describes the vascular and cellular events of acute inflammation. The process involves diapedesis and phagocytosis. The various chemical mediators involved in the process have been discussed. Fate of acute inflammation and conversion into chronic inflammation is described.

1. INFLAMMATION- BASIC CONCEPT
Dr. Anushri Gupta
PG 1st year
Department of Periodontology
Date: 27-04-20

2. Definition
• Inflammation is a response of vascularized tissues to
infections and tissue damage that bring cells and molecules
of host defense from the circulation to the sites where they
are needed, to eliminate the offending agents.
- Robbins, 10th edition
• It is a body defense reaction in order to eliminate or limit
the spread of injurious agent, followed by removal of the
necrosed cells and tissue.

3. Agent causing inflammation
• Infective agent – like bacteria, viruses and toxins,
fungi, parasites.
• Immunological agent- like cell-mediated and antigen
antibody reaction.
• Physical agent- like heat, cold, radiation, mechanical
trauma.
• Chemical agent- like organic and inorganic poison.
• Inert material- such as foreign bodies.

4. Signs of inflammation
• 4 cardinal signs of inflammation are-
 Rubor (redness)
 Tumor (swelling)
 Calor (heat)
 Dolor (pain)
-Celsus, Roman encyclopedist
• 5th sign is functio laesa (loss of function)
-Virchow, Father of Modern Pathology

5. Types of inflammation
• Depending upon the defense capacity of host
and duration of response, inflammation can
be classified as –
A. Acute inflammation
B. Chronic inflammation

6. Acute inflammation
• Short duration (lasting less than 2 weeks)
• Represent the early body reaction
• Resolves quickly and is usually followed by healing.
• The main feature of acute inflammation are-
1) Accumulation of fluid and plasma at the affected
site.
2) Intravascular activation of platelets
3) Polymorphonuclear neutrophils as inflammatory
cells.
• Fulminant acute inflammation.

7. Chronic inflammation
– longer duration
– causative agent of acute inflammation persists
for a long time
• Another variant, Chronic active inflammation :
stimulus is such that it induces chronic
inflammation from the beginning.

8. A. Acute Inflammation
• The main features of acute inflammation are:
– accumulation of fluid and plasma at the affected
site;
– intravascular activation of platelets;
– polymorphonuclear neutrophils as inflammatory
cells.

9. • Divided into following two events
– Vascular events
– Cellular events
• This 2 events are followed intermittently by
release of mediators of acute inflammation.

10. A. Vascular events
• Alteration in the microvasculature (arterioles,
capillaries and venules ) is the earliest
response to tissue injury.
• These alteration include –
• hemodynamic changes and
• changes in vascular permeability.

11. a. Haemodynamic changes
• The sequence of these changes is as under –
Transient vasoconstriction:
• immediate vascular response
• irrespective of the type of
• injury, mainly arterioles
• – Mild injury - 3-5 seconds
• – Severe injury - 5 minutes

12. Persistent Progressive vasodilatation - involve
mainly the arterioles venules and capillaries
– obvious within half an hour of injury
– increased blood volume in microvascular bed of the
area
– redness and warmth
Local hydrostatic pressure-
_elevate the local hydrostatic pressure
– transudation of fluid into the extracellular space
– swelling

13. Slowing or stasis- of microcirculation causes
increased concentration of red cells and thus raised
blood viscosity.
Leucocytic margination –
• peripheral orientation of leucocytes (mainly
neutrophils) along the vascular endothelium
– stick to the vascular endothelium briefly
– move and migrate through the gaps between the
endothelial cells - extravascular space
– This is known is emigration

14. Lewis experiment
• Features of hemodynamic changes was best
demonstrated by Lewis.
• Lewis induced the changes in the skin of inner
aspect of foramen by firm stroking with a
blunt point.
• The reaction elected was triple response or
red line response consisting of the following-

15. 1) RED LINE- Appears within a few seconds following stroking and is
due to local vasodilation of capillaries and venules.
2) FLARE- Is the bright reddish appearance or flush surrounding the
red line and result from vasodilatation of the adjacent arterioles.
3) WHEAL –is the swelling or oedema of the surrounding skin
occurring due to transudation of fluid into the extravascular space.
A, ‘Triple response’ elicited by firm stroking of skin of forearm with a pencil.
B, Diagrammatic view of microscopic features of triple
response of the skin.

