Hirsch Sprung

Background
Hirschsprung disease is a developmental disorder characterized by absence of ganglia in the

distal colon, resulting in a functional obstruction. [1] See the images below.
A: Plain abdominal

radiograph showing a transition zone on a plain radiograph (PARTZ) at the rectosigmoid
(arrow). B: Plain abdominal radiograph showing a PARTZ at the
midsigmoid (arrow). C: Plain abdominal radiograph showing a
PARTZ at the descending colon (arrow). D: Contrast enema
showing a contrast enema (CETZ) at the rectosigmoid (arrow). E:
Contrast enema showing a CETZ at the midsigmoid (arrow). F:
Contrast enema showing a CETZ at descending colon (arrow). Images courtesy
of Pratap A, Gupta DK, Tiwari A, et al. BMC Pediatr. 2007 Jan 27;7:5. [Open
access.] PMID: 17257439, PMCID: PMC1790893.
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Most cases of Hirschsprung disease are diagnosed in the newborn period. Hirschsprung
disease should be considered in any newborn that fails to pass meconium within 24-48 hours
of birth. Although contrast enema is useful in establishing the diagnosis, full-thickness rectal
biopsy remains the criterion standard. Once the diagnosis is confirmed, the definitive
treatment is to remove aganglionic bowel and to restore continuity of the healthy bowel with
the distal rectum, with or without an initial intestinal diversion.
Historical notes
Although this condition was described by Ruysch in 1691 and popularized by Hirschsprung
in 1886, the pathophysiology was not clearly determined until the middle of the 20th century,
when Whitehouse and Kernohan reported aganglionosis of the distal colon as the cause of
obstruction in a case series. [2]
In 1949, Swenson described the first consistent definitive procedure for Hirschsprung
disease, rectosigmoidectomy with coloanal anastomosis. Since then, other operations have
been described, including the Duhamel and Soave techniques. More recently, earlier
diagnosis and advances in surgical technique have resulted in decreased morbidity and
mortality in patients with Hirschsprung disease.
Also see Pediatric Hirschsprung Disease and Hirschsprung Disease Imaging.
Pathophysiology
Three nerve plexuses innervate the intestine: the submucosal (Meissner) plexus, the
myenteric (Auerbach) plexus, and the smaller mucosal plexus. All of these plexuses are
finely integrated and involved in all aspects of bowel function, including absorption,
secretion, motility, and blood-flow regulation.
Normal motility is primarily under the control of intrinsic neurons. In the absence of extrinsic
signals, bowel function remains adequate, owing to the complex reflexive architecture of the
enteric nervous system (ENS). For this reason, the ENS is often referred to as the “second
brain.” Intestinal smooth muscle contraction and relaxation are under the control of enteric
ganglia. Most enteric nervous activation causes muscle relaxation, mediated by nitric oxide
and other enteric neurotransmitters. Extrinsic neural afferents to the ENS contain cholinergic
and adrenergic fibers. The cholinergic fibers generally cause contraction, whereas the
adrenergic fibers mainly cause inhibition.
In patients with Hirschsprung disease, both myenteric and submucosal plexuses are absent.
The anus is invariably affected, and aganglionosis continues proximally for a variable
distance. In the absence of ENS reflexes, control of the intestinal smooth muscle is
overwhelmingly extrinsic. The activity of both the cholinergic system and the adrenergic
system is 2-3 times that of normal intestine. The adrenergic (excitatory) system is thought to
predominate over the cholinergic (inhibitory) system, leading to an increase in smooth
muscle tone. With the loss of the intrinsic enteric relaxing impulses, the increased muscle
tone is unopposed. This phenomenon leads to an imbalance of smooth muscle contractility,
uncoordinated peristalsis, and a functional obstruction.
Enteric ganglion cells are derived from the neural crest during embryonic development. In
normal development, neuroblasts are found in the esophagus by the fifth week of gestation,
and they migrate to the small intestine by the seventh week and to the colon by the twelfth
week. [3] One possible etiology of Hirschsprung disease is the arrest of aboral neuroblast
migration. Alternatively, although normal cell migration may occur, neuroblasts may be
subject to apoptosis, failure of proliferation, or improper differentiation within the affected
distal intestinal segment. Fibronectin, laminin, neural cell adhesion molecule (NCAM), and
neurotrophic factors present in the intestinal stroma are necessary for normal enteric ganglion
development, whereas their absence or dysfunction may also have a role in the etiology of
Hirschsprung disease. [4, 5, 6]
Investigators have also identified several genes whose improper expression results in a
Hirschsprung disease phenotype. The RET protooncogene has been implicated in several
studies of Hirschsprung pathogenesis.
In 2011, So and colleagues discovered that rare variants of RET were associated with more
severe phenotypes among Chinese Hirschsprung patients. [7] Leon and colleagues in 2012
determined that sporadic RET coding sequence mutations in Hirschsprung patients resulted in
protein truncations that would deter cell membrane translocation and anchoring. [8]
In 2013, Qin and colleagues performed microarray analyses of aganglionic colon and normal
tissue. They discovered 622 genes with anomalous expression in the aganglionic tissue, and
myenteric HAND2 expression was significantly attenuated. [9]
In a comparison of gene expression among normal and aganglionic colon, Chen and
colleagues determined that overexpression of DVL1 and DVL3 genes was associated with the
Hirschsprung phenotype. [10]
In a 2013 review, Butler Tjaden and colleagues report that mutations in the genes, RET,
GDNF, GFRα1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10, and SHH are present in
approximately 50% of Hirschsprung disease patients. [11]
These studies indicate the complexity of Hirschsprung pathogenesis. Ongoing studies of
genetic and environmental factors will continue to elucidate this problematic disease in the
future.
Although enteric ganglion cells are the primary pathogenic entity in Hirschsprung disease,
some studies suggest that other cell types may also be implicated. [12, 13,14, 15, 16] When
extrinsically stimulated, smooth muscle cells in aganglionic colon are electrically
inactive. [12] Furthermore, interstitial cells of Cajal, pacemaker cells connecting enteric nerves
and intestinal smooth muscle, have also been postulated as an important contributing
factor. [13, 14, 15] These findings suggests that Hirschsprung pathophysiology is not limited to
cells normally present within enteric ganglia, alone.
Epidemiology
United States statistics
Hirschsprung disease affects approximately 1 case per 5400-7200 newborns annually.
International statistics
Although the exact worldwide incidence is unknown, international studies have reported rates
ranging from approximately 1 case per 1500-7000 newborns. [17, 18]
Race-, sex-, and age-related demographics
Hirschsprung disease affects all races; however, it is roughly 3 times more common among
Asian-Americans. [19]
This disease occurs more often in males than in females, with a male-to-female ratio of
approximately 4:1; however, the ratio in long-segment disease decreases to 2:1.
Hirschsprung disease is uncommon in premature infants. However, the age at which
Hirschsprung disease is diagnosed has progressively decreased over the past century. In the
early 1900s, the median age at diagnosis was 2-3 years; from the 1950s to 1970s, the median
age was 2-6 months. Currently, approximately 90% of patients with Hirschsprung disease are
diagnosed in the newborn period.[20]
Prognosis
Reports of long-term outcomes after definitive repair for Hirschsprung disease are conflicted.
Some investigators report a high degree of satisfaction, whereas others report a significant
incidence of constipation and incontinence. In general, more than 90% of patients with
Hirschsprung disease report satisfactory outcomes; however, many patients experience
disturbances of bowel function for several years before normal continence develops.
Approximately 1% of patients with Hirschsprung disease have debilitating incontinence
requiring a permanent colostomy.
Total colonic aganglionosis is associated with a poorer outcome, with 33% of patients
experiencing persistent incontinence and 14% requiring a permanent ileostomy. Patients with
associated chromosomal abnormalities and syndromes also have poorer clinical outcomes.
Mortality/Morbidity
Hirschsprung disease is confined to the rectosigmoid region in about 75% of cases.
Approximately 60% of infants with Hirschsprung disease have an associated condition,
ranging from subtle to severe. Ophthalmologic problems affect 43% of infants, 20% have
congenital anomalies of the genitourinary tract, 5% have congenital heart disease, 5% have
hearing impairment, and 2% have central nervous system anomalies. [21, 22]
Hirschsprung disease is associated with chromosomal abnormalities or syndromes in
approximately 9% of cases. [22] It may be associated with the following syndromes:
 Down syndrome: Trisomy 21 is characterized by physical growth delays, characteristic
facial features, and varying degrees of intellectual disability.
 Neurocristopathy syndromes: Neurocristopathies represent a broad range of disorders
characterized by aberrant neural crest development.
 Waardenburg-Shah syndrome: Patients have a sensorineural hearing deficit and
hypopigmentation of the iris and hair.
 Yemenite deaf-blind syndrome: Affected patients have a mutation in the SRY-related
HMG-box gene. The syndrome is characterized by a severe hearing deficit, nystagmus,
patchy pigmentation abnormalities, and defects of the iris and cornea.
 Piebaldism: Patients have patches of hypopigmentation due to a congenital disorder of
melanocytes. Underlying pathology in the neural crest development is also common to
Hirschsprung disease.
 Multiple endocrine neoplasia type II (MEN2): Mutations in the RET protooncogene are
associated with medullary thyroid cancer in MEN2 and with Hirschsprung disease.
 Congenital central hypoventilation syndrome (CCHS): CCHS is characterized by absent
autonomic control of ventilation. PHOX2B transcription factor mutations may be
associated in both CCHS and Hirschsprung disease.
Untreated aganglionic megacolon in infancy may result in a mortality rate as high as 80%.
Operative mortality rates for any of the interventional procedures are very low. Even in cases
of treated Hirschsprung disease, the mortality rate may approach 30% as a result of severe
enterocolitis.
Possible complications of surgery include anastomotic leak (5%), anastomotic stricture (5-
10%), intestinal obstruction (5%), pelvic abscess (5%), and wound infection (10%). Long-
term complications mostly affect patients with long-segment disease. They include chronic
obstructive symptoms, incontinence, chronic constipation, enterocolitis, and late mortality.
Although many patients encounter one or more of these problems postoperatively, long-term
follow-up studies have shown that greater than 90% of children experience significant
improvement. [23]Patients with a syndromic association and those with long-segment disease
have poorer outcomes. [24, 25, 26]
Complications
Potential complications for the complex operations associated with Hirschsprung disease
encompass the entire spectrum of GI surgical complications. The incidence rates of these
complications do not appear to vary significantly with the surgeon’s experience.
The most frequent postoperative complications include enterocolitis after the Swenson
procedure, constipation following the Duhamel repair, and diarrhea and incontinence after the
Soave pull-through procedure.
Overall, the most common complications are anastomotic leakage and stricture formation in
5-15%, wound infection in 10%, intestinal obstruction in 5%, pelvic abscess in 5%, and re-
operation in 5% of patients. After intestinal diversion, patients may also develop enterostomal
complications, such as prolapse, herniation, or stricture.
Enterocolitis, chronic obstruction, incontinence, constipation, and late mortality may occur
late after surgery for Hirschsprung disease. Rectovesical fistulas have also been reported in
the literature. [27] Enterocolitis accounts for significant morbidity and mortality in patients
with Hirschsprung disease. Enterocolitis is characterized by inflammation of the colon or
small intestinal mucosa. As the disease progresses, the intestinal lumen fills with a fibrinous
exudate, and the risk of perforation increases. This process may occur in either aganglionic or
ganglionic segments of the bowel. Patients typically present with explosive diarrhea,
abdominal distension, fever, emesis, and lethargy. Approximately 10-30% of patients with
Hirschsprung disease develop enterocolitis. Long-segment disease is associated with an
increased incidence of enterocolitis. The risk of enterocolitis does not decrease with surgical
correction.
Treatment of enterocolitis consists of intravenous antibiotics and aggressive colonic
irrigations. Some experts advocate decompression of the bowel, especially in patients with
long-segment disease, by placing an enterostomy proximal to the transition zone.
Patients may present postoperatively with abdominal distension, emesis, or constipation
indicative of ongoing obstruction. [28] Mechanical obstruction can be diagnosed with digital
rectal examination and barium enema. Serial anorectal dilatations or surgical revision of the
pull-through may be required. [4]
Persistent aganglionosis occurs rarely and may be due to pathologic error, inadequate
resection, or loss of ganglion cells after the pull-through. [29] If a rectal biopsy does not show
ganglion cells, revision of the pull-through must be done.[30, 31, 32, 33]
Hirschsprung disease may be associated with other disorders of intestinal motility. Contrast
studies, manometry, and biopsy may be necessary to evaluate for intestinal neuronal
dysplasia. [34, 35]
Internal sphincter achalasia may result in persistent obstruction. This can be treated with
internal sphincterotomy, intrasphincteric botulinum toxin, or nitroglycerin paste. Most cases
resolve by age 5 years. [36, 37]
Functional megacolon may be present due to stool-holding behavior. Bowel management
regimens may be implemented with cecostomy and antegrade enemas reserved for refractory
cases. [38]
Incontinence may be the result of abnormal sphincter function, decreased sensation, or
overflow incontinence secondary to constipation. [28] Anorectal manometry and
ultrasonography are useful to distinguish between these entities.
History
The majority of Hirschsprung cases are sporadic. Approximately 10% of Hirschsprung
patients have a family member who was also affected. This predisposition is more common
in patients with longer-segment disease.
Prenatal ultrasound demonstrating bowel obstruction is rare, except in cases of total colonic
involvement. [39]
Hirschsprung disease should be considered in any newborn with delayed passage of
meconium or in any child with a history of chronic constipation since birth. Other symptoms
include bowel obstruction with bilious vomiting, abdominal distension, poor feeding, and
failure to thrive.
Older children with Hirschsprung disease usually have chronic constipation since birth. They
may also show evidence of poor weight gain.
Older presentation is more common in breastfed infants who will typically develop
constipation around the time of weaning.
Despite significant constipation and abdominal distension, children with Hirschsprung
disease rarely develop encopresis. In contrast, children with functional constipation or stool-
withholding behaviors more commonly develop encopresis.
About 10% of children present with diarrhea caused by enterocolitis, which is hypothesized
to stem from stasis and bacterial overgrowth. This may progress to colonic perforation,
causing life-threatening sepsis. [40]
In a study of 259 consecutive patients, Menezes and colleagues reported that 57% of patients
presented with intestinal obstruction, 30% with constipation, 11% with enterocolitis, and 2%
with intestinal perforation. [27]
Wu and colleagues developed a diagnostic scoring system for elements of the patient’s
history. Risk factors identified include age younger than 3 years, failed or delayed passage of
meconium, and male sex. Scaled scores indicating Hirschsprung disease predict the disease
with a sensitivity of 83%, specificity of 90%, and accuracy of 86%. [41]
Physical Examination
Physical examination in the newborn period is often nondiagnostic; however, it may reveal a
distended abdomen and/or anal spasm. In older children, abdominal distension may result
from the inability to release flatus.
A low imperforate anus with a perineal orifice may have a similar presentation to that of a
patient with Hirschsprung disease. Meticulous physical examination is compulsory to
distinguish the two.
Differential Diagnoses
 Acute Megacolon
 Chronic Megacolon
 Constipation
 Hypothyroidism
 Intestinal Motility Disorders
 Irritable Bowel Syndrome
 Toxic Megacolon
Laboratory Studies
Chemistry panel
For most patients, electrolyte and renal panel findings are within reference ranges. Children
presenting with diarrhea may have findings consistent with dehydration. Test results may aid
in directing fluid and electrolyte management.
Complete blood count (CBC)
This test is obtained to ensure that the preoperative hematocrit and platelet count are suitable
for surgery. In most cases, values are within reference ranges.
Coagulation studies
These studies are obtained to ensure that clotting disorders are corrected before surgery.
Coagulation parameters are expected to be within reference ranges.
Imaging Studies
Plain abdominal radiographs may show distended bowel loops with a paucity of air in the
rectum.
With regard to barium enema, avoid washing out the distal colon with enemas before
obtaining the contrast enema because this may distort a low transition zone. The catheter is
placed just inside the anus without inflation of the balloon to avoid distortion of a low
transition zone and perforation. Radiographs are taken immediately after hand injection of
contrast and 24 hours later.
The classic finding of Hirschsprung disease is a narrowed distal colon with proximal dilation;
however, findings are difficult to interpret in neonates (age <1 mo) and do not demonstrate
this transition zone approximately 25% of the time.[42] Retention of rectal contrast for longer
than 24 hours after the barium enema has been performed also suggests a diagnosis of
Hirschsprung disease.
Other Tests
Anorectal manometry detects the relaxation reflex of the internal sphincter after distension of
the rectal lumen. This normal inhibitory reflex is presumed absent in patients with
Hirschsprung disease. [43] Swenson initially used this test. In the 1960s, it was refined but has
fallen out of favor because of its many limitations. Sedation is usually necessary. Although
some authors find this test useful, false-positive results have been reported in up to 62% and
false-negative results have been reported in up to 24% of cases. Because of these limitations,
anorectal manometry is not commonly performed in the United States.
Echocardiography and chromosomal analyses may be warranted to evaluate for associated
congenital conditions.[#WorkupProcedures]
Procedures
Full-thickness rectal biopsy
The definitive diagnosis of Hirschsprung disease is confirmed by a full-thickness rectal
biopsy demonstrating absence of ganglion cells. The specimen must be obtained at least 1.5
cm above the dentate line because aganglionosis may normally be present below this level.
Disadvantages of full-thickness rectal biopsy include the frequent necessity of general
anesthesia and risks of bleeding and scarring.
Suction rectal biopsy
Recently, simple suction rectal biopsy has been used to obtain tissue for histologic
examination. Rectal mucosa and submucosa are sucked into the suction device, and a self-
contained cylindrical blade excises the tissue. The distinct advantage of the suction biopsy is
that it can be easily performed at the bedside. The diagnostic yield of the full-thickness rectal
biopsy is significantly better than that of the suction biopsy.
Histologic Findings
Acetylcholinesterase staining reveals hypertrophied nerve trunks throughout the lamina
propria and muscularis propria layers of the bowel wall. Recent studies suggest that
immunohistochemical (IHC) staining for calretinin might be more accurate than
acetylcholinesterase staining in diagnosing congenital aganglionosis in suction biopsy
specimens. [44, 45]
Guinard-Samuel and colleagues evaluated the diagnostic value of calretinin
immunochemistry for Hirschsprung disease in 131 pediatric rectal biopsies. Of 131 biopsies,
130 were accurately diagnosed based on calretinin staining. When an additional 12 cases
were considered doubtful based on the standard evaluation method, they were accurately
diagnosed with calretinin IHC. The investigators found calretinin superior to
acetylcholinesterase to complete histology. [45]
Yang and colleagues in 2013 correctly identified the presence or absence of ganglion cells via
IHC staining for calretinin and microtubule associated protein-2 (MAP-2) in 52 samples of
normal and aganglionic bowel. Calretinin IHC correctly identified ganglia in 11 samples
originally reported as false positives from surgical pathology reports. [46]
Approach Considerations
If Hirschsprung disease is suspected, neonates and children should be assigned to a center
where pediatric specialists are available to make the diagnosis and to provide definitive
care. [47]
Consult with pediatric surgeons and pediatric gastroenterologists. Genetic consultation may
be indicated (if a heritable or chromosomal anomaly is suspected).
Hirschsprung disease cannot be prevented; however, perceptive clinical acumen may prevent
delays in diagnosis.
Medical Care
The general goals of medical care are 3-fold: (1) to treat the manifestations and complications
of untreated Hirschsprung disease, (2) to institute temporizing measures until definitive
reconstructive surgery, and (3) to manage postoperative bowel function.
The goals of medical care are to maintain normal fluid and electrolyte balance, to minimize
bowel distension and prevent perforation, and to manage complications. Intravenous fluid
resuscitation and maintenance, nasogastric decompression, and administration of intravenous
antibiotics (as indicated) remain the cornerstones of initial medical management.
Colonic lavage, consisting of mechanical irrigation with a large-bore rectal tube and large
volumes of irrigant, may be required.
Intravenous administration of balanced salt solutions may help prevent electrolyte
imbalances.
Postoperative medical management
Postoperatively, routine colonic irrigation and prophylactic antibiotic therapy may decrease
the risk of developing enterocolitis. [48, 49] For patients who do develop enterocolitis,
nasogastric decompression, intravenous fluids, antibiotics, and colonic lavage may be
necessary. Sodium cromoglycate, a mast cell stabilizer, has also been reported to benefit
these patients. [50]
Botulinum toxin injections within the contracted internal sphincter mechanism have been
reported to induce more normal patterns of bowel movements in postoperative patients with
enterocolitis. [51]
Diet and activity
The patient should have nothing by mouth for 6-8 hours prior to operation.
Postoperatively, the patient will receive intravenous fluids and antibiotics; however, nothing
may be administered by mouth until passage of flatus or stool signifies return of bowel
function. If a newborn undergoes creation of a diverting colostomy, the passage of flatus or
stool from the stoma is necessary prior to institution of oral feeding.
Upon resumption of bowel function, tube feeding or formula/breast milk may resume. Clear
liquids are delivered by mouth, and the diet may be advanced until feeding goals are met.
Feedings are usually initiated 24-48 hours after the creation of a colostomy. The patient may
be discharged from the hospital upon attaining full feedings.
Diets consisting of fresh fruits, vegetables, and high-fiber articles may improve postoperative
bowel function.
With regard to activity, limit physical activity for about 6 weeks to allow incisions to heal
properly (applies more to older children).
Surgical Care
Surgical management of Hirschsprung disease begins with the initial diagnosis, which often
requires a full-thickness rectal biopsy. Traditionally, a diverting colostomy was created at the
time of diagnosis, and definitive repair was delayed until the child grew to a weight of 10
kilograms.
This standard of treatment was developed in the 1950s after Swenson reported relatively high
leak and stricture rates with a single-stage operation. Advancements in anesthesia
administration and hemodynamic monitoring have led many surgeons to advocate a single-
stage pull-through procedure without initial diversion. Contraindications to a single-stage
procedure include severely dilated proximal bowel, severe enterocolitis, perforation,
malnutrition, and inability to accurately determine the zone of transition between healthy and
aganglionic bowel, intraoperatively.
For neonates undergoing creation of a diverting colostomy, the transition zone is identified
and the colostomy is placed proximal to this area. The presence of ganglion cells at the
colostomy site must be unequivocally confirmed by histological evaluation of a frozen-
section biopsy. Either a loop- or end-colostomy is created at the surgeon’s discretion.
A number of definitive procedures have demonstrated excellent results when performed by
experienced surgeons. The most commonly performed repairs are the Swenson, Duhamel,
and Soave procedures. In any elective operation for Hirschsprung disease, a robust
preoperative colon cleanse must be performed.[52] Intraoperatively, histological examination
of a frozen-section biopsy must confirm the presence of ganglion cells at the proximal margin
of bowel intended for anastomosis. A meta-analysis performed by Friedmacher and Puri in
2011 reported that residual aganglionosis and transition-zone tissue account for persistent
bowel symptoms in one third of patients undergoing a second, corrective pull-through
procedure. [29]
However, long-term complications of pullthrough procedures may include intermittent
enterocolitis, severe stool retention, as well as intestinal obstruction.[47]
Swenson procedure
The Swenson procedure was the original pull-through procedure used to treat Hirschsprung
disease. The aganglionic segment is resected down to the sigmoid colon and rectum, and an
oblique anastomosis is performed between the normal colon and the low rectum.
Duhamel procedure
The Duhamel procedure was first described in 1956 as a modification to the Swenson
procedure. A retrorectal approach is used, and a significant segment of aganglionic rectum is
retained.
The aganglionic bowel is resected down to the rectum, and the rectum is oversewn. The
proximal bowel is then brought through the retrorectal space (between rectum and sacrum),
and an end-to-side anastomosis is performed with the remaining rectum.
A single-institution retrospective review (2002-2014) of 72 children who underwent surgical
intervention for Hirschsprung disease found satisfactory outcomes with the Duhamel
procedure, but 40% of the patients had to undergo further surgery. [53] The early complication
rate was 15%, with 11 patients (15%) experiencing Hirschsprung associated enterocolitis
(HAEC).
Soave (endorectal) procedure
The Soave procedure was introduced in the 1960s. The mucosa and submucosa of the rectum
are resected, and the ganglionic bowel is pulled through the aganglionic muscular cuff of the
rectum.
The original operation did not include a formal anastomosis, relying on scar tissue formation
between the pull-through segment and the surrounding aganglionic bowel. The procedure has
since been modified by Boley to include a primary anastomosis at the anus.
Anorectal myomectomy
For patients with extremely short-segment Hirschsprung disease, anorectal myomectomy is
an alternative surgical option.
The surgeon removes a 1-cm-wide strip of extramucosal rectal wall, beginning immediately
proximal to the dentate line and extending to the normal ganglionic rectum. The mucosa and
submucosa are preserved and closed.
Procedures for long-segment Hirschsprung disease
Patients with total colonic involvement require modified procedures to exclude the
aganglionic colon while preserving maximal absorptive epithelium. The goal of these
procedures is to bypass dysfunctional bowel while maximizing the chance of postoperative
nutritional function and growth.
Most procedures include a side-to-side anastomosis of healthy small bowel with a short
segment of the aganglionic/absorptive colon. Either a short right colonic patch or the small
bowel is anastomosed to the rectal wall, similar to a Duhamel procedure. Importantly, a short
patch (< 10 cm) is maintained.
Long-segment anastomoses, such as the Martin procedure, are no longer advocated.
Laparoscopic approach
A laparoscopic approach to the surgical treatment of Hirschsprung disease was first described
in 1999 by Georgeson. [54] The transition zone is first identified laparoscopically, after which
the rectum is mobilized below the peritoneal reflection. A transanal mucosal dissection is
performed, and the rectum and aganglionic bowel is prolapsed through the anus. The healthy
proximal bowel is anastomosed to the rectal cuff. Functional outcomes of this laparoscopic
approach appear to be equivalent to open techniques based on short-term results. [54, 55, 56]
Transanal pull-through procedures
Transanal pull-through procedures have been described in which no intra-abdominal
dissection is performed. [24, 30] The entire procedure is performed transanally in a manner
similar to perineal rectosigmoidectomy.
The mucosa is incised circumferentially above the dentate line, and a submucosal dissection
is directed proximally. The muscularis is incised circumferentially, and the remainder of the
dissection is carried external to the rectal wall until the transition zone is identified. Upon
confirmation of ganglion cells on frozen section, the aganglionic bowel is resected and an
anastomosis is performed.
Outcomes of the transanal pull-through procedure have been similar to open single-stage
approaches, and analgesia requirements and hospital stays are decreased. [24, 57, 58] Studies
have also reported lower rates of postoperative incontinence and shorter operating times in
transanal pull-through procedures.[59, 60]
Novel strategies
Several other creative approaches have been described, including a modification of the
transanal approach with transabdominal open or laparoscopic assistance, single-incision
laparoscopic endorectal pull-through (SILEP), and natural orifice transluminal endoscopic
surgery (NOTES). [61, 62, 63, 64]
Regenerative strategies are under investigation to restore function in aganglionic intestine.
Stem cell transplantation to regenerate the enteric nervous system is the subject of many
recent experimental series. [65] Stem cells derived from the neural crest persist into adulthood,
and several are capable of proliferation and differentiation within the intestine. Hotta and
colleagues recently reported successful generation of functional enteric neurons from
precursor cells transplanted into recipient colon. [66] Though auspicious, these discoveries
warrant further study to translate cell-based therapies into clinical practice.
Outpatient Monitoring
After a definitive pull-through procedure is performed, the patient should achieve normal
growth and development.
Patients should be monitored for their bowel habit. Patients with no other underlying
disorders and no postoperative complications often develop improved bowel function;
however, normal bowel habit may take years to develop.
After definitive surgical repair, patients may experience persistent abnormal gastrointestinal
motility. Postoperative hypomotility is relatively common, and many patients require a
prolonged course of laxative treatment. Patients who retain stool despite laxative therapy may
require enemas. [67]
Medication Summary
The goals of pharmacotherapy are to eradicate infection, to reduce morbidity, and to prevent
complications.
Immediately after the diverting colostomy is created or a definitive pull-through procedure is
performed, patients often remain on broad-spectrum intravenous antibiotics (eg, ampicillin,
gentamicin, and metronidazole) until bowel function has returned and feeding goals are
achieved.
After a definitive pull-through procedure is performed and normal bowel function is
obtained, no additional medication is required.
Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and cover all likely pathogens in the
context of this clinical setting. Antibiotic selection should be guided by blood culture
sensitivity whenever feasible.
Ampicillin (Marcillin, Omnipen, Principen)
 View full drug information
Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to
take medication orally.
Gentamicin (Garamycin, Jenamicin)
Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an
agent against gram-positive organisms and one that covers anaerobes. Not the DOC. Consider
if penicillins or other less-toxic drugs are contraindicated, when clinically indicated, and in
mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of
distribution. May be administered IV/IM.
Metronidazole (Flagyl)
Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used
in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).
Toxins
Class Summary
Induce more normal patterns of bowel movements in postoperative patients with
enterocolitis.
OnabotulinumtoxinA (BOTOX®)
Binds to receptor sites on motor nerve terminals and inhibits release of acetylcholine, which
in turn inhibits transmission of impulses in neuromuscular tissue.
Toxic Megacolon
Background
Toxic megacolon is the clinical term for an acute toxic colitis with dilatation of the colon.
The dilatation can be either total or segmental. A more contemporary term for toxic
megacolon is simply toxic colitis, because patients may develop toxicity without megacolon.
For the purposes of this article, the term toxic megacolon (toxic colitis), or TM (TC), is used,
but either toxicity or megacolon can occur exclusively of each other. [1]
The hallmarks of toxic megacolon (toxic colitis), a potentially lethal condition, are
nonobstructive colonic dilatation larger than 6 cm and signs of systemic toxicity. TM (TC)
was recognized by Marshak and Lester in 1950. [2] Jalan et al described the diagnostic criteria,
which are as follows [3] (see Presentation and Workup):
 Radiographic evidence of colonic dilatation - The classic finding is more than 6 cm in
the transverse colon
 Any 3 of the following - Fever (>101.5°F), tachycardia (>120 beats/min), leukocytosis
(>10.5 x 10 3/µL), or anemia
 Any 1 of the following - Dehydration, altered mental status, electrolyte abnormality, or
hypotension
TM (TC) was first thought to be a complication only of ulcerative colitis. In fact, TM (TC)
may complicate any number of colitides, including inflammatory, ischemic, infectious,
radiation, and pseudomembranous. [4, 5] Indeed, the incidence of TM (TC) is expected to
increase due to the rising prevalence of pseudomembranous colitis (see the images below).
(See Etiology.)
A 22-year-old man presented with

