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INFLAMMATION

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 Objectives
At the end of this session students will:-
– Define inflammation
– Mention causes of inflammation
– List types of inflammation
– List outcomes of inflammation

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 OVERVIEW OF INFLAMMATION

 Inflammation is a local response (reaction) of living

vascularized tissues to injurious stimuli
 It is a physiologic (protective) response intended to
localize and eliminate the causative agent and to limit
tissue injury.
 It accomplish the protective mission by:
– diluting,
– destroying, or
– neutralizing harmful agents (e.g., microbes or
toxins)
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 Role players in inflammation

1. Circulating cells : WBCs and platelets

2. Circulating proteins: Clotting factors, kininogens…
3. Vascular wall cells: Endothelial and smooth muscle cells
4. Connective tissue cells: Mast cells, macrophages, and
lymphocytes
5. Extracellular matrix (ECM): Collagen and elastin

– All this interact to resolve a local injury and

restore normal tissue function

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 Inflammation is divided into two basic patterns:

1.Acute inflammation
– It is of relatively short duration, lasting from a few minutes up to a
few days,
 characterized by
-- Exudation of fluid and plasma protein, and
-- a predominant neutrophilic accumulation
2.Chronic inflammation
– It is of longer duration (days to years)
 characterized by
– associated with vascular proliferation (angiogenesis)
and scarring
– influx of lymphocytes and macrophages
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 ACUTE INFLAMMATION

 Acute inflammation is the immediate and

early response to injury designed to
deliver leukocytes to sites of injury which
clear invading microbes and break down
necrotic tissues

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 Stimuli for Acute Inflammation
 Infections (bacterial, viral, fungal, parasitic)
 Trauma (blunt and penetrating)
 Chemical agents
 Necrosis (from any cause)
 Foreign bodies (splinters, dirt, sutures)
 Immune reactions (hypersensitivity reactions)
against environmental substances or against
self tissues.

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 The 5 classic (cardinal)local signs of acute inflammation:

1. Heat (calor):- due to increased blood flow (hyperemia)

from vasodilatation
2. Redness (rubor): due to dilation of small blood vessels
within damaged tissue
3. Swelling (tumor): due to increased permeability of venules
4. Pain (dolor) resulted from:
-- Stretching & tissue destruction from inflam. edema
-- From pus under pressure in as abscess cavity
-- Bradykinins, prostaglandins and serotonin induced
pain
5. Loss of function (functio laesa): due to the pain and
swelling
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 The two main components of acute inflamn are:-
1. Vascular changes: vasodilatation resulting in
increased blood flow and increased vascular
permeability that permit plasma proteins to leave
the circulation
2. Cellular events: Emigration of the leukocytes
from the microcirculation and accumulation in the
focus of injury (cellular recruitment and
activation)

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 Cellular Events
 The sequence of events in the extravasation of
leukocytes from the vascular lumen to the
extravascular space is divided into
1. Margination and rolling,
2. Adhesion and transmigration between endothelial
cells,
3. Migration in interstitial tissues toward a chemotactic
stimulus

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 Cellular event…
 leukocyte recruitment at an inflammatory site
involve:
1. Endothelial activation, increasing the expression
of selectins and selectin ligands;
2. Leukocyte rolling, facilitated by relatively loose
selectin binding to carbohydrate ligands;
3. Firm adhesion, facilitated by chemokine-induced
changes in integrin affinity for endothelial
ligands; and
4. Transmigration between endothelial cells

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 The type of recruited leukocyte depends on the nature
.
of the inciting stimulus as well as the age of the
inflammatory site
 In most forms of acute inflammation, neutrophils
predominate for the first 6 to 24 hours and are
replaced by monocytes in the subsequent 24 to 48
hours
 Neutrophils are rather short-lived, undergoing
apoptosis within 24 to 48 hours after exiting
the bloodstream,
 While monocytes survive substantially longer
and may persist for long periods
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 Chemotaxis and Activation
Chemotaxis is a unidirectional attraction of leukocytes from
vascular channels towards site of inflammation within
tissue space