16. b. Altered Vascular Permeability
• Accumulation of oedema fluid – interstitial compartment
which comes from blood plasma by its escape through the
endothelial wall of peripheral vascular bed.
• Escape of fluid is due to vasodilatation and consequent
elevation in hydrostatic pressure - transudate.
• Subsequently, the characteristic inflammatory
oedema, appears by increased vascular permeability of
microcirculation – exudate.

18. Difference between transudate and
exudate-
Transudate
• Filtrate of blood plasma
without changes in
endothelial permeability
• It is a non- inflammatory
edema
• Protein content is low
mainly albumin, low
firbrinogen hence no
tendency to coagulate
Exudate
• Edema of inflamed tissue
associated with increased
vascular permeability
• Inflammatory edema
• High protein content,
coagulates due to high
content of fibrinogen and
the other coagulation
factors.

19. Transudate
• Glucose content is same as
in plasma
• pH > 7.3
• Cells- few cells, mainly
mesothelial cells and
cellular debris
• Example- edema in
congestive cardiac failure
Exudate
• Glucose content is low
• pH <7.3
• Many cells, inflammatory as
well as parenchymal.
• Purulent exudate such as
pus.

20. Starling hypothesis-
• Apperance of inflammatory oedema due to increased vascular
permeability of microvascular bed is explained by this hypothesis.
The fluid balance is maintained by two opposing sets of forces –
 Forces that causes outward movement of fluid from
microcirculation are intravascular hydrostatic pressure and
colloid osmotic pressure of intestinal fluid.
 Forces that causes inward movement of interstial fluid into
circulation are intravascular colloid osmotic pressure and
hydrostatic pressure of interstitial fluid.

21. Fluid interchange between
blood and extracellular fluid
(ECF).
(HP = hydrostatic pressure,
OP = osmotic pressure

22. Mechanism of increased vascular permeability-
• In acute inflammation non-permeable endothelial
layer of microvasculature becomes leaky.

23. Contraction of endothelial cells
• Affects venules exclusively.
• Endothelial cells develop
temporary gaps
• Contraction resulting in
vascular leakiness.
• Mediated by the release of
histamine, bradykinin and
other chemical mediators.
• Short duration (15-30
minutes) - immediately
after injury.

24. Retraction of endothelial cells
• Structural re-organisation of
the cytoskeleton of
endothelial cells - Reversible
retraction at the intercellular
junctions.
• Mediated by cytokines such
as interleukin-1 (IL-1) and
tumour necrosis factor
(TNF)-α.

25. Direct injury to endothelial cells
• Causes cell necrosis and
appearance of physical gaps.
• Process of thrombosis is initiated
at the site of damaged endothelial
cells.
• Affects all levels of
microvasculature.
• Either appear immediately after
injury and last for several hours or
days – severe bacterial infections
• Or delay of 2-12 hours and last for
hours or days - moderate thermal
injury and radiation injury

26. Endothelial injury mediated by
leucocytes
• Adherence of leucocytes to the endothelium
at the site of inflammation.
• Activation of leucocytes - release proteolytic
enzymes and toxic oxygen.
• Cause endothelial injury and increased
vascular leakiness.
• Affects mostly venules and is a late response.

27. Leakiness and neovascularisation
• Newly formed capillaries under the influence
of vascular endothelial growth factor (VEGF).
• Process of repair and in tumours are excessively
leaky

28. B. Cellular events
Consist of 2 process-
Exudation of leucocytes
Phagocytosis
a. Exudation of leucocytes-
• The escape of leucocytes from the lumen of microvasculature to
the interstitial tissue is the most important feature of
inflammatory response.
• In acute inflammation, polymorphonuclear neutrophils (PMNs)
comprise the first line of body defense.
• The changes leading to migration of leucocytes are-

