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Define inflammation Response to injury (including infection)
Inflammatory reaction of blood vessels leads to: Accumulation of fluid and leukocytes in extravascular tissues
5 cardinal signs of inflammation Rubor (erythema [redness]); Tumor (swelling); Calor (heat); Dolor (pain); functio laesa (loss of function)
2 signs of inflammation characterized by vasodilatation & increased blood flow Rubor (erythema [redness]); Calor (heat)
Under what circumstances is inflammation potentially harmful? Hypersensitivity reactions to insect bites, drugs, contrast media in radiology; chronic diseases (arthritis, atherosclerosis); disfiguring scars, visceral adhesions
Components of inflammatory response Vascular reaction; Cellular (exudative) reaction
Types of Inflammation Acute inflammation; Chronic inflammation; Granulomatous inflammation
Characteristics of acute inflammation Short duration, edema, and mainly neutrophils
Characteristics of chronic inflammation Longer duration, lymphocytes & macrophages predominate, fibrosis, new blood vessels (angiogenesis)
Characteristics of granulomatous inflammation Distinctive pattern of chronic inflammation; activated macrophages (epithelioid cells) predominate
Three major components of acute inflammation Increase in blood flow (redness & warmth); Edema results from increased hydrostatic pressure (vasodilation) and lowered intravascular osmotic pressure (protein leakage); Leukocytes emigrate from microcirculation and accumulate in the focus of injury
Transudate vs. exudate Transudate, SpGr <1.012; Exudate (cell- and protein-rich), SpGr >1.020
Benefits of Fluid Accumulation at Injury Site Dilution of toxins; Pains decreases use and prevents additional injury; Antibodies in blood can kill microbes; Blood plasma proteins can amplify responses against the injurious agent
Definition of Extravasation Delivery of leukocytes from the vessel lumen to the interstitium
Types/Examples of Extravasation In the lumen: margination, rolling, and adhesion; Migration across the endothelium (diapedesis); Migration in the interstitial tissue (chemotaxis)
Diapedesis Migration across the endothelium
Chemotaxis Migration in the interstitial tissue
Role of Leukocytes Ingest offending agents (phagocytosis); kill microbes; degrade necrotic tissue and foreign antigens
Leukocyte adhesion and migration across vessel wall are determined largely by ______ Binding of complementary adhesion molecules on the leukocyte and endothelial surfaces
Morphologic Patterns of Acute Inflammation Serous inflammation; Fibrinous inflammation; Suppurative (purulent) inflammation; Ulcers
Serous inflammation Outpouring of thin fluid (serous effusion, blisters)
Fibrinous inflammation In body cavities; leakage of fibrin; may lead to scar tissue (adhesions)
Suppurative (purulent) inflammation Pus or purulent exudate (neutrophils, debris, edema fluid); abscess: localized collections of pus
Ulcers Local defect of the surface of an organ or tissue produced by the sloughing (shedding) of inflammatory necrotic tissue
Chronic Inflammation Inflammation of prolonged duration (weeks or months)
What is occurring during chronic inflammation? Active inflammation, tissue destruction, and attempts at repair are proceeding simultaneously
Examples of chronic inflammation Persistent infections (Treponema pallidum [syphilis], viruses, fungi, parasites); Exposure to toxic agents; Autoimmunity (Rheumatoid arthritis, systemic lupus erythematosus)
Exposure to toxic agents (leading to chronic inflammation) Exogenous: silica (silicosis); Endogenous: toxic plasma lipid components (atherosclerosis)
Histological features of chronic inflammation Infiltration with mononuclear cells (macrophages, lymphocytes, and plasma cells); Tissue destruction (induced by the inflammatory cells); Healing by replacement of damaged tissue by connective tissue (fibrosis) and new blood vessels (angiogenesis)
Macrophages predominate by _____ hours 48 hours
Role of Lymphocytes in Chronic Inflammation Produce inflammatory mediators; Participate in cell-mediated immune reactions; Plasma cells produce antibody; Lymphocytes and macrophages interact in a bi-directional fashion
Eosinophils in Chronic Inflammation Immune reactions mediated by IgE; Parasitic infections (Eosinophil granules contain a protein that is toxic to parasites)
Mast cells in Chronic Inflammation Release mediators (histamine) and cytokines
What characterizes Granulomatous Inflammation? Predominant cell type is an activated macrophage with a modified epithelial-like (epithelioid) appearance; Giant cells may or may not be present
