The document discusses the stages of gingival inflammation. It begins by defining inflammation and providing background on its history. It then discusses 4 stages of gingival inflammation: initial lesion, early lesion, established lesion, and advanced lesion. The initial lesion involves dilation of capillaries and leukocyte recruitment. The early lesion develops within 1 week and may show clinical signs like erythema. The established lesion evolves over months and is characterized by plasma cell predominance. The advanced lesion extends inflammation into alveolar bone, potentially leading to periodontitis in susceptible individuals. Microscopic examination shows features corresponding to the stage of inflammation.

1. Gingival inflammation

2. Contents
 Inflammation
 History
 Gingival diseases
 Classification
 Gingival inflammation
 Stages of inflammation
 Conclusion
 References

3. Definitions
Inflammation is the protective response intended to eliminate the initial cause of cell injury as
well as necrotic cells and tissues resulting from original insult.
( R o b b i n s ’ B a s i c P a t h o l o g y, S i x t h E d i t i o n )

4. Inflammation is an immunological defence against injury, infection, or allergy
marked by increase in regional blood flow, immigration of white blood cells and
release of chemical toxins.
( Ta b e r ` s M e d i c a l D i c t i o n a r y )
Inflammation is one mechanism the body uses to protect itself by foreign organisms
and to repair tissue trauma.
( S t e d m a n ’s M e d i c a l D i c t i o n a r y )

5. History
Although clinical features of inflammation were described in an Egyptian papyrus
dated around 3000 BC, Celsus, a Roman writer of the first century AD, first listed
the four cardinal signs of inflammation: rubor (redness), tumor (swelling), calor
(heat), and dolor (pain).
dr. Ipsita Jayanti

6. A fifth clinical sign, loss of function (functio laesa), was added by Rudolf Virchow
in the 19th century.
In the 1880s the Russian biologist Elie Metchnikoff discovered the process of
phagocytosis by observing the ingestion of rose thorns by amebocytes of starfish
larvae and of bacteria by mammalian leukocytes.

7. Sir Thomas Lewis, studying the inflammatory response in skin, established the
concept that chemical substances, such as histamine (produced locally in response
to injury), mediate the vascular changes of inflammation.

8. GINGIVAL DISEASES
Gingivitis is the most common of the gingival diseases.
Bacterial plaque that causes inflammation & irritating factors which favour
plaque accumulation are often present in Gingival environment.
The role of inflammation in Gingival Disease varies in 3 ways :
Inflammation may be primary & only a pathologic change.
Inflammation may be secondary feature, superimposed on systemically
caused Gingival disease. For eg. Inflammation commonly complicates
Gingival hyperplasia caused by Phenytoin.
Inflammation may be the precipitating factor for clinical changes, in
patients with systemic conditions, that themselves do not produce
clinically detectable gingival disease. Eg- Gingivitis in pregnancy.

9. Classification of gingival Diseases

12. Increased Vascular Permeability (Vascular Leakage)
A hallmark of acute inflammation is increased vascular permeability leading
to the escape of a protein-rich exudate into the extravascular tissue, causing
edema.

13. Several mechanisms are responsible for the increased vascular permeability:
Contraction of endothelial cells resulting in increased interendothelial spaces .
Endothelial injury, resulting in endothelial cell necrosis and detachment.
Increased transport of fluids and proteins, called transcytosis, through the
endothelial cell

14. Recruitment of Leukocytes to Sites of Infection and
Injury
 The journey of leukocytes from the vessel lumen to the interstitial tissue,
called extravasation, can be divided into the following steps
 In the lumen: margination, rolling, and adhesion to endothelium. Vascular
endothelium in its normal, unactivated state does not bind circulating cells or
impede their passage. In inflammation the endothelium is activated and can
bind leukocytes, as a prelude to their exit from the blood vessels.
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16. Leukocyte Adhesion to Endothelium
 In margination there is leukocytic redistribution & white cells
assume a peripheral position along the endothelial surface.
 Subsequently, individual and then rows of leukocytes adhere
transiently to the endothelium, detach and bind again, thus rolling on
the vessel wall. The cells finally come to rest at some point where
they adhere firmly (resembling pebbles over which a stream runs
without disturbing them).
 The adhesion of leukocytes to endothelial cells is mediated by
complementary adhesion molecules on the two cell types whose
expression is enhanced by secreted proteins called cytokines
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17. The initial rolling interactions are mediated by a family of proteins called
selectins .
There are three types of selectins: one expressed on leukocytes (L-selectin),
one on endothelium (E-selectin),
one in platelets and on endothelium (P-selectin).
The expression of selectins and their ligands is regulated by cytokines
produced in response to infection and injury.

