Inflammation is defined as the body's response to injury or infection. It can be caused by infectious agents like bacteria, viruses, and parasites, or non-infectious agents like physical trauma, chemicals, or foreign bodies. The signs of inflammation are redness, swelling, heat, pain, and loss of function. Acute inflammation involves vascular changes like increased blood flow and permeability, as well as cellular events like exudation of leukocytes and phagocytosis of microbes. The type and severity of inflammatory response depends on factors related to the infectious agent, host defenses, and type of tissue involved.

1. INFLAMMATION
by- vidyalakshmi, jayashri vidya
and kavyashree

2.  INTRODUCTION
 DEFINITION AND CAUSES Inflammation is defined as the local response of
living mammalian tissues to injury from any agent. It is a body defense
reaction in order to eliminate or limit the spread of injurious agent, followed
by removal of thE cells and tissues.
 The injurious agents causing inflammation may be as under:
 1. Infective agents like bacteria, viruses and their toxins, fungi,
 parasites.
 2. Immunological agents like cell-mediated and antigen antibody
 reactions.
 3. Physical agents like heat, cold, radiation, mechanical
 trauma.
 4. Chemical agents like organic and inorganic poisons.
 5. Inert materials such as foreign bodies.

3.  Thus, inflammation is distinct from infection—inflammationis a protective
response by the body to variety of etiologic agents (infectious or non-
infectious), while infectiois invasion into the body by harmful microbes and
theirresultant ill-effects by toxins.
 Inflammation involves 2 basic
 processes with some overlapping, viz. early inflammatory
 response and later followed by healing.
 Though both these processes generally have protective role against
injurious agents, inflammation and healing may cause considerable harm
to the body as well e.g. anaphylaxis to bites by insects or reptiles, drugs,
toxins, atherosclerosis, chronic rheumatoid arthritis, fibrous bands.

4.  SIGNS OF INFLAMMATION:
 4 cardinal signs of
 inflammation as:
 i) rubor (redness);
 ii) tumor (swelling);
 iii) calor (heat); and
 iv) dolor (pain).
 To these, fifth sign functio laesa (loss of function/immobility)
 Vi)Exudation(escape of fluid from vascular system to intestinal space)
 Vi) Transudation (escape of fluid with less protin content)
 Vii)edema (accumulation of fluid)
 Viii)pusformation/

5. ETIOLOGY

6. CLASSIFICATION OF ACUTE INFLAMATION
 I)VASCULAREVENTS
 II) CELLUAR EVENTS
( TWO CHANGES ) ALTERED VASCULAR PERMIABILITY


PHAGOCYTOSIS
 HEAMODYNAMIC EXUDATION(ESCAPE
 CHANGES(EARLIEST EVENT) OF FLUID)

7. ACUTE INFLAMMATION
Acute inflammatory response by the host process
but for the purpose of discussion it can be divided
in to two types
 Vascular events
 Cellular events
Intimately linked to these two process is the release of mediators of acute
inflammation

8. VASCULAREVENTS :
Alternation in the microvasculature is the earliest response to cell injury.
This alternations includes haemodynamic changes and changes in
vascular permeability .

9. HAEMODYNAMIC CHANGES
 Irrespective of the type of cell injury immediate vascular response is of translent
vasoconstriction of arterioles. With mild form of injury the blood flow may be re-established in
3-5sec while with more severe injury the vasoconstriction may last for about 5min.
 Next follow persistent progressive vasodilation which involves mainly arterioles but to a lesser
extent affects other components of the microcirculation like venules and the capillaries.This
changes is obvious within half a hr of the injury. Vasodilation results in the increased blood
volume in the microvascular bed of the area which is responsible for the redness andwarmth
at the site of acute inflammation.
 Progressive vasodilation in the turn may elevate the local hydrostatic pressure resulting in
transudation of fluid in to the extracellular space . This is responsible for the swelling at the
local site of acute inflammation.
 Slowing or stasis of microcirculation follows which causes increased concentration of red cells
and thus raised blood viscosity.
 Stasis or slowing is followed by leucocytic margination or peripheral orientation of leucocytes
along the vascular endothelium . This process is known as emigration .

10. TRIPLE RESPONSE
 Lewis induced the changes in the skin of inner aspect of forearm by
firm stroking with a blunt point . The reaction so elicited is known as
triple response or red line response.
 Red line appears within a few sec after stroking and is due to local
vasodilatation of capillaries and venules.
 Flare is the bright reddish appearance or flush surrounding the red
line and results from vasodilatation of the adjacent arterioles.
 Wheals is the swelling or oedema of the surrounding skin occurring
due to transudation of fluid in to the extravascular space .

