of gestation Distal midgut (Cecum to splenic flexure) & hindgut (splenic flexure to rectum)
2
Q
Colon & rectum - Size
A
1m long
2L capacity
3
Q
Colon & Rectum - Regions
A
Cecum Ascending Colon Transverse Colon Descending Colon Sigmoid Colon Rectum
4
Q
Colon - 5 layers
A
Mucosa Submucosa Circular muscle Longitudinal muscle Serosa
5
Q
Colon - Haustra
A
Tonic contractions of rings of circular muscle (plicae semilunares coli)
6
Q
Colon - Circular muscle layer control
A
Thin layer of cells, interstitial cells of Cajal on submucosal surface of smooth muscle layer
7
Q
Colon & Rectum - Histo
A
Mucosa:
Columnar cells
Goblet cells
Enteroendocrine cells (mainly located in the crypts)
No Villi
Epithelial cells proliferate in lower parts of crypts, migrate toward surface
8
Q
Blood supply: Cecum, Ascending Colon, Transverse Colon
A
SMA
9
Q
Blood Supply: Transverse Colon, Descending Colon, Sigmoid Colon, Rectum
A
IMA
10
Q
Venous drainage
A
Analogous to arterial supply
11
Q
Colon - Neuronal supply
A
Intrinsic and extrinsic neurons
Extrinsic - Autonomic
Parasympathetic innervation supplied by vagal fibers (midgut derivatives) or the nerves of the pelvic plexus from sacral spinal cord (hindgut derivatives)
12
Q
Colon & Rectum purpose
A
Maintain fluid & electrolyte balance
Salvage products of intra-colonic fermentation
Store waste materials
Recover 1.5L fluid per day (mostly in proximal colon)
1 - 2 bowel movements/day
Can absorb sodium against high electrochemical gradient!
13
Q
Colon & Rectum - Pharmacology
A
Most drugs already absorbed by that point
EXCEPT Sulfasalazine (used to treat UC)
14
Q
Sulfasalazine
A
Composed of sulfapyridine (sulfonamide antibacterial) linked by a diazo bond with 5-Aminosalicylic acid (5-ASA, or mesalamine)
15
Q
5-ASA
A
The active therapeutic moiety of sulfasalazine.
The sulfapyridine just prevents 5-ASA from being absorbed earlier. The diazo bond is broken by bacterial action.
5-ASA decreases inflammation in the colon.
16
Q
Microbiome
A
10^10 organisms/mL
Represent a pool of metabolic enzymes
Anaerobes, can thrive in low-oxygen tension
Modify oxygen tension, pH, mucopolysaccharide composition & hydration capacity of stool solids.
Normal flora protects against pathogenic bacterial proliferation. Homeostasis between types of bacteria.
17
Q
Colon & Rectum - Vascular Diseases
A
Ischemic colitis
Diverticular bleeding
Hemorrhoidal bleeding
18
Q
Colon & Rectum - Neoplastic Diseases
A
Colon polyps
Colorectal cancer
19
Q
Colon & Rectum - Infectious Diseases
A
Appendecitis
Bacerial/Viral Colitis
Clostridium Difficile
Diverticulitis
20
Q
Colon & Rectum - Mechanical Diseases
A
Volvulus
Large bowel obstruction
21
Q
Colon & Rectum - Immunologic Diseases
A
IBD
Collageneous/Microscopic Colitis
Ileus
22
Q
Colon & Rectum - Motility Diseases
A
Ileus
IBD
23
Q
Ischemic Colitis - Presentation
A
Crampy, mild LLQ abdominal pain
Urge to defecate
Pass bright red (or maroon) blood mixed with stool
24
Q
Ischemic Colitis - Morphologic Changes
A
Vary with duration & severity of injury
25
Ischemic Colitis - Watershed Areas
Splenic Flexure
Rectosigmoid
Due to limited collateral flow
26
Ischemic Colitis - Mildest injuries
Reversible
Mucosal & submucosal hemorrhage & edema
with or without partial necrosis of the mucosa
27
Ischemic Colitis - Unresorbed Hemorrhage
Overlying mucosa sloughs off, forming an ulcer.
28
Ischemic Colitis - Prolonged Severe Ischemia
Muscularis propria is damaged, replaced with fibrous tissue.
Stricture.
