Constipation


Primary (idiopathic) constipation

 Simple constipation

Factors include exercise, dietary fiber intake, hydration

 Chronic constipation

Delayed colonic transit and/or pelvic floor dysfunction

Constipation predominant irritable bowel syndrome

Idiopathic megacolon or megarectum (rare)

Secondary constipation

 Gastrointestinal causes

  Colorectal

Malignant neoplasms, inflammatory strictures, diverticular disease

Secondary megacolon or megarectum (Hirschsprung disease and other rare causes)

  Anal

Atresia or malformation (after corrective surgery)

Hereditary internal anal sphincter hypertrophy

Anal stenosis

 Extragastrointestinal causes

  Metabolic and endocrine

Hypothyroidism, diabetes, hypercalcemia, chronic renal failure, pregnancy

  Neurological

Degenerative central nervous system diseases (e.g., multiple sclerosis, Parkinson disease)

Spinal or pelvic nerve lesions

Autonomic neuropathies

  Drugs

Opioids, anticholinergics, antidepressants, anticonvulsants

  Psychological

Severe endogenous depression

Eating disorders

  Other

Scleroderma, Ehlers Danlos syndrome, Chagas disease, amyloidosis


Modified from Knowles [1]



The various etiologies of secondary constipation are not considered further here, although these inform clinical history taking and investigations (see below). Simple constipation can result from various factors including diet, lack of exercise or immobility, and poor fluid intake. There is no single unified etiology for chronic (idiopathic) constipation. Rather, clinicians are faced with piecing together a multitude of clinical and research observations based on a variety of disparate approaches. These are summarized below.


10.1.1 Observed Colonic Physiological Abnormalities


Colonic motility problems, abnormalities of colonic reflexes, and the lack of a normal response to physiological stimuli may all contribute to constipation and can be directly recorded using pancolonic manometric methods [2]. High-amplitude propagated contractions (HAPCs) are responsible for luminal transit (mass movements) and defecation. Several studies have shown a reduced frequency of HAPCs in patients with slow-transit constipation [3]. In addition, constipated patients may demonstrate a lack of spatiotemporal regional linkage between propagated sequences (in health, a series of two or three colonic propagated sequences may be linked to span the length the colon) [4].

There is normally an increase in the frequency of HAPCs after a meal. This response is often absent in patients with constipation. Colonic motor activity normally increases upon awakening and decreases upon sleeping, with conflicting reports as to whether such increases are absent or reduced in patients with constipation [5]. Similarly, some studies have shown no difference in the nocturnal suppression of colonic motor activity in constipated patients when compared with controls [5], whereas others have reported an absence of nocturnal suppression. It is suggested that the lack of diurnal variation may indicate a neuropathic cause of constipation. In healthy controls, intravenous injection of the cholinergic agonist edrophonium and rectal infusion of chenodeoxycholic acid [6] increased the frequency of HAPCs; this response is absent in constipated patients and might signify disturbed cholinergic function [6].

It is known that mechanical stimulation of the rectum can inhibit the activity of the small intestine and colon. These studies point toward the existence of reflex pathways [4], abnormalities of which may potentially lead to constipation. Voluntary suppression of evacuation can lead to prolonged total and regional intestinal transit time, indicating that constipation can be “learned” [7] and reinforcing the concept that problems of defecation cannot be divorced from those of the colon (an important point in therapy).


10.1.2 Observed Anorectal Physiological Abnormalities


Defecation is dependent not only on the delivery of stool of an appropriate consistency to the rectum but also on the combined functions of the rectum and pelvic floor to permit subsequent voluntary evacuation. The analogy of a “tube of toothpaste” is useful in considering the act of defecation: the tube needs to be full, and the user needs to know that it is full, be able to squeeze it, and remove the cap at the appropriate time. Such coordinated actions incorporate biomechanical properties, structural integrity, and an intact nerve supply to the rectum and anus [8]. Decreased rectal sensation (rectal hyposensitivity) [9], reduced or uncoordinated rectal motor activity, and abnormal biomechanical properties of the rectal wall (usually increased rectal compliance) have all been reported in patients with chronic constipation. The important contribution of dynamic structural abnormalities of the rectum (mainly rectocele and intussusception) and pelvic floor dysfunction (dysynergic defecation) to the etiology of constipation are addressed in Chap. 11.


