Inflammation/Repair
Quiz yourself by thinking what should be in
each of the black spaces below before clicking
on it to display the answer.
Help!
|
|
||||
|---|---|---|---|---|---|
| What is inflammation? | A protective response intended to rid the body of the initial cause of injury and the dead and dying cells.
🗑
|
||||
| What is the sequence of events leading to the repair process? | 1. Recognition 2. Recruitment 3. Removal 4. Regulation 5. Repair
🗑
|
||||
| What are the two types of inflammation and how are they Characterized? | Acute (Characterized by fluid, plasma exudate, and Neutrophil accumulation) and Chronic (Characterized by presence of lymphocytes and macrophages w/ vascular proliferation and scarring).
🗑
|
||||
| What are the 2 major components of ACUTE inflammation? | 1) Vascular changes. 2) Cellular events.
🗑
|
||||
| What mediates the cascade of events in ACUTE inflammation? | Local release of chemical mediators.
🗑
|
||||
| What do the vascular changes of ACUTE inflammation result in? | 3 of the FIVE CLASSIC SIGNS: HEAT, REDNESS AND SWELLING
🗑
|
||||
| What are the consequences of mediator elaboration and leukocyte-mediated damage? | 2 of the FIVE CLASSIC SIGNS: PAIN and LOSS OF FUNCTION
🗑
|
||||
| 5 Triggers of Acute inflammation | 1. Infections 2. Trauma 3. Tissue Necrosis 4. Foreign bodies 5. Immune reaction (hypersensitivity)
🗑
|
||||
| What causes REDNESS? | Increased blood flow to the region.
🗑
|
||||
| What causes HEAT? | Increased blood flow to the region and increased cellular metabolism.
🗑
|
||||
| What causes SWELLING? | EDEMA from increased hydrostatic pressure and increased vascular permeability
🗑
|
||||
| What causes PAIN? | Due to edema, kinins and prostaglandins
🗑
|
||||
| What causes LOSS OF FUNCTION? | Due to edema, pain, fibrosis and leukocyte-mediated damage.
🗑
|
||||
| What causes the increase in vascular blood? | Vasoconstriction and arterial vasodilation resulting in engorged capillary beds. This causes RBCs to be more concentrated and blood viscosity to INCREASE.
🗑
|
||||
| What is STASIS? | The numerous small vessels packed with erythrocytes.
🗑
|
||||
| What does stasis cause? | A disruption of the normal flow of blood so that WBCs will migrate there and adhere to the endothelium
🗑
|
||||
| Mechanism involved in icreased vascular permiability | Early phase of vasodilation resulting in increased blood flow which cause hydrostatic pressure in blood vessels. (Endothelial cell Contraction, Direct Endothelial Injury, Leukocyte-mediated Injury, Increased Transcytosis, Leakage from blood vessels).
🗑
|
||||
| What is TRANSUDATE? | The name for the fluids and low molecular weight solutes moving into tissue, typically clear, brought on by hydrostatic imbalance.
🗑
|
||||
| What is EXUDATE? | The name for fluids and plasma proteins moving into the tissue. Cloudy, results from inflammation and injury.
🗑
|
||||
| When fluids move out of vessels into the tissues that is called what? | EDEMA.
🗑
|
||||
| What is Endothelial Cell Contraction and how is it mediated? | Widening of intercellular junctions or gaps, mediated by histamine, bradykinin, leukotrienes, and other mediators.
🗑
|
||||
| How long does Endothelial Cell Contraction last and what structures are involved. | Short-lived (10-30 min, Post-capillary Venules.
🗑
|
||||
| What is Direct Endothelial Injury and what causes it? | Endothelial cell Necrosis and detachment, occurs from severe injury (burns or infection) and detachment is associated with adhesion and thrombosis.
🗑
|
||||
| How long does Direct Endothelial Injury last and what vessels are involved? | It can last from hours to days, responses involve ALL vessels in the area of injury.
🗑
|
||||
| Leukocyte-mediated endothelial injury | Endothelial cells that are damaged of killed by Reactive Oxygen Species (ROS) or proteolytic enzymes from leukocytes.
🗑
|
||||
| Transcytosis | Movement of proteins via intracellular vesicles to augment the permeability.
🗑
|
||||
| Leakage from Blood Vessels | Repair involves new blood vessel formation, these vessels are leaky until Endothelial Cells proliferate and differentiate to form tight junctions.
🗑
|
||||
| Name the Cellular Events associated with WBC delivery to site of injury. | 1. Margination and Rolling 2. Adhesion to Endothelium 3. Transmigration 4. Migration
🗑
|
||||
| What two main WBC are found in acute inflammation and their associated time frame? | Neutrophils (6-24 hrs), Monocytes (24-48 hrs).
