Hemodynamic Disorders and Thromboembolic Disease and Shock pdf - د. نهلة

Hemodynamic Disorders, Thromboembolic

Disease, and Shock

OBJECTIVES



Edema



Hyperemia and Congestion



Hemorrhage



Hemostasis and Thrombosis



Embolism



Infarction



Shock

Definitions



Homeostasis

 maintaining blood as a liquid



Thrombosis

 Clotting at inappropriate sites



Hemostasis

 Clotting at appropriate site (site of

injury)



Embolism

 migration of clots



Infarction

 obstruction of blood flow to tissues

and leads to cell death



Hemorrhage

 inability to clot after vascular

injury



Shock

 extensive hemorrhage can result in

hypotension and death

•Normal fluid homeostasis is
maintained by

vessel wall integrity

intravascular

pressure

and

osmolarity

within certain physiologic ranges.

•Changes in

intravascular volume

pressure

,or

protein content

, or

alterations in endothelial function

will affect the movement of water
across the vascular wall

Edema

Increased fluid in the interstitial tissue spaces



Anasarca:

Severe and generalized edema + profound

subcutaneous swelling



Pathophysiology

Increased Hydrostatic Pressure



Most common cause -

Congestive heart failure

others - DVT

2. Decreased oncotic or osmotic Pressure

(hypoproteinemia)



Nephrotic syndrome, Cirrhosis, malnutrition, GIT.

3. Sodium retention



Renal failure, Renin- Angiotensin - Aldosterone

4. Inflammation: Acute or chronic,

5. Lymphatic obstruction



Type of edema



exudate

in inflammatory and

transudate

in non inflammatory conditions

• Increased Hydrostatic Pressure
• Localized increase in intravascular pressure

can result from impaired venous return

DVT, edema in distal portion of affected leg.
• Generalized increases in venous pressure with

resultant systemic edema occur most
commonly in congestive heart failure,
affecting right ventricular cardiac function

• In congestive heart failure, reduced cardiac

output translates into reduced renal perfusion

• Renal hypoperfusion triggers renin-

angiotensin- aldosterone axis, inducing
sodium and water retention by the kidneys.

• Mechanism normally increase intravascular

volume and thereby improve cardiac output
to restore normal renal perfusion.

• If the failing heart cannot increase cardiac

output, the extra fluid load causes increased
venous pressure and then edema

Edema - Pathogenesis

• Reduced plasma osmotic pressure: albumin

is the serum protein most responsible for
maintaining intravascular colloid osmotic
pressure.

• If there is albumin loss or inadequately

synthesized in diffuse liver disease, in each
case, reduced plasma osmotic pressure leads
to movement of fluid into interstitial tissues,
reduced intravascular volume leads to renal
hypoperfusion followed by secondary
aldosteronism. But the retained salt and
water cannot correct plasma volume deficit
generalized edema will occur.

Edema


Morphology

= Mostly involve

Subcutaneous tissues

Lung

Brain



Subcutaneous

– can be pitting (Cardiac or renal disorders) or

non

– pitting ( Thyroid disorders)



Pitting edema can be in dependent parts (at ankles in
ambulatory and Back or sacrum in bedridden patients-
cardiac disorders) nondependent area ( periorbital in renal
disorders)



Lung or Pulmonary edema

– Most common in Left Heart

failure, lungs are wet and heavy, pink frothy fluid in alveoli



Cerebral edema

–

localized ( Abscess, Neoplasms) /

Generalized ( Encephalitis), narrowed sulci and distended gyri,
fatal if edema develops rapidly (due to cerebellar or Tonsillar
Herniation)

Clinical significance

In Almost disorders causing edema, excess sodium re-absorption
( via Renin Angiotensin-Aldosterone pathway) is key factor
Treatment  

salt intake, Diuretics (↑sodium Excretion), Aldosterone

antagonists

Types of edema

•

Anasarca

:Generalized edema

•

Dependent edema:

Prominent feature of

congestive heart failure, particularly of the
right ventricle.

•

Renal edema:

Edema as aresult of renal

dysfunction or nephrotic syndrome is
generally more severe than cardiac
edema and affects all parts of the body
equally

•

Peri-orbital edema:

is acharacteristic

finding in severe renal disease.

•

Pitting

edema

:finger pressure over

substantially edematous
subcutaneous tissue displaces the
interstitial fluid and leaves a finger-
shaped depression

•

Pulmonary edema

: most typically

seen in the setting of left ventricular
failure

Fetal Anasarca

Hyperemia

and

Congestion

•Both indicate alocal increased
volume of blood in aparticular
tissue

Hyperemia

versus

congestion.