10.1.3 Observed Colonic Histological Abnormalities


The subject of gastrointestinal (GI) neuromuscular pathology is one that is, in general, fraught with technical and interpretative uncertainties [10, 11] – and the study of colonic tissue in chronic constipation is no exception. The interested reader should access more detailed information from specific reviews (see Ref. [10]). Accepting issues of selection bias (patients undergoing colectomy are not representative of the whole), technical processing (many data are based on outdated histologic techniques, such as silver staining), reporting (do subtle differences actually deviate from normality?), and interpretation (do findings have a causal relationship with the observed clinical phenotype?), the following observations of patients with chronic constipation (mainly based on the study of patients with slow-transit constipation) are briefly summarized:


  1. 1.


    Bona fide enteric neuropathy [11] is probably not a common finding.

     

  2. 2.


    Widely reported changes in functional subsets of enteric neurons [12, 13] or glia may have biological relevance but currently have little diagnostic utility.

     

  3. 3.


    Well-established developmental, degenerative, and inflammatory myopathic phenotypes [11] are at best an uncommon finding.

     

  4. 4.


    Quantitative reductions in the numbers of interstitial cells of Cajal (pacemaker cells) are the most consistent finding [14], although standardized approaches are required for diagnosing individual patients in clinical practice [10].

     


10.1.4 Brain-Gut Influences


The central nervous system can influence GI functions by hard wiring (autonomic nervous system), neuroendocrine functions (hypothalamo-pituitary axis), and immune modulation. Depression, anxiety, and traumatic life events such as sexual and physical abuse are more common among women with severe constipation [15, 16]. While in general such studies have shown clearer associations with irritable bowel syndrome and dysynergic defecation, it is known from studies of healthy volunteers that transit can be delayed at will [7], suggesting that behavioral factors may also influence colonic function. This may be the mechanism involved in constipation arising from toilet avoidance behavior, which is often seen in young children or in frequent travelers such as airplane crewmembers.


10.1.5 Other Etiologies


A plethora of studies have addressed hypotheses such as altered intestinal absorption, changes in sex hormones, altered endogenous opioid balance, autoimmune mechanisms, infective agents, and laxative toxicity. None provide conclusive evidence; however, in light of the strong female predominance of slow-transit constipation (see below), experimental evidence for downregulation of smooth-muscle contractile G proteins and upregulation of inhibitory G proteins caused by the overexpression of progesterone receptors [17] is probably the most attractive current line of reasoning.



10.2 Incidence


Constipation is one of the most common chronic disorders of the digestive tract, affecting between 2 and 35 % of the general population [18]. Similar prevalence rates of 0.7–29.6 % have been reported for constipation in the pediatric literature [19]. Systematic review and meta-analysis of general adult population studies, excluding convenience sampling and using a mix of self-reporting and specific diagnostic criteria, yielded a pooled prevalence of 14.0 % [20]. In the United States alone, constipation accounts for approximately 2.5 million physician visits a year, and tertiary care for constipation was estimated to cost an average of US$2,752 per patient in the late 1990s. The wide range of prevalence estimates for constipation is secondary to variations in populations studied, definitions used for constipation (see below), and methods used for the surveys.

It is readily evident (and fortunate) that these survey estimates cannot possibly represent the prevalence of clinically significant chronic constipation – that is, one in five of the UK population will not be attending my clinic! A recent UK cohort study of 3.8 million patients in primary care helps provide some sense regarding this question [21]. In that cohort, 1.3 % per annum consulted their general practitioner for constipation. This figure remained constant over a 5-year period and included all common causes (e.g., pregnancy and drug use). Approximately 40 % of patients required repeat prescriptions for laxatives, and 32 % were refractory to two or more laxatives, suggesting a maximum prevalence of chronic constipation of approximately 0.4 % (i.e., 1 in 250 adults).


10.3 Epidemiology


Most studies have reported a higher prevalence of self-reported constipation among women than men, with a male-to-female ratio ranging from 1.01 to 3.77 [18, 22] and a median of 2.2 [20]. This ratio is much more pronounced in patients with chronic idiopathic constipation attending tertiary care [23]. There is an increased prevalence of constipation among nonwhites, with white-to-nonwhite ratios between 1.13 and 2.89 [18, 20, 24]. Some geographic variations exist, with lower prevalence in southeast Asia [20]. Subjects with a low income have a significantly higher rate of constipation than subjects with a high income [20]. Several studies have reported an increase trend toward constipation with increasing age, and a meta-analysis confirmed this relationship [20].


10.4 Classification



10.4.1 Etiology


The classification of constipation based on etiology has already been presented here (primary vs. secondary). One further method of classification is based on bowel diameter. While this seems logical, in practice (excluding acute causes such as mechanical obstruction and acute colonic pseudo-obstruction) bowel dilatation (megacolon) is extremely rare, thus limiting the usefulness of this approach (megacolon and megarectum are addressed separately at the end of the chapter in Sect. 10.7).


