By: Jade A.

Domasing

Definition: Inflammation is a protective response intended to remove injurious stimuli as well as the necrotic cells and tissues resulting from original insert. OR Repair process that causes the replacement of damaged tissues by regeneration of parenchyma cells or by filling of any residual defect by fibrous scar tissues

It causes destruction of microbes. Causes detoxification of toxins. Clears infections. Helps in healing process. Causes repair of damaged tissues.

Inflammatory responses are sometimes harmful as they cause: Life threatening anaphylactic reactions to insects bites, drugs and other chronic diseases like Rheumatoid arthritis, Atherosclerosis etc.

Inflammation of peritoneum leads to fibrous bands that causes obstruction of intestines. Pericardial inflammation causes the formation of dense pericardium that impairs cardiac functions.

The inflammatory responses have many players. They include: 1) CIRCULATING CELLS: I. Bone marrow derived polymorphonuclear leukocytes e.g., Basophils, Esinophils and Neutrophils. II. Lymphocytes III. Monocytes IV. Platelets. 2) CIRCULATING PROTEINS: I. Clotting factors II. Kininogens III. Complement proteins

3) VASCULAR WALL CELLS: I. Connective tissue cells II. Smooth muscle cells III. Epithelial cells 4) EXTRA CELLULAR MATRIX: I. Fibrous structural proteins e.g., Elastin & Fibrinogen II. Gel-forming proteoglycans III. Adhesive glycoprotein e.g., Fibronectin, that are cell-ECM and ECM-ECM connectors.

Inflammatory stimulus Chemical mediators Inflammatory response until injurious stimulus is removed When the inflammatory stimulus is removed these mediators are then dissipated, catabolized or removed.

TYPES OF INFLAMMATION:
Acute inflammation And Chronic inflammation

Acute inflammation has two major components: Vascular component Cellular (leukocytes) component Which result in the classic clinical pentad of: Calor (Heat) Rubor (Redness) Tumor (Swelling) Dolor (Pain) Functio laesa (Loss of funtion)

Arteriolar vasodilation results in locally increased blood flow, engorgement of the capillary bed, and increased transudation Exudationof protein-rich fluid from the lumen into the extracellular space results in Outflow of water and ions into the interstitial space (edema) Increased blood viscosity and decreased flow (stasis) Stasis helps leukocytes escape the flow and attach to the vascular endothelium (margination) Margination leads to transmigration of leukocytes out of the vessel into the interstitial space

1 Endothelial gap formation Endothelial cell contraction Cytoskeletal reorganization 2 Endothelial cell injury Direct Leukocyte-mediated 3 Increased transcytosis(vesicular trafficking) 4 Angiogenesis

Margination and rolling Adhesion and transmigration Migration in the interstitial space

Plasma-derived:

Complement, kinins, coagulation factors Many in pro-form requiring activation (enzymatic cleavage)
Preformed, sequestered and released (mast cell histamine) Synthesized as needed (prostaglandin)

Cell-derived:

Complete resolution

Little tissue damage Capable of regeneration In tissues unable to regenerate Excessive fibrin deposition organized into fibrous tissue

Scarring (fibrosis)

Abscess formation occurs with some bacterial or fungal infections Progression to chronic inflammation

Chronic inflammation is the inflammation with prolonged duration usually from weeks to months and sometimes to years in which active inflammation, tissue injury and healing process proceed simultaneously. DISTINGUISHING FEATURES: Infiltration of mono-nuclear cells like lymphocytes, macrophages and plasma cells. Destruction of tissue by inflammatory cells. Proliferation of new vessels leading to repair (angiogenesis & fibrosis).

ORIGIN AND PROCESS: Chronic inflammation arises from acute inflammation. This transition takes place if the acute responses cannot be resolved either because of the persistence e.g., of injurious stimuli or by interference of the normal healing process e.g., peptic ulcer. Some types of injuries engender responses with chronic inflammation initially e.g., viral infections. SETTINGS LEADING TO CHRONIC INFLAMMATION: I. Viral infections II. Persistent microbial infections III. Prolonged exposure to potentially toxic materials IV. Autoimmune diseases

CHRONIC INFLAMMATORY CELLS & MEDIATORS: 1) MACROPHAGES: Macrophages are white blood cells within tissues, produced by the division of monocytes. A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of dust is likely to occur. Each type of macrophage, determined by its location, has a specific name: In liver Kupffer cells Spleen and lymph nodes - Sinus histocytes Nervous system - Microglial cells Lungs - Alveolar macrophages

FUNCTIONS OF MACROPHAGES: They help to: Filter the particulate matter Kill microbes Alert immune system of the body. Their life is 1-2 days. ACTIVATION OF MACROPHAGES: Activation of macrophages means: Increase in size Increase in lysosomal content Increase in metabolism Increase in microbial killing activity

ACTIVATION SIGNALS: Different signals required to activate macrophages are: Cytokines produced by T-lymphocytes Bacterial endotoxins Different mediators produced during acute inflammation Extra cellular matrix proteins e.g., Fibrinogen When macrophages become activated they produce different type of biologically active substances that either cause ; Cell injury OR Fibrosis.

2) LYMPHOCYTES: Lymphocytes are mobilized in the setting of any immune stimulus as well as in non-immune mediated inflammation. They are initially activated by interaction with macrophages presenting processed antigen fragments on their cell surface. 3) EOSINOPHILS: Are characteristics found in inflammation sites around parasitic infections or as part of immune reactions mediated by IgE, typically associated with allergies.

4) MAST CELLS: Are sentinel cells widely distributed in connective tissues throughout the body and can participate in both acute and chronnic inflammatory responses.

TYPES OF CHRONIC INFLAMMATION: 1) A GRANULOMATOUS: Granuloma is not formed, Inflammation is characterized by all features of chronic inflammation. Examples: Chronic viral infections e.g., Hepatitis Chronic autoimmune diseases e.g., Rheumatoid arthritis and Ulcerative colitis Chronic chemical intoxication e.g., Chronic alcoholic liver disease Allergic reactions e.g., Bronchial asthma

2) GRANULOMATOUS INFLAMMATION: Characterized by aggregates of activated macrophages that assume a squamous cell like epithelloid appearance. GRANULOMA is defined as aggregates of macrophages formed due persistant response of T-lymphocytes to particular antigens. This has a granular cheesy appearance called as caseous necrosis. Examples are: Bacterial: Tuberculosis , Leprosy, Syphilis gumma etc.

Serous Inflammation. This is characterized by the outpouring of a watery, relatively protein poor fluid (effusion) that depending on the site of injury, derives either from the serum or from the secretions of mesothelial cells lining the peritoneal, pleural and pericardial cavities. Fibrinous Inflammation. This occurs as a consequence of more severe injuries, with a resultant greater vascular permeability allowing larger molecules to pass the endothelial barrier.

Suppurative (Purulent) Inflammation. This is manifested by the presence of large amounts of purulent exudate (pus) consisting of neutrophils, necrotic cells and edema fluid. Ulceration. This refers to a site of inflammation where an epithelial surface has become necrotic and eroded, often with associated subepithelial acute and chronic inflammation.

Anyone who has suffered through a severe bout of a viral illness has experienced the systemic effects of inflammation, collectively called acute-phase reaction. Fever is only one of the more obvious of these systemic effects of inflammation; others include increased somnolence. Malaise, anorexia, accelerated degradation of skeletal muscle proteins, hypotension, hepatic synthesis of a variety of proteins.

Thank you so much for listening! *God bless