This document provides an overview of inflammation, including its definition, history, types (acute and chronic), classical signs, vascular and cellular events, chemical mediators, and outcomes. Inflammation is defined as a protective response to injury or infection that involves increased blood flow, blood vessel permeability, and the migration of white blood cells. The classical signs of inflammation are heat, redness, swelling, pain, and loss of function. Key events in acute inflammation include increased vascular permeability, chemotaxis of white blood cells, phagocytosis of pathogens, and the release of chemical mediators like histamine and cytokines. Chronic inflammation is long-lasting inflammation that involves ongoing tissue damage and repair. Systemic inflammatory response syndrome (SIRS)

3. Overview

4. Introduction
 Inflammation is a protective response intended to
eliminate the initial cause of cell injury as well as
necrotic cells and tissues resulting from the original
insult.
 It sets into motion the events that eventually heal and
reconstitute the sites of injury.

5. Inflammation
 Definition
Inflammation (Latin, inflamatio, to set
on fire) is a localized protective response
elicited by injury or destruction of tissues,
which serves to destroy, dilute or wall off
(sequester) both the injurious agent and
the injured tissue.
(Dorland’s medical dictionary; 30th
ed)

6. Inflammation
 Definition
Inflammation is a complex reaction to
injurious agents such as microbes and
damaged, usually necrotic, cells that consists
of vascular responses, migration and activation
of leukocytes and systemic reactions.
(Robins and Cotran; 7th
ed.)

7. History
 Egyptian papyrus (3000 BC)
 Celsus (1st
century AD) – 4 cardinal signs of
inflammation
 Virchow – fifth clinical sign i.e. functio laesa
 John Hunter (1973)– inflammation is not a
disease but a non-specific response that has a
salutary effect on its host.

8. History
 Julius Cohnheim (1839-1884) – described
the process of inflammation
 Ellie Metchnikoff – Phagocytosis
 Sir Thomas Lewis – chemical substances,
such as histamine locally induced by injury,
mediate the vascular changes of
inflammation

9. Inflammation
 Inflammation is divided into two basic patterns:
Acute Inflammation : It is the immediate and early
response to injury, designed to deliver leukocytes to
the site of injury.
(Robbins 7th
ed.)
Also defined as inflammation usually of sudden
onset characterized by classical signs, with
predominance of vascular and exudative processes.
(Dorlands Dic.)

10. Inflammation
 Chronic Inflammation : It is considered to be
inflammation of prolonged duration (weeks to
months to years) in which active inflammation,
tissue injury and healing proceed simultaneously.
(Robbins 7th
ed.)
 Inflammation of slow progress and marked chiefly
by the formation of new connective tissue.
(Dorlands Dic.)

11. Inflammation
 The inflammatory
response has many
players
 These include:
 Circulating cells
 Neutrophils
 Eosinophils and
Basophils
 Lymphocytes and
Monocytes
 Platelets

12. Inflammation
 Circulating Proteins :
 Clotting Factors
 Kininogens
 Complement
components
 Vascular wall cells :
 Endothelial cells in
direct contact with
blood
 Smooth muscle cells
that impart tone to
vessels

13. Inflammation
 Connective tissue cells
 Mast cells
 Macrophages
 Lymphocytes
 Fibroblast
 Extra cellular Matrix :
 Fibrous Structural
Proteins (e.g. Collagen &
Elastin)
 Gel forming
proteoglycans
 Adhesive glycoprotein
(e.g. Fibronectin)

14. Acute Inflammation
STIMULI FOR ACUTE INFLAMMATION
Infections (bacterial, viral, parasitic) and microbial toxins
 Trauma (blunt and penetrating)
 Physical and chemical agents (thermal injury, e.g., burns or
frostbite; irradiation; some environmental chemicals)
Tissue necrosis (from any cause)
Foreign bodies (splinters, dirt, sutures)
Immune reactions (also called hypersensitivity reactions)

15. Acute Inflammation
 Lewis experiment. Lewis induced the changes in
the skin of inner aspect of forearm by firm stroking
with the blunt point eliciting the triple response
Red line appears in a few seconds due to local
vasodilation.
Flare is the bright reddish appearance also due
to vasodilation of the adjacent arterioles.
Wheal is the swelling or edema due to
transudation of fluid into extravascular space.

