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MID2163 TOPIC 3
 

MID2163 TOPIC 3

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Notes about inflammation

Notes about inflammation

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    MID2163 TOPIC 3 MID2163 TOPIC 3 Presentation Transcript

    • TOPIC 3:INFLAMMATION
    • OBJECTIVES Causes of inflammation Inflammation classifications – Acute Inflammation – Chronic Inflammation Systemic effects of inflammation
    • INFLAMMATION Latin word, inflammare = to burn Bodys response to injury DEFINITION: − Local defence mechanism initiated by tissue injury
    • INFLAMMATION Physiological response to tissue damage & accompanied by a characteristic series of local changes – Inflammatory reaction takes place in the surviving adjacent vascular & connective tissues
    • INFLAMMATION Purpose: Protection ⇨to localize & isolate toxic substances ⇨remove/destroy the injurious stimuli (pathogens) and damaged tissue ⇨initiate the healing and repair process – remove the cellular debris from the area
    • NOMENCLATURE Inflammatory lesion are usually indicated by the suffix ~itis Example: ⇨Appendicitis = inflammation of the appendix ⇨Meningitis = inflammation of the meninges Some exceptions, example: pneumonia, typhoid fever
    • CAUSES Physical agents →Mechanical injuries, alteration of temperature & pressure, radiation injuries, ultraviolet Chemical agents →Organic – microbial toxins & organic poisons (weedkillers) →Inorganic – acids, alkaline, drugs Biological agents/microbes →Infectious = bacteria, viruses, fungi, protozoa
    • CAUSES Immunologic disorders →Hypersensitivity reactions, autoimmunity, immunodificiency states Genetic/metabolic disorders → Gout, diabetes mellitus Antigens that stimulate immunological response
    • CLASSIFICATIONS
    • CLASSIFICATION Based on duration of the lesion and histologic appearances 2 classifications ⇨Acute inflammation ⇨Chronic inflammation
    • ACUTEINFLAMMATION
    • ACUTE INFLAMMATION Immediate & early response to an injurious agent = protective response! →Early vascular response and late cell response Relatively non-specific response →eliminate dead tissue, protect against local infection & allows immune system to response = beneficial
    • ACUTE INFLAMMATION Relatively short duration → lasting for minutes, several hours of a few days → may range from normal to severe
    • ACUTE INFLAMMATION 5 cardinal signs 1)Rubor 2)Calor 3)Tumor 4)Dolor 5)Functio laesa - latin words
    • ACUTE iNFLAMMATION1) Rubor  Redness  Due to dilation of small blood vessels within damaged tissue as it occurs in cellulitis by the action of mediators*cellulitis: inflammation spread to the connective tissue
    • ACUTE iNFLAMMATION2) Calor  Heat  Results from increased blood flow (hyperemia) due to:  regional vascular dilation  cellular metabolism
    • ACUTE iNFLAMMATION3) Tumor  Swelling  Due to accumulation of fluid in the extravascular space = increased vascular permeability
    • ACUTE iNFLAMMATION4) Dolor  Pain  Partly results from the stretching & destruction of tissues due to inflammatory edema & part from pus under pressure in as abcess cavity  Some chemicals of acute inflammation are also known to induce pain  Bradykinins, prostaglandin & serotonin
    • ACUTE iNFLAMMATION5) Functio leasa  Loss of function  Inflamed area is inhibited by pain while severe swelling may also physically immobilize the tissue
    • Steps ofAcute Inflammation
    • Steps of acute inflammation1) Increased blood flow = hyperemia2) Exudation of fluids & plasma proteins  Exudate: discharge of fluid or substances from cells or blood vessels onto the skin or organ surface3) Emigration of leucocytes
    • Capillaries become engorged & dilated with blood (congestion) Leakage of fluids and protein into the tissues = infiltration of leukocytes into the area of injuryLeukocytes engulf and digest the pathogens and help remove it from the area (phagocytosis)
