Ace Virgil F. Clemente BACON B Prof.

Razel Albano
BSN II-1

THROMBOSIS
Thrombosis refers to the formation of a clot from elements of the circulating blood
within the vascular system during life. This clot is known as a thrombus (plural,
thrombi). The development of a clot is life-saving when a large vessel ruptures or
is severed. However, when a thrombus develops within the vascular system, it
may be life-threatening because:

• -- It may decrease of obstruct vascular flow causing ischemic/hypoxic in-

jury to cells, tissues and organs.
• -- It may become dislodged or fragmented to create emboli (an embolus is
an intravascular mass carried in the bloodstream to some site removed
from its origin).

The ischemic necrosis created by a thrombus (embolus) is referred to as an in-

farct (thrombosis and embolism are so closely interrelated as to give rise to the
term thromboembolism). To a considerable extent, thrombosis is the con-
sequence of inappropriate activation of the processes of normal hemostasis.

HEMOSTASIS & THROMBOSIS

Hemostasis: Arrest bleeding. Physiologic response to vascular damage and

provides a mechanism to seal an injured vessel to prevent blood loss.

NOTE: Normal hemostasis is the result of a well-regulated process which main-

tains blood in a fluid, clot-free state within a normal vessel. Rapid clot formation
(hemostatic plug) will occur at vessel injury. The pathological form of hemostasis
is thrombosis where a clot (thrombus) forms within a vessel which is not injured.
Thrombosis can be considered an inappropriate activation of normal hemostatic
processes.
3 general components required for hemostasis and thrombosis

1. Vascular wall “ endothelial cells primarily

2. Platelets
3. Coagulation Cascade

NORMAL HEMOSTASIS
Sequence of events following vascular injury

1. Arteriolar vasoconstriction (transient effect)

Reflex neurogenic mechanism
Local secretion of endothelin

2. Primary hemostasis - PLATELET

Damage to the endothelium exposes platelets to the subendothelial extracellular
matrix (ECM).
Platelets adhere to the ECM and become activated (Activation)
a. Shape Change
b. Release granules
c. Recruit other platelets to site (Aggregation)
Form a HEMOSTATIC plug

3. Secondary Hemostasis - COAGULATION

a. Tissue factor, a membrane-bound procoagulant factor synthesized by en-

dothelium is exposed at the site of injury. It acts in conjunction with the
material secreted by platelets to activate the coagulation cascade.
b. Phospholipid complex expression
c. Thrombin activation
a. Formation of thrombin induces more platelet recruitment and gran-
ule release
d. Fibrin Polymerization – resulting in local fibrin admixed with platelets
Form plug to prevent further hemorrhage.
 4. Antithrombotic Counter-Regulation
a. Release of components to limit the size of hemostatic plug

ENDOTHELIAL FACTORS Injury to the endothelium is the major initiating event

for thrombosis and coagulation. Modulate many aspects of normal hemostasis.
The normal endothelium provides a surface that promotes the smooth, nonturbu-
lent flow of blood (antithrombotic). However when necessary the endothelium
produces and respond to substances to form a thrombus or blood clot. The en-
dothelium can also enhance vasodilation and inhibit platelet adhesion, aggrega-
tion and coagulation when necessary. Antithrombotic (Anticoagulant) Properties
of Endothelial Cells

THROMBOSIS and INFARCTION

PATHOGENESIS: - 3 primary influences - Virchows triad

1. Endothelial injury Dominant influence = can lead to thrombosis by itself
eg: inflammation of heart valves
Expose of subendothelial ECM, platelet adherence, release of tissue factor,
Depletion of prostacyclin, primary and secondary hemostatic plug formation.

2. Alterations in normal blood flow - turbulence or stasis

Normal blood flow is laminar - cellular elements in the middle, surrounded by
plasma.

Disrupt normal laminar flow

º allows platelets to contact endothelium
º Prevents dilution of activated clotting factors by fresh-flowing blood
º allows the build up of thrombi (slows the inflow of anticoagulants)
º promotes endothelial cell activation.

