Topography of the Nasal Glands in Rats and Some Other Mammals FINN BOJSEN-MBLLER Department of A n a t o m y a n d Histology, Royal Dental College, Copenhagen, Denmark ABSTRACT The topography of nasal glands in rats, guinea-pigs, rabbits, cats, and monkeys was studied in osmium tetroxide and PAS-stained whole mounts and ordinary sections. In rats Bowman's glands in the olfactory region were arranged i n rows between the branches of the olfactory nerve. Mucous acini were only found o n the rat septum in connection with Jacobson's organ, and serous acini were found on the septum posteriorly in the respiratory region, and on the lateral wall of the nasal cavity around the maxillary sinus ostium. No mixed glands were present. All the serous glands discharged their secretion through long excretory ducts into the ostium internum of the vestibule of the nose. In this area rats had 15-20 duct openings on each side. On the basis of considerations regarding airstream and pressure in the vestibule, the hypothesis is advanced that the openings act as small nozzles humidifying the inspired air by their atomized secretion. Since no serous or mucous glands in the rat open on the surface in the nasal cavity proper, it is concluded that the surface mucous sheet is derived exclusively from the goblet cells and Bowman's glands. In the other mammals the opening of the serous glands showed a similar pattern. The nasal cavity is provided with mucous and serous glands in the lamina propria and with goblet cells in the epithelial layer. The secretion of the mucous cells forms a sheet of mucus which lines the surface of the nasal cavity. By the ciliary function of the epithelium, this sheet is exchanged several times an hour (Hilding, '32). There is a constant flow of mucus in rodents in two directions, from the posterior, larger part of the nasal cavity toward the pharynx and from the anterior part toward the nostrils (Lucas and Douglas, '34). This mucus exerts a protective effect. It can entrap foreign particles and bacteria and remove them from the nasal cavity. Moreover, it has a waterproofing action, preventing an excessive transudation from the tissue into the lumen and an inward osmotic passage of water which becomes condensed on the surface during expiration (Negus, '58). The ciliary function depends on the mucous sheet and its viscosity. Lastly, the moist surface subserves the sense of smell, being the medium in which the olfactory molecules are dissolved. Humidification of the inspired air is effected by transudation through the thin ANAT. REC., 250: 11-24. epithelium and by the function of the serous glands, while the mucus itself is not believed to be concerned with this process (Negus, '58). According to the type of the epithelium and glands, the mucous membrane on the septum as well as on the lateral nasal walls is divided into a respiratory and an olfactory region. On a fresh specimen the junction between the two is discernible, as the olfactory region often shows marked yellow pigmentation. The glands in the respiratory region may be divided into a medial group on the septum and a lateral group on the lateral wall of the nasal cavity. This latter group includes a gland whose body is beneath the mucosa of the maxillary sinus, as a rule in its anterior wall or around the ostium of the maxillary sinus. From this site, a large excretory duct proceeds beneath the mucosa of the middle meatus, opening at the nostril, frequently just anterior to the nasoturbinal. This gland is called the lateral nasal gland or Steno's gland, as it was described by the Danish anatomist Steno in 1664. Meyer ('03) described this gland in a number of domestic animals, int. al., dogs, cats, goats, pigs, and horses. He found it to be par11 12 FINN BO JSEN-M@LLER ticularly large in dogs, in which the mucous membrane of the maxillary sinus may be several millimeters thick. In cats, on the other hand, the gland and duct are demonstrable only microscopically, and in the cow it is absent. It is a serous gland, and it has intercalated ducts as well as secretory ducts. The main excretory duct is lined with simple or pseudostratified columnar epithelium changing into stratified squamous epithelium a short distance from the opening. Broman ('21 ) studied the occurrence and development of the nasal glands in a number of rodents, using serial sections of the nasal cavity from fetuses of various stages and from newborn young. On this basis, he made plastic reconstructions of the nasal mucosa, its glands and ducts. He found the following groups of glands: ( 1 ) olfactory glands specific of the olfactory region, ( 2 ) anterior lateral nasal glands whose acini and ducts are situated in the lateral wall of the nasal cavity and open into the vestibular part or into the anterior part of the respiratory