Hemodynamic Disorders Thrombosis

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Hemodynamic Disorders

Thrombosis

& Shock

1

Dr. Riad ShraimAl-Quds University

Faculty o !edicine

"atholo#y De$artment



%irculatory disorders

• 'dema

• Hy$eremia and %on#estion

• Hemorrha#e• Thrombosis

• 'mbolism

• (narction

• Shock2



• Total body )aterTotal bod

y )ater

– *aries rom +,-, o body )ei#ht*aries rom +,-, o body )ei#ht

– /oun#0 healthy men 1 ,2-32 /oun#0 healthy men 1 ,2-32

– /oun#0 healthy )omen 1 +,-,2 /oun#0 healthy )omen 1 +,-,2

– decreases )ith a#edecreases )ith a#e

3

Distribution o 4ody 5aterDistribution o 4ody 5ater



• (ntracellular com$artment(ntracellular co

m$artment

– 2/3 of body water (+2 body )ei#ht+2 body )ei#ht)

• '6tracellular com$artment'6tracellular com

$artment

– 1/3 of body water (72 body )ei#ht72 body )ei#ht)

• "lasma"lasma (water = 4% - 5% body weight)

• (nterstitial luid(nterstitial luid (water = 15% body weight)

4




'dema 8ormal luid balance

32 o body )ei#ht is )ater

79: ;3< o this luid is intracellular

=9: ;::< is e6tracellular0 mostly asinterstitial luid

> , o total body luid is in thevascular com$artment

Fluid in 2 ?# man@5



•(n a healthy 2 k# male(n a healt

hy 2 k# male

• Total body water is ~ +7 +7 ~ !% "#

• This is contained in t)o maBor com$artmentsThis is contained in t)o maBor com$artments

1$ the itra&ell'lar fl'id (7C 7C ~ 4!% "#)

2$ the etra&ell'lar fl'id (=+ =+ ~ 2!% "#)

– the iterstitial fl'id (=2., =2., ~ 15% "#)

– *las+a (:., :., ~ 5% "#) , rterial , .eo's




8ormal luid balance The bala&e betwee vascular hydrostatic $ressure ad

$lasma colloid osmotic $ressure is the driig for&e that

+aitais +oe+et of fl'ids betwee as&'lar ad

iterstitial s*a&es

0or+ally the eit of fl'id ito the iterstiti'+ at the

arteriolar end is al+ost bala&ed by iflow of fl'id fro+ the

iterstiti'+ ba& ito the as&'lar bed at the venular end

s+all a+o't of fl'id stays i the iterstiti'+ be&a'se of

little higher hydrostati& *ress're to *'sh fl'ids o't

This little a+o't of fl'id is draied ba& by lym$hatics





8ormal luid balance



1!



'dema'dema

'dema is increased luid in the interstitial

tissue s$aces

olle&tio of fl'id i body &aities is a+ed

a&&ordig to *la&e6 hydrothora6-hydrothora6- *le'ral eff'sio

hydro$ericardium-hydro$ericardium- *eri&ardial eff'sio

hydro$eritonium-hydro$eritonium- as&ites

Anasarca is seere ad geerali7ed ede+a

with *rofo'd s'b&'taeo's tiss'e swellig11





"atho$hysiolo#ic %ate#ories o 'dema

(ncreased hydrostatic $ressure(ncreased hydrostatic $ressure

(m$aired venous return

1- ogestie heart fail're

2- ostri&tie *eri&arditis

3- s&ites (lier &irrhosis)

4- .eo's obstr'&tio or &o+*ressio6

a- Thro+bosisa- Thro+bosisb- 8teral *ress're (t'+or)b- 8teral *ress're (t'+or)

&- 9a&tiity of lower li+b&- 9a&tiity of lower li+b

13



Reduced plasma osmotic pressure:Reduced plasma osmotic pressure:

1- Protein losing glomerulopathies (nephrotic

syndrome)

2- Liver cirrhosis

3- Malnutrition4- Protein losing gastroenteropathy

Lymphatic obstruction:Lymphatic obstruction:

1-Infammatory2- Neoplastic

3- Post-surgical

4- Post-irradiation 14

"atho$hysiolo#ic %ate#ories o 'dema"atho$hysiolo#ic %ate#ories o 'dema



ym$hedemaym$hedema inin

the arm aterthe arm aterlet mastectomylet mastectomy

ym$hatic obstructionym$hatic obstruction

15



'le$hantiasis'le$hantiasis a case o ilariasis a case o ilariasis

ym$hatic obstruction

1



$eau dEoran#e ;oran#e $eel< a$$earance$eau dEoran#e ;oran#e $eel< a$$earance

1



Sodium retentionSodium retention

1- 8&essie 0a itae with real is'ffi&ie&y

2- 9&reased t'b'lar absor*tio of 0a

a- Renal hy$o$erusionRenal hy$o$erusion

b- (ncreased renin-an#iotensin-(ncreased renin-an#iotensin-

aldosterone secretionaldosterone secretion

(nlammation(nlammation &'te ifla++atio

1

"atho$hysiolo#ic %ate#ories o 'dema"atho$hysiolo#ic %ate#ories o 'dema



Subcutaneous edema

• :ae differet distrib'tios de*edig o the &a'se

• 9t &a be diff'se or it +ay be +ore *ro+iet i theregios with the highest hydrostati& *ress'res (the

ede+a distrib'tio is ifl'e&ed by graity ad is

ter+ed de$endent).