abdominal pain, passage of blood and mucus per rectum, abdominal distention, fever, and
disorientation. Findings from sigmoidoscopy confirmed ulcerative colitis. Abdominal
radiographs obtained 2 days apart show mucosal edema and worsening of the distention in
the transverse colon. The patient's clinical condition deteriorated over the next 36 hours
despite steroid and antibiotic therapy, and the patient had to undergo a total colectomy and
ileostomy.
View Media Gallery
Gross pathology specimen from a
case of pseudomembranous colitis demonstrating characteristic yellowish plaques.
View Media Gallery
Computed tomography scan from

a patient with pseudomembranous colitis demonstrating the classic accordion sign.
View Media Gallery
Colonic dilatation may be present in other conditions, such as Hirschsprung
disease, [6] idiopathic megacolon/chronic constipation, and intestinal pseudo-obstruction
(Ogilvie syndrome). However, these patients do not develop signs of systemic toxicity and,
therefore, do not fall into the category of having TM (TC) (see the image below). (See
Etiology, Presentation, and Workup.)
A 72-year-old woman presented
with vomiting and abdominal distention. The supine (right) and erect (left) plain abdominal
radiographs show gross dilatation of the colon with multiple air-fluid levels. On further
questioning, the patient revealed that she was taking diuretics for hypertension. Blood
biochemical tests revealed markedly lowered potassium levels. After potassium replacement
therapy, the patient's pseudo-obstruction completely resolved.
View Media Gallery
Complications
The dreaded complication of TM (TC) is perforation, even in the absence of colonic
dilatation. Numerous studies have demonstrated that classic physical signs of peritonitis are
absent in the majority of patients with free perforation, possibly because of the effects of
steroids. (See Prognosis and Presentation.)
Pathophysiology
Although the precise pathophysiology of toxic megacolon/colitis TM (TC) is unproven,
several factors may contribute to its development and precipitation. In cases of
uncomplicated colitis, the inflammatory response is confined to the mucosa. The microscopic
hallmark of TM (TC) is inflammation extending beyond the mucosa into the smooth-muscle
layers and serosa. Whereas the typical ulcerative colitis inflammatory response is limited to
the mucosa, toxic megacolon is characterized by severe inflammation extending into the
smooth muscle layer, thus paralyzing the colonic smooth muscle and leading to dilatation.
The extent of dilatation seems to be correlated with the depth of inflammation and
ulceration. [7]
Studies by Mourelle et al showed significantly increased amounts of inducible nitric oxide
synthetase in the muscularis propria of patients with toxic megacolon, particularly in the
more dilated colonic segments. [8, 9] Inflammation and upregulated nitric oxide synthetase are
thought to increase local nitric oxide levels, which inhibits colonic smooth muscle and causes
dilatation. [8, 9, 10]
As inflammation progresses into the smooth-muscle layers of the colon, nitric oxide and local
inflammatory modulators appear to be involved in the pathogenesis of TM (TC). In toxic
megacolon, neutrophils also invade the muscle layer and directly damage muscle cells by the
release of proteolytic enzymes, cytokines, and leukotriene B4. [7] Systemic uptake of
cytokines and other inflammatory mediators leads to fever, tachcardia, hypotension, and other
signs of systemic toxicity. Nitric oxide is generated by inflammatory cells such as neutrophils
and macrophages in the inflamed portions of the colon, inhibiting smooth-muscle tone and
leading to colonic dilatation.
Myenteric plexus involvement is not consistent and likely does not contribute to colonic
dilatation. Hypokalemia and other electrolyte disturbances probably do not contribute to
dilatation in most patients. [7]
Etiology
Inflammatory causes of toxic megacolon (toxic colitis), or TM (TC), include the following:
 Ulcerative colitis [11]
 Crohn colitis
 Pseudomembranous colitis
Infectious causes of TM (TC) include:
 Salmonella species
 Shigella species
 Campylobacter species
 Yersinia species
 Clostridium difficile [12, 13, 14]
 Entamoeba histolytica
 Cryptosporidium [15]
 Cytomegalovirus [16]
 Rotavirus [17]
 Invasive aspergillosis [18]
In a murine model, spread of type 1 herpes simplex virus infection from the sensory nervous
system to the autonomic ganglia of the colonic enteric nervous system has been associated
with toxic megacolon and lethality, primarily via viral gene transcription, pathologic
inflammatory responses, and neutrophil-mediated destruction of the enteric neurons. [19] The
use of laxatives prevented lethality in the mice following genital HSV-1 infection.
TM (TC) may also be caused by:
 Radiation colitis
 Ischemic colitis
 Nonspecific colitis secondary to chemotherapy [20, 21]
 Rarely as a complication of collagenous colitis [22, 23]
 Behçet syndrome - Patients with this syndrome can rarely develop TM (TC) as a
complication [24, 25]
 Kaposi's sarcoma [7]
 Methotrexate therapy induced pseudomembranous colitis
Often, triggering or predisposing factors can be identified. Signs and symptoms of acute
colitis may be present for as long as 1 week before dilatation develops. Although the risk of
TM (TC) increases with the severity of colitis, rapid tapering or abrupt discontinuation of
medications such as steroids, sulfasalazine, and 5-aminosalicylic acid may precipitate
toxemia and dilatation.
Medications that negatively impact bowel motility also are implicated in the development of
toxic megacolon. These include, but are not limited to, anticholinergics, antidepressants,
loperamide, and opioids. Procedures such as barium enema or colonoscopy may cause
distention, impair blood supply, or exacerbate a microperforation and cause subsequent
toxemia.
A retrospective study by Tschudin-Sutter et al indicated that the incidence of TM (TC) is
higher in pediatric patients with community–associated, rather than healthcare facility–
associated, C difficile infection. The study involved 202 pediatric patients with C
difficile infection, including 38 with community–associated infection, 144 with healthcare
facility–associated infection, and 20 with an indeterminate source of infection. Compared
with the healthcare facility–associated group, children with a community–associated infection
had a higher rate not only of TM (TC) but also of toxic shock and recurrence. (They were less
likely, however, to have comorbidities than were children with healthcare facility–associated
infection.) [26]
Epidemiology
The incidence of toxic megacolon (toxic colitis), or TM (TC), cited in the literature of
depends on the etiology. The lifetime risk of TM (TC) in ulcerative colitis has been estimated
to be 1-2.5%. In one series of 1236 patients admitted to the hospital over a 19-year period,
toxic megacolon was present in 6% of patients, specifically 10% of ulcerative colitis
admissions and 2.3% of Crohn disease admissions. [27]
TM (TC) has been reported to occur in approximately 5% of severe attacks of ulcerative
colitis. In pseudomembranous colitis, toxic megacolon occurs in 0.4-3% of patients. This
number is expected to increase in proportion to the increasing prevalence of
pseudomembranous colitis, which is thought to be due to the increased use of broad-spectrum
antibiotics.
In the United States, Jewish people are more prone to ulcerative colitis than are people who
are not Jewish. In Israel, Ashkenazi Jewish people have a higher incidence of ulcerative
colitis than do Sephardic Jewish people. No data exist regarding race and the incidence of
TM (TC).
Regarding ulcerative colitis, most studies demonstrate that both sexes are affected equally.
Young adults (aged 20-40 y), primarily, are affected by ulcerative colitis, but this disease
may present at any age. With TM (TC), no predilection appears to exist for any particular age
group. All ages may be affected. Many individuals present with TM (TC) during their first
flare. The mean duration of disease has been reported to be 3-5 years.
Prognosis
A few studies have shown that the prognosis is poor with medical management of toxic
megacolon (toxic colitis), or TM (TC). A study by Grant and Dozois followed the clinical
course and ultimate outcome in 38 patients with TM (TC) who were successfully treated
nonoperatively. [28] Thirty-two patients had ulcerative colitis and 6 had Crohn disease, with
complete follow-up ranging 3-22 years (average, 13 y). Eleven of 38 patients (29%)
eventually suffered a second episode of fulminant acute colitis or recurrent TM (TC).
Ultimately, a total of 18 patients (47%) underwent colon resection, which was performed on
an emergency or urgent basis in 15 patients. [28]
The survival prognosis of TM (TC) should be excellent in the absence of perforation. Indeed,
the mortality rates for TM (TC) have improved substantially over the past few decades, from
20% in 1976 to 4-5% currently. The decrease is a result of earlier recognition, intensive
medical management, early surgical consultation, and improved surgical technique and
postoperative care. If perforation occurs, the mortality rate is approximately 20%.
In the case of ulcerative colitis, a proctocolectomy cures patients of the disease. In the case of
Crohn disease, proctocolectomy does not necessarily cure the patient, because Crohn disease
can occur in any portion of the gastrointestinal tract.
With the use of tumor necrosis factor (TNF)-alpha inhibitors, it is hoped that more cases can
be managed medically in future. More studies are needed.
Patient Education
Educating the patient about toxic megacolon (toxic colitis), or TM (TC), is crucial. First,
educate the patient about the causes of the disease. The most common cause of TM (TC) is
inflammatory bowel disease. However, with the rising incidence of C difficile,
pseudomembranous colitis must always be considered, even in patients with inflammatory
bowel disease. Educate the patient about ulcerative colitis, Crohn disease, and indeterminate
colitis.
The patient should be clearly informed that, if an operation is required for this acute problem,
an ostomy likely will be the procedure needed, regardless of the cause.
Secondly, educate the patient about the operation. Patients require at least a temporary, and
possibly a permanent, ostomy. Most patients require a thoughtful, compassionate discussion
regarding this aspect of their treatment. The psychological aspects of dealing with an ostomy
can be extremely difficult.
Finally, educate patients so that they understand that this disease is a process that may require
several months to overcome if an operation is needed and that a 2- or 3-stage procedure is
usually required.
History
Patients with toxic megacolon (toxic colitis), or TM (TC), typically have signs and symptoms
of acute colitis that may be refractory to treatment. Common complaints include diarrhea,
abdominal pain, rectal bleeding, tenesmus, vomiting, and fever. The patient may already have
a diagnosis of inflammatory bowel disease or another cause of colitis, although in some
patients, TM (TC) may be the initial presentation of inflammatory bowel disease.
A careful history may reveal recent travel, antibiotic use, chemotherapy, or
immunosuppression. Patients are usually very ill, with the toxic definition including some or
all of the following symptoms:
 High fever
 Abdominal pain and tenderness
 Tachycardia
 Dehydration
The diagnostic criteria developed by Jalan et al may be helpful to guide the history of patient
suspected of having toxic megacolon (toxic colitis). They are as follows [3] :
 Radiographic evidence of colonic dilatation - The classic finding is more than 6cm in
the transverse colon
 Three of the following - Fever (>101.5°F), tachycardia (>120 beats/min), leukocytosis
(>10.5 x 10 3/μL), or anemia
 One of the following - Dehydration, altered mental status, electrolyte abnormality, or
hypotension
The vital signs in a patient with toxic megacolon (toxic colitis), or TM (TC) generally reveal
tachycardia and fever. If the condition is severe, the patient may be hypotensive or
tachypneic.
In inflammatory colitides (ie, ulcerative colitis, Crohn colitis), physical findings may be
minimal, because high-dose steroids are routinely used; however, the abdomen maybe
distended, and bowel sounds are usually decreased. Signs of perforation may also be masked
by high-dose steroids, as in inflammatory bowel disease. With toxemia, patients may be
obtunded.
Peritoneal signs may indicate perforation. They include the following:
 Rebound
 Rigidity
 Peritoneal irritation
The form of megacolon usually associated with ulcerative colitis is defined by a transverse
colon that is 6cm or more in diameter, with loss of haustration.
Irritable bowel syndrome
Practice Essentials
Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain
and altered bowel habits in the absence of a specific and unique organic pathology, although
microscopic inflammation has been documented in some patients. [1] Population-based studies
estimate the prevalence of irritable bowel syndrome at 10-20% and the incidence of irritable
bowel syndrome at 1-2% per year.
Signs and symptoms
Manifestations of IBS are as follows:
 Altered bowel habits
 Abdominal pain
 Abdominal distention
Altered bowel habits in IBS may have the following characteristics:
 Constipation variably results in complaints of hard stools of narrow caliber, painful or
infrequent defecation, and intractability to laxatives
 Diarrhea usually is described as small volumes of loose stool, with evacuation preceded
by urgency or frequent defecation
 Postprandial urgency is common, as is alternation between constipation and diarrhea
 Characteristically, one feature generally predominates in a single patient, but significant
variability exists among patients
Abdominal pain in IBS is protean, but may have the following characteristics:
 Pain frequently is diffuse without radiation
 Common sites of pain include the lower abdomen, specifically the left lower quadrant
 Acute episodes of sharp pain are often superimposed on a more constant dull ache
 Meals may precipitate pain
 Defecation commonly improves pain but may not fully relieve it
 Pain from presumed gas pockets in the splenic flexure may masquerade as anterior
chest pain or left upper quadrant abdominal pain
Additional symptoms consistent with irritable bowel syndrome are as follows:
 Clear or white mucorrhea of a noninflammatory etiology
 Dyspepsia, heartburn
 Nausea, vomiting
 Sexual dysfunction (including dyspareunia and poor libido)
 Urinary frequency and urgency have been noted
 Worsening of symptoms in the perimenstrual period
 Comorbid fibromyalgia
 Stressor-related symptoms
Symptoms not consistent with irritable bowel syndrome should alert the clinician to the
possibility of an organic pathology. Inconsistent symptoms include the following:
 Onset in middle age or older
 Acute symptoms (irritable bowel syndrome is defined by chronicity)
 Progressive symptoms
 Nocturnal symptoms
 Anorexia or weight loss
 Fever
 Rectal bleeding
 Painless diarrhea
 Steatorrhea
 Gluten intolerance
See Clinical Presentation for more detail.
Diagnosis
The Rome III criteria for the diagnosis of irritable bowel syndrome [2] require that patients
have had recurrent abdominal pain or discomfort at least 3 days per month during the
previous 3 months that is associated with 2 or more of the following:
 Relieved by defecation
 Onset associated with a change in stool frequency
 Onset associated with a change in stool form or appearance
 Supporting symptoms include the following:
 Altered stool frequency
 Altered stool form
 Altered stool passage (straining and/or urgency)
 Mucorrhea
 Abdominal bloating or subjective distention
Four bowel patterns may be seen with irritable bowel syndrome. These patterns include the
following:
 IBS-D (diarrhea predominant)
 IBS-C (constipation predominant)
 IBS-M (mixed diarrhea and constipation)
 IBS-U (unclassified; the symptoms cannot be categorized into one of the above three
subtypes)
The usefulness of these subtypes is debatable. Notably, within 1 year, 75% of patients change
subtypes, and 29% switch between constipation-predominant IBS and diarrhea-predominant
IBS.
A comprehensive history, physical examination, and tailored laboratory and radiographic
studies can establish a diagnosis of irritable bowel syndrome in most patients. The American
College of Gastroenterologists does not recommend laboratory testing or diagnostic imaging
in patients younger than 50 years with typical IBS symptoms and without the following
“alarm features” [3] :
 Weight loss
 Iron deficiency anemia
 Family history of certain organic GI illnesses (eg, inflammatory bowel disease, celiac
sprue, colorectal cancer)
Screening studies to rule out disorders other than IBS include the following:
 Complete blood count with differential to screen for anemia, inflammation, and
infection
 A comprehensive metabolic panel to evaluate for metabolic disorders and to rule out
dehydration/electrolyte abnormalities in patients with diarrhea
 Stool examinations for ova and parasites, enteric pathogens, leukocytes,Clostridium
difficile toxin, and possibly Giardia antigen
History-specific studies include the following:
 Hydrogen breath testing to exclude bacterial overgrowth in patients with diarrhea and to
screen for lactose and/or fructose intolerance
 Tissue transglutaminase antibody testing and small bowel biopsy in IBS-D to diagnose
celiac disease.
 Thyroid function tests
 Serum calcium testing to screen for hyperparathyroidism
 Erythrocyte sedimentation rate and C-reactive protein measurement are nonspecific
screening tests for inflammation
See Workup for more detail.
Management
Management of irritable bowel syndrome consists primarily of providing psychological
support and recommending dietary measures. Pharmacologic treatment is adjunctive and
should be directed at symptoms.
Dietary measures may include the following:
 Fiber supplementation may improve the symptoms of constipation and diarrhea
 Polycarbophil compounds (eg, Citrucel, FiberCon) may produce less flatulence than
psyllium compounds (eg, Metamucil)
 Judicious water intake is recommended in patients who predominantly experience
constipation
 Caffeine avoidance may limit anxiety and symptom exacerbation
 Legume avoidance may decrease abdominal bloating
 Lactose, fructose, and/or FODMAPs (fermentable oligosaccharides, disaccharides,
monosaccharides, and polyols) should be limited or avoided in patients with these
contributing disorders
 Probiotics are being studied for their use in decreasing IBS symptoms
Although the evidence is mixed regarding long-term improvement in GI symptoms with
successful treatment of psychiatric comorbidities, the American College of Gastroenterology
has concluded the following:
 Psychological interventions, cognitive-behavioral therapy, dynamic psychotherapy, and
hypnotherapy are more effective than placebo
 Relaxation therapy is no more effective than usual care
Pharmacologic agents used for the management of symptoms in IBS include the following:
 Anticholinergics (eg, dicyclomine, hyoscyamine)
 Antidiarrheals (eg, diphenoxylate, loperamide)
 Tricyclic antidepressants (eg, imipramine, amitriptyline)
 Prokinetics
 Bulk-forming laxatives
 Serotonin receptor antagonists (eg, alosetron)
 Chloride channel activators (eg, lubiprostone)
 Guanylate cyclase C (GC-C) agonists (eg, linaclotide)
 Antispasmodics (eg, peppermint oil, pinaverium, trimebutine,
cimetropium/dicyclomine) [4]
 Potentially, rifaxamin (this is still investigational and not FDA approved)
See Treatment and Medication for more detail.
Background
Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain
and altered bowel habits in the absence of a specific and unique organic pathology. Osler
coined the term mucous colitis in 1892 when he wrote of a disorder of mucorrhea and
abdominal colic with a high incidence in patients with coincident psychopathology. Since
that time, the syndrome has been referred to by sundry terms, including spastic colon,
irritable colon, and nervous colon.
In the past, irritable bowel syndrome has been considered a diagnosis of exclusion; however,
it is no longer considered a diagnosis of exclusion, but it does have a broad differential
diagnosis. [5] No specific motility or structural correlates have been consistently demonstrated;
however, experts suggest the use of available guidelines can minimize testing and aid in the
diagnosis.
Pathophysiology
Traditional theories regarding pathophysiology may be visualized as a 3-part complex of
altered GI motility, visceral hyperalgesia, and psychopathology. [6] A unifying mechanism is
still unproven.
Altered GI motility
Altered GI motility includes distinct aberrations in small and large bowel motility.
The myoelectric activity of the colon is composed of background slow waves with
superimposed spike potentials. Colonic dysmotility in irritable bowel syndrome manifests as
variations in slow-wave frequency and a blunted, late-peaking, postprandial response of spike
potentials. Patients who are prone to diarrhea demonstrate these alterations to a greater degree
than patients who are prone to constipation.
Small bowel dysmotility manifests in delayed meal transit in patients prone to constipation
and in accelerated meal transit in patients prone to diarrhea. In addition, patients exhibit
shorter intervals between migratory motor complexes (the predominant interdigestive small
bowel motor patterns).
Current theories integrate these widespread motility aberrations and hypothesize a
generalized smooth muscle hyperresponsiveness. They describe increased urinary symptoms,
including frequency, urgency, nocturia, and hyperresponsiveness to methacholine challenge.
Visceral hyperalgesia
Visceral hyperalgesia is the second part of the traditional 3-part complex that characterizes
irritable bowel syndrome. [7]
Enhanced perception of normal motility and visceral pain characterizes irritable bowel
syndrome. Rectosigmoid and small bowel balloon inflation produces pain at lower volumes
in patients than in controls. Notably, hypersensitivity appears with rapid but not with gradual
distention.
Patients who are affected describe widened dermatomal distributions of referred pain.
Sensitization of the intestinal afferent nociceptive pathways that synapse in the dorsal horn of
the spinal cord provides a unifying mechanism.
Psychopathology
Psychopathology is the third aspect. Associations between psychiatric disturbances and
irritable bowel syndrome pathogenesis are not clearly defined.
Patients with psychological disturbances relate more frequent and debilitating illness than
control populations. Patients who seek medical care have a higher incidence of panic
disorder, major depression, anxiety disorder, and hypochondriasis than control populations. A
study has suggested that patients with irritable bowel syndrome may have suicidal ideation
and/or suicide attempts strictly as a result of their bowel symptoms. [8] Clinical alertness to
depression and hopelessness is mandatory. This is underscored by another study that revealed
that patient complaints that relate to functional bowel disorders may be trivialized.
An Axis I disorder coincides with the onset of GI symptoms in as many as 77% of patients. A
higher prevalence of physical and sexual abuse has been demonstrated in patients with
irritable bowel syndrome. Whether psychopathology incites the development of irritable
bowel syndrome or vice versa remains unclear.
Microscopic inflammation
Microscopic inflammation has been documented in some patients. [1] This concept is
groundbreaking in that irritable bowel syndrome had previously been considered to have no
demonstrable pathologic alterations.
Both colonic inflammation and small bowel inflammation have been discovered in a subset
of patients with irritable bowel syndrome, as well as in patients with the onset of irritable
bowel syndrome after infectious enteritis (postinfectious irritable bowel syndrome). Risk
factors for developing postinfectious irritable bowel syndrome include longer duration of
illness, the type of pathogen involved, smoking, female gender, an absence of vomiting
during the infectious illness, and young age. [9]
Laparoscopic full-thickness jejunal biopsy samples revealed infiltration of lymphocytes into
the myenteric plexus and intraepithelial lymphocytes in a subset of patients in one
study. [10] Neuronal degeneration of the myenteric plexus was also present in some patients.
Patients with postinfectious irritable bowel syndrome may have increased numbers of colonic
mucosal lymphocytes and enteroendocrine cells. Enteroendocrine cells in postinfectious
irritable bowel syndrome appear to secrete high levels of serotonin, increasing colonic
secretion and possibly leading to diarrhea.
Alterations in the intestinal biome
Small bowel bacterial overgrowth has been heralded as a unifying mechanism for the
symptoms of bloating and distention, common to patients with irritable bowel syndrome. This
has led to proposed treatments with probiotics and antibiotics.
The fecal microflora also differs among patients with irritable bowel syndrome versus
controls. A sophisticated molecular analysis suggested an alteration in the patterns and the
contents of gut bacteria. [11]
Etiology
The causes of irritable bowel syndrome remain poorly defined, but they are being avidly
researched.
Postulated etiologies of irritable bowel syndrome
Abnormal transit profiles and an enhanced perception of normal motility may exist. Up to
one third of patients with irritable bowel syndrome may have altered colonic transit. Delayed
colonic motility may be more common in patients with constipation-predominant irritable
bowel syndrome than in healthy controls. Similarly, accelerated colonic transit may be more
common in patients with diarrhea-predominant disease than in healthy controls. [12] Local
histamine sensitization of the afferent neuron causing earlier depolarization may occur.
Causes related to enteric infection
Colonic muscle hyperreactivity and neural and immunologic alterations of the colon and
small bowel may persist after gastroenteritis. Psychological comorbidity independently
predisposes the patient to the development of postinfectious irritable bowel syndrome.
Psychological illness may create a proinflammatory cytokine milieu, leading to irritable
bowel syndrome through an undefined mechanism after acute infection.
Infection with Giardia lamblia has been shown to lead to an increased prevalence of irritable
bowel syndrome, as well as chronic fatigue syndrome. In a historic cohort study of patients
with G lamblia infection as detected by stool cysts, the prevalence of irritable bowel
syndrome was 46.1% as long as 3 years after exposure, compared with 14% in controls. [13]
Central neurohormonal mechanisms
Abnormal glutamate activation of N- methyl-D- aspartate (NMDA) receptors, activation of
nitric oxide synthetase, activation of neurokinin receptors, and induction of calcitonin gene–
related peptide have been observed.
The limbic system mediation of emotion and autonomic response enhances bowel motility
and reduces gastric motility to a greater degree in patients who are affected than in controls.
Limbic system abnormalities, as demonstrated by positron emission tomography, have been
described in patients with irritable bowel syndrome and in those with major depression.
The hypothalamic-pituitary axis may be intimately involved in the origin. Motility
disturbances correspond to an increase in hypothalamic corticotropin-releasing factor (CRF)
production in response to stress. CRF antagonists eliminate these changes.
Additional etiologic factors
Intestinal permeability
Intestinal permeability appears to be increased, especially in diarrhea-predominant irritable
bowel syndrome. [14]
Alterations in the intestinal biome
As discussed in Pathophysiology, Pimentel and colleagues have proposed that small bowel
bacterial overgrowth provides a unifying mechanism for the common symptoms of bloating
and gaseous distention in patients with irritable bowel syndrome. [15]
There is a relationship between the organisms that live in the intestine and the immune
system, and this relationship is not yet fully understood. [14]
Dietary intolerance
Bloating and distention may also occur from intolerance to dietary fats. Reflex-mediated
small bowel gas clearance is more impaired by ingestion of lipids in patients with irritable
bowel syndrome than in patients without the disorder.
Studies of elimination and challenge diets have suggested that poorly absorbed short-chain
carbohydrates, in the form of fructose and fructans, may create symptoms among patients
with irritable bowel syndrome, as measured by a visual analogue scale. [16]
Research suggests that neuronal degeneration and myenteric plexus lymphocytosis may exist
in the proximal jejunum. Additionally, colonic lymphocytosis and enteroendocrine cell
hyperplasia have been demonstrated in some patients.
Epidemiology
Population-based studies estimate the prevalence of irritable bowel syndrome at 10-20% and
the incidence of irritable bowel syndrome at 1-2% per year. Of people with irritable bowel
syndrome, approximately 10-20% seek medical care. An estimated 20-50% of
gastroenterology referrals relate to this symptom complex. The incidence is markedly
different among countries.
American and European cultures demonstrate similar frequencies of irritable bowel syndrome
across racial and ethnic lines. However, within the United States, survey questionnaires
indicate a lower prevalence of irritable bowel syndrome in Hispanics in Texas and Asians in
California. Populations of Asia and Africa may have a lower prevalence of irritable bowel
syndrome. The role of different cultural influences and varying health care–seeking behaviors
is unclear.
In Western countries, women are 2-3 times more likely to develop irritable bowel syndrome
than men, although males represent 70-80% of patients with irritable bowel syndrome in the
Indian subcontinent. Women seek health care more often, but the irritable bowel syndrome–
specific influence of this occurrence remains unknown. Other factors, such as a probably
greater incidence of abuse in women, may confound interpretation of this statistic.
Patients often retrospectively note the onset of abdominal pain and altered bowel habits in
childhood. Approximately 50% of people with irritable bowel syndrome report symptoms
beginning before age 35 years. The development of symptoms in people older than 40 years
does not exclude irritable bowel syndrome but should prompt a closer search for an
underlying organic etiology.
Prognosis
Irritable bowel syndrome is a chronic relapsing disorder characterized by recurrent symptoms
of variable severity; however, life expectancy remains similar to that of the general
population. Clinicians must be forthcoming with patients because knowledge of the condition
may help allay undue fears as their disease waxes and wanes. Irritable bowel syndrome does
not increase the mortality or the risk of inflammatory bowel disease or cancer.
Patients with IBS may carry an increased risk of ectopic pregnancy and miscarriage, but not
stillbirth. The reasons for this are unknown. Whether the risk increases because of the
irritable bowel syndrome itself, or because of another factor such as medications used for
IBS, is also unknown. [17]
The principal associated physical morbidities of irritable bowel syndrome include abdominal
pain and lifestyle modifications secondary to altered bowel habits. Work absenteeism
resulting in lost wages is more frequent in patients with irritable bowel syndrome.
Patient Education
Patient education remains the cornerstone of successful treatment of irritable bowel
syndrome. Teach the patient to identify stressors and to develop avoidance techniques. Many
patients successfully manage their symptoms with attention to dietary triggers.
For patient education resources, see Digestive Disorders Center, as well as Irritable Bowel
Syndrome (IBS), Inflammatory Bowel Disease (IBD), and Chronic Pain.
History and Physical Examination
History
A meticulous history is the key to establish a diagnosis of irritable bowel syndrome. The
Rome criteria provide the construct upon which questions are based (see Diagnostic
Considerations).
Altered bowel habits
Constipation results in complaints of hard stools of narrow caliber, painful or infrequent
defecation, and intractability to laxatives. Diarrhea usually is described as small volumes of
loose stool, with evacuation preceded by urgency or frequent defecation. Postprandial
urgency is common, as is alternation between constipation and diarrhea. Characteristically,
one feature predominates in a single patient, but significant variability exists among patients.
Abdominal pain
Descriptions are protean. Pain frequently is diffuse without radiation. Common sites of pain
include the lower abdomen, specifically the left lower quadrant. Acute episodes of sharp pain
are often superimposed on a more constant dull ache. Meals may precipitate pain, and
defecation commonly improves pain. Defecation may not fully relieve pain, however.
Pain from presumed gas pockets in the splenic flexure may masquerade as anterior chest pain
or left upper quadrant abdominal pain. This splenic flexure syndrome is demonstrable by
balloon inflation in the splenic flexure and should be considered in the differential of chest or
left upper quadrant abdominal pain.
Abdominal distention
Patients frequently report increased amounts of bloating and gas. Quantitative measurements
fail to support this claim. People with irritable bowel syndrome may manifest increasing
abdominal circumference throughout the day, as assessed by CT scan. They may also
demonstrate intolerance to otherwise normal amounts of abdominal distention.
Additional symptoms consistent with irritable bowel syndrome
Clear or white mucorrhea of a noninflammatory etiology is commonly reported.
Epidemiologic associations with dyspepsia, heartburn, nausea, vomiting, sexual dysfunction
(including dyspareunia and poor libido), and urinary frequency and urgency have been noted.
Symptoms may worsen in the perimenstrual period, and fibromyalgia is a common
comorbidity. Stressor-related symptoms may be revealed with careful questioning (emphasize
avoidance of stressors).
Symptoms inconsistent with irritable bowel syndrome
Symptoms not consistent with irritable bowel syndrome should alert the clinician to the
possibility of an organic pathology. Inconsistent symptoms include the following:
 Onset in middle or older age
 Acute symptoms (irritable bowel syndrome is defined by chronicity)
 Progressive symptoms
 Nocturnal symptoms
 Anorexia or weight loss
 Fever
 Rectal bleeding
 Painless diarrhea
 Steatorrhea
 Gluten intolerance
Physical examination
The patient with irritable bowel syndrome has an overall healthy appearance but may be tense
or anxious. The patient may present with sigmoid tenderness or a palpable sigmoid cord.
Criteria for Diagnosis
A consensus panel created and then updated the Rome criteria to provide a standardized
diagnosis for research and clinical practice. The Rome III criteria for the diagnosis of irritable
bowel syndrome [2] require that patients have had recurrent abdominal pain or discomfort at
least 3 days per month during the previous 3 months that is associated with 2 or more of the
following:
 Relieved by defecation
 Onset associated with a change in stool frequency
 Onset associated with a change in stool form or appearance
Supporting symptoms include the following:
 Altered stool frequency
 Altered stool form
 Altered stool passage (straining and/or urgency)
 Mucorrhea
 Abdominal bloating or subjective distention
Four bowel patterns may be seen with irritable bowel syndrome. These patterns include the
following:
 IBS-D (diarrhea predominant)
 IBS-C (constipation predominant)
 IBS-M (mixed diarrhea and constipation)
 IBS-U (unclassified; the symptoms cannot be categorized into one of the above three
subtypes)
The usefulness of these subtypes is debatable. Notably, within 1 year, 75% of patients change
subtypes, and 29% switch between constipation-predominant IBS and diarrhea-predominant
IBS.
Intestinal motility disorder
Background
The phrase intestinal motility disorders applies to abnormal intestinal contractions, such as
spasms and intestinal paralysis. This phrase is used to describe a variety of disorders in which
the gut has lost its ability to coordinate muscular activity because of endogenous or
exogenous causes. [1, 2, 3] Such disorders may be primary or secondary and may manifest in a
variety of ways, including the following:
 Abdominal distention
 Recurrent obstruction
 Severe abdominal colicky pain
 Severe constipation
 Gastroesophageal reflux disease
 Intractable, recurrent vomiting
In a broad sense, any alteration in the transit of foods and secretions into the digestive tract
may be considered an intestinal motility disorder. The following are considered intestinal
motility disorders [4, 5] :
 Intestinal pseudo-obstruction ( Ogilvie syndrome )
 Irritable bowel syndrome ( IBS )
 Fecal incontinence
 Constipation
Chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIP) is a clinical syndrome caused by ineffective
intestinal propulsion and characterized by symptoms and signs of intestinal obstruction in the
absence of an occluding lesion of the intestinal lumen. [6] CIP is caused by a group of
heterogeneous nerve and muscle disorders and results in obstructive intestinal symptoms in
the absence of any mechanical obstruction. Usually, CIP occurs in patients with severe
comorbid clinical conditions or after traumas (even surgical) or in patients with other
underlying medical diseases.
A consensus working group defined CIP as a “rare, severe disabling disorder characterized by
repetitive episodes or continuous symptoms and signs of bowel obstruction, including
radiographic documentation of dilated bowel with air-fluid levels, in the absence of a fixed,
lumen-occluding lesion.” [7] However, this definition is really applicable only to the most
severe forms of CIP; air-fluid levels may not always be present.
Thus, the criteria for diagnosis should include definite symptoms and signs of obstruction,
with documentation of air-fluid levels on plain radiographs of the abdomen or a dilated
duodenum, small intestine, or colon on barium radiographs. Even though severe dysmotility
may otherwise be present, the term pseudo-obstruction should not be used when these
radiographic findings are absent.
Pathophysiology
Coordinated movements of the stomach and intestines are required to digest and propel
intestinal contents along the digestive tract. The complex patterns of contraction and
relaxation necessary for proper motility of the gastrointestinal (GI) tract are generated in the
nerves and muscles within the GI walls.
Every day, at any time, many factors can influence GI motility (eg, physical exercise,
emotional distress). The pathogenesis of primary intestinal motility disorders probably is
multifactorial, but neither biochemical abnormality nor structural abnormality has been
demonstrated commonly, except in some forms of intestinal pseudo-obstruction. More
recently, there is evidence that low-grade mucosal inflammation and immune activation
(particularly with mast cell involvement) in association with impaired epithelial barrier
function and aberrant neuronal sensitivity may play a role in functional gastrointestinal
disorders. [8]
Although the overall structural organization is similar throughout the digestive tract, each
part has distinct motor activities. The musculature of the digestive tract has either extrinsic
innervation (both sympathetic and parasympathetic) or intrinsic innervation (Auerbach plexus
or myenteric plexus).
Intrinsic innervation is fundamental to coordinating GI motor activity. A neural network
branching between longitudinal and circular muscle layers of the GI tract constitutes intrinsic
innervation. Another nervous intrinsic plexus in the GI tract (Meissner plexus or submucosal
plexus) helps to modify mucosal absorption and secretion without influencing motility.
Random, unorganized motor activity with occasional peristaltic and antiperistaltic complexes
occurs during feeding, and this allows gastric remixing of foods. After this, another motor
activity occurs, which is more regular, and this begins the peristaltic waves (ie, contractions
of the circular musculature of the small intestine) that allow progression of undigested food
through the intestines.
These events happen because the gastric pacemaker area, which originates electric slow
waves with a frequency of 3 cycles per minute, occurs at the junction between the body and
the antrum of the stomach. These electric waves, called migrating myoelectric complexes,
determine the frequency of muscular contractions in the antral and pyloric areas through
electromechanical coupling.
Migrating myoelectric complexes regulate gastric emptying and move gastric contents
distally. Every 90 minutes, a cluster of migrating myoelectric complexes arises in the
stomach and migrates distally beyond the ileum. Vagal function and the release of nitric
oxide, vasoactive intestinal polypeptide, motilin, and nutrients of the meal and other
enterohormones also affect GI motility.
Knowles and Martin attempted to define a novel classification for intestinal motility
disorders, [9] in which these conditions are categorized as well-defined entities, entities with a
variable dysfunction-symptom relation, questionable entities, and entities associated with
behavioral disorders.
Well-defined entities in the Knowles-Martin classification include the following:
 Delayed colonic transit - Slow transit constipation (eg, enteric neuropathy, enteric
myopathy, Parkinson disease, endocrine disorders, spinal injury)
 Dilated colon (diffuse or segmental) - Ogilvie syndrome, megacolon
 Absent rectoanal inhibitory reflex - Hirschsprung disease
Entities with a variable dysfunction-symptom relation include the following:
 Abnormally low anal canal pressure fecal incontinence (eg, diabetes mellitus, spinal
injury)
Questionable entities include the following:
 Accelerated transit bile salts
 Short bowel
 Rare endocrine and metabolic disorders
Entities associated with behavioral disorders include the following:
 Impaired pelvic floor relaxation, prolonged storage in the rectosigmoid, outlet delay,
anismus
 Avoidance of defecation, functional fecal retention (eg, poor pelvic floor training, poor
diet, fear of pain, learned suppression)
Etiology
Causes of intestinal motility disorders seem to be multifactorial, and only a few have been
detected.
Degenerative disorders cause pseudo-obstruction along with other problems; however, in
patients with pseudo-obstruction, only changes in the nervous and muscular systems have
been observed.
Many drugs that are commonly used (eg, tricyclic antidepressants, diuretics, laxatives) or
have specific indications (eg, lithium salts, vinca alkaloids, and other chemotherapy agents)
may interfere with intestinal motility. Stypsis may be related to drug abuse. Drugs such as
benzodiazepines, lithium salts, laxatives, and codeine cause secondary stypsis. The latter can
produce narcotic bowel syndrome, which is usually observed in patients who abuse opiates
for chronic pain.
Endocrine disorders (eg, myxedema) can also cause pseudo-obstruction.
IBS, the more commonly diagnosed disorder of intestinal motility, has been considered a
disease of the colon for decades, but research on GI motility has demonstrated that
underlying motility disturbances can occur in the small bowel.
The causes of irritable bowel syndrome (IBS) remain unknown. According to some reports,
the small intestine and colon of patients with IBS are more sensitive and reactive to mild
stimuli than usual. IBS could be related to immature status of muscles and nerves in the
intestinal wall of these persons.
Fecal incontinence
Aging, dementia, stroke, Parkinson disease, spinal cord injuries, rectal tears during birthing,
diabetes, surgical complications, and neuromuscular disorders (eg, myasthenia gravis) may
cause fecal incontinence.
Occasionally, fecal incontinence may occur after ingestion of certain foods. Sugars, insoluble
fibers, and starches (except rice) are broken down in the intestines, forming a variable amount
of gas that must be expelled. Most people who have lactase deficiency cannot digest lactose,
a sugar common in several foods (eg, milk, cakes). People who have lactose deficiency may
experience uncontrolled liquid diarrhea after lactose ingestion.
Constipation
Constipation commonly has several causes, either primary or secondary. The most frequent
of these are the following:
 Diet that is very poor in fiber and high in animal fats and refined sugars
 Pregnancy
 Psychological constipation related to lifestyle changes (eg, travel, a new job, or
divorce), in which the patient ignores the urge to defecate
 Hypothyroidism
 Electrolyte imbalance, especially if it involves Ca ++ or K +
 Tumors producing mechanical compression on an intestinal tract, either internally or
externally
 Nervous system injuries
 Intoxication from lead, mercury, phosphorus, or arsenic
 Constipation also may be secondary to rhagades (anal fissures) and piles.
Genetic factors
In a retrospective study investigating the association between mitochondrial disorders and
CIP in 80 patients, Amiot et al determined that 15 patients (19% of the study cohort) had
mitochondrial defects, including mutations in the thymidine phosphorylase gene (5 patients),
the DNA polymerase-gamma gene (5 patients), and tRNA(leu(UUR)) (2 patients); 3 of the
patients had no identifiable genetic defects. [10] Extradigestive symptoms occurred in all 15
patients.
Unlike other CIP patients, patients in whom the condition was associated with a
mitochondrial defect tend to require frequent and long-term parenteral nutrition.[10] Because
of the frequent occurrence of digestive and neurologic complications, these patients also had
a high incidence of premature death. The authors suggested that mitochondrial defects are an
important cause of CIP and recommended that CIP patients be tested for such defects,
particularly those with severe CIP who experience associated neurologic symptoms.
Epidemiology
According to some epidemiologic reports, as many as 30 million Americans have intestinal
motility disorders. Available data from the medical literature indicate that worldwide, 30-
45% of all GI conditions are referable to intestinal motility disorders.
When intestinal motility disorders are idiopathic and not related to either malignancies or
systemic diseases, morbidity is minimal and mortality from complications is low (1-1.5%);
complications usually occur in patients with intestinal pseudo-obstruction.
Persons of any age group may be affected, depending on the specific intestinal motility
disorder. For example, IBS occurs more frequently in people aged 20-40 years, whereas
intestinal pseudo-obstruction may occur in either newborns or elderly patients. Most patients
are female, with a female-to-male ratio of 2.8:1. Primary intestinal motility disorders are most
common in white persons and are usually thought to be related to diet.
Prognosis
Primary intestinal motility disorders or disorders that are not secondary to malignancy or
debilitating pathology have a good prognosis. According to many reports, the prognosis is
excellent for patients with IBS and mild fecal incontinence.
The prognosis is worse for patients with intestinal pseudo-obstruction, which has a high
mortality.
History
The clinical presentation of patients with intestinal motility disorders is protean and may
range from simple nausea and indigestion to severe abdominal pain, vomiting, diarrhea,
inability to eat, weight loss, and other symptoms. It should be kept in mind that during
pregnancy, intestinal motility disorders may worsen as a consequence of uterine compression
of intestinal loops.
Obtain a complete patient history, recording information about the following:
 Feelings of abdominal discomfort, cramping, nausea or vomiting, pain, excessive gas,
and rectal fullness
 Frequency, amount, and timing of normal defecation and any recent change
 Amount, consistency, and color of last passed feces
 Type of diet, use of laxatives or enemas, and drug use

