Hirschsprung Disease

Hirschsprung disease (HD), also known as congenital Congenital Chorioretinitis aganglionosis or congenital Congenital Chorioretinitis megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon, is a congenital Congenital Chorioretinitis anomaly of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy caused by the failure of neural crest-derived ganglion cells Ganglion Cells The Visual Pathway and Related Disorders to migrate into the distal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy. The lack of innervation always involves the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy and extends proximally and contiguously over variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables distances. Most cases are diagnosed in the neonatal period, with a classic triad of symptoms including delayed passage of meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate, abdominal distension, and bilious vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia. Individuals having less severe degrees of functional obstruction may not be diagnosed until later in infancy or childhood when they present with symptoms of chronic refractory constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation, abdominal distension, and failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive. The diagnosis of HD is confirmed by the absence of ganglion cells Ganglion Cells The Visual Pathway and Related Disorders on rectal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma after noninvasive testing such as anorectal manometry Manometry Measurement of the pressure or tension of liquids or gases with a manometer. Achalasia and the use of contrast enema. Surgical resection of the aganglionic segment is the standard treatment.

Last updated: Aug 15, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Hirschsprung disease (HD), also known as congenital Congenital Chorioretinitis aganglionosis or congenital Congenital Chorioretinitis megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon, is a congenital Congenital Chorioretinitis anomaly of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy caused by the failure of neural crest-derived ganglion cells Ganglion Cells The Visual Pathway and Related Disorders to migrate into the distal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy.

Classification

  • Sporadic:
    • Most common (70%)
    • ⅓ of cases have > 1 RET mutations.
  • Familial forms: Approximately half of the cases have > 1 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (RET) mutations.
  • As part of a genetic syndrome:
    • Down syndrome Down syndrome Down syndrome, or trisomy 21, is the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Both boys and girls are affected and have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, gastrointestinal, ocular, and auditory systems. Down syndrome (Trisomy 21) (DS)/ trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21: 
      • Approximately 10% of individuals with HD have DS.
      • < 1% of individuals with DS have HD.
    • Waardenburg syndrome: 
    • Mowat-Wilson syndrome:
      • Intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment, microcephaly Microcephaly A congenital abnormality in which the cerebrum is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (desk reference for neuroscience, 2nd ed. ). Fetal Alcohol Spectrum Disorder
      • 41%–71% of cases have HD.
    • MEN type 2A (MEN2A): medullary thyroid cancer Thyroid cancer Thyroid cancer is a malignancy arising from the thyroid gland cells: thyroid follicular cells (papillary, follicular, and anaplastic carcinomas) and calcitonin-producing C cells (medullary carcinomas). Rare cancers are derived from the lymphocytes (lymphoma) and/or stromal and vascular elements (sarcoma). Thyroid Cancer and pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma with or without primary hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism

Epidemiology

  • Annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is approximately 1 in 5,000 live births in the US.
  • The men:women ratio is 3–4:1, but is closer to 1:1 when the entire colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy is involved.
  • More common in populations of Asian descent

Etiology

  • HD is associated with mutations in multiple genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure that are important for the growth and differentiation of neural crest cells Neural crest cells Gastrulation and Neurulation, most commonly in the RET gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics.
  • Environmental factors and modifying genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure (some sex-linked) are likely contributors.

Pathophysiology

The pathophysiology in HD is the complete absence of ganglion cells Ganglion Cells The Visual Pathway and Related Disorders (aganglionosis) in the intrinsic nerve supply of the bowel due to the failure of neural crest-derived ganglion cells Ganglion Cells The Visual Pathway and Related Disorders to migrate completely into the myenteric plexuses of the wall of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy.

