Table of Contents
Definition of Inflammation
Inflammation is defined as the body’s response to injurious stimuli in the form of trauma or colonization with bacterial organisms. It is a protective reaction focused on getting rid of the original source of cell injury as well as the cells and tissues that have undergone necrosis. Without inflammation, infections would be rampant and wounds would fail to heal normally. Inflammation forms part of innate immunity.
Inflammatory response and repair mechanism can also cause significant harm when its components are destroyed and eliminated. Microbes and dead tissues can contribute to the destruction of normal tissues if the inflammatory response is severe or prolonged.
Causes of Inflammation
Some common causes of inflammation include:
- Pathogenic Infections by bacteria, viruses, fungi and, parasites
- Injuries such as scratches and trauma from foreign bodies
- Chemical injury, e.g. toxins and alcohol
- Hypersensitivity reactions against environmental substances or against self-tissues (Autoimmune reactions)
The five cardinal signs of inflammation form the basic principle of pathology and include:
- Rubor/redness: arises from increased blood flow and accumulation at the point of injury or inflammation.
- Calor/Hotness due to an accumulation of warm flow of blow and the heat produced from local reaction/ irritation.
- Tumor/Swelling the released inflammatory mediators at the site lead to increased fluid extravasation causing edema and swelling.
- Dolor/Pain is mediated by cytokines like bradykinins and prostaglandins
- Functional laesa/loss of bodily functions occurs with the affection of an organ.
Pathophysiology and Stages of Inflammation
Inflammation can be acute or chronic. Acute inflammation is the immediate innate body response to harmful agents which are usually bacterial pathogens and physical tissue injuries. The involved cells which are part of the cellular complexity of the inflamed tissue e.g. macrophages, histiocytes, and Kupffer cells, recognize pathogens and damaged cellular debris through pathogen-associated molecular patterns and damage-associated molecular patterns, PAMs and DAMs. These are surface receptors that recognize pathogenic antigens and cellular debris.
Activation of these surface receptors leads to a release of histamine, nitric oxide, and prostaglandins from tissue macrophages, mast cells, and vascular endothelial cells. These mediators are responsible for the dilatation of blood vessels at the inflamed area and increase capillary permeability known as a vascular phase.
Fluid shift into the inflamed tissue space will establish an inflammatory response which results in redness and hotness with exudation of fluids containing proteins e.g. fibrin, antibodies, and complement proteins. These proteins function to fight the invading pathogen and limit the infection process.
Exudation of plasma from the blood will lead to stasis with subsequent extravasation of inflammatory cells from stagnant blood to the injured tissues which are known as a cellular phase.
Tissue macrophages and mast cells release inflammatory mediators, which lead to vasodilatation and increase tissue permeability. These mediators are also responsible for recruiting more inflammatory cells from the blood to the site of injury.
Inflammatory cells function to phagocytize foreign materials, promote the immune response and secrete other mediators. Inflammatory cells in acute inflammation are mainly granulocytes while in chronic inflammation they are lymphocytes and monocytes.
Extravasation of cells from the blood to the tissue space starts with margination of the cell towards the endothelial surface of the blood vessels due to interleukins and TNF-α. These mediators enhance the expression of ICAM-1, P-selectin and E-selectin on the endothelial cell surface to induce their adhesion with blood leukocytes before their migration.
Chemokines-activated leukocytes find their way to the inflamed tissue through transmigration across the endothelium and basement membrane via acquiring foot processes to move between endothelial cells; a process called diapedesis.
Chemotactic factors e.g. C3a and C5 then guide leukocytes towards the site of tissue injury within the intercellular space via protein adhesions and binding to tissue integrins.
Neutrophils that migrate to the inflammation site act as phagocytes for the foreign organisms and cellular debris. The cells destroy the engulfed microorganisms via lysosomal enzymes and reactive oxygen species that can be introduced later as antigen presenting cells.
