Prafussur al Pathology' and Senior' C11nsultant Patholog,ist

Pathology Department, Faculty Di Medicine, M'ansoura University·, Egypt

2021-2022
Objectives
By the end of this lec t ure you willll be able to:
1. Define hemostasis, thrombosis, em b, o l is m, isc he mia and in fa rct io n.

2. En [Link] In o rde r the stages . of hemostasis and compare it to thro m bos is.
3, Appl y the rules of he mos tas is in understanding the mecha nis ms of thmrnbosis
Traid).
4. De scri be t he morphology of th rom bi, know how to nominate it and differentiate it s types.
5. Classify the so urces and distant sites for lo ca Bzat ilo n of emboli.
6. Discuss brie f ly the pathogenesis and mo r pho lo gy of pu il mo na ry and syste mic thrombo-
embolism.
7. E nlist the causes of is [Link] rn ia.
8. Differentiate the types of infarcts as regards incfting circumstances and' mo rpho l o gy.
9. Antidpate the possi ble consequences and fates of thrombosis, e m bo lis m, isc he m ia, and
infarction.
 DVT, Paget Schroetter

he
-

Disease (apilary)

infarction
e -Vessel Myocardial
Budd-chiari syn
>
=> <hepatic vein)
[Link] Thrombosis
of
out lever

a en
- -> vessels"
Blood stable in
Hemostasis I Thrombosis "Blood clot

Process Physio lo gic al process. Pat ho l ogical process.

-> eg:.
Arterialwombosare
Definition Ar rest of bl eeding from a Forma ition of a so li:d mass form circulating blood elements . veins
-
Embolism
- -

blood vessel after injury. {thrombus) within the circulatory sy,;tem d ur ing life.
- - -
·

-
- e
Pathogen esis Followinga vessel walllinjurY: Virchow's tr iad:

imE
=>
*1. Vasoconstr iction. Three abnorma li tie lead to thro mbus formation
-

-
- 2. Platelet p'l ug formation. [Link]
he lial injury,
nee -
et
3. Blood coa,gul at ion (clot). 2. Abnormal blood flow (turbu lence or stasi.s),
ne
- -
E-
coagulating 3. Hypercoagul,abi lity of the blood.
I Res t rict e d to the site of injury.
> - -
I
Extent Can occlude the vessel, propagate and embo li ze. - -
= - -

Fibronlysis -

o
"
Regeneration F1UJN lD IUl()D

S - loss
Pathogenesis of thr,ombosis=Vich ti d
re ow' tria
1
"SE"
,-
loss, expose
↓ bentotelial
Endothelial Injury Abnormal blood flow HypercoagulabIIlty
audic
arterial, men
- -
-
-

- Fa,vors thrombus form at io n • - Tur bule nce : Favors cardl c and

-
- l ncre a,se d tendency of the
--

arterial
- -

in the h111 (a ft e r i nfa rc t io n) rt rt I thrombi (helps blood t o Cl d ot (due , to i n creased

are to
-
- -

and & r (athe ros cle ros is,

-
endot heliaI' in iu ry).
nee
bloo d iseoslty ,o r eo ul tlon
⑦
-
hype rte ns io n}. trauma
men,
e
Favors v nous th ombl
- Sta s is :-
-
f cto acNvity or aimou n t . }
(helps hypercoagulabi
mean
lity by - I nhe rite d or acq uire d.
accum ulatiing plat elet s and clotting Favo rs Ve nous thrombi,. :le ss
factors). .. im porta nt i n ca rd iac and art ,erial
th rombi.