• 'dema o the de$endent $arts o the body'dema o the de$endent $arts o the body (e$g$

the legs whe stadig) is a $rominent eature ois a $rominent eature o

cardiac ailure0 $articularly o the ri#ht ventriclecardiac ailure0 $articularly o the ri#ht ventricle.

• ;iger *ress're oer sigifi&atly ede+ato's

s'b&'taeo's tiss'e dis*la&es the iterstitial fl'id

ad leaes a in#er-sha$ed de$ressiona in#er-sha$ed de$ression so-&alled

$ittin# edema$ittin# edema. 1



$ittin#

edema

2!



21

'dema d'e to renal dysunction or ne$hrotic syndrome

is +ore seere tha &ardia& ede+a and aects all $arts o

the body eually. 9t +ay be iitially +aifested i tiss'es with

a loose &oe&tie tiss'e +atri e$g$ eyelids &a'sig

$eriorbital edema$eriorbital edema



PulmonaryPulmonary

edemaedemaresults in

difuse

opacicatio

n o the lung

22



The s'rfa&e of the brai with cerebral edema de+ostrates

a flatteed s'rfa&e$ The s'l&i are arrowed$

23



The t)o ty$es o edema luid

'6cudate6

9fla++atory ede+a has a high *rotei

&otet ad is asso&iated with a

ifla++atory rea&tio$

Transudate6

0oifla++atory ede+a has a low *rotei

&otet is &a'sed by alteratios i

he+odya+i& for&es a&ross the &a*illary wall

(he+odya+i& ede+a)$24

H i d % ti



Hy$eremia and %on#estionHy$eremia

9t<s a active *ro&ess that res'lts fro+ i&reased blood flow

be&a'se of arteriolar dilationarteriolar dilation$

Tiss'es that hae hy*ere+ia +eas that they have morehave more

o6y#enated bloodo6y#enated blood ad will a$$ear more reda$$ear more red

%on#estion

9t<s a $assive *ro&ess it +ay res'lt fro+ im$aired venousim$aired venous

returnreturn fro+ the tiss'e ioled

Tiss'es will have deo6y#enated blood

The tiss'e has a blue-red &olor (cyanosiscyanosis)

a'ses +ay be lo&al or syste+i&6 &ardia& or he*ati&25



Hy$eremia versus con#estion

9 both &ases there is a increasedincreased

volume and $ressurevolume and $ressure of blood i a

gie tiss'e with asso&iated ca$illaryca$illary

dilationdilation ad a *otetial for luidluid

e6travasatione6travasation

9 hy$eremia i&reased iflow leads

to egorge+et with oygeated

blood res'ltig i erythemaerythema$

9 con#estion di+iished o'tflow

leads to a &a*illary bed swolle with

deoygeated eo's blood ad

res'ltig i cyanosiscyanosis$

2



(n chronic $assive con#estion0 there )ill be

=- Stasis of *oorly oygeated blood

7- hroi& hy$o6ia d'e to i+*aired &ir&'latio

:- De#eneration & Death of the *are&hy+al &ells i that tiss'e

+- ersistet &ogestio of the &a*illaries will &a'se their

r'*t're res'ltig i oci o hemorrha#e

,- >ed &ells frag+ets ad e&roti& tiss'e will be *hago&ytosed

res'ltig i a##re#ates o hemosiderin macro$ha#es

2

%on#estion



Hemorrha#eHemorrha#e

Hemorrha#eHemorrha#e si+*ly +eas bleedin#bleedin#

4leedin#4leedin# +ay o&&'r d'e to clottin# disordersclottin# disorders or

fro+ traumatrauma

%a$illary bleedin# &a o&&'r be&a'se of

con#estioncon#estion traumatrauma or inlammationinlammation

4leedin#4leedin# +ay be e6ternal or internal (withi the

tiss'es)

olle&tio of blood withi a tiss'e is &alled

hematomahematoma$ ar#e hematomas can be atalar #e hematomas can be atal2



2

hematoma



8ail bed - Hematoma

3!

H h



?igifi&a&e of bleedig de$ends on the amount

ad the $lace where bleedig o&&'rs$

?+all a+o'ts of bleedig i the &raial &aity +ay

be fatal whereas 1$5 liters of blood i the sto+a&h

+ay *ass 'oti&ed by the *atiet$

Ra$id bleedin#Ra$id bleedin# of '* to 72 of total body blood

+ay be &o+*esated for by the body ad does ot

&a'se serio's &lii&al +aifestatios

Slo) bleedin#Slo) bleedin# +ay res'lt i iron deiciency

anemia *arti&'larly i elderly *eo*le 31

Hemorrha#e



Hemorrha#eHemorrha#e

?+all he+orrhages of =-7 mm ito the si or

+'&o's +e+braes are &alled $etechiae$etechiae

"etechiae are caused because o"etechiae are caused because o

=- increased intravascular $ressure

7- lo) $latelet count

:- deective $latelet unction

+- clottin# actor deiciency

32



"etechial he+orrhages of the &oloi& +'&osa as a

&ose@'e&e of thrombocyto$eniathrombocyto$enia$ 33

Hemorrha#e



PurpurasPurpuras: larger hemorrhages: 3-53-5

mmmm

auses:auses:

1- increased intravascular pressure

2- lo! platelet count

3- deective platelet unction

4- clotting actor deciency

!" vasculitis

#" increased vascular ragility

$" trauma 34

Hemorrha#e

H h



• 'cchymosis6 are s'b&'taeo's he+ato+a

They are =-7 cm=-7 cm i area

The erythrocytes i these he+orrhages are

$ha#ocytosed ad degraded$

Their hemo#lobin ;red-blue in color<hemo#lobin ;red-blue in color< will be

&oerted to bilirubinbilirubin whi&h is blue #reenblue #reen i &olor

8et'ally bilir'bi will be &oerted to

hemosiderinhemosiderin a #olden-bro)n#olden-bro)n &olored +aterial35

Hemorrha#e



bruise or 'cchymosis'cchymosis is a id of iA'ry 's'ally &a'sed

by bl't i+*a&t i whi&h the &a*illaries are da+aged

allowig blood to see* ito the s'rro'dig tiss'e$

3



ar#er accumulations o blood

=- hemothora66 blood i the *le'ral &aity

7- hemo$ericardium6 blood i the *eri&ardial &aity

:- hemoarthrosis6 blood i the Aoit

+- hemo$eritoneum6 blood i the *eritoeal &aity

3

Hemorrha#e

( ti



(narction• (narction is a areas of ischemic necrosis that is

&a'sed by o&&l'sio of either the arterial s'**ly or the

venous draiage i a *arti&'lar tiss'e$

• '6am$les

• Byo&ardial ifar&tio

• erebral ifar&tio

• 'l+oary ifar&tio

• "owel ifar&tio

• 8tre+ities e&rosis (gagree)

3

5h t l l i l d t



5hat vascular lesions lead to

inarction@

Thrombosis

'mbolism

8teral &o+*ressio

Twistig of *edi&le

rterial s*as+

:e+orrhage fro+ a tra'+a3

GG



Uncommon causes o inarction

• *asos$asm o vessels6 &oroaries i

ri7+etal agia

• %om$ression fro+ o'tside by t'+ors or ede+a

• T)istin# of the essels as i torsio of testis or

itestial it'ss's&e*tio or ol'l's

• 'ntra$ment of essels as i strag'lated heria

• Traumatic r'*t're of the blood s'**ly

4!

9testialtorsio of testis

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41

9testial

it'ss's&e*tio

Stran#ulated hernia

torsio of testis

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http://rds.yahoo.com/_ylt=A9iby4PeS0JF374AGhmJzbkF;_ylu=X3oDMTBjMHZkMjZyBHBvcwMxBHNlYwNzcg--/SIG=1hdjm2qf4/EXP=1162059102/**http://images.search.yahoo.com/search/images/view?back=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253Dstrangulated%252Bhernia%2526ei%253DUTF-8%2526fr%253Dyfp-t-501%2526x%253Dwrt&w=250&h=175&imgurl=www.misc-asia.com%252Fimages%252Fpatient_leaflet%252Fhernia2.jpg&rurl=http%253A%252F%252Fwww.misc-asia.com%252Feducation_events%252Fpatient_information%252Fsurgery_for_inguinal_hernia&size=9.3kB&name=hernia2.jpg&p=strangulated+hernia&type=jpeg&no=1&tt=64&oid=f2960f4efce0d108&ei=UTF-8



42

T ( t



Ty$es o (narcts

• 5hite inarcts ;anemic<5hite inarcts ;anemic< o&&'rs i arterial

occlusions or i solid or#ans (s'&h as heart

s*lee ad idey)

•Sha$e o inarctsSha$e o inarcts – 9far&ts are geerally )ed#e sha$ed$ The a*e

of the wedge is at the site of the o&&l'ded

essel ad the base *oits towards the*eri*hery of the orga

– 9f the base of the ifar&ts is a sero's s'rfa&e

there will be ibrinous e6udate o that s'rfa&e43

The inarcts are $ale



44

The inarcts are $ale

and )ed#e-sha$ed0

relectin# the

distribution o the

blood su$$ly

T ( t



Ty$es o (narctsRed inarcts are hemorrha#ic inarcts and occur

• 9 loose tiss'es lie l'g that *er+its &olle&tio ofblood

• 9 tiss'es with dual blood su$$ly6 lie i the l'gs

ad itestie

• 9 venous occlusion (e$g$ oaria torsios)

• 9 tiss'es that are already &ogested fro+ i+*aired

venous flow (e$g$ lier con#estion)

• 9 re$erusion of tiss'es after arterial o&&l'sio that

has &a'sed e&rosis 45



'6am$les o (narction

4

)hite inarct in s$leen

Hemorrha#ic0 rou#hly )ed#e-

sha$ed $ulmonary inarct

"U!8AR/ (8FAR%T"U!8AR/ (8FAR%T



"U!8AR/ (8FAR%T"U!8AR/ (8FAR%T

• 8B"CD9ET9C0 TC

?BDD F9?TD

.8??8D? 90 DG0H

BI G?8

(S%H'!(%(S%H'!(%

8'%RS(S8'%RS(S C;