  • Extends proximally from the anal sphincter and involves varying lengths of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy
  • Always involves the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy 
  • Results in functional obstruction due to the arrest of peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility at the point of the arrest of the migration
  • Aganglionic segment also has abnormal alterations in the expression of receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, channels Channels The Cell: Cell Membrane, cytoskeletal proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, and neurotrophic factors.
  • Gross pathology:
    • Rectosigmoid colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy is most common (“short-segment disease”): 80%
    • Extension Extension Examination of the Upper Limbs proximal to the sigmoid colon Sigmoid colon A segment of the colon between the rectum and the descending colon. Colon, Cecum, and Appendix: Anatomy (“long-segment disease”): 15%–20% 
    • Total colonic aganglionosis: 5% of cases; rarely involves the ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy or entire small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
    • Muscular hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation and dilatation of bowel proximal to obstruction, with possible progression to megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon and rupture (usually in the cecum Cecum The blind sac or outpouching area of the large intestine that is below the entrance of the small intestine. It has a worm-like extension, the vermiform appendix. Colon, Cecum, and Appendix: Anatomy)
  • Microscopic pathology:
    • Absent enteric ganglion cells Ganglion Cells The Visual Pathway and Related Disorders in the submucosal (Meissner) and myenteric (Auerbach) plexuses in the distal rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy and variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables length of the proximal contiguous intestine
    • Hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation of aganglionic myenteric nerves ( variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables)

Clinical Presentation

Most individuals with HD are diagnosed in the 1st month of life. Individuals with less severe disease may not present with symptoms until 3 years of age in approximately 10% of cases.

  • Classic triad of symptoms:
    • Delayed passage of meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate (> 48 hours in a term infant)
    • Abdominal distension
    • Bilious vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Additional signs and symptoms in the neonatal period:
    • Explosive expulsion of gas and stool after digital rectal examination Digital Rectal Examination A physical examination in which the qualified health care worker inserts a lubricated, gloved finger of one hand into the rectum and may use the other hand to press on the lower abdomen or pelvic area to palpate for abnormalities in the lower rectum, and nearby organs or tissues. The method is commonly used to check the lower rectum, the prostate gland in men, and the uterus and ovaries in women. Prostate Cancer Screening, signifying temporary relief of obstruction
    • Enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis (more common if the diagnosis is delayed): 
      • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
      • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, and abdominal distension, which can lead to toxic megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon
    • Sigmoid Sigmoid A segment of the colon between the rectum and the descending colon. Volvulus or other volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus
    • Appendiceal perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
  • Later presentations: 
    • Less severe degrees of functional obstruction
    • Some cases may have “ultrashort-segment HD” (< 4 cm from the internal anal sphincter Internal anal sphincter Rectum and Anal Canal: Anatomy).
    • Symptoms and signs:
      • Chronic refractory constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
      • Abdominal distension
      • Failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive
  • Associated congenital Congenital Chorioretinitis anomalies:
    • Present in 20%–25% of individuals with HD
    • Congenital Congenital Chorioretinitis heart disease in 50% of syndromic cases, especially in those with DS
    • Genitourinary anomalies:
      • Hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis
      • Renal hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS)
    • Visual anomalies: refractory and other visual defects
    • Hearing impairment Hearing impairment Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
    • Anorectal malformations

Diagnosis and Management

Diagnosis

If HD is suspected based on the clinical presentations in the neonatal or postnatal periods, the following diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests are used:

  • Contrast enema: may show the pathognomonic sign of the “ transition zone Transition Zone Pediatric Gastrointestinal Abnormalities” (funnel-shaped segment between the aganglionic rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy and the proximal dilated colon Dilated colon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon)
  • Anorectal manometry Manometry Measurement of the pressure or tension of liquids or gases with a manometer. Achalasia:
  • Abdominal X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests: not usually necessary, but shows decreased or no air in the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy
  • Rectal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: necessary for confirmation of the diagnosis, and documents the absence of ganglion cells Ganglion Cells The Visual Pathway and Related Disorders
Hirschsprung disease seen on contrast barium enema study

Hirschsprung disease as seen on contrast barium enema Barium enema X-ray examination of lower gastrointestinal tract. Imaging is done while a barium compound (e.g., barium sulfate) fills the large intestine via the rectum as a contrast material. Diarrhea study, with the arrow showing the “ transition zone Transition Zone Pediatric Gastrointestinal Abnormalities” between the normal and aganglionic bowel

Image: “Contrast enema showing a CETZ at rectosigmoid, arrow” by Pratap, A., et al AL Amyloidosis. License: CC BY 2.0, cropped by Lecturio.