Patients with chronic intestinal pseudo-obstruction (CIP) generally experience abdominal
distention, pain, dizziness, fatigue, nausea, and vomiting for several days or months before
their condition is recognized.
One type of pain is directly related to intestinal distention and improves or temporarily
disappears if intestinal distention decreases. A second type is probably secondary to smooth
muscle spasm or visceral hyperalgesia and is independent of intestinal distention.
Abdominal distention ranges from almost none to the equivalent of a 9-month pregnancy,
depending on the nature and extent of the underlying pathology. An audible succussion
splash and loud borborygmi may be present. Pain and distention may be almost continuous or
may be interrupted by periods of clinical improvement. The vomitus frequently consists of
food ingested 12 or more hours previously and may be feculent.
In patients with predominant small intestinal involvement, bacterial overgrowth and stagnant
loop syndrome often develop and may lead to steatorrhea and diarrhea. Predominant colonic
involvement usually results in constipation, megacolon, or both. Patients with both types of
involvement may cycle from diarrhea to constipation, depending on the severity of
steatorrhea and the relative involvement of each organ.
Many patients have involvement of the esophagus, which may be asymptomatic or may
produce dysphagia, chest pain, regurgitation, reflux, and heartburn. Visceral neuropathies
may manifest as symptoms resembling achalasia or diffuse esophageal spasm.
Gastric involvement produces gastroparesis. The abdominal distention and pain produced by
any combination of gastric, small intestine, and colonic involvement result in decreased food
intake, weight loss, and malnutrition, especially when combined with malabsorption.
Patients with involvement limited to the colon and distal small bowel may have relatively
normal weights because their unaffected proximal bowel allows for normal absorption.
Patients may have a history of weight loss or previous abdominal operations with no
obstructing lesion found, or they may have a family history positive for the condition.
Abdominal pain, nausea, and irregular bowel habits that intensify during stress are the most
common symptoms in patients with irritable bowel syndrome (IBS).
Fecal incontinence
Fecal incontinence can be a life-threatening condition. In the mild form, patients may
experience abdominal bloating and uproar, but in the severe form, they may experience
serious abdominal pain. Patients may not experience symptoms if incontinence is related to a
comorbid condition (eg, dementia, Parkinson disease, or a demyelinating disease of the spinal
cord).
Constipation and fecal incontinence
Constipation can also be a life-threatening condition. Patients with constipation report
abdominal discomfort, cramping, pain, rectal fullness, or, more rarely, nausea and vomiting.
The clinical picture of patients with intestinal motility disorders is protean and may vary
greatly, depending on the specific condition present.
Always perform a digital rectal examination in any patient with an intestinal motility disorder
to detect the presence of a mass (eg, feces, tumor, or a foreign body) or blood in the rectum.
Decreased or absent bowel sounds and progressive loss of bowel movements are the most
common signs in patients with CIP. [11] Patients’ symptoms increase in the 4-7 days before
clinical onset and recognition of the disorder.
Physical examination findings may include weight loss, cachexia, and abdominal distention.
Patients with small intestinal involvement usually have a succussion splash located in the
midabdomen, whereas patients with gastric involvement may have a splash in the left upper
quadrant.
Hypertympany to percussion is usually present, and contracting bowel loops are occasionally
observed pushing up against the abdominal wall. Bowel sounds are of no value in making a
diagnosis of pseudo-obstruction.
Evidence of central and peripheral nervous system disease should be sought, and autonomic
nervous system testing should be performed when indicated.
Involvement of the genitourinary system may be indicated by the presence of a palpable
urinary bladder. Patients may have positive neurologic findings with signs of systemic
disease (eg, progressive sclerosis, amyloidosis, or myxedema).
Patients with IBS commonly have bloating, heartburn, burping, vomiting, and difficulty
swallowing. Symptoms can fluctuate, disappearing during sleep and occurring again during
stressing occasions. Heartburn, burping, and difficulty swallowing are usually due to
concomitant gastroesophageal reflux disease, a very common condition in such patients.
Fecal incontinence
In the first stage of the disease, passing gas more than the normal 14-23 times a day
characterizes fecal incontinence. In the second stage, liquid incontinence occurs, and patients
are unaware that stools are being passed (stage of passive fecal incontinence). In the third
stage, which is more severe, involuntary passage of feces through normal sphincter muscles
occurs (stage of urge incontinence).
Constipation
The pattern of at least 3 stools per week and no more than 3 per day is considered normal
defecation. Any reduction in the frequency of defecation may be considered constipation.
Abdominal colicky pains are frequent in these patients.
Complications
Complications of intestinal motility disorders vary greatly, depending on the specific type of
disorder under consideration.
Intestinal pseudo-obstruction is often associated with a high mortality (15-30%), in most
cases due to delayed diagnosis.
Constipation may have a severe complication, impaction. If this condition is not recognized
early, the patient may die. Impaction is the collection of dry and hardened feces in the rectum
or colon. Symptoms of impaction may be similar to those of constipation or may be unrelated
to the gastrointestinal system.
If abdominal distention occurs, movements of the diaphragm are compromised and cause
insufficient aeration with subsequent hypoxia and left ventricular dysfunction. In addition,
hypoxia can precipitate angina or tachycardia. When a vasovagal response begins, the patient
may have hypotension. Patients with impaction may experience vomiting, diarrhea, and
resultant dehydration. They may present in an acutely confused and disoriented state, with
tachycardia, fever, and altered blood pressure.
IBS is not usually associated with complications. Fecal incontinence may cause
psychological problems in affected patients.
Hipotiroidism
Practice Essentials
Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid
hormone. In the United States and other areas of adequate iodine intake, autoimmune thyroid
disease (Hashimoto disease) is the most common cause of hypothyroidism; worldwide, iodine
deficiency remains the foremost cause.
The image below depicts the hypothalamic-pituitary-thyroid axis.
The hypothalamic-pituitary-thyroid
axis. Levels of circulating thyroid hormones are regulated by a complex feedback system
involving the hypothalamus and pituitary gland.
See 21 Hidden Clues to Diagnosing Nutritional Deficiencies, a Critical Images slideshow, to
help identify clues to conditions associated with malnutrition.
Signs and symptoms
Hypothyroidism commonly manifests as a slowing in physical and mental activity but may be
asymptomatic. Symptoms and signs are often subtle and neither sensitive nor specific.
The following are symptoms of hypothyroidism:
 Fatigue, loss of energy, lethargy
 Weight gain
 Decreased appetite
 Cold intolerance
 Dry skin
 Hair loss
 Sleepiness
 Muscle pain, joint pain, weakness in the extremities
 Depression
 Emotional lability, mental impairment
 Forgetfulness, impaired memory, inability to concentrate
 Constipation
 Menstrual disturbances, impaired fertility
 Decreased perspiration
 Paresthesia and nerve entrapment syndromes
 Blurred vision
 Decreased hearing
 Fullness in the throat, hoarseness
The following are symptoms more specific to Hashimoto thyroiditis:
 Feeling of fullness in the throat
 Painless thyroid enlargement
 Exhaustion
 Transient neck pain, sore throat, or both
Physical signs of hypothyroidism include the following:
 Weight gain
 Slowed speech and movements
 Dry skin
 Jaundice
 Pallor
 Coarse, brittle, straw-like hair
 Loss of scalp hair, axillary hair, pubic hair, or a combination
 Dull facial expression
 Coarse facial features
 Periorbital puffiness
 Macroglossia
 Goiter (simple or nodular)
 Hoarseness
 Decreased systolic blood pressure and increased diastolic blood pressure
 Bradycardia
 Pericardial effusion
 Abdominal distention, ascites (uncommon)
 Hypothermia (only in severe hypothyroid states)
 Nonpitting edema (myxedema)
 Pitting edema of lower extremities
 Hyporeflexia with delayed relaxation, ataxia, or both
Myxedema coma is a severe form of hypothyroidism that most commonly occurs in
individuals with undiagnosed or untreated hypothyroidism who are subjected to an external
stress. Features are as follows:
 Altered mental status
 Hypothermia
 Bradycardia
 Hypercarbia
 Hyponatremia
 Cardiomegaly, pericardial effusion, cardiogenic shock, and ascites may be present
Diagnosis
Third-generation thyroid-stimulating hormone (TSH) assays are generally the most sensitive
screening tool for primary hypothyroidism. [1] If TSH levels are above the reference range, the
next step is to measure free thyroxine (T4) or the free thyroxine index (FTI), which serves as
a surrogate of the free hormone level. Routine measurement of triiodothyronine (T3) is not
recommended.
Results in patients with hypothyroidism are as follows:
 Elevated TSH with decreased T4 or FTI
 Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 or FTI is considered mild
or subclinical hypothyroidism
Abnormalities in the complete blood count and metabolic profile that may be found in
patients with hypothyroidism include the following [2] :
 Anemia
 Dilutional hyponatremia
 Hyperlipidemia
 Reversible increases in creatinine [2]
 Elevations in transaminases and creatinine kinase
No universal screening recommendations exist for thyroid disease for adults. The American
Thyroid Association recommends screening at age 35 years and every 5 years thereafter, with
closer attention to patients who are at high risk, such as the following [3] :
 Pregnant women
 Women older than 60 years
 Patients with type 1 diabetes or other autoimmune disease
 Patients with a history of neck irradiation
Management
Monotherapy with levothyroxine (LT4) remains the treatment of choice for hypothyroidism.
Aspects of LT4 treatment are as follows:
 Otherwise young and healthy patients can be started on LT4 at anticipated full
replacement doses
 In elderly patients and those with known ischemic heart disease, begin with one fourth
to one half the expected dose and adjust the dose in small increments after no less than
4-6 weeks
 For most cases of mild to moderate hypothyroidism, a starting LT4 dose of 50-75 µg
daily will suffice
 Clinical benefits begin in 3-5 days and level off after 4-6 weeks
 Achieving a TSH level within the reference range may take several months
 LT4 dosing changes should be made every 6-8 weeks until the patient’s TSH is in target
range
After dose stabilization, patients can be monitored with annual clinical evaluations and TSH
monitoring. Patients should be monitored for symptoms and signs of overtreatment, which
include the following:
 Tachycardia
 Palpitations
 Atrial fibrillation
 Nervousness
 Tiredness
 Headache
 Increased excitability
 Sleeplessness
 Tremors
 Possible angina
In patients who continue to have symptoms (eg, weight gain, fatigue) despite normalization
of their TSH level, consideration should be given to causes other than hypothyroidism. In
some cases, however, the persistence of symptoms results from impaired conversion of T4 to
T3 in the brain; these patients may benefit from combination LT4/liothyronine (LT3)
therapy. [4]
The updated guidelines on hypothyroidism issued by the American Thyroid Association in
2014 maintain the recommendation of levothyroxine as the preparation of choice for
hypothyroidism, with the following considerations: [5, 6]
 If levothyroxine dose requirements are much higher than expected, consider evaluating
for gastrointestinal disorders such as Helicobacter pylori –related gastritis, atrophic
gastritis, or celiac disease; if such disorders are detected and effectively treated, re-
evaluation of thyroid function and levothyroxine dosage is recommended.
 Initiation or discontinuation of estrogen and androgens should be followed by
reassessment of serum TSH at steady state, since such medications may alter
levothyroxine requirement.
 Serum TSH should be reassessed upon initiation of agents such as tyrosine kinase
inhibitors that affect thyroxine metabolism and thyroxine or triiodothyronine
deiodination.
 Serum TSH monitoring is advisable when medications such as phenobarbital,
phenytoin, carbamazepine, rifampin, and sertraline are started.
 When deciding on a starting dose of levothyroxine, the patient’s weight, lean body
mass, pregnancy status, etiology of hypothyroidism, degree of TSH elevation, age, and
general clinical context, including the presence of cardiac disease, should be
considered. The serum TSH goal appropriate for the clinical situation should also be
considered.
 Thyroid hormone therapy should be initiated as an initial full replacement or as partial
replacement with gradual increments in the dose titrated upward using serum TSH as
the goal.
 Dose adjustments should be made upon significant changes in body weight, with aging,
and with pregnancy; TSH assessment should be performed 4-6 weeks after any dosage
change.
 Reference ranges of serum TSH levels are higher in older populations (eg, >65 years),
so higher serum TSH targets may be appropriate.
Updated recommendations concerning hypothyroidism treatment in pregnant women are as
follows: [5, 6]
 Pregnant women with overt hypothyroidism should receive levothyroxine replacement
therapy with the dose titrated to achieve a TSH concentration within the trimester-
specific reference range.
 Serial serum TSH levels should be assessed every 4 weeks during the first half of
pregnancy to adjust levothyroxine dosing to maintain TSH within the trimester-specific
range.
 Serum TSH should be reassessed during the second half of pregnancy.
 In women already taking levothyroxine, 2 additional doses per week of the current
levothyroxine dose, given as one extra dose twice weekly with several days’ separation,
may be started as soon as pregnancy is confirmed.
Treatment of myxedema coma is as follows:
 Intravenous (IV) LT4 at a dose of 4 µg/kg of lean body weight, or approximately 200-
250 µg, as a bolus in a single or divided dose, depending on the patient’s risk of cardiac
disease
 After 24 hours, 100 µg LT4 IV, then 50 µg/day IV
 Stress doses of IV glucocorticoids
 Subsequent adjustment of the LT4 dose can be based on clinical and laboratory findings
Background
Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid
hormone. It usually is a primary process in which the thyroid gland is unable to produce
sufficient amounts of thyroid hormone.
Hypothyroidism can also be secondary—that is, the thyroid gland itself is normal, but it
receives insufficient stimulation because of low secretion of thyrotropin (ie, thyroid-
stimulating hormone [TSH]) from the pituitary gland. In tertiary hypothyroidism, inadequate
secretion of thyrotropin-releasing hormone (TRH) from the hypothalamus leads to
insufficient release of TSH, which in turn causes inadequate thyroid stimulation.
Worldwide, iodine deficiency remains the foremost cause of hypothyroidism. In the United
States and other areas of adequate iodine intake, autoimmune thyroid disease (Hashimoto
disease) is the most common cause. Hypothyroidism may also be drug-induced or otherwise
iatrogenic. (See Etiology.)
The patient’s presentation may vary from asymptomatic to myxedema coma with
multisystem organ failure. Because nearly all metabolically active cells require thyroid
hormone, deficiency of the hormone has a wide range of effects. Classic signs and symptoms,
such as cold intolerance, puffiness, decreased sweating, and coarse skin, may not be present,
especially in younger patients. (See Presentation.)
Third-generation TSH assays are readily available and are generally the most sensitive
screening tool for primary hypothyroidism. The generally accepted reference range for
normal serum TSH is 0.40-4.2 mIU/L.
If TSH levels are above the reference range, the next step would be to measure free thyroxine
(T4). Subclinical hypothyroidism, also referred to as mild hypothyroidism, is defined as
normal serum levels of free T4 and triiodothyronine (T3) with a slightly high serum TSH
concentration. (See Workup.)
For hypothyroidism, thyroid hormone is administered to supplement or replace endogenous
production. In general, hypothyroidism can be adequately treated with a constant daily dose
of levothyroxine (LT4). (See Treatment and Medication.)
Congenital hypothyroidism, which affects 1 of every 4000 newborns, is due to congenital
maldevelopment of the thyroid (see Pediatric Hypothyroidism). This disorder is included in
the newborn screening panel in the United States and many other countries, and it is readily
treatable once detected. Cretinism refers to severe hypothyroidism in an infant or child. This
is classically the result of maternal iodine deficiency, and thankfully is increasingly rare.
Pathophysiology
The hypothalamic-pituitary-thyroid axis governs thyroid hormone secretion (see the image
below).
The hypothalamic-pituitary-thyroid
axis. Levels of circulating thyroid hormones are regulated by a complex feedback system
involving the hypothalamus and pituitary gland.
Although hypothalamic or pituitary disorders can affect thyroid function, localized disease of
the thyroid gland that results in decreased thyroid hormone production is the most common
cause of hypothyroidism. Under normal circumstances, the thyroid releases 100-125 nmol of
T4 daily and only small amounts of T3. The half-life of T4 is approximately 7-10 days. T4, a
prohormone, is converted to T3, the active form of thyroid hormone, in the peripheral tissues
by 5’-deiodination.
Early in the disease process, compensatory mechanisms maintain T3 levels. Decreased
production of T4 causes an increase in the secretion of TSH by the pituitary gland. TSH
stimulates hypertrophy and hyperplasia of the thyroid gland and 5’-deiodinase activity,
thereby increasing T3 production.
Deficiency of thyroid hormone has a wide range of effects. Systemic effects are the result of
either derangements in metabolic processes or direct effects by myxedematous infiltration (ie,
accumulation of glucosaminoglycans in the tissues).
The hypothyroid changes in the heart result in decreased contractility, cardiac enlargement,
pericardial effusion, decreased pulse, and decreased cardiac output. In the gastrointestinal
(GI) tract, achlorhydria and prolonged intestinal transit time with gastric stasis can occur.
Delayed puberty, anovulation, menstrual irregularities, and infertility are common. TSH
screening should be a routine part of any investigation into menstrual irregularities or
infertility.
Decreased thyroid hormone effect can cause increased levels of total cholesterol and low-
density lipoprotein (LDL) cholesterol and a possible change in high-density lipoprotein
(HDL) cholesterol because of a change in metabolic clearance. In addition, hypothyroidism
may result in an increase in insulin resistance.
Etiology
In the United States and other areas of adequate iodine intake, autoimmune thyroid disease
(Hashimoto disease) is the most common cause of hypothyroidism. The prevalence of
antibodies is higher in women and increases with age.
Primary hypothyroidism
Types of primary hypothyroidism include the following:
 Chronic lymphocytic (autoimmune) thyroiditis
 Postpartum thyroiditis
 Subacute (granulomatous) thyroiditis
 Drug-induced hypothyroidism
 Iatrogenic hypothyroidism
Chronic lymphocytic (autoimmune) thyroiditis
The most frequent cause of acquired hypothyroidism is chronic lymphocytic (autoimmune)
thyroiditis (Hashimoto thyroiditis). The body considers the thyroid antigens as foreign, and a
chronic immune reaction ensues, resulting in lymphocytic infiltration of the gland and
progressive destruction of functional thyroid tissue.
The majority of affected individuals will have circulating antibodies to thyroid tissue. Anti–
thyroid peroxidase (anti-TPO) antibodies are the hallmark of this disease. It should be noted
that antibody levels can vary over time, may not be present early in the disease process, and
usually disappear over time. Given this change in antibody concentration, it should be
understood that the absence of antibodies does not exclude the diagnosis of chronic
lymphocytic (autoimmune) thyroiditis.
Postpartum thyroiditis
Up to 10% of postpartum women may develop lymphocytic thyroiditis (postpartum
thyroiditis) in the 2-12 months after delivery. The frequency may be as high as 25% in
women with type 1 diabetes mellitus. Although a short course of treatment with
levothyroxine (LT4) may be necessary, the condition is usually transient (2-4 months).
However, patients with postpartum thyroiditis (anti-TPO–positive) are at increased risk of
permanent hypothyroidism or recurrence of postpartum thyroiditis with future pregnancies.
The hypothyroid state can be preceded by a short thyrotoxic state. High titers of anti-TPO
antibodies during pregnancy have been reported to have high sensitive and specificity for
postpartum autoimmune thyroid disease.
In a 12-year longitudinal study, Stuckey et al found that hypothyroidism developed in 27 of
71 women (38%) who had a past history of postpartum thyroid dysfunction (PPTD). In
comparison, only 14 of 338 women (4%) who had not had PPTD developed
hypothyroidism. [7]
Subacute granulomatous thyroiditis
Also known as de Quervain disease, subacute granulomatous thyroiditis is a relatively
uncommon disease that occurs most frequently in middle-aged women. Disease features
include low grade fever, thyroid pain, dysphagia, and elevated erythrocyte sedimentation rate
(ESR).
The disease is usually self-limited and does not normally result in longstanding thyroid
dysfunction. It is important to note that inflammatory conditions or viral syndromes may be
associated with transient hyperthyroidism followed by transient hypothyroidism (ie, de
Quervain or painful thyroiditis and subacute thyroiditis).
Drug-induced and iatrogenic hypothyroidism
The following medications reportedly have the potential to cause hypothyroidism:
 Amiodarone
 Interferon alfa
 Thalidomide
 Lithium
 Stavudine
 Oral tyrosine kinase inhibitors – Sunitinib, imatinib [8]
 Bexarotene [9]
 Perchlorate
 Interleukin (IL)-2
 Ethionamide
 Rifampin
 Phenytoin
 Carbamazepine
 Phenobarbital
 Aminoglutethimide
 Sulfisoxazole
 p -Aminosalicylic acid
 Ipilimumab
Use of radioactive iodine (I-131) for treatment of Graves disease generally results in
permanent hypothyroidism within 3-6 months after therapy. The frequency of
hypothyroidism after I-131 treatment is much lower in patients with toxic nodular goiters and
those with autonomously functioning thyroid nodules. Patients treated with radioiodine
should be monitored for clinical and biochemical evidence of hypothyroidism.
External neck irradiation (for head and neck neoplasms, breast cancer, or Hodgkin disease)
may result in hypothyroidism. Patients who have received these treatments require
monitoring of thyroid function.
Thyroidectomy of course results in hypothyroidism. Patients who undergo a thyroid
lobectomy, with or without isthmectomy, have an approximately 15-30% chance of
developing thyroid insufficiency.
Genetics
Genome-wide association studies have suggested that a single-nucleotide polymorphism
located near the FOXE1 gene is associated with risk of developing thyroid disease and that
the strongest association is with hypothyroidism. Persons found to have GG at the described
location had an odds ratio (OR) of 1.35 for development of hypothyroidism, whereas persons
found to have AG at the location had an OR of 1.00, and persons found to have AA at the
location had an OR of 0.74. [10]
Approximately 10% of patients with congenital hypothyroidism have an error in thyroid
hormone synthesis. [11] Mutations in the TPO gene appear to be the most common error of
hormone synthesis, causing failure to produce adequate amounts of TPO. [12]
Mutations in the TSHR and PAX8 genes are known to cause congenital hypothyroidism
without goiter. [13, 14] Mutations in the TSHR gene can cause hypothyroidism due to
insensitivity to TSH, though most cases are notable for a clinically euthyroid state despite
abnormal laboratory test results (elevated TSH with normal serum thyroid hormone
concentrations). Mutations in the PAX8 gene cause hypothyroidism due to dysgenesis or
agenesis of the gland .
Syndromic forms of hypothyroidism are also well described. Pendred syndrome is caused by
a mutation in the SLC26A4 gene, which causes a defect in the organification of iodine (ie,
incorporation into thyroid hormone), congenital sensorineural hearing loss, and, usually, an
enlarged thyroid gland. It is inherited in an autosomal recessive manner. [15]
Autoimmune polyendocrinopathy type I is caused by a mutation in the AIRE gene and is
characterized by the presence of Addison disease, hypoparathyroidism, and mucocutaneous
candidiasis. A subset of patients with this disease also have a high prevalence of autoimmune
thyroiditis and hypothyroidism and a novel mutation in the AIRE gene that is inherited in an
autosomal dominant fashion. [16]Autoimmune polyendocrinopathy type 2 (Schmidt syndrome)
is associated with adrenal insufficiency and hypothyroidism.
Iodine deficiency or excess
Worldwide, iodine deficiency is the most common cause of hypothyroidism. Excess iodine,
as in radiocontrast dyes, amiodarone, health tonics (herbal and dietary supplements), and
seaweed, can transiently inhibit iodide organification and thyroid hormone synthesis (the
Wolff-Chiakoff effect). Most healthy individuals have a physiologic escape from this effect.
In patients with iodine overload, the sodium-iodide symporter shuts down, and this allows
intracellular iodine levels to drop and hormone secretion to resume.
The Wolff-Chiakoff effect is short-lived because the sodium-iodide symporter is capable of
rapidly downregulation. However, exposure to excess iodine can produce more profound and
sustained hypothyroidism in individuals with abnormal thyroid glands (eg, from autoimmune
thyroiditis, subtotal thyroidectomy, or prior radioiodine therapy). [17]
Central hypothyroidism
Central hypothyroidism (secondary or tertiary) results when the hypothalamic-pituitary axis
is damaged. The following potential causes should be considered[18, 19] :
 Pituitary adenoma
 Tumors impinging on the hypothalamus
 Lymphocytic hypophysitis
 Sheehan syndrome
 History of brain or pituitary irradiation
 Drugs (eg, dopamine, prednisone, or opioids)
 Congenital nongoiterous hypothyroidism type 4
 TRH resistance
 TRH deficiency
Tumors in or around the pituitary cause impaired pituitary function by exerting pressure on
normal pituitary cells and thereby affect the secretion of TRH, TSH, or both. Radiation,
hypophysitis, and Sheehan syndrome cause death of these cells. Drugs such as dopamine and
corticosteroids result in decreased TSH secretion.
Congenital nongoiterous hypothyroidism type 4 is caused by a mutation in the TSHB gene
and is inherited in an autosomal recessive pattern. Patients have hypothyroidism and a low
TSH level that does not rise with administration of TRH. Many patients with this condition
were the products of consanguineous unions.[20]
TRH resistance is caused by a mutation in the TRHR gene and is inherited in an autosomal
recessive manner. Patients with this condition have hypothyroidism and, unsurprisingly, have
insensitivity to thyrotropin secretion. [21] That only a handful of cases of TRH resistance have
been reported in the literature suggests that this is a rare condition.
TRH deficiency is caused by mutation in the TRH gene and is inherited in an autosomal
recessive manner. [22] The index case was a girl evaluated for short stature who was found to
have an isolated deficiency of TRH. [23]
Epidemiology
The National Health and Nutrition Examination Survey (NHANES 1999-2002) of 4392
individuals reflecting the US population reported hypothyroidism (defined as TSH levels
exceeding 4.5 mIU/L) in 3.7% of the population. [24] Hypothyroidism is more common in
women with small body size at birth and low body mass index during childhood. [25]
Iodine deficiency as a cause of hypothyroidism is more common in less-developed countries.
Routine supplementation of salt, flour, and other food staples with iodine has decreased the
rates of iodine deficiency.
World Health Organization (WHO) data from 130 countries taken from January 1994 through
December 2006 found inadequate iodine nutrition in 30.6% of the population. The WHO
recommends urinary iodine concentrations between 100 and 199 μg/L in the general
population and a range of 150-249 μg/L in pregnant women. In developed countries, death
caused by hypothyroidism is uncommon.
Age-related demographics
The frequency of hypothyroidism, goiters, and thyroid nodules increases with age.
Hypothyroidism is most prevalent in elderly populations, with 2-20% of older age groups
having some form of hypothyroidism. The Framingham study found hypothyroidism (TSH >
10 mIU/L) in 5.9% of women and 2.4% of men older than 60 years. [26] In NHANES 1999-
2002, the odds of having hypothyroidism were 5 times greater in persons aged 80 years and
older than in individuals aged 12-49 years. [24]
Sex-related demographics
Community studies use slightly different criteria for determining hypothyroidism; therefore,
female-to-male ratios vary. Generally, thyroid disease is much more common in females than
in males, with reported prevalences ranging from 2 to 8 times higher in females.
Race-related demographics
NHANES 1999-2002 reported that the prevalence of hypothyroidism (including the
subclinical form) was higher in whites (5.1%) and Mexican Americans than in African
Americans (1.7%). African Americans tend to have lower median TSH values. [24]
Prognosis
Undertreatment of hypothyroidism leads to disease progression, with gradual worsening of
symptoms and further metabolic derangements. Ultimately, untreated hypothyroidism can
cause profound coma or even death. Untreated hypothyroidism in infants can cause
irreversible mental retardation.
In most patients, fortunately, thyroid hormone treatment reverses the signs and symptoms of
hypothyroidism. With treatment, other secondarily affected laboratory values (eg, circulating
lipid levels and elevated prolactin levels) should improve.
Using disease-specific (ThyPRO questionnaire) and generic (36-item Short Form Health
Survey [SF-36]) measures of health-related quality of life (HRQL), Winther et al discovered
that levothyroxine treatment resulted in improvement in some, but not all, aspects of HRQL
in patients with hypothyroidism resulting from autoimmune thyroiditis. This included
significant improvements in nine of 13 ThyPRO scales after 6 weeks of therapy. [27]
Patient Education
Emphasize proper compliance at each visit. Clearly discuss the lifelong nature of
hypothyroidism, the need for lifelong levothyroxine therapy, the proper way to take
medicine, and the need for TSH testing at least annually.
Patients should take thyroid hormone as a single daily dose. Thyroid hormone is better
absorbed in the small bowel; therefore, absorption can be affected by malabsorptive states,
small bowel disease (eg, celiac sprue), and the patient’s age. Many drugs (eg, iron, calcium
carbonate, calcium acetate aluminum hydroxide, sucralfate, raloxifene, and proton pump
inhibitors) can interfere with absorption and therefore should not be taken within 2-4 hours of
LT4 administration. [28]
Estrogen/progestin oral contraceptives and pregnancy are associated with changes in thyroid-
binding globulin. These changes may impact thyroid hormone dosing.
For patient education information, see the Thyroid & Metabolism Center as well as Thyroid
Problems and Chronic Fatigue Syndrome.
History
Hypothyroidism commonly manifests as a slowing in physical and mental activity but may be
asymptomatic. Symptoms and signs of this disease are often subtle and neither sensitive nor
specific. Classic signs and symptoms (eg, cold intolerance, puffiness, decreased sweating,
and coarse skin) may not be present as commonly as was once believed.
Many of the more common symptoms are nonspecific and difficult to attribute to a particular
cause. Individuals can also present with obstructive sleep apnea (secondary to macroglossia)
or carpal tunnel syndrome. Women can present with galactorrhea and menstrual disturbances.
Consequently, the diagnosis of hypothyroidism is based on clinical suspicion and confirmed
by laboratory testing.
Myxedema coma is a severe form of hypothyroidism that results in an altered mental status,
hypothermia, bradycardia, hypercarbia, and hyponatremia. Cardiomegaly, pericardial
effusion, cardiogenic shock, and ascites may be present. Myxedema coma most commonly
occurs in individuals with undiagnosed or untreated hypothyroidism who are subjected to an
external stress, such as low temperature, infection, myocardial infarction, stroke, or medical
intervention (eg, surgery or hypnotic drugs).
The following are symptoms of hypothyroidism:
 Fatigue, loss of energy, lethargy
 Weight gain
 Decreased appetite
 Cold intolerance
 Dry skin
 Hair loss
 Sleepiness
 Muscle pain, joint pain, weakness in the extremities
 Depression
 Emotional lability, mental impairment
 Forgetfulness, impaired memory, inability to concentrate
 Constipation
 Menstrual disturbances, impaired fertility
 Decreased perspiration
 Paresthesias, nerve entrapment syndromes
 Blurred vision
 Decreased hearing
 Fullness in the throat, hoarseness
Hashimoto thyroiditis is difficult to distinguish clinically, but the following symptoms are
more specific to this condition:
 Feeling of fullness in the throat
 Painless thyroid enlargement
 Exhaustion
 Transient neck pain, sore throat, or both
Signs found in hypothyroidism are usually subtle, and their detection requires a careful
physical examination. Moreover, such signs are often dismissed as part of aging; however,
clinicians should consider a diagnosis of hypothyroidism when they are present.
Physical signs of hypothyroidism include the following:
 Weight gain
 Slowed speech and movements
 Dry skin
 Jaundice
 Pallor
 Coarse, brittle, straw-like hair
 Loss of scalp hair, axillary hair, pubic hair, or a combination
 Dull facial expression
 Coarse facial features
 Periorbital puffiness
 Macroglossia
 Goiter (simple or nodular)
 Hoarseness
 Decreased systolic blood pressure and increased diastolic blood pressure
 Bradycardia
 Pericardial effusion
 Abdominal distention, ascites (uncommon)
 Hypothermia (only in severe hypothyroid states)
 Nonpitting edema (myxedema)
 Pitting edema of lower extremities
 Hyporeflexia with delayed relaxation, ataxia, or both
Additional signs specific to different causes of hypothyroidism, such as diffuse or nodular
goiter and pituitary enlargement or tumor, can occur.
A study by Piantanida et al indicated that an increased risk of masked hypertension exists
with subclinical and overt hypothyroidism. The study included 64 newly diagnosed
hypothyroid patients, with masked hypertension found in 26.3% of those with the subclinical
condition and 15.4% of those with overt hypothyroidism, compared with 10% of controls. [29]
Konstipasi
Practice Essentials
Constipation is the most common digestive complaint in the United States. It is a symptom
rather than a disease. Despite its frequency, it often remains unrecognized until the patient
develops sequelae, such as anorectal disorders or diverticular disease. (See the image below.)
Large amount of stool throughout colon.