16. Acute Inflammation
Red line – direct
vasodilating effect of
histamine
Flare – indirect vasodilating effect
of histamine by stimulating axon
reflex
Wheal – Histamine induced
increased permeability

17. Acute Inflammation
 Classical signs of inflammation (Celsus)
1. Heat (Calor)
2. Redness (Rubor)
3. Swelling (Tumor)
4. Pain (Dolor)
5. Loss of function (Functio laesa) (Virchow)

18. Acute Inflammation
 Acute inflammation has two main components:
Vascular Changes : Alteration in the vessel caliber
resulting in increased blood flow (vasodilation) and
structural changes that permits plasma proteins to
leave circulation (increased vascular permeability).
Cellular Events : Emigration of leukocytes from the
microcirculation and accumulation in the focus of
injury (cell recruitment and activation).

19. Vascular Changes

20. Vascular Changes
Starling’s Law:
Movement of fluid in and out of arterioles, capillaries and
venules is regulated by the balance between
1.Intravascular hydrostatic pressure – tends to force fluid
out of vessels
2.Osmotic pressure of the plasma proteins – tends to retain
fluid within the vessels

21. Vascular Changes

22. Transudate Vs Exudate
Transudate Exudate
Filtrate of blood plasma without
changes in endothelial
permeability
Oedema of inflamed tissue with
increased vascular permeability
Non-Inflammatory Oedema Inflammatory Oedema
Protein < 1g/dl Protein -- High 2.5-3.5 g/dl
Glucose – same as plasma Glucose – Low (<60 mg/dl)
Specific Gravity < 1.015 Specific Gravity > 1.018
pH > 7.3 pH < 7.3
Few Cells, mainly mesothelial
cells and cellular debris
Inflammatory as well as
parenchymal cells
eg. Oedema in congestive
cardiac failure Purulent exudate such as pus

23. Increased vascular permeability
Endothelial cell contraction leads to intercellular
gaps in venules.

24. Increased vascular permeability
Endothelial cell retraction :
 Reversible mechanism
 Induced by cytokine mediators (TNF & IL-1)
 Cause structural reorganization
 Cells retract
 Takes 4 to 6 hrs to develop and persists for 24hrs
or more

25. Increased vascular permeability
 Direct endothelial injury :
 Seen in severe injuries (burns, infections etc.)
 Leakage begins immediately after surgery and persists for
several hours. (immediate sustained response)

26. Increased vascular permeability
 Leukocyte dependent endothelial injury :
 Leukocytes may accumulate during inflammatory response.
 These leukocytes may release toxic oxygen species and
proteolytic enzymes causing injury.

27. Increased vascular permeability
 Leakage from new blood vessels :

28. Cellular Events

29. Cellular Events

30. Transendothelial Migration
 E-selectins are expressed at low levels or are not present at
all on normal cells. They are upregulated after stimulation by
specific mediators. eg.IL-1 and TNF.
 P-selectins are found intracellularly in Weibel-Palade bodies,
which once stimulated by mediators such as histamine are
distributed over the cell surface.
 L-selectins interact with carbohydrate molecules known as
vascular addresins (eg.sialomucin) on the luminal surface of
endothelial cells. This brief interaction manifests itself as
rolling of the leukocyte along the luminal surface of
endothelium.

31. Transendothelial Migration

32. Chemotaxis and Activation
 After extravasating from the blood, leukocytes
migrate toward sites of injury along a chemical
gradient in a process called chemotaxis.
 Both exogenous and endogenous substances can
be chemotactic for leukocytes.
 Soluble bacterial products : N-formylmethionine termini.
 Components of complement system : C5a
 Products of lipoxygenase pathway : leukotriene B4
 Cytokines : IL-1, IL-8

33. Chemotaxis and Activation

34. Biochemical Events In Leukocyte Activation

35. Phagocytosis and Degranulation
 Phagocytosis and the elaboration of degradative
enzyme are two major benefits of having recruited
leukocytes at the site of inflammation.
 Phagocytosis consists of three distinct but
interrelated steps:
 Recognition and attachment of the particle to the
ingesting leukocyte.
 Engulfment with subsequent formation of a
phagocytic vacuole
 Killing and degradation of the ingested material.