29
Ischemic Colitis - Most Severe
Trans-mural infarction
Gangrene
Perforation
30
Diverticulae
Herniations of colonic mucosa through defects in the muscularis layer, resulting in formation of pseudodiverticulae (wall is only made of mucosa and serosa)
Common. Found in 50% of individuals over age 60 on western diet, and 2/3 of patients over 80
Cause unknown
31
Hypothesis of diverticulae origins
```
Low fiber western diet
Lower stool volume
Smaller stools
More colon segmentation
High pressures in colonic lumen
Mucosa forced through wall of colon where nutrient vessels enter.
```
32
Diverticulosis
Only 5% of these patients bleed significantly
Still, however, one of the most common causes of Lower GI Bleed
33
Diverticulae most common in
Left colon
34
Diverticular bleeding most common in
Right colon
35
Diverticular bleed - Pathway
Diverticulum expands
Small arterioles running adjacent bleed briskly.
Painless!!
Most episodes stop spontaneously.
50% recur
36
Diverticular bleeding
Sudden
Painless
May be severe
May present with hypovolemia before blood appears in the rectum (a large amount of blood can be stored in the colon)
Nutrient arteriole ruptures at the base of the diverticulum (maybe due to a fecalith impaction?)
37
Small amounts of blood in stool, or intermittent rectal bleeding
Probably not diverticular bleed.
More likely hemorrhoids, proctitis, polyps or carcinoma
38
Iron deficiency anemia
NEVER explained by diverticular bleeding.
Typically a long-standing microcytic anemia, where patients are unaware that they're losing blood.
Diverticular bleeds are FAR too overt and large volume for that.
39
NSAIDs or Aspirin
Increase likelihood of diverticular bleeds
40
Diverticular Bleeding - Treatment
```
Resuscitate patient (IV fluids, packed RBC)
Assess blood loss
```
```
Administer ADH
Selectively embolize the bleed
Surgery may be necessary
Often the bleeding stops spontaneously
We may also have to clip the diverticulum.
```
After the bleeding stops, we must do a colonoscopy to check.
41
Differentiate Diverticular Bleed from Upper GI Bleed
BUN Elevated in an Upper GI Bleed because the body resorbs the blood.
Sometimes also a lavage via NG tube would also reveal an upper GI bleed too.
42
Tagged Radionuclide Red Blood Cell Scan
Localize where the bleeding is coming from.
Send patient to interventional radiology where they can administer ADH, then selectively embolize by angiography.
43
Hemorrhoidal Bleeding
Occur in >50% of individuals in USA
Most common cause of Lower GI Bleed in adults
Present with scant hematochezia usually.
Occasionally bleed massively
Path unknown
44
Hemorrhoidal Bleeding - Conservative Treatment
Topical anti-inflammatory agents
| Increased dietary fiber
45
Hemorrhoidal Bleeding - More extreme measures
```
Rubber band ligation
Injection sclerotherapy
Cryosurgery
Electrocoagulation
Laser ablation
Photocoagulation
```
46
Lower GI Bleed - Differential
```
Diverticular
Hemorrhoidal
Arteriovascular Malformations
Stercoral Ulcers
Neoplasms
Mechanical Injury (post-polypectomy bleeding)
```
47
Arteriovascular Malformation - Colon
Typically leads to iron deficient anemia.
If patient is on Warfarin, it can lead to massive bleed, but this is less common.
48
Stercoral Ulcers
Pressure necrosis
Patients constantly impacted
Stool pressing against the wall causes the wall to necrose.
Mentally-impaired patient not receiving enough attention to their bowel movements.
49
Colon Cancer
Can bleed, but typically presents with an iron deficiency anemia.
50
Colon Neoplasia
```
Colorectal adenoma
Colorectal adenocarcinoma
Colorectal hyperplastic polyp
Colorectal sessile polyp
Carcinoids of the colon and rectum
Leiomyomas of the colon and rectum
Gastrointestinal stromal cell tumors of the rectum and colon
```
51
FAP
Familial Adenomatous Polyposis
52
Appendicitis - Lifetime risk in western populations
7%
| Slightly higher male predominance in 2nd and 3rd decades of life
53
Appendix
Previously thought to be vestigial
Now thought to have a role in intestinal immunity
```
Has many lymphoid follicles
# of follicles peaks between ages 10 - 30.
```
54
Appendicitis - Causes
70% due to obstruction of the appendiceal lumen:
Fecaliths
Tumors
Parasites
Lymphoid hyperplasia
55
Obstruction of the appendiceal lumen is followed by
```
Mucus secretion
Bacterial overgrowth
Increasing intra-luminal pressure and wall tension
Vascular congestion
Gangrene and perforation.