🗑
|
||||
| What is Margination? | Due to increased vascular permeability, WBC are pushed to the Margins of the blood vessels.
🗑
|
||||
| What is Rolling? | As a consequence of Margination, WBC will tumble and occasionally stick to the endothelial cell surface. This results in interaction of receptors and their ligands.
🗑
|
||||
| What are the steps of TRANSMIGRATION? | First adhesion of Leukocyte to endothelial cells. Then DIAPEDESIS - movement through the basement membrane into the extravascular space.
🗑
|
||||
| How does WBCs move to the site of inflammation? | A process of moving along a chemical gradient known as CHEMOTAXIS.
🗑
|
||||
| Endogenous and Exogenous substances that act as CHEMOTACTIC agents. | Endotoxins of bacteria. Cytokines. Complement System (C5a). Arachodonic acid (AA) metabolism (leukotrinene B4). Receptors see these and increase cellular uptake of calcium. Cellular activation also occurs on the pathway.
🗑
|
||||
| What is the mechanism by which Leukocytes move extravascularly? | Binding of chemotactic agent to receptor on cell surface, trigger cytoskeletal contractile element. Move by extension of pseudopods to anchor to extracellular matrix and pull the cell.
🗑
|
||||
| What are the two major benefit of having Leukocyte at the site of inflammation? | Phagocytosis and Degradative enzyme (Degranulation).
🗑
|
||||
| What are the 3 stages of Phagocytosis? | 1) Recognition and attachment. 2) Engulfment. 3) Killing and degradation.
🗑
|
||||
| How are Recognition and Attachment mediated? | By serum factors called OPSONINS that coat the surface (Fc fragments of IgG, C3b).
🗑
|
||||
| How does Engulfment occur? | Phagocytic vacuole formation around the target and fuse with lysosome to form Phagolysosome. Secondary messengers (mainly Ca)are initiated that cause activation of protein kinase C.
🗑
|
||||
| How does Killing and degradation occur? | Following the engulfment, a release of lysosomal granule content and degranulation of leukocytes. The leukocytes increases in metabolic activity with increased O2 & glycogenolysis "Oxidative or Respiratory Burst".
🗑
|
||||
| What are the 2 mechanism of Phagocytic killing and degradation? | Oxygen Dependent Mechanism & Non-Oxygen Dependent Mechanism.
🗑
|
||||
| Oxygen dependent mechanism | O2 is reduced to form free radicals that convert to hydrogen peroxide (H2O2). With Myeloperoxidase, it forms HOCl which is an antimicrobial agent. Reactive oxygen intermediate is toxic to bacteria.
🗑
|
||||
| Non-oxygen dependent mechanism | Involves lysosomal granuesl of leukocytes like elastase, lysozyme, major basic protein, bactericidal permeability-increasing protein, and defensins.
🗑
|
||||
| How does Mycobacterium Tuberculosis contribute to the spread of infection? | They form a lipid component in their cell wall which prevents phagocytic killing, although ingested by phagocytes, they remain viable and migration back to the lymphatic system can = spreading throughout the body.
🗑
|
||||
| Leukocyte-Induced Tissue Injury | Phagocytosis can result in releasing of HOCL-, lysosomal enzyme, and arachidonic acid metabolites. These can further injury and damage tissue, thus amplify the initial inflammatory stimuli. Left unchecked can detrimental to organism.
🗑
|
||||
| Common causes of Defective Leukocyte Function | 1) NEUTROPENIA - decrease in # of circulating cells due to bone marrow supression associated with tumors, chemotherapy, or radiotherapy. 2) Metabolic Disorders like Diabetes Mellitus = abnormal leukocyte function.
🗑
|
||||
| Genetic (inherited) disorders causint Defective Leukocyte Function | 1) Leukocyte Adhesion Deficiency (LAD-1, LAD-2) 2) Lazy Leukocyte Syndrome 3) Chediak-Higashi Syndrome 4) Chronic Granulomatous Disease
🗑
|
||||
| Leukocyte Adhesion Deficiency | Defects in Leukocyte adhesion
🗑
|
||||
| Lazy Leukocyte Syndrome | Defects in transmigration and chemotaxis
🗑
|
||||
| Chediak-Higashi Syndrome | Defects in Phagocytosis (phagolysosome formation)
🗑
|
||||
| Chronic Granulomatous Disease | H2O2 production is deficient and neutrophils do not develop the "Respiratory Burst"
🗑
|
||||
| 2 types of Chemical Mediators of Inflamation | 1) Cell-derived - produced locally by cells at the site of inflammation 2) Plasma protein-derived - derived from circulatin inactive precursors made in the liver that are activated at the site of inflammation.