region, (3) maxillary gland opening along the edge of the maxillary sinus, ( 4 ) anterior medial nasal glands whose acini and ducts are situated on the nasal septum and which open into the vestibular part or the anterior part of the respiratory region, (5) posterior medial nasal glands, an inconspicuous group of glands situated below Jacobson's organ, ( 6 ) glands which open into Jacobson's organ, and (7) infraseptal glands situated below the anterior part of the septum and opening on the lateral wall of the vestibule. Acini belonging to the anterior lateral nasal glands are scattered in the respiratory region on the nasoturbinal, on the maxilloturbinal, and in the middle meatus, right back to the area surrounding the maxillary ostium. Hence, the ducts proceed forward, and all open at the junction to the vestibule, either on the free edge of the maxillo- or nasoturbinal or in the middle meatus. Broman numbered the glands chronologically according to the stage at which they were laid down. Thus, Steno's gland, which was laid down first in all the animals, he called gld nasalis lateralis anterior I. In the mouse he found about 20 and in the rabbit about 40 lateral glands. Acini belonging to the anterior medial nasal glands are situated in the respiratory region above Jacobson's organ as well as anterior and inferior to the olfactory region. In many species they may be divided into an upper and a lower group. The ducts proceed forward and all open at the junction to the vestibule. These glands were also numbered chronologically according to the time at which they were laid down. In the mouse he found four and in the rabbit about 13 medial glands. The glands belonging to Jacobson's organ are situated, also according to Broman, in two rows along the borders of the olfactory epithelium. Their degree of development differs in the various rodents. It is characteristic of the mouse and rat that gland no. 2 in the upper row from the anterior aspect gets particularly large and branches into the septa1 mucosa. Bang and Bang ('59) found in histological sections that the lateral nasal gland in most vertebrates, e.g., chickens and carnivores, is a compound gland with a single efferent duct opening into the vestibule, whereas rodents and rabbits have a network of accessory ducts in addition to the primary duct of Steno, each draining its particular portion of the gland and discharging into the vestibule. In guinea-pigs, hares, and dogs the glands of the respiratory region are said to be purely serous, while in cats they are purely mucous (Negus, '58). In man these glands are compound tubulo-alveolar, of the mixed type in which mucous acini predominate. The acini are usually purely mucous or purely serous, although mixed acini with serous demilunes may be found (Heiss, '36). The glands have no intercalary or secretory ducts. The small excretory ducts pass obliquely to the surface, ending in a funnel-shaped opening. The larger excretory ducts are scattered in the respiratory region, but chiefly at its junction to the vestibular part. The epithelium lining these ducts is simple columnar, but in the largest ones sometimes pseudostratified. Close to the opening it assumes the nature of the surface epithelium, acquiring ciliated cells and goblet cells (Schiefferdecker, 00). According to Brunner ('42), the human glands open into crypts in the mucous membrane, but as the excretory THE GLANDS IN THE MAMMALIAN NASAL CAVITY 13 ducts are long the openings are seldom tated. After removal of the lower jaw, the seen. heads were divided sagittally, on each side Lastly, there are in the respiratory re- of the septum, by a sawblade mounted in gion numerous goblet cells placed singly in a dental burr drill. Another sagittal secthe epithelium or in groups forming the tion was applied through the maxillary so-called intra-epithelial glands. sinus, as close as possible to the nasal The olfactory region has only one kind mucosa. This gave three specimens, one of gland, viz. Bowman's. In man, these are compound tubulo-alveolar glands, of each lateral wall and one of the septum. As a rule, the mucosa on one side of the while in the rat they are simple tubular. septum was dissected with a blunt instruMorphologically they resemble the serous glands, but DeVanna and Salonna ('53) ment, the entire specimen being divided consider them mucous, as they stain by into two equal parts, each consisting of a the periodic-acid-Schiff (PAS ) technique. lateral wall and the mucous membrane Bang ('61) described the surface pat- from the corresponding part of the septern of mucous glands in PAS stained tum. In some cases, especially when dealwhole mounts of nasal organs of chickens ing with the small animals, this partition and herring gulls. She found the glands was not quite successful, so that