Acute and chronic Acute and chronic inflammation. Repair: cell inflammation. Repair: cell growth and regeneration. growth and regeneration.

Wound healing. Wound healing.

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Acute inflammationAcute inflammation

is early, immediate, response of is early, immediate, response of vascularized living tissue to local injury, vascularized living tissue to local injury, non-specificnon-specific

its purpose isits purpose is 1) to destroy injurious agent1) to destroy injurious agent 2) to reconstitute a damaged tissue (healing)2) to reconstitute a damaged tissue (healing)

repair already begins during early phases repair already begins during early phases of inflammationof inflammation

injured tissue is replaced by regeneration injured tissue is replaced by regeneration of parenchymal cellsof parenchymal cells

by by connectiveconnective tissue tissue formation formation -- scarringscarring

Causes of inflammationCauses of inflammation

microbial infections: bacteria, viruses, microbial infections: bacteria, viruses, fungi, etc.fungi, etc.

hypersensitivity reactionshypersensitivity reactions physical agents: burns, UV light, radiation, physical agents: burns, UV light, radiation,

traumatrauma chemical agents: acids, alkalis, oxidising chemical agents: acids, alkalis, oxidising

agents, toxins, endotoxins, even toxic agents, toxins, endotoxins, even toxic catabolites derived from endogenous catabolites derived from endogenous processes, such as in uraemia, etc.processes, such as in uraemia, etc.

tissue necrosis: ischemiatissue necrosis: ischemia

Main clinical signs and Main clinical signs and symptoms of inflammationsymptoms of inflammation

Acute inflammation is characterised by five Acute inflammation is characterised by five major signs described by major signs described by Celsus and Celsus and VirchowVirchow ruborrubor = redness from dilatation of blood vessels = redness from dilatation of blood vessels calorcalor = increased heat and fever- redness and = increased heat and fever- redness and

heat -due to an increased rate and volume of blood heat -due to an increased rate and volume of blood flow because of vasodilatation, release of pyrogensflow because of vasodilatation, release of pyrogens

tumotumorr = swelling from edema= swelling from edema dolordolor = pain form oedema and histamine release, = pain form oedema and histamine release,

pain is said to be due to an accumulation of acid pain is said to be due to an accumulation of acid metabolites that stimulate nerve endingsmetabolites that stimulate nerve endings

functio laesafunctio laesa = loss of function form pain and = loss of function form pain and swellingswelling

MMorphologic and functional orphologic and functional changes in acute changes in acute

inflammationinflammation microcirculatory responsemicrocirculatory response cellular responsecellular response

CELLS OF THE CELLS OF THE INFLAMMATORY RESPONSEINFLAMMATORY RESPONSE

Neutrophilic leukocytesNeutrophilic leukocytes leukocytes are the first cells to appear at the site of leukocytes are the first cells to appear at the site of

acute inflammationacute inflammation is to degrade cell debris and to ingest and kill microbes- is to degrade cell debris and to ingest and kill microbes-

phagocytosisphagocytosis Eosinophilic leukocytesEosinophilic leukocytes

associated with hypersensitivity responses associated with hypersensitivity responses Basophils and mast cellsBasophils and mast cells

mast cells are usually seen in tissues in type I mast cells are usually seen in tissues in type I hypersensitivity reactions mediated by IgEhypersensitivity reactions mediated by IgE

binding of IgE to the receptor on mast cells and binding of IgE to the receptor on mast cells and basophils leads to basophils leads to degranulation of granules degranulation of granules and and release of the granule contents (heparin, histamine, and release of the granule contents (heparin, histamine, and enzymes, such as acid hydrolase) into the tissuesenzymes, such as acid hydrolase) into the tissues

Monocytes and macrophagesMonocytes and macrophages macrophages are major scavenger cells of the bodymacrophages are major scavenger cells of the body enzymes, such as lysozyme and hydrogen peroxide- enzymes, such as lysozyme and hydrogen peroxide-

degrade particulate material including micro-organismsdegrade particulate material including micro-organisms they control many of the cellular, vascular and they control many of the cellular, vascular and

reparative responses of inflammation by releasing reparative responses of inflammation by releasing chemotactic factors, cytokines (tumour necrosis factor) chemotactic factors, cytokines (tumour necrosis factor) and growth factors (PDGF) and transforming growth and growth factors (PDGF) and transforming growth factor beta (TGF-beta)factor beta (TGF-beta)

