Lecture 5 Inflammation 2024-2025 PDF

2024-2025 General Pathology Dr Ali Al khafaji Lecture 5 Inflammation Inflammation:- It is Complex biological response of vascularized living tissues to local injury or harmful stimuli, such...

2024-2025 General Pathology Dr Ali Al khafaji Lecture 5 Inflammation Inflammation:- It is Complex biological response of vascularized living tissues to local injury or harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is induced by chemical mediators that are produced by host cells in response to injurious stimuli. Terminology Inflammatory conditions are termed by adding the suffix (-itis) to the affected organ or tissue For example:- Pulpitis : inflammation of pulp Gingivitis: inflammation of gingiva Hepatitis: inflammation of liver Appendicitis: inflammation of appendix Significance of inflammation 1- It can cause life-threatening hypersensitivity reaction. 2- It can cause progressive organ damage from chronic inflammation and subsequent fibrosis like rheumatoid arthritis and atherosclerosis. The components of acute and chronic inflammatory responses: circulating cells and proteins, cells of blood vessels, and cells and proteins of the extracellular matrix. Components of inflammation: Many tissues and cells are involved in the inflammatory reaction, including 1- plasma fluid proteins. 2- circulating leukocytes (neutrophils, monocytes, eosinophils, lymphocytes, basophils, in addition to platelets). 3- blood vessels. 4-The connective tissue cells are mast cells, fibroblasts, macrophages, and lymphocytes. 1 2024-2025 General Pathology Dr Ali Al khafaji 5-The extracellular matrix consists of structural proteins (collagen, elastin), adhesive glycoproteins (fibronectin, laminin), and proteoglycans. Inflammation is divided into 1- Acute inflammation 2-Chronic inflammation Acute inflammation Chronic inflammation Early onset (sec. – min) Later onset (days) Short duration (min. – days) Longer duration (wks – yrs) Fluid exudation (edema( Inducing B.V. proliferationand scarring Polymorph nuclearleukocyte Involving lymphocytes and emigration.(neutrophils) macrophages infiltration The cardinal signs of inflammation The classical signs of inflammation are: 1-Redness 2- Swelling 3--Heat 4-Pain 5-loss of function These signs are typically more prominent in acute inflammation than in chronic inflammation General characters of inflammation: - A- Inflammation is generally characterized by two main components: 1- Vascular wall response. 2- Inflammatory cell response. B- The effects of inflammation are mediated by inflammatory mediators which are:1- Circulating plasma proteins 2- Factors produced locally by vessel wall or inflammatory cells. C- Termination: Active anti-inflammatory mechanism begins when: 1- The causative agents is eliminated 2- The secreted mediators are removed Acute Inflammation has Two Major Components I-VASCULAR CHANGES: the main vascular reactions are increased blood flow secondary to vasodilation and increased vascular permeability, both designed to bring blood cells and proteins to site of injury A-change in vascular caliber and flow 1- Initial transient vasoconstriction, followed by 2 2024-2025 General Pathology Dr Ali Al khafaji 2- Vasodilation causing increasing in blood flow to the area of injury. (this is the cause of heat and redness). B- Increased Vascular Permeability (Vascular Leakage) increased vascular permeability leading to the escape of a protein-rich fluid (exudate) into the extravascular tissue. The loss of protein from the plasma reduces the intravascular osmotic pressure and increases the osmotic pressure of the interstitial fluid. results in edema ( which is the cause of swelling) The most common mechanism of vascular leakage 1-endothelial cell contraction leading to the formation of endothelial gaps in venules which is elicited by histamine, bradykinin, leukotrienes, , and many other classes of chemical mediators. 2- Direct endothelial injury as by burns or infections Edema Excessive fluid in the interstitial tissue or body cavities which may be either exudates or transudate Exudate is an inflammatory extravascular fluid that has a high protein concentration, cellular debris,. It implies significant alteration in the normal permeability of small blood vessels in the area of injury. Transudate is a fluid with low protein content that results from increase hydrostatic pressure as a consequence of reduced venous return. transudate is accumulate in non inflammatory conditions Purulent exudates, is an inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells and, in many cases, microbes. Formation of transudates and exudates. , A transudate is formed when fluid leaks out because of increased hydrostatic pressure or decreased osmotic pressure. C, An exudate is formed in inflammation because vascular permeability increases as a result of the increase in interendothelial spaces. 3 2024-2025 General Pathology Dr Ali Al khafaji II-CELLULAR CHANGES: LEUKOCYTE RECRUITMENT AND ACTIVATION A critical function of inflammation is to deliver leukocytes to the site of injury and to activate the leukocytes to perform their normal functions in host defense. Leukocytes ingest offending agents, kill bacteria and other microbes, and get rid of necrotic tissue and foreign substances. The sequence of events in the recruitment of leukocytes from the vessel lumen to the extravascular spaces consist of:- 1-Margination and rolling 2-Adhesion 3-Transmigration across the endothelium (also called diapedesis) Mechanisms of leukocyte migration through blood vessels. The leukocytes (neutrophils shown here) first roll, then become activated and adhere to endothelium, then transmigrate across the endothelium, pierce the basement membrane, and migrate toward chemoattractants emanating from the source of injury. Different molecules play predominant roles in different steps of this process: selectins in rolling; integrins in firm adhesion. Leukocyte Activation Once leukocytes have been recruited to the site of infection or tissue necrosis, they must be activated to perform their functions. Stimuli for activation include microbes, products of necrotic cells, and several mediators Phagocytosis Phagocytosis: Is the engulfment and degradation of the bacteria and cellular debris by neutrophils and macrophages. Phagocytosis involves three distinct but interrelated steps:- (1) Recognition and attachment of the particle to be ingested by the leukocyte (adherence and opsonization). (2) Its engulfment, with subsequent formation of a phagocytic vacuole. (3) Killing or degradation of the ingested material..