Book - Oral Histology and Embryology (1944) 7
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Orban B. Oral Histology and Embryology (1944) The C.V. Mosby Company, St. Louis.
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Chapter VII - Periodontal Membrane
The periodontal membrane is the connective tissue which surrounds the root of the tooth and attaches it to the bony alveolus; it is continuous with the connective tissue of the gingivae. Various terms have been given to this tissue: peridental membrane; pericementum; dental periosteum; and alveolodental membrane. The variety of terms may be explained by the difficulty of classifying this tissue under any anatomic group. The term periodontal is derived from the Greek pert meaning around, and odous meaning tooth, thus signifying the relationship of the tissue to the tooth. This tissue is called a membrane though it does not resemble other ﬁbrous membranes, like fasciae, capsules of organs, perichondrium, and periosteum. It has some structural and functional similarities to these tissues, but is different in that it not only serves as a pericementum for the tooth, a periosteum for the alveolar bone, but mainly as the suspensory ligament for the tooth. Therefore, the term periodontal ligament would be most appropriate.
The functions of the periodontal membrane are formative, supportive, sensory and nutritive. The formative function is fulﬁlled by the cementoblasts and osteoblasts which are essential in building cementum and bone, and by the ﬁbroblasts forming the ﬁbers of the membrane. The supportive function is that of maintaining the relation of the tooth to the surrounding hard and soft tissues. This is achieved by connective tissue ﬁbers which comprise the bulk of the membrane. Functions which are sensory and nutritive to the cementum and alveolar bone are carried out by the nerves and blood vessels.
The periodontal membrane is derived from the follicle, or sac which envelops the developing tooth germ. Around the tooth germ three zones can be seen: an outer zone containing ﬁbers related to the bone; an inner zone of ﬁbers adjacent to the tooth; and an intermediate zone of unorientated ﬁbers between the other two (Fig. 137). During the formation of cementum, ﬁbers of the inner zone are attached to the surface of the root. As the tooth moves toward the oral cavity, gradually a functional orientation of the ﬁbers takes place.“ Instead of loose and irregularly arranged ﬁbers, ﬁber bundles extend ﬁ'om the bone to the tooth. When the tooth has reached the plane of occlusion, and the root is fully formed, this functional orientation is complete. However, due to changes in functional stresses, some changes in the structural arrangement of the periodontal membrane occur throughout life.
First dratt submitted by Helmuth A. Zander.
Fig. 137. Three zones in the periodontal membrane of a developing tooth.
4. Structural Elements
The main tissue elements in the periodontal membrane are the principal ﬁbers, all of which are attached to the cementum?’ 3 The ﬁber bundles extend from the cementum to the alveolar wall, or over the alveolar wall to the cementum of the adjacent tooth, or into the gingival tissue. The principal ﬁbers of the periodontal membrane are white collagenous connective tissue ﬁbers and cannot be lengthened. There are no elastic ﬁbers in the periodontal membrane. The apparent elasticity of the periodontal membrane is due to the arrangement of the principal ﬁber bundles. They follow a wavy course from bone to cementum, thereby allowing slight movement of the tooth upon stress. Near the bone the fibers seem to form larger bundles before their insertion into it. Although the bundles run directly from bone to cementum, it is most probable that the single ﬁbers do not all span the entire distance. The bundles are “spliced" together from shorter ﬁbers and held together by a cementing substance. The principal ﬁbers are so arranged that they can be divided into the following groups:
Fig. 138. Gingival fibers of the periodontal membrane pass from the cementum into ' the gingiva.
The ﬁbers of the gingival group (Fig. 138) attach the gingiva to the cementum. The ﬁber bundles pass outward from the cementum into the free and attached gingiva. Usually they break up into a meshwork of smaller bundles and individual ﬁbers, interlacing terminally with the fibrous tissue of the gingiva.