Lymphocytes and plasma cellsLymphocytes and plasma cells these are principal cells of specific immune responses- these are principal cells of specific immune responses-

produce antibodiesproduce antibodies

MMicrocirculatory icrocirculatory responseresponse

increased blood flow and permeability of blood vesselsincreased blood flow and permeability of blood vessels Vasodilatation leads to hyperaemia (= increased Vasodilatation leads to hyperaemia (= increased

amount of blood in infl. area )- amount of blood in infl. area )- heat and rednessheat and redness increased permeability of blood vessels- associated increased permeability of blood vessels- associated

with slowing of the circulation- called with slowing of the circulation- called stasisstasis increased passage of fluid out of microcirculation increased passage of fluid out of microcirculation

because of increased permeability in acute because of increased permeability in acute inflammation = inflammation = exudation of fluidexudation of fluid

vascular leakagevascular leakage-- loss of loss of protein-rich fluidprotein-rich fluid from blood from blood vesselsvessels reduction of osmotic pressure within blood vesselsreduction of osmotic pressure within blood vessels increase increase inin interstitium- accumulation of fluid out of blood interstitium- accumulation of fluid out of blood

vesselsvessels inflammatory oedemainflammatory oedema- major feature of acute inflammation- major feature of acute inflammation

Formation of transudate and exudate

The major local manifestations of

acute inflammation, compared

to normal.

(1)Vascular dilation

(2) extravasation of plasma fluid and proteins (edema)

(3)leukocyte emigration

Composition of Composition of inflammatory exudateinflammatory exudate

exudateexudate is fluid is fluid rrich in plasma proteinsich in plasma proteins ( (albumins, immunoglobulins, albumins, immunoglobulins,

fibrinogenfibrinogen)) converted into fibrin by tissue tromboplastinconverted into fibrin by tissue tromboplastin

FibrinFibrin can be recognised microscopically-pink fibres can be recognised microscopically-pink fibres or clumps, macroscopically- most easily seen on or clumps, macroscopically- most easily seen on acute infl. of serosal surfaces-acute fibrinous acute infl. of serosal surfaces-acute fibrinous pericarditis- „bread and butter„ appearance.pericarditis- „bread and butter„ appearance.

TransudationTransudation= increased passage of fluids (very low = increased passage of fluids (very low level of plasma proteins, and no cells) through level of plasma proteins, and no cells) through blood vessels with normal permeability- increased blood vessels with normal permeability- increased hydrostatic pressure or decreased plasma osmotic hydrostatic pressure or decreased plasma osmotic pressure -composition similar to ultrafiltrate of pressure -composition similar to ultrafiltrate of plasmaplasma

Significance of the process Significance of the process of exudationof exudation

ExudationExudation helps to destroy infectious agent by its dilutinghelps to destroy infectious agent by its diluting by flooding the area with blood rich in by flooding the area with blood rich in

immunoglobulins and other important defensive immunoglobulins and other important defensive proteinsproteins

by increasing lymphatic flow by increasing lymphatic flow --lymphatic drainage lymphatic drainage may to spread infectious agentsmay to spread infectious agents

acute inflammation of lymphatics= acute inflammation of lymphatics= lymphangitislymphangitis

acute inflammation of lymph nodes= acute inflammation of lymph nodes= lymphadenitislymphadenitis

CCellular responseellular response

NEUTROPHILIC LEUKOCYTESNEUTROPHILIC LEUKOCYTES remain predominant cell type for several days in acute remain predominant cell type for several days in acute

inflammation.inflammation. emigration of neutrophils -leukocytes actively leave the blood emigration of neutrophils -leukocytes actively leave the blood

vessel by moving through dilated intercellular junctions, pass vessel by moving through dilated intercellular junctions, pass through basement membrane and reach the extracellular spacethrough basement membrane and reach the extracellular space

MACROPHAGES MACROPHAGES LYMPHOCYTES LYMPHOCYTES

movements of these cells are similar to that of neutrophils- movements of these cells are similar to that of neutrophils- chemotactic mediators for macrophages- complement factor C5 chemotactic mediators for macrophages- complement factor C5 and lymphokines (secreted by lymphocytes)and lymphokines (secreted by lymphocytes)

