Fecal incontinence is a major health hazard and has significant impact on the quality of life. It has a prevalence of 2% to 7% in the community and affects up to 15% of adults in the United States older than 50 years of age. The pathophysiology of fecal incontinence is not well understood. The focus of our work is to better define the anal sphincter function. Specifically, we will investigate the role of puborectalis muscle (PRM) in the anal continence mechanism. The muscle fibers of the internal anal sphincter (IAS) and external anal sphincter (EAS) are arranged in a circular fashion. The PRM, on the other hand, is a """"""""U"""""""" shaped muscle, the two ends of which are attached anterior to the pubic bone. It is not known if PRM muscle contributes to the anal canal pressures at rest or during squeeze. Our preliminary studies using 3D ultrasound and manometry show that during voluntary contraction, the PRM increases pressure in the proximal (cranial) part of the anal canal and the EAS increases pressure in the distal part of the anal canal. Our preliminary studies also show that resting and squeeze pressure in the vagina are due to contraction of the PRM. Fecal incontinence secondary to anal sphincter dysfunction may be due to defect in any one, two or all three components of the anal sphincter complex, i.e., IAS, EAS, and PRM. We propose that the PRM is a major player in the fecal continence mechanism and its dysfunction leads to fecal incontinence. The specific goals of our studies are to determine, 1; Correlation between anal canal anatomy (as seen on 3D ultrasound images) and anal sphincter function measured by manometry, 2; contribution of the IAS, EAS and PRM to the anal canal pressure: effect of skeletal muscle relaxation on the anal canal pressure, 3; vaginal pressure as a measure of PRM function and finally, 4; the role of the PRM in fecal incontinence. We are certain that the novel investigational approach proposed in this grant will significantly enhance our understanding of the anal sphincter function in health and disease, and allow us to develop better treatment strategy for treatment of fecal incontinence in the future. ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Clinical and Integrative Gastrointestinal Pathobiology Study Section (CIGP)
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Hamilton, Frank A
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University of California San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
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Zifan, Ali; Ledgerwood-Lee, Melissa; Mittal, Ravinder K (2016) A Predictive Model to Identify Patients With Fecal Incontinence Based on High-Definition Anorectal Manometry. Clin Gastroenterol Hepatol 14:1788-1796.e2
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Raizada, Varuna; Bhargava, Valmik; Jung, Sung-Ae et al. (2010) Dynamic assessment of the vaginal high-pressure zone using high-definition manometery, 3-dimensional ultrasound, and magnetic resonance imaging of the pelvic floor muscles. Am J Obstet Gynecol 203:172.e1-8
Weinstein, Milena M; Pretorius, Dolores H; Jung, Sung-Ai et al. (2009) Transperineal three-dimensional ultrasound imaging for detection of anatomic defects in the anal sphincter complex muscles. Clin Gastroenterol Hepatol 7:205-11
Raizada, Varuna; Mittal, Ravinder K (2008) Pelvic floor anatomy and applied physiology. Gastroenterol Clin North Am 37:493-509, vii
Jung, Sung-Ae; Pretorius, Dolores H; Padda, Bikram S et al. (2007) Vaginal high-pressure zone assessed by dynamic 3-dimensional ultrasound images of the pelvic floor. Am J Obstet Gynecol 197:52.e1-7