REVERSIBLE & IRREVERSIBLE CELL INJURY MORPHOLOGICAL ALTERATIONS AND MECHANISM OF CELL INJURY

LEARNING OBJECTIVES At the end of lecture student should be able to Describe the cell injury & its causes Define reversible & irreversible cell injury Describe the morphological alterations in the cell. Describe the mechanism of cell injury. CELL INJURY If cells are: Exposed to injurious agents or stress Deprived of essential nutrients Become compromised by mutations Exceeded of adaptive responses A se uence of events follo!s termed as CELL INJURY CAUSES OF CELL INJURY Oxygen deprivation "ypoxia Physical agent #echanical trauma Extremes of temprature $udden changes in atmospheric pressure Electric shoc% Chemical agents & drugs Electrolyte imbalance &oisons' arsenic( cyanide( mercuric salts) Environmental & air pollutant *ndustrial & occupational ha+ards ,verdosing of therapeutic drugs CAUSES OF CELL INJURY Infectious agents Bacteria & viruses &arasites -ungi .ic%ettsiae /ape!orms Immunologic reactions $everal autoimmune diseases *mmune reaction against infectious agents Genetic derangements e.g.

 Nutritional imbalance

Do!n syndrome $ic%le cell anemia &rotien0calori deficiency 1itamin deficiency Excess of cholesterol' atherosclerosis) ,besity'diabetes)

TYPES OF CELL INJURY Reversible cell in ury in early stages or mild forms of injury( the functional & morphologic changes are reversible if the damaging stimulus is removed. Irreversible cell in ury!cell death" 2ith continuing damage the injury becomes irreversible. #$o types 3ecrosis Apoptosis

REVERSIBLE CELL INJURY #$o features 4. 5ellular s!elling 6. -atty change Cellular s$elling -irst menifestation of almost all form of cell injury because cells are incapable of maintaining ionic & fluid homeostasis -ailure of energy0dependent ion pumps in plasma membrane %orphology causes some pallor( increase turgor( & increased in !t. of organ %icroscopic features small clear vacuoles in cytoplasm'represent distended & pinched off segments of E.). *ncreased eosinophilic staining REVERSIBLE CELL INJURY &atty change ,ccure in hypoxic( toxic & metabolic injury Appearance of lipid vacoules in cytoplasm #he ultrastructural changes of reversible cell in ury

Plasma membrane alterations Blebing( blunting( & loss of microvilli %itochondrial changes $!elling & appearance of small amorphous denisities 'ilation of (R 2ith detachment of polysomes intracytoplasmic myelin figures may be present Nuclear alterations 2ith disaggregation of granular & fibrillar elements IRREVERSIBLE CELL INJURY

N(CRO)I) $evere membrane damage 7ysosomal en+ymes digest the cell 5ellular contents lea% out .esulting in necrosis *POP#O)I) characteri+ed by 3uclear dissolution -ragmentation of cell *ncomplete loss of membrane integrity 5ell %ills itself

%echanisms of Cell In ury: Depletion of A/& #itochondrial Damage *nflux of *ntracellular 5alcium and 7oss of 5alcium "omeostasis Accumulation of ,xygen0Derived free radical 'Oxidative stress) Defects in #embrane &ermeability

Ischemic in ury

%icro

&indings:

4. 6. 8.

5ell s!elling( cytoplasm contains coarse granules. 3ucleus not affected in light microscopy.. &igmented cast( hyaline cast.

'+ Others: 4. /he first manifestation of cell injury and is reversible. 6. *ncreasing hydration of the cell due to alteration in ion transport at cell membrane. 8. 5ause9 infection( physico0chemical injury ' toxic )( ischemia

%(C,*NI)%) O& C(-- IN./R0: /he cellular response to injurious stimuli depends on the type of injury( its duration( and its severity. /he conse uences of an injurious stimulus depend on the type( status( adaptability( and genetic ma%eup of the injured cell. 5ell injury results from functional and biochemical abnormalities in one or more of several essential cellular components 'epletion of *#P:

'amage to %itochondria 9 #itochondria can be damaged by9 increases of cytosolic 5a6: reactive oxygen species oxygen deprivation and so they are sensitive to virtually all types of injurious stimuli( including hypoxia and toxins. Conse1uences : Failure of oxidative phosphorylation and progressive depletion of ATP, culminating in necrosis of the cell. mitochondria also contain several proteins that are capable of activating apoptotic path!ays( including cytochrome c 'the major protein involved in electron transport).

 Influx of Intracellular Calcium and -oss of Calcium ,omeostasis:

*ccumulation of Oxygen2'erived &ree Radicals !Oxidative )tress)9 /he ,xidation0.eduction reaction 'normal metabolic processes) 0superoxide anion ',60) 0hydrogen peroxide '"6,6) 0hydroxyl ion '," ) (ffects of the free radicals on cell in ury: 7ipid peroxidation of #embranes 0 &lasma membrane 0 ,rganellar membrane ,xidative modification of proteins 0,xidation of amino acid side chains &rotein0protein cross0lin%ages 0,xidation of the protein bac%bone &rotein fragmentation 7esions in D3A .eaction !ith /hymine

D3A single0stranded brea% D3A fragmentation

'efects

in

%embrane Permeability: #itochondrial Dysfunction 0Decreased phospholipid synthesis 0&hospholipase activation 7oss of #embrane phospholipid Defects in #embrane &ermeability 5ytos%eletal Abnormality .eactive ,xygen species 7ipid brea%do!n products 'detergen effect on membrane)

R(&(R(NC():

.obbin;s basic boo% of pathology 0 <th edition.

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