Paper - Pouches of the pharynx and oesophagus with special reference to the embryological and morphological aspects

From Embryology
Embryology - 23 Jun 2024    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Raven RW. Pouches of the pharynx and oesophagus with special reference to the embryological and morphological aspects. (1933) The British Journal of Surgery 21(83): 235-252.

Online Editor  
Mark Hill.jpg
This historic 1933 paper by Raven presented to the Royal College of Surgeons (Feb. 17, 1933.) describes development of the pharynx and the associated endodermal pouches.

Modern Notes:

Head Links: Introduction | Medicine Lecture | Medicine Lab | Science Lecture | Lecture Movie | Science Lab | pharyngeal arch | Craniofacial Seminar | mouth | palate | tongue | placode | skull | neural crest | Head and Face Movies | head abnormalities | Category:Head
Historic Head Embryology  
1910 Skull | 1910 Skull Images | 1912 Nasolacrimal Duct | 1921 Human Brain Vascular | 1923 Head Subcutaneous Plexus | 1919 21mm Embryo Skull | 1920 Human Embryo Head Size | 1921 43 mm Fetal Skull | Historic Disclaimer
Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Pouches of the Pharynx and Oesophagus with Special Reference to the Embryological and Morphological Aspects

(The Arris and Gale Lecture delivered before the Royal College of Surgeons, Feb. 17, 1933.)

By R. W. Raven, London.

Pouches of the pharynx and oesophagus have been subject to much speculation for nearly two hundred years. Contributions have been made by many orders of our profession——surgeons, physicians, morphologists, and embryologists. In spite of this there is probably no other subject in surgery in which so many inaccurate observations have been made or so many erroneous theories perpetrated. At the present day the literature is full of errors, and these are present even in the latest standard works of surgery. In this paper I wish to consider the subject especially from the embryological and morphological aspects. Certain facts already known will be emphasized, doubt will be cast on some views which are held, and several new varieties of pouches will be described.


Pouches of the pharynx and oesophagus may be classified as follows :—

Pouches of the PHARYNX.—

1. Congenital : a. Lateral pouch in connection with second embryonic endodermal pouch. b. Lateral pouch derived from third embryonic endodermal pouch. c. Lateral pouch derived from fourth embryonic endodermal pouch.

2. Acquired : a. Posterior pulsion. b. Anterior pulsion.


a. Associated with oesophago-tracheal fistula.

b. Associated with imperfect separation of (esophagus and trachea. (2. Associated with localized imperfect development of muscle coats. d. Associated with multiple pouches of the colon.

c. Single pouch in the posterior wall.

2. Acquired : a. Tuberculous pouches. b. Secondary to oesophageal stricture. c. Secondary to oesophageal ulceration. 236 THE BRITISH JOURNAL OF SURGERY



Development of the Pharynx.— In all Craniota bilateral symmetrical pouches are formed from the anterior region of the foregut. At the same time corresponding invaginations form in the ectoderm. As a result of outward growth, the pouches press aside the lateral mesoderm of the head and come into apposition with the corresponding ectodermal invaginations (fig. 154). The temporary fusion of endoderm with ectoderm forms the epithelial closing membrane.

In animals with branchial respiration, clefts are formed by perforation of the epithelial closing membrane; the number of branchial clefts varies from five to nine in different forms. The closing membrane in the human embryo and in the majority of mammals rem lhs impcrforate, and open clef’-. do not normally occur.

As growth proceeds, dorsal a11d ventral angles are formed in each pouch with the exception of the first, and simultaneously the epithelial closing membrane elongates. The connection of each pouch with the pharynx becomes constricted owing to the disparity of growth between the lateral part and the medial part; this 1‘-,,,_ 1‘-,4__Ph,,,ym. of embm, about 3 mm constriction forms the endodermal

_F]E,§ltV..rDIi:Eictod§:-xn;ls:h.é Iéhaprrtrllgeealull membrlane; }'Il'h.. ductus pharyngo-brachialis. . ; . .v 1 R ; #1!‘ I1 88. 0110 8 . (A fter Keibel and Mall——“ Hump» E;1b§yologF;”.) S The Structure Of the early

pharynx is very transitory. The entire region is in a state of continuous growth. As a result of the disproportionate size and growth of the outer pharyngeal arches,‘ the precervical sinus appears on the surface at the early stage of 5 mm.

I wish to call attention to the broad strip of thickened ectoderm running from before backwards, along the upper ends of the arches and ‘grooves (fig. 155). This is the placodal area. In certain parts the cells of this area are continuous with the cellular masses of the nerve rudiments of the pharyngeal arches; two of these parts are indicated in fig. 155 by dotted lines and are the plaeodal areas of the ninth and tenth cranial nerves. The ninth nerve placode is situated at the upper end of the third arch, some distance down the side of the second groove.

The Ultimate Fate of the Ninth Nerve Placodal Area and its Connections.-— The importance of the ninth nerve placodal area in the interpretation of certain vestigial structures in the neck has been overlooked.

The area of the preeervical sinus deepens markedly owing to the rapid growth of its boundaries. There is also a large increase in the paraxial mesoderm. Consequently the ninth plaeodal area comes to lie at the bottom

fiG. l55.—The early pharynx, showing : 0t., Otocyst; P. Perieerdium; pl. a. ix.. Plaeodal area of the gloseopharyngeal nerve ; p|.a.x., Placodsl area of the vagus nerve. (After J. Ernest Fmzer—‘Jo'ur. of Anat.’. lxi.)

of a short recess which opens into the upper part of the second groove. Later the ninth placodal area is completely covered and folded in, so that it lies at the enlarged end of a deep tunnel which opens on the surface. Very soon the plaeodal area is completely shut off from the surface, and there is formed a buried cyst in intima.te relation with the endodermal wall of the pharynx and connected with the surface by ectodermal cells (fig. 156). If growth is normal, the ectodermal cyst and duct disappear at 12 mm.

fiG. l56.—The early pharynx, showing: n|.d.ix., Placodal duct of the glossopharyngeal nervo; nI.d.x., Placodal duct of the vagus nerve; I, II, III, first, second, end t-hird branehial arches; P, Perieardium. (After J. Ernest Frazer—‘ Jour. of Anat.’, lxi.)