In both cases there is an increased
volume and pressure of blood in a
given tissue with associated capillary
dilatation and apotential for fluid
extravsation

Hyperemia:

active

process, increased in
flow leads to
engorgement with
oxygenated blood,
resulting in

erythema.

ngestion:

passive process
diminished outflow
leads to a capillary
bed swollen with
deoxygenated
venous blood and
resulting in

cyanosis.

Hyperemia

• Congestion and edema commonly occur

together .

• Chronic passive congestion: or long-standing

congestion, stasis of poorly oxygenated blood

cause

chronic hypoxia, degeneration or death

of parenchymal cells and subsequent tissue
fibrosis.

• Capillary rupture cause small foci of

hemorrhage, phagocytosis and catabolism of
erythrocyte debris results in accumulation of
hemosiderin-laden macrophages.

• Acute pulmonary congestion
• Alveolar capillary engorged with blood.
• Alveolar septal edema, and focal intra-

alveolar hemorrhage

• Chronic pulmonary congestion
• Septa thickened and fibrotic, alveolar spaces

contain numerous hemosiderin-laden
macrophages(heart failure cells)

• Acute hepatic congestion

• Central vein and sinusoids distended with blood,

and central hepatocyte degenerated but periportal
hepatocytes better oxygenate may develop fatty
change

• Chronic passive congestion
• Gross: central regions of hepatic lobule are red-

brown and depressed because of a loss of cells and
are accentuated against the surrounding zones of
uncongested tan, sometimes fattyliver (nutmeg liver)

• Mic: centrilobular necrosis, hemorrhage and

hemosiderin-laden macrophages.

• Hepatic fibrosis: (cardiac cirrhosis) in long standing

cases sever hepatic congestion in case of heart failure

Congestion

Varicose Veins

3-Hemorrhage

Extravasation of blood due to vessel
rupture .
Chronic congestion.
Rupture of a large A. due to vascular
injury, trauma, atherosclerosis,
inflammatory or neoplastic erosion

Types

•

Hematoma: accumulation

of blood

within tissue.

•

Petechiae:

minute 1 to 2 mm

hemorrhages into skin, mucous
membranes, or serosal surfaces.

•

Purpura:

slightly larger (≥3mm)

hemorrhages

Ecchymoses:

larger (>1to2cm)

subcutaneous hematomas (i.e.,bruises)

•

Hemothorax, hemopericardium,

hemoperitoneum, or hemarthrosis
(injoints):

Large accumulations of blood

in one of the body cavities

Petechial hemorrhages of the
colonic mucosa

Intracerebral bleeding

Subarachnoid Haemorrhage:

Petechiae &
Ecchymoses

Conjunctival Petechiae

Hemorrhage: Epidural hematoma

Hemothorax

4-Thrombosis

Hemostasis and Thrombosis

Normal hemostasis result of a set of
well regulated processes that
accomplish two important functions:

(1)

They maintain blood in a fluid, clot-

free state in normal vessels.

(2)

They are aimed to induce a rapid

and localized hemostatic plug at a site
of vascular injury

•

Thrombosis:

an inappropriate

activation of normal hemostatic
processes, such as the formation
of a blood clot

(thrombus)

uninjured vasculature

thrombotic occlusion of a vessel
after relatively

minor injury

Both

hemostasis

and

thrombosis

are

regulated by three general
components:-

–the vascular wall

–platelets

–the coagulation factors

Absence of B.V damage:

• Platelets repelled from each other and from

endothelium of B.V which is a simple squamous epi.
That overlies C.T collagen and other proteins that
are capable of activating platelets , so it separates
blood from collagen and other platelet activator.

• Endothelial cells also secrete prostacyclin PGI2(type

of prostaglandin) and nitric oxide(NO) which act as
vasodilators and also inhibit platelet aggregation.

• Plasma mem. of endothelial cells contains enzyme

CD39 which breakdown ADP in blood to AMP and
P1 (ADP is released from activated platelets and
promotes platelet aggregation)

Injury of blood vessel

• Platelet plasma mem. now able to bind to exposed collagen

fibers but the force of blood flow might pull the platelets off the
collagen

• Another protein produced by endothelial cells VON

WILLEBRAND factor which binds to both collagen andplatelet

• Platelet contains secretary granules when they stick to collagen,

they degranulate and release their products which include
(ADP, serotonin, and prostaglandin called thromboxane A2).
These products recruits new platelet to the vicinity and make
them sticky and stuck on other platelets on the collagen, and
those on 2

layer release their products and additional

platelets aggregate at the site of injury, this produce platelet
plug.

Platelet plug

• Activated platelets help to activate plasma clotting factors.
• Exposure of plasma to a negatively charged surface such as

collagen at the site of a wound, This activates a plasma protein
called factor X11 Hagmen factor which is a protein digesting
enzyme (protease).