⑧
AC:..QUI ED FACTO S
It [Link] S:
--
[Link]

t
- [Link]
--
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-

--[Link].V
- MA OA TAAU"4A/SlllGEA't
- [Link] IMMOBIUZATION
nee

-
=Anticong
procojangluti
-
flow
- -
- -

>
>
=> laminar
-
-
->
I -
↓ Heridetar Acquired
nee - -
turbulent ne ↓
RBC plate
is
- aggregat
a
"I icdysfunction
I

3.
I2.
sat
in
-

stasis --. (Veins)

 heart
Venous thrombosis
- -> artery
I Morphology of Thrombi
⑭rombosis
Thromphlebitis rein
O
are -
No inflammation, Stesis

-
ne- * n
vern <immbolis
-> Inflamation
-> vessell a:ny
wall Site: - w,he
e re wit h i n t he ca
e
rd in
i o vasc ula r system.
Attachment: focailly aittached to the unde rllying
yi ng surface.
stetive on-sterice en

Occlusion of vascular lumen: Occllusive or non -occlusive.

-

Di1rection: propagate s to wa rds the hea rt.

-

Grossly (and microscopically}: shows

brin

S-
Lines
pale: of Zahn: ut??_Im clinical
1. La mi natio ns. of p.a l,e (p late le t and f ib ri n- rich ) layers ↑
a lt e rn at i ng with darker red ,( RB Cs- rich ) layers. Ischemia, R
2. More manifost in tardl c and arterial thrombi than Infarction
venous ones. P
3. Import ance : diff erent iat e ante -mort em thromb i (present)
from post-mo rte m clots (a bse nt ).
According to color, thro mbi may be:
1. Pa le : 2. Red:
• Grayish white, rough a,nd fiirm. • Dark red, sm oo t h and soft er.
" Consis t ,of pfatelets and fi br in. • Consists of excess erythrocyt es + platelet s
• Pro minent lines of Zahn.. and fibrin.
• f u r m ed mai nly in arteries and heart. • Less prominent lines ,of Zah n.
• Fo,rmed mainly in veins.

Location and nomenclature of thrombi

⑧ .1. Mural throm bi: in heart chambers or in ao rta . eg: Myocardial
infarction
⑧ 2. Arteria,lt hrombi: in art er1ies.

veins 3. Phlebothrombosb,:Sis
lo er limb ve ns (90%cf veno us thrombose }. (no
in veins . M ain ly in the mi inflamation)
[Link]
-

&
lihrombophlebitis: I nfect ed veno us thro m bi.
n e (inflammation)
S. Vegetatio ns: on heart valves may i nfect i ve or no n-bacte ri.a l.
- -

6. Disse minated I·ntravascular coagulat io n (DIC): Wid es p re ad th rombos is within the

micro circul atio n. Cau ses:-
sepsis, advanced cancer and severe tissu e injury.
ene - -

Ph [Link]
-

( lower limb deep veins)

 Outcomes [Fate] of Thrombi Fr-brinogen
-
-
brinolyt ic system or aft e1r the
1. Dissolution ot r ecent ly formed thrombi by fin t h erapy
- ee
r storation of blood f low.
mbi
-
dis The
to war
-

3.
2. Propagation: Enla rgem ent by adding more pl at elet s and fi brin 1

vaseular ,aed us ion . heart

u
-
-

tootherC
⑧8. 3. [Link]: Pa rt o r all of the thrombus is det ached embolus. <travel
-
e
-

i
4. Organizat[on and re£anal' 'z:atii on: (venous)
Seein
- -

Olde r t hrom b i heal by organ i zat ion (fibrosis ),

rten
- -

Capillary channels open with in the organized

t hrom bus .
Restoration of the blood flow . al thronbi
en
enzymatic digestion
5. Shrinkage (contraction), dystiro ph·c
e

,catcifie:ation. ↓ 08
Ba
Embolism (e,mbol'izat10n)
Definition: lnt ravascu lar circulat io n of a solid, liquid, or gaseous
mass in t he blood je .mholus) fol lowed by it s im paction in a
sm alller blood vessel at a distant .site from its origin.
Brain ... ".'..
\

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r m
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eac1...... H d ol ;,Jqo n nliJlllllill .,.,, 00,

f I \ \! \r r i
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tm bollom ombolilm IJ<lphobl.. tl< oml><!li [Link].I