The ﬁbers of the transseptal group (Fig. 139) connect adjacent teeth. The ﬁber bundles run mesially and distally from the cementum of one tooth, over the crest of the alveolus, to the cementum of the neighboring tooth. The ﬁbers of the alveolar group (Fig. 140) attach the tooth to the bone of the alveolus; they are divided into ﬁve groups: (1) Alveolar crest group: the ﬁber bundles of this group radiate from the crest of the alveolar process, and attach themselves to the cervical part of the cementum. (2) Horizontal group: these ﬁbers run at right angles to the long axis of the tooth, directly to the bone. (3) Oblique group: the ﬁbers run obliquely; arising from the bone, they are attached in the cementum somewhat apically from their attachment to the bone. These ﬁbers are ‘most numerous and constitute the main support of the tooth against occlusal stress. (4) Apical group: the ﬁbers are irregularly arranged and radiate from the apical region of the root to the surrounding bone (Fig. 1-11). (5) I ntermdicular group: From the crest of the interradicular septum ﬁbers extend to the bifurcation of multiradicular teeth.
Fig 139. Transseptal fibers of the periodontal membrane connect adjacent teeth.
The arrangement of the ﬁbers in the different groups is Well adapted to fulﬁll the functions of the periodontal membrane. No matter from which direction a force is applied to the tooth, it is counteracted by some or all of the ﬁber groups. The principal ﬁbers, as a whole, may be regarded as a ligament, alveolodental ligament, by which the tooth is attached to the alveolar bone. Its function is, primarily, to transform pressure exerted upon the tooth into traction on cementum and bone." The ﬁbers are arranged in response to functional stimuli. The structure of the periodontal membrane changes continuously to meet the requirements of the continuously moving tooth.
Fig. 140. AJveo1a.r ﬁbers or the periodontal membrane.
Most cells of the periodontal membrane are typical ﬁbroblasts. They are long, slender, stellate connective tissue cells whose nuclei are large and oval in shape. They lie at the surface of the ﬁber bundles and are, probably, active in the formation and maintenance of the principal ﬁbers.
Fig. 141. Apical ﬁbers of the periodontal membrane.
( Orban.“ )
Bone is in a constant state of transition. As elsewhere in the body, the bone of the alveolus is constantly locally resorbed and rebuilt. Resorption of bone is brought about by the osteoclasts; formation of new bone is initiated by the activity of the osteoblasts.
Where bone formation is in progress osteoblasts are found along the surface of the wall of the bony socket, the periodontal membrane ﬁbers passing between them. These cells are, usually, irregularly cuboid in shape, with large single nuclei containing large nucleoli and ﬁne chromatin particles. The ﬁbers of the periodontal membrane are secured to the bone by the formation of new bone around the ends of the ﬁbers. Therefore, osteoblasts seem to be necessary for the attachment and reattachment
of the ﬁbers to the alveolar bone. Osteoclasts are mostly multinucleated, and are believed to originate from undifferentiated mesenchymal cells in the periodontal membrane; they are found only during the process of active bone resorption. Presumably, the cytoplasm of the osteoclasts produces a substance which dissolves the organic components of bone, while its mineral
Fig. 142. Interstitial spaces in the periodontal membrane consist of loose connective tissue and carry blood vessels and nerves. (0rban.=°)
contents are liberated and either removed in the tissue ﬂuid or ingested by macrophages. Wherever their cytoplasm lies in contact with bone, hollows or grooves called “Howship’s lacunae,” or resorption lacunae, are formed. When bone resorption ceases the osteoclasts disappear. These cells are also active when resorption of the roots of teeth occurs (see chapters on Bone and Shedding). PERIODONTAL Il1EMBR.-\NE 183
Cementoblasts are connective tissue cells found on the surface of °°me’1*°b135t9 cementum betvveen the ﬁbers. They are large cuboidal cells with spheroid or ovoid nuclei, which are active in the formation of cementum (see chapter on Cementum). The cells have irregular, ﬁngerlike projections which ﬁt around the ﬁbers as they extend from the cementum.
The blood vessels, lymphatics, and nerves of the periodontal membrane Interstitial are contained in spaces between the principal ﬁber bundles (Fig. 142). mm‘ They are surrounded by loose connective tissue (interstitial tissue) in which ﬁbroblasts and some histiocytes, undifferentiated niesenchymal cells and lymphocytes are found.
