Pathogenesis can be defined as the unfolding of a

disease process, or the sequence of events in the devel-

G)
opment of a disease from its earliest beginnings. Con-
cepts of pathogenesis are based to a large extent upon
the natural history of the disease and upon its histo-
pathologic and ultrastmctural features.
Until recently there was insufficient information
upon which to develop a unified concept of the patho-
genesis of inflammatory gingival and periodontal dis-
ease. Indeed, views have been uniquely divergent, with
emphasis being placed upon the multifactorial nature
Of the disease. This need be the case no longer.
The structural manifestations of the advanced sta"e o
of the disease were described accurately over haH a
century ago;33,7U,S9the natural history of the disease,
at least as it occurs in the beagle dog, has been c1ari-
fied;37,60 and recently the events occurring during
the initial and early stages of the disease were de-
scribed.6,39,4o,56,62.64.65,69,7o,s7
Thus, while the obser-
vations are far from complete and many of the details
remain unclear, the overall features of the pathogenesis
are beginning to emerge. It is our intent to organize
and present selected portions of the available data in
order to make these principal features apparent. This
approach has admitted shortcomings and constraints,
especially in that coverage is incomplete; however,
these are outweighed by the clarity introduced.
The periodontium is the primary seat of severd
inflammatory lesions that may differ from one another
etiologically and in their natural histories, but which
may exhibit similar clinical :md histopathologic rnani-
festations. Among the better delined of these are acute

Structure necrotizing ulcer2.tive gingivitis; hormonaL I1ntritionai,

and drug-related gingivitis; periodontosis or juvenile
periodontitis; and inflammatory gingivitis and per.jo-
dontitis associated with the accumulation of mic3'obial

and plaque. In addition, the supporting structures are af-

fected by several atrophic and degenerative diseases
such as occlusal traumatism, alveolar atrophy, and
desquamative gingivitis. However, the plaque-associ-

Pathogenesis ated inflammatory lesion makes up the bulk by far, of

the lesions encountered by the dentist, and it is the
only lesion for which sufficient information is available
to develop even an elementary understanding of its
'ROY C. Ef\GE pathogenesis. Thus. the discussion that follows relates
to the plaque-associated inflammatory lesion only.
AND H~BERT E. SCHROEDER

Efforts directed toward gaining an understanding of

the pathogenesis of inflammatory gingival and perio-
dontal disease span more than a centnr~'. These -tudies
can he divided roughly into three categories: clinical
observation, structural analysis, and experimental ma-
nipulation and quantitative measurement.
Clinical Observation
During the initial period, which extended thr011gh-
out most of the nineteenth century, the predominant
technique Llsed was clinical observation, and efforts
wele directed almost completely toward documenta-
tion of the clinical signs and symptoms of the disease,
classification, delineation of associated etiologic fac-
tors, and development of techniques for treat-
ment.1O,13,25,31,3<1,55
..'57,58,78The observations of these
early investigators established several important
points: (1) the disease is not homogeneous, but rather it
is a combination of several different diseases with a
common manifestation; (2) both local and systemic
factors are involved in the etiologv; (.3) the lesion is
basically a form of suppurative inflammation with
associated resorption of the alveolar bone; (4) pus
formation and exudation are the common features of
advanced disease; and (5) debridement, stabilization of
the teeth, and oral cleanliness are important aspects of
successful treatment.
Structural Analysis
It was not until the turn of the nineteenth century,
that investigators began to examine the microscopic
structure of the naturally occurring lesion. During the
ensuing 50 years, numerous papers appeared, describ-
ing structural features of advanced spontaneous perio-
dontal disease.3,4.8,1l,15,27,33,H,79.8<1.89
These studies es-
tablished the cardinal histopathologic features of the
advanced stages of the disease, as well as its route of
progress. Little attention "vas directed toward study of
the initiallesion.7,<lH7,86
During the past decade, the increased resolving
power of the electron microscope has been brought to
bear on the problem, and this has provided an insight
into many of the '-'ellular and ultrastructural alterations
seen in man and other animals. 16,17, 18,<12,<16,52,61, 70,
71,51,8:<,38
Experimental Manipulation
and Quantitative Measurement
A more recent development has been the applica-
tion of an experimental approach and quantitative
analytic techniques to problems of pathogenesis. The
histopathologic and ultrastructural features of experi-
mental gingivitis have been examined in both cross-
sectional and longitudinal studies,4o,56,87 and morpho-
metric techniques have been adapted to problems of
quantitative analysis of the components of the affected
tissues.o:Z·(j:J,67,68
Further studies employing these tech-
niques have led to a redefinition of the nature of the
early inflammatory lesion and have permitted, for the
first time, a better understanding of the temporal pro-
gression of events in the pathogenesis.6,5(j,i)5,i)f},70
EARLY CONCEPTS OF PATHOGENESIS
One of the
•
earl\est concepts of the pathogenesis held
that proliferatiol1" and apical migration of the cells of
the epithelial attachment (junctional epithelium) with
pocket formation are the initial and most significant
pathologic changes associated with inflammatory gin-
gival and periodontal disease.~~·~3.33.79,s8 Attention
appears to have been focused upon this aspect of the'
disease by the intense interest of oral histologists in
determining the nature of the normaJ epithelial at-
tachment apparatus.21,49,83,85 :\Iuch of the early work
was directed toward discovering the basic cause of the
prolifel:ation and migration, and this objective became
synonymous with that of understanding the pathogen-
esis of the disease. '
Numerous hypotheses were devised to account for
the proliferation and apical migration. Gottlieb con-
sidered a limited amolmt of alveolar atrophy and re-
cession of the marginal bone to be a normal conse-
quence of aging and continuous eruption of the teeth.~l
He felt that pocket formation and "pyorrhea" were a
consequence of irregularity or accentuation of this
normal process. This idea was strongly opposed b:-'
James and Counsel],3·3 In 1946, Gottlieb presented his
concept of "cementopathia."23 According to this h:-'-
pothesis, interference with continuous cemental depo-
sition results in a lack of attachment of the collaO'en b
fibers of the gingival and periodontal ligaments to the
root surface and permits migration of the epithelial
cells apically with pocket formation, On the other
hand, Goldman noted that migration of the epithelial
cells along the root surface could not occur so long as
the dense connective-tissue fibers underlying the at-
tachment apparatus were intact, and he postulated an
initial degenerative change in these fibers followed hy
epithelial-cell proliferation and migration.2o Still an-
other view was expressed by Aisenberg and .\isenberg,
who showed that tongues of epithelial cells migrate
apically between presumably normal connective-tissue
bundles, and they proposed that the epithelial cells
might exert a lytic effect upon the underlying connec-
tive tissues.1
The importance of the epithelial proliferation and
migration as the initial and cardinal event was ques-
 tioned by Fish,11 He maintained that long before this
event occurred, an accumulation of inflall1I11,ltL)r:-'cells
could be observed just deep to the junctional epithe-
lillln where proliferation subsequently occurs, Fish and
James and Counsell referred to this area as the primary
zone of inj"I'v, 11,:n Their work served to divert atten-
tion from the proliferative phenomena and direct it
to\nud alterations within the underlying connective
tissues.
In spite of its conceptual limitations and a large
body of evidence to the contrary, the idea that epithe-
lial prolife:'atioll and apical migration with pocket
formation are a cardinal event in pOlthogenesis of peri-
odontal disease continues to pervade current thought.
For example, attention is still focused upon the prime
importance of pocket depth in evaluation of periodon-
tal status, and most therapeutic measures are directed
to\vard reducticn in the pocket depth. In light of our
present understanding of the destr: [dive aspects of
inflammation and immunologic reactions and of recent
ach,lllCes in definition of the morplt'llogic features of
gingivitis ancl periodontitis, this view should be re-
examined. Generally, the data support the idea [hlt
epithelial proliferation and migration and pocket for-
mation may only be secondary features of one stage of
a multifaceted disease process. Indeed, the enhanced
exudation, the infiltration and transformation of
lymphoid cells, and the early loss of connective tissue
substance, which occur prior to pocket formation, may
fl!:' mure imjx'rtant pathogenic aspects of the disease
than pocket formation, especially from the point of
viewofuresting its progress.
The natural history of inflammatory gingival and
perior.bntal disease is not \vel! lmderstood, and impor-
tant aspects of its pathogenesis remain unknown. It has
been a';~;F;ned, especially by epidemiologists and clini-
cians, that gingivitis progresses ''lith time to destruc-
tive per1odont~'] disease. Although this assumption re-
mains unproved and it appears that, at least in some
C:I."e,';.this pn)C;r(~s,)i(m does not occur '2.'; [ recent clata
indicate tbat tlle early stages of periodontitis are mani-
"" For eX:ll~1ple. Whe'll plaque is al-
lowed to accumulate on the teeth of the dog, gingivitis
clevcJc.ps within a I11atter of days, and with the passage
of years progresses to periodontitis.::'·;)I' In addition,
the pr,:.-valence uf spontaneous periodontitis l)eginnjn~
as g:Ltt:iti~ in the dog increases with increasing age.:30
\VhJ1e ClllTent cLt;l :lre incomp:t"J' ,C[](l mallY of :b~·
details of Lhe progression from inclpieut gingivitis to
advunc",d periodontitis are unclear, the overall feat'lJi::;;
of the patl}()gene~is are beginning to emerge, On the
basis of the clinical manifestations and measurement of
gingival exudate, the chronic plaque-associated lesion
has been sllbdi\'ided into three stages. The~e are sub-
clinical !2;ingi\'itis, cliniLai gingivitis, and periodontal
breakdown,:' [ Ho\\'e\'er. the distinguishing features of
these stages have not been defined clearly. Analysis of
the histopathologic and ultrastructural featmes of the
disease permits a more clear-cut suhdivision into ini-
tial, earl!!, cstalJfisl/cd. and advanced stages.ii:3 \Vhile
this subdiyision too is somewhat arbitran', it is gener-
aliy supported h:-' the morphologic elata, amI it permits
focusing ,lttenticm upon important pathologic aspects
of the disease anelupon associated pathogenic mecha-
nisms.
The Initial Lesion
One of tbe major problems in uuderstanding the
pathogenesis of periodontal dise:tse Ius he en the in-
ability to disting',li~h c1ettrly betv\!(~ell normal and path-
ologically altered tissue" In other wCI'ds, it h~ls not
been possible to determine exactly whu] the disease
begins. This problem was first acknowledged almost a
half century ago,3;3 and it has still not been resolved
completely. In the absence of clefiuitive evidence, it
has been held, generall:--. that features characterizing
the initial lesion mereh' reflect enhanced lewls of
activity of mechanisms of host defense normally oper-
ative within the gingival tissues.
In experimental situations in which the tls~ues of
humans and dog': ha\'e been kept relative]\' fre(~ of
plaque, sm~lll numbers of leukocytes may be observed
migrating towards the gingival ,uk..]s and ]',::siding
within the junctional epithelium. In addition. a k.\'
isolated lymphoi'vtes and plasma ceils may be associ,-
ated with blood '.essels of the subepithelial plc-".llsauel
1------ ----,--,---
--
--------,
I 1, ClaSSIC ';asculiris of vessels subjacent to the junc-
I tional "pitheiium
I
I 3, Increased migration of !''':J!-;o~ytes intc the JU'1~:icncil
I
I
epithelium and 9in9;'oI3.: SUlCUS
I 4. Presence of serum prQtc', :;:"especially fibrin -:::~:~tra-
I v3scularly
I
I tlonai epithelium
L~~_~s~~~eriv~~uI~~~~~a:en
FIG. 7-1. Schematic illustration of the normal marginal gingiva as it appears on the buccal aspect of a tooth. GS, gingival sulcus; OE,
oral epithelium; OSE, oral sulcular epithelium; JE, junctional epithelium; N, neutrophilic granulocyte; L, lymphocyte; V, vessel of the
gingival plexus; Co, collagen fibers in long and cross section; Fi, fibroblast; P, plasma cell; MAB, marginal alveolar bone: POL,

