Physiology, Pathophysiology

Robert E. Gutman

INTRODUCTION

Disorders of the anus and rectum are numerous and transcend any individual specialty. Anorectal dysfunction is a nonspecific term referring to any condition that disrupts normal anorectal function. Anorectal dysfunction can be subdivided into conditions that cause defecatory dysfunction and fecal incontinence. This chapter will discuss the physiology of anorectal function, followed by the epidemiology and pathophysiology of defecatory dysfunction and fecal incontinence. Subsequent chapters will focus on the evaluation and management of specific conditions relevant to providers caring for women with pelvic floor dysfunction.

OVERVIEW OF NORMAL COLO-RECTAL-ANAL FUNCTION

The normal physiologic processes of anal continence and defecation are complex, requiring intact and coordinated neurological and anatomical function. The key components for normal function include colonic absorption and motility, rectal compliance, anorectal sensation, and the multifaceted continence mechanism. Providers must have a sound understanding of normal physiology and pathophysiology to properly treat women with anorectal dysfunction.

Stool Formation and Colonic Transit

The colon transfers fecal material to the rectum via peristaltic contractions mediated by the parasympathetic system. The rate of transfer depends on colonic absorption and regulation of water and electrolytes. Under normal conditions, average flow through the colon is approximately 1.5 to 2 liters per day, with only a fraction of that (100 to 150 mL) excreted. However, the colon is capable of absorbing up to 5 liters of water and electrolytes in 1 day. Stool transit is further delayed at the rectosigmoid, allowing for maximal absorption of water and sodium.

Storage

The accumulation of stool in the rectosigmoid triggers a key reflex known as the rectoanal inhibitory reflex. Rectal distention results in a transient decrease in internal anal sphincter tone, followed by an increase in external anal sphincter tone. Relaxation of the internal anal sphincter exposes the sensory receptors of the proximal anal canal near the dentate line with a small sample of fecal matter for the purpose of sampling. The sensory nerves assess stool consistency in order to differentiate between solid, liquid, or gas. The rectum is normally compliant and relaxes in response to the increased volume, which is known as accommodation. Increased rectal distention stimulates an urge to defecate, which can be voluntarily suppressed through cortical control, resulting in further accommodation and activation of the continence mechanism.

Continence Mechanism

Muscles

The anal canal is roughly 4 cm in length, extending from the anorectal angle to the anal verge. Anal canal pressure must exceed rectal pressure for continence to occur. The three muscles responsible for maintaining adequate anal canal pressure are the puborectalis, internal anal sphincter, and external anal sphincter. The puborectalis forms a U-shaped sling around the genital hiatus. Contraction of the
puborectalis muscle pulls the anorectal junction toward its origin at the pubic rami (at the arcus tendineus levator ani), narrowing the genital hiatus and developing the anorectal angle. The angle between the lower rectum and upper anal canal should normally be near 90 degrees and is felt to be the critical component for continence of solid stool. This is substantiated by numerous women that are continent of solid stool despite complete disruption of the internal and external anal sphincter. Several theories have been proposed, but the exact mechanism of continence remains uncertain. Kinking of the rectal lumen is implicated in most theories.

Normal external anal sphincter function is critical for abrupt situations that stress the continence mechanism. In the upper anal canal, the puborectalis muscle fibers blend together with the external anal sphincter, which encircles the anal canal and internal anal sphincter. The external anal sphincter inserts posteriorly to the anococcygeal ligament and anteriorly to the perineal body. The puborectalis and external anal sphincter are striated muscles with predominantly type I (slow twitch) muscle fibers that provide constant tone. Rapid contraction of the type II (fast twitch) muscle fibers respond to sudden increases in intra-abdominal pressure. Consequently, the external anal sphincter is ultimately responsible for preventing incontinence associated with fecal urgency and stress incontinence. The puborectalis and external anal sphincter muscles optimize function through a combination of cognitive control and involuntary spinal reflexes.