Fig. 143. Blood vessels enter the periodontal membrane through openings in the alveolar bone. (Orban.=‘)
The blood supply of the periodontal membrane is derived from three Blood Vessels sources: (1) blood vessels enter the periapical area together with the blood vessels for the pulp; (2) vessels branching from the inter-alveolar arteries pass into the membrane through openings in the wall of the alveolus (Fig. 143); they are the main source of supply; and (3) near the Lymphatic:
184 om. msronoey AND nmmzvonoor
gingivae, the vessels of the periodontal membrane anastomose with vessels passing over the alveolar crest from the gingival tissue. The capillaries form a rich network in the periodontal membrane, intertwining between the ﬁbers.”
A network of lymphatic vessels, following the path of the blood vessels, provides the lymph drainage of the periodontal membrane. The ﬂow is from the membrane toward and into the adjacent alveolar bone, continuing to the lymph nodes.
Fig. 144. Epithe!tal rests in the periodontal membrane.
Generally, the nerves of the periodontal membrane follow the path of the blood vessels, both from the periapical area and from the interdental and interradicular arteries through the alveolar wall. A rich plexus is formed in the periodontal membrane. Three types of nerve endings are found: one terminating in a knob-like swelling; another, forming loops or rings around bundles of the principal ﬁbers; lastly, free endings of ﬁbers branching from the main axon. These terminal branches are free of myelin sheaths. Most of the nerve endings are receptors for proprioceptive stimuli (deep sensibility). The slightest touch at the surface of the tooth is transmitted to the nerve endings through the medium of the periodontal membrane. All sense of localization is through the periodontal membrane. The sense of touch is not impaired by removal of the apical parts of the membrane, as in root resection, nor by removal of its gingival portion (gingivectomy). As elsewhere in the body, ﬁbers from the sympathetic system supply the blood vessels of the periodontal membrane." 13
Cementnm (tangential ‘ section) ‘ '
Network of 9"" epithelial '. rests
Network of ‘ epithelial } rests -f‘
. .—N tw k t ithelial rests in the periodontal membrane. (Tangential section Fig 145 e or 0 ep almost parallel to root surface.)
In the periodontal membrane epithelial cells are found which, usually, Elgtglictﬂl-llm lie close to the cementum but not in contact with it (Fig. 144). They were ﬁrst described by Malassez in 1885.“ Since then much research has been done as to their origin, structural arrangement and function. They 186 omu. I-IISTOLOGY AND EMBRYOLOGY
are, undoubtedly, remnants of the epithelium which forms Hertwig’s epithelial root sheath“ (see chapter on Tooth Development). At the time of formation of cementum the continuous layer of epithelium, bordering the dentin surface, breaks into strands which persist as a network parallel‘ to the surface of the root (Fig. 145). Only in a surface View, as in sections almost parallel to the root, can the true arrangement of these epithelial
Fig. 146.-—Long strand or epithelium in the periodontal membrane.
strands be seen.“ Cross or central sections through the tooth cut through the strands of the network and, thus, only isolated nests of epithelial cells appear in the sections. It is not clear whether the epithelial sheath breaks up because of degeneration of the epithelial cells, or due to active proliferation of the mesenchyme, or both. This disintegration of the epithelium enables the connective tissue to approach the outer surface of the dentin and to deposit cementum on its surface. The frequent appearane of the epithelial rests, in long strands (Fig. 146) or in tubules (_Fig. 147 l, has given rise to the assumption that they may have endocrine function. Under pathologic conditions they may proliferate and give rise to epithelial masses, associated with grannlomas, cysts, or tumors of dental origin.
Fig. 1l7. Pseuclo-tubular structure of epithelial rest in the periodontal membrane.
Calciﬁed bodies, cementicles, are sometimes found in the tissues of the periodontal membrane, especially in older persons. These bodies may remain free in the connective tissue; they may fuse into large calciﬁed masses, or they may be joined with the cementum (Fig. 148). As the cementum thickens with advancing age, it may envelop these bodies in which event the cemcnticles become interstitial in location. When they are adherent to the cementum they form excementoses. The origin of
these calciﬁed bodies is not established; it IS presumed that degenerated cells, usually epithelial, form the nidus for their calciﬁcation.