one half aligned in rows on the lateral wall as well of these preparations had to be excluded. as on the septum and the direction of the One part of each specimen (comprising flow of the mucous sheet to be consistent a lateral wall and the corresponding septa1 with this pattern. Apart from the study of mucosa) was fixed for an hour in 0.2% Broman ('21) mentioned above, no similar osmium tetroxide buffered to pH 7.2 by studies of the glandular topography in the veronal sodium (Palade, '52). The tissue nasal cavity of mammals and man appear was dehydrated in alcohol and cleared in to have been reported. Moreover, the study anise oil as described by Aurell ('38). of Broman does not seem to be mentioned From electron microscopic studies it is in the recent literature. A knowledge of well-known that osmium tetroxide does not the situation of the glands and the course merely fix, but also stains tissue. This and opening of their excretory ducts is technique of preparation distinctly sets important, if their function is to be under- out all acini and excretory ducts; vessels stood. The present paper describes the are only faintly visible, whereas nerves findings in rats and some other mammals stain deeply. Connective tissue stains on the basis of a combination of sections faintly, whereas cartilage shows marked and whole mounts stained with PAS and blackening. Therefore, the technique often osmium tetroxide respectively. This gives fails in handling specimens which are a good three-dimensional understanding more than a couple of mm in thickness without any need for serial sectioning of and which contain these elements. They these large specimens. turn a diffuse black which masks all details. Another disadvantage is the slow MATERIAL AND METHODS penetration of osmium into the tissue. In The material comprises nasal cavities thick specimens the superficial structures from 16 rats, two guinea-pigs, two rabbits, stain too deeply before the osmium has one cat, and one monkey. Four of the had time to penetrate into and stain the rats were adult, six were four weeks of deep parts. This may be counteracted to age, five were two weeks and one was one some extent by using a weaker dilution of week of age. All the other animals were osmium tetroxide and a correspondingly adult. Histological sections were made : longer staining period. We selected a of the entire nasal cavity from four rats, 0.2% solution which proved suitable in of a septum from a guinea-pig, and of a the majority of cases. lateral nasal wall from a rabbit. The reThe method is applicable even though mainder of the material was studied in the tissue has already been fixed in forwhole mounts. malin and stored in alcohol. If so, the The animals were anesthetized with staining with osmium tetroxide also has Nembutal intraperitoneally and decapi- to be prolonged. 14 FINN BOJSEN-MGLLER The remaining part of the septum and the other lateral wall were fixed for 24 hours in formol: alcohol (1 : 2 ) , PAS stained, dehydrated, and cleared in anise oil (Moe, '52). India ink (diluted with 0.9% sodium chloride 1 : l ) heated to 37°C was injected into the aorta of two rats. The septum was then removed and fixed for 24 hours in formalin, dehydrated, and cleared in anise oil. The whole mounts were studied in a stereo microscope. The nasal cavity from four rats was dissected in toto, fixed in formol: alcohol ( 1 : 9 ) for 24 hours, and decalcified in formic acid. Two of these specimens were cut into frontal serial sections and stained with hematoxylin-eosin. The other two were cut in three areas, viz. at the junction of the vestibule and nasal cavity, centrally and posteriorly in the cavity. These sections, 7-10 CI in thickness, were stained with hematoxylin-eosin, PAS, PAS after being pre-treated with diastase for an hour, and PAS hematoxylin. Lastly, a few sections were stained with a pentachromic stain containing Alcian Blue (Movat, '55). + RESULTS Rat As is apparent from figure 1 and table 1 the nasal septum may be divided into five zones according to its surface epithelium and glandular content. Serous glands are present only in Zones I and 11. They do not stain with PAS or ,;---/' '\. Fig. 1 Diagram of the right side of the rat nasal septum. For classification into zones cf. table 1. Alcian Blue. On each side of the septum there are four or five glands, two large and two or three smaller ones (figs. 2 and 3 ) . Each gland consists of acini situated mainly in the posterior half of Zone 11, and a long excretory duct opening into the vestibule. The openings of the two largest glands may be seen superiorly and centrally on the vestibular part of the septum. From this site, the ducts course together upward-backward, parallel to the dorsum nasi. A short distance from the olfactory region they curve downwards, forming