    • 1) Hyperemia(a) Injured tissues by any agents(b) Following injury, both the arterioles supplying the damaged area and local capillaries dilate – increasing blood flow to the site • this causes redness (rubor) & increased heat (calor) in the affected region
    • 1) HyperemiaCaused mainly by local released of a number of chemical mediators from damaged cellsMast cells release histamine in response to tissue injury or infection
    • INJURY Damaged Cells Nervous Direct reactioneffect on (axon vessels CHEMICAL reflex) MEDIATORS VASCULAR DILATATION
    • 2) Exudation of Fluids* Exudation: increased passage of protein-rich fluid through the vessel wall into the interstitial tissue Fluid leaving local blood vessels & entering interstitial space = swelling / oedemaCaused by → Increased permeability of small blood vessels wall → Increased hydrostatic pressure
    • 2) Exudation of FluidsINCREASED PERMEABILITY Caused by → inflammatory mediators released by injured cells– prostaglandin, histamine & serotonin → cells that formed the single-layered venules pull apart from one another
    • 2) Exudation of FluidsINCREASED PERMEABILITY The opening of channels that allow the movement of → Excess fluid = leaves blood & enters tissues → Plasma proteins =albumin, globulin etc – normally retained in bloodstream  reduced osmotic pressure of blood
    • 2) Exudation of FluidsINCREASED HYDROSTATIC PRESSURE Increased blood flow into the capillary bed forces fluid out of the vessels & into the tissues Some interstitial fluid returns to capillaries but most of the inflammatory exudates, phagocytes & cell debris removed in lymph vessels → pores of the lymph vessels larger & pressure inside it is lower than blood capillaries
    • 3) Emigration of LeukocytesLoss of fluid → thicken the blood → reduced the flow → allowing leukocytes make contact & adhere to the vessel wall = selectin & integrins
    • 3) Emigration of LeukocytesMost important leukocyte = neutrophil → Adhere to the blood vessels lining → Squeeze between endothelial cells → Enters tissue and went to the inflamed area by chemotaxis → Main function: phagocytosis of antigen
    • 3) Emigration of LeukocytesMacrophages → larger and longer lived than neutrophils → phagocytose dead/dying tissue, microbes & other antigenic material and dead/dying neutrophils → predominently in inflamed tissue after 24hours → persist in the tissue if the situation is not resolved = chronic inflammation
    • CHEMOTAXISMovement of a motile cell/organism in a directioncorresponding to a gradient of increasing or decreasingconcentration of the particular chemotactic agent – Chemical attraction of leukocytes to an area of inflammation
    • PHAGOCYTOSIS eating CellMacrophages & neutrophils attracted to theinflammatory & infectious site by chemotaxisChemo-attractans released by injured cells & invadingmicrobesPhagocytes trap particles either by engulfing them withtheir body mass or by extending long psedopodia towardsthemNon-selective = bind, engulf and digest foreign cells orparticles
    • CHEMICAL MEDIATORSVarious chemical mediators have roles ininflammatory processThey may be circulating in plasma and requireactivation or may be secreted by inflammatory cells  Mast cells = histamine  Platelets = serotoninMany of these mediators have overlapping actions
    • Chemical mediators of InflammationVasodilating Histamine, serotonin,chemicals bradykinins, prostaglandinChemotactic Fibrin, collagen, mast cell,factors bacterial peptidesSubstances with Complement fragments ofboth vasodilating C5a and C3a, interferons,& chemotactic interleukines and plateleteffects secretion
    • Morphology ofAcute Inflammation