11. PATHOGENESIS
 The appearance of inflammatory oedema due to increased vascular
permeability of microvascular bed is explained on the basis of
starling’s hypothesis.
 Force that cause outwards movement of the fluid from microcirculation
.
 Forces that causes inward movement of the fluid in to the
microcirculation.
 forces are intravascular hydrostatic pressure and colloidal osmotic
pressure .

12. PATTERNS OF INCREASED VASCULAR PERMEABILITY
 Endothelial cell contraction
 Contraction or mild endothelial injury
 Direct endothelial cell injury
 Leucocyte-mediated endothelial injury
 Neovascularisation .

13.  1)Endothelial cell contraction
microvasculature : venules
Response type: immediate transient
pathogenesis: histamine, bradykinin
Example :mild thermal injury
 2)Contraction or mild endothelial injury
microvasculature : venules ,capillaries
Response type: somewhat delayed
Pathogenesis: IL-1 , TNF-cx
example :sunburns

14.  3)Direct endothelial injury
microvasculature : arterioles ,venules ,capillaries
Response type: immediate prolonged
Pathogenesis: cell necrosis and detachment
example: moderate to severe burns
4)Leucocyte-mediated endothelial injury
microvasculature :venules ,capillaries
Response type: delayed, prolonged
Pathogenesis: leucocytes activation
Example :pulmonary venules and capillaries

15.  5)Neovasularisation :
microvasculature : all levels
Response type :any type angiogenesis ,VEGF
pathogenesis : angiogenesis ,VEGF
example : healing , turmours

16. II]CELLULAR EVENTS
 The cellular phase of inflammation consist of 2 processes :
exudation of leucocytes
1. Exudation
2. Phagocytosis
1.exudation of leucocytes :
1.Changes in the formed elements of blood
2.Rolling and adhesion
3.Emigration
4.Chemotaxis

17.  2.Phagocytosis:
 Phagocytosis is defined as the process of engulfment of solidparticulate
material by the cells (cell-eating). The cellsperforming this function are called
phagocytes. There are 2 main types of phagocytic cells.
i) Polymorphonuclear neutrophils (PMNs) which appearearly in acute
inflammatory response, sometimes called as MICROPHAGES.
 II)Circulating monocytes and fixed tissue mononuclearphagocytes, commonly
called as macrophages.

18. THE MICROBE UNDERGOES THE PROCESS OF
PHAGOCYTOSIS BY POLYMORPHS AND MACROPHAGES AND INVOLVES
THE FOLLOWING 3 STEPS

 1. Recognition and attachment:
 2. Engulfment
 3. Killing and degradation

19. A. INTRACELLULARMECHANISMS
 i) Oxidative bactericidal mechanism by oxygen free
 radicals. An important mechanism of microbicidal killing is
 by oxidative damage by the production of reactive oxygen
 metabolites (O’2 H2O2, OH’, HOCl, HOI, HOBr).A phase of increased oxygen
consumption (‘respiratoryburst’) by activated phagocytic leucocytes requires
theessential presence of NADPH oxidase.
NADPH-oxidase present in the cell membrane ofphagosome reduces oxygen to
superoxide ion (O’2):2O2 2O’2NADPH (Superoxideoxidase anion)NADPH NADP
+ H+
 Superoxide is subsequently converted into H2O2 whichhas bactericidal
properties:
 2O’2 + 2H+ H2O2
 (Hydrogen peroxide)This type of bactericidal activity is carried out either
viaenzyme myeloperoxidase (MPO) present in the azurophilicgranules of
neutrophils and monocytes, or independent ofenzyme MPO, as under:

20.  a) MPO-dependent killing. In this mechanism, the enzyme :MPO acts on H2O2 in the presence of
halides (chloride, iodideor bromide) to form hypohalous acid (HOCl, HOI, HOBr).
 This is called H2O2-MPO-halide system and is more potent antibacterial system in polymorphs than
H2O2 alone:
 MPO: H2O2 HOCl + H2O {Cl’, Br’, I’ (Hypochlorous acid)
 b) MPO-independent killing. Mature macrophages lack the enzyme MPO and they carry out
bactericidal activity by producing OH– ions and superoxide singlet oxygen (O’) from
 H2O2 in the presence of O’2 (Haber-Weiss reaction) or in the presence of Fe++ (Fenton reaction):
 Reactive oxygen metabolites are particularly useful in eliminating microbial organisms that grow
withinphagocytes e.g. M. tuberculosis, Histoplasma capsulatum.
 ii) Oxidative bactericidal mechanism by lysosomal
 granules. In this mechanism, the preformed granule-stored products of neutrophils and
macrophages are discharged orsecreted into the phagosome and the extracellularenvironment.
 While the role of MPO is already highlighted above, others liberated by degranulation of macrophages
andneutrophils are protease, trypsinase, phospholipase, and alkaline phosphatase.
 Progressive degranulation of neutrophils and macrophages along with oxygen free radicals
 degrades proteins i.e. induces proteolysis.

