Inflammation and Repair

Learning Objectives:
1. Describe the sequence of vascular changes in acute inflammation
(vasodilation, increased permeability) and their purpose.
2. Know the mechanisms of increased vascular permeability. Know
which vessels are affected in the immediate transient response.
3. Describe the steps involved in extravasation of leukocytes from the
blood to the tissues. Know the steps at which selectins and integrins
act.
4. Define the terms edema, transudate, and exudate.
5. Describe the meaning and utility of chemotaxis. Understand the
role that chemokines play in inflammation.
6. Describe the steps involved in phagocytosis and the role of IgG
and C3b as opsonins and receptors. Know the leukocyte receptors for
these opsonins. Understand the role that collectins play in
phagocytosis.
Learning Objectives:
7. Chemical mediators of inflammation are numerous). You should learn the
cellular sources and major effects of the mediators and, conversely, list the
most likely mediators of each of the steps of inflammation (There is no need to
memorize all the information.)
8. Compare and contrast acute vs chronic inflammation with respect to
causes, nature of the inflammatory response, and tissue changes.
9. Compare and contrast the clinical settings in which different types of
inflammatory cells (eg, neutrophils, eosinophils, monocyte-macrophages, and
lymphocytes) accumulate in tissues. Compare and contrast the contents of
neutrophil and eosinophil granules.
10. Describe the differences between the various cell types (ie, labile, stable,
and permanent cells) in terms of their regeneration potential. List examples of
each cell type.
11. Distinguish between fibrinous, purulent, and serous inflammation. Define
an abscess.
12. Describe the systemic manifestations of inflammation and their general
physiology, including fever, leukocyte left shift, and acute phase reactants.
Inflammation:
Definition: The reaction of vascularized living
tissue to local injury.
Inflammation serves to destroy, dilute or
isolate the injurious agent (microbes, toxins)
and eliminate the necrotic cells and tissues
arising as a consequence to such injury.
It also starts a series of events which leads as
far as possible to the healing and
reconstitution of the damaged tissue.
Inflammation
During repair, the injured tissue is replaced
by :
Regeneration of native parenchyma cells
Filling of the defect by fibroblastic tissue or
both
Inflammation and repair are protective
response, however they may induce harm
e.g.anaphylactic reaction, rheumatoid
arthritis, atherosclerosis or pericarditis.
Inflammation
The inflammatory response consists of two main components:
1. a vascular reaction
2. a cellular reaction.
Tissues and cells involved in inflammatory response :
The fluid and proteins of plasma, circulating cells, blood vessels and connective
tissue
The circulating cells: neutrophils, monocytes, eosinophils, lymphocytes,
basophils, and platelets.
The connective tissue cells are the mast cells, the connective tissue
fibroblasts, resident macrophages and lymphocytes.
The extracellular matrix, consists of the structural fibrous proteins
(collagen, elastin), adhesive glycoproteins (fibronectin, laminin, nonfibrillar
collagen, tenascin, and others), and proteoglycans.
The basement membrane is a specialized component of the extracellular
matrix consisting of adhesive glycoproteins and proteoglycans.
The
connective
tissue cells
The circulating cells:
The
extracellular
matrix
Inflammation
Inflammation is divided into:
Acute inflammation.
Chronic inflammation.
Acute inflammation
rapid in onset (seconds or
minutes)
of relatively short duration,
lasting for minutes, several
hours, or a few days
its main characteristics are
the exudation of fluid and
plasma proteins (edema)
and the emigration of
leukocytes, predominantly
neutrophils.
is of longer duration
associated histologically with
the presence of lymphocytes
and macrophages, the
proliferation of blood
vessels, fibrosis, and tissue
necrosis.
Less uniform.
Chronic inflammation
Inflammation
The vascular and cellular reactions of both acute and
chronic inflammation are mediated by chemical
factors that are derived from plasma proteins or cells
These chemical factors are produced in response to
or activated by the inflammatory stimulus.
Such mediators, acting singly, in combinations, or in
sequence, then amplify the inflammatory response
and influence its evolution.
Necrotic cells or tissues themselves-whatever the
cause of cell death-can also trigger the elaboration of
inflammatory mediators e.g. acute inflammation after
myocardial infarction.
Inflammation
Inflammation is terminated when the offending agent
is eliminated and the secreted mediators are broken
down or dissipated.
In addition, there are active anti-inflammatory
mechanisms that serve to control the response and
prevent it from causing excessive damage to the
host.
Acute Inflammation
Acute inflammatory reactions are triggered by a variety
of stimuli:
Infections (bacterial, viral, parasitic) and microbial
toxins
Trauma (blunt and penetrating)
Physical and chemical agents (thermal injury, e.g.,
burns or frostbite; irradiation; some environmental
chemicals)
Tissue necrosis (from any cause)
Foreign bodies (splinters, dirt, sutures)
Immune reactions (also called hypersensitivity
reactions)
Acute Inflammation
Local clinical signs of acute inflammation :
Heat
Redness
Swelling
Pain
o Loss of function
Redness
Swelling
Swelling
Acute Inflammation
Acute inflammation is a rapid response to an injurious agent
that serves to deliver mediators of host defense-leukocytes
and plasma proteins-to the site of injury.
Acute inflammation has three major components:
(1) alterations in vascular caliber that lead to an increase in blood flow
(2) structural changes in the microvasculature that permit plasma
proteins and leukocytes to leave the circulation (increased vascular
permeability)
(3) emigration of the leukocytes from the microcirculation, their
accumulation in the focus of injury, and their activation to eliminate
the offending agent