Good Morning

INFLAMMATION

BY: M. AHMED
2

CONTENTS
Historical highlights
Patterns of inflammation- ACUTE AND CHRONIC
Acute inflammation

Vascular changes
cellular events
Chemical mediators of inflammation
Chronic inflammation
Types
pathogenesis
Outcomes of inflammation
Conclusion
References

HISTORY
To inflame ; to set a fire
Ancient Greeks used the term flegmonh to mean

the inflammation, - to burn.

Cornelius Celsusroman writer in 1st century

rubor (redness)
calor(heat)
dolor(pain)
tumor(swelling)

-A

fifth cardinal sign of inflammation was

added by the famous 19th century Pathologist
Rudolph Virchow

Redness and swelling with heat and pain and also loss of function

Julius Cohnheim(1889)
provided first microscopic
description of
inflammation

Elie Metchnikoff(1880s)
discovered the process of
phagocytosis

Paul Ehrlich and

Metchnikoff
theory of immunity

Robbins And Cotran, Pathologic basics of diseases,2005, 7 th ed

 Thomas Lewis demonstrated

lewis experiment that

inflammation is brought about
by chemical mediators, most
of which act locally.
This test is known as triple
response or red line response.
Red line(due to
vasodilatation of capillaries
and venules)
Flare(bright reddish
appearance surrounding red
line and results from
vasodilatation)
7
Wheal(swelling or oedema

DIFFERENCE BETWEEN EXUDATE AND TRANSUDATE

Harsh Mohan, Essentials of pathology ,4thed

definition
Inflammation is a local response of living
mammalian tissues to injury due to any agent. It
is a body defense reaction in order to eliminate or
limit the spread of injurious agent.
[Harsh mohan . 3rd edi]

Non living

CAUSES

10

Living

CAUSES

11

The 5 Cardinal Signs of

12

a. Rubor {redness}
b. Calor {heat}
c. Tumor {swelling}
d. Dolor {pain}
e. Functio laesa {loss of function}

CLASSIFICATION

13

ACUTE INFLAMMATION
Acute inflammation is a rapid response to an injurious
agent that serves to deliver mediators of host defence
leukocytes and plasma proteinsto the site of injury .
Sometimes, the acute inflammatory response may be quite
severe & is termed as Fulminant Acute Inflammation
A variant, Chronic Active Inflammation , is the type of
chronic inflammation in which during the course of disease
there are acute exacerbations of activity.
In some instances, the term Subacute Inflammation is used
for the state of inflammation between acute and chronic
14

Acute inflammation
Vascular events
Hemodynamic changes

cellular events
Altered vascular exudation of leucocytes
permeability

Transient
Vasoconstriction

Contraction of
endothelial cells

Vasodilatation

Retraction of
endothelial cells

Increased local
Hydrostatic
pressure
Slowing or stasis
Leucocytic
margination
15

Direct injury to
endothelial cells
Endothelial injury
mediated by
leucocytes
Leakiness in
neovascularisation

Changes in
the formed
elements of
blood
Rolling and
adhesion
Emigration
chemotaxis

phagocytosis

Recognition
and
attachment
Engulfment
Killing and
degradation

VASCULAR EVENTS:
Hemodynamic changes
Irrespective of the type of injury, immediate vascular response is a TRANSIENT
VASOCONSTRICTION of arterioles. In mild injury- 3 to 5 sec and in severe injury it
lasts for 5 min
Persistent VASODILATATION follows this, which involves arterioles. This results in
increased blood volume in vasucular bed of the area affected(Redness and warmth at
the site of inflammation)
In turn it elevates local HYDROSTATIC PRESSURE resulting in trasudation of fluid
into exrtacellular spaces- this causes swelling at the site of injury
SLOWING OR STASIS which causes increased concentration of RBCs and thus
causes raised blood viscosity
Stasis is followed by LEUCOCYTIC MARGINATION (mainly neutrophils)- here cells
of first line defense move out of the vessels into extravascular spaces.

16

Increased Vascular permeability

In the initial stage , the escape of fluid is due to vasodilatation and consequent elevation
in hydrostatic pressure. This is transudate in nature.
But subsequently inflammatory oedema or exudate appears by increased vascular
permaeability
The inflammatory oedema may be explained by starlings hypothesis that is,
It states that in normal circumstances , the fluid balance is mainained by two
opposing sets of forces,
1.Forces that cause outward movement of fluid from microcirculation are intravascular
hydrostatic pressure and colloid osmotic pressure of interstitial fluid
2.Forces that cause inward movement of interstitial fluid into circuation are intravascular
colloid osmotic pressure and hydrostatic pressure of interstitial fluid.

