Gen Patho - Midterms PDF

Inflammation Definition of Response of vascularized tissues to infections and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed Designated by the suffix "-itis" 2. Eosinophi...

Inflammation Definition of Response of vascularized tissues to infections and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed Designated by the suffix "-itis" 2. Eosinophil Involved in parasitic infections and allergies Inflammation of the appendix? Appendicitis Stain bright red with eosin dye Inflammation of the pancreas? Pancreatitis Phagocytic for immune complexes Inflammation of the gingiva? Gingivitis Inflammation of the skin? Dermatitis Inflammation of the joints? Arthritis Occurs to eliminate the offending agents Generally, a beneficial response, but can be harmful Causes of Inflammation 3. Basophil 1. Infections and Microbial Releases histamines (biogenic amine for The most common cause of inflammation allergies) Can be bacterial, viral, fungal, or parasitic In the bloodstream: basophils In the tissues: mast cells 2. Tissue Necrosis Elicits inflammation regardless of the cause 3. Foreign Bodies Elicits inflammation regardless of the cause 4. Immune Reactions Hypersensitivity reactions Autoimmune diseases 4. Monocyte Phagocytosis; release of cytokines Components of Inflammation Largest WBC Cellular In the bloodstream: monocytes Vascular In the tissues: macrophages Large, kidney shaped nucleus Release of TNF-a (tumor necrosis factor) Cellular Components and IL-1 (interleukin) which causes fever, 1. Neutrophil leukocytosis, recruitment of other Key leukocyte of acute inflammation phagocytes Increased in bacterial infections Multilobed nucleus, 3-5 lobes connected by a thin filament 5. Lymphocyte I-lymphocytes ○ Kills intracellular microbes ○ Releases cytokines B-lymphocytes ○ Kills extracellular microbes ○ Produces antibodies Natural Killer Cells ○ Recognizes and directly kills pathogens Scanty cytoplasm, large nucleus 6. Erythrocytes Also called red blood cells Most abundant blood cell Carries oxygen from the lungs to all parts of the body Discoid in shape  2. Calor Heat Due to the increased movement of blood through the dilated vessels into the environmentally cooled extremities 3. Tumor Swelling/edema Due to the increased passage of fluid from dilated and permeable blood vessels into the surrounding tissues 4. Dolor Pain Due to either the direct effects of inflammatory mediators, from the initial damage that resulted to the inflammatory response itself, and stretching of sensory nerves due to edema 5. Functio Laesa Loss of function Due to loss of mobility in a joint, due to edema and pain, or to the replacement of functional cells with scar tissue Part II Vascular Components 1. Dilation of Small blood vessels Increase in the caliber of blood vessels Results in increased blood flow and stasis of blood Results to erythema Histamine: the most notable mediator that produces vasodilation 2. Increased microvascular Mechanisms: Endothelial cell contraction (most common mechanism) Endothelial injury Increased transport of substances across Cardinal Signs of Inflammation endothelial cells (transcytosis) 1. Rubor Results in edema Redness Due to the additional number of 3. Lymphatic Vessel erythrocytes passing through the area  In inflammation , lymph flow is increased to ○ Diapedesis help drain edema fluid that accumulates Transmigration of WBCs across the Lymphatic vessels proliferate during endothelium mediated by CD31/ PECAM-1 inflammatory reactions to handle the ○ Chemotaxis increased load Movement towards a chemotactic signal Lymphangitis: secondary inflammation of Exogenous signal: N-formylmethionine lymph vessels due to the primary source Endogenous signals: IL-8, C5a, leukotriene Lymphadenitis: lymph node inflammation B4 N-formylmethionine General Steps in Inflammation ○ A prominent protein used in protein 1. Recognition of the injurious synthesis among bacterial microbes 2. Recruitment of leukocytes 3. Removal of the agent 4. Regulation of the response 5. Resolution and repair 1. Recognition of Injurious Agent Extracellular Microbes (pathogens) possess Pathogen-Associated Molecular Patterns (PAMPs) These PAMPs will be detected by Toll-Like Receptors (TLRs) found in immune cells Intracellular Microbes Sensors of Intracellular Damage: Uric acid (product of DNA breakdown) DNA when released in the cytoplasm ATP (released from damaged mitochondria) Potassium (reflecting loss of ions due to plasma membrane injury) Acute Inflammation - Neutrophils Chronic Inflammation - Lymphocytes 2. Recruitment of Leukocytes Present in - Macrophages Mediated by adhesion molecules and chemokines (chemoattractant cytokines) 3. Removal of the Agent ○ Margination Leukocyte → Phagocytosis —> Intracellular killing Peripheral positioning of the leukocytes along the endothelial surface Production of reactive oxygen species and Results from slower