Pathophysiology cell injury

Cell injury and its pathophysiology
Apoptosis, Necrosis, Cellular adaptations, Cell morphology
Cell injury types, etiology

2. Theword‘Pathology’isderivedfromtwoGreekwords—pathos
meaningsuffering,andlogosmeaningstudy.Pathologyis,thus,
scientificstudyofstructureandfunctionofthebodyindisease.
Anothercommonlyusedtermwithreferencetostudyof
diseasesis‘pathophysiology’comprisedbytwowords:pathos
=suffering;physiology=studyofnormalfunction.
Pathophysiology,thus,includesstudyofdisorderedfunctionor
breakdownofhomeostasisindiseases.

3. SOME CONFUSING TERMINOLOGIES
Healthmaybedefinedasaconditionwhentheindividualisincomplete
accordwiththesurroundings,Whilediseaseislossofease(orcomfort)to
thebody(i.e.dis-ease).
Atermcommonlyconfusedwithdiseaseisillness.Whilediseasesuggests
anentitywithacause,illnessisthereactionoftheindividualtodiseasein
theformofsymptoms(complaintsofthepatient)andphysicalsigns
(elicitedbytheclinician).
Inadditiontodiseaseandillness,therearesyndromes(meaningrunning
together)characterizedbycombinationofsymptomscausedbyaltered
physiologicprocesses.

4. IMPORTANT TERMINOLOGIES
•Patientisthepersonaffectedbydisease.
•Lesionsarethecharacteristicchangesintissuesandcells
producedbydiseaseinanindividualorexperimentalanimal.
•Pathologicchangesormorphologyconsistofexaminationof
diseasedtissues.
•Pathologicchangescanberecognizedwiththenakedeye
(grossormacroscopicchanges)orstudiedbymicroscopic
examinationoftissues.
•Causalfactorsresponsibleforthelesionsareincludedin
etiologyofdisease(i.e.‘why’ofdisease).

5. IMPORTANT TERMINOLOGIES
•Mechanismbywhichthelesionsareproducedistermedpathogenesis
ofdisease(i.e.‘how’ofdisease).
•Functionalimplicationsofthelesionfeltbythepatientaresymptoms
andthosediscoveredbytheclinicianarethephysicalsigns.
•Clinicalsignificanceofthemorphologicandfunctionalchanges
togetherwithresultsofotherinvestigationshelptoarriveatananswer
towhatiswrong(diagnosis),whatisgoingtohappen(prognosis),
whatcanbedoneaboutit(treatment),andfinallywhatshouldbe
donetoavoidcomplicationsandspread(prevention)(i.e.‘what’of
disease).

6. CELL INJURY
&
CELL ADAPTATIONS

7. THE NORMAL CELL
QUIZ
TIME
QUIZ
TIME

8. THE NORMAL CELL

9. THE NORMAL CELL
•Nucleus:TheCentreofcellwithgeneticinformation
•Nucleosome:CondensedchromosomesandDNA
•RoughEndoplasmicReticulum&SmoothEndoplasmicReticulum
•Ribosomes:ProteinFactory
•Golgibody&Lysosomes:Thepackagingunit
•Mitochondria:Thepowerhouseofthecell
•Centrioles:Transportersofcellorganellesduringcelldivision

10. ➢In1859,Virchowfirstpublishedcellulartheoryofdisease,bringinginthe
conceptthatdiseasesoccurduetoabnormalitiesatthelevelofcells.
➢Thus,mostformsofdiseasesbeginwithcellinjuryfollowedbyconsequentloss
ofcellularfunction.
➢“Cellinjury”isdefinedasavarietyofstressesacellencountersasaresultof
changesinitsinternalandexternalenvironment.
Thecellularresponsetostressmayvaryanddependsuponthefollowing
variables:
a)Thetypeofcellandtissueinvolved.
b)Extentandtypeofcellinjury.
CELL INJURY

12. ETIOLOGY OF CELL INJURY
1. Hypoxia and ischemia
2. Physical agents
3. Chemical agents and drugs
4. Microbial agents
5. Immunologic agents
6. Nutritional derangements
7. Aging
8. Psychogenic diseases
9. Iatrogenic factors
10. Idiopathic diseases

14. MORPHOLOGY OF CELL INJURY

15. REVERSIBLE CELL INJURY
1.Hydropic change (cloudy swelling)
2. Hyaline change
3. Mucoid change
4. Fatty change

16. 1.Hydropic change (cloudy swelling)

18. GROSS APPEARANCE OF CLOUDY
SWELLING
CHARACTERISTICS
•ORGAN ENLARGED
•WEIGHT INCREASED
•PALE COLORATION

19. Hydropicchange:thisisduetoparalysisofenergy-dependentionpumpsoftheplasma
membrane.Itisthefirstmanifestationofalmostallformsofcellinjury.Microscopically,
thereareclearvacuoles(ofwater)withinthecytoplasm.
MICROSCOPIC VIEW

20. 2. Hyaline change
The word ‘hyaline’ means glassy (hyalos = glass).
extracellular.intracellular
Types
•Varioushistologicalorcytologicalalterationscharacterizedby
homogeneous,glasslikeappearanceinhematoxylinandeosin
stainedsections.

21. Hyalinization Arteriolar Sclerosis
MICROSCOPIC VIEW

22. INTRACELLULAR HYALINE
•Itsmainlyseeninepithelialcells.
•HyalinedropletsinthePCTNephronepithelialcells:excessive
reabsorptionofplasmaproteins.
•HyalinedegenerationofrectusabdominismusclecalledZenker’s
degeneration,occurringintyphoidfever.
•Mallory’shyalinerepresentsaggregatesofintermediatefilaments
inthehepatocytesinalcoholiclivercellinjury.

23. IntracellularhyalineasRussell’sbodiesintheplasmacells.Thecytoplasm
showspinkhomogeneousglobularmaterialduetoaccumulated
immunoglobulins.

24. •Extracellularhyalineisseeninconnectivetissues.
•HyalinedegenerationinFibroidsoftheuterus
•Hyalinizedoldscaroffibro-collagenoustissues.
•Hyalinearteriolosclerosisinrenalvesselsin
hypertensionanddiabetesmellitus.
•Hyalinizedglomeruliinchronicglomerulonephritis.
EXTRACELLULAR HYALINE

25. Thecentersofwhorlsofsmoothmuscleandconnectivetissueshowpink
homogeneoushyalinematerial(connectivetissuehyaline)

26. MICROSCOPIC VIEW

27. 3. Mucoid degeneration
•Mucuscontainingmucin(glycoprotein)secretedbymucous
glands.
•Incertaincellularinjury,thereischangecharacterizedby
accumulationofmucininintracellularorextracellularloci.
Epithelial:
•Composedofsialomucinandneutralmucopolysaccharide
•mayaccumulateinintracellularorextracellular(ifsecreted)
locations.
Connectivetissue:
•predominantlyacidmucopolysaccharide,sulfatedor
carboxylated

28. EPITHELIAL MUCIN
•Catarrhalinflammationofmucousmembrane(e.g.ofrespiratory
tract,alimentarytract,uterus).
•Obstructionofductleadingtomucoceleintheoralcavityand
gallbladder.
•Mucin-secretingtumors(e.g.ofovary,stomach,largebowel,etc.)
•Cysticfibrosisofthepancreas.

29. CONNECTIVE TISSUE MUCIN
•Mucoidormyxoiddegenerationinsometumorse.g.myxomas,
neurofibromas,fibroadenoma,softtissuesarcomas,etc.

30. 4. Fatty change
•Thereistheaccumulationoffatinnon-fattycells.
•AlsoknownasSTEATOSIS
Morphologicchange:
•Grossfeatures:Theorganenlargesandbecomesyellow,soft,and
greasy.
•Microscopy:AnFattychangeappearsasclearvacuoleswithin
parenchymalcells.

31. Fatty change: Liver
•Sincethisorganplaysacentralrolein
fatmetabolism,
•Theaccumulationoffatintoxic
conditionscanbeverydangerous.
•Dependinguponthecauseand
amountofaccumulation,fattychange
maybe
•mildandreversible,
•orsevereproducingirreversible
cellinjuryandcelldeath

32. •Conditionswithexcessfat:STRESSONORGAN
–Obesity
–Diabetesmellitus
–Congenitalhyperlipidaemia
•Livercelldamage:LOOSEITSCAPABILITY
–Alcoholicliverdisease(mostcommon)
–Starvation
–Proteincaloriemalnutrition
–Chronicillnesses(e.g.tuberculosis)
–Acutefattyliverinlatepregnancy
–Hypoxia(e.g.anaemia,cardiacfailure)
–Hepatotoxins(e.g.carbontetrachloride,chloroform,ether,aflatoxinsandother
poisons)
–Drug-inducedlivercellinjury(e.g.administrationofmethotrexate,steroids,
CCl4,halothaneanaesthetic,tetracyclineetc)
–Reye’ssyndrome
Etiology

33. •Grossly
–the liver in fatty change is
enlarged with a tense,glistening
capsule and roundedmargins.
–The cut surface bulges slightly
and is pale-yellow to yellow and
is greasy totouch
•Microscopically
–characteristic feature is the
presence of numerous lipid
vacuoles in the cytoplasmof
hepatocytes.
MORPHOLOGIC FEATURES

34. Cellular Adaptation
•Cell can adapt themselves by undergoing 5
differentconditions
1.Hyperplasia
2.Hypertrophy
3.Atrophy
4.Metaplasia
5.Dysplasia

35. Cellular Adaptations

36. 1. HYPERPLASIA
An increase in the
number of cells in
an organ or tissue,
which may then
have increased
volume.
Types
PhysiologicalPathological

37. A.Hormonal:Influenceofhormonalstimulation
•Hyperplasiaofthefemalebreastepitheliumatpuberty
orinpregnancy
•pregnantuterus
•normalendometriumafteranormalmenstrualcycle.
B.Compensatory:hyperplasiaoccurringfollowingremoval
ofpartofanorgan
•Regenerationoftheliverfollowingpartialhepatectomy
•Regenerationofepidermisafterskinabrasion
•Followingnephrectomyononeside,thereishyperplasia
ofnephronsoftheotherkidney.
Physiological Hyperplasia

38. Excessivestimulationofhormonesorgrowthfactors
–Endometrialhyperplasia
–woundhealing-ofgranulationtissuedueto
proliferationoffibroblastsandendothelialcells.
–skinwartsfromhyperplasiaofepidermisduetohuman
papillomavirus.
–Pseudocarcinomatoushyperplasiaoftheskin
Pathological Hyperplasia

39. HYPERTROPHY
Definition:Anincreaseinthesizeofcells,andwithsuch
change,anincreaseinthesizeoftheorgan.
Types
•Physiologic:physiologicgrowthoftheuterusduring
pregnancyinvolvesbothhypertrophyandhyperplasia.
•Pathologiccauses:increasedworkload,hormonal
stimulationandgrowthfactorsstimulationlikeinCardiac
muscleinHeartdiseases.

40. THE RELATIONSHIP BETWEEN
HYPERPLASIA ANDHYPERTROPHY
ALTHOUGHHYPERTROPHYANDHYPERPLASIAARETWO
DISTINCTPROCESSES,FREQUENTLYBOTH OCCUR
TOGETHER,ANDTHEYWELLBETRIGGEREDBYTHESAME
MECHANISM.

41. ATROPHY
Types:Physiologic orPathological
Acquired loss of the size of cells, due to reduction in cell
size or number of parenchymal cells in an organ.

42. PHYSIOLOGICATROPHY
A normal process of aging in some tissues, which could be dueto loss
of endocrine stimulation or arteriosclerosis.
•Atrophy of lymphoid tissue in lymphnodes, appendix andthymus.
•Atrophy of gonadsaftermenopause.
•Atrophy of brainwith aging.

43. PATHOLOGICATROPHY.
•Starvationatrophy.
•Ischaemicatrophy
•Disuseatrophy.
•Neuropathicatrophy.
•Endocrineatrophy
•Pressureatrophy.
•Idiopathicatrophy

44. METAPLASIA
Definition:Metaplasiaisareversiblechangeinwhichoneadultcell
typeisreplacedbyanotheradultcelltype.
•ItisLossofDifferentiationpropertyofcell
Causes:
•Changesinenvironment
•Irritationorinflammation
•Nutritional
SquamouscellsturnintoColumnarcells:Intestinalmetaplasiain
healedchronicgastriculcerandBarrett’sesophagus

45. DYSPLASIA
•Disordered or Abnormal cellulardevelopment.
•Also referred to as ‘AtypicalHyperplasia'
•Epithelial dysplasia is characterised by cellular proliferation and cytologicchanges
–Increased number of layers of epithelialcells
–Disorderly arrangement of cells from basal layer to the surface layer
–Loss of basal polarity i.e. nuclei lying away from basementmembrane
–Cellular and nuclearpleomorphism
–Increased nucleocytoplasmicratio
–Nuclearhyperchromatism
–Increased mitoticactivity.
•The two most common examples of dysplastic changes are theuterinecervix
and respiratorytract

46. CELLDEATH

47. NECROSIS
•Definedasalocalisedareaofdeathoftissuefollowedbydegradationof
tissuebyhydrolyticenzymesliberatedfromdeadcells.
•Itisinvariablyaccompaniedbyinflammatoryreaction.
•Variousagentssuchashypoxia,chemicalandphysicalagents,microbialagents,
immunologicalinjury,etc
•Twoessentialchangescharacterizeirreversiblecellinjuryinnecrosisofall
types
–Denaturationofproteins(Structural&Functional)
–Celldigestionbylyticenzymes(Autolysis&Heterolysis)

48. TYPES OFNECROSIS
Morphologically, there are five typesof necrosis
✓Cogulative
✓Liquefaction
✓Caseous
✓Fat
✓Fibrinoid

49. Coagulative Liquefaction Caseous
Fat Fibrinoid

50. APOPTOSIS

51. APOPTOSIS
•Aformof‘coordinatedandinternallyprogrammedcell
death’
•Pathwayofcelldeaththatisinducedbyatightlyregulated
suicideprograminwhichcellsdestinedtodieactivate
enzymescapableofdegradingthecells'ownnuclearDNA
andnuclearandcytoplasmicproteins
•Apoptosisisresponsibleformediatingcelldeathinawide
varietyofphysiologicandpathologicprocesses

53. •Theplasmamembraneoftheapoptoticcellremainsintact,but
themembraneisalteredinsuchawaythatthecellandits
fragmentsbecomeavidtargetsforphagocytes.
•Thedeadcellisrapidlyclearedbeforeitscontentshave
leakedout,andthereforecelldeathbythispathwaydoesnot
elicitaninflammatoryreactioninthehost
•Thus,apoptosisdiffersfromnecrosis
•However,apoptosisandnecrosissometimescoexist,and
apoptosisinducedbysomepathologicstimulimayprogressto
necrosis

54. APOPTOSIS V/SNECROSIS

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