3. Hypercoaguability
Definition: any alteration of the coagulation pathways that predisposes to thom-
bosis.
8 Coagulation factors
9 Inhibitory factors

Endothelial injury plays a dominant role in the formation of thrombi in arteries and
in the heart. Once the endothelium is damaged, subendothelial collagen may be
exposed and tissue thromboplastic, etc., is released and the sequence of platelet
adherence and activation of the clotting sequence follows.

Alterations in Normal Flow as encountered with stasis and turbulence of blood

contributes to the development of arterial and cardiac thrombi and are probably
requisite for venous thrombosis. In the normal flowing bloodstream, the larger
particles, such as erythrocytes and leukocytes, occupy the central or more rap-
idly moving axial stream. The smaller platelets are carried in the more slowly
moving laminar stream outside the central column. The periphery of the blood-
stream adjacent to the endothelial layer moves more slowly and is free of all
formed blood elements. If stasis or turbulence occurs, this laminar flow is disrup-
ted and platelets are brought in contact with the endothelium. Evidence suggests
that stasis and turbulence assume the greatest degree of importance in the form-
ation of venous thrombi.

Alterations in blood that induce hypercoagulability have been proposed to explain

the increased incidence of thrombosis encountered in certain clinical states (fol-
lowing surgical procedures, parturition, accidental trauma, etc.) Hyper-coagulabil-
ity has been defined as "an altered state of circulating blood that requires a smal-
ler quantity of clot-promoting substances to induce intravascular coagulation than
is required to produce comparable thrombosis in a normal host." Increased num-
bers of platelets, increased platelet stickiness, elevated levels of fibrinogen, in-
creased generation of thrombin, etc., have been identified as causing hyperco-
agulability in various clinical conditions.
TERMINOLOGY AND MORPHOLOGY:

THROMBOSIS:
Formation, development or presence of a solid mass within the blood
vessels or heart. Adherent to the vascular endothelium and must be differentiated
from a simple (post mortem) blood clot.

THROMBUS:
An aggregation of blood factors, primarily platelets and fibrin with entrap-
ment of cellular elements, frequently causes vascular obstruction at the point of
its formation or embolism.

THROMBI:
Pleural of thrombus ie: several aggregations within the blood vascular
system. Thrombi may develop anywhere in cardiovascular system Cardiac cham-
bers, Valves, Arteries (usually endothelial injury), Veins (often a result of stasis),
Capillaries. Arterial thrombi are attached and grow away from the heart.

Venous thrombi are attached and grow in the direction of blood flow (to
heart). Arterial and venous thrombi differ in appearance.

ARTERIAL: Generally due to endothelial injury, initial thrombus is composed of

aggregated platelets with variable numbers of erythrocytes (RBC's) consequently
is soft, friable and red. As arterial thrombi grow, flow patterns adjacent to the
thrombi cause fibrin to be deposited and the platelet mass that persists is trans-
formed into a fibrin mass. Fibrin strands polymerize between the separating and
degenerating platelets. The alternating lines of yellow platelets and fibrin separat-
ing RBC's forms the lines of Zahn.

VENOUS: A venous thrombi is composed of fibrin strands with entrapped RBC's,

since the dominant mechanism of formation is coagulation.
OUTCOME OF THROMBI:

1. Lysis of thrombus (due to potent thrombolytic/fibrinolytic activity of blood).

2. Propagation of a thrombus (8 in size) - may eventually obstruct the vessel.
3. Embolization - possible.

4. Organization - The presence of a thrombus stimulates reaction which will res-

ult in inflammation and fibrosis. Smooth muscle cells and fibroblasts will prolifer-
ate and invade. The thrombus will become firm and grey-white.
and Recanalization - New lumina, lined by endothelial cells form to allow blood
flow through the damaged vasculature.

Embolism

EMBOLISM:
Passage through the venous or arterial circulations of any material cap-
able of lodging in a blood vessel and thereby obstructing the lumen. The usual
embolism is a thromboembolus. -or- Sudden blocking of an artery by a clot or for-
eign material which has been brought to its site of lodgment by the blood current.

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

EMBOLI:
Pleural of embolus, ie: several emboli become dislodged and travel
downstream of the blood current.

THROMBOEMBOLUS:
A thrombus formed in one location that detaches from the vessel wall
and travels to a distant site. (99% of all emboli arise from a thrombus).

