Chapter 4 Tissue Response to Injury Inflammation, Swelling, ：4章组织损伤的炎症反应肿胀.ppt

Chapter 4. Tissue Response to Injury: Inflammation, Swelling, and Edema,Inflammation,The local response of the body to an irritant Purpose Defend the body against alien substances Dispose of dead and dying tissue so repair can take place,Cardinal Signs of Inflammation,Rubor: redness Calor: heat Edema: swelling Dolor: pain Funca laesa: functional loss Each of these signs will occur to some degree when tissue is injured and the body responds with the inflammatory process.,Common Misconceptions of Inflammation,Do you need to limit or eliminate inflammation? No. Inflammation is necessary. Repair will not occur without inflammation. You cannot eliminate inflammation. You can only minimize the signs of inflammation.,Common Misconceptions of Inflammation (cont.),Swelling, edema, and inflammation are synonymous Swelling and edema occur during inflammation. Edema and swelling are not the same. All edema causes swelling, but not all swelling is caused by edema.,Phases of Inflammation,Inflammation consists of sequential and overlapping events. Primary injury Ultrastructural changes Chemical mediation Hemodynamic changes Metabolic changes Permeability changes Leukocyte migration Phagocytosis,Primary Injury,Any occurrence that impairs tissue structure or function Most sports injuries are caused by Macrotrauma (impact or contact) Microtrauma (overuse, cyclic loading, or friction) There are many other types of injury, each of which results in the same basic inflammatory reaction. Other examples?,Primary Injury (cont.),Other causes of injury include Physical agents (trauma, burns, radiation) Metabolic processes (hypoxia) Biological agents (bacteria, viral, parasitic, infection) Chemical agents (acids, gasses, organic solvents, endogenous chemicals) Endogenous chemicals Normal secretions In abnormal locations (gout) In increased quantity in a normal location (stomach ulcers) The magnitude after each phase varies according to the causative agent,Ultrastructural Changes,Cellular membrane is disrupted and eventually breaks down. Contents spill out into the extracellular spaces, thereby killing the damaged cell.,Two causes Direct Trauma (primary injury) Indirect Hypoxia (oxygen deficiency) Enzymes (chemicals) In cells adjacent to the primary injury,Ultrastructural Changes (cont.),Occur as a direct result of trauma (primary injury) and indirectly as a result of hypoxia (secondary injury) We will discuss this in more detail later in this chapter (see “Orthopedic Injury Model”).,Ultrastructural Changes (cont.),Lysosome Supplies chemicals that digest foreign material within the cell and gets rid of it. If the membrane of the lysosome ruptures, its contents will attack and digest other material.,Chemical Mediation,Histamine, bradykinin, and other chemicals Modify and regulate the rest of the inflammatory response to: Neutralize the cause of the injury Remove cellular debris so repair can take place,Hemodynamic Changes,Arteries dilate, increasing blood flow to the injured area. However, blood vessels that were previously inactive open, so blood flow through individual vessels decreases. Slowing of blood flow is necessary, so WBCs can move to the margins.,Hemodynamic Changes (cont.),Leukocytes Marginate Tumble along the vessel wall Adhere to the vessel wall near an opening,Hemodynamic Changes (cont).,Leukocytes begin passing though the vessel wall.,Metabolic Changes, Energy Oxygen, causes cell to switch to anaerobic metabolism Membrane functions slow down. Sodium pump maintains the concentration of intracellular sodium at a very low level.,Metabolic Changes (cont.), Sodium concentration in cell and organelles Water in cell Cells swell and burst Intracellular acidosis (lactic acid) Membrane attacked Lysosome digests cell.,Permeability Changes,Histamine and bradykinin increase the permeability of small blood vessels. The endothelial cells contract, pulling away from each other. Gaps are left, through which the WBCs can move out of the vessel and to the injury site.,Leukocyte Migration,WBCs adhere to the endothelium (vessel wall) and/or to other white blood cells.,(Reprinted with permission from McLeod I. Inflammation. Kalamazoo, MI: Upjohn, 1973.),Leukocyte Migration (cont.),WBCs move out of the vessel by squeezing through the endothelial gaps. Neutrophils first, then larger macrophages,(Reprinted with permission from McLeod I. Inflammation. Kalamazoo, MI: Upjohn, 1973.),Leukocyte Migration (cont.),Neutrophils Macrophages,Leukocyte Migration (cont.),Neutrophils Travel fast and arrive at the injury site first Provide the first line of defense When they die, they release chemical mediators that attract macrophages. Death of neutrophils results in a large concentration of chemical mediators released by the cells.,Leukocyte Migration (cont.),Macrophages Live for months Long-lasting second line of defense Release potent enzymes that may destroy connective tissue, thus adding to the injury Release chemical mediators that may prolong inflammation Release factors that aid in healing Secrete proteins that are important in defense mechanisms,Phagocytosis,Digestion of cellular debris and other foreign material into pieces small enough to be removed from the injury site,Chronic Inflammation,Results from microtrauma but does not necessarily involve an inflammatory reaction Example: clinically diagnosed Achilles tendinitis and patellar tendinitis in which there is no evidence of an inflammatory reaction Structural disruption and microvascular damage may occur (causing pain and other symptoms) before the classic inflammatory process is set into action.,Orthopedic Injury Model,What happens when a muscle is pulled or an ankle is sprained? Just put an ice bag on it, right? WRONG. This is overly simplistic. Techniques must be based on sound theory if they are to be developed and improved. It is essential to understand the bodys response to injury.,Orthopedic Injury Model (cont.),Example: typical tissue undergoing a typical muscular injury Used to illustrate inflammation in relation to orthopedic injuries,Orthopedic Injury Model (cont.),Normal tissue Cells Two blood vessels (A, B) Two nerves (1, 2),Orthopedic Injury Model (cont.),Contusion with injury to: Three cells Nerve 1 Blood vessel B,Orthopedic Injury Model (cont.),Immediate ultrastructural change Local nerves and blood vessels may be disrupted or broken. This damage is called primary traumatic damage.,Orthopedic Injury Model (cont.),Hemorrhage Few minutes only (usually) Clot forms, stopping hemorrhage. Pain, from damaged nerve Hematoma forms.,Orthopedic Injury Model (cont.),Pain, from damaged nerve Muscle spasm and more pain Inhibition of muscular strength, range of motion, etc. Body attempts to protect itself by splinting the area, thus preventing aggravation of injury.,Orthopedic Injury Model (cont.),The damaged cells release chemical mediators as a signal to the body that an injury has taken place. Extravascular hemorrhage occurs from broken blood vessels. Swelling occurs.,Injury site,Orthopedic Injury Model (cont.),Fibrin forms into strands, creating a network somewhat like a fishnet. This net captures circulating platelets. A plug forms to seal the damaged vessel.,Orthopedic Injury Model (cont.),Chemical mediators released from dying cells cause Hemodynamic changes Permeability changes Leukocyte (white cell) migration,Orthopedic Injury Model (cont.),Secondary enzymatic injury begins.,Orthopedic Injury Model (cont.),Hemodynamic changes Blood flow slows down OR Blood flow ceases,Tissue oxygen decreases Hypoxia Metabolic changes Secondary hypoxic injury soon seen,No flow,Orthopedic Injury Model (cont.),Phagocytosis Free protein Causes edema,Orthopedic Injury Model (cont.),Secondary hypoxic injury begins. Secondary enzymatic injury continues.,Orthopedic Injury Model (cont.),Phagocytosis and secondary injury continue.,Orthopedic Injury Model (cont.),Pressure on undamaged nearby pain fibers cause additional Pain Muscle spasm and inhibition,Orthopedic Injury Model (cont.),Total injury: Primary injury (yellow) Secondary injury,Secondary Injury Model in Review,Orthopedic Injury Model (cont.),The inflammatory response is not all positive. Example Slowed blood flow in the vessels on the periphery of an injury and decreased blood flow from the damaged vasculature result in less oxygen to the cells. If prolonged, secondary hypoxic injury occurs. The total amount of damaged tissue is increased, and more debris is added to the hematoma.,Secondary