Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Secretory Otitis Media Pathology and Pathogenesis Related to Clinical Picture M. Tos To cite this article: M. Tos (1976) Secretory Otitis Media Pathology and Pathogenesis Related to Clinical Picture, Acta Oto-Laryngologica, 82:1-6, 286-288, DOI: 10.3109/00016487609120907 To link to this article: http://dx.doi.org/10.3109/00016487609120907
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 1
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [New York University]
Date: 17 April 2016, At: 03:47
Acta Otolaryng 82: 286-288, 1976
SECRETORY OTITIS MEDIA
Pathology and Pathogenesis Related to Clinical Picture M. Tos
Downloaded by [New York University] at 03:47 17 April 2016
From the ENT University Clinic, Gentofte Hospital, Copenhagen, Denmark
Abstract. Secretory otitis is divided into three stages, and from a description of the pathogenic processes taking place in each stage it is attempted to explain how secretion is generated, and why it stops. The initial stage is characterized by inflammatory changes by way of capillary dilatation and proliferation, lymphatic infiltration, increased goblet-cell density and formation of mucous glands; the secretion is exudative with admixture of mucus. The secretory stage is dominated by secretion of mucus from the metaplastic mucosa with extremely high density of goblet cells and glands. I n the degenerative stage, the production of mucus abates because the goblet-cell density decreases, and the glands degenerate.
The fluid accumulating behind the intact drum in chronic secretory otitis is a product of various processes in the tubal and middle-ear mucosa. These processes have started long before the principal symptom-hearing lossmanifests itself; but also after the clinical symptoms have abated, processes are taking place in the middle ear and the auditory tube which may lead either to cure or relapse of the disease. In the present study, these processes are reviewed and related to the clinical picture of the disease. For a century, many investigators have been concerned with the question of how and why middle-ear secretion is generated (for literature, see Tos, 1976), and several theories have been advanced: the hydrops ex vucuo theory (Politzer, 1878), which is based on the assumption that the fluid is a transudate resulting from the low pressure in the middle ear; the exudation theory (Zollner, 1936), which Acta Otolaryngol82
assumes that the fluid is an exudate with a higher protein content than serum. The demonstration of the secretory ability of the middle-ear mucosa (Sade, 1966; Bak-Pedersen & Tos, 1971) marks a great step forward and forms the basis of the secretory theory. MATERIALS AND METHODS The entire tubal and middle-ear mucosa was studied in necropsy specimens from foetuses, prematures and infants, normal children, children with secretory otitis in the initial stage, normal and abnormal adults. Furthermore, a study was made of over 5000 biopsy specimens taken from the middle-ear mucosa during surgery in 496 patients with disorders of the middle ear; 85 were children with secretory otitis in the secretory stage, and 48, mainly adults, had chronic adhesive otitis, which is the terminal stage of secretory otitis. All specimens were stained by the PASalcian blue whole-mount method, and the density of goblet cells and mucous glands was determined quantitatively. Subsequently, the preparations were cut into serial sections, stained by haematoxylin-eosin and alcian blue and then investigated. RESULTS The disease was divided into three stages: (1) The initial stage, i.e. the time from the action
Downloaded by [New York University] at 03:47 17 April 2016
Secretory otitis media
287
