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