29.  Changes in the formed elements of blood-
• Central stream of cells
comprised by leucocytes and
RBCs and peripheral cell free
layer of plasma close to vessel
wall.
• Later, central stream of cells
widens and peripheral plasma
zone becomes narrower
because of loss of plasma by
exudation.
• This phenomenon is known as
margination.
• Neutrophils of the central
column come close to the vessel wall - pavementing

30. Rolling and adhesion –
• Peripherally marginated and
pavemented neutrophils slowly
roll over the endothelial cells
lining the vessel wall (rolling phase).
• Transient bond between the
leucocytes and endothelial cells
becoming firmer (adhesion phase).
• The following molecules bring
about rolling and adhesion
phases
– Selectins
– Integrins
– Immunoglobulin gene superfamily adhesion molecule

31. Events of Exudation of Leucocytes

32. EMIGRATION
• After sticking of neutrophils to endothelium,
• The former move along the
endothelial surface till a
suitable site between the
endothelial cells is found
where the neutrophils throw
out cytoplasmic pseudopods.
• Cross the basement
membrane by damaging it
locally – collagenases and
escape out into the extravascular space - emigration
• Diapedesis - escape of red cells through gaps between the endothelial
cells
– passive phenomenon.
– raised hydrostatic pressure
– haemorrhagic appearance to the inflammatory exudate

33. Sequence of changes in the exudation of leucocytes.
A, Normal axial flow of blood with central column of cells and peripheral zone of
cell-free plasma.
B, Margination and pavementing of neutrophils with narrow plasmatic zone.
C, Adhesion of neutrophils to endothelial cells with pseudopods in the
intercellular junctions.
D, Emigration of neutrophils and diapedesis with damaged basement
membrane.

34. Chemotaxis –
• After extravasating from the blood, Leukocytes migrate
toward sites of infection or injury along a chemical gradient by a
process called chemotaxis
• They have to cross several barriers - endothelium,
basement membrane, perivascular myofibroblasts and matrix.
• The following agents act as potent chemotactic substance or
chemokines for neutrophils-
1. Leukotrine b4
2. Components of complement system
3. Cytokines (Interleukins, in particular IL-8)
4. Soluble bacterial products (such as formylated peptides)

35. b. Phagocytosis-
 It is a process of engulfment of solid particulate material by the
cells. (cell eating)
 Cells performing this function is phagocytic cells.
 2 main types of phagocytic cells-
a. PMNs –appears early in acute inflammatory response
sometimes known as microphages.
b. Macrophages-Circulating monocytes and fixed tissue
• This phagocytic cells releases proteolytic enzymes- lysozyme,
protease, collagenase, elastase, lipase, proteinase, gelatinase and
acid hydrolases

36. • The microbe undergoes the process of phagocytosis
and involve the following 3 steps-
Recognition and attachment-
• the process of coating a particle such as microbe to
target it for phagocytosis is called as
OPSONISATION.
• substance are called OPSONINS.
• The main opsonin present in serum are – IgG, C3b
and lectin.

37. Engulfment –
• Formation of cytoplasmic pseudopods around
the particle due to activation of actin filaments
around cell wall.
• Eventually plasma membrane gets lysed and
fuses with nearby lysosomes – phagolysosome.

38. Killing and degradation-
• the micro-organism after being killed by organism after being
killed by anti- bacterial substance are degraded by hydrolytic
enzyme.
• Sometimes this process fails to kill and degrade some bacteria
like tubercle bacilli.

39. Stages in phagocytosis of a foreign particle.
A, Opsonisation of the particle.
B, Pseudopod engulfing the opsonised particle.
C, Incorporation within the cell (phagocytic vacuole) and degranulation.
D, Phagolysosome formation after fusion of lysosome of the cell.