periodontal ligament.

mulation are characteristic of a classic acute e:\lldative

deep within the connective tissue.6,56 These are not
inflammatory response,5,37,48,56,65The characteristics
accompanied by manifestations of tissue damage per-
of this initial lesion are listed in Table 7-1 and are
ceptible in the light microscope or ultrastructurally,
illustrated schematically in Figure 7-2.
they do not form an infiltrate, and therefore their
The initial lesion is localized to the region of the
presence is not considered to indicate pathologic
gingival sulcus. The tissues affected include a portion
change, The junctional epithelium uniformly joins the
of the junctional epithelium, the oral sulcular epithe-
connective tissue without rete ridges, and it is sup-
lium, and the most coronal portion of the connective
ported by dense, highly oriented connective tissue fiber
btU1dles(Fig, 7_1).5,6,51,56In these tissues, the earliest tissue. Rarely is a fraction of gingival connective tissue
exceeding.s to 10 percent involved, although as pocket
developments following the beginning of plaque accu-

.~ . ------.3..--- 3<'
 FIG 7-2. Schematic illustration of the initial lesion. GS, gingival
junctional epithelium; N, neutrophiiic granulocytes: L. lymphocyte;
and cross section; Fi, fibroblast: P. plasma cell; MAS. marginal
formation occurs during the subsequent stages of the
disease, the oral sulcular and junctional epithelia are
converted to pocket epithelium and the reaction site
extends both apically and laterally. During the initial
stage, the vessels of the gingival plexus become en-
gons",d and dilated, and large numbers of polymorpho-
nuclear leukocytes migrate into the junc:tionai epithe-
lium and gingival sulcus ,Fig. 7-2). A few ma.cwphages
and blast-transforming lymphocytes rna;: appear
within the junctional epithelium and in the connective
tissue. A portion of the perivascular colL.:;en may
sulcus; OE. oral epithelium; OSE. oral sulcular epithelium; JE.
V. vessel of the gingival plexus; Co, collagen filJer bundles in long
alveclar bone; POL periodontal ligament. -
disappear, and the resultant space becomes occupied
by fluid. SCl'IlllJproteins, and inf1alYlillcttC]'\cells. Fibrin
is especially apparent,53 'While immunoglobulins, es-
pecially IgG and complement, are probably present in
the extravascular gingival tissues,'" ,.) there is insuffi-
cient evidence to determine the role. if any, tklt tbese
substances may play at this stage in the p"thcgenbis.
.\s sIlo-.nl in Fignre 7-:3, signific~ili: inc;-e<l<":~s in thi"
levels of leu],ocvte migration and Bud exudation occur
by day :2 in experimental gingivitis in the dog. In
humans and other species, there ,l'-r~ dib.lion uf the

