2. Contents
Introduction
Definition
Cardinal Signs
Types of inflammation
Acute inflammation – Pathogenesis
Chemical mediators of acute inflammation
Systemic & laboratory manifestations
Exudate Vs Transudate
Out comes of Acute Inflammation
Chronic inflammation
Chronic inflammatory cells
Chronic inflammation types
Summary and conclusion
References
3. Introduction
Inflammation is the reaction of living tissue to injury or infection.
It is a protective vascular connective tissue reaction or response intended to
remove injurious stimuli as well as the necrotic cells.
Repair-causes the replacement of damaged tissues by regeneration of
parenchyma cells or by filling of any residual defect by fibrous scar tissues.
(Healing)
4. Definition
A local response to cellular injury that is marked by capillary dilatation,
leukocytic infiltration, redness, heat, and pain and that serves as a
mechanism initiating the elimination of noxious agents and of damaged
tissues.
(Websters medical dictionary)
5. Sometimes harmful – hypersensitivity reactions,immune diseses.
Repair also can cause scarring ,fibrosis that may lead to obstruction of
movement.
Anti inflammatory drugs - enhance favourable effects of inflammation
and controls its harmful sequelae.
The nomenclature used to describe inflammation in different tissues
employs the tissue name and the suffix “- itis ” e.g pancreatitis meningitis
pericarditis arthritis
6. Cardinal Signs (Celsus)
Rubor- redness due to increased blood flow and vasodilation
Calor- or heat due to increase blood flow to the periphery
Tumor- swelling from inflammatory edema
Dolor-pain from swelling and presence of inflammatory mediators
Functio laesa-loss of function due to main and structural necrosis
(Virchow 1793)
7. :
Types of inflammation
Acute inflammation – immediate and early response to an injurious
agent,short duration usually less than 48 hrs
PMN as inflammatory cells
Chronic inflammation – longer duration,occurs either after the causative
agent of acute inflammation persist for a long time or the stimulus induces
chronic inflammation from the beginning
Lymhocytes,plasma cells,macrophages –inflammatory cells
9. Stimuli for acute inflammation
Infections (bacterial, viral, fungal, parasitic) and microbial toxins.
Tissue necrosis from any cause, including ischemia (as in a myocardial
infarct),trauma, and physical and chemical injury
Foreign bodies Dirt, sutures etc
Immune reactions (hypersensitivity reactions) are reactions in which the
normally protective immune system damages the individual's own tissues.
10. Acute inflammation - Pathogenesis
3 major components:
1. Alteration of vascular flow and caliber (vasodilation leads to increased blood flow)
2. Increased Vascular Permeability (Vascular Leakage)
3. Emigration of leukocytes from microcirculation (leukocyte activation leads to elimination of
offending agent)
13. 1.Changes in Vascular Flow and Caliber
Transient constriction of arterioles – immediate vascular response after an
injury.
Vasodilation
Arterioles are involved, and leads to increased blood flow, which is the cause of
heat and redness at the site of inflammation.
Induced by the action of mediators like histamine and nitric oxide, on
vascular smooth muscle.
14. Increased permeability of the microvasculature leads to exudation of
protein rich fluid into the extravascular space causing swelling (tumor).
Stasis of the blood flow -Loss of fluid from the vessels leads to
Concentration of red cells resulting in decreased velocity and stasis of the
blood flow
Leukocytic margination-Neutrophils, accumulate along the vascular
endothelium.At the same time endothelial cells are also activated by
mediators produced at sites of injury, and express increased levels of
adhesion molecules.
15. 2.Increased Vascular Permeability 15
Hallmark of acute inflammation as it causes escape of protein rich exudate
leading to edema.
loss of protein from plasma reduces intravascular osmotic pressure, and
increases that of interstitium.
So marked outflow of fluid Edema
16. Mechanism of vascular leakage
Contraction of endothelial cells
Resulting in gaps in endothelium.
most common mechanism.
Elicited by histamine, bradykinin, leukotrienes,and substance P.
It is called the immediate transient response because it occurs rapidly and is
short-lived.
17. Endothelial retraction
Structural reorganization of cytoskeleton of endothelial cells
Reversibile retraction of intercellular junctions
Delayed and prolonged
Direct endothelial injury
Resulting in endothelial cell necrosis.Eg:Burns,bacterial infections
Immediate and sustained reaction.
