5BBB0206-Tissue Pathology - Lectures 1 - 2 9th Jan 2014

8/12/2019 5BBB0206-Tissue Pathology - Lectures 1 - 2 9th Jan 2014

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Lectures

25lectures

4revisionseminars

1sessiononthe


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Practicals Generalclassroom,

HodgkinBuilding

Cellularadaptations(today)

Immunecells

Vascularhisto atholo

Tumourhistopathology

CNShistopathology

esesess onsare mpor an ore n orce e ec ures. sosome

ofthe

exam

essay

questions

will

be

image

based.


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In

course

assessment

(30%)A2,000wordessayonpathologicprocessesindisease:

Youwillneedtoprovideanaccuratewordcountonyourcoverpage

PathologicalProcess Disease

Hypertrophy Asthma

Metaplasia Interstitial lung disease

Neoplasia Glomerulonephrosis

Atrophy Systemic Lupus Erythematosus

Apoptosis Psoriasis

Fibrosis Lymphoma

th

Necrosis Cirrhosis

campus

by

4:00


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Structure

of

dissertation1. Descriptionofthedisease

2. Descriptionofthepathologicalprocess}50%

3. Relevanceofthepathologyunderconsiderationto

theaetiology,progressionandseverityofthedisease}50%

FAQs:1. Figureandtablelegends,plusthereferencesarenotincludedinthe2,000wordlimit

2. Requiredto

use

the

Harvard

system

for

citing

and

formatting

references:

htt : www.kcl.ac.uk librar hel la iarism citin index.as x

3. Referencesshouldbefrompeerreviewedpapers(originalarticlesandreviews)andbook,

ratherthanwebsites,nonscientificliterature.Theuseofrecentpublicationsand

particularlyrecentresearcharticleswillresultinabettergrade.

4. Use ubmed htt ://www.ncbi.nlm.nih. ov/ ubmed,orsciencedirect

(http://www.sciencedirect.com/ )to

find

suitable

material

5. Generalrulesonplagiarismapply bestnottousedirectquotes

6. Academicqueriesaboutessaysshouldbydirectedtome:[email protected]

7. FailuretohandintotheacademiccentreatGu sb 4:00onthe24th ofMarchwillresultin

azeromark,unless,youhaveareallygood/validreason&havesubmittedtherequired

paper

work.


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Exam(70%)

Answer3ofnineessayquestions

Approx25minutesperquestion

nswers pages


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Supportingtextbooks

28.45 31.99


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Pathologyisthestudyofstructuraland

diseasesororgansandsystems

RudolphVirchow

18211902

T eFat ero

ModernPatholo

Proposedthatinjurytothe

cellisthebasisofalldisease


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PatholoInflammation

o ogy

Pathogenesis

D

ise

Morphologyase


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Toprovide

agrounding

in

the

generic

process

es eciall inflammation involvedincellin ur /tissue

damageanddisease

mechanismsunderpinningtissueadaptationto

toxicity/stressandtheconsequencestheir

breakdownor

evolution

into

pathological

states


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Histologyfiguresarenotalwaysreproduced

wellin

black

and

white

handouts.

Therefore

linkswillbeprovidedtothesourcewhere

appropriate.


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Manifestationsofcellandtissue

n uryPh sical Chemical Infectious Immunolo ic

Atro h

Stress

Adaption

Biochemical

Hypertrophy

Hyperplasia

Meta lasiaD

e u argrowDysplasia

Intracellularstorage

CelldeathNeoplasia

ApoptosisNecrosis


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Cellularada tationisthebod smethodfordealin

withstressors

(both

physiologic

and

pathologic)

to

maintainhomeostasis

Ifthestressorisremoved,allformsofadaptation

(hyperplasia,hypertrophy,

atrophy

and

metaplasia)

arepotentiallyreversible;however,thestressormustbeidentifiedandremoved

Eventually,ifthestressorissevereenough,adaptationwillfailandorganinjury(celldeath)occurs


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underpathophysiologic

stress

Reducedfunctionaldemand

Alteredbalancebetweenproteinsynthesisand

proteindegradation

n errup onso

rop c

s gna s

Normalphysiologicageing(senileatrophy)


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Adaptiveresponsesresultingin


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Cellularatrophy

Structuralproteinsandorganellesaredestroyedreducingcellsize

andthefunctionalcapacityofthecell.Theadaptationallowsthe

cell

to

survive

by

reducing

its

metabolic

requirements.