ERYTHROCYTESERYTHROCYTES enter extracellular space passively – enter extracellular space passively – RBCs are pushed out from the blood vessel by hydrostatic RBCs are pushed out from the blood vessel by hydrostatic

pressure- the process is called erythrodiapedesispressure- the process is called erythrodiapedesis when large numbers of erythrocytes enter the inflamed area = when large numbers of erythrocytes enter the inflamed area =

haemorrhagic inflammationhaemorrhagic inflammation

Major events in Major events in phagocytosisphagocytosis

recognitionrecognition and attachment of bacteria by the and attachment of bacteria by the phagocytic cells - either directly (large inactive phagocytic cells - either directly (large inactive particles) or after opsonization (antigen is coated by particles) or after opsonization (antigen is coated by opsonins)opsonins)

engulfmentengulfment - extensions of cytoplasm (pseudopods) - extensions of cytoplasm (pseudopods) flow around the particles - formation of phagocytic flow around the particles - formation of phagocytic vacuole, this vacuole fuses with membrane of vacuole, this vacuole fuses with membrane of lysosomal vacuoles-degranulation of leukocyteslysosomal vacuoles-degranulation of leukocytes

bacterial killingbacterial killing and degradation-killing of bacterial and degradation-killing of bacterial organisms is accomplished by activities of reactive organisms is accomplished by activities of reactive oxygen species oxygen species

Failure of oxidative metabolism during phagocytosis - Failure of oxidative metabolism during phagocytosis - leads to a severe disorder of immunity = in chronic leads to a severe disorder of immunity = in chronic granulomatous disease of childhoodgranulomatous disease of childhood

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

MORPHOLOGIC PATTERNS MORPHOLOGIC PATTERNS IN ACUTE INFLAMMATIONIN ACUTE INFLAMMATION

Serous inflammationSerous inflammation is characterised by abundant serous exudateis characterised by abundant serous exudate derived either from the blood stream or from derived either from the blood stream or from

the secretory activity of mesothelial cellsthe secretory activity of mesothelial cells pleural or pericardial cavities,pleural or pericardial cavities, skin, mucosal skin, mucosal

surfacessurfaces serous exudate is easily removed- complete serous exudate is easily removed- complete

regenerationregeneration

Acute inflammationAcute inflammation

SerousSerous

Serous inflammationSerous inflammation

Fibrinous inflammationFibrinous inflammation

Caused byCaused by more serious injuries more serious injuries permeability of blood vessel is greaterpermeability of blood vessel is greater and more proteins including large molecules of and more proteins including large molecules of

fibrinogen pass the vascular wallfibrinogen pass the vascular wall Fibrinous exsudate Fibrinous exsudate cancan be removed- be removed-process process

calledcalled resolutionresolution wwhen fibrinous exsudate is not removedhen fibrinous exsudate is not removed

fibrin may stimulate the ingrowth of fibroblasts fibrin may stimulate the ingrowth of fibroblasts into the blood vessel wall, thus leading to into the blood vessel wall, thus leading to scarringscarring- this process is called - this process is called organizationorganization

Acute inflammationAcute inflammation FibrinousFibrinous

Fibrinous Fibrinous inflammationinflammation

Suppurative or purulent Suppurative or purulent inflammationinflammation

is characterized by production of large is characterized by production of large amounts of amounts of purulent exsudate (pus)purulent exsudate (pus) AbscessAbscess localized collection of purulent localized collection of purulent

exudateexudate UlcerUlcer = is a local defect in the tissue, = is a local defect in the tissue,

mainly in the mucosal or cutaneous mainly in the mucosal or cutaneous surfacessurfaces

Acute inflammationAcute inflammation

Purulent Purulent (suppurative(suppurative))

Purulent-suppurative Purulent-suppurative inflammationinflammation

Bronchopneumonia

Purulent inflammationPurulent inflammation

Acute inflammationAcute inflammation

Purulent (suppurative) peritonitisPurulent (suppurative) peritonitis

Ulcerative, Ulcerative, pseudomembranous pseudomembranous

inflammationinflammation acute ulcer-acute ulcer- intense leukocyte intense leukocyte

infiltrate and vascular dilatation in infiltrate and vascular dilatation in the marginsthe margins

chronic ulcerchronic ulcer -more developed -more developed fibroblastic reaction, scarring and fibroblastic reaction, scarring and infiltration of lymphocytes, infiltration of lymphocytes, macrophages and plasma cellsmacrophages and plasma cells

