ACUTE & CHRONIC

INFLAMMATION

BETHY S HERNOWO
 Inflammation is the response of vascularized
living tissue to injury
 Intented to:
 Contain & isolite injury
 Destroy invading microorganism & inactivate toxins
 Prepare tissue for healing & repair

 Evoked by:
 Microbial infection
 Physical agents
 Chemical
 Necrotic tissue
 Immune reaction
 Inflammation generally characterized by:
 Component of vascular wall response and
inflammatory cell response
 Effects mediated by circulating plasma
protein & factors produced by vessel wall or
inflammatory cells
 Termination when the offending agent is
eliminated and the secreted mediators are
removed
INFLAMMATION
SEQUENCE OF SPECIFIC PHYSIOLOGICAL BEHAVIORS
THAT OCCUR IN RESPONSE TO A NONSPECIFIC AGENT.

ACTS TO:
1) NEUTRALIZE OR DESTROY OFFENDING AGENT
2) RESTRICTS TISSUE DAMAGE TO SMALLEST
POSSIBLE AREA
3) ALERTS BODY TO TREAT OF TISSUE INJURY
4) PREPARES INJURED AREA FOR HEALING

CAUSES: EXOGENOUS OR ENDOGENOUS

TRAUMA, SURGERY, INFECTION, CAUSTIC CHEMICALS,
EXTREMES OF HEAT OR COLD, IMMUNE RESPONSES,
ISCHEMIC DAMAGE
 Acute inflammation:
 Early onset
 Short duration
 Involving fluid exudation
 Polymorphonuclear cells migration
 Chronic inflammation:
 Later onset
 Longer duration
 Involving lymphocytes & macrophage
 Inducing blood vessel proliferation & scarring
 CARDINAL SIGNS OF ACUTE INFLAMMATION

Heat Redness Swelling Pain Loss of

function
Celsius (30 BC) Virchow (1902)
INFLAMMATION – “HOT THING”
 SIGNS OF INFLAMMATION

DESCRIBED
BY CELSUS

ADDED BY
VIRCHOW
Acute Inflammation Components

Physiological Symptoms
Responses
Release of soluble mediators
Heat (calor)
Vasodilation

Increased blood flow Redness (rubor)

Extravasation of fluid (permeability) Swelling (tumor)

Cellular influx (chemotaxis)
Pain (dolor)
Elevated cellular metabolism
 Acute Inflammation Components

Physiological Symptoms
Responses
Release of soluble mediators
Heat (calor)
Vasodilation
Redness (rubor)
Increased blood flow
Swelling (tumor)
Extravasation of fluid (permeability)
Pain (dolor)
Cellular influx (chemotaxis)

Elevated cellular metabolism

 Acute Inflammation Components

Physiological Symptoms
Responses
Release of soluble mediators

Vasodilation Heat (calor)

Increased blood flow Redness (rubor)

Extravasation of fluid (permeability)
Swelling (tumor)
Cellular influx (chemotaxis)
Pain (dolor)
Elevated cellular metabolism
 Acute Inflammation Components

Physiological Symptoms
Responses
Release of soluble mediators
Heat (calor)
Vasodilation
Redness (tubor)
Increased blood flow
Swelling (tumor)
Extravasation of fluid (permeability)

Cellular influx (chemotaxis) Pain (dolor)

Elevated cellular metabolism

 Acute Inflammation Components

Physiological Symptoms
Responses
Release of soluble mediators

Vasodilation Heat (calore)

Increased blood flow Redness (tubor)

Extravasation of fluid (permeability)
Swelling (tumor)
Cellular influx (chemotaxis)
Pain (dolor)
Elevated cellular metabolism
 Edema: excess fluid in interstitial tissue or
body cavities
 Exudate: an inflammatory extravascular
fluid that has a high protein concentration
and cellular debris, spesific gravity > 1.020
 Exudation: extravasation of fluid,
proteins,and blood cells from vessels into
the interstitial tissue or body cavities
 Pus: a purulen inflammation exudate rich
in neutrophils and cell debris
 Transudate: extravascular fluid with low
protein content, spesific gravity < 1.012
ACUTE INFLAMMATION: SHORT TERM RESPONSE
INVOLVES:
HEMODYNAMIC CHANGES
EXUDATE FORMATION
PRESENCE OF GRANULAR LEUKOCYTES

CHRONIC INFLAMMATION: PERSISTANT

INVOLVES:
PRESENCE OF NONGRANULAR LEUKOCYTES
RESULTS IN MORE EXTENSIVE SCARRING.
 Acute inflammation
caused arteriolar
dilatation, increase
capillary pressure,
reduced osmotic
pressure. The net
result is an excess
of extravasated
fluid
LEUKOCYTE NOMENCLATURE
 STAGES OF INFLAMMATION
NEUROLOGIC RESPONSE - SYMPATHETIC NERVOUS SYSTEM,
CAUSES CONSTRICTION OF BLOOD VESSELS