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Hyddli,[Link],
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"n"f"o"al 'l'l!!MtwO,nl,l
,n . , F'T9gr,a,icy TtaT>JUr Ivo r IVtnleWllf1 Sw or; q

Sources (origin) and types of emboli:

1. . Thrombo mbo ism (commonest): from detached thrombi .
2. Fat embolism (bone fracture, burn ), choleste rol em lbo lli sm (athe rosc e rosis }.
3. Gas: air embolism (Trauma, surgery, injec·tons), Caisson's o·sease (nitrogen
embolism in deep sea divers).
4. . Amniotic f lUid embolism.
5. Tumor tissue embolism- me ta stas:is.
6. Parastt·c embolism as bi lharzi a ova and worms.

Distant locatio .ns of emboli:

1. Vessels of tl1e lung=Pulmona iry embolism.
2. Vesse ls of any other organ= Systemic embolism .
 Pu
z
-
-

4- Embolu pas thl'

Definitio n: Em b olizat ion of the pulmonary hearu01n
-= pu!mon,ar, ve nls
vessels by detached thrombi.
-
It is the commonest form of thrombo-
embolism .

Origtn of em boli: ;[Link] ha

travels, In lager
Oetached deep venous thrombi IDVTs) of velns la the
meet hurt
thedo
e .

-
ower im bs.

Detached thrombi pass t hrough the right

e -

side of th e heart then arrest in t he

e n - -

pu lmonary ves sels.

e

Distant sites and effects of pulmonary emboli:

Embolus blocking main/major
-
pulmonairy artery---t sudden death.
-

Embolus at the bifu rcat ion of the right and left pulmonary arteries aire called saddle -

-
embolus .
Emboli at pulmonary medium -sized arteries and end-arteri oles - may ,[Link]
infarction or-
hemorrhag,e.
e

Emboli at pullm on ary capillarie s ---+ i f r ecurr ent - pulmonary hypert ension 1 heart
-
- nee
failure .
- -
About 60-80% areeil
d nically sile nt.

2
systemic vessels by detached thrombi.
Definit ion: Embolization of the-
-
Origin of detached throm bi:
Heart . -

E
Valve veget ations .-
Aorta a,n d it s main branch es., m

Distant sites for embolization:

Lower [Link] s (75%),
Centra l n ervou s system (10%1; -
Int est ine s, kidneys, and .spleen.. -

Consequences: May cause· sch e mia or in farction . This depen ds on- caliber of the
affected vessel, the collateral bloo d supply, andl the t ype of tissue .
nee
7. -
lschemia
Definition: Decreased arterial blood supply to an organ or tissue.

Causes :
Acute . Sudden complete vessel occlusion !thrombosis, embolism, trauma, t wi,sting) .
Chronic
: Gradual inc,ompl et,e vessel occlusion by:
Pressu r,e on the vessel wall from out side: tumor or enlarged lym ph node.
11 Vessel walll disease: as atherosclerosis or vasculitis.

Eff ects:
1. Tissues with efficient collaterals: no tissue damage.
2. Tissues with inefficient coUaterals (with end-arter ies):
Acute lschemia: necrnsis ;;;;;infarction or gangrene.
Chronic· schemia:
Manifostations differ according to affected organ (see exam ples).

Examples, of chronic isc'hem1a:

Myoca rdia l! f heart] ischemia: Chronic ischemia of the lower limbs:
Angina (chest pain) intermittent claud icatio ns: Pain during wa,l king
that is rapid ly re lieved by rest .

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cause5,di e-s1 llla t rna rsmle co t3w s:houldef ,
bedii rt Arm M, 1Jh1 'Slfilted

8. lnfarction
Definition: It is an area of ischemic necrosis (coagulative or lliquefactive) caused by
occlusion of the vascular supply (arterial or venous or both) to the affected tissuie.

Cau ses: same as ischem ia. Mainly thrombosis and embo lism .
Common sites of infarctio n:
1. M yocardia l infarction, cerebral infa rction, pu lmo111 ary in farction.
2. Intest ina l inf arction (intestinal gangrene), ext remit ies l liimb gangrene}.