🗑
|
||||
| Name the cells that are capable of chemical mediators | Macrophage, Mast Cells, Endothelial Cells, Activated Leukocytes, and Platelets
🗑
|
||||
| Cell-Derived Mediators components | 1 vasoactive amines 2 arachidonic acid metabolites 3 platelet-activating factor 4 cytokines 5 reactive oxygen species 6 nitric oxide 7 lysosomal enzymes of leukocytes
🗑
|
||||
| Plasma Protein-Derived Mediator components | 1 complement 2 kinin 3 proteases activated during coagulation
🗑
|
||||
| Vasoactive Amines | Principal mediator is HISTAMINE, major source is granules of MAST CELLS. Another vasoactive mediator similar to histamine is SEROTONIN.
🗑
|
||||
| Arachidonic Acid Metabolites (AA) (aka Eicosanoids) | AA is released from cell membrane by enzymes due to inflammation. Important to note that Corticosteroids drugs inhibit AA release by inhibiting phospholipase A.
🗑
|
||||
| AA is metabolized in two pathways | Cyclooxygenase Pathway & Lipoxygenase Pathway
🗑
|
||||
| Cyclooxygenase Pathway | AA converted to Prostaglandins (PG) and Thromboxanes (TX). PGI2 is a vasodilator and inhibit platelet aggregation. TXA2 causes vasoconstrictor and induce platelet aggregation. NSAIDs drugs inhibit cyclooxygenase pathway.
🗑
|
||||
| Lipoxygenase Pathway | AA is converted to Leukotrienes (LT - potent inflammatory mediator) and to anti-inflammatory mediator called Lipoxins (inhibit chemotaxis and adhesion).
🗑
|
||||
| Platelet-Activating Factor | Phospholipid derived, cause platelet aggregation, increase vascular permeability, leukocyte adhesion, chemotaxis, degranulation, and oxidative burst. Also stimulate AA synthesis and 100 to 1000 more potent that Histamine.
🗑
|
||||
| Cytokines | Polypeptides produced by activated Macrophage, Mast cell, and Endothelial cells. Acute inflammation is due to Interkeukin-1 (IL-1), (IL-6), Tumor Necrosis Factor (TNF) and Chemokines.
🗑
|
||||
| Reactive Oxygen Species (ROS) | Synthesized via Phagocytes Oxydase Pathway. At low levels - amplify cascade of inflammatory mediators, high levels - can cause tissue injury. ROS are regulated by catalase, superoxide dismutase, and glutathione.
🗑
|
||||
| Nitric Oxide | Short-lived free radical, roles are - vasodilation, antagonism of platelet activation, reduction of leukocyte recruitment, microbe killing w/in activated macrophages.
🗑
|
||||
| Lysosomal Enzyme of Leukocytes | Acid Protease & Neutral Proteases are released during phagocytosis or after cell death. Kept in check by antiprotease (alpha-antitrypsin, alpha-macroglobulin).
🗑
|
||||
| Plasma Protein-Derived Mediators are mediated by what 3 system? What factor initiates them? | Complement, Coagulation, and Kinin systems. Hageman Factor initiates the 3 system.
🗑
|
||||
| Complement System | Plasma proteins that activate a cascade of reaction (Classical Pathway, Alternate Pathway, and Lectin Pathway)
🗑
|
||||
| Kinin System | Leads to formation of Bradykinin which causes arteriolar dilation and increased vascular permeability.
🗑
|
||||
| Coagulation System | Series of plasma protein: Thrombin - form fibrin clots. Fibrinopeptes - vascular permeability and chemotactics for leukocytes. Plasmin - cause vasodilation and vascular permeability.
🗑
|
||||
| Morphologic Patterns of Acute Inflammation | 1) Serous Inflammation 2) Fibrinous Inflammation 3) Supporative (purulent) Inflammation and Abscess Formation 4) Ulcer
🗑
|
||||
| Serous Inflammation | leakage from blood vessels fo watery, protein-poor fluid (eg. blister)
🗑
|
||||
| Fibrinous Inflammation | accumulation of extravascular fibrin (eg. pericarditis)
🗑
|
||||
| Supporative Inflammation and Abscess Formation | collections of pus (neutrophils, nerotic cells, edema - eg. staphylococcal infection)
🗑
|
||||
| Ulcer | loss of epithelial surface due to necrosis and acute inflammation (peptic ulcer)
🗑
|
||||
| Outcomes of Acute Inflammation | 1) Resolution 2) Progression to chronic inflammation 3) Scarring or fibrosis
🗑
|
||||
| Characteristic of Chronic inflammation vs. Acute inflammation | Chronic: infiltration with mononuclear cells (macrophage, lymphocytes, plasma), tissue destruction, and repair.