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Signs and symptoms
According to the Rome III criteria for constipation, a patient must have experienced at least 2
of the following symptoms over the preceding 3 months:
 Fewer than 3 bowel movements per week
 Straining
 Lumpy or hard stools
 Sensation of anorectal obstruction
 Sensation of incomplete defecation
 Manual maneuvering required to defecate
A constipated patient may be otherwise totally asymptomatic or may complain of 1 or more
of the following:
 Abdominal bloating
 Pain on defecation
 Rectal bleeding
 Spurious diarrhea
 Low back pain
The following also suggest that the patient may have difficult rectal evacuation:
 Feeling of incomplete evacuation
 Digital extraction
 Tenesmus
 Enema retention
The following signs and symptoms, if present, are grounds for particular concern:
 Rectal bleeding
 Abdominal pain (suggestive of possible irritable bowel syndrome [IBS] with
constipation [IBS-C])
 Inability to pass flatus
 Vomiting
Diagnosis
An extensive workup of the constipated patient is performed on an outpatient basis and
usually occurs after approximately 3-6 months of failed medical management. Features of the
workup are as follows:
 Rectal and perineal examination should already have been performed but should be
repeated
 Laboratory evaluation does not play a large role in the initial assessment of the patient
 Imaging studies are used to rule out acute processes that may be causing colonic ileus or
to evaluate causes of chronic constipation
 In patients with acute abdominal pain, fever, leukocytosis, or other symptoms
suggesting possible systemic or intra-abdominal processes, imaging studies are used to
rule out sources of sepsis or intra-abdominal problems
 Lower gastrointestinal (GI) endoscopy, colonic transit study, defecography, anorectal
manometry, surface anal electromyography (EMG), and balloon expulsion may be used
in the evaluation of constipation
Management
Initial treatment measures for constipation include manual disimpaction and transrectal
enemas. A well-lubricated gloved finger might be required in patients with lower anorectal
impactions. These initial measures are then followed by elective evaluation of the causes of
constipation.
Medical care should focus on dietary change and exercise rather than laxatives, enemas, and
suppositories, none of which really address the underlying problem.
The key to treating most patients with constipation is correction of dietary deficiencies, which
generally involves increasing intake of fiber and fluid and decreasing the use of constipating
agents (eg, milk products, coffee, tea, alcohol).
Medications to treat constipation include the following:
 Bulk-forming agents (fibers; eg, psyllium): arguably the best and least expensive
medication for long-term treatment
 Emollient stool softeners (eg, docusate): Best used for short-term prophylaxis (eg,
postoperative)
 Rapidly acting lubricants (eg, mineral oil): Used for acute or subacute management of
constipation
 Prokinetics (eg, tegaserod): Proposed for use with severe constipation-predominant
symptoms
 Stimulant laxatives (eg, senna): Over-the-counter agents commonly but inappropriately
used for long-term treatment of constipation
Newer therapies for constipation include the following:
 Prucalopride (not approved in the United States), a prokinetic selective 5-
hydroxytryptamine-4 (5-HT4) receptor antagonist that stimulates colonic motility and
decreases transit time
 The osmotic agents lubiprostone and linaclotide, [1] which are FDA approved for
chronic idiopathic constipation, constipation caused by irritable bowel syndrome, and
(in the case of lubiprostone) opioid-induced constipation in adults with chronic,
noncancer pain
 Naloxegol (Movantik) is a peripherally-acting mu-opioid receptor antagonist
(PAMORA) that is indicated for opioid-induced constipation in adults with chronic
noncancer pain
 Methylnaltrexone (Relistor) is a PAMORA indicated for opioid-induced constipation in
adults with chronic noncancer pain or those with advanced illness who are receiving
palliative care, when response to laxative therapy has been insufficient
Background
Constipation is the most common digestive complaint in the United States. It is a symptom
rather than a disease and, despite its frequency, often remains unrecognized until the patient
develops sequelae, such as anorectal disorders or diverticular disease.
No widely accepted clinically useful definition of constipation exists. Health care providers
usually use the frequency of bowel movements (ie, less than 3 bowel movements per week)
to define constipation. However, the Rome criteria, initially introduced in 1988 and
subsequently modified twice to yield the Rome III criteria, have become the research-
standard definition of constipation. [2]
According to the Rome III criteria for constipation, a patient must have experienced at least 2
of the following symptoms over the preceding 3 months:
 Fewer than 3 bowel movements per week
 Straining
 Lumpy or hard stools
 Sensation of anorectal obstruction
 Sensation of incomplete defecation
 Manual maneuvering required to defecate
The Rome III criteria also stipulate that a patient should not meet the suggested criteria
for irritable bowel syndrome (IBS) and that loose stools are rarely present without the use of
laxatives.
For surgical purposes, the most useful definition of constipation is simply a change in bowel
habit or defecatory behavior that results in acute or chronic symptoms or diseases that would
be resolved with relief of the constipation.
Acute or subacute constipation in middle-aged or elderly patients should prompt a search for
an obstructing colonic lesion. Acute constipation must be carefully distinguished
from ileus secondary to intra-abdominal emergencies, including infections.
Constipation is frequently chronic, can significantly affect an individual’s quality of life, and
may be associated with significant health care costs. It is considered chronic if it is present
for at least 12 weeks (in total, not necessarily consecutively) during the previous year.
Chronic constipation may be associated with psychological disturbances, and the reverse is
true as well. However, these issues are beyond the scope of this article.
Laboratory evaluation does not play a large role in the initial assessment of the patient.
Imaging studies are used to rule out acute processes that may be causing colonic ileus, to
evaluate causes of chronic constipation, or to rule out sources of sepsis or intra-abdominal
problems. Lower gastrointestinal (GI) endoscopy, anorectal manometry, electromyography
(EMG), and balloon expulsion may be used in the evaluation of constipation.
Medical care should focus on dietary change and exercise rather than laxatives, enemas, and
suppositories, none of which really addresses the underlying problem. Surgical care is
generally restricted to the evaluation of underlying causes; it may also be indicated for the
management of acute complications of constipation. Once acute constipation has resolved
and the associated medical or surgical conditions have been ruled out, additional inpatient
care is rarely indicated.
Pathophysiology
Constipation is divided, with considerable overlap, into issues of stool consistency (hard,
painful stools) and issues of defecatory behavior (infrequency, difficulty in evacuation,
straining during defecation). Although hard stools frequently result in defecatory difficulties,
soft bulky stools may also be associated with constipation, particularly in elderly patients
with anatomic abnormalities and in patients with impaired colorectal motility.
Constipation may originate primarily from within the colon and rectum or may originate
externally. Processes involved in constipation originating from the colon or rectum include
the following:
 Colon obstruction (neoplasm, volvulus, stricture)
 Slow colonic motility, particularly in patients with a history of chronic laxative abuse
 Outlet obstruction (anatomic or functional) - Anatomic outlet obstruction may derive
from intussusception of the anterior wall of the rectum on straining, rectal prolapse, and
rectocele; functional outlet obstruction may derive from puborectalis or external
sphincter spasm when bearing down, short-segment Hirschsprung disease, and damage
to the pudendal nerve, typically related to chronic straining or vaginal delivery
 Hirschsprung disease in children
 Chagas disease
Factors involved in constipation originating outside the colon include poor dietary habit (the
most common factor, generally involving inadequate fiber or fluid intake and/or overuse of
caffeine or alcohol), medications, systemic endocrine or neurologic diseases, and
psychological issues.
Constipation results in various degrees of subjective symptoms and is associated with
abnormalities (eg, colonic diverticular disease, hemorrhoidal disease, anal fissures) that occur
secondary to an increase in colonic luminal pressure and intravascular pressure in
the hemorrhoidal venous cushions.
Nearly 50% of patients with diverticular or anorectal disease, when asked, deny experiencing
constipation. On careful questioning, however, nearly all of these patients report having
symptoms suggestive of defecatory straining or infrequency, mostly constipation related,
although occasionally diarrhea related in patients with irritable bowel or other chronic
diarrheal disorders.
Etiology
The etiology of constipation is usually multifactorial, but it can be broadly divided into 2
main groups: primary constipation and secondary constipation.
Primary constipation
Primary (idiopathic, functional) constipation can generally be subdivided into the following 3
types:
 Normal-transit constipation (NTC)
 Slow-transit constipation (STC)
 Pelvic floor dysfunction (ie, pelvic floor dyssynergia)
NTC is the most common subtype of primary constipation. Although the stool passes through
the colon at a normal rate, patients find it difficult to evacuate their bowels. Patients in this
category sometimes meet the criteria for IBS with constipation (IBS-C). The primary
difference between chronic constipation and IBS-C is the prominence of abdominal pain or
discomfort in IBS. Patients with NTC usually have a normal physical examination.
STC is characterized by infrequent bowel movements, decreased urgency, or straining to
defecate. It occurs more commonly in female patients. Patients with STC have impaired
phasic colonic motor activity. They may demonstrate mild abdominal distention or palpable
stool in the sigmoid colon.
Pelvic floor dysfunction is characterized by dysfunction of the pelvic floor or anal sphincter.
Patients often report prolonged or excessive straining, a feeling of incomplete evacuation, or
the use of perineal or vaginal pressure during defecation to allow the passage of stool, or they
may report digital evacuation of stool.
Secondary constipation
Dietary issues that may cause constipation include inadequate water intake; inadequate fiber
intake; overuse of coffee, tea, or alcohol; a recent change in bowel habit paralleled by
changes in the diet; and ignoring the urge to defecate. Reduced levels of exercise may play a
role as well.
Structural causes of secondary constipation include anal fissures, thrombosed hemorrhoids,
colonic strictures, obstructing tumors, volvulus, and idiopathic megarectum.
Systemic diseases that may cause constipation include the following:
 Endocrinologic and metabolic disorders - Hypercalcemia,
hyperparathyroidism, hypokalemia, hypothyroidism, pregnancy, and diabetes
mellitus (constipation is the most common gastrointestinal problem affecting the
diabetic population)
 Neurologic disorders - Stroke, Hirschsprung disease, Parkinson disease,multiple
sclerosis, diabetic autonomic neuropathy, spinal cord lesion, head injury,
cerebrovascular accident, Chagas disease, and familial dysautonomia
 Connective-tissue disorders - Scleroderma, amyloidosis, and mixed connective-tissue
disease
Often, what appears to be an acute or subacute constipation may represent a colonic or small
bowel ileus from systemic or intra-abdominal infection or other intra-abdominal emergencies.
In appropriate settings, this should be addressed and not missed, lest the patient’s condition
deteriorate acutely.
Medications that may contribute to constipation include the following:
 Antidepressants (eg, cyclic antidepressants and monoamine oxidase inhibitors
[MAOIs])
 Metals (eg, iron and bismuth)
 Anticholinergics (eg, benztropine and trihexyphenidyl)
 Opioids (eg, codeine and morphine)
 Antacids eg, (aluminum and calcium compounds)
 Calcium channel blockers (eg, verapamil)
 Nonsteroidal anti-inflammatory drugs (NSAIDs; eg, ibuprofen and diclofenac)
 Sympathomimetics (eg, pseudoephedrine)
 Many psychotropic drugs [3]
 Cholestyramine and stimulant laxatives (long-term use) - Although laxatives are
frequently used to treat constipation, chronic laxative use becomes habituating and may
lead to the development of a dilated atonic laxative colon, which necessitates increasing
laxative use with decreasing efficacy
 Inadequate thyroid hormone supplementation
Constipation may be of toxicologic origin, as with lead poisoning.
Psychological issues (eg, depression, anxiety, somatization, and eating disorders) may also
contribute to the development of constipation.
Epidemiology
United States statistics
Chronic constipation is highly prevalent and affects approximately 15% of persons in the
United States. [4] In 2006, the number of constipation-related physician visits reached 5.7
million, and of these, 2.7 million visits had constipation as the primary diagnosis. [5] About
2% of the population describes constant or frequent intermittent episodes of constipation.
International statistics
Prevalence of self-reported constipation varies substantially because of differences among
ethnic groups in how constipation is perceived. In North America alone, chronic constipation
affects approximately 63 million people. Worldwide, approximately 12% of people suffer
from self-defined constipation; people in the Americas and the Asian Pacific suffer twice as
much as their European counterparts.
A meta-analysis of patients in Europe and Oceania cited prevalence rates as high as 81%,
with a general incidence of approximately 17%. Female sex, age, and educational class were
strongly associated with the prevalence of constipation. [6]
Age-related demographics
Constipation can occur in all ages, from newborns to elderly persons. An age-related increase
in the incidence of constipation has been observed, with 30-40% of adults older than 65 years
citing constipation as a problem. [7] The increased frequency of constipation in adults older
than 65 years may reflect a combination of dietary alterations, a decrease in muscle tone and
exercise, and the use of medications that may result in relative dehydration or colonic
dysmotility. [8] Some researchers suggest that cumulative exposure to environmental
neurotoxins may play a role.
In some patients, chronic or repeated pelvic injury (eg, from pregnancies) or the development
of anatomic abnormalities (eg, rectal prolapse or rectocele [weakness in the posterior vaginal
wall that allows the rectum to prolapse into the vagina upon straining]) may lead to functional
outlet obstruction.
Sex-related demographics
In the United States, self-reported constipation and admissions to hospital for constipation are
more common in women than in men. The overall female-to-male ratio is approximately 3:1.
Women are also more likely to receive care for constipation. The condition is seen fairly
frequently during pregnancy and is a common problem after childbirth. Surveys of apparently
healthy young men and women demonstrate a slightly higher stool frequency among women.
Race-related demographics
In the United States, the prevalence of constipation is 30% higher among nonwhite
populations than among white populations. [4] Both self-reported constipation and
constipation requiring admission to a hospital are more frequent in black people than in white
people.
Whereas constipation is less common in Asians, it is more frequent in those who adopt a
Western diet.
In contrast, constipation is less frequent among black Africans than white Africans, further
suggesting that diet and other environmental factors play an important role.
Prognosis
Most active patients do well with medical management and appropriate dietary management.
Recurrence depends on the patient’s long-term compliance with therapy. A small percentage
of patients are quite debilitated as a result of constipation. Some patients with functional
(primary or idiopathic) constipation (ie, colonic inertia) require total abdominal colectomy
with ileorectal anastomosis.
After a careful preoperative workup that includes physical and psychological assessment,
patients with outlet obstruction generally respond well to surgical correction and have a good
prognosis.
Dyskinesias of the pelvic floor musculature and of the sphincter mechanism may be managed
via biofeedback therapy, but the results are mixed.
Patients who are chronically dependent on increasing doses of self-prescribed laxatives are
perhaps the most difficult patients to treat. Most such patients can be treated with a
combination of fiber, water, and osmotic agents (eg, polyethylene glycol ,sorbitol). However,
the need for increasing doses of laxatives and the intermittent use of other agents becomes
problematic.
In rare situations in which patients are virtually refractory to laxatives, total abdominal
colectomy may be performed after careful workup. Postoperatively, these patients often
experience a greatly improved quality of life. A careful preoperative evaluation and a detailed
informed consent discussion are required.
Complications
Difficulty in defecation may cause substantial discomfort, abdominal cramping, and a general
feeling of malaise.
Actual or perceived constipation typically results in self-medicating with various laxatives.
Although laxatives may correct the acute problem, chronic use of these agents leads to
habituation, necessitating ever-increasing doses that result in drug dependency and,
ultimately, a hypotonic laxative colon. Melanosis coli from prolonged laxative use is an
incidental finding at endoscopy.
Acute or chronic episodes of straining may cause acute or chronic hemorrhoidal disease
(characterized by pain, itching, or bleeding) or acute hemorrhoidal thrombosis (characterized
by intense pain and acute engorgement of 1 or more of the hemorrhoidal columns).
Generally, hemorrhoids are medically managed; surgical intervention is reserved for when
medical management fails.
Whether constipation actually causes hemorrhoidal disease is viewed as controversial by
some authors. However, upon careful questioning, these patients frequently provide a history
of recent defecatory difficulties, most commonly constipation related, although less
commonly diarrhea related (with the exception of patients in the early postpartum period).
Furthermore, conservative management of hemorrhoidal disease is more likely successful
when future straining is prevented.
The passage of hard stools may result in an acute anal fissure, which is a painful tear in the
anoderm that may bleed. The regular passage of hard stools and the painful anal spasms
during defecation that impinge the hard stools against the fresh wound prevent the anal
fissure from healing. Generally, fissures are managed medically. In addition to local wound
care and analgesia, softening of stools is essential for successful management. Surgical
intervention is reserved for when medical management fails.
Constipation may be one cause of pelvic floor damage in women. Using structured
questionnaires, Amselem et al determined that 61 out of 596 women (10%) attending a
gynecologic clinic had pelvic floor damage; constipation was present in 19 of the 61 (31%),
rivaling the frequency of obstetric trauma (also 19 women) among these patients. [9]
Amselem et al also determined that of the 535 women without pelvic floor damage, 86 (16%)
had constipation and 83 (15.5%) had obstetric trauma. [9]Employing univariate analysis, they
reported odds ratios of 2.36 for constipation and 2.46 for obstetric trauma associated with
pelvic floor damage. On the basis of their data, the authors suggested that constipation and
obstetric trauma are equally important in the development of pelvic floor damage.
The chronic pressure effect of hard stools against the anterior rectal wall when the patient
strains during defecation is believed to cause solitary rectal ulcers. This is usually a self-
limiting process and responds to treatment of constipation. In adults, surgical or
gastroenterologic consultation may be required to differentiate benign solitary rectal ulcers
from rectal malignancy.
Other complications of constipation may include the following:
 Fecal impaction
 Bowel obstruction
 Fecal incontinence
 Stercoral ulceration/perforation
 Megacolon
 Volvulus
 Rectal prolapse
 Urinary retention
 Syncope
 Fistula in ano
Patient Education
Patient education typically involves instructions for improving dietary management. Dietary
deficiency requires increased fluid and fiber supplementation for life. For patients who
implement recommended dietary changes, the prognosis is excellent.
For patient education resources, see the Digestive Disorders Center, as well as Constipation
in Adults and Constipation in Children.
History
Basing the diagnosis of constipation on simply asking the patients whether they are
constipated is associated with marked underreporting of the problem in patients who have
physical evidence of constipation, such as the presence of hemorrhoidal
disease. [10] Accordingly, a careful history must be obtained, including inquiries into current
medications (including over-the-counter, herbal agents, and prescription medications),
previous colonoscopy, and any other medical problems present.
A constipated patient may be otherwise totally asymptomatic or may complain of one or
more of the following:
 Abdominal bloating
 Pain on defecation
 Rectal bleeding
 Spurious diarrhea
 Low back pain
The following also suggest that the patient may have difficult rectal evacuation:
 Feeling of incomplete evacuation
 Digital extraction
 Tenesmus
 Enema retention
The following signs and symptoms, if present, are grounds for particular concern:
 Rectal bleeding
 Abdominal pain (suggestive of possible irritable bowel syndrome [IBS] with
constipation [IBS-C])
 Inability to pass flatus
 Vomiting
 Unexplained weight loss
The history should begin with a detailed inquiry into the patient’s normal pattern of
defecation, the frequency with which the current problem differs from the normal pattern (eg,
“missing a day”), the perceived hardness of the stools, whether the patient strains in order to
defecate, and any other symptoms the patient may be experiencing.
An inquiry concerning the amount of time spent on the toilet while waiting to defecate may
also be illuminating. Patients should be asked to describe in detail what happens when they
try to defecate and what maneuvers (pharmacologic or physical) they have used to facilitate
this process. The answers to these questions may suggest chronic laxative abuse or less
common causes, such as colonic outlet obstruction.
The duration of the problem is important. In adolescents or young adults, the duration of the
problem may differentiate congenital defects from acquired causes. Neoplastic obstruction is
less likely in younger patients or in patients older than 50 years who have had symptoms for
at least 2 years and/or have recently had a screening colonoscopy. However, colon cancer
certainly occurs in younger adults and even rarely in teenagers, while a previous screening
colonoscopy may have missed a neoplasm.
The onset of symptoms is also very important, in that intestinal obstruction can present as
acute constipation. In the hospital setting, ileus from another illness or Ogilvie syndrome
should also be considered. Questions regarding the onset of constipation may provide useful
etiologic information, whether in terms of changes in diet, new medications, or associated
psychosocial difficulties at that time.
In addition to defining the nature of the patient’s bowel habit, it is necessary to try to identify
the factors likely to be responsible for the abnormal bowel habit. Most patients who are
constipated consume either too little fiber or too little water; therefore, assessing the patient’s
diet is useful. For acute changes in the bowel habit, a parallel dietary change should be
ascertained.
Learning how much fluid and what types of fluids the patient drinks on an average day is
important. Epidemiologic studies have clearly established a link between coffee consumption
and worsening constipation. The diuretic effects of coffee, tea, and alcohol are likely
counterproductive. Milk products may cause constipation in some individuals.
The state of patients’ bowel motility represents a balance between factors that promote
motility and factors that inhibit it. The most important influencing factor is exercise, which
stimulates bowel motility. Conversely, narcotics, antipsychotic agents, and other constipating
medications reduce motility. Diuretics or substantial amounts of coffee, tea, or alcohol
decrease available water in the colon. Chronic laxative abuse also causes refractory
constipation.
If the patient shows evidence of diseases or symptoms associated with constipation, such as
diverticular disease, hemorrhoids, anal fissures, or fistula in ano, delineating these conditions
historically and determining the nature of any previous therapy for them is appropriate. For
instance, patients with hemorrhoids may neglect to mention that they were previously treated
for this problem or that they have been receiving medications for constipation for several
years.
Rectal bleeding should be taken seriously and evaluated carefully, particularly in patients
who are older than 50 years or have a family history of colorectal disease. Patients with
hemorrhoids may also have rectosigmoid cancer. Both cancer and hemorrhoids can produce
bright red blood from the rectum. Most patients older than 50 years or with a family history
of colorectal disease should be screened for colorectal cancer. A full colonoscopy is
preferable, although in some cases flexible sigmoidoscopy or barium enema may be used if
colonoscopy cannot be performed. The role of computed tomography (CT) colography in this
setting awaits definition, although it offers an attractive alternative in the patient in whom
colonoscopy is attempted and fails.
Finally, the evaluation should include the patient’s description of the act of defecation. Pain
during defecation might suggest a fissure or tenesmus from a rectal tumor. Painless inability
to pass an otherwise soft stool suggests a rectal outlet obstruction.
Neurologic and endocrine disorders also can cause constipation. Most notably, diabetes may
be associated with chronic dysmotility. Patients with hypothyroidism may exhibit decreased
motility and slow transit times. [11] Patients with panhypopituitarism, pheochromocytoma, or
multiple endocrine neoplasia 2B are also at risk for constipation. When no other cause can be
determined, a careful endocrine review is particularly important for patients with a recent
onset of constipation and for patients who are refractory to conservative treatment.
Similarly, central nervous system (CNS) diseases, such as Parkinson disease, multiple
sclerosis, stroke, CNS syphilis, and spinal injury or tumors, may cause constipation and
should be considered in the patient’s history and evaluation.
Some cases of constipation may have a psychogenic component. On one hand, constipation is
a frequent somatic expression of psychological distress; on the other, constipation itself may
give rise to psychological disturbances.
A history of sexual abuse is observed with unusual frequency in patients who are chronically
constipated, particularly those with anismus. A history of other psychological abnormalities
is often found, particularly among patients who are refractory to medical treatment and have
normal bowel transit times and normal results from anorectal studies.
Such factors should be gently explored in patients in whom first-line conservative treatment
has failed. Psychiatric referral may be appropriate in such patients when medical evaluation
and therapy have been exhausted or when gentle questioning reveals some unexpected
information.
General physical examination often is of no benefit in determining the etiology or in deciding
the treatment. In addition to the general evaluation, the abdomen, pelvis, and rectum,
specifically, should be physically examined. Both the cause of constipation and its effects
should be sought. [10]
Abdominal distention or masses may indicate the presence of colonic stools or tumors. Large
abdominal wall hernias, especially ventral hernias, may interfere with generation of the intra-
abdominal pressure required for the initiation of defecation. Rarely, a left-sided sliding
inguinal hernia with an incarcerated sigmoid colon may cause difficulties in bowel
movements.
It was once widely held that elderly patients with new inguinal hernias should be assumed to
have occult constipation due to partially obstructing colonic neoplasms and that these patients
therefore required colorectal cancer screening. At present, the requirement for colorectal
cancer screening in such patients remains controversial. The pathophysiology underlying a
link between colonic neoplasms and hernias is unknown, because the lesions detected on
screening are early lesions and are unlikely to have caused constipation.
Pelvic examination in women should specifically address the posterior vaginal wall, with
particular attention to any evidence of internal prolapse or rectocele. This region should be
palpated while the patient is at rest and then while she is straining to defecate. Many women
with rectocele do not experience constipation. Good surgical results are not guaranteed, and a
thorough preoperative workup to rule out other potential causes of constipation should always
be performed.
During the anorectal examination, the patient should be assessed for the following:
 Perianal excoriation
 Skin tags/ hemorrhoids
 Anal fissure
 Anocutaneous reflex
 Prolapse during straining
 Stool amount and consistency - More stool is present within the rectal vault in pelvic
outlet dysfunction than in colonic inertia or IBS, in which little or no stool remains in
the rectum between defecations; pelvic floor dysfunction is manifested by failure of
descent of the examining finger and contraction of the upper segment of the sphincter
during straining
Digital rectal examination provides information about the following:
 Anorectal masses
 Tone of the internal anal sphincter
 Strength of the external anal sphincter and puborectalis muscle
 Presence of a rectocele (an outpouching usually present in the anterior rectal wall)
 Presence of gross blood or occult bleeding by checking the stool guaiac
 Presence of fecal impaction
The anorectal examination should attempt to ascertain the cause of the constipation. Causes
that may be defined include the following:
 Anal fissure, particularly in children who retain their feces in order to avoid painful
defecation
 Anal stenosis
 Partially obstructing rectal masses
 Rectal prolapse
Rectal prolapse may be either external or internal. The anus should be carefully examined for
prolapse at rest and during a Valsalva maneuver. Care should be taken to distinguish a true
full-thickness rectal prolapse from a mucosal prolapse, which is unlikely to cause
constipation. Asking the patient to perform a Valsalva with the examining finger in the
rectum in order to seek evidence of an internal prolapse may be worthwhile, although this is a
relatively insensitive way of diagnosing prolapse.
In contrast to inguinal hernias, rectal prolapse is typically related to constipation. At least 1
retrospective study has demonstrated a strong association between rectal prolapse and
rectosigmoid neoplasms in patients older than 50 years. Sigmoidoscopy is probably indicated
for these patients, and full colonoscopy should be performed if they are otherwise due for
colorectal cancer screening.
In addition to delineating the cause of the constipation, the anorectal examination should be
used to determine the effects of the constipation. The presence of fissures or fistulae, any
evidence of scars from previous perirectal abscess drainages or other surgeries, and the nature
of the patient’s hemorrhoidal columns should be noted and characterized. Enlarged
hemorrhoids do not require treatment unless they cause symptoms.
Although the effectiveness of fecal occult blood testing has been hotly debated, performing
such a test after a rectal examination in patients older than 50 years is probably worthwhile.
The presence of blood in the stool warrants further evaluation. Never assume that the patient
is bleeding from hemorrhoids or fissures until other sources of bleeding have been ruled out.
A complete physical evaluation of the patient should also include a search for the evidence of
systemic diseases that may be contributing to constipation. Such systemic diseases include
the following:
 Endocrine dysfunctions (eg, hypothyroidism, hypopituitarism, and diabetes mellitus)
 Neurologic abnormalities (eg, brain or spinal cord injury, peripheral neuropathy,
multiple sclerosis, and Parkinson disease)
Chronic megacolon
Background
Megacolon, as well as megarectum, is a descriptive term. It denotes dilatation of the colon
that is not caused by mechanical obstruction. [1, 2] Although the definition of megacolon has
varied in the literature, most researchers use the measurement of greater than 12 cm for the
cecum as the standard. Because the diameter of the large intestine varies, the following
definitions would also be considered: greater than 6.5 cm in the rectosigmoid region and
greater than 8 cm for the ascending colon.
Megacolon can be divided into the following 3 categories:
 Acute megacolon ( pseudo-obstruction)
 Chronic megacolon, which includes congenital, acquired, and idiopathic causes
 Toxic megacolon
This article is devoted to chronic (noncongenital) megacolon.
Pathophysiology
The pathophysiology of chronic megacolon is incompletely understood. It likely represents
an amalgam of primary disorders involving muscular and nervous systems of the intestine.
Much basic science work has been performed in this area.
For example, with respect to the large bowel reacting to its luminal contents, fatty acids
appear to reduce the volume of the proximal large bowel. Opiate narcotics, on the other hand,
reduce the propensity of the colon to constrict.
Control of colonic contractility is through a complex interaction of intrinsic colonic nerves,
splanchnic nervous control, and central nervous system input. The final common pathway of
intrinsic nervous control of colonic motility is via postganglionic nerves: stimulatory
cholinergic nerves and inhibitory nitric oxide-releasing nerves. Evidence suggests that
excessive production of nitric oxide may be the mechanism for toxic megacolon in ulcerative
colitis; as yet, there is no evidence for a possible role of nitric oxide in chronic megacolon
unrelated to inflammatory bowel disease.
Studies in mouse models and in children with chronic colonic pseudo-obstruction show
abnormalities involving the number and function of the interstitial cells of Cajal (intestinal
pacemaker cells). Inherited disorders likely involve abnormal maturation and function of
these cells, whereas acquired disorders demonstrate decreased numbers of them.
Animal studies show that the splanchnic nerves can dramatically affect colonic motility, both
to contract and relax the colon. Extrinsic adrenergic nerves seem mainly to act by reducing
acetylcholine release from intrinsic postganglionic nerves, although a direct action on smooth
muscle cells cannot be excluded. At this time, the respective roles of the intrinsic and
splanchnic nerves in inducing megacolon have yet to be clarified.
Wallukat et al reported their experience in distinguishing distinct patterns of autoantibodies
against G-protein-coupled receptors in Chagas cardiomyopathy and megacolon. [3] The
investigators measured beta1-autobodies, beta2-autoantibodies, and muscarinergic2
autoantibodies, generally considered to be involved in the pathogenesis of Chagas
cardiomyopathy and megacolon, from asymptomatic Chagas patients and those with
cardiomyopathy and/or megacolon.
Autoantibodies were found in almost all patients with Chagas cardiomyopathy and/or
megacolon; beta1 autoantibodies and muscarinergic2 autoantibodies were predominant in
those with Chagas cardiomyopathy, whereas beta2 autoantibodies and muscarinergic2
autoantibodies were predominant in those with Chagas megacolon. [3] Of the 34% of
asymptomatic patients who demonstrated similar patterns of autoantibodies, 84% of these
individuals also had levels of beta1 autoantibody that are typical for Chags cardiomyopathy,
which the authors stated mirrored the epidemiologic situation in Latin America: clinical
manifestations develop in approximately 30% of Chagas patients and cardiomyopathy in
about 90% of them. [3]
Wallukat et al concluded that measuring the levels of beta1-autobodies, beta2-autoantibodies,
and muscarinergic2 autoantibodies may be useful for potentially identifying patients at high
risk of developing life-threatening complications of Chagas disease, but they cautioned
further studies are needed. [3]
In another study, Sanchez-Mejias et al examined the potential roles of
the EDNRB and EDN3 genes in the pathogenesis of Hirschsprung disease in 196 Spanish
patients. [4] The investigators found several novel mutations in both genes as well as a
truncating mutation in alternative isoform of EDNRB. In addition, an overrepresentation of a
specific EDN3 haplotype was present in affected patients compared with control subjects. [4]
Sanchez-Mejias indicated their findings suggest "the isoform EDNRB Delta 3 might be
playing an essential role in the formation of enteric nervous system" and "based on the
haplotype distribution, EDN3 might be considered as a common susceptibility gene for
sporadic Hirschsprung disease in a low-penetrance fashion." [4]
Some experts believe it is common practice to separate the disorders associated with chronic
megacolon into the following: (1) colonic inertia (eg, generalized delayed transit), and (2)
rectosphincteric dyssynergy (eg, functional outlet obstruction).
Etiology
Causes of acquired megacolon
Neurologic diseases include the following:
 Chagas disease
 Parkinson disease
 Myotonic dystrophy
 Diabetic neuropathy
 Spinal cord injury
 Paraneoplastic neuropathy
 Amyloidosis
Systemic diseases include the following:
 Scleroderma
 Dermatomyositis/polymyositis
 Systemic lupus erythematosus
 Mixed connective tissue disease
Metabolic diseases include the following:
 Hypothyroidism
 Hypokalemia
 Porphyria
 Pheochromocytoma
Medication-induced conditions can cause acquired megacolon.
Idiopathic include the following:
 Nonfamilial visceral neuropathy (sporadic hollow visceral neuropathy or chronic
idiopathic intestinal pseudo-obstruction)
 Results from damage to the myenteric plexus from drugs or viral infections
The most common nonmechanical cause of acquired megacolon is infection with T
cruzi (Chagas disease). [2] This infection results in the destruction of the enteric nervous
system. [5, 6, 7] Although this disease was originally confined to South America, recent
estimates indicate that 350,000 people in the United States are seropositive, one third of
whom are thought to have chronic Chagas disease.
Causes of congenital megacolon
Enteric neuropathies include the following:
 Hirschsprung disease (congenital aganglionosis) [2, 8] : It is caused by a single gene
mutation of the RET proto-oncogene on band 10q11.2. The defect occurs in 1 in 5000
live births. Some cases are familial, with an overall incidence of 3.6% among siblings
of index cases.
 Waardenburg-Shah syndrome (piebaldism, neural deafness, megacolon)
 Multiple endocrine neoplasia type 2A (MEN 2A) or 2B (MEN 2B)
Visceral myopathies include the following:
 Mitochondrial neurogastrointestinal encephalopathy (MNGIE) - Only type III involves
marked dilatation of the colon
 Oculogastrointestinal neuropathy (OGIN)
 Idiopathic
In the newborn period, an unrecognized imperforate anus may be the cause of megacolon.
Epidemiology
United States data
No large-scale studies have been conducted to determine prevalence/incidence of acquired
megacolon.
International data
The most common cause of megacolon worldwide is infection with Trypanosoma
cruzi (Chagas disease).
Race has not been documented to play a role in megacolon.
The frequency of acquired megacolon is equally distributed between the sexes. The
congenital megacolon, Hirschsprung disease, predominantly occurs in males.
Although clinically chronic megacolon can occur in any age group, inherited types usually
present in young patients, and acquired types usually present in older patients.
Prognosis
Prognosis is related to the severity of the megacolon and the severity of the patient's
comorbid diseases.
Although some patients cannot be managed on any type of bowel program and quickly
require surgery, other patients may be maintained on a strict bowel program. No detailed
longitudinal studies, however, have been performed to assess strict prognostic associations or
indicators.
Mortality/morbidity
No large-scale studies have been conducted to determine prevalence/incidence of acquired
megacolon. However, once present, the approximate risk of a spontaneous perforation from
nontoxic megacolon is 3%.
Complications
The most dangerous complication is perforation, which rarely occurs. Perforation is generally
due to overdistention of the bowel or to stercoral ulcer. If the etiology is overdistention,
perforation typically occurs in the cecum. Stercoral ulcers typically occur in the
sigmoid/rectosigmoid region.
Patient Education
Education of the patient with regard to the strict bowel program is essential to management.
Maintaining effective management requires extensive effort and discipline from both the
health care provider and the patient. To this end, educating the patient about the entire
process is crucial.
History and Physical Examination
Historically, chronic megacolon has been categorized into 2 groups, according to when
symptoms begin. The congenital group experiences onset of constipation before age 1 year.
The acquired group develops symptoms after age 10 years until adulthood.
Physical examination generally reveals a distended abdomen, which may or may not be tense.
Tympany is invariably present.
Digital rectal examination may demonstrate a hard mass of stool just above the anorectal
ring. Digital rectal examination in a patient with Hirschsprung disease may bring about a
large gush of retained fecal material.
Megarectum with a rectum distended with stool, if chronic, tends to cause the anus to gape
open secondary to the dysfunction of the internal sphincter mechanism. These patients may
present with factitious diarrhea secondary to overflow incontinence.
Acute megacolon
Background
Megacolon, like megarectum, is a descriptive term. Megacolon denotes dilatation of the
colon that is not caused by a mechanical obstruction. While the definition of megacolon has
varied in the literature, most use a cecum measurement of greater than 12 cm in diameter to
define megacolon. Adding to this definition, because the diameter of the large intestine is
different in different areas, measurements of greater than 6.5 cm for the rectosigmoid region
and greater than 8 cm for the ascending colon may also be significant.
Megacolon may be divided into 3 categories by acuity of onset, as follows: (1) acute
megacolon (pseudo-obstruction); (2) chronic megacolon, which includes congenital,
acquired, and idiopathic causes; and (3) toxic megacolon.
The Gastroenterology section of the Medscape Drugs & Diseases journal contains 3 articles
devoted to megacolon, and they are separated based on the 3 aforementioned categories (see
also Differentials). This article is devoted to the acute development of megacolon.
Pathophysiology
Whether dilatation is a result of abnormal motility of the colon remains unresolved. Much
basic science research has been performed in this area. It is well known that the colonic
distensibility changes in the presence of luminal contents. For example, fatty acids infused
into the cecum appear to reduce the volume of the proximal large bowel. Long-term opiate
narcotic use (including diphenoxylate and loperamide) may lead to colonic dilatation and
may limit the ability of the colon to constrict when dilated.
Many pathophysiologic mechanisms have been proposed in an attempt to explain the altered
motility seen in acute megacolon; these include the following:
 Reflex motor inhibition through splanchnic nerves in response to noxious stimuli
 Excess sympathetic motor input (failure to contract)
 Excess parasympathetic motor input (failure to relax)
 Decreased parasympathetic motor input (failure to contract)
 Excess stimulation of peripheral opioid receptors by endogenous or exogenous opioids
(initially excess activation followed by prolonged inhibition)
 Inhibition of nitric oxide release from inhibitory motor neurons
Etiology
Causes of acute megacolon include the following:
 Electrolyte abnormality
 Metabolic abnormality, including hypothyroidism and hyperparathyroidism
 Certain medications, including anticholinergics, antidiarrheals, opiates, digitalis, and
certain antipsychotic drugs
 Inflammatory bowel disease, including ulcerative colitis and Crohn colitis
 Infections, including Clostridium difficile (pseudomembranous colitis), Trypanosoma
cruzi (Chagas disease), and Entamoeba histolytica (amebic dysentery). [1]
Note that in any setting, a mechanical cause (eg, a tumor) and a toxic cause (eg, acute
ulcerative colitis) must be ruled out first because the treatments are very different for these
conditions.
Epidemiology
United States data
No large-scale studies have been performed to determine the prevalence or incidence of acute
megacolon.
Race and sex have not been documented to play a role in acute megacolon.
Most patients are middle-aged or older; however, the increased incidence seen in older
populations is more likely a reflection of their medical and surgical comorbidities rather than
age alone.
Prognosis
Mortality/morbidity
Prognosis is determined in part by the underlying cause of the megacolon, the presence of
any comorbidities, and the development of complications.
The mortality rate associated with spontaneous perforation of nontoxic megacolon is 50%;
however, most patients respond to treatment prior to the onset of this complication. [2]
Complications
The most severe complication is perforation with an associated mortality rate of
approximately 50%. In a study by Vanek et al, perforation rates were 0% for cecal diameters
of less than 12 cm, 7% for cecal diameters of 12-14 cm, and 23% for cecal diameters of
greater than 14 cm. [3]
Mortality was also shown to increase with a delay of decompression therapy.
If surgical therapy is required, mortality increases based on age, comorbidities, and functional
status.
History
The typical patient is an elderly person who is in the hospital, usually for an unrelated reason
(eg, recovering postoperatively from surgery), and may or may not already be taking oral
feeds.
Orthopedic surgery, cesarean delivery, and cardiovascular or lung surgery are procedures that
commonly predispose to acute megacolon.
Acute megacolon can occur on the medical wards as frequently as on the surgical wards (eg,
in patients with unrelated problems, such as pneumonia, sepsis, myocardial infarction, or
stroke).
Systemic diseases that affect the neuromuscular component of the GI tract, such as
amyloidosis, may first present with an acute episode of pseudo-obstruction.
Not having a history of similar episodes of abdominal distension in the past is common.
Colic-type pain may be present, but the absence of this pain does not imply a less severe
condition.
Patients often will experience nausea and vomiting as well as constipation and obstipation.
Physical examination findings may include the following:
 The vital signs can all be normal.
 Depending on the duration of the megacolon and the fluid status, the patient may
become tachycardic.
 With distension of the abdomen pushing on the lungs, the patient also may develop
tachypnea. In this regard, the lung fields may be decreased.
 The abdominal examination generally reveals a distended abdomen, which may or may
not be tense. Serial measurement of the abdominal girth is routinely unreliable.
 Bowel sounds vary from absent to diminished to high-pitched, mimicking mechanical
obstruction.
 Tympany invariably is present.
 Digital rectal examination should generally be performed to exclude fecal impaction.
HIRSCHSPRUNG DISEASE (HD)
Sejarah
Penyakit ini ditemukan oleh herald hirschsprung ditahun 1886 dan diberi nama "Megacolon
Congenital" namun belum bisa beliau jelaskan secara patofisiologi terjadinya. Kemudian oleh
Robertson ditahun 1938 menyatakan bahwa penyakit megacolon congenital yang dimaksud
oleh hirchsprung diakibatkan oleh gangguan peristaltik usus dimana terjadi defisiensi
ganglion.
Definisi
HD adalah suatu kelainan kongenital yang ditandai dengan tidak adanya sel ganglion
parasimpatik pleksus auerbach dan meissner pada kolon distal mulai dari spinkter ani kearah
proksimal dengan panjang yang bervariasi dan memberikan gejala klinis akibat gangguan
pasase kolon fungsional.
Epidemiologi
HD ini terjadi 1 dari tiap 5000 kelahiran dan lebih banyak mengena kepada laki - laki dari
pada perempuan dengan perbandingan 4 : 1.
Anatomi dan Fisiologi
Vaskularisasi rektum dan anus :

