INFLAMMATION

Assoc. prof. Kameliya Bratoeva, M.D., PhD

ES of pathophysiology, MU-Varna
INTRODUCTION TO INFLAMMATION

Inflammation is a complicated local and

non specific pathological process that
develops in response to cellular and
tissue damage, and consists of vascular
response, cellular reaction, and systemic
reactions.
 INTRODUCTION TO INFLAMMATION

Inflammation is part of the body’s defense

mechanism. It is the process by which the immune
system recognizes and removes harmful stimuli
and begins the healing process.
 INTRODUCTION TO INFLAMMATION

Causes:
 Physical agents (heat, cold, radiation, mechanical
injury).
 Chemical agents (organic and inorganic poisons).
Infective agents (bacteria, viruses, parasites).
Immunological agents (cell-mediated and antigen-
antibody reactions).
 INTRODUCTION TO INFLAMMATION

 The innate immunity includes two lines of defense:

natural barriers and inflammation.

 If the surface barriers are breached, a highly efficient
local and systemic response- inflammation is mobilized to
limit the extent of damage, and to protect the body from
further injury and infection, and promote healing.
Inflammation
Inflammation is the reaction of vascularized tissues to injury.
 Types of inflammation:

Depending upon the defense capacity of the host and

duration of response, inflammation can be classified as:
– acute
– chronic
 INFLAMMATION

Phases of inflammation:
1. Alteration – degeneration and necrosis of the cells,
tissue.
2. Exudation – formation of exudate.
3. Proliferation- proliferation, which leads to restoration
of tissue
The 2nd phase "exudation" include:
microcirculatory disturbances of blood rheology,
 increased vascular permeability,
 exudation of main blood components,
 emigration of blood cells,
 phagocytosis,
 development of inflammatory infiltration
 INFLAMMATION

Inflammation begins with damage to

parenchymal cells, connective tissue,
microcirculatory vessels and blood cells.
 INFLAMMATION

The complex of structural, microcirculatory,

metabolic and functional disorders determine
the local signs and systemic clinical
manifestations of inflammation.
 Acute inflammation

The manifestations of an acute inflammatory response begin

with the immediate vascular changes that occur- vasodilation
and increased capillary permeability, influx of inflammatory
cells such as neutrophils, and in some cases the widespread
effects of inflammatory mediators, which produce fever and
other systemic signs and symptoms
 Injury

Endothelial binding of Vasoactive

neutrophils and chemicals Chemokines
macrophages

Vasodilation

Emigration of
neutrophils and
macrophages into
tissue

Phagocytosis
 Acute inflammation

Acute inflammation involves:

1. Alterarion of vascular caliber:
Vasoconstriction (for a seconds)
Vasodilataton leads to increased
blood flow and blood pooling creating
redness and warmth (rubor and calor)
 Acute inflammation

2. Changes of microvasculature,
includes:
Increased permeability for plasma
proteins and cells crearing swelling
(tumor).
Fluid loss leads to concentration of
red blood cells and slowed blood flow
(stasis)
 Acute inflammation

3. Emigration of leukocytes

Neutrophils migrate mainly from

the microcirculation to the damaged
tissue.
4. Phagocytosis
Neutrophils migrate mainly from the microcirculation to the
damaged tissue

Emigration of neutrophils from the bloodstream into tissue is

mediated by receptor interactions with the capillary endothelium.
With inflammation and injury, endothelial cells begin to express
binding molecules on their cell surfaces (selectins).
The selectin interactions cause the leukocytes to stick and roll.
Chemokines on the surface of the endothelial cells interact with
neutrophils (and macrophages) to increase the binding affinity of
integrin receptors on leukocytes.