VASCULAR RESPONSE - INCLUDES TRIPLE RESPONSE

A. VASODILATION
B. CAPILLARY PERMEABILITY, EDEMA
C. PAIN

RIPLE RESPONSE –
1) 3-50 SEC. - THIN RED LINE (VASODILATION OF CAPILLARIES)
2) 30-60 SEC. - FLUSH (VASODILATION OF ARTERIOLES)
3) 1-5 MIN - WHEAL (INCREASED VASCULAR PERMEABILITY,
EDEMA)

WHEAL - PALE, SOFT, SWOLLEN AREAS ON THE SKIN CAUSED

BY LEAKAGE OF FLUID FROM THE CAPILLARIES
 PATTERNS OF INFLAMMATORY
RESPONSE

MMEDIATE TRANSIENT RESPONSE – RESPONSE TO

MINOR INJURY

MMEDIATE SUSTAINED RESPONSE – RESPONSE TO

MORE SERIOUS INJURY, CONTINUES FOR SEVERAL
DAYS, DAMAGE TO VESSELS

DELAYED RESPONSE – INCREASES IN CAPILLARY

PERMEABILITY, DELAYED 4-24 HR, RADIATION
INJURIES, SUNBURN
III. CELLULAR RESPONSE –
A. MARGINATION AND PAVEMENTING
OF WHITE BLOOD CELLS
B. EMIGRATION
C. CHEMOTAXIS
D. PHAGOCYTOSIS
MARGINATION OF NEUTROPHILS
PAVEMENTING
EMIGRATION OF NEUTROPHILS
Emigration of Neutrophils
 Extravasation of Neutrophils

Di
ap
ed
es
is

Chemotaxis
 Involves binding of chemotactic agents to
specific leukocyte surface G protein-
coupled receptors, cause increased
cytosolic calcium & GTPase activities that
polymerize actin & pseudopods that binds
the extracellular matrix and can then pull
the cells forward
CHEMOTAXIS
Phagocytosis
 Involves three steps:
 Recognition & binding. Microorganism coated
by opsonin that enhance phagocytosis
efficiency by binding leukocyte receptors.
 Engulfment by encircling pseudopods and
enclosure of the particle within an intracellular
phagosome
 Killing & degradation of phagocytosed
particles
PHAGOCYTOSIS
PHAGOCYTOSIS
IV. INFLAMMATORY EXUDATES –
CONTAIN PLASMA, CELLS AND FLUID
A. SEROUS – LARGELY PLASMA, LOW IN PROTEIN,
OCCURS EARLY OR IN MILD INFLAMMATION
B. FIBRINOUS – LARGE AMOUNTS OF FIBRINOGEN,
FORMS A THICK, STICKY MESHWORK. ONLY
REMOVED BY FIBROLYTIC ENZYMES. FAILURE
OF REMOVAL LEADS TO INFLUX OF FIBROBLASTS
AND SCAR TISSUE FORMATION
C. PURULENT – CONTAINS PUS (REMAINS OF WBCs,
PROTEIN AND TISSUE DEBRIS).
D. HEMORRHAGIC – DAMAGE TO BLOOD VESSELS,
OCCURS WITH OTHER FORMS OF EXUDATE.
E. CATARRHAL – MUCUS HYPERSECRETION THAT
ACCOMPANIES INFLAMMATION OF A MUCUS
MEMBRANE.
SEROUS EXUDATE
FIBRINOUS EXUDATE
PURULENT EXUDATE
V. RESOLUTION –
A. INJURED AREA RETURNS TO NORMAL
B. MAY PROCEED AND FORM ABSCESSES
C. MAY PROCEED TO CHRONIC PHASE
Outcomes of Acute Inflammation

 Complete resolution with regeneration of

native cells & restoration to normalcy
 Healing by connective tissue replacement
(fibrosis) after substantial tissue
destruction
 Progression to chronic inflammation
CHRONIC INFLAMMATION

• SELF PERPETUATING, MAY DEVELOP IN THE COURSE

OF RECURRENT OR PROGRESSIVE ACUTE
INFLAMMATION OR LOW GRADE IRRITANTS THAT
FAIL TO ELICIT AN ACUTE RESPONSE

• CHRONIC INFLAMMATION IS A PROLONGED

PROCESS (WEEKS OR MONTH)
 CHRONIC INFLAMMATION
Can occur by:
 Following acute inflammation because the
inciting stimulus persist or normal healing
somehow interrupted
 Repeated bouts acute inflammation
 Smoldering response without prior acute
inflammation due to:
 Persistentinfection by intracellular microbes
 Prolonged exposure to potentially toxic
exogenous
 Immune reactions
CHRONIC INFLAMMATION