....
Vl
Z 150
::l
o
~
<{ 100
024791114161821
DAYS
FIG. 7-3. Amounts of crevicular leukocytes and gingival fluid
during developing gingivitis in dogs. Vertical lines indicate the
standard error of the mean. (From Attstrom. R.. and Egelberg.
J.: Presence of leukocytes within the gingival crevices during
developing gingivitis in dogs. J. Periodont. Res., 6:110, 1971.)
vessels of the gingival plexus, aclherence of leukocytes
to the vessel walls (Figs. 7-4C.D), and migration of
leukocytes through the wall into the connective tissues
(Fig. 7-5). The gingival sulcus contains migrating leu-
kocytes, sloughed epithelial cells, and microorganisms
(Figs. 7-4A,B, 7-6, 7-7A). In the superficial regions of
the jlillctional epithelilill1, intact and degenerating
neutrophils may be seen (Figs. 7-'iB, 7-8A). The extra-
cellular space is occupied by granular material of W1-
known composition and dead-cell debris (Fig. 7-7B).
'Within the deeper regions of the junctional epithelium,
numerous intact neutrophils and other leukocytes may
be present (Fig. 7-8B).
The initial lesion may be a response to the genera-
tion of chemotactic and antigenic substances in the
region of the gingival sulcus.38,so In fact, the acute
inflammatory phenomenon can be provoked simply by
applying plaque-derived chemotactic substances to the
gingival margin.26
The initial lesion emerges within a matter of 2 to 4
days when previously normal, infiltrate-free gingival
tissue is resubjected to the accwnulation of microbial
plaque.6,56 Under less strict experimental conditions,
the initial lesion as described earlier may not be ob-
served at all. Instead, a preestablished chronic lymph-
oid infiltrate resembling the early lesion may be pres-
ent in an othel\",ise healthy gingival tissue.39,4o,69 This
tissue, when reacting to the onset of plaque accWTIula-
tion, mimics the initial lesion in that it responds with
an exacerbation of acute exudative inflammation that is
superimposed upon the lymphoid infiltrate. These tis-
sues manifest clinical signs and symptoms of gingivitis
earlier than previously normal, infiltrate-free tissue.65
The Early Lesion
The early lesion overlaps with and evolves from the
initial lesion with no clear-nit dividing line.56.6;) Fea-
tures of the early lesion were first described hy James
and Counsell (1927) as fo11O\vs:
In the early stage lymphocytes are the characteristic cclls.
They are dijJusely arranged immediately under the epithe-
lium at the :::one of iniury (sllhjaccnt to the junctional epi-
thelium) occHpyil'ig the papillae f<mned hy the prolif<'rtltcd
epithelium and also the adjacent corium. The Iymphoc/ftic
infiltration remains locali:::edand does not extend deep III into
the tissues. This stage may be seen in young sulJjects and
ecen rcith temporary teeth. Later stages shOlL' the prescncc of
plasma cells.33
'More recently, the early lesion has been studied mor-
phologically, and its characteristic manifestations have
been measured stereologically.62.69, 70The hallmarks of
the early lesion are listed in Table 7-2 and illustrated
schematically in Figure 7-9.
The early lesion in hmnans appears at the site of the
initial lesion within 4 to 7 days following the beginning
of plaque accumulation (Table 7_3).56 In essence, it is
the result of the formation and maintenance of a dense
lymphoid cell infiltrate within the gingival connective
tissues.
Acute exudative inflammatory phenomena persist in
the early lesion. The exudation of serum components as
measured by gingival fluid flow and the number of
crevicular leukocytes reach their maximum and level
off between 6 and 12 days after the onset of clinical
gingivitis.37 The quantity of sulcular fluid appears to be
indicative of the size of the reaction site within the
connective tissue.39,59,65 Although the oral sulcular
epithelium and the oral epithelium generally do not
become infiltrated, the junctional epithelium contains
1. Accentuation of the features described for the initial
lesion
2. Accumulation of lympQoid cells immediately sub-
jacent to the junctional epithelium at the site of acute
inflammation
3. Cytopathic alterations in resident fibroblasts, possi-
bly associated with interactions with lymphoid cells
4. Further loss of the collagen fiber network supporting
the marginal gingiva
5. Beginning proliferation of the basal cells of the junc-
tional epithelium
174. BASIC PHENOMENA
FIG. 7-5. A collapsed blood vessel in the connective tissues subjacent to the junctional epithelium of a marmoset. Several
neutrophils (N) have migrated from the vessel (V) and are located between the endothelial cells and the basal lamina (bl)
(magnification 6300 x). (Schectman, L. R., et al.: Host tissues response in chronic periodontal disease. J. Periodont. Res., 7:195,
1972.)

FIG. 7-4. The initial lesion in inflammatory gingival and periodontal disease. A. Biopsy from the free marginal gingiva adjacent to the
gingival sulcus of a human free of plaque and of manifestations of disease. Note the sloughing surface of the junctional epithelium
(JE) and the oral sulcular epithelium (ose) (magnification 500 x). B. Biopsy from the free marginal gingiva adjacent to the gingival
sulcus of a human in whom plaque was allowed to accumulate for 2 days. Large numbers of leukocytes are present in the junctional
epithelium (JE) but the oral sulcular epithelium (ose) is free of infiltrating cells (magnification 500 x). C. Biopsy from the inter-
proximal region of an adult marmoset exhibiting clinical manifestations of early gingival inflammation. Note the presence of calculus
(c) adjacent to the enamel space (es) with a dense band of leukocytes (arrow) interposed between the deposit and the epithelial
tissue. Many of the vessels in the connective tissue contain adhering leukocytes (magnification 640 x). D. Section through a vessel
located subjacent to the junctional epithelium in a biopsy taken from a human 2 days after the cessation of plaque control. Note the
presence of neutrophils (n) within the vessel and possibly adherent to the wall (magnification 1250 x). (A, B, and D-Payne, W. A,
et al.: Histopathologic features of the initial and early stages of experimental gingivitis in man. J. Periodont. Res., 10:51, 1975.
C-Schectman, L. R., et al.: Host tissues response in chronic periodontal disease. J. Periodont. Res., 7:195, 1972.)
FIG. 7-6. Electron microscopic view of the contents of the gingival sulcus of a human exhibit:ng early inflammatory gingival disease.
Note the large number of neutrophils (N) and sloughing epithelial cells (E) within the sulcus (magnification 5700 X). (Lange. D.. and
SGhroeder, H. E.: Cytochemistry and ultrastructure of gingival sulcus cells. Helv. Odontal. Acta, 15(Suppl. 6):65, 1971.)

