Pathophysiology of Anorectal Disorders

PROJECT SUMMARY/ABSTRACT
Defecation is a viscerosomatic process that requires increased rectal pressure coordinated with anal sphincter
and pelvic floor relaxation. Defecatory disorders (DD) are defined by symptoms and objective features of
impaired defecation. Our understanding of normal and disordered defecation are derived either from
measurements of pressures (high-resolution manometry [HRM]) or emptying (defecography, rectal balloon
expulsion test), but never both. HRM is usually conducted in the left lateral position with an empty rectum. This
may partly explain why the rectoanal gradient (rectal – anal pressure) during evacuation is negative, even in
most asymptomatic people, which undermines our concept of the mechanisms of normal defecation. Among
patients, results of these tests are often inconsistent, hindering the diagnosis of DD. Excessive straining and
“maladaptive” pelvic floor contraction during defecation is implicated to cause DD. However, abdominal wall
motion during defecation and its coordination with pelvic floor motion have not been studied in healthy people
or those with DD. Finally, even in controlled clinical trials, pelvic floor biofeedback therapy, the cornerstone of
managing DD, only benefits 60% of DD patients. This treatment is not widely available or reimbursable;
therefore additional therapies are necessary. Each study is designed to improve patient care in humans.
Specific Aim 1: Address fundamental gaps in our knowledge of the mechanisms of normal and disordered
defecation and the diagnosis of DD: 1a) Redefine the phases of normal evacuation using manodefecography;
1b) Identify the primary causes of DD in men versus women.
Recto anal pressures and evacuation will be measured with HRM, barium, and MR manodefecography in 120
male and female healthy controls and 120 male and female DD patients.
Specific Aim 2: Role of abdominal wall motion in normal and disordered defecation: 2a) Evaluate
abdominopelvic coordination during defecation in healthy and DD women; 2b) Evaluate abdominopelvic
coordination during defecation before and after biofeedback therapy.
Abdominal wall motion and rectoanal pressures will be evaluated at rest and during various maneuvers,
including simulated evacuation, in 30 healthy women and 60 women with DD.
Specific Aim 3: Incorporating these concepts to manage DD: 3a) To assess the effects of a footstool on recto-
anal functions in DD; 3b) To assess the symptoms in DD.
Recto anal pressures and emptying as well as bowel symptoms will be evaluated before and after 85 female
DD patients are randomized to a footstool. A multi-disciplinary collaborative team will apply innovative
approaches to address these hypotheses in a highly refined manner.

Grant Number: 5R01DK078924-14
NIH Institute/Center: NIH
Principal Investigator: ADIL BHARUCHA