Hirschprung Disease

Other Known Aliasescongenital aganglionic megacolon, congenital intestinal aganglionosis

Definitionmotor disorder of the intestines due to failure of the neural crest cells, which are precursors of ganglion cells) to fully migrate during embryonic development of the colon.

Clinical SignificanceAs a result of this aganglionosis of the colon, the distal intestines are unable to relax and cause a functional obstruction. Children affected by this condition fail to pass their meconium stool in the first 48 hours of life and may have abdominal distention, bilous emesis, and/or enterocolitis. Diagnosis is made with contrast enema and suction rectal biopsy.

HistoryNamed after Harald Hirschprung (1830-1916), who was a Danish physician and received his medical doctorate from the University of Copenhagen in 1855. In 1870, he became the first Danish pediatrician and was appointed chief physician of Queen Louisa Hospital for Children in 1879. He presented his eponymous findings at the Berlin Congress for Children’s Diseases in 1886 where he described two infants who had died from “constipation associated with dilation and hypertrophy of the colon”. He published his findings a year later in an article entitled “Stuhlträgheit Neugeborener in Folge von Dilatation und Hypertrophie des Colons”. Other notable contributions of Dr. Hirschprung include being one of the first physicians to successfully reduce intussuception by pneumatic means and being an advocate for free health care for all children.


  1. Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  2. Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
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  5. Up To Date. www.uptodate.com
  6. Hirschsprung H. Stuhlträgheit Neugeborener in Folge von Dilatation und Hypertrophie des Colons. [Constipation of newborns as a result of dilatation and hypertrophy of the colon] Jahrbuch für Kinderheilkunde und physische Erziehung 1888;27:1–7
  7. Hirschsprung H. Fälle von Angeborenen Pylorusstenose, Beobachtet bei Säuglingen. Jahrbuch für Kinderheilkunde und physische Erziehung 1888;27:61-8
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#48 – Hirschsprung Disease



  • Motor gut disorder characterized by failure of the neural crest cells (which are precursors to the enteric ganglion cells) to fully migrate to the distal portions of the colon.
    • Most accepted theory is there is a defect in the craniocaudal migration of neuroblasts that occurs between 4-7 weeks gestation
      • 12 genetic mutations currently identified predominantly affecting the RET proto-oncogene
        • Produces a tyrosine kinase protein that transduces growth and differentiation signals in developing tissues
  • The absence of these cells in the mucosal and muscular layer of the colon results in the failure of the colonic muscles to relax.


  • Occurs in 1:5000 live births
  • Male:Female ratio of 3-4:1
  • 80% of cases affect the rectosigmoid junction (termed short-segment disease)
  • 15-20% of cases extend to the proximal sigmoid colon (termed long-segment disease)
  • <5% of cases affect the entire colon

Associated Syndromes

  • Trisomy 21(up to 16% of cases)
  • Bardet-Biedi
  • Cartilage-hair hypoplasia
  • Congenital central hypoventilation syndrome
  • Familial dysautonomia
  • Multiple endocrine neoplasia type 2
  • Mowat-Wilson
  • Smith-Lemli-Opitz
  • Waardenburg

Associated Congenital Anomalies

Up to 25% of Hirschsprung patients have other congenital anomalies including:

  • Genitourinary (20-40%)
    • Hydronephrosis, renal agenesis
  • Visual/Hearing Impairment (5-40%)
    • Most are refractive errors
  • Congenital Heart Disease (50%)
    • Almost exclusively in syndromic Hirschsprung
  • Anorectal Malformations

Signs and Symptoms

  • Failure to pass meconium in first 48 hours
    • 100% of normal full-term infants pass meconium in first 48 hours in contrast to only 10-40% of infants with Hirschsprung
  • Abdominal distention
    • Squirt/Blast Sign
      • Explosive expulsion of gas and stool after digital rectal examination
  • Bilious emesis
  • Enterocolitis and volvulus are rare, life-threatening complications or presentations
  • Most are diagnosed in the neonatal period, but less-severe short-segment disease can present as late as 3 years old

Diagnostic Work-Up

  • Indications for testing include:
    • Symptoms of obstruction
    • Failure to pass meconium after 48 hours
    • Constipation and Trisomy 21 (or other associated syndrome)
    • Constipation and physical examination suggestive of Hirschsprung
  • If fever, lethargy, and/or obstipation are present, emergent evaluate for enterocolitis is needed
  • Studies
    • “Unprepped” contrast enema
      • Identification of transition zone
        • Change from normal caliber/narrowed rectum to dilated proximal colon
  • Anorectal manometry
    • Useful in ultrashort segment disease
    • Can approach 100% NPV is performed properly
    • Suction rectal biopsy
      • GOLD STANDARD for diagnosis
      • Location should be 2cm above the level of the dentate line
  • Histology findings
    • Presence of hypertrophic nerve fibers
    • Increased acetylcholinesterase activity or staining in the muscularis mucosae
    • Decreased or absent calretinin-immunoreactive fibers in the lamina propria
Abnormal acetylcholine esterase (AchE)-positive nerve fibers (brown) in the mucosa


