Hemodynamic disorders (2&3 of 3)
Hemodynamic disorders (2&3 of 3)
Thrombosis
-exposed ECM -tissue factor release -reduced production of: -PGI2 -plasminogen activators
Turbulent VS laminar flow
See next slide
Hypercoagulability states
More in venous thrombosis
The most common of genetic causes
2-15% of whites carry this mutation
Its allele is in 1-2% of general population
Also increases atherosclerosis
Inherited causes of hypercoagulability should be considered in young patients (<50 years of age), even when other acquired risk factors are present
More hepatic synthesis of coagulation factors and decreased synthesis of antithrombin III
Procoagulant tumor products
Also obesity Also aging
Less PGI2 & more platelet aggregation
Primary VS secondary
Immobilization-vascular Injury-procoagulant release-increased hepatic synthesis of coagulation factors-reduced t-PA production
Migratory thrombophlebitis …also called: ….
Morphology of thrombosis
• Arterial thrombi grow in a retrograde direction from the point of attachment
• Venous thrombi grow with blood flow direction
• Lines of Zahn: Gross/microscopic laminations…important
• Venous thrombi VS postmortem clots
• Thrombi on heart valves = vegetations…infective endocarditis or other causes of endocarditis (sterile endocarditis)
Fate of the thrombus
• Propagation
• Embolization
• Dissolution
• Organization and recanalization
Venous thrombosis (phlebothrombosis)
Mainly due to stasis or hypercoagulability
Disseminated intravascular coagulation
• Widespread activation of thrombin
• Many causes, such as obstetric complications or advanced malignancies
• Widespread microscopic thrombi followed by bleeding catastrophe
= consumption coagulopathy
Embolism
• Thromboembolism…systemic or venous…discussed before
• Gas embolism
• Amniotic fluid embolism
• Fat embolism
Fat embolism
• Long bone fractures and soft tissue crush injuries…<10% are clinically significant
• Vigorous cardiopulmonary resuscitation…mostly asymptomatic
• If symptomatic: -pulmonary insufficiency -neurologic symptoms -anemia -thrombocytopenia -diffuse petechial rash
Fatal in 10%
Fat embolism, mechanisms
• Both mechanical obstruction and biochemical injury
• Direct obstruction and platelet aggregation
• Fatty acid release…endothelial injury
• Granulocyte recruitment and the injury they cause
Amniotic fluid embolism
• Uncommon
• Mortality rate: 80%... the most common cause of maternal death in the developed world
• 85% of survivors suffer some form of permanent neurologic deficit
• Sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and coma
Amniotic fluid embolism, cont’d
• If survived initial crisis:
-pulmonary edema
-DIC (50%)…thrombogenic
substances from amniotic fluid
also may find lanugo hair, fat or mucin
Air embolism
• Examples:
-bypass surgery…coronary artery
-neurosurgery…cerebral artery
-venous such as in obstetric surgery or chest trauma…pulmonary
-decompression sickness
• The bends, chokes, and caisson disease
Red VS white infarcts
Shock
= systemic hypoperfusion of tissues
Other causes of shock
• Neurogenic…anesthesia or spinal cord injury
…loss of vessel tone
• Anaphylactic shock…IgE-mediated hypersensitivity
…systemic vasodilation and increased permeability
Septic shock
• The most common cause of death in intensive care units
• 20% mortality rate
• The most common cause: Gram (+) bacteria
• Not necessary for the microbe to disseminate via blood
Septic shock mechanisms
• Vasodilation…tissue hypoperfusion
• Widespread endothelial cell activation and DIC
• If no microbial cause: systemic inflammatory response syndrome
(SIRS)
…extensive trauma or burns
…pancreatitis
…diffuse ischemia
Septic shock mechanisms, cont’d
• Innate response TNF, IL-1, ROS, lipid mediators, PAF & complement activation…etc.
• The derangement in coagulation is sufficient to produce disseminated intravascular coagulation in up to half of septic patients
**The resultant hypoperfusion and ischemia will cause multiorgan
failure
Stages of shock
• Nonprogressive stage:
…reflex compensatory mechanisms are activated
…vital organ perfusion is maintained
• Progressive stage:
…hypoperfusion
…onset of worsening circulatory and metabolic derangement, including acidosis
• Irreversible stage:
…cellular and tissue injury is so severe
…even if the hemodynamic defects are corrected, survival is not possible