Inflammation and Repair- PRELIMS L4

INFLAMMATION

Is a response of vascularized tissues to infections and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed, in order to eliminate the offending agents.

TYPICAL INFLAMMATORY REACTION DEVELOPS THROUGH A SERIES OF SEQUENTIAL STEPS

• The offending agent

• Leukocytes and plasma proteins

• The leukocytes and proteins

• The reaction is controlled and terminated.

• The damaged tissue is repaired.

OFFENDING AGENT

Which is located in extravascular tissues, is recognized by host cells and molecules

LEUKOCYTES AND PLASMA PROTEINS

Are recruited from the circulation to the site where the offending agent is located.

THE LEUKOCYTES AND PROTEINS

Are activated and work together to destroy and eliminate the offending substance

FUNDAMENTAL PROPERTIES OF INFLAMMATORY PROCESS

• Components of the inflammatory response.

• Harmful consequences of inflammation.

• Local and systemic inflammation

• Mediators of inflammation

COMPONENTS OF INFLAMMATORY RESPONSE

The major participants in the inflammatory reaction in tissues are blood vessels and leukocytes

HARMFUL CONSEQUENCES OF INFAMMATION

Protective inflammatory reactions to infections are often accompanied by local tissue damage and its associated signs and symptoms

ONSET OF ACUTE INFLAMMATION

Fast, minutes or hours

ONSET OF CHRONIC INFLAMMATION

Slow, Days

CELLULAR INFILTRATE OF ACUTE INFLAMMATION

Mainly neutrophil

CELLULAR INFILTRATE OF CHRONIC INFLAMMATION

Monocytes/ macrophages and lymphocytes

TISSUE INJURY FIBROSIS OF ACUTE INFLAMMATION

Usually mild and self- limited

TISSUE INJURY FIBROSIS OF CHRONIC INFLAMMATION

May be severe and progressive

LOCAL AND SYSTEMIC SIGNS OF ACUTE INFLAMMATION

Prominent

LOCAL AND SYSTEMIC SIGNS OF CHRONIC INFLAMMATION

Less

EXTERNAL MANIFESTATIONS OF INFLAMMATION (CARDINAL SIGNS)

• Redness (rubor)

• Heat (calor)

• Swelling (tumor)

• Pain (dolor)

• Chemicals of acute inflammation:

  • Bradykinins

  • Prostaglandins

  • Serotonin

• Loss of function

RUBOR

• Dilation of the blood vessels within damaged tissue (increased blood flow)

• Manifests redness due to high blood flow

CALOR

Transfer of heat to the site of injury, brought by increased blood content

TUMOR

Accumulation of fluids outside the blood vessel

DOLOR

Results from stretching & destruction of tissue (damage of nerves)

FUNCTIO LAESA

Inflamed area is inhibited by pain; severe swelling may physically immobilize the tissue (inflamed makes nerves not functional losing senses due to aches)

CAUSES OF INFLAMMATION

• Infections

• Trauma, Physical and Chemical agents, Irradiation

• Tissue necrosis

• Foreign bodies

• Immune reactions

INFECTIONS

(bacterial, viral, fungal, parasitic) are among the most common and medically important causes of inflammation

TRAUMA AND PHYSICAL & CHEMICAL AGENTS, IRRADIATION

• Trauma (blunt and penetrating)

• Physical and chemical agents (thermal injury, e.g. burns or frostbite)

• Irradiation: (chemicals some environmental) injure host cells and elicit inflammatory reactions.

TISSUE NECROSIS

(from any cause), including ischemia (as in a myocardial infarct) and physical and chemical injury.

FOREIGN BODIES

(splinters, dirt, sutures)

IMMUNE REACTIONS

(also called hypersensitivity reactions) against environmental substances or against self- tissues.

MAIN COMPONENTS OF INFLAMMATION

I. Vascular reaction

II. Cellular response

MECHANISM OF VASCULAR RESPONSE

• Vasoconstriction

• Vasodilatation of arterioles and venules

• Stasis of blood flow

• Due increased vascular permeability

• Oozes protein-rich fluid into extravascular tissues.