Rektum mendapat vaskularisasi dari 3 pembuluh darah, yaitu arteri hemoroidalis superior
yang memperdarahi rektum bagian superior, arteri hemoroidalis media yang memperdarahi
rektum bagian media dan arteri hemoroidalis inferior yang memperdarahi rektum bagian
inferior dan juga anus. Pada wanita arteri hemoroidalis media digantikan dengan arteri
uterina.
Arteri hemoroidalis superior dan media berasal dari arteri mesenterika inferior sedangkan
arteri hemoroidalis inferior berasal dari arteri pudendalis yang merupakan cabang dari arteri
iliaka interna.
Persarafan rektum dan anus :

Rektum dan anus dipersarafi oleh sistem saraf somatik dan otonom. Sistem saraf somatik
dijalankan oleh nervus pudendalis yang mengatur fungsi pada spinkter ani eksternus untuk
relaksasi maupun konstriksi spinkter ani eksternus secara sadar sehingga fungsi inilah yang
dimanfaatkan oleh manusia untuk menunda defekasi saat ada rangsangan untuk segera
mengeluarkan feses yang penuh pada rektum. Sistem saraf otonom terbagi atas sistem saraf
ekstrinsik dan intrinsik Sistem saraf ekstrinsik dijalankan oleh sistem saraf simpatis
(dijalankan oleh nervus hipogastrik dari persarafan spinal T12 sampai L2) yang berfungsi
untuk konstraksi otot spinkter ani internus dan sistem saraf parasimpatis (dijalankan oleh
nervus splanknikus dari persafaran spinal S2 sampai S4) berfungsi sebagai relaksasi spinkter
ani internus dan kontraksi otot longitudinalis dan sirkuler rektum dan usus. Sistem saraf
intrinsik dilakukan oleh saraf “auerbach” yang terletak diantara otot sirkuler dan longitudinal
usus, kemudian saraf “meissner” yang terletak pada submukosa usus.
Patofisiologi
Tidak adanya ganglion pleksus auerbach dan meissner menyebabkan spame terus menerus
otot usus dan spinkter ani berkontraksi terus menerus karena tidak mendapat rangsangan
perintah terhadap hasrat untuk defekasi karena rektum tidak terisi feses sehingga
terjadiPenyempitan kolon distal dan kesulitan relaksasi spinkter ani dan
menyebabkan gangguan pasase usus yang memberikan gejalaKonstipasi
lalu Obstipasi sehingga muncul Gejala Klinis dan komplikasi.
DIAGNOSIS
Diagnosis penyakit ini didasarkan dari alloanamnesis dan atau autoanamnesis pada anak yang
lebih besar, pemeriksaan fisik yang dilakukan dan pemeriksaan penunjang untuk memastikan
diagnosis.
Anamnesis
Gejala yang ditimbulkan dari penyakit ini didasarkan pada usia pasien karena meskipun
penyakit ini bergejala beberapa hari setelah lahir namun banyak juga yang dapat
bertahan sampai beberapa tahun.
Neonatus :
1. Mekonium terlambat keluar > 24 jam.

2. Distensi abdomen.
3. Konstipasi dengan gejala muntah yang awalnya berisi ASI kemudian berwarna hijau
(karena bercampur dengan empedu) kemudian bercampur feses.
Anak yang lebih besar :
1. Susah buang air besar atau tidak teratur.
2. Distensi abdomen
3. Gangguan gizi : anak kurus dan berat badan turun, anemis (akibat defisiensi Fe atau
perdarahan mikro pada mukosa usus yang terjadi akibat usus yang overdistensi) ,
edema (akibat malnutrisi khususnya protein)
Selain gejala diatas, pasien biasanya datang terlambat dengan berbagai komplikasi yang
muncul.
Komplikasi Gastrointestinal seperti enterokolitis dengan gejala diare, demam, distensi
abdomen, muntah, dan feses berbau busuk. Jika komplikasi ini terus dibiarkan maka dapat
menyebabkan perforasi sehingga terjadi peritonitis yang bisa menjadi sepsis yang kemudian
kegagalan multiorgan dan akhirnya kematian.
Komplikasi respiratorius seperti gagal nafas yang dilihat dari gejala sianosis dan sesak nafas
akibat distensi abdomen yang menekan diafragma sehingga pengembangan paru paru
terganggu.
Komplikasi kardiovaskuler seperti takikardi è bradikardi è aritmia, akibat penekanan jantung
dan pembuluh darah oleh distensi abdomen.
Pemeriksaan Fisis
- Inspeksi :
Perut kembung (Jarak prosessus xiphoideus ke umbilikis > Umbilikus ke tulang
pubis)
Gerakan peristaltik usus dapat terlihat pada dinding abdomen.
- Palpasi :
Perut teraba lunak sampai tegang
- Perkusi :
Tympanistik akibat penumpukan gas oleh fermentasi bakteri yang berlebihan didalam
usus, retensi gas akibat sumbatan didaerah distal, dan pertukaran gas yang berkurang
akibat overdistensi usus.
- Auskultasi :
Pada awal distensi terdengar hiperperistaltik namun jika sudah overdistensi maka
kolon tidak dapat lagi melakukan fungsi peristaltik sehingga pada auskultasi terdengar
lemah bahkan tidak ada sama sekali.
DRE (Digital rectal examination) / Rectal touche
- Spinkter mencekik
- Ampulla kosong dan menyempit pada ujung jari didapatkan kolon yang melebar.
- Saat jari ditarik keluar feses keluar menyemprot.
- Keadaan feses : konsistensi semi liquid seperti pasta dan berbau busuk.
Pemeriksaan Penunjang
- Foto BNO (Foto polos abdomen)
Didapatkan dilatasi kolon (inverted U) dan jika terjadi perforasi dapat terlihat udara bebas
dibawah diafragma.
- Foto Barium enema / in loop
Didapatkan 3 tanda khas :
1. Daerah yang menyempit atau aganglionosis
2. Daerah transisi yang berbentuk corong
3. Daerah melebar diproksimal kolon.
Jika ketiga tanda khas diatas belum ditemukan maka dapat dilakukan foto retensi barium
dimana barium yang telah dimasukkan dibiarkan berbaur dengan feses terlebih dulu
selama 24 jam kemudian difoto. Jika daerah menyempit (aganglionosis) terjadi pada
seluruh kolon maka tidak didapatkan daerah transisional yang berbentuk corong.
4 manfaat barium enema pada HD :
1. Menegakkan diagnosis
2. Menentukan panjang segmen yang menyempit.
3. Menentukan tempat yang akan dilakukan biopsi
4. Menentukan lokasi pembedahan definitif.
- Histopatologi
Untuk memastikan bagian kolon yang aganglionosis dapat dilakukan biopsi. Letak dan
cara pengambilan sampel tergantung dari gambaran barium enemanya.
Jika aganglionosisnya pada seluruh kolon maka biopsi dilakukan dengan eksisi seluruh
kolon dan dilakukan pemeriksaan PA.
Jika aganglionosisnya pada kolon yang distal saja, maka cukup dengan biopsi hisap
dengan menggunakan alat biopsi hisap noblett. Daerah yang diambil adalah ketiga zona
dari pemeriksaan barium enema. Jangan mengambil sampel pada daerah 1 cm diatas linea
dentata karena pada daerah itu normalnya tidak memiliki ganglion.
- Monometri :
Pemeriksaan ini dilakukan untuk lebih memastikan diagnosis hirschsprung diasease
dengan tanda :
1. Hiperaktivitas pada segmen yang dilatasi
2. Tidak ada peristaltik pada segmen aganglionik
3. Tidak ada relaksasi spinkter ani interna.
Penatalaksanaan
Penanganan HD dilakukan dengan 2 tahap :
1. Dekompresi
Tujuan dekompresi ini adalah :
- Mengatasi obstruksi usus untuk mengurangi distensi abdomen
- Mencegah komplikasi
- Mengecilkan bagian usus yang melebar untuk memudahkan operasi karena usus yang
melebar dapat menutupi lapangan operasi dan menyulitkan anatomose saat operasi
definitif.
Dekompresi dapat dilakukan dengan cara :
- Wash out dengan bilasan NaCl kedalam rektum dan dilakukan 2 kali sehari.
- Kolostomi jika dengan wash out tidak dapat mengatasi distensi abdomen.
2. Operasi Definitif (pull through)

Prinsip pull through adalah mendekatkan kolon yang ganglionik ke anus.
Tujuan operasi definitif ini adalah mengembalikan fungsi anorektal menjadi normal
atau mendekati normal yaitu agar pasien dapat menahan defekasi hingga diperoleh
tempat dan waktu yang tepat untuk defekasi.
Ada 4 macam prosedur yang dapat dilakukan :
1. Prosedur swenson (pertama kali dilakukan ditahun 1946) dengan cara
rektosigmoidektomi.
2. Prosedur Duhamel (pertama kali dilakukan ditahun 1956) dengan cara retrorektal.
3. Prosedur Soave (ditahun 1966) dengan cara endorektal ekstramukosa.
4. Metode Rehbein dengan tehnik deep anterior resektion.
Komplikasi dari operasi :
1. Kebocoran anastomose yang berakibat abses dan peritonitis
2. Stenosis otot usus yang berakibat distensi abdomen berulang
3. Enterokolitis
4. Gangguan fungsi spinkter ani yang berakibatinkontinensia alvi
Megacolon Congenital / Hirschprung Disease