in the posterior part of Zone 11 a spiral-shaped or S-shaped coil (fig. 2 ) . The two or three somewhat smaller glands are situated at the upper and lower limits of Zone 11, where they send a fairly straight excretory duct to the vestibule. They open in varying sites on the anterior part of the tuberculum septi. In the anterior third the ducts receive no tributaries, while in the posterior twothirds they receive branches at right angles (monopodic branching). These branches arise in the acini which are situated as TABLE 1 Types of epithelium and distribution of glands i n the different zones o f the nasal septa1 mzicosa i n the rat Region Epithelium Serous glands Vestibule zone I stratified squamous - Respiratory area zone I1 pseudo-stratified ciliated columnar I Respiratory area zone I11 pseudo-stratified ciliated columnar Respiratory area zone IV pseudo-stratified ciliated columnar - Olfactory area zone V olfactory - Mucous glands Goblet cells Bowman's glands - - - + + - Fig. 2 Part of nasal septum viewed from the right, comprising Zone I1 and the adjacent parts of Zones I, 111, and V. Two-week old rat. Osmium tetroxide stained whole mount. S: serous glands in Zone 11. M: mucous glands in Zone 111. B : Bowman’s glands in Zone V. Posteriorly in Zone I1 a spiral-shaped curling of a serous gland. Note the acini situated as clusters along the excretory ducts. x 23. \ ’ I f rnUCOUS Y / a n d 5 Fig. 3 Diagram showing serous and mucous glands on the nasal septum of the rat. The ducts of the serous glands course forward and open into the vestibule. The mucous glands empty into Jacobson’s organ which is situated along the lower margin of the septum (the organ is not shown in the diagram). In the olfactory region note the olfactory nerves, some of which continue to Jacobson’s organ. 16 FINN BOJSEN-MQLLER small clusters along the main excretory ducts. They are particularly densely arranged posteriorly, while more anteriorly they decrease in size as well as in number. The glandular ducts on the septum are situated fairly deeply in the lamina propria and anteriorly they are frequently sur- rounded by pseudocavernous tissue (fig. 4). At the opening they curve obliquely towards the surface and may open at its level or on a small conical elevation. The ducts are lined with simple columnar epithelium. The nuclei are centrally located in the cells, the cytoplasm eosinophilic Fig. 4 Frontal section through the nasal cavity at the junction to the vestibule. Twoweek-old rat. Hematoxylin-eosin. The cavity is lined with stratified squamous epithelium except i n its upper part where the epithelium is pseudostratified columnar. Numerous excretory ducts in the middle meatus and on the niaxilloturbinal. On the septum inferiorly there are two and superiorly three ducts surrounded by cavernous tissue. Note the glandular openings on the free edge of the nasoturbinal and in the middle meatus (arrows). S: duct of lateral nasal gland of Steno. L: nasolacrimal duct. Below the septum three excretory ducts ( x ) surrounded by serous acini. x 45. THE GLANDS I N THE MAMMALIAN NASAL CAVITY with basal striation. Before reaching the opening, the epithelium changes into pseudostratified and thereupon assumes the nature of the surface epithelium, viz. stratified cornified squamous epithelium. The ducts are 30-40 u in diameter. The study did not reveal any acini opening direct on the surface in the respiratory region. In the India ink-injected whole mounts there was pseudocavernous tissue surrounding the anterior part of the glands and the openings of the ducts. For instance, the tuberculum septi contained a good deal of pseudocavernous tissue, In the sections serous acini were found also in a cavity in the osseous tissue below the anterior third of the septum (= Broman’s gld. infraseptalis) (x, fig. 4 ) . These acini empty into two large excretory ducts which may be followed in the serial sections. The ducts course forward and open 17 anteriorly on the floor of the vestibule or somewhat higher up on its lateral wall. Glands in which the cytoplasm showed diastase-resistant PAS positivity and which stained with Alcian Blue were interpreted as mucous glands. They are situated as a coherent cluster indicating Zone I11 (figs. 3 and 5). These glands fill the entire lamina propria in this zone. All acini empty into one or two large excretory ducts coursing forward - downward and opening into Jacobson’s organ at the junction between its posterior two-thirds and anterior third. In addition, the mucinous acini situated within the capsule of the organ, i.e. the actual glands of Jacobson, send numerous small excretory ducts into the two parallel grooves found at the junction between the olfactory and columnar epithelium of the organ. Thus, the secretion of all the mucous glands of the respiratory region of the septum is discharged Fig. 5 Nasal septum. Four-week-old rat. PAS stained whole mount. The apex nasi on the right, choana at the bottom on the left. In the olfactory region Bowman’s glands are visible as delicate dots arranged in a linear pattern. In the respiratory region the mucous glands may be seen collected in one area i n the lamina propria (Zone 111, cf. fig. 1 ) . x 10. 