Fibrinopurulent and Fibrinopurulent and pseudomebranouspseudomebranous

Pseudomembranous colitis

SYSTEMIC CLINICAL SIGNS SYSTEMIC CLINICAL SIGNS OF ACUTE INFLAMMATIONOF ACUTE INFLAMMATION

feverfever results either of direct activity of cytokines or through results either of direct activity of cytokines or through

local activity of prostaglandinslocal activity of prostaglandins changes in the peripheral white blood cellschanges in the peripheral white blood cells

leucocytosisleucocytosis- the total number of neutrophils in the - the total number of neutrophils in the peripheral blood is increasedperipheral blood is increased

is common feature especially in bacterial infectionsis common feature especially in bacterial infections „ „ shift to the leftshift to the left“ means an increased number of “ means an increased number of

immature neutrophils in peripheral bloodimmature neutrophils in peripheral blood Leukocyte count-may reach levels of about 15 or 20 Leukocyte count-may reach levels of about 15 or 20

thousands cells per mm3- extreme levels (more than 40 thousands cells per mm3- extreme levels (more than 40 thousand)- referred to as leukemoid reactionthousand)- referred to as leukemoid reaction viral infections tend to produce neutropenia (decreased viral infections tend to produce neutropenia (decreased

number of leukocytes) with lymphocytosis (excess of number of leukocytes) with lymphocytosis (excess of lymphocytes in the blood)lymphocytes in the blood)

CHRONIC INFLAMMATIONCHRONIC INFLAMMATION

acute inflammation usually disappears after a few acute inflammation usually disappears after a few days and tissue returns to normaldays and tissue returns to normal Complete resolutionComplete resolution -means total restoration and -means total restoration and

regeneration of injured area.regeneration of injured area. Healing by scarringHealing by scarring -occurs after tissue destruction, in -occurs after tissue destruction, in

case of tissue defects, with abundant fibrin leakage, case of tissue defects, with abundant fibrin leakage, secondary infection, secondary infection,

Progression to chronic inflammationProgression to chronic inflammation chronic inflammatory response may follow acute chronic inflammatory response may follow acute

inflammation that failed to destroy injurious inflammation that failed to destroy injurious agent or may be chronic from the onset (without agent or may be chronic from the onset (without a clinically apparent acute phase)a clinically apparent acute phase)

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

chronic inflammationchronic inflammation

Causes of chronic Causes of chronic inflammationinflammation

persistent infectionpersistent infection - caused by distinctive - caused by distinctive infectious agents, such as mycobacterium, infectious agents, such as mycobacterium, treponema pallidum, some fungi, by organisms of treponema pallidum, some fungi, by organisms of lower toxicity, by intracellular organismslower toxicity, by intracellular organisms

prolonged exposureprolonged exposure to undegradable material, to undegradable material, such as silica particles, carbon particles which, such as silica particles, carbon particles which, after being inhaled, set up a chronic inflammatory after being inhaled, set up a chronic inflammatory response in lungsresponse in lungs

autoimmune diseasesautoimmune diseases= immune reaction set up = immune reaction set up against own tissues or cells - reveal a chronic against own tissues or cells - reveal a chronic inflammatory pattern- for example rheumatoid inflammatory pattern- for example rheumatoid arthritisarthritis

MORPHOLOGIC FEATURES AND MORPHOLOGIC FEATURES AND CLINICAL SIGNS OF CHRONIC CLINICAL SIGNS OF CHRONIC

INFLAMMATIONINFLAMMATION chronic inflammation is an inflammatory response chronic inflammation is an inflammatory response

characterized by the presence of characterized by the presence of lymphocytes, lymphocytes, plasma cells and macrophagesplasma cells and macrophages

it is distinguished from acute inflammation it is distinguished from acute inflammation by the by the absence of cardinal signs such as rubor, absence of cardinal signs such as rubor,

calor, dolor, tumorcalor, dolor, tumor active hyperemia, fluid exudation and neutrophilic active hyperemia, fluid exudation and neutrophilic

emigration are absentemigration are absent it is distinguished from acute inflammation by its it is distinguished from acute inflammation by its

long duration, which permits a manifestation of long duration, which permits a manifestation of immune responseimmune response Often associated with scarring, fibroproliferationOften associated with scarring, fibroproliferation

chronic

acute

Histologic hallmarks of Histologic hallmarks of chronic inflammationchronic inflammation

infiltration by infiltration by macrophages, lymphocytes macrophages, lymphocytes and plasma cellsand plasma cells

proliferation of fibroblasts and proliferation of fibroblasts and myofibroblasts and proliferation of small myofibroblasts and proliferation of small blood vessels, together known as formation blood vessels, together known as formation of of granulation tissuegranulation tissue

in most cases, the process of chronic in most cases, the process of chronic inflammation is accompanied by a inflammation is accompanied by a proliferation of connective tissue (deposition proliferation of connective tissue (deposition of collagen fibres), referred to as of collagen fibres), referred to as fibrosisfibrosis

