Hemodynamic Disorders Quiz

Hemodynamic Disorders, Thrombosis, and Shock

• Cell and tissue health relies on intact circulation for oxygen delivery and waste removal.
• Normal fluid homeostasis keeps blood in a liquid state until clotting is necessary.

Hemostasis and Thrombosis

• Normal hemostasis involves processes that maintain clog-free blood flow while enabling localized clot formation at injury sites.
• Three components of hemostasis and thrombosis: vascular wall, platelets, coagulation cascade.

Endothelium

• Endothelial cells regulate both pro- and anti-thrombotic activities.
• Balance between these activities influences thrombus formation, propagation, or dissolution.
• Antithrombotic properties include:
  • Antiplatelet effects: Prevent platelets from adhering and aggregating.
  • Anticoagulant effects: Inhibition of the coagulation cascade via heparin-like molecules and thrombomodulin.
  • Fibrinolytic effects: Enable clot dissolution using plasminogen activator (t-PA).

Prothrombotic Properties

• Injury to endothelium promotes platelet adhesion through von Willebrand factor (vWF).
• Endothelial cells can produce tissue factor, initiating the extrinsic clotting cascade, especially in response to cytokines.
• Antifibrinolytic effects include secretion of plasminogen activator inhibitors (PAIs).

Platelets

• Central to normal hemostasis, platelets adhere to the extracellular matrix mediated by vWF.
• Platelet activation leads to granule secretion, releasing ADP, calcium, histamine, and other substances.
• Aggregation occurs through ADP and thromboxane A2 (TXA2), forming a reversible primary hemostatic plug.
• Thrombin enhances irreversible aggregation and converts fibrinogen to fibrin, solidifying the secondary hemostatic plug.

Coagulation Cascade

• Consists of a series of enzymatic conversions leading to thrombin production, which converts fibrinogen into fibrin.
• Restriction of coagulation to the injury site is critical to prevent excessive clotting.
• Natural anticoagulants like antithrombin III, proteins C and S, and tissue factor pathway inhibitor (TFPI) regulate this process.
• Fibrinolysis, primarily through plasmin