5. Peysiologig Changes
Several studies of the width of the periodontal membrane, in human specimens, have been reportecl.“ 3- “r 12 All reports agree that the thickness of the periodontal membrane varies in different individuals, in different teeth in the same person, and in different locations on the same tooth as is illustrated in Tables III to V1.5
Measurements and changes in Dimensions During
Table III Thickness Or Periodontal Membrane Of 172 Teeth From 15 Human Jaws
AVERAGE AT AVERAGE AT AVERAGE AT AVERAGE OF‘
ALV. CREST MIDROOT APEX TOOTH
14:); MM MM MM A es 11-10 83 teeth from 4 jaws 0 23 0 17 0 24 0 21 Ages 32-50 36 teeth from 5 jaws 0.20 0.14 0.19 0.18 Ages 51457 [ _ 35 teeth from 5 jaws 0.17 0.12 0.16 0.1::
Table III shows that the width of the periodontal membrane decreases with age, and that it is wider at the crest and apex than at the midroot. (Coo1idge.8)
Table IV Thickness of Pe1Uobontal Trssuns In Varying Conmtxons Or Function
ALV. CREST MIDROOT APEX AVERAGE
MM. MM. MM. MM. Teeth in heavy function 44 teeth from 8 jaws 0.20 0.14 0.19 0.18 Teeth not in function 20 teeth from 12 jaws 0.1-1 0.11 0.15 0.13 Embedded teeth 5 teeth 0.09 0.07 0.08 0.08
Table IV shows that the width of the periodontal membrane is greater around teeth which are subjected to heavy stress and decreases with loss of function. (Coolidgeﬁ)
TABLE V COMPARISON or THICKNESS or PERIODONTAL MEMBRANE or Foua INGISORS AND FOUR MoLABs (SUBJECT AGED 11 YEARS)
ALv. CREST MIDROOT APEX AVERAGE MM. MM. MM. MM. 4 incisors 0.33 0.25 0.28 0.29 4 molars 0.22 0.15 0.26 0.21
Table V demonstrates that there is a diﬁerenee in the width of the membrane in different teeth in the same individual. (Coolidge!)
TABLE VI COMPARISON or PERIODONTAL MEMBRANE IN DIFFERENT LocAT1oNs AROUND THE SAME '1‘ooTH (SUBJECT AGED 11 YEARS)
MESIAL DISTAL LABIAL LINGUAL MM. MM. MM. MM. Upper ri ht central incisor, mesial and bial drift 0.12 0.24 0.12 _ 0.22 Upper left central incisor, no drift 0.21 0.19 0.24 0.24 Upper right lateral incisor, distal and labial drift 0.27 0.17 0.11 0.15
Table VI shows the variation in width of the mesial, distal, labial, and lingual sides of the same tooth. (Coolidge!)
The measurements shown in the tables indicate that it is not feasible to refer to an average ﬁgure of normal width of the periodontal membrane. Measurements of large number of cases range from 0.15 to 0.38 mm. The ‘fact that the periodontal membrane is the thilmest in the m1ddle region of the root shows that the fulcrum of physiologic movement Is in this reglon. The thickness of the periodontal membrane seems to be maintained by the ftmctional movements of the tooth. It is thinner in flmctionless and embedded teeth. The fact that cementum and bone do not fuse even in functionless teeth might be due to the fact that both lose their growth potential if function is lost.
Fig. 148. Cementicles in the periodontal membrane.
Physiologic movement of human teeth is characterized by their tendency to migrate mesially in compensation for the wear at their contact points.” In mesial migration a difference can be observed in the periodontal membrane in the distal and mesial areas (Fig. 149, A and B). On the distal side of the tooth, the interstitial spaces with their blood vessels, lymph spaces and nerves, appear in sections elliptic in contrast to those on the mesial side that appear round.” Bone resorption on the mesial side of the tooth sometimes opens marrow spaces which become continuous with the periodontal membrane (Fig. 149, A). Frequently, however, the drift is so gradual that bone formation in the marrow spaces keeps pace with the resorption on the periodontal membrane side, and the thickness of the alveolar bone is maintained. Due to the shift of the tooth, epithelial rests may become incorporated in the bone on the side from which the tooth is shifting.“
Fig. 149. Interstitial spaces between the principal ﬁber bundles are round on the pressure side (A) and elliptic on the tension side (B). Marrow spaces open up on the pressure side and become interstitial spaces. C : Cementum. D : Dentin.