21.  iii) Non-oxidative bactericidal mechanism. Some agentsreleased from
the granules of phagocytic cells do not require oxygen for bactericidal
activity.
 These include the following:
 a) Granules. Some of liberated lysosomal granules do not kill by oxidative
damage but cause lysis of within phagosome.
 These are lysosomal hydrolases, permeability increasing factors, cationic
proteins (defensins), lipases, ptoteases, 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 isproduced by endothelial cells as well as by activated
macrophages.

22. B. EXTRACELLULARMECHANISMS
 i) Granules. Degranulation of macrophages and neutrophils explained
above continues to exert its effects of proteolysis outside the cells as well.
 ii) Immune mechanisms. :immune-mediated lysis of microbes takes
place outside the cells by mechanisms of cytolysis, antibody-mediated
lysis and by cell-mediated cytotoxicity

23. FACTORS DETERMINING VARIATION IN
INFLAMMATORYRESPONSE
 1. Factors Involving the Organisms
 i to herpes simplex infection by
formation of vesicle and to streptococcal infection by formation of boil; lung reacts to
 pneumococci by occurrence of lobar pneumonia while to tubercle bacilli it reacts by
granulomatous inflammation.
 ii) Virulence. Many species and strains of organisms may have varying virulence e.g. the
three strains of c.diphtheria(gravis,intermedius and mitis) produce the same diphtherial
exotoxin but in different amount.
 iii) Dose. The concentration of organism in small doses produces usually local lesions
while larger dose results inmore severe spreading infections.
 iv) Portal of entry. Some organisms are infective only if
 administered by particular route e.g. Vibrio cholerae is not pathogenic if injected
subcutaneously but causes cholera if swallowed.
 v) Product of organisms. Some organisms produce enzymes
 that help in spread of infections e.g. hyaluronidase by Clostridium welchii, streptokinase by
streptococci, staphylokinase and coagulase by staphylococci

24.  2. Factors Involving the Host
 i) Systemic diseases. Certain acquired systemic diseases
 in the host are associated with impaired inflammatory response e.g. diabetes mellitus,
chronic renal failure, cirrhosis of the liver, chronic alcoholism, bone marrow suppression
from various causes (drugs, radiation, idiopathic). These conditions render the host more
susceptible to infections.
 ii) Immune status of host. Patients who are immunosuppressed from congenital or
acquired immunodeficiency have lowered inflammatory response and spread of
infections occurs rapidly e.g. in AIDS, congenital immunodeficiency diseases, protein
calorie malnutrition, starvation.
 iii) Congenital neutrophil defects. Congenital defects in neutrophil structure and
functions result in reduced
 inflammatory response.
 iv) Leukopenia. Patients with low WBC count with neutropenia or agranulocytosis
develop spreading infection.
 v) Site or type of tissue involved. For example, the lung has loose texture as
compared to bone and, thus, both tissues react differently to acute inflammation.
 vi) Local host factors. For instance, ischaemia, presence of foreign bodies and
chemicals cause necrosis and are thuscause more harm.

25.  3. Type of Exudation
 The appearance of escaped plasma determines the morphologic type of
inflammation as under:
 i) Serous, when the fluid exudate resembles serum or is watery e.g.
pleural effusion in tuberculosis, blister formation in burns.
 ii) Fibrinous, when the fibrin content of the fluid exudate is high e.g. in
pneumococcal and rheumatic pericarditis.
 iii) Purulent or suppurative exudate is formation of creamy pus as
seen in infection with pyogenic bacteria e.g. abscess, acute appendicitis.
 iv) Haemorrhagic, when there is vascular damage e.g. acute
haemorrhagic pneumonia in influenza.
 v) Catarrhal, when the surface inflammation of epithelium produces
increased secretion of mucous e.g. common cold