36. Phagocytosis and Degranulation

37. Phagocytosis and Degranulation

38. Phagocytosis and Degranulation
 2O2 +NADPH NADPH oxidase 2O2
-
+ NADP+
+ H+
 Superoxide is then converted by spontaneous
dismutation to hydrogen peroxide.
 O2
-
+ 2H+
H2O2
Cl-
 H2O2 Myeloperoxidase HOCl + H2O

39. Chemical Mediators Of
Inflammation

40. Vasoactive Amines
 Histamine – widely distributed in mast cells; also
present in circulating basophils and platelets.
 Preformed histamine is stored in mast cell granules and
released in response to a variety of stimuli :
 Physical injury
 Immune reactions involving binding of IgE antibodies to Fc
receptors on mast cells.
 Anaphylatoxins; C3a and C5a
 Leukocyte derived histamine releasing proteins.
 Neuropeptides
 Certain cytokines (IL-1; IL-8)

41. Vasoactive Amines
 Histamine causes arteriolar dilatation and is the
principal mediator of immediate phase of
increased vascular permeability.
 Soon after its release it is inactivated by
histaminase.
 Serotonin is also a preformed vasoactive mediator
with effects similar to those of histamine.
 Found in platelets and released during platelet
aggregation.

42. Neuropeptides
 Like vasoactive amines neuropeptides can initiate
inflammatory responses
 Nerve fibers that secrete neuropeptides are
prominent in lungs and GIT
 They are small proteins, such as substance P, that
transmit pain signals, regulate vascular tone and
modulate vascular permeability.

43. Plasma Proteases
 Many effects of inflammation are mediated by
three interrelated plasma derived factors :
 The Kinins all linked by initial
activation of
 The clotting system Hageman Factor( factor XII)
 The complement system
 Hageman factor is a protein synthesized by liver
that circulates in an inactive form until it
encounters collagen, basement membrane or
activated platelets.

44. Plasma Proteases

45. Complement system

46. Arachidonic acid metabolites

47. Platelet-Activating Factor
(PAF)
 Platelets, basophils, mast cells, neutrophils,
monocytes/macrophages and endothelial cells
 Vasoconstriction and bronchoconstriction
 Increased leucocyte adhesion to endothelium
 Chemotaxis, degranulation and oxidative burst

48. Cytokines

49. Nitric Oxide

50. Summary

51. References
 Robbins & Cotran. Pathologic basis of
disease; 7th
ed.
 Dorland’s medical dictionary; 30th
ed
 Harsh Mohan. Essential Pathology for Dental
Students.; 3rd
ed.
 Henry Trowbridge. Inflammation A review of
the process; 4th
ed.

54. Contents
 Fate of Acute Inflammation
 Morphologic patterns of Acute
Inflammation
 Chronic Inflammation
 SIRS & Sepsis
 Anti-Inflammatory agents

55. Fate of Acute Inflammation

56. Fate of Acute Inflammation
Abscess
A localized collection of pus (suppurative inflammation)
appearing in an acute or chronic infection, and associated
with tissue destruction, and swelling.
Pathogenesis: the necrotic tissue is surrounded by
pyogenic membrane, which is formed by fibrin and help in
localize the infection.

57. Abscess

58. Fate of Acute Inflammation
Abscess
Pathogenesis: the necrotic tissue is surrounded by
pyogenic membrane, which is formed by fibrin and help in
localize the infection.

59. Morphologic Patterns
Serous Inflammation
Inflammation of serous membrane
characterized by clear fluid in serous cavity
(pleural, peritoneal pericardial & synovial
cavities)
E.g. skin Blisters caused by Burns OR viral
infection

60. Morphologic Patterns

61. Morphologic Patterns
Fibrinous Inflammation
Severe injury with excessive deposition of Fibrin in serous
cavity
Exudate and Fluid is removed by lymphatic
Fibrinous exudate may be degraded by Fibrinolysis and
removed by macrophage resulting in Resolution.
Incomplete Removal of fibrin resulting in organization and
scarring with
Fibrous Adhesion of pleura OR pericardium.

