Ashoka Abeynayaka

MSc, BSc, Dip. in Teaching and Supervision,

Dip. in psychiatric Nursing, RN,RM
ashokabey@yahoo.com
The act of inflaming or the
state of being inflamed.
A localized protective reaction
of tissue to irritation, injury, or
infection.
A local and non-specific
defensive response of the tissues
to an injurious or infectious agent.
It is an adaptive mechanism that
destroys or dilutes the injurious
agent , prevents further spread of
the injury and promotes the repair
of damaged tissue.
Cardinal signs
Pain (Dolor)
Swelling (Tumor)
Redness (Rubor)
Heat/Warm (Calor,Color)
Impaired Function (Funtio
laesa)
The classic signs and symptoms of
acute inflammation: English Latin
Redness Rubor* Swelling Tumor
/Turgor* Heat Calor* Pain Dolor*
Loss of function Functio laesa** All the
above signs may be observed in specific instances, but no single

sign must, as a matter of course, be present These are the original,

or "cardinal signs" of inflammation.
Functio laesa is an apocryphal notion, as it is not unique to
inflammation and is a characteristic of many disease states
The acronym that may
be used for this is
"PRISH" for Pain,
Redness, Immobility
(loss of function),
Swelling and Heat
.


Acute Inflammation: The Good Side of Inflammation

The acute inflammatory response to tissue damage is of great value. By isolating the damaged area,
mobilizing effector cells and molecules to the site, and — in the late stages —
promoting healing
inflammation protects the body.


Its importance is demonstrated by the problems people with inherited defects in components of the process have with infections.
Some examples:
A cu t e In fla mma tio n : T h e G o o d S id e o f In fla mm a tio n


T h e acu t e in flam mat o ry resp o n s e to tis su e d ama g e i s o f g r eat v alu e. By iso lati n g th e d am ag ed are a,

 m o b ilizi n g effe cto r cells an d mo lec u les to th e s ite, an d — in th e late s tag e s —

 p ro m o ti n g h ea lin g ,


i n fla mma tio n p ro te cts th e b o d y .


I ts im p o rtan ce i s d e mo n strat ed b y th e p ro b lem s p e o p l e w ith in h erited d e fects in co m p o n en t s o f th e p r o ces s h a v e w ith in fe ctio n s.

 S o m e ex amp les:


a fail u re to p ro d u c e reac tiv e o x y g en s p eci es (R OS ) lead s t ch
o ro n ic g ra n u lo ma t o u s d i sea se(CG D) [ Lin k to d i scu s sio n]


i n h e rited d efect s in th e ab il ity to p ro d u c e th e late r co mp leme n t c o mp o n e n ts
C5( , C 6 , C 7 , C 8 , C9) in creas e th e ris k o f ce rtain in f ectio n s.


C h ro n ic In fla m ma tio n : Th e B a d S id e o f In f la m ma t io n


I n ch ro n ic in fl amm atio n , th e in fla mma to ry resp o n se is o u t o f p r o p o rtio n to th e th reat it is d ea lin g w ith o r d irect ed a g ain st in ap p ro p ria te ta rg et s. I n th e fi rst ca se, t h e r esu lt ca n b e mo re d amag e t o th e b o d y th a n th e a g en t its elf w o u l d h av e p ro d u ced .

 A ller g ies a n d A u to imm u n e Dis ea s es

 A ll t h e m an y ty p es o f a llerg ies an d


m an y o f th e au to im mu n e d iseas es


a re ex amp les o f in fl amma tio n in res p o n se t o wh at s h o u ld h av e b een a h ar mles s ag en t . S o me e x am p les :


A sth ma


R h eu mat o id Ar th ri tis(R A)


M u l tip l e S clero sis (M S )


S y st emic Lu p u s Er y th e mato su s (S LE)


I n m an y o f th e se ca ses, t h e p ro b lem is mad e wo rse b y t h e fo rm atio n o f an tib o d i es ag ain st sel f an tig e n s o r

 p ersi sten t an tig en s fro m smo ld e rin g in fect io n s .


