ORENBURG STATE MEDICAL UNIVERSITY

Department of pathophysiology

THEME: INFLAMMATION

Lecturer: associate professor

Sarycheva Yuliya Aleksandrovna
 INFLAMMATION is a typical
pathological process characterized by
alteration, exudation and proliferation.

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 tissues.
 Inflammation
is a protective response by the body to variety of
etiologic agents (infectious or non-infectious), while
infection is invasion into the body by harmful
microbes and their
resultant ill-effects by toxins.

Inflammation involves 2 basic steps:

early inflammatory response and later followed by
healing.
 ETIOLOGY OF AN INFLAMMATION

-physical factors (strong pressure on a tissue, high

and low temperature, ionizing and ultra-violet rays,
high and low barometric pressure);
-chemical factors (acids, organic and inorganic
poisons, salts of heavy metals);
-biological factors (microorganisms – bacteria,
viruses);
-immunological agents (cell-mediated and antigen-
antibody reactions);
-inert materials (foreign bodies)
 LOCAL SIGNS OF INFLAMMATION

Local
hyper-
thermia
-Swelling is the result of increased vascular
permeability).

-Redness is the result of local arterial hyperemia.

-Heat (the local rise of temperature) is the result of

arterial hyperemia and intensive metabolism in the
focus of inflammation.

- Pain is the result of the irritation of painful receptors

by biological active substances, metabolites, and
pressing.

-The loss of the function is the result of the functional

active tissue injury
1. Fever occurs due to action of primary pyrogens (microbes,
products of tissue distruction).
It is thought to be mediated through release of factors like
prostaglandins, interleukin-1 and TNF-a (secondary
pyrogens)in response to infection.

2. Leuкocytosis commonly accompanies the inflammatory

reactions. Usually, in bacterial infections there is neutrophilia;
in viral infections lymphocytosis; and in parasitic infestations,
eosinophilia. Sometimes leukemoid reaction can occur
3. Lymphangitis-lymphadenitis is one of 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.

This response represents either a nonspecific reaction to

mediators released from inflamed tissue or is an immunologic
response to a foreign antigen. The affected lymph nodes may
show hyperplasia of lymphoid follicles (follicular hyperplasia)
and proliferation of mononuclear phagocytic cells in the
sinuses of lymph node (sinus histiocytosis)
4. Shock may occur in severe cases. Massive release of
cytokine TNF-a, a mediator of inflammation, in response to
severe tissue injury or infection results in profuse systemic
vasodilatation, increased vascular permeability and
intravascular volume loss.
The net effect of these changes is hypotension and shock.
Systemic activation of coagulation pathway may occur
leading to microthrombi throughout the body and result in
disseminated intravascular coagulation (DIC), bleeding and
death.
 CLASSIFICATION OF AN INFLAMMATION

 Depending on clinical course, there are two types of

inflammation: acute and chronic.
1. Acute inflammation is characterized by a short duration
(from minutes to few weeks), exudation of fluid and
plasma proteins and emigration of leukocytes,
predominantly neutrophils. (Sometimes, the acute
inflammation may be quite severe and is termed as
fulminant inflammation)
2. Chronic inflammation is manifested by prolonged
duration, accumulation of cells, predominantly
macrophages and their derivates, lymphocytes, fibroblasts
and sclerosis.
The term «subacute inflammation» is used for the state of
inflammation between acute and chronic
  There are normoergic, hyperergic and hypoergic
inflammation.

 The normoergic inflammation is characterized by the

adequate reaction of the body, as the response to the
invasion of the pathological agent.

 The hyperergic inflammation is characterized by a very

strong reaction of the body even on an insignificant
influence of the pathological agent.

 The hypoergic inflammation is characterized by

insignificant changes in the body.
 CLASSIFICATION ACCORDING TO
STAGES OF INFLAMMATION
 Thealterative inflammation is characterized by
hard damage of tissues (dystrophy, necrosis).

 The exudative inflammation is characterized by

increased vascular permeability and formation of
exudate.

 Theproliferative inflammation has a reparative

character.
 IN PATHOLOGICAL PHYSIOLOGY
THERE ARE
4 STAGES OF INFLAMMATION

1.Alteration (primary and secondary).