T9??G8 C>

(8FAR%T(8FAR%T4



Factors that aect develo$ment o inarctFactors that aect develo$ment o inarct

=.=. 8ature o the vascular su$$ly8ature o the vascular su$$ly

That<s why orgas with d'al blood s'**ly do ot

deelo* ifar&tios if there is obstr'&tio to s+all

blood essels

The l'g has *'l+oary ad bro&hial blood

s'**ly

G**er etre+ities with radial ad 'lar blood

s'**ly

#hereas orgas s'&h as s*lee idey ad the

eye has ed-arterial blood s'**ly 4





7. Rate o develo$ment o occlusionRate o develo$ment o occlusion

?lowly deelo*ig o&&l'sio +ay gie ti+e for

alteratie *athway

:. Susce$tibility o involved tissue to hy$o6iaSusce$tibility o involved tissue to hy$o6ia

8eurons8eurons 'dergo irreersible da+age if they are

de*ried of their blood s'**ly for oly 3-4 +i'tes

!yocardial cells die after 2!-3! +i'tes

+. 6y#en content o the blood6y#en content o the blood

%yanotic *atiets or anemics are +ore liely to deelo*

ifar&tio as &o+*ared to or+al *eo*le

4

Hemostasis & Thrombosis




8ormal Hemostasis8ormal Hemostasis the *ro&ess by whi&hthe *ro&ess by whi&h

the blood is +aitaied i a &lot-free fl'id statethe blood is +aitaied i a &lot-free fl'id state

ad *rod'&es a lo&al he+ostati& *l'g at sitesad *rod'&es a lo&al he+ostati& *l'g at sites

of as&'lar iA'ryof as&'lar iA'ry

ThrombosisThrombosis ia**ro*riate a&tiatio of the

he+ostati& *ro&ess i 'iA'red as&'lat're or

for+atio of thrombus i the settig of

relatiely +ii+al as&'lar iA'ry5!



Hemostasis

*asoconstriction

"latelet activation

"latelet a##re#ation

%oa#ulation cascade

Stable clot ormation

%lot dissolution

51

"rimary hemostasis"rimary hemostasis

Secondary hemostasisSecondary hemostasis

;$rimary hemostatic $lu#<;$rimary hemostatic $lu#<

;secondary hemostatic $lu#<;secondary hemostatic $lu#<



Seuence o hemostasis

(- *asoconstriction• 9++ediately after iA'ry there is a iitial

vasoconstriction$

• This is sti+'lated by the release of endothelin

fro+ the edothelial &ells$

• TheThe endothelinendothelin is a i+*ortat aso&ostri&tor is a i+*ortat aso&ostri&tor

52

Seuence o hemostasisSeuence o hemostasis



Seuence o hemostasisSeuence o hemostasis

((- "rimary hemostasis

Activation & adherence of platelets: latelets

adhere to e*osed etra&ell'lar +atri (8B) ia

o #illebrad fa&tor (v5F) ad are a&tiated$

&tiated *latelets 'dergo a sha*e &hage ad

gra'le releaseJ released F ad thro+boae 2

(TK2) lead to f'rther platelet aggregation to for+

the $rimary hemostatic $lu#the $rimary hemostatic $lu#$53




Seuence o hemostasis(((- Secondary hemostasis

Do&al a&tiatio of the &oag'latio &as&ade (iolig tissue

actor ad *latelet *hos*holi*ids) res'lts i fibri

*oly+eri7atio reifor&ig the *latelets ito a defiitie

secondary hemostatic $lu#secondar y hemostatic $lu#$

The tissue factorThe tissue factor ;;cellular li$o$rotein< has the followinghas the following

characteristics:characteristics:

is a $ro-coa#ulant actor is a $ro-coa#ulant actor

synthesied by endotheliumsynthesied by endothelium

is released at the site o inBuryis released at the site o inBury

54




Seuence o hemostasis(*- Antithrombotic counter re#ulation

ti&oag'latio +e&hais+ is triggered after thefor+atio of *er+aet &lot by *oly+eri7atio of

fibri ad aggregatio of *latelets

o'ter-reg'latory +e&hais+s s'&h as releaseof Tissue plasminogen activator (t-"A0 a

fibriolyti& *rod'&t) ad thrombomodulin

(iterferig with the &oag'latio &as&ade) are

a&tiated to *reet f'rther e*asio of the &lot

ad li+it the he+ostati& *ro&ess to the site of iA'ry$

55




• 4oth hemostasis and thrombosis are

de$endent on

=. The vascular )all ;'ndothelium<The vascular )all ;'ndothelium<

7.7. "latelets"latelets

:.:. The coa#ulation cascadeThe coa#ulation cascade

5


%om$onents

= 'ndothelium=. 'ndothelium



=. 'ndothelium=. 'ndotheliumThe endothelial cells normally $osses

ati*latelet ati&oag'latio ad fibriolyti& *ro*erties

( the endothelial cells are inBured or activated0

they deelo* *ro-&oag'lat f'&tios

These activators i&rease *ro&oag'lat a&tiity ad

de&rease ati&oag'lat a&tiity

'6am$les o endothelial cells activators

=- %ytokines (-= and T8F=- %ytokines (-= and T8F

7- "lasma mediators7- "lasma mediators

:- (nectious a#ents:- (nectious a#ents 5

'ndothelial cells synthesie



'ndothelin aso&ostri&tor

Tissue actor 6 a&tiate the &oag'latio &as&ade the etrisi& *athway

"I(7 L 86 asodilators ad ihibit *latelet aggregatio

Adenosine di$hos$hatase degrades F ad ihibits *latelet

aggregatio

He$arin like molecules6 allow atithro+bi to ia&tiate thro+bi

fa&tor Ka ad other &aog'latio fa&tors

Thrombomodulin6 &oert thro+bi fro+ *ro&oag'lat to ati&oag'lat

t-"A6 *ro+otes fibriolysis of the fibri &lot

v5F that hel*s bid *latelets to &ollage 5





"#

" #

!