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Lipofuscin incellularatrophy

Myocardiumof90yearoldfemale


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Physiologic

Regressioninsizeofbreastsanduterusafterpregnancy

Disuse(skeletalmuscleatrophy)

Lossof

endocrine

stimulus

adrenal

atro h

in

atients

onsteroids)

Denervation

Inadequatenutrition

Ischemia(atrophyofkidneyduetorenalartery


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Muscularatrophy:

ecrease

nmusc e

mass

Musculardystrophy Sarcopenia:musclewasting

Limb

inactivityStarvation

Ageing:sarcopenia

Cachexia comorbidityof:

CongestiveHeartFailure

COPDyoung old

AIDS

Burns

Liverfailure


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Mechanismsofmusclewasting

Distinguishingsarcopenia

fromcachexia

ThomasDR.

Clin

Nutr.

2007

Aug;26(4):389

99.


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Atropy ofskeletalmusclewith

denervation

Stevenset

al.

Core

Pathology,

3rd

edition,

2009


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Cerebralatrophyinapatientwith

z e mer

sease

ower

The ri arenarrowed

andtheintervening

sulci widened,

inferiorfrontalgyrus

towardthefrontallobe

region.


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Hypertrophy

Anadaptivechangeresultinginanincreasein

cellularsizeto(a)satisfyincreasedfunctional

demand,

or

(b)

in

response

to

trophic

signals

Skeletalmusclehypertrophyassociatedwithexercise

Compensatoryhypertrophy

of

kidney

after

removal

of

other

kidney

PathologicCardiach ertro h duetoh ertension valvular stenosis or

insufficiencyAsthmasmoothmusclehypertrophy


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Hypertrophyofskeletalmusclein

responseto

exerc se

Transversesectionofsoleus muscle Soleus muscleinmarathonrunner

Stevens

et

al.

Core

Pathology,

3rd

edition,

2009


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Myocardialhypertrophy

Leftventricularhypertrophy

developsinresponsetosomePathologicalandphysiological

, ,

thatrequirestheleftventricleto

workharder.Astheworkload

increases,thewallsofthechamber

growthicker,loseelasticityand

eventuallymayfailtopumpwithas

muchforceasahealthyheart.

http://library.med.utah.edu/WebPath/CINJHTML/CINJ005.html


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Normal

cardiac

muscle Hypertrophied

muscle


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An

adaptive

increase

in

the

numberofcellsinanorgan/

tissue.Oftenoccurs

concurrentlywith

hypertrophy.

Hormonalstimulation

Increased functional demand

Chronicinjury

/inflammation


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Hyperplasia

Physiologic:

Uterineenlargement

during

pregnancy

(and

hypertrophy)

Liverregrowth afterpartialresection

Inflammation,repair

Pathologic:Ductal hyperplasiaofbreast(duetoestrogen)

Benignprostatichyperplasia

Viralinfections

Endocrineorganswithincreasedstimulus(e.g.,adrenalglandenlargementduetoACTHsecretingpituitaryadenoma;goiter)


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Asthmasmoothmuscleh ertro h

Healthy

bronchiole

Fatalasthma

Asthmatic

bronchiole


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Normalepidermis Epidermalhyperplasia

Stratumcorneum

Stratumlucidum

Stratum ranulosum

Stratumspinosum

Stratumgerminativum

Dermis

From

Rubins

Pathology


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Hyperplasia

and

hypertrophy

can

be

difficult

to

separatenotpossiblebygrossexam;difficultby

microscopicexam. Insomecases,bothhyperplasia

andhypertrophyoccurtogether(e.g.,breastand

.