Phagocytosis is the process of engulfing foreign materials by phagocytes. These foreign materials include pathogens, dead cells, foreign debris, and abnormal cells. Phagocytes can recognize the foreign material via surface receptors including PRRs that bind to PAMPs, opsonin receptors that bind to bacteria coated with complement and antibodies opsonization proteins and scavenger receptors.
Opsonization occurs after complement protein C3b with the foreign antigen binds to CR1 complement receptor on the surface of phagocytes to facilitate its immune destruction.
Types of Inflammation
Serous inflammation occurs with mild irritation of the epithelial or mesothelial surfaces with resultant homogenous watery exudate from the plasma or lymph. It is more common on the skin and mesothelial membranes.
Mucinous or catarrhal inflammation occurs with cuboidal cells where the exudate is mainly mucin. It is more common in the respiratory tract.
Purulent inflammation occurs when the inflammatory process is secondary to violent organisms e.g. staphylococci that result in large amounts of pus composed of neutrophils and dead cells. Pus isolation with fibrosis and histiocytes is known as an abscess.
Fibrinous inflammation occurs in fibrin-rich exudate which will organize to form a fibrous mesh. It occurs mainly in viral inflammation and chemical or physical irritation. Fibrinous inflammation will lead to a permanent dysfunction in the affected tissue as fibrosis lack parenchymal cells e.g. scars on the skin surface, liver fibrosis in viral and alcoholic hepatitis. Fibrosis can also occur on the surface of tissues leading to the pseudo-membrane formation which is a devitalized membrane of fibrous tissue as in pseudomembranous colitis.
Hemorrhagic inflammation occurs with exudate full of erythrocytes or blood. It is common with a viral infection and physical irritation. The hemorrhagic exudate is rich in cellular components and fibrin, which form into a clot limiting organ functions.
Ulcerative inflammation occurs with loss of necrotic epithelial integrity leading to ulcer formation on epithelial surfaces.
Granulomatous inflammation occurs with persistent inflammation leading to formation of walls of histiocytes, known as granulomas, surrounding the area of inflammatory focus. It is common in chronic inflammatory conditions e.g. tuberculosis and sarcoidosis. They can be either caseating where the central area is made up of dead foreign body surrounded by immunocompetent cells or non- caseating granulomas.
Fate of Acute Inflammation
The results of acute inflammation are dependent on the nature and intensity of the injury, the site and tissue affected, and the ability of the host to evoke a response. Interestingly, these mediators are short-acting and they are active only as long as there is a pathogenic stimulation. After resolution of the offending stimulus, fibrin mesh act to guide wound healing and resolution of the inflammatory products by macrophages and lymphatic drainage to the regional lymph nodes.
Persistence of the offending agent will lead to fibrosis to control the infection, abscess formation or chronic inflammation lasting for months or years with delayed healing. Chronic inflammation is characterized by replacement of neutrophils with macrophages and fibroblasts releasing IFN-γ and reactive oxygen species characterized by more fibrosis and more tissue destruction.
Chronic inflammation is a prolonged inflammation where active inflammation, tissue injury, and healing proceed concurrently, leading to an increased number of lymphocytes and macrophages resulting in vascular proliferation and fibrosis.
Acute inflammation may progress to chronic inflammation. This is evident when the acute response cannot be regulated, either due to persistence of the injurious agent or as a result of interference with the normal healing process.
Chronic inflammation arises in the following settings:
- Persistent infections – by microbes that are difficult to eradicate. For example, mycobacteria and certain viruses and fungi.
- Immune-mediated inflammatory diseases (hypersensitivity diseases) – These arises from excessive and inappropriate activation of the immune system.
Prolonged exposure to potentially toxic agents – They include non-degradable exogenous materials such as inhaled particulate silica, which causes a chronic inflammatory known as silicosis and endogenous agents that chronically elevated plasma lipid components, which leads to atherosclerosis.