17

18

19

20

Emigration- once the suitable site is found the neutrophils throw out cytoplasmic
pseudopods and moves out, this is called emigration. Due raised hydrostatic pressure
RBCs also moves passively out of the compartment, this is called as Diapedesis.
Chemotaxis- there is transmigration of leucocytes after crossing several
barriers(endothelium,basement menbrane,perivascular myofibroblasts and matrix) to
reach the interstitial tissue by chemotactic factors like
For neutrophils: products of complement,C567 complex, C3a, C5a.
For monocytes: C567 complex, C3a, C5a,bacterial products etc.
For eosinophils: products of parasites.

21

This concept of chemotaxis is well illustrated by Boydens chamber experiment.

In this a millipore filter(3 micron m pore size) seperates the suspension of
leucocytes from the test solution in tissue culture chamber. If the test solution
contains chemotactic agent,the leucocyte migrate through the pores of filter
towards the chemotactic agent.

22

PROCESS OF
EXUDATION OF
LEUCOCYTES

23

23

Phagocytosis:
Phagocytosis is defined as the process of engulfment of solid particulate material by
cells(cell eating). There are 2 main phagoctes PMNs(microphages) and Macrophages.
This takes place in 3 steps,
1.Recognition and Attachment: macrophages has surface receptors which recognise
the opsonised bacteria coated with opsonins. This opsonin establish bond between
bacteria and macrophages. The opsonins are IgG opsonin(present in serum), C3b
opsonin(generated by complement pathway) and lectins(carbohydrate binding protein
present in plasma)
2.Enfulfment: There is formation of cytoplasmic pseudopods around the particle and
envelops it into phagocytic vacuole(phagosome). This fuses with lysosome to form
phagolysosome.

24

3. Killing and Degradation: The microorganisms after killed by antibacterial

substances are degraded by hydrolytic enzymes.
This disposal of micro organisms can proceed by following mechanisms,
A. Oxidative bactericidal mechanism by oxygen free radicals
MPO dependent
MPO independent
B. Oxidative bactericidal mechanism by lysosomal granules
C. Non-oxidative bactericidal mechanism

25

1. oxidative bactericidal mechanism by oxygen free radicals:

NADPH oxidase present in the cell membrane of phagosome reduces oxygen to
superoxide ion which is subsiquently reduced to H2O2 which has bactericidal activity.
This type of bactericidal activity is carried out either with MPO(myeloperoxidase
enzyme) or without MPO
NADPH Oxidase
2O2
2O2(superoxide)
2O2- + 2H+ H2O2
a) MPO dependent killing:
H2O2 in presence of MPO and Cl, Br, I forms hypochlorous acid and water
which is more potent antibacterial system than H2O2 alone.
b) MPO independent killing:
mature macrophages lack this enzyme MPO hence they carry out bactericidal
activity by producing OH- ion and superoxide singlet oxygen from H2O2 in
presence of oxygen(Haber Weiss rxn) or in presence of Fe+2 ion(fenton
reaction)
26

2. oxidative bactericidal mechanism by lysosomal granules:

The preformed granules i.e stored products of neutrophils
and macrophages are discharged into phagosome. Progressive
degranulation of neutrophils and macrophages along with
oxygen free radicals degrades proteins by the enzymes
protease, trypsinase, phospholipase and alkaline phosphatase.

27

3. Non oxidative bactericidal mechanism:

some agents released from granules of phagocytic cells do not require
oxygen for bactericidal activity. These include,
a) Granules: some of liberated lysosomal granules do not kill by
oxidative damage but cause lysis within phagosome. These are
lysosomal hydrolases, permeabilty increasing factors, cation
proteins, lipases, proteases, DNAases.
b) Nitric oxide: Nitric oxide reactive free radicals similar to oxygen free
radicals are formed by nitric oxide synthase and is a potent
mechanism of microbial killing. Nitric oxide is produced by
endothelial cells as well as by activated macrophages.