The internal anal sphincter contributes the majority of resting tone to the continence mechanism. The inner circular layer of the rectum condenses to form the internal anal sphincter, which is made up of smooth muscle. The internal and external anal sphincters are essential for continence of flatus and liquid stool. However, the internal sphincter maintains the majority of resting tone for the sphincter complex through autonomic reflex arcs and is essential for passive continence. The anal cushions (hemorrhoids) serve as the final anatomic barrier by filling with blood to occlude the anal canal.

Nerves

A basic understanding of the neurophysiology is helpful for recognizing and treating anorectal dysfunction associated with denervation. The internal anal sphincter receives its sympathetic supply from L5, which passes through the pelvic plexus via the hypogastric plexus. The parasympathetic supply from S2-4 synapses at the pelvic plexus, where it joins the sympathetic nerves. The internal anal sphincter is under autonomic control and acts through reflex arcs at the spinal cord. The puborectalis (levator ani) is innervated by branches of the S2-4 sacral roots and does not receive direct innervation from the pudendal nerve (1). The external anal sphincter is innervated bilaterally by the pudendal nerve (S2-4) via Alcock’s canal. The pudendal nerve fibers cross over at the level of the spinal cord, allowing for preservation of external anal sphincter function in the event of unilateral damage. The rich sensory supply from the anal canal travels along the inferior rectal branch of the pudendal nerve.

Coordinated muscular control through afferent and efferent nerve supply of the anal canal and receptors in the levator ani muscles is critical to maintain continence. Proper function of these nerves ensures appropriate involuntary responses such as the rectoanal inhibitory reflex, sampling, and accommodation. Sensory nerves of the anal canal distinguish stool consistency and with the help of levator ani sensory nerves establish the degree of rectal distention. Equally important are the voluntary responses to conditions of fecal urgency and increased intra-abdominal pressure.

Evacuation

Initiation of defecation is normally under cognitive control. As previously discussed, delivery of stool to the rectum activates the rectoanal inhibitory reflex, permitting sampling followed by accommodation. Further rectal distention results in an urge to defecate. Voluntary relaxation of the pelvic floor muscles (puborectalis muscle and external anal sphincter) in conjunction with increased intra-abdominal and intrarectal pressure from Valsalva widens the anorectal angle and shortens the anal canal. These actions, along with the coordinated peristaltic activity of the rectosigmoid, facilitate evacuation. After emptying is completed, the closing reflex is initiated through contraction of the pelvic floor muscles and activation of the continence mechanism.

EPIDEMIOLOGY OF ANORECTAL DYSFUNCTION

The epidemiology of anorectal dysfunction is difficult to define as a single entity and is better analyzed in terms of fecal incontinence and defecatory dysfunction. The incidence and prevalence of fecal incontinence has been estimated, but few have done this for defecatory dysfunction. The following sections describe the epidemiology for both fecal incontinence and defecatory dysfunction.
Subsequent sections will consider the vast array of conditions associated with these symptoms.

Defecatory Dysfunction

The term “defecatory dysfunction” is often used synonymously with the symptom of constipation. When patients complain of constipation, they may be referring to a variety of symptoms, including infrequent stools, dyschezia, straining, variation in stool consistency and caliber, incomplete emptying, bloating, and abdominal pain. Therefore, constipation is an imprecise term, with straining and hard stools being the most common associated complaints (2,3). Many physicians focus on stool frequency and define constipation as infrequent stools, less than three bowel movements per week. This definition originates from stool frequency studies in which 95% of women have greater than three bowel movements per week. Based on this definition, the prevalence of constipation should be 5% (4). However, the prevalence of constipation has been estimated to range from 2% to 28%, depending on the definition applied (5, 6, 7).

With such a broad range of estimated prevalence, it is not surprising that constipation disproportionately affects certain members of society. Epidemiological studies indicate that constipation is more prevalent among women and elderly individuals (5, 6, 7) nonwhites, and people with low income and low education (5).

