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)
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
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).
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
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
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.
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.
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
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.
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.
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.
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.
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
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.
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
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.
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.
74.
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
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
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