28

Chemical mediators of inflammation which increases the vascular permeability

29

INFLAMMATORY CELLS

30

LEUKOCYTES & ITS CONSTITUENTS

NEUTROPHIL

31

EOSINOPHIL

32

32

BASOPHIL

33

33

LYMPHOCYTE

34

34

35

MONOCYTE

36

Gaint cells in
inflammation
Foreign body gaint cell- These contains numerous nuclie with uniform in size and
shape and are scattered through out cytoplasm
Seen in chronic infective granuloma, leprosy, and tuberculosis.
Langhans gaint cell- seen in TB and sarcoidosis, their nuclie are arranged in
horse shoe or ring form.
Touton gaint cell- seen in Xanthoma which are multinucleated cells with
vacuolated cytoplasm
Aschoff gaint cells- seen in rheumatic nodules. These gaint cells are derived from
cardiac histiocytes.

37

video

38

MORPHOLOGIC PATTERNS OF
MORPHOLOGIC PATTERNS OF
ACUTE
INFLAMMATION
ACUTE INFLAMMATION

39

39

Serous Inflammation
Catarrhal inflammation
Fibrinous inflammation
Suppurative inflammation
Hemorrhagic inflammation
Allergic inflammation

40

CATARRHAL INFLAMMATION
DEFINITION: a form affecting mainly a mucous surface, marked
by a copious discharge of mucus and epithelial debris. (in
mucous membrane of GIT or respiratory tract eg: common
cold).

Acute inflammation with exudation of

fibrinogen-containing serum that polymerizes to fibrin
outside the blood vessels.
DEFINITION:

41

SUPPURATIVE INFLAMMATION
DEFINITION: Inflammation

with exudate consisting primarily of

neutrophils and cellular debris.
ABSCESS[ localised]

PHLEGMON[ diffuse]

phlegmon is characterized by the diffuse

spread of the exudate through tissue
spaces
caused by virulent bacteria like
streptococci
without either
localization or marked pus
formation
DEFINITION :

42

HEMORRHAGIC INFLAMMATION
DEFINITION: Acute inflammation involving microvascular injury with

massive microvascular bleeding, producing an exudate with a high

erythrocyte content

ALLERGIC INFLAMMATION
DEFINITION:

This is an inflammation of the mucous membrane

caused by powerful necrotizing toxin which produces coagulation

necrosis and cause pseudomembrane formation.

43

CHRONIC INFLAMMATION
Definition:
It is defined as prolonged process in which tissue destruction and inflammation occur
at the same time.(Harsha Mohan 4th edition)
Chronic inflammation can be caused by one of the following three ways,
1.Chronic inflammation following acute inflammation- osteomylitis,pneumonia
terminating in lung abscess
2.Recurrent attacks of acute inflammation- recurrent UTI leading to chronic
pyleonephritis, repeated acute infection of gallbladder leading to chronic cholecystitis
3.Chronic inflammation starting de novo- mycobacterium tuberculosis

44

General features of chronic inflammation:

1.Mononuclear cell infiltration- Mononuclear inflammatory cells like
phagocytes(circulating monocytes, tissue macrophages, epitheloid cells) and
lymphoid cells are infiltrated. Other chronic inflammatory cells includes of plasma
cells, eosinophils and mast cells .
2.Tissue desturuction- Tissue macrophages on activation release protease,
elastase, collagenase, lipase, reactive oxygen radicals, cytokines(IL-1,8, TNF-alpha)
nitric oxide etc These products bring about tissue destruction and necrosis.
3.Proliferative changes- as a result of necrosis, proliferation of small blood vessels
and fibroblasts are stimulates resulting in formation of inflammatory granulation
tissue.

45

Types of chronic inflammation:

Conventionally , chronic inflammation is divided into 2 types,
1.Non specific: when the irritant substance produce a non specific
inflammatory reaction with formation of granulation tissue and healing by
fibrosis
eg; chronic ulcer
2.
Specific: when the injurious agent causes a characteristic histologic
tissue response
eg; tuberculosis, leprosy, syphilis.

46

However for a more descriptive classification histological features

are used for classifying chronic inflammation into following
types
1. Chronic non-specific inflammation: charcterised by non specific
inflammatory cell infiltrate seen in lung abscess, chronic
osteomyelitis
2. Chronic suppurative inflammation: infiltration of PMNs and
abscess formation is seen eg-actinomycosis
3. Chronic granulomatous inflammation: characterised by
formation of granulomas, seen in tuberculosis,
syphilis,actinomycosis,sarcoidosis etc.