T h e an ti b o d ies co m p lex wi th t h e an ti g en s trig g er in g thcoe mp l emen t sy stem wi th a ll it s med iat o rs o f i n fla mma tio n . T h e resu l im
t: mu n e co m p lex d is o rd ers
.

a failure to produce reactive oxygen species (ROS) leads to chronic granulomatous disease (CGD) [Link to discussion]
inherited defects in the ability to produce the later complement components (C5, C6, C7, C8, C9) increase the risk of certain infections.
Chronic Inflammation: The Bad Side of Inflammation
In chronic inflammation, the inflammatory response is out of proportion to the threat it is dealing with or directed against inappropriate targets. In the first case, the result can be more damage to the body than the agent itself would have
produced.
Allergies and Autoimmune Diseases
All the many types of allergies and
many of the autoimmune diseases
are examples of inflammation in response to what should have been a harmless agent. Some examples:
Asthma
Rheumatoid Arthritis (RA)
Acute Inflammation: The Good Side of Inflammation
The acute inflammatory response to tissue damage is of great value. By isolating the damaged area,
mobilizing effector cells and molecules to the site, and — in the late stages —
promoting healing,
inflammation protects the body.
re examples of inflammation in response to what should have been a harmless agent. Some examples:
Asthma
Rheumatoid Arthritis (RA)
Multiple Sclerosis (MS)
Systemic Lupus Erythematosus (SLE)
In many of these cases, the problem is made worse by the formation of antibodies against self antigens or
persistent antigens from smoldering infections.
The antibodies complex with the antigens triggering the complement system with all its mediators of inflammation. The result: immune complex disorders.
Its importance is demonstrated by the problems people with inherited defects in components of the process have with infections.
Some examples:
a failure to produce reactive oxygen species (ROS) leads to chronic granulomatous disease (CGD) [Link to discussion]
inherited defects in the ability to produce the later complement components (C5, C6, C7, C8, C9) increase the risk of certain infections.
Chronic Inflammation: The Bad Side of Inflammation
In chronic inflammation, the inflammatory response is out of proportion to the threat it is dealing with or directed against inappropriate targets. In the first case, the result can be more damage to the body than the agent itself would have
produced.
Allergies and Autoimmune Diseases
All the many types of allergies and
many of the autoimmune diseases
are examples of inflammation in response to what should have been a harmless agent. Some examples:
Asthma
Rheumatoid Arthritis (RA)
Multiple Sclerosis (MS)
Systemic Lupus Erythematosus (SLE)
In many of these cases, the problem is made worse by the formation of antibodies against self antigens or

 persistent antigens from smoldering infections.

