- Email: [email protected]
Embryology of the midgut
Seminars in Pediatric Surgery (2011) 20, 145-151
Embryology of the midgut Roman Metzger, MD, PhD,a Ulrike Metzger, MD,a Henning C. Fiegel, MD, PhD,b Dietrich Kluth, MD, PhDa From the aDepartment of Pediatric Surgery, University of Leipzig, Leipzig, Germany; and b Department of Pediatric Surgery, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. KEYWORDS Malrotation; Midgut; Rotation; Scanning electron microscopic (SEM)
In most textbooks of embryology and pediatric surgery, the puzzling spectrum of midgut “malrotations” is explained by an “impaired” process of rotation of the midgut. However, this “process of rotation” is explained in a rather schematic way and aims more to explain pathologic findings whereas detailed embryologic investigations are still rare in this field. Good animal models which would allow the comparison of normal and abnormal midgut development are missing. In this paper we describe the development of the midgut in form of an atlas. Scanning electron microscopy is used in rat embryos to illustrate the crucial embryologic processes of midgut development. The main result shown in these illustrations is that clear signs of a process of rotation are missing. © 2011 Elsevier Inc. All rights reserved.
Since the work of Mall1 and Frazer and Robbins,2 it has generally been believed that the normal position of the gut inside the abdominal cavity is the result of a complex embryologic process called “rotation of the midgut loop.” Consequently, disorders of the positioning of the gut are called “malrotation.”1,3-5 However, in most textbooks of embryology and pediatric surgery, this process of “rotation” is described with the help of schematic drawings. Instructive illustrations representing results of detailed embryologic studies of midgut development are sparse. Animal models, which may allow embryologic studies on “malrotations” of the midgut have recently been discussed but still remain controversial.6,7 In this paper we present an atlas of midgut development with the use of scanning electron microscopic (SEM) photographs. These illustrations give a 3-dimensional impression of normal embryonic midgut development in rats. In this model the main steps of midgut positioning starts at the embryonic day (ED) 13 and ends with the return of the gut into the abdominal cavity at embryonic day 18. This means that all
developmental stages between the appearance of the first gut loop in the extraembryonic coelom of the umbilicus and the complete “return” of the midgut are shown within this time frame in rat embryos. Using microsurgical techniques, gut loops inside the abdomen and in the extraembryonal coelom are exposed.
Loop formation at ED 13 In embryos of this age group (Figure 1) the midgut can be easily identified as a loop, with its tip in the extraembryonic coelom of the umbilicus. The midgut can be subdivided into 3 parts: a central (dorsal) part, an umbilical (ventral) part, and a straight part.
Elongation of the bowl at ED 14 Address reprint requests and correspondence: Roman Metzger, MD, PhD, Department of Pediatric Surgery, University of Leipzig, Liebigstrasse 20a, 04103 Leipzig, Germany. E-mail: [email protected].
1055-8586/$ -see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2011.03.005
In this age group, the small gut elongates in its middle part. This longitudinal growth pushes the cecum inside the umbilical coelom to the left and the first gut loop
146
Seminars in Pediatric Surgery, Vol 20, No 3, August 2011
Figure 1 Rat midgut at ED 13; view is from the right (A) and from ventral (B) sides. (A and B) Note the “physiological herniation” of the tip of the bowel loop (asterisk in A and B) into the coelom of the umbilicus. The arrow indicates the pyloric area. Li, right liver lobes; Du, anlage of the duodenum; Sm B, small bowel; Ce, cecum; GT, genital tubercle; Um C, umbilical cord; Li B, limb bud.
inside the umbilical cord appears (Figure 2). Further rapid longitudinal growth of the small gut is followed by the formation of gut loops inside the coelom of the umbilicus (Figure 3).
Discrimination of 3 midgut segments at ED 15 At ED 15 (Figure 4), the 3 distinct parts of the midgut are clearly discernable:
Figure 2 Rat midgut at ED 14; view is from dorsal (A, B) and left lateral (C, D) sides. (A-D) The dotted line marks the border between the intra- and extraembryonic coelom. The arrows indicate the direction of the longitudinal growth of the small bowel (Sm B). As a result the cecum (Ce) is pushed to the left, mimicking “rotation.” The first gut loop (1 GL) appears. MV, mesentery of the gut loop; La B, large bowel; Bo W, body wall.