usually marked usually marked tissue destructiontissue destruction

Granulation tissueGranulation tissue

Reparation component of inflammation is represented by granulation tissue composed of budding

capillaries, fibroblasts and occasional inflammatory cells

CHRONIC INFLAMMATORY CHRONIC INFLAMMATORY CELLSCELLS

MACROPHAGESMACROPHAGES play central role in chronic inflammatory infiltrate-play central role in chronic inflammatory infiltrate-

macrophages are the most effective phagocytic cells in macrophages are the most effective phagocytic cells in acute and chronic inflammatory responseacute and chronic inflammatory response

enzymatic degradation and phagocytic activityenzymatic degradation and phagocytic activity following activation-macrophagesfollowing activation-macrophages produce produce

biologically active products, such as:biologically active products, such as: enzymes - neutral and acid proteasesenzymes - neutral and acid proteases chemotactic factors for leukocyteschemotactic factors for leukocytes growth factors and promoting factors for fibroblasts and growth factors and promoting factors for fibroblasts and

blood vessels- thus macrophages may modulate a blood vessels- thus macrophages may modulate a formation of non-specific granulation tissueformation of non-specific granulation tissue

cytokines, such as interleukin I , TNF,etc.cytokines, such as interleukin I , TNF,etc.

PLASMA CELLSPLASMA CELLS produce antibodies directed against persistent produce antibodies directed against persistent

antigens or against altered tissue componentsantigens or against altered tissue components LYMPHOCYTESLYMPHOCYTES

when activated by the contact with antigen, when activated by the contact with antigen, lymphocytes release lymphokines- many of them lymphocytes release lymphokines- many of them stimulate macrophagesstimulate macrophages

on the other hand, lymphocytes may be on the other hand, lymphocytes may be stimulated by cytokines released by activated stimulated by cytokines released by activated macrophagesmacrophages

EOSINOPHILSEOSINOPHILS are characteristic of immunologic reaction are characteristic of immunologic reaction

mediated by IgE and of parasitic infectionsmediated by IgE and of parasitic infections

NEUTROPHILIC LEUKOCYTESNEUTROPHILIC LEUKOCYTES in chronic inflammation of bone marrow in chronic inflammation of bone marrow

(osteomyelitis)- large numbers of neutrophils (osteomyelitis)- large numbers of neutrophils may persists for monthsmay persists for months

also chronic inflammation of fallopian tube may also chronic inflammation of fallopian tube may have the pattern of chronic suppuration with have the pattern of chronic suppuration with large numbers of neutrophilslarge numbers of neutrophils

FIBROBLASTFIBROBLASTS S fibroproduction and accumulation of fibroproduction and accumulation of

extracellular proteins- characteristic features of extracellular proteins- characteristic features of chronic inflammatory responsechronic inflammatory response

MORPHOLOGIC TYPES OF MORPHOLOGIC TYPES OF CHRONIC INFLAMMATORY CHRONIC INFLAMMATORY

RESPONSERESPONSE GRANULOMATOUS CHRONIC INFLAMMATIONGRANULOMATOUS CHRONIC INFLAMMATION

is characterized by formation of is characterized by formation of epithelioid granulomasepithelioid granulomas granuloma- is defined as an aggregate of macrophages, two granuloma- is defined as an aggregate of macrophages, two

types of granulomas are recognisedtypes of granulomas are recognised

epithelioid granulomaepithelioid granuloma-- represents immune represents immune responseresponse macrophages are activated by T-lymphocytesmacrophages are activated by T-lymphocytes „ „ epithelioid cell“ are activated macrophages - large cells epithelioid cell“ are activated macrophages - large cells

with abundant pale foamy cytoplasm - superficial with abundant pale foamy cytoplasm - superficial resemblance to epithelial cellsresemblance to epithelial cells

typical feature of epithelioid granulomas is formation of typical feature of epithelioid granulomas is formation of Langhans-type giant cells- are derived from macrophagesLanghans-type giant cells- are derived from macrophages

Chronic granulomatous Chronic granulomatous inflammationinflammation

Langhans cell

Epithelioid histiocytes

Granuloma (also called „specific granulation tissue“) is composed of modified macrophages)

Epithelioid granulomas occur Epithelioid granulomas occur inin

infection due to intracellular organismsinfection due to intracellular organisms Tuberculosis (Mycobacterium Tuberculosis)Tuberculosis (Mycobacterium Tuberculosis) Leprosy (Mycobacterium leprae)Leprosy (Mycobacterium leprae) Syphilis (Treponema pallidum)Syphilis (Treponema pallidum) Cat-scratch disease (Gram negative bacillus)-rounded Cat-scratch disease (Gram negative bacillus)-rounded

or stellate granulomas usually within lymph nodes or stellate granulomas usually within lymph nodes containing the central granular debris and leukocytescontaining the central granular debris and leukocytes

