‫بسم هللا الرحمن الرحيم‬

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General pathology
Circulatory
disturbance 2
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Mehad Alfatih Alashir

 Thrombosis
There are three primary influences on thrombus
formation (called Virchow's triad): (1)
Endothelial injury.
(2) Stasis or turbulence of blood flow.
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(3) Blood hypercoagulability

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 1.Endothelial injury :
Loss of endothelium leads to exposure of
subendothelial ECM, adhesion of platelets,
release of tissue factor, and local depletion of
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PGI2 and plasminogen activators

 2.Alterations in Normal Blood Flow
Normal blood flow is laminar, such that platelets
flow centrally in the vessel lumen, separated from
the endothelium by clear zone of plasma.
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Stasis and turbulence disrupt laminar flow and

bring platelets into contact with the endothelium
promote endothelial cell injury, resulting in local
thrombosis, leukocyte adhesion, etc.
 3.Hypercoagulability :
Defined as any alteration of the coagulation
pathways that predisposes to thrombosis, and
it can be divided into primary (genetic) and
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secondary (acquired) disorders.

 Examples Hypercoagulability states:
Primary (Genetic)
Mutation in factor V gene (factor V Leiden).
Mutation in prothrombin gene.
Antithrombin III deficiency .
Protein C deficiency.
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Protein S deficiency .
Secondary (Acquired)
High risk for thrombosis Prolonged bed rest or immobilization
Myocardial infarction.
Tissue damage (surgery, fracture, burns).
Cancer.
 Examples of thrombosis:
Arterial thrombi
Produced by platelet and coagulation
activation; they are typically a friable
meshwork of platelets, fibrin, erythrocytes,
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and degenerating leukocytes.

Usually superimposed on an atherosclerotic
plaque, other vascular injury (vasculitis,
trauma).
 Venous thrombosis
Result of activation of the coagulation cascade, and
platelets play a secondary role.
Because these thrombi form in venous circulation, they
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contain more erythrocytes and are therefore called red,

or stasis, thrombi.
The veins of the lower extremities are most commonly
affected (90% of venous thromboses).
-Phlebothrombosis(e.g in varicose veins)
-Deep venous thrombosis
 Mural thrombi:
Thrombi occurring in heart chambers or in the
aortic lumen.
caused by:
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Abnormal myocardial contraction.

Endomyocardial injury.
Ulcerated atherosclerotic plaques.
Aneurysmal dilation of the aorta.
 Vegetations :
Thrombi on heart valves .
Bacterial or fungal blood-borne infections can
cause valve damage, subsequently leading to
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large thrombotic masses (infective

endocarditis). Sterile vegetations can also
develop on noninfected valves in
hypercoagulable states, so-called nonbacterial
thrombotic endocarditis
 Fate of the Thrombus :
1.Propagation:
Thrombi accumulate additional platelets and fibrin, eventually
causing vessel obstruction
2.Embolization:
Thrombi dislodge or fragment and are transported elsewhere in
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the vasculature
3.Dissolution:
Thrombi are removed by fibrinolytic activity.
4.Organization and recanalization:
Thrombi induce inflammation and fibrosis (organization). These
can eventually recanalize (re-establishing some degree of flow)
 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 resulting in partial or
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complete vascular occlusion

 The consequences of embolism include
ischemic necrosis (infarction) of downstream
tissue.
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Clinical outcomes of emboli depending on the

site of origin, and lodge of in the vascular
tree.
 Examples of embolism :
1. Pulmonary embolism
Emboli originate from deep leg vein thrombi
above the level of the knee . They are carried
through progressively larger channels and pass
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through the right side of the heart before entering

the pulmonary vasculature. Depending on the size
of the embolus, it may occlude the main
pulmonary artery, impact across the bifurcation or
pass out into the smaller, branching arterioles .
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 2.Systemic Thromboembolism
Is emboli in the arterial circulation. Arise from
intracardiac mural thrombi, aortic
aneurysms, thrombi on ulcerated
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atherosclerotic plaques, or fragmentation of

valvular vegetations .
 • The major sites for arteriolar embolization are
the lower extremities (75%) and the brain
(10%), with the intestines, kidneys, and
spleen affected to a lesser extent.
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 3.Fat Embolism
Microscopic fat globules can be found in the
circulation after fractures of long bones or after
soft-tissue trauma.
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Fat embolism syndrome is characterized by

pulmonary insufficiency, neurologic symptoms,
anemia, and thrombocytopenia. Typically, the
symptoms appear 1 to 3 days after injury.
 4.Air Embolism
Gas bubbles within the circulation can
obstruct vascular flow . Air may enter the
circulation during obstetric procedures or as a
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consequence of chest wall injury. Generally,

more than 100 mL of air are required to
produce a clinical effect.
 INFARCTION
Is an area of ischemic necrosis caused by
occlusion of either the arterial supply or the
venous drainage in a particular tissue.
Tissue infarction is a common and extremely
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important cause of clinical illness.