Classificatio n of lnfa rcts

• According to colo r:
-Red (hemorrh agiic ) infarcts -White (anemic, pale) infarcts
• According to presence or absence of .infection:
-Septic (Infected) -Bland (non -infected )
 References
th
Robbins Basic Pathology, 10 edition 2017, ELSEVIER, ISBN: 978-0-323-35317-5, by Kumar Vinay, Abbas Abul K.,
Aster Jon C
Webpath. [Link]
 E
HORUS 'UN IV ERSIT Y IN EGYPT

Semester I, Module 3
Pathology of Cir culato ry msturbances (Part I - Hemoidynamic Dis,nrders)
1

Dr. Amal Ahd E hafe,z

Ph.D.•M.O.
Profess or of P,athology and Senior Cons ult ant Pa1th0Jogist
Pathology De partment, Fac uhy ofi Me dicine , Manso ui:-a Un iversity, Egypt
2021-2022

Object ives
B:-t the end ohhis le ct ure you will be able to:
1. Define hype re m ia, congestion, edema and hemorrhage.
2. Diffe re nt ia t e between hyperemia and conge stio n in re lat io n to def i nit io n, duration,
morphology and pathogenesis with exam ple s.
3. Des cri be the ma i n mo rpho lo gic f i nd i ngs in pu l mo na ry and he pat ic co nges t io n.
4. list the pat hop hys iolo gic mechanisms & ca. uses of edema and effus io n.
5. Differentiate infla mmato ry from no n-i nfla mmato ry edema fluid and the other types of
edema flu id.
6. Discuss in brief the states of lo ca li e d and, ge ne ra l ize d edema, and body cavit,y e ffus io ns
with clinical correlations.
7. Enlist the causes and diffe re ntiate the ty pes of hemorrhage with reference to med ical
terms used to nominateeach.

l .Hyperemia1 ,& 2. -
Congestion passive hepe

&
blood

Vero Pi
sslv process re sult ing from inc re ased blood
·

Def. Actl process le ad i ng to i ncr ease d >

blood vo l ume within a tissue. volume wit hi n a tissue .
-

, o ur ation Usually of short durat io n. Acute (short duration) or chronic Uong-standing).

Pathogenesis Vasod i l at:io n of arterioles. Im pa i rme nt of venus return.

m--
incre ased blood inflow). (decreased blood outf llo w}.
accumul
Tissue color Red (o)(ygenate c! b l ood) IBlue -red (cyanosis) (deo xygenat ed
e
blood)

Eti'ology/ - Phys io lo gical: Exercising s eletal Pat ho lo gical:

Example s musde, emotional f l ushing. Syste mic (ge ne rali ze, d}: e.g., heart fail ure .
Pat ho llo gica l: l nflam mat fo n. Loc alize d: lower lim bs (diseases of ve i ns ).
--

, c o NGE.ST10N1
Pathological effects of chronic congestion:
8 ⑧
Hypoxia
(deoxygenated blood) + Increased vascular
hydrostatic pressure

* reve rsible cell i

cell death
rupture of capillaries

local hemorrhages

↓ ↓
reptacement by fibrosis hemosiderin pigment
- deposition - fibrosis
Examples of congestion:
1. Chronic putmonary venous
-
-
--
congestion: S
D
Cause: Left-sided heart failure, mit ral st e nos is . -
firme -
-

ion(hard ening) ofthe lung. luglearsy

-

NJ E: Brown-indurath:m
~

rusty
M./!:->
en
-

heavy, firm
brown

• e
[Link] s.
E
rusty brown -

• Heart fa ilure ceUs (macrophages laden wit h hemosiderin from

-

digested red bloodcells.).

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eono lirc w.1.1

iltiROli CMIC ;Jii'iinf!