47

Granulomatous inflammation:
Granuloma is defined as a circumscribed, tiny lesion, about 1mm in diameter,
composed predominantly of collection of modified macrophages called epithelioid
cells and rimmed at periphery by lymphoid cells.
Pathogeniesis of granuloma:
Macrophages and monocytes engulf the antigen and try to destroy it but since the
antigen is poorly degradable, these cells fail to digest and degrade the antigen and
instead undergo morphological changes to epitheloid cells
When these macrophages failed to deal with antigen, it present the antigen to
CD4+T lymphocytes.
These CD4+ T lymphocytes gets activated and release cytokines, there functions
are,
IL-1 and IL-2 stimulates proliferation of more T cells
Interferon- gamma activates macrophages
TNF-alpha this promotes fibroblast proliferation
Growth factors activated by macrophages stimulate fibroblast growth.

48

Thus ,a granuloma is formed of macrophages

modified as epitheloid cells in the centre, with
some interspersed multinucleated giant cells,
surrounded peripherally by lymphoytes(T cells)
and healing by fibroblasts or collagen depending
upon the age of granuloma

49

Composition of Granuloma:
1.Epitheloid cells- These are called because of epithelial cell like appearance, are
modified macrophages/histiocytes which are weakly phagocytic in nature.
2.Multinucleated Gaint cells- They are formed by fusion of epitheloid cells and have
20 or more nuclie. This is also weakly phagocytic in nature but produces secretory
products which help in removing the invading agents.
3.Lymphoid cells- As a cell mediated immune reaction to antigen, the response by
lymphocytes is integral to composition of a granuloma.
4.Necrosis- This may be a feature of some granulomatous conditions like in case of
central caseation necrosis of tuberculosis.
5.Fibrosis- This is a feature of healing by proliferating fibroblasts at perphery of
granuloma.

50

video

51

HEALING

Is the body response to injury in an attempt to restore normal structure and function.

2 types :

1.REGENRATION :
When healing takes place by proliferation of parenchymal cells and usually results
in complete restoration of the original tissues.
2.REPAIR :
when healing takes place by proliferation of connective tissue elements resulting in
fibrosis and scarring.

52

52

Repair / Wound healing :

Primary union / healing by 1st intention
takes place in :
1.Clean and uninfected.
2.Surgically incised.
3.Less loss of cells and tissues
Within 24 hrs :
Neutrophils appear at margins
Epidermis starts to thicken
24-48 hrs :
Migration of epithelial cells from the edges to midline
By day 3 :
Neutrophils largely replaced by macrophages.
Granulation tissue involves the incision space.
Vertically oriented collagen fibres present at margins
Continued thickening of epidermis
53

53

By day 5 :
Incisional space filled with granulation tissue.
Max. neovascularization

Collagen fibrils begin to bridge the incision

Epidermis recovers its normal thickness

2nd week :

Continued accumulation of collagen and proliferation of fibroblasts.

Disappearance of edema, leukocytic infiltrate and increased

vascularity.

By first month :

Scar formation

Tensile strength of wound increases.

54

54

Secondary union / healing by 2nd intention :

Loss of more cells and More intense inflammatory reaction.

Much larger amount of granulation tissue formed

Phenomenon of wound contraction seen in larger defects.

55

55

PATHOLOGIC ASPECT OF INFLAMMATION AND REPAIR

56

Protein deficiency and vit. C deficiency inhibit collagen synthesis and

retard healing.

Glucocorticoids have antiinflammatory effect.

Presence of infection delays healing.

Mechanical factors like increased pressure may cause wound dehiscence.

Arteriosclerosis or venous abnormalities impair healing.

Foreign bodies retard healing.

Aberration growth of collagen may result in Keloid.

conclusio
n
Without inflammation,
infections would go unchecked,
wounds would never heal, and injured organs may remain
as permanent festering sores.
In our day to day lives we come across many cases
starting from gingivitis to oral cancer wherein inflammation
exerts a direct or an indirect effect.
So understanding inflammation helps us to know the
various vascular and cellular changes, mediators involved
and therefore help us to evaluate the significance of
various anti-inflammatory drugs that we do prescribe, for
controlling the same.
57

References:
Basic pathology : Robbins 9th edition
Text book of pathology: Harsh mohan 6 th edition
Complete review of pathology: Praveen kumar
and vandana puri
Text book of pathology: Ivan Damjanov 7 th
edition
Essentials of physiology for dental students:
58
shambulingam
k and prema shembulingam

Thank you

59