• Active factor X11 I in turn activate another clotting factor, it

requires Ca and phospholipids which is provided by platelets,
these resulted in conversion of an inactive glycoprotein
prothrombin into active enzyme thrombin.

• Thrombin converts a soluble plasma protein fibrinogen into

insoluble fibrous protein fibrin, binding sites on platelets
plasma mem. Binds to fibrinogen and fibrin, which helps to join
them together and strengthen the plug.

•Three primary causes for thrombus
formation, theso-called

Virchow

triad:

(1)Endothelial injury
(2)Stasis or slowing of blood flow
(3)Blood hyper-coagulability

•

Virchow triad

in thrombosis.

Endothelial integrity

is the

single most important factor. Note that

injury to

endothelial

cells can affect local blood flow and/or

coagulability;

abnormal blood flow

(stasis or

turbulence) can, in turn, cause endothelial injury. The
elements of the triad may act independently or may
combine to cause thrombus formation.

• High blood flow rates might hamper

clotting by preventing platelet adhesion or
diluting coagulation factors.

•An area of attachment to the underlying

vessel or heart wall, frequently firmest at
the point of origin, is characteristic of all
thrombosis

•Thrombi may develop anywhere in the
cardiovascular system, but stasis is a
major factor in the development of
venous thrombi

Abnormal aortic and arterial dilations called
aneurysms create local stasis and a fertile site
for thrombosis

Acute myocardial infarction results in focally

noncontractile myocardium, ventricular
remodeling can lead to aneurysm formation

• Measurement of fibrin D-dimer are helpful in

diagnosing abnormal thrombotic states including
disseminated intravascular coagulation CIC, deep
venous thrombosis DVT, or pulmonary
thromboembolism PTI.

• Thrombus formation within the cardiac chambers

after endocardial injury due to myocardial
infarction, over ulcerated plaques in atherosclerotic
arteries, or at sites of traumatic or inflammatory
vascular injury, is largely a function of endothelial
injury. So exposure of subendothelial ECM, adhesion
of platelets, release of tissue factor, and local
deplation of PGI2, and plasminogen activators.

• However, it is important to note that endothelium

need not to denuded or physically disrupted to
contribute to the development of thrombosis, any
perturbation in the dynamic balance of the
prothrombotic and antithrombotic activities of
endothelium can influence local clotting events.

• Dysfunctional endothelium may elaborate greater

amounts of procoagulant factors like platelet
adhesion molecules, tissue factor, plasminogen
activator inhibitors or may synthesize fewer
anticoagulant effectors (thrombomodulin, PG2, t-PA)

• Endothelial dysfunction may occur with

hypertension, turbulent flow over scarred valves, or
by the action of bacterial endotoxins.

•The propagating tail may not be well
attached and, particularly in veins, is
prone to fragmentation, creating an
embolus.

•Mural thrombi-arterial thrombi that
arise in heart chambers or in the aortic
lumen, that usually adhere to the wall
of the underlying structure

Lines of Zahn:
alternating layers
of platelets and
fibrin in the
thrombus

•Mural thrombi. Thrombus in the left and
right ventricular apices, overlying awhite
fibrous scar.

Thrombosis

•Fate of the Thrombus.

1. Propagation: Thrombi accumulate additional

platelet and fibrin

2. Embolization: Thrombi dislodge or fragment
are transported elsewhere in the vasculature
3. Dissolution: Thrombi removed by fibrinolytic
activity
4. Organization and recanalization: Thrombi
induce inflammation and fibrosis, these can
eventually recanalize, or they can be
incorporated into a thickened vessel wall

•Potential outcomes of venous thrombosis.

Mural thrombi.

Laminated thrombus in a dilated abdominal
aortic aneurysm.

Dissolution of clots

• As damaged B.V wall is repaired, activated

factor X11 promotes the conversion of an
inactive molecule in plasma into the active
form called Kallikrein which in turn
catalyzes the conversion of inactive
plasminogen into the active molecule
plasmin .

• Plasmin is an enzyme that digests fibrin into

split products, promoting dissolution of the
clot.

5-Embolism

•An

embolus

is a detached intravascular solid,

liquid, or gaseous mass that is carried by the
blood to a site distant from its point of origin.

•

Emboli

lodge in vessels too small to permit

further passage, resulting in partial or complete
vascular occlusion

Pulmonary Thrombo-embolism

•95% of venous emboli originate from deep
leg vein thrombi above the level of knee,
carried through large channels and pass
through right side of the heart before entering
pulmonary vasculature.
May occlude the main pulmonary artery
impact across the bifurcation, saddle
embolus, or pass out into the smaller
branching arterioles.
patient who has had one pulmonary embolus
is at high risk of having more

•Large embolus
derived from a lower
extremity deep venous
thrombosis and now
impacted in a
pulmonary artery
branch.