    • MORPHOLOGY Involves production of exudates (edema fluid with high protein concentration, frquently contain inflammatory cells)*Transudate? Non-inflammatory edema Caused by cardiac, renal, undernutritional and other disorders
    • MORPHOLOGY Different morphologic types of accute inflammation i. Serous inflammation - watery ii. Fibrinous inflammation - haemorrhagic iii.Suppurative (purulent) inflammation - pus iv.Catharral inflammation – mucous membrane v. Pseudomembranous inflammation
    • BLISTER, “Watery”, i.e., SEROUS
    • i. Serous Inflammation Characterized by an outpouring of a thin fluid that is derived from either the blood serum or secretion of mesothelial cells lining the peritoneal, pleural, and pericardial cavities It resolves without reactions
    • FIBRINOUS
    • ii. Fibrinous Inflammation More severe injuries Result in greater vascular permeability that ultimately leads to exudation of larger molecules such as fibrinogens through the vascular barrier Fibrinous exudate is characteristic of inflammation in serous body cavities such as the pericardium (butter and bread appearance) and pleura
    • ii. Fibrinous Inflammation Course of fibrous inflammation include: – Resolution by fibrinolysis – Scar formation between perietal and visceral surfaces i.e. the exudates get organized – Fibrous strand formation that bridges the pericardial space
    • PUS =PURULENT ABSCESS = POCKET OF PUS
    • iii. Suppurative Inflammation Characterized by the production of a large amount of pus – Pus is a thick creamy liquid, yellowish or blood stained in colour and composed of • A large number of living or dead leukocytes (pus cells) • Necrotic tissue debris • Living and dead bacteria • Edema fluid
    • iii. Suppurative Inflammation 2 types:A) Abscess formation: – abscess = a circumscribed accumulation of pus in a living tissue – encapsulated by a so-called pyogenic membrane, which consists of layers of fibrin, inflammatory cells and granulation tissue
    • iii. Suppurative Inflammation 2 types:B) Acute diffuse (phlegmonous) inflammation – characterized by diffuse spread of the exudate through tissue spaces – caused by virulent bacteria (eg. streptococci) without either localization or marked pus formation – example: Cellulitis (in palmar spaces)
    • iv. Catharral Inflammation Mild and superficial inflammation of the mucous membrane Commonly seen in the upper respiratory tract following viral infections where mucous secreting glands are present in large numbers example: Rhinitis.
    • v. Pseudomembranous Inflammation Basic elements – extensive confluent necrosis of the surface epithelium of an inflamed mucosa – severe acute inflammation of the underlying tissues The fibrinogens in the inflamed tissue coagulate within the necrotic epithelium
    • v. Pseudomembranous Inflammation Fibrinogen, necrotic epithelium, neutrophilic polymorphs, red blood cells, bacteria and tissue debris form a false (pseudo) membrane = forms a white or colored layer over the surface of inflamed mucosa Example: – Dipthetric infection of the pharynx or larynx – Clostridium difficille infection in the large bowel following certain antibiotic use
    • Effects ofAcute Inflammation
    • EFFECTS2 types of effects(a) Beneficial effects(b) Harmful effects
    • BENEFICIAL EFFECTSa) Dilution of toxins: ►concentration of chemical and bacterial toxins at the site of inflammation reduced by dilution in the exudate ►removal from the site by the flow of exudates from the venules through the tissue to the lymphatic
    • BENEFICIAL EFFECTSb) Protective antibodies: ►Formation of tissue exudation allows protective proteins including antibodies at the site of inflammation ►Thus, antibodies promote microbial destruction by phagocytosis or complement- mediated cell lysis = neutralise their toxins
    • BENEFICIAL EFFECTS(c)Fibrin formation: – Tissue damage is repaired and scars can form if fibroblasts are involved.