Discussing the development of this region, Frazer states, “the placodal areas certainly stand forward as the structures that are mainly affected”. It is conceivable that the ninth placodal cyst lying in close relation to the second pharyngeal pouch may persist along with the duct connecting it with the surface. This is the only connection between the skin and pharynx which has been proved to exist in embryonic life. The schematic representations of internal pharyngeal ducts opening into a large covered cervical sinus from which external duets open on the surface is incorrect and does not rest on proved facts. In the schematic representations the only structures proved to exist are the endodermal pharyngeal pouches with their endodermal ducts, and the placodal cysts with their ectodermal duets.

The relations of the endodermal pouches in the adult pharynx are fixed. The position of the second is at the ‘tonsil, the third in the pyriform fossa, and the fourth at the lower end and lateral aspect of the pharynx.

Lateral Pouches.

It is unjustifiable in the present state of our knowledge to dogmatize in assessing the embryological significance of vestigial structures in the neck, and in presenting three lateral pouches of the pharynx I suggest the most likely modes of origin.

Case 1.—Boy, aged 16 years, under the care of Mr. Keynes, to whom I am indebted for permission to record the case. The patient had noticed a small hole in the right side of the neck for four years. On examination a small pin-point opening was seen at the junction of the upper two-thirds and lower third of the anterior border of the right sternomastoid. A cord one inch long was felt running upwards from the orifice. At operation a cyst was found in the right side of the neck with an external opening and an internal duct passing upwards and inwards under the posterior belly of the digastric muscle and between the internal and external carotid arteries. The duct opened into the pharynx immediately below and lateral to the right tonsillar fossa. Microscopic examination of the duct close to the pharynx showed a lining of squamous stratified epithelium.

In this specimen, therefore, there is a large pouch in the neck connected with the pharynx and skin by slender ducts. In embryonic life the only structures proved to connect endoderm and ectoderm in this region are the placodal cyst and duct in connection with the ninth cranial nerve. I regard this vestigial structure as a derivative of the ninth placodal cyst in relation with the second endodermal pouch.

Watson has described a similar pouch opening into the pharynx at the posterior faucial pillar whose walls were innervated by several branches from the ninth cranial nerve.

Case 2.—Infant, aged 3 Weeks, under the care of Mr. Eric Lloyd. I am indebted to the Medical Committee of Great Ormond Street Hospital for Children and to Mr. Lloyd for permission to study this specimen. The child was born with a swelling on the left side of the neck which caused choking attacks during feeding.

I.-IG_ 15-,-__C,,_,¢ 2_ Pouch on At autopsy the condition shown in fig. 157 the left lateral aspect of the was found.

pharynx opening by a. duct into - - the bottom of the left pyriform On exammmg the specimen I found a small

fem,“ (specimen in me Museum round orifice at the bottom of the left pyriform of Great Ormond Street Hospital fossa, and careful dissection revealed a small duct f0’ Children-) passing upwards and inwards from the cyst to

the pharyngeal orifice. Microscopic examination of the cyst wall showed a. lining of granulation tissue, fibrous tissue with numerous inflammatory cells, and an external muscle coat. I regard this as a derivative of the third endodermal pharyngeal pouch and duct lying in relation with the left pyriform fossa.

Case 3.—The specimen is from the Shattock Museum of St. Thomas’s Hospital, studied through the kindness of Professor Dudgeon, and is shown in fig. 158. Along the left side of the pharynx and oesophagus is a thin membranous pouch 3 in. long, which communicates with the lowest part of the pharynx by a circular aperture situated in the fibres of the inferior constrictor of the pharynx, immediately behind the posterior border of the thyroid cartilage. The neck of the pouch passes behind the termination of the common carotid artery.

From the anatomical relations of this pouch, it appears to be derived from the fourth embryonic endodermal pouch. The ultimate size of the pouch is due to repeated distension with food.

Importance of the Hypoglossal Nerve in relation to Embryonic Cervical V cstigial Structures.—-Frazer has drawn attention to the importance of the course of the hypoglossal nerve in relation to these structures. The hypoglossal nerve in the beginning of its course lies behind the region of the arches

fiG. 158.—C'aao 3. Pouch on the left lateral aspect of the pharynx with an opening into the lowest part of the pharynx through the fibres of the inferior constrictor muscle. A. Common carotid showing bifurcation into internal and éxternal branches; 3, Pouch with bent rod passed through orifice into pharynx; 0. Common carotid artery; D. Orifice of pouch in fibres of inferior pharyngeal constrictor; E, Inferior cornu of thyroid cartilage; F. Left pyriform fossa. (Specimen in the Museum of St. Thomas’: Hospital.)

and grooves. In passing to its ultimate distribution the nerve is deep to structures connected with the ectoderm, and superficial to structures connected with the pharynx. Consequently any connection persisting between the surface and pharyngeal wall, or its derivatives, would be caught up over the hypoglossal nerve. On this account it is not surprising that few cervical vestiges have a deep connection, as this is usually severed by tension caused by the hypoglossal nerve.

Acquired Pouches

Pharyngeal Divertlculum—Posterior, Acqulred.—

The first description of this condition is contained in a letter written in 1764 by Ludlow, of Bristol, to William Hunter. His method of examination was thorough, and included the introduction of a probang, whalebones, flexible catheters, and finally the patient was told to swallow a great quantity of quicksilver, and, as it did not enter the stomach, the surgeon was at a loss to localize it. However, the quicksilver was recovered at post-mortem from a large pharyngeal pouch.

Sir Charles Bell in 1816 first shed light on the etiology, by calling attention to spasmodic contraction at the oesophageal entrance followed by repeated ineffectual attempts to swallow. Zenker and Von Ziemssen in their classical study of 1877 contributed to the morbid anatomy, symptomatology, and diagnosis of the condition.

E'rIoLocY.—Many theories have been advanced in regard to the pathogenesis of the condition. There is no evidence that the structure is atavistlc in origin. Some authorities have likened it to the pouch which occurs in the domestic pig, but the morphology of this structure is entirely different. Various erroneous congenital theories have been advanced. It may be stated at once that the pouch is a prolapse of the mucous membrane of the pharynx in an area bounded by two different sets of musculature, innervated by different nerves. A consideration of the structure of this area surprises one that the condition is not more frequent.

fiG. l59.—The arrangement of the fibres of the cricopharyngeus muscle in monkeys. A, The orang: the muscle is composed of superficial constrictor fibres; there is a special sphincteric muscle arising from the thyroid cartilage (red rod). B, The chimpanzee: the white rod (:1) is under the superficial constrictor fibres; the red rod is under the deep sphincteric fibres. C. The silver gibbon: arranged as under B.