Several Several parasitic and fungal infectionsparasitic and fungal infections (schistosomiasis, cryptococcus)(schistosomiasis, cryptococcus)

Sarcoidosis Sarcoidosis (Mycobacterium)(Mycobacterium) disorders due to chemical agents such as beryllium disorders due to chemical agents such as beryllium

(berylliosis)(berylliosis) Crohn diseaseCrohn disease

TuberculosisTuberculosis

TuberculosisTuberculosis is characterized by specific granulomas, caseous necrosis and finding of

Mycobacterium tuberculosis (Ziehl-Nielsen stain)

Chronic granulomatous Chronic granulomatous inflammationinflammation

SarcoidosisSarcoidosis

?allergic reaction to the presence of non-virulent mycobacteria?

Chronic granulomatous Chronic granulomatous inflammationinflammation

SarcoidosisSarcoidosis

Granuloma without caseous necrosis

Asteroid inclusions

Schaumann´s inclusions

Hamazaki – Wesenberg inclusions

NONGRANULOMATOUS NONGRANULOMATOUS CHRONIC INFLAMMATIONCHRONIC INFLAMMATION

accumulation of sensitised lymphocytes, plasma cells and accumulation of sensitised lymphocytes, plasma cells and macrophages macrophages

chronic viral infectionschronic viral infections persistent infection of parenchymal cells by viruses evokes an persistent infection of parenchymal cells by viruses evokes an

immune response- the affected tissue shows presence of lymphocytes immune response- the affected tissue shows presence of lymphocytes and plasmacytes, cytotoxic effect is mediated either by killer- T-and plasmacytes, cytotoxic effect is mediated either by killer- T-lymphocytes or by cytotoxic antibodieslymphocytes or by cytotoxic antibodies

in chronic autoimmune diseasesin chronic autoimmune diseases immune response is also mediated by killer- T-lymphocytes or by immune response is also mediated by killer- T-lymphocytes or by

cytotoxic antibodiescytotoxic antibodies the antigen is a host cell molecule which is recognised as foreign by the antigen is a host cell molecule which is recognised as foreign by

immune systemimmune system pathologic result is cell necrosis, resulting in fibrosis and lymphocytic pathologic result is cell necrosis, resulting in fibrosis and lymphocytic

and plasmacytic infiltrationand plasmacytic infiltration in chronic inflammation in chronic inflammation due to chemical toxic substancesdue to chemical toxic substances

alcohol produces chronic inflammation – liver, pancreasalcohol produces chronic inflammation – liver, pancreas cell necrosis - alteration in host molecule - becomes antigenic and cell necrosis - alteration in host molecule - becomes antigenic and

evoke immune responseevoke immune response

REPAIR. CELL GROWTH AND REPAIR. CELL GROWTH AND REGENERATION. WOUND REGENERATION. WOUND

HEALINGHEALING resolutionresolution -removal of debris associated with a -removal of debris associated with a

complete restoration of the tissue to preinjury statecomplete restoration of the tissue to preinjury state regenerationregeneration - complete replacement of necrotic - complete replacement of necrotic

parenchymal cells by new parenchymal cells of the parenchymal cells by new parenchymal cells of the same qualitysame quality

resolution and regenerationresolution and regeneration- ideal outcome of - ideal outcome of healing- is possible only in the tissues with healing- is possible only in the tissues with prevailing labile cells (cells capable of mitotic prevailing labile cells (cells capable of mitotic division- complete regeneration)division- complete regeneration)

if complete resolution and regeneration is not if complete resolution and regeneration is not possible, necrotic foci may be replaced by collagenpossible, necrotic foci may be replaced by collagen this process is termed organisation this process is termed organisation repair by scar repair by scar

formationformation

REGENERATIONREGENERATION

replacement of lost parenchymal cells is replacement of lost parenchymal cells is dependent ondependent on regenerative capacity of the cellsregenerative capacity of the cells number of surviving cellsnumber of surviving cells maintenance of basement membranes or presence of maintenance of basement membranes or presence of

stem cell layerstem cell layer The cells of the body can be divided into 3 groups The cells of the body can be divided into 3 groups

on the basis of their regenerative capacity and on the basis of their regenerative capacity and their relation to the cell cycle:their relation to the cell cycle: Labile cell (intermitotic)Labile cell (intermitotic) Stable cell (reversible postmitotic )Stable cell (reversible postmitotic ) Permanent cell (irreversible postmitotic)Permanent cell (irreversible postmitotic)