```
56
Appendicitis - Atypical presentation
Appendix lies in atypical positions (Retrocecal, retroileal)
Increased risk of perforation (due to delayed diagnosis)
57
Most common microbes for appendicitis
E. Coli is most common gram-negative
B. Fragilis is most common anaerobe, second only to E. Coli overall
Most infections are polymicrobial
58
Appendicitis - Diagnosis
```
H&P are major
Abdominal pain is primary symptom.
Classically peri-umbilical, but may be epigastric or suprapubig
After 1 - 12 hours, pain migrates to RLQ (McBurney's Point), becomes more intense
Anorexia
Nausea
Rovsing's Sign
Fever
Elevated WBC
```
59
Appendicitis - When should you question your diagnosis?
If vomiting precedes abdominal pain.
60
McBurney's Point
2/3 of the distance from umbilicus to ASIS
61
Rovsing's Sign
Palpation of LLQ produces pain in RLQ
62
Appendicitis - Imaging
Abdominal CT = Gold Standard
Dilated appendix
Edema
Mesenteric stranding around the appendix in the RLQ
63
Appendicitis - Treatment
Appendectomy for nearly all patients.
Give prophylactic antibiotics to prevent infection.
Patient presents late in course after perforation, we give a course of antibiotics and see what happens
64
Appendectomy - Most common complication
Infection.
This is why we give single dose broad spectrum antibiotics as prophylaxis. Without these, the wound infection rate is 9 - 30% in early appendicitis. Late appendicitis, this approaches 80%.
With ppx, infection risk is
65
Appendectomy - Perforation
Rates of 20 - 30% over the last 70 years
Precedes surgical evaluation in most cases
Increases risk of second laparotomy by more than 250%
66
Diverticulitis - Average Age
44 years
67
Appendicitis - Average Age
Much Younger
68
Diverticulitis - Duration
3.3 days
69
Appendicitis - Duration
24 hours
70
Diverticulitis - Location
RLQ of abdomen
71
Appendicitis - Location
Epigastrium initially, then RLQ
72
Diverticulitis - Nausea
20%
73
Appendicitis - Nausea
80%
74
Infectious causes of colitis - Bacterial
```
Campylobacter
C. Difficile
E. Coli
Salmonella enteritidis
Shigella
Yersinia
Aeromonas
```
75
Infectious causes of colitis - Viral
Adenovirus
Norwalk virus
Rotavirus
Others
76
Infectious causes of colitis - Parasitic/Protozoal
Entamoeba histolytica
Giardia lambia
Cryptosporidium
Cyclospora
77
Food Poisoning - Microbes
```
B. Cereus
C. Perfringens
Salmonella
Staphylococcus
Vibrio
Shigella
Campylobacter
E. Coli
Yersinia Enterocolitica
Listeria Monocytogenes
```
78
Clostridium Difficile
Most common cause of nosocomial infectious diarrhea
Present in 3 - 5% of healthy, asymptomatic adults.
79
Clostridium Difficile - Range of Clinical Presentation
Varies.
Mild self-limited illness
Diarrhea
Resolves soon after withdrawal of offending antibiotic
OR
```
Severe pseudomembranous colitis
Fever
Profuse watery, non-bloody diarrhea
Toxicity
Toxic megacolon
Significant mortality
```
Small bowel rarely affected
Diarrhea often associated with fever, crampy abdominal pain, leukocytosis
80
C. Diff - More serious complications
Toxic megacolon
| Colonic perforation
81
Toxic Megacolon
The colon shuts down
Adynamic ileus
Severe risk of gangrene and perforation.
82
C. Diff - Endoscopy
Pseudomembranes!!