(reactive oxygen and nitrogen species and lysosomal enzyme) 4 2024-2025 General Pathology Dr Ali Al khafaji 1-Recognition and Attachment (adherence and opsonization) Phagocytosis of microbes and dead cells is initiated by recognition of the particles by receptors expressed on the leukocyte surface; these receptors recognize microbes and host protein (opsonins). Contact of the bacteria or antigen with the phagocyte cell membrane is essential for trapping the agent and triggering the final steps of phagocytosis. The efficiency of phagocytosis is greatly enhanced when microbes are opsonized by specific proteins (opsonins) for which the phagocytes express high-affinity receptors. Opsonization: it is coating the antigen with antibody or complement. This coating enhances or increases the binding of the antigen to the leukocyte cell membrane. The major opsonins are IgG antibodies, the C3b breakdown product of complement, and certain plasma lectins, all of which are recognized by specific receptors on leukocytes 2-Engulfment During engulfment, extensions of the cytoplasm (pseudopods) flow around the particle to be engulfed, eventually resulting in complete enclosure of the particle within a phagosome created by the plasma membrane of the cell. The limiting membrane of this phagocytic vacuole then fuses with the limiting membrane of a lysosome resulting in discharge of the granule's contents into the phagolysosome. 3-Killing and Degradation: The ultimate step in the elimination of infectious agents and necrotic cells is their killing and degradation within neutrophils and macrophages of the. Microbial killing is accomplished largely by oxygen-dependent mechanisms. (reactive oxygen and nitrogen species and lysosomal enzyme) Phagocytosis. Phagocytosis of a particle (e.g., a bacterium) involves (1) attachment and binding of the particle to receptors on the leukocyte surface, (2) engulfment and fusion of the phagocytic vacuole with granules (lysosomes), and (3) destruction of the ingested particle.iNOS, inducible nitric oxide synthase; NO, nitric oxide; ROS, reactive oxygen species. 5 2024-2025 General Pathology Dr Ali Al khafaji Outcomes of Acute Inflammation depends on:- 1-The nature and intensity of the injury. 2-The site and tissue affected. 3-The responsiveness of the host. Outcomes of acute inflammation 1-Resolution: Regaining normal histological & functional tissue. It occurs when there is: a- Limited or short lived injury. b. Minimal or no tissue damage. c. Tissue which is capable of replacing any irreversibly injured cells. 2- Progression to chronic inflammation: Occur if a. The offending agent is not removed. b. There is continuing tissues injury. c. There is decreased capacity of the affected tissue to regrow. Chronic inflammation may be followed by restoration of the normal structure and function or may lead to scarring. 3-Suppuration : means pus formation Pus: A purulent inflammatory exudate caused by pyogenic bacteria Pus is a mixture of:- 1. Living & dead neutrophils. 2. Bacteria. 3. Cellular debris. 4. edema fluid Abscesses are focal collections of pus, typically have a central, largely necrotic region rimmed by a layer of preserved neutrohils with a surrounding zone of dilated vessels and fibroblast 4- Scarring and fibrosis It means replacement of the injured tissue by fibrous connective tissue. This occurs if we have large tissue destruction as in abscess or if the inflammation occur in tissue that do not regenerate 6 2024-2025 General Pathology Dr Ali Al khafaji (Outcomes of Acute Inflammation) Morphology of acute inflammation Depend on 1- The nature and intensity of injury 2- The site and tissues affected 3- The responsiveness of the host Types 1- Serous inflammation 2- Suppurative (purulent) inflammation 3- Ulcers 1- serous inflammation characterized by Outpouring of thin fluid (plasma or mesothelial secretion). Example (Pleural, pericardial cavities &peritoneal.) The Fluid called effusion 2-Fibrinous inflammation characterized by Inflammation of lining body cavities Example (Meninges, pericardium & pleura) More severe injury with more vascular permeability Large molecules pass (fibrinogen) lead to fibrin deposited in extracellular 7 2024-2025 General Pathology Dr Ali Al khafaji 3- Suppurative (purulent) inflammation characterized by Formation of Large amount of pus or purulent exudates Infiltration of Neutrophile, with necrotic cells and edema Causative agents mostly Bacteria (staph , strepto, pneumo……. Example (Acute appendicitis) The Pus is thick creamy yellow or blood stain 4- Pseudomembranous inflammation of mucous membrane characterized by Sever injury cause extensive epithelial necrosis and sloughing Made greates large shallow ulcers Cover by mixture of fibrin +dead epithelium +neutrophils +red cells +bacteria Forming white-creamy color pseudo-memberane Diphtheria Abcess It’s a Localized collection of purulent inflammatory exudates in the tissue or organ. Abscesses have central mass of necrotic leukocyte and tissue debris surrounded by preserved neutrophile without vascular dilatation My be wall off and replace by CT 8 2024-2025 General Pathology Dr Ali Al khafaji Ulcer It's a local defect or exracavation of surface of an organ that is shedding by inflammatory necrotic tissue. Most common in 1- inflammatory necrosis of mucosa-lined cavities ( mouth , larynx, stomach…) 2- subcutaneous inflammation of lower extremities ( old age with vascular defect) Effects of acute inflammation Effects of acute inflammation Beneficial Harmful effects effect 1- swelling and edema like acute 1- dilution of toxin by edemas fluid. epiglositis 2- production of Ab. 2- increased tissue pressure that may lead 3-fibrin network formation form scaffold to tissue necrosis for inflam. Cells & limits spread of infection 3-digestion of viable tissue 4- sever damage in allergic reaction 5-generalized increased vascular permeability ---shock (anaphylactic shock) The end 9