yperp as a

essen a y

oes

no

occur

n

e

ra n

andheart


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Anadaptiveresponsetochronicinjuryin

w c t et ssuea optst emostprotect ve

phenotype:

Squamousmetaplasia ofthelungs

Glandularmeta lasia of

the

eso ha us

(Barrettesophagus)

fullyreversibleoncethestresshasbeen


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Metaplasia oflaryngealrespiratory

epitheliumto

tobacco

smoke


Themetaplasic responseprotectstheairwayfromthedamagingactionofcigarette

smoke,but

impairs

mucus

clearance

and

the

function

of

the

mucociliary

elevator


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Metaplasia ofthenormal

esop agea squamousmucosa



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Squamous metaplasia ofthebladder


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Dysplasia

Thedisorderedgrowthandmaturationof

cellswithinatissue/or an.Oftenviewedas

aprecursor

to

malignancy

Variationincellsizeandshape

Nuclearenlargement,irregularityandhyperchromatism

Disor anisedarran ement

of

cells

within

the

e ithelium

Occursmostcommonlyinareasofsquamous

metaplasia,such

as

the

bronchus

or

cervix.

Likemetaplasia willregressoncestress/

injuriousstimuliisremoved


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Dysplasticepitheliumofthe

uterinecervix

Cellulardysplasiaofthe

uterinecervix.

squamousepitheliumhas

becometransformedtoa

moredisorderly

growth

pattern,ordysplastic

epithelium.

This is farther down the

roadtoward

neoplasia,

but

dysplasiaisstilla

potentiallyreversible

process.



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Acute

ce u ar

a aptions EffectsofOzone(powerfuloxidizingair

pollutant)on

the

nasal

Mucosa

of

a22

Year

OldMaleMigrantaftermovingtoMexicoCity


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Effects

of

Ozone

on

Nasal

Mucosa22YearOldMaleMigranttoMexicoCity

Meandailymax.

O3=260ppb

.

NO2


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Intracellularstorageofendogenous

/exogenous

material

may

indicate

Degradedphospholipids:lipofucsin

norma a accumu a on: a e es,a c o sm,

atheroscleroticplaques

Substancesthat

cannot

be

metabolised:

protein

aggregates,exogenousparticulates,hereditarystorage

disorders,endogenouspigments

Abnormalproteins:

Lewy bodies

in

Parkinson

disease,

tau

proteininAlzheimerdisease,Malloryhyalineintermediate

amen s na co o c ver sease,mu an an ryps n n

liverdisease


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Too

slow

of

clearance

Lack of enz me decreased enz me activit

Blockageofoutlet

Cellularaccumulationsareasignofinjury;cellular

accumulationsresultfrominjury,or,their

accumulationcan

cause

cellular

injury


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Lipidaccumulationinmacrophagesina

FromRubinsPathology

Cholesterol accumulation in a


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Cholesterolaccumulationina

From

Rubins

Pathology

i f i l i i h li f


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Lipofuscin accumulationintheliverofan

FromRubinsPathology

P i bl i f li d i


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Prussianbluestainofliverdemonstrating

hereditaryhaemachromatosis

FromRubins

Pathology

h i b l i


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Anthracosis:carbonaceousaccumulation

Alveolaranthracosis

Elementalcarbonaccumulationin


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D stro hic localcauses

Patientshaveanormalcalciumlevel

Calcificationaffectspreviouslydamagedtissue

Metastatic(systemiccauses)

Patientshaveanelevatedlevelofcalcium

,

Calcificationaffectsnormaltissueandpreviouslydamagedtissue

**Out

of

all

forms

of

cellular

adaptation,

calcification

is

theonlyonewhichisnotroutinelyreversible

Dystrophic calcification in the wall of


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Dystrophiccalcificationinthewallof

.


M t t ti l ifi ti i th l f ti t ith


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Metastaticcalcificationinthelungofapatientwitha

.



