Hemodynamic disorders (2&3 of 3) Ali Al Khader, M.D. Faculty of Medicine Al-Balqa’ Applied University Email: ali.alkhader@bau.edu.jo

Thrombosis See next slide -exposed ECM -tissue factor release -reduced production of: -PGI2 -plasminogen activators Thrombosis Turbulent VS laminar flow See next slide

Hypercoagulability states More in venous thrombosis 2-15% of whites carry this mutation The most common of genetic causes Its allele is in 1-2% of general population Immobilization-vascular Injury-procoagulant release-increased hepatic synthesis of coagulation factors-reduced t-PA production Hypercoagulability states Also increases atherosclerosis Procoagulant tumor products Migratory thrombophlebitis …also called: …. Primary VS secondary More hepatic synthesis of coagulation factors and decreased synthesis of antithrombin III Inherited causes of hypercoagulability should be considered in young patients (<50 years of age), even when other acquired risk factors are present Also obesity Also aging Less PGI2 & more platelet aggregation

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 also may find lanugo hair, fat or mucin If survived initial crisis: -pulmonary edema -DIC (50%)…thrombogenic substances from amniotic fluid

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

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