blood flow due to nitric oxide (intracellular) vessel dilation Lysosomal enzymes (through ○ Rolling phagolysosome formation) Transient binding and detachment of Neutrophil extracellular traps (NETs) leukocytes to the endothelium ○ Extracellular fibrillar networks that ○ Adhesion trap microbes and concentrate Firm adhesion of leukocytes to endothelium, antimicrobial substances, helping to stronger and more permanent adhesion prevent their spread than rolling Neutrophil Extracellular Traps Note: Killing mechanisms can also damage normal tissues 4. Regulation of the Response Mediators of Inflammation Substances that initiate or regulate inflammatory reactions Can be cell derived or plasma derived Active mediators are produced only in response to various stimuli Most mediators are short-lived 3. Cytokines and Chemokines Proinflammatory Cytokines TNF-a Interleukin-1 (IL-1) Anti-inflammatory Cytokines Lipoxin Acute inflammation Transforming Growth Factor-Beta (TGF-B) Interleukin-10 (IL-10) Mediators of Inflammation 1. Vasoactive amines 2. Arachidonic acid metabolites or eicosanoids 3. Cytokines and chemokines 4. Complement system 5. Other mediators of inflammation 1. Vasoactive Amines Chronic inflammation 2. Arachidonic Acid 4. Complement System Collection of soluble proteins that function in host defense against microbes and in pathologic inflammatory reactions Inactive in the plasma; become activated to become proteolytic enzymes that degrade other complement proteins  Patterns of Acute Inflammation 1. Serous inflammation Looks like a serum of the blood Marked by the exudation of cell-poor fluid into spaces Derived from the plasma or from secretions of mesothelial cells because of local irritation (effusion) Seen in viral infections, burns, and transudations 5. Other 2. Fibrinous inflammation Exudation of fibrinogen and fibrin deposition in the extracellular fluid because of increased vascular permeability Fibrin- coagulation factor that prevent excessive bleeding Fibrin is a protein formed in blood clots; appears as an eosinophilic meshwork of threads Seen in fibrinous pericarditis ACUTE INFLAMMATION Morphologic Hallmarks 1. Dilation of small blood vessels 2. Accumulation of leukocytes (neutrophils) 3. Fluid in the extravascular tissue  Outcomes of Acute Inflammation Complete Resolution Involves removal of cellular debris and microbes by macrophages, and resorption of edema fluid by lymphatics Scarring/Fibrosis Involved in tissues that are incapable of regeneration Progression to Chronic Inflammation Results if there is persistence of the injurious agent If there is interference with the normal process of healing 3. Purulent inflammation Chronic Inflammation Exudation consisting of neutrophils and Response of prolonged duration (weeks or necrotic debris months) in which inflammation, tissue injury, Seen in abscess formation (collection of and attempts at repair coexist pus) May follow acute inflammation, or may begin insidiously Causes of Chronic Inflammation 1. Persistent Infections Microorganisms that are difficult to eradicate These microorganisms evoke a delayed-type hypersensitivity Takes a pattern called granulomatous reaction 2. Hypersensitivity Diseases Excessive and inappropriate activation of 4. Ulcers the immune system Excavation of the surface on an organ or Auto-antigens evoke a self-perpetuating tissue due to shedding of inflamed necrotic immune reaction that results in chronic tissue tissue damage and inflammation 3. Prolonged exposure to potentially toxic agents Atherosclerosis, which is thought to be a chronic inflammatory process of the arterial wall, brought about by excessive production and tissue deposition of endogenous cholesterol Morphologic Hallmarks 1. Infiltration with mononuclear cells  Lymphocytes, macrophages, and plasma cells Systemic Effects of Inflammation 2. Tissue Destruction Induced by the persistent offending agent or by the inflammatory cells Fever 37.8 temperature in fever Acute phase response IL-6 - systemic Cells of Chronic Inflammation 1. Macrophages Septic shock The most dominant cells in most chronic Potentially fatal condition inflammatory reactions A severe complication of sepsis where Secrete cytokines and growth factors bacterial infection causes dangerously low Destroy foreign invaders and tissues by blood pressure, and multisystem organ activating other cells failure Activation: ○ Induced directly by endotoxins 5. Resolution and repair ○ Activated by cytokines (IL-4, IL-13) Restoration of tissue architecture and function after an injury 2. Lymphocytes General Types: Defense against infectious pathogens ○ Regeneration: happens in labile When activated, the inflammation tends to and stable tissues, influenced by be persistent and severe growth factors Elicits the strongest chronic inflammatory ○ Connective tissue deposition: reactions happens in chronic inflammation, Dominant especially