26. MORPHOLOGY OF ACUTE INFLAMMATION
 1. PSEUDOMEMBRANOUS INFLAMMATION. It is inflammatory response
of mucous surface (oral, respiratory,bowel) to toxins of diphtheria or irritant
gases. plasma exudes on the surfacewhere it coagulates, and together with
necrosed epithelium,forms false
2. ULCER. Ulcers are local defects on the surface of an organ produced by
inflammation. Common sites for ulcerations are the stomach, duodenum,
intestinal ulcers in typhoid fever, intestinal tuberculosis, bacillary and amoebic
dysentery,ulcers of legs due to varicose veins etc.
 3. SUPPURATION (ABSCESS FORMATION). When acute bacterial
infection is accompanied by intense neutrophilic infiltrate in the inflamed
tissue, it results in tissuenecrosis. A cavity is formed which is called an
abscess and contains purulent exudate or pus and the process of abscess
formation is known as suppuration.
 The bacteria which cause suppuration are called pyogenic.

27.  An abscess may be discharged to the surface due to increased pressure
inside or may require drainage by thesurgeon. Due to tissue destruction,
resolution does not occur but instead healing by fibrous scarring takes
place.
 i) Boil or furruncle which is an acute inflammation via hair follicles in the
dermal tissues.
 ii) Carbuncle is seen in untreated diabetics and occurs as a loculated
abscess in the dermis and soft tissues of the neck.

28.  4. CELLULITIS. It is a diffuse inflammation of soft tissues resulting from
spreading effects of substances like hyaluronidase released by some bacteria.
 5. BACTERIAL INFECTION OF THE BLOOD. This includes the following 3
conditions:
 i) Bacteraemia is defined as presence of small number of bacteria in the
blood which do not multiply significantly.
 They are commonly not detected by direct microscopy. Blood culture is done for
their detection e.g. infection with Salmonella typhi, Escherichia coli,
Streptococcus viridans.
 ii) Septicaemia means presence of rapidly multiplying, highly pathogenic
bacteria in the blood e.g. pyogenic cocci, bacilli of plague etc. Septicaemia is
generally accompanied by systemic effects like toxaemia, multiple
smallhaemorrhages, neutrophilic leucocytosis and disseminatedintravascular
coagulation (DIC).

29.  iii) Pyaemia is the dissemination of small septic thrombi in the blood
which cause their effects at the site where they arelodged. This can result
in pyaemic abscesses or septic infarcts.
 a) Pyaemic abscesses are multiple small abscesses in various organs
such as in cerebral cortex, myocardium, lungs and renal cortex, resulting
from very small emboli fragmented from septic thrombus. Microscopy of
pyaemic abscess shows a central zone of necrosis containing numerous
bacteria, surrounded by a zone of suppuration and an outer zone of acute
inflammatory cells.
 b) Septic infarcts result from lodgement of larger fragments of septic
thrombi in the arteries with relatively larger foci of necrosis, suppuration
and acute inflammation e.g. septic infarcts of the lungs, liver, brain, and
kidneys from septic thrombi of leg veins or from acute bacterial
endocarditis

30. SYSTEMICEFFECTSOF ACUTE INFLAMMATION
 1. Fever occurs due to bacteraemia. It is thought to be mediated through
release of factors like prostaglandins,interleukin-1 and TNF-α in response to
infection.
 2. Leucocytosis commonly accompanies the acute inflammatory reactions,
usually in the range of 15,000- 20,000/μl. When the counts are higher than this
with ‘shift to left’ of myeloid cells, the blood picture is described as leukaemoid
reaction.
 3. Lymphangitis-lymphadenitis is the important manifestations of
localised inflammatory injury. The lymphatics and lymph nodes that drain the
inflamed tissue show reactive inflammatory changes in the form of
lymphangitis and lymphadenitis.

31.  4. Shock may occur in severe cases. Massive release of cytokine TNF-
α, a mediator of inflammation, in response to severe tissue injury or
infection results in profusesystemic vasodilatation, increased vascular
permeability and intravascular volume loss.

32. FATE OF ACUTE INFLAMMATION
1. Resolution. It means complete return to normal tissue following acute inflammation.
This occurs when tissue changes are slight and the cellular changes are reversible e.g.
resolution in lobar pneumonia.
 2. Healing. Healing by fibrosis takes place when the tissue destruction in acute
inflammation is extensive so that there is no tissue regeneration. But when tissue loss is
superficial,it is restored by regeneration.
 3. Suppuration. When the pyogenic bacteria causing acute inflammation result in
severe tissue necrosis, the process progresses to suppuration. Initially, there is intense
neutrophilic infiltration. Subsequently, mixture of neutrophils,bacteria, fragments of
necrotic tissue, cell debris and fibrin comprise pus which is contained in a cavity to form
an abscess.
 The abscess, if not drained, may get organised by dense fibrous tissue, and in time, get
calcified.
 4. Chronic inflammation. Persisting or recurrent acute inflammation may progress to
chronic inflammation in which the processes of inflammation and healing proceed side by
side.