Looks almost like oral thrush
83
C. Diff - Risk factors - Antibiotics
Within 4 - 8 weeks of presentation:
```
Clindamycin
Ampicillin
Amoxicillin
Cephalosporins
Fluoroquinolones (eg Levofloxacin or Ciprofloxacin)
```
84
C. Diff - Risk factors - Non antibiotics
```
Hospitalization
Recent surgery
Uremia
Crohn's Disease
Severe concurrent infection
Recent cancer chemotherapy
```
85
C. Diff - Diagnostic
Gold standard - Tissue Culture Assay
Rarely have to do that, though. Frequently just send a stool sample for latex particle agglutination immunoassays(Sensitivity 87%, Specificity 99%)
Endoscopic/Histologic pseudomembranes are pathognomonic
86
C. Diff - Treatment
Offending antibiotic should be discontinued if possible
Oral antibiotic therapy prescribed for 14 days
If patient can't handle oral medication, give metronidazole 500mg IV q 8 hours
Do NOT give IV vancomycin. It will not work. PO will, though.
87
C. Diff - Surgery
In the cases of:
Refractory colitis
Toxic megacolon
Perforation
88
C. Diff - Metronidazole
500 mg po TID
OR
250 mg po QID
Response rate: 98%
Relapse rate: 7%
89
C. Diff - Vancomycin
125 mg po QID
Response rate: 96%
Relapse rate: 18 %
90
C. Diff - Bacitracin
25,000 U QID
Response rate: 83%
Relapse rate: 34%
91
C. Diff - Cholestyramine
4 gm po TID
Response rate: 68%
Relapse rate: Unknown
Binds to the toxin of C. Diff and helps patient expel that toxin.
92
C. Diff - Relapses
10 - 20% of cases
Usually due to incomplete eradication of initial infection
Spores can live for 2 weeks after completion of antibiotic course
93
C. Diff - Relapse treatment
Metronidazole 500 mg po TID
PLUS
Rifampin 300 mg po BID
OR
Vancomycin 125 mg po QID and TAPER steadily (over 6 weeks) down to one tablet every 2nd or 3rd day.
94
Diverticulitis
Infected diverticulum
Most frequently occurs in sigmoid colon
10 - 25% of patients with previously-recognized diverticulosis
Risk increases over time. 10% after 5 years with diverticulosis, 35% after 20 years with diverticulosis
60% of patients with a first episode will have mild illness, can be treated as outpatients with abx
95
Diverticulitis - Antibiotic regimen
Should cover:
Enterobacteriacea
Bacteroides
Pseudomonas (less frequent)
Enterococci (less frequent)
96
Diverticulitis - Path
Inspissated fecal matter in a diverticulum may form a fecalith
Causes impaction within diverticulum
Local mucosal inflammation
Ensuing necrosis
Microperforation of macroperforation
97
Diverticulitis - Microperforation
Initially contained by pericolonic tissues (mesentery, fat, adjacent organs)
See peritoneal air, but you don't see contrast spilling out. Air has perforated through the diverticulum, but then it healed.
This results in an inflammatory mass or phlegmon
Can be treated with antibiotics, bowel rest, supportive care.
98
Diverticulitis - Repeated Microperforation
May lead to fibrosis of colonic wall, then stricture
99
Diverticulitis - Macroperforation
Result of free perforation with generalized peritonitis
Needs surgery
100
Diverticulitis - Peri-diverticular abscess
May result in a fistula
101
Diverticulitis - Imaging
Abdominal CT
| Fat stranding and/or a mass in the LLQ
102
Diverticulitis - Clinical Picture
LLQ pain in 93 - 100% of patients
Change in bowel habits
Fever (86% of patients)
Leukocytosis (in up to 90% of patients)
If fistula to bladder formed:
Frequency, urgerncy, pneumaturia, fecaluria
LLQ abdominal tenderness
Mass may be palpable
Involuntary guarding & rebound tenderness (if peritonitis)
103
Diverticulitis - Diagnostic Studies
Abdominal/Pelvic CT with IV contrast
Colonoscopy or Sigmoidoscopy not done in acute setting (fear of worsening perf)
104
Diverticulitis - Treatment (Mild Disease)
Liquid or low residue diet
Oral antibiotics 7 - 10 days:
Metronidazole + either Levofloxacin, TMP-Sulfa, Ciprofloxacin or Amoxicillin-Clavulanate
105
Diverticulitis - After resolution of acute attack
Colonoscopy 4 - 6 weeks to rule out colitis, polyps, cancer
106
Diverticulitis - Surgery
Not indicated after first episode, since only 20 - 30% recur.