18 FINN BOJSEN-MGLLER into the organ of Jacobson, which is situated along the base of Zone 111. In this way these mucous glands are analogous to Bowman’s glands of the olfactory region. E n route to the olfactory region and the lamina cribrosa, the large nerves which issue from Jacobson’s organ divide the mucous glandular area into four or five wide belts. Goblet cells are present throughout Zone 11, 111, and IV. As a rule, they occur singly and seldom make up intraepithelial groups. They are most densely arranged in Zone IV around the choanae and inferiorly in Zone 111. Bowman’s glands are present only in Zone V which corresponds to the olfactory region. They are PAS positive, simple tubular glands traversing the entire lamina propria. The PAS positive granules are localized particularly in the subepithelial portion of the glands, although scattered granules may be seen in the cells found in the profound part of their intraepithelial course. As is evident from figure 5 the glands are arranged in rows converging towards the lamina cribrosa. Presumably, this represents a purely mechanical phenomenon, caused by the olfactory nerves which partly supply the region itself and partly proceed to Jacobson’s organ. As is apparent from the sections, the nerves fill almost the entire lamina propria, the glands being situated in the interstitial spaces (fig. 6). The lateral wall of the nasal cavity in the rat may be divided into three zones according to its surface epithelium and its glandular content (fig. 7 and table 2). The serous acini are situated immediately beneath the surface epithelium in the entire middle meatus and anterior as well as inferior to the maxillary sinus ostium (fig. 8 ) . They empty into 10-12 long ducts, coursing forward in the middle meatus. A short distance before reaching the vestibule, a number of the ducts curve, either cranially or caudally, until they reach the root of the nasoturbinal and the maxilloturbinal respectively and continue out to open on their side or on their free edge (fig. 4 ) . The remaining ducts open anteriorly in the meatus. Just as on the septum, the simple epithelium of the ducts changes, before the opening, into pseudo- stratified, and then into stratified q u a mous epithelium. There is, moreover, a large group of acini around the maxillary sinus ostium, extending from the above-mentioned acini and further lateral into the anterior wall and the floor of the maxillary sinus. The acini have a narrow lumen surrounded by epithelial cells which have basal nuclei and a cytoplasm which stands out dark and granular when stained with hematoxylin-eosin. Morphologically, they resemble serous acini, but the cytoplasm stains red with PAS and blue with Alcian Blue, although the stain is much paler than in the typical mucous glands. By the present technique, therefore, it is impossible to group these acini either as mucous or serous. Presumably, they are serous. Between the acini there are many secretory ducts which empty into a large excretory duct running forward-upward in the middle meatus. A short distance from the root of the nasoturbinal it curves forward and courses parallel to the line of attachment of the turbinal to the vestibule (fig. 8 ) . In the whole mounts it stands out darker and thicker than the other ducts and is consequently easy to trace. This is the gland which has been described as the lateral nasal gland or Steno’s gland. In the sections it shows a pseudostratified epithelium with two rows of cuboidal cells unlike the other excretory ducts which have predominantly a simple epithelium. Its diameter is about 60 11, that of the other ducts 30-40 ~1 (fig. 4). Goblet cells are present only in the respiratory region in which they are particularly densely arranged on the medial aspect of the maxilloturbinal. As on the septum, there are only a very few intraepithelial groups of goblet cells. Bowman’s glands are found in the olfactory region where they are aligned, as on the septum, between the nerves which converge towards the lamina cribrosa. In the whole mounts the nasolacrimal duct is visible inferiorly on the lateral wall where it runs forward, medial to the upper incisor. It also opens in the vestibule, but even farther anteriorly than the other glands, the opening being on a level with the ala of the nose. THE GLANDS IN THE M A M M A L I A N N A S A L CAVITY Fig. 6 Frontal section through the nasal septum showing the olfactory region. Two-weekold rat. PAS stained. Bowman’s glands are situated between the olfactory nerves. The subepithelial part and some of the intra epithelial part of the glands are stained. Close to the osseous septum there are branches of the ethmoidal artery. x 120. I Fig. 7 Diagram showing the lateral wall of the nasal cavity in the rat. For classification into zones, cf. table 2. 