18. Leukocyte-dependent endothelial cell injury
Marginating leukocytes may damage the endothelium through activation and
release of toxic oxygen radicals and proteolytic enzymes making the vessel
leaky.
Transcytosis occurs across cellular channels.
22. 3.Emigration of leukocytes
critical function of inflammation is to deliver leukocytes to the site of injury
and to activate the leukocytes to eliminate the offending agents.
Leukocytes leave the vasculature routinely through the following sequence of
events:
1. Margination, rolling, and adhesion to endothelium
2. Diapedesis (trans-migration across the endothelium)
3. Migration toward a chemotactic stimuli from the source of tissue injury.
23. Margination and Rolling
With increased vascular permeability, fluid leaves the vessel causing leukocytes
to settle-out of the central flow column and “marginate” along the endothelial
surface
Endothelial cells and leukocytes have complementary surface adhesion
molecules which briefly stick and release causing the leukocyte to roll along
the endothelium until it adhire firmly.
Rolling and adhesion are mediated by selectins, integrins, Immunoglobulin
superfamily adhesion molecules.
24. Transmigration (diapedesis)
After adhesion leukocytes insert their pseudopods into endothelial cell junction
and squeeze through this layer into the extarvascular space..
It cross basement membrane by damaging it locally with Collagenases
25. Chemotaxis.
Once they have exited the capillary, the leukocytes move through the tissue
guided by secreted cytokines, bacterial and cellular debris, and complement
fragments (C3a, C5a),leukotrienes (LTB4).
Most chemotactic agents signal via G-protein-coupled receptors resulting in
intracellular Ca2+ release and activation of small GTPases. This leads to
actin/myosin polymerization and filopodia formation directed to the chemical
agent.
27. Phagocytosis and Degranulation
During the next and final stage of the cellular response, the neutrophils and
macrophages engulf and degrade the bacteria and cellular debris in a process
called phagocytosis.It involves
Recognition
Engulfment
Killing (degradation/digestion)
28. Recognition and Binding
The phagocytic cells are recognized by chemotactic factors released by
bacterial products.It is made easier by opsonisation-coating with natural
opsonins like C3b, IgG,lectins.
Engulfment
After a particle is bound to phagocyte receptors,pseudopods flow around it,
and form a vesicle (phagosome) that encloses the particle.It fuses with
lysosome-phagolysosome.
30. Killing (degradation/digestion)
Triggers an oxidative burst which forms Reactive oxygen species.it causes
Increased oxygen consumption
Glycogenolysis
Increased glucose oxidation
Formation of superoxide ion
Killng by halogenation, or lipid/protein peroxidation
34. Chemical mediators
Cell derived or plasma derived
Have “triggering” stimuli
Usually have specific targets
Can cause a “cascade”
Are short lived
39. Cyclooxygenase pathway
PGD2,PGE2,PGF2α
Causes Vasodilation,capillary permeability, and the pain and fever that accompany
inflammation.
PGI2(prostacyclin)
Produced by prostacyclin synthase in endothelial cell,Vasodilation, Inhibits Platelet
aggregation
TxA2
Produced by Thromboxane synthase in platelets,Vasoconstriction & stimulates
platelets aggregation
40. Lipoxygenase Pathway
LTB4
Produced by neutrophils & some macrophages
Chemotactic agent for neutrophils
LTC4,LTD4 & LTE4
Produced by mast cells
Vasoconstriction,bronchospasm
Lipoxins -Endogenous antagonists of Leukotrienes,Vasodilatation Inhibit
chemotaxis,
41. Platelet-Activating Factor (PAF)
Produced by WBCs & endothelial cells
Activate platelets, induces platelet aggregation, Causes Vasoconstriction,
Bronchoconstriction
It contributes to extravascularization of plasma proteins and so, to edema.
42. Nitric oxide
Potent vasodilator
Produced from the action of nitric oxide synthetase from arginine
43. Cytokines/chemokines
Cytokines are proteins produced mainly by LYMPHOCYTES and
MACROPHAGES.
Includes interferon, interleukin, TNF etc.
Interferon -Activation of macrophages
CHEMOKINES are small proteins which are attractants for PMN.