Should be considered 4 - 6 weeks after THIRD episode inflammation has resolved
107
Diverticulitis - Recurrence
Usually take place within 5 years of the initial episode
108
Diverticulitis - Indications for hospitalization
Severe pain
Inability to tolerate oral diet
Failure of symptoms to resolve with outpatient therapy
Clinical toxicity (High fever, worsening leukocytosis)
109
Vovlulus
Twisting of colon around the mesentery
180 degrees minimum for significant obstruction to occur
If intraluminal pressure exceeds capillary perfusion pressure, vascular compromise may occur. Leads to ulcer, necrosis, grangrene and perforation.
If obstruction persists, strangulation is initiated by venous thrombosis, followed by arterial occlusion and infarction.
110
Volvulus - Locations
Stomach
Cecum
Sigmoid
111
Volvulus - Predisposing Factors
Congenital or Acquired:
Long, redundant (from long-standing constipation), mobile sigmoid colon
Elongated, freely movable sigmoid mesentery
Narrow mesenteric attachment frequently scarring at the base (from repeated twisting)
112
Sigmoid Volvulus
Axial torsion of sigmoid volvulus usually occurs in counterclockwise direction around mesenteric base.
Attacks can be subacute or acute fulminating.
60% of patients with sigmoid volvulus report prior attacks that spontaneously resolved
113
Sigmoid Volvulus - Barium Enema
Bird's beak in the sigmoid. No more contrast beyond that point very dilated loop of bowel.
114
Sigmoid Volvulus - Epi
Highest prevalence - Underdeveloped countries with high-residue diet with vegetable fiber.
Accounts for 3 - 10% of colonic obstructions in the western world
M:F
3:1 (men have longer sigmoids, women have wider pelvises)
115
Most common cause of Lower Bowel Obstruction in pregnancy
Sigmoid Volvulus
116
Chronic constipation leads to
Lengthening of the sigmoid
117
Sigmoid volvulus - Physical findings
Markedly distended abdomen
Tympanic
No (or low) bowel sounds
118
Sigmoid volvulus - Diagnosis
Plain films are diagnostic in 2/3 or cases
Contrast studies:
Bird's beak
Ace of spades
119
Sigmoid volvulus - Therapeutic Goals
Relief of acute torsion
| Prevention of recurrence
120
Sigmoid volvulus - Treatment
85 - 90% of subjects can be decompressed by sigmoidoscopy (if mucosa is not ischemic or necrotic)
121
Sigmoid volvulus - Recurrence
High recurrence rate
| Mortality higher after recurrence than it was after initial episode.
122
Sigmoid volvulus - Surgery
Best to do it electively after 2nd or 3rd occurrence. Typically a complete sigmoid resection is indicated.
If patient presents emergently and is peritoneal, surgery may be indicated earlier.
123
Large Bowel Obstruction
Result of any mechanical obstruction in the large intestine not permitting the passage of stool or gas.
Can be secondary to tumor, stricture, extrinsic compression
124
Large Bowel Obstruction - Presentation
Obstipation
Abdominal Distention
Abdominal Pain
Can be toxic on presentation, depending on degree of ischemia caused
125
Large Bowel Obstruction - Perforation
Occurs if underlying mechanical obstruction is not treated.
126
Large Bowel Obstruction - Treatment
Surgery
| Enteral stents
127
Large Bowel Obstruction - Imaging (Tumor)
Barium enema:
Apple core lesion in the colon
Very dilated upstream colon
128
Crohn's Disease
Full thickness inflammation of bowel wall.
Results in:
Strictures
Fistulas
Abscesses
Relapsing remitting course treated by topical anti-inflammatory agents & immunomodulators
129
Ulcerative Colitis
Superficial colitis of bowel beginning in rectum and extending proximally contiguously for varying lengths
(Proctitis vs. Pancolitis)
Clinically, patients present most often with bloody diarrhea, weight loss
Total colectomy - Curative
130
Collagenous / Lymphocytic Colitis
Microscopic Colitis
Typically elderly patients on long-standing NSAIDS
Syndrome:
Watery diarrhea
No specific endoscopic or radiographic abnormalities of the bowel
May be the same disease with a part of the spectrum containing collagen, but may be separate. We don't know.
