Chemical Mediators of Inflammation

• Chemical mediators are substances derived from damaged tissues, inflammatory cells, and plasma during acute inflammation.
• These mediators initiate and promote vascular phenomena.

Types of Chemical Mediators: Cellular

• Amines like histamine and serotonin are released from mast cells, basophils, and platelets.
• Arachidonic acid metabolites include prostaglandins and leukotrienes.
• Cytokines include Interleukin-1 (IL-1), Interferon (INF), and Tumor Necrosis Factor (TNF).
• Lysosomal enzymes are released from neutrophils, macrophages, and platelets.
• Oxygen-derived free radicals include hydrogen peroxide (H2O2) or superoxide.

Types of Chemical Mediators: Plasma

• Peptides include fibrin and fibrin degradation products.
• The clotting system converts fibrinogen into fibrin.
• The complement system involves plasma proteins C1-C9 and their active products like C3a & C5a.
• Kinines include bradykinin.
• The fibrinolytic system converts fibrin into osmotically active fibrin degradation products.

Role of Chemical Mediators

• Vasodilation is caused by prostaglandins.
• Increased vascular permeability results from vasoactive amines (histamine, serotonin), C3a and C5a (inducing vasoactive amine release), bradykinin, leukotrienes C4, D4, E4, and platelet-activating factor.
• Chemotaxis and leukocyte activation are caused by C5a, leukotriene B4, bacterial products, and cytokines like interleukin 8 (IL-8).
• Fever is caused by IL-1, IL-6, and tumor necrosis factor, and prostaglandins.
• Pain is caused by prostaglandins and bradykinin.
• Tissue damage results from neutrophil and macrophage lysosomal enzymes, and oxygen metabolites.

Morphological Changes in Acute Inflammation

• Includes necrosis of Cardinal signs and microscopic features

Cardinal Signs of Acute Inflammation

• Redness is due to vasodilation and increased blood flow.
• Hotness results from increased blood flow.
• Swelling is due to fluid exudates.
• Pain arises from stimulation of nerve endings by chemical mediators (bradykinin and prostaglandin) or pressure from inflammatory oedema.
• Loss of function results from pain and tissue damage.

Microscopic Features of Acute Inflammation

• Necrotic tissues and degenerated cells are present.
• Acute inflammatory cells, such as neutrophils, are numerous in pyogenic infections; dead neutrophils are called pus cells.
• Macrophages are derived from blood monocytes and tissue histiocytes.
• Eosinophils appear in allergic inflammation.
• Lymphocytes appear in viral infections.
• Blood vessels become thin-walled, dilated, and congested.
• Acute inflammatory oedema (fluid exudate) separates tissues and causes pale staining of fibers and fibrin

General (Systemic) Reaction in Acute Inflammation

• Involves changes in blood cells, fever, loss of weight and appetite.
• The liver secretes C-reactive proteins and Amyloid material A.
• Hyperplasia of the draining lymph nodes may occur in the reticuloendothelial system.
• Changes in blood cells include variations in WBCs (normal count: 5000-10000| mm3)
• Leucocytosis is an increased number of WBCs (more than 10,000/mm3).
• IL-1 & TNF, released from macrophages, stimulate bone marrow for proliferation of leucocytes
• Neutrophils increase in pyogenic or suppurative inflammation, while eosinophils increase in parasitic infection and allergic reaction
• Leucopenia is a decreased number of leucocytes, seen eg., in typhoid fever.
• Some degree of anemia results due to toxic depression of bone marrow and haemolysis of RBCs (e.g., malaria).
• Fever arises from the release of pyrogens (fever-producing materials) by bacteria, leucocytes, and macrophages, leading to disturbance of the thermoregulatory center in the hypothalamus.
• Loss of weight and appetite is due to increased catabolism and toxins.
• The liver secretes C-reactive proteins and amyloid material A.
• Hyperplasia occurs in the draining lymph nodes and the reticuloendothelial system (e.g., liver, spleen, and bone marrow) as a generalized defense mechanism

Fate of Acute Inflammation

• Resolution occurs if body resistance overcomes the irritant and minimal tissue damage occurs, allowing tissue to return to normal.
• Spread occurs if the irritant overcomes the body defenses
• Direct spread is by fluid exudate passing to surrounding tissues.
• Blood spread produces bacteremia, toxemia, and septicemia.
• Lymphatic spread produces lymphangitis and lymphadenitis.
• Chronicity arises if the cause of inflammation cannot be completely destroyed by defensive measures.
• Suppuration results in abscess formation.
• Healing (repair) occurs if tissue damage is present, happening either by regeneration or fibrosis.