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Cellin ur

Causes: hypoxia,ischemia,trauma,infections,, , ,

oxidativestress

DNA

Proteingeneration


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Subcellular changes


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Subcellular changesMitochondria:

swelling,

amorphous

densities

rich

in

phospholipid

Plasmamembrane:blebbing

Nucleus: fibrillar and ranular com onents of the nucleous ma

segregate

Endoplasmicreticulum:

Cisternae become

distended

by

hydropic

.

detachfromthesurfaceoftheroughER


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Cellin urReversibleandirreversible

Reversibleinjury*DecreasedATPlevels

Irreversibleinjury*Amor housdensities in

* Ionimbalance

*

mitochondria

*Severe

membrane

DecreasedpH damage

* L sosomal ru ture a yc ange ver

ExtensiveDNA

damage

Mechanisms and morphology of


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Mechanismsandmorphologyof

ce

n uryReversiblecellinjuryHydropic swelling:Characterisedbycells withlarge, pale

cytoplasm,reflecting

increased

water

content

withtoxichepaticinjury

Membrane Blebbing


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MembraneBlebbing

Cell injury: Necrosis and Apoptosis


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Cellinjury:NecrosisandApoptosis

Apoptosis and Necrosis


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ApoptosisandNecrosis

Morphologicfeaturesofapoptosisvs.necrosis

Feature Necrosis A o tosis

Cell size Enlarged (swollen) Reduced (shrinkage)

Nucleus Pyknosis

karyorrhexiskaryolysis Fragmentation intonucleosome size fragments

Disru ted contents s illed Intact with altered structureespecially the orientation oflipids (insideoutside)

Cellular contents Enzymatic digestion,

extracellular leaka e

Intact, may be released as

a o totic bodiesAdjacent inflammation Frequent (see above) No

Pathologic The culmination of

irreversible cell injury,alwa s atholo ic

Often physiologic (a

process for removingunwanted unneeded or

aged cellsMay be pathologic, a

damaged cell (especially

DNA dama e ma commit

suicide.

Cellular events in necrosis


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Cellulareventsinnecrosis


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Coa ulative necrosisist icall seeninh oxic

environments,suchasaninfarction.Celloutlinesremain

aftercell

death

and

can

be

observed

by

light

microscopy.

Liquefactive necrosisisusuallyassociatedwithcellular

destructionandpusformation(e.g.,pneumonia).Thisis

,

,

becauseoftheirabilitytostimulateinflammation.

Gummatous necrosisisrestrictedtonecrosisinvolvin

spirochaetal infections(e.g.,

syphilis).

Haemorrhagic necrosisisduetoblockageofthevenous

drainageofanorganortissue(e.g.,intesticulartorsion).


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Caseous necrosisisaspecificformofcoagulation

necrosistypically

caused

by

mycobacteria (e.g.,

tuberculosis ,fun i,andsomeforei nsubstances.Itcanbeconsideredacombinationofcoagulative andliquefactive necrosis.

tissues(e.g.,acutepancreatitis,breasttissuenecrosis).

Fibrinoid necrosisiscausedbyimmunemediated.

proteinaceous materialin

arterial

walls,

which

appears

smudgyandeosinophilic onlightmicroscopy.

l i i

Coagulative necrosis of

the left ventricular wall


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C a lativ n cr i : the left ventricular wallGrossfeatures:Thenecrotic

, .

LM:celldetailislost but

architecturepreserved.The

deadcellsretaintheiroutline

Earl

.

Thistypeofnecrosisis

frequentlycausedbylackof

blood

supply

and

is

exemplifiedwellininfarctsofLate

.

Special types of coagulative necrosis


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Specialtypesofcoagulativenecrosis

Tuberculosis

Grossfeatures:soft,

granular,

appearance.Granularand

eosinophilic.Surroundedby

(granulomatous reaction)

destroyed:Tuberculosis,

syphilis,somesarcomas.


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WETGANGRENE


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Conditions:Both

arterial

and

venousobstruction;wet

.

Character:wet

swollen,

foul

, .

Commonlyinsmallintestine,

appendix,lung,anduterus,

alsoinlimbs.

DRY GANGRENE


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DRYGANGRENE

Conditions:onlyoccursontheskinsurfacefollowing

.

particularlyliable

to

affect

thelimbs,especiallythetoes.