Metzger et al
Embryology of the Midgut
147
Figure 3 Ventral view of the developing small bowel inside the extraembryonal coelom of the umbilicus in rats at ED 13 (A), ED 14 (B) and ED 15 (C). (A-C) Notice the changing position of the first gut loop (1 GL) and the growing number of loops attributable to the rapid longitudinal lengthening (arrows) of the small bowel (Sm B). GL, gut loop; VV, vitteline vessels; Ce, cecum.
a. The central (dorsal) part with the duodenum as the main feature; b. The umbilical (ventral) part inside the umbilical coelom where gut loops develop as the result of rapid lengthening of the small gut; and c. The straight intra-abdominal part. The development of these areas is demonstrated in more detail in the subsections to follow.
ach and the proximal part of the duodenal loop is pushed forward. As a result, the duodenal loop moves from a sagittal plane into a frontal plane. At ED 15, the duodenojejunal loop has not yet reached the root of the mesentery. At ED 16/17, the duodenum grows rapidly and the duodenojejunal loop is pushed beneath the root of the mesentery. In a view from caudal, the tip of the duodenojejunal loop has reached a position left to the midline.
Development of the central (duodenal) part
Development of the umbilical part
Initially (ED 13), the duodenal part of the midgut appears as a loop caudal to the right liver lobes (Figure 5). Because of the expansion of the liver lobes the distal part of the stom-
The midgut development is demonstrated in embryos at ED 15 and 16 (Figure 6). Although there is much growth activity (lengthening) in the umbilical part of the midgut, the
148
Seminars in Pediatric Surgery, Vol 20, No 3, August 2011 growth of the intra-abdominal small gut is sparse. The position of the cecum is changing frequently. This seems to be a phenomenon secondary to the growth of the intraumbilical loops.
Development of the straight intra-abdominal part In embryos of ED 15 and 16 growth activities of the intraabdominal small and large gut are minimal (Figures 4 and 7), most likely because the liver occupies most of the intraabdominal cavity. Signs of rotation of the midgut are completely missing in this age group.
Growth and “return” of the gut at ED 17 Figure 4 Abdominal cavity and midgut at rat ED 15, cranial view. The complete liver is removed. The 3 parts of the midgut are easily identifiable. In the dorsal (central) part the stomach (St) and the duodenum (Du) are seen. Ventrally small bowel loops (GL) and the cecum (Ce) are found inside the umbilical cord (umbilical part). In between, the straight part of the small bowel (Sm B) and large bowel (La B) are located.
In this age group 2 important changes take place: a. Growth of intra-abdominal gut loops (Figure 8). At early ED 17, the first intra-abdominal jejunal loops can be seen. They appear on the left side inside the abdomen. b. The “return of the gut” into the abdominal cavity (Figure 9). In late day 17 embryos, the cecum can be found in an
Figure 5 Magnification of the duodenal region in a 13-day-old rat embryo (A), 15-day-old rat embryo (B), and 17-day-old rat embryo (C and D). View from the right lateral side (A) and caudal view (B-D). The longitudinal growth of the duodenum (Du) forces the tip of the DJL beneath the mesenteric root (arrow in B). Note the formation of bowel loops (asterisks in C) inside the abdomen in 17-day-old rat embryos. Arrows indicate the position of the mesenteric root in (B) and (C). The DJL has crossed the midline (arrow in D). Ce, cecum; Li, liver lobes; St, stomach; Je, jejunum; Sm B, small bowel; Um C, umbilical cord; GT, genital tubercle.
Metzger et al
Embryology of the Midgut
149
Figure 6 Close-up of the umbilical (ventral) region of the midgut, view from the right-lateral side. Rat ED 14 (A), ED 14.5 (B), ED 15 (C) and ED 16 (D). (A-D) Longitudinal growth of the small bowel (Sm B; arrows in A and B) leads to the formation of loops inside the umbilical cord. The cecum (Ce) moves passively. In the older age groups (days 15 and 16; C and D) the umbilical cord is filled with bowel loops (GL). Note the lack of signs of rotation around the axis of the mesenteric vessel as they run in parallel within the cavity (arrows in C and D). Li, liver; St, stomach; Du, duodenum; 1 GL, first gut loop; La B, large bowel.
intra-abdominal position. Simultaneously, gut loops, which initially developed inside the umbilical cord, enter the abdominal cavity, too. Not the cecum but other ileal gut loops are the last to enter the abdominal cavity. c. On rat ED 18, all of the gut is inside the abdominal cavity.
