Inflammation
Dr. Najla Aldaoud, MD
School of Medicine, JUST
Inflammation

The body is exposed to wide range of
causes of injury (trauma, infection,
heat / cold, infarction, radiation,
chemicals).

How does the body protect itself
against injury?
Inflammation


Non-specific mechanisms:
 Mechanical barriers
 skin barrier
 acid in stomach
 mucus and cilia in lungs
 Inflammation
 Phagocytosis
Specific mechanisms:
 specific immune response
 humoral (antibody) mediated
 cell-mediated.
Inflammation



Definition: A dynamic process of
chemical and cytological reactions that
occur in
response of vascularized
living tissue to stimuli that cause cell
injury.
Inflammation results in:
 accumulation
of leukocytes, and
fluid in extravascular tissue.
 systemic effects.
Inflammation is a protective response.
Inflammation

Inflammation is a protective response
that aims to:
 clear the body of the cause of the cell
injury.
 destroy,
dilute or isolate the
injurious agent (microbes, toxins).
 Eliminate the consequences of that
injury of the
 necrotic cells and tissues.
 Paves the way for repair
Participants of Inflammation

Inflammatory
responses
involve
an
interaction of:
 Blood vessels (endothelial cells and
smooth muscles of vessels)
 White blood cells and platelets
 Neutrophils,
monocytes, basophils
lymphocytes, eosinophils.
 Plasma
proteins
and
chemical
mediators:
 Coagulation
/ fibrinolytic system,
kinin system, complement system
Participants of Inflammation
(Cont..)

Inflammatory responses involve also an
interaction of:
 Extracellular matrix and stromal cells
 Mast cells, fibroblasts, macrophages
& lymphocytes
 Structural fibrous proteins, adhesive
glycoproteins, proteoglycans,
basement membrane
Participants of Inflammation
Inflammation

Inflammation and repair may have potentially
harmful outcomes such as digestion of normal
tissues,
swelling,
and
inappropriate
inflammatory response.
 Rheumatoid
arthritis.
 Life threatening hypersensitivity reactions.
 Fibrous scarring after pericarditis.
Inflammation Nomenclature

-itis (- after name
 Appendix
 Dermis
 Gallbladder
 Duodenum
 Meninges
of tissue) e.g.
Appendicitis
Dermatitis
Cholecystitis
Duodenitis
Meningitis, etc
Inflammation

Inflammation is divided into acute and
chronic patterns.
Acute Inflammation




Acute inflammation is a non-specific
immediate and early response to tissue
damage.
It begins within seconds and lasting
hours to several days, or longer if the
cause persists.
It aims to mediate local defences,
destroy any infective agents and remove
debris.
Causes: any cause of cell injury.
Causes of Acute
Inflammation





Infections (bacteria, fungal, viruses,
and parasites).
Physical agents (heat, cold, burns,
radiation, and trauma).
Chemicals
(acids,
alkali,
bacterial
toxins, metals, and caustic substances).
Necrotic tissue (infarction)
All types of immunologic reactions, i.e.,
hypersensitivity (contact with some
substances), autoimmune reactions
Local Signs of Acute
Inflammation
Heat
 Redness
 Swelling
 Pain
 Loss of function

Features of Acute
Inflammation


Vascular changes
Cellular events
 Emigration of leukocytes from microvessels
Acute Inflammation
Vascular Changes




Transient vasoconstriction
Vasodilatation
Slowing of the circulation and stasis
Leukocytic margination
Acute Inflammation
Vascular Changes

Transient vasoconstriction of arterioles
disappears within 3-5 seconds in mild
injuries may last several minutes in more
severe injury (burn).
Acute Inflammation
Vascular Changes

Vasodilatation: 1st involves the arteriole
and it is the cause of heat and redness).
Increased blood volume lead to increased
local hydrostatic pressure leading to
transudation of protein -poor fluid into the
extravascular space.
Acute Inflammation
Vascular Changes
 Slowing
of
the circulation due to
increased
permeability
of
the
microvasculature,
this
leads
to
outpouring of protein-rich fluid in the
extravascular tissues.
 This results in concentration of the red
cells in small vessels and increased
viscosity of the blood (stasis: dilated
small vessels packed with red cells).
Acute Inflammation
Vascular Changes
 Persistence
of stasis leads to peripheral
orientation
of
leukocytes
(mainly
neutrophils)
along
the
vascular
endothelium [leukocytic margination].
leukocytes 1st stick transiently then
more strongly, then they migrate
through the vascular wall into the
interstitial tissue [emigration].
Features of acute
inflammation

Components of exudate
 Fluid.
 Fibrin (insoluble): derived from the plasma
protein fibrinogen (soluble), also important in
clotting
 Cells: neutrophils predominate (6-72 hours), also
macrophages (involved slightly later: 48+ hours)

Exudate arises in inflammation due to increased
vascular permeability and has a high protein
content.
Transudate results from hydrostatic imbalances
between vessel and extravascular tissues, vascular
permeability is normal, has a low protein content.)

