Inflammation
In 1863, Rudolf Virchow hypothesized that the origin of cancer was at sites of chronic inflammation. This observation links a biological defense mechanism to long-term disease processes. Inflammation is part of the biological defence response of body tissues. It acts as a generic response and serves as a mechanism of innate immunity rather than adaptive immunity. The process involves immune cells, blood vessels, and molecular mediators working together to eliminate an initial cause of cell injury. It also clears out damaged cells and tissues while initiating tissue repair. Without this response, progressive tissue destruction by harmful stimuli like bacteria could compromise survival. However, too much inflammation can have negative effects. Chronic inflammation is associated with various diseases such as hay fever, periodontal disease, atherosclerosis, and osteoarthritis. Five cardinal signs characterize this response: heat, pain, redness, swelling, and loss of function. These traditional names come from Latin as calor, dolor, rubor, tumor, and functio laesa. The first four classical signs were described by Celsus between 30 BC and 38 AD. The fifth sign, loss of function, is believed to have been added later by Galen, Thomas Sydenham or Rudolf Virchow.
A short-term process usually appears within a few minutes or hours and begins to cease upon removal of the injurious stimulus. Acute inflammation occurs immediately upon injury and lasts only a few days. In contrast, chronic inflammation is inflammation that lasts for months or years. A series of biochemical events propagates and matures the inflammatory response involving the local vascular system and immune system. Prolonged inflammation leads to a progressive shift in the type of cells present at the site of inflammation. Mononuclear cells predominate in chronic inflammation unlike neutrophils which dominate acute inflammation. Diabetes, cardiovascular disease, allergies, and chronic obstructive pulmonary disease are examples of diseases mediated by chronic inflammation. Obesity, smoking, stress and insufficient diet are some factors that promote chronic inflammation. Inflammation lasting two to six weeks is designated subacute inflammation. Normal healthy responses become activated, clear the pathogen and begin a repair process before ceasing. Acute inflammatory response requires constant stimulation to be sustained because mediators are short-lived and quickly degraded in tissue. When the injurious agent persists then chronic inflammation will ensue. This process may lead to the formation of a chronic wound marked by inflammation lasting many days, months or even years.
Upon contact with pathogen-associated molecular patterns, tissue macrophages and mastocytes release vasoactive amines such as histamine and serotonin. These mediators vasodilate and permeabilize blood vessels resulting in net distribution of blood plasma from vessel into tissue space. Increased collection of fluid causes swelling known as edema. Vasodilation occurs first at arteriole level progressing to capillary level bringing about redness and heat of inflammation. Increased permeability results in movement of plasma into tissues with resultant stasis due to concentration of cells within blood. Stasis allows leukocytes to marginate along endothelium critical for their recruitment into tissues. The cellular component involves leukocytes which normally reside in blood and must move into inflamed tissue via extravasation. Various leukocytes particularly neutrophils are critically involved in initiation and maintenance of inflammation. Leukocyte margination and endothelial adhesion see white blood cells move peripherally towards walls of vessels. Activated macrophages release cytokines like IL-1 and TNFα leading to production of chemokines that bind proteoglycans forming gradient in inflamed tissue. Cytokines induce immediate expression of P-selectin on endothelial cell surfaces causing leukocytes to roll along surface as bonds made and broken. Migration across endothelium known as transmigration via diapedesis sees adhered leukocytes move between adjacent endothelial cells. Movement of leukocytes within tissue follows chemotaxis where they bind extracellular matrix proteins via integrins and CD44.
Specific patterns of acute and chronic inflammation appear during particular situations such as when inflammation occurs on epithelial surface or pyogenic bacteria involved. Granulomatous inflammation characterized by formation of granulomas results from limited but diverse number of diseases including tuberculosis, leprosy, sarcoidosis, and syphilis. Fibrinous inflammation resulting in large increase vascular permeability allows fibrin to pass through blood vessels. If appropriate procoagulative stimulus present such as cancer cells a fibrinous exudate deposited commonly seen in serous cavities. Purulent inflammation resulting in large amount pus consists of neutrophils dead cells and fluid. Infection by pyogenic bacteria such as staphylococci characteristic of this kind of inflammation. Large localised collections of pus enclosed by surrounding tissues called abscesses. Serous inflammation characterized by copious effusion non-viscous serous fluid commonly produced by mesothelial cells of serous membranes. Skin blisters exemplify this pattern of inflammation. Ulcerative inflammation occurring near epithelium can result necrotic loss tissue from surface exposing lower layers. Subsequent excavation in epithelium known as ulcer. These morphological patterns help categorize specific inflammatory responses found in pathology.
