PATHOLOGY

Cellular Swelling
Hypertrophy Fatty Change
Hyperplasia
Atrophy
Metaplasia

By changing… By
- size a) Depletion of ATP
-shape b) Mitochondrial damage
-number c) Influx of Ca++ & loss of Ca++
-phenotype homeostasis
-metabolic d) Accumulation of Oxygen derived free
activity radicals (oxidative stress)
-function e) Defects in membrane permeability
f) Damage to DNA & Proteins

Cell Injury occurs due to…

- If limits of adaptive response are exceeded
- If cells are exposed to injurious agents or stress
- Deprived of essential nutrients
- Mutation affecting essential cellular constituents
HYPERTROPHY
Increase in size of cell, results in an increase in size of organ.
Due to: increased workload & hormone induced
No new cell, just larger cells.
Maybe…
Physiological Pathological
- Body builder’s muscles - Left ventricular hypertrophy due to chronic hemodynamic
- Hormone induced (estrogenic) enlargement of overload resulting from hypertension or faulty valve
uterus during pregnancy Cardiac hypertrophy is associated with increased
- Compensatory hypertrophy of one kidney after expression of Atrial Natriuretic Factor gene
removal of other - Cell enlargement in CMV infection due to increased
uptake of iron into cytoplasm

Hypertrophy of an organ is prone to ischemia

HYPERPLASIA
Increase in number of cells in response to stimuli.
Occurs only if tissue contains cells capable of dividing
Hyperplasia & Hypertrophy frequently occur together
Hyperplasia is the result of growth factor driven proliferation of mature cells
Physiological Pathological
- Breast in puberty, pregnancy, lactation - Endometrial hyperplasia due to increased estrogen.
- Uterus during pregnancy Increases risk of endometrial cancer.
- Bone marrow hyperplasia in hemolytic anemia - BPH by increased sensitivity to DHT
- Ductal hyperplasia of breast (malignant)
- Regenerative nodules in alcoholic cirrhosis
- Hypocalcemic parathyroid hyperplasia
- Iodine deficiency induced goitre
- Hyperthyroidism in Grave’s disease due to Thyroid
Stimulating Antibodies (IgG)
- Wart from HPV infection

ATROPHY
Reduction in the size of an organ or tissue due to a decrease in cell size and number.

Physiologic: - Atrophy of notochord & thyroglossal duct

- Decrease in size of uterus after parturition
- Physiologic atrophy of endometrium, vaginal epithelium & breast after menopause due to loss of
estrogen stimulation

Pathologic:
- Decreased workload (atrophy of disuse): plaster cast, completely bed ridden patients
- Loss of innervation (denervation atrophy)
- Diminished blood supply: atherosclerosis, progressive atrophy of brain in elderly (senile atrophy)
- Inadequate nutrition: marked muscle wasting in PEM, Cancer patients, Chronic inflammation due to increased TNF.
BROWN ATROPHY: excessive accumulation of lipofuscin. Seen in HEART
- Loss of endocrine stimulation: hypopituitarism causing atrophy of thyroid gland and adrenal cortex
- Pressure: atrophy of renal cortex & medulla in hydronephrosis, atrophy of surrounding compressed tissue in BPH
 Mechanism of Atrophy
- Decreased protein synthesis & Increased degradation by ubiquitin-proteasome pathway
- Cellular shrinkage
- Organelles & cytoplasm forms autophagic vacuoles

METAPLASIA
Reversible change.
Replacement of one type of fully differentiated cell type (epithelial or mesenchymal) by another fully differentiated
cell type.
Results from reprogramming of stem cells that differentiate along a new pathway.
Substituted cells are less sensitive to particular stress.

Types:
a) Epithelial metaplasia:
1. Squamous Metaplasia
2. Columnar Metaplasia
b) Connective tissue metaplasia

Epithelial Metaplasia
1. Squamous Metaplasia:
- Pseudo-stratified ciliated columnar to Squamous. Most common metaplasia. Occurs in habitual smokers.
Associated with increased risk of SCC.
- Vitamin A (retinoid) deficiency induced squamous metaplasia of respiratory epithelium.
- In Schistosoma hematobium infection, transitional epithelium of urinary bladder may get replaced by stratified
squamous epithelia. Associated with increased risk of developing SCC of bladder.

2. Columnar Metaplasia:
- Barrett esophagus: esophageal squamous epithelium is replaced by intestinal columnar epithelium under
influence of gastric acid reflux. Increased risk of developing Distal Adenocarcinoma.
- Chronic H. pylori induced gastritis causes replacement of gastric columnar epithelia by intestinal goblet and
paneth cells. Increased risk of developing Antral/Pyloric Ca.

Connective Tissue Metaplasia

Development of bone tissue in an area of muscle trauma. Known as Myositis ossificans (osseous metaplasia).
There is NO RISK of developing Cancer.

MECHANISM
- Reprogramming of Stem cells to utilise progeny cells with a different pattern of gene expression.
- Signals that may initiate change: -Hormone - Chemical irritants
- Vitamins - Expression of gene

* Metaplasia is a double edged sword. It is a fertile soil of cancer development.

* Sometimes Reversible if irritant stimuli is removed

DYSPLASIA
Disordered, non-neoplastic cell growth involving cell shape & organisation (differentiation) that is potential precursor
to cancer if irritant is not removed.
Premalignant, Reversible
Increased Mitosis, Abnormal mitotic figures.
No Invasiveness: Differentiates from invasive malignancy.
Hyper-chromatic nuclei with altered nuclear to cytoplasm ratio
Diminished cellular polarity.
Presence of Koilocytes - cytoplasmic vacuolation around nucleus
Site:
- Cervix - Respiratory tract of chronic smokers
- Skin - Gall bladder - Adjacent to foci of cancerous transformation
- Larynx - Oral mucosa - Urinary bladder

Complete removal of dysplastic area is curative.

CAUSES OF CELL INJURY

-Hypoxia & Ischemia
-Toxin: air pollutants, insecticides, CO, asbestos, cigarette smoke, ethanol, and drugs. Innocuous substances, such as
glucose, salt, water and oxygen can be toxic.
- Infectious agents: virus, bacteria, prions, fungi, parasites.
- Immunologic reactions: hypersensitivity, autoimmune disease.
- Nutritional imbalance: PEM, Vitamin deficiency, Obesity
- Genetic abnormality: inborn errors of metabolism, accumulation of damaged DNA or misfolded proteins
- Physical agents: Trauma, extremes of temperature, radiation, electric shock, and sudden changes in atmospheric
pressure.
- Ageing

REVERSIBLE INJURY
2 types: Cellular swelling (hallmark) & Fatty change
Cellular swelling appears when cells are incapable of maintaining ionic & fluid homeostasis as energy dependent ion
pumps in plasma membrane fails.
Fatty change occurs in hypoxic injury & toxic/metabolic injury, manifested by appearance of lipid vacuoles in
cytoplasm. Seen mainly in cells involved in and dependent on fat metabolism (hepatocytes, myocardium)

Ultrastructural change in Reversible Injury

- Cell membrane: cellular swelling (hydropic change), Blebbing & blunting, Loss of microvilli
- Endoplasmic reticulum: Dilation, Detachment of polysomes, Denaturation of phospholipids (both ER & Cell
membrane) producing small spiral fragments of intracytoplasmic Myelin figures.
- Mitochondria: Increased Ca++ accumulation resulting swelling & appearance of small amorphous densities.
- Nucleus: Disaggregation of granular & fibrillar elements. Clumping of chromatin leading to patchy deposition of
chromatin materials.

IRREVERSIBLE INJURY
Increased eosinophilia, vacuolisation of mitochondria
Loss of glycogen particle More glassy homogenous appearance
Cytoskeletal alteration, lipid breakdown
Lysis of ER, appearance of Myelin figure
Rupture of lysosome Autolysis
Nuclear changes: -Pyknosis (nuclear shrinkage, basophilia, condensation)
- Karyorrhexis (fragmentation of pyknotic nucleus)
- Karyolysis (loss of DNA due to degradation by endonuclease)

Hallmark of irreversible injury: plasma membrane & mitochondrial membrane damage

H
CelCell Death due to rvever sible Imjwy earosis
Apoptosis

itochondrial dysfuntion Neerosis

Cytoehrom C leakage - ATP (ue to ypoxia)

into eytoplasm Faxle oenery dependent
Pump
Apoptosts
c inside cel
Cell death
L
Mitoehondrual En bgme aetivaken
deniie ('sosomal
Phospholipan
cell death Nueleanes

On 61EL eleetrephonesis
Nermal. uceie acid an Singfe band.
Neerotie nucleie add >appeart an smeart poter
Apoptotic nueleie acid > appeart an Ster adder pattern.

Phospho lipne damager cell membrane Phorphoüp

%Nueleanes knosts ink dot nudleus)
Kaye rrchex (nuckean fragmentatem)
Koyolyis (Tötal reakdoan nualeus)

NECRoSIS|
Cel deatk in iving
tissue resutint rom Puogressive degradative
actim f enymen om lethal inured ces, oten auompanied b an
u t o phils.
acue nflammahoy mfrate eomtaining
Gqangenoun neurosîs
Speial yfen
Coagulati ve neerosis
-Aseb nerois
Enymohie
iauefaetive neerosis FaFat neerosis
-Fibrnoid neurosis Traumadic
 Genertal_ Morphology aneerdsis
.nerened Bosinophilta
.Loss ytoplannmie RAA
Vacuolaked aytoplanm aypeavs
la Moti-eaten
homo genowa apreatance onecrotic cell
Myaun fares ; lone, whorded phospholipid masses deruved P.rm damajed
cell membrane. Replaees damaaes cell
.Ouclear
dhomge akhosl s Coutleot shrünkage, t booophilia, ndensadon
Kanyorurhes (fragmentation oPyunetie nuelea)
Karyolsis (Loss f DNA due teo dezradatHon by
endonueleanes.)
#COA
COAGULATIVE NECROSISs
Artehl bec-ture of dead issue is presewed or a span o ime .