Relapsing remitting course over years
131
Collagenous Colitis
Watery Diarrhea
Sub-epithelial collagen band in colonic mucosa
Chronic inflammatory infiltrate in lamina propria
132
Lymphocytic colitis
Watery diarrhea
No collagen band in the colonic sub-epithelium
Intraepithelial lymphocytes present
133
Lamina propria of normal colonic mucosa
Scattered lymphocytes, monocytes, eosinophils
If there is subepithelial collagen, it is very narrow (3 microns or less in diameter)
134
Collagenous Colitis - Histo
Thickened subepithelial collagen layer (20 -60 microns)
Collagen band not a marker for disease severity, no correlation between thickness and age/duration of disease
135
Collagenous / Lymphocytic Colitis - Appears like
Celiac Sprue. If they don't get better on a gluten free diet, they may have collagenous/lymphocytic colitis.
136
Collagenous / Lymphocytic Colitis - Endoscopy
NORMAL
137
Collagenous / Lymphocytic Colitis - Symptoms
```
Secretory diarrhea, so persists even when fasting
Watery stools
8 stools/day average
Cramping pain
Nausea
Weight loss
Fecal urgency
Fecal incontinence
```
138
Collagenous Colitis - Epi
50 - 70 year olds
M:F
20:1
139
Lymphocytic Colitis - Epi
51 years old
M:F
1:1
140
Collagenous/Lymphocytic Colitis - Physical Exam
Unremarkable or mild abdominal tenderness
141
Collagenous Colitis - Associated with
```
Rheumatoid Arthritis
Seronegative Polyarthritis
Thyroid disease
Diabetes Mellitus
CREST Syndrome
```
142
Lymphocytic Colitis - Associated with
Rheumatoid Arthritis
Sicca Syndrome
Uveitis
Diabetes Mellitus
143
Collagenous / Lymphocytic Colitis - Diagnosis
Characteristic histopathologic changes in colonic mucosal biopsies from patient with chronic watery diarrhea
Blood/stool studies are USELESS!!!!
144
Collagenous / Lymphocytic colitis - Treatment
Remove NSAID use
Bismuth subsalicylate tablets induce remission
Mild/Intermittent - Antidiarrheal drugs:
Diphenoxylate with Atropine, loperamide, psyllium or methylcellulose
Troublesome/Persistent - Anti-inflammatory agents such as sulfasalazine and mesalamine
Unresponsive to anti-inflammatories - Corticosteroids
Last resort - Surgery
145
Adynamic Ileus or Pseudo-Obstruction
Failure of effective peristalsis without mechanical obstruction
146
Adynamic Ileus or Pseudo-Obstruction - Causes
Metabolic abnormalities (uremia, electrolyte abnormalities)
Drugs (Narcotics, opiates, anti-cholinergics)
Local or systemic infections (C. Diff)
Non-infectious Inflammatory Processes (Pancreatitis)
Neurogenic causes (spinal cord injury)
Post-operative Ileus (Ogilvie Syndrome)
147
Adynamic Ileus or Pseudo-Obstruction - Presentation
Abdominal Pain
Lack of bowel sounds
or
High pitched bowel sounds
148
Distinguish Ileus from Obstruction
Barium Enema
Obstruction - Contrast doesn't make it all the way across the colon.
Ileus - Air fluid levels
149
Ileus - Management
Supportive care through fluid & electrolyte management
Remove precipitating agent
Decompress EARLY
150
Ileus - If patient doesn't get better with only supportive care
Try neostygmine
| Get a surgical consult, in case emergency surgery is needed (rare).
151
Irritable Bowel Syndrome
22% of the US population
28% of GI visits
Chronic disorder (unknown origin). Maybe visceral hypersensitivity?
Alterations in bowel habits and exacerbations/remissions of abdominal pain and discomfort
Diagnosis of exclusion
152
Irritable Bowel Syndrome - Presentation
Abdominal pain/discomfort
Relieved with defecation
Associated with a change in frequency of bowel movements and/or altered stool form
Passage of mucus or bloating/distention
153
Irritable Bowel Syndrome - Types
Diarrhea predominant
Constipation predominant
Mixed
154
Irritable Bowel Syndrome - Treatment
```
Bulking agents
Anti-diarrheal agents
Smooth muscle relaxants
Pro-kinetic agents
Antidepressants
Anxiolytics
Psychologic and behavioral treatments.
```