Atherosclerosis formerly considered lipid storage disorder now understood chronic inflammatory condition involving arterial walls. Research established fundamental role for inflammation mediating all stages of atherosclerosis from initiation through progression ultimately thrombotic complications. Clinical studies show elevation markers inflammation predicts outcomes people acute coronary syndromes independently myocardial damage. Low-grade chronic inflammation indicated levels inflammatory marker C-reactive protein prospectively defines risk atherosclerotic complications adding prognostic information provided traditional risk factors like LDL levels. Inflammatory processes triggered negative cognition consequences stress violence deprivation contribute developing major depressive disorder. A 2019 meta-analysis found chronic inflammation associated 30% increased risk developing major depressive disorder supporting link between inflammation mental health. It long recognized infection HIV characterized not only development profound immunodeficiency but also sustained inflammation immune activation. Chronic inflammation critical driver immune dysfunction premature appearance aging-related diseases immune deficiency. Many now regard HIV infection evolving virus-induced immunodeficiency also chronic inflammatory disease. Even introduction effective antiretroviral therapy effective suppression viremia HIV-infected individuals chronic inflammation persists. Cancer orchestrates microenvironment around tumours contributing proliferation survival migration. As of 2012 chronic inflammation estimated contribute approximately 15% to 25% human cancers.
Certain drugs or exogenous chemical compounds known affect inflammation. Vitamin A deficiency causes increase inflammatory responses anti-inflammatory drugs work specifically inhibiting enzymes produce inflammatory eicosanoids. Recent developments treatment atherosclerosis focused addressing inflammation directly. New anti-inflammatory drugs monoclonal antibodies targeting IL-1β studied large clinical trials showing promising results reducing cardiovascular events. These drugs offer potential new avenue treatment particularly patients do not respond adequately statins. However concerns long-term safety cost remain significant barriers widespread adoption. Outcomes determined tissue injury occurred injurious agent causing it. Resolution complete restoration inflamed tissue back normal status inflammatory measures cease damaged parenchymal cells regenerate. Fibrosis large amounts tissue destruction damage tissues unable regenerate cannot regenerated completely body. Fibrous scarring occurs areas damage forming scar composed primarily collagen. Scar will contain any specialized structures such parenchymal cells hence functional impairment may occur. Abscess formation cavity formed containing pus opaque liquid dead white blood cells bacteria general debris destroyed cells. Chronic inflammation acute inflammation injurious agent persists ensues process marked inflammation lasting many days months even years. This process almost always accompanied tissue destruction. Failure terminate inflammation when no longer needed prevent unnecessary bystander damage tissues results chronic inflammation cellular destruction.
Common questions
What did Rudolf Virchow hypothesize about cancer in 1863?
Rudolf Virchow hypothesized that the origin of cancer was at sites of chronic inflammation. This observation links a biological defense mechanism to long-term disease processes.
When were the five cardinal signs of inflammation described by Celsus and Galen?
Celsus described the first four classical signs between 30 BC and 38 AD. The fifth sign, loss of function, is believed to have been added later by Galen, Thomas Sydenham or Rudolf Virchow.
How does acute inflammation differ from chronic inflammation in duration and cell types?
Acute inflammation occurs immediately upon injury and lasts only a few days while neutrophils dominate the response. Chronic inflammation lasts for months or years and is characterized by mononuclear cells predominating over neutrophils.
Which diseases are associated with chronic inflammation according to the text?
Chronic inflammation is associated with various diseases such as hay fever, periodontal disease, atherosclerosis, osteoarthritis, diabetes, cardiovascular disease, allergies, and chronic obstructive pulmonary disease. It also contributes to major depressive disorder and HIV infection outcomes.
What percentage of human cancers did chronic inflammation contribute to as of 2012?
As of 2012 chronic inflammation estimated contribute approximately 15% to 25% human cancers. Cancer orchestrates microenvironment around tumours contributing proliferation survival migration.