-高血压英文课件Pathology-of-blood-and-lymphatic-

Pathologyofblood

and

lymphatic

vesselsThe

main

cellular

componentsofthe

wallsofvesselsare:1)

endothelial

cells

2)

smooth

muscle

cells

3)

pericytes(the

cells

normally

arranged

along

capillaries

and

venules)

Pathologyofblood

and

lymphatic

vesselsPathologyofblood

and

lymphatic

vesselsEndothelial

cells:

a)

serveasasemipermeable

membrane,

b)

regulate

thrombosis,thrombolysis

and

platelet

adherence,c)

influate

vasculartoneand

blood

flow,d)

metabolize

hormones,

e)

regulate

immune

and

inflammatory

reactions,f)

modify

lipoptoteinsinthe

artery

wall,g)

regulate

the

growthofothercelltypes,including

smooth

muscle

cells.Pathologyofblood

and

lymphatic

vesselsEndothelial

injury

is

criticaltothe

formationofthrombi,tothe

initiationofatherosclerosis

and

the

vascular

effectsofhypertension

and

other

disorders!!Pathologyofblood

and

lymphatic

vesselsEndothelial

dysfunctionEndothelial

activationPathologyofblood

and

lymphatic

vesselsThetermendothelial

dysfunction

is

often

usedtodescribe

several

typesofpotentially

reversible

changesinthe

functional

stateofendothelial

cells

that

occurinresponsetoenvironmental

stimuli.Pathologyofblood

and

lymphatic

vesselsThetermendothelial

activation

reflects

alterationsingeneexpression

andproteinsynthesis.Inducersofendothelial

activation

include

cytokines

and

bacterial

products(whichcauseinflammatory

injury

and

septic

shock),hemodynamicstressandlipidproducts(involvedinpathogenesisofatherosclerosis),advanced

glycosylationofend

products(involvedinpathogenesisofdiabetes),aswellasviruses,complement

components

and

hypoxia.Activated

endothelial

cells

also

elaborate

adhesion

molecules,other

cytokines

and

chemokines,growth

factors,moleculesofthemajorhistocompatibility

complex(MHC),procoagulant

or

anticoagulant

factors

and

vasoactive

molecules

thatareinvolved

eitherinvasoconstriction

orinvasodilatation.Pathologyofblood

and

lymphatic

vessels2)

Smooth

muscle

cellsarecapable:a)tomediate

vasoconstriction,b)tomediate

vasodilatation,c)tosynthesize

the

collagen,elastin,and

proteoglycans,d)toelaborate

the

growth

factors

and

cytokines,e)toproliferate,and

f)tomigratetothe

intima.

3)Pericytes

haveroleassupportive

and

connective

elements.Pathologyofblood

and

lymphatic

vesselsThe

final

resultofvascular

injury

is

intimal

thickening!!Vascular

DiseasesDiseasesofarteriesDiseasesofveins

and

lymphaticsTumorsDiseasesofarteriasA)

Congenital

anomaliesB)

AtherosclerosisC)

Hypertensive

vascular

diseaseD)

Inflammatory

disease–Arteritides(Vasculitides)E)

Raynaud

diseaseF)

AneurysmsadissectionsDiseasesofarteriasA.Congenital

AnomaliesAberrationsofthe

usual

anatomic

patternofbranching,shape

and

anastomosing.Importance

have

only:berry

aneurysms(developmental

aneurysms

involving

cerebral

vessels)and

arteriovenous

fistulas

or

aneurysms(abnormal

communications

between

arteries

and

veins

usually

arisedasdevelopmental

deffect,from

ruptureofan

arterial

aneurysm

into

adjacent

vein,or

from

injury,or

from

inflammatory

necrosisofadjacent

vessels).Their

clinical

significance

dependsonshort-circuit

blood

from

the

arterialtothe

venous

side,causing

the

hearttopumpadditionalvolume,sometimes

inducing

cardiac

failure.DiseasesofarteriasB.AtherosclerosisIt

isagenerictermforthree

pattersofvascular

disease

that

haveincommon

thickening

and

lossofelasticityofarterial

walls:

1)

Atherosclerosis

–characterizedbythe

formationofintimal

fibrous

plaques

that

often

haveacentral

core

richinlipid(fibrofatty

plaques). 2)Mönckeberg

medial

calcific

sclerosis–characterizedbycalcific

depositsinmedium-sized

muscular

arteriesinpersons

older

than50years.Thesemedial

lesions

forming

irregular

medial

plates

or

discrete

transverse

rings

havemuchless

clinical

importance. 3)Arteriosclerosis–the

hyaline

and

hyperplastic

thickeningofsmall

arteries

and

arterioles

which

causes

luminal

narrowing

and

down

stream

ischemic

injury.DiseasesofarteriasB.AtherosclerosisIntroductionAtherosclerosis

significantly

contributestoseriousmorbidityandmortality–approximately

half

ormoreofall

deaths.It

primarily

affects

elastic

arteries(e.g.,aorta,carotid

and

iliac

arteries)and

large

andmediumsized

muscular

arteries(e.g.,coronary

and

popliteal

arteries).The

disease

often

beginsinchildhood,but

symptomsarenotusually

evident

until

middle

age.Symptomatic

atherosclerotic

disease

ismostoften

localizedtothe

arteries

supplying

the

heart,brain,kidneys,lower

extremities,and

small

intestine.Myocardial

infarction(heart

attack),cerebral

infarction(stroke),and

aortic

aneurysmsarethemajorconsequencesofthis

disease.Therearealso

other

important

consequencessuchasgangreneofthe

legs,mesenteric

occlusions,sudden

cardiac

death,chronic

ischemic

heart

disease,and

ischemic

encephalopathy.DiseasesofarteriasB.Atherosclerosis

MorphologyThe

key

processesareintimal

thickening

andlipidaccumulation,producing

the

characteristic

atheromatous

plaques(AP).Their

precursorsarefatty

dots(FD)and

streaks(FS).DiseasesofarteriasB.Atherosclerosis

Fatty

streaks

present

nearly

universallyinchildren.Theydonotcauseany

disturbanceinblood

flow,however,they

may

be

precursorsofAP.FSs

beginasmultiple

yellow

flat

spots–fatty

dots(FD)whichareless

than1mmindiameter.Subsequently

they

merge

into

elongated(1cmlong

and

longer)FSs.Theyarecomposedoflipid-filled

foam

cells

withT-lymphocytes

and

extracellular

lipids.

DiseasesofarteriasB.Atherosclerosis

Atheromatous

plaques

arethe

basic

lesions

within

the

intima,havingacoreoflipid(mainlycholesterolandcholesterolesters)and

acovering

fibrouscap.APsarealso

called

fibrous,fibrofatty,lipid,or

fibrolipid

plaques

which

have

whitetowhitish

yellow

colour

and

rise

intima

slightly

into

thelumenofthe

artery.The

centersoflarger

plaques

may

containayellow

debris,hencethetermatheroma.Their

distributioninhumans

is

characteristic.The

abdominalaortais

usuallymuchmoreinvolved

than

thoracicaorta,and

aortic

lesions

tendtobemuchmoreprominentaround

the

origins(ostia)ofitsmajorvessel

branches.DiseasesofarteriasB.AtherosclerosisAtheromatous

plaques

have3principal

components:1)

cells,including

smooth

muscle

calls,macrophages,and

other

leukocytes,2)

connective

tissue

extracellular

matrix,including

collagen,elastic

fibers,and

proteoglycans,and

3)

intracellular

and

extracellularlipiddeposits.Inadvanced

atherosclerosis,the

fatty

atheroma

may

be

convertedtoafibrous

scar.DiseasesofarteriasB.Atherosclerosis

The

complicated

lesionsaredefinedby:a)

patchy

or

massive

calcification,b)

focal

rupture

or

gross

ulceration,c)

thrombus

formation(thrombosis)producing

emboli,d)

hemorrhage

intoaplaque,e)