The oesophageal Orifice in Different Species

ln the dogfish the oesophagus is not more than 3 in. in length and entirely composed of a muscular sphincter of strong circular fibres. In the crocodile the eornua of the hyoid bone guard the oesophageal entrance and form a well—marked sphincter. This mechanism is complicated still further in the tortoise. In niammalia the hyoid bone no longer controls the msophageal entrance; the cricoid cartilage new forms the basis of the sphincteric mecha.nism. Negus has shown that such a mechanism is necessary in all lung-breathing forms to prevent air suction into the oesophagus during respiration. The ornithorhyncus has a well—marked band of muscle encircling the ocsophageal entrance, forming a sphincter with a weak attachment to the fused crieothyroid ring. The arrangement of the muscles in monkeys is shown in fig. 159.

In the human foetus the cricopharyngeus muscle is divided into an upper superficial constrictor part, incorporated in the pharyngeal constrictor musculature, and a lower deeper sphincteric part which blends posteriorly with the muscle of the oesophagus. In a four-months’ foetus (fig. 160A) this division is evident, and the constrictor portion pa.sses obliquely upwards whilst the sphincteric part passes transversely round the oesophagus. In a five-months’ foetus (fig. 1608) the direction of the sphincteric portion is obliquely downwards. Consequently a weak area is produced in the posterior wall of the pharynx between the superficial and deep portions of the cricopharyngeus muscle. It is through this weak area that the pharyngeal mucosa prolapses in the adult (fig. 161). A fully formed pouch is shown in 162.

I have satisfied myself in examining a large number of these pouches that the mucous membrane of the pharynx only herniates through this area.

Fig. 160.—The arrangement of tho cricopharyngeus muscle in the foetus. A, Four months; 3, five months. The black rod is under the superficial constrictor fibres; the red rod is under the superficial constrictor and deep sphincteric fibres.

The cricopharyngeus muscle therefore consists morphologically and functionally of two distinct sets of musculature with a congenital weakness between them. If either of the two following conditions is present, prolapse of the mucous membrane will occur.

1. Loss of elasticity or degeneration of the muscles composing the lower pharyngeal constrictors. At best, this musculature is poor material, and even under normal conditions this region is one of stress and strain.

2. Persistence of contraction of the sphincteric portion of the cricopharyngeus muscle during deglutition is probably the more important factor.

We know this occurs from the histories of patients with pouches. Consequently the intrapharyngeal pressure increases and the weakest part of the wall gives way.

During the second stage of normal deglutition the pharyngeal constrictors contract, and simultaneously the sphincteric portion of the cricopharyngeus muscle relaxes. This is a complex and involuntary reflex action. Why the sphincter fails to relax in certain individuals we do not know. It is feasible to suggest that it is due to a breakdown in the neuromuscular mechanism. We are familiar with such breakdowns in certain other regions of the alimentary canal, but as yet we do not know the site of the primary lesion, whether it is central, ganglionic, peripheral, or due to some internal secretion.

fiG. l(il.—~Early prolapse of pharyn- fiG. l62.—Pharyngea.l pouch. The goal mucosa between the two parts of the two parts of the_cncop1'.1m-yngous muscle cricopharyngeus muscle. (Specimen in the are seen. (Specimen lcmdly lent by Mr. Itiuseum of the Royal College of Surgeons.) Cawthorne.)

The nerve—supply around the oesophageal entrance is complex. The pharyngeal constrictors, including the constrictor portion of the cricopharyngeus, are supplied by the intricate pharyngeal plexus. The upper end of the (esophagus, including the sphincteric part of the cricopharyngeus, is supplied by numerous motor nerves from the recurrent laryngeal nerves. Contributions to the innervation of this region are also made by the sympathetic system, but the role of these nerves is obscure. The association of goitre with this type of pouch has been noted by German writers and is of interest in connection with derangement of the neuromuscular mechanism. It has been suggested that the enlarged thyroid gland raises the intrapliaryngeal pressure by pressing on the (esophagus and thus herniation of the pharyngeal mucosa occurs. It is more likely, however, that the motor nerves to the oesophageal orifice are mechanically stimulated by the enlarged thyroid gland, with consequent spasm of the sphincter. I suggest the possibility of oesophageal spasm in these cases being due to increased excitability of the vagosympathetic nerves to the sphincter, caused by deranged thyroid metabolism.

Pharyngeal Pouch—Anterlor, Acquired.—This type of pouch is very rare. Hurst and Briggs have recorded an example in a female aged 57 years which was discovered by radiological methods immediately in front of the entrance to the oesophagus and behind the larynx.



Pouch Associated with an (Esophago-tracheal fistula.—The marked constancy of the morphology of this condition has been recognized by numerous observers and is a sign of an early fundamental change in the embryo, as changes occurring late in embryonic life give rise to anomalies which do not conform to a definite pattern. There may be a genetic basis for this malformation, as Mackenzie found it present in all the children of one father by three Wives.

The pathological picture is very constant (fig. 163). The (esophagus commences in the usual way and ends blindly, forming a uniformly dilated pouch with thin walls. The large size of the pouch may be due to distension with amniotic fluid or to an abnormal growth stimulus. In most cases the lower portion of the oesophagus opens into the trachea at the bifurcation or a short distance above.

Numerous theories have been put forward to account for this anomaly. Malformation of the oesophago-tracheal septum has been widely accepted, but as we do not know precisely how the (esophagus and trachea separate, the theory

Fig. 163.—(Esophago-tracheal fistula does not satisfy. Others have advanced associated with a pouch of the upper end

theories of intra-uterine inflammation and °f the

B, Anterior aspect. intra-uterine trauma.

