Hemodynamic disorders 2
Thrombosis
• Thrombosis Is the formation of blood clot inside blood vessels.
• Both hemostasis and thrombosis involve three components:
1. Vascular wall.
2. Platelets.
3. Coagulation cascades.
Pathogenesis of thrombus
• There are three primary abnormalities that lead to thrombus
formation called Virchow’s triad.
1. Endothelial injury.
2. Stasis or turbulence of blood flow.
3. Blood hypercoagulability.
1. Endothelial injury
• Is an important cause of thrombosis, particularly in the heart and
arteries.
• Normally high flow rates of blood in the heart and the arterial
circulation prevent clotting by preventing platelets adhesion or
diluting coagulating factors.
• Physical loss of endothelium lead to exposure of subendothelium
ECM, adhesion of platelets, release of coagulating factors that help in
thrombus formation.
• Location of thrombus-within cardiac chambers after myocardial
infarction, over ulcerated plaques in atherosclerotic arteries., at site
of traumatic or inflammatory vascular injury ( vasculitis).
2. Alteration in normal blood flow
• Turbulence contribute to thrombosis by causing endothelial injury or
dysfunction, as well as by forming countercurrent and local pockets of
stasis.
• Stasis is the major contributor to the development of venous
thrombie, normal blood flow is laminar, such as platelets flow
centrally in the vessel lumen, separated from endothelium by a
slower moving clear zone of plasma.
• Stasis and turbulence will: disrupt laminar flow, prevent dilution of
activated clotting factors, retard the inflow of clotting factor inhibitors
and promote endothelial cell injury leading to platelet adhesion
• Causes of turbulence and stasis:
1. Ulcerated atherosclerotic plaque-.
2. Abnormal aortic or arterial dilatation called aneurysm.
3. Acute myocardial infarction lead to focally noncontractile
myocardium.
4. Mitral valve stenosis.
5. Hyper viscosity syndrome ( such as polycythemia) increase
resistance to flow and cause small vessels stasis.
6. Deformed red cells in sickle cell anemia cause vascular
occlusions
3. Hypercoagulability.
• It is any alteration of coagulation pathway that predispose to
thrombosis.
• It is contribute infrequently to arterial or intracardiac thrombosis but
important underlying risk factor for venous thrombosis and can be
divided into:
1. Primary ( genetic) disorders like mutation in the factor V gene and
the prothrombin gene.
2. Secondary (acquired) disorders, the pathogenesis frequently
multifactorial and more complicated and include:- cardiac failure,
oral contraceptive use and pregnancy due to increase hepatic
synthesis of coagulation factors, disseminated cancer due to
procoagulatory tumor products, smoking and obesity also cause
hypercoagulation.
Morphology of thrombus
• Thrombosis can have grossly and microscopically apparent
laminations called lines of Zahn; these represent pale
platelets and fibrin layers alternating with darker erythrocyte
rich layers.
• These lines distinguish antemorten thrombosis from the
bland nonlaminated clots that occur in postmortem state.
Types of thrombus
1. Mural thrombus: occur in heart chamber or in the aortic lumen and
caused by .
a. Arrhythmia and myocardial infarction causing abnormal myocardial
contraction.
b. Myocarditis or catheter trauma causing endomyocardial injury.
c. Ulcerated atherosclerosis plaque and aneurysmal dilatation.
2. Arterial thrombi: frequently occlusive and produced by platelet and
coagulation factor activation; they are typically friable meshwork of
platelets, fibrin, erythrocytes and degenerating leukocytes, caused by
vascular injury (vasculitis) or atherosclerosis plaque .
3. Venous thrombosis (phlebothrombosis: almost occlusive,
result of coagulation cascade activation, platelets play
secondary role, vein of lower limb are most commonly
affected.
4. Vegetation: thrombi on heart valves, bacterial and fungal
blood borne infection can cause valve damage, subsequently
leading to large thrombotic masses ( infective endocarditis)
Fate of thrombus
1. propagation: thrombi accumulate more platelets and fibrin
causing vessels obstruction.
2. Embolization: thrombi dislodged or fragmented and are
transported elsewhere in the vasculature.
3. Dissolution: thrombi removed by fibrinolytic activity which
leads to rapid shrinkage and even total lysis of recent
thrombi.
4. Organization and recanalization: thrombi induce
inflammation and fibrosis with recanalization
Embolism
• Detached intravascular solid, liquid or gaseous mass carried by the
blood to a site distant from its point of origin.
• 99% of all emboli represent dislodged
thrombus so called
thromboembolism.
• Rare emboli includes fat droplets, bubbles of air or nitrogen (chest
wall injury), cholesterol emboli, tumor fragments, bits of bone
marrow, or foreign bodies.
• Emboli lodged in vessels too small to permit further passage, resulting
in partial or complete vascular occlusion end in ischemic necrosis
(infarction) ofg downstream tissue.
Fat embolism
• Microscopic fat globules can be found in circulation after
fractures of long bones (which contain fatty marrow) or after
soft tissue trauma.
• Although fat and marrow embolism occur in some 90% of
individuals with sever skeletal injuries, fewer than 10% of
such patients show any clinical finding.
Infarction
• Area of ischemic necrosis caused by occlusion of either the
arterial supply or the venous drainage in a particular tissue.
• Nearly 99% of all infarcts result from thrombotic or embolic
event, and almost all result from arterial occlusion.
• Morphology classified on the basis of their color (reflecting
amount of hemorrhage ) and presence and absence of
microbial infection, therefore, infarcts may be either red
(hemorrhagic) or white (anemic) and may be either septic or
non septic.
Morphology
• Dominant histological features of infarction is ischemic
coagulative necrosis.
• In stable or labile tissue, parenchymal regeneration can
occur in periphery. However most infarct are ultimately
replaced by scar.
• The brain is an exception to these generalization; where
liquefactive necrosis occur.
Factors that influence development of infarct
1. Nature of vascular supply: presence of alternative blood supply is
the most important, lung, liver, hand, forearm have a double
arterial supply; all are resistant to infarct, while kidney and spleen
has end-arterial blood supply so obstruction generally cause infarct.
2. Rate of occlusion development: slow developing occlusions are less
likely to cause infarct.
3. Tissue susceptibility to hypoxia: neurons undergo irreversible
damage when deprived of blood supply for only 3-4 min,
myocardial cells are also sensitive and die after20-30 min of
ischemia, in contrast fibroblasts remain viable after many hours.
4. Oxygen content of blood: anemic and cyanotic patient more liable
to tissue infarct.
Shock
• Final step for a number of potentially lethal clinical events including :
1. Sever hemorrhage.
2. Extensive trauma or burn.
3. Large myocardial infarct.
4. Large pulmonary embolism.
5. Microbial sepsis.
• Regardless underlying pathology, shock lead to systemic
hypoperfusion caused either by decrease cardiac output or by reduce
circulatory blood volume.
Types of shock
1. Cardiogenic shock: cardiac pump failure caused by myocardial
infarction, pulmonary embolism and ventricular arrhythmia.
2. Hypovolemic shock: blood loss may be caused by hemorrhage,
sever burn, fluid loss or trauma.
3. Septic shock: by microbial infection, gram positive and negative or
fungal infection.
4. Neurogenic shock: spinal cord injury or anesthetic accident.
5. Anaphylactic shock: systemic vasodilatation and increase vascular
permeability caused by immunoglobulin E hypersensitivity reaction.
Morphology
• Shock will induce cellular and tissue necrosis due to hypoxia
or combination of decrease blood supply and fibrin thrombi
which may be identified in any tissue, mostly visualized in
kidney glomeruli.