Constipation negatively impacts quality of life, and caring for this condition contributes to the tremendous economic burden of the health care industry. Based on an estimated 2.5 million U.S. physician visits per year for constipation (8), with an average cost for evaluation of $2,752 per patient (9), the annual cost for evaluation would be approximately $6.9 billion. This estimate is conservative, and the current cost is probably much greater when we consider inflation and the growing elderly population. Additionally, Sonnenberg and Koch estimated that physicians prescribe medications to treat constipation at 85% of these visits, substantially increasing the overall economic impact (8).

For individuals with constipation, studies have confirmed a detrimental effect on health-related quality of life (3,10). Irvine et al discovered decreased mental and physical subscores on the SF-36 for quality of life in a Canadian population-based survey (10).

Fecal Incontinence

Fecal incontinence is a common condition that is underreported because of social stigmata and a lack of public awareness. Over the past decade, individuals and society as a whole have become more comfortable discussing issues related to urinary incontinence. Patients are more likely to seek treatment for urinary incontinence and physicians are more likely to refer them for evaluation and consultation. Commercials about medical treatments and sanitary products frequent televisions across the country. However, this same trend has not occurred for fecal incontinence. Physicians are unlikely to inquire about fecal incontinence and patients are unlikely to volunteer this information. One population-based study showed that women with severe symptoms were more likely to consult a physician than those with mild or moderate symptoms, yet less than half of those with severe symptoms sought assistance (11). The reported prevalence of fecal incontinence varies between 2% and 3% for community-dwelling persons, 3% and 17% with increased age, and 46% and 54% for nursing home residents (12). Boreham et al recently reported a prevalence of 28% among patients seeking benign gynecologic care (13).

Epidemiological studies of fecal incontinence are compromised by the tremendous social stigmata noted above as well as the lack of a uniform definition. There is debate about whether incontinence of flatus constitutes fecal incontinence. Therefore, definitions vary with respect to the type of material passed (solid, liquid, or gas). There is also a lack of consensus regarding the required frequency and duration of incontinent episodes to qualify as having the condition. Is it sufficient to have one or two lifetime episodes in the remote past, or should there be two a week over the past 3 months? Each study sets a different cutoff for the minimum number of incontinent episodes and the duration of events in order to establish the prevalence of fecal incontinence. Also, some consider a negative impact on quality of life essential to the definition of fecal incontinence. Interestingly, in 2002 the International Continence Society removed impact on quality of life from the definition of urinary incontinence (14).

A large U.S. health survey found age, female sex, physical limitations, and poor general health to be independent risk factors associated with fecal incontinence (15). Another study of identical twin sisters indicated that the major risk factors for female anal incontinence are age, menopause, obesity, parity, and stress urinary incontinence (16). The authors discovered a cumulative and persistent detrimental effect on sphincter function with increasing parity. Women tend to develop this condition at a younger age than men because of birth-related trauma. The difference in prevalence between
men and women narrows with increasing age. Although the mechanism by which fecal incontinence rates become similar among elderly men and women is uncertain, decreased nerve function has been implicated. This will be discussed further in the pathophysiology section on fecal incontinence.

Similar to defecatory dysfunction, fecal incontinence carries major psychosocial and economic implications for individuals and society as a whole. The loss of such a basic function can be emotionally devastating, leading to poor self-esteem, depression, social isolation, and decreased quality of life (13,17). Fecal incontinence is the second leading reason for nursing home placement in the United States, even though less than one third of individuals with this condition seek medical attention (13,17). The overall annual cost to treat fecal incontinence is difficult to pinpoint, but it accounts for over $400 million per year in adult diapers alone (17). This estimate does not account for physician visits and evaluation, including diagnostic testing, surgical and nonsurgical treatments, management of complications (e.g., skin breakdown, bacteriuria, vaginitis), loss of productivity from missed work or disability, and time costs of health care providers. Thus, annual costs are likely to be grossly underestimated, considering the multitude of indirect and direct costs.

