Chronic Inflammation : Causes, Morphologic features, Mediators, Examples, & Clinical manifestations

inflammation is a non-specific host protective mechanism to get rid of foreign invaders and damaged or necrotic tissues from our body there are two components of inflammation acute inflammation and chronic inflammation i have done a separate lecture on acute inflammation if you haven't watched it already please watch it first so that this video would make more sense chronic inflammation is the type of inflammation of prolonged duration there are two major characteristic features in chronic inflammation ongoing tissue destruction and attempts at repair by fibrosis repairing process may occur with or without cell regeneration depending on the involved tissue chronic inflammation may develop soon after an acute inflammatory response or it may be insidious in onset whatever the onset chronic inflammation is associated with significant morbidity due to the ongoing tissue destruction therefore controlling the chronic inflammatory reaction is essential to reduce further complications in certain disease conditions which we will be discussing about in the following sections first let's discuss about some causes of chronic inflammation one is persistent infections some organisms may difficult to be eradicated from our body and they may persist within cells or tissues for a longer period of time common organisms include mycobacterium tuberculosis which causes tuberculosis mycobacterium leprey which causes leprosy treponema pallidum which causes syphilis some fungi and some parasites these organisms evoke a type 4 hypersensitivity reaction in the body and the inflammatory mediators secreted during the reaction will contain the inflammatory process for a long period of time another cause is persistent in digestible material these may be either endogenous or exogenous endogenous ones include necrotic bone and adipose tissue calcium and uric acid deposits exogenous ones include silica asbestos fibers and suture material another cause of chronic inflammation is immune mediated reactions these reactions can be categorized into several subtypes including the following autoimmune reactions where an immune response occurring against our own body antigens such as rheumatoid arthritis systemic lupus arithmatisis hashimoto's thyroiditis and chronic autoimmune gastritis organ transplant rejections where the immune response occurs against the antigens of the donor organ unregulated immune responses against a particular organism such as inflammatory bowel disease and ulcerative colitis and hypersensitivity reactions which is an inappropriate immune response to a generally harmless antigen such as chronic bronchial asthma a type 1 hypersensitivity reaction against various inhaled antigens and hypersensitivity pneumonitis a type 3 hypersensitivity reaction another situation where chronic inflammation takes place is following an acute inflammatory response most common example is persistent abscesses usually abscesses are formed during acute inflammation if the acute inflammatory abscess cannot be drained out either surgically or spontaneously it becomes a chronic abscess repeated episodes of acute inflammation also causes chronic inflammation for example repeated attacks of acute pancreatitis such as in chronic alcohol abusers can cause development of chronic pancreatitis and repeated attacks of acute may result in chronic cholecystitis in patients with gallstone disease tissue destruction and fibrosis during chronic inflammation give rise to certain morphological features that can be seen both macroscopically and microscopically first let's see what are the macroscopic features due to tissue destruction involvement of an epithelial surface may result in formation of an ulcer such as chronic gastric ulcers in parenchymal tissue chronic inflammation gives rise to cavitatory lesions for example in secondary pulmonary tuberculosis there is formation of cavities due to the extensive tissue destruction these cavities get filled with the inflammatory exudate and when coughing this exudate may come out as sputum another feature of chronic inflammation is formation of chronic abscesses an abscess is usually a pus filled cavity surrounded by a pyogenic membrane areas of granulation tissue may be seen around the abscess in contrast to acute inflammatory abscesses in chronic inflammation there will be a fibrous capsule surrounding the pus-filled cyst when an abscess extends into a surface through destruction of the tissues in between a sinus is formed the major function of these sinuses is to discharge out the contents within the abscess examples include perianal sinuses and sinuses in osteomyelitis if the chronic inflammation related tissue destruction connects two epithelial surfaces a fistula is formed for example in crohn's disease fistulae are formed connecting the mucosa of the anal canal with perianal skin now let's see what are the morphological features of chronic inflammation due to fibrosis if the