    • BENEFICIAL EFFECTSd) Promotion of phagocytosis ►Neutrophils & macrophages actively recruited to the inflamed areas = engulf biological & non-biological origin ►Phagocyte activity promoted by increasing temperature (local & systemic) ►Phagocytes may die at the inflamed area if the material they ingest resist digestion or excessive = disintegrate & released material that cause further damage
    • BENEFICIAL EFFECTSe) Cell nutrition: ►The flow of inflammatory exudates brings with it glucose, oxygen and other nutrients to meet the metabolic requirements of the greatly increased number of cells ►It also removes their solute waste products via lymphatic channels
    • BENEFICIAL EFFECTSf) Promotion of immunity: ►Micro-organisms and their toxins are carried by the exudates, either free or in phagocytes, along the lymphatics to local lymph nodes • they stimulate an immune response with the generation of antibodies and cellular immune mechanisms of defence
    • HARMFUL EFFECTS Tissue swelling ⇨Result of the increased blood flow & exudation ⇨Often accompanies by loss of function ⇨Effects can be harmful = depending on the site • Joint = limitation of movement • Larynx = interference with breathing
    • HARMFUL EFFECTS Pain ⇨Occurs when local swelling compress sensory nerve endings ⇨Exacerbated by chemical mediators of the inflammatory process that potentiate the sensitivity of the sensory nerve endings • Bradykinin • Prostaglandin
    • Course ofAcute Inflammation
    • COURSE OF ACUTE INFLAMMATIONpossible outcomes depend on removalof inflammatory exudate and replacementby either regenerated cells or scar tissue4 possible outcomes (1) Resolution (2) Healing by fibrosis (3) Abscess formation (4) Chronic inflammation
    • COURSE OF ACUTE INFLAMMATIONFactors affecting outcome of acuteinflammation (1) severity of tissue damage (2) capacity of stem cells to divide (3) type of agent causing damage
    • (1)Resolution involves complete restitution of normalarchitecture and function 3 main features which potentiate thissequel are → Minimal cell death & tissue damage → Rapid elimination of the causal agent → Local conditions favouring of fluid & debris
    • (1)Resolution Inflammatory process is reversed and → damaged cells are phagocytosed → fibrin strands are broken down by fibrinolytic enzymes → waste material is removed in lymph and blood vessels → repair is complete leaving only a small car
    • (1)Resolution Arises from damage to parenchyma inlabile/stable tissues  cells replaced by regeneration  normal function restoredCan only occur if the connective tissueframework of the tissue is intact & the tissueinvolved has the capacity to replace anyspecialised cells that have been lost
    • (2)Healing by Fibrosis Occurs when  connective tissue framework damage  tissue lacks the ability to regenerate specialised cells 1St: dead tissues & acute inflammatoryexudate removed by macrophages Defect filled by ingrowth of a specialisedvascular connective tissue called granulationtissue
    • (2)Healing by Fibrosisgranulation tissue - gradually producescollagen = form a fibrous (collagenous) scar =repairloss of some specialised cells & somearchitectural distortion by fibrous scar =structural integrity is re-established any impairment of function = dependent on theextent of loss of specialised cells
    • (2)Healing by Fibrosis Modified forms of repair occur in ► bone after a fracture when new bone is created ► brain with the formation of an astrocytic scar
    • (3)Abscess Formation Takes place when  acute inflammatory reaction fails to destroy/remove the cause of tissue damage  continues with a component of chronic inflammation Most common: infection by pyogenic bacteria As the acute inflammation progresses, there isliquefaction of the tissue to form pusPeripherally, a chronic inflammatory component& fibrous tissue surrounds the area = localising puss
    • (3)Abscess Formation If abscess left untreated, it can lead to  sinus formation  fistula formation
    • (3)Abscess FormationSinus  tract lined by granulation tissue  leading from a chronically inflamed cavity to a surface  cause the continuing presence of foreign or necrotic material  Example: sinus associated with osteomyelitis & pilonidal sinus
    • A pilonidal dimple is a small pit or sinus in the sacral areajust at the top of the crease between the buttocks - deeptract, rather than a shallow depression, leading to a sinusthat may contain hair.During adolescence the pilonidal dimple or tract maybecome infected forming a cyst-like structure called apilonidal cyst = may require surgical drainage or totalexcision to prevent reinfection
    • (3)Abscess FormationFistula  tract open at both ends  Abnormal communication b etween two surfaces is established  2 main types  congenital = development abnormality  acquired = trauma, inflammation or necrosis
    • (4)Chronic Inflammation May result following acute inflammationwhen an injurious agent persists over aprolonged period Causing concomitant tissue destruction,inflammation, organisation and repair Some injurious agents induced a chronicinflammatory type of response from theoutset
    • CHRONICINFLAMMATION
    • CHRONIC INFLAMMATION prolonged inflammatory process (weeks or months) where an active inflammation, tissue destruction and attempts at repair are proceeding simultaneously
    • Causes Persistent infections →Certain microorganisms associated with intracellular infection = tuberculosis, leprosy, certain fungi characterictically cause chronic inflammation →These organisms have low tosicity and evoke delayed hypersensitivity reactions
    • Causes Prolonged exposure to nondegradable but partially toxic substances →endogenous lipid components which result in atherosclerosis →exogenous substances such as silica, asbestos
    • Causes Progression from acute inflammation →acute inflammation almost always progresses to chronic inflammation following persistent suppuration as a result of • uncollapsed abscess cavities • foreign body materials (dirt, cloth, wool, etc) • sequesterum in osteomylitis • sinus/fistula from chronic abscesses
    • Causes Autoimmunity →autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosis are chronic inflammations from the outset
    • Morphology Cells of chronic inflammation – Monocytes & macrophages = main cells – T-lymphocytes – B-lymphocytes & plasma
    • Classification Classified into 2 types based on histologic features 1. Non-specific chronic inflammation 2. Specific inflammation (granulomatous inflammation)
    • Classification1. Non-specific chronic inflammation – involves a diffuse accumulation of macrophages and lymphocytes at site of injury that is usually productive with new fibrous tissue formations – example: Chronic cholecystitis.