18. Chemokines
Chemokines are a family of small (8 to 10 kD) proteins that act primarily as
chemoattractants for specific types of leukocytes
About 40 different chemokines and 20 different receptors for chemokines have been
identified.
They are classified into four major groups, according to the arrangement of the
conserved cysteine (C) residues in the mature proteins
C-X-C chemokines (also called α chemokines). The C-X-C chemokines act primarily
on neutrophils. IL-8 is typical of this group. It is secreted by activated macrophages,
endothelial cells, and other cell types, and causes activation and chemotaxis of
neutrophils, with limited activity on monocytes and eosinophils. Its most important
inducers are microbial products and other cytokines, mainly IL-1 and TNF.

19. Chemokines mediate their activities by binding to seven-transmembrane G protein–
coupled receptors. These receptors (called CXCR or CCR, for C-X-C or C-C
chemokine receptors) usually exhibit overlapping ligand specificities, and leukocytes
generally express more than one receptor type.
Chemokines have two main functions: they stimulate leukocyte recruitment in
inflammation and control the normal migration of cells through various tissues. Some
chemokines are produced transiently in response to inflammatory stimuli and promote
the recruitment of leukocytes to the sites of inflammation.

22. STAGES OF GINGIVITIS

24. Gingival alterations which occurred during a 28-day period of plaque accumulation
and gingivitis development in beagles. (a) Normal gingiva. (b) Day 4. (c) Day 7. (d)
Day 14. (e) Day 21. (f) Day 28 of undisturbed plaque accumulation. Note the
gradually developing plaque on the tooth surfaces and the inflammatory changes in the
gingiva.

27. Stage I Gingivitis : The Initial Lesion -
SUBCLINICAL GINGIVITIS.
• Dilation of capillaries & increase in blood flow.
• Initial inflammatory changes in response to microbial
activation of resident leukocytes, subsequent stimulation of
endothelial cells.
• Clinically- initial response of gingiva to bacterial
plaque(sub clinical gingivitis)- not apparent.
Changes in JE and perivascular connective tissue- detected

28. •Perivascular connective tissue matrix-altered
•Exudation & deposition of fibrin in affected area
•Accumulation of lymphocytes
•Increase in migration of leukocytes and accumulation within
gingival sulcus corelated with increase in flow of gingival
fluid into sulcus.

29. •Character and intensity of host response determines whether
initial lesion resolves rapidly with restoration of tissue to
normal state or into chronic inflammatory lesion.
•Inflammatory lesion- infiltrate of macrophages and lymphoid
cells appears within few days.

30. Microscopically:
Some classic features of acute inflammation seen in connective
tissue beneath the junctional epithelium.
Changes in blood vessel morphologic features (e.g., widening
of small capillaries or venules)

31. adherence of neutrophils to vessel walls (margination) occur within 1 week
and sometimes as early as 2 days after plaque has been allowed to
accumulate.
Leukocytes, mainly polymorphonuclear neutrophils (PMNs), leave the
capillaries by migrating through the walls - increased quantities in the
connective tissue, junctional epithelium, and the gingival sulcus
Exudation of fluid from gingival sulcus and extravascular proteins present.

32. Human biopsy sample, experimental gingivitis. After 4 days of plaque accumulation,
the blood vessels immediately adjacent to the junctional epithelium are distended and
contain polymorphonuclear leukocytes ( PMNs, neutrophils). Neutrophils have also
migrated between the cells of the junctional epithelium. OSE, Oral sulcular
epithelium.

33. STAGE II GINGIVITIS : THE EARLY
LESION:
•Early lesion evolves from the initial lesion within 1 week after beginning
of plaque accumulation.
•Clinically may appear as early gingivitis & overlaps with and evolves from
the initial lesion with no clear-cut dividing line.
•As time goes, clinical signs of erythema may appear, mainly because of
proliferation of capillaries and increased formation of capillary loops
between rete pegs.

34. •Bleeding on probing- evident.
•Gingival fluid flow and numbers of transmigrating leukocytes
reach their maximum between 6 and 12 days after onset of
clinical gingivitis.

35. Amount of collagen destruction increases;
70% - collagen is destroyed around the cellular infiltrate.
The main fiber groups affected appear to be the CIRCULAR
and DENTOGINGIVAL fiber assemblies.
Alterations in blood vessel morphologic features and vascular
bed patterns.