THROMBOEMBOLISM:
 Obstruction of a blood vessel with thrombotic material carried by the
blood stream from the site of origin to plug another vessel.

EMBOLISM: Varies in composition - most are primarily fibrin (thrombi).

Etiology:
1. Parasites
A. Dirofilaria immitis
B. Nematode larvae
i) Ascarid larvae
ii) Strongyle larvae

2. Fibrocartilaginous emboli
A. Spinal cord infarcts
B. Origin intervertebral disk material
C. Necrotizing myelopathy

3. Fat
A. Bone fractures
B. Prolonged surgery
C. Osteomyelitis
D. Hyperlipidemia
i) "Lipid glomerulopathy"

4. Systemic infections
Any disease that causes widespread damage to endothelium
i) Bacterial diseases
ii) ii) Viral diseases eg: hog cholera (swine fever)
5. Other
- Air bubbles
- Hair
- Tumour cell clusters
- Amnionic fluid
HEMORRHAGE

Hemorrhage is the technical term for bleeding. It means a loss of blood

from the circulatory system by a ruptured or severed vessel. It may be arterial,
venous or capillary. Bleeding can occur internally, where blood leaks from blood
vessels inside the body or externally, either through natural opening such as
mouth, vagina and anus or through a break in the skin. The complete blood loss
is called exsanguinations while a massive blood loss is referred to as
desanguination.
Hemorrhage can be caused by trauma from some injuries such as the
following:

Abrasion
-caused by transverse action of a foreign object against the skin and
usually does not penetrate through the epidermis.

Hematoma
– caused by damage to a blood vessel that in turn cause blood to collect
under the skin.
Laceration
- irregular wound caused by blunt impact to soft tissues overlying hard
tissue or tearing such as in childbirth.
Incision
- a cut into a body tissue or organ.
Contusion
- also known as bruise. A blunt trauma damaging the tissue under the skin.

Symptoms of massive hemorrhage are related to hypovolemic shock:

rapid, thread pulse; thirst; cold, clammy skin; sighing respirations; dizziness;
syncope; pallor; apprehensions; restlessness; and hypotension. If bleeding is
contained within the cavity or joint, pain will develop as the capsule or cavity is
stretched by the rapidly expanding volume of blood.
ISCHEMIA

Ischemia is a restriction in blood supply generally due to factors in the

blood vessels, with resultant damage or dysfunction of tissue.

Rather than in hypoxia, a more general term denoting a shortage of

oxygen (usually a result of lack of oxygen in the air breathed), ischemia is an
absolute or relative shortage of the blood supply to an organ. Relative shortage
means the mismatch of blood supply (oxygen delivery) and blood request for
adequate oxygenation of tissue. Ischemia results in tissue damage because of
lack of oxygen and nutrients. Ultimately, this causes great damage because of
buildup of metabolic wastes. It can also be described as an inadequate flow of
blood to a part of a body, caused by constriction or blockage of the blood vessels
supplying it.

Ischemia can be due to:

Tachycardia
- abnormally rapid beating of the heart
Atherosclerosis
- lipid-laden plaques obstructing the lumen of the arteries.
Hypotension
- low blood pressure
Embolism
- foreign bodies in the circulation
Variations:
>Cardiac Ischemia
>Bowel Ischemia
HEART FAILURE

Physiology of heart failure

- Physiology of heart failure involves interplay between two factors:

● the inability of the failing heart to maintain sufficient cardiac

output to support body functions

● the recruitment of compensatory mechanisms designed to

maintain the cardiac reserve,

Cardiac Reserve
- it is the ability of the heart to increase cardiac output during increased
activity.

Cardiac Output
- it is the amount of blood that the heart pumps each minute.

Preload
- is used to describe the tension that exists in the walls of the heart as a
result of diastolic filling.
- reflects venous return and the filling of the ventricles and is the work load
that the heart encounters before it begins to contract.
- end-diastolic ventricular volume and end- diastolic ventricular pressure
are measures of preload.