Discussion In most papers and textbooks of embryology8,9 and pediatric surgery,4,10,11 the development of the midgut begins with the subdivision of the primitive gut into foregut, midgut, and hindgut at the fourth developmental week.8,9 At this stage, the midgut is still connected to the yolk sac through the omphaloenteric duct. Many researchers believe that the midgut lies straight in the midline of the embryo in this stage. It is believed that the process of “rotation” can be subdivided into 2 to 3 subsequent developmental steps3,8,9: a. The early development of the gut anlage into the extraembryonic coelom with a sagittal orientation of the prim-
Figure 7 The straight region of the midgut from a cranial view in rat ED 16. To allow a better view, part of the liver (Li) has been removed. Note the increase of gut loops (GL) inside the umbilical cord in the 16-day-old embryo as compared to Figure 4. Signs of rotation of the gut along the axis of the mesenteric vessels are still lacking (arrows). Du, duodenum; Je, jejunum.
150
Seminars in Pediatric Surgery, Vol 20, No 3, August 2011
Figure 8 Intra-abdominal development of local gut loops from the right-lateral (A) and from the left (B) view. Rat ED 17. (A and B) Note the development of local gut loops inside the abdominal cavity (Je, l GL). The asterisks in (B) mark gut loops in the umbilical cord. Du, duodenum; Ce, cecum; 1 GL, first gut loop; Je, jejunum.
itive loop (approximately fourth week of development in humans). In this stage, the first “rotation” of the gut anlage inside the extra embryonic coelom is thought to take place. It is a 90° rotation in an anticlockwise direction around the axis of the mesentery vessels (approximately eighth week in human embryos). As a result, the midgut loop is now horizontally oriented with the small gut to the right and the colorectum to the left. b. At the 10th week of gestation, the extraembryonic part of the gut enters the abdominal cavity. The details of this process are still unclear. Some authors believe that the process of rotation ends at this stage with another “rotation” in an anticlockwise fashion (180°).11 As a result, the flexura duodeni is pushed into a position below and to the left of the root of the mesentery while the cecum and the colon are forced to the right side of the abdominal cavity thus, overcrossing the mesenteric root. The result of these 2 rotations is a complete “rotation” of 270°. In a subsequent step, the cecum grows downwards from the upper quadrant of the right abdominal cavity into the right iliac fossa. In contrast to this description, Grob3 subdivides the last rotation of 180° into 2 steps of 90° each. It is interesting to note that the developmental processes proposed here are not found in our illustrations. The first “rotation” of the gut (step 1) looks completely different from what we would expect from the schematic drawings and descriptions in the literature. It seems that the rotation takes not place in an anticlockwise but rather in a clockwise direction (Figure 1), with the small bowel crossing large bowel from right to the left. However, in the following stages the further developmental steps are characterized by the rapid lengthening of the small bowel inside the intraumbilical coelom and the formation of numerous loops. In the phase of the “return” of the cecum and the small bowel loops, loops can already be seen inside the abdominal cavity, which seem to arise from local growth of jejunal loops (Figure 8). The space of the abdominal cavity varies initially. Obviously, the actual size of the liver and other
neighboring organs influence this developmental step. Interestingly, not the cecum but ileal loops are the last to enter the abdominal cavity (Figure 9). Because of minimal growth activities, the contribution of the colorectal part to the development of the midgut loop is only small. The main part of the colorectum remains inside the abdominal cavity and only the cecum can be found inside the umbilical coelom (Figure 7). This is in contrast to the assumption that major parts of the colon can be found inside the umbilicus.10 In the 17.5-day-old rat embryo, the cecum enters the abdominal cavity and takes a ventral position close to the abdominal wall and the liver. We never saw the cecum (Figure 9) in the left abdominal cavity or in a more dorsal position as it has been suggested by some schematic drawings. The straight (intra-abdominal) part, as the colorectum, shows only minimal developmental movements. This is surprising because the rotation, if it is occurring, should result in clearly notable morphologic changes in this area (Figure 7). Most schematic drawings indicate that in the conventional theory the rotation of the midgut is thought to take place in an “en bloc” fashion. However, it remains completely obscure, which force should be responsible for this developmental movement.