number of goblet cells, the production of mucus is also increased, and the exudate therefore becomes admixed with mucus. The secretory stage is dominated by secretion of mucus from the metaplastic middleear mucosa. The number of goblet cells (Tos & Bak-Pedersen, 1972, 19756) and active mucous glands is greatly increased. The inflammatory processes continue, in the severest cases leaving the mucosa thickened and polypous. Exudation also occurs at this stage, but, since the mucus-producing capacity of the mucosa is now maximal, the secretion is predominantly mucous. Quantitative studies of goblet cells and mucous glands revealed great individual differences, which is in good agreement with the varying degrees of severity of the disease. With low density of mucous glands the accumulation of mucus will PATHOLOGY AND PATHOGENESIS be small, and the clinical symptoms will abate The initial stage is characterized by inflamma- rapidly without or after a short treatment. tory changes starting in the lamina propria by Conversely, with pronounced metaplasia and way of capillary proliferation and dilatation, a high density of mucous elements, mucus as well as lymphocytic infiltration. These will continue to accumulate, and repeated changes soon induce hyperplasia and differen- drainage is required. It is a well-known fact that even in the tiation of the epithelial cells with subsequent metaplasia of the epithelium into pseudostrati- severest cases the accumulation of mucus will fied columnar ciliated epithelium with in- gradually diminish, and this is possible only if creased goblet-cell density and formation of the mucus-producing capacity of the mucosa mucous glands (Tos & Bak-Pedersen, 1975a). is impaired. Processes to this effect take place The most crucial process is the gland forma- in the degenerative stage. The number of tion which sets in with invasion of undifferen- goblet cells decreases, and the inflammatory tiated epithelial cells into the lamina propria; changes subside; the epithelium returns to these cells differentiate into ciliary and normal cubical epithelium in one or two mucous cells; the glands become canalized layers, or is transformed by metaplasia into and secretion and transport of mucus from the secretorily inactive stratified squamous epiglands to the epithelial surface commence. thelium (Tos, 1976). The most important The final result of the metaplastic changes is process is the degeneration from active to a middle-ear mucosa reminiscent of that of the completely inactive cystic glands. This derespiratory tract, i.e. with great density of generation has been demonstrated quantitagoblet cells and glands with a high mucus- tively: in the secretory stage 93 % of the glands producing capacity. It is obvious that in- were found to be active against only 11% in flammatory and metaplastic changes of this the terminal stage (Tos & Bak-Pedersen, type cause exudation through the epithelium, 1973). The end result is a decline in both an exudation which is accompanied by expul- exudation and mucus production. Provided sion of epithelial cells and lymphocytic migra- that tubal function returns to normal, the tion. Owing to the considerably enhanced remaining secretion will be carried to the of the aetiological factor on the middle-ear mucosa till secretion accumulates and causes symptoms, during which the first metaplastic changes occur in the middle-ear mucosa; clinical symptoms are mild, originating mainly from the tubal occlusion which is always present. (2). The secretory stage, which is dominated by mucous secretion with the wellknown symptoms of fluid accumulation. (3) The degenerative stage during which the mucus production decreases and the clinical symptoms vanish, provided that irreversible adhesive changes have not developed-if so, the disease has gone into its terminal stage, chronic adhesive otitis.
Actu Otolarynyol82
288
M . Tos
rhinopharynx, and the patient becomes free of symptoms. Whether secretion will reaccumulate in the middle ear depends on the mucusproducing capacity of the mucosa and on the ability of the tube to carry the mucus away.
Downloaded by [New York University] at 03:47 17 April 2016
DISCUSSION
as those seen in the initial stage of secretory otitis. ZUSAMMENFASSUNG Sekretorische Otitis wird in drei Stadien eingeteilt, und durch eine Beschreibung der pathogenetischen Prozesse jedes Stadiums wird versucht zu erklaren, wie die Sekretion entsteht, und warum sie aufhort. Im Initialstadium werden inflammatorische Veranderungen in Form von Kapillardilatation und Proliferation, Lymphozyteninfiltration, Vermehrung der Becherzellanzahl sowie Glandelbildung gesehen; das Sekret ist ein mit Schleirn vermischtes Exsudat. Im Sekretionsstadium dominiert die Sekretion von Mukus aus der metaplastisch veranderten Schleimhaut mit sehr hoher Becherzell- und Glandeldichte. Im Degenerationsstadium nimmt die Mukusproduktion ab, weil die Becherzelldichte abnimmt, und die Driisen degenerieren.