Foreign body granulomas form when ______ Foreign material is too large to be engulfed by a single macrophage
Immune granulomas Insoluble or poorly soluble particles elicit a cell-mediated immune response
Endocrine and Metabolic Manifestations of Inflammation Secretion of acute phase proteins by the liver; Increased production of GCs (stress response); Decreased secretion of vasopressin leads to reduced volume of body fluid to be warmed
Role of Fever in Inflammation Improves efficiency of leukocyte killing; Impairs replication of many offending organisms
Autonomic Nervous System Manifestations of Inflammation Redirection of blood flow from skin to deep vascular beds minimizes heat loss; Increased pulse and blood pressure; Decreased sweating
Behavioral Manifestations of Inflammation Shivering (rigors), chills (search for warmth), anorexia (loss of appetite), somnolence, and malaise
Leukocytosis Increased leukocyte count in the blood
Neutrophilia seen in inflammatory response to ______ Bacterial infections
Lymphocytosis seen in inflammatory response to ______ Infectious mononucleosis, mumps, measles
Eosinophilia seen in inflammatory response to ______ Parasites, asthma, hay fever
Leukopenia seen in inflammatory response to ______ Typhoid fever, some viruses, rickettsiae, protozoa
Predisposing factors to orbital mucormycosis Diabetic ketoacidosis; Leukemia
Vasoactive mediators Histamine; Bradykinin; Complement (C3a, C5a); Prostaglandins/leukotrienes; Platelet activating factor; Nitric oxide; Neuropeptides
Chemotactic factors Complement (C5a); Leukotriene (B4); Platelet activating factor; Cytokines (IL-1, TNF); Chemokines; Nitric oxide
Action of histamine Dilates arterioles and increases permeability of venules (wheal and flare reaction)
Release mechanisms of histamine Binding of antigen (allergen) to IgE on mast cells releases histamine containing granules; Release by nonimmune mechanisms such as cold, trauma, or other chemical mediators; Release by other mediators
Bradykinin Small peptide released from plasma precursors; Increases vascular permeability; Dilates blood vessels; Causes pain; Rapid inactivation
Arachidonic Acid Metabolites Prostaglandins; Leukotrienes
Actions of Prostaglandins Vasodilatators (prostacyclin); Vasoconstrictors (thromboxane A2); produce pain (PGE2 makes tissue hypersensitive to bradykinin) and fever
Actions of Leukotrienes Increase vascular permeability; Vasoconstriction; Leukocyte adhesion & chemotaxis
Platelet Activating Factor is synthesized by ______ Stimulated platelets, leukocytes, endothelium
Proteins produced by many cell types (principally by activated lymphocytes and macrophages) = Cytokines
_____ and ______ are the major cytokines that mediate inflammation Interleukin-1 (IL-1) and tumor necrosis factor (TNF)
Inflammatory effects of Platelet Activating Factor Stim plt aggregatn; Vasoconstrictn & bronchoconstrictn; Vasodilatn & inc’d ven. permeability; Inc’d leukocyte adhesion to endothel., chemotaxis, degranulatn, & oxidative burst; Inc. synthesis of arachid. acid metabolites by leukocytes etc
Chemokines Small proteins that act primarily as chemoattractants for specific types of leukocytes
Actions of Chemokines Stimulate leukocyte recruitment in inflammation; Control the normal migration of cells through tissues (organogenesis and maintenance of tissue organization)
Substance P and neurokinin A are _______ Neuropeptides
Substance P nerve fibers are prominent in the _______ Lung and gastrointestinal tract
Neuropeptides are produced in the __________ nervous system Central and peripheral nervous systems
Effects of neuropeptides Vasodilation (direct and through mast cell degranulation); Increased vascular permeability
Other chemical mediators of inflammation Neutrophil granules; Oxygen-Derived Free Radicals
Steps in Wound Healing Injury induces acute inflamn; Parenchymal cells regenerate; parenchymal & conn. tissue cells migrate and proliferate; Extracellular matrix produced; parenchymal & conn. tissue matrix remodel; Increase in wound strength due to collagen deposition
The hallmark of healing is ______ Granulation tissue
Histology of granulation tissue Proliferation of small blood vessels and fibroblasts; tissue often edematous
Neutrophils are pathognomonic for _______ Acute Inflammation
Plasma cells are pathognomonic for ________ Chronic inflammation
Granulomatous inflammation for _______ Epithelioid macrophages are pathognomonic
Function of cytokines Modulate the function of other cell types
Created by: Abarnard
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