"rothrombotic $ro$erties o endothelium"rothrombotic $ro$erties o endothelium



(ntact endothelial cells serve $rimarily to inhibit $latelet

adherence & blood clottin#. Ho)ever0 inBury or activation

o endothelial cells results in a $rocoa#ulant $henoty$e

that contributes to localied clot ormation

latelets adhere to the e*osed s'b-edothelial &ollage$ This

is fa&ilitated by v5F se&reted by edothelial &ells

8dothelial &ells secrete tissue actor whi&h a&tiates the

etrisi& &lottig *athway

8dotheli'+ secretes $lasmino#en activator inhibitors

whi&h de*ress fibriolysis

1

"rothrombotic $ro$erties o endothelium"rothrombotic $ro$erties o endothelium

7 "latelets



• t iA'ry site *latelets &o+e i &ota&t with

8B ad they 'dergo three general

reactions6

=- Adhesion and sha$e chan#e

7- Secretion

:- A##re#ation

2

7. "latelets

"latelets



"latelet adhesion"latelet adhesion

Adhesion of *latelets )ith colla#en i the 8B at

the ti+e of iA'ry is fa&ilitated by v5F$

#; a&t as a bridge betwee *latelet s'rfa&e

re&e*tors ad e*osed &ollage

Heeti& defi&ie&ies of #; (o #illebrad

disease) or its re&e*tors res'lt i serio's bleedig

disorders$

3

"latelets

"latelets



"latelet a##re#ation"latelet a##re#ation

The aso&ostri&tor thro+boae 2 (TK2 se&reted by

*latelets) is a *otet sti+'l's for *latelet aggregatio$ This is

the *ri+ary he+ostati& *l'g ad is reersible

Thrombin for+ed i the &oag'latio &as&ade bids to

*latelet s'rfa&e ad with AD" ad TJA7 &a'ses f'rther

*latelet aggregatio followed by *latelet &otra&tio ad

be&o+ig irreersible (se&odary he+ostati& *l'g)

Thro+bi &oert ribrino#en to ibrin that adds to

&e+etig of the *latelet *l'g4

"latelets



"latelet a##re#ation"latelet a##re#ation

The clinical use o as$irin

;a cycloo6y#enase inhibitor< in

$atients at risk or coronary

thrombosis is related to its ability to

inhibit the synthesis o TJA7$

5

: %oa#ulation %ascade: %oa#ulation %ascade





:. %oa#ulation %ascade:. %oa#ulation %ascade

(tKs com$osed o t)o $ath)ays

1$ The intrinsic $ath)ayintrinsic $ath)ay iitiated by the a&tiatio of

:age+a fa&tor

2$ The e6trinsic $ath)aye6trinsic $ath)ay whi&h is a&tiated by the tiss'e

fa&tor

9t<s a series of rea&tios i whi&h ia&tie *roe7y+es

are &oerted ito a&tie e7y+es This res'lts i the for+atio of thrombin that

&oerts the sol'ble fibrioge ito isol'ble ibrin

%oa#ulation cascade%

oa#ulation cascade



#

0ote the &o++o li

betwee the itrisi& ad

etrisi& *athways at the

leel of fa&tor 9K a&tiatio

;a&tors i red boes

re*reset ia&tie

+ole&'les

&tiated fa&tors are

idi&ated with lo)er-casea ad gree bo$

:B#M6 high-+ole&'lar-

weight iioge$

%oa#ulation %ascade



%oa#ulation %ascade

Intrinsic PathwayIntrinsic Pathway (12, 11, 9, 8)

Extrinsic PathwayExtrinsic PathwayTissueTissue factor, (7)

Fibrinogen Fibrin

CommonCommon

PathwayPathway

(5,2)

(Factor 1)

Prothrombin

Thrombin



%oa#ulation %ascade%oa#ulation %ascade



• lottig is reg'lated i a way to be &ofied to the site

of iA'ry by t)ot)o natural anticoa#ulantsnatural anticoa#ulants6

=.=. Antithrombins ;e.#.0 antithrombin (((<Antithrombins ;e.#.0 antithrombin (((<

9t ihibits the a&tiity of thro+bi fa&tor 9Ka Ka K9a L K99a

tithro+bi is a&tiated by bidig to he*ari lie

+ole&'les o edothelial &ells

7.7. "rotein % and S"rotein % and S

They are two vitamin ? de$endent *roteis

They ia&tiate &ofa&tors .a ad .999a

!