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 Phagocytosis and Degranulation.
 Phagocytosis and the elaboration of degradative enzymes
are two major benefits of having recruited leukocytes at the
site of inflammation
 Phagocytosis consists of three distinct but interrelated
steps
1. Recognition and attachment of the particle to the ingesting
leukocyte
2. Engulfment, with subsequent formation of a phagocytic
vacuole; and
3. killing and degradation of the ingested material

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 Chemical Mediators
 Substances that direct the vascular and cellular events in acute
inflammation are:-
 Exogenous
– Endotoxins
 Endogenous
–Plasma
–Leukocytes
–Endothelial cells
–Fibroblasts

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Characteristics of chemical mediators
– They may circulate in the plasma or produced locally
by cells at site of inflammation
– Need “triggering” stimuli for synthesis, secretion and
activation
– They are short lived with tightly regulated function
because they have the potential to cause harmful effect
– induce their effects by binding to specific receptors on
target cells(usually) or by direct enzymatic and/or
toxic activities
– Their outcomes depending on which cell type they
affect

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 Major Effects of Chemical mediators
Vasodilation
– Prostaglandins
– Nitric oxide
Increased Vascular Permeability
– Vasoactive amines (histamine, serotonin)
– C3a and C5a (by inducing release of vasoactive amines)
– Bradykinin
– Leukotrienes C4, D4, E4
Fever
– IL-1, IL-6, tumor necrosis factor
– Prostaglandins

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Chemotaxis, Leukocyte Activation
– C5a
– Leukotriene B4
– Bacterial products
– Chemokines (e.g., interleukin 8 [IL-8])
Pain
– Prostaglandins
– Bradykinin
Tissue Damage
– Neutrophil and macrophage lysosomal enzymes
– Oxygen metabolites
– Nitric oxide

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 Outcomes of Acute Inflammation
 The consequences of acute inflammation depend on
– the nature and intensity of the injury,
– the site and tissue affected, and
– the ability of the host to mount a response
 Acute inflammation generally has one of three
outcomes :
1. Resolution
2. Scaring or fibrosis
3. Abscess formation
4. Progression to chronic inflammation
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 1.Resolution
1.Resolution: is restoration to histologic and functional normalcy
• Made possible by :
– neutralization or removal of the chemical mediators
– normalization of vascular permeability, and
– cessation of leukocyte emigration with subsequent death
(by apoptosis) of extravasated neutrophils.
– the combined efforts of lymphatic drainage and
macrophage ingestion of necrotic debris

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 2.Scarring or fibrosis
Resulted if :
– substantial tissue destruction
– when inflammation occurs in tissues that do not regenerate
or
– extensive fibrinous exudates organized by in growth of
connective tissue (fibrosis)

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 3.Abscess formation
Resulted if
– extensive neutrophilic infiltration ,or
– Infection by Pyogenic microbes
 Since there is extensive underlying tissue destruction the only
outcome of abscess formation is scarring

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 4.Progression to chronic inflammation
 Depending on the extent of the initial and
ongoing tissue injury, the capacity of the
affected tissues to regrow,
 chronic inflammation may be followed by
regeneration of normal structure and function
(regeneration) or may lead to scarring.

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 CHRONIC INFLAMMATION

 Inflammation of prolonged duration in which

active inflammation, tissue injury, and healing
proceed simultaneously
 Characterized by :
– Infiltration with mononuclear cells,
– Tissue destruction, largely directed by the
inflammatory cells
– Repair, involving angiogenesis and fibrosis

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 Causes of Chronic inflammation:
1. Viral infections.
2. Persistent microbial infections
e.g. less pathogenic microbes like Mtb ,T.pallidum ,and certain
fungi.
3. Prolonged exposure to potentially toxic agents
e.g. silicosis, atherosclerosis
4. Autoimmune diseases
e.g., rheumatoid arthritis or multiple sclerosis