62. Morphologic Patterns

63. Morphologic Patterns
Suppuration (purulent ) Inflammation
Large amount of Purulent exudates (pus) caused by
pyogenic Bacteria staph aureus and Streptococcus
pyogenes
E.g Boil = Furuncle = Abscess of Hair follicles .

64. Morphologic Patterns
Pseudomembraneous Inflammation
Very severe ulcerative inflammation of mucous membranes
Extensive Necrosis of surface epithelium
Severe acute Inflammation of underlying tissue
Pseudo membrane, consisting of exudate, fibrin,
neutrophils RBC, Bacteria and tissue debris
e.g. Diphtheria – Larynx . pseudomembraneous Colitis –
clostridium difficile

65. Morphologic Patterns
Pseudomembraneous Inflammation

66. Morphologic Patterns
Ulceration
An ulcer is a local defect, or excavation, of the surface of an
organ or tissue that is produced by the sloughing of
inflammatory necrotic tissue
Tissue necrosis and resultant inflammation exist on or near
a surface
e.g Gastric (peptic) ulcer

67. Chronic Inflammation
 Inflammation of prolonged duration (weeks or
months) in which active inflammation, tissue
destruction, and attempts at repair are proceeding
simultaneously
(Robbins 7th
ed.)

68. Chronic Inflammation
 Characterized by the following:
Chronic inflammatory cell infiltration lymphocytes,
plasma cells and macrophage
Tissue destruction by Inflammatory cells
Healing and Repair – involving New Blood Vesel
proliferation (Angiogenesis) and Fibrosis

69. Chronic Inflammation
Causes:
Persistent infections
Prolonged exposure to potentially toxic agents
 Silica  silicosis
 Toxic plasma lipid components  atherosclerosis
Autoimmunity
 Rheumatoid arthritis & LE

70. SIRS & Sepsis
 Systemic inflammatory response syndrome
(SIRS) is the clinical expression of the
action of complex intrinsic mediators of the
acute phase reaction.
 SIRS can be precipitated by events such
as infection, trauma, pancreatitis, and
surgery.

71. SIRS & Sepsis

72. SIRS & Sepsis

73. SIRS & Sepsis
 SIRS can compromise the function of various
organ systems resulting in Multiple Organ
Dysfunction Syndrome (MODS).
 Clinicians should learn to identify SIRS in their
patients at an early stage to determine the
underlying cause and treatment before the
SIRS progresses to a more severe form.

75. H1 Anti-histaminics
 Blocks histamine induced
bronchoconstriction, contraction of
intestinal and other smooth muscle
 Blocks triple response
 Suppresses manifestations of type I
hypersensitivity reactions

76. Corticosteroids
 Corticosteroids have an anti-inflammatory
action – Hench et al (1949)
 Average rate of cortisol secretion–15-20
mg/day
 Increase in response to stress

77. Corticosteroids

79. Corticosteroids
 Blocking the cleavage of arachidonic
acid  inhibit PG synthesis
 Stabilizes intracellular lysosome
membranes  decreased release of
mediators

80. Corticosteroids
 Decreases permeability of capillary
membranes & reduces amount of
plasma lost  reduced amount of
edema
 Decreased migration of WBC in
inflamed tissues  diminished
phagocytosis

81. Corticosteroids
 Primary effect – marked reduction in post-
operative edema
Therapeutic uses in OMFS:
 Removal of impacted teeth (Beirne &
Hollander)
 Multiple extractions with alveoloplasty
 Removal of tori
 Apicoectomy

82. Corticosteroids
 Orthognathic surgeries (Schaberg et al)
 Rhinoplasty (Koopmann)
 Management of TMJ disorders – intraarticular
injection of corticosteroid provides relief of
symptoms in acute osteoarthritis of TMJ
 No more than 3 injections at a minimal interval of
1-3 months are recommended

