Acute Inflammation Overview

Acute Inflammation

• Acute inflammation is a rapid response to tissue injury, characterized by four major components
• These components include vascular changes, microvascular changes, cellular events, and mediators.

Vascular Changes

• Alteration in vascular caliber results in increased blood flow, known as vasodilation
• The increased blood flow enables the movement of more cells and proteins to the affected area

Microvascular Changes

• Increased permeability of the microvasculature allows plasma proteins and white blood cells (WBCs) to leak into the injured tissue
• This leakage is crucial for the inflammatory response

Cellular Events

• Involves the recruitment, accumulation, and activation of white blood cells (WBCs) at the site of injury
• WBCs migrate to the site of injury driven by chemical signals

Mediators

• Chemical substances derived from plasma proteins and cells that trigger different processes in the inflammatory response
• The mediators are categorized into cell-derived and plasma-derived mediators

Cell-Derived Mediators

• Cell-derived mediators are differentiated according to their origin

• Some mediators are preformed and stored in granules, while other mediators are synthesized as needed

• Mediators and Sources:*

• Histamine: Mast cells, basophils, platelets

• Serotonin: Platelets

• Lysosomal enzymes: Neutrophils, macrophages

• Prostaglandins: All leukocytes, platelets, endothelial cells (ECs)

• Leukotrienes: All leukocytes

• Platelet-activating factors (PAFs): All leukocytes, ECs

• Activated oxygen species: All leukocytes

• Nitric oxide: Macrophages

• Cytokines: Lymphocytes, macrophages, ECs

Principles of Mediators

• Initially bind to specific receptors and act
• Initiate the release of other mediators
• Affect one or a few specific target cell types
• Have short lifespans
• Can be harmful (in certain contexts)

Active Mediators

• Produced in reaction to injurious stimuli, like microbial products or necrotic cells
• Include proteins from the complement, kinin, and coagulation systems activated by microbes and injured tissues
• Ensures the inflammation response is localized and triggered only when and where needed

Roles of Mediators

• Affect blood vessels
• Affect inflammatory cells
• Affect other cells within the body
• Have diverse effects on the body (vasodilation, vasoconstriction, altered permeability, activation of inflammatory cells and cells within the body)

Effects of Mediators

• Vasodilation: widening of blood vessels
• Vasoconstriction: narrowing of blood vessels
• Altered vascular permeability: increased leakage of fluid from blood vessels to affected tissue
• Activation of inflammatory cells: stimulation of white blood cells to migrate into injured tissue
• Chemotaxis: recruitment of inflammatory cells to the affected area
• Cytotoxicity: destruction of cells
• Degradation of tissue: breakdown of tissue
• Pain: sensation of pain
• Fever: elevation of body temperature

(A) Cell-Derived Mediators

• Vasoactive amines (Histamine): Most notable example; originating in mast cells, basophils, and platelets. Effects: (1) vasodilation, (2) increased venular permeability, (3) endothelial activation

• Arachidonic Acid (AA) Metabolites (Prostaglandins & Leukotrienes): Prostaglandins (PGI2, PGD2, PGE2): mediate vasodilation, pain, and fever. Leukotrienes (LTB4, LTC4, LTD4, LTE4): mediate increased vascular permeability, chemotaxis, and leukocyte adhesion and activation. Originating in mast cells and leukocytes (mainly neutrophils). Involved in all stages of inflammation

• Platelet-Activating Factors (PAFs): Produced by mast cells and other leukocytes (mainly neutrophils). Effects: vasodilation, increased vascular permeability, leukocyte adhesion, oxidative burst, chemotaxis, and induced platelet degranulation.

• Cytokines: Proteins produced by many cell types that modulate the functions of other cells. Produced by activated lymphocytes and macrophages to modulate other cell types. Involved in both acute and chronic inflammation

• Nitric Oxide (NO): A potent vasodilator. Source: Soluble gas produced by endothelial cells and macrophages. Acts as a regulator of inflammation, actively reducing the effects of other pro-inflammatory mediators.

(B) Plasma protein-derived mediators

• Circulate in an inactive form

• Require activation from an activator

• Numerous, both specific and non-specific activators

• Include natural in-activators to maintain an inflammatory balance

• Three Interrelated Protein Systems:*

• Complement: Derived from plasma

• **Bradykinin:**Derived from plasma

• Factor XII: Derived from plasma

Morphological Patterns of Acute Inflammation

• Serous: Outpouring of thin fluid from plasma or mesothelial cells; examples include skin blisters
• Fibrinous : Deposition of fibrin in extra-cellular spaces occurs with sever injuries; examples include fibrinous exudate
• Purulent (Suppurative Inflammation): Production of pus encompassing neutrophils, liquefactive necrosis, and edema fluid; caused by pyogenic bacteria like staphylococci. Often seen as localized collections (abscesses)
• Haemorrhagic: presence of blood
• Ulcers: a local defect or excavation on an organ or tissue surface; occurs when tissue necrosis and inflammation exist on, or near, a surface