Based on the description of the secretory pathogenesis and of the pathological findings in the mucosa, an attempt is made to explain how middle-ear secretion is generated, and why it ceases. The secretion must be regarded as a mixture of exudate and mucus, with the exudate dominating in the initial and the mucus in the secretory stage. At all stages REFERENCES fluid is also absorbed (Lim, 1975). Bak-Pedersen, K. & Tos, M. 1971. The mucous glands Whether transudation ex vucuo also occurs in chronic secretory otitis media. Acta Otolaryngol (Stockh)72, 14. . in the initial stage could not be proved histologically, but we could prove that exudation Lim, D. J. 1974. Functional morphology of the lining membrane of the middle ear and Eustachian tube. takes place which, at all stages, accounts for Ann Otol Rhinol Laryngol, Suppl. 1 1 , 3. the non-mucous element of the secretion. Politzer, A. 1878. Lehrbuch der Ohrenheilkunde, 1-2, p. 84. Enke, Stuttgart. In the initial and the secretory stage, the Proud, G. 0. & Odoi, H. 1970. Effects of Eustachian middle-ear pressure is always negative. During tube ligation. Ann Otol Rhinol Laryngol79, 30. the period with the drain operating well, the Renvall, U. 1975. Secretory otitis media studies by Eustachian tube function test and impedance audiofunction of the auditory tube is usually metry. Elanders Tryckeri, Goteborg. markedly pathological (Renvall, 1975). In the Sade, J. 1966. Pathology and pathogenesis of serous otitis media. Arch Otolaryngol84, 297. degenerative stage, i.e. after expulsion of the drain, the middle-ear pressure is likewise Tos, M. 1976. Pathologie und Pathogenese der Chronischen Sekretorischen Otitis im Kindesalter. HNO 24, negative. Tuba1 occlusion may be present for 37. a long time without giving rise to transudation Tos, M. & Bak-Pedersen, K. 1972. Density of mucous glands in a biopsy materi'al of chronic secretory otitis ex vucuo. By experimental tubal occlusion media. Acta Otolaryngol (Stockh) 75, 55. with simultaneous drainage of the drum no - 1973. Density of mucous glands in chronic adhaesive otitis media. Arch Ohren Nasen Kehlkopfieilkd 206, fluid formed in the middle ear (Proud & Odoi, 39. 1970), and this is taken to be the most impor- 197Sa. The outset of chronic secretory otitis media. tant evidence in support of the hydrops ex A histopathological study of the earliest stage. Arch Otolatyngol101, 123. vucuo theory. In my view, these experiments demonstrate only that tubal occlusion is the - 197Sb. Density of goblet cells in chronic secretory otitis media. Findings in a biopsy material. Laryngoprincipal aetiological factor in the production scope 85, 377. of fluid, whereas they reveal nothing of how Zollner, F. 1936. Widerstandsmessungen an der Ohrtrompete zur Priifung ihrer Wegsamkeit. Ein neues the fluid is generated. Our histological studies Verfahren und bisherige Ergebnisse an Ohrgesunden of the infantile middle-ear mucosa, however, und -kranken. Arch Ohren Nasen Kehlkopfieilkd 140, 137. showed the same changes in tubal occlusion
Acta Otolaryngol82
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Secretory Otitis Media Pathology and Pathogenesis Related to Clinical Picture M. Tos To cite this article: M. Tos (1976) Secretory Otitis Media Pathology and Pathogenesis Related to Clinical Picture, Acta Oto-Laryngologica, 82:1-6, 286-288, DOI: 10.3109/00016487609120907 To link to this article: http://dx.doi.org/10.3109/00016487609120907
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 1
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [New York University]
Date: 17 April 2016, At: 03:47
Acta Otolaryng 82: 286-288, 1976
SECRETORY OTITIS MEDIA
Pathology and Pathogenesis Related to Clinical Picture M. Tos
Downloaded by [New York University] at 03:47 17 April 2016
From the ENT University Clinic, Gentofte Hospital, Copenhagen, Denmark
Abstract. Secretory otitis is divided into three stages, and from a description of the pathogenic processes taking place in each stage it is attempted to explain how secretion is generated, and why it stops. The initial stage is characterized by inflammatory changes by way of capillary dilatation and proliferation, lymphatic infiltration, increased goblet-cell density and formation of mucous glands; the secretion is exudative with admixture of mucus. The secretory stage is dominated by secretion of mucus from the metaplastic mucosa with extremely high density of goblet cells and glands. I n the degenerative stage, the production of mucus abates because the goblet-cell density decreases, and the glands degenerate.