  • Surgery is the mainstay of treatment
    • Resect the affected segment
    • Bring the normal ganglionic bowel down to anus
    • Preserve internal sphincter function
  • Originally, this was an open, two-stage procedure with a diverting colostomy
    • To allow the dilated segement to decompress back to normal size
  • Now, it can be performed as a single-stage operation either laparoscopically or transanally
  • 3 types of Pull-Through Procedures
  • Complications
    • Anastomotic stricture, constipation, incontinence, or enterocolitis

The Cottage Physician (1893)

Chapter – Children and Their Diseases


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PAINE #PANCE Pearl – Pediatrics


You are consulted to see a 2-day old baby boy for failure to pass the first meconium stool and an episode of bilious emesis. He was 37-weeks gestation at the time of a normal spontaneous vaginal delivery without any complications. Physical examination reveals a distended abdomen and digital rectal exam results in an explosive expulsion of stool and gas. A contrast enema was ordered and is attached. What is the specific cause (not the diagnosis) of this infant’s condition and what is the next diagnostic step?


This infant has congenital aganglionic megacolon, or Hirschprung Disease. It is caused by the failure of the neural crest cells (precursors to enteric ganglion cells) to migrate completely during intestinal development in utero. This results in the failure of the colon to be able to relax and causes a functional obstruction.

Diagnosis is made with bedside suction rectal biopsy 2cm above the level of the dentate line. Confirmatory findings on histology are abnormal acetylcholine esterase-positive nerve fibers in the mucosa.

AchE-positive Nerve Fibers (brown)


Sphincter of Oddi

Other known aliaseshepatopancreatic sphincter, Glisson’s sphincter

Definitionmuscular ring surrounding the major duodenal papilla at the 2nd portion of the duodenum.

Clinical Significancethe sphincter of Oddi allows for drainage of the biliary and pancreatic systems and dysfunction (mainly spasming) can can cause pancreatitis.  It is in a constant state of contraction unless relaxed by cholesytokinin released by vasoactive intestinal peptide.  Opioids, specifically morphine, has been shown to increase the risk of sphincter of Oddi dysfunction.

HistoryNamed after Ruggero Ferdinando Antonio Guiseppe Vincenzo Oddi (1864-1913), who was an Italian physiologist and anatomist from Perugia.  He spent is formative years studying medicine at Perugia, Bologna, and Florence and was appointed head of the Physiology Institute at the University of Genoa in 1894.  In 1887, at only 23 years old, he described his eponymous structure in his paper “D’une disposition a sphincter speciale de l’ouverture du canal choledoque”.  His career, unfortunately, was derailed and cut short due to opioid addiction many believe was as a result of using morphine derivatives to study dysfunction of the sphincter.


  • Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  • Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  • Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  • Whonamedit – dictionary of medical eponyms. http://www.whonamedit.com
  • Up To Date. www.uptodate.com
  • Helm JF, Venu RP, Geenen JE, et al. Effects of morphine on the human sphincter of Oddi. Gut. 1988; 29(10):1402-7. [pubmed]
  • Behar J.  Physiology and Pathophysiology of the Biliary Tract: the Gallbladder and Sphincter of Oddi – A Review.  ISRN Physiology, vol. 2013, Article ID 837630, 15 pages, 2013. https://doi.org/10.1155/2013/837630
  • Oddi R. D’une disposition a sphincter speciale de l’ouverture du canal choledoque. Arch Ital Biol. 1887;8:317–322
  • Loukas M, Spentzouris G, Tubbs RS, Kapos T, Curry B. Ruggero Ferdinando Antonio Guiseppe Vincenzo Oddi. World journal of surgery. 2007; 31(11):2260-5. [pubmed]


Duct of Santorini

Other known aliases accessory pancreatic duct

Definitionportion of the dorsal duct distal to the dorsal-ventral fusion point during embryonic development

Clinical Significance85% of the population have a single, main pancreatic duct and 15% can have an accessory duct that either drains into the duodenum by a separate ampulla (2/3), or drains into the main duct (1/3).  These anatomical variants need to be explored prior to instrumentation for pancreatic pathology as it can occur with pancreas divisum, which makes the accessory duct the principle drainage duct for the pancreas.

HistoryNamed after Giovanni Domenico Santorini (1681-1737), who was an Italian anatomist and son of an apothecary.  He spent his formative years studying medicine throughout Bologna, Padua, and Pisa, where he received his medical doctorate in 1701.   He performed anatomical dissection demonstration in Venice for 23 years, during which he published his most famous work entitled Observationes Anatomicae.  This work was considered one of the most detailed and important anatomical texts of the time and gave way to descriptions of twelve different anatomic eponyms accredited to Santorini.


  • Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  • Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  • Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  • Whonamedit – dictionary of medical eponyms.
  • http://www.whonamedit.com
  • Up To Date. www.uptodate.com

#44 – Celiac Disease


History of the Disease

The term “celiac” has Latin and Greek roots as Aretaeus of Cappadocia named this disease in the 1st century AD “koiliakos” meaning abdomen/abdominal in patients with chronic diarrhea.  The first modern medical description of the disease was in 1888 by Samuel Gee in an paper entitled “On the Coeliac Affection”. The specific medical term for Celiac Disease is “gluten-sensitive enteropathy”. It was still relatively unexplained until Willem Dicke, a Dutch pediatrician, noted improvement in his patient’s abdominal symptoms during bread and grain shortages of World War II.


  • Primarily in northern European white
  • Prevalence is widely variable due to differing rates and types of population screening throughout the world


High association with genetic predisposition to gluten sensitivity, specifically HLA-DQ2 and/or DQ8, and because of these genetic changes, serum autoantibodies are produced that attack the endomysium of the enterocytes of the small bowel.

Signs and Symptoms

Originally thought to be a disease of infancy, it is being diagnosed later and later in life, with adults first being diagnosed as late as the fifth decade.  Often, this is in the setting of failure to thrive in an infant.


  • Diarrhea
  • Steatorrhea
  • Malabsorption
    • Anemia (iron), weight loss, metabolic bone disease (vitamin D and calcium), vitamin deficiencies (B-complex vitamins)
      • Peripheral neuropathy, ataxia

Associated Clinical Findings

  • Dermatitis herpetifomis
    • Pruritic papules and grouped vesicles on the elbows, forearms, knees, scalp, back, and buttock.
    • 1:369 patients diagnosed with celiac disease
    • Diagnosed with biopsy histologic evidence of IgA deposition in basement membrane
  • Down Syndrome
    • As high as 16% association, which isa 20-fold increase compared with general public
  • Also associated with liver disease, diabetes, thyroid disease, inflammatory bowel disease

Screening and Diagnosis

  • Who should be screened?
    • Patients with chronic diarrhea, malabsorption, weight loss, or abdominal distension and bloating
    • Patients without other explanations for extraintestinal diseases such as anemia, elevated transaminases, peripheral neuropathy, ataxia, etc.
    • Patients with type 1 DM and signs or symptoms of celiac disease
    • Asymptomatic first-degree relatives of patients with confirmed celiac disease
  • Immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) is the initial screening test of choice
    • If positive, then proceed with duodenal biopsy via endoscopy
    • If negative, HLA-DQ2/DQ8 testing is performed to evaluate for nonceliac gluten sensitivity
      • If negative, then celiac is ruled-out
      • If positive, then slow introduction of gluten-containing foods is started
        • If unable to tolerate, then proceed with biopsy
        • If serology changes to positive, then celiac disease is confirmed
  • Endoscopic biopsy is the confirmatory test of choice in patients with positive serologic screening and high probability of celiac disease.
    • Duodenal mucosa may appear atrophic with loss of folds, visible fissures, nodular folds, and/or scalloped appearance
  • Histologic features of small bowel biopsy include increased intraepithelial lymphocytes, flat mucosa with complete loss of villi and atrophy, and/or crypt hyperplasia


Celiac disease can present as a spectrum of signs and symptoms and thus, have different classifications.

  • Classic Disease
    • 3 key features
      • Villous atrophy
      • Symptoms of malabsorption
        • Steatorrhea, weight loss, nutrient deficiencies
      • Improvement in symptoms with withdrawal of gluten-containing foods
  • Atypical Disease
    • Minor gastrointestinal complaints
    • Anemia, osteoporosis, tooth enamel issues,
    • Severe mucosal damage is present on endoscopy
  • Asymptomatic (Silent) Disease
    • Incidental finding on screening without symptoms


Six key elements of successful management of celiac disease and it has a nice acronym:

  • Consultation with a skilled dietician
  • Education about the disease
  • Lifelong adherence to a gluten-free diet
  • Identification and treatment of nutritional deficiencies
  • Access to an advocacy group
  • Continuous long-term follow-up by a multidisciplinary team

Cottage Physician

This is an excerpt from the pediatric disease section on diarrhea:


  1. Impact – A Publication of the University of Chicago Celiac Disease Center. 2007;7(3):1-3. [article]
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  9. Guandalini S, Assiri A. Celiac disease: areview. JAMA pediatrics. 2014; 168(3):272-8. [pubmed]
  10. Bibbins-DomingoK, Grossman DC, et al. Screening for Celiac Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2017; 317(12):1252-1257. [pubmed]
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