2. Inflammation
Inflammation is a complex reaction to
injurious agents such as microbes and
damaged, usually necrotic, cells that
consists of vascular responses, migration
and activation of leukocytes and systemic
reactions(Robins and Cotran; 7th ed.)
3. History
Egyptian papyrus (3000 BC)
Celsus (1st century AD) – 4 cardinal
signs of
inflammation
Virchow – fifth clinical sign i.e. functio
laesa
John Hunter (1973)– inflammation is not
a disease but a non-specific response that
has a salutary effect on its host.
4. Inflammation
Inflammation is the body's normal response
to injuries or infections. Cells of the
immune system travel to the site of injury or
infection and cause inflammation.
9. Inflammation is divided into
two basic patterns:
Acute Inflammation : It is the immediate
and early response to injury, designed to
deliver leukocytes to the site of injury.
Chronic Inflammation : It is considered to
be inflammation of prolonged duration
(weeks to months to years) in which active
inflammation, tissue injury and healing
proceed simultaneously.
10. Acute inflammation
Acute Inflammation : It is the immediate
and early response to injury, designed to
deliver leukocytes to the site of injury.
Characterized by 5 cardinal signs
11. Classical Signs of
Inflammation
Heat (Calor)
2. Redness (Rubor)
3. Swelling (Tumor)
4. Pain (Dolor)
5. Loss of function (Functio laesa)
(Virchow)
12. Acute Inflammation
STIMULI FOR ACUTE INFLAMMATION
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)
13. Acute inflammation has
three main components:
Vascular Component
Cellular Cellular Component
Mediator Component
14. Acute inflammation
(Vascular Componet)
Vascular Changes :
Alteration in the vessel
caliber resulting in
increased blood flow
(vasodilation) and
structural changes that
permits plasma
proteins to leave
circulation (increased
vascular permeability).
15. Vascular changes & fluid leakage during
acute inflammation lead to edema in a
process called as exudation
25. Acute inflammation Cellular
Event:
Cellular Events : Emigration of leukocytes from
the microcirculation and accumulation in the focus
of injury (cell recruitment and activation).
29. Chemotaxis and Activation
After extravasating from the blood,
leukocytes migrate toward sites of injury
along a chemical gradient in a process
called chemotaxis.
30. Chemotaxis and Activation
Both exogenous and endogenous substances can be
chemotactic for leukocytes.
Soluble bacterial products : N-formylmethionine
termini.
Components of complement system : C5a
Products of lipoxygenase pathway : leukotriene B4
Cytokines : IL-1, IL-8
31. Antimicrobial mechanisms of
neutrophils.
Phagocytosis involves the ingestion of
the microorganism into a phagocytic
vacuole that upon maturation becomes a
phagolysosome. In this new organelle,
the microorganism is destroyed by the
action of low pH, and degrading
enzymes. Neutrophils also degranulate
and release to their environment the
contents of their granules. When the
microorganism is too large to be
ingested, neutrophil can also produce
extracellular traps (NETs) formed by
DNA fibers and proteins from the
granules
32. Phagocytosis and Degranulation
Phagocytosis and the elaboration of degradative enzyme
are two major benefits of having recruited leukocytes at the
site of inflammation.
Phagocytosis consists of three distinct but interrelated
steps:
1. Recognition and attachment of the particle to the ingesting
leukocyte.
2. Engulfment with subsequent formation of a phagocytic
vacuole
3. Killing and degradation of the ingested material.
50. The coagulation cascade is a starting point for both the
kallikrein-kinin system (KKS) and the complement
system. Activation is indicated by solid arrows and
inhibition by dotted arrows
Cardiovasc Hematol Agents Med Chem. 2009 Jul; 7(3): 234–250.
52. Outcomes of acute inflammation
1. resolution - restoration to normal, limited injury
– chemical substances neutralization
– normalization of vasc. permeability
– apoptosis of inflammatory cells
– lymphatic drainage
2. healing by scar
– tissue destruction
– fibrinous inflammtion
– purulent infl. abscess formation (pus, pyogenic
membrane, resorption - pseudoxanthoma cells - weeks
to months)
3. progression into chronic inflammation
53. Abscess
A localized collection of pus (suppurative
inflammation) appearing in an acute or
chronic infection, and associated with tissue
destruction, and swelling.
Pathogenesis: the necrotic tissue is
surrounded by pyogenic membrane, which
is formed by fibrin and help in localize the
infection.
55. Chronic inflammation
Inflammation of prolonged duration (weeks
or months) in which active inflammation,
tissue destruction, and attempts at repair are
proceeding simultaneously
63. 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)
64.
65.
66.
67.
68.
69. Granulomatous inflammation
Distinctive chronic inflammation type
Cell mediated immune reaction (delayed)
aggregates of activated macrophages
epithelioid cell multinucleated giant cells
(of Langhans type x of foreign body type)
NO agent elimination but walling off
Intracellular agents (TBC)
84. Ulceration - inflammatory necrosis of the surface -
ulcer (skin, gastric)
Morphologic patterns of
inflammation
85. Complication of suppurative
infection
Bacteremia (no clinical symptoms!; danger of
formation of secondary foci of inflammation
(endocarditis, meningitis)
Thrombophlebitis - secondary inflammation of
wall of the vein with subsequent thrombosis -
embolization - pyemia - hematogenous abscesses
(infected infarctions)
Lymphangiitis, lymphadenitis
SEPSIS: life-threatening organ dysfunction
caused by dysregulated host response to
infection
86. SIRS & Sepsis
Systemic inflammatory response syndrome
(SIRS) is the clinical expression of the
action of complex intrinsic mediators of the
acute phase reaction.
SIRS can be precipitated by events such
as infection, trauma, pancreatitis, and
surgery.