INFLAMATION

Ph.D

Definition
Inflammation - is the reaction of tissue
and
its microcirculation to a pathogenic
insult,
aimed to localize and remove the
altered
cells & harmful factor followed by
2

Basic forms of inflammation

Acute exudative inflammation
Chronic inflammation
Chronic granulomatous inflammation

Main features of acute

inflammation
local process
genetically determined
strictly sequentially
positive influence on tissue
usually has positive ending

Biological significance of
inflammation
to eliminate the pathogenic agent,
to remove injured tissues components,
to repair the tissue.

Etiology
Infections factors (toxins)
Trauma (blunt and penetrating)
Physical and chemical agents
(burns or frostbite; irradiation;
chemicals)
Tissue necrosis (from any cause)
Foreign bodies (splinters, dirt,
sutures)
Immune reactions
( hypersensitivity)

Spread of Inflammation
Local inflammation is limited to
circumscribed area of tissue in
the vicinity of its port of entry.
Metastatic inflammation transmission of the
inflammatory pathogens into
other organs and tissues.
Generalized inflammation pathogen spreads diffusely
throughout the entire body.

The cardinal symptoms of

inflammation

The cardinal symptoms of inflammation:

rubor (redness, hyperemia)
calor (local hyperthermia, fever)
tumor (tissue swelling, inflammatory
tumor)
dolor (burning pain)
lose of function (functional
impairment)
These features correspond to
inflammatory events of
vasodilatation, edema, and tissue
damage.

Pathogenesis
The stages of inflammation
Vascular stage (vasodilatation,
increasing of vascular permeability,
expression of vascular receptors)

Cellular stage (phagocytosis, O2dependent cytotoxicity)

Stage of tissue recovery (fibroplasia,

angiogenesis, cell division/tissue remodeling)

Vascular stage

Phases of acute inflammation

Primary alteration
Secondary alteration

Cellular stage

Vascular changes (reactions)

Exudation and migration of
leucocytes in site of
inflammation
Cellular proliferation and
tissue regeneration.

Cellular phase
The acute inflammatory response begins with direct
injury (alteration) or stimulation of cellular or structural
components of a tissue, including:

Endothelium
Tissue macrophages and mast cells
Neutrophils
Platelets
Mesenchymal cells (e.g., fibroblasts)
Parenchymal cells

Endothelial cells are key players of inflammation.

Provide selective permeability barrier (to exogenous
and endogenous inflammatory stimuli);
Regulate leukocyte migration (by expression of cell
adhesion molecules and receptors);
Regulate & modulate immune responses (by synthesis
& release of inflammatory mediators);
Regulate immune cell proliferation (by secretion of
hematopoietic colony-stimulating factors (CSFs)).

I.

Alteration

primary alteration is the result of

tissue insult by the harmful factor, that
leads to activation of
secondary alteration via activation of
soluble mediators and
recruitment of inflammatory cells
(leucocytes) to the area of damage.

During primary alteration macrophages

and granulocytes mount phagocytic
responses (engulf and destroy bacteria).
These are accompanied by the release of
mediators and reactive oxygen species
into adjacent tissues that may cause
tissue injury (secondary alteration).

Secondary alteration

Primary
alteration

Secondary alteration begins with releasing of

secondary endogenous mediators of
inflammation:
Humoral mediators (Complement sytem, Kinin
sytem, Clotting sytem, Fibrinolytic system).

Cellular mediators (preformed, newly

synthesized (both from leukocytes).

Mediators of inflammation (supported of secondary

alteration)

Cellular (leukocyte) mediators

IL 1- IL33

Humoral mediators
(Clotting factor)

exudate

(anaphylotoxins)

Effects of inflammatory mediators

Vascular phase
The vascular changes in inflammation
involve the:
arterioles,
capillaries,
venules of microcirculatory bed.
These changes begin almost immediately after
injury and are characterized by vasodilation and
changes in blood flow followed by increased
vascular permeability and leakage of protein-rich
fluid (exudate) to extravascular tissues.

Capillary bed changes in inflammation area

The types of increasing vascular permeability in

site of inflammation (S.L.Robbins)

. Earlier (transiently)
type of permeability.
Permeability measuring

B. Immediately (longer)
type of permeability

C. Delayed type of
permebility.

1/2

3
time, hours

Edema is accumulation of fluid within the

extravascular compartment and interstitial
tissues.
Edema

Transudate

Exudate
Serous
Fibrinous
Purulent
Suppurative
Serosagnuineous

Transudate
is edema fluid with low protein
content (specific gravity < 1.015, <
0.03 mg/ml

Exudate
is edema fluid with a high protein
concentration (specific gravity > 1.015),
which frequently contains inflammatory
cells.
Exudates are observed early in acute
inflammatory reactions and are produced by
mild injuries, such as sunburn or traumatic
blisters.

Types of exudate
Type

Serum

Proteins

Cells

Serous

albumins

Fibrous

albumins, fibrin

Purulent

albumins, fibrin

leukocytes, cells
debris

Sero -sangvinous

albumins, fibrin

leukocytes,
erythrocytes

Cellular events: leukocyte transmigration

in vascular lumen:

1.marinating,
2.rolling,
3.adhesion to endothelium.
through vascular wall:

4. transmigration across the endothelium

(diapedesis)
in the tissue:

5. migration to interstitial tissues toward a

chemotactic stimulus.

The type of emigrating leukocyte varies with:

Age
Inflammatory response
Type of stimulus.
In most forms of acute inflammation,
neutrophils predominate in the inflammatory
infiltrate during the first 6 to 24 hours, then
are replaced by monocytes in 24 to 48 hours

Phagocytosis
is responsible for eliminating the injurious agents
(the major benefits derived from the accumulation of
leukocytes at the inflammatory focus).

Phagocytosis involves the following steps:

1. recognition and attachment of the particle to be
ingested by the leukocyte;
2. its engulfment, with subsequent formation of a
phagocytic vacuole;
3. killing or degradation of the ingested material

Recognition & attachment to bacteria

bacteria

leukocyte

20

Macrophages attack on bacteria

leukocyte

capillary

bacteria

24

Bacteria digestion
bacteria
leukocyte

lysosomes

phagolysosomne

26

Proliferative events in inflammation

(by W.Bcker, H.Denk, Ph.U.Heitz)

macrophage
- tGF

FGF

fibroblast

proliferation

TGF

- TNF

capillaries

angiogenesis
41

Tissue recovery

Thank you for

your attention