45. Plasma protein derived mediators
Complement System
Coagulation & Kinin System
Fibrinolytic system
46. Complement System
Consists of Plasma proteins
Upon activation different complement proteins(C3b) coat/opsonize
microbes for phagocytosis & destruction
C3a & C5a cause mast cells to release histamine which inturn causes
Vasodilation thus increasing vascular permeability
C5a activates lipoxygenase pathway causing release of more inflammatory
mediators
C5a also helps in leukocyte activation, adhesion & chemotaxis
47. Coagulation System
Hageman factor/Factor12a
A protein synthesized by liver
Activated factor12 further activates Kinin System,Clotting
System,Fibrinolytic System,Complement System
48. Kinin System
Ultimately leads to formation of bradykinin
Bradykinin causes arteriolar dilation, increases vascular permeability &
broncho constriction,also pain.
49. Fibrinolytic System
Ultimately leads to formation of plasmin
Plasmin
converts C3 to C3a
Converts factor-12 to factor-12a
Breaks down fibrin to fibrin degradation products which further
increases the vascular permeability
50. Morphological patterns of acute
inflammation
Serous (watery)
Fibrinous (hemorrhagic, rich in FIBRIN)
Suppurative -Produce pus & purulent exudates- neutrophil, necrotic cells &
edema fluid
Ulcerative
52. Exudate
Its presence implies an increase in
the normal permeability of small
blood vessels in an area of injury
and, therefore, an inflammatory
reaction.
A filtrate of blood plasma.
High protein concentration
Contains cellular debris & High
specific gravity.
Transudate
It is an ultrafiltrate of plasma,
resulting from osmotic or hydrostatic
imbalance across the vessel wall
without an increase in vascular
permeability.
A fluid with low protein content
Little or no cellular material & Low
specific gravity.
52
58. Chronic inflammation is the inflammation with prolonged duration usually
from weeks to months and sometimes to years in which active inflammation,
tissue injury and healing process proceed simultaneously.
60. Features:
Infiltration of mono-nuclear cells like lymphocytes, macrophages and plasma
cells.
The dominant cellular player in chronic inflammation is the tissue macrophage
Destruction of tissue by inflammatory cells.
Proliferation of new vessels leading to repair (angiogenesis & fibrosis).
61. Chronic inflammatory cells
1) MACROPHAGES:
Formed from monocytes.
Activated by cytokines,endotoxins,Extra cellular matrix proteins and cause
tissue destruction, Neovascularisation, fibrosis.
In liver _ Kupffer cells
Spleen and lymph nodes _ Sinus histocytes
Nervous system _ Microglial cells
Lungs _ Alveolar macrophages
62. 2) LYMPHOCYTES:
Both T- & B-lymphocytes are involved.
Activated macrophages release TNF & IL1 and activate lymphocytes which
produce different antibodies that cause destruction of antigens at the
inflammatory site.
3) EOSINOPHILS:
Found in parasitic infections and IgE mediated allergic reactions.
63. 4) MAST CELLS:
Mast cells are tissue cells which are like basophils in shape.
They are present in bone marrow and around blood vessels and do not enter
the blood.
They release histamines and amino acid metabolites. They cause initial
changes in acute inflammation and also cause anaphylactic reactions.
64. Types of chronic inflammation
1) Agranulomatous:
Granuloma is not formed,
Inflammation is characterized by all features of chronic inflammation.
Examples:
• Chronic viral infections e.g., Hepatitis
• Chronic autoimmune diseases e.g., Rheumatoid arthritis and Ulcerative colitis
• Chronic chemical intoxication e.g., Chronic alcoholic liver disease
• Allergic reactions e.g., Bronchial asthma
65. 2) Granulomatous inflammation
Characterized by aggregates of activated macrophages that assume a
squamous cell like epitheloid appearance.
GRANULOMA is defined as aggregates of macrophages formed due
response of T-lymphocytes to particular antigens.
This has a granular cheesy appearance called as caseous necrosis.
68. conclusion
Inflammation is fundamentally a protective response, designed to eliminate the
cause of injury (e.g., microbes, toxins) and the consequences of such injury
(e.g., necrotic cells and tissues).
Inappropriately triggered or poorly controlled inflammation is the cause of
tissue injury in many disorders.
69. REFERENCES
Robbins and Cotran Pathologic Basis of Disease eighth edition
Essential pathology for dental students-Harsh Mohan 3rd edition