Afterload
- represents the force that the contracting heart must generate to eject
blood from the filled heart. In the left heart, it represents all of the pre-ejection
work that the left ventricle must do to generate sufficient pressure to open the
aortic valve and eject blood into the aorta.
Cardiac contractility
- refers to the mechanical performance of the heart- the ability of the
contractile elements of the heart muscle to interact and shorten against load. The
ejection of blood from the heart during systole is dependent upon cardiac
contractility. Sympathetic stimulation of the heart increases cardiac contractility,
whereas hypoxia and ischemia decrease contractility. A decrease of cardiac
contractility can result from loss of functional muscle tissue due to myocardial
infarction or from conditions, such as cardiomyopathy, that diffusely affect the
myocardium.

COMPENSATORY MECHANISMS
In heart failure, the cardiac reserve is largely maintained through four
compensatory mechanisms: 1) sympathetic nervous system support
mechanisms;2) salt and water retention; 3) the Frank- Starling mechanism; 4)
myocardial hypertrophy. In the failing heart, early decreases in cardiac function
may go unnoticed because these compensatory mechanisms maintain the
cardiac output. This is called compensated heart failure,

●Sympathetic Nervous System Support

Both afferent cardiac sympathetic tone and catecholamines levels are
elevated during the late stages of most forms of heart failure. By direct
stimulation of both heart rate and cardiac contractility as well as by regulation of
vascular tone, the sympathetic nervous system helps to maintain perfusion of the
various organs, particularly the heart and the brain.

●Sodium and Water Retention

During heart failure, sodium and water retention increase vascular volume
and venous return to the heart in a misdirect effort to increase the ventricular
end-diastolic volume and cardiac output via the Frank- Starling Mechanism.

● Frank- Starling Mechanism

The Frank- Starling mechanism produces an increase in stroke volume by
means of an increase in ventricular end-diastolic volume (preload). With
increased diastolic filling, there is increased stretching of the myocardial fibers,
more optimal approximation of the actin and myosin filaments, and a resultant
increase in the force of the next contraction.
●Myocardial Hypertrophy
Myocardial hypertrophy is a long- term compensatory mechanism. Cardiac
muscle, like skeletal muscle, responds to an increase in work demands by
undergoing hypertrophy. Hypertrophy increases the number of contractile
elements in myocardial cells as a means of increasing their contractile
performance.

CONGESTIVE HEART FAILURE

● It is a state of circulatory congestion produced by myocardial dysfunction.
●MI compromises myocardial function by reducing contractility and producing
abnormal wall motion.
● The ability of the ventricle to empty lessens, the stroke volume falls, residual
volume increases.
● Heart failure is the inability of the heart to pump the amount of oxygenated
blood necessary to effect venous return and to meet the metabolic requirements
of the body.

TYPES OF HEART FAILURE

Heart failure may be described as high-output or low- output failure,
systolic or diastolic failure, and right-sided or left sided failure.

● High Output v.s. Low Output Level

High output failure- caused by excessive need for cardiac output. With
high output failure the function of the heart may be supra normal but inadequate
wing to excessive metabolic needs.
Low output failure- caused by disorders that impair the pumping ability of
the heart.

●Systolic v.s. Diastolic Failure

Systolic dysfunction- there is impaired ejection of blood from the heart
during systole.
Diastolic Dysfunction- there is impaired filling of the heart during diastole.
●Right Sided v.s. Left Sided Failure
Right Sided Failure
- The right heart moves deoxygenated blood from the systemic
circulation in to the pulmonary circulation; consequently, when the right heart
fails, there is accumulation or damming back of blood in the systemic venous
system. This causes an increase in right atrial, right ventricular end diastolic , and
systemic venous pressures, with subsequent development of edema in the
peripheral tissues and congestion of the abdominal organs.

Left Sided Heart Failure

- The left side of the heart moves blood from the low- pressure
pulmonary circulation in to the high- pressure arterial side of the systemic
circulation. With impairment of left heart function, there is a decrease in cardiac
output, an increase in left atrial and ventricular diastolic pressures, and
congestion in the pulmonary circulation.

MANIFESTATIONS
●Fluid Retention and Edema
●Respiratory Manifestations
●Fatigue and Weakness
●Cachexia and Malnutrition
●Cyanosis