• Exudates clinically appears as swelling. (edema)

STAGES OF VASCULAR RESPONSE

• Vascular dilation and increased blood flow (causing erythema and warmth)

• Extravasation and deposition of plasma fluid and proteins (edema)

• Leukocyte (mainly neutrophil) emigration and accumulation in the site of injury.

STAGES OF CELLULAR RESPONSE

1. Margination is a peripheral positioning of white cells along the endothelial cells.

2. Transmigration of leukocytes

3. Chemotaxis

4. Phagocytosis

MARGINATION IS A PERIPHERAL POSITIONING OF WHITE CELLS ALONG THE ENDOTHELIAL CELLS

• Rolling

• Pavementing

• Selectins, immunoglobulins, integrins

ROLLING

Rows of leukocytes tumble slowly along the endothelium

PAVEMENTING

Endothelium can be lined by white cells the binding of leukocytes with endothelial cells is facilitated by cell adhesion molecules

TRANSMIGRATION OF LEUKOCYTES

Diapedesis

DIAPEDESIS

The movement of leukocytes by extending pseudopodia through the vascular wall.

CHEMOTAXIS

Unidirectional attraction of leukocytes from vascular channels towards the site of inflammation within the tissue space guided by chemical gradients.

IMPORTANT CHEMOTACTIC FACTORS FOR NEUTROPHILS

(C5a) – complement system

MITOCHONDRIAL PRODUCTS OF ARACHIDONIC ACID METABOLISM

• Leukotriene B4

• Cytokines (IL-8).

PHAGOCYTIC (PHAGOCYTIC CELLS)

• Polymorphonuclear leukocytes (neutrophiles)

• Monocytes

• Tissue macrophages

CHEMICAL MEDIATORS OF INFLAMMATION

PLASMA DERIVED MEDIATORS

I. Complement activation

II. Factor XII (Haegman factor) activation

COMPLEMENT ACTIVATION

• Increases vascular permeability

• Activates chemotaxis

• Opsonization

C3a, C5a

Increases vascular permeability

C5a

Activates chemotaxis

C3b, C3bi

Opsonization

FOUR FACTORS OF FACTOR XII (HAEGMAN FACTOR) ACTIVATION

• The kinin

• The clotting

• The fibrinolytic

• The complement systems

CELLULAR MEDIATORS

• Histamine

• Serotonin

• Lysosomal Enzymes

• Prostaglandins

• Leukotrienes

• Chemoattractant

• Platelet activating factor

• Activated Oxygen Species

• Nitric Oxide

• Cytokines

CELL OF ORIGIN OF HISTAMINE

Mast cells, Basophils

CELL OF ORIGIN OF SEROTONIN

Platelets

ALL LEUKOCYTES CELL ORIGIN

• Prostaglandins

• Leukotrienes

• Activated Oxygen Species

• Platelet activating factor

CELLS OF ORIGIN OF LYSOSOMAL ENZYMES

Neutrophils

CELLS OF ORIGIN OF CHEMOATTRACTANT

LC4, LCD4, & LE4

CELLS OF ORIGIN OF NITRIC OXIDE

Macrophage

CELLS OF ORIGIN OF CYTOKINES

Lymphocyte, Macrophages

FUNCTION OF HISTAMINE

Vascular leakage and platelets

FUNCTION OF SEROTONIN

Vascular leakage

FUNCTION OF LYSOSOMAL ENZYMES

• Bacterial and tissue destruction

• Macrophage

FUNCTION OF PROSTAGLANDINS

• Vasodilation

• Pain

• Fever

FUNCTION OF LEUKOTRIENS

LB4

FUNCTION OF CHEMOATTRACTANT

Broncho and vasoconstriction

FUNCTION OF PLATELET ACTIVATING FACTOR

Bronchoconstriction and WBC priming

FUNCTION OF ACTIVATED OXYGEN SPECIES

Endothelial and tissue damage

FUNCTION OF NITRIC OXIDE AND CYTOKINES

Leukocyte activation

STEPS OF INFLAMMATORY RESPONSE

• Recognition of the injurious agent

• Recruitment of leukocytes

• Removal of the agent

• Regulation of the response

• Resolution (repair)

MORPHOLOGIC TYPES OF ACUTE INFLAMMATION

1. Serous inflammation

2. Fibrinous inflammation

3. Suppurative

TYPES OF SUPPURATIVE INFLAMMATION

A) Abscess formation

B) Acute diffuse inflammation

ACUTE DIFFUSE INFLAMMATION

Diffuse spread of the exudate through tissue spaces.