Firm attachment and diapedesis through the capillary wall is

facilitaded by integrins that allow the neutrophils to bind to
endothelial cells and extracellular matrix and then pull themselves
into the tissue.
 Inflammatory exudates

The main effects of inflammatory exudate are

dilution of the damaging agent;
facilitates the inflow of leukocytes that engulf the
invading microorganisms
facilitates the inflow of antibodies through the plasma to
the inflamed area
limiting the spread of the damaging agent outside the
inflamed area
 Inflammatory exudates

Morphological types of exudative inflammation (according to character of

exudates and prevailing location
• Serous, when the fluid exudate resembles serum or is watery with low
proteins.
• Fibrinous, when the fibrin content is high, fibrinous exudate is thick,
sticky, and high in protein.
• Purulent or suppurative exudate is formation of pus in infection with
pyogenic bacteria, leukocytes, and cellular debris.
• Hemorrhagic, when there is vascular damage and abounding with red
blood cells.
• Catarrhal, when the surface of epithelium in case of inflammation
produces increased amount of mucus.
• Mixed
Inflammatory exudates
 PHAGOCYTOSIS

Neutrophils and macrophages have a

number of different receptors on their
surface that enable them to bind to
components of microbes or to opsonins
like IgG and complement.
Bound microbes are internalized into
phagosomes that fuse with lysosomes
containing numerous enzymes.
 PHAGOCYTOSIS

Some of the enzymes degrade proteins (proteolytic), and others

such as oxidase and inducible nitric oxide synthase (iNOS)
produce free radicals that attack molecular bonds in the cell
membranes.
When phagocytes are strongly stimulated or microbes are too
large to internalize, the lysosomal enzymes may be activated or
released at the cell surface, causing tissue damage and
inflamation- called secondary damage (alteration)
 Chronic inflammation

The manifestations of chronic inflammation are due to

infiltration with macrophages, lymphocytes, and fibroblasts,
leading to persistent inflammation, fibroblast proliferation,
and scar formation.
Attention!
The differences between acute and chronic inflammation are:
- duration of development
- cell types that emigrate to damaged tissues
- proliferative processes

In both types of inflammation, the inflammatory response proceeds

by the same mechanism and the same signs and symptoms.
 Key functions of macrophages in the chronic inflammatory response

Macrophages are essential for wound healing because of their phagocytic functions.
Macrophages produce proteases that help in removing foreign protein from the
wound.
Macrophages release tissue thromboplastin to facilitate hemostasis and stimulate
fibroblast activity.
Macrophages secrete other peptide growth factors such as angiogenic factor, wich
encourages the growth of new blood vessels.
Macrophages also phagocytose spent neutrophils and their degradation products so
they do not interfere with healing
Key functions of macrophages in the chronic inflammatory response

Prolonged inflammation may impair healing and result in an

accumulaton of macrophages, fibroblasts, and collagen, called a
granuloma.
Granulomas are usually evident on examinaton of tissue biopsy
as clusters of macrophages surrounding particulate matter or
resistant microbes such as Mycobacterium tuberculosis.
Fibrosis and scarring are evident because normal parenchyma is
replaced with fibrous tissue.
Pyogenic Granulomas
 Chemical mediators of inflammation

Complement- The complement system consist of about 30

plasma proteins that interact to enchance inflammation,
chemotaxis, and lysis of target cells.
Complement proteins are synthesized in the liver and by
macrophages and neutrophils. They circulate in the blood in an
inactive form.
Activation of the complement system occurs via three different
pathways: classical, alternative and lectin.
 Chemical mediators of inflammation

Kinins- Bradykinin and Kallikrein- Activated kinins

cause increased vascular permeability, vasodilation, and
smooth muscle contraction. They are responsible for
pain.
 Chemical mediators of inflammation

Clotting Factors- The key linkage between the

inflammatory response and clotting system is activated
factor XII (Hageman factor). This activation results in
the formation of an effective fibrin barrier to the spread
of infection. Some of the fibrin degradation products are
chemotactic signals for neutrophils
 Chemical mediators of inflammation
Cytokines and Chemokines

(platelet-activating- factor)
 Systemic manifestation of inflammation

Systemic responses include:

 Fever,
 Neutrophilia (increased blood neutrophil count)
 Lethargy
 Muscle catabolism
 Increased acute phase proteins (CRP)
 Increased serum amyloid A
 Systemic manifestation of inflammation
Three macrophage-derived cytokines – IL-1, IL-6, TNFa are responsible for
most of the systemic effects of inflammation.
 Systemic manifestation of inflammation

The liver is a target for cytokines. In

response to these cytokines (IL-1, IL-6,
TNF a) the liver releases a number of
proteins, collectively called acute
phase proteins.
Thank you for your attention!