inflammatory process involves a hollow organ its wall may become thickened due to fibrosis such as in chronic gallstone disease if the involved organ is a narrow tube wall thickening may cause narrowing of the lumen called a stricture such as esophageal stricture allele stricture in crohn's disease and pyloric stenosis it is important to note that strictures are also formed by malignant tumors especially if the tumor has a dense fibrous stoma another feature due to fibrosis and chronic inflammation is distortion of the affected organ when formed 5 breast tissue tends to contract due to the presence of myo5 problems the main goal of this contraction is to reduce the size of the scar however in situations where extensive fibrous contraction takes place distortion of the organ may occur most common example is our glass contracture of the stomach in addition liver cirrhosis may also cause distortion of the liver microscopically mononuclear cell infiltration can be seen predominantly macrophages and lymphocytes and in parasitic infections there may be more eosinophils as well in acute inflammation the predominant cell type is neutrophil however in chronic inflammation it is macrophage tissue necrosis is another feature of chronic inflammation along with tissue regeneration as the repairing process is in progress granulation and fibros tissue are also seen in the area and in granulomatous inflammation there may be multi-nucleated giant cells as well granulomatous inflammation is a special type of chronic inflammation which is commonly seen in tuberculosis i have done a separate video on granulomatous inflammation if you are interested watch that video as well i will put a link in the description now let's see what is the role of macrophage in chronic inflammation during chronic inflammation macrophages accumulate at the site by following mechanisms continuous recruitment from the blood to the site of inflammation actually macrophages are derived from blood monocytes when a monocyte migrates from the blood into a tissue it is then called a tissue macrophage this is the most important source of macrophages and it is mediated by transforming growth factor beta and platelet-derived growth factor second mechanism is proliferation of macrophages at the site of inflammation and the third mechanism is immobilization of macrophages at the site of inflammation to prevent them from migrating elsewhere this is mediated by the migration inhibition factor secreted by activated t lymphocytes the macrophage has to get activated in order to perform its functions macrophage activation is enabled by interferon gamma secreted by activated t cells and certain exotoxins secreted by pathogenic organisms activated macrophages have several functions they secrete destructive agents to get rid of the offending organism or foreign material these agents include reactive oxygen species nitric oxide proteases coagulation factors and arachidonic acid metabolites like prostaglandins and leukotrienes activated macrophages have an increased phagocytic activity they also secrete growth promoting agents for the repairing process these include growth factors like platelet-derived growth factor fibroblast growth factor and transforming growth factor beta angiogenic factors like vascular endothelial growth factor and fibrogenic cytokines finally let's see some common clinical manifestations caused by chronic inflammation some of them we have already discussed in the morphological features of chronic inflammation topic these include ulceration of epithelial surfaces sinus and fistula formation cavitatory lesion formation loss of function wall thickening of hollow organs stricture formation distortion of the organ and fibrous adhesion formation fibrous adhesions are formed when two inflammatory surfaces come into contact with each other commonly seen in the small intestine and tuberculosis of meninges fibrous adhesions in the subarachnoid space can obstruct the csf flow and produce hydrocephalus in children and in tuberculosis of the pericardium fibrous adhesions may cause constrictive pericarditis another less common manifestation is end arteritis obliterans where the small blood vessels within the areas of chronic inflammation undergo progressive internal proliferation due to this the lumen of these arteries become narrowed resulting in chronic ischemia and diffuse fibrosis of the affected area supplied by these arteries and sometimes epithelial surfaces involving chronic inflammation may undergo metaplasia if persistent metaplasia may lead to dysplasia and ultimately malignant proliferation of the epithelium some common systemic manifestations of chronic inflammation include splenomegaly and hepatomegaly due to hyperplasia of the mononuclear phagocytic system lymphadenopathy amylodosis due to prolonged production of acute phase reactants anemia of chronic disease high esr low-grade long-term fever due to circulating cytokines loss of appetite and loss of weight due to the inhibitory effect of tumor necrosis factor