The fluid accumulating behind the intact drum in chronic secretory otitis is a product of various processes in the tubal and middle-ear mucosa. These processes have started long before the principal symptom-hearing lossmanifests itself; but also after the clinical symptoms have abated, processes are taking place in the middle ear and the auditory tube which may lead either to cure or relapse of the disease. In the present study, these processes are reviewed and related to the clinical picture of the disease. For a century, many investigators have been concerned with the question of how and why middle-ear secretion is generated (for literature, see Tos, 1976), and several theories have been advanced: the hydrops ex vucuo theory (Politzer, 1878), which is based on the assumption that the fluid is a transudate resulting from the low pressure in the middle ear; the exudation theory (Zollner, 1936), which Acta Otolaryngol82
assumes that the fluid is an exudate with a higher protein content than serum. The demonstration of the secretory ability of the middle-ear mucosa (Sade, 1966; Bak-Pedersen & Tos, 1971) marks a great step forward and forms the basis of the secretory theory. MATERIALS AND METHODS The entire tubal and middle-ear mucosa was studied in necropsy specimens from foetuses, prematures and infants, normal children, children with secretory otitis in the initial stage, normal and abnormal adults. Furthermore, a study was made of over 5000 biopsy specimens taken from the middle-ear mucosa during surgery in 496 patients with disorders of the middle ear; 85 were children with secretory otitis in the secretory stage, and 48, mainly adults, had chronic adhesive otitis, which is the terminal stage of secretory otitis. All specimens were stained by the PASalcian blue whole-mount method, and the density of goblet cells and mucous glands was determined quantitatively. Subsequently, the preparations were cut into serial sections, stained by haematoxylin-eosin and alcian blue and then investigated. RESULTS The disease was divided into three stages: (1) The initial stage, i.e. the time from the action
Downloaded by [New York University] at 03:47 17 April 2016
Secretory otitis media
287
number of goblet cells, the production of mucus is also increased, and the exudate therefore becomes admixed with mucus. The secretory stage is dominated by secretion of mucus from the metaplastic middleear mucosa. The number of goblet cells (Tos & Bak-Pedersen, 1972, 19756) and active mucous glands is greatly increased. The inflammatory processes continue, in the severest cases leaving the mucosa thickened and polypous. Exudation also occurs at this stage, but, since the mucus-producing capacity of the mucosa is now maximal, the secretion is predominantly mucous. Quantitative studies of goblet cells and mucous glands revealed great individual differences, which is in good agreement with the varying degrees of severity of the disease. With low density of mucous glands the accumulation of mucus will PATHOLOGY AND PATHOGENESIS be small, and the clinical symptoms will abate The initial stage is characterized by inflamma- rapidly without or after a short treatment. tory changes starting in the lamina propria by Conversely, with pronounced metaplasia and way of capillary proliferation and dilatation, a high density of mucous elements, mucus as well as lymphocytic infiltration. These will continue to accumulate, and repeated changes soon induce hyperplasia and differen- drainage is required. It is a well-known fact that even in the tiation of the epithelial cells with subsequent metaplasia of the epithelium into pseudostrati- severest cases the accumulation of mucus will fied columnar ciliated epithelium with in- gradually diminish, and this is possible only if creased goblet-cell density and formation of the mucus-producing capacity of the mucosa mucous glands (Tos & Bak-Pedersen, 1975a). is impaired. Processes to this effect take place The most crucial process is the gland forma- in the degenerative stage. The number of tion which sets in with invasion of undifferen- goblet cells decreases, and the inflammatory tiated epithelial cells into the lamina propria; changes subside; the epithelium returns to these cells differentiate into ciliary and normal cubical epithelium in one or two mucous cells; the glands become canalized layers, or is transformed by metaplasia into and secretion and transport of mucus from the secretorily inactive stratified squamous epiglands to the epithelial surface commence. thelium (Tos, 1976). The most important The final result of the metaplastic changes is process is the degeneration from active to a middle-ear mucosa reminiscent of that of the completely inactive cystic glands. This derespiratory tract, i.e. with great density of generation has been demonstrated quantitagoblet cells and glands with a high mucus- tively: in the secretory stage 93 % of the glands producing capacity. It is obvious that in- were found to be active against only 11% in flammatory and metaplastic changes of this the terminal stage (Tos & Bak-Pedersen, type cause exudation through the epithelium, 1973). The end result is a decline in both an exudation which is accompanied by expul- exudation and mucus production. Provided sion of epithelial cells and lymphocytic migra- that tubal function returns to normal, the tion. Owing to the considerably enhanced remaining secretion will be carried to the of the aetiological factor on the middle-ear mucosa till secretion accumulates and causes symptoms, during which the first metaplastic changes occur in the middle-ear mucosa; clinical symptoms are mild, originating mainly from the tubal occlusion which is always present. (2). The secretory stage, which is dominated by mucous secretion with the wellknown symptoms of fluid accumulation. (3) The degenerative stage during which the mucus production decreases and the clinical symptoms vanish, provided that irreversible adhesive changes have not developed-if so, the disease has gone into its terminal stage, chronic adhesive otitis.