%oa#ulation %ascade%oa#ulation %ascade

Fibrinolytic %ascadeFibrinolytic %ascade



Fibrinolytic %ascadeFibrinolytic %ascade

• "esides id'&ig &oag'latio a&tiatio of the &lottig

&as&ade also sets ito +otio a fibrinolytic cascade that

will li+it the si7e of the fial &lot by a&tiatio of plasmin$

• "lasmin is obtaied fro+ the *re&'rsor *las+ioge

either by K99a or by *las+ioge a&tiators (+aily t-)

• "lasmin breas dow fibri *rod'&ig fibri s*lit *rod'&ts

(also &alled fibri degradatio *rod'&ts)• ;ibriolysis is blo&ed by Plasminogen activator inhibitors

1

*ircho) triad in thrombosis are



=. 'ndothelial inBury

7. 4lood hy$ercoa#ulability

:. Stasis or turbulence o blood lo)

Thrombosis

2

=. The endothelial cell inBury=. The endothelial cell inBury



=. The endothelial cell inBury=. The endothelial cell inBury

• Doss of edotheli'+ leads to e*os're of 8B adhere&e

of *latelets release of tiss'e fa&tor lo&al de*letio of H92

ad t-

• arti&'larly i+*ortat i thro+b's for+atio i the heart ad

arterial &ir&'latio

• Fysf'&tioal edotheli'+ +ay elaborate greater a+o'ts

of *ro&oag'lat fa&tors (e$g$ adhesio +ole&'les to bid

*latelets tiss'e fa&tor) ad s+aller a+o'ts of

ati&oag'lat effe&tors (e$g$ thro+bo+od'li H92 t-)$

3

The endothelial cell inBuryThe endothelial cell inBury



%auses o endothelial cell inBury

hysi&al disr'*tio

:y*ertesio

T'rb'let flow oer s&arred ales

"a&terial edotois

>adiatio

:y*er&holesterole+ia Toi& s'bsta&es (e$g$ &igarette s+oe)

4

The endothelial cell inBuryThe endothelial cell inBury

7 Alteration in normal blood lo)7 Alteration in normal blood lo)



7. Alteration in normal blood lo)7. Alteration in normal blood lo)

;low of *latelets i the blood is la+iar

Turbulence or stasis )ill result in

1) brig *latelets ito &ota&t with the edotheli'+

2) *reet dil'tio of a&tiated &lottig fa&tors by fresh-flowig blood

3) *ro+ote edothelial &ell a&tiatio *redis*osig to

lo&al thro+bosis ad le'o&yte adhesio

4) delay the iflow of &lottig fa&tor ihibitors ad *er+it

the b'ild-'* of thro+bi

5

: Hy$ercoa#ulability: Hy$ercoa#ulability



:. Hy$ercoa#ulability:. Hy$ercoa#ulability

• %onditions associated )ith an increased risk%onditions associated )ith an increased risk

o thrombosiso thrombosis

"rimary ;Ienetic< causes

=- Factor * mutations

7- "rothrombin mutations

:- Antithrombin ((( deiciency

+- "rotein % and S deiciency

Hy$ercoa#ulabilityHy$ercoa#ulability



• Secondary ;Acuired< causes

'6am$les

1$ rologed bed rest or i++obili7atio

2$ Byo&ardial ifar&tio3$ Tiss'e da+age (s'rgery fra&t're b'rs)

4$ a&er

5$ rostheti& &ardia& ales

$ Fisse+iated itraas&'lar &oag'latio

$ D'*'s ati&oag'lat

Hy$ercoa#ulabilityHy$ercoa#ulability

$hrombosis: %&RP'&L&%&RP'&L&



$hrombosis: %&RP'&L& %&RP'&L&

• Thro+bi +ay deelo* aywhere i the &ardioas&'lar

syste+

• Thro+bi are of ariable si7e ad sha*e

• area of atta&h+et to the 'derlyig essel or heart wallfre@'etly fir+est at the *oit of origi is &hara&teristi& of all

thro+bi$

• Thrombi are si#niicant becauseThrombi are si#niicant because

1) they &a'se obstruction of arteries ad eis

2) they are *ossible so'r&es of emboli

Thrombosis in heart chambers & aorta



&

• !ural thrombi!ural thrombi are those thro+bi that for+ o the

walls of the heart chambers and aorta

• %auses%auses arrhyth+ias dilated &ardio+yo*athy B9

+yo&arditis &atheter tra'+a

ines o Lahnines o Lahn

*rod'&ed d'e to alteratig

*ale layers of *latelets ad

fibri with dar layers of

>" i thro+bi for+ed i

the heart or aorta

%oronary artery0 ri#ht0 )ith thrombus fillig ad



&o+*letely o&&l'dig the l'+e$ Thro+bi i &oroary

arteries are almost al)ays d'e to edothelial da+age

res'ltig rom atherosclerosis$

!

%ross section o a coronary artery. The intima0 to )hich a

th b i tt h d i k dl thi k d b



thrombus is attached0 is markedly thickened by

atherosclerosis. The thrombus nearly ills the lumen0 but

in one area0 it has retracted rom the vessel )all.