,d
millkf'Q flq:i,
H!UT l'AJLU [ CElll

2. Chronic pdssiv h ePAtic veno.u sti.a

us conget n:
cause: RiJ ht -s ide d heart failure.

vineMoxygenwould
be
-

Anepatic
·"
N/E
-
• Nutme1 live r .- --
Alternating red-b
-
rown areas and yell lo w al"e as .
-

E ---
M / E:
• He pat ocytes: fatty change and necros is .
-

• Congest io n, hemorrhage,
-
he mo,Ss ide ri n.

↑Vercirrhosis (card
Fate: Lh1er 5 S iac cin [Link])
- nee
 3. -
Edema (and the Related Conditions)

IDefiniton:
• dern :
-
I
• Accumulat i on of excess interstit ii al fliuid within the tissues.
an
- ~ e

Effusion:
Accumulation of 1luid within the body-
caivities.
Include: effusions in the pleural cavity (hydrothorax), the pericardia! cavity
- - -

(hy,dropericardium) , the peritoneal

e
cavity (hydroperitoneum = ascit es) or Joint
-

-
·
cavity (hydrart hrosis) .

• [Link]:
Severe, edema characterized by marked swelling of subct1taneous tissues and
accumu l ati on of fluii d in all body cavities.
1

Pathophysiology of Edema
Introductio n: ~

The nuid balance between the circurl at io n and in

, terst itia l t issu e depends on two opposit e
forces:
1. -
Vascular hydrostatic pressure (pushing fl uid outside the circulat i on).
-

2. Colloid osmotic pressure produced by plasma proteins (p ulling flu id insi de the
circu la tio n).

E Note: The small net

outflow of fluid into the
inil:er sti t:ial space, is
en drained by lymphaUc

E
vesse'l s and returned to
circulat ion .

Arti!:[Link]!il and [Link] 8£0 Vt:riCIUi i!irfld

P,atho,physiology Causes of Edem

3
⑧1. lncrea,[Link] hydrostatic [Link] (impaired venous return): e -

• Lo ca li ze d: Pro l on ged standing, hrombosis, External pressure onveins.

E • Generalized: Heart failure, Liver ci rr hos is.
-

2. Decreased plasma osmotic pressure = Hypoproteinemia:

nee

• De cre ased prote i n i nt a ke {, ma l nut rit io , n}, or s yn t hes is {chronic liver d ise ases).
[ -
• Increased protein loss: renal diseases.
-

-en

3.-
Salt and water retention:
-

• Excess salt inta e with re nal diseases.

-
• Hormonal: Increase d a,ctivity of renin-angiot ensin -aldo sterone system..
en

Exudate 4. l'n creased-

2 • Inf lam mation.
vascular permeability: 1

I •-
Angioedema (Angioneu rot ic edema).

- 5. Lymphatic obstrnctio n/rupture:

• Congenita,I .
• Acquired ; Inflammat ion, filarias!s, t umors, post-surgica l, post-irradiation (breast cancer).
Types of edema and effusion fluids:

->>
> -
>
> >
>

Ma in mec:hanis m/ s • Increased hydrostatic press,ure. • M ainly inc,reased vasCLJlar

e

• Decreased ,pl asma ,osmotic pressure. perm eabilit y.

e
• Salt and wat,er retentfon.
• Lymp hatic [Link],on..
[Link]
1

• Appea rance Clear

-
Turbid
• Prot ein conten t Low <4 gm% High 4-8gm%
-

• Spe cificgravi ty Low about 1.012 High above 1.018

• Fibrinogen
-
No Yes
-

• Clotting on standing -
No >
Yes
-
-

• Inflam
-
mato ry cel,l s Few or no High content

-
causes Organ fa,illur e!cardiac-renal-hepatic),
nutrit ional edema, angio ed!ema.
Inflammato ry edema ,
-

Other types of ed'ema and effusion flui d:

3.. l y mph (chyle·J:
M il ky-w hite fluid, rich in e
lymphocytes and lipid s.
-- n -
Chylous
Causes: lymph at ic obst ru ct ion and ru pt ure .
-
-
ascites
=
>
> >

4. Hemorrhagic efl!'usion (seri

nee
osa111gufne.01.1s)
Cause: mostly
-
t ra um a and s,p read of ma ll: lg na ncy.
-

5. Pure pu.s = emp,yema : Co lled io n of pus in a bod y Gallbladder

cavity. Cause: mostly bacte rial Inf ection. e.g. in the empyema
1

:Plle u ral cavity and gall blad de r.