83. NSAIDs
 Peripheral acting analgesics
 Anti-inflammatory, antipyretic and anti-thrombotic
activity
 Most effective when administered preoperatively
or immediately postoperatively, before the effects
of anesthesia have been reversed completely

84. NSAIDs
 COX1 – present in platelets, stomach, kidney
(cytoprotective to GIT)
 COX 2– induced by cytokines & endotoxins at
the site of inflammation
 Newer NSAIDs safer because they are selective
for COX-2

85. NSAIDs
 NSAIDs – control postoperative pain
 Corticosteroids – control postoperative edema
 Combination provides best results, since
NSAIDs potentiate the anti-inflammatory action of
steroids
Steroids add to the analgesic effect of NSAID

86. Leukotriene antagonists
 Montelukast & Zafirlukast
 Antagonize cysLT1 mediated
bronchoconstriction, increased vascular
permeability and recruitment of eosinophils
 Indicated for prophylactic therapy of mild to
moderate asthma

87. Omalizumab

88. Omalizumab
 Does not bind to cell-bound IgE
 Therefore, does not trigger cell activation
by crosslinking of the IgE molecules on cell
membranes.

89. Omalizumab

90. Omalizumab
 Omalizumab reduces the allergen induced
late asthmatic response, airway
hyperresponsiveness and sputum
eosinophilia
 Reduces both asthma exacerbations and
corticosteroid requirement
 Agent may have a long-term anti-
inflammatory effect

91. Enzymes as anti-
inflammatory agents
 Cleave the antigenic surface protein of organisms
and digest their outer coat
 Reduce number and activity of receptors for
pathogen on host cells
 Detoxify blood and remove viruses from circulation
 Cause enhancement of immune cells to kill
bacteria, viruses, molds and fungi

92. Enzymes as anti-
inflammatory agents
 Break down immune complexes which block the
immune cells
 Accelerate the volume and fluidity of blood flow
 Bromelain modulate arachidonate pathway in
such a way that thromboxane production is
decreased with no effect on cyclooxygenase

93. Enzymes as anti-
inflammatory agents
 Powerful anti-oxidants and effectively combat the
harmful free radicals such as nitric oxide
 Block pro-inflammatory metabolites that
propagate the inflammation
 Possess anti-secretory and mucolytic qualities
and decrease acute phase reactions

94. Serratiopeptidase
 Proteolytic enzyme isolated from the
non-pathogenic enterobacteria Serratia
E15 found in silkworms
 Acts upon inflammation by thinning the
fluids in the body that collect around
injured areas and increases fluid
drainage

95. Serratiopeptidase
 Enhances tissue repair and reduces pain
 Ability to block the release of pain-inducing
amines from inflamed tissues
 Ability to dissolve dead and damaged
tissue
 Modifies cell-surface adhesion molecules

96. References
 Robbins & Cotran. Pathologic basis of disease; 7th
ed.
 Harsh Mohan. Essential Pathology for Dental Students.; 3rd
ed.
 Henry Trowbridge. Inflammation A review of the process; 4th
ed.
 Goodman & Gilman's The Pharmacologic Basis of Therapeutics -
11th Ed. (2006)
 Laskin DM, Giglio JA. The use of steroids and NSAID in Oral and
Maxillofacial Surgery. Oral and Maxillofacial Surgery Clinics of
North America. 2001 Feb; 13(1): 31-41.

97. References
 M. Soler et al. The anti-IgE antibody omalizumab reduces
exacerbations and steroid requirement in allergic asthmatics Eur
Respir J 2001; 18: 254–261
 G. Hanf et al. Omalizumab inhibits allergen challenge-induced nasal
response. Eur Respir J 2004; 23: 414–418.
 Shahid S . Role of Systemic Enzymes in Infections . WebmedCentral
COMPLEMENTARY MEDICINE 2012;3(1):WMC002504
 Chopra et al. A randomized, double-blind, placebo-controlled study
comparing the efficacy and safety of paracetamol, serratiopeptidase,
ibuprofen and betamethasone using the dental impaction pain
model. Int. J. Oral Maxillofac. Surg. 2009; 38: 350–355