PATHOPHYSIOLOGY/SYMPTOM-BASED APPROACH TO COLORECTAL DISORDERS

There are numerous medical conditions that cause defecatory dysfunction, fecal incontinence, or combined symptoms. This section discusses the breadth of differential diagnosis and proposes a classification system based on systemic factors, anatomical and structural abnormalities, and functional disorders.

Breadth of Differential Diagnosis

Disordered Defecation

The etiology of defecatory dysfunction has traditionally been divided into systemic disorders and idiopathic constipation by the gastrointestinal community. The term “idiopathic constipation” is a nonspecific term used to describe all nonsystemic causes. In this chapter, idiopathic constipation has been divided into anatomical and structural abnormalities plus functional disorders (Table 20.1).

Systemic disorders are subclassified into metabolic/endocrine, neurological, collagen vascular/muscular disorders, and medications. Of the most common endocrine factors, diabetes, hypothyroidism, and pregnancy all cause some degree of decreased gastrointestinal motility and intestinal transit. Feldman and Schiller discovered gastrointestinal symptoms in 76% of diabetic patients, including constipation in 60% (18). These symptoms are believed to be the result of decreased bowel motility and a delayed or absent gastrocolic reflex from diabetic intestinal autonomic neuropathy. This enteric neuropathy has also been known to cause gastroparesis and diarrhea. Consequently, diabetes should be considered as both an endocrine and neurological cause of constipation. Pregnancy is grouped with these disorders but should not be considered a disease state. Nevertheless, there is an 11% to 38% prevalence of constipation during pregnancy that is primarily attributed to smooth muscle relaxation from elevated progesterone levels (19).

Neurological systemic factors can be divided into central and peripheral processes. Central processes such as spinal cord lesions, multiple sclerosis, and Parkinson’s disease affect the autonomic nervous system. Sacral nerve lesions from meningomyelocele, damage to the lumbosacral spine, and pelvic floor trauma often lead to severe constipation secondary to decreased left-sided colonic motility, decreased rectal tone and sensation, and increased distention (20,21). Higher spinal cord lesions result in delayed sigmoid transit and decreased rectal compliance. Colonic reflexes remain intact in upper motor neuron lesions, and defecation can be initiated by digital stimulation of the anal canal (22,23). The lesions associated with multiple sclerosis can cause absence of the gastrocolic reflex, decreased colonic motility, decreased rectal compliance, and even rectosphincteric dyssynergia (24,25). Constipation in those suffering from multiple sclerosis worsens with the duration of illness and may be compounded by the side effects of medical therapy. Similar findings of rectosphincteric dyssynergia and medication side effects are present in Parkinson’s disease.

Defecatory dysfunction from peripheral neurogenic disorders originates at the level of the enteric nerves. Congenital aganglionosis (Hirschsprung’s disease) is the classic example because it involves absence of intramural ganglion cells in the submucosal and myenteric plexuses of the rectum. This results in loss of the rectosphincteric inhibitory reflex. Individuals with this illness usually present with functional obstruction and proximal colonic dilation. The majority are diagnosed prior to 6 months of age, although milder cases can be seen later in life.

TABLE 20.1 Causes of Defecatory Dysfunction and Fecal Incontinence

Fecal Incontinence			Defecatory Dysfunction
SYSTEMIC FACTORS
	Metabolic/Endocrine
•		Diabetes mellitus	•
•		Thyroid disease	•
		Hypercalcemia	•
		Hypokalemia	•
	Neurological
•		Central Nervous System	•
		Multiple sclerosis, Parkinson’s disease, stroke, tumor, dementia
•		Peripheral Nervous System	•
		Hirschprung’s disease, spina bifida, autonomic neuropathy, pudendal neuropathy
	Infectious
•		Bacterial, viral, parasitic diarrhea
	Collagen Vascular/Muscle Disorder
		Systemic sclerosis, amyloidosis, myotonic dystrophy, dermatomyositis	•
	Idiopathic/Autoimmune
•		Inflammatory bowel disease
•		Food allergy
	Medications
•		Prescription, over-the-counter	•
ANATOMICAL/STRUCTURAL ABNORMALITIES
	Pelvic Outlet Obstruction
•		Pelvic organ prolapse	•
•		Descending perineum syndrome	•
		Anismus/rectosphincteric dyssynergia	•
•		Intussusception, rectal prolapse	•
		Volvulus	•
•		Neoplasia	•
•		Benign strictures	•
•		Hemorrhoids	•
	Anal Sphincter Disruption/Fistula
•		Obstetrical trauma
•		Surgical trauma
•		Anal intercourse
•		Injury (trauma, radiation proctitis)
FUNCTIONAL
	Motility Disorders
		Global motility disorder	•
		Colonic inertia/slow transit constipation	•
•		Irritable bowel syndrome	•
		Functional constipation	•
•		Functional diarrhea
	Functional Limitations
•		Decreased mobility	•
•		Decreased cognition	•
From Gutman RE, Cundiff GW. Anorectal dysfunction. In: Berek J, ed. Novak’s gynecology, 14th ed. Chapter 25, table 1. Philadelphia: Lippincott Williams & Wilkins, 2006, with permission.

Other systemic factors to consider are collagen vascular/muscular disorders such as systemic sclerosis, amyloidosis, myotonic dystrophy, and dermatomyositis. Pharmacologic agents are commonly overlooked among the systemic factors. In fact, some of the most commonly used prescription and over-the-counter medications result in defecatory dysfunction, including aluminum antacids, beta blockers, calcium channel blockers, anticholinergics, antidepressants, and opiates (Table 20.2). Lifestyle issues related to inadequate fiber intake and insufficient fluid intake can have similar effects independently or in conjunction with other disorders.

The nonsystemic factors, considered by many to be idiopathic causes, are subdivided into anatomical and structural abnormalities and functional disorders. Anatomical and structural abnormalities refer to the obstructive disorders such as pelvic organ prolapse, perineal descent, intussusception, rectal prolapse, anismus, and tumors. Functional disorders, by default, do not have an identifiable anatomical/structural or systemic etiology. The majority of the functional disorders are motility disorders, including slow transit constipation/colonic inertia, irritable bowel syndrome (IBS; constipation-predominant), and functional constipation. Patients also may have functional limitations of decreased mobility and cognition resulting in constipation. Several of the obstructive
and motility disorders will be reviewed later in this chapter.

TABLE 20.2 Drugs Associated with Constipation

Over-the-counter medications
Antidiarrheals (loperamide, Kaopectate)
Antacids (with aluminum or calcium)
Iron supplements
Prescription medications
Anticholinergics	Others
Antidepressants	Iron
Antipsychotics	Barium sulfate
Antispasmodics	Metallic intoxication (arsenic, lead, mercury)
Antiparkinsonian drugs	Metallic intoxication (arsenic, lead, mercury)
	Opiates
	Nonsteroidal anti-inflammatory agents
Antihypertensives	Anticonvulsants
Calcium channel blockers	Vinca alkaloids
Beta blockers	5-HT₃ antagonists (ondansetron, granisetron)
Diuretics
Ganglionic blockers
From Gutman RE, Cundiff GW. Anorectal dysfunction. In: Berek J, ed. Novak’s gynecology, 14th ed. Chapter 25, table 2. Philadelphia: Lippincott Williams & Wilkins, 2006, with permission.

It is important to understand the somewhat arbitrary nature of this classification system. Strict lines of demarcation should be avoided as several of these conditions are interrelated and defecatory dysfunction is often multifactorial.

Fecal Incontinence

Anal continence depends on the complex interaction between cognitive, anatomical, neurological, and physiologic processes. The continence mechanism is capable of compensating for a deficiency in one of these processes. However, even a normal continence mechanism can be overwhelmed if the deficiency is of sufficient severity. Similarly, a stable deficiency may result in fecal incontinence if the basic function of the continence mechanism gradually declines over time. Causes of fecal incontinence will be divided into similar categories of systemic factors, anatomical and structural abnormalities, and functional disorders.

Systemic etiologies of fecal incontinence are subclassified into metabolic/endocrine, neurological, infectious, idiopathic/autoimmune, and medications. Disease states that cause diarrhea represent the majority of systemic factors. The rapid transport of large volumes of liquid stool to the rectum can produce urgency and incontinence even in healthy individuals (26). Diabetes mellitus and hyperthyroidism are endocrine factors that can lead to fecal incontinence. In diabetics, diarrhea can develop from autonomic dysfunction, bacterial overgrowth, pancreatic insufficiency, and sugar substitutes causing osmotic diarrhea. Infectious diarrhea caused by bacteria (e.g., Clostridium, Escherichia coli, Salmonella, Shigella, Yersinia, Campylobacter), viruses (e.g., Rotavirus, Norwalk, HIV), and parasites (e.g., Entamoeba, Giardia, Cryptosporidium, Ascaris) frequently results in fecal incontinence. Inflammatory bowel disease and food allergies are considered idiopathic/autoimmune factors. Ulcerative colitis and Crohn’s disease cause fecal incontinence during exacerbations with bouts of bloody diarrhea. Inflammatory bowel disease is also associated with structural abnormalities like anal fissures, fistulas, abscesses, and operative complications that lead to fecal incontinence. Numerous drugs and dietary items such as laxatives, magnesium antacids, diuretics, prostaglandins, and sugar and fat substitutes cause diarrhea and fecal incontinence (Table 20.3).

As with defecatory dysfunction, neurological etiologies of fecal incontinence are divided into central and peripheral disorders. Among the central nervous system disorders, upper motor neuron lesions above the level of the defecation center (located in the sacral cord) cause spastic bowel dysfunction. Impaired cognitive control and sensory deficits occur with disrupted cortical communication. The anal sphincter spastically contracts, but digital stimulation initiates reflex evacuation. Head trauma, neoplasms, and cerebrovascular accidents that damage portions of the frontal lobe result in loss of control of both micturition and defecation. Greater loss of inhibition is observed with lesions in the anterior frontal lobe. Spinal cord trauma and lower motor neuron lesions above the defecation center sever cortical control more permanently. “Spinal shock” occurs for 2 to 4 weeks following spinal cord injury, during which there is a temporary loss of reflexes below the level of the lesion, flaccid bowel function, constipation, and fecal impaction. After the early “shock” phase, spastic paralysis ensues, with hyperactive bowel function. Digital stimulation in conjunction with the gastrocolic reflex initiates reflex evacuation in the absence of cortical inhibition. Fortunately, internal anal sphincter tone is maintained despite the loss of external anal sphincter control for stress
and urge situations. Individuals with spinal cord disruption often present with both constipation and fecal incontinence symptoms.

TABLE 20.3 Drugs and Dietary Items Associated with Diarrhea

Over-the-counter medications
Laxatives
Antacids (with magnesium)
Prescription medications
Laxatives	Chemotherapy
Diuretics	Colchicine
Thyroid preparations	Cholestyramine
Cholinergics	Neomycin
Prostaglandins	Para-aminosalicylic acid
Dietary items
Dietetic foods, candy or chewing gum, and elixirs with sorbitol, mannitol, or xylitol
Olestra
Caffeine
Ethanol
Monosodium glutamate
From Gutman RE, Cundiff GW. Anorectal dysfunction. In: Berek J, ed. Novak’s gynecology, 14th ed. Chapter 25, table 3. Philadelphia: Lippincott Williams & Wilkins, 2006, with permission.