Acute: vascular changes, edema, and mainly neutrophil infiltrate.
🗑
|
||||
| Chronic inflammation arises from... | Persistent microbial infection, Viral infection, Prolonged exposure to toxic agents, and Hypersensitivity, including autoimmune diseases.
🗑
|
||||
| Chronic Inflammatory cells and Mediators | Macrophages, Lymphocytes, Plasma Cells, Eosinophils and Mast Cells.
🗑
|
||||
| Macrophage | Name of a macrophage that exits the blood into tissue is call HISTIOCYTE. Macrophages can fuse to ingest foreign materials and foreign body reactions - MULTINUCLEATED GIANT CELLS.
🗑
|
||||
| Lymphocytes | Activated lymphocytes are the principal cells involved in cell-mediated immune response.
🗑
|
||||
| Plasma Cells | Differentiated end product of B-cell activation, produce Ab.
🗑
|
||||
| Eosinophils | Primarily in parasitic infections or IgE-mediated immune reactions (allergic reaction). Contain Major Basic Protein that is toxic to parasites and may cause epithelial cell necrosis.
🗑
|
||||
| Mast Cells | Key players in allergic reaction including Anaphylactic Shock
🗑
|
||||
| Granulomatous Inflammation | Distinctive pattern of chronic inflammation characterized by Epithelioid Macrophages surrounded by a collar of lymphocytes. Effective at "walling off" offending agents.
🗑
|
||||
| Systemic Manifestations of Inflammation "The Acute-phase Reaction" causes what clinical and pathologic changes? | Fever, Elevated Levels of Acute-Phase Proteins, Leukocytosis, and Other Manifestations
🗑
|
||||
| Important mediators of acute-phase reaction | TNF, IL-1, and IL-6
🗑
|
||||
| Characteristics of FEVER | Mediated by cytokines IL-1 and TNF (endogenous pyrogens) which act in response to exogenous pyrogens by bacteria.
🗑
|
||||
| Characteristics of Elevated Levels of Acute-Phase Proteins | 1) C-reactive proteins (CRP) 2) Fibrinogen 3) Serum Amyloid A Protein (SAA). CRP and SAA oposonizes and fix compliment, Fibrinogen causes stacks (Rouleaux) that sediment (Increased Erythrocyte Sedimentation Rate). Elevated CRP is an indication of MI.
🗑
|
||||
| Leukocytosis | Elevated # of circulating Leukocytes in the blood due to prolonged infection. Infection can also cause NEUTROPHILIA, LYMPHOCYTOSIS, and EOSINOPHILIA.
🗑
|
||||
| Leukopenia | Infections that causes a decrease in circulating white blood cells.
🗑
|
||||
| Other Manifestations | 1) increased heart rate 2) increased bp 3) decreased sweating, chills, anorexia, somnolence, and malaise.
🗑
|
||||
| Cachexia | A wasting syndrome in terminally ill pts with metastatic cancer, associated with chronic inflammation. TNF mediated appetite suppression and mobilization of fat stores.
🗑
|
||||
| Septic Shock | consists of Disseminated Intravascular Coagulation (DIC), hypoglycemia, and hypotensive = chronic inflammation
🗑
|
||||
| REPAIR involves what two dichotomous processes? | Regeneration and Scar formation
🗑
|
||||
| What are Growth Factors? What are the 3 types? | Proteins that drive cell proliferation. Autocrine, Paracrine, and Endocrine.
🗑
|
||||
| Autocrine | substances that act on the cell that secreted it
🗑
|
||||
| Paracrine | substances that affects cells in the immediate vicinity
🗑
|
||||
| Endocrine | regulatory substances like hormones, released into the bloodstream and acts on target cells that distant from its origin
🗑
|
||||
| 2 factors in determining the quality of repair | 1) capacity of the damaged cell to regenerate 2) maintenance of stromal framework or extracellular scaffold for regeneration
🗑
|
||||
| Components of Capacity of Cells to Regnerate | 1) Labile (continuously dividing cells 2) Stable (quiescent) cells 3) Permanent (nondividing cells
🗑
|
||||
| Labile Cells | Cells are continuously dividing (and continuously dying). eg. hematopoietic cells in bone marrow and majority of surface epithelia of the skin, oral cavity, etc...