It is not surprising that congenital anomalies should occur sometimes, when we consider the intricacies of the developmental process, each species negotiating the various stages at specific rates, which vary within certain normal limits. If these normal limits are transgressed, the product of development is distorted. Stockard has performed experiments in which the rate of development was modified at will and various congenital malformations were produced. He showed that temporary arrest of growth at certain critical

moments in development is followed by disastrous results.

fiG. l64.—Pouch in anterior wall of (esophagus above the bifurcation of the trachea. The wall of the pouch is intimately incorporated in the wall of the trachea. The lymph-gland is merely attached to the lower border of the pouch. (Specimen in the Museum of the Royal College of Surgeons.)

Stockard states that practically any deformity recorded in the literature, other than those resulting from germinal variations or mutations, may be induced by lowering the temperature, which modifies the rate of growth. The malformation under review, therefore, may be due to changes in the rate of growth in the cells which normally separate the trachea from the oesophagus. The exact nature of the forces causing these changes is little understood at present. Changes in temperature and environment may play a. prominent part.

oesophageal Pouch due to Imperfect Separation of the Trachea and (Esophagus.~ Pouches of this nature occur in the anterior wall of the oesophagus a short distance above the bifurcation of the trachea or in the angle of bifurcation. Careful comparison with pouches due to adherent tuberculous lymph-glands show marked differences. Whereas pouches due to inflamed lymph glands are small and taper towards the apex, to which a mass of lymph-glands are attached, with the long axis placed obliquely upward or downward according to the direction of the glandular pull, the pouch under consideration

fiG. l65.——Pouch in anterior wall of oesophagus with the up

wall of the trachea. fundus of the pouch.

per wall incorporated in the There is a. depression in the right bronchus corresponding with the (Specimen in the Illuseum of St. Bartholomew's Hospital.)

is round, with a broad fundus and circular orifice, with the long axis at right angles to the oesophagus, or obliquely upward towardsithe trachea or bronchus (figs. 164, 165). Moreover, a part of the wall of the pouch adjoining the trachea is firmly incorporated in the tracheal wall. The muscle bundles are clearly demarcated on each side of the pouch.

If development is pursuing a normal course, the oesophagus and trachea separate at 5 mm. and the musculature of the tubes is formed at 10 mm. Hence the primary defect in the wall must be epithelial. In this connection Ribbert has demonstrated primitive ciliated cylindrical epithelium in the walls of these pouches.

In a series of transverse sections of a 17-mm. human embryo kindly lent to me by Professor J. E. Frazer, there is imperfect separation of the trachea and oesophagus with epithelial connection between the two tubes in three sections (fig. 166). Such a defect may manifest itself in adult life as an oesophago-tracheal fistula, or partial closure may occur and the epithelium of the oesophagus become incorporated in the wall of the trachea at the site of the original fistula. Further development of the pouch is due to tension at the site of union due to elongation of the

oesophagus, a certain degree of rota- Fm. l66.—-Transverse section of 17-mm.

- - h a embryo showing epithelial connection tlon whlch the (Esophagus undergoes bialtiiivegn the trachea and oesophagus. The

when the stomach rotates, and longi- position of the oesophagus is shown by the

t 1 t t. d 1 . f solid cord of cells. (Serial sections of an11 Ina con I-‘ac [On an re axatlon 0 embryo kindly lent by Professor J. E. Frazer.)

the whole oesophagus.

oesophageal Pouch Associated with Defect in the Muscular Coats.

According to Keith the (esophagus is of double origin: the upper or paratracheal part is derived with the trachea from the retropharyngeal segment of the foregut, and the lower or retropharyngeal part arises from the pregastric segment of the foregut.

I have noticed the marked difference in the upper and lower halves of the oesophagus in animals, the former being largely a membranous tube and the latter a strong muscular tube. In a four months’ foetus the muscle coat of the lower half is well developed, whilst the upper half remains membranous. In the main, the muscle is unstriated in the lower half and striated in the upper half. Oppel regards the striated muscle as derived from the branchial muscle which arises from the lower head myotomes.

fig. 167 shows a pouch of this nature occurring immediately below the bifurcation of the trachea, composed entirely of mucous membrane which does not bulge. The muscular defect is round, with clean-cut edges encircling the pouch. The two lymph-glands have no connection with the pouch. In fig. 168 there are two small pouches immediately below the bifurcation of the trachea; the other coats of the (esophagus are absent.

fiG. 1(S8.——TWo small pouches below

fiG. 1fi'i.—Pouch in anterior wall of the bifurcation of the tra.chea.. (Specimen the oesophagus below the bifurcation of in the Jluseum of St. Bartholomew’s the trachea. Hospital.)

fiG. 169.—oesophageal pouch associated with multiple diverticula of the colon. (Specimen in the Ivlueeum of Oharing Cross

It is obvious that this type of pouch is not due to traction or pulsion, and I consider it to be due to a primary muscular defect in the region of union between muscle derived from the lower head myotomes and unstriated muscle developing in situ. Such muscular defects have been described in embryos of various ages. Happich found that the circular muscle in embryos of three and four months was completely interrupted in small areas. Shridde found a larger muscular defect in the oesophageal muscle in contact with the trachea.

oesophageal Pouch Associated with Multiple Diverticula of the Colon (fig. 169).—The association of oesophageal diverticula with those in other regions of the alimentary canal has been noted by Morrison and Smelt. The view is gaining ground that acquired diverticula of the whole intestinal tract from the (Esophagus to the anus owe their origin to similar tendencies and are local variations of the same morbid process. Barsony and Polgar have described multiple cesophageal diverticula which they consider to be due to disturbed innervation.

Keith regards colonic diverticula as the manifestation of irregular contractions of the circular muscle of the colon due to disturbed innervation. This may be true for the colonic and certain multiple oesophageal diverticula, but it is difficult to apply this theory to the example under review. Lewis and Thyng have demonstrated knob-like intestinal diverticula occurring regularly in embryos of man, rabbit, and pig, which usually degenerate but sometimes persist, in various regions. In connection with this specimen it is reasonable to suppose the presence of such congenital defects with the manifestation of well-marked pouches in later life.

fiG. 170. Pouch in the posterior wall of the (esophagus. (Specimen in the Jvluseum of St. Barthalomew‘.s Hospital.)