11
 Morphology of Edem.a
-

A. Edema of organ failure. 2

I
General C1(teria of Grgan fa'ilure edema:
• Fluid type : [Link].
-ex
• Sit e s: Involve subcutaneous tissue and body cavities (generalized ed m aJ.
>

• Usual ly e
marked in the feet and legs in ambulant patients and the sacrum in
- -

r,e,cumbent pat :i ents (dependent edema }.

-

• finger pressure over the edematous subcutaneous tissue displa,ces t he interstitial fllu
i d, leaving a [Link] (pitting edema )1.

• Inc ud 3 Conditions:
1 . Card·ac edema (heart failu re).
-
• Usually dependent edema.
ne

⑧
2. R
-
nal d m (Ren f ilur or dysfunctio n)·
es

• Noticed first in loose connective tissues [as eyeli ds=

[Link] edema, and face].
--

Pu1orhl <1l e.d•ma

3 H p tic d m (llv r I ur or chron c

i
• Common:ly manifest with aseites. sperotinal care
-
• Other signs:
• Hepato splenomegaly a,nd esophag al [Link].
nee

B.. Localized edema:

e

-
1. Pulmonary edem a: Caused by:
-
a. Left -sided heart failure (transudate),.
- - -
1

h. Pulmonary inflammat ory and infections

- - -
(ex u date).
-

N/ E: Oozi n g fr othy, blood-t inged nlu id.

-

7
D 2. !Brain {c,erebrall edema· Caused by:
11 Focail: Abscess, tumor, or trauma.

• Diffuse: Hypertensive encephalopat hy,

⑧
C. Angioedema (Angioneurotic edema):
• Generalized, sudde .n o nset ,. .tife -thre at ,en ing edem,a ( beca us e
of upper respiratory t ract o bst ru ct io n ).
• Acquired (alle rgic; hist amine-b
-
[Link] ininl.
ne
• Hereditar,y {genet ic; abno r m al complement act ivat ion ).
• It am be itch)I o.r pain ful.

D. Nutritional edema: E. lymphath:: e de ma:

E
• Generalized, usuallyaffect infants • [Link],eralized., orloca/;ze d.

2
and children due to protein energy
• Non-pitti ngedema.
malnutrition.
• Example: Fil aria·ss.
• What are theother causes?

4..Hemorrhage
Definitlon: Ext ravasat io n of blood outs ide the ca rdiovas cu la r system.

Causes. e,1,[Link].

1. Traum tic :t he vasc ula r wal l.

2. Vessel wall disease.

3. Defect in the dotting factors or platelet s.

4. Gynecological and obstet ric: me nst rua l,

··-- --
+ IIICI IDUI

i rregular uterine bleeding, antepart um

he mo rrhage .

Types of hemorrhage:
A. ln1!e rs·t ttal Hem orrh age: Def. Es ca pe ,of blood into tisstll!-s.
• Acco rd ing t o size it is classified as:
1, Petet:hlae. 2. Purpura:
• Pin s head size (1 -2 mm.) • Sl ight l:y larger (3 -5 mm .).
• Sites: skin, mucous membranes and • Sites : Same as petechiae.
se rosal s u rfaces .
• Causes: Same as petechiae + vessel
• Causes : defect in plate lets or capillaries.
trauma, inflammation, fra1gilit y.
 References
Robbins Basic Pathology, 10th edition 2017, ELSEVIER, ISBN: 978-0-323-35317-5, by Kumar Vinay, Abbas Abul K.,
Aster Jon C
Webpath. [Link]