Pathophysiology 1000

Term Definition
Three lines of defense Skin & mucous membranesPhysical & mechanical barriersBiochemical barriersInflammatory response (non-specific) *Immune response (specific)
Inflammatory response is an Adaptive & protective response
Acute inflammatory response is essential for healing and includes: -The ability to recognize the injury-Activate a response-Shut down the response when injury has passedEnd result is either repair & regeneration / scarring or chronic inflammation
Acute Inflammation: Sudden onset- Begins immediately after injury. Goal is to remove injurious agent & limit extent of tissue damage. How? Increase blood flow to site (vascular response)Increase healing cells at site (cellular response)Prepare for tissue repair
Vascular Response-Inflammatory mediators (mast cell) are? Histamine/ leukotrienes/ prostaglandins
Vascular Response-Localized vasodilation is? Dilation of the blood vessel for ^ blood flow
Vascular response (Cont'd)-Increased permeability allows? Allows movement of cells into damaged tissueExudate exits the tissues
Vascular Response (Cont'd)-Plasma protein system (3 parts) -Complement-Clotting-KininEach system is in an inactive form but will be activated by tissue damage or injury
Plasma Protein System- Complement: Assists or complements antibodies & phagocytic cellsOpsonization & cell lysisDestroys pathogens directly
Plasma Protein System- Complement cascade is activated by: Anaphylatoxic activityLeukocyte chemotaxisOpsonizationCell lysis
Plasma protein system: Clotting is a 4 role system- What are the First 2 Roles in Clotting? 1. Activation of the clotting cascade through factor XI.2. Control of clotting through conversion of plaminogen proactivator to plasminogen activator, resulting in the generation of plasmin.
What are the Last 2 roles in Clotting? 1. Activation of the kinin system by activated Hageman factor (prekallikrein activator).2. Activation of C1 in complement cascade.
Plasma Protein System:Role of Kinin -Increases (^) vascular permeability-Dilates blood vessels-Induces pain-Causes smooth muscle contraction
Control of plasma protein system Activation of one system results in the activation of the other systemControl is essential:Inflammatory process is needed for survivalMediators are so potent they can damage the host cells therefore must be confined to injured or infected tissue
Cellular Response Uses many different types of cells to act at the site of injury & prepare for healingInvolves:Mast cellsPhagocytic cellsNeutrophilsMacrophages
Mast cellWhere is this cell located? Located in the loose connective tissues close to blood vessels. They are found in large numbers in areas directly exposed to environment including the skin and the lings of the GI and respiratory tracts.
Mast Cell: Central cell of inflammationActivated by:Physical injuryChemical agentsImmunologic agents
Mast Cell: Role in inflammation:-Degranulation to release histamine-Allow for chemotaxis of neutrophils-Synthesize inflammatory mediators (leukotrienes, prostaglandins)
Mast cell degranulation Histamine is released from mast cells-Histamine:–Causes constriction of large vessel walls–Dilation of venules -> increased blood flow–Increases vascular permeability
Cellular Response- Phagocytes Consist of granulocytes, and monocytes/ macrophages
Cellular Response- Phagocytes Role is to ingest and dispose of damaged cells & foreign material
Cellular Response- Phagocytes Predominant phagocyte in early inflammation –> neutrophil
Neutrophils -Appear in early stages of inflammation (within 6 hours)-Ingest bacteria, dead cells and cellular debris-Incapable of division
Neutrophils -Sensitive to the acidic environment of inflammatory lesions-Life span is short (approx. 4 days)-Become a component of purulent exudate
Macrophages -Better for long term defence-Replace the neutrophils-Can survive and divide in acidic inflammatory environments-Remove cells and cellular debris-Suppress further inflammation and initiate healing
Natural Killer cells (NK) Natural Killer cells seem more efficient in this role when they encounter an infected cell within the circulatoy system as opposed to within tissues.
Natural Killer cells (NK) The main function of natural killer cells is recognition and elimination of cells infected with viruses, although they are also somewhat effective at elimination of other abnormal host cells, specifically cancer cells.