10.4.2 Symptoms


There is no universally agreed definition of constipation. It is a general term that embraces a range of conditions where a subject is dissatisfied with their ability to expel stool. Symptoms can include infrequent bowel movements (usually fewer than three movements a week), hard stools that are difficult to pass, a need to strain excessively (or a need for manual maneuvers to pass stool), a sense of incomplete bowel movement, and excessive time spent on the toilet. Others may describe even more diverse symptoms such as general abdominal discomfort, nausea, lethargy, and back pain. Patients and doctors often have different perceptions of what constitutes “constipation.” Clinicians often use the frequency of defecation, stool weight, colonic transit studies, and other anorectal physiology investigations to diagnose constipation [25], whereas self-reported constipation is subjective and influenced by social customs. A traditional criterion for constipation (i.e., fewer than three bowel movements per week) was only reported by 9 % respondents with constipation in an epidemiological survey in the United States. By contrast, 38 % reported a sense of incomplete bowel movement, 24 % reported unsuccessful attempts at moving their bowels, and 20 % reported abdominal pain, bloating, or a sense of outlet blockage. Bowel infrequency is also a less common symptom than defecatory difficulty (especially straining) in other general population studies [22] and in patient cohorts with well-defined chronic constipation [22].

Because of the variation in perceptions of constipation, consensus criteria have been proposed by experts to aid diagnosis, evidence-based management, and further research. One of the most widely used diagnostic criteria, the Rome criteria, was proposed by an international panel of experts and is presently in its third iteration (Rome III) [26]. Rome III defines functional constipation solely based on symptoms: the presence of two or more of six listed symptoms in at least 25 % of defecations (over the past 3 months, with symptom onset at least 6 months before diagnosis and only in the absence of sufficient criteria to diagnose irritable bowel syndrome [IBS]): hard stools, straining, sensation of incomplete evacuation, sensation of anorectal blockage, the use of manual maneuvers during evacuation, and infrequent bowel movements (<3 movements/week). The Rome III criteria recognize subgroups of functional constipation based on symptoms and physiological tests, which implies that the experts consider symptoms alone to be inadequate to identify subtypes of functional constipation in clinical practice. The other widely accepted diagnostic criterion was proposed by the American College of Gastroenterology Chronic Constipation Task Force. They defined constipation more simply, as unsatisfactory defecation characterized by infrequent stools, difficult stool passage, or both for at least the previous 3 months. Difficult stool passage includes straining, hard/lumpy stool, difficulty passing stool, incomplete evacuation, prolonged time on toilet, or the need for manual maneuvers to pass stool [27].


10.4.3 Measurements


Patients with chronic constipation may be referred for specialist investigations (see below). Using measures of transit and evacuation, constipation can be subdivided into two main categories: slow-transit constipation and evacuatory disorders; a large proportion of patients has both findings. Another group has no obvious abnormality; this is sometimes termed normal-transit constipation. Ragg et al. [28] investigated 541 patients with chronic constipation and found that 53 % had outlet obstruction, 5 % had isolated slow-transit constipation, 29 % had coexistent outlet obstruction and slow-transit constipation, and 12 % had normal-transit constipation. In another series of >5,000 UK patients, these figures were similar (45 %, 10 %, 35 %, and 10 %, respectively).

Slow-transit constipation is defined by a prolonged colonic transit time (in reality, most methods actually determine a prolonged whole-gut transit time). As an isolated phenomenon, this is most commonly observed in young women with constipation dating from early childhood and is associated with infrequent spontaneous bowel movements (once a week or fewer), bloating, and abdominal discomfort or pain [23] (the term colonic inertia has been applied to this relatively rare condition in a subgroup of patients). It is more commonly observed in combination with a defecation disorder, where the transit disturbance may be secondary to outlet obstruction and reflex inhibition of colonic contractile activity (see section on observed colonic physiology).

Defecatory disorders (also referred to as evacuation disorders and outlet obstruction) are characterized by difficulty evacuating stool once it reaches the rectum. Common causes include functional abnormalities of the anal sphincter or pelvic floor and dynamic structural abnormalities such as rectocele, intussusception, and excessive perineal descent (see Chap. 11).

Normal-transit constipation is an ill-defined condition in which stool passes through the intestine at a normal rate, the frequency of bowel movements and evacuation are normal, yet patients perceive that they are constipated [29]. Patients frequently also experience abdominal pain and bloating, and may have psychosocial issues [16, 25]. This group probably has considerable clinical overlap with constipation-predominant IBS.


