Embryology of the hindgut

doi:10.1053/j.sempedsurg.2011.03.002

Seminars in Pediatric Surgery

Volume 20, Issue 3, August 2011, Pages 152-160

https://doi.org/10.1053/j.sempedsurg.2011.03.002 Get rights and content

Normal and abnormal development of the hindgut is still in debate. Normal development of the hindgut critically depends on the cloacal membrane. In this study, scanning electron microscopy of staged rat embryos between the gestational days 10-15 was performed to show the normal development of the hindgut and the abnormal development in Danforth's short tail (SD) mice. Our studies in normal and abnormal development indicate that the embryonic cloaca never passes through a stage that is similar to any form of anorectal malformation in neonates, including the so-called “cloacas” in females. To explain the abnormal development in anorectal malformations, further studies are mandatory.

Section snippets

Theories of the normal embryology of the hindgut

Two major theories exist to explain the differentiation of the hindgut into a urogenital (ventral) and anorectal (dorsal) part: (1) septation of the cloaca; and (2) migration of the rectum.

The normal hindgut development in rat embryos

We studied the normal hindgut development by using SEM in a series of staged rat embryos between the 10th and the 15th ED. At this embryonic age rats are comparable to human embryos between the third and seventh week of gestation.⁴ Our studies were focused on the following:

1
The development of the cloacal shape.
2
Signs of fusion of lateral cloacal wall components.
3
Signs of disintegration of the cloacal membrane.
4
Signs of a migration of the anal opening.

Theories and recent advances studying the embryology of ARM

A number of animal models for ARM have been developed and used for embryologic studies. Depending on the nature of the model, the following observations were made:

1
After feeding of 60 mg kg⁻¹ etretinate (a long acting synthetic retinoid) to pregnant mice on ED 9, Kubota et al¹¹ observed a specific pattern of cell proliferation and apoptosis in treated and untreated animals at ED 11 and 12. While in developmental normal embryos proliferation was noted in the area of the cloacal membrane,

The abnormal hindgut development in SD mouse embryos

The embryology of the abnormal hindgut development was unclear because of a lack of appropriate animal models that would allow systematic studies in malformed embryos. In 1940, a mouse SD mutant had been described by Dunn et al.¹⁴ These mutant-mice, first bred by Danforth¹⁵, prominently feature a short tail and are therefore also known as “Danforth's short tail mice” (Figure 6A).¹⁶ However, the SD gene influences not only the axial skeleton but also the rectum and the urogenital system, causing

Nomenclature

The term “cloaca” is used in 3 ways: It describes a transitional organ system in human embryos, a congenital anomaly, and a normal organ in birds. This nomenclature may lead to the false conclusion that the morphology of these 3 entities is similar. Embryonic cloacas are morphologically completely different from cloacas in females and in birds. The main difference is the presence/absence of the area of the future anal opening. In embryonic cloacas, the future anal region is always present,

References (21)

D. Kluth et al.
The principles of normal and abnormal hindgut development
J Pediatr Surg
(1995)
D. Kluth et al.
The embryology of foregut malformations
J Pediatr Surg
(1987)
D. Kluth et al.
Rotation of the gut: Fact or fantasy?
J Pediatr Surg
(1995)
S.C. van der Putte
Normal and abnormal development of the anorectum
J Pediatr Surg
(1986)
Y. Kubota et al.
Development of anorectal malformations using etretinate
J Pediatr Surg
(1998)
B.Q. Qi et al.
Clarification of the processes that lead to anorectal malformations in the ETU-induced rat model of imperforate anus
J Pediatr Surg
(2002)
R. Mo et al.
Anorectal malformations caused by defects in sonic hedgehog signaling
Am J Pathol
(2001)
D. Kluth et al.
The developmental anatomy of congenital diaphragmatic hernia
Pediatr Surg Int
(1987)
F. Tourneux
Sur le premiers developments due cloaque du tubercle genitale et de 1 Anus chez 1'embryon mouton s, avec quelques remarques concernant le development des glandes prostatiques
J Anat Physiol
(1888)
E. Retterer
Sur 1Origin et de 1evolution de la region ano-genitale des mammiferes
J Anat Physiol
(1890)

There are more references available in the full text version of this article.

