acute and chronic inflammation. repair: cell growth and regeneration. wound healing. 2011

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  • Acute and chronic inflammation. Repair: cell growth and regeneration. Wound healing. 2011

  • Acute inflammationis early, immediate, response of vascularized living tissue to local injury, non-specificits purpose is1) to destroy injurious agent2) to reconstitute a damaged tissue (healing)repair already begins during early phases of inflammationinjured tissue is replaced by regeneration of parenchymal cellsby connective tissue formation - scarring

  • Causes of inflammationmicrobial infections: bacteria, viruses, fungi, etc.hypersensitivity reactionsphysical agents: burns, UV light, radiation, traumachemical agents: acids, alkalis, oxidising agents, toxins, endotoxins, even toxic catabolites derived from endogenous processes, such as in uraemia, etc.tissue necrosis: ischemia

  • Main clinical signs and symptoms of inflammationAcute inflammation is characterised by five major signs described by Celsus and Virchowrubor = redness from dilatation of blood vesselscalor = increased heat and fever- redness and heat -due to an increased rate and volume of blood flow because of vasodilatation, release of pyrogenstumor = swelling from edemadolor = pain form oedema and histamine release, pain is said to be due to an accumulation of acid metabolites that stimulate nerve endingsfunctio laesa = loss of function form pain and swelling

  • Morphologic and functional changes in acute inflammationmicrocirculatory responsecellular response

  • CELLS OF THE INFLAMMATORY RESPONSENeutrophilic leukocytesleukocytes are the first cells to appear at the site of acute inflammationis to degrade cell debris and to ingest and kill microbes- phagocytosisEosinophilic leukocytesassociated with hypersensitivity responses Basophils and mast cellsmast cells are usually seen in tissues in type I hypersensitivity reactions mediated by IgEbinding of IgE to the receptor on mast cells and basophils leads to degranulation of granules and release of the granule contents (heparin, histamine, and enzymes, such as acid hydrolase) into the tissues

  • Monocytes and macrophagesmacrophages are major scavenger cells of the bodyenzymes, such as lysozyme and hydrogen peroxide- degrade particulate material including micro-organismsthey control many of the cellular, vascular and reparative responses of inflammation by releasing chemotactic factors, cytokines (tumour necrosis factor) and growth factors (PDGF) and transforming growth factor beta (TGF-beta)Lymphocytes and plasma cellsthese are principal cells of specific immune responses- produce antibodies

  • Microcirculatory responseincreased blood flow and permeability of blood vesselsVasodilatation leads to hyperaemia (= increased amount of blood in infl. area )- heat and rednessincreased permeability of blood vessels- associated with slowing of the circulation- called stasisincreased passage of fluid out of microcirculation because of increased permeability in acute inflammation = exudation of fluid vascular leakage- loss of protein-rich fluid from blood vesselsreduction of osmotic pressure within blood vesselsincrease in interstitium- accumulation of fluid out of blood vesselsinflammatory oedema- major feature of acute inflammation

  • Formation of transudate and exudate

  • The major local manifestations of acute inflammation, compared to normal. Vascular dilation extravasation of plasma fluid and proteins (edema)leukocyte emigration

  • Composition of inflammatory exudateexudate is fluid rich in plasma proteins (albumins, immunoglobulins, fibrinogen)converted into fibrin by tissue tromboplastinFibrin can be recognised microscopically-pink fibres or clumps, macroscopically- most easily seen on acute infl. of serosal surfaces-acute fibrinous pericarditis- bread and butter appearance.Transudation= increased passage of fluids (very low level of plasma proteins, and no cells) through blood vessels with normal permeability- increased hydrostatic pressure or decreased plasma osmotic pressure -composition similar to ultrafiltrate of plasma

  • Significance of the process of exudation Exudation helps to destroy infectious agent by its dilutingby flooding the area with blood rich in immunoglobulins and other important defensive proteinsby increasing lymphatic flow -lymphatic drainage may to spread infectious agentsacute inflammation of lymphatics= lymphangitisacute inflammation of lymph nodes= lymphadenitis

  • Cellular responseNEUTROPHILIC LEUKOCYTES remain predominant cell type for several days in acute inflammation.emigration of neutrophils -leukocytes actively leave the blood vessel by moving through dilated intercellular junctions, pass through basement membrane and reach the extracellular spaceMACROPHAGES LYMPHOCYTES movements of these cells are similar to that of neutrophils- chemotactic mediators for macrophages- complement factor C5 and lymphokines (secreted by lymphocytes)ERYTHROCYTES enter extracellular space passively RBCs are pushed out from the blood vessel by hydrostatic pressure- the process is called erythrodiapedesiswhen large numbers of erythrocytes enter the inflamed area = haemorrhagic inflammation