Actu Otolarynyol82
288
M . Tos
rhinopharynx, and the patient becomes free of symptoms. Whether secretion will reaccumulate in the middle ear depends on the mucusproducing capacity of the mucosa and on the ability of the tube to carry the mucus away.
Downloaded by [New York University] at 03:47 17 April 2016
DISCUSSION
as those seen in the initial stage of secretory otitis. ZUSAMMENFASSUNG Sekretorische Otitis wird in drei Stadien eingeteilt, und durch eine Beschreibung der pathogenetischen Prozesse jedes Stadiums wird versucht zu erklaren, wie die Sekretion entsteht, und warum sie aufhort. Im Initialstadium werden inflammatorische Veranderungen in Form von Kapillardilatation und Proliferation, Lymphozyteninfiltration, Vermehrung der Becherzellanzahl sowie Glandelbildung gesehen; das Sekret ist ein mit Schleirn vermischtes Exsudat. Im Sekretionsstadium dominiert die Sekretion von Mukus aus der metaplastisch veranderten Schleimhaut mit sehr hoher Becherzell- und Glandeldichte. Im Degenerationsstadium nimmt die Mukusproduktion ab, weil die Becherzelldichte abnimmt, und die Driisen degenerieren.
Based on the description of the secretory pathogenesis and of the pathological findings in the mucosa, an attempt is made to explain how middle-ear secretion is generated, and why it ceases. The secretion must be regarded as a mixture of exudate and mucus, with the exudate dominating in the initial and the mucus in the secretory stage. At all stages REFERENCES fluid is also absorbed (Lim, 1975). Bak-Pedersen, K. & Tos, M. 1971. The mucous glands Whether transudation ex vucuo also occurs in chronic secretory otitis media. Acta Otolaryngol (Stockh)72, 14. . in the initial stage could not be proved histologically, but we could prove that exudation Lim, D. J. 1974. Functional morphology of the lining membrane of the middle ear and Eustachian tube. takes place which, at all stages, accounts for Ann Otol Rhinol Laryngol, Suppl. 1 1 , 3. the non-mucous element of the secretion. Politzer, A. 1878. Lehrbuch der Ohrenheilkunde, 1-2, p. 84. Enke, Stuttgart. In the initial and the secretory stage, the Proud, G. 0. & Odoi, H. 1970. Effects of Eustachian middle-ear pressure is always negative. During tube ligation. Ann Otol Rhinol Laryngol79, 30. the period with the drain operating well, the Renvall, U. 1975. Secretory otitis media studies by Eustachian tube function test and impedance audiofunction of the auditory tube is usually metry. Elanders Tryckeri, Goteborg. markedly pathological (Renvall, 1975). In the Sade, J. 1966. Pathology and pathogenesis of serous otitis media. Arch Otolaryngol84, 297. degenerative stage, i.e. after expulsion of the drain, the middle-ear pressure is likewise Tos, M. 1976. Pathologie und Pathogenese der Chronischen Sekretorischen Otitis im Kindesalter. HNO 24, negative. Tuba1 occlusion may be present for 37. a long time without giving rise to transudation Tos, M. & Bak-Pedersen, K. 1972. Density of mucous glands in a biopsy materi'al of chronic secretory otitis ex vucuo. By experimental tubal occlusion media. Acta Otolaryngol (Stockh) 75, 55. with simultaneous drainage of the drum no - 1973. Density of mucous glands in chronic adhaesive otitis media. Arch Ohren Nasen Kehlkopfieilkd 206, fluid formed in the middle ear (Proud & Odoi, 39. 1970), and this is taken to be the most impor- 197Sa. The outset of chronic secretory otitis media. tant evidence in support of the hydrops ex A histopathological study of the earliest stage. Arch Otolatyngol101, 123. vucuo theory. In my view, these experiments demonstrate only that tubal occlusion is the - 197Sb. Density of goblet cells in chronic secretory otitis media. Findings in a biopsy material. Laryngoprincipal aetiological factor in the production scope 85, 377. of fluid, whereas they reveal nothing of how Zollner, F. 1936. Widerstandsmessungen an der Ohrtrompete zur Priifung ihrer Wegsamkeit. Ein neues the fluid is generated. Our histological studies Verfahren und bisherige Ergebnisse an Ohrgesunden of the infantile middle-ear mucosa, however, und -kranken. Arch Ohren Nasen Kehlkopfieilkd 140, 137. showed the same changes in tubal occlusion
Acta Otolaryngol82