1

*enous thrombosis ;$hlebothrombosis<



• hara&teristi&ally o&&'r i sites of stasis

• +ay ot be well atta&hed ad are *roe to

e+boli

• They &otai +ore >"s therefore ow

as red0 or stasis0 thrombi

• !% of &ases iole the eis of loweretre+ities

2

*enous thrombosis ;$hlebothrombosis<



• ?'*erfi&ial eo's

thro+bi 's'ally o&&'r

i the sa*heo's

syste+ *arti&'larly i

ari&osities

• Su$ericial thrombi

+ay &a'se swellig

ad *ai b't seldo+

e+boli7e3

Dee$ thrombi i



4

the large eis

*arti&'larly those

aboe the ee

Aoit i the

*o*liteal fe+oral

L ilia& eis are

+ore serio's as

they +ay

e+boli7e

;5here @<

Dee$ *ein Thrombosis ;D*T<



5

dee* eo's thro+boses are asy+*to+ati& i 5!% of

&ases$ da&ed age bed rest ad i++obili7atio

i&rease the ris of dee* ei thro+bosis

Fate o ThrombusFate o Thrombus



=.=. "ro$a#ation"ro$a#ation thro+bi +ay a&&'+'late +ore

fibri L *latelets &a'sig obstr'&tio7.7. 'mboliation'mboliation thro+bi +ay deta&hed ad be

tras*orted to other sites i the as&'lat're

:.:. DissolutionDissolution thro+bi +ay be re+oed byfibriolyti& a&tiity

+.+. r#aniation and Recanaliationr#aniation and Recanaliation Thro+bi +ay

id'&e ifla++atio ad fibrosis ( organization ) ad +ay be&o+e recanalized (re-establish

as&'lar flow) or they +ay be i&or*orated ito a

thi&eed as&'lar wall$ (i old thro+bi)





*ein )ith or#aniin# and recanaliin# thrombus

;illig this essel is a red thro+b's atta&hed to the essel wall$ 9

oe area it has retra&ted for+ig a &res&et-sha*ed l'+e

'mbolism



'mbolism

• bor+al solid +ass &arried i blood$

• Ty*es$ – Thromboembolism - atheros&lerosis

– Fat - ;ra&t'res

– Ias – Naisso disease<

– iuid – +ioti& fl'id

• C't&o+e of 8+bolis+ – ollateral &ir&'latio

– 9far&tio

– :e+orrhage



'mbolism'mbolism

'mbolus'mbolus

'mbolus'mbolus

!

'mbolism'mbolism



embolusembolus is a deta&hed itraas&'lar solid liuid

or #aseous mass that is &arried by the blood to a site

distat fro+ its *oit of origi

GG of all e+boli re*reset *art of thro+b's he&e

the &o++oly 'sed ter+ thromboembolismthromboembolism

Rare orms o emboli include

dro*lets of fat b'bbles of air or itroge

atheros&leroti& (cholesterol emboli), t'+or frag+ets

bits of boe +arrow or foreig bodies s'&h as b'llets$1

"ulmonary Thromboembolism"ulmonary Thromboembolism



9t is &o++o i hos*itali7ed *atiets

Crigiates +aily i dee* eis of the lower

etre+ities

8+boli trael to the right side of the heart to the

*'l+oary arteries

Bay be so large to blo& the +ai *'l+oary

artery at the site of bif'r&atio &alled saddlesaddleembolusembolus

Bay be s+all to *ass ito s+aller bra&hes

2



Fate o $ulmonary embolism



?'dde death right etri&'lar fail're or

&ardioas&'lar &olla*se o&&'r whe !% or +ore ofthe *'l+oary &ir&'latio is obstr'&ted with e+boli$

!-!% are clinically silent be&a'se they are

s+all 'dergo dissol'tio or re&aali7atio

8+boli& obstr'&tio of +edi'+-si7ed arteries +ay

res'lt i $ulmonary hemorrha#e

B'lti*le e+boli oer ti+e +ay &a'se $ulmonary

hy$ertension with right etri&'lar fail're

4

Systemic Thromboembolism >efers to e+boli tra elig ithi the arterial &ir& latio



>efers to e+boli traelig withi the arterial &ir&'latio

!% arise fro+ itra-&ardia& +'ral thro+bi asso&iated with

let ventricular wall ifar&ts (2/3)with dilated let atria (1/3)

The rest ori#inates rom6

• Atherosclerosis i aorta or fro+ aorti& ae'rys+s

• "arado6ical embolism rarely e+boli +ay trael fro+eo's to arterial &ir&'latio ia a &o++'i&atio

betwee arterial L eo's &ir&'latio

!aBor sites or lod#in# o systemic emboli!aBor sites or lod#in# o systemic emboli

the lower etre+ities (5%) ad the brai (1!%)

arterial e+boli &a'se inarction of tiss'es i the distrib'tio

of the obstr'&ted essel$ 5

Fat 'mbolismFat 'mbolism



'tiolo#y +aily after fra&t'res of log boes or

rarely i the settig of soft tiss'e tra'+a ad b'rs

Fat embolism syndromeFat embolism syndrome ;atal i abo't 1!% of &ases

>es*iratory6 ta&hy*ea dys*ea

0e'rologi&al6 irritability restlessess ad &o+a

Thro+bo&yto*eia with &hara&teristi& *ete&hiae

9t geerally deelo*s 1 to 3 days after iA'ry

The *athogeesis ioles both +e&hai&al obstr'&tio

ad toi& iA'ry to edotheli'+ by ;;