Injury Model,Bodys response to tissue damaged by trauma (primary injury) leads to further tissue damage, known as secondary injury. Two separate mechanisms result in secondary injury: Enzymatic Hypoxia,Decreased Metabolism Theory,O2 needed,O2 available,In normal tissue,Decreased Metabolism Theory (cont.),After injury,Decreased Metabolism Theory (cont.),Decreased Metabolism Theory (cont.),O2 needed,O2 available,After injury and cryotherapy,Secondary Injury Model in Review,Swelling, Edema, and Vessel Fluid Pressures,What Is Edema?,Accumulation of fluid in the tissue What causes it? Must first understand normal fluid dynamics,Fluid Filtration in Normal Tissue,Fluid Filtration in Normal Tissue (cont.),All fluid leaving the capillary is returned Two-thirds via capillary One-third via lymphatic system,Fluid Filtration in Normal Tissue (cont.),Occurs constantly between capillary and tissue Sum of multiple forces In capillary and tissue Oncotic (osmotic) pulls Hydrostatic pushes,O,H,Hydrostatic Pressure,Pressure exerted by a column of water The higher the column of water, the greater the pressure. Example: swimming The deeper you go, the higher the column of water above you and the greater the pressure. The depth of the water, not the amount of water, is important. Hydrostatic pressure is exerted by the water portion of the blood.,Hydrostatic Pressure (cont.),Hydrostatic pressure pushes water. Capillary hydrostatic pressure pushes fluid out of the capillary. Tissue hydrostatic pressure pushes fluid into the capillary.,CHP,tissue,capillary,THP,Oncotic Pressure,Also called colloid osmotic pressure Results from the attraction of fluid by free protein Tissue oncotic pressure pulls fluid out of the capillary. Capillary oncotic fluid pulls fluid into the capillary.,Fluid Filtration in Normal Tissues, Revisited,Sum of all forces,Capillary Filtration Pressure Components,CFP = (CHP + TOP) (THP + COP + EFP) CFP: Capillary filtration pressure CHP: Capillary hydrostatic pressure TOP: Tissue oncotic pressure COP: Capillary oncotic pressure THP: Tissue hydrostatic pressure EFP: External force pressures,Normal Capillary Filtration Pressure Forces,Fluid Filtration in Normal Tissue, Revisited,What Causes Edema?,Imbalance of fluid filtration caused by an injury,Capillary Filtration Pressure Changes after Injury,Hematoma (tissue debris and hemorrhage) dumps large amounts of free protein into tissue spaces. Increased tissue oncotic pressure,Fluid Filtration in Injured Tissue,Injury results in a great increase in the tissue oncotic pressure.,Fluid Filtration in Injured Tissue (cont.),Fluid Filtration in Injured Tissue (cont.),Fluid accumulates in tissue.,Fluid Filtration in Injured Tissue (cont.),More fluid accumulates in tissue.,Fluid Filtration in Injured Tissue (cont.),Even more fluid accumulates in tissue.,What Is Swelling?,Hemorrhaging and edema Can do nothing about hemorrhaging Can minimize edema,What Causes Swelling?,How Do You Prevent Swelling?,How Do You Prevent Swelling? (cont.),How Do You Prevent Swelling? (cont.),How Does Cold Decrease Swelling?,As cold decreases secondary hypoxic injury, the amount of free protein in tissues decreases. This causes less tissue oncotic pressure (the major factor for edema). Cold can prevent edema from occurring only if applied soon after injury. Once edema develops, cold application cannot decrease that edema.,Decreased Metabolism Theory, Revisited,Secondary hypoxic injury,Injured tissue,Injured and with cryotherapy,O2 needed,O2 available,Time Course of Swelling,Swelling immediately after injury is the result of direct hemorrhaging. Edema begins minutes to hours after injury and continues to develop over many hours. Accounts for the delayed nature of most swelling.,Secondary Injury and Edema,Secondary injury results in increased edema, and increased edema can contribute to increased secondary injury. Two mechanisms As edema develops, the distance between blood vessel and tissue cells increases. More difficult for oxygen and other substances to diffuse from the circulatory system to the tissue Edema can compress the blood vessel, thus decreasing circulation to the area.,Capillary Filtration Pressure Changes after Injury, Revisited,If swelling is the result of edema, why does the area turn black and bl