  • Major events in phagocytosisrecognition and attachment of bacteria by the phagocytic cells - either directly (large inactive particles) or after opsonization (antigen is coated by opsonins)engulfment - extensions of cytoplasm (pseudopods) flow around the particles - formation of phagocytic vacuole, this vacuole fuses with membrane of lysosomal vacuoles-degranulation of leukocytesbacterial killing and degradation-killing of bacterial organisms is accomplished by activities of reactive oxygen species Failure of oxidative metabolism during phagocytosis - leads to a severe disorder of immunity = in chronic granulomatous disease of childhood

  • Phagocytosis of a particle (e.g., a bacterium) involves:

  • MORPHOLOGIC PATTERNS IN ACUTE INFLAMMATIONSerous inflammationis characterised by abundant serous exudatederived either from the blood stream or from the secretory activity of mesothelial cellspleural or pericardial cavities, skin, mucosal surfaces serous exudate is easily removed- complete regeneration

  • Acute inflammationSerous

  • Serous inflammation

  • Fibrinous inflammationCaused by more serious injuriespermeability of blood vessel is greaterand more proteins including large molecules of fibrinogen pass the vascular wallFibrinous exsudate can be removed-process called resolutionwhen fibrinous exsudate is not removedfibrin may stimulate the ingrowth of fibroblasts into the blood vessel wall, thus leading to scarring- this process is called organization

  • Acute inflammationFibrinous

  • Fibrinous inflammation

  • Suppurative or purulent inflammation

    is characterized by production of large amounts of purulent exsudate (pus)Abscess localized collection of purulent exudateUlcer = is a local defect in the tissue, mainly in the mucosal or cutaneous surfaces

  • Acute inflammationPurulent (suppurative)

  • Purulent-suppurative inflammationBronchopneumonia

  • Purulent inflammation

  • Acute inflammationPurulent (suppurative) peritonitis

  • Ulcerative, pseudomembranous inflammationacute ulcer- intense leukocyte infiltrate and vascular dilatation in the marginschronic ulcer -more developed fibroblastic reaction, scarring and infiltration of lymphocytes, macrophages and plasma cells

  • Fibrinopurulent and pseudomebranousPseudomembranous colitis

  • SYSTEMIC CLINICAL SIGNS OF ACUTE INFLAMMATIONfeverresults either of direct activity of cytokines or through local activity of prostaglandinschanges in the peripheral white blood cellsleucocytosis- the total number of neutrophils in the peripheral blood is increasedis common feature especially in bacterial infections shift to the left means an increased number of immature neutrophils in peripheral bloodLeukocyte count-may reach levels of about 15 or 20 thousands cells per mm3- extreme levels (more than 40 thousand)- referred to as leukemoid reactionviral infections tend to produce neutropenia (decreased number of leukocytes) with lymphocytosis (excess of lymphocytes in the blood)

  • CHRONIC INFLAMMATIONacute inflammation usually disappears after a few days and tissue returns to normalComplete resolution -means total restoration and regeneration of injured area.Healing by scarring -occurs after tissue destruction, in case of tissue defects, with abundant fibrin leakage, secondary infection, Progression to chronic inflammation chronic inflammatory response may follow acute inflammation that failed to destroy injurious agent or may be chronic from the onset (without a clinically apparent acute phase)

  • Outcomes of acute inflammation: resolution, healing by scarring, or chronic inflammation

  • Causes of chronic inflammationpersistent infection - caused by distinctive infectious agents, such as mycobacterium, treponema pallidum, some fungi, by organisms of lower toxicity, by intracellular organismsprolonged exposure to undegradable material, such as silica particles, carbon particles which, after being inhaled, set up a chronic inflammatory response in lungsautoimmune diseases= immune reaction set up against own tissues or cells - reveal a chronic inflammatory pattern- for example rheumatoid arthritis

  • MORPHOLOGIC FEATURES AND CLINICAL SIGNS OF CHRONIC INFLAMMATIONchronic inflammation is an inflammatory response characterized by the presence of lymphocytes, plasma cells and macrophagesit is distinguished from acute inflammation by the absence of cardinal signs such as rubor, calor, dolor, tumoractive hyperemia, fluid exudation and neutrophilic emigration are absentit is distinguished


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