10.5 Diagnostics



10.5.1 Clinical History


When a patient presents with constipation, a thorough history determines whether constipation represents a new complaint, that is, one that may indicate a change in bowel habits. The patient should be asked specifically about the frequency and consistency of bowel movements and the progress of such changes over time (as well as other alarming symptoms such as rectal bleeding, anorexia, and weight loss). On this basis, with additional information regarding family history, previous colon cancer screening, and other GI investigations, an informed decision can be made regarding whether structural intraluminal investigation of the colon is required. Other organic causes of constipation may be deduced by appropriate history-taking and biochemical investigation. With the exclusion of treatable secondary causes, if the history is short and multiple previous therapies have not already been tried, then the patient may be first considered to have “simple” constipation that can be managed with reassurance and lifestyle advice (fiber, fluids, and exercise), with or without simple laxative therapy.

In patients with chronic symptoms, after excluding a secondary cause, the focus should shift to the investigation and management of chronic (idiopathic) constipation. This decision is helped by overwhelming epidemiological evidence that patients with chronic idiopathic constipation are usually female (≥90 %) [23] and often have symptoms from early childhood or puberty (at least 50 %) [23] or problems that start after pelvic surgery (e.g., hysterectomy, childbirth). Thus the history should ascertain the duration and mode of onset of symptoms. In relation to onset, it may sometimes be necessary to tactfully query regarding a history of physical or sexual abuse [15, 16]. It is helpful to systematically document the main symptoms that in the patient’s mind constitute a problem, since this has some bearing on treatment decisions and subsequent monitoring of effectiveness. Several questions form detailed scoring systems to systematically facilitate this in a research context (e.g., the Cleveland Clinic Constipation [30] and Knowles Eccersley Scott Symptom scores); psychometrically validated patient-reported outcome measures are also now available (e.g., the Patient Assessment of Constipation Symptoms and Patient Assessment of Constipation Quality of Life questionnaires) [31]. In routine practice, however, it is sufficient to list in the patient’s record the presence or absence (with some indication of degree) of each symptom. I specifically ask about the following, with and without laxative use (if relevant):




















Frequency of spontaneous or assisted bowel opening

Painful defecation

Stool consistency

Digitation (vaginal or anal)

Straining

Abdominal pain

Incomplete/unsuccessful evacuation

Bloating

In addition, brief questioning can determine the coexistence of other symptoms attributable to pelvic floor disorders, such as stress and urge urinary incontinence, vaginal bulging, or prolapse. The remaining history should document prescribed and self-administered laxatives (and the therapeutic benefit of each) and also provide an impression of the quality of the diet with respect to fiber and fluid intake.


10.5.2 Clinical Examination


A poor nutritional status should prompt a search for a secondary cause, including occult carcinoma, widespread dysmotility syndromes such as chronic intestinal pseudo-obstruction (see below), and eating disorders. An abdominal examination should be conducted to look for scars, any significant abdominal distention, tenderness, or masses. Bloating is a common and expected finding with idiopathic constipation, but significant distension, tenderness, or masses should prompt a full investigation.

All patients presenting with constipation should undergo a rectal examination. The perineum and anus should be examined for evidence of fecal incontinence, which may indicate impaction and overflow. Fecal incontinence and chronic constipation coexist to some degree in 40 % patients; marked soiling of the underwear is especially associated with the rare diagnosis of megarectum. Scarring (e.g., from episiotomy), sentinel pile formation secondary to underlying fissure, external hemorrhoids, or prolapse may also be present. The degree of perineal descent upon straining, indicative of pelvic floor weakness, should also be determined visually (>3 cm is usually considered abnormal, and complete effacement of the natal cleft or ballooning of the perineum indicates significant global pelvic floor weakness). A digital rectal examination can allow a diagnosis of impaction, provide a rough measure of anal tone at rest and upon squeezing, and ascertain obvious sphincter defects. Further, an effort should be made to look for any anterior defect in the rectovaginal septum leading to a rectocele. Upon removing the digit from the anus, it is sometimes possible to appreciate the presence of an intra-anal intussusception/mucosal prolapse, which is “dragged out” with the examining digit. It is questionable whether digital examination gives a reliable diagnosis of pelvic floor dyssynergia. It is, however, usual practice to ask the patient to simulate defecation (push maneuvre) two or three times, whereupon an experienced examiner can gain an impression of pelvic floor contraction or failure to relax during straining. Further, significant intussusception (intrarectal or intra-anal) may push on the examining finger. Anoscopy and proctoscopy should be performed if there is any history of rectal bleeding and may indicate fissure or internal piles. A urogynecological examination is desirable in all patients with suspected pelvic multiorgan prolapse.