Conclusions In newborns, the normal position of the gut seems to depend on 2 distinct embryologic processes. Of those, the proper development of the duodenal loop seems to be of major importance. This loop appears through localized growth and lengthening of the duodenum in an early period of development. Further growth pushes the tip of the duodenojejunal loop beneath the mesenteric root, which then reaches its normal position left to the spine. This process seems to be crucial for the normal arrangement of the gut inside the abdominal cavity. This is backed up by clinical observations in cases of malrotations12: in the vast majority, the duodenal loop presents with an ab-
Metzger et al
Embryology of the Midgut
151
Figure 9 The “return” of the gut into the abdominal cavity in rat ED 17 (A-C) and ED 17.5 (D), view from the right (A), the left (B), cranial (C) and from the right and ventrolateral (D). (A-D) The cecum (Ce) can be seen inside the abdomen (A). Locally formed gut loops from the jejunum (Je) are seen together with “returned” gut loops (r GL). The complete large gut (cecum, colon and rectum) is localized inside the abdomen (B). Gut loops are sparse on the left side. Note that some gut loops are still outside in the umbilical cord (arrow in B). Note the position of the cecum on the right of the ventral abdominal wall in (C). The arrow in (C) points to gut that is connected to gut loops inside the umbilicus. The “return” of the last intraumbilical loops (eE GL) occurs between ED 17 and 18 and is documented in (D). Co, colon; Re, rectum; 1 GL, local gut loops; Bl, bladder.
normal course, whereas the position of the cecum is less indicative for the presence of malrotation. Thus, we conclude that in all forms of “isolated” malrotations the improper formation of the duodenal loop is the crucial step. The other important developmental step is the “return” of the intestines from the umbilicus into the abdominal cavity. During this developmental phase the cecum immediately reaches its final position in the right side of the abdomen. However, this is not the result of growth activities but rather that of passiveness.
References 1. Mall FP. Development of the human intestine and its position in the adult. Bull Johns Hopkins Hosp 1898;9:197-208. 2. Frazer TE, Robbins RF. On the factors concerned in causing rotation of the intestine in man. J Anat Physiol 1915;50:74-100. ¨ ber Lageanomalien des Magen-Darm-Traktes infolge 3. Grob M. U Störungen der fetalen Darmdrehung. Basel: Schwabe, 1953.
4. Gross RE. The Surgery of Infancy and Childhood. Philadelphia, PA: W. B. Saunders, 1953. 5. Snyder WR, Jr, Chaffin L. Embryology and pathology of the intestinal tract: Presentation of forty cases of malrotation. Ann Surg 1954;110: 368-80. 6. Pitera JE, Smith VV, Woolf AS, et al. Embryonic gut anomalies in a mouse model of retinoic acid-induced caudal regression syndrome: Delayed gut looping, rudimentary cecum, and anorectal anomalies. Am J Pathol 2001;159:2321-9. 7. Baoquan Q, Diez-Pardo JA, Tovar JA. Intestinal rotation in experimental congenital diaphragmatic hernia. J Pediatr Surg 1995;30: 1457-62. 8. Gray SW, Skandalakis JE. Embryology for Surgeons. Philadelphia, PA: W. B. Saunders, 1972:129-141. 9. Starck D. Embryologie. Stuttgart: Thieme, 1975:135-163. 10. Smith EI, Welch KJ. Malrotation of the intestine. In: Randolph JG, Ravitch MM, O’Neill JA Jr, et al. (eds) Pediatric Surgery, 4th ed. Chicago, London: Boca Raton, Year Book Medical Publishers, 1986: 882-895. 11. Lister J. Malrotation and volvulus of the intestine. In: Irving IM (eds). Neonatal Surgery. ed 3. London: Butterworth, 1990:442-452. 12. Rehbein F. Kinderchirurgische Operationen. Stuttgart: Hippokrates, 1976:248-254.