2. Exudation.

3. Emigration of the formed blood elements.

4. Proliferation
 1.ALTERATION (PRIMARY AND
SECONDARY)
Primary alteration is caused by the action of initial stimuli.

Secondary alteration is the result of changes in the focus of

inflammation after primary alteration. These conditions
include:
- oxygen deficiency
-metabolic acidosis
-high osmotic pressure
-ionic imbalance
-toxic effect of cellular enzymes
-the action of inflammatory mediators
 2. EXUDATION
Phases of vascular changes:

-Vasoconstriction (ischemia)
-Arterial hyperemia
-Venous hyperemia
-Stasis Exudation
 VASOCONSTRICTION (ISCHEMIA)

 Catecholamines and other

mediators stimulate the
contraction of smooth
muscles of vascular wall
(mainly, arterioles).
 The duration of first stage is short.
- easy injury (3-5 sec.)
-severe injury (5 min.)
 ARTERIAL HYPEREMIA
Arterial hyperemia is an increase of blood flow into
organ or tissue due to the increased inflow of arterial
blood by dilation of arterioles and capillaries
Arterial hyperemia is caused by inflammatory mediators
such as histamine, some complement fragments,
bradykinin, NO, prostaglandins.
Symptoms:
- redness (rubor) of the skin
- warmth (increase of local body temperature)
- increased metabolism in the inflammatory focus
the volumetric flow rate, (also known as volume flow rate,
rate of fluid flow or volume velocity) is the volume of fluid
which passes per unit time through a cross section of the
vessel; usually represented by the symbol Q.
 Δ P- difference in the hydrostatic pressure between the
arterioles and venules
 R- Peripheral resistance in vessels
The linear velocity of blood flow (V) is
the distance traveled by a particle of
blood per unit time.
Q- the volumetric flow rate
S- cross-section of the
vessel
 VENOUS HYPEREMIA
The mechanism of venous hyperemia and stasis is
complex. Inflammatory mediators increase
permeability of venules and capillaries for plasma
proteins.
Plasma proteins leak into interstitial space causing
fluid retention.
It results in the chain of events: increasing in blood
viscosity, reduction of the local blood flow,
microthrombosis and adhesion of leukocytes to the
vessel wall
Symptoms of venous hyperemia:

-dark red color of skin

-increased tissue or organ volume
-lowering of local temperature
-slowing of blood flow
-edema
STASIS
 Exudation is a output of protein-
containing liquid portion of the blood in
the inflamed tissue
 Inflammatory mediators and other factors
involved in the increase of vascular permeability

- histamine, bradykinin, leukotrienes cause endothelial

cell contraction in venules that leads to formation of
endothelial gaps
- direct endothelial injury may result from action of
toxic oxygen species and proteolytic enzymes
derived from leukocytes, bacterial toxins, some
components of complement, antibodies and antigen-
antibody complexes.
 TYPES OF EXUDATE
 The serous exudate is a clear serum-like fluid containing
small amounts of protein.
 The fibrinous exudate contains a plenty of fibrinogen, which
forms clots of fibrin in tissues. Such inflammation occurs when
an organism is affected by corinebacterium diphtheriae,
pneumococcus, mycobacterium of tuberculosis.
 The causes of purulent inflammation are staphylococcus,
streptococcus, gonococcus, meningococcus. Purulent exudate
consists of many viable leukocytes and purulent
bodies (perishing leukocytes), cells detritus, microorganisms,
plenty of proteins (especially globulines).
 The hemorrhagic exudate contains the red blood cells
released from ruptured vessels.
 Catarrhal exudate is characterized by a high content of
mucus.
 3. EMIGRATION OF THE FORMED BLOOD
ELEMENTS

Stages:
1) The adhesion of leukocytes to vascular endothelium
2) Leukocyte locomotor phenotype ( ability of
leukocytes to locomotion)
3) Leukocyte diapedesis
4) Leukocyte chemotaxis
5) Formation of the infiltrate
 THE ADHESION OF LEUKOCYTES TO
VASCULAR ENDOTHELIUM

 The adhesion receptors involved belong to four

molecular families:
-the selectins
-the integrins,
-the immunoglobulin superfamily,
-mucin-like glycoproteins.
 Leukocyte rolling is a process of transient adhesion and
movement of leukocytes along the endothelial surface (loose
adhesion).
Rolling is mediated through a redistribution of P- selectins to the
endothelial cell surface and synthesis of E-selectins de novo.
Selectins bind mucin-like glycoproteins located on the surface of
leukocytes.
Histamine, thrombin and platelet-activating factor induce a
redistribution of P-selectin while interleukine-1 and tumor
necrosis factor stimulate of E-selectin.
Firm adhesion is mediated via binding integrin molecules that
are located on the leukocyte surface with intercellular adhesion
molecule 1 (ICAM-1) located on the endothelial surface.
Interleukine-8 and other cytokines increase the affinity of integrin
molecules to ICAM-1
LEUKOCYTE LOCOMOTOR PHENOTYPE (
ABILITY OF LEUKOCYTES TO
LOCOMOTION)
 After firm adhesion, leukocytes insert pseudopods
into the junctions between the endothelial cells,
squeeze through endothelial junctions, and assume
position between the endothelial cells and the
basement membrane.
 LEUKOCYTE DIAPEDESIS
 The next step in the process is migration of the leukocytes
through the endothelium, called transmigration or
diapedesis.
Chemokines act on the adherent leukocytes and stimulate the
cells to migrate through interendothelial spaces toward the
chemical concentration gradient, that is, toward the site of
injury or infection.
 LEUKOCYTE CHEMOTAXIS