a variably increased number of transmigrating neutro-
philic granulocyt'Os and infiltrating mononuclear cells
inducling lymphoc\·tes, macrophages, plasma cells, and
m!.ist cells.6e! The leukocytes insinuate between the
epithelial cells cmd may be present in numbers suffi-
ciently large as to disrupt the continuity of the epithe-
lial barrier (Figs. 7-10, 7-11A-H).
The area of affected connective tissue can bedistin-
guished clearly from the surrounding normal tissue by
the presence of inHammatory cells and the decreased
collagen content (Figs. 7-10, 7-11. 7-1:2, 7-l.3). The
percent cell composition of the infiltrated connective-
tissue zone, exclusive of vascular structures, is fibro-
blasts 14.8, neutrophilic granulocytes 2.6, monocytes
and macrophages 2.1, plasma cells 2.0, smalllympho-
cytes .39.3, medium lymphocytes 34.9, immunoblasts
1.9, and mast cells 2...J (Figs. 7-14, 7-15), vVhile ncutro-
phili c granulocytes densely infiltrate the junctional
epithelium and gingival sulcus and a few may be ob-
served within the blood vessels, they are seen only
infrequently within the substance of the connective
tissu"S.·1:JThe largest portion of the infiltrating cells
(about 74 percent) are lymphocytes, and main' of these
are intermediate in size, an indication that blast trans-
formation and differentiation into sensitized T- and
B-lymphocytes and plasma cells mav be OCC'dl'l'ing
(Fig. 7-15). A significant number can be identified as
immunoblasts.
The coHagen fiber content of the affected tissue is
reduced (Figs. 7-1.3,7-14, Table 7-4\. There is·;l reduc-
tion in collagen content of about 70 pt:rcent relative to
the noninfhl1;l,.:'d connective-tissue ':OJ.ie.12,·'U,';9 This al-
teraticJIl, which occurs at an early stage of the disease,
affects especially the dentogingival and circular fiber
groups that normally support the jtmctional epithe-
lium. The loss of collagen may therefore be a major
factor in the continuing loss of tissue integrity and
normal gingival function as the disease progresses.
Specific cytopathic alterations OCClU' in the fibro-
blasts of the infiltrated connective-tissue zooe (Figs.
7_10,7_11,7_15,7_16).52.69.70,72,7.3 '\Vhile the fibrohlasts
are equally numerous in the inmtL,ted and noninfil-
trated regions of the gingival connective tissues, the
fibroblasts in the pathologically ~tltcrcd tissues exl1ibit a
 '~'Q
<II .
O,,:<Q

FIG. 7-S. A. Two mononuclear cells (M) and portions of neu-

trophils (N) just beneath the surface of the junctional epithe-
lium (JE) of the mandibular left first molar of a marmoset. The
epithelial cell at the upper right is a sloughing surface cell
FIG. 7-7. Electron micrographs of gingival sulcus of adult
(magnification 3,150 x). (Page, R. C., et al.: Host tissue re-
marmoset. A. Bacteria (b) associatedwith sloughed junctional
sponse in chronic periodontal disease. J. Periodont. Res.,
epithelial cells (magnification 2,600 x). B. Intact (ig) and
7:283, 1972.) B. The junctional epithelium (JE), noted on the
degenerating (dg) granulocytes within the junctional epithe-
lium near the base. Note the granular intercellular material (g) left side of the picture, is separated from the connective tis-
and dead cell debris (d) (magnification 2,900 x). (Page, R. C., sues by a basement lamina, and contains a portion of a
et al.: Host tissue response in chronic periodontal disease. neutrophil. An apparently intact neutrophil (N) is present in the
J. Periodont. Res., 7:283, 1972.) connective tis$ues uppermost in the picture, and a portion of a
neutrophil (N) with extracellular lysosomal granules is noted in
the lower portion (magnification 2,850 X). (Schectman, L. R.,
et al.: Host tissues response in chronic periodontal disease.
J. Periodont. Res., 7:195, 1972.)

GRANULAR LEUKOCYTES I SMALL MONONUCLEAR I

I PER UNIT AREA CELLS PER UNIT AREA AREA OF COLLAGEN AREA OF LEUKOCYTE
I
.:
TIME
I
JUNCTIONAL EPITHELIUM OF CONNECTIVE TISSUE ALTERATION INFILTRATION
II
Day 0 0.32 (0.3SY 11.50 (3.76)'
I 2.35 (1.13)" 6.10 (2.79)

Day 1 1.64 (1.35) 12.25 (5.71) I 5.04 (2.00) 5.94 (3.63)

Day 4 I 1.63 (1.10) 23.S7 (5.6S) 4.36 (1.44) 10.11 (11.73)

Day 8 I 2.87 (1.26) 30.73 (17.42) 9.74 (4.87) 14.18 (5.95)

i I
From Payne, W. A., et al.: Histopathologic featu'res of the initial and early stages of experimental gingivitis in man. J. Periodon!. Res., 10:51, 1975.
"Reported as the Mean (SO)
FIG, 7-9, Schematic illustration of the early lesion, Note the presence of increased numbers:;f leukocytes in the junctional epithelium
and gingival sulcus and the accumulation of Iymohocytes in the connective tissues immediately subjacent to the junctional
epithelium. Fibroblasts within the zone of infiltration appear to be cytopathica/ly altered ana a large portion of the collagen has been
lost. GS, gingival sulcus; 05E, oral sulcular epithelium; OE, oral epithelium; PE, pocket epithelium, AFi. altere:! r;t;::Li:12t; Re,
developing rete ridges of the pocket epithelium; L. Iym:)hocytes; ML, medium-sized lymphocytes possibly representr,':'] U'ist-tr,~ns-
forn7;ng ceHs: P, plasrrra cells; V, iJessals: Co. (;c/{::;g::r: bundles: ,\1;2,1j, rnarginai alve,~Aar bone: PDL, pencdonta/ /igarr;er7t.

FIG. 7-10. Histopathologic features of the early gingival lesion in man, Note the enamel space (es:, surtace c!eposit (d), }i;ncticnal
eoithe/ium (JEJ, oral su/cu/ar epithelium (OSE), residual collagen ;·,bets (Co), vessels 0{ the gii'giv2.1 vascular pie>.us ( La"ge
numbers of leuKocyles, predominantly neulraphils, are present bef\'men the cells of th," ;Ur',~!ic/;al epithelium and in ':'-,' r;ingival
sulcus. The nurnbers of these celfs are .so g:'eat as to (jjsrupt the ccnrfnuity of the junct:,c~r?a/ epithelium in sOlne areas ('::;e~ arrovv
lower lett-/land corner, B), In the subjacent connecti,!e tissues vasculitis is evidenced by the promine'7ce of the vascular ;:!""w.';. and
the collagen bundles have been replaced by a dense infiltrate of inflammalory cells, Most of these ceil., are lymphocytes, :he :,17e of
demarcation between infiltrated and noninfiltrated connective tissue is reasonably distinct in A. (Compare with Fig. 1- 3, ilh;.c;traifng a
relatively normal gingival sulcus) (Epon-embedded 1 micron sections; rnagnification (,'<) ; 00 ;<, (8; 150 x)
 ,;,,"
I

••.... ,'.
••••"I'

"

·
c.. .."-.*,. }.
r.
.. ~~,
i' (;,

'"
• t~to
t't.~~ :-

'••; I i

..',.~~
...
~,#" ~ ••

·'.f. -",t,
'-
.(.