Embryology of the midgut Roman Metzger, MD, PhD,a Ulrike Metzger, MD,a Henning C. Fiegel, MD, PhD,b Dietrich Kluth, MD, PhDa From the aDepartment of Pediatric Surgery, University of Leipzig, Leipzig, Germany; and b Department of Pediatric Surgery, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. KEYWORDS Malrotation; Midgut; Rotation; Scanning electron microscopic (SEM)
In most textbooks of embryology and pediatric surgery, the puzzling spectrum of midgut “malrotations” is explained by an “impaired” process of rotation of the midgut. However, this “process of rotation” is explained in a rather schematic way and aims more to explain pathologic findings whereas detailed embryologic investigations are still rare in this field. Good animal models which would allow the comparison of normal and abnormal midgut development are missing. In this paper we describe the development of the midgut in form of an atlas. Scanning electron microscopy is used in rat embryos to illustrate the crucial embryologic processes of midgut development. The main result shown in these illustrations is that clear signs of a process of rotation are missing. © 2011 Elsevier Inc. All rights reserved.
Since the work of Mall1 and Frazer and Robbins,2 it has generally been believed that the normal position of the gut inside the abdominal cavity is the result of a complex embryologic process called “rotation of the midgut loop.” Consequently, disorders of the positioning of the gut are called “malrotation.”1,3-5 However, in most textbooks of embryology and pediatric surgery, this process of “rotation” is described with the help of schematic drawings. Instructive illustrations representing results of detailed embryologic studies of midgut development are sparse. Animal models, which may allow embryologic studies on “malrotations” of the midgut have recently been discussed but still remain controversial.6,7 In this paper we present an atlas of midgut development with the use of scanning electron microscopic (SEM) photographs. These illustrations give a 3-dimensional impression of normal embryonic midgut development in rats. In this model the main steps of midgut positioning starts at the embryonic day (ED) 13 and ends with the return of the gut into the abdominal cavity at embryonic day 18. This means that all
developmental stages between the appearance of the first gut loop in the extraembryonic coelom of the umbilicus and the complete “return” of the midgut are shown within this time frame in rat embryos. Using microsurgical techniques, gut loops inside the abdomen and in the extraembryonal coelom are exposed.
Loop formation at ED 13 In embryos of this age group (Figure 1) the midgut can be easily identified as a loop, with its tip in the extraembryonic coelom of the umbilicus. The midgut can be subdivided into 3 parts: a central (dorsal) part, an umbilical (ventral) part, and a straight part.
Elongation of the bowl at ED 14 Address reprint requests and correspondence: Roman Metzger, MD, PhD, Department of Pediatric Surgery, University of Leipzig, Liebigstrasse 20a, 04103 Leipzig, Germany. E-mail: [email protected].
1055-8586/$ -see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2011.03.005
In this age group, the small gut elongates in its middle part. This longitudinal growth pushes the cecum inside the umbilical coelom to the left and the first gut loop
146
Seminars in Pediatric Surgery, Vol 20, No 3, August 2011
Figure 1 Rat midgut at ED 13; view is from the right (A) and from ventral (B) sides. (A and B) Note the “physiological herniation” of the tip of the bowel loop (asterisk in A and B) into the coelom of the umbilicus. The arrow indicates the pyloric area. Li, right liver lobes; Du, anlage of the duodenum; Sm B, small bowel; Ce, cecum; GT, genital tubercle; Um C, umbilical cord; Li B, limb bud.
inside the umbilical cord appears (Figure 2). Further rapid longitudinal growth of the small gut is followed by the formation of gut loops inside the coelom of the umbilicus (Figure 3).
Discrimination of 3 midgut segments at ED 15 At ED 15 (Figure 4), the 3 distinct parts of the midgut are clearly discernable:
Figure 2 Rat midgut at ED 14; view is from dorsal (A, B) and left lateral (C, D) sides. (A-D) The dotted line marks the border between the intra- and extraembryonic coelom. The arrows indicate the direction of the longitudinal growth of the small bowel (Sm B). As a result the cecum (Ce) is pushed to the left, mimicking “rotation.” The first gut loop (1 GL) appears. MV, mesentery of the gut loop; La B, large bowel; Bo W, body wall.