Management

  • Assess for associated anomalies:
    • Genitourinary ultrasound to assess for urinary system malformations
    • Screening Screening Preoperative Care for hearing impairment Hearing impairment Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
    • Screening Screening Preoperative Care for visual impairment
    • Clinical geneticist consultation, if needed, in case of possible MEN2A
  • Surgical resection of the aganglionic segment of the bowel
  • Ultrashort-segment HD (aganglionosis < 4 cm from the internal anal sphincter Internal anal sphincter Rectum and Anal Canal: Anatomy):
    • Medical management with diet, stool softeners, laxatives Laxatives Laxatives are medications used to promote defecation. Most often, laxatives are used to treat constipation or for bowel preparation for certain procedures. There are 4 main classes of laxatives: bulk-forming, stimulant, osmotic, and emollient. Laxatives, or botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism injections
    • Surgical management with myomectomy may be needed.

Complications

  • Enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis:
  • Stercoral ulcers: sharply demarcated shallow ulcers with mucosal inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation due to pressure of feces on an obstructed colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy
  • Potential complications of surgery:
    • Bowel obstruction Bowel obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis
    • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
    • Mechanical obstruction Mechanical Obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Imaging of the Intestines (e.g., stricture Stricture Primary Sclerosing Cholangitis)
    • Persistent or acquired aganglionosis → use rebiopsy to evaluate
    • Increased internal anal sphincter Internal anal sphincter Rectum and Anal Canal: Anatomy tone → botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism may help
    • Behavioral stool-withholding behavior
    • Enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis (HD-associated enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis):
      • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency rate: up to 45% postoperatively
      • Etiology: probably due to intestinal stasis
      • Signs and symptoms: abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, foul-smelling bloody diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock, intestinal necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage, and perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
      • Increased risk in long-segment disease, especially total colonic aganglionosis
      • Time course: usually occurs < 1 year after surgery
      • Treatment: IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids, antibiotics, repeated rectal irrigation
    • More common in long-segment disease:
      • Perianal excoriations Excoriations Excoriation is a linear abrasion produced by mechanical means (scratching, rubbing, or picking) that usually involves only the epidermis but can reach the papillary dermis. Secondary Skin Lesions
      • Electrolyte imbalance
      • Anastomotic leak Anastomotic leak Breakdown of the connection and subsequent leakage of effluent (fluids, secretions, air) from a surgical anastomosis of the digestive, respiratory, genitourinary, and cardiovascular systems. Most common leakages are from the breakdown of suture lines in gastrointestinal or bowel anastomosis. Bariatric Surgery
    • Volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus
    • Incontinence and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea:
    • Most individuals with DS/HD have long-term bowel disturbances:
      • Incontinence, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, soiling, enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis
      • May need a permanent colostomy
    • Urologic and sexual complications may occur:
      • Urinary incontinence Urinary incontinence Urinary incontinence (UI) is involuntary loss of bladder control or unintentional voiding, which represents a hygienic or social problem to the patient. Urinary incontinence is a symptom, a sign, and a disorder. The 5 types of UI include stress, urge, mixed, overflow, and functional. Urinary Incontinence
      • Erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • Long-term outcomes:
    • Overall: > 90% of affected individuals with HD report satisfactory outcomes.
    • Many affected individuals have disturbances of bowel function for several years.
    • Approximately 1% of affected individuals have debilitating incontinence requiring a permanent colostomy.
  • Worse outcomes are seen in:
    • Affected individuals with total colonic aganglionosis:
      • 33% have persistent incontinence.
      • 14% require a permanent ileostomy Ileostomy Surgical creation of an external opening into the ileum for fecal diversion or drainage. This replacement for the rectum is usually created in patients with severe inflammatory bowel diseases. Loop (continent) or tube (incontinent) procedures are most often employed. Large Bowel Obstruction.
    • Individuals with associated chromosomal abnormalities and syndromes

Differential Diagnosis

Causes of intestinal obstruction Intestinal obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis in the neonatal period can be distinguished from HD based on their clinical features and the presence of ganglia on a rectal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma.