Cited by (18)

Expertise Area 1.7: Ano-uro-rectal malformations
2024, Rare and Complex Urology
This chapter covers the spectrum of anorectal malformations (ARM) and its present-day classification. This classification aids in comparing data for counselling, research, and benchmark purposes. Recently, Orphanet codes have been introduced, adopting the ARM terminology and providing standardisation of nomenclature. Associated anomalies, mainly urogenital, are covered briefly.
Next, neonatal management is described, explaining what physical signs and diagnostic studies help define the actual ARM type. An algorithm for surgical care introduces the steps needed to provide appropriate care. The different procedures, such as colostomy or primary repair, and the different approaches, such as the posterior sagittal anorectoplasty (PSARP), are described in detail. Surgical key steps are presented, depending on the different ARM types. Follow-up and its key features, such as treatment and prevention of constipation, multi-disciplinary behavioural treatment (MBT), and care of potential sequelae of additional associated anomalies, are included. Finally, outcomes and transition to adult care are discussed.
The Importance of Screening for Additional Anomalies in Patients with Anorectal Malformations: A Retrospective Cohort Study
2023, Journal of Pediatric Surgery
Citation Excerpt :
According to the Krickenbeck classification for ARM, a spectrum of malformations can be encountered ranging from relatively simple types (e.g., recto-perineal or recto-vestibular fistula) to more complex and rare types (e.g., recto-urethral fistula, cloacal anomalies or rare/regional variants such as rectal atresia) [2]. Presumably, altered spatiotemporal gene expression and multifactorial disturbances in early embryogenesis (2–4 weeks) can cause complex type ARM (e.g., recto-vesical fistula or cloacal anomaly) as well as malformations of other organ systems [3–6]. ARM can occur as an isolated anomaly (non-syndromic), but may also be part of the VACTERL-association or genetic syndromes [7–12].
In children with anorectal malformations (ARM), additional anomalies can occur within the VACTERL-association. Routine screening is of great importance for early identification and potential treatment. However, uniformity in screening protocols is lacking and only small cohorts have been described in literature. The aim of this study was to assess and describe a unique large cohort of ARM patients who underwent VACTERL screening in the neonatal period.
A retrospective mono-center cohort study was performed. Included were all neonates born between January 2000 and December 2020 who were diagnosed with ARM and screened for additional anomalies. Full screening consisted of x-ray and ultrasound of the spine, cardiac and renal ultrasound, and physical examination for limb deformities, esophageal atresia, and ARM. Criteria for VACTERL-classification were predefined according to the EUROCAT-definitions.
In total, 216 patients were included, of whom 167 (77.3%) underwent full VACTERL-screening (66% in 2000–2006 vs. 82% in 2007–2013 vs. 86% in 2014–2020). Median age at follow-up was 7.0 years (IQR 3.0–12.8). In 103/167 patients (61.7%), additional anomalies were identified. Some 35/216 patients (16.2%) fulfilled the criteria of a form of VACTERL-association. In 37/216 patients (17.1%), a genetic cause or syndrome was found.
The majority of ARM patients underwent full screening to detect additional anomalies (77%), which improved over time to 86%. Yet, approximately a quarter of patients was not screened, with the potential of missing important additional anomalies that might have severe consequences in the future. Forms of VACTERL-association or genetic causes were found in 16% and 17% respectively. This study emphasizes the importance of routine screening.
III.
Embryology and anatomy of anorectal malformations
2022, Seminars in Pediatric Surgery
Citation Excerpt :
However, recent embryologic studies have not been able to confirm URS/CM fusion. Instead, the cloaca appears to remain undivided until the CM ruptures.8,10,31 Normal anorectal and genitourinary development also appears to depend on the dorsal and ventral CM,10 with apoptotic cells concentrating in the CM and the dorsal rectum from the sixth to the eighth week of embryonic development causes the CM to rupture locally allowing the URS to come into contact with it.
The etiology of anorectal malformations (ARM) is complicated because of the spectrum of anomalies seen clinically, many of which are isolated and seemingly unique. Recent studies suggest that ARMs result from abnormal cloacal membrane (CM) development that contributes to disrupt normal local muscle and nerve development. If CM maldevelopment is severe, the rectal pouch lies above the pelvic floor, resulting in asymmetric and/or deviated musculature, so a midline incision is likely to cause trauma or be detrimental. Autonomic nerve plexuses can be associated with a fistula tract in ARMs and are also at risk for damage during surgery and contribute to genitourinary complications. Understanding the anatomy and development of the perineum is crucial for treating the broad spectrum of anomalies associated with ARMs and may assist in predicting/managing other related morbidity.
Correlation of anorectal malformation complexity and associated urologic abnormalities
2021, Journal of Pediatric Surgery
Citation Excerpt :
