Download Inflammation 1

‫بسم هللا الرحمن الرحيم‬
Inflammation 1
Dr. Mansoor Laharwal
Associate Professor Pathology
UCM
Objectives
At the end of this lecture, the students should be able to:
Define inflammation.
List purposes of inflammation.
Mention the cardinal signs of acute inflammation.
List the vascular events in acute inflammation and explain
the mechanism of increased vascular permeability.
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Definition
“Essential to the survival of organisms is the ability to
get rid of damaged or necrotic tissues & foreign
invaders (microbes)”
• The host response that accomplishes these goals is called
Inflammation.
• Inflammation is a complex reaction in tissues, consisting
mainly of responses of blood vessel and leukocytes,
triggered by mediators that are produced by various cells or
derived from plasma proteins and activated in response to
inflammatory stimulus.
is the local protective physiological response of the living
tissue to injury .
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Purposes of Inflammation
• Fundamentally a protective host response that delivers
leukocytes and plasma proteins from the blood to the sites of
infection.
- without inflammation, infections would go unchecked &
wounds would never heal
• Serves to eliminate:
- the initial cause of injury (microbes, toxins , causative agent )
- consequences of such injury (necrotic cells or tissue).
• Inflammation induces the process of repair to heal the
damaged tissue at the same time as it destroys, dilutes or
walls off the injurious agent.
- by regeneration of parenchymal cells
- filling of the defect with fibrous tissue (scarring)
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• Inflammation is terminated when the offending agent is
eliminated.
- mediators are broken down
- leukocytes have short life span in tissues
- anti-inflammatory mechanisms activated (prevent
excessive damage to the host).
- If the response fails to clear the invading agent, it can
progress to a chronic phase.
• May be harmful in some situations
- when inappropriately directed against self tissues (RA,
atherosclerosis, lung fibrosis) autoimmune disease
- when not adequately controlled in some life threatening
hypersensitivity reactions (snake/scorpion/spider bites)
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• Inflammation may contribute to a variety of diseases not
primarily due to abnormal host response
- chronic inflammation may play a role in atherosclerosis,
type II DM, degenerative diseases (Alzheimer disease)
and cancer
– “the silent killer”
• May be acute or chronic, depending on the nature of the
stimulus and the effectiveness of the initial reaction in
eliminating the stimulus or the damaged tissues
• * ( distinguished by the duration and the type of
infiltrating inflammatory cells )
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Acute inflammation
Rapid onset (minutes)
Short duration (hours /days)
Main cells - neutrophils
Exudation of fluid and plasma
proteins (edema)
Chronic inflammation
Insidious onset (may follow ac.
Inflammation)
Longer duration
Main cells - lymphocytes,
macrophages
Tissue destruction, proliferation of
blood vessels, & fibrosis
The nomenclature used to describe inflammation
- described by the suffix “itis” preceded by the name of the
organ/tissue involved.
Pancreatitis, Meningitis, Appendicitis, Pericarditis, Arthritis,
Gastritis
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Cardinal signs of (acute) inflammation
 Rubor (redness)
 Tumor (swelling)
 Calor (heat)
 Dolor (pain)
 Functio laesa (loss of function)
• These manifestations are
consequences of :
 the vascular changes
 leukocyte recruitment
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Acute inflammation
• Acute inflammation is a rapid host response that serves to
deliver leukocytes and plasma proteins to sites of infection or
tissue injury
• 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.
(3) Emigration of the leukocytes from microcirculation,
their accumulation at the site of injury, and their
activation to eliminate the offending agent.
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Major local manifestations of acute inflammation,
compared to normal
(1) Vascular dilation and increased blood
flow (causing erythema and warmth)
(2) Extravasation and extravascular
deposition of plasma fluid and
proteins (edema)
(3) Leukocyte emigration and
accumulation in the site of injury.
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Stimuli for Acute Inflammation
• Infections (bacterial, viral, fungal, parasitic) and microbial
toxins
- are the most common and medically important causes of
inflammation
- the microbial products are sensed by the family of Toll-like
receptors (TLRs)
- engagement of these receptors triggers signalling
pathways that stimulate the production of various
mediators.
• Foreign bodies (splinters, dirt, sutures)
- elicit inflammation because they cause traumatic tissue
injury or carry microbes.
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• Tissue necrosis from any cause
- ischemia (myocardial infarct), trauma, physical and
chemical injury (thermal injury, as in burns or frostbite;
irradiation; exposure to some environmental chemicals).
• Immune reactions (also called hypersensitivity reactions)
- are reactions in which the normally protective immune
system damages the individual’s own tissues.
- the injurious immune responses may be directed against
self antigens, causing autoimmune diseases (RA) , or may
be excessive reactions against environmental substances
( allergy )or microbes.