Metzger et al
Embryology of the Midgut
147
Figure 3 Ventral view of the developing small bowel inside the extraembryonal coelom of the umbilicus in rats at ED 13 (A), ED 14 (B) and ED 15 (C). (A-C) Notice the changing position of the first gut loop (1 GL) and the growing number of loops attributable to the rapid longitudinal lengthening (arrows) of the small bowel (Sm B). GL, gut loop; VV, vitteline vessels; Ce, cecum.
a. The central (dorsal) part with the duodenum as the main feature; b. The umbilical (ventral) part inside the umbilical coelom where gut loops develop as the result of rapid lengthening of the small gut; and c. The straight intra-abdominal part. The development of these areas is demonstrated in more detail in the subsections to follow.
ach and the proximal part of the duodenal loop is pushed forward. As a result, the duodenal loop moves from a sagittal plane into a frontal plane. At ED 15, the duodenojejunal loop has not yet reached the root of the mesentery. At ED 16/17, the duodenum grows rapidly and the duodenojejunal loop is pushed beneath the root of the mesentery. In a view from caudal, the tip of the duodenojejunal loop has reached a position left to the midline.
Development of the central (duodenal) part
Development of the umbilical part
Initially (ED 13), the duodenal part of the midgut appears as a loop caudal to the right liver lobes (Figure 5). Because of the expansion of the liver lobes the distal part of the stom-
The midgut development is demonstrated in embryos at ED 15 and 16 (Figure 6). Although there is much growth activity (lengthening) in the umbilical part of the midgut, the
148
Seminars in Pediatric Surgery, Vol 20, No 3, August 2011 growth of the intra-abdominal small gut is sparse. The position of the cecum is changing frequently. This seems to be a phenomenon secondary to the growth of the intraumbilical loops.
Development of the straight intra-abdominal part In embryos of ED 15 and 16 growth activities of the intraabdominal small and large gut are minimal (Figures 4 and 7), most likely because the liver occupies most of the intraabdominal cavity. Signs of rotation of the midgut are completely missing in this age group.
Growth and “return” of the gut at ED 17 Figure 4 Abdominal cavity and midgut at rat ED 15, cranial view. The complete liver is removed. The 3 parts of the midgut are easily identifiable. In the dorsal (central) part the stomach (St) and the duodenum (Du) are seen. Ventrally small bowel loops (GL) and the cecum (Ce) are found inside the umbilical cord (umbilical part). In between, the straight part of the small bowel (Sm B) and large bowel (La B) are located.
In this age group 2 important changes take place: a. Growth of intra-abdominal gut loops (Figure 8). At early ED 17, the first intra-abdominal jejunal loops can be seen. They appear on the left side inside the abdomen. b. The “return of the gut” into the abdominal cavity (Figure 9). In late day 17 embryos, the cecum can be found in an
Figure 5 Magnification of the duodenal region in a 13-day-old rat embryo (A), 15-day-old rat embryo (B), and 17-day-old rat embryo (C and D). View from the right lateral side (A) and caudal view (B-D). The longitudinal growth of the duodenum (Du) forces the tip of the DJL beneath the mesenteric root (arrow in B). Note the formation of bowel loops (asterisks in C) inside the abdomen in 17-day-old rat embryos. Arrows indicate the position of the mesenteric root in (B) and (C). The DJL has crossed the midline (arrow in D). Ce, cecum; Li, liver lobes; St, stomach; Je, jejunum; Sm B, small bowel; Um C, umbilical cord; GT, genital tubercle.
Metzger et al
Embryology of the Midgut
149
Figure 6 Close-up of the umbilical (ventral) region of the midgut, view from the right-lateral side. Rat ED 14 (A), ED 14.5 (B), ED 15 (C) and ED 16 (D). (A-D) Longitudinal growth of the small bowel (Sm B; arrows in A and B) leads to the formation of loops inside the umbilical cord. The cecum (Ce) moves passively. In the older age groups (days 15 and 16; C and D) the umbilical cord is filled with bowel loops (GL). Note the lack of signs of rotation around the axis of the mesenteric vessel as they run in parallel within the cavity (arrows in C and D). Li, liver; St, stomach; Du, duodenum; 1 GL, first gut loop; La B, large bowel.
intra-abdominal position. Simultaneously, gut loops, which initially developed inside the umbilical cord, enter the abdominal cavity, too. Not the cecum but other ileal gut loops are the last to enter the abdominal cavity. c. On rat ED 18, all of the gut is inside the abdominal cavity.