Labile cellsLabile cells

continuously dividing cells- they continue to continuously dividing cells- they continue to proliferate, remain all the time in cell cycleproliferate, remain all the time in cell cycle Healing in tissues with many labile cells:Healing in tissues with many labile cells: injury is followed by rapid and complete injury is followed by rapid and complete

regenerationregeneration surgical removal of endometrium by curettage surgical removal of endometrium by curettage

is followed by complete regeneration from the is followed by complete regeneration from the basal germinative layer within short timebasal germinative layer within short time

or destruction of erythrocytes stimulates rapid or destruction of erythrocytes stimulates rapid erythroid hyperplasia in bone marrow which erythroid hyperplasia in bone marrow which results in complete regeneration of results in complete regeneration of erythropoesiserythropoesis

Stable cells-quiescentStable cells-quiescent

they are considered to be in G0 phase, may they are considered to be in G0 phase, may undergo rapid proliferation after appropriate undergo rapid proliferation after appropriate stimuli, they may be recruited back to the cell cyclestimuli, they may be recruited back to the cell cycle Healing in tissues with prevailing stable cells:Healing in tissues with prevailing stable cells: regeneration in tissues with most stable cell is possible but regeneration in tissues with most stable cell is possible but

the following conditions must be fulfilled:the following conditions must be fulfilled: sufficient amount of viable tissue must remainsufficient amount of viable tissue must remain intact fibrous interstitial network and original basement intact fibrous interstitial network and original basement

membranes preservedmembranes preserved if complete necrosis involves both parenchyma and if complete necrosis involves both parenchyma and

interstitium- no regeneration is possible and interstitium- no regeneration is possible and necrosis heals by scar formationnecrosis heals by scar formation

Permanent cells- non-Permanent cells- non-dividingdividing

cells have no regenerative capacitycells have no regenerative capacity Healing in tissues with permanent cells:Healing in tissues with permanent cells: injury to tissue with permanent cells is injury to tissue with permanent cells is

always followed by scar formation, no always followed by scar formation, no regeneration is possibleregeneration is possible

REPAIR BY SCAR REPAIR BY SCAR FORMATIONFORMATION

scar=mass of collagen that is the final scar=mass of collagen that is the final result of the process of organizationresult of the process of organization

repair by scar occurs:repair by scar occurs: if resolution failsif resolution fails if the injurious agent continuously causes if the injurious agent continuously causes

injury in chronic inflammationinjury in chronic inflammation if parenchymal necrosis cannot be if parenchymal necrosis cannot be

repaired by regeneration because of repaired by regeneration because of prevalence of permanent cellsprevalence of permanent cells

Process of repair by scar Process of repair by scar formationformation

PreparationPreparation removal of the inflammatory exudateremoval of the inflammatory exudate Debris is liquefied by lysosomal enzymes derived of neutrophil Debris is liquefied by lysosomal enzymes derived of neutrophil

leukocytesleukocytes is removed by lymphatics, residual particle are phagocytosed is removed by lymphatics, residual particle are phagocytosed

by macrophagesby macrophages Ingrowth of granulation tissueIngrowth of granulation tissue

granulation tissue is highly vascularized connective tissue granulation tissue is highly vascularized connective tissue composed of newly formed capillaries, proliferating fibroblasts composed of newly formed capillaries, proliferating fibroblasts and myofibroblasts, cell debris and residual inflammatory cellsand myofibroblasts, cell debris and residual inflammatory cells

major role of the granulation tissue is to occupy the tissue major role of the granulation tissue is to occupy the tissue defects lost by injurydefects lost by injury

Grossly granulation tissue is deeply red (because of numerous Grossly granulation tissue is deeply red (because of numerous capillaries) and soft, with granularity of the surfacecapillaries) and soft, with granularity of the surface

CollagenizationCollagenization collagens are the major fibrillary extracellular proteinscollagens are the major fibrillary extracellular proteins

Maturation of the scarMaturation of the scar collagen content of granulation tissue collagen content of granulation tissue

progressively increases with the time, progressively increases with the time, particularly the amount of type I collagen particularly the amount of type I collagen increasesincreases

the scar becomes less cellular and less vascularthe scar becomes less cellular and less vascular the mature scar is composed of hypovascular the mature scar is composed of hypovascular

poorly cellular collagenous mass- composed poorly cellular collagenous mass- composed mostly of collagen type Imostly of collagen type I