Pouch in the Posterior Wall of the (Esophagus.—Pouches in the posterior wall of the (Esophagus are rare, and the appearances differ from all we have already discussed (fig. 170). 248 THE BRITISH JOURNAL OF SURGERY

The character of the pouch suggests that it may have originated in a cyst which has acquired a lumen into the msophagus. Cysts of the oesophagus probably arise early in embryonic life from two sources. In human embryos about 20 mm. vacuoles of various sizes occur in the oesophageal epithelium. In some places they open directly into the lumen, in others they are separated from it by a partition of epithelium. The vacuoles are more numerous in the lower half of the tube and in the anterior and posterior walls. Vacuolation increases the size of the lumen of the oesophagus. These epithelial cavities may persist, forming either cysts or (liverticula.

In later embryonic life the epithelium of the (esophagus is markedly irregular (fig. 171). In circumscribed areas epithelial proliferation is taking place and epithelial bridges across the lumen occur. In other areas there is an active moving apart of the cells, resulting in well—marked depressions.

Fig. 171. Diagram reconstructed from serial sagittal sections of a. 10-weeks embryo, showing the developing oesophagus. These depressed areas may be isolated from the main lumen and covered in by proliferating epithelium. Such cavities may remain closed, forming cysts, or may secondarily acquire an opening into the oesophagus, forming a diverticulum.

Acquired Pouches

oesophageal Pouch due to Adhesion with Tuberculous Lymph-glands.—— Kragh has made important contributions to the pathology of this type of pouch and prefers the term ‘tuberculous diverticulum’. The pouch is conical in shape with an oval orifice with the long axis obliquely upward or downward. The muscle coat of the oesophagus seldom stops at the margin of the diverticulum. The apex of the pouch is firmly attached to diseased lymphglands. The commonest site for their occurrence is in the anterior wall of the oesophagus in the area following the bifurcation of the trachea, where the (rsophagus is in relation with the bronchial lymph-glands (fig. 172).

Adhesions between lymph-glands and the msophageal wall are not frequent; Kragh found adhesions in 14 out of 556 cases examined.

This type of pouch is uncommon in children. Dr. Allan Brown kindly searched the records of the large Children’s Hospital in Toronto for me and could find no example. Mediastinal tuberculous lymphadenitis is more common in Toronto than in this country.

Pouches Associated with Obstruction at the Lower End ot the (Esophagus. ——Pouches associated with cardiospasm are found in two regions—namely,

fiG. 17 2.—-—Pouches in the uasophagus due to lymphadenitis. (Specimen in the Museum of the Royal College ’- ._'_ of Surgeons.) ‘ ' fiG. l'13.—Fusiform pouch , associated with stricture of the

terminal (esophagus in a child. fiG. 174.—La1'ge pouch in the lateral wall of the oeso(Specimen in the Museum of phagua. The lumen of the lower end of the oesophagus Great Ormdmd Street Hospital is much diminished. (Specimen in the Museum of the for Children.) Royal College of Surgeons.)

between the fibres of the cricopharyngeus muscle and in the lower third of the oesophagus. Twelve cases of pharyngeal pouch secondary to cardiospasm have been reported in the literature. Dessicker believes that a history of cardiospasm may be elicited in the majority of cases of pouches in the lower third of the oesophagus.

Pouches due to an organic stricture at the lower end of the oesophagus are fusiform or saccular. In the former the oesophagus is dilated throughout a localized area proximal to the stricture (fig. 173). Abel has recorded an example of a saccular pouch situated above a stricture.

The effects of a stricture at the lower end of the oesophagus may be either uniform dilatation of the whole oesophagus, or partial dilatation with the formation of a fusiform pouch, or the muscle bundles may diverge in a localized area with consequent herniation of the mucous membrane (fig. 174).

oesophageal Pouch of Inflammatory 0rigin.—The relation of pouches and ulcers has excited interest. Percy and Shaw have drawn attention to the connection in the duodenum. fig. 175 shows a diver Fm_ 175._POuch ticulum in the right postero-lateral in the right lateral segment of the oesophagus 4- in. above Segment of the 9380- the cardiac orifice, with a wide oval orifice whose long axis is in the B,m;w;,,,,,ew~,, H,,8_ line of the (esophagus. The overpizal.) lying muscle is absent and there is evidence of ocsophagitis. It appears that this pouch is of inflammatory origin and Very probably originated in an ulcer.

Natural Pouches in Animals

The Sloth Bear.—There are two nasopharyngeal pouches, which Mayer (leseribed in 1830 (fig. 176). According to Killian, they are not homologous with any structure in the pharynx of man.

Domestic Pig.—The nasopharyngeal pouch of this animal was described by Mayer in 1840. It is a large sac passing downward and backward from the lower end of the nasopharynx (fig. 177). The orifice is guarded by a prominence formed by the lower part of the plica pharyngopalatini. The apex commonly projects backwards between the two divisions of the POUCHES OF PHARYNX AND (ESOPHAGUS 251

fiG. 176.—Na.sopha1'yngeal pouch of the slot-h bear. (Specimen in the Jluseum of the Royal College of Surgeons.)

fiG. 177.—Nasophn'ryngeul pouch of the domestic pig.

fiG. 178.—Anteriox- pharyngeal pouch of the great anteater.

fiG. 179.—Upper and lower cesophageal pouches of the fruit bat.


thyropharyngcus muscle. The upper part of this muscle acts as a loose sling, and the lower part is firmly blended with the inferior border of the pouch. An oblique muscle on each side passes deep to the thyropharyngeus to an attachment at the apex of the pouch. There is thus concerted muscular action at the apex to prevent excessive increase in size. The lower part of the thyropharyngeus muscle is divided into superficial and deep portions continuous above, and there is no space through which a pharyngeal pouch could occur as in man. It is clear that the morphology of this pouch is entirely different from the posterior pulsion pouch in man.

fiG. 180.—Large cesophageal pouch in fiG. l8l.iPouch at lower end of oesoa horse. (Specimen in the lliuseum of the phagus in a. dog, containing a. foreign body. Royal College of Surgeons.) (Specimen in the .Museum of the Royal Veterin ary College.)