40. Disposal of microorganisms
• Intracellular mechanisms
– Oxidative bactericidal mechanism by oxygen free
radicals
– Oxidative bactericidal mechanism by lysosomal
granules
– Non-oxidative bactericidal mechanism
• Extracellular mechanisms
– Granules
– Immune mechanisms

41. A. INTRACELLULAR MECHANISMS
• Kill microbes by oxidative mechanism and less often non-oxidative
pathways
a). Oxidative bactericidal mechanism by oxygen free radicals.
– production of reactive oxygen metabolites (O’2, H2O2, OH’, HOCl, HOI,
HOBr)
– activated phagocytic leucocytes requires the essential presence of
NADPH oxidase
- present in the cell membrane of phagosome reduces oxygen to
superoxide ion (O’2)
• Superoxide is subsequently converted into H2O2 which has
bactericidal properties
2O2’ + 2H+ H2O2

42. b). Oxidative bactericidal mechanism by lysosomal granules
– preformed granule-stored products of neutrophils and macrophages.
– secreted into the phagosome and the extracellular environment.
c). Non-oxidative bactericidal mechanism
– Some agents released from the granules of phagocytic cells do not
require oxygen for bactericidal activity
• Granules : cause lysis of within phagosome, ex: lysosomal hydrolases,
permeability increasing factors, cationic proteins (defensins), lipases,
ptoteases, DNAases.
• Nitric oxide : reactive free radicals similar to oxygen free radicals
– potent mechanism of microbial killing
– produced by endothelial cells as well as by activated macrophages

43. B. EXTRACELLULAR MECHANISMS
• Granules
– Degranulation of macrophages and neutrophils
• Immune mechanisms
– immune-mediated lysis of microbes
– takes place outside the cells
– by mechanisms of cytolysis, antibody-mediated lysis
and by cell-mediated cytotoxicity

44. Chemical mediators of inflammation
• Chemical mediators that are
responsible for vascular and
cellular events.
• Knowledge of this mediators
– basis of anti-inflammatory
drugs.
• It may either of two types,
– Cell Derived - produced
locally by cells at the site of
inflammation
– Plasma derived – mainly
from liver
• Some mediators are derived
from Necrotic cells

45. Chemical mediators of inflammation

46. A. Cell derived mediators
• Induce their effects by binding to specific receptors on target cells
– it may be one or a very few targets, or multiple
• Some may have direct enzymatic and/or toxic activities. Ex:
lysosomal proteases
• Some may stimulate target cells to release secondary effector
molecules
• Once activated and released from the cell, mediators either
– quickly decay. Ex: arachidonic acid metabolites
– inactivated by enzymes ex: kininase inactivates bradykinin
– eliminated Ex: antioxidants scavenge toxic oxygen metabolites
– Inhibited. Complement-inhibitory proteins

47. – Rapidly secreted upon cellular activation. Ex: histamine in mast cells
– synthesized from beginning in response to a stimulus. Ex:
Prostaglandins and cytokines
• Tissue macrophages, mast cells, and endothelial cells –
capable of producing different mediators.
• Various cell derived mediators
1. Vasoactive amines
2. Arachidonic acid metabolites
3. Lysosomal component
4. Platelet activating factors (PAF)
5. Cytokines
6. Reactive Oxygen Species (ROS) and nitrogen oxide (NO)
7. Neuropeptides

48. 1. Vasoactive Amines
• Stored as preformed molecules in mast cells or early inflammatory
cells.
• Histamine
– many cell types, particularly mast cells adjacent to vessels, circulating
basophils and platelets
– variety of stimuli responsible for release of histamine:
• physical injury like heat, cold, radiation, trauma etc.
• immune reactions involving binding of IgG antibodies to Fc receptors
on mast cells
• C3a and C5a fragments of complement – anaphylatoxins
• Leukocyte-derived histamine-releasing proteins
• Neuropeptides e.g., substance P
• Certain cytokines e.g., IL-1 and IL-8

49. • Actions:
- arteriolar dilation & increased vascular permeability : endothelial
contraction and interendothelial gaps
– itching and pain
– Histamine inactivated by histaminase
• Serotonin
– 5-hydroxytryptamine
– preformed vasoactive mediator - effects similar to those of
histamine but less potent
– Released from platelet, GIT, spleen, nervous system, mast cells

50. 2. ARACHIDONIC ACID (AA)
METABOLITES
• Also known as eicosanoids.
• Most potent mediators of inflammation.
• short-range hormones that act locally at the site of generation and
then decay spontaneously or are enzymatically destroyed
• Derived from cell membranes phospholipids of Leukocytes, mast
cells, endothelial cells, and platelets by the action of
phospholipases.