aneurysmal

dilatationoflarge

vessels.DiseasesofarteriasB.AtherosclerosisEpidemiologyAtherosclerosis

is

virtually

ubiquitous

among

the

populationsofNorth

America,Europe,Australia,New

Zealend,Russia.Incontrast,it

ismuchless

prevalentinCentral

and

South

America,Africa,and

Asia.Manyevidences

exist

that

it

dependsonthe

lifestyleand

dietary

customs.DiseasesofarteriasB.AtherosclerosisRiskFactorsAge(advanced

age),sex(male,postmenopausal

women,the

protective

effectofestrogens),genetics(polygenic

familiar

predisposition,genetic

abberrationsinlipoprotein

metabolism

resultinginexcessively

high

bloodlipidlevels),diet,lifestyle,personal

habit.Thereare6majorwell-accepted

conditionssuchas:

hyperlipidemia,

hypertension,

smoking,

diabetesmellitus,

elevatedplasmahomocysteine,

factors

affecting

hemostasis

and

thrombosis.Diseases

ofv

arteriasB.AtherosclerosisHyperlipidemia:It

should

beamajorriskfactor.Mostofthe

evidences

implicates

hypercholesterolemia(hypertriglyceridemia

isaless

significant,but

its

effect

may

be

greaterinwomen

than

men).Themajorcomponentofthe

total

serumcholesterolis

low-density

lipoprotein

(LDL)cholesterol.Incontrast,there

is

aninverserelationship

between

symptomatic

atherosclerosis

and

high-density

lipoprotein

(HDL)

level.HDLis

believedtomobilizecholesterolfrom

existing

atheroma

andtransportittothe

liverforexcretioninthe

bile(cholesterolboundtoHDLis

designatedasthe

“goodcholesterol“.The

various

classesofblood

lipidsaretransportedaslipoproteins

complexedtospecific

apoproteins.They

havemanyfunctions

including

activation

and

inhibition

enzymes,facilitating

transmembranetransportofcertain

lipoproteins,servingasligandstohigh.affinity

cellular

receptors

that

guide

the

lipoproteinstospecific

sitesofcatabolism.DiseasesofarteriasB.AtherosclerosisHyperlipidemia:

Dyslipoproteinemias

result

either

from

genetic

mutations

involving

genesforapolipoproteins

or

from

some

other

underlying

disorder,suchasthe

nephroticsyndrome,alcoholism,hypothyreoidism,ordiabetesmellitus.

Four

typesoflipoprotein

abnormalitiesarefrequently

foundinthe

population:1)

increasedLDLcholesterollevel,2)

decreasedHDLcholesterollevel,3)

increased

chylomicron

remnants

and

intermediate-density

lipoproteins–IDL,4)

increased

levelofan

abnormal

lipoprotein

Lp(a).DiseasesofarteriasB.AtherosclerosisHypertension:

It

isastrongerriskfactor

than

hypercholesterolemia

after

age45years.Men

whose

blood

pressure

exceeds169/90mmHg

haveamorethan5-fold

greaterriskofischemic

heart

disease

than

those

with

blood

pressuresof140/90mmHg

or

lower.Smoking:

When

one

ormorepacksofcigarettesaresmokedperdayforseveral

years,the

death

rate

from

ischemic

heart

disease

increases

twice.Diabetesmellitus:DMinduces

hypercholesterolemia

andamarkedly

increases

predispositiontoatherosclerosis.Theincidenceofmyocardial

infarction

is

twiceashigh,theincidenceofstrokes

is4-fold

greater,and

theincidenceofgangreneofthe

lower

extremities100-fold

greater.DiseasesofarteriasB.AtherosclerosisElevatedPlasmaHomocysteine:

Recent

clinical

and

epidemiologic

studies

have

indeed

shownamoregeneral

relationship

between

total

serum

homocysteine

levels

and

coronary

artery

disease,peripheral

vascular

disease,stroke,or

venous

thrombosis.There

isevidencethat

homocysteine

maycauseendothelial

dysfunction,through

formationofreactiveoxygenspecies.It

also

interferes

with

with

the

vasodilator

and

antithrombotic

functionsofnitricoxide.Factors

Affecting

Hemostasis

and

Thrombosis:

Several

other

markersofhemostatic

and

thrombotic

functionarepotent

predictorsofriskformajoratherosclerotic

events(plasminogen

activatorinhibitor-1level,plasmafibrinogen

level,C-reactiveproteinlevel).DiseasesofarteriasB.AtherosclerosisPathogenesisofatherosclerosis

The

contemporary

viewofthe

pathogenesis:Atherosclerosis

is

achronic

inflammatoryresponseofarterial

wall

initiatedbysome

formofendothelial

injury!!Therearedescribed

the

following

steps:a)

chronic

endothelial

injury,b)

insudationoflipoproteins(mainlyLDLandVLDL)into

the

vessel

wall,c)

modificationofsuchlipoproteinsbyoxidation,d)

adhesionofblood

monocytestothe

endothelium,e)

migrationofmonocytes

into

the

intima

and

their

transforamtion

into

macrophages

and

foam

cells,f)

adhesionofplateletstofocal

areasofdenudation

ortoadherent

leukocytesDiseasesofarteriasB.AtherosclerosisPathogenesisofatherosclerosis

The

contemporary

viewofthe

pathogenesis:Atherosclerosis

is

achronic

inflammatoryresponseofarterial

wall

initiatedbysome

formofendothelial

injury!!

Continuation:g)

releaseoffactors

from

activated

platelets,macrophages

or

vascular

cells,h)

migrationofsmooth

muscle

cells

frommediainto

intima,i)

proliferationofsmooth

muscle

cellsinthe

intima

and

elaborationofextracellular

matrix,j)

accumulationofcollagen

anf

proteoglycans,k)

enhanced

accumulationoflipids

within

macrophages,smooth

muscle

cells

and

extracellularly.DiseasesofarteriasC.Hypertensive

Vascular

DiseaseOneofthemostimportantriskfactorsinboth

coronary

heart

disease

and

cerebrovascular

accidents.It

may

also

leadtocardiac

hypertrophy

with

heart

failure,aortic

dissectin,and

renal

failure.About90-95%ofhypertension

is

idiopathic

and

apparenly

primary–essential

hypertension.Ofthe

remaining,5-10%is

secondarytorenal

disease

or,less

often,tonarrowingofthe

renal

artery(usuallybyan

atheromatous

plaque)–renovascular

hypertension.Infrequently,secondary

hypertension

is

the

resultofdiseases

relatedtothe

adrenal

gland(suchasprimary

aldosteronism,Cushingsyndrome,pheochromocytoma

etc.).About5%ofhypertensive

personsshow

arapidly

rising

blood

pressure,which,if

untreated,leadstodeath

within1or2years–malignant

hypertension.DiseasesofarteriasC.Hypertensive

Vascular

DiseaseMorphologyHypertension

accelerates

atherogenesis

and

causes

changesinthe

structureofthe

wallofblood

vessels

that

potentiate

both

aortic

dissection

and

cerebrovascular

hemorrhage.Inaddition,hypertension

is

associated

with2formsofsmall

blood

vessel

disease–hyaline

arteriolosclerosis(inelderly

patients,moresevereinpatients

with

hypertesion

anddiabetes,ahomogenous,pink,hyaline

thickeningofthe

wallsofarterioles

with

narrowingofthelumen)and

hyperplastic

arteriolosclerosis

(inpatients

withmoresevereelavationofblood

pressure,there

is

typical

onion-skin,concentric

thickeningofthe

wallsofarterioles

with

progressive

narrowingofthe

lumens).DiseasesofarteriasD.Inflammatory

Disease–Arteritides,Vasculitides

Infectious

Vasculitides:

bacterial-Neisserial,Rickettsial,Spirochetal,fungal,viral,

Non-Infectious

Vasculitides:

so-called

systemic

necrotizing

vasculitides(affectingaorta,medium-sized

vessels)and

small

vessel

vasculitides(affecting

arterioles,venules

and

capillaries).Pathogenesis

involves

immune

compexes,antineutrophil

cytoplasmic

antibodies

(ANCA)

and

antibodiestoendothelial

cells.