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 Chronic Inflammatory Cells and Mediators
1. Macrophages
 They are the primary cells in chronic inflammation
 They are tissue cells derived from circulating blood monocytes
after their emigration from the blood
 E.g.Kupffer cells, sinus histiocytes, microglial cells, and
alveolar macrophages
 Functions
– phagocyzed foreign matter, microbes, and senescent cell
– Assist and activate lymphocytes

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 2. Lymphocytes
 Mobilized in the setting of any specific immune stimulus
(i.e., infections) as well as in non-immune-mediated
inflammation
 T lymphocytes have a reciprocal relationship to
macrophages in chronic inflammation ; they are initially
activated by interaction with macrophages presenting
"processed" antigen fragments on their cell surface
 Plasma cells are the terminally differentiated end product
of B-cell activation; they can produce antibodies directed
against antigens in the inflammatory site or against
altered tissue components.
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 3.Eosinophils
 Are characteristically found in inflammatory sites around
parasitic infections or as part of immune reactions mediated
by IgE, typically associated with allergies
 Eosinophil-specific granules contain major basic protein
(MBP), a highly charged cationic protein that is toxic to
parasites but also causes epithelial cell lysis.

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 MORPHOLOGIC PATTERNS OF ACUTE AND
CHRONIC INFLAMMATION
 The basic morphologic patterns of acute
and chronic inflammation depend on
– The severity of the inflammatory
response,
– Its specific cause, and
– The particular tissue involved

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 SEROUS INFLAMMATION
 This is characterized by the outpouring of
a watery, relatively protein-poor fluid
(effusion)
 Sources of serous fluid
– Serum, Eg. skin blisters, or
– Mesothelial cells, Eg. Pleural Effusions

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 FIBRINOUS INFLAMMATION
 Occurs as a consequence of more
severe injuries, with a resultant
greater vascular permeability
allowing larger molecules
(specifically, fibrinogen)
 Fibrin appears as an eosinophilic
meshwork of threads histologically
 Fate of the Fibrinous exudates are :
1 Fibrin  degraded by fibrinolysis 
degradation products removed by
macrophages  resolution, or
2. failure to completely remove the
fibrin  ingrowth of fibroblasts and
blood vessels  scarring
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 SUPPURATIVE (PURULENT) INFLAMMATION

 Manifested by the presence of

large amounts of purulent exudate
(pus) consisting of neutrophils,
necrotic cells, and edema fluid.
 Abscesses are focal collections of
pus that may be caused by deep
seeding of pyogenic organisms
into a tissue or by secondary
infections of necrotic foci.
 Sometimes abscess may become
completely walled off and
eventually replaced by connective
tissue
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 ULCERATION
 This refers to a site of inflammation where an
epithelial surface (skin, gastric epithelium, colonic
mucosa, bladder epithelium) has become necrotic and
eroded, often with associated sub epithelial acute and
chronic inflammation
 Causes
 Injury to the epithelial surface
• e.g. Peptic ulcers
– Vascular compromise
• eg. Diabetic foot ulcers

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 SYSTEMIC EFFECTS OF INFLAMMATION

 The systemic effects of inflammation, collectively

called acute-phase reaction.
 Fever is only one of the more obvious of these
systemic effects of inflammation;
 others include increased somnolence, malaise,
anorexia, accelerated degradation of skeletal muscle
proteins, hypotension, hepatic synthesis of a variety
of proteins
– (e.g., complement and coagulation proteins), and
alterations in the circulating white blood cell
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 Leukocytosis
Leukocytosis (increased white blood cell count)
 common feature of inflammatory reactions
 The leukocyte count increases to 15- 20,000 per μL
(normal = 4000 to 10,000 cells per μL)
 It is resulted from, IL-1 and TNF induced increase in :-
– release of immature cells ("left-shift")
 Selective increase in leuckocytes and their causes:
– Neutrophilia: cause bacterial infections
– Eosinophilia : parasitic infections, allergic responses
– Lymphocytosis : viral infections ,such as IM,
mumps, and rubella 39
 Leukopenia
 Leukopenia - a decreased number of circulating white cells
 Causes :
– most viral infections,
– Rickettsial infections
– protozoal, and
– certain bacterial infections (typhoid fever)

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THANK YOU!

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