19 20 FINN BO JSEN-MC~LLER TABLE 2 T y p e s of e p i t h e l i u m a n d distribution of glands in t h e different zones of t h e lateral wall of the nasal cavity in t h e r a t Region Serous glands Epithelium Mucous glands Goblet cells Bowman’s glands Vestibule zone I stratified squamous - - - - Respiratory area zone I1 pseudo-stratified columnar + - + - Olfactory area zone I11 olfactory -t g l . na salis l a t Stenonis OQSO turb6 fhmo f urbinals ostium sinus ma.uUaris audio turbina Fig. 8 Diagram showing the glands on the lateral wall of the nasal cavity in the rat. The posterior parts of the nasoturbinal and the maxilloturbinal have been removed so that the course of the glandular ducts i n the middle meatus may be traced. Only a few of the ducts are demonstrated. Around the maxillary sinus ostium there is a large glandular body whose main part makes up the lateral nasal gland of Steno. Subepithelially in the same area the other serous glands take their origin. Unlike the former, the latter glands receive tributaries from the acini during their course through the middle meatus. Note the openings of the ducts anteriorly i n the vestibule and on the free edges of the turbinals. Apart from the rat, another two rodents, as well as a cat and a monkey, were studied. The same whole mount technique was used, with fixation and staining in osmium tetroxide and subsequent clearing in anise oil. In these larger animals, however, the lateral wall of the nasal cavity was so thick that during osmium staining the preparations became so black that they could hardly be cleared. Consequently, the main stress was laid on the study of the septum. Guinea-pig On the nasal septum of the guinea-pig there is a large group of serous acini in the posterior two-thirds of the respiratory region. These acini are particularly dense posteriorly below the olfactory region. In this area the mucosa is 1.0 mm thick, while in the other parts of the septum it is about 0.2mm. From these acini at least ten long excretory ducts run all the way to the vestibule. These excretory ducts course in three strands, one along the dorsum nasi, one along the floor, and one in the middle of the septum. In the vestibule the openings may be seen on and immediately anterior to the tuberculum septi. In the most anterior portion of the respiratory region there are, moreover, some small glands whose ducts course right forward, opening in the vestibule together with the larger ducts. In the THE GLANDS I N THE MAMMALIAN NASAL CAVITY sections, the acini present themselves with a small lumen, round basal nuclei, and a delicately granular, eosinophilic cytoplasm. The excretory ducts are lined with simple columnar epithelium, the nuclei are centrally located and the cytoplasm eosinophilic with basal striation. On the lateral wall there are acini around the maxillary sinus ostium, extending forward in the middle meatus. From this site, about ten excretory ducts proceed to the vestibule. Rabbit On the rabbit septum there are about 20 glands on each side. Their acini occupy a horseshoe-shaped area on the septum, being localized in the posterior half of the respiratory region and in two strands along 21 the upper and lower boundary of the septum all the way to the vestibule. The excretory ducts may be traced throughout the glandular area, the majority running superiorly or inferiorly on the septum to the openings in the vestibule (fig. 9). Posteriorly, they undergo dichotomous division a few times, but otherwise they receive only tributaries at right angles. On the lateral wall acini are present around the maxillary sinus ostium and hence all the way forward, in the middle as well as inferior meatus, there being about 20 excretory ducts in the middle and about ten in the inferior meatus. Most of the ducts in the middle meatus proceed anteriorly to the nasoturbinal and open on its inferior, free edge. In contrast to the rat, Fig. 9 Vestibule in an adult rabbit; septum viewed from the right. Osmium tetroxide stained whole mount. Four ducts and their openings are visible. One duct courses downward-forward, opening a bit more apically than the others. x 45. 