Discussion In most papers and textbooks of embryology8,9 and pediatric surgery,4,10,11 the development of the midgut begins with the subdivision of the primitive gut into foregut, midgut, and hindgut at the fourth developmental week.8,9 At this stage, the midgut is still connected to the yolk sac through the omphaloenteric duct. Many researchers believe that the midgut lies straight in the midline of the embryo in this stage. It is believed that the process of “rotation” can be subdivided into 2 to 3 subsequent developmental steps3,8,9: a. The early development of the gut anlage into the extraembryonic coelom with a sagittal orientation of the prim-
Figure 7 The straight region of the midgut from a cranial view in rat ED 16. To allow a better view, part of the liver (Li) has been removed. Note the increase of gut loops (GL) inside the umbilical cord in the 16-day-old embryo as compared to Figure 4. Signs of rotation of the gut along the axis of the mesenteric vessels are still lacking (arrows). Du, duodenum; Je, jejunum.
150
Seminars in Pediatric Surgery, Vol 20, No 3, August 2011
Figure 8 Intra-abdominal development of local gut loops from the right-lateral (A) and from the left (B) view. Rat ED 17. (A and B) Note the development of local gut loops inside the abdominal cavity (Je, l GL). The asterisks in (B) mark gut loops in the umbilical cord. Du, duodenum; Ce, cecum; 1 GL, first gut loop; Je, jejunum.
itive loop (approximately fourth week of development in humans). In this stage, the first “rotation” of the gut anlage inside the extra embryonic coelom is thought to take place. It is a 90° rotation in an anticlockwise direction around the axis of the mesentery vessels (approximately eighth week in human embryos). As a result, the midgut loop is now horizontally oriented with the small gut to the right and the colorectum to the left. b. At the 10th week of gestation, the extraembryonic part of the gut enters the abdominal cavity. The details of this process are still unclear. Some authors believe that the process of rotation ends at this stage with another “rotation” in an anticlockwise fashion (180°).11 As a result, the flexura duodeni is pushed into a position below and to the left of the root of the mesentery while the cecum and the colon are forced to the right side of the abdominal cavity thus, overcrossing the mesenteric root. The result of these 2 rotations is a complete “rotation” of 270°. In a subsequent step, the cecum grows downwards from the upper quadrant of the right abdominal cavity into the right iliac fossa. In contrast to this description, Grob3 subdivides the last rotation of 180° into 2 steps of 90° each. It is interesting to note that the developmental processes proposed here are not found in our illustrations. The first “rotation” of the gut (step 1) looks completely different from what we would expect from the schematic drawings and descriptions in the literature. It seems that the rotation takes not place in an anticlockwise but rather in a clockwise direction (Figure 1), with the small bowel crossing large bowel from right to the left. However, in the following stages the further developmental steps are characterized by the rapid lengthening of the small bowel inside the intraumbilical coelom and the formation of numerous loops. In the phase of the “return” of the cecum and the small bowel loops, loops can already be seen inside the abdominal cavity, which seem to arise from local growth of jejunal loops (Figure 8). The space of the abdominal cavity varies initially. Obviously, the actual size of the liver and other
neighboring organs influence this developmental step. Interestingly, not the cecum but ileal loops are the last to enter the abdominal cavity (Figure 9). Because of minimal growth activities, the contribution of the colorectal part to the development of the midgut loop is only small. The main part of the colorectum remains inside the abdominal cavity and only the cecum can be found inside the umbilical coelom (Figure 7). This is in contrast to the assumption that major parts of the colon can be found inside the umbilicus.10 In the 17.5-day-old rat embryo, the cecum enters the abdominal cavity and takes a ventral position close to the abdominal wall and the liver. We never saw the cecum (Figure 9) in the left abdominal cavity or in a more dorsal position as it has been suggested by some schematic drawings. The straight (intra-abdominal) part, as the colorectum, shows only minimal developmental movements. This is surprising because the rotation, if it is occurring, should result in clearly notable morphologic changes in this area (Figure 7). Most schematic drawings indicate that in the conventional theory the rotation of the midgut is thought to take place in an “en bloc” fashion. However, it remains completely obscure, which force should be responsible for this developmental movement.
