inflammation and Repair

INFLAMMATION AND REPAIR

Overview

Inflammation is the biological response of living, vascularized tissue to injury. This response involves the microcirculation reacting to different forms of injury.

INFLAMMATION: ADVANTAGES AND DISADVANTAGES

Advantages

  1. Protection: An immediate response that helps protect the body from further injury.

  2. Destruction: Destroys, dilutes, or walls off injurious agents, preventing their spread.

  3. Repair Mechanisms: Sets into motion events leading to tissue repair.

Disadvantages

  1. Autoimmune & Hypersensitivity Reactions: These can be life-threatening.

  2. Fibrosis: Leads to scars and fibrous bands that can contribute to complications such as intestinal obstruction or limitation of range of motion.

  3. Chronic Diseases: Conditions like rheumatoid arthritis and lung fibrosis can arise from sustained inflammation.

CARDINAL SIGNS OF INFLAMMATION

  1. Heat (Calor): Increased blood flow to the site of inflammation.

  2. Redness (Rubor): Caused by vasodilation and increased blood flow.

  3. Edema (Tumor): Accumulation of fluid in the interstitial spaces.

  4. Pain (Dolor): Due to release of inflammatory mediators that sensitize nerve endings.

DEFINITIONS

  • Exudation: The process by which fluid, proteins, and blood cells escape from the vascular system into interstitial tissues or body cavities.

  • Exudates: An inflammatory fluid that is rich in protein and cells, typically with a specific gravity over 1.020.

  • Transudate: A fluid with low protein content, resulting from alterations in hydrostatic pressure across the vascular endothelium, characterized by a specific gravity less than 1.012.

  • Edema: The presence of excess fluid in interstitial tissue or body cavities.

  • Pus: A purulent exudate rich in leukocytes and dead cellular debris.

ACUTE INFLAMMATION

Major Components

  1. Increased Blood Flow: Alterations in the vascular caliber lead to increased blood flow.

  2. Increased Vascular Permeability: Structural changes in the microvasculature result in greater permeability.

  3. Leukocyte Emigration: Leukocytes exit the microcirculation and accumulate at the injury site.

Vascular Phase

  1. Vasoconstriction: Initial constriction of blood vessels.

  2. Vasodilation: Active hyperemia increases blood flow, leading to redness and heat (rubor & calor).

  3. Increased Vascular Permeability: Results in vascular leakage, contributing to edema.

Mechanisms of Vascular Leakage

  1. Endothelial Contraction: Immediate response mediated by substances like histamine.

  2. Endothelial Retraction: A delayed response resulting from cytoskeletal reorganization due to several mediators.

  3. Increased Transcytosis: Involves changes in endothelial permeability and is modulated by factors like VEGF.

  4. Direct Endothelial Injury: Results in sustained leakage occurred immediately following injury.

ACUTE INFLAMMATION CELLULAR PHASE

Steps of Cell Response

  1. Margination: Leukocytes occupy the periphery of blood vessels.

  2. Rolling: Leukocytes roll along the endothelium due to temporary adhesion.

  3. Firm Adhesion: Strong attachment of leukocytes to endothelial cells mediated by adhesion molecules.

  4. Emigration: Leukocytes exit blood vessels to reach the site of injury.

  5. Chemotaxis: Movement of leukocytes towards the site influenced by chemical signals.

  6. Phagocytosis: Engulfment and destruction of pathogens or debris, involving recognition, engulfment, and degradation.

PHAGOCYTOSIS

Killing and Degradation Mechanisms

  1. Oxygen-Dependent Killing: Utilizes reactive oxygen species produced by leukocytes.

  2. Oxygen-Independent Killing: Involves the release of enzymes from leukocytes.

OUTCOMES OF ACUTE INFLAMMATION

  1. Resolution: Return to normal state mediated by various factors.

  2. Abscess Formation: Results from localized inflammation and necrosis.

  3. Chronic Inflammation: Occurs if the acute response fails to eliminate the cause of inflammation.

  4. Scarring and Fibrosis: Replacement of tissue by fibrous connective tissue, leading to functional loss.

CHEMICAL MEDIATORS OF INFLAMMATION

General Principles

  1. Mediators can be plasma-derived or cell-derived and are short-lived.

  2. They can have systemic effects or act locally at injury sites.

  3. Majority of mediators bind to specific receptors on target cells.

Cell-Derived Chemical Mediators

  • Vasoactive Amines: Including histamine and serotonin, contribute to increased vascular permeability.

  • Arachidonic Acid Metabolites: Derivatives such as prostaglandins and leukotrienes play roles in inflammation.

  • Cytokines: Cell signaling proteins like IL-1 and TNF regulate immune responses.

CHRONIC INFLAMMATION

Chronic inflammation is characterized by prolonged duration, comprised of active inflammation, tissue damage, and healing processes occurring simultaneously. Features include mononuclear cell infiltration, ongoing tissue destruction, and attempts at repair through connective tissue replacement.

HEALING AND REPAIR

Healing can occur through regeneration, which restores normal tissue structure, or repair, which involves scar formation. Factors influencing wound healing include systemic factors like nutrition and local factors such as infection.

PATHOLOGICAL ASPECTS OF REPAIR

Complications in wound healing can manifest as deficient scar formation, excessive scar formation (keloids), or contractures, leading to functional impairment.