After diapedesis , leukocytes emigrate in tissues toward the site

of injury by a process called chemotaxis.
The following agents act as potent chemotactic substances or
chemokines:

- Leukotriene B4 (LT-B4), a product of lipoxygenase pathway of

arachidonic acid metabolites
-Components of complement system (C5a, C3a)
-Cytokines (interleukins, in particular IL-4)
-Soluble bacterial products
 SIGNIFICANCE OF LEUKOCYTE
EXTRAVASATION IN THE FOCUS OF
INFLAMMATION

1)Taking up and destruction of inflammatory agents

2) Taking up and destruction of injured cells and extracellular
structures
3) Synthesis and release of mediators which regulate the
course of inflammation
4) Presentation of antigens to T-lymphocytes (development of
immune or allergic reactions)
 FORMATION OF THE INFILTRATE

 Early infiltrate (neutrophils)- cleaning of inflammatory focus

from microbes and tissue fragments

 Late infiltrate (monocytes, macrophages)- regulation of the

reparative regeneration
 IV. PROLIFERATION
 The blood monocytes on reaching the extravascular space
transform into tissue macrophages.

 Besides the role of macrophages in phagocytosis, they may get

activated in response to stimuli such as cytokines
(lymphokines) and bacterial endotoxins.

 On activation, macrophages release several biological active

substances ( oxygen-derived reactive metabolites, cytokines)

 These products bring about tissue destruction,

neovascularisation and fibrosis
THE INFLAMMATORY CELLS
 POLYMORPHONUCLEAR NEUTROPHILS

The function of neutrophils in

inflammation:

- initial phagocytosis;
- engulfment of antigеn-antibody
complexes and non-microbal material.
- harmful effect – basement membrane
destruction
Phagocytosis involves following steps:

а) attachment of particles to the leukocyte and

recognition of particle by the leukocyte
b) engulfment , with formation of a phagocytic
vacuole
c) killing and degradation of the ingested material
 MONONUCLEAR –PHAGOCYTE SYSTEM
-blood monocytes
-tissue macrophages

Role of macrophages in inflammation:

- Phagocytosis and pinocytosis;
- Macrophages on activation by lymphokines
released by T-lymphocytes or by non-
immunologic stimuli elaborate a variety of
biologically active substances:
1) Proteases like collagenase and elastase
which degrade collagen and elastic tissue.
2) Plasminogen activator which activates the
fibrinolytic system.
3) Сomponents of complement system

4) Some coagulation factors

5) Chemotactic agents

6) Metabolites of arachidonic acid

7)Growth factors of fibroblasts, vessels, granulocytes

8) Cytokines

9) Oxygen-derived free radicals

 LYMPHOCYTES

Naive lymphocytes encounter the antigen-

presenting cells and become antigen-specific
lymphocytes.

Activated T-lymphocytes regulate the

macrophage activation and recruitment by
secreting specific mediators - cytokines
(lymphokines) (INF-γ) and modulate the antibody
production and cell-mediated cytotoxicity and
maintain the immunological memory
 OUTCOMES OF ACUTE INFLAMMATION
1. resolution - restoration to normal, limited
injury
chemical substances neutralization
normalization of vascular permeability
apoptosis of inflammatory cells
lymphatic drainage

 2. healing

 3. progression into chronic inflammation

 HEALING

1. Induction of an inflammatory process in response

to the initial injury, with removal of damaged and
dead tissue.
2. Proliferation and migration of parenchymal and
connective tissue cells.
3. Formation of new blood vessels (angiogenesis) and
granulation tissue.
4. Tissue remodeling.
5. Wound contraction.
6. Acquisition of wound strength.
 CHRONIC INFLAMMATION
 reasons:
persisting infection or prolonged exposure
to irritants (intracellular surviving of agents
- TBC)
repeated acute inflammations (otitis,
rhinitis)
primary chronic inflammation - low
virulence, sterile inflammations (silicosis)
autoimmune reactions (rheumatoid arthritis,
glomerulonephritis, multiple sclerosis)
 CHRONIC INFLAMMATION
 chronic inflammatory cells ("round cell"
infiltrate)
lymphocytes
plasma cells
monocytes/macrophages
 lymphocytes  plasma cells, cytotoxic (NK)
cells, coordination with other parts of immune
system
 plasma cells - production of Ig
 monocytes-macrophages-specialized cells
(siderophages, gitter cells, mucophages)
 MEDIATORS OF CHRONIC INFLAMMATION

-Transforming growth factor (TGFβ) -antiproliferative and

fibrosis enhancing effect.

-Platelet derived growth factor (PDGF)-fibroblast and smooth

muscle cells stimulation

-Fibroblast growth factor -mostly fibroblasts-endothelial cell

proliferation, macrophage and fibroblast activation.

-Vascular endothelial growth factor (VEGF) -major

angiogenesis factor
thank you for
your attention!