22 FINN BOJSEN-M#LLER the rabbit has no openings on the maxilloturbinal. The ducts are lined with simple epithelium and are 40-50 LI in diameter. Around the maxillary sinus ostium there is, as in the rat, a large cluster of glands occupying the entire wall between the nasal cavity and the maxillary sinus (the lateral nasal gland). The acini resemble serous glands in hematoxylin - eosin stained preparations. They stain with PAS, but not as deeply as e.g. the mucous glands which are scattered subepithelially throughout the maxillary sinus. In the glandular cluster the sections show numerous secretory ducts. They empty into a large excretory duct which proceeds upward-forward in the middle meatus until it reaches the nasoturbinal. At this site it turns straight forward and runs parallel to the soot of the turbinal until it opens into the vestibule. It has a pseudostratified epithelium with two rows of cuboidal cells and is surrounded by a lamina propria. In cross section i t is oval and measures 300 X 80 p. The opening is so large that the canal can easily be injected with a dye which may be traced to the acini. Cat In the cat there are 8-10 PAS positive glands anteriorly on the septum. Their ducts proceed parallel, downward-forward, to the vestibule. In the whole mounts the openings may be seen aligned on the tu- berculum septi. The pattern is similar to that seen in the monkey (fig. lo), although the glands are shorter. In addition, there are small groups of PAS positive acini scattered in the entire respiratory region. From each of these groups a small excretory duct proceeds straight up to the surface where it penetrates the epithelium. Cynomolgus Monkey (inacacus irus) The monkey is a microsmatic animal and has only a small olfactory region. On the septum there are a number of glands whose ducts cousse parallel with the dorsum nasi down into the vestibule (fig. 10). The longest of these ducts takes its origin in the olfactory region. The glands are shorter in the lower part of the septum. In the posterior parts there are several divisions of the ducts, and there are a few anastomoses. At the openings into the vestibule there are 15-20 ducts. As in the cat, acini are scattered in the entire respiratory region. Current studies on the human septum have shown that infero-anteriorly in the region of the internal ostium there is ail area of about one square cm which has densely placed glandular openings, 300400 LI in diameter. Whole mounts stained with osmium tetroxide exhibit ducts proceeding upward-backward from this site. Hematoxylin-eosin stained sections of the pn. oifoctorii n.nusopafatinus Fig. 10 Diagram of the nasal septum of a monkey (macacus irus) viewed from the right. The olfactory region is small. The course of the glands and their openings into the vestibule are visible. Only some of the ducts are demonstrated. THE GLANDS I N THE MAMMALIAN NASAL CAVITY anterior part of the respiratory region show mixed acini in the lamina propria. Excretory ducts of two sizes are discernible: 70-80/~ ducts of a rather superficial level which often open on the surface and 200400/cl ducts of a deeper situation which open in the vestibular region. In this respect, the glandular topography in man appears to resemble that found in the monkey, although the ducts might be shorter. DISCUSSION It is a basic pattern in all the animals studied that a large group of serous glands open around the internal ostium of the nasal cavity. This was particularly striking in rodents in which all the serous glands of the nose opened into this zone. In the rat there were 15-20 glands and in the rabbit not less than 50 on each side, apart from the large lateral nasal gland. The last-mentioned gland was described as early as 1664 by Steno. Meyer (’03),who called it Steno’s gland, described the site of the body of this gland and the course of its excretory ducts in 15 large animals in which he could dissect the gland macroscopically, e.g. dog, lion, hyena, camel, sheep, and horse. In all animals he found the site of opening in or close to the vestibule except in the horse in which it was deeper in the nose. On histological study Meyer found that the glandular cells in Steno’s gland did not show mucus reaction and that they had to be interpreted as serous. He assumed that the function of the gland was to moisten the inspired air. Broman (’21) demonstrated that in rodents a number of serous glands, apart from Steno’s gland, open into the vestibule, in mice and rats 20-25 and in rabbits about 55 on each side. This is in keeping with the present results. Broman assumed that the function of these glands was to moisten the inspired air and, that the serous fluid flowing down past the opening of Jacobson’s organ could carry with it smelling substances which could temporarily be sucked into this organ. In a previous paper (Broman, ’18) on the architecture and function of Jacobson’s organ in some mammals, he also mentioned these nasal glands. He pointed out that in animals in which Jacobson’s 23 organ opens into the nasal