Pharyngeal Pouches.—These are uncommon in animals. fig. 178 shows an anterior pharyngeal pouch which I removed from a great anteater. The membranous sac projects upwards and forwards above the‘ hyoid bone. The orifice lies in the pharynx above the base of the epiglottis. It is difficult to assign a function to this pouch. It is certainly not for the storage of food, and I suggest it secretes mucus for the lubrication of the food passages.

oesophageal Pouches.—In the fruit bat I found a pouch at the upper end of the oesophagus which has escaped the notice of earlier observers (fig. 17 9). The pouch was present in three animals I examined, and consisted of a rounded sac situated between a tight circular sphincter mechanism above and weaker constrictor muscle fibres below. This animal spends many hours hanging head downwards from trees, and since there is no sphincter at the lower end of the oesophagus, fluid runs up the tube, but is prevented from entering the pharynx by the strong sphincter at the junction of pharynx with oesophagus. Hence the pouch is a pressure pouch, and the manner of production, lying as it does between a -tight sphincter and a weak constrictor, is remarkedly similar to the mechanism of production of the pressure pouch of man. Immediately below the diaphragm there is a fusiform pouch which is morphologically part of the stomach.

Pathological Pouches in Animals.—Pathological pouches in the pharynx of animals are rare, as they are not systematically looked for. In monkeys there is no reason why they should not occur, except in the orang, where the lower end of the pharynx is strengthened by a specialized muscular band. Negus has recorded a pharyngeal pouch occurring in a mangabey ape.

Pathological pouches commonly occur in the oesophagus of animals. The horse is specially prone to pouch formation owing to rupture of the muscle coats (fig. 180). Pouches occur frequently in the dog (fig. 181).

I wish to thank the Council for the privilege of delivering this Arris and Gale Lecture. My best thanks are due to Mr. Burne for much kindness and help and to Mr. Wilson. I gratefully acknowledge the help of Professor G. E. Gask, Colonel Argyle, Sir Thomas Dunhill, Professor J . Ernest Frazer,

Mr. Carwardine, Mr. Capps, Dr. finzi, Dr. Sparks, and Dr. Simon, and the Curators of many hospital museums.


MOYNIHAN, LORD, “ Diverticula of the Alimentary Canal”, Lancet, 1927, i, 1061. MAES, U., “ Pharyngo-oesophageal Diverticula : General Considerations ”, New Orleans Med. and Surg. Jour., 1929, lxxxii, 126.

JUD1), E. S., and Mormscn, H. J., “ Pharyngo-oesophageal Diverticulum ”, Surg. Clin. N. Amer., 1929, ix, 793.

PUMPELLY, W. C., “ Pharyngo-oesophageal Diverticulum: Case ”, Southern Mad. Jam-.. 1928, xxi, 1021. .

EVLLRINGIIAM, S., “Pharyngo-oesophageal Diverticula”, Surg. Ctin. N. Amer., 1927'. vii 1343.

JACOD,,lVI., “ Pharyngo-oesophageal Diverticula and their Surgical Treatment”, Lyon méd., 1927, cxxxix, 199. ,

HILL, W., “ Pharyngeal and oesophageal Diverticula ”, Brit. Med. Jour., 1926, ii, 1163.

ANGLESIO, B., “ Contribute allo Studio dei Diverticoli faringo-esofagei ”, Arch. ital. dt Chir., 1924-, ix 469.

VERNIEUWE, “ Diverticules multiples de l’Hyopharynx ”, Bull. d’Oto-rhino-laryngol., 1924, N.S. xxii, 20.

VEN DEN WILDENBERG, L., “ Diverticules du Pharynx et de 1’(Esophage ”, Ann. (188 Mal. de l’0reilte, 1922, xii, 783.

fiNZI, N- S-, “ Pharyngeal Pouches ”, Arch. of Radial. and Electrotherap., 1917, xviii. 342VOL. XXI.-—NO. 82. 17 254 THE BRITISH JOURNAL OF SURGERY

SCHONING, D. M. J. C., “ Ueber pulsion Divertikel dcs Hypoplmrynx und ihre Behandlung ”, Zeits. f. 0hrenheilk., 1921, lxxxi, 1.

Mosinsn, H. P., “ Pouch of Esophagus ”, Arch. Otolaryngol., 1929, ix, 5-1.7.

HARRINGTON, S. W., “ Pharyngo-oesophageal Diverticulum ”, Surg. Clin. N. Amer., 1929, ix, 123.

STURGEON, C. T., “Esophageal Diverticula”, Jour. Amer. Med. Assoc., 1929, xcii, 379.

RUSH, L. V. and STINGILY, C. R., “Congenital Diverticulum of (Esophagus: Case Report”, Southern Med. Jour., 1929, xxii, 546.

RICE, G. E., “ oesophageal Diverticula: Report of Two Cases ”, Colorado Med., 1929, xxvi. 34.

Bonus, C. W., “ Diverticulum of (Esophagus : Report. of Two Recent. Cases ”, Canud. Med. Assoc. Jour., 1929, xx, 622.

KENNEDY, C. C., “Surgical Treatment of Pharyngeal and Esophageal Diverticula: Case ”, Minnesota Med., 1928, xi, 669.

BARSONY, T., “ Mechanism involved in Esophageal Diverticulum ”, Arch. f. Verdauungskr., 1928, xliii, 56.

SMITI-I, M. K., “ Deep Pulsion Diverticula of (Esophagus ”, Ann. of Surg., 1928, lxxxviii, 1022.

SMITH, L. A., “Diverticula of Thoracic (Esophagus ”, Amer. Jour. Roentgenol., 1928, xix, 27.

LAHEY, F. H., “ Pulsion Diverticulum of Esophagus ”, Surg. Clin. .\~". Amer., 1928, viii, 51.

fiNEMAN, A. H., “ Unusually Long Diverticulum of Esophagus", Jam. Amer. ll/led. Assoc., 1928, xc, 1943.

PAUCHIIT, V., “Technique of Operative Treatment of Diverticula of the Esophagus", Rev. prat. d. Mal. d. Pays chauds, 1926, vi, 409.

BARSONY, T., and POLGAR, F., “ Roentgen-ray Diagnosis of Symptomless and Functional Diverticula of Esophagus ”, Forts. a. d. Gab. d. Riintgenstrahlen, 1927, xxxvi, 593.

MUIILMANN, “ Rontgcn Diagnosis of Traction Diverticula ”, Ibid., 119.

