Professional Documents
Culture Documents
Inflammation
"Inflammation is one of the most important
and most useful of our host defense
mechanisms, and without an adequate
inflammatory response none of us or our
patients would be living.
It is not a disease but a manifestation of a
disease
Ironically it is also one of the most common
means whereby our own tissues are injured."
GENERALITIES REGARDING THE
INFLAMMATORY RESPONSE:
Resolution
Mediators
INJURY Acute inflammation Abscess formation
Healing
Mediators Regeneration
Persistent infection
Chronic inflammation Scarring
Persistent toxins
Autoimmune diseases
Inflammation
“Is a reaction of a tissue and its
microcirculation to a pathogenic insult”
2- Amplification:
Both soluble mediators and cellular inflammatory
systems are activated and amplified
3- Termination:
Specific inhibition or dissipation of the mediators
Acute Inflammation
Acute inflammation involves several processes:
Vascular Changes
- Vasodilation (change in caliber and flow)
- increased vascular permeability
- acute local active hyperemia
Cellular Events
- Movement from capillaries and post
capillary venules - emigration
-Accumulation of leukocytes at sites of
injury - migration
-Activation of inflammatory cells
Sequence of events
Increased Vascular
permeability
Escape of protein
rich fluid into
extravascular space
-immunoglobulins
-coagulation factors
-fibrinogen
Results in edema
Inflammation
Pathogenesis of Edema
Inflammatory edema:
few cells-
Hydrostatic Oncotic
pressure pressure
Inflammation
Increased Vascular Permeability
EDEMA -EXUDATE
(protein content high:
numerous neutrophils:
specific gravity >1.020)
Hydrostatic Oncotic
pressure pressure
Diapedesis
Mechanisms of increased vascular
permeability
1- Formation of endothelial gaps in
post capillary venules
2- Direct injury to endothelial cell
3-Leukocyte Dependent Endothelial
Injury
4-Increased Transcytosis
5- Leakage from new capillaries
COMPONENTS OF THE INFLAMMATORY
RESPONSE
Vascular Changes
- Vasodilation (change in caliber and flow)
-Increased Vascular Permeability – Acute
Local Active Hyperemia
Cellular Events
- Movement from capillaries and post
capillary venules - emigration
-Accumulation of leukocytes at sites of
injury - migration
-Activation of inflammatory cells
Cellular component
Accumulation of
neutrophil
polymorphs in the
extracellular space
is the diagnostic
histologic feature of
acute inflammation
Increased
Permeability
Post capillary venules
Concentration of RBC’s
increases as fluid decreases
Blood flow decreases (slows-
stasis)
Leucocytes interact with
endothelium
Margination
Slowing and stagnation of blood
flow
WBC’s fall out of the central column
Tumble slowly and roll along the
endothelium of venules
Pavementing
endothelium appears to be essentially
lined by white cells
Adhesion and Emigration
Process by which
leukocytes escape
from their location
in the blood to reach
the perivascular
tissues, (sometimes
referred to as
Diapedesis…)
Emigration - Process
Margination
Pavementing
Emigration
Chemotaxis
Phagocytosis and
Synthesis of
biochemical Mediators
Intracellular
Degradation
Extracellular Release of
Leukocyte Products
Phases of Acute Inflammation
1- Initiation:
1- Stimulation (injury) with changes in microvasculature
2- Structural changes leading to fluid extra-vasation
3- Emigration of WBCs to the site of injury
2- Amplification:
Both soluble mediators and cellular inflammatory
systems are activated and amplified
3- Termination:
Specific inhibition or dissipation of the mediators
Regulation
of Leucocyte
Recruitment
Binding of
chemical
agents to
specific
receptors of
leukocyte cell
membranes
stimulates a
variety of
events
including
chemotaxis
Chemotaxis
Chemotaxis: Directional migration in response
to a chemical gradient of chemoattractant.It is a
dynamic and energy dependent activity –
-process is receptor mediated.
-implies directed locomotion
Recruitment of inflammatory
cells
Increased vascular
permeability Acute Chronic
inflammation inflammation
2) Oxygen-independent
Oxygen Independent Mechanisms
Substances within granules
Lysozyme
- attacks bacterial cell walls
- especially gram + bacteria
Bacterial permeability increasing protein
(BPI)
- activates phospholipase degrades cell
membranes
Lactoferrin
- Iron binding glycoprotein
Defensins
- Cytotoxic to microbes and certain
mammalian
Termination of the acute inflammatory
response
· Mediators have short half lives
· Mediators are degraded after release
· Produced in short bursts when stimulus
persists
· Switch to anti-inflammatory lipoxins from
arachidonic acid
· Production of anti-inflammatory cytokines
(TGF-•)
· Inhibit the production of TNF in
macrophages
Inflammation - Systemic
• Fever - clinical Manifestations
hallmark of inflammation
- Endogenous pyrogens: IL-2 ,TNF-α
• Constitutional symptoms - malaise, anorexia,nausea
• Weight loss - due to negative nitrogen balance
• Hyperplasia of mononuclear phagocyte system
• Leukocytosis - may be neutrophils, eosinophils, or
lymphocytes
• Anemia –blood loss,chronic due to toxic depression of
bone marrow
• Acute Phase Reactants - non-specific elevation of
many serum proteins
• marked increase in ESR
• Amyloidosis – longstanding chronic infection
Inflammation
Systemic Manifestations
Leukocytosis: most bacterial infection
Lymphocytosis: Infectious mononucleosis,
mumps,
German measles
Eosinophilia: bronchial asthma,
hay fever,
parasitic infestations
Leukopenia: typhoid fever,
infection with
rickettsiae/protozoa
Systemic effects of Inflammation
Persistent
inflammation
(chronic
inflammation)
Organisation-
scar formation
Resolution
Means complete restoration of the tissues to normal
Favouring factors
Minimal cell death and tissue damage
Occurrence in an organ or tissue which has
regenerative capacity (eg the liver) rather than in one
which cannot regenerate (eg. the central nervous
system)
Rapid destruction of the causal agent
(eg. phagocytosis of bacteria)
Rapid removal of fluid and debris by good local
vascular drainage