cavity, e.g. rodents, the nasal glands are highly developed, while they are less developed or absent if Jacobson’s organ is absent, as e.g. in man, or if Jacobson’s organ communicates with the oral cavity, as e.g. in the cow in which even the most constant of the large nasal glands, the lateral nasal gland of Steno, atrophies already in the embryo. These studies by Broman of the nasal glands appear to have been unheeded by recent literature, and we were not aware of them until after we had found the named glandular course. In the area at the internal ostium there is the junction of the cutaneous lining of the vestibule to the mucosa of the nasal cavity. The internal ostium is at the same time the narrowest place that the inspired air passes on its way through the nose. According to the equation of Bernoullis, known from hydrodynamics, the pressure will fall where a flowing fluid or gas is accelerated in the direction of the stream, and it will increase where the flow slows down (= accelerated in the opposite direction). During inspiration the pressure in the nasal cavity is low and must be particularly low on a level with the openings of the glands in the internal ostium, as this is where the acceleration of the airstream is at a maximum. It is tempting to imagine that the process of humidification is increased also by the way in which the glandular openings are placed at the internal ostium. The opening is on a small conical elevation, on the tuberculum septi or on the free edge of the conchae. This orients the ducts against the airstream in a way which, combined with the low pressure, might permit or favor the process of humidification by atomizing the discharge, and in addition this atomized fluid might entrap olfactory molecules and carry them to the olfactory region. During expiration the pressure over the openings is high and the airstream quieter and slower than during inspiration. Thus, during expiration the conditions are less favorable for a possible nozzle effect with unnecessary loss of fluid. The ducts and their openings are surrounded by pseudocavernous tissue which swells during the resting phase of the nasal cycle and thereby slows down the 24 FINN BOJSEN-MCbLLER passage of air through one-half of the nose (Stoksted, '56). It might be imagined that during this process the ducts too are greatly narrowed, so that the glands do not discharge any secretion. This centers new interest on the opening of the nasolacrimal duct in the vestibule, since owing to its distant position it must be assumed to act, in the animals studied, in the same way as the nasal glands proper. If so, the lacrimal fluid takes part in the air conditioning. During inspiration there must be a pressure gradient over the canal. This involves the possibility that it is not solely by capillary action that the fluid in the lacus lacrimalis is sucked into the nasolacrimal duct, but that this difference in pressure may be contributory. During expiration there is a pressure gradient in the opposite direction. If the diameters of the canals may be taken to indicate their share in the nozzle function, the lacrimal fluid must represent an important supplement to the humidification of the air, as the nasolacrimal duct in the rat measures 350 X 150 CI and in the rabbit 1.6 X 0.5 mm. While all the serous glands in the rat open into the nasal vestibule, the secretion of the mucous glands flows into Jacobson's organ which in turn opens on the floor of the nasal cavity. Therefore, in this animal at least, the blanket of mucus which lines the nasal mucosa can be derived only from the goblet cells and from Bowman's glands. It has been claimed that transudation of fluid through the nasal mucosa makes up the main source of humidification of the inspired air (Negus, '58). Ingelstedt and Ivstam ('48) and Messerklinger ('51), however, could not demonstrate transudation from capillaries and tissue fluid to the nasal secretion under normal conditions and conclude that nasal secretion is normally a pure glandular product. This assumption is supported by the present findings. ACKNOWLEDGMENT The author is grateful to Professor H. Moe, M.D., Department of Anatomy and Histology, The Royal Dental College, Copenhagen, for helpful discussions and criticism during the preparation of this manuscript. LITERATURE CITED Aurell, G. 1938 Kolophonium - Chininhydrochloridgemische als Einschlussmittel f u r sehr dicke Schnitte zu mikroskopischen Zwecken. Z.wiss.Mikr., 55: 256-273. Bang, B. G. 1961 The surface pattern of the nasal mucosa and its relation to mucous flow. J. Morph., 109: 51-72. Bang, B. G.,and F. B. Bang 1959 A comparative study of the vertebrate nasal chamber in relation to upper respiratory infections. Bull. Johns Hopkins Hosp., 104: 107-149. 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