Anorectal malformations (ARMs) are rare congenital anomalies that affect the developing hindgut and occur at a rate of approximately 1 in 5000 births [1]. Children born with ARMs are often found to have coexisting urologic anomalies, likely because of the intimate relationship of the developing gastrointestinal and urologic systems [2–12]. The reported incidence of urologic anomalies in patients with ARM varies considerably but is estimated to occur in as many as one half of patients in large cohorts [3,4].
Patients with anorectal malformations (ARM) commonly have associated urologic anomalies. Few large studies exist to accurately characterize the incidence or associations between severity of malformation and urologic diagnosis. The purpose of our study was to determine the incidence of urologic diagnoses in a large cohort of children with ARM and evaluate for any correlation between severity of ARM and the incidence and number of associated urologic diagnoses.
A retrospective review was performed of patients with ARM treated at our pediatric colorectal center. All patients underwent protocolized urologic screening. ARM subtypes were ordered with increasing severity as follows in males: perineal, bulbar, prostatic and bladder neck fistulae. Females were similarly categorized as perineal, vestibular and vaginal fistulae followed by cloaca with <3 cm common channel and cloaca with >3 cm common channel. The following urologic diagnoses were assessed to determine whether a correlation existed with the severity of the ARM subtype: hydronephrosis, vesicoureteral reflux (VUR), solitary kidney, renal ascent anomalies (ectopic or pelvic), renal fusion anomalies (horseshoe or cross fused kidney), duplex kidney, hypospadias and undescended testicle. ARM subtypes were defined by distal rectal anatomy.
A total of 712 patients were included in our study with a mean age of 4 years and of whom 45% were male. The overall rate of urologic anomalies was greater in males than females (65% vs 56% p < 0.026). In both sexes, the rate of urologic anomalies increased with increasing severity of ARM subtype (p<0.00010) finding that males with bladder neck fistula and females with cloacal malformations, particularly with long common channels, being the highest incidence. In males and females, the rate of hydronephrosis increased as the complexity of ARM increased and this correlated significantly (p < 0.0001 vs p < 0.0003 respectively). Similarly, the incidence of VUR also increased as complexity of ARM increased in both males and females (p = 0.01 and p<0.0001 respectively). The remaining urologic diagnoses were not significantly correlated with severity of ARM.
Urologic anomalies occur at a high rate in children with ARM and appear to increase in frequency with increasing complexity of ARM subtype. These findings stress the importance of proper ARM screening and proactive collaboration with a clinician with expertise in pediatric urology early in the management of such children to improve early recognition of urologic diagnoses.
Level III.
Inter-rater Reliability of Sacral Ratio Measurements in Patients with Anorectal Malformations
2020, Journal of Surgical Research
Citation Excerpt :
Anorectal malformation (ARM) represents a spectrum of disease processes resulting from dysgenesis of the hindgut structures during embryological development.1,2
Anorectal malformations (ARMs) are a spectrum of congenital anomalies with varying prognosis for fecal continence. The sacral ratio (SR) is a measure of sacral development that has been proposed as a method to predict future fecal continence in children with ARM. The aim of this study was to quantify the inter-rater reliability (IRR) of SR calculations by radiologists at different institutions.
x-Rays in the anteroposterior (AP) and lateral planes were reviewed by a pediatric radiologist at each of six different institutions. Subsequently, images were reviewed by a single, central radiologist. The IRR was assessed by calculating Pearson correlation coefficients and intraclass correlation coefficients from linear mixed models with patient and rater-level random intercepts.
Imaging from 263 patients was included in the study. The mean inter-rater absolute difference in the AP SR was 0.05 (interquartile range, 0.02-0.10), and in the lateral SR was 0.16 (interquartile range, 0.06-0.25). Overall, the IRR was excellent for AP SRs (intraclass correlation coefficient [ICC], 81.5%; 95% confidence interval, 75.1%-86.0%) and poor for lateral SRs (ICC, 44.0%; 95% CI, 29.5%-59.2%). For both AP and lateral SRs, ICCs were similar when examined by the type of radiograph used for calculation, severity of the ARM, presence of sacral or spinal anomalies, and age at imaging.
Across radiologists, the reliability of SR calculations was excellent for the AP plane but poor for the lateral plane. These results suggest that better standardization of lateral SR measurements is needed if they are going to be used to counsel families of children with ARM.
Development of the Gastrointestinal Tract
2020, Pediatric Gastrointestinal and Liver Disease, Sixth Edition

View all citing articles on Scopus

View full text

Embryology of the hindgut

Section snippets

Theories of the normal embryology of the hindgut

The normal hindgut development in rat embryos

Theories and recent advances studying the embryology of ARM

The abnormal hindgut development in SD mouse embryos

Nomenclature

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

Am J Pathol

The developmental anatomy of congenital diaphragmatic hernia

Pediatr Surg Int

Sur le premiers developments due cloaque du tubercle genitale et de 1 Anus chez 1'embryon mouton s, avec quelques remarques concernant le development des glandes prostatiques

J Anat Physiol

Sur 1Origin et de 1evolution de la region ano-genitale des mammiferes

J Anat Physiol