    • Classification2. Specific inflammation – Granulomatous inflammation – characterized by the presence of granuloma • granuloma is a microscopic aggregate of epithelioid cells (modified macrophages)
    • Classification2. Specific inflammation – Epithelioid cell • is an activated macrophage, with a modified epithelial cell-like appearance (hence the name epithelioid) • can fuse with each other & form multinucleated giant cells – foreign body- type giant cells & Langhans giant cells
    • Classification2. Specific inflammation – granuloma is basically a collection of epithelioid cells, it also usually contains multinucleated giant cell & is usually surrounded by a cuff of lymphocytes and occasional plasma cells
    • Pathogenesis 2 types of granuloma 1. Foreign body granuloma 2. Immune granuloma
    • Pathogenesis1.Foreign body granuloma – initiated by inert foreign bodies such as talc, sutures (nonabsorbable), fibers, etc… – these foreign bodies are large enough to preclude phagocytosis by a single macrophage and do not incite an immune response
    • Pathogenesis2.Immune granulomas – antigen presenting cells (macrophages) engulf a poorly soluble inciting agent – then, the macrophage processes and presents part of the antigen and activated lymphocytes – the activated lymphocytes produce cytokines that activate another lymphocytes = transform macrophages into epitheloid & multinucleated giant cells & maintain the granuloma – Macrophage inhibitory factor helps to localize activated macrophages & epitheloid cells
    • Causes Major causes of granulomatious inflammation: – Bacterial: Tuberculosis, Leprosy, Syphilis, Cat scratch disease, Yersiniosis – Fungal: Histoplasmosis, Cryptococcosis, Coccidioidomycosis, Blastomycosis – Helminthic: Schistosomiasis – Protozoal: Leishmaniasis, Toxoplasmosis – Chlamydia: Lymphogranuloma venerum – Inorganic material: Berrylliosis – Idiopathic: Acidosis, Cohn’s disease, Primary biliary cirrhosis
    • SYSTEMIC EFFECTSOF INFLAMMATION
    • Systemic effects of Inflammation Include 1. Fever 2. Endocrine & metabolic responses 3. Autonomic responses 4. Behavioural responses 5. Leukocytosis 6. Leukopenia 7. Weight loss
    • 1.Fever most important systemic manifestation of inflammation. It is coordinated by the hypothalamus & by cytokines released from macrophages and other cells2. Endocrine & metabolic responses the liver secrets acute phase proteins such as C- reactive proteins, Serum Amyloid A, complement and coagulation proteins Glucocorticoids (increased) Vasopressin (decreased)
    • 3. Autonomic responses redirection of blood flow from the cutaneous to the deep vascular bed pulse rate and blood pressure (increased) sweating (decreased)4. Behavioural responses Rigor, chills, anoroxia, somnolence and malaise
    • 5. Leukocytosis also a common feature of inflammation, especially in bacterial infections its usual count is 15,000 to 20,000 cells/mm3 most bacterial infections induce neutrophilia some viral infections such as infectious mononucleosis, & mumps cause lymphocytosis parasitic infestations & allergic reactions such as bronchial ashma & hay fever induce eosinophilia
    • 6. Leukopenia Also a feature of thyphoid fever and some parasitic infections7. Weight loss Catabolism of skeletal muscle, adipose tissue and the liver with resultant negative nitrogen balance