...
~-'

JE
FIG. 7-12. Characteristic features of a biopsy specimen taken
after 4 days of plaque accumulation. Note the oral sulcular
epithelium (OSE), the residual junctional epithelium (JE) and
the rather distinct lineaf demarcation between them. The
plaque-associated leukocyte infiltrate (L) is present subjacent
to the junctional epithelium, and the location of vessels deep
within the gingival connective tissue with associated inflam-
matory cells is indicated by (P). Paraffin section stained with
Gomod trichrome (magnification 50 X). (Payne, W. A, et a/.:
Histopathologic features of the initial and early stages of ex-
perimental gingivitis in man. J. Periodont. Res., 10:51, 1975.)
threefold increase in size relative to those in the nor-
mal tissue (Fig. 7-14) . Furthermore, distinctive cyto-
logic alterations are present. These include electron
lucency of the nucleus suggestive of a reduced chro-
matin content, frequent absence of nucleoli, widely
dilated cisternae of the endoplasmic reticulum, swollen
mitochondria frequently with loss of cristae, and rup-
ture of the plasma membrane. These alterations are
characteristically exhibited by sick or dying cells. The
changes do not appear to be a consequence of defec-
tive tissue fixation and processing, since they are not
seen in fibroblasts or other cells of the normal tissues.
nor in the nonfibroblastic cells in the lesion. These
cytopathic alterations appear to be associated with the
activity of lymphoid cells. There is a positive correla-
tion between the increasing mmlbers of medium-sized
lymphocytes ane! immunoblasts and increasing fibro-
blast size.69 Furthermore, lymphocytes were observed
frequently in intimate contact \vith the altered fibro-
blasts.
Recently it was shown that peripheral blood lym-
phocytes obtained from patients with inflammatory
gingival disease are sensitized to antigenic substances
inhuman dental plaque. 28,29,.32 These cells undergo blast-
transformation when cultured in citro in the presence
of plaque antigens, and fluids from these cultures exert
a cytotoxic effect on gingival fibroblaSts.29 The mor-
phologic and morphometric data now available sup-
port the idea that a phenomenon similar to that ob-
served in DUro may be occurring in the gingival tissues
in humans during the early s'tageof inflammatory gin-
gival and periodontal disease.7o If this is the case, a
form of cellular hypersensitivity to pl\lque-derived
antigens may be an important component in the devel-
opment of the early lesion.
The Established Lesion
The distinguishing feature of the established lesion is
a predominance of plasma cells within the affected
connective tissues at a stage prior to extensive bone
loss. Lesions of this type appear to be extremely wide-
spread in human and animal populations and have
been described by many investigators,u,.33,.J,.3,52,79The
lesion has been described by James and Counsell as
follows:

FIG. 7-11. Cells encountered in the junctional epitheliUm in biopsy specimens from humans during the early stage of gingival and
periodontal inflammatory disease. A. Neutrophils located near the gingival sulcus in the junctional epithelium (magnification
4500 X). (Lange, D., and Schroeder, H. E.: Cytochemistry and ultrastructure of gingival sulcus cells. Helv. Odontol. Acta, 15(Suppl.
6):65, 1971. B, Two neutrophils within the junctional epithelium .and surrounded by intercellular space (s) and debris (d) (magnifi-
cation 9900 X). C. A mast cell located within the junctional epithelium. Note the presence of dense granules and the microvilli of the
plasma membrane. These are dIstinguishing characteristics of mast cells. A desmosome (d) is seen connecting two epithelial cells
(magnification 6900 X). D. Two mononuclear cells within the iunctional epithelium. One of these contains masses of phagocytized
material (pm) and is therefore likely to be a macrophage. The other cell probably belongs to the lymphoid series (magnification
9000 X). E. A "clear cell," not further identified, in the junctional epithelium in contact with the tooth surface (magnification
5900 X). F A mononuclear cell located in the basal layer of the junctional epithelium. Note the basal lamina (arrows). The cell
exhibits rosettes of ribosomes, scattered mitochondria, a few lamallae of rough endoplasmic reticulum, a pale nucleus with a large
nucleolUS. and an irregular cell surface. These features· are consistent with identification of the cell as an immunoblast (magnifica-
tion 6900 X).
FIG. 7-13. A. Epon-embeddi3d specimen taken from the most lagen fibers and extracellular matrix material and the infiitrate
coronal portion of the connective tissue lateral to the gingival of mononuclear cells of various sizes in the connective tissue
sulcus prior to the beginning of plaque accumulation and (magnification 250 ><). D. Epon-embedded specimen taken
iliustrating the normally dense collagenous tissue along with a from the region af the base of the gingival sulcus after a days
very few cells which occupy the connective tissues (CT) plaque accumulation illustrating the features of the inriltrete.
subjacent to the junctional epithelium (JE) (magnification The cells are clearly mononuclear and do not exhibit features
250 X). B. Epan-embedded specimen taken from a region characteristic of plasma cells. Some of the ceils exhibit fea-
comparable to (A) after 8 days of plaque accumulation. Note tures typical of small lymphocytes (SL). including a sm3-/l.
the increased cellularity and the decreased coflagen fiber round. densely basophilic nucleus with scanty cytopin.s:". and
content of the connective ttssues. An enlarged btood vessel others exhibit features consistent with their being mecJium-
(V) courses the central portion of the connective tissue core sized lymphoid cells (ML) (magnification 625 X). (Payne,
(magnification 250 X). C. Epon-embedded specimen taken W. A., et a/.: i-/istcpathologic features of the initial and early
from the region lateral to the base of the gingival sulcus after 8 stages of experimental gingivitis in man. J. Periodont. Res.,
days of plaque accumulation. Note the disruption of the col- 10:51, 1975.)
 Ilg HYDROXYPROLINE"
DENSITY COLLAGEN PER }ig DRY CONNECTIVE
. FIBERSimm3a TISSUE

Non infi Iterated

Infilterated
Connective Tissue

"Schroeder,.H. E., Munzel-Pedrazzoli, S., and Page, R. C.: Correl..-ted morphometric and
biochemical an!;lysis of gingival tissue in early chronic gingivitis in man. Arch. Oral Biol.,··18:899.
103. .
bFlieder, D. E., Sun, C. H., and Schneider, B. C.: Chemistry of normal and inflamed human
gingival tissues. Periodontics, 4:302, 1966.