Posted on April 27, 2010 by dokterugm
Penyakit Hirschsprung adalah kelainan kongenital pada kolon yang ditandai dengan tiadanya
sel ganglion parasimpatis pada pleksus submukosus Meissneri dan pleksus mienterikus
Auerbachi. 90% kelainan ini terdapat pada rektum dan sigmoid. Hal ini diakibatkan oleh
karena terhentinya migrasi kraniokaudal dari sel krista neuralis di daerah kolon distal pada
minggu ke lima sampai minggu ke dua belas kehamilan untuk membentuk sistem saraf usus.
Aganglionik usus ini mulai dari spinkter ani interna kearah proksimal dengan panjang yang
bervariasi, tetapi selalu termasuk anus dan setidak-tidaknya sebagian rektum dengan gejala
klinis berupa gangguan pasase usus fungsional (Kartono,1993; Fonkalsrud,1997).
Penyakit ini pertama kali ditemukan oleh Herald Hirschsprung tahun 1886, namun
patofisiologi terjadinya penyakit ini tidak diketahui secara jelas hingga tahun 1938, dimana
Robertson dan Kernohan menyatakan bahwa megakolon yang dijumpai pada kelainan ini
disebabkan oleh gangguan peristaltik dibagian distal usus akibat defisiensi ganglion
(Kartono, 1993; Fonkalsrud, 1997).
Mutasi pada Ret proto-oncogene akhir-akhir ini telah dihubungkan dengan penyakit
Hirschsprung. Gen lain yang berhubungan dengan kelainan ini ialah Endothelin-B reseptor,
endothelin-3 dan Glial cell derived neurotrophic faktor (Abe et al, 2000; Kim et al, 2006).
Goldstein (2006) menyatakan bahwa migrasi sel-sel krista neuralis yang kemudian
mengadakan proliferasi dan diferensiasi didalam dinding usus akan meningkatkan
pembentukan sel saraf dan sel glial pada sistem saraf intestinal. Kegagalan proses ini selama
fase embriogenesis akan mengakibatkan gangguan motilitas usus seperti yang terlihat pada
penyakit Hirschsprung. Insidens penyakit Hirschsprung adalah satu dalam 5000 kelahiran
hidup, dan laki-laki 4 kali lebih banyak dibanding perempuan ( Holschneider dan Ure, 2005 ).
Diagnosis penyakit Hirschsprung harus dapat ditegakkan sedini mungkin mengingat berbagai
komplikasi yang dapat terjadi dan sangat membahayakan jiwa pasien seperti terjadinya
enterokolitis, perforasi usus serta sepsis yang dapat menyebabkan kematian. Diagnosis
kelainan ini dapat ditegakkan dengan anamnesis, pemeriksaan fisik, pemeriksaan Rontgen
dengan enema barium, pemeriksaan histokimia, pemeriksaan manometri serta pemeriksaan
patologi anatomi. Manifestasi klinis penyakit Hirschsprung terlihat pada neonatus cukup
bulan dengan keterlambatan pengeluaran mekonium pertama yang lebih dari 24 jam yang
kemudian diikuti dengan kembung dan muntah. Pada pemeriksaan fisik ditemukan perut yang
kembung hebat, gambaran usus pada dinding abdomen dan bila dilakukan pemeriksaan colok
dubur, feses akan keluar menyemprot dan gejala tersebut akan segera hilang (Teitelbaum,
2003; Swenson, 1990).
Pada pemeriksaan enema Barium didapatkan tanda-tanda khas penyakit ini yaitu adanya
gambaran zone spastik, zone transisi serta zone dilatasi. Gambaran mukosa yang tidak teratur
menunjukkan adanya proses enterokolitis (Proctor, 2003; Pratap, 2007).
Pada penyakit Hirschsprung terdapat kenaikan aktivitas asetilkolinesterase pada serabut saraf
dalam lamina propria dan muskularis mukosa. Pewarnaan untuk asetilkolinesterase dengan
tehnik Karnovsky dan Roots akan dapat membantu menemukan sel ganglion di submukosa
atau pada lapisan muskularis khususnya dalam segmen usus yang hipoganglionosis.
Pemeriksaan elektromanometri dilakukan dengan memasukkan balon kecil kedalam rektum
dan kolon, dengan kedalaman yang berbeda-beda dan akan didapatkan kontraksi pada
segmen aganglionik yang tidak berhubungan dengan kontraksi pada segmen yang
ganglionik Pemeriksaan patologi anatomi dilakukan dengan memeriksa material yang
didapatkan dari biopsi rektum yang dilakukan dengan cara biopsi hisap maupun biopsi
manual. Diagnosis penyakit ini dapat ditegakkan bila tidak ditemukan sel ganglion Meissnner
dan sel ganglion Auerbach serta ditemukan penebalan serabut saraf (Holschneider dan Ure,
2005).
Kartono (2004) menyatakan bahwa bila hasil pemeriksaan klinis dan radiologis enema
barium ditemukan tanda khas penyakit Hirschsprung, maka tidak seorang pasienpun yang
tidak menderita penyakit Hirschsprung
Pengobatan penyakit Hirschsprung terdiri atas pengobatan non bedah dan pengobatan bedah.
Pengobatan non bedah dimaksudkan untuk mengobati komplikasi-komplikasi yang mungkin
terjadi atau untuk memperbaiki keadaan umum penderita sampai pada saat operasi definitif
dapat dikerjakan. Pengobatan non bedah diarahkan pada stabilisasi cairan, elektrolit, asam
basa dan mencegah terjadinya overdistensi sehingga akan menghindari terjadinya perforasi
usus serta mencegah terjadinya sepsis. Tindakan-tindakan nonbedah yang dapat dikerjakan
adalah pemasangan infus, pemasangan pipa nasogastrik, pemasangan pipa rektum, pemberian
antibiotik, lavase kolon dengan irigasi cairan, koreksi elektrolit serta penjagaan nutrisi.
(Kartono, 2004)
Tindakan bedah pada penyakit Hirschsprung terdiri atas tindakan bedah sementara dan
tindakan bedah definitif. Tindakan bedah sementara dimaksudkan untuk dekompresi
abdomen dengan cara membuat kolostomi pada kolon yang mempunyai ganglion normal
bagian distal. Tindakan ini dapat mencegah terjadinya enterokolitis yang diketahui sebagai
penyebab utama terjadinya kematian pada penderita penyakit Hirschsprung. (Langer, 2005).
Tindakan bedah definitif yang dilakukan pada penyakit Hirschsprung antara lain prosedur
Swenson, prosedur Duhamel, prosedur Soave, prosedur Rehbein, prosedur transanal dan
bedah laparoskopik. Saat ini prosedur transanal satu tahap telah berkembang dan dikerjakan
pada saat penderita masih neonatus (Pratap et al., 2007)
Permasalahan-permasalahan bedah definitif yang disebut diatas masih cukup banyak antara
lain masalah lama waktu operasi, tindakan kolostomi, kebocoran anastomosis (5%) , striktura
(10%), obstruksi usus (5%), abses pelvis (5%), dan infeksi jaringan (10%) (Lee, 2002).
Angka mortalitas penyakit Hirschsprung pada neonatus yang tidak ditangani masih sangat
tinggi yaitu mencapai 80%, sedang kematian pada kasus-kasus yang telah ditangani 30%
disebabkan oleh karena enterokolitis. (Lee, 2002).
Angka mortalitas operasi yang didapatkan setelah beberapa prosedur operasi antara lain
prosedur Swenson 2,5%, prosedur Soave 4,5% dan prosedur Duhamel 6,2%. (Swenson,
1990).
Sawaf et al (2007) telah membandingkan hasil prosedur transanal pull-through dengan
prosedur transabdominal pull-through, 20 pasien dilakukan transanal endorectal pull-through
dan 21 pasien dilakukan transabdominal pull-through. Hasil evaluasi 41 pasien tersebut
ternyata 6 pasien harus dilakukan operasi kembali akibat terjadinya obstruksi intestinal pada
3 pasien, enterokolitis pada 2 pasien dan puntiran kolon pada 1 pasien. Enterokolitis terjadi
pada 13 kasus (61,9%) pada prosedur transabdominal dan 9 kasus (45%) pada prosedur
transanal. Dari hasil penelitian tersebut disimpulkan bahwa penurunan insidensi enterokolitis
lebih baik pada prosedur transanal.
Leeuwen et al (2002) membandingkan prosedur transperineal dan transabdominal untuk
operasi penyakit Hirschsprung dan enterokolitis yang terjadi 53% pada prosedur
transabdominal sedangkan pada prosedur transperineal 56%.
Di Rumah Sakit Dr.Sardjito Yogyakarta sejak tahun 2005 oleh Rohadi telah ditemukan
tehnik operasi baru yaitu PSNRHD Posterior Sagittal Neurektomi Repair for Hirschsprung
Desease. Sedangkan prosedur yang lain meliputi: prosedur Duhamel, prosedur Soave
modifikasi, prosedur transanal dan prosedur miomektomi rektal. Setiap tahun penderita
Penyakit Hirschsprung tercatat rata-rata 50 pasien (Rochadi, 2007).
Tehnik Posterior Sagittal Neurektomi Repair for Hirschsprung Desease, dilakukan dengan
irisan intergluteal untuk mencapai derah rektum, satu tahap tanpa kolostomi dan tanpa
dilakukan proses pull through atau tarik terobos endorektal (Rochadi, 2007).
Costa et al (2006) menyatakan bahwa enterokolitis tetap merupakan penyebab
utama terjadinya mortalitas maupun morbiditas pada penderita penyakit Hirschsprung yang
telah dilakukan operasi definitif. Enterokolitis merupakan komplikasi yang amat berbahaya
sehingga mortalitasnya mencapai 30% apabila tidak ditangani secara sempurna. Keadaan ini
diakibatkan oleh karena stasis usus yang memicu proliferasi bakteri didalam lumen usus
diikuti invasi ke mukosa sehingga terjadilah inflamasi lokal maupun sistemik.
Etiologi Penyakit Hirschsprung
Laporan pertama mengenai penderita penyakit Hirschsprung telah disampaikan oleh
Frederick Ruysch pada tahun 1691, akan tetapi baru pada tahun 1886 Harold
Hirschsprung pertama kali menerangkan bahwa penyakit ini adalah sebagai penyebab
terjadinya konstipasi pada neonatus. Penyakit Hirschsprung adalah kelainan kongenital pada
kolon yang ditandai dengan tiadanya sel ganglion parasimpatis pada pleksus submukosus
Meissneri dan pleksus mienterikus Auerbachi. 90% kelainan ini terdapat pada rektum dan
sigmoid. Hal ini diakibatkan oleh karena terhentinya migrasi kraniokaudal dari sel krista
neuralis di daerah kolon distal pada minggu ke lima sampai minggu ke dua belas kehamilan
untuk membentuk sistem saraf usus. Aganglionik usus ini mulai dari spinkter ani interna
kearah proksimal dengan panjang yang bervariasi, tetapi selalu termasuk anus dan setidak-
tidaknya sebagian rektum dengan gejala klinis berupa gangguan pasase usus fungsional
(Kartono,1993; Fonkalsrud,1997).
Untuk mengetahui penyebab terjadinya penyakit Hirschsprung diperlukan pemahaman yang
mendalam perihal perkembangan embriologis sistem saraf intestinal. Sel-sel krista neuralis
berasal dari bagian dorsal neural tube yang kemudian melakukan migrasi keseluruh bagian
embrio untuk membentuk bermacam-macam struktur termasuk sistim saraf perifer, sel-sel
pigmen, tulang kepala dan wajah serta saluran saluran pembuluh darah jantung. Sel-sel yang
membentuk sistim saraf intestinal berasal dari bagian vagal krista neuralis yang kemudian
melakukan migrasi ke saluran pencernaan. Sebagian kecil sel-sel ini berasal dari sakral krista
neuralis untuk ikut membentuk sel-sel saraf dan sel-sel glial pada kolon. Selama waktu
migrasi disepanjang usus, sel-sel krista neuralis akan melakukan proliferasi untuk mencukupi
kebutuhan jumlah sel diseluruh saluran pencernaan. Sel-sel tersebut kemudian berkelompok
membentuk agregasi badan sel. Kelompok-kelompok ini disebut ganglia yang tersusun atas
sel-sel ganglion yang berhubungan dengan sel bodi saraf dan sel-sel glial. Ganglia ini
kemudian membentuk dua lingkaran cincin pada stratum sirkularis otot polos dinding usus,
yang bagian dalam disebut pleksus submukosus Meissnerr dan bagian luar disebut pleksus
mienterikus Auerbach (Fonkalsrud,1997).
Secara embriologis sel-sel neuroenterik bermigrasi dari krista neuralis menuju saluran
gastrointestinal bagian atas dan selanjutnya meneruskan kearah distal. Pada minggu ke lima
kehamilan sel-sel saraf tersebut akan mencapai esofagus, pada minggu ke tujuh mencapai
mid-gut dan akhirnya mencapai kolon pada minggu ke dua belas. Proses migrasi mula
pertama menuju ke dalam pleksus Auerbachi dan selanjutnya menuju kedalam pleksus
submukosa Meissneri. Apabila terjadi gangguan pada proses migrasi sel-sel kristaneuralis ini
maka akan menyebabkan terjadinya segmen usus yang aganglionik dan terjadilah penyakit
Hirschsprung. (Fonkalsrud,1997).
Berdasar pada segmen kolon yang aganglionik, penyakit Hirschsprung dibagi menjadi
Hirschsprung short segmen bila segmen aganglionik tidak melebihi batas atas sigmoid (S-
HSCR, 80% kasus) dan Hirschsprung long segmen bila segmen aganglionik melebihi
sigmoid (L-HSCR, 20% kasus). Ada empat varian penyakit Hirschsprung yang dilaporkan
yaitu total kolon aganglionosis, total intestinal aganglionosis, ultra short dan suspended
HSCR. (Holschneider dan Ure, 2005; Amiel dan Lyonnet, 2001).
Puri (1997) menyatakan bahwa banyak keadaan yang secara klinis menyerupai penyakit
Hirschsprung akan tetapi didapatkan sel ganglion pada kolonnya. Keadaan tersebut adalah
Intestinal neuronal displasia, Hipoganglionosis, Immature ganglia, Pleksus argyrophyl yang
negatif, Akhalasia sfingter interna dan kelainan otot polos. Untuk membedakannya
diperlukan pemeriksan-pemeriksaan histokimia, immnohistokimia silver staining dan
mikroskop elektron.
Pada tahun 1994 ditemukan dua gen yang berhubungan dengan kejadian penyakit
Hirschsprung yaitu RET (receptor tyrosin kinase) dan EDNRB (endothelin receptor B). RET
ditemukan pada 20% dari kasus penyakit Hirschsprung dan 50% dari kasus tersebut bersifat
familial, sedang EDNRB dijumpai pada 5 sampai 10% dari semua kasus penyakit
Hirschsprung. Interaksi antara EDN-3 dan EDNRB sangat penting untuk perkembangan
normal sel ganglion usus. Pentingnya interaksi EDN-3 dan EDNRB didalam memacu
perkembangan normal sel-sel krista neuralis telah dibuktikan dengan jelas. Baik EDN-3
maupun EDNRB keduanya ditemukan pada sel mesenkim usus dan sel neuron usus, dan ini
memperkuat dugaan bahwa EDN-3 dan EDNRB dapat mengatur regulasi antara krista
neuralis dan sel mesenkim usus yang diperlukan untuk proses migrasi normal (Duan, 2003).
Genom lain yang berperan sebagai penyebab terjadinya penyakit Hirschsprung adalah Glial
cell line Derived Neurothrophic Factor (GDNF), Neurturin (NTN), Endotelin Converting
Enzym 1, SOX 10 dan SIP 1 (Amiel dan Lyonnet, 2001)
Nakatsuji et al (2007) menyatakan bahwa terjadinya penyempitan pada zone aganglionik
disebabkan oleh karena adanya hiperaktifitas saraf kolinergik, defisiensi saraf inhibitor non
adrenergik dan adanya hipoaktifitas otot polos. Berdasar pada pemeriksaan histologis dan
biokemis pada spesimen aganglionik ternyata ditemukan adanya proliferasi serabut saraf
kolinergik, peningkatan aktifitas enzim asetilkolinesterase dan kenaikan pengeluaran
mediator asetilkolin. Kecuali hal-hal tersebut diatas pada zone aganglionik juga diketemukan
penurunan jumlah sel-sel penghasil nitric oxyde (NO) dan peptidergik, penurunan kadar
kalsium akibat kehilangan gen EDNRB sehingga kolon akan ditempati oleh sel – sel prekusor
yang mengakibatkan degenerasi pada otot polosnya.
Berdasar tipe ketinggian segmen yang aganglionik, 80% adalah short segmen dan 20%
adalah long segmen. Kelainan-kelainan penyerta yang sering didapatkan adalah palatoskisis,
polidaktili, defek katub jantung, malformasi kraniofasial dan sindrom hipoventilasi (Kim et
al, 2006; Yang et al, 2007).
Cherian et al (2008) menyatakan bahwa 70% penyakit Hirschsprung adalah tanpa disertai
kelainan bawaan yang lain dan melaporkan terjadinya kelainan penyerta Bardet-Biedl
sindrom pada saudara kandung keluarga Arab. Bardet-Biedl sindrom merupakan kelainan
pleiotropic autosomal recessive dengan tanda-tanda obesitas, polidaktili, hipogenitalisme,
kelainan ginjal, retardasi mental dan gangguan tumbuh kembang. Ekema et al (2006)
menyatakan bahwa Cytomegalovirus kongenital merupakan infeksi intra uterin yang paling
kerap dijumpai pada manusia. Prevalensi kelainan ini adalah 0,2% sampai 2,2% dan
merupakan bagian dari virus herpes. Virus ini ditularkan secara kontak langsung antar
manusia. Penderita CMV dapat mengekskresi CMV lewat urin, saliva, sekresi cerviks atau air
susu. Sel usus yang telah terinfeksi CMV dihubungkan dengan terjadinya enterokolitis
nekrotikans pada neonatus yang dapat menyebabkan terjadinya striktur kolon dengan
manifestasi klinis mirip dengan penyakit Hirschsprung.
Flageole et al (1996) melaporkan penderita dengan trisomi 21 pada penderita penyakit
Hirschsprung yang disertai atresia ani dan menyarankan bahwa adanya penyakit
Hirschsprung harus dicurigai pada neonatus dengan kelainan trisomi 21 yang disertai
konstipasi.
B. Anatomi
Kanalis analis berasal dari proktoderm yang merupakan invaginasi ektoderm, sedangkan
rektum berasal dari endoderm. Dengan adanya perbedaan embriologi antara anus dan rektum
ini maka sistim vaskularisasi, persarafan serta sistem limfatika berbeda pula. Rektum dilapisi
mukosa glanduler sedangkan kanalis analis dilapisi epitel gepeng. Batas rektum dan kanalis
analis ditandai dengan adanya perubahan jenis epitel. Kanalis analis dan kulit luar
disekitarnya kaya akan persarafan sensorik somatik yang peka terhadap rangsang nyeri,
sedang mukosa rektum mempunyai persarafan autonom yang tidak peka terhadap rasa nyeri.
Darah vena diatas garis anorektum mengalir melalui sistem porta sedangkan yang berasal dari
dari anus dialirkan kesistem kava melaui vena iliaka. (Guyton, 1986)
1. KANALIS ANALIS.
Makroskopis kanalis analis terdiri atas kolumna analis, valvula analis, sinus analis, papila
analis, zona transisi garis Hilton dan kelenjar analis. Kolumna analis merupakan lipatan
vertikal dari selaput mukosa, sedang valvula analis merupakan lipatan melintang berbentuk
bulan sabit pada ujung bawah kolumna analis yang terdapat disepanjang linea pektinata dan
garis ini merupakan batas antara endoderm dan ektoderm. Sinus analis terdiri dari lekukan-
lekukan kecil tepat diatas valvula analis dan tonjolan mukosa dari valvula analis disebut
papila analis. (Shafik, 2000)
Secara mikroskopis kanalis analis terdiri atas tiga macam epitel dimana diatas linea pektinea
strukturnya menyerupai kolon, antara linea pektinea dan garis Hilton dilapisi epitel
transitional berlapis dan dibawah garis Hilton epitel pipih berlapis (Guyton, 1986).
Fu dan Zhang (1997) menemukan adventitia rectalis, lapisan jaringan fibrous yang terluar
pada dinding rektum yang berfungsi membatasi gerakan ekspansi dinding rektum.
Pemotongan jaringan ini akan mengakibatkan pengurangan pengkerutan rektum sehingga
retum dapat ditarik lebih panjang dan lebih elastis.
Gambar 1. Anatomi Rektum dan Saluran Anal (Yamada, 2000)
1. SISTEMA MUSKULARE.
Pada individu normal, struktur otot seran lintang yang berfungsi pada kontrol feses
membentuk bangunan seperti cerobong. Muskulus levator merupakan bagian paling atas dan
muskulus sfingter eksternus merupakan bagian paling bawah dari cerobong. Otot-otot lain
yang membentuk bangunan cerobong ini yaitu muskulus ischiococcygeus, ileococcygeus,
pubococcysigeus, puborektalis dan muskulus sfingter ani internus. Sfingter terdiri atas otot
polos dan otot lurik yang membentuk saluran anal. Otot polos sfingter interna adalah intrinsik
pada dinding usus yang menempati 2/3 bagian distal saluran anal, sebagian besar terletak
distal dari garis pektinea, otot tersebut merupakan penebalan muskulus sirkular yang
diperkuat oleh muskulus longitudinal di bagian luarnya (Shafik, 2000).
Sfingter eksterna merupakan lingkaran otot memanjang mengelilingi katub anal sampai
orifisium anal. Otot ini berupa kumpulan otot-otot parasagittal yang betemu pada ujung
anterior dan posterior anus. Bangunan otot yang terletak antara muskulus levator dan
muskulus sfingter ani eksternus membentuk serabut-serabut otot vertikal disebut “muscle
complex”.Stimulasi pada muskulus levator ani akan menyebabkan kontraksi yang menarik
rektum kedepan, sedangkan stimulasi pada “muscle complex” akan mengangkat anus keatas.
Stimulasi pada serabut otot parasagital akan menimbulkan gerakan yang searah dengan
serabutnya sehingga menyebabkan anus akan tertutup. Otot-otot dasar panggul yang terletak
pada pintu keluar rongga pelvis, dibentuk oleh otot-otot levator ani , pubococcygeus,
ileococcygeus, ischiococcygeus dan puborectalis (Shafik, 2000).
Gambar 2. Anatomi Muskulare (Yamada, 1999)
1. VASKULARISASI.
Vaskularisasi untuk daerah sigmoid dan bagian atas rektum berasal dari arteria mesenterika