6. Clinical Considerations
The complex functional relationship between the teeth and their supporting tissues brings about continuous structural changes during life. Between the two extremes of occlusal trauma and loss of function there are many intermediate stages. In loss of function the periodontal membrane becomes narrower, due to decreased use of that particular tooth.‘ 1°’ 1‘ The regular arrangement of the principal ﬁbers is lost and the periodontal membrane appears as an irregularly arranged connective tissue. The cementum becomes thicker but ﬁnally aplastic; it contains no Sharpey’s ﬁbers. Also, the alveolar bone is in an aplastic (inactive) state and lacks Sharpey’s ﬁbers (Fig. 150, B).
Fig. 150. Periodontal membrane or a. functioning (A) and nontunctioning (B) tooth. In the functioning tooth the periodontal membrane is wide, principal ﬁbers are present. cementum (C) is thin; bundle bone with Sharpey's ﬁbers. In the nonfunctioning tooth the periodontal membrane is narrow, no principal fiber bundles are present. Cementu_m is thick (0 and 0') ; alveolar bone is lamellated with no Shar-pey's ﬁbers. D = Dentin.
For restorative dentistry the importance of these changes in structure is obvious.” The supporting tissues of a tooth long out of function are unable to carry the load suddenly placed upon the tooth by restoration. This applies to bridge abutments, teeth opposing bridges or dentures, and teeth used as anchorage for removable bridges. This may account for the inability of a patient to use a restoration immediately following its placement. Some time must elapse before the supporting tissues are again rearranged in response to the new functional demands. This may be termed an adjustment period which, likewise, must be permitted to follow orthodontic treatment.
The stress, especially of a lateral type, often placed upon the supporting apparatus may be more than the tissue can tolerate. Sudden trauma of the periodontal membrane, such as in accidental blows, condensing of foil, rapid mechanical separation, may produce pathologic changes: fractures or resorption of the cementum, tears of the ﬁbers, hemorrhage and necrosis. The adjacent alveolar bone is resorbed and the periodontal membrane thickened; the tooth becomes loose. When trauma is eliminated repair may take place. For practical purposes it is important that, in the construction of ﬁllings and bridges, the occlusion be carefully considered, and interference in lateral movements (cusp interference) avoided or eliminated. It is also important that missing teeth be immediately replaced to avoid tipping and migration of remaining teeth; failure to do so may result in loss of function and traumatism.
Orthodontic tooth movement depends upon bone resorption and bone formation stimulated by properly regulated pressure and tension." These stimuli are transmitted through the medium of the periodontal membrane. If the movement of teeth is within physiologic limits (Which may vary with the individual) the initial thinning of the periodontal membrane on the pressure side, is compensated for by bone resorption, whereas the thickening of the periodontal membrane, on the tension side, is balanced by bone apposition. If new bone formation is impaired by faulty manipulation or disease, the periodontal membrane may become wider and the tooth may loosen, or even be completely lost. Under the stimulus of inﬂammation such as occurs in a dental granuloma the epithelial rests of the periodontal membrane may proliferate to form a periodontal cyst around the root end of the tooth. The dental granulomas are found frequently, and very careful studies“: 9“ have shown that 100 per cent of dental granulomas have either proliferating or resting epithelium. Since all dental granulomas contain this material, they must" all be considered as potential periodontal cysts.
1. Berkelbach van der Sprenkel, H.: Zur Neurologie des Zahnes (Neurology of the Tooth), Ztschr. f. mikr.- anat. Forsch. 38: 1, 1935.
2. Black, G. V.: A Study of the Histological Characters of the Periosteum and Peridental Membrane, Chicago, 1887, W. T. Keener Co.