Latcr stages show the presence of plas17w cells. Tllesc arc

mm3Vv/cm3VICT / NeT

1000 11.52 NG 0.14 NG seen .~rst around the vessels of the subgingical (functio/Jo!i

.
0.17 MO
12.82 MO
O.72MC
epithelium. They eventlwlly almost entirely supercede the
950 2.41 Me 72.02 SL
0.95 SL
14.12 ML
lymphocytes of the early stage, and their deep infiltration is
0.901 confined to the vessels of the qoTiUl1l.Later they are seen to
6.87P
5.18MA spread in diffuse masses from the ;:;one cf in;ury along the
pericascular channels to the bone of the alceo/ar crest. 33
750 11.35 I

700
18.55
9.57
p
MA The characteristic featmes of the established lesion
are listed in Table 7-5 and illustrated schematicallv in
650
Figme 7-17. As in the earlier stages, the lesion is still
600
centered around the bottom of the sulcus and is con-
550
fined to a relatively small portion of the gingival con-
500 nective tissue. However, plasma cells are not confined
450 to the reaction site; they also appear in clusters along
400 the blood vessels and between collagen fiber bundles
350 deep within the connective tissues. Although most of
300
the plasma cells produce IgG (Fig. 7-18), a small num-
ber contain IgA; cells containing Igl'vI are seen
250
rarely,9,19
200

150

!OO

50
1. Persistence of the manifestations of acute inflamma-
0
Nan- infiltrated
Infiltrated tion
connective connective
tlssue (ICT) tissue (NCT)
2. Predominance of plasma cells but without apprecia-
FIG. 7-14. A"verage volumetric density (mm3) of tissue compo- ble bone loss
nents residing in 1 cm3 of infiltrated (lCT) and noninfiltrated
(NCT) gingival connective tissue. NG, Neutrophilic granulo- 3. Presence of immunoglobulins extravascularly in the
cyte; MO, monocytes; MC, macrophages; I, immunoblasts; P, connective tissues and in junctional epithelium
plasma cells; MA, mast cells; SL, small lymphocytes; ML, 4. Continuing loss of connective tissue substance
medium lymphocytes; FI, fibroblasts; CO, Collagen; R, lym- noted in the early lesion
phatic and blood vessels, nerves, unidentified cell portions,
and ground substance. (Schroeder, H. E., MDnzel-Pedrazzoli, 5. Proliferation, apical migration, and lateral extension
S., and Page, R. C.: Correlated morphometric and biochemical of the junctional epithelium; early pocket formation
analysis of gingival tissue in early chronic gingivitis in man. mayor may not be present
Arch. Oral Bioi., 18:899, 1973.)
FIG. 7-15. The infiltrated area of connective tissue immediately subjacent to the junctional epithelium (JE) in a human bicosy
specimen il/ustrating c/1aracteristic features of tl7e eaoy stage of 1I7e lesion. Medium iymphocyte (ML). fibroblast (Ft), small
lymphocyte (SL). macrophage (MC), immunoblast (I), and collagen fibers (Co). Note the predominance of Iympholu ce/ls. nuclear
alterations and vacuolization of the fibroblasts, and the paucity of collagen fibers. In many areas (arrows) lymphoid cells imimate!y
contact pathologically altered fibroblasts (original magnification 9.000 X). (Schroeder, H. E.. Munzel-Pedrazzoli and P'1ge. F! C..
Correlated !7JorpJ7ometric and biochemical analysis of gingi'/al tissue in early chronic gingivitis in man. Arch. 0: at Bio! .. 18:399.
1973.)

FIG 7-16. A. Electron micrograph of a fibroblast (Fi) located
adjacent to the pocket epithelium in a young chimpanzee. A
medium-sized lymphocyte (ML) is in intimate contact with the
fibroblast and appears to have invaginated its surface. Altera-
tions of the fibroblast consist of dilation of the granular endo-
plasmic reticulum (arrows) and enlargement of the mitochon-
dria which lack cristae and appear empty (original
magnification 3,900 X). (Page, R. C., Ammons, W. F., and
Simpson, D. M.: Host tissue response in chronic inflammatory
periodontal disease. IV. The periodontal and dental status of a
group of aged apes. J. Periodontal., 46: 144, 1975.) B. Fibro-
blast-lymphoid eel! interaction in the gingival connective tis-
In addition to plasma cells, features described for the
earlier stages of the lesion are still present, frequently
in an accentuated form (Fig. 7-19). The junctional and
oral sulcular epithelium may proliferate and migrate
into the infiltrated connective tissue and along the root
surface with conversion to pocket epithelium (Fig.
7-19). In some cases, the pocket epithelium may be
thick and exhibit a tendency toward keratinization
(Figs. 7-20A, 7-21), but more frequently it becomes
thin and ulcerated (Fig. 7-19A,B). Vascular prolifera-
tion is a prominent feature in some animal species.36,65
sues of a human during the early stage of inflammatory gingi-
val and periodontal disease. Fibroblast (Fi) with closely
neighboring lymphocyte (ML) residing in the infiltrated con-
nective tissue. Note the electron lucency. dilated cisternae of
rough endoplasmic reticulum and mitochondrial alterations in
the fibroblast, and the well-preserved lymphocyte structures.
In one area (arrow) the two cells may communicate, although
this cannot be clearly established morphologically (magnifi-
cation 6,900 X). (Schroeder, H. E., and Page, R. C.. Lympho-
cyte-fibroblast interaction in the pathogenesis of inflammatory
gingival disease. Experentia, 28: 1228, 1972.)
If pocket epithelium is present, blood vessels loop high
within the epithelium and may be separated from the
external environment by only one or two epithelial
cells (Fig. 7-19B). Large amounts of immunoglobulin
are present throughout the connective and epithelial
tissues, ~J,19 and there is evidence for the presence of
complement and antigen-antibody complexes, espe-
cially arOlUld the blood vessels.19 A subpopulation of
degenerating plasma cells may be encountered (Fig.
7_22).14,51,73 Continuing loss of collagen is apparent in
the zone of infiltration (Figs. WC, 20B); in other more
 FIG 7 ~~ 7' Schemat:c i//ustratfc'; Ji fe3-
tures of the established les,or.. Ti";s
junctional epitheli •..m is being CQr-
verted into a poc,"-;et epitt;ei;um ar.c:
there is beginning pocket fcrr,;aNcr.
Plasma cells predominate the lesle;,,·.
There is a continuing :;o!fagen Joss ai-
though the al'ise/at t~:'Ir;:~janc: per-:;-
Gontai ligament are not yet :jffected :0
any significant extent. GS. gingiva! St;-
cus: OSE. orai sulcular epU;:j'-.u:Ti; C=
oral epithelium: PE, ,:Jocket er:ft.'ie!;:...;---·
Re. rete ridges of pOcKet af~ithellu;i~_· .-
b/ocd vessels: Co. cc)l{agr:n bunc1/es: ~
fibroblasts: L. Iympr;·.)cytes: N. re~'--;-
onilie granuiocytes: MAB. margina; a-
vea/ar bone; POL. per;oc!ont3.i i"'!;af-:'6'~~.