Systemic Thromboembolism

•Emboli traveling within the arterial circulation.

•Most (80%) arise from intra-cardiac mural
thrombi,

•Two thirds of which are associated with left
ventricular wall infarcts and another quarter with
dilated left atria

•The major sites for arteriolar embolization:
1.

Lower extremities (75%)

Brain (10%)

A-Fat Embolism

•Microscopic fat globules may be
found in the circulation after fractures
of long bones (which have fatty
marrow) or, rarely, in the setting of soft
tissue trauma and burns

•Bone marrow embolus in the pulmonary circulation.
The cleared vacuoles represent marrow fat that is now
impacted in a distal vessel along with the cellular
hematopoietic precursors.

B-Air Embolism

•Gas bubbles within the circulation
can obstruct vascular flow.

•Enter the circulation during
obstetric procedures or as
aconsequence of chest wall injury.

•In excess of 100mL is required to
have a clinical effect

C-Amniotic Fluid Embolism

•Underlying cause is the infusion of
amniotic fluid or fetal tissue into the
maternal circulation via a tear in the
placental membranes or rupture of
uterine veins.

•Characterized by sudden severe
dyspnea, cyanosis, and hypotensive
shock, followed by seizures and coma.

6-Infarction

•An

infarct

is an area of ischemic necrosis

caused by occlusion of either the

arterial

supply

the venous

drainage

in a

particular tissue.

•Nearly 99% of all infarcts result from
thrombotic or embolic events, and almost
all result from arterial occlusion

•Infarcts are classified on the basis
of their

color

(reflecting the amount

of hemorrhage) and

the presence or

absence of microbial infection

•Red (hemorrhagic) infarcts occur

(1)

With venous occlusions (such as in

ovarian torsion);

(2)

In loose tissues (such as lung)

(3)

In tissues with dual circulations

(e.g.,lung and small intestine).

•White (anemic) infarcts occur

With arterial occlusions in solid organs
with end-arterial circulation (such as
heart,spleen,and kidney)

Examples of infarcts. (A)
Hemorrhagic, roughly wedge-
shaped pulmonary infarct. (B)
Sharply demarcated white infarct in
the spleen.

•The dominant histologic
characteristic of infarction is

ischemic coagulative necrosis

•most infarcts are ultimately replaced
by

scar tissue

•The brain is an exception to these
generalizations; ischemic injury in
the central nervous system results in
liquefactive necrosis

•

Septic infarctions

may develop

when embolization occurs by
fragmentation of a bacterial
vegetation from a heart valve or
when microbes seed an area of
necrotic tissue.

100

7-Shock

101

•Shock

, or

cardiovascular collapse

is the final common pathway for a
number of potentially lethal clinical
events, including severe
hemorrhage, extensive trauma or
burns, large myocardial infarction,
massive pulmonary embolism, and
microbial sepsis.

102

•gives rise to systemic hypo-
perfusion caused by reduction in:

1.Cardiac output
2.The effective circulating blood
volume.

•The end results are hypotension,
followed by impaired tissue
perfusion and cellular hypoxia

103

Type of shock

Clinical examples

Principal mechanism

Cardiogenic

-ventricular rupture
-arrythmia
-cardiac tamponade
-pulmonary embolism
-M.I

Failure of myocardial
pumps owing to intrinsic
myocardial damage,
extrinsic pressure,
or outflow obstruction in
pulmonary Embolism.

Hypo-volemic

-hemorrhage
-fluid loss ; e.g . Vomiting ,
diarrhea , burns , trauma

Inadequate blood or
plasma volume

Septic

-overwhelming microbial
infection
-endotoxic shock
-Gram positive septicemia
-Fungal sepsis.

Peripheral vasodilatation &
pooling of blood,
endothelial activation /
injury;leukocytes induced
damage;DIC ;activation of
cytokine cascade

104

Less commonly:

1.Neurogenic shock

-in the setting of

anesthetic accident or spinal cord injury,
owing to loss of vascular tone and
peripheral pooling of blood.

2.Anaphylactic shock,

initiated by a

generalized IgE-mediated
hypersensitivity response, is associated
with systemic vasodilatation and
increased vascular permeability

105

Clinical Course

•The clinical manifestations depend on the
precipitating insult.

•In

hypovolemic

and

cardiogenic shock

the patient presents with hypotension;
aweak, rapid pulse; tachypnea; and cool,
clammy, cyanotic skin.

•In

septic shock

, the skin may initially be

warm and flushed because of peripheral
vasodilation