Cellular Response- Needed for phagocytosis -Chemotaxis (movement) —Moving certain cells to the site—Neutrophils? phagocytosis/ release chemical messengers
Cellular Response- Needed for phagocytosis -Adherence—Endothelial walls become sticky so neutrophils can adhere—Allows for phagocytosis
Cellular Response- Needed for phagocytosis -Migration (diapedesis)—Ability of leukocytes (WBC) to move across endothelial cells and get to the exact site of the injury
Manifestations of Inflammation- Local -Redness-Heat-Pain-Swelling-Exudate
Systemic Manifestations of Inflammation -Fever–Aids in killing microorganisms-Leukocytosis–Bone marrow triggered to produce more neutrophils–Left shift to more immature neutorphils
Systemic Manifestations of Inflammation-Plasma protein synthesis Plasma protein synthesisProduced by the liver (acute phase reactants)Detectable with blood tests (C-reactive protein and ESR)
Blood Values with Inflammation WBC Count (differential)–Measures number of WBC’s. Helps identify the presence of infection or inflammation
Blood Values with Inflammation Erythrocyte Sedimentation Rate (ESR)–Tests the speed RBC’s settle in a blood sample–Inflammation causes the RBC to become heavier
Blood Values with Inflammation C-Reactive Protein (CRP)–Tests for abnormal protein substances that is only present with inflammatory conditions
Chronic Inflammation-Etiology: Injurious agent not eliminated in acute inflammation? response can progress to chronicRepeated episodes of infection? chronic inflammationCertain autoimmune diseases
Chronic Inflammation- Definition: The difference between Acute and Chronic is simply duration. Chronic lasts 2 weeks or longer, regardless of cause. Acute lasts less time than chronic.
Acute Inflammation -Immediate Cells involved:-Neutrophils Resolution:-Regeneration & Restoration
Chronic Inflammation -Lasts weeks or yearsCells involved:-Macrophages, lymphocytes & plasma cellsResolution:-Granuloma formation/ scarring
Resolution & Repair Healing involves: filling, sealing and shrinkingOffending agent destroyed and removed.Then, feedback systems (plasma system) deactivate the inflammatory response. Then, allows the tissue to heal. Leading to Resolution & Repair.
Chronic Inflammation Repair Repair –> scar formationReplacement of destroyed tissue with collagen tissue (non-functional tissue)
Chronic Inflammation Repair Granuloma formationOccurs when invading organism cannot be eliminatedExterior- contained by wall of lymphocytesInterior-differentiated macrophages
Regeneration Regeneration occurs if normal function & anatomy is restored-Eg) primary intention healing- wound has well approximated edges
Healing If damage it too extensive- healing occurs through replacement (scar)-Eg) 2nd intention healing- wound is not approximated
Reconstructive phase Requires granulation tissue-Angiogenesis: growth of new capilaries.-Filled with new capillaries-Appears red & granular-Surrounded by fibroblasts & macrophages-Includes wound contraction
Dysfunctional wound healing Can occur if any process during repair or healing is abnormalCauses:Ineffective inflammatory responseAdhesionsInfectionScar formationDysfunction during reconstructive phase
Dysfunctional wound healing Causes:Impaired cellular matrix Excessive production of collagen (keloid)Impaired epthilializationImpaired contraction (contracture)Wound dehiscense
Adhesions Definition: joining of 2 surfaces.fibrous connection between serous cavity & nearby tissues.
Adhesions-When connected tissue cannot move freely, what can this lead to? Connected tissues cannot move freely it can lead to strangulation and distortion or nearby organs.
Infection & ulceration Open area leads to the potential for microorganismsResistant to heal due to:-Lack of perfusion-Persistent miroorganismsMore prone in wounds healing by 2nd intention
Scar Tissue Caused by damage to tissue – destroyed the supporting network
Scar Tissue: Why is scar tissue considered a non-functioning tissue? Fills the gap, therefore it lacks follicles or glans (e.g, sweat glands)

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