🗑
|
||||
| Stable cells | Cells retain the capacity to regenerate but usually do not unless stimulated, eg. liver, kidney, pancreas, endothelial cells, fibroblasts, and smooth muscle cells.
🗑
|
||||
| Permanent cells | considered to be terminally differentiated and nonproliferative in postnatal life. eg. neurons and cardiac muscle cells
🗑
|
||||
| Maintenance of Stromal Framework (Extracellular Matrix) 2 basic forms | 1) Interstitial matrix 2) Basement membrane
🗑
|
||||
| Purpose of Extracellular Matrix (ECM) | Serves as a reservoir for growth factors, regulates proliferation, movement, and differentiation into cells.
🗑
|
||||
| Components of ECM | Fibrous structural protein, water-hydrated gels such as proteoglycans & hyaluronan, adhesive glycoproteins.
🗑
|
||||
| Repair by Connective Tissue - Granulation Tissue | specialized type of tissue that is a hallmark of healing (usually by 3-5 days)
🗑
|
||||
| 4 sequential process of Repair by Connective Tissue | 1) Formation of new blood vessels (ANGIOGENESIS) 2) Migration and proliferation of fibroblasts 3) Deposition of extracellular matrix (scar formation) 4) Maturation and reorganization of fibrous tissue (remodeling)
🗑
|
||||
| Factors which modify/alter the Repair Process | 1) Systemic Influences 2) Local Influences 3) Aberration in Healing
🗑
|
||||
| Systemic Influences | Factors like Nutrition, Systemic Diseases, and Hormones (corticosteroids) can greatly influence the repair process. Systemic diseases like Diabetes Mellitus predisposes individuals to infection and affect healing.
🗑
|
||||
| Local Influences | Adequate blood supply to the injured area is one of the most important factor in repair. Other local factors are foreign bodies, infection, immobilization of wound, and location of wound all influence repair.
🗑
|
||||
| Aberration in Healing | Keloid & "Proud Flesh" (exuberant granulation). Keloid - raised tumor-like scar. Proud Flesh - excess granulation tissue, must be removed to permit restoration of epithelium.
🗑
|
||||
| sequence the WOUND HEALING process | 1) induction of acute inflammatory response 2) parenchymal cell regeneration 3) migration and proliferation of parenchymal and connective tissue cells 4) synthesis of ECM 5) remodeling of parenchymal elements 6) remodeling connective tissue for strength
🗑
|
||||
| HEALING follow one of two patterns | 1) Healing by Primary union or first intention 2) Healing by secondary union or second intention
🗑
|
||||
| Healing by Primary union | occurs in small, clean, uninfected, sutured sounds
🗑
|
||||
| Healing by Secondary union | Occurs in wounds where there is extensive loss of tissue without closure by sutures
🗑
|
||||
| Major difference between Primary and Secondary union | Healing by secondary union/second intention is that it the wound undergoes a process of gradual constriction called WOUND CONTRACTION. This activity is thought to be accomplished by MYOFIBROBLASTS.
🗑
|
||||
| difference in Healing of Bone vs. soft tissue healing | Repair of bone follows the same process as soft tissue except osteoblasts and chondroblasts are involved.
🗑
|
||||
| Sequential process of Healing of Bone | 1) fractured bone is filled with blood clot 2) inflammation and granulation tissue replaces clot 3) within several days, Chondroblasts and Osteoblasts proliferate from adjacent bone 4) w/in one week small island of cartilage matrix w/in granulation tissue
🗑
|
||||
| Sequential process continued... | 4)...semi-rigid union form (PROCALLUS) 5) 2nd week, cartilage and osteoid begin to calcify 6) 4-6 wks forms BONY CALLUS that unite the two ends of fractured bone.
🗑
|
||||
| Healing of bone in tooth socket | Follows the sequential process of Healing of Bone except it does not involve cartilage formation.
🗑
|
Review the information in the table. When you are ready to quiz yourself you can hide individual columns or the entire table. Then you can click on the empty cells to reveal the answer. Try to recall what will be displayed before clicking the empty cell.
To hide a column, click on the column name.
To hide the entire table, click on the "Hide All" button.
You may also shuffle the rows of the table by clicking on the "Shuffle" button.
Or sort by any of the columns using the down arrow next to any column heading.
If you know all the data on any row, you can temporarily remove it by tapping the trash can to the right of the row.
To hide a column, click on the column name.
To hide the entire table, click on the "Hide All" button.
You may also shuffle the rows of the table by clicking on the "Shuffle" button.
Or sort by any of the columns using the down arrow next to any column heading.
If you know all the data on any row, you can temporarily remove it by tapping the trash can to the right of the row.
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Created by:
ddde227
Popular Science sets