36. •PMNs that have left the blood vessels in response to
chemotactic stimuli from plaque components travel to the
epithelium, cross basement lamina, and are found in the
epithelium, emerging in pocket area.
•PMNs are attracted to bacteria and engulf them in the process
of phagocytosis.
•PMNs release their lysosomes in association with ingestion of
bacteria.
• Fibroblasts show cytotoxic alterations, with decreased capacity
for collagen production.

37. MICROSCOPIC:
Microscopic examination of the gingiva reveals a leukocyte infiltration in
the connective tissue beneath the junctional epithelium, consisting mainly
of lymphocytes (75%, with the majority T cells)
Also composed of some migrating neutrophils, as well as macrophages,
plasma cells, and mast cells.

38. All the changes seen in the initial lesion continue to intensify
with the early Iesion.
The junctional epithelium- densely infiltrated with neutrophils,
as does the gingival sulcus, and the junctional epithelium may
begin to show development of rete pegs.

39. Scanning electron micrograph of leukocyte emerging to pocket wall and covered with
bacteria and extracellular lysosomes. EC, Epithelial cells; B, bacteria; L, lysosomes.

40. STAGE III GINGIVITIS : THE ESTABLISHED
LESION -
•Over time, the established lesion evolves
•Characterized by a predominance of plasma cells B
lymphocytes in conjunction with the creation of a small gingival
pocket lined with a pocket epithelium.
•The B cells - predominantly of immunoglobulin G1 (IgG1) and
G3 (IgG3) subclasses

41. In chronic gingivitis, which occurs 2 to 3 weeks after the beginning of
plaque accumulation, blood vessels- engorged and congested,
venous return- impaired,
blood flow - sluggish.
bluish hue on the reddened gingiva
Extravasation of erythrocytes into the connective tissue and breakdown
of hemoglobin into its component pigments can also deepen the color of
the chronically inflamed gingiva.
The established lesion can be described as moderately to severely
inflamed gingiva.

42. The predominance of plasma cells is thought to be a primary characteristic of
the established lesion.
Increases in the proportions of plasma cells were evident with long-standing
gingivitis, but the time for the development of the classic "established lesion"
may exceed 6 months.

43. Inverse relationship exist between the number of intact collagen bundles and
the number of inflammatory cells.
Collagenolytic activity Is increased in inflamed gingival tissue

44. TWO TYPES :
Some remain stable and do not progress for months or years
Others become more active and convert to progressively destructive lesions.

45. HISTOLOGIC SECTIONS
Intense, chronic inflammatory reaction.
A key feature that differentiates the established lesion is the increased number of
plasma cells, which become the preponderant inflammatory cell type.
Plasma cells invade the connective tissue not only immediately below the junctional
epithelium, but also deep into the connective tissue, around blood vessels, and between
bundles of collagen fibers

46. The junctional epithelium reveals widened intercellular spaces filled with granular
cellular debris, including lysosomes derived from disrupted neutrophils, lymphocytes,
and monocytes
Lysosomes contain acid hydrolases - destroy tissue components.
The junctional epithelium develops rete pegs or ridges that protrude into the
connective tissue, and the basal lamina is destroyed in some areas.
In the connective tissue, collagen fibers are destroyed around the infiltrate of intact
and disrupted plasma cells, neutrophils, lymphocytes, monocytes, and mast cells

48. Established gingivitis in a human subject. Area of crevicular epithelium exhibiting
enlarged intercellular spaces with numerous microvilli and desmosomal junctions.
Several lymphocytes, both small and large, are seen migrating through the epithelial
layer. (x3000.)

49. STAGE IV GINGIVITS : THE
ADVANCED LESION :
Extension of the lesion into alveolar bone characterizes a
fourth stage known as the advanced lesion.
Gingivitis - periodontitis only in individuals who are susceptible.

50. MICROSCOPICALLY:
Fibrosis of the gingiva and widespread manifestations of
inflammatory and immunopathologic tissue damage.
Plasma cells continue to dominate the connective tissues, and
neutrophils continue to dominate the junctional epithelium and
gingival crevice

51. CONCLUSION

52. References:
Clinical periodontology, carranza- 8th edition
Clinical periodontology, carranza- 10th edition
Clinical periodontoogy and implant dentistry- lindhe 5th edition
Robbins Basic Pathology- 6th edition
Internet sources.