FIG. 7-18. A section of human gingiva treatee NJ:";; .'!i.,·){3sc= -

anN-/gG antisera to demonstrate the pO;:::..jia::'c,: ;;f ,'g::-:: -:-

ducing plasma cells (P) in the connective tfssl:ec":lmeu;a:s .
deep to the pocket epithelium rpE) (mei]n:ficar.:or; 4C'; .'
(Court9S\'- ')r J. Clagett.)
FIG. 7-19. Characteristic alterations in the zone of the pocket epithelium in the established lesion in chimpanzees. A. Paraffin-
embedded section showing the pocket epithelium (PE) and the adjacent connective tissue densely infiltrated with plasma cells. Note
the long extension of epithelium into the connective tissue (hematoxylin-eosin stain; magnification 50 X). B. Paraffin-embedded
section from a periodontal pocket. Note the deposit (0) made up of degenerating cells and microorganisms. In some areas the
pccker;,;pithelium (PE) is only one or two cells thick and blood vessels closely approach the surface deposit. Some oithe vessels are
engorged with leukocytes (hematoxylin-eosin stain; magnification 125 x). C. Features of the connective-tissue zone subjacent to
the pecKet epithelium. Note the strands of pocket epithelium (PE) and two blood vessels (V) engorged with neutrophilic granulo-
cytes. There is a dense plasma cell (P) infiltrate with a few scattered lymphocytes (hematoxylin-eosin stain; magnification 800 X).
(Page, ii. c., Ammons, W. F., and Simpson, O. M.: Host tissue response in chronic inflammatory periodontal disease. IV. The
periodontal and dental status of a group of aged great apes, J. Periodontal., 46: 144, 1975.)
 FiG. 7-20. Histopathologic features of the established lesion in
a 30-year-old chimpanzee exhibiting gingivitis but without
radiographic evidence of bone loss. A. Epon-embedded sec-
FIG. 7-21. Higher power view of a portion of the biopsy shown
tion from a biopsy. Note thEit most of the connective tissue has
in ,c=igure 7-20A. Most of the coilagen fibers (co) have been
been replaced by a cellular infiltrate and vascular proliferation
replac3d by plasma cells: the connective tissue papillae loop
(magnification 50 X). (See higher magnification in Fig. 7-21).
high within the epithelium. In contrast to the thin, sometimes
B. Higher power view from A. Note the strands of residual
ulcerated pocket epithelium iilustrated in Figures 7-19A,B, the
collag3!J'Jundles separated by nests of inflammatory cells
peeker epithelium (PE) here is generally thick, ana' in some
which are usually associared with blood vesseis (magnification
areas keratinization has occurred (magnification 150 X).
i SO /;. (P2;J-~, /1. C", Ai/?rnons, W. F., and SiIi7DSCl7, D. A1.:
(Page, R. C., Ammons, W P., and Simpson, 0, M.: Host tissue
/'-!cst tisSL"3 .'espcnse In chronic infiammatory periodontal dis-
response in chronic inflammatory periodontal disease, IV. The
ease. //. The peT/odontal and dental status of a group of aged
periodontal and dental status of a group of aged great apes.
great aoes. J. Periodontal., 46i144, 1975.) J. Periodontal., 46: 144, 1975.)

FIG. 7-22. A group of plasma cells demonstrating various

stages of degeneration. The prin7ary changes are early nu-
clear pyknosis, severe dilation and fragmentation of granuiar
endo,nit-J.:;;rnfc reticulum, and formation of numeroL;S:;Y"[OP:"~1D-
mic I.'esjc/(~S, presumably arisir:g frorn the C1c/,;'/ "-:;;::,TC.(;,-'
Porti:~'{l,'~ ;)f 9f7dopJa3!T7ic reric,:j/Lii";7 ~.¥,it/"J .-ibc,3crr;es 5.:n// at-
tacned can be seen within the extracellular space (magnifica-
tion 2. ?50 ). (Pat;'e, R. C., Amr:?D'7S. ~:/. F., and Sirnp::.cn,
O. M.' .!-fost tissue response in chronic inflamm3t'Jr'j ,oeriodcn-
ta/iJi',ease. IV. The periOdontal and dental staws of a group of
aged great apes. J Periodontal., 46:144, t975.)
----------------_ ...•..._---
p

distant regions, fibrosis and scarring may begin to
occur. \Vhether the established lesion is reversible and
whether, or under what conditions, it progresses to an
advanced lesion remain unknown, although the prob-
lem is being studied.66 Indeed, it appears that most
established lesions do not progress.41,52, 74, 75, 76, 77
The Advanced Lesion
Feahrres of the advanced inflammatory periodontal
lesion have been described classically in clinical
terms.13.31,.'jS,79 These may 'include periodontal pocket
formation, surface ulceration and suppuration, fibrosis
of the gingiva, destruction of the alveolar bone and
periodontal ligament, tooth mobility and drifting, and
eventual tooth exfoliation. In other words, the ad-
vanced lesion represents frank and overt periodontitis.
The histopathologic and some of the ultrastructural
features of the advanced lesion have been de-
scribed.s, 11,1·f.15, 18,27,33,44,4.5,.52,54, 71,84,89
Characteristic,'>, of the advanced lesion are listed in
Table 7-6 and are illustrated schematically in Figure
"

FIG. 7-23. Schematic illustration of the advanced lesion. The oral sulcular epithelium (OSE) and junctional epithelium (JE) have been
converted into pocket epithelium (PE), and a deep periodontal pocket (Po) filled with inflammatory cells and debris has formed.
Portions of the marginal alveolar bone (MAS) and periodontal ligament (POL) have been destroyed. Plasma cells (P) with scattered
lymphocytes (L) dominate the lesion, and the blood vessels (V) may exhibit adhering leukocytes. A large part of the collagen within
the affected connective tissues has been lost and in some areas fibrotic, scarlike collagenous materIal (S) may be observed. A small
strand of relatively normal junctional epithelium (JE) frequently persists near the base of the pocket.
distant regions, fibrosis and scarring may begin to
occur. Whether the established lesion is reversible and
whether, or under what conditions, it progresses to an
advanced lesion remain w1known, although the prob-
lem is being studied. 56 Indeed, it appears that most
established lesions do not progress.41,52, 74,75,76,77
The Advanced Lesion
Feahrres of the advanced inflammatory periodontal
lesion have been described classically in clinical
terms.l3· 31,58,79 These may 'include periodontal pocket
formation, surface ulceration and suppuration, fibrosis
of the gingiva, destruction of the alveOlar bone and
periodontal ligament, tooth mobility and drifting, and
eventual tooth exfoliation. In other words, the ad-
vanced lesion represents frank and overt periodontitis.
The histopathologic and some of the ultrastructural
features of th'e advanced lesion have been de-
scribed. R, 11.H.15,18,27,33,44,45,.52,54,
71,84,89
Characteristics of the advanced lesion are listed in
Table 7-6 and al'e illustrated schematically in Figure
"

FIG. 7-23. Schematic illustration of the advanced lesion. The oral sulcular epithelium (OSE) and junctional epithelium (JE) have been
converted into pocket epithelium (PE), and a deep periodontal pocket (Po) filled with inflammatory cells and debris has formed.
Portions of the marginal alveolar bone (MAB) and periodontal ligament (POL) have been destroyed. Plasma cells (P) with scattered
lymphocytes (L) dominate the lesion, and the blood vessels (V) may exhibit adhering leukocytes. A large part of the collagen within
the affected connective tissues has been lost and in some areas fibrotic, scarlike collagenous material (S) may be observed. A small
strand of relatively normal junctional epithelium (JE) frequently persists near the base of the pocket.
-;--2:3. Plasma cells predominate in the lesioll, although
h-mphoc:ytes and macrophages are also present. Signs
of acute vasculitis persist in the presence of chronic
fibrotic inflammation (Figs. 7-24, 7-2.'5, 7-2(-:n. Clusters
of plasma cells reside deeply within the connective
tissues between remnants of collagen fiber bundles and
around blood vessels (Fig. 7-26). The lesion is no longer
localized: it may extend apically as well as laterally to
form a variablv broad band around the necks and ioots
of the teeth. The size of the bane! depends upon the
extent of the disease, the amount of perirxlontal tissue
recession, and the pocket depth. While the highl>
organized fiber bundles of the marginal gingiva lose
their characteristic orientation and an.:hitectme com-
pletely (Fig. 7-2.5),"1 the transseptal fiLer Inmelles ap-
pear to be continuously regenerated as the lesion pro-
gresses apically.o3 This band of filwrs appears to
separate the coronally located infiltrate from the re-
maining alveolar bone, even when the inkrdentaJ bone
septum has been resorhed to the apical third of the
root. \Vitfjin the hypercellular infiltrated tissue por-
tion, collagen fihers are practiccllly absent Figs. -;--24C,