The fat e+bol's eters the &ir&'latio fro+ +arrowFat 'mbolismFat 'mbolism



The fat e+bol's eters the &ir&'latio fro+ +arrow

after r'*t're of boe as&'lar si'soids or fro+

adi*ose tiss'e thro'gh r'*t're of tiss'e e'les

4one marro) embolus in the $ulmonary circulation0 the

cleared vacuoles re$resent marro) at

Air 'mbolism



ir +ay eter the &ir&'latio d'rig s'rgi&al

obstetri& *ro&ed'res or as a &ose@'e&e of &hest

wall iA'ry

Heerally O 1!! +D of air is re@'ired to *rod'&e a

&lii&al effe&t

+ay &a'se fo&al is&he+ia i the brai ad heart

+ay &a'se ede+a he+orrhages ad fo&alatele&tasis or e+*hyse+a leadig to res*iratory

distress i the l'gs

Amniotic Fluid 'mbolismAmniotic Fluid 'mbolism



• The 'derlyig &a'se is the leaage of a+ioti&

fl'id (ad its &otets) ito the +ateral &ir&'latioia a tear i the *la&etal +e+braes ad r'*t're

of 'terie eis$

• The *rese&e of the followigs i the *'l+oary

&ir&'latio will &ofir+ the diagosis6

– ?@'a+o's &ells fro+ fetal si

– hair

– +'&i deried fro+ fetal res*iratory or H9 tra&ts

Shock ;cardiovascular colla$se<



• ?yste+i& hy*o*erf'sio d'e to a red'&tio either

i &ardia& o't*'t or i the effe&tie &ir&'latigblood ol'+e

• Ty$es o shockTy$es o shock

=. %ardio#enic shock

• '+* fail're

7. Hemorrha#ic ;hy$ovolemic< shock

• Fe&rease i blood ol'+e

:. Se$tic shock

• ;ail're of +i&ro&ir&'latio to retai *ress're leadig

to wide s*read *eri*heral asodilatatio1!!

(- %ardio#enic shock



• ;ail're of +yo&ardial *'+* owig to itrisi& +yo&ardial

da+age etrisi& *ress're or obstr'&tio to o'tflow

%auses%auses

1$ +yo&ardial ifar&tio

2$ &ardia& ta+*oade

3$ o'tflow obstr'&tio i *'l+oary e+bolis+4$ etri&'lar arrhryth+ia

Si#ns and sym$toms

• Ta&hy&ardia

• :y*otesio

• Ta&hy*ea

• >estlessess agitatio

• allor L sweatig 1!1

((. Hy$ovolemic shock



>es'lts fro+ loss of blood or *las+a ol'+e

%auses%auses

1$ :e+orrhage

2$ ;l'id loss fro+ seere o+itig diarrhea

b'rs or tra'+a

?igs ad sy+*to+s of hy*oole+i& sho&

are the sa+e as i &ardiogei& sho&

1!2

(((. Se$tic Shock



• >es'lts fro+ s*read of a iitially lo&ali7ed ife&tio (e$g$

abs&ess *eritoitis *e'+oia) ito the bloodstrea+$

• C&&'rs whe a oerwhel+ig ife&tio leads to low blood

*ress're ad ital orgas +ay ot f'&tio *ro*erly

• :as 25% to 5!% +ortality rate

• Ce of the +ost &o++o &a'ses of death i itesie &are

'its

• %aused by systemic microbial inection%aused by systemic microbial inection

– Bost &o++oly (~ !%) #ram-ne#ative ife&tios

(endotoxic shock)

– &a also o&&'r with gra+-*ositie ad f'gal ife&tios$1!3

"atho#enesis o Se$tic Shock



• 8dotois are ba&terial wall li*o*olysa&&harides (D?s)

• D? a&tiate +oo'&lear &ell with *rod'&tio of &he+i&al

+ediators

• The &olle&tie effe&t of these +ediators res'lt i6

– ;eer a&'te-*hase rea&tio e'tro*hilia – .asodilatio6 hy*otesio

– #ides*read edothelial &ell iA'ry

– &tiatio of the &oag'latio syste+ – B'ltiorga syste+ fail're

1!4

Shock ;less common ty$es<



8euro#enic shock8euro#enic shock

• he+odya+i& sho& d'e to loss o vascular tone ad*eri*heral *oolig of blood res'ltig i asodialtio

• %auses6 s*ial &ord iA'ry or tra'+a

Ana$hylactic shockAna$hylactic shock

• iitiated by a geerali7ed i++'oglob'li 8-+ediatedhy*ersesitiity res*ose

• asso&iated with systemic vasodilatation ad i&reasedas&'lar *er+eability

• &a'ses a s'dde i&rease i the &a*a&ity of the as&'larbed whi&h &aot be filled ade@'ately by the or+al&ir&'latig blood ol'+e$ Th's tiss'e hy*o*erf'sioad &ell'lar aoia res'lt$

1!5

Sta#es o Shock



• (nitial non$ro#ressive sta#e(nitial non$ro#ressive sta#e the &a'satie fa&tors of

sho& are &otaied ad *erf'sio of ital orgas is

+aitaied (ade@'ate &o+*esatory +e&hais+)

• "ro#ressive sta#e"ro#ressive sta#e tiss'e hy$o$erusion &oti'es

res'ltig i tiss'e hy$o6ia ad +etaboli& dist'rba&es

(e$g$ aaerobi& gly&olysis *rod'&ed la&ti& a&idosis)$

o+*esatory +e&hais+ is o loger ade@'ate

• (rreversible sta#e(rreversible sta#e the *atiet has +'lti*le orga

fail're ad death be&o+es ieitable

Documents

Hemodynamic Disorders Thrombosis