 Types:
(i)Red infarcts
(1) with venous occlusions (such as in ovarian
torsion).
(2) in loose tissues (such as lung).
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(3) in tissues with dual circulations such as

lung and small intestine.
 (ii)White infarcts
Occur with arterial occlusions or in solid
organs (such as heart, spleen, and kidney),
where the solidity of the tissue limits the
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amount of hemorrhage.
 (iii)Septic infarctions
Occur when microbes seed an area of necrotic
tissue. In these cases the infarct is converted
into an abscess, with greater inflammatory
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response.
 Red and white infarcts.
A, Hemorrhagic, roughly wedge-shaped pulmonary infarct (red infarct).
B, Sharply demarcated pale infarct in the spleen (white infarct).
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 Examples of infarctions:
1.Myocardial infarction caused by occlusion of
coronary arteries.
2.Pulmonary infarction is a common
complication in several clinical settings.
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3. bowel infarction .
4.Ischemic necrosis of the extremities
(gangrene) is a serious problem in diabetics.
 Gangrenous necrosis
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 SHOCK
• Shock is the final common pathway for a
number of potentially lethal clinical events.
Regardless of the underlying pathology, shock
gives rise to systemic hypotension, impaired
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tissue perfusion, and cellular hypoxia.

 It can be caused either by reduced cardiac
output or by reduced effective circulating
blood volume and microbial sepsis.
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It has tree types cardiogenic, hypovolemic

and septic shock.
 Causes:
Type of Shock
Myocardial infarction
Ventricular rupture
Arrhythmia
Cardiac tamponade
Cardiogenic Pulmonary embolism
Hypovolemic Hemorrhage
Fluid loss (e.g., vomiting,
diarrhea, burns, or trauma)
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Septic Overwhelming microbial
infections
Endotoxic shock
Gram-positive septicemia
Fungal sepsis
Superantigens (e.g. toxic
shock syndrome)
Principal Mechanisms
Failure of myocardial pump
resulting from intrinsic
myocardial damage,
extrinsic pressure, or
obstruction to outflow
Inadequate blood or
plasma volume
Peripheral vasodilation and
pooling of blood;
endothelial
activation/injury;
leukocyte-induced damage;
disseminated intravascular
coagulation; activation of
cytokine cascades.
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 Stage of shock:
1. An initial non progressive stage during which
reflex compensatory mechanisms are activated
and perfusion of vital organs is maintained.
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2. A progressive stage characterized by tissue

hypoperfusion and onset of worsening
circulatory and metabolic imbalances.
 • 3.An irreversible stage that the body has
incurred cellular and tissue injury and even if
the hemodynamic defects are corrected,
survival is not possible
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 Effects of shock :
• The cellular and tissue changes induced by
shock are essentially those of hypoxic injury ,
due to combination of hypoperfusion and
microvascular thrombosis.
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• Shock is characterized by failure of many

organ systems, particularly evident in the
brain, heart, kidneys, adrenal glands, and
gastrointestinal tract
 • The adrenal changes in shock there is cortical
cell lipid depletion.
• The kidneys typically reveal acute tubular
necrosis so that oliguria, anuria, and
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electrolyte disturbances dominate the clinical

picture.
• The gastrointestinal tract may mainfest focal
mucosal hemorrhage and necrosis.
 • The lungs are seldom affected in pure
hypovolemic shock, because they are
somewhat resistant to hypoxic injury. However,
when shock is caused by bacterial sepsis or
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trauma, changes of diffuse alveolar damage

may develop.
• Unfortunately, most patients with irreversible
changes due to severe shock die before the
tissues can recover.
 The clinical manifestations of shock:

Depend on the precipitating factor.

In hypovolemic and cardiogenic shock, the
patient presents with:
hypotension; a weak, rapid pulse; tachypnea;
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and cool, cyanotic skin.

In septic shock, in addition the skin may be
warm and flushed as a result of peripheral
vasodilation.
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