1. بسم الله الرحمن الرحيم Inflammation 1
Dr. Mansoor Laharwal
Associate Professor Pathology
UCM

2. 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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3. 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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4. 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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5. 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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6. 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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7. Short duration (hours /days) Main cells - neutrophils
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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8. 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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9. 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:
Alterations in vascular caliber – that lead to an increase in blood flow.
Structural changes in the microvasculature – that permit plasma proteins and leukocytes to leave the circulation.
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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10. 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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11. 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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12. 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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13. 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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14. 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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15. 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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17. Leakage from newly formed vessels
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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19. 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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20. Increased vascular permeability (mainly)
Extravasation of fluid, proteins, RBCs and WBCs from intravascular compartment to extravascular compartment
Due to:
Increased vascular permeability (mainly)
Increased hydrostatic pressure
Decreased plasma osmotic pressure
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21. Formation of Inflammatory exudates
Extravasation of fluid, proteins, RBCs and WBCs from intravascular compartment to extravascular compartment due to:
Increased vascular permeability
Increased hydrostatic pressure
Decreased plasma osmotic pressure
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22. Formation of Inflammatory exudates
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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23. 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:
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24. THE END
ALL IS WELL THAT ENDS WELL
mansoor laharwal