Contraction and strengtheningContraction and strengthening contraction decreases the size of scar- allows contraction decreases the size of scar- allows

optimal function of the remaining tissueoptimal function of the remaining tissue

HEALING OF SKIN HEALING OF SKIN WOUNDSWOUNDS

Healing by first intention (primary Healing by first intention (primary union)union) healing of clean uninfected surgical healing of clean uninfected surgical

incision joined by surgical suturesincision joined by surgical sutures limited number of dead cells, minor limited number of dead cells, minor

discontinuity of basement membranediscontinuity of basement membrane the incisional space immediately fills the incisional space immediately fills

with clotted blood containing fibrinwith clotted blood containing fibrin

Healing by second intention Healing by second intention (secondary union)(secondary union)

differs from primary healing in several aspects:differs from primary healing in several aspects: large tissue defects, such as large infarctions, large tissue defects, such as large infarctions,

ulcerations, abscessesulcerations, abscesses large wounds- have always more fibrin in exudate, large wounds- have always more fibrin in exudate,

thus more intense inflammatory reactionthus more intense inflammatory reaction much greater amount of granulation tissue is formedmuch greater amount of granulation tissue is formed final scar is much smaller than original wound due to final scar is much smaller than original wound due to

wound contraction (mostly results of activities of wound contraction (mostly results of activities of myofibroblasts) - myofibroblasts) - tissue retractiontissue retraction

PATHOLOGIC ASPECTS OF PATHOLOGIC ASPECTS OF REPAIRREPAIR

The factors that modify the quality of The factors that modify the quality of tissue repair include:tissue repair include: nutrition deficiency, particularly vitamin C nutrition deficiency, particularly vitamin C

deficiency decreases the ability to heal woundsdeficiency decreases the ability to heal wounds glucocorticoids have anti-inflammatory effectglucocorticoids have anti-inflammatory effect persistent infection is the most important persistent infection is the most important

cause of delayed healingcause of delayed healing mechanical factors, as wound dehiscencemechanical factors, as wound dehiscence low blood supply, presence of foreign bodieslow blood supply, presence of foreign bodies disorders of lymphatic flow may slow down the disorders of lymphatic flow may slow down the

removal of necrotic cells and cause delayed removal of necrotic cells and cause delayed healinghealing

the presence or absence of diabetes mellitus the presence or absence of diabetes mellitus and other underlying diseasesand other underlying diseases

adequate levels of circulating white blood adequate levels of circulating white blood cells cells

type of injured tissue type of injured tissue perfect repair may occur only in tissues built up of perfect repair may occur only in tissues built up of

labile and stable cells,labile and stable cells, while injuries to permanent cells results in scarring, while injuries to permanent cells results in scarring,

such case is myocardial infarction (no regeneration such case is myocardial infarction (no regeneration of specialised heart muscle elements)of specialised heart muscle elements)

large amounts of exudate slows down a healing -large amounts of exudate slows down a healing - healing of exudate includehealing of exudate include::

digestion of the exudate initiated by proteolytic enzymes digestion of the exudate initiated by proteolytic enzymes of leukocytes-resorption of dissolved exudate= process of leukocytes-resorption of dissolved exudate= process called „ resolution“called „ resolution“

the presence of extensive necrosis or large amounts of the presence of extensive necrosis or large amounts of fibrin in the exudate or low blood and lymphatic ratefibrin in the exudate or low blood and lymphatic rate

the process of resolution cannot occur and the exudate the process of resolution cannot occur and the exudate is replaced by granulation tissue and transformed into is replaced by granulation tissue and transformed into fibrous tissue -fibrous tissue -organization of exudateorganization of exudate

for example lung carnification in pathologic healing of for example lung carnification in pathologic healing of pneumoniapneumonia

aberration of growth -hyperplastic scarring- aberration of growth -hyperplastic scarring- if excessive amounts of collagen if excessive amounts of collagen accumulate within the scar= accumulate within the scar= keloidkeloid

-keloid formation appears to an -keloid formation appears to an individual predisposition of unknown individual predisposition of unknown reasons or excessive formation of reasons or excessive formation of granulation tissue= granulation tissue= exuberant granulationexuberant granulation - - granulation tissue protrudes over the granulation tissue protrudes over the surface of the wound and in fact blocks the surface of the wound and in fact blocks the reepithelization- granulation tissue must be reepithelization- granulation tissue must be removed surgicallyremoved surgically