51. • AA is released from these phospholipids via cellular phospholipases
– that have been activated by mechanical, chemical, or physical
stimuli, or by inflammatory mediators such as C5a.
• Metabolism proceeds along either of this two major enzymatic
pathways
• Cyclooxygenase : prostaglandins and thromboxanes - AUTOCOIDS
• Lipoxygenase : leukotrienes and lipoxins

52. Cyclo-oxygenase Pathway
• Cyclooxygenase - a fatty acid enzyme present as COX-1 and
COX-2,
• Metabolizes AA to following derivative
– Prostaglandins (PGD2, PGE2 and PGF2-α)
– Thromboxane A2 (TXA2)
– Prostacyclin (PGI2)
– Resolvins
• Major anti-inflammatory drugs act by inhibiting activity of the
enzyme COX – NSAIDs & COX-2 inhibitors

53. Arachidonic acid metabolites via cyclooxygenase
pathway

54. Lipo-oxygenase Pathway

55. 3. LYSOSOMAL COMPONENTS
• Inflammatory cells like neutrophils and monocytes – lysosomal
granules.
Its of 2 types :
• Granules of neutrophils
– Primary or azurophil : myeloperoxidase, acid hydrolases, acid
phosphatase, lysozyme, defensin (cationic protein), phospholipase,
cathepsin G, elastase, and protease
– Secondary or specific: alkaline phosphatase, lactoferrin, gelatinase,
collagenase, lysozyme, vitamin-B12 binding proteins, plasminogen
activator
– Tertiary: gelatinase and acid hydrolases
• Granules of monocytes and tissue macrophages
– acid proteases, collagenase, elastase and plasminogen activator
– more active in chronic inflammation

56. 4. PLATELET ACTIVATING FACTOR (PAF)
• released from IgE-sensitised basophils or mast cells, other
leucocytes, endothelium and platelets. Apart from its action
on platelet aggregation and release reaction, the actions of
PAF as mediator of inflammation are:
• increased vascular permeability;
• vasodilatation in low concentration and vasoconstriction
otherwise;
• bronchoconstriction;
• adhesion of leucocytes to endothelium; and
• chemotaxis.

57. 5. CYTOKINES
• Polypeptide substances produced by activated lymphocytes
(lymphokines) and activated monocytes (monokines).
• Major cytokines in acute inflammation
– TNF-alpha and IL-1,
– Chemokines - a group of chemoattractant cytokines
• Chronic inflammation : interferon-γ (IFN-γ) and IL-12

58. Tumor Necrosis Factor and Interleukin-1
• Produced by activated macrophages, as well as mast cells, endothelial
cells, and some other cell types
• Stimulated by microbial products, such as bacterial endotoxin,
immune complexes, and products of T lymphocytes
• Principal role in inflammation – endothelial activation
– expression of adhesion molecules on endothelial cells results in
increased leukocyte binding and recruitment,
– enhance the production of additional cytokines (notably chemokines)
and eicosanoids
• TNF – increases thrombogenicity of endothelium and causes
aggregation and activation of neutrophils
• IL-1 - results in increased proliferation and production of fibroblasts
in extracellular matrix

59. • May enter the circulation - systemic acute-phase reaction
– Fever & lethargy
– hepatic synthesis of various acute-phase proteins,
– metabolic wasting (cachexia),
– neutrophil release into the circulation,
– release of adrenocorticotropic hormone (inducing
corticosteroid synthesis and release).

60. Chemokines
Chemokines are a family of chemoattractants for
inflammatory cells and include:
• IL-8 chemotactic for neutrophils;
• platelet factor-4 chemotactic for neutrophils,
monocytes and eosinophils;
• MCP-1 chemotactic for monocytes; and
• eotaxin chemotactic for eosinophils

61. 6. Nitric Oxide
• short-lived, soluble, free-radical gas
• formed by activated macrophages during the oxidation of arginine by the action of
enzyme, NO synthase (NOS).
• Three isoforms of NOS
– Type I (nNOS) – neuronal, no role in inflammation
– Type II (iNOS) – induced by chemical mediators, macrophages and endothelial cells
– Type III (eNOS) - primarily (but not exclusively) within endothelium
• NO plays many roles in inflammation including
– relaxation of vascular smooth muscle (vasodilation),
– antagonism of all stages of platelet activation (adhesion, aggregation, and
degranulation)
– reduction of leukocyte recruitment at inflammatory sites
– action as a microbicidal (cytotoxic) agent (with or without superoxide radicals) in
activated macrophages.