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Reaction of Blood Vessels in Ac. Inflammation
Consist of changes in the flow of blood and the permeability
of vessels.
1. Changes in Vascular Flow and Calibre
- Begin early after injury.
• One of the earliest manifestations of acute inflammation is
vasodilation
• Sometimes it follows a transient constriction of arterioles,
lasting a few seconds.
• Vasodilation first involves the arterioles and then leads to
opening of new capillary beds in the area (induced by the action
of mediators like histamine and nitric oxide (NO), on vascular smooth
muscle).
• The result is increased blood flow, which is the cause of heat
and redness (erythema) at the site of inflammation.
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• Vasodilation is quickly followed by increased permeability of
the microvasculature, with the outpouring of protein-rich fluid
into the extravascular tissues.
• The loss of fluid and increased vessel diameter lead to slower
blood flow (stasis), seen as vascular congestion (producing
localized redness), concentration of red cells in small vessels,
and increased viscosity of the blood.
• As stasis develops, blood leukocytes, principally neutrophils,
accumulate along the vascular endothelium.
• At the same time endothelial cells are activated by mediators,
produced at sites of infection and tissue damage, and express
increased levels of adhesion molecules.
• Leukocytes then adhere to the endothelium, and subsequently
migrate through the vascular wall into the interstitial tissue.
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2. Increased Vascular Permeability (Vascular Leakage)
• A hallmark of acute inflammation, leading to the escape of a
protein-rich exudate into the extravascular tissue, causing edema.
Mechanisms responsible for vascular leakage:
• Contraction/retraction of endothelial cells, resulting in increased
inter-endothelial spaces
- the most common mechanism - elicited by mediators
(histamine, bradykinin, leukotrienes, etc....)
• It is called the immediate transient response because vascular
leakage occurs rapidly after exposure to the mediator and is
usually short-lived (15–30 minutes)
• In some forms of mild injury (burns, x-irradiation, u v radiation,
certain bacterial toxins), the leakage begins after a delay of 2 to
12 hours, and lasts for several hours or even days - delayed
prolonged leakage
- caused by contraction of endothelial cells or mild endothelial
damage (e.g. late-appearing sunburn)
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• Severe endothelial injury - resulting in endothelial cell
necrosis and detachment.
- as seen in deep burns, microbes targeting endothelial
cells and injury by adhered neutrophils during
inflammation.
• Transcytosis
- increased transport of fluids and proteins through the
endothelial cell via channels consisting of vesicles and
vacuoles (vesiculo-vacuolar organelle) located close to
intercellular junctions.
- mediated by VEGF, which increases the number and
perhaps the size of these channels.
• Leakage from newly formed vessels
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3. Responses of Lymphatic Vessels
• Although reactions of blood vessels are more important
in inflammation, lymphatic vessels also participate in the
response.
• In inflammation, lymph flow in lymphatics is increased
and helps drain edema fluid that accumulates due to
increased vascular permeability.
• In addition leukocytes, cell debris as well as microbes,
may find their way into lymph.
• Like blood vessels, lymphatic vessels proliferate during
inflammatory reactions to handle the increased load.
• The lymphatics may become secondarily inflamed
(lymphangitis) – seen as red streaks near a skin wound.
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• Extravasation of fluid, proteins, RBCs and WBCs from
intravascular compartment to extravascular
compartment
• Due to:
1. Increased vascular permeability (mainly)
2. Increased hydrostatic pressure
3. Decreased plasma osmotic pressure
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Formation of Inflammatory exudates
Extravasation of fluid, proteins, RBCs
and WBCs from intravascular
compartment to extravascular
compartment due to:
1.
2.
3.
Increased vascular permeability
Increased hydrostatic pressure
Decreased plasma osmotic
pressure
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Formation of Inflammatory exudates
Exudate
• High protein content
•
•
• Contains cellular debris
•
• High specific gravity
(↑1.020)
•
• Its presence implies an
increase in the normal
permeability of small blood
vessels and, therefore, an
inflammatory reaction
Transudate
Low protein content (mostly
albumin)
Little/no cellular material
Low specific gravity
(↓1.020)
It results from osmotic or
hydrostatic imbalance
across the vessel wall
without an increase in
vascular permeability (CCF,
venous obstruction)
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References
• Robbins and Cotran “Pathologic Basis of Disease”. 8th
edition. Kumar, Abbas, Fausto, Aster. Saunders
Elsevier, Philadelphia. Chapter 2
• Robbins Basic Pathology 9th edition. Saunders
Elsevier, Philadelphia. Chapter 2
• Video link for Inflammation:
http://www.youtube.com/watch?v=suCKm97yvyk
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