CELLULAR

unrumm
RESPONSE
muumuus

stimuli
1 Altered Physiologicstimuli
OR CELLUR ADAPTATION
Non Lethalstimuli Eg DAtrophy
ii hypertrophy
iii yperplasia
Iv Metaplasia
2 LethalStimuli Transient Reversible cellinjury
Lethalstimuli Persistent Irreversible injury
1
Celldeath
1 NECROSIS
MORPHOLOGICAL CHANGES APOPTOSIS
NECROPTOSIS
PYROPTOSIS
3 Chronic InjuryStimuli Intracellularaccumulation
Eg FatsGlycogen Proteins
calcification
4 Sublethal Stimuli Persistent Induce cellularageing
CELLULAR
mmmm
ADAPTATIONS
mmmm

Stimuli Cell Changeintheir NumberSizePhenotypefunctions

Removal Comeback to
N State
CELLULAR ADAPTATIONS ARE REVERSIBLE
These are both Physiologic Pathologic

PregnanetUterus Barrett'sEsophagus
HYPERTROPHY
unnummmm
definition Sizeofcell 4 but NumberofcellSanne
Mechanism T in synthesis ofcellularprotein
Isalsoboth Physiological
mummmm Pathological
unmmunn

Eg Pregnantuterus Eg CardiacEnlargement
bothhypertrophy dit Valvulardefect
hyperplasia
HYPERPLASIA
muumuu

def No ofcell Increased Butsizeofcellremainssame

Mechanism D GrowthFactor Mostimportant mechanism
Cell
N ANuTranscriptionFactor
K
ACellproliferation
iis Atissuestem cells
t
Anoofcells
Both Punhygielegie Pathological

Pregnant uterus 14Estrogenontheendometrium

Pregnant Breast In
EenmpenngudionryHyperphagia EndometrialHyperplasia

Liverregeneration
afterLiverResection
ATROPHY
muumuu

def size no ofcellare decreased

Mechanisms it t protein synthesis
i UbiquitinProteasome 3 IiiAutophagy
mum mum
Degradationpathway

c
felf Hating

INTRACELLULAR PROTEIN
DEGRADATION PATHWAY
Ubiquitin Ligase activation
Ubiquitin
1
Targetprotein
v Thesearetakeninto
y t y
Activateproteasome Doublemembrane bound
organelle Autophagosome
Hi Contain ubitar.pro
degradationof Iv
Ubiquitin Tarprotein combinewithLysosome
14 HI
ATROPHY Degradationof
Protein
 Both Pmhysmighongie Pathologicatmm
X y
duringfetal development Denervationatrophy
a Muscle
lossof notochord
Thyroglossalduct Ngeyrypey
3J fophy
Trauma
EndometrialAdenocarcinoma alw BOTH HUYEEEEKEELAtATROPHYm.ba
w talw
Type 1Endometrial Type 2Endo
Adenocarcinoma Adenocarcinoma
k k
GoodPrognosis Poorprognosis

I
i Bothareprecancerouslesion
METAPLASIA
unmurrumm

def 1maturecell replaced byanothertype ofmaturecell

Mechanism CYTOKINEIGF
1
Alterationoftissuestemcell Reprogramming
Both Physiologic
unnummmm Pathologic
murmur
k
Incervixlduringmenustruation x n
Squamousmetaplasia EPITHELIAL CONNECTIVETISSUE
at squamocolournharjunction MESENCHYMALMETA
Eg Myositisossificans
Trauma Musing
t
Bonewithin
V Muscle
MCType BARRETT'SEOSOPHAGUS
MCC Gastroesophageal Reflux
Smoking Disease GERD
Mucinin
ofio
Vacoules
o on
stress Tissuestemcell OOOGERB Moon
GIBLET
ppm
Colournnar
Reprogramming 000 cell
Squamous Columnar CELL
cell
Squamouscell Csquarelelongated
Stemoell 2
Columnar Metaplasia
SquamousMetaplasia ofRespTract dittothepresenceofGOBLETCELL
CMCTypeofmetaplasia aka INTESTINALMETAPLASIA
dit Vitamin A deficiency Hallmark ofBarret's
Vitamin A excess StainforGOBLETCEhh
AlcianBluestain p11 2 b acidic
forintestinalGoblet pH alkaline
 Risk of Barret's Esophagus Adenocarcinoma ofEsophagus

Metaplasia Dysplasia Carcinoma

db
Exception Apocrine metaplasia ofbreasttissue
have no risk ofmalignancy

CELL
nvm
INJURY
ummm

MCC of cell injury ISCHAEMIA

t
HYPOXIA OXIDATIVESTRESS
onmitochondria
I
Freeradicalsproduction
FREE
mum
RADICALS
mmmm
aka Oxidants
ReactiveoxygenspeciesCROS
FR are normally produced dft incompleteoxidation within
mitochondria
Def Anychemicalspecieswithunpaired e outerorbit
Mechanismofaction byoxidativedamage
k Damage of
1 Cellmembrane
N Iii Cytoplasmic
proteins
organelle
iiiNumembrane
Iv Nuchromatin
DNAdamage
FREE RADICAL Oxidant Anti Oxidant
i OH MOSTREACTIVE
i
D Vitamins AKIE
ii 11202 IDProteins Transferrin Ceruloplasmin
iii 02 iii Enzymes CatalaseGlutathione
ID ONOO SOD Superoxidedismutase
 1 Catalase PERO
2 Glutathione MOSTPOTENTANTIOXIDANT hffyMMA
s
3 SOD

ResponsibleforBrainprotection
i
from FRdamage
Mutation inSODgene AmyotrophicLateralSclerosis
Motorneurondisease
HYPOXIA
NEURONSSurvival
time
Most susceptible 3 4min
CARDIAC 2040Min
n30Min
FIBROBLAST hrstodays
n un of
Types cellw un
n un injury

Transientstimuli Persistentstimuli
Reversibleinjury irreversibleInjury

REVERSIBLE
unmurrunn
INJURY
mmmm
Ischaemia Hoz
v
t oxidative phosphorylationin mitochondria
t ATPproduction
Iv 5 lot ofNormal
N Injury
Nats 1 Firstsign cellswelling
ATP
in Nat
H2O exceptfor Apoptosis
KT 7 Kt
unmrumm
Firstsign Cellshrinkage
2 Vacuolar Degeneration
HydropicDegeneration
6 ditintracellularwateraccumulation
AKA CLOUDYSWELLING
Eg AcuteTubularnecrosisofkidney
Organelle changes EM Examination
0
omg
O OJO y L 1h20
i i
i
Ribosomes
ERswelling
a Ribosomaldetachment
 Basta
Iii Mitochondria
AbsenceofCristal
Cristal Mitochondrial
Puca Swelling
cellinj Yoo o smallamorphous
densities
N
IV Important Factorforcellinjury Cat
cytosolic
ID
PLtcazt
Na41420
Ca c cast WHORLLIKE
v MYELINFIGURES
Mild9 AM ummm mmmm
I irreversible madeuptoPLtCa2t
Reversible seeninbothreversible irreversible
H injuryCMD
cytosolic CaucmildM e
I t
Phospholipase
Iv
DLConcellmembrane
Nucleus damage
Eosinophilic CPinklred
Bas.co
ohificgraygyoanrfaffbnrillarY

In Reversible
injury
i Disaggregationofgranulartfibrillary Nu chromatin

REVERSIBLE INJURY
Bunnummmm ummm
because of Persistentlethalstimuli
I
14CytosolicCadet
Activates
y
v v v
Phospholipase Proteases Endonuclease
Hi Hi Hi
Cellmembranedamage damageofcytoskeleton Nu damage
t protein k
i N'Myelinfiguresimax H DNAchromatin
ii EM Large flocculent amorphous Lossofcellarchitecture 1 Pyknosis
densitiesin mitochondria sE9YEAh
qarryyoj.fryhe.fi DAMAGE
it PYKNOSIS O
i Clumpingcondensation
ofchromatid
V 1
Shrinkage ofNucleus
iilkaryo rrhexis Nuclearfragmentation
Fragmentednuclei
E
iii karyolysis chromatin Lysis dissolution
decreasedbasophilia
Thrownout

Irreversibleinjury celldeath
Morphologicalchanges

Necrosis AFoptosis Necroptosis ptosis

Pyro

NECROSIS
murmur

2patternsof Necrosis
i COAGULATIVENECROSIS ii LIQUEFACTIVE NECROSIS
MCpatternofnecrosis
Denaturation ofProtein DATLysosomalpermeability
1 k
Tissuearchitecture Preserved Enzymesleakout
Ischaemic infarction ofsolid to
Eg Enzymaticdamage ofcell
organsEg Heart Mc
Kidney HYDROLYTIC DAMAGE
Liver Tissuearchitecture Lost
EXCEPT INBRAIN Eg i Ischaemicinfarction of
Ischaemicinfarction Brain
thereisnostromalsupport
ofabsence ofcollagen
alsobrainisrichin
Liquefactive enzymes
ii Infections
SPECIAL
mmmm
TYPES
mm

1 GANGRENE
MCsite LOWERLIMB
a Dry gangrene b Wetgangrene
tissuearchitectureispresevered Bacterialcontamination
i EgofCoagulativenecrosis ToxinEnzymerelease
TypeofLiquefactivenecrosis
 2 CASEOUS NECROSIS
i
It'scalledlikethis ofcheesy
mum appearance
Gross

YellowishWhitedebris
Seen in TB cheesy dit presence of MYCOLICACID
Onmicroscopic examination Coagulative LiquefactiveNecrosis
Amorphous GranularPinkstructure
considered as Variantofcoagulative Necrosis

3 FATNECROSIS
Itmay bedue to
a Enzymes bTrauma
Acutepancreatitis EgBreastinj
4
Lipase released
to
act onLipids
t
Release FA
combinewithCaa
calledsaponification
i GROSS Chalkywhite
appearance
MIE 2EccentricNu
Normal
I 08
Anucleated GHOSTCELL
Fat
cell Fat
cell
PinkCytop
Ba Ba M
Amorphous
Basophilicdeposits
510Calciumdeposits
80
d

5 FIBRINOLDNECROSIS
Presence of Fibrin 1 Immune
Complex AgtAb
Pathology Vesselwalldamage
k
Coagulationpathway Fibrinformation
 seen in i Vasculitis PolyarteritisNodosa
ii Malignant HTN
ME
Bloodvessel
L

Pinkamorphous
homogenous
HI
FIBRINOID
NECROSIS

NECROSIS APOPTOSIS

Lysosomalpermeability dit Amitochondrialpermeability

k ti
Enzymes IntactCellmembraneintact
k Noleading
cellmembranedamage k
t NOINFLAMMATION
Kcontentleakoutside
Ractsaschemoattractant

INFLAMMATION

Always pathological Apoptosisbothphysiological

pathological

APOPTOSIS
munrunrunn

falling offthecellsfromthetissue literalmeaning

Programmed celldeath isseen in i Apoptosis
ii Necroptosis
iii Pyroptosis
iv NeutrophilicExtracellularTrapCNED
Energy depend process D Programmed CellDeath
active process
Apoptosis is PHYSIOLOGICAL MC
unnummmun
PATHOLOGICAL
unmmnmmm

Eg 1 Organogenesis Embryogenesis Eg 1 Chemotherapyor Radio

2 Neovascularisation
3 Killingofinflammatorycells
aftercompletingtheirfunction
4 Elimination ofautoreactive
centopreventAutoimmunity
therapy Apoptosis1Necrosis
2 Glucorticoidinduce
apoptosisEpreventautoimmu
3GraftVsHostdisease
4 Councilmanbodiesin
ViraHepatitisTheseare
apoptoticbodies
5 Misfolding ofprotein
 MORPHOLOGY a Cell Shrinkage
mmmmmm
b MOSTCHARACHERISTICFEATURE Chromatincondensation
c 2ndMOST
i
Cell Membraneintact
d NO INFLAMMATION
e HypereosinophilicCytoplasm Notspecific
By
chromatin condensation
PhosphatidylserineReceptor
f N cell 7 LipidReceptor
ApoInduction EAT ME SIGNAL
FlippedReceptors
XIN V MARKEROF
ANNE
APOPTOSIS

g b

J aetach
Mitochondria

theeetentieBedies
Membraneboundstructure
with organelle theymay
ormaynothavenuclear
remenents
Councilmanbodies
Eg
h

J ups rscangerrtgEYFna Ef.ME

yGce
BIOCHEMISTRY pro Caspase prod
t activation
re caspase Endonucleaseactivation
t
chromatincondensation

Function Nu DNAdamageasspecificfragments
INTER NUCLEOSOMALDNADAMAGE
sizeoffragments 180200Basepairs
canbeobservedAgaroseGetElectrophoresis

ftp.smeapraiffern
Stepladderseenin y
i Apoptosis Charachteristic seenin
ii Necrosis STEPLADDER Necrosis
 MECHANISM OF APOPTOSIS
unnummmm in rumrunner
2events
V y
INITIATION EXECUTIONAL
Pathways t
v G a 3 activation
INTRINSICPATHWAY EXTRINSICPATHWAY k
i t t t Endonuclease
CD C 8 Unloweranimal t
C 10 11hHumans Chromatincondensation
Apoptosis
TRINSIC PATHWAY
Hmmmm mmmm
PROTO ONCOGENE
aka Mitochondrialpathway
as mitochondriais the v v
M importantorganelle a PROAPOPTOTIC b ANTI APOPTIC
It's amajorpathway BAX Bch 2
BAK BCL XL
STRESSANISTIMULI BCLXs MCL 1
BHzonlyproteinsfamily
BH3proteins concellsurface
501 v STRESS SENSORS
BAX
a Cyt MaBCL2
y
I
i BAkq.dz
v v
o
Bim PUMA
mmietaf.it
ufyr
SMANDIABLO CYTOSOLIC
CytC Bad NOXA
lap 0 t Bid
Cinhibitorotapo
Apaf I
khmHTpoptosome
5M IAP
Inhibits
v µzo
Theyareproapoptic
pro CD CD
EXTRINSIC PATHWAY
unmmunn mmmm

aka Death Reeptormediated pathway

unmarmm

4 TNF Receptor MOSTWELLDEFINED

ii FAS CDD5
Death R 1 DLigand EgTNFRTTNFL

2 AdapterProtein
proC810 C810
FLIP Present in NCell
Attntiapoptotic Viruses HIV
Apoptosis in Ext pathway