63. 7. Neuropeptides
• initiate inflammatory responses
• small proteins, such as substance P
• transmit pain signals, regulate vessel tone,
and modulate vascular permeability
• prominent in the lungs and gastrointestinal
tract

64. B. Plasma-protein-derived mediators
• Circulating proteins of four interrelated systems - the
complement, kinin, clotting and fibrinolytic systems
• Inactive precursors that are activated at the site of
inflammation – action of enzyme.
• Each of these systems has its inhibitors and accelerators in
plasma - negative and positive feedback mechanisms
respectively.
• Hageman factor (factor XII) of clotting system – a key role in
interactions of the four systems

65. Hageman factor (factor XII)
• protein synthesized by the liver.
• initiates four systems involved in the inflammatory response
– Kinin system - vasoactive kinins;
– Clotting system - inducing the activation of thrombin,
fibrinopeptides, and factor X,
– Fibrinolytic system - plasmin and inactivating thrombin;
– Complement system - anaphylatoxins C3a and C5a
• Gets activated - collagen, basement membrane, or activated
platelets.

66. 1. Clotting system
• factor XIIa-driven proteolytic cascade leads to activation of
thrombin.
• Functions of thrombin
– cleaves circulating soluble fibrinogen to generate an insoluble
fibrin clot
• Fibrinopeptides - increase vascular permeability & chemotactic
for leukocytes.
– In i/m, Binding of thrombin to the receptors on endothelial cells -
activation and enhance leukocyte adhesion

68. 2. Fibrinolytic System
• Hageman factor induces clotting system and fibrinolytic system
concurrently – control over the 2 system
• Limit clotting by cleaving fibrin - solubilizing the fibrin clot.
• In absence of this – even minor injury could lead to
coagulation of entire vasculature.
• Plasminogen activator - released from endothelium,
leukocytes, and other tissues) and kallikrein from kinin system
– Cleave plasminogen, a plasma protein – further forms
PLASMIN

69. • Multifunctional protease that cleaves fibrin.
• Cleaves the C3 complement protein - production of
C3a
• Activate Hageman factor - amplify the entire set of
responses

70. 3. Kinin System
• Haegman Factor activates Prekallikrein activator -
acts on plasma prekallikrein to give kallikrein.
• Kallikrein acts on kininogen (HMW) to give Bradykinin.
• Bradykinin are short-lived - rapidly degraded by
kininases present in plasma and tissues

71. Bradykinin
• Slow contraction of smooth muscle
• Bradykinin acts in the early stage of i/m :
– vasodilatation;
– increased vascular permeability
– pain

72. 4. Complement System
• The activation of complement system can occur either:
i) by classic pathway through antigen-antibody complexes;
or
ii) by alternate pathway via non-immunologic agents such as
bacterial toxins, cobra venoms and IgA.
• Complement system on activation by either of these two
pathways yields activated products which include anaphylatoxins
(C3a, C4a and C5a), and membrane attack complex (MAC) i.e.
C5b,C6,7,8,9.

73. • The actions of activated complement system in inflammation are as
under:
• C3a, C5a, C4a (anaphylatoxins) activate mast cells and
basophils to release of histamine, cause increased vascular
permeability causing oedema in tissues, augments phagocytosis.
• C3b is an opsonin.
• C5a is chemotactic for leucocytes.
• Membrane attack complex (MAC) (C5b-C9) is a lipid
dissolving agent and causes holes in the phospholipid
membrane of the cell.