Features of Acute
Inflammation
Features of acute
inflammation
Acute Inflammation
Leukocyte Cellular Events

Margination, rolling and adhesion

Transmigration between endothelial cells

Migration in the interstitium toward the
site
of
stimulus
(chemotaxis
activation)


Phagocytosis and degranulation
Release of leukocyte products
and
Neutrophil Margination
Neutrophil Margination
Effects of Chemotactic
Factors on Endothelial Cells
Effects of Chemotactic
Factors on Leukocytes
Diapedesis
Leukocyte Cellular Events
The Process of Extravasation
of Leukocytes

Selectins
and
their
carbohydrate
counterligands
mediate
leukocyte
binding and rolling.

Leukocyte integrins and their ligands
mediate firm adhesion.
The Process of Extravasation
of Leukocytes (Cont..)

Chemokines play a role in firm
adhesion by activating integrins on
the leukocyte cell surface.

The leukocytes are directed by
chemoattractant gradients to migrate
across the endothelium, and through
the extracellular matrix into the
tissue.
The Process of Extravasation
of Leukocytes
Lobar Pneumonia
Chemotaxis


Migration of cells along a chemical gradient
Chemotactic factors:
 Soluble bacteial products, e.g. N-formylmethionine termini
 Complement system products, e.g. C5a
 Lipooxygenase pathway of arachidonic
acid metabolism, e.g. LTB4
 Cytokines, e.g. IL-8
Effects of Chemotactic
Factors on Leukocytes




Stimulate locomotion
Degranulation of lysosomal enzymes
Production of AA metabolites
Modulation of the numbers and affinity
of leukocyte adhesion molecules
Effects of Chemotactic
Factors on Endothelial Cells
Effects of Chemotactic
Factors on Leukocytes
Generation of AA Metabolites
Phagocytosis

The process of ingestion and digestion by
cells of solid substances, e.g., other cells,
bacteria, necrotic tissue or foreign
material.

Steps of phagocytosis:
 Recognition,
attachment and binding to
cellular receptors.
 Engulfment
 Fusion of phagocytic vacuoles with lysosomes
 Killing or degradation or ingested material
Phagocytosis
How Do Leukocytes Kill
Infectious Agents





Oxygen burst products (free radical)
Lysosomal enzymes
Bactericidal permeability increasing
protein
Major basic protein
Defensins
General principles for chemical
mediators



Mediators derive from plasma or by local
production from cells.
Most mediators perform their activity by
initially binding to specific receptors on
target cells. However, some have direct
enzymatic or toxic activities.
Mediators may stimulate target cells to
release secondary effector molecules,
which
may
have
activities
similar
(amplifying)
or
opposing
(counterregulating) the initial stimulus.
Slide 3.23
Slide 3.30
Outcomes of Acute
Inflammation
 Complete
resolution
 Healing by scarring or fibrosis
 Abscess formation
 Progression to chronic inflammation
Outcomes of Acute
Inflammation

Complete resolution
 Occurs
when the injury is limited or
short-lived and when the tissue is
capable of regeneration
Outcomes of Acute
Inflammation (Cont..)

Scarring or fibrosis
 Occurs
when
 there
is
destruction.
substantial
tissue
 when
the inflammation occurs in
tissue not capable of regeneration.
 there
is extensive fibrinous exudate
that cannot completely absorbed.
Outcomes of Acute
Inflammation (Cont..)

Abscess formation: may occur in the
setting of certain bacterial or fungal
infection (pyogenic or “pus forming”)

Progression to chronic inflammation
Morphologic Appearance
of Acute Inflammation



Catarrhal
 Acute inflammation + mucous
hypersecretion (e.g. common cold)
Serous
 Abundant protein-poor fluid with low
cellular content, e.g. skin blisters and body
cavities
Fibrinous:
 Accumulation of thick exudate rich in fibrin,
may resolve by fibrinolysis or organize into
thick fibrous tissue (e.g. pericarditis)
Burn Blister
Fibrinous Pericarditis
Morphologic Appearance of
Acute Inflammation (Cont..)