inferior dan arteria kolika sinistra sedangkan vaskularisasi rektum dan kanalis analis berasal
dari arteri hemorrhoidalis superior, media dan inferior. Arteria hemorrhoidalis superior
merupakan akhir dari arteria mesenterika inferior yang melalui dinding posterior rektum
turun sampai ke linea pektinea. Arteria hemorrhoidalis media merupakan cabang dari arteria
iliaka interna yang pada wanita berupa arteria uterina. Arteria hemorrhoidalis inferior
merupakan cabang arteria pudenda interna (Shafik, 2000) .
Vena pada rektum dan dan anus mengikuti sistem arteri. Vena hemorrhoidalis superior
berasal dari pleksus hemorrhoidalis internus, berjalan ke kranial kedalam vena mesenterika
inferior dan melalui vena lienalis ke vena porta. Vena hemorrhoidalis media dan inferior
mengalirkan darah ke vena pudenda interna, ke vena iliaka interna untuk selanjutnya ke vena
kava inferior. Anastomosis vena hemorrhoidalis superior, media dan inferior disebut
portosistemic shunt (Shafik, 2000).
1. PERSARAFAN.
2. Sistem Syaraf Intestinal.
Sistem saraf intestinal merupakan sekumpulan sel-sel saraf pada saluran pencernaan yang
fungsinya tidak tergantung pada sistem saraf pusat. Sistem ini mengatur gerakan usus, sekresi
eksokrin, sekresi endokrin dan mikrosirkulasi saluran pencernaan disamping mengatur proses
immunitas dan inflamasi. Sistem saraf intestinal mula-mula diperkirakan sebagai bagian
otonom dari sistem saraf perifer dan sel saraf pada dinding usus dianggap sebagai sel saraf
parasimpatis postganglion. Akan tetapi pada penelitian–penelitian selanjutnya ternyata
menunjukkan bahwa usus mempunyai sistem pengaturan tersendiri, kontraksi peristaltik
diatur oleh reflek-reflek yang melibatkan saraf intramural dan kebanyakan sel saraf usus tidak
berhubungan dengan axon parasimpatis sistem saraf pusat secara langsung (Goyal dan
Hirano, 1996).
Penelitian selanjutnya mengenai fungsi dan dan aktivitas kimiawi sistem saraf intestinal
ternyata sangat mirip dengan sistem saraf pusat dimana jumlah sel saraf mencapai 100 milyar
mendekati jumlah sel saraf pada medula spinalis. Bagian sistem saraf pusat yang
berhubungan dengan sistim saraf intestinal adalah jaringan saraf sentral otonom. Sistem saraf
intestinal bersama jaringan-jaringan penghubung dengan sistem saraf pusat tersebut secara
simultan mengontrol seluruh fungsi saluran pencernaan (Goyal dan Hirano, 1996).
Pada sistem saraf intestinal, sel bodi saraf akan berkelompok menjadi ganglion yang
dihubungkan dengan bundel-bundel saraf untuk membentuk dua pleksus besar yaitu pleksus
mienterius Auerbach yang terletak antara lapisan sirkuler dan lapisan longitudinal serta
pleksus submukosus Meissner yang terletak pada submukosa antara lapisan sirkuler dan
muskularis mukosa. Pleksus mienterikus Auerbach berfungsi sebagai inervasi motorik pada
kedua lapisan otot dan inervasi sekretomotor pada mukosa sedang pleksus submukosus
Meissner berperan pada pengaturan fungsi sekresi (Goyal dan Hirano, 1996).
Nervus parasimpatis berasal dari cabang anterior nervi Sakralis 2, 3, 4. Persarafan
preganglion ini membentuk dua saraf erigentes yang memberikan cabang langsung ke rektum
dan melanjutkan diri sebagai cabang utama ke pleksus pelvis untuk organ-organ intra pelvis.
Didalam rektum serabut saraf ini berhubungan dengan pleksus ganglion Auerbach.
Persarafan simpatis berasal dari ganglion lumbal 2, 3, 4 dan pleksus praaorta. Persarafan ini
menyatu pada kedua sisi membentuk pleksus hipogastrikus didepan vertebra lumbal lima dan
melanjutkan diri kearah postero lateral sebagai persarafan presakral yang bersatu dengan
ganglion pelvis pada kedua sisi (Shafik, 2000).
Persarafan simpatis dan parasimpatis ke rektum dan saluran anal berperan melalui ganglion
pleksus Auerbach dan Meissner untuk mengatur peristaltik dan tonus sfingter interna. Serabut
simpatis sebagai inhibitor dinding usus dan motor sfingter interna sedang parasimpatis
sebagai motor dinding usus dan inhibitor sfingter. Sistem saraf parasimpatis juga merupakan
persarafan sensorik untuk rasa distensi rektum (Shafik, 2000).
Inervasi somatik pada otot-otot seranlintang terutama pada bagian atas muskulus levator,
musculus ischiococcygeus dan pubococcygeus mendapat inervasi dari radix anterior nervus
sakralis 3 dan 4. Nervus pudendalis yang berasal dari nervus sakralis 2, 3 dan 4 juga
memberikan persarafan pada otot-otot tersebut. Bagian bawah muskulus levator yaitu
muskulus puborektalis dan muskulus sfingter eksternus membentuk bangunan terpisah dan
menerima inervasi cabang perineal nervus sakralis 4, hemorrhoid inferior dan cabang perineal
nervus pudendus (Shafik, 2000).
Inervasi sensoris kanalis anal, termasuk daerah 1 cm diatas linea pectinea dan kebawah
sampai kulit anus merupakan daerah-daerah yang sangat sensitif. Terdapat akhiran-akhiran
saraf yang mampu mendeteksi rasa nyeri (intra epitelial), sensasi sentuhan (Meissner’s
corpuscle), sensasi dingin (Krause’s end-bulb) sensasi tekanan atau regangan (Pacini dan
Golgi-Mazzoni) dan sensasi gesekan (genital corpuscles). Bagian atas kanalis anal rektum,
tidak sensitif terhadap rangsangan-rangsangan tersebut diatas akan tetapi sensitif pada
rangsangan distensi yang diberikan oleh inervasi parasimpatis pada otot polos dan reseptor
proprioseptiv yang terletak pada otot seranlintang disekitar rektum (Shafik, 2000).
Rektum menerima saraf otonom bersama pasokan darah arteria rektalis. Saraf – saraf pleksus
pelvikus memberikan cabang ke viscera genitourinarius yang terletak disebelah depan rektum
dan didepan fascia Denonvilliers (Davies, 1997).
1. Inervasi traktus gastrointestinal.
Pleksus saraf pada usus merupakan jaringan saraf dengan fungsi tersendiri yang disebut
sistem saraf intestinal yang dihubungkan melalui jaringan saraf sentral otonom ke sistem
saraf pusat dengan saraf parasimpatis maupun saraf simpatis. Sistem saraf intestinal dapat
mempengaruhi sistem efektor pada usus secara langsung maupun secara tidak langsung lewat
sel perantara yang berujud sel endokrin, sel interstisial Cajal dan sel sistem immun seperti sel
mast. Gerakan normal traktus gastrointestinal tergantung pada sistem saraf intestinal dan sel
interstitial Cajal yang bertindak sebagai sel-sel pacemaker. Lokasi sel-sel Cajal terdapat pada
lapisan mienterikus maupun muskularis, yang berfungsi untuk motilitas usus, perkembangan
traktus gastrointestinal serta membawa Tyrosine Kinase Receptor. Pada zone aganglionik
tidak diketemukan sel Cajal sedang pada daerah zone transisi sel-sel ini sangat terbatas dan
pada zone ganglionik sel ini lebih sedikit jika dibandingkan dengan usus normal (Tam et al
2003).
Sel bodi saraf saraf vagal primer dan splanchnic primer afferen terletak pada ganglia nodosa
dan ganglia radik dorsalis yang membawa bermacam informasi dari usus ke sistem saraf
pusat (Goyal dan Hirano, 1996).
Kamimura et al (1997); Bealer et al (1994) menyatakan bahwa nitric oxide (NO) merupakan
transmiter saraf nonadrenergik noncholinergik dan pada penyakit Hirschsprung ternyata
terdapat kekurangan inervasi saraf nonadrenergik noncholinergik pada zone aganglioniknya.
1. Patofisiologi
1. Motilitas.
Gerakan peristaltik
merupakan gabungan gerakan kontraksi diproksimal bolus dan gerakan relaksasi pada distal
bolus. Gerakan ini terutama dilakukan oleh stratum sirkularis dan ditambah kontraksi stratum
longitudinale tepat diatas bolus. Sirkuit reflek peristaltik terdiri atas terjadinya distensi usus
dan depolarisasi sel Cajal pada otot polos yang lewat saraf kolinergik akan memicu
interneuron pada pleksus Auerbach dan pleksus Meissnerr yang meupakan saraf
nonadrenergik nonkolinergik. Mediator-mediator yang bekerja pada interneuron ini antara
lain adalah ATP, VIP dan NO. Nitrogen Oxyde adalah neurotransmiter yang berfungsi
sebagai mediator untuk relaksasi otot polos usus oleh karena itu ketiadaan NO akan
menyebabkan kegagalan gerakan relaksasi pada segmen usus yang aganglionik. Sehingga
dapat ditarik kesimpulan bahwa terjadinya kontraksi permanen pada segmen aganglionik
kolon diakibatkan oleh karena tidak adanya interneuron nonadrenergik nonkolinergik
sehingga produksi NO menjadi berkurang atau tidak ada. Namun demikian oleh karena
dinding kolon bersifat elastis maka tetap akan ada gerakan-gerakan tapi tanpa koordinasi dan
ini menjadikan alasan mengapa diagnosis penyakit Hirschsprung kadang-kadang
terlambat (Goyal dan Hirano, 1996).
1. 2. Kontinensi .
Kontinensi merupakan kemampuan untuk menahan feses, dan hal ini tergantung pada
konsistensi feses, tekanan dalam lumen anus, tekanan rektum dan sudut anorektal. Kontinensi
diatur oleh mekanisme volunter dan involunter yang menjaga aliran secara anatomi dan
fisiologi jalannya feses ke rektum dan anus (Scharli, 1987).
Penghambat yang berperan adalah sudut anus dan rektum yang dihasilkan oleh otot levator
ani bagian puborektal anterior dan superior. Adanya perbedaan antara tekanan dan aktivitas
motorik anus, rektum dan sigmoid juga menyebabkan progresivitas pelepasan feses
terhambat. Kontraksi sfingter ani eksternus diaktivasi secara involunter dengan distensi rektal
dan dapat meningkat selama 1-2 menit. Mekanisme kontinensi dipengaruhi oleh beberapa
faktor yaitu sfingter ani, mekanisme valf, reservoar rektum dan faktor sensoris (Miller dan
Bartolo, 1991).
Sfingter interna dipengaruhi oleh 4 mekanisme persarafan : 1. Alfa adrenergik sebagai
eksitator stimuli, berjalan pada nervus Hipogastrikus yang berfungsi mempertahankan tonus
sfingter intena , 2. Beta adrenergik sebagai reseptor inhibisi yang berfungsi untuk relaksasi, 3.
Saraf kolinergik dan 4. Saraf nonadrenegik non kolinergik untuk relaksasi sfingter interna
dengan mediator NO, VIP dan Peptidergik lain (Scharli, 1987).
Banerjee dan Wilkin (1993) menyatakan bahwa sfingter ani interna merupakan bagian
terpenting pada proses kontinensi dan 80% tekanan dalam anal kanal berasal dari organ
tersebut. Sfingter ani internus berada dalam kontrol syaraf otonom yang distimulasi oleh
saraf simpatis dan dihambat oleh saraf parasimpatis melalui pleksus sakralis dan pelvis.
Dalam keadaan istirahat tekanan pada daerah sfingter ani internus lebih besar dibanding
tekanan pada bagian atas anal kanal sehingga akan dapat mengatur kontinensi dan flatus.
Tekanan pada saat istirahat ini hanya 20% dilakukan oleh aktivitas sfingter eksternus yang
terdiri atas serabut otot seran lintang yang persarafannya berasal dari cabang somatik nervus
pudendus.
Faktor lain yang mengatur fungsi kontinensi adalah muskulus puborektalis dan sudut
anorektal, dimana perlukaan pada otot ini pasti akan terjadi inkontinensia yang tidak dapat
dihindari. Muskulus puborektalis merupakan otot seran lintang yang persarafannya berasal
dari cabang somatik nervus pudendus Sakral 2, 3 dan 4 yang berfungsi mempertahankan
sudut anorektal dalam keadaan normal yang berkisar antara 60 derajat sampai 105 derajat.
(Banerjee dan Wilkin, 1993).
Dasar pathofisiologi terjadinya penyakit Hirschsprung adalah gangguan propagasi gelombang
propulsi usus serta gangguan atau tiadanya relaksasi sfingter ani interna (Holschneider dan
Ure, 2005).
3. Defekasi
Dalam keadaan istirahat lumen saluran anus akan menutup akibat puborektal sling yang
terletak disebelah kranial linea pektinea dan oleh tonus istirahat sfingter interna dan eksterna
yang terletak setinggi dan dibawah katub anal. Feses dan material-material sisa yang telah
berada di rektum akan menyebabkan kenaikan tekanan didalam rongga rektum sehingga akan
memacu reseptor regangan dan mulailah reflek defekasi. Reflek defekasi akan menyebabkan
relaksasi sfingter interna, kontraksi pada sigmoid dan rektum. Distensi rektum ini akan
disertai kemauan sadar untuk melakukan buang air besar dan apabila otot sfingter eksterna
juga mengalami relaksasi maka defekasi akan terjadi. Bilamana keadaan lingkungan tidak
memungkinkan untuk defekasi maka sfingter eksterna akan kontraksi sehingga defekasi akan
dapat dicegah. Penundaan defekasi akan menyebabkan rektum secara bertahap melakukan
gerakan relaksasi dan kemauan untuk defekasi akan menurun sampai gerakan “mass
movement” berikutnya yang akan mendorong lebih banyak feses. Selama periode non
aktivitas keadaan sfingter interna dan eksterna tetap berada pada posisi kontraksi untuk
menjaga kontinensi. (Scharli, 1987)
Proses defekasi dibantu oleh gerakan mengejan yang melibatkan kontraksi otot dinding perut
dan ekspirasi kuat dalam posisi glotis tertutup yang akan menyebabkan tekanan
intraabdominal meningkat. Sfingter interna merupakan bagian akhir otot pendorong yang
secara aktif mengeluarkan feses atau flatus melalui anus. Serabut otot ini yang terdiri atas
otot sirkuler dan longitudinal membantu peristaltik diseluruh saluran anal sampai ke
orifisium. Bagian longitudinal yang sebagian berasal dari otot pubococcygeus dan sebagian
dari otot rektum involunter, secara aktif menimbulkan ektropion anus selama fase peristaltik
pengeluaran feses (Scharli, 1987).
D. Insidensi
Insidens penyakit Hirschsprung adalah 1 dalam 5000 kelahiran hidup. Dengan jumlah
penduduk Indonesia 200 juta dan tingkat kelahiran 35 permil, maka diprediksikan setiap
tahun akan lahir 1400 bayi dengan penyakit Hirschsprung. Kartono mencatat 20-40 pasien
penyakit Hirschsprung yang dirujuk setiap tahunnya ke RSUPN Cipto Mangunkusomo
Jakarta dengan rasio laki-laki : perempuan adalah 4 : 1. Insidensi ini dipengaruhi oleh group
etnik, untuk Afrika dan Amerika adalah 2,1 dalam 10.000 kelahiran, Caucassian 1,5 dalam
10.000 kelahiran dan Asia 2,8 dalam 10.000 kelahiran. (Holschneider dan Ure, 2005;
Kartono,1993)
Menurut catatan Swenson, 81,1 % dari 880 kasus yang diteliti adalah laki-laki. Sedangkan
Richardson dan Brown menemukan tendensi faktor keturunan pada penyakit ini (ditemukan
57 kasus dalam 24 keluarga). Beberapa kelainan kongenital dapat ditemukan bersamaan
dengan penyakit Hirschsprung, namun hanya 2 kelainan yang memiliki angka yang cukup
signifikan yakni Down Syndrome (5-10 %) dan kelainan urologi (3%). Hanya saja dengan
adanya fekaloma, maka dijumpai gangguan urologi seperti refluks
vesikoureter,hydronephrosis dan gangguan vesica urinaria (mencapai 1/3 kasus) (Swenson
dkk,1990).
E. Diagnosis
1. Gambaran Klinis
Gambaran klinis penyakit Hirschsprung dapat kita bedakan berdasarkan usia gejala klinis
mulai terlihat :
(i). Periode Neonatal. Ada trias gejala klinis yang sering dijumpai, yakni pengeluaran
mekonium yang terlambat, muntah hijau dan distensi abdomen. Pengeluaran mekonium yang
terlambat (lebih dari 24 jam pertama) merupakan tanda klinis yang signifikans. Swenson
(1973) mencatat angka 94% dari pengamatan terhadap 501 kasus sedangkan Kartono
mencatat angka 93,5% untuk waktu 24 jam dan 72,4% untuk waktu 48 jam setelah lahir.
Muntah hijau dan distensi abdomen biasanya dapat berkurang manakala mekonium dapat
dikeluarkan segera. Sedangkan enterokolitis merupakan ancaman komplikasi yang serius bagi
penderita penyakit Hirschsprung ini, yang dapat menyerang pada usia kapan saja, namun
paling tinggi saat usia 2-4 minggu, meskipun sudah dapat dijumpai pada usia 1 minggu.
Gejalanya berupa diarrhea, distensi abdomen, feces berbau busuk dan disertai demam.
Swenson mencatat hampir 1/3 kasus Hirschsprung datang dengan manifestasi klinis
enterokolitis, bahkan dapat pula terjadi meski telah dilakukan kolostomi (Kartono,1993;
Fonkalsrud et al,1997; Swenson et al,1990).
(ii). Anak. Pada anak yang lebih besar, gejala klinis yang menonjol adalah konstipasi kronis
dan gizi buruk (failure to thrive). Dapat pula terlihat gerakan peristaltik usus di dinding
abdomen. Jika dilakukan pemeriksaan colok dubur, maka feces biasanya keluar menyemprot,
konsistensi semi-liquid dan berbau tidak sedap. Penderita biasanya buang air besar tidak
teratur, sekali dalam beberapa hari dan biasanya sulit untuk defekasi. (Kartono,1993;
Fonkalsrud et al,1997; Swenson et al,1990). (Gambar 7)
Gambar 10. Foto anak yang telah besar, sebelum dan sesudah tindakan definitif bedah.
Terlihat status gizi anak membaik setelah operasi (Kartono, 2004).
2. Pemeriksaan Radiologi
Pemeriksaan radiologi merupakan pemeriksaan yang penting pada penyakit Hirschsprung.
Pada foto polos abdomen dapat dijumpai gambaran obstruksi usus letak rendah, meski pada
bayi sulit untuk membedakan usus halus dan usus besar (Gambar. 11). Pemeriksaan yang
merupakan standard dalam menegakkan diagnosa Hirschsprung adalah barium enema,
dimana akan dijumpai 3 tanda khas:
1. Tampak daerah penyempitan di bagian rektum ke proksimal yang panjangnya
bervariasi.
2. Terdapat daerah transisi, terlihat di proksimal daerah penyempitan ke arah daerah
dilatasi;
3. Terdapat daerah pelebaran lumen di proksimal daerah transisi
(Kartono,1993).
Apabila dari foto barium enema tidak terlihat tanda-tanda khas penyakit Hirschsprung, maka
dapat dilanjutkan dengan foto retensi barium, yakni foto setelah 24-48 jam barium dibiarkan
membaur dengan feces. Gambaran khasnya adalah terlihatnya barium yang membaur dengan
feces kearah proksimal kolon. Sedangkan pada penderita yang bukan Hirschsprung namun
disertai dengan obstipasi kronis, maka barium terlihat menggumpal di daerah rektum dan
sigmoid (Kartono,1993, Fonkalsrud dkk,1997; Swenson dkk,1990).
Gambar 11. Foto Polos Abdomen tampak dilatasi sistema usus dan tiadanya gas di rektum
(Obstruksi Usus Letak Rendah)
Gambar. 12. Gambar barium enema penderita Hirschsprung. Tampak rektum yang
mengalami penyempitan, diikuti zona transisi kemudian sigmoid yang melebar (zona
dilatasi).
3. Pemeriksaan patologi anatomi
Diagnosa histopatologi penyakit Hirschsprung didasarkan atas absennya sel ganglion pada
pleksus mienterik (Auerbach) dan pleksus sub-mukosa (Meissner). Disamping itu akan
terlihat dalam jumlah banyak penebalan serabut syaraf (parasimpatis). Akurasi pemeriksaan
akan semakin tinggi jika menggunakan pengecatan immunohistokimia asetilkolinesterase,
suatu enzim yang banyak ditemukan pada serabut syaraf parasimpatis, dibandingkan dengan
pengecatan konvensional dengan haematoxylin eosin. Disamping
memakai asetilkolinesterase, juga digunakan pewarnaan protein S-100, metode peroksidase-
antiperoksidase dan pewarnaan enolase. Hanya saja pengecatan immunohistokimia
memerlukan ahli patologi anatomi yang berpengalaman, sebab beberapa keadaan dapat
memberikan interpretasi yang berbeda seperti dengan adanya perdarahan (Kartono, 2004).
Biasanya biopsi hisap dilakukan pada 3 tempat : 2, 3, dan 5 cm proksimal dari anal verge.
Apabila hasil biopsi hisap meragukan, barulah dilakukan biopsi eksisi otot rektum untuk
menilai pleksus Auerbach. Dalam laporannya, Polley (1986) melakukan 309 kasus biopsi
hisap rektum tanpa ada hasil negatif palsu dan komplikasi (Kartono,1993; Swenson
dkk,1990; Swenson,2002).
4. Manometri anorektal
Pemeriksaan manometri anorektal adalah suatu pemeriksaan obyektif mempelajari fungsi
fisiologi defekasi pada penyakit yang melibatkan spinkter anorektal. Dalam prakteknya,
manometri anorektal dilaksanakan apabila hasil pemeriksaan klinis, radiologis dan histologis
meragukan. Pada dasarnya, alat ini memiliki 2 komponen dasar : transduser yang sensitif
terhadap tekanan seperti balon mikro dan kateter mikro, serta sisitem pencatat
seperti poligraph atau komputer (Shafik, 2000; Wexner, 2000; Neto et al, 2000).
Beberapa hasil manometri anorektal yang spesifik bagi penyakit Hirschsprung adalah :
1. Hiperaktivitas pada segmen yang dilatasi;