Classificationonthebasisofthe

sizeofthe

involved

blood

vessels,the

anatomic

site,clinical

manifestation

and

histological

characteristicsofthe

lesion:DiseasesofarteriasD.Inflammatory

Disease–Arteritides,Vasculitides

Large

Vessel

Vasculitis

Giantcell(temporal)arteritis:

Granulomatous

arteritisoftheaortaand

itsmajorbranches,withapredilectionforextracranial

branchesofthe

carotid

artery

and

the

temporal

artery.Usually

occursinpatients

older

than50years

and

often

is

associated

with

polymyalgia

rheumatica.Takayasu

arteritis(pulseless

disease):

Granulomatous

inflammationoftheaortaand

itsmajorbranches.Usually

accursinpatients

younger

than50years.DiseasesofarteriasD.Inflammatory

Disease–Arteritides,Vasculitides

Medium-Sized

Vessel

VasculitisPolyarteritis

nodosa:

Necrotizing

inflammation

without

glomerulonephritis

or

vasculitisinarterioles,capillaries,or

venules.Kawasaki

disease:

Arteritis

associated

with

mucocutaneous

lymph

nodesyndrome.Coronary

arteriesareoften

involved.Aortaand

veins

may

be

involved.Usually

occursinchildren.Thromoangitis

obliterans(Buerger

disease):

Segmental,thrombosing

acute

and

chronic

inflammationofmedium-sized

and

small

arteries,principally

the

tibial

arteryinyounger

men

who

were

heavy

smokers.DiseasesofarteriasD.Inflammatory

Disease–Arteritides,Vasculitides

Small

Vessel

VasculitisWegener

granulomatosis:

Granulomatous

inflammation

involving

the

respiratory

tract

and

necrotizing

vasculitis

affecting

capillaries,venules,arterioles

and

arteries.Necrotizing

glomerulonephritis

is

common.Churg-Strausssyndrome:

Eosinophil-rich

and

granulomatous

inflammation

involving

the

respiratory

tract

and

necrotizing

vasculitis

affecting

small

andmedium-sized

vessels

associated

with

asthma

and

blood

eosinophilia.Microscopic

polyangiitis:

Necrotizing

vasculitis

with

few

ornoimmune

deposits

affecting

small

andmedium-sized

vessels.Necrotizing

glomerulonephritis

is

common.Pulmonary

capillaritis

often

occurs.Henoch-Schönleinpurpura:

Vasculitis

with

IgA-dominantimmune

deposits

affecting

small

vessels.Typically

involvesskin,gut,and

glomeruli.Associated

with

arthralgia

orarthritis.Goodpasturesyndrome:

Glomerulitis

and

pneumonitis

causedbyanti-basement

membraneofcapillaries

antibodies.DiseasesofarteriasE.Raynaud

DiseaseParoxysmal

pallor

or

cyanosisofthe

digitsofthe

hands

or

feet

and

infrequently

the

tipsofthenoseor

ears(acral

parts)causedbyintensevasospasmoflocal

small

arteries

or

arterioles.Typicallyinyoung,otherwise

healthy

women.Noorganic

changesarepresentinthe

arterial

walls

except

late,when

intimal

proliferation

can

appear.DiseasesofarteriasF.Aneurysms

and

DissectionAneurysm–localized

abnormal

dilatationofblood

vessel

that

occursmostcommonlyintheaortaor

the

heart.It

can

be

true(complete

but

often

attenuated

arterial

wall

components)or

false(extravascular

hematoma

that

communicates

with

the

intravascular

space).The2mostimportant

causesoftrue

aortic(or

any

vessel)aneurysmsareatherosclerosis

and

cystic

medial

degeneration.Typical

is

also

syphilitic

aneurysm(tertiary

stageofsyphilis).DiseasesofarteriasF.Aneurysms

and

DissectionAortic

Dissection(Dissecting

Hematoma)–is

characterizedbydissectionofwall

and

penetrationofbloodinbetween

and

along

the

laminar

planesofthemedia,with

the

formationofablood-filled

channel

within

the

aortic

wall–adissecting

intramural

hematoma(aneurysm).It

can

rupture,causing

massive

hemorrhage.Incontrasttoatherosclerotic

and

syphilitic

aneurysms,it

isnotusually

associated

with

marked

dilatationoftheaorta.Themorecommon

and

dangerous

proximal

lesions

involving

either

the

ascending

postionofaortaonly

or

both

the

ascending

and

the

descendingaortaarecalled

typesIandIIofDeBakey´sclassification(often

calledtypeA).Distal

lesionsnotinvolving

the

ascendingpartofaortaand

usually

beginning

distaltothe

subclavian

arteryarecalled

DeBakeytypeIII(typeB).Diseasesofveins

and

lymphaticsA)Varicose

VeinsB)Thrombophlebitis

and

PhlebothrombosisC)Syndromeofvena

cavasuperiorD)Syndromeofvena

cava

inferiorE)Lymphangitis

and

Lymphedema

Diseasesofveins

and

lymphaticsA)Varicose

VeinsAbnormally

dilated,tortuous

veins

producedbyprolonged,increased

intraluminal

pressure

and/orbylossofsupportofthe

vessel

wall.Usually

the

superficial

veinsofthelegareinvolved.There

is

marked

variationinthe

thicknessofthe

wall.Intraluminal

thrombosis

and

valvular

deformitiesarefrequently

found.Despite

thrombosisofsuperficial

varicose

veins,embolism

is

rare(sharpcontrasttothe

relatively

frequent

thrombembolism

that

arises

from

thrombosed

deep

veins).Diseasesofveins

and

lymphaticsTherearetwo

special

sitesofvarix

formation:Esophagus(inpatients

who

have

cirrhosisofthe

liver

and

portal

hypertension,rupturaofan

esophageal

varix

followedbyhemorrhage

may

be

very

serious)and

anorectal

junction(varicose

dilationofthe

hemorrhoidal

plexusofveins

called

hemorrhoids

resultingofprolonged

pelvic

congestion,sourceofbleeding

and

siteofthrombosis).Diseasesofveins

and

lymphaticsB)

Thrombophlebitis

and

PhlebothrombosisVenous

thrombosis

causedbyinflammation

orbydifferent

mechanisms(hypercoagulability,immobilization,postoperative

state,pregnancy

etc.).The

deeplegveins

accountformorethan90%ofcasesofthrombophlebitis.The

venous

thromboses

have

atendencytoembolization

into

lung.Diseasesofveins

and

lymphaticsC)Syndromeofvena

cavasuperiorUsually

causedbyneoplasms(occasionallybyother

lesionssuchasaortic

aneurysm)that

compress

or

invade

thev.cavasuperior(primary

bronchogenic

carcinoma,mediastinal

lymphoma).The

consequent

obstruction

producesadistinctive

clinical

complex(dusky

cyanosis,marked

dilationofthe

veinsofthe

head,neck,and

arms.Commonly

the

pulmonary

vesselsarealso

compressed,and

consequently

resipartory

distress

may

develop.Diseasesofveins

and

lymphaticsD)Syndromeofvena

cava

inferiorThissyndromemay

be

causedbythe

similar

processes(hepatocellular

carcinoma,renalcellcarcinoma,thrombus).Obstruction

induces

marked

edemaofthe

legs,distentionofthe

superficial

collateral

veinsofthe

lowerabdomen,and,when

the

renal

veinsareinvolved,massive

proteinuria.Diseasesofveins

and

lymphaticsE)

Lymphangitis

and

LymphedemaPrimary

diseases–extremely

uncommon.Secondary

processes–developinassociation

with

inflammation

or

cancer.Lymphangitis:bacterial

infections

spreading

into

and

through

the

lymphatics.Obstructi