BREITENECKER, L., “ Traction Diverticula ”, Virchow’s Arch., 1927, cclxv, 9().

ABELL, 1., “ Diverticulum of Esophagus ”, Surg. Clin. N. Amer., 1930, x, 905.

JACKSON, C., and BABCOCK, W. W., “ Diverticulosis of Esophagus : One-stage Operation with Esophagoscopic Assistance ”, 1bid., 1249.

ZUKSCIIVVERDT, L., “ The Surgical Treatment of oesophageal Diverticula ”, Dent. Zcits. f. Chir., 193(), ccxxiv, 15().

JENKINSON, E. L., “ Diverticula of the Esophagus ”, Radiology, 1930, xiv, 508.

SIGORA, B., “Perforation of Esophagus at Traction Divcrticulum”, Ronlgenpraztfs, 1930, ii, 140.

FEDOROFF, S. P., “ Two Cases of 1)iverticula in Cervical Portion of Esophagus "', Zentralb. f. Chir., 1930, lvii, 777.

HEACOCK, C. H., “ Diverticula of Thoracic Portion of (Esophagus ”, Southern Med. Jour., 1930, xxiii, 517.

GooI)wIN, P. B., “ Diverticulum of the Esophagus ", Radiology, 1929, xiii, 472.

GALLY and BERNARD, “ Congenital Diverticulum in Lower Third of (Esophagus ”, Bull. et Mém. Soc. de Radiol., 1929, xvii, 226.

HEINE, J., “ Fatal Pulmonary and Gastro-intestinal Hazmorrhage from Perforation of Bronchi by Traction Diverticulum: Case ”, Deut. med. Woch., 1929, iv, 1135.

Poxnowsxv, S. A., “Low Traction Diverticulum with Cardiospasm ”, Ro'ntgenprcm'.s-, 1929, l, 333.

MAnIAN'rscIIIK, L. P., “Two Cases of Esophageal Diverticula”, Arch. f. klin. Chir., 1929, clv, 333.

VINSON, P. P., “ Cardiospasm associated with Esophageal Diverticula ”, N. Y. Med. Jour., 1923, cxvii, 540.

fiTZGIBBON, J. H., Cardiospasm and Concomitant Esophageal Diverticulum ”, Jour. Amer. Med. Assoc., 1926, lxxxvi, 1614; 1928, xci, 64-4.

ZOIILI-.‘.N, J. P., “ Cardiospasm and Concomitant Esophageal Spasm : Case ”, ¥Visconsin Med. Jour., 1929, xxviii, 526.

ADAMS, A. W., “ Thoracic Stomachs : A Study of Pharyngeal Pouch and Cardiospasm, with Report of Three Cases ”, Brit. Med. Jour., 1930, ii, 208.

KEITH, SIR A., “Diverticula of the Alimentary Tract of Congenital or of Obscure Origin ”, lbid., 1910, i, 376; Human Embryology and Morphology, 1921. London.

MORLEY, J ., “ Diverticula. of the Esophagus ”, Brit. Med. Jour., 1926, i, 981.

WHEELER, VV. 1., “ Pharyngocele and Dilatation of Pharynx with Diverticulum at Lower Portion of Pharynx ”, Dublin Med. Jom‘., 1886, lxxxii, 349.

MARESCH, R., “ Kong. Defekt der Ichilddriisse ”, Zeits. f. Heilk., 1898, xix.

BALLANTYNE, Manual of Antenatal Pathology and Hygiene, 1904.

HUNTER, Jonx, Essays and Observations, 1861, xi.

FRAZER, J. E., “ The Disappearance of the Preccrvical Sinus ", Jour. of Anat., lxi, 132 ; “ The Pharyngeal End of Rathke’s Pouch”, 1bid., xlv, 190 ; “ The Nomenclature of Diseased States caused by Certain Vestigial Structures in the Neck ”, Brit. Jour. Surg., 1923, July, 131 ; Manual of Embryology, 1931. London.

HEBB, R. G., “ Peri—<I:s0phageal Cyst ”, Trans. Pathol. Soc. Lond., 1897-8, xlix, 88.

LANDOIS, F., “ Ueber multiple Cysten des Esophagus ”, Deut. Zeits. f. Chir., 1908, xciv, 000.

LUND, R., “ Esophaguscystc prominierend in die Pars laryngea Pharyngis ”, Zeils. f. Ilals-, Nasen- u. 0hrenheillc., 1922, i, 236.

PAPPENHEIMER, A. M., “ Ciliated Cysts of the Esophagus ”, Proc. N. Y. Pathol. Soc., 1913, xiv, 60.

STOEBER, H., “ Dic Entwicklung des Speiserohrenepithels in einer kongenitalen Cystc des (Esophagus ”, Beitr. z. pathol. Anat., 1912, lii, 512.

STARCK, H., Die Divertilcel der Speiserohre, 1900. Leipzig

CBAUVEAN, C., Le Pharynz, Anatomic et Physiologic, 1901. Paris.

])lSSE, J ., “ Anatomic des Rachens ”, Ilandb. d. Laryngol. u. Rhinol., 1896-9, ii, 1.

ALT!-‘IELD, E., “ Zur Beurtheilung des Schlunddivcrtikels bei Pferden ”, Berl. thierfirzll. Woch., 1894, x, 147.

COLEMAN, J. W., “ Case of oesophageal Pouch in a Horse ”, Jour. Comp. Pathol. and Therap., 1904, xvii, 62.

DIECKERIIOFF, “Zur Beurtheilung der Schlunddivertikel bei Pferden”, Berl. thieriirztl. Woch., 1893, ix, 523.

SIIATTOCK, S. G., “ Pharyngeal Diverticulum ”, Trans. Pathol. Soc. Lond., 1893, xliv, 62.

REESE, A. M., “ The Occlusion of the (Esophagus and Traehea in Crocodilia and Snakes ”, Amer. Jour. Anat., 1926, xxxvii, 195.

MCGILL, CAROLINE, “ The Early Histogenesis of Striated Muscle in the Esophagus of the Pig and the Dogfish ”, Anatomical Record, 1910, iv, 23.

FLINT, J . M., “ The Organogenesis of the (Esophagus ", Anal. Anzeiger, 19()7, xxx, 442.