OUTCOME OF ACUTE INFLAMMATION

• Elimination of the noxious stimulus

• Decline of the reaction

• Repair of the damaged tissue

• Persistent injury resulting in chronic inflammation.

CHRONIC INFLAMMATION

Is inflammation of prolonged duration (weeks to months to years) in which active inflammation, tissue injury, and healing proceed simultaneously.

CAUSES OF CHRONIC INFLAMMATION

1. Persistent infections

2. Prolonged exposure to nondegradable but partially toxic substances either endogenous lipid components which result in atherosclerosis or exogenous substances such as silica, asbestos.

3. Progression from acute inflammation

4. Autoimmunity

ACUTE INFLAMMATION ALMOST ALWAYS PROGRESSES TO CHRONIC INFLAMMATION FOLLOWING…

Persistent suppuration as a result of uncollapsed abscess cavities, foreign body materials (dirt, cloth, wool, etc), sequesterum in osteomylitis, or a sinus/fistula from chronic abscesses.

CELLS OF CHRONIC INFLAMMATION

• Monocytes

• Macrophages

MACROPHAGES

Scavenger cells of the body

LIVER

Kuppfer cells

SPLEEN, LYMPH NODES

Sinus histiocytes

LUNGS

Alveolar macrophages

BONE MARROW, BRAIN

Microglia

SKIN

Langerhan’s cells

CELLS CONSTITUTE THE MONONUCLEAR

Phagocytic system

OTHER CELLS IN CHRONIC INFLAMMATIONS

1. T-Lymphocytes

2. B-lymphocytes and Plasma cells

3. Mast cells and eosinophils

CLASSIFICATION OF CHRONIC INFLAMMATION

• Nonspecific chronic inflammation

• Specific inflammation (granulomatous inflammation)

SPCIFIC/ GRANULOMATOUS INFLAMMATION

Characterized by the presence of granuloma

GRANULOMA

Is a microscopic aggregate of epithelioid cells

EPITHELIOID

• Cell is an activated macrophage, with a modified epithelial cell-like appearance.

• The epitheloid cells can fuse with each other & form multinucleated giant cells

TYPES OF GIANT CELLS

• Foreign body-type giant cells

• Langhans giant cells

FOREIGN BODY- TYPE GIANT CELLS

Which have irregularly scattered nuclei in presence of indigestible materials

LANGHANS GIANT CELLS

The nuclei are arranged peripherally in a horse –shoe pattern which is seen typically in tuberculosis, and sarcoidosis.

TYPES OF GRANULOMAS

• Foreign body granuloma

  • Granulomas are initiated by inert foreign

  • Immune granulomas

• Antigen presenting cells (macrophages) engulf a poorly soluble inciting agent.

• Macrophage inhibitory factor helps to localize activated macrophages and epithelioid cells

MAJOR CAUSES OF GRANULOMATOUS INFLAMMATION

• Bacterial

• Fungal

• Helminthic

• Protozoal

• Chlamydia

BACTERIAL

Tuberculosis, Leprosy, Syphilis, Cat scratch disease, Yersiniosis

FUNGAL

Histoplasmosis, Cryptococcosis, Coccidioidomycosis, Blastomycosis

HELMINTHIC

Schistosomiasis

PROTOZOAL

Leishmaniasis, Toxoplasmosis

CHLAMYDIA

Lymphogranuloma venerum

SYSTEMIC EFFECTS OF INFLAMMATIONS

a. Fever

b. Endocrine & metabolic responses

c. Autonomic responses

d. Behavioral responses

e. Leukocytosis

f. Leukopenia

g. Weight loss

TISSUE REPAIR

Restoration of tissue architecture and function after an injury

TISSUE REPAIR OCCURS IN TWO WAYS

• Regeneration of injured tissue

• Replacement by connective tissue (scarring)

TISSUE REPAIR INVOLVES BOTH PROCESSES

• Cell proliferation

• Interaction between cells and extracellular matrix

PROCESSES IN THE PROLIFERATION OF CELLS

1. DNA replication

2. Mitosis