Suppurative (purulent):
 Pus: Creamy yellow or blood stained fluid
consisting of neutrophils, microorganisms
& tissue debris e.g. acute appendicitis
 Abscess: Focal localized collection of pus
 Empyema: Collection of pus within a
hollow organ
Ulcers:
 Defect of the surface lining of an organ or
tissue, mostly GI tract or skin
Subcutaneous Abscess
Lung Abscess
Foot Ulcer
Chronic inflammation
Chronic inflammation



Chronic inflammation is a process in
which ongoing inflammation and tissue
damage proceed at the same time as
attempts at healing, seen as scarring.
It aims to eradicate and/or contain the
harmful agent and heal areas of tissue
damage.
It last longer duration and can persist,
sometimes
for
years,
until
the
damaging stimulus is eradicated.
Chronic inflammation



Chronic inflammation may follow acute
inflammation because of persistence of
the injurious agent or interference with
the normal process of healing.
Changes are superimposed upon and/or
replace those of acute inflammation
several days after onset.
In some cases it has an insidious onset:
 infections
(TB)
 autoimmune disease (rheumatoid arthritis)
 repeated or prolonged exposure to toxic
(asbestos).
Chronic inflammation
• Is characterized histologically by:
•Infiltration with mononuclear (“chronic
inflammatory”) cells including
macrophages, lymphocytes, and plasma
cells
•Tissue destruction (induced mainly by
inflammatory cells)
•Repair involving new vessel formation
(angiogenesis) and fibrosis.
Causes of Chronic
Inflammation

Follow acute inflammation
 Persistence of injurious agent
 Interference in the normal process of
healing
Causes of Chronic
Inflammation (Cont..)

Begin insidiously as a slow response to
various agents:
 Microorganisms
that are intracellular
(viruses)
or
are
of
low
direct
pathogenicity, but evoke a delayed
immune
response
(mycobacteriatubercle bacillis)
 Prolonged exposure to potentially toxic
agents. E.g., (silicosis)
 Autoimmune diseases: immune response
to self antigens and tissues (which are
constantly renewed) e.g., rheumatoid
arthritis.
Cell Types in Chronic
Inflammation
 Macrophages
 Plasma
cells
 Eosinophils
 Lymphocytes
Chronic Inflammation
Cell types

Plasma cells:
Are the terminally differentiated B-cell lymophocytes.
Produce antibodies directed against antigens in the
inflammatory site

Lymphocytes:
 antibodies and cell mediated immunologic reactions
 non-immune-inflammation
 reciprocal relationship to macrophages
Chronic Inflammation
Cell types





Eosinophils:
immunologic reactions mediated by IgE
(allergy)
Seen in parasitic infections
respond to chemotactic agents derived
largely from mast cells
contain major basic protein: toxic to
parasites and lead to lysis of mammalian
epithelial cells
Chronic Granulomatous
Inflammation
 Granulomatous
inflammation is a specific
type/pattern
of
chronic
inflammation
characterised by the presence of activated
macrophages
that
either
become
‘epithelioid’ in appearance or become giant
multinucleate cells.
 Tuberculosis,
leprosy, schistosomiasis,
sarcoidosis, Crohn’s disease, reactions to
foreign material (e.g. suture),
Chronic Granulomatous
Inflammation
 Characterized
by formation of granulomas:
0.5 - 2 mm.
 Nodules composed of :
 Modified macrophages (epithelioid cells)
 Langhan’s or foreign body giant cells
 Fibroblasts, plasma cells, lymphocytes,
neutrophils
 Necrosis
is
present
(necrotizing
granulomatous
inflammation)
with
certain causes e.g TB, but not in
sarcoidosis for example. The patterns of
granulomatous
inflammation
vary
depending on the cause
Role of lymphatic & Lymph
Nodes in Inflammation
 Represents
a second line of defense
 Delivers antigens and lymphocytes to the
central lymph nodes
 Lymph flow is increased in inflammation
 May become involved by secondary
inflammation (lymphangitis, reactive
lymphadenitis)
Systemic effects of
inflammation


Fever, chills
acute phase reactions:
 increased slow wave sleep
 decreased appetite
 increased degradation of protein
 hypotension and other hemodynamic
changes
 synthesis of acute phase proteins by the
liver:
 C-reactive proteins and serum amyloid A
 complement and coagulation proteins
Systemic effects of
inflammation (cont.)
 leukocytosis
(neutrophilia, lymphocytosis,
eosinophilia)
 leukopenia (typhoid fever, viruses,
rickettsia, &certain protozoa)
 Role of IL-1, and TNF