in autoimmune and severe inflammation, and in other hypersensitivity diseases permanent tissues Subtypes of Lymphocytes: Classification of Tissues by Regenerative Capacity Events in Connective tissue disposition Formation of new blood vessels from existing ones 5.Wound Contraction Mediated by Vascular Endothelial Growth Factor (VEGF) 2. Proliferation Factors that Impede Repair Infections Diabetes mellitus Vitamin C deficiency Glucocorticoids (inhibit TGF-B) Pressure Poor perfusion Foreign bodies Location of injury Abnormalities in Tissue Repair Wound Dehiscence Wound rupture along a surgical incision Due to inadequate granulation tissue 3. Formation of Granulation Tissue Proud Flesh Excessive granulation tissue 4. Remodelling Occurs when granulation tissue grows too Begins 3 weeks after initial injury much and interferes with the healing Granular tissue becomes scar tissue process Affected tissue becomes avascular  Hemodynamics Definitions The study of blood flow and its behavior in blood vessels Begins with the heart which supplies the driving force for all blood flow in the body Ends with fluid homeostasis and equilibrium Contracture in different body compartments Due to excessive wound contraction As a result, skin becomes constricted and EDEMA & EFFUSION cause a functional limitation of movement Edema Accumulation of fluid in tissues (edema) or body cavities (effusion) Keloid Scar Due to excessive collagen formation Scar tissue grows beyond the boundaries of Mechanisms the original wound 1. Increased Hydrostatic Pressure More common Pressure that exists within standing or stationary fluids Pressure of the blood against the wall "Kicking force" out of the capillaries Example: Congestive heart failure Hypertrophic Scar Due to excessive collagen formation 2. Decreased Oncotic Pressure Force exerted by plasma proteins (albumin) in a blood vessel to pull back fluid into the capillary Albumin and plasma proteins are synthesized in the liver Examples: Liver cirrhosis, Nephrotic syndrome Hemodynamic Disorders  Gross Morphology 1. Lungs Heavy, 2-3x its normal weight On sectioning, yields frothy, fluid-tinged fluid 3. Increased Vascular Permeability Example: Burns 2. Brain Direct vascular thermal injury Narrow sulci, distended gyri Example: Infections Through release mediators Histologic Features Clearing and separation of extracellular matrix and subtle cell swelling Most common sites are lungs, brain, subcutaneous tissues 4. Lymphatic Obstruction Lymphatic system has a role in removal of surplus extracellular fluid drainage Examples: Mass, post-surgery Hyperemia and Congestion Increase in blood volume tissues Hyperemia and Congestion Morphology of Congestion Step 1 - Arteriolar Vasoconstriction Exposed collagen from injured skin sends signals for vascular smooth muscles to contract Causes a transient decrease in blood flow Step 2 - Primary Hemostasis Formation a platelet plug (primary hemostatic plug) Exposed collagen also signals for platelet releases adhesion, activation, and aggregation Step 3 - Secondary Hemostasis Involvement of coagulation factors Fibrin (a tough protein substance in chains) forms around the plug Hemostasis Formation of blood clots at the sites of endothelial injury Step 4 - Clot Stabilization and Resorption Stasis - stop Fibrin and platelet aggregates form solid Three Elements: plug to prevent further hemorrhage Platelets Plug will then be resorbed to the blood Coagulation Factors stream Endothelium Counterregulatory mechanisms are set into motion to limit the hemostatic plug at the site of injury Tissue repair ensues Thrombosis Pathologic counterpart of hemostasis Caused by conditions under the Virchow triad  Major Types of Embolism Endothelial injury - start ng cycle of blood clots Stasis of blood flow - Hypercoagulability - excessive coagulation factors Arterial Thrombosis vs. Venous Thrombosis Infarction Area of ischemic necrosis caused by occlusion of either the arterial supply of the venous drainage Most common cause: arterial thrombosis or embolism Fates of Thrombus Shock State in which diminished cardiac output or reduced effective circulating blood volume Embolism impairs tissue perfusion and leads to Detached intravascular solid, liquid, or cellular hypoxia gaseous mass that is carried by the blood from its point of origin to a distant site where Types of Shock it often causes tissue dysfunction or Hypovolemic Shock infarction Occurs due to lack of blood volume Most common form is pulmonary Cardiogenic Shock embolism Caused by the heart's inability to pump blood effectively Anaphylactic Shock Caused by a severe allergic reaction to an allergen, drug, or foreign protein, causing blood vessels to dilate Septic Shock Occurs due to an overwhelming infection that causes blood vessels to dilate Neurogenic Shock Caused by damage to the nervous system, which causes blood vessels to dilate and drop blood pressure