ACUTE INFLAMMATION Acute inflammation has three major components 1 dilation of small vessels leading to an increase in blood flow 2 increased permeability of the microvasculature enabling plasma proteins and leukocytes to leave the circulation 3 emigration of leukocytes from the microcirculation their accumulation in the focus of injury and their activation to eliminate the offending agent 4 When an individual encounters an injurious agent such as a microbe or dead cells phagocytes that reside in tissues try to eliminate these agents 5 At the same time phagocytes and other sentinel cells in the tissues recognize the presence of the foreign or abnormal substance and react by liberating cytokines lipid messengers and other mediators of inflammation 6 Some of these mediators act on small blood vessels in the vicinity and promote the efflux of plasma and the recruitment of circulating leukocytes to the site where the offending agent is located Reactions of Blood Vessels in Acute Inflammation 1 The vascular reactions of acute inflammation consist of changes in the flow of blood and the permeability of vessels both designed to maximize the movement of plasma proteins and leukocytes out of the circulation and into the site of infection or injury 2 The escape of fluid proteins and blood cells from the vascular system into the interstitial tissue or body cavities is known as exudation 3 An exudate is an extravascular fluid that has a high protein concentration and contains cellular debris 4 Its presence implies the existence of an inflammatory process that has increased the permeability of small blood vessels 5 In contrast a transudate is a fluid with low protein content most of which is albumin little or no cellular material and low specific gravity 6 It is essentially an ultrafiltrate of blood plasma that is produced as a result of osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability 7 Edema denotes an excess of fluid in the interstitial tissue or serous cavities it can be either an exudate or a transudate 8 Pus a purulent exudate is an inflammatory exudate rich in leukocytes mostly neutrophils the debris of dead cells and in many cases microbes Changes in Vascular Flow and Caliber Changes in vascular flow and caliber begin early after injury and consist of the following Vasodilation 1 is induced by the action of several mediators notably histamine on vascular smooth muscle 2 It is one of the earliest manifestations of acute inflammation 3 Vasodilation first involves the arterioles and then leads to opening of new capillary beds in the area 4 The result is increased blood flow which is the cause of heat and redness erythema at the site of inflammation Vasodilation is quickly followed by increased permeability of the microvasculature with the outpouring of protein rich fluid into the extravascular tissues The loss of fluid and increased vessel diameter lead to slower blood flow 1 concentration of red cells in small vessels and increased viscosity of the blood 2 These changes result in engorgement of small vessels with slowly moving red cells a condition termed stasis which is seen as vascular congestion and localized redness of the involved tissue As stasis develops blood leukocytes principally neutrophils accumulate along the vascular endothelium 1 At the same time endothelial cells are activated by mediators produced at sites of infection and tissue damage and express increased levels of adhesion molecules 2 Leukocytes then adhere to the endothelium and soon afterward they migrate through the vascular wall into the interstitial tissue in a sequence 3 Increased Vascular Permeability Vascular Leakage Several mechanisms are responsible for the increased permeability of postcapillary venules a hallmark of acute inflammation Contraction of endothelial cells resulting in opening of interendothelial gaps is the most common mechanism of vascular leakage 1 It is elicited by histamine bradykinin leukotrienes and other chemical mediators It is called the immediate transient response because it occurs rapidly after exposure to the mediator and is usually short lived 15 to 30 minutes 2 In some forms of mild injury e g after burns irradiation or ultraviolet radiation and exposure to certain bacterial toxins vascular leakage begins after a delay of 2 to 12 hours and lasts for several hours or even days 3 this delayed prolonged leakage may be caused by contraction of endothelial cells or mild endothelial damage 4 Sunburn is a classic example of damage that results in late appearing vascular leakage Often the immediate and delayed responses occur along a continuum Endothelial injury resulting in endothelial cell necrosis and detachment 1 Direct damage to the endothelium is encountered in severe physical injuries for example in thermal burns or is induced by the actions of microbes and microbial toxins that damage endothelial cells 2 Neutrophils that adhere to the endothelium during inflammation may also injure endothelial cells and thus amplify the reaction 3 In most instances leakage starts immediately after injury and is sustained for several hours until the damaged vessels are thrombosed or repaired 4 Although these mechanisms of increased vascular permeability are described separately all probably contribute in varying degrees in responses to most stimuli 5 For example at different stages of a thermal burn leakage results from chemically mediated endothelial contraction and direct and leukocyte dependent endothelial injury 6 The vascular leakage induced by these mechanisms can cause life threatening loss of fluid in severely burned patients Responses of Lymphatic Vessels and Lymph Nodes 1 In addition to blood vessels lymphatic vessels also participate in acute inflammation 2 The system of lymphatics and lymph nodes filters and polices the extravascular fluids 3 Lymphatics drain the small amount of extravascular fluid that seeps out of capillaries in the healthy state 4 In inflammation lymph flow is increased and helps drain edema fluid that accumulates because of increased vascular permeability 5 In addition to fluid leukocytes and cell debris as well as microbes may find their way into lymph 6 Lymphatic vessels like blood vessels proliferate during inflammatory reactions to handle the increased load 7 The lymphatics may become secondarily inflamed lymphangitis as may the draining lymph nodes lymphadenitis 8 Inflamed lymph nodes are often enlarged