FiG 7-24. {:J;stopatholagio features ofthe adv'cnced leSion in the beagle dog. (Paraffin-embeddf:·d and sta/.rJed.,virh nen:.;':.'Viin al: 'j
eosin). ;1. Low power view of the lateral pocket wail. Note the extensive oroliferation and extenSion of the pooi<et epi'hGi'/·' anC 'he
dense infiitrate extending from the pocket epithelium into the oral epithelium (original magnification 12.5 x). B. Higher power 'fiew
from A. Pclcket epithelium extends onto the oralepithelial surface, and long fingers of epithelium e;: tend into the COiJn&c',.c" '!SC:."3S
(magnification 25 X). C. Higher power view from B. Note the blood vessel completely engorged with granulocytes in the central part
of the section and surrounded by plasma cells (magnification 125 X). O. A higher power view from C demonstrating the dense
accumulation of plasma cells (magnification 500 x).
 FIG. 7-26. A. A paraffin-embedded section from the central
portion of an interdental papilla region of a chimpanzee. Note
FIG. 7-25. Paraffin-embedded section through the marginal the perivascular islands of plasma cells (P) associated with
periodontium and tooth of a specimen taken from a human blood vessels interspersed with dense scarlike collagenous
autopsy illustrating the features of advanced periodontal dis- (CT) material (magnification 75 x). (Page, R. C., et al. Host
ease (van Gieson's stain; magnification 25 x). A. The oral tissue response in chronic periodontal disease. J. Periodont.
epithelium (OE) and the oral sulcular epithelium (ose) are Res., 7:283, 1972.) B. A section similar to A except embedded
intact. The pocket epithelium (PE) exhibits areas of ulceration, in Epon and illustrating two blood vessels with the surrounding
and long projections extend into the deep connective tissues. plasma cells (P) and scattered polymorphonuclear granulo-
The periodontal pocket contains calculus adherent to the root cytes (PMN) (magnification 400 X). (Page, R. C., Ammons.
surface, and residual plaque (PL) is apparent on the surface of W. F., and Simpson, D. M.: Host tissue response in chronic
the soft tissue. The connective tissue has been almost totally inflammatory periodontal disease. IV The periodontal and
replaced by a dense infiltrate of inflammatory cells and an dental status of a group of aged great apes. J. Periodontal.,
accumulation of dense. disoriented scarlike collagen (SC).
46:144, 1975.)
B. Horizontal section through a specimen similar to that shown
in A taken from a region about one half of the way to the most
apical extent of the pocket. The edge of the tooth root (R) and
a small portion of the oral epithelium (OE) can be seen. The
most prominent feature is the presence of strands of scarlike
1. Persistence of features described for the established
collagen (SC) running circumferentially around the tooth and
lesion
at right angles to it and separated by zones of inflammatory
cells. Projections of pocket epithelium (PE) are also apparent. 2. Extension of the lesion into alveolar bone and perio-
dontal ligament with significant bone loss

3. Continued loss of collagen subjacent to the pocket

epithelium with fibrosis at more distant sites

4. Presence of cytopathicallyaltered plasma cell~ in the

absence of altered fibroblasts

5. Formation of periodontal pockets

6. Periods of quiescence and exacerbation

7. Conversion of the bone marrow distant from the

lesion into fibrous connective tissue

8. Widespread manifestations of inflammatory and

immunopathologic tissue reactions
 7-2.5.\), while dense fibrosis may be apparent in the
surrounding area. Strands of the proliferating pocket
epitheJium"extend apically along the root surfaces and
fingerlike projections extend into the deep connective
tissues. Bone destruction (Figs. 7-27 and 7-29), presum-
ably b:' osteoclastic resorption (Fig. 7-28), begins along
the crest of the alveolar bone usually in the interdental
septum around the communicating blood ves-
sels.33.·Hs4,\s the marrow spaces are opened, both red

FIG. 7-28. Resorbing bone surface. Note the presence of

osteoclasts (arrows) located in Howship's lacunae, the moth-
eaten surface, and the replacement of the bone by fibrous
connective tissue (magnification 50 X). (Courtesy Dr. B.
Moffett.)

~l11dwhite marrow become hypercellular, undergo

fibrosis. and become transformed into scarlike COImec-
ti \'e tissue.
Periods of acute exacerbation and quiescence occur
and they determine, to some extent, the histopatho-
logic picture seen. Frank tissue necrosis is generally
not observed. i\'Iany of the features resemble clo~;elv
those of other long-term chronic inHaIl1Inator;: diseases
'If connective tissne of unknown etiology, SIkh as
rheumatoid arthritb.

Re,ferences
FIG. 7-27. A. Decalcified block section from the maxillary left
l. AiscnlJerg, ~l. /I.., and Aisenberg, A. 1).: A new cOllcept
queCfrant of an adult marmoset, exhibiting advanced inflam-
of pocket furmation. Oral Smg., 1: lOr;', LAS.
matory periodontal disease. There has been extensive re-
sorption of the alveolar bone and the lamina dura along with
l. Ammons, \Y. E. Schectman, L. R., and Page, R c.: Hmt
loss of the periodontal ligament (hematoxylin-eosin stain; tissue response in chronic periodontal disease. 1. The
original magnification 10 X). B. oefleshed lower left mandible nonnal perl{)donl'iU111 and clinical alldan8t')n~ic .'r;;J.;il-

of an adult marmoset with advanced periodontal disease. Note festations of periodontal disease in the mannu,;et.
the abnormal porosity of the buccal and interproximal cortical J. PeriudUilt. He.s .. 7': 1:.3 J, l!-{;2.
bone resulting from enlargement of the nutrient foramina. :3. April E. C:., de: _-\proposito de Ius celu'Ll:, reticuloli,i.~tc
marginal resorprion, and formation of dehiscences on the citarias '{lit' eOllfol'lll:ln cl sistema ref icuiculdotheliaL
buccal aspect of the canine and lateral incisor. (Page, R. C., et Rev. Odontol., 42: 115, 1954.
a/.: Host tissue response in chronic periodontal disease.
-I. Arnim. S. S., and rIolt, R. T.: The ,.It:I' •..nse c;lechanisllis
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of tIle gingiva. J. PeriudOlltol., 26:i9. 'U5.5.
FIG. 7-29. Gross morphology of the alveolar bone in the advanced stages of inflammatory periodontal disease. A. and B. Normal
bone architecture of an adult human. Note the gentle scalloping of the alveolar margin. The margin mimics the contours of the
cementoenamel junction and is removed from it apically only 2 to 3 mm. C. and D. There is marked apical recession affecting one
half to two thirds of the total root length with grossly abnormal surface contours and furcation involvement. Deposits are present on
most of the root surfaces. E. and F. Recession of the bone margin affecting the mandibular anterior teeth. Note the moth-eaten
surface (arrow). (Courtesy Or. W. Avery.)

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