34. CHRONIC INFLAMMATION

35. CHRONIC INFLAMMATION:-
 Defined as prolonged process in which tissue destruction and
inflammation occurs at the same time.
 Chronic inflammation following acute inflammation:-
 Tissue destruction is extensive or bacteria survive and persist in small
numbers at site of inflammation. Eg:-osteomyletis
 Recurrent attacks of acute inflammation:-
 When recurrent attacks of acute inflammation culminate to chronic
inflammation. Eg:-recurrent urinary tract infection leads to chronic
pyleronephritis.
 Chronic inflammation starting denovo:-when the infection with
organisms persist from beginning eg:-infection with M.tubercle

36. GENERAL FEATURES OF CHRONIC INFLAMMATION:-
 Mononuclear cell infiltration:-
 Chronic inflammatory leison are infiltrated by mononuclear inflammatory
cells like phagocytes and lymphoid cells.
 Phagocytes are represented by circulating monocytes
tissue macrophages
epitheloid cells
Macrophages comprise the most important cells of inflammation from
1.Chemotactic factors and adhesion molecules
2.Local proliferation of macrophages
3.Longer survival of macrophages at site of inflammation.

37.  Blood monocytes reaching the extravascular space
transform into tissue macrophages
These macrophages may also get activated upon cytokines and bacterial
endotoxins.
On activation macrophages release cytokines,oxygen derived reactive metabolites
etc.
Tissue destruction or necrosis:-
This is brought by activated macrophages release biologically
active compounds
proteases elastases collagenses

38.  Proliferative changes:-
 As a result of necrosis proliferation of small blood vessels & fibroblasts
are stimulated and resulting in
formation of inflammatory granulation tissue

39. SYSTEMIC EFFECTS OF CHRONIC INFLAMMATION:-
 Fever
 Anaemia
 Leukocytosis
 ESR –Erthrocyte sedimentation rate elevated
 amyloidosis

41. TYPES OF CHRONIC INFLAMMATION
 Chronic non specific
inflammation
 When the irritant substance
produces non specific chronic
inflammatory reaction with the
formation of granulation tissue
and healing of fibrosis.
 Eg:-osteomyletis
 Chronic granulomatous
inflammation
 In this injurious agent causes
characteristic histolytic tissue
response by formation of
granules.
 Eg:-Tuberculosis,leprosy etc.

42. GRANULOMATOUS INFLAMMATION
 Granuloma is defined as tiny leision composed of collection of
modified macrophages called epitheloid cells and lymphoid cells.
 Granule=circumscribed granule like leision
 Oma=tumours

44. PATHOGENESIS
 1.engulfment by macrophages:-
 Macrophages,monocytes are engulfed by antigen and destroy it.
 But antigen poorly degradable
these cells fail to digest
and they transform into epitheloid cell.

45.  2.CD4+T cells:-
 Macrophages present the antigen to CD4+T lymphocytes
these lymphocytes gets activated and release cytokines
{IL-1,IL-2,Interferon etc.}

46.  Cytokines:-
 Different cytokines formed perform different function:-
 IL-1,IL-2 Stimulate proliferation of more T-cells.
 INF-gamma activate macrophages.
 TNF-alpha promotes fibroblast proliferation,activate
endothelium to secrete prostaglandin
 Growth factors:- stimulate fibroblast growth.

47. COMPOSITION OF GRANULOMA
 Epitheloid cells:-modified macrophages,elongated cells with slipper
like nucleus.
 Nuclear chromatin is vesicular,cytoplasm becomes abundant,and they
are weakly phagocytic.
 Multinucleate giant cells:-formed by fusion of abjacent eitheloid
cells.
 Commonly seen in TB.
 Lymphoid cells:-as a cell mediated immune reaction to antigen host
response is done by leukocyte. For humoral response it is done by
plasma cells.

48.  Necrosis:-feature of granulomatous inflammation
 Eg:-central casseous necrosis in TB.
 Fibrosis:-feature of healing by proliferating fibroblast at periphery of
granuloma.

49. EXAMPLES OF GRANULOMATOUS INFLAMMATION

50. EXAMPLES OF GRANULOMATOUS INFLAMMATION

51. DIFFERENCE BETWEEN ACUTE AND CHRONIC INFLAMMATION