77. Outcomes of acute inflammation
1. Resolution - restoration to normal, limited injury
– chemical substances neutralization
– normalization of vasc. permeability
– apoptosis of inflammatory cells
– lymphatic drainage
2. Healing by scar
3. Suppuration
- Neutrophilic infiltration
- pus formation
- Dense fibrous tissue formation leading to calcification
4. Progression into chronic inflammation

80. B. Chronic inflammation
• Definition - Chronic inflammation is also referred to as slow,
long-term inflammation lasting for prolonged periods of
several months to years. Generally, the extent and effects of
chronic inflammation vary with the cause of the injury and
the ability of the body to repair and overcome the damage.
• Occur either after the causative agent of acute inflammation
persists for a long time, or the stimulus is such that it induced
chronic inflammation from the beginning.

81. • Characteristic feature of chronic inflammation
is presence of chronic inflammatory cells such
as lymphocytes, plasma cells and
macrophages, granulation tissue formation
and in specific situation.

82. • Chronic inflammation can be caused by one of the following 3 ways-
• Following acute inflammation
– persistence of the injurious agent or because of interference with the
normal process of healing
– e.g. in osteomyelitis, pneumonia terminating in lung abscess
• Recurrent attacks of acute inflammation
– repeated bouts of acute inflammation culminate in chronicity of the
process
– Ex: Recurrent urinary tract infection - chronic pyelonephritis,
Repeated acute infection of gall bladder – chronic cholecystitis
• Chronic inflammation starting de novo
– low pathogenicity is chronic from the beginning
– Ex: infection with Mycobacterium tuberculosis, Treponema pallidum

83. Chronic Inflammatory Cells and
Mediators
• PMNs
• Macrophages
• Lymphocytes,
• Plasma Cells,
• Eosinophils,
• Mast Cells

84. Polymorphonuclear Neutrophils
• along with basophils and eosinophils are known as granulocytes due
to the presence of granules in then cytoplasm.
• These granules contain many substances like proteases,
myeloperoxidase, lysozyme, esterase, aryl sulfatase, acid and alkaline
phosphatase, and cationic proteins.
• The functions of neutrophils in inflammation are as follows:
• i) Initial phagocytosis of microorganisms as they
form the first line of body defense in bacterial infection.
• ii) Engulfment of antigen-antibody complexes and
nonmicrobial material.
• iii) Harmful effect of neutrophils in causing
Basement membrane destruction of the glomeruli and
small blood vessels.

85. Eosinophils
• share many structural and functional similarities with neutrophils like
their production in the bone marrow, locomotion, phagocytosis,
lobed nucleus and presence or granules in the cytoplasm containing a
variety of enzymes, of which major basic protein and eosinophil
cationic protein are the most important which have bactericidal and
toxic action against helminthic parasites.
• The absolute number of eosinophils is increased
in the following conditions:
• i) allergic conditions;
• ii) parasitic infestations;
• iii) skin diseases; and
• iv) certain malignant lymphomas.

86. Basophils
• The basophils comprise about 1% of circulating leucocytes and are
morphologically and pharmacologically similar to mast cells of tissue.
• granules are laden with heparin and histamine.
• The role of these cells in inflammation are:
i) in immediate and delayed type of
hypersensitivity reactions; and
ii) release of histamine by IgE-sensitised
basophils.

87. Lymphocytes
• Apart from blood, (20-45%), lymphocytes are present in large numbers in spleen,
thymus, lymph nodes and mucosa-associated lymphoid tissue (MALT).
• They play role in antibody formation (B lymphocytes) and in cell-mediated
immunity (T lymphocytes).
• These cells participate in the following types of inflammatory responses:
i) In tissues, they are dominant cells in chronic inflammation and late stage of acute
inflammation.
ii) In blood, their number is increased (lymphocytosis) in chronic infections like
tuberculosis.

88. Plasma Cells
• Plasma cells are normally not seen in peripheral blood.
• They develop from B lymphocytes and are rich in RNA and γ-globulin
in their cytoplasm.
• These cells are most active in antibody synthesis.
• Their number is increased in the following conditions:
• i) prolonged infection with immunological responses e.g. in syphilis,
rheumatoid arthritis, tuberculosis;
• ii) hypersensitivity states; and
• iii) multiple myeloma.

