Acute and Chronic

Inflammation
By Dr C A Okolo MBBS, FMCPath
Dept of Pathology, College of
Medicine
University of Ibadan
Inflammation
 This is the response of living vascularised tissue to
injury.
 Inflammation is fundamentally a protective
response, the ultimate goal of which is to rid the
body of both the initial cause of cell injury and the
consequences of such injury
 The inflammatory process is closely intertwined with
the process of repair
 Acute inflammation is of relatively short duration,
lasting from minutes to a few days & its main
characteristics are the exudation of fluid and plasma
proteins and the migration of leukocytes
Historical Highlights
 Signs of inflammation were 1st described in
an Egyptian papyrus in 300BC
 Cardinal signs of inflammation
 Rubor – Redness
 Tumor – Swelling
 Calor – Heat
 Dolor – Pain
 Elie Metchnikoff (Russian) discovered
“phagocytosis” in 1882
Acute Inflammation
 This is the immediate or early response of of living
vascularised tissues to an injurious agent.
 It has three major components
(3) Alteration in vascular caliber that leads to an
increase in blood flow.
(4) Structural changes in the microvasculature that
permits the plasma proteins and leukocytes to
leave the circulation.
(5) Emigration of the leukocytes from the
microcirculation & their accumulation at the focus
of injury
Events in Acute Inflammation
 Vascular events
 Cellular events

 Chemical mediators of inflammation

Vascular events
 Changes in vascular flow and caliber.
 Transient vasoconstriction (inconstant)

 Vasodilation

 Stasis

 Increased vascular permeability

Stasis
 Peripheralorientation of leukocytes
 Leukocyte margination

 Rolling

 pavementing
Increased vascular
permeability
 Mainly at the arterioles, capillaries and
venules
 Endothelial contraction

 Cytoskeletal reorganisation

 Direct injury

 Leukocyte-dependent injury

 Increased transcytosis

 Angiogenesis with leaky blood vessels

Cellular events
 Leukocyte extravasation
(2) In the lumen – margination, rolling and
adhesion
(3) Transmigration across the endothelium
(diapedisis)
(4) Migration in the interstitial tissues towards
the chemotactic stimulus
Adhesion and transmigration
 P-selectins – rolling
 E-selectins- rolling adhesion to activated
endothelium
 ICAM-1 - Adhesion, arrest, tranmigration

 VCAM-1 – adhesion

 GlyCam -1 - Homing
Chemotaxis
 This is the movt of leukocytes towards the
site of injury propelled by a chemical gradient
 Chemoattractants – C5a, B4 Cytokins eg IL-
8, Bacterial products
Leukocyte Activation
 Production of arachidonic acid metabolites
from phospholipids
 Degranulation and secretion of lysosomal
enzymes and activation of the oxidative burst
 Modulation of leukocyte adhesion molecules
Phagocytosis
 Recognition and attachment – opsonins –
C3b, IgG Fc fragment
 Engulfment

 Killing or degradation
Chemical mediators of
inflammation
 Mediators from plasma
 Mediators from cells
 Most mediators perform by initially binding to
specific receptors on target cells
 A chemical mediator can stimulate the
release of mediators by target cells
themselves
 Mediators can act on one or few target cell
types and have wide spread effect.
Preformed mediators
 Histamine

 Serotonin

 Lysosomal enzymes
 They are produced by mast cells, platelets
and neutrophils and macrophages
Newly synthesised
 Prostaglandins

 Leukotrienes

 Platelet activation factor

 Activated O2 species

 Nitric Oxide

 Cytokins

 Produced by all leukocyte

Complement factors
 C3a-- Anaphylatoxins
 C5a-- ‘’

 C3b

 C5b-9
Clotting factors
 Factor XII Hageman factor
Outcome of Acute
Inflammation
 Resolution

 Healingby fibrosis
 Abscess formation

 Progression to chronic inflammation

Chronic Inflammation
 This is inflammation of prolonged duration in
which active inflammation, tissue destruction,
and attempt at repair are proceeding
simultaneously.
 It frequently begins insidiously as a low-
grade, smoldering, often asymptomatic
response
 It is responsible for most common and
disabling human diseases such as
rheumatoid arthritis, tuberculosis etc
Chronic inflammation arises
under the following setting
 Persistent infection by certain
microorganisms e.g. TB , Treponema
pallidum, fungi
 Prolonged exposure to potentially toxic
agents either exogenous or endogenous e.g.
silica –silicosis, toxic plasma lipid
components – atherosclerosis
 Autoimmunity – immune reactions are set up
against the individuals own tissues
Histologic features
 Infiltration
by mononuclear cells which
include macrophages, lymphocytes,
eosinophils, mast cells and plasma cells –
reflecting persistent reaction to injury
 Tissue destruction induced by inflammatory
cells
 Attempt at healing by connective tissue
replacement of damaged tissue
Macrophages
 These are the most important cells in chronic
inflammation.
 Derived from blood monocytes, they home to
different tissues as tissue macrophages
 Lung – alveolar macrophages
 Liver – kupffer cells
 Spleen – sinus histiocytes
 Bone – osteoclasts
 They undergo phagocytosis and are capable of
activation into cell with larger cytoplasm, increased
level of lysosomal enzyme production, greater ability
to phagocytose & kill ingested microbes
 They secrete a wide variety of biologically
active products, e.g. enzymes, complement
components, coagulation factors, reactive O2
species cytokines, growth factors, nitric oxide
 Induce continued recruitment of monocytes
from circulation
 Local proliferation of macrophages

 Immobilization of macrophages
Lymphocytes
 Mobilized in both antibody mediated and cell
mediated immune responses and also in non
immune mediated chronic inflammation.
 Various types of lymphocytes T & B
 Lymphocytes can be activated on contact
with antigen to produce lymphokines
 Plasma cells produce antibodies directed at
persistent antigen at the inflammatory site or
against altered tissue components
Other cell types
 Mast cells are widely distributed in connective
tissue and participate in both acute and
chronic inflammation eg asthma, parasitic
infections
 Eosinophils are also characteristic of immune
reactions mediated by IgE and parasitic
infections
Chronic non-specific
inflammation of the cervix
Granulomatous inflammation
 This is a special type of chronic inflammation
in which the predominant cell type is an
activated macrophage with modified
epithelial-like appearance (epithelioid).
 A granuloma is a focal area of inflammation
consisting of aggregation of macrophages
that are transformed into epithelioid cells
surrounded by a rim of lymphocytes and
sometimes plasma cells.
Types of granulomas
 Foreign body granulomas – these are incited
by relatively inert foreign bodies eg talc,
suture or other fiber. Foreign body giant cells
are typically formed.
 Immune granulomas – caused by insoluble
particles that are capable of inducing a cell
mediated immune response
Examples of granulomas
 Tuberculosis- Caseating
 Leprosy
 Syphilis
 Cat-scratch disease
 Schistosomiasis
 Fungal granulomas
 Foreign body granulomas
 Lymphogranuloma venereum – chlamydia spp
Lung
Granulomatous
inflammation
Histology of a granuloma-
langhans giant cells
Epithelioid cells in a
granuloma
Caseous granuloma in TB
Foreign body type giant cell
(suture material)