Meeh anism
Denatwratien emen &ruttuval pruotels , so blecks
roteosts dead sels siophilic, Onueleate eel ponsis
For severa dan.
Osuns may be dne to intmcelorr accuMulaRon
Laeake
- »aenton heA
mtas C?b, D
Joninradiatin
ex Posur (uv, Yr)
Neutrophil & maerop hage from somoundnarea phagooytose
the eellalar debris dgasts des ell by ysosomal entymu
fsehemia due to obstruelion a v24sel leads to coazdattve neoras.
Oceurs in a orgoms ExCEPT:BRAIN.
AA lodalized a r e ocoaulative neerosis is ealled INFAReT

DIS ussed in
Hemody namic thap

|LIQUE FACTIVE NECROS|S

Also knoon an Colliquative neerosis.
ecroHe degradation o ssue that softens & betomen laueffed.
Mechanism
Releoe fysoso mal entymes by necrotic cells &/or
Re eme of ydroytie en n by invading neumophils
Results in rastornatim i s s u e into a iGnid viseou ma
 Examples; - eNS infanctim Auteaataly He effeek ydroytie
tells
entymes teleaoed by meurogGal
Producen a git pace in Beains.
Absees m a bacternal &oeeanie nall ungal 1feehion
Hydro ytHe n y m e releaped by meutrophils liqueg
dead issue, producing a cavik Rled wita Crea
gelon nearoic mataiial ealled Pus.

#GANGRE NO US NECROsIS
Not aspeeihie atern oF cell deat but Comonly wed In prach e
an lost ts
APpLedt a
lim, nera e lovoev lea. hot
blcod spp
AAlse in undev one necrosis (tyrealuy eeatalaie).
&han
GIT
Ohen terual infeehen 1is. superImpaged,Ahere is more
baeteria
iaesachve neexosis due t actenm
Degrad otive enymen in te backerda
OEntmes fom attraeked leuko yhn.

D anarene - Isthemia Coagulative neerosis ReSembles

tissw
e t Gamrene -

Isehemia + Sreondaruy inRen liuefaettve

necrosis.
D Gan Gomrene - Subtyre of wet aene
anaocatnd u1A .ddhsde /welchi.
parnrantens
CAS
CAS EOUS
EOUS NECROSISAellule,maturia Preedu
Arom el oals
eed by teleone of tpid
M.tberulosis, emti,
heese -uke neerotRe materia ter mune deotrueton oy maerepheier
In Granulama. (ela yed ljAartsentijt
Stru ehural outline not presereved
Teaei

Coagulakive + liquelachve
neerosis Predoi nantly Coagulak
Seen i n : -T6
-Systemic
- Syphilis
fn Nen ubertemat eauoe
Granuoma formaten by ysed eells amor pho u ranular debris
enalosed tedn a shstinehve injanrnatery berrder.
Momoeyte, meerophaed, Cb4 helper Teells, multinueleated iat cells
Sertreounds he canepwn materdal.
ttFAT NECROSIS| Fe area of at+ destuekhon. Assodahd
=l engs 7 high fat OY Lipooe aehtvatm.
Seen in - to brent issue
Infuy
- Ranereahitis.

Enty mathe fat e ereis Enme medtated necros hais peeulion

to adpose Assue loeaed around am aeutely iAmmed panerean

MechaniSm- Aetvatim 4paneveohic ligme & phesphoupaae

Releone FA.
CConbinen tR FA to produee soap saponilicahen)
Chalk-Like yelovo-udkite depoits primarily Rocnted in peri-pancreate
ond omental adi pose Hssue
Im pancreahis , thee is iolvement of
Pnere am: liauafattve neero
Peri pomereatie fat Far neerosis.
saponiReahon 'is An example Dystrorhie caüfiution.

TFaumkeat negrosts Non-emyme medtatad neerois hat

eeeres n

e e n u of
( female bres,t Assue, abdomen)
m a
Satty s s ue
blunt rauma dr sue.
reackioms mvolvin
Ë|EIBRINOID NECROS1S|Seen m Fmmune
lood.esselh.
tuien, anteruoln
neerosis, 'nvolvas small mwweulast
Acelualart

Venues, omerularr aapillarien,valve leojtes moeardium

5wbeutaneom tssue.
Mechanism Endotheltal mumy
Emmut vanulihs (tS)
Complex tomakion
m mune
Malignant HTN
vessel wad Rheumatic furr
Domage to plaoma Proteins 1n -Endoeartditis
- Myoeamditis

DeposRem plama pmoteiro

i nstde -
As ehof bodies.
Vesel wad
fbunid neerosS.
 Bel-2 qene is assoc)ated witb Follteulae ymphan4
Mey-1
A
development of eistanee to ehemettyerapy

APOPTOSIS || hrgrammed, enzyme - meiated cell deat, that may

or
oce u t an a rnes ponse to developmenta / envirmmental tra2aers
deteeted by cells intamal surrveilante
a to fumelional
rtepor9e damae
System.
Cam edB
Physiologie Conditiens
o v m a l destrueton celly dureht mbrpeeais
Mullerian
in testes syteesize
n male 4etwa , Serctol eel!
ohiech res ut in
len f Mullerum
Mudlerion

Iwhibitos Substanee,
Stueures (nonmally developsorga) in male fetm.
famale
k toes,
nemaval oissue Cardiac fngen
between
Wormal
mner ea, mbr phogenesis.
shapin he
tRedrowal
dependent issue pen hormone
homone
Invo utHm
witkdrtaal oEstrogen g Progestercone signals fr aptosis
eell Menstruatton.
endometria aand
.

Ovarian folicudrt atresia after menopaue

breast Ajter veanin.
LRegression. laetati
darhration.
Preostatic ohopkm afèr
Normal nvelutien ymw increoin

Cell les 'm pralifenatin cel pepulahtn

eenter 2 apoptosi ofindividual
AppptosiS oLN 8ereainal
seleetim.
8cells undezeing Angen
',

hamfd se{f-meastie phoeytam,aithr

aittr
Eliminatien fPetuntially
maturafion'.
before or
ofter celus eutaophi) rom healin
acute mstamatory
Removal
Sttu 'n aute injfamahm

E Patholotical Conditians ( Deat tumer cells

ODNA damage (oy radiaioFR/Terins) Vio

Teel.
infeered cel by LD8
Accuml otien ofolue proteins corHecgter end destreion
O Duet.obstruaim sativ arny/pone ve n
phoeytt.
TFAnstlant rejeehon Gaaftvs host iseae Exeessie apoptois oeob
ceue in Retritis
elametusa.
P53 GeneLocaked on hromosome 7
damae DNA. Inereanes apopto*is
AeRvates on
-frevents acumulatien al ered celly Guandian t qene me.
-Mutatt on P 5 3 t Caneer (50y. human canters are anocinke)

MorphelbR
eM shrdnkage (eartiest manrtetatiow)
Comahn condensatiem (most characterustie) Rknosis
=

Glebbi opl asmie membrane

-

oYmatin ocpopte tie bodien (ytoplam+ ti2ltly Packes orane

nulean rmen1í)
-

Phao tytosis t apoptoie bod

No inlamakon ,an membrane.
cell 1s rdtack
ma oro pha2

Parth voan 3 Extrinsie / Death receptor aettvaton Pwthua

Intinsie /n) iodhondrial Patuan
-

Exrinsie Porth nay (1o)

.FAS ligand binds FAs death reeptor(ab9s) target cell

Achvain FADD
uo-apane 8 Canpane 3 Cinitiakony

Aettvation o anpone 3/6/7 (eutoe

Prupteanes Endonuckeanes

ceu deah.
Sntaansie Athy (9o,) Bybneain
easistar awA200
o.g0- o bone
imtenueeosowmal
pors eah frmen
cellular Injuy n bibiHenthathvaionanti apopthtie Bcl-2/s
DA dama .
Atoteln misoldins Actvahon Pro-poptotie BAx 8AK
Hormonal stmulaion
Tmito hondrtial patmealoilt
Laakage f ytochrtome'e (Prra apepbtic\
moleeule /
AchvaRen of eonpone- 9 (Initiator
Cell death otem-e Attvalisn ot canPone 3/6/z(exeeui oner
- AtHvaion o
LEndonu elease-
nNomal cel Phosphaiyl $ordne s Pnesent n the immer memlorane
Apoptetie eelU- Et moves rom imner to ouzr membrome.

NECROSI15 vs APOPTDSls

Featuyes Neerosis Apoptosis

aell size
Enlorged Csuueltin) Shrankase
Nueteu Pykmoss+ Fraamertation
Kayorothexis » (o Kaolgis)
Kgolysis
Twtaet but altered sthueare
Plaama membrane Disrpted
eelulan ontents Enmatte
Itat. Thly aaked 'n
digeiom &. apoptoie body
eakae u t tell

AdjaLent Frequent No
Infammakon
In vartiably phlikeloae MAy be pattologBe ov

Pathogenesîs one physiologie.

Markers Anrein-V

Neeroptesis
Py roptosis| Marphologealiy neerosisPgrammes
Infeehn , .i
Meehani sHeally.apoptosis) ecell death.

Canfane ndependent
Iracella lat rteeptor bu
od like Reeeptor) Dependent on sîqnalina by RIP13
Kinane
.
Srhtarmmasome RAP-1 RIP-oplex iznalin7TNFa)
ROS No eanpare aehvahion
Canpane 1 Canone (eleva

IL-1 cell deat Lysosormal /mítethondrial damae

ATP
Fever Celt membrane damage , suellin
Feakure n stammalien
Caspane depemdent(Canp111)

mierobial înteekon seen i -formaion bene groth

Assoe azs i t Plate
Produeen y t o k m
tofrmmal ell deak. - PamreatH$
Repefaion înjuvy
StetohepaRis
-Pavrcirsonism ,
 MECHANISM OF CEL [NJURY
Depleiom oATP
Mitoehondrtlad damate
nftux of c*le% st c* hemeostanis
Acumulatan of O2-dedved Free Radiends
Defees in mêmbrne
Petmeability
Damae to bNA. proteins.

DEPLETION OF ATP|
Reduchon m ATP level is undamenta tame t Neerosis.
Oeuurts in
Hypoxi a
-

-ehemiea (toxic) in Juy.