89. Mononuclear-Phagocyte System
(Reticuloendothelial System)
• This cell system includes cells derived from 2 sources with common
morphology, function and origin:
• Blood monocytes: These comprise 4-8% of circulating leucocytes.
• Tissue macrophages: These include the following cells in different
tissues:
• i) Macrophages in inflammation.
• ii) Histiocytes which are macrophages present in connective tissues.
• iii) Kupffer cells are macrophages of liver cells.
• iv) Alveolar macrophages (type II pneumocytes) in lungs.
• v) Macrophages/histiocytes of the bone marrow.
• vi) Osteoclasts in the bones.
• vii) Microglial cells of the brain.
• xiii) Langerhans’ cells/dendritic histiocytes of the skin.
• ix) Hoffbauer cells of the placenta.
• x) Mesangial cells of glomerulus.

90. • Role of macrophages in inflammation:
i) Phagocytosis (cell eating) and pinocytosis (cell drinking).
ii) Macrophages on activation by lymphokines released by T lymphocytes or by non-
immunologic stimuli elaborate a variety of biologically active substances as under:
• a) Proteases like collagenase and elastase which degrade collagen and elastic
tissue.
• b) Plasminogen activator which activates the fibrinolytic system.
• c) Products of complement.
• d) Some coagulation factors (factor V and thromboplastin) which convert
fibrinogen to fibrin.
• e) Chemotactic agents for other leucocytes.
• f) Metabolites of arachidonic acid.
• g) Growth promoting factors for fibroblasts, blood vessels and granulocytes.
• h) Cytokines like interleukin-1 and TNF-α.
• i) Oxygen-derived free radicals.

91. General features of chronic inflammation
Mononuclear cells infiltration-
o The macrophages comprise the most
important cells in chronic inflammation
o Comprise blood monocytes and when it reach
to extravascular space transform into tissue
macrophages.

92. Tissue destruction or necrosis-
o It is central features of most forms of chronic
inflammatory lesion.
o This is brought about by activated
macrophages which release a variety of
biologically active substance.
Eg- protease, elastase, collagenase, lipase,
reactive oxygen radicals, cytokines, nitric oxide
etc.

93. Proliferative changes-
o As a result of necrosis, proliferation of small
vessels and fibroblasts is stimulated resulting
in formation of inflammatory granulation
tissue.
o Healing by fibrosis and collagen laying takes
place.

94. Systemic effects of chronic inflammation
• Fever : infectious form of inflammation
• Anaemia : accompanied by anaemia of varying degree
• Leucocytosis : leucocytosis but generally there is relative
lymphocytosis in these cases.
• ESR : elevated
• Amyloidosis : develop secondary systemic (AA) amyloidosis.

95. Types of chronic inflammation
• Non specific- when irritant substance produces a non-
specific chronic inflammatory reaction with formation
of granulation tissue and healing by fibrosis.
Eg- chronic osteomylitis
chronic ulcer
• Specific- when the injurious agent causes a
characteristic histologic tissue response.
Eg – tb
syphilis
leprosy

96. CONCLUSION
• The primary role of inflammation is protection of the host.
• The vascular and cellular events achieve the ideal outcome of
inflammation, namely resolution, with return to pre-disease
homeostasis.
• A clinician should have through knowledge of the basic
concept of the disease inorder to achieve desired outcome
and health of the patient.

97. REFERENCES
• Robbinson's basic pathology 10 edition
• Harsh Mohan - Textbook of Pathology 6th Edition
• Henry Trowbridge. Inflammation A review of the process; 4th ed.
• Color atlas of pathology
• Marcelo O. Freire, Thomas E. Van Dyke :Natural resolution of
inflammation; Periodontol 2000. 2013 Oct; 63(1): 149–164.
• Flannagan RS, Jaumouillé V, Grinstein S: The cell biology of
phagocytosis, Ann Rev Pathol Mech Dis 7:61–98, 2012.
• Khanapure SP, Garvey DS, Janero DR, et al: Eicosanoids in
inflammation: biosynthesis, pharmacology, and therapeutic frontiers,
Curr Top Med Chem 7:311, 2007.
• Roma Pahwa; Amandeep Goyal; Pankaj Bansal; Ishwarlal Jialal:
Chronic Inflammation, Treasure Island (FL):StatPearls Publishing;
2020.