(‘,oAKL1-;v, C. G., “ The Arrangement of the Muscular fibres of the (Esophagus ", Researcher of Loomis Lab., 1892, ii, 113.

HEwL15T'r, A. W., “ Superficial Glands of the (Esophagus ”, Jour. of Emper. Med., 1901, v. 319.

ROSENTHAL, A. H., “Congenital Atresia of the Esophagus with Trachea-msophageal fistula ”, Arch. of Pathol., 1931, xii, 756.

Wiucirr, W. R., “ On the Function of oesophageal Divertieula in the Adult Female Mosquito ”, Ann. Trop. Med. and Parasitol., xviii, No. 1.

Patten BM. Embryology of the Pig. (1951) The Blakiston Company, Toronto.

EDGEWORTH, F. H., “ On the Development and Morphology of the Pharyngeal, Laryngeal and Hypobranchial Muscles of Mammals ”, Quart. Jour. of Mic. Sci., 191546, lxi, 333.

KUNTZ, A., The Autonomic Nervous System, 1902. London.

JACKSON, CHEVALIER, and SWALLOW, '1‘. A., “ Diverticula of the (Esophagus ”, Trans. Coll. of Phys. of Philadelphia, 1925, xlvii, 39.

Johnson FP. The development of the mucous membrane of the oesophagus, stomach and small intestine in the human embryo. (1910) Amer. J Anat., 10: 521-559.

JOHNSON, F. P., “ The Development of the Mucous Membrane of the Esophagus, Stomach and Small Intestine in the Human Embryo ”, Amer. Jour. Anat., 1910, X, 541.

PLUMMER, H. S., “ Divertieula of the Esophagus with a Report of Six Cases ”, Collected Papers of the Mayo Clinic, 1905, ix, 11.

Juno, E. STARR, and MAYO, C., “Pharyngo-oesophageal Diverticulum”, Ibid., 193], xxiii, 3.

ZURN, “ Schlunddivertikel bei einem Pferdc ”, Deuts. tieriirztl. Woch., 1904, xii, 505.


KINGSBURY, B. F., “ The Development of the Human Pharynx : the Pharyngeal Derivatives ”, Amer. Jour. Anat., 1915, xviii, 329.

GOE'1‘SCH, E., “ The Structure of the Mammalian (Esophagus ”, Ibid., 1910, x, 1.

“-’i«:BI-JR, A., “ Reeherches sur le Dévcloppement de l’Esophage chez quelques Reptiles algériens ”, Comptes. rend. Soc. de Biol, 1921, lxxxv, 417.

Roy, D. N., “Physiology and Function of Esophageal Divertieula and of Salivary Glands in Mosquitoes ”, Indian Jour. Med. Research, 1927, xiv, 995.

Mosnizn, H. P., and MCGREGOR, G. W., “Study of Lower End of Esophagus”, Ann. of Otol. lthinol. and Laryngal., 1928, xxxvii, 12.

ZIMMERMANN, E., “ Esophagus divertikel beim Pferd”, Wein. tierfirztl. Monats., 1928, xv, 826.

\VO0LLARD, H. H., “Potency of Pharyngeal Entoderm”, Jour. of Anat., 1932, lxvi, 242.

Nacus, V. E., “ Evolutionary Factors in the Production of Pharyngeal Diverticula ”. Jour. of Laryngol., 1925, xl, 702; “Ein Pharynx divertikel bein einem Mangabeyaffen ”, Monats. f. 0hreneilk., 1931, lxv, 1388.

ABEL, A. L., Esophageal Obstruction : its Pathology, Diagnosis and Treatment, 1929. 256 THE BRITISH. JOURNAL OF SURGERY

WILKIE, D. P. D., and HARTLEY, J. N. J ., “ Pharyngeal Diverticulum and its Surgical Treatment ”, Brit. Jam‘. Surg., 1922, x, 81.

MIXTER, S. J ., “ Congenital oesophageal Pouch”, Trans. Amer. Surg. Assoc., 1895, xiii, 357. '

Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.

KEIBEL and MALL, Manual of Human Embryology, 1912.

RIEBOLD, G., “flisophageal Diverticula ”, Virchow’s Arch., 1908, cxcii, 126.

HALSTEAD, A. E., “ Diverticula of the (Esophagus ”, Ann. of Surg., 1904, xxxix, 171.

LUDLOW, “ A Case of Obstructed Deglutition from a Preternatural Dilation of, and Bag formed in, the Pharynx ”, Medical Observations and Enquiries, 1764, iii, 85.

KILLIAN, G., “ Ueber die Bursa und Tonsilla pharyngea ”, Morph. Jahrb., 1888, xiv, 618.

Hunsr, A. F., “ Two Cases of Divetticula from the Lower End of the (Esophagus ”, Guy‘s Hosp. Rep., 1925, lxxv, 361.

Hunsr, A. F., and BRIGGS, P. J ., “ Anterior Pharyngo-oesophageal Pouch as a Cause of Dysphagia ”, Ibid., 367.

BUTLIN, Sm HENRY, “ On the Removal of a ‘ Pressure Pouch ’ of the (Esophagus ”, Med.-Chir. Trans., 1893, lxxvi, 269.

GODLEE, R. J ., and BUCKNALL, “ A Pharyngeal Pouch of Large Size removed by Operation ”, Lancet, 1901, i, 1387.

BELL, Sm CHARLES, “ A Pretematural Bag formed by the Membrane of the Pharynx “, Smg. Obser., 1817, i, 64.

KRAGH, J ., “ Tuberculous Diverticula of the (Esophagus ”, Acta Ota-Laryngol., 1922-3, iv, 49.

KOSTANECKI, “ Congenital Gill fistulae in Man ”, Arch. f. Pathol. Anal., 1890, cxxi, 247.

KREUTER, E., “ Congenital Narrowings and Closures of the Intestinal Canal in the Light of Embryology ”, Deut. Zeits. . Chir., 1905, lxxix, 1.

FLETCHER, H. MORLEY, “ A Congefnital Cyst of the Mediastinum ”, Trans. Pathol. Soc. Lond., 1897, xlviii, 249.

Cite this page: Hill, M.A. (2024, June 23) Embryology Paper - Pouches of the pharynx and oesophagus with special reference to the embryological and morphological aspects. Retrieved from

What Links Here?
© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G