  • Intestinal atresia Atresia Hypoplastic Left Heart Syndrome (HLHS): results in complete obstruction of the lumen in neonates, but is rare overall. About 50% of cases involve the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy and 20% of cases involve individuals with an associated chromosomal anomaly.
  • Duplication cyst: causes symptoms similar to that observed in an abdominal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast due to compression Compression Blunt Chest Trauma of the adjacent bowel; rare, usually in the small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy.
  • Intestinal malrotation Intestinal malrotation Intestinal malrotation is a congenital anomaly that results from failure of the GI tract to undergo normal rotation around the mesenteric vessels during embryologic development. This condition can result in several anatomic patterns characterized by abnormal location and attachments of the abdominal cavity’s intestines. Intestinal Malrotation with volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus: occurs due to arrest of the normal rotation Rotation Motion of an object in which either one or more points on a line are fixed. It is also the motion of a particle about a fixed point. X-rays of the embryonic gut. Bilious vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia in an infant could indicate an obstructive lesion.
  • Meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction ( MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction) due to cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans (CF): obstruction at the terminal ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy with inspissated meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate. Approximately 80%–90% of infants with MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction have CF. Prenatal carrier Carrier Vaccination testing and prenatal ultrasound help with proactive management.
  • MEN2: MEN2A is associated with HD; MEN2B may be associated with ganglioneuromatosis, skeletal deformations, and Marfanoid habitus Marfanoid Habitus Multiple Endocrine Neoplasia.
  • Intestinal neuronal dysplasia and other chronic or acute intestinal pseudo-obstructions: functional dysmotility disorders and not mechanical obstructions. Intestinal neuronal dysplasia and other chronic or acute intestinal pseudo-obstructions usually constitute neuropathic or myopathic causes in infants.
  • Meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate plug syndrome: a condition occurring in 1 among 500 newborns due to colonic dysmotility or abnormal consistency Consistency Dermatologic Examination of the meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate. About 15% of cases have HD. A contrast enema is both diagnostic and therapeutic.

Causes of intestinal obstruction Intestinal obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis in older infants and children:

  • Internal anal sphincter Internal anal sphincter Rectum and Anal Canal: Anatomy achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia: Diagnosis is made by anorectal manometry Manometry Measurement of the pressure or tension of liquids or gases with a manometer. Achalasia, revealing an absence of the rectosphincteric reflex on rectal balloon inflation.
  • Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism: a condition associated with increased birth weight and macroglossia Macroglossia The presence of an excessively large tongue, which may be congenital or may develop as a result of a tumor or edema due to obstruction of lymphatic vessels, or it may occur in association with hyperpituitarism or acromegaly. It also may be associated with malocclusion because of pressure of the tongue on the teeth. Wilms Tumor. Neonatal screening Screening Preoperative Care permits the early diagnosis of congenital Congenital Chorioretinitis hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism.
  • Chronic intestinal pseudo-obstruction Intestinal pseudo-obstruction A type of ileus, a functional not mechanical obstruction of the intestines. This syndrome is caused by a large number of disorders involving the smooth muscles or the nervous system. Large Bowel Obstruction: functional dysmotility disorders and not mechanical obstructions. Chronic intestinal pseudo-obstruction Intestinal pseudo-obstruction A type of ileus, a functional not mechanical obstruction of the intestines. This syndrome is caused by a large number of disorders involving the smooth muscles or the nervous system. Large Bowel Obstruction usually constitutes neuropathic or myopathic causes in infants.

References

  1. Kumar, V., Abbas, A.K., Aster, J.C. (Eds.). (2020). Hirschsprung Disease. In Robbins & Cotran Pathologic Basis of Disease. 10th ed. pp. 755–756.
  2. Wesson, D.E., Lopez, M.E. (2021). Congenital aganglionic megacolon (Hirschsprung disease). UpToDate. Retrieved July 14, 2021, from https://www.uptodate.com/contents/congenital-aganglionic-megacolon-hirschsprung-disease
  3. Wesson, D.E., Lopez, M.E. (2021). Emergency complications of Hirschsprung disease. UpToDate. Retrieved July 15, 2021, from https://www.uptodate.com/contents/emergency-complications-of-hirschsprung-disease
  4. Zhang, Z., et al. (2017). Sporadic Hirschsprung disease: Mutational spectrum and novel candidate genes revealed by next-generation sequencing. Scientific Reports. 7(1), 14796. https://doi.org/10.1038/s41598-017-14835-6
  5. Kapur, R.P., Smith, C., Ambartsumyan, L. (2020). Postoperative pull-through obstruction in Hirschsprung disease: Etiologies and diagnosis. Pediatric and Developmental Pathology. 23, 40–59. https://doi.org/10.1177/1093526619890735
  6. Wagner, J.P., Shekherdimian, S., Lee, S.L. (2020). Hirschsprung disease: Background, pathophysiology, epidemiology. Retrieved July 15, 2021, from https://emedicine.medscape.com/article/178493-overview#a2

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