2. Tidak dijumpai kontraksi peristaltik yang terkoordinasi pada segmen usus
aganglionik;
3. Sampling reflex tidak berkembang. Tidak dijumpai relaksasi spinkter interna setelah
distensi rektum akibat desakan feces. Tidak dijumpai relaksasi spontan (Kartono,
1993).
Gambar 13. Tampak gambar skema dari manometri anorekatal, yang memakai balon berisi
udara sebagai transducernya. Pada penderita Hirschsprung (kanan), tidak terlihat relaksasi
spinkter ani (Kartono, 1993)
1. F. Diagnosis Banding.
Diagnosis banding kelainan ini antara lain mekonium ileus akibat penyakit fibrokistik, atresia
ileum, atresia rekti, malrotasi, duplikasi intestinal dan sindrom pseudo obstruksi intestinal.
Puri (1997) menyatakan banyak kelainan-kelainan yang menyerupai penyakit Hirschsprung
akan tetapi pada pemeriksaan patologi anatomi ternyata didapatkan sel-sel ganglion.
Kelainan-kelainan tersebut antara lain Intestinal neuronal dysplasia, Hypoganglionosis,
Immature ganglia, Absence of argyrophyl plexus, Internal sphincter achalasia dan kelainan-
kelainan otot polos (Puri, 1997).
G. Terapi Penyakit Hirschsprung.
Pada prinsipnya, sampai saat ini, penyembuhan penyakit Hirschsprung hanya dapat dicapai
dengan pembedahan. Tindakan-tindakan medis dapat dilakukan tetapi hanya untuk sementara
dimaksudkan untuk menangani distensi abdomen dengan pemasangan pipa anus atau
pemasangan pipa lambung dan irigasi rektum. Pemberian antibiotika dimaksudkan untuk
pencegahan infeksi terutama untuk enterokolitis dan mencegah terjadinya sepsis. Cairan infus
dapat diberikan untuk menjaga kondisi nutrisi penderita serta untuk menjaga keseimbangan
cairan, elektrolit dan asam basa tubuh (Kartono, 2003).
Penanganan bedah pada umumnya terdiri atas dua tahap yaitu tahap pertama dengan
pembuatan kolostomi dan tahap kedua dengan melakukan operasi definitif. Tahap pertama
dimaksudkan sebagai tindakan darurat untuk mencegah komplikasi dan kematian. Pada
tahapan ini dilakukan kolostomi, sehingga akan menghilangkan distensi abdomen dan akan
memperbaiki kondisi pasien.Tahapan kedua adalah dengan melakukan operasi definitif
dengan membuang segmen yang aganglionik dan kemudian melakukan anastomosis antara
usus yang ganglionik dengan dengan bagian bawah rektum. (Kartono, 2004).
Dikenal beberapa prosedur operasi yaitu prosedur Swenson, prosedur Duhamel, prosedur
Soave, prosedur Rehbein dengan cara reseksi anterior, prosedur Laparoskopic Pull-Through,
prosedur Transanal Endorectal Pull-Through dan prosedur miomektomi anorektal. (Lee,
2002; Teitelbaum, 2003).
Persiapan operasi.
Setelah diagnosis penyakit Hirshprung ditegakkan maka sejumlah tindakan preoperasi harus
dikerjakan terlebih dahulu. Apabila penderita dalam keadaan dehidrasi atau sepsis maka
harus dilakukan stabilisasi dan resusitasi dengan pemberian cairan intra vena , antibiotik dan
pemasangan pipa lambung. Apabila sebelum operasi ternyata telah mengalami enterokolitis
maka resusitasi cairan dilakukan secara agresif, peberian antibiotika broad spektrum secara
ketat kemudian segera dilakukan tindakan dekompresi usus ( Langer, 2005 ).
Teitelbaum (2003) melakukan serial pencucian rektum dengan memberikan 10 ml/kg BB
pada setiap kali pencucian dengan menggunakan pipa rektum ukuran 18-20. Pada penderita
kemudian diberikan antibiotik intavena.
1. Prosedur Swenson
Prosedur ini adalah prosedur pertama untuk operasi penyakit Hirschsprung dengan metode
“pull-through”. Tehnik ini diperkenalkan pertama kali oleh Swenson dan Bill pada tahun
1948. Segmen yang aganglionik direseksi dan puntung rektum ditinggalkan 2-4 cm dari garis
mukokutan kemudian dilakukan anastomosis langsung diluar rongga peritoneal. Pada
prosedur ini enterokolitis masih dapat terjadi sebagai akibat spasme puntung rektum yang
ditinggalkan. Untuk mengatasi hal ini Swenson melakukan sfingterektomi parsial posterior.
Prosedur ini disebut prosedur Swenson I (Lee, 2003; Kartono , 2004; Teitelbaum, 2003 ).
Pada 1964 Swenson memperkenalkan prosedur Swenson II dimana setelah dilakukan
pemotongan segmen kolon yang aganglionik, puntung rektum ditinggalkan 2 cm di bagian
anterior dan 0,5 cm di bagian posterior kemudian langsung dilakukan sfingterektomi parsial
langsung. Ternyata prosedur ini sama sekali tidak mengurangi spasme sfingter ani dan tidak
mengurangi komplikasi enterokolitis pasca bedah dan bahkan pada prosedur Swenson II
kebocoran anastomosis lebih tinggi dibanding dengan prosedur Swenson I (Lee, 2003;
Kartono , 2004; Teitelbaum, 2003 ).
Gambar 14. Prosedur Swenson
2. Prosedur Duhamel.
Prosedur ini diperkenalkan pada tahun 1956 sebagai modifikasi prosedur Swenson oleh
karena pada metode Swenson dapat terjadi kerusakan nervi erigentes yang memberi
persarafan pada viscera daerah pelvis. Duhamel melakukan diseksi retrorektal untuk
menghindari kerusakan tersebut dengan cara melakukan penarikan kolon proksimal yang
ganglionik melalui bagian posterior rektum. Penderita ditidurkan dalam posisi litotomi,
dipasang kateter sehingga vesika urinaria kosong dengan maksud agar visualisasi rongga
abdomen lebih jelas. Irisan kulit abdomen dilakukan secara paramedian atau transversal.
Arteria hemorrhoidalis superior dipotong diikuti pemotongan mesorektum dan rektum. Kolon
proksimal dimobilisir sehingga panjang kolon akan mencapai anus. Perhatian khusus
ditujukan pada viabilitas pembuluh darah dan kolon proksimal dengan cara menghindari
regangan yang berlebihan. Setelah segmen kolon yang aganglionik direseksi, puntung rektum
dipotong sekitar 2-3 cm diatas dasar refleksi peritonium dan ditutup dengan jahitan dua lapis.
Rongga retrorektal dibuka sehingga seluruh permukaan dinding belakang rektum dibebaskan.
(Holschneider, 2005; Langer, 2005).
Pada dinding belakang rektum 0,5 cm dari linea dentata dibuat sayatan endoanal setengah
lingkaran dan dari lobang sayatan ini segmen kolon proksimal yang berganglion ditarik ke
distal keluar melewati lubang anus dan dibiarkan bebas menggelantung kemudian dilakukan
anastomosis “end to side” setinggi sfingter ani internus. Anastomosis dilakukan dengan
pemasangan 2 buah klem Kocher dimana dalam jangka waktu 6-8 hari anastomosis telah
terjadi. Stenosis dapat terjadi akibat pemotongan septum yang tidak sempurna (Holschneider,
2005; Langer, 2005).
Gambar 15. Prosedur Duhamel
3. Prosedur ENDORECTAL PULL THROUGH ( SOAVE ).
Pada prinsipnya tehnik ini adalah merupakan diseksi ekstramukosa rektosigmoid yang mula-
mula dipergunakan untuk operasi atresia ani letak tinggi. Persiapan preoperasi yang harus
dilakukan adalah irigasi rektum, dilatasi anorektal manual serta pemberian antibiotik. (
Kartono, 2004 )
Tahun 1960 Soave melakukan pendekatan abdominoperineal, dengan membuang lapisan
mukosa rektosigmoid. Posisi pasien terlentang dengan fleksi pelvis 30 derajat, irisan kulit
abdomen pararektal kiri melewati lubang kolostomi dan dipasang kateter ( Kartono, 2004 )
Dinding abdomen dibuka perlapis sampai mencapai peritonium kemudian dilakukan
preparasi kolon kiri. Kolon distal dimobilisasi dan direseksi 4 cm diatas refleksi peritoneum.
Dibuat jahitan traksi pada kolon distal yang telah direseksi kemudian mukosa dipisahkan dari
muskularis kearah distal. Lapisan otot secara tumpul didorong kedistal hingga 1-2 cm diatas
linea dentata. Lewat anus dibuat insisi melingkar 1 cm diatas linea dentata. Kolon yang
berganglion kemudian ditarik kedistal melewati cerobong endorektal. Sisa kolon yang
diprolapskan lewat anus dipotong setelah 21 hari. ( Kartono, 2004 ).
Gambar
16. Prosedur Endorectal Pull Through (SOAVE)
4. Prosedur Boley.
Prosedur Boley sangat mirip dengan prosedur Soave akan tetapi anastomosis dilakukan
secara langsung tanpa memprolapskan kolon terlebih dulu ( Kartono, 2004 ).
5 . Prosedur Rehbein.
Setelah dilakukan reseksi segmen yang aganglionik kemudian dilakukan anastomosis “end to
end” antara kolon yang berganglion dengan sisa rektum, yang dikerjakan intraabdominal
ekstraperitoneal. Tehnik ini sering menimbulkan obstipasi akibat sisa rektum yang
aganglionik masih panjang (Rehbein, 1966; Holschneider dan Ure, 2005).
Gambar 17. Prosedur Rehbein
6. Prosedur miomektomi anorektal.
Pada pasien-pasien dengan penyakit Hirschsprung segmen ultra pendek, pengangkatan satu
strip otot pada linea mediana dinding posterior rektum dapat dilakukan dan prosedur ini
disebut miomektomi anorektal, dimana dengan lebar 1 cm satu strip dinding rektum
ekstramukosa diangkat, mulai dari proksimal linea dentata sampai daerah yang berganglion (
Teitelbaum at al, 2003 ).
7. Prosedur Transanal Endorectal Pull-Through.
Tehnik ini dilakukan dengan pendekatan lewat anus. Setelah dilakukan dilatasi anus dan
pembersihan rongga anorektal dengan povidon-iodine, mukosa rektum diinsisi melingkar 1
sampai 1,5 cm diatas linea dentata. Dengan diseksi tumpul rongga submukosa yang terjadi
diperluas hingga 6 sampai 7 cm kearah proksimal. Mukosa yang telah terlepas dari
muskularis ditarik ke distal sampai melewati anus sehingga terbentuk cerobong otot rektum
tanpa mukosa (Tore, 2000 ).
Keuntungan prosedur ini antara lain lama pemondokan dan operasi lebih singkat, waktu
operasi lebih singkat, perdarahan minimal, feeding dapat diberikan lebih awal, biaya lebih
rendah, skar abdomen tidak ada. Akan tetapi masih didapatkan komplikasi enterokolitis,
konsipasi dan striktur anastomosis.
8. Posterior Sagital Neurektomi Repair for Hirschsprung Disease
Teknik ini diperkenalkan oleh Rochadi, 2005. Rincian teknik operasi adalah sebagai berikut:
Pesiapan preoperasi :
Pemeriksaan fisik yang teliti, penilaian keadaan umum penderita, adanya kelainan bawaan
yang lain, pemeriksaan laboratorium rutin, albumin dan pemeriksaan rontgen dievaluasi
secara cermat untuk menentukan ada tidaknya kontraindikasi pembedahan dan pembiusan.
Bila ada dehidrasi, sepsis, gangguan eletrolit, enterokolitis, anemia atau gangguan asam basa
tubuh semuanya harus dikoreksi terlebih dahulu. Pencucian rektum dilakukan dengan cara
pemasangan pipa rektum dan kemudian dimasukkan air hangat 10 ml/kg berat badan.
Informed consent dilakukan kepada keluarga meliputi cara operasi, perkiraan lama operasi,
lama perawatan, komplikasi-komplikasi,cara-cara penanganan apabila terjadi komplikasi dan
kemungkinan-kemungkinan terburuk yang mungkin terjadi (Rochadi, 2007).
Jalannya operasi :
Setelah dilakukan pembiusan, kemudian dipasang pipa lambung dan kateter. Dipasang infus
pada tangan dengan menggunakan abbocath yang sesuai dengan umur penderita. Tehnik ini
dilakukan dengan posisi pasien tertelungkup Rochadi, 2007).
Setelah dilakukan desinfeksi pada daerah anogluteal kemudian daerah operasi ditutup doek
steril. Irisan pertama dimulai dengan irisan kulit intergluteal dilanjutkan membuka lapisan-
lapisan otot yang menyusun “muscle complex” secara tumpul dan tajam sehingga terlihat
dinding rektum. Lapisan otot dinding rektum dibuka memanjang sampai terlihat lapisan
mukosa menyembul dari irisan operasi. Identifikasi daerah setinggi linea dentata dilakukan
dengan cara memasukkan jari telunjuk tangan kiri ke anus. Panjang irisan adalah 1 cm
proksimal linea dentata sampai zone transisi yang ditandai dengan adanya perubahan
diameter dinding rektum. Agar supaya tidak melukai mukosa rektum maka setelah mukosa
menyembul, muskularis dinding rektum dipisahkan dari mukosa dengan cara tumpul
sehingga lapisan muskularis benar-benar telah terpisah dari mukosa. Strip muskularis dinding
rektum dengan lebar 0,5 cm dilepaskan dari mukosa sepanjang zone spastik sampai zone
transisi. Material ini dikirim ke bagian Patologi Anatomi untuk pemeriksaan pewarnaan
hematoksilin-eosin guna identifikasi sel ganglion Auerbach dan Meissner (Rochadi, 2007).
Lapisan-lapisan otot muscle complex ditutup kembali seperti semula dengan benang Vicryl
3/0 diikuti lapisan subkutis dengan benang plain cat-gut 2/0 dan lapisan kulit dijahit intra
kutan dengan benang Vicryl 3/0. Dipasang pipa rektum untuk mencegah terjadinya infeksi
pada irisan operasi (Rochadi, 2007).
Tehnik Posterior Sagittal Repair for Hirschsprung’s Disease ini dilakukan satu tahap, tanpa
kolostomi dan tanpa pull –through (Rochadi, 2007).
Perawatan pasca operasi :
Penderita dirawat langsung dibangsal perawatan, kecuali apabila ada indikasi dirawat terlebih
dahulu di Intensive Care Unit (ICU) untuk pengamatan pasca operasi yang ketat. Pipa
lambung dilepas apabila fungsi gastrointestinal telah kembali normal dan kateter dilepas pada
hari kedua perawatan. Antibiotik diberikan sampai 2 hari pasca operasi. Pengawasan yang
teliti pada daerah perineum untuk mencegah terjadinya infeksi dengan melihat ada tidaknya
eritema atau selulitis. Untuk mencegah ekskoriasis diberikan salf zinc dan tiap hari kasa
betadin diganti untuk menutup irisan operasi. Apabila tidak ada komplikasi penderita dapat
dipulangkan pada hari ke empat pasca operasi. Dilatasi anorektal dimulai pada hari ke tujuh
pasca operasi dengan menggunakan busi hegar nomer enam, mula-mula dikerjakan di
poliklinik dan kemudian dilanjutkan dirumah. Tindakan ini dilakukan untuk mencegah
terjadinya striktur. Apabila terjadi enterokolitis maka diperlukan tindakan pencucian rektum,
pemberian antibiotik dan suspensi kaolin-pektin (Rochadi, 2007).
Gambar 18. Prosedur PSNRHD (Rochadi, 2007).
Pada tehnik operasi ini penderita ditidurkan dalam posisi tertelungkup dengan pertimbangan
bahwa secara topografi rektum berada pada rongga pelvis, sehingga tindakan bedah secara
PSNRHD akan dapat langsung menuju target operasi, sedangkan pada tehnik ERPT target
operasi hanya dapat dicapai dengan membuat sayatan pada dinding depan perut, membuka
peritonium posterior, memotong arteri dan vena hemorrhoidalis superior, memotong arteri
dan vena sigmoidea dan bahkan kadang-kadang harus memotong arteri dan vena kolika
sinistra. Kecuali hal tesebut diatas posisi telungkup pada operasi PSRHD akan memberikan
lapangan pandangan operasi yang lebih jelas oleh karena masuknya persarafan menuju
dinding rektum adalah lewat bagian posterior sehingga tindakan neurektomi akan lebih
mudah dikerjakan (Rochadi, 2007).
H. Permasalahan-Permasalahan Pembedahan
Permasalahan pembedahan yang sering dijumpai adalah masalah komplikasi pasca bedah.
Kebocoran anastomosis, stenosis, gangguan fungsi sfingter ani ,enterokolitis serta mortalitas
masih merupakan permasalahan yang serius. Komplikasi yang timbul dalam 4 minggu
pertama merupakan komplikasi dini pasca bedah. Prosedur bedah manapun yang dipilih
mempunyai kecenderungan untuk menimbulkan komplikasi. Usia pada saat pembedahan,
keadaan umum prabedah, prosedur bedah yang digunakan, ketrampilan dan pengalaman ahli
bedah, antibiotika yang dipakai serta perawatan pasca bedah sangat berpengaruh untuk
terjadinya komplikasi. Lebih muda usia pasien serta keadaan umum praoperasi yang kurang
optimal umumnya lebih sering mengalami komplikasi (Rehbein, 1966; Langer, 2005).
Prosedur –prosedur operasi tersebut dapat menyebabkan trauma pada persarafan traktus
genitourinarius dan otot-otot dasar panggul yang akan mengakibatkan masalah pada traktus
urinarius bagian bawah. Inkontinensia urin yang terjadi setelah operasi dengan prosedur
Rehbein 5,4%, prosedur Swenson 10,4%, prosedur Soave 15,3% dan prosedur Duhamel
14,3%.
H. 1. Perawatan Pasca Operasi.
Pipa lambung dilepas apabila fungsi gastrointestinal telah kembali normal, sedangkan kateter
dilepas pada hari kedua pasca operasi. Antibiotik dapat diberikan sampai 2 hari pasca operasi.
Perhatian khusus ditujukan pada daerah perineum untuk terjadinya eritema dan selulitis yang
dapat merupakan tanda awal dari kebocoran anastomosis (Teitelbaum et al, 2003).
Dilatasi anorektal dapat dilakukan tiga minggu setelah operasi. Pada penderita neonatus
dilatasi anorektal dapat dilakukan dengan insersi Hegar dilator nomer 6-7 yang dilakukan
dengan hati-hati untuk mencegah terjadinya striktur anastomosis. Irigasi anorektal dapat
dilakukan tiga bulan setelah operasi untuk mencegah enterokolitis (Teitelbaum et al, 2003).
Beberapa pasien mendapatkan fungsi usus yang normal setelah dilakukan operasi, akan tetapi
pada reseksi usus yang panjang dapat tejadi buang air besar yang frekwen dan berair sehingga
menyebabkan ekskoriasis pada perineum. Pada kasus yang demikian loperamid dapat
diberikan untuk menurunkan frekwensi buang air besar. Untuk agar feses menjadi padat
dapat diberikan kaolin-pectin (Holschneider dan Ure, 2005).
Hartman et al (2006) meneliti masalah fisik dan psikososial penderita penyakit Hirschsprung
yang telah dilakukan operasi dan menyarankan pengamatan pada inkontinensi feses,
inkontinensi urin, konstipasi dan disfungsi sex. Perawatan pasca operasi yang disarankan
adalah dilatasi anus, pemberian laxatif, enema, diet dan toilet. Perawatan medis harus
dilakukan bersama perawatan paramedis yaitu fisioterapi, pengobatan psikososial dan
konsultasi diet.
H. 2. Komplikasi.
Komplikasi bedah pasca operasi yang dapat terjadi antara lain perdarahan, infeksi, perlukaan
pada organ sekitar serta risiko anaestesi. Pada penderita yang dilakukan kolostomi dapat
terjadi komplikasi retraksi stoma, striktur, prolaps dan ekskoriasis kulit. Komplikasi
kebocoran usus, striktur dan retraksi setelah tindakan anastomosis dapat dicegah dengan cara
pengamatan yang teliti pada keadaan vaskularisasi kolon yang akan dilakukan pull-through
serta menjaga agar anastomosis usus tidak dalam keadaan teregang. Komplikasi-komplikasi
lain dapat muncul terlambat antara lain obstruksi, inkontinensi serta enterokolitis yang dapat
terjadi pada 50% kasus (Langer, 2005).
Komplikasi yang terjadi pasca operasi definitif dapat dibagi menjadi komplikasi awal dan
komplikasi terlambat. Disebut komplikasi awal apabila terjadi dalam 4 minggu pertama pasca
operasi dan apabila terjadi setelah waktu tersebut disebut sebagai komplikasi terlambat.
Komplikasi awal dapat terjadi akibat kesalahan prosedur operasi atau disebabkan oleh karena
infeksi. Penelitian internasional dari 16 pusat bedah anak menunjukkan kejadian kebocoran
anastomosis (7%), striktur anastomosis (15%), infeksi jaringan (11%), retraksi kolon pada
metode Swenson(3%) dan retraksi kolon dengan tehnik Soave (7%). Kompikasi terlambat
yang terjadi setelah operasi definitif meliputi konstipasi kronis, enterokolitis dan enkopresis.
Konstipasi kronis dapat terjadi akibat akhalasia sfingter ani, reseksi inkomplit, striktur dan
fekaloma. Konstipasi menetap dilaporkan terjadi pada prosedur Swenson (6%), prosedur
Duhamel (10%) dan setelah prosedur Rehbein (7%) (Elhalaby et al, 1995).
Inkontinensi feses (soiling, enkopresis) adalah ketidak mampuan untuk menahan isi rektum
dapat terjadi pada prosedur Swenson (12%), Duhamel (7%) dan Soave (3%) (Holschneider,
2005).
Surana et al (1994) melakukan evaluasi faktor-faktor risiko terjadinya enterokolitis pada 135
penderita penyakit Hirschsprung dan mendapatkan 41 (30%) mengalami enterokolitis.
Insidens enterokolitis terjadi pada 27,6% pasien dengan tipe segmen pendek dan 37,8% pada
segmen panjang. Faktor-faktor risiko tersebut adalah umur, jenis kelamin, panjang segmen
yang aganglionik, kelainan penyerta dan prosedur operasi.
H. 3. Komplikasi Enterokolitis
Enterokolitis telah dilaporkan sampai 58% kasus pada penderita penyakit Hirschsprung yang
diakibatkan oleh karena iskemia mukosa dengan invasi bakteri dan translokasi. Perubahan-
perubahan pada komponen musin dan sel neuroendokrin, kenaikan aktivitas prostaglandin
E1, infeksi Clostridium difficile atau rotavirus dicurigai sebagai penyebab terjadinya
enterokolitis (Holschneider dan Ure, 2005).
Pada keadaan yang sangat berat enterokolitis akan menyebabkan terjadinya megakolon toksik
yang ditandai dengan demam, muntah hijau, diare hebat, distensi abdomen, dehidrasi dan
syok. Terjadinya ulserasi da nekrosis akibat iskemia mukosa diatas segmen aganglionik akan
menyebakan terjadinya sepsis, pnematosis dan perforasi usus (Holschneider dan Ure, 2005).
Enterokolitis merupakan ancaman komplikasi yang serius bagi penderita penyakit
Hirschsprung ini, yang dapat menyerang pada usia kapan saja, namun paling tinggi saat usia
2-4 minggu, meskipun sudah dapat dijumpai pada usia 1 minggu. Gejalanya berupa diarrhea,
distensi abdomen, feces berbau busuk dan disertai demam. Swenson mencatat hampir 1/3
kasus Hirschsprung datang dengan manifestasi klinis enterokolitis, bahkan dapat pula terjadi
meski telah dilakukan kolostomi (Kartono,1993; Fonkalsrud dkk,1997; Swenson dkk,1990)
Kejadian enteokolitis berdasar prosedur operasi yang dipergunakan Swenson 16,9%, Boley-
Soave 14,8%, Duhamel 15,4% dan Lester Martin 20%. Gambaran klinis distensi abdomen
29, diare 38, darah pada feses 2, muntah 31, panas 22 dan takikardi 12. Storey ( 1994 )
meneliti penyebab terjadinya enterokolitis pada penderita penyakit Hirschsprung dan
menyimpulkan bahwa penyebab enterokolitis adalah multi faktoral yaitu hipersensitif pada
antigen bakteri, dilatasi kolon proksimal yang mengakibatkan iskemia, kelainan mukosubstan
kolon, kenaikan aktifitas prostaglandin E1, kelainan immunologis dan infeksi bakteri patogen
clostridium difficile, rotavirus, psudomonas (Storey, 1994).
Mattar et al (2003) menyatakan bahwa ekspresi protein MUC-2 mengalami penurunan pada
penderita penyakit Hirschsprung dan tidak terdeteksi pada penderita yang mengalami
enterokolitis. Disarankan untuk memeriksa ekspresi protein MUC-2 dari material feses
penderita untuk memprediksi enterokolitis yang dapat terjadi sebelum, selama dan sesudah
dilakukan tindakan operasi.

Hirsch Sprung

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Hirsch Sprung

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Background

Hirschsprung disease is a developmental disorder characterized by absence of ganglia in the

<em>A:</em> Plain abdominal

A 22-year-old man presented with

Computed tomography scan from

Chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction

Large amount of stool throughout colon.

Anatomi dan Fisiologi

Vaskularisasi rektum dan anus :

Persarafan rektum dan anus :

1. Mekonium terlambat keluar > 24 jam.

2. Operasi Definitif (pull through)

Megacolon Congenital / Hirschprung Disease

1. Hiperaktivitas pada segmen yang dilatasi;

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