Conclusions In newborns, the normal position of the gut seems to depend on 2 distinct embryologic processes. Of those, the proper development of the duodenal loop seems to be of major importance. This loop appears through localized growth and lengthening of the duodenum in an early period of development. Further growth pushes the tip of the duodenojejunal loop beneath the mesenteric root, which then reaches its normal position left to the spine. This process seems to be crucial for the normal arrangement of the gut inside the abdominal cavity. This is backed up by clinical observations in cases of malrotations12: in the vast majority, the duodenal loop presents with an ab-
Metzger et al
Embryology of the Midgut
151
Figure 9 The “return” of the gut into the abdominal cavity in rat ED 17 (A-C) and ED 17.5 (D), view from the right (A), the left (B), cranial (C) and from the right and ventrolateral (D). (A-D) The cecum (Ce) can be seen inside the abdomen (A). Locally formed gut loops from the jejunum (Je) are seen together with “returned” gut loops (r GL). The complete large gut (cecum, colon and rectum) is localized inside the abdomen (B). Gut loops are sparse on the left side. Note that some gut loops are still outside in the umbilical cord (arrow in B). Note the position of the cecum on the right of the ventral abdominal wall in (C). The arrow in (C) points to gut that is connected to gut loops inside the umbilicus. The “return” of the last intraumbilical loops (eE GL) occurs between ED 17 and 18 and is documented in (D). Co, colon; Re, rectum; 1 GL, local gut loops; Bl, bladder.
normal course, whereas the position of the cecum is less indicative for the presence of malrotation. Thus, we conclude that in all forms of “isolated” malrotations the improper formation of the duodenal loop is the crucial step. The other important developmental step is the “return” of the intestines from the umbilicus into the abdominal cavity. During this developmental phase the cecum immediately reaches its final position in the right side of the abdomen. However, this is not the result of growth activities but rather that of passiveness.
References 1. Mall FP. Development of the human intestine and its position in the adult. Bull Johns Hopkins Hosp 1898;9:197-208. 2. Frazer TE, Robbins RF. On the factors concerned in causing rotation of the intestine in man. J Anat Physiol 1915;50:74-100. ¨ ber Lageanomalien des Magen-Darm-Traktes infolge 3. Grob M. U Störungen der fetalen Darmdrehung. Basel: Schwabe, 1953.
4. Gross RE. The Surgery of Infancy and Childhood. Philadelphia, PA: W. B. Saunders, 1953. 5. Snyder WR, Jr, Chaffin L. Embryology and pathology of the intestinal tract: Presentation of forty cases of malrotation. Ann Surg 1954;110: 368-80. 6. Pitera JE, Smith VV, Woolf AS, et al. Embryonic gut anomalies in a mouse model of retinoic acid-induced caudal regression syndrome: Delayed gut looping, rudimentary cecum, and anorectal anomalies. Am J Pathol 2001;159:2321-9. 7. Baoquan Q, Diez-Pardo JA, Tovar JA. Intestinal rotation in experimental congenital diaphragmatic hernia. J Pediatr Surg 1995;30: 1457-62. 8. Gray SW, Skandalakis JE. Embryology for Surgeons. Philadelphia, PA: W. B. Saunders, 1972:129-141. 9. Starck D. Embryologie. Stuttgart: Thieme, 1975:135-163. 10. Smith EI, Welch KJ. Malrotation of the intestine. In: Randolph JG, Ravitch MM, O’Neill JA Jr, et al. (eds) Pediatric Surgery, 4th ed. Chicago, London: Boca Raton, Year Book Medical Publishers, 1986: 882-895. 11. Lister J. Malrotation and volvulus of the intestine. In: Irving IM (eds). Neonatal Surgery. ed 3. London: Butterworth, 1990:442-452. 12. Rehbein F. Kinderchirurgische Operationen. Stuttgart: Hippokrates, 1976:248-254.