Typified by:
 Infiltration with mononuclear inflammatory cells
(macrophages, lymphocytes, plasma cells)
 Tissue destruction induced by persistent injury &
inflammatory cells
 Attempts at healing by connective tissue
replacement
CHRONIC INFLAMMATION
A. NONSPECIFIC CHRONIC INFLAMAMTION-
DIFFUSE ACCUMULATION OF MACROPHAGES AND
LYMPHOCYTES AT INJURY SITE

MACROPHAGES FROM 3 SOURCES:

1) RECRUITMENT
2) LOCAL PROLIFERATION
3) PROLONGED SURVIVAL

B. GRANULOMATOUS-
GRANULOMA FORMATION – MASSING OF
MACROPHAGES SURROUNDED BY LYMPHOCYTES,
ASSOCIATED WITH FOREIGN BODIES
GRANULOMA FORMATION
GIANT FOREIGN BODY CELL
Chemical mediators of Inflammation
INFLAMMATORY MEDIATORS:

1) HISTAMINE – 1st mediator of initial inflammatory

response, causes dilation of arterioles and an inc. in
permeability of capillaries and venules.

2) SEROTONIN – Causes vasodilation and inc.

vascular permeability
 INFLAMMATORY MEDIATORS
3) PLASMA PROTEINS
a) BRADYKININ – Causes an inc. in capillary
permeability and pain, may inc. leukocyte
chemotaxis
b) COMPLEMENT COMPONENTS – Make up 10% of
circulating serum proteins, chemotactic to neutrophils
and monocytes, complement cascade can damage
bacteria
c) COAGULATION SYSTEM – Responsible for making a
fibrous network at the site of a lesion to trap
exudate, microorganisms, and foreign bodies, stops
bleeding and provides a framework for repair to
begin.
 COMPLEMENT CASCADE
Classic Pathway Alternative Pathway

Antigen – Antibody Bacterial cell

complex walls (endotoxin)

Activated
C1 C3b

C4 Factors B and D

Properdin
C2

C3

Inflammation C3b C5b Antigen

Chemotaxis C3a C5a opsonization
Analphylatoxins
Membrane attack
C5 C6 C7 C8 C9
Complex and
cell lysis
EFFECTS OF COMPLEMENT
COAGULATION CASCADE
Extrinsic Pathway Intrinsic
Pathway
Injured cells Collagen or other activators
XIIa XII
X Xa
Va
Phospholipi
d
Prothrombin Thrombin

Fibrinogen Fibrin + Fibrinopeptide

monomer

Fibrin polymer
INFLAMMATORY MEDIATORS

4) PROSTAGLANDINS AND OTHER PRODUCTS OF

THE CYCLOOXYGENASE PATHWAY – Derived from
arachidonic acid, contribute to vasodilation, capillary
permeability, pain and fever

5) LEUKOTRIENES – Derived from arachidonic acid via

the lipoxygenase pathway,most contribute to inc.
vascular permeability, can induce
bronchoconstriction, transient wheal and flare
response, “Slow Reacting Substance of Anaphylaxis”
Generation of
Arachidonic Acid
Metabolites & their
roles in
Inflammation
Generation of
Arachidonic Acid
Metabolites &
their roles in
Inflammation
(continued)
6) WHITE BLOOD CELL
PRODUCTS –
a. NEUTROPHILS - LTs,
PROTEASES, REACTIVE
OXYGEN INTERMEDIATES,
THROMBOXANE A2, PGE2,
HYDROLASES

b. MONOCYTES/
MACROPHAGES -
REACTIVE OXYGEN AND
NITROGEN
INTERMEDIATES, LTs, IL-1,
IL-6, TNF-α, COLONY
STIMULATING FACTORS
c. LYMPHOCYTES
1. T HELPER CELLS - IL-2, IL-3, IL-4, IL-5, IL-6, IL-7,
IL-8,
T CELL-INTERFERON,
MEDIATED KILLINGCOLONY STIMULATING
FACTORS, TUMOR NECROSIS FACTOR - α
2. T CYTOTOXIC CELLS –
TUMOR NECROSIS FACTOR - α, PERFORINS
3. B CELLS - IMMUNOGLOBULIN
d. MAST CELLS – HISTAMINE, SEROTONIN, LTB4,
PROSTAGLANDINS, PLATELET ACTIVATING
FACTOR, NEUTROPHIL CHEMOTACTIC FACTOR
(IL-8), EOSINOPHIL CHEMOTACTIC FACTOR

e. EOSINOPHILS – CONTROL MEDIATORS THAT ARE

RELEASED BY MAST CELLS
The roles of activated
macrophages in
chronic inflammation
Consequences of defective or
excessive inflammation
 Defective inflammation typically result in
increased susceptibility to infections & delayed
healing of wounds and tissue damage.
 Excessive inflammation is the basis of many
categories of human disease, ex. Allergies and
autoimmune diseases. Inflammation also play
critical role in cancer, neurodegenerative
diseases, atherosclerosis.
THANK YOU