 The antibodies complex with the antigens triggering the comp lemen t system with all its mediators of inflammation. The result: immune complex disorders.
Chronic Inflammation: The Bad
Side of Inflammation
In chronic inflammation, the
inflammatory response is out of
proportion to the threat it is dealing
with or directed against inappropriate
targets. In the first case, the result can
be more damage to the body than the
agent itself would have produced.
Allergies and Autoimmune
Diseases
All the many types of allergies
and
many of the autoimmune
diseases
are examples of inflammation in
response to what should have
been a harmless agent
. Some examples: Asthma ,Rheumatoid Arthritis
(RA) Multiple Sclerosis (MS)
Systemic Lupus Erythematosus (SLE)
In many of these cases, the problem is made
worse by the formation of antibodies against self
antigens or
persistent antigens from smoldering infections.
The antibodies complex with the antigens
triggering the complement system with all its
mediators of inflammation. The result: immune
complex disorders.
Primary mediators Vasoactive amines,
eicosanoids IFN-γ and other
cytokines, growth factors, reactive
oxygen species, hydrolytic enzymes
Onset Immediate Delayed
Duration Few days Up to many
months, or years
Outcomes Resolution, abscess
formation, chronic inflammation Tissue
destruction, fibrosis, necrosis
Process of acute inflammation
The process of acute inflammation is
initiated by cells already present in all
tissues, mainly resident macrophages,
dendritic cells, histiocytes, Kupffer cells
and mastocytes. At the onset of an
infection, burn, or other injuries, these
cells undergo activation and release
inflammatory mediators responsible for
the clinical signs of inflammation.
inf
Vasodilation and its resulting
increased blood flow causes the
redness (rubor) and increased heat
(calor). Increased permeability of
the blood vessels results in an
exudation (leakage) of plasma
proteins and fluid into the tissue (
edema), which manifests itself as
swelling (tumor).
 Some of the released
mediators such as
bradykinin increase the
sensitivity to pain (
hyperalgesia, dolor).
The mediator molecules also alter
the blood vessels to permit the
migration of leukocytes, mainly
neutrophils, outside of the blood
vessels (extravasation) into the
tissue. The neutrophils migrate along
a chemotactic gradient created by
the local cells to reach the site of
injury.
[
The loss of function
(functio laesa) is probably
the result of a
neurological reflex in
response to pain
In addition to cell-derived mediators,
several acellular biochemical cascade
systems consisting of preformed plasma
proteins act in parallel to initiate and
propagate the inflammatory response.
These include the complement system
activated by bacteria, and the
coagulation and fibrinolysis systems
activated by necrosis, e.g. a burn or a
trauma.
 The acute inflammatory
response requires constant
stimulation to be sustained.
Inflammatory mediators have
short half lives and are quickly
degraded in the tissue. Hence,
inflammation ceases once the
stimulus has been removed.
Acute inflammation normally
resolves by mechanisms that have
remained somewhat elusive.
Emerging evidence now suggests
that an active, coordinated program
of resolution initiates in the first few
hours after an inflammatory
response begins.
After entering tissues, granulocytes
promote the switch of arachidonic acid
–derived prostaglandins and
leukotrienes to lipoxins, which initiate
the termination sequence. Neutrophil
recruitment thus ceases and
programmed death by apoptosis is
engaged.
These events coincide with
the biosynthesis, from
omega-3 polyunsaturated fatty
acids
, of resolvins and protectins,
which critically shorten the
period of neutrophil infiltration
by initiating apoptosis.
Consequently, apoptotic neutrophils
undergo phagocytosis by
macrophages, leading to neutrophil
clearance and release of anti-
inflammatory and reparative
cytokines such as transforming
growth factor-β1. The anti-
inflammatory program ends with the
departure of macrophages through
the lymphatics.
The outcome in a particular
circumstance will be
determined by the tissue in
which the injury has occurred
and the injurious agent that is
causing it. Here are the
possible outcomes to
inflammation
Resolution
The complete restoration of the inflamed
tissue back to a normal status.
Inflammatory measures such as
vasodilation, chemical production, and
leukocyte infiltration cease, and
damaged parenchymal cells regenerate.
In situations where limited or short lived
inflammation has occurred this is usually
the outcome.
Fibrosis
Large amounts of tissue destruction, or
damage in tissues unable to regenerate,
can not be regenerated completely by
the body. Fibrous scarring occurs in
these areas of damage, forming a scar
composed primarily of collagen. The
scar will not contain any specialized
structures, such as parenchymal cells,
hence functional impairment may occur.
Abscess Formation
A cavity is formed containing
pus, an opaque liquid
containing dead white blood
cells and bacteria with
general debris from destroyed
cells
.
Chronic inflammation
In acute inflammation, if the
injurious agent persists then
chronic inflammation will ensue.
This process, marked by
inflammation lasting many days,
months or even years, may lead to
the formation of a chronic wound
Chronic inflammation is
characterised by the dominating
presence of macrophages in the
injured tissue. These cells are
powerful defensive agents of the
body, but the toxins they release
(including reactive oxygen
species
Consequently, chronic
inflammation is almost
always accompanied by
tissue destruction.
Treating Inflammation
Inappropriate inflammation can be
treated with
steroids like the glucocorticoid
cortisol
nonsteroidal anti-inflammatory drugs
(NSAIDs) like aspirin and ibuprofen
(e.g., Motrin®, Advil®).
a number of proteins produced by
recombinant DNA technology
NonSteroidal Anti-Inflammatory
Drugs (NSAIDs)
The NSAIDs achieve their effects by
blocking the activity of
cyclooxygenase.
In addition to reducing the fever and
pain of inflammation, NSAIDs also
inhibit clotting.
But regular use of NSAIDs has a downside: a
tendency to develop ulcers in the stomach and
duodenum. Enter the COX-2 inhibitors.
COX-1 and COX-2
The body produces several different forms of
cyclooxygenase (COX), including COX-1, which is
involved in pain, clotting, and protecting the
stomach; COX-2, which is involved in the pain
produced by inflammation.
Most of the NSAIDs inhibit them both. However,
some newer drugs, the so-called COX-2 inhibitors,
such as rofecoxib (Vioxx®)
celecoxib (Celebrex®)