3. Black, G. V.: The Fibers and Glands of the Peridental Membrane, Dental Cosmos 41: 101, 1899.
4. Box, K. F.: Evidence of Lymphatics in the Periodontium, J. Canad. D. A. 15: 8, 194.9.
5. Brunn, A. v.: Ueber die Ausdehnung des Schmelzorganes und seine Bedentung fur die Zahnbildung (The Extension of the Enamel Organ and Its Signiﬁcance in Tooth Development), Arch. f. mikr. Anat. 29: 367, 1887.
6. Bruszt, P.: Ueber die netzartige Anordnung des paradentalen Epithels (The Network Arrangement of the Epithelium in the Periodontal Membrane), Ztschr. f. Stomatol. 30: 679, 1932.
7. Coolidge, E. D.: Clinical Pathology and Treatment of the Dental Pulp and _Periodontal Tissues, Philadelphia, 1939, Les. & Febiger.
8. Coolidge, E. D.: The Thickness of the Human Periodontal Membrane, J. A. D. A.
9. Gottlieb, B.: Paradental Pyorrhoe und Alveolar atrophie (Paradental Pyorrhea and Alveolar Atrophy), Fortschr. d. Zahnheilk. 2: 363, 1926.
9a. Hilli J.: The Epithelium in Dental Granulomata, J. Dent. Research 10: 323,
10. Kellner, Histologische Befunde an antagonistenlosen Ziihnen (Histologic Findings on Teeth Without Antagonists), Ztschr. f. Stomatol. 26: 271, 1928.
11. Klein, A.: Systematische Untersuchungen iiber die Periodontalbreite (Systematic Investigations on the Width of the Periodontal Membrane), Ztschr. f. Stomatol. 26: 417, 1928.
12. Kronfeld, R.: A Case of Tooth Fracture, With Special Emphasis on Tissue Repair and Adaptation Following Traumatic Injury, J. Dent. Research 15: 429, 1935/6.
13. Lehner, J., and Plenk, H.: Die Ziihne (The Teeth), Moellendorfs Handbuch. d. mikrosk. Anat. vol. 3, Berlin, 1936, J. Springer, p. 449.
14. Malassez, M. L.: Sur l’existence de masses epithéliales dans le ligament alveolodentaire (On the Existence of Epithelial Masses in the Periodontal Membrane), Compt. rend. Soc. de biol. 36: 241, 1884.
15. McCrea, M. W.: Histologic Studies on the Occurrence of Epithelium in Dental Granulomata, J. A. D. A. 24: 1133, 1937.
16. Noyes, F. B.: A Review of Work on the Lyniphatics of Dental Origin, J. A. D. A. 14: 714, 1927.
17. Oppenheim, A.: Human Tissue Response to Orthodontic Intervention of Short and Long Duration, Am. J. Orthodont. & Oral Surg. 28: 263, 1942.
18. Orban, B.: Entwicklungsgeschichte und Histogenese (Embryology and Histogenesis), Fortschr. d. Zahnheilk. 3: 749, 1927.
19. Orban, B.: Biologic Considerations in Restorative Dentistry, J. A. D. A. 28: 1069 1941.
20. Orban, B’: A Contribution to the Knowledge of the Physiologic Changes in the Periodontal Membrane, J. A. D. A. 16: 405, 1929.
21. Orban, B.: Dental Histology and Embryology, Philadelphia, 1929, P. Blakiston’s Son & Co.
22. Robinson, H. B. G.: Some Clinical Aspects of Intra-Oral Age Changes, Geriatrics 2: 9 1947.
23. Schweitzer, G.: Die Lymphgeflisse des Zahnﬁeisches und der Ziihne (Lymph Vessels of the Gingivae and Teeth), Arch. 1:‘. mikr. Anat. 69: 807, 1907; '74: 927, 1909.
24. Sicher, H.: Ban und Funktion des Fixationsapparates der Meerschweinchenmolaren ( tructure and Function of the Supporting Apparatus in the Teeth of Guinea Pigs), Ztschr. f. Z. Stomatol. 21: 580,.1923. .
25. Weinmann, J. P.: Progress of Gingival Inﬂammation into the Supporting Structures of the Teeth, J. Periodont. 12: 71. 1941.
26. Weinmann, J. P.: Bone Changes Related to Eruption of the Teeth, Angle
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