Character:mummification

Liquefactive necrosis:


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o tan

qu

gross y.

nzymes

digestthecellandconvertitto

aformless roteinaceous mass.

Ultimately,dischargeofthe

contentsforms

acystic

space.

. .

afterischemicinjury;abscesses.

http://library.med.utah.edu/WebPath/

CINJHTML/CINJ020.html

http://library.med.utah.edu/WebPath/CI

NJHTML/CINJ024.html

Liverabscessisanexampleoflocalized


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p

liquefactive necrosis


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a necros sGrossl : O a ue andchalky

LM:outlineofnecroticfatcellsfilledwithamorphousbasophilic

patientwithacutepancreatitis

ma er a

ca c umsoaps .

i.e.Digestionof

pancreaticenzymes

in

ancreaticinflammation.

Fibrinoid necrosis


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Definition:Fibrinoidnecrosis isaform

of necrosisin

which

there

isaccumulationof

Fibrinoid necrosisinanartery

amorphous,basic,proteinaceous materialinthetissuematrixwithas a n ng

pa ern

reminiscentoffibrin.

Location:interstitialcollagen

and

blood

vessels

(smallarteryandarteriole)

Patternsoftissuenecrosis


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Coaggulative necrosis:

kidney

Liquefactive necrosis:

brain

Caseous necrosis:

kidney

Gummatousnecrosis:

liver

Hemorrhagicnecrosis:

testis

Fibrinoid necrosis:

artery


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1. Acute or c ron c n ammat on

2. Immunological reactions to subcellular

componen s re ease y ea ssue or se antigens altered by denaturation.

.4. Isolation and discharge: ulceration and cavity

5. Encapsulation,calcification.

Inductionofapoptosis


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ys o og capop os s

Embryogenesis

HormonalInvolution

Cellpopulationcontrol,e.g.,crypts

EliminationofHARMFULcells

Cytotoxic TCells

cleaning

up

Histologyofapoptosis


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Whatyoushouldknow?

1. Youshould

be

able

to

describe

the

major

pathologic

examplesoftheirroleinavarietyofdiseases

injuryinducescelldeathandthepathology

associatedwithdifferentformsofnecrosis


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. , , .

pathogenesisofheartdisease:mechanismsand

significance.Annu RevPhysiol.2010Mar17;72:1944.[Gooddiscussionofnecrosisandapoptosisinavarietyofcardiacdisease]

. oc

,

ono .

e

n ammatoryresponse

to

ce

death.Annu RevPathol.2008;3:99126.[discussesnecrosisandapoptosis leadsintonextweekslectures

Previousexaminationquestions


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Q)Outlinethevariousformsofnecrosisobservedclinicallyandtheirgrossand

microscopicappearance.(25min)

Thestudentshouldcoverthefollowingareas:Liquefactive necrosis(brain,lung),wetand

drygangrene

(extremities,

bowel),

plus

fibrinoid,

caseous (tuberculosis),

fat

(Breast,

any

fat ischemic nons ecific andavascular necrosis.Grossor anandmicrosco icfeatures

ofnecrosiswerepresentedinthelectureandpracticalsandthestudentswouldbe

expectedtocommentonchangestonuclearmorphology(pyknosis,karyorrhexis and

karyolysis),lossoffinestructureandeosinophilicstainingpatterns.

Q)Outlinethecellularadaptivechangesthatoccurintheairwayepitheliumasaresult

oftheinhalationoftoxicgasesandparticles,suchasincigarettesmoke.(25min)

Thestudentshouldcoverthefollowingareas:Inductionofacuteinflammation,celldeath

(necroticand

apoptotic),

loss

of

cilia,

hyperplasia,

with

loss

of

columnar

epithelial

cells

andtheappearanceofalessstructuredintermediateepithelium,endothelialhyperplasia,

.

5BBB0206-Tissue Pathology - Lectures 1 - 2 9th Jan 2014

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Transcript of 5BBB0206-Tissue Pathology - Lectures 1 - 2 9th Jan 2014