10.5.3 Investigations


While the findings from the history or physical examination may indicate a possible secondary cause of constipation, making further investigation mandatory, it is also typical practice in patients with chronic constipation to exclude certain secondary causes by investigation, even though the diagnostic utility of such investigations is acknowledged to be low (the most common undiagnosed systemic disease is hypothyroidism). Thus serum electrolyte, creatinine, calcium, and glucose hemoglobin concentrations are usually measured and thyroid function tests performed. The approach taken for a structural investigation of the colon when patients have no suspected intraluminal pathology varies internationally and on the basis of available resources. In the United States, for patients older than 50 years, the baseline risk of colorectal cancer is sufficiently high that screening colonoscopy is recommended, even in the absence of alarming symptoms. These older patients should therefore undergo routine colonoscopy, and many authors recommend that patients younger than 50 years undergo routine flexible sigmoidoscopy. Routine biopsies have no benefit. This approach is being increasingly adopted in Europe. My view is that at some stage it is worth assessing the rectum and colon so that subsequent management (which may be protracted or unsuccessful) can start with baseline reassurance that no organic disease is present. Barium enema (or, as an alternative, computed tomography pneumocolon) can still be a useful investigation in this instance because it yields more information on colonic diameter (for rare cases of megacolon) and the distribution and severity of diverticular disease, which may coexist and be responsible in part for symptomatology (Fig. 10.1).

A80952_2_En_10_Fig1_HTML.gif


Fig. 10.1
(a) Slow colonic transit: radio-opaque marker study. All markers remain in the proximal colon at 100 h. (b) In111 Isotope scintigraphy showing normal progression of an isotope in a healthy control, generalized slow transit, and distal delay (Courtesy of Dr. Mark Scott, Barts Health NHS Trust)

In patients with chronic constipation in whom basic laxatives have failed, further specialist investigative tests may be warranted, although opinions differ on how rigorous such investigations should be and when in the treatment algorithm they should be performed. While there is a general lack of evidence that targeted management strategies are superior to empirical stepwise treatments in early pharmacologic and behavioral interventions, it is at least generally agreed that such tests are mandatory if surgery is considered [32, 33]. Finally, it should be noted that all tests are dependent on adequate normative data (relevant for the patient’s sex and age), the expertise of the investigator, and correct interpretation in the context of the clinical information. Table 10.2 lists standard and advanced tests. A plain abdominal radiograph that can be reviewed immediately in the outpatient setting is particularly useful as a screening tool for determining whether the symptoms mentioned by patients actually correlate with evidence of fecal loading, and they may be shown to the patient to aid discussion.


Table 10.2
Specialist investigations for chronic constipation







































Measure

Standard

Advanced

Colonic transit

Radio-opaque marker study

Colonic isotope scintigraphy

Colonic contractile activity


Colonic manometry

Rectal evacuation

Balloon expulsion test

Magnetic resonance proctography

Fluoroscopic evacuation proctography

Isotope scintigraphic proctography

Anal sphincter contraction

Anal manometry

High-resolution anorectal manometry

Rectal sensory testing

Simple balloon distension

Rectal barostat distension

Rectoanal inhibitory reflex

Balloon and anal manometry

Integrated barostat-manometry

The mainstay for the rapid evaluation of colonic transit is the radiopaque marker study [34]. Though variations in technique exist in terms of the number of markers, the interval to radiography, and the definition of slow transit, the basic premise is that a number of markers (small pieces of plastic tubing prepackaged in gelatin capsules) are ingested, and an abdominal radiograph (which includes the pelvis) is taken at a particular interval. The patient abstains from using laxatives for the duration of the study. In patients with significant numbers of retained markers (based on control data), slow whole-gut transit is diagnosed (Fig. 10.2a). Alternatively, regional transit can be measured by radioscintigraphy [35] (Fig. 10.2b) or using a wireless motility capsule [36]. These techniques are valid but not widely available. On the basis of radio-opaque marker studies, approximately 40 % of patients with chronic constipation have delayed transit [32]. Abnormal transit may be demonstrated either throughout the colon or within a limited portion thereof (most commonly the sigmoid colon and the rectum). With regard to the latter, it is unresolved whether such markers represent a primary disturbance of rectosigmoid motility or are retained secondary to a primary problem of evacuation, which is also present in more than half of patients with slow-transit constipation.
Oct 30, 2017 | Posted by in ABDOMINAL MEDICINE | Comments Off on Constipation

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