ATP in mammallan ealus ane pro duced by
-oxidative Phosphorulatien ADP by eleeren rasfere
stam in mitoehendria
Anaerobie uolysts, waint ueote from eiter bod uds
or frem.golysis yogen.
Depletm ATP to 5 - 10 f nerrmad level hov widesprand etel
widesprad efe
Ischemia
Oxidattve Phesphor laien Gn mi toohodrel)

ATP

eneraydependent AHerted cellalar enury otens. becomt MI9*

Na pump. (Na-K* Atfone) metaboism
nfo lded pautein
Tn fux k aeeumulatm Angerobic oaysis Re ponse

Na H20 &Ca Cell deat.

ithin oell. Grlyea en Lace acid JPH
Stere

Cames -cellular Swelliry

clumplng
nudeon thvumaRn
-- Dilaton ERetahmemt rbaane
Loss oH,mittrovil; dissoeiahion
-blels formaton Preotein
Syntheats
 MITOCHON DRIAL DAMAG1E ||
Mitochondrda can be damaged by Inereed ytosolic Ca
Reacttve Oyaen Spedes
-
Oa de prdvation
-
Mutaiom in mitoolondråal gene).

3 major conse eneen

ehannel in mitoehondrual membrane
Formathion Hi eondue e

ealled Mitochondreial Pore

Paamecabil TroansiHen Pore

Los mitoehondrttad
Leakae severral proti
membrame Potental sequeltered between oubr
&imer membrane
Faiy o oxidative Abd ormal O xdave
Phosphdr lation yt e Proteins activectin
Phesphorlatiom Capones>in gtoplaam
depletion of ATP Fermatien Ros
Aettvahien
Apoptois ransie
Necrosis cellulor abnotmol paha
meeresis
Cell deatA.

Eotx oCcalei um Total c 445-2 mEa,/L (9- l0°5 mad)

Lors ealedum Homesstavsis eni2ed in ECf 3 mmel ( 4:5-56 m/d)
Sequestered in ICF o1umol.
Most intacellulan Ca 1s
Centain toxin ncre anen
seauestereed in mitochondrela k ER. ,ehemia &
en ytosolie ta", initiallyby neleaint senestered ca*
by imereoned infun acro% ploma membTAne
Inereaned Cytasolie ca
Activathen of eaulon enaymen
Dhereed Mitoehondrtial
hespholReN breaks dovwn
Phos phoU pi ds Pemeability transition
Membrane
Fteag»Disroupts
&
membrone dama{e
etoso lüe skeletal Ne eois
Proteins ApoPtosis
EEndonualeane >Damage nueleus (DNA eareomatin\
TmentatRon
» ATPae ATP
EDEFECTS IN MEMBRANE PERMEABILUTY

CaR:- ATP depletion

Cmediated acH vation of phosphsüpones
-Bacferi al to n , virt potenm
t e eomplement tomponets
- Variety ofpysieal & themica eomponens.
Mechanism
-Reactive omaen ypaelea by pid parconidaHon
Deeemed phesphatipid nhests Aue to defeciva
wtouhm drial tanctn Y ATP, 0r both.

-Increaned Phosphattpid breakeouon y cmedad

ytoskeletal abnoYm alitien activatm o
En2ym
Cmseqnenc an membrme dmaje
Mitothon dtial membrane damae -Neerosis
Apoptesis
Plaoma membrane
damae- cellat wellin
-

ER swelling
Pro bein hers ne to
S o crak m of nibosom

ysosomal membrane doma

Enzynatie diastim of reelrí,
RNA, DNA, &ly»t &eels die
y Neerosis.

DNA& Potein DAMAG E

Drugs/ Radiatien /OidaHve stress

DNA& Protein damae

Reparable domare Net epertakole
DNA isfolded prutel s
Healin to
moymalhõmeostams Jitation of suid
przogam
Apoptosis
 Oxidahve Stress
Free radieals arce chemical species kavin a sinde unpured

elecron
Generahon :
-
RedueHon-oxidation reactons tha oeeurt durdra nortmp
metalbolism
Radiation: Uv
light, Xrays.
- Rapid mespiratory bwrst durtdng initammaton.
Enymathe metabousm f ex ogenous
ahemieals (drugs
- Transition metas: Fe, u Ctey metal int)
-NO enerated by rndethelium, Mocrophege, Neunons.
- Repersusion inj )

damage
Lipid petoxidation membrane Membnane da
-Oxidatie moifiecationf protoins Unfotdhd/misfolded
-Lesio n in DNA . oteins.

Free Radieals
(02) Ineom pl te nedueon Cf o2 durdna oxidaivè
Supertoxide in
phesphortylation lgy phagouyte oxidase'
leueoetes.
oxide Dis mutane
Converhed to HaO2 %0gby Super
$OD 2
ypes -Manganese soD :' Mitoohondrua
Cu-2n SoD ytoplosm
H202 By SoD from 0 and oxidas és in PertoXisorme
Converted to H2o % 02 by Cotalase-in Peroxisome
6 &nlutothione Pertoxidase
in cytoso| & mitoehondrüa
OH
Gheneratedrom H20 by
hydrolysis. Most potent rineipal
Rosor damaging DNA lipid & Pruoteins.
,

Cenvertted to ho by Glutathtone
Perroxidase
ONOO iIntertaetion
neurors
02&No
kleueoeytes,by
NO symthane 'in Cndothelium,
Convertted to HNO2 by |ferroxirtedoxin31 in ytosol mitoomdrua.
 Antioxidants
Enaymes - Supertoxide dismutane Gob)
Catalase
luta thione
1lutathione. Perto xi daMe
s : vitA, vit
Vitamins e, 'it E ,

Plasma pretems -Transtertrin

-Lasto Fertrin
9

- Ceruulopl anmin

Trace elements Zn , 5e ***** *****

Tsehe mia Repertusion Insun

Restoraton bleod sew to sehemie tssues ater
P
iving thertapies
jollen isehemie fhenomenon MI, tenebral înfartetion
Meehanism
Oxi dathve Stress 24 Ro0S
Causes eontinued rise
-Intracell ulat. a overload
cartdiae mzymne
Jntanmaton; TFoponin
-

Activation, complement system

+is noamooiated, t apoptosis or near osis ov irreversible injun
 Tnracellulan Aecu mulatiom
Noma cellulat eonsituerts - water - oten
ipid - Qartboydrales

Abn ormal substancen

Endegene
Bilirubin Kertnicteruus Cin basal qangta)
. A+herrosalernosis (cholestercol laylen smoorth muele cell
&
Cholesterol
macrophaes foam eel)
Xonthoma/Xarthelama (cholestereol euihin macropha
cholesterolosis : Focal a ceumulatien o eholesheral-Iaden
maerophage m lamma pnopnua o GB
Neimarm- Piok disease
Protein)
Moteins.Amyloid Caeeumul ation misfolded
nenal tubda.
ReabsorpHon drtoplets in Proximal
KuSsel boie munoglobulin asoumulaion itkin ER
.Aceumulatiom eftoskelet poteirs
- Galyeogen DM
Von Giercke ayeogenosis

-Pigments
-Pigmens Lipo tuaein nsoluble, oeat & tearr pigment. Yeln a
Also knnon an, Ii pocome. Derdved rom
lipid partomidation polyunsakuratad tipids
Sub-cellulan membAneS.
Not injurdo wa
t cell.
Acumalaro peranueleart, in ier, hearvt
Bruaon
oil-Red-o/Smdan Blsck8 Arophy
dhna to canr
stin we. PEM
Melanim > 8rown -Blaek piamert.' dipositet in Melandey
Deived om Tyrosine. by
seached t2o2.
Related oMauignant Melanoma
Sykesized by melanoeyte dendrutic ceS.
Hemosiderin > Conditions t o n over load poducesit.
fes ert at storaa site of Txon BM)
aolden YellodGolden Bruoon color
( Stan: PussionBluePerl's stain.
Homo on tiste acid
>lask plament in alkaptonurua duae to
ehronosis) LackK of homo gontisie oxidane. seen in Skin.
Fatty Live
Abmoremal acumulahon T G wihin Parrenema.
eaue -Toxins . cel4 DM -PEM
- Alcohol aluse
-OlbestQ
- Anoia - StarrvdHon

Commonl* Seen in - Livep (most eommor)

- Heartt

-Musdee
- Kdney

Meahanism
FFA synthesis rom aceBate
T etry FFA rom aipose tissue

testerifcation FA to T
anoxia
-voidatiom FFA due te
due to PEM, Ccl4
-Synthes's Apo-potein
lipopnotein synthesis from &ver,
Impaired
 PATHOL06|C AL CALCIFICATIONI
Abnormal deposition with amourt of
Oealclum salt toaether smaller
irton,magnesiam& othey minerad salts.
2 +yRe Dysrophic
MetantaHe
srophie Caldfeatton bepotm ofc* g4t in dead or degenerakea.*se
site,-Ares onecress
Atherom
- Ag
o aduaneed atAereoselereosis
/dAmazed heatt valves
- TBLN

umors/cancers s4mmoma boshen

Meninoma Tnid
papillarj oarteinma
ofsaivary ar
-seistosoma e varies
ma undao Dystrophie Calefication.
Meehanism- enter oeorotie cells &binds to phosphate (releaned Fow
damaged membranes by phosphataneto pro duee casdum phosphate .

Caleium phrsphae i barephile

in Fy/e stainin. stanin
Wherre Serm ctlevel. ic nortma
t hyperteal cemia aecentuates dysto phie calakcatn,
Caleification 1s rane
in_he_walls ofveind, povsibly beeaune
of c02| cmtet
ovenow blood &Le pH

MetastaHe Caleicaton
Serum ca" is sigoikcantly naised CHypencaleemia) . This aawwes
Hssues.
depesihon f cadclum sal witin iving
aauses
Inereane PTH to paratuuid adenma.
yperrpanatyeidism *ue
Primay
seereion of PTH-rrelahed potein by malignat tumors.
Eetopie
(Resorption bone tssue
BM (eltiple eloma,leukemia)
secondany to Pumarytumors
Di fme skelehal metastaais CEmeant canter)
Accelerated bone tuwnver CPagat disease)
(vitD ostaoclant number & actvity, Tbone reserptia,
V i t D rrelated disorder Calsorphiom in inteskne Pexealeemia)
Hy
- vit dintoxication vitD preutsor
(maerophages achvates calcitriol, a
Sarcoi dosis
-

due
-
Idiopatkit hyperaaleemia o
infaney (wiliams syndrome)
vt D.
tabnomal sensikvity to

Renal jüure due to end jaiure cames

-Hypercphos phatemia L

Infte o cinto ell

Setondary hyeex patatridism
fomaion Caleum phosphaa
Salt.

5 other cawaes (in dialnsis patient)

-
Huminum intoieation
Milkalkali smdrome

- Gaotric mucssa
Mam oc@urt an
Kidney - Non anstalline amerphown deporits
Lumg alveoli (est uomme
Systemj artterties O Hdroyapatite aenstrls.
-Paumo nary veins in
Cortnea Corinetiva C deposits n itochon drein, extept
Rena cels dapeis in Bopement membrane.
**
Parcatfprcoi d gand is not caleified.
aline chon Depositien ot aasy, homogoneun ,eotophile (p) matenals.
In acellulars Exhra eellularr
-Hyaune Reabsorption droplels in Pet -Hyalinied trod vessels k
-yaline degenandn
-Rssel bolen (exeAve omerdi m HTN,
Tan ER } Plasma eeul DM, ehrune omesdonepit
-Malorums alane (in hepatocytes ne to aluoholie injum-llaqenous Kssie n oldlscan
CELLUAR AGING |
Faelors - Genetie
' - Envirtonment

-Free adical injury

TelomeYe Talo mereame hypotes .

Pomoten Aqina ahlbits a

Maximum telemerane achit- Gen eell

-Cancer eells
Telomere shosttenin caunes
agint
- DNA dama

SIRT UINS||
Causes DNA altexaiom,apop , A4 LIfe spam
- Free tadieoal InjuM
&Protein foldtna
Insulin Resistance DM
2ueose metabolsm
Sirnpins ane mereaned by
deeremed calerue mtake
Red wine cmsumptim .

CACHeXIA
Found i n - PEM (manasmun)
- Caneer (IT,.pom erean, Lu
- Chronie inflammatoy diser de Te, sancoidosis,180.

Meehanism ; -

Poteoysts mdudnt taehor oifanadory eytokines

- Lipid mobilitin nctors L-6, TNE(cadheetin)

Suppnessed Appetite
wantig& Arrp
Pepleton ipid
 INFLAMMAT(ON|
Intlamamahon is a reopense onwlotined tsue to infecflons
& damaed tissues tkat bung cells molecules ohost
Aefensem the eirulaton to the siten ohere needed, in
ovder t eléminate the ffend Rnts
2
ypen : Aue Shoret durr at on
Neutro phils
Chronic Lon duration
Mono nuelear lymphoeyten
Mono eyten.

EDseat 0auned b SftammatoryKeactions

Aue
ARDS Neuto phis
Asthma- Eosino phil,E
Galomerulo nephruhs-nttbody & Complement, neuttophils. monoeyan.
Septie Sheek Cyto kined
hnie
Arhutis -

Lympheyts, Haerophagen, Antibodie

Asthma Eosinophil, aE
-

Athertosoleruosis - Maeropha lymphoetan

Pal monay rosis-Maerophage, bodant.
Aeute vs Chnuonic tamnnat
-Aeute chonc
OnseF Fant min hous Slo dms
Cetlul at
infrate any Neutrophil MenoytaMaeioph
Tissue im Usuall mild
fbneis self Limited severe Progressive
Local &shede hominent Less
sns
##Cases o tammaton
Jntections; Bacterial, vreal, Jurgal, Parasihic.
&Miero bial touns
Tissue netrois: - fsehemla
Trauma
sica or ehemicol inu
Ferei g Godien -
ExDagend un: splinter, drt, suture
-

Endoganowa; ate erystal e

ahslen taral nstl athero m)
Kipid anno clated matalbo l
nrm
ywmwhe Reachons;- Auto imm une iseane
-Altexy

AcUTE INP LAMMATION

Trans ient rponse to 1nuy,èharacherite
d
2art
byreleane f numerrown ohemical: mediatous & lead to
Sturteotypie Sma vessel &euo te rvporoes
There is Presenee df Edema & reutrophils.
Imate mmuni y kieks im.
Carndinal s - calon: TTempertature.
Rnoor Redness
-
Tumer : Swella
-

Dolor : pún
- Funto lesa Loss ofmtien
*Redyess + Calor ; VaaodilatHen by histamne
Tamor: leakaje fid fom pest eapillarm venues
Delor: cady nin) PGE2 nduted Sensiaien rerive eSs
FeveY: Rmoqens (LPS) induced relonse f L-i &TNE from matroal.
.
Mediatoms ofAuute nfammathon
OToll-Lke Recertos-fnesent on eells mnnahe immunity
maeropht, dendrdtie Zelus)
also pheent on celb o adapHve munity
Cgmpho y t ) , henee me atan al. imfiowa
Hon
(2)Araci donic Atid metabou ten

pathavan Pro ducn rostagandins (P&)

&tvnoular
PLa, D2, Ez mediaten vmodi lation penmea ity
PGE: mediatar poin

5-lipoogenase pauao preo duue- Leukotrdenen (LT)

ls
LT B4 ohe moathrnctant to neutophi
LTCA, DA, E Mediates vono conJrieti on,3monchoseanm
von lar permEabi lity
Susstanes anapyxis .

(Mant cells
Aetivakrd by-fi$ue tranma
Complement ateins : C3a, aSA
Cress lanlant l surfare by antige

Tmmedina rupome imvolves release preforved. thstamime

fuanuulatm Arterddlar modk latien , t vaneular pen mtali
onehnsoAm.
bolayed repome invo ve Pmoduckitn Leudzotrienea

(4)Cmplem enk
Pruo Hammato Sertum Poteinb
Attvated by elthe edasic
AlternaHe Patnway.
-MBL
pettpattws nenlts in
c3a, cSa AnAPlatin, 3 : Opsoni2ahiom.
5 a chemotneie for neutro phils
esb,6,79,9 MA Clyses cell)
 AComponents Aute oftammatiom.|
Reactin bleod vessels: bilaHon o
V o n c la

toan mcreme in blod

smal
Smau vessels leadin
vent flrd
Onereaned Vanculart anmeabity (mieyo vanulakar)era
Plaama fuotnd &leulo etn to teave ereaHen
col
Cellulare

Leskota. kecruahmenk ts tita

maton
Venb
tamnaAon
Gmirahim m rocirwati'on
Aumu atn 'mhe sdewm inury
Attivatm t
elimanate' stedin oR

Vanula en | .

Transient vonoeonsttdetion artterioles due to meurogeude rte

Oantint emky a Peus seonds .

Vanodilahin in duted Hstamine , NO

Snvolves arttardolen rst ,
hen capillay bed.
Resuls im: inereaned
Hd flo
Inereaned traluminal mdrosthe pressuTR
nereened permeabiit 3 iero van culature
leading to axndatio (enule
Loss ot Ruid 9 inereaned vessel dhameter lead to slrwer blnd
Flo, Comeentrain Rbi small vessels , mereared
A hne caune
iseogi
Stais
Stanis leads to leuko e
alon vaaulan endethellum.(incipally neutrep il) aeemmalahim
Meehanism o arulas eamealaiu4
Endotteliad eell sontaetitm T nerendo hettal Pace (mastammo)
En dottelial injwy Endothelial eell neurosis & detachment
Relrack m.endotAelial eells > voneulirt eAKte.
mphangitis , ymphndeniHs ma.6eaurta Srep fjozanan 'inaehn)
E-seleetin Erdothelium
P -seletthn Platelet

Cellulat Events
Intra lumina Cevents
Maginahion
Rollingalong
vssel wall due to upnelatin
Pseeefin (weibearade
.

selein eoed unps

Speed mps body)
E- seletkin (TNE, CL

Adheen eellulart adheriem moleeules

JCAM: Inter Cellulart Adherion Moleeude
-vCAM:vaseulart Cellular Adheion Moleaule
- Integnins.
C5a LT84 upezulaten Inteardns.
TNF & IL-I pnegalaten fLAM, veAM.
Transmigratin/diapedes is

(8) Extra uminal Events

: novement leukoeyte toroand e sik F
O hemotBazds
inguny. Unidreetiona movement
chamicals Nes po nai be
Baeteral pmoducehs Exoenowo.
ChemoaeHe C5
faetors TL-88 Endoganewa.
LLTB4

Phagoeytsis
Reconi tfon target cell
y Mannose neceptors
Scavenger teeeptors
-

Receptos or orsonins
Leukeeyte mediated mjwn
Glomerulonephri is
Reperuwoion
ArtitHs
ARDS
Eng1ment
-

Pseudopd fovmaion b achn peumenitkian

OpsomitHan bFe kizment aa
Frbrimogen /eRr
AnH bo d raton

OTrhacelulart destmetion Miere bn /Dek

- ReaRe 0a speien by Raspiratory bunst.
ROs Reaetve Na pecier (malny No)
Sipatoide, O2
Hz0 MO Lysosomaemzymen.
C O2inependent Sys kem by
ElaatAge datheli eiin Majan &pnic
uten
.Dejansins 35ome fermealoity
LAatortrun inereain Prun
PREFoRMED CHEMICAL MEDIAtORS OP INPLAMMATION

Cellul Plarma
Kinm s t m
Breformed freshly med Coaaen
Histamine NO Cemplemen 9*
Sercotenin ytokinen
ugosomal entjman Artaclidanie
Aeid metabolites
Vanodi lakon VoooC onsteictons Facton T neulan parmeaoili
His tamine PhDaho E , E2, S TXAz C3a, 4a,Sa
istamine
Serotomin Low tone. PAF PAF Sercotoninn
(izh cone) 8ody kinin LT 4, DA, EA
Buadykinin
Sulstome P PG E
NO -T CA , D4, E4
c3A, C4a,C5a fAF

Histamine Sourrte Mant ceu

Goophil
.-PlateleF.
wnckion -

Vasodi lakion - Endotelial actvafon

-vanelart -Bronchoponm.
parimealol
serotonin (5HT):
SDurtee
- GIT (entenochnomoftn eelus)
-Platelr
- aNS

Funchien;-Same n istamine
-Vonoconstrichen Small vessels.
vanodilatRen l g e vessels

Arachidonic Aid Metabetes

cell membvane Phos pholi pids
Phosphoüpane A2 Inhibited by STERoIDE
Arrachidorie Add (20e pojunsaturated FA)

leuren ibis
Cyelo oxyaenne nhibited by 5-li ynane porlfkrao
pacthoo NSAID

PGT 12 chermotaxis LTB4

PGH2
T C4/D4/E4
PGIn} Vonodi lation
PP62 Inhibits platoe Brtonehopanm
vaoulart
T8aRon fenmealoikty
DaE/ : Vonodilation 5-lipoxy&Rnane patiuay
VAneulart pernmenoiley
5 HETE
E2 Pain & PytExia
12-ipoxyAenm
Vanoconstrü eH on | Lipoxin A4,B4
TXA2
Plateler +2 atem Inhibitien
Ilammathón
 Cytokman
Aeute Snjtarmaton : IL-I, IL-6, TNFx
chronie Jitawmation IL-12, IFNY, ThF P

CytoKines Sourme -MaYo phag¬

-Endotheli al ceu
-Mmt cell

Lncluder
:Inteleukins rL-1, fL-
TNF-o
- Enter errons

FunetoM Loeal stemie

Endothelkal -fever (IL-1, fL-6, TNF )
acttvai on Metabolie aunormali
-Hypotews en Shock
Anti-intlamatony yen
- IL-lo M s t L-6
- T&If eowwon IL-4 Sn Seme onhen
AXiponee-tin
Intor erons
TFN Leukote* AnAred action.
TFN Fibroblas 9Gmunomodulatoy
ENY Teell MAero phage acHvahm.

Chemokimes ; Sournee -
Leu koeyten
AeRvard maenpha

Funcion -themotaxis
Leuksye attahm,
Platelet AetivoinFackor
Sourtee: -Len kocmfe
-Mant cel
Funetim, veno dlation - Leukoeyte adhenjon
deranulati en -T Vanunl an permeabiti -ehemats
Most important Cutolanes
d Aute in fammahon, sePHt Shock, SR$ Cachaia ; TNE
Fever:IL-1 .Synthesis 1 Awte phaoe oteis: fL-6
Angiogenesis: vEGF Gromulorma fvmaRen: CFN-
Hbhosis; TGF-*
Kinins (Bradyinim)
Plooma (roduced in iver)
Sounee
Ffunehon - vaotulost pemmeaity
Paun
- Vanodilatien
Breomehospaam

Comple ment details from Mierobiolo.

Comple ment deficieney dise anes
&1c2/04 (early protein) Autoimmune dis eame ($LE)

c3 (cehe molecule Severre Pygenie infeeions.

cs/e6/e7 /c8 (lare protein) .+ Nässerda infeckion.
f Toxoplamosis
e9 N o diseane.

Complement regulatony Sstem defeut meiatecl diseane

inhibitr
e1 de ffceney Hereedieo oangoedema.
non prtin
cD 46/Factor 8/factor H defect Atypieal Hemolytie
Unemic Syndroe.
eD 55CD59 defee Paromsmad Nockurna
Hemolobinunia

Coagulattion Cancade
A Intin sic Blorbd vesse K>X
Pccthwan nju
(6) ExtansicTissue »2- frotua thro mbinThrombin
atho Fackor
Fun oen Rbrun
Suda) Ansalule
Exudatees (ransueae_ ,
TB perutonitis
oeteri purutmitis O Huydrostahte Pyesgure Oncotic fhesue
*Hearet faiure Hearet elare
ntnabdorminal maliqnomees Liver cirhosis LiveY irrhosis
HepaRe venoun obstruehiom Nephinic Syneevne
anereakie neite ettnmdism pvT
Malnurdtim,
Exudate || Extra van aular ud z higk pmoein toneentvatiom.
Contains eellulart debnds kon higl. spuife traity to1)
Due fo- t peremealbilit Smal blnd essles de to
tAmmakim,
Tramsud ae ,
Contalns
Extravoaseuart uid a
Smal amount albumin,
Oerro totein eontent.
iHe o1 no cellulan mataria
han o peifi rovity i o12)
Due to UrafHroahian of Planma tes utint rom
Osmetie mdrostatie imbatante acros vesue ua
wit wi lent mereane in pertmealoilu.
Exudar2 vs Transuda

Tai Bxudate Transudahe

Total puotein Hgnin plama) usually albumin

bnogen Pesent Not psent

May eat spontanawiy does net etst

sp gravity Hia(1-o2n)
Cells
Polymorphs Nonefew mesotetad
colls.
Cause pertmeaLidy due to
Hydrostatie imbalanee
Snflamatien aLros voneuat
ndotthelium.

Bene t Eudate
Flid, Component Exudae
Dilutiom ireritant sustanee
Cary inftammahoruy ces, osonins, omplements , Lmmuenogobulins.
Lo p* due to lnctic aeid fovmaton mhibis aeterual voit.
eonteans fbin that
ais phaoytosis &
Jorms a
baruuere
agaist bacterûal fnvanion.
 cellulan Conpormens Exudate
Neutrophils, Matrophager g s t bacheria k eeu debris
Plaoma cells seLrehe mmund fobulins

Hartmd Efes Exuelates

lacterial grow-t
Hig Protein
Hig% content acs an a good medium
Exeesive ibun ma ead t adharien.

PGE,5 HT, Dnadsinin cawe iuru Bafim onenve endings

ents in pain .

Morpholo_ic Padterms oAute nftamatim

Serrom Snftammation brino n infammain.
pevelops shen tfere is lange
Exudation celu poor udd vaneulan eak or otal Pucsaaulant
OcUarb in orutoneun, PleunA or Stimud pesent.
Perdcarrdtum Oecures m inslammation sinin cavities
Fluid is not infeeted. c h an merina, pericardium, plewa|
Hud is deried from Exudahes may be dissol vad byflarinoly
Plama Ctvapulat Penmeaoility) aleared by maerophagen
- Seereim ofmemo1ereli aalls | not nemoved, it may shmulate
Can a nenudt loeal iruutahion ingrovot o fAbroblants & blepd vassels
lead t scarrin.

Rurd ent mtammattn

P (neutaphilliquejaehe debris ttretic cellu +
Pro detion ERema udd)
byeess is Qocalited colleehen puruent njiammatory tissue

FATEoUTCOME OF ACUTE 1NFLAM MATION

Complete Resdluti on
t3sue replaemet CAtu n
Healipt by comnecive
bnosis
Progresim t ohui tlamaion
 Modified Macophager jn tiSL Bo ne 0skeoclasts.
Braln: Mieroaial ce Spleen: Litoral ceu
Lungs: Dut celualvebl maeopoge Kidney: Mesangial telu
Liver; Kupffer el PlaLent:Hofbauer tuk
CHRONIe TNFLAMM ATION || Delaed but Sypeiie respm)e
Response Prole nged dlureation w eeks oy months) in shuch
-Inlammahm
- TTssue m u Co-axiss in varming combnati
Attempt af epair
Can
Paresistent mfeeton
Hypertsensitivity diseames - Auteimmuoe diseare (RA SLE
-Allergii diseane (EA)
tere brosks may dominata the Late stae.
Prslomges xpeosure t potentiallm tonie agenks, ekher exonona
CAlicosii) or
endogenoun Cathoeseerrosi)
Onsonvenonad diseones- jeuurrodagenerave diseare(Alzheimerts)
Metabolic Syndrome
Re 2 DM

#Morphologic Featres
Inlraion ut mononueleart cells-Maerophages
-Lmphoote
- Planma cel.
Tissue destruehom Halmartk oeh. inflammation)
Atampts at healing y - Angiogenesis
- Fbrosis

Cells Chroninftammatim
.Maerophajen Eosinophil Neutrophils (in ostomyelits
Mant eell acte on th. tun domag
phoyfes 7 Smokn otter tnitant
Marophae Aeth vadion
elassical (M) Aterhafive (M2)
Aettvated by micrebial Prtodueadoti)Aad by mierebn
Seeretes lL-1, IL-12 seeret £L-10, TAFA
Funien; Ari inftammadoy.
Functhm; Mierobial l r Tisse rtepoir, Prromotn
Y No, RoS, upnasulakon waio emea, Kbroblant
Sosomal entme keiahon Collajem ntkems.
Most mpovtant aytoline t aronuloma Tmatiom 1FN-
Mov Imporhant T-cells in qronulema amatim: eb4 Thi e l .

#6rranulomatou njtammatirn{
ounic
-
inftammátloin
AtHvated
aharacherited by
macrophaten
eolectiom f
T-ymphoyra
Sometimen central yeerosis,
Activated maerophage Aevelop abundont ytoplaam t i n to retmde
epiRelial aells.
cells Tun ealed Epittetioid ells.
Some acivated macrophazen may fme to form Muutinueteated
imt cels.
iat Cell Sub n
Lonerchans ant cell:-Seen 'n Te
(Lomgerhams cell is a normal cell)

Horse- Shoe arucmemew aruckei.

Tumor Giant cel
Giant cell tumor bore.
Fertelq body ant ceu :Tale, sute
Touton iiant eel : Xanthoma Cft droplek preset)
Wartin- Finkeldey Gint Cell Meaales. ..
Reed Stertnbarg &iant cell
Achoff Giantcell Rheumatit Hodakn's mphoma (ouoeye
hearct Aseaae.
'Tyrn 6anuloma Pensistamee
(A) Ymmune aranulo ma spee Ttell mediated immuune refome,
TO
San toidosis
'-Lap eosy Histo plasmosis
-Cat sertateh' iseane
chnons isease -Bl4atonmuis,
Htodga ympho ma
forreign body_ovomuloma Absenee 6 Tee meiad imune
Tale
vesponse
- Sutare

- silicosis

Accorling tr cameein
Caneai sto plonmbsis
Tb Non-CAmeakin
-Sariidois
-Coteidtodo msisS -Crohns diseane
Fe ranmloma
- Hodains wmphem,
-TB
 Gramlomatoun Disenes3
Tuwoereulois Caneating RANulo ma
Sarrtidosis Non caneain Absence yphoute esllar ,
HHstoplan mo si's
Cocei dodoeoS Caneatin
yphils : Gumma Ceaneat
'Cat serateh dseane Stelat franuloma
Lepros Caneaki n
Crohns dseane/1BD Non-taneahir mmune ranulem,
'.

Acuta Phane priobeims

:-reackve PLoteins SyResa ed in iver in teponde t
- Fibrumoge

Sarum Aleid ACsAA) ytoine stimulahH

L-6 or CRP {lruno
Hepeidn IL-6.TNF r SA.
.Th aet opsonins &
fx caplement.
Hepci din i
rtesponsible r anem,In
it tedueen avadlabili
chnonie injtammahm, an
y ieon.
LYSDSOMALL E2YMES | 1ysosomen han 3 type Giranlen
Prum avy / Aurrophilie 3ttondo/ seedsie JerthiuL-Paxhele
More destruetia Less destruretive Involved in ehemotaxis,
Contodns |. Contains diapedesis &makux
AMyelopertoxi dane (MP) Lacteferudn dermdalhon
Elatase ysoymes Contls
Defensin T y e R eallagenane
ALathepsin &
gmieruglabulin LGelatinane.
Acid hydrolane Gnelatinane
Phos pholipane A yto erome B
backerial Portmenbiliky
Pruteins. vit. B12 bindin Proteins
Nen speifi collaje nase|
 TISS UE REPAIR

3 yeen ofcelus contadning hssue

Labile (continuoualy diridin ceu
in BM
Hematopoiehie cells
-Surtface epiRela ; straifed a. epihelda osvan, oral eait
Vaina, endometrium & cerevia.
Cubeidal epiteelia due drraining exoerine and
bilia ra
Setivary and, anerean,
tubes
Columnareepitfelia of GIT, utereu, fallopian
-Transitional epithelium wrina rac,

uiescent /stable tHssues athvy.

Go stag. Minimally
proljferak ve w
54ams in
os 4issue man».
tissue mann.

cApablk iding in ponse t iun o

res
Panerean.
Seld tissue Lver, Kidney,
-Paen euyma of
- Endo heli al cels - Osteoblant
Smoot munale cells.
Fiboblants.

omdividin/Amanent tissues
cells ane terminaluy Aiferentiatd
&nonpuabfenahie
-Neuruons
-Cardial munele.
munele (sateli ta attached to ndomysial
cells
Skeletal
sheatA povide some agenerakive
Capacity jo male.)
Here Trepair i s r e a dominatad by scanormaho

*Al he cell
roliferahan s driven by siamls provded by
-
6ace t fastors (Pradu ed by cellh mRar he Ate tf Ramasa)
-Ecracellula matrux
 #|Wound healing Consists o 3 ProteWes
- Res olukon
- Regeneratian

Repoir y sear tiBut femation.

Resoluhon
Ldeal outeome healin
Seem m autr 'manatim to minor inuies
Reene reh
Pruoteedve meehamism st epilhetat eells ohere lost
pareneymal aells
ate
relaced by divisien tadiacent nrma Parentpmal tell, Pevided
+ha
underint boement membrane s intaet
There. will be complete restoratien onemal issue .
hssue
D
Regeneration 3F iver oecurt b to meehonim
-

Prupuferatin remainir hopakeeylon.5 907. urrechm

Repopulatt'on rom Proaenitor cells
Prenitev
ce Hesl e n c'ands
bilè eanalieu
emeit uH enger bile ek.
Herunhere
Repodr by Connechve tissue eposiho
.Replacement of damaged sse brocollagenoun ssu
Consis 5 Formoatien Chonulaion tissue
Haimartk awound healia
Wound tontraetion& Sean
formation,
Gtramlation ise
Gronudaliom Hsue utains
ansis reiad
f Prroliferakng blo d vessels
Cneovan eularútahien)
P collan.
sean tiss ue tomtains type I rerakth tbnodans
collaen collagen
L tenvarsion trem in to f ellagen Non-speepecfte ammatin,.
is knouom an we und tissue
rtemodelln
LRemodelin) dapends n MMP
matr mefaloproteiname
| LMost important Co-jatlor tpr
MMP S ine.
GAnl atHon issue Ubherte ound
Pink,Sft, aranudn ppeomAnte Absees oau Avod stul
Ulcer bane edge a ramuloma
Enailbleeds m toue
Sinun /fistla raut wOne hendns
ncewile tosistat to mecHn
weund com traehn sean fomahi
wll bring weund eorraction collaen ill be
Myoibublants
ssde.
depeited to orm seat
kssue is wnan
Replacement ranulatiom tisue to scan

n tissue Yemodalun.

Reporbegins uitin 24 hous ainju,

y - 5 & s , ranulahon s u e beeomen apparent

Aniosemesis Proeess nes llred essel developmert om exisKn

vessels. Steps ane
Vanodilat'm in espo ns e2 NO & inereaned pnmealbiliy
bVEf
Separtaion f periuyes, rom the abluminal (outzy sids) smmfnce
&breakdauon bnement nembrane

Mitratim of'endottelial es to-oands arvea E inju

LProlferation fendethelial cel.
Remodeli n mto aapillan b e .
LReerutment f perien dathela cellb
-Perieya. mal eapillae.
-Smoet mele ells jor larger vesels .

suppreien Rndatteltal *sferahim mirakien.

LDeposKm bacement menmbrane
Fautors Afeekin wound Healina|
Lea
Inseetian
shemi .Mal nu tru hon
Vit A,L,E
bleod pply .AnemioaCHyPoxi<) de ficieme
Denertvoti on Glueetorite (turaid) Paunsakuran
Forein boy ytotonie drus fayad
Hemaoma Diabeten meli tuo defiieney.
Linedekieny
.

meehonical Stres obesitM nemia

Poer SurReal tedmiome
Malimomem Peror pen Fwmon.
 #Phases fweund healin
Inftammator phahe
-Begins iwmedately , Laots 2-3 dans.
-Gleedinz >Vaneconstnietion>Tombun tormahon>ümts Hod lm.
Roiseraive Phase
Frem 3d dayto ok.
-

Gvmulaion tissue f i atiom.

Remedeln thawe
- Maturaton & eplacemet of type
-wound colagen by te1.
vaneulardy
& wound
eontrachn.
Healing f SKn upund
,i 1 intentiomima Union
Ohen injuy mvolves ony epithetal amer
:Wound edgen ate apposed wead is mnfeeled ,elean.
Normal healtng n i m a l scar
Day Features
Immediate - fibin k plataletss toorm alot
Dax 1
24 heu Neutrophill blnd ttot
Da Neutvopils replaeas by maerophager.
24-48hmm Earty romudadin Hssue
Neovanelaritaton
Collagen depotikn at mar ut no brudin 6 a

Do S Maximum ranulatim tssue depeilkion

Collaten bridges the nisien ap
Ttal recovery epidermol thekress
Day 14 -Maximum eólajan depontf n k
DisappeaTamce"sf edema kukoyte

Da2 Searrinoplekes
Dermal
by remodelin
ineiion
appendagen destnyed in t na f
ane
permomently Lost.
 Sand mtenhn 6eeond ary union
Lnyuy is more extensive
Repair Proeess velves a
tombj ration esenerai en &

seortei n
Weund islek open.
romulatiom & more scacrdrs
Hea by more mflammatim, moYe

Heain seporaked ed er due te

nts Soos5 tirsue.
woumd eontractin is most minent

CTertiay ntentimDelaned prümany menti

Oounnd initia left *pen.
ater OPPOsed hen healkn comditi om
are favounasle.
Edsen

Wound Strengi
Cross-Unkngeoll4gen is
fthe mest impertant ator for tensile shargh
ocoagen.
vit eis reauired for dvolation ne& roline to eover
trcopo eollagen to eoll agen kor enhomein ensile strenn.

Gainin shren starts affer g day * iny.

Wound Strenh - Dat the end f * o - 16 normnal skin.
a r the and month - #o -80y, sf
mo mal skinn CMaimam stength)
NeveY 2ans normal Strenath

Repair
#Pathotogie Aspaels f
fovmatim df Granuahion hss ue 7seat
tssue
Inadeuate
O Dehiscence /Rup ture s wound

Uleexation,
a Seurteas of Ault Stem cells
Bleed
ene martu
Adipose tissue
Unbilieal comd bleos

rlakionsean Hose
Exeive fomouhi on
Hypertrophie Sear
Exteve eola2en aceumulaion
Ralsed sean uittin wound b bundaruen. .

Obet % leu tham 3 mats.

Spontaneuy negres win - montuy.
Develops
deee aftahina traum ahit inýny mwol vin
p s ofdermis.
Keloid
Searr progressin beymd he original bou
hda Fwowne
Onse wn n 1 morto 1n.
Maybe anetiea ano e amd

Most eommy seen 'n hean, Ameticans

Comenest ite affeeked is Stermum.
Doesnot rezress ontaneouy

Exubercant Samulation
Formation ax ceive amount romulahi n , Protrudi n
abrve ortrzoundin tse.
tbloeks heepithelialigaton.
Also knovon an oud ftesh.
OWoun d Contracture
Exaaerated prm weund heatlir
Cawae wwLnd dekov mt
farvticuloarly Prone t develop on he padm, Sole&
aMzrdor apeut F hova
Cowmm mew afr bunn.
**Fetal utaneown wumh healint Oeeurs aiteut Scaving due da
Prves ence sfnon fbroaanie pY) of T&E
Laek oosteoporrin produeim.
AAbsence of CD4 Th2, hi acHvak maeropho1 t
rodue brognie mea ILi, TGF-P)
 HEMODYNAMIC DISORDERS
#DEMA||:Gxcetiva 'terskkal tuid depori Hn . ovur dme b
Inereaned capillanydrbstafe presg ure or Dimnshed eell eida
oSmoti Pressu
Cauyes

Ineveae Hdrostahie Pressue

Impaired Vaneu Keturn Arteriolare dilaho

Congas ive hearet faire Heat
Consticive perieoruditis Neungm mora shelakM.
Ascl bes (ivar eirhons)
venouo obstuetiom
Thrombotis
/Compres sim
-Extermal fnessuse mana)
Lewer exhamiy maetity
prolenmged depe ndene
2

Reduted Plama 0smotie Paessure CHePoPnoteinemia)

Protein- Josing gtomerlopaleies (wephruotie ndrome)
Ltvey rdhosis (Aseites)
Malntrutiom
Protein Losin
-

antroenterro pot.
ymphahie Obsrue tn
Inslamahe
Neoploote
Post srical
ost iradiation
Sodi um Rehen i n
Exeesive salt intoke w renal ins fiene
Inereaned tubulan reabsovpiom oSodkum
Rena hypopernfwmim
nereaned Renm -AngiotensinAldosterone Seeretion

Ltammatm
Aeute 1ntammatitn
Chronie ijtagmmaion
Angioeneis
 Loealia-ed Oedemal|
burn
Aeute inflmmatoy edema injuHon, trauma,

percsansiti edema: Alerge reastim , uniecaru a

Edema afvenow obstruehim; ve obstruetim

mphahke edema: Malignane, lariaris.

Generralited Oed em
Cardiae ecF, Perieavdlial efiom, Comstrichve perucaediis .
Renal edema : Nepmoti* sndro me

Mainutrutiom: PEM, Potein losin zaotroertenopaty.

Hepahe : chrshoss
Hormonal Cushin SyndroneAdtena hov mne exte)
.Paumonar edema.
.Myxedema
D ndmted

Serum
Serum Albumin Asdtes Gradient AA6)
Under norma drtums tante, SAA 1s 41 loeeaune seruam oneotie
CPlama calloid ad smotie) Pessure tCat pulls fuid bock into cdirulation
sxaetly dountexbalanced ySerum hdrostatie fnessure
Hi Gradient (>ri m/d) >thydrestaie phessuvetPortal ressure
Lo Gradient C%r1m/di) -> Asites mot amrociated i teYreaned
SAAhPevtal HTN &, Portal pnessure.
enertpneal eae o eneiten SAAG/Peritonealothey ttN poraa
Cirrhosis, Heart jaauy . HT eawme s anelten
Constnucive periarrdi is NS
Por tal vein tvembosts, obstruchen Recheising Aatzaegot
AHepho h' hepahRS Perteneal aarürematosis
Fulmnant hepaht aiure Tdaastelar pezitenitis
|Budd chiani Synakeme Pamcreahhs
Chis bsomiais Bilkouy aneten
TdopaHi e por fnasis Paukmon y ets
Sertbstis
 Hypere emia & Lonaotiom

Hhyperremia Aetve porocess

lation
.

lation
ncveaned blood ftoud Aue to
atteriolan
Afeeted issue tunns red Ceruthem) ne to engorgemert uit
Omaenated blod.
Oeeurk at the t e intmaution ov S. mwele in exereise
N o Oedema. menopawsal fush, arode av.
CoesnPassive ProeessS
Impared tutflt fem a tissue
u e to accumulation f
Tissue tunns
deemgemaked
blue rred
hemegfobîn
Cyanosis)
frem 2Be stasis.
LVF: 'n un

C o n be systemie: Cardiae saulure (HF)RYF: emti ody ax

obstructim; portal v newn
Local sdlated
venous
OY,
obskrueion in iver cirthosis.
Oedema stis dercmatitis af

EAfect Cometi
alveot cotain hemosiderin
loden
In ehronk pulmonary ongestiom, Bnewn indunatiem ung
Ren (heart ailare cell)
naropha gen
maeropha
seen in iver wik ehronic pasve congeotion
Numea iver
neerosis. Here central arean are ed &
sugltly
sigltly
hemorrhoagic iable
the soreeunin t n
arenemma
eomparted to
depressed
HEMOSTASIS| Nermal puysiologie Prroees to mamtaim dood ma fuid
at the
Sthe w1ttin nonal vessels while nducing hemostatie pua
inuned ite.

oe dvanoconsteietim:Transient mehex neunoaenk arttarielaz

Vaso Longtieh on by endorthelin
TXA2
5 5 HT
Prima Hamostais:
via von Willermd
-Platelets adheve to expored £cM
fetot WF) ame aeivated- wnderqoes
8ape ahomgin &ranue neleane.
- Raleased ADP & TKA2 kad to funthen ageqatiom
tform p>imary hemostatie plu
-Platelet binds uth msoluble ibun ie GaPTb-Ra.

Seeonday temostis :pepovition f i n )

-Loeal aetivatien Coagdation tancade (volvin
Hssue faetor & platalet phosphoipid) nesudlks in
ibun polmeriRation ; there by eemering the
Plateles mto a detfnitive Secondany hmestabic r
elot stabiitatienResorption
Achvatien ounter -relatoz meenanism-
tPA rrestachs te hemestatie pl« to the site f

*Coagulation factors * Naturae Shibthrs

I fibino gen Coalatim
Prohzuom bin Antthrombin 0
»Tissue fackor/Tissue teromboplar -maeroqlobulin
Calelum Heponin Co-cbr R
>Proaeee lerin/lable foetor Protein C&Prstrin S.
s t a b l e faetor /Proeorvertin
V Antihemophilie actor
Antihemophi ie achor 5/hreistman fattor
Stuart frower nch
Plaome hnomb oplatKn antece dent
ageman Jactor A i b i n Sailisns r
aetor
Endotheli um

Anbidbrorohetis fropentieg
platelet inhibitory c f e t Releanes: - Pruostmeyetnna
NO
1nhibits flateet ADPane (adeneire
ation d phos phatame)

Antitoagalant gffect
Ithet endettetium shields eoaqulahen eors m hsue
faetor
Expesses moleules tAaoppose Coamlatiom, meh
converts it
Thrombemo dulin Cbinds to ttomombin t a t is
rrn pPro coagulant ta nticoaalant,
capalbe a e t i v a h n ProtinC

Cleave, aetor &

hronmbomo dudns poduced in au endatfelial
ceus ex eept m cerebra ierocuroulatim.

0Heparen-ike molecule einds to antHrombin

amd inaothvate, factr P, ,2,A,Ai.

Endottelil proten C aeaptur

TTsseactor pathnaM inhibito

Inasvat aetr 2.
ilrinoe Hee synthesibe tPA
Plaminogen asHve Planmin

aleaves fbun into i a n

earadation Prroduers, tum
intexferes i polymeritaton.
Platelet Platelet acttvahon mvol ves
Adheman k ghape chme
nds wite WF tor
Platelet GP ib mecepto
adhenon to EcM.

Secrehon from Gramules

Alpha Gvamulets-factor , Y
flunegan
vWf
- PDGF

-TF-P 4
-PlateteF Faetor -

Detta Giramule Elebon dens:- aDpP , ATP

Caliumn , Epinephiune
-Histamine, Sercstonim
Lombda aromules (Gmall)Aid Hdrolaoe.

A8areation
ADP&thrambexane promohes platelet aqatim
i GP Nb-a.
*Platel et Agaregators aele a{rezahion mhibitoYs

ADP Epinepline Rrostcy etin (PG1

yWF Tombospondi Endothein
Thrombin TXA2 NO
Colaen Serrotemim Bradgkinin.
Inune complex i b i a n
 APTT
PT
Norml, 30-40 s
NoTmad lU-16s k eoaulaHom a t w a assessment
6ed fov intrensie
common
uselfor assessmet ef exwinsie fackor T , a , K , X , 9 ,
Common tooulatHan pathu oLonge in: Heporun evedose k
, Proorombin tleunegan,
holene in, Warnfarin overdose
Coagulation Cancade | ABloeked by warfarün
Btecked by Hegarn
Tntrnsie fatevam Extrunsic athoag
(assese by PTENR
assessed by aPTT)
THALma indide yessel sao Tissue traurma
Ble ed rauma or
contatt with collagen
eaatively ehanged substone Tissue fetor ( )
a s s , sirca, kaolin ) CA
(Va)
a

CT

Prottambin >Thrrombin(Ta)

fibrinoqen () AbranTa)
fbrin ot

Fackor R ET; Fin-fbrm elot z xm ApY

dN 463 D activatin Thrombin (T
Ca 2 reqire in - ZA

Ma
> Na t KAependent.
fotombin thoe Praleme im Extrin patkuoy defeejs.
Factor , L, 2, A ,2 ( r *T) 7z P)
APTT Prolonaed in nsie Pata Aefees
FactoY 1, I, N,2 , B, , , 2
rombosis napprepruate achahion bleplt6r.in
uninfuned or tombetie occum Messel atter neltnn
win u .
Virehos Ta
Endo thkold
Dominant & Cm independenty cne trombosis.
Caned seonlariy th
Myo candial menckim
Ulcerate attenoselereote plaue
CorrSiae Suner.
Mpcatdiis
Ineeted valve dseane
fros tAeht valves
Raiathion inu.
'Traumaie mfammatom vaneular mganyeaoenditi
Hypetenion
Enotoain
Chemicals molking yperchulestero lemda
bun.
NOmoe steinemia,batkeruoad

Alteratim in nosnalblo Ststunbulere)

Stais: caunes rom bois in venown eireulatm
Turtbulente caunesorombosis m atterial eàreulaki'am
Thine pwmote tvombris b P
isrunpton nortmal lamina tnd , euhoneing platele
contact a endottelium
ginhibits Auhom taetivatee elothinfaetovs
Deexeanes o v eurtin inhibitors.
tnhan cin 9otRelial cell achtvatim.

tans 'ist9piealiy Seen m wpert iscogty synohromes &

Ptyetemis
Tunbulenee s cmo nlm soiated a
wpertemin.
 ypen eoaulaoiit

Preimarhenetie) Seuond a (Aeauare

OCommo
Fattor Y mutaiem
- Protfnombin mwhaRom
- Immabiliaatton/autorged bal rest
-Tssue i y Guongany,, bun
Rarte -rassteyete valves
-frotein C Sdefedene -Cantee
Atrial flilation
- Anituombn detcier MI
DC
von Rore Avrti phesphpupid antbody stkone
-Fbrimysis Aefeet -Heparun 'mduces tvambouiopepr
Homoaoo homomstainunna
Looisk
- Carcio mo partm
-OCP wme
ypenetrogeuie Staten
CPananopstpantu)
Nephruotic eqndrome
-Sickle cell amemi
- Smekin
Trombwal Solid /semi-Solid mam m ireulakion em Constite nts
streormiblnd
T

Banc on Site
,Avterda Hhovambun; -Begn itot e twbulenee endoktottas inwy.
e% |-Tends o m a Retregrade direckiem from
Thrombn n alearated Point attaehmert.
ateromato un plaque mn - Firmly ctmehed to iuned endot.eltum.
Cortonay anteny.
Tombeangiis obliteran Pale, composed plakelets RBe

Buererrs Asene -cholestenal

leukoeyte (maere
Laminaked throm bua m Phoe
neurysm. - Fruable eamly mbolizes.
Trauma.
 Arternal thrombi Venoue tmombi

Cawse Turoulente stasis

Location Most tormonly. toreno Swpena deep eg veins@
Cerelral , temonal artterie

chaaehere Frriable Not Fraable

Frequentlyoeelusie nvontiablypeeluve

PropagaHon -
Retrograde Aterogrode
Incomplete obsruetion umen Complete obstruekion

to oall.
firmly adtached to wall Loosely attachel
Frmuentia emboliete Not So

White thnonbi, consising° Red thombi, due ts more

pale platelet layer unth RBC less platelet.
dark RBC,. laye
Line 2ahn Distinct
ot.oell developed,lbu
maybe seen
eeial in mural homb

mbolism, Oedem
fate Tsehemi a / Intanetim
uleertation
vital organs
 Fate oThrombu
-Propagakion Instammation &brsisir
- Emboisaion
-Organaaton & rrecanaliation
- Dissoution A
ngrouoHth oendothelial cels, smooth
* * * *

mnele flbroblasts.

Clot Antemortem dlot/Thomb

Solid mass bruni solid mdss platelet & fbrin

No platelet: sealfo ld Platelet sea jold Poesert&
Vivo Only n vivo (within Gvinq bed)
Found in Vitro &

Fortmed in Stahie blood

*********************

Formed m: Streamina blood

***********

Fruable. Take shape vesse Not S0 friablé Don't take shape.

.

Easily detaehable. from Wall

******

Firmn attached to the all.

***********
********

Distinet Line 2ahn.

No lineof Zahn
6relatimen, saft & rubber Dru, Grranulan , Frm.
Dark ned, dependent pontion
is ealled curtnent jelly.
Yelle Supernetant RBC
free ayer is ealled chicken at
 P
Red Tnfartet White arner
Avteri al 6eeluion
Cane Venown 0celw>10n

Jnvol ved Heat, Spleen, Kidney

Brain, Lungs,
organs
Small ntetine, ova
Pale
Colour after Red
24-48 hour»

fulmon embolism

5 6ruginates from deep leg vein tnombosis.

tcan occlude main pumonaru antern at bifuncai on embolw.
Saddle

Kastel fasses thonogh an nteriaterial/intestvetricalarn desee-

Cane systemie embdi Partadoxical embolism.

elinicaleffecr
60,-80% Silent.
Sudden death
oksrues 407,
Rig hert faiure (eor pumonale) oen emboli edreulaion.
Cardiovarculart cllapse y pulmonu
Common Souiee
Lange deep veins at above Knee Popliteal, femonad, iliae vens.
-Calf veis
Superfcial vanieose vem
-Pelic vein

C Heartt thromb'i om
rom
MI (t. verhrcle), MS (t.akrial thrombi, Prosthetie
valves
- Atheroselentie planues , Aortie aneumsm.
Fat Embolism

Cue Fraeture of lorg bone ohich have faky mannru.

Trauma fadipose tissue
-bunn aipose ssue
Rartel in the setking tf soft tissue tvauma urns.

Pathogenesis
-Oceluion of pulmona & eenelonal mierovanaulature loy
fat gtooules
- Releane FFAlocal 4oxie injusto ehdothelium,
Platelet activatHon aanuloeyte
"Hee tment leads completa vaneulasz
asD auE.

Palmonay insuffíierey: Tatypnea,duspnea,taauyeardia,

-Neurteloie mpto iruitabiit restlesness, delirtam,oma.
Anemia a: Due to RBc aqaregation /hemdysis.
-Thromboeutopenia : Due to plateletadhesim to fat aobules
Splenie seauestrasibn.
-Diffwse peteehial ash, Conunchva miechon. Subonjunctiva
peteolia.
F a t a in 5-S%ases.
 Air Embolism
odee aar is necessarty to prroduce dinical san.

Acute deeompression Sickness

-Bends : Rapid formation an buloble
im mumele joints.
Paut
- ehoke s : In lungs, aan bubles produce edema, hemorsha,
enphysema Lesds to mespirator
jocal ateléctanis Or

distress.
Chroni deeompression sickness
- Caisson diseane
humeruu.
Comom Site femorcal head, ibia,
wonkers.
Hig risk: Bridge sonstruetion heads to isehemie
fernsistense qaa bubbles in sk $ystem
neerosis.

R to fonce Hhe
ba k i o
2am bubble bauk ito
ehamber
High comprtession - radual
slano deompression
Soluion then subsequent bubbe
nefommaion
,

resorrhon
exhalahon f 2 , Preventing

Amniotie Fluid Enmbolism

complication olalboun
pestpartun perued
an a

-Irmediate
shok
Severe dspmea, caanosis, coma.
Hendache, Seizue,
-Neunologieal mpaurment :
edema, DIC
- Complicatim . Pulm6may

On autops frresente squameun eeM

lanuao
rom Jetal sin, lanugo
vernix aneosa mucn om fetal ClT,
koir, fat fom
,

tepiat Stem
edema aifue alveol a r damage,
, -
Martked pulmonart ,

due to Dle.
fbsun hrombi
NEOPLASIA
 Benign Malignant
-RApid
- sleo aruouom

well num sorubed

Pooru arteuwmserubed
Has distinet borders - EnFrative

Mobile -
Fixed to sotoundmg Hssue
well dierentiated cells -
Poott to well difeneriated
- Onganised artouwth - Diserganised
- Uitonn nuele
Nucleast pleom ortphiism th
h perchruonasa
-Low nulearn cytoplanm taho - High

Mimmum mitotie activit - Hig

- Mitoie iares arte rarte -
Numertou albnonna
ortrna.
-

Lak o nvion Ivanion

-
Han no metantahe potential

Hamartoma Neoplai a
-

Disorgarised Soal rowth omature -

Abnomad, exeestive, untegulatad,
isse autonomous pouferrafion
Plylonal -Mbmoclonal
well diferentated cell resemble -
welu dferentiated to pootly
nortmald entiated
A uoays bernian Benam or Mauiznart
Ex temanaioma SCC, Adenocaanoma et.
Bsuonelial hamortoma

feute-Jaghers PolyP bowel

 Pruotooncogenes be eome2 Oncogenes b
- Point mutation
-

ehnomosomatras lation
-Inereaned protein expnession

Proto-oneoaene
Bladder Ca
RAS (most eommon)-Colm, fanereoan, lung, Kidnet,
Melanoma.

N-mM - Neunoblaatoma

TGF - Hee

AbL - Leukemia

sIs
aene (PDGF-P) -

Astroutoma
Bcl2 Folli culan ymphoma
HST -Melanoma
HST-1 -Osteasarmeom
ERB-61 /02
Turmor Suppness o7t Chene2
APC -VHL -WT1
RB -TP53 - MEN 1
-
NF 1 2 - BRCA 1& 2

Hormone Dependent Tumer

Tumor
Horumones to Treat
Papillor & Folieular Ca
o Tud :
Toxane
ca Brneast
Proaesterrone
Endome4rial ca Progenterone
Maianant melanoma Regess in Preananey telated hanmen-
Cafruostate oserrelin HRH)
Biealutamide (An-andrusgan
 tortmone froduuung Tumots
Small eell
cen ea T lung
ca
ADH: biLutional ponatnemia GIADA)
($1ADA)
3 ACTH: ********
Cushia sundTuone
,A ',,
.sauanmows celI Ca lung
Ca Breant + Kidney (RL *******
EPTHr P-> Hypencalter
******** ******* *******

RCC
Hepatoma
tertebell an hemangioblantoma Ewthroprietkn-Pol*thema
.oruid wteruu ********** ****** ***************

Bruonehiial ca lung
Pheo ehomo Ctoma

Mesenchymal tumor- FGF 23 rophosphateriie osteomalacia

Insulinoma - Insulin
gpeeacemia
Cardno1d 5HT (serotoni)
Gwanulasa lell tumor foyaryt- Oestrogen
Chotiocarteinoma- B HeG
 Tumon mar kers
Honmones
HC Trophoblasic tumorg, Non-s eminonatous testieulan tumons
Caletorin - Medullony Ca o touid

Cateeoamines & metabolite, Pheosuomoayema

Oncofetad antzem
-fetoprotein -

Non-semihomaou aerm eell tumor

Hee,
CEA Ca Colon, panerean, lung, Stomaeh
Isoentmes
Prostatic acd phosphatane - Prostatie eameinoma
Neurto specifse enolane Small cel a of leng, Nettoblaotoma
Muein other 6alyeoprotein
CA- 1S-3 Ca Bneant
CA-1)- Ca tol on, Panerea, Mucineu tumex 56var
Ca Stomach
CA-12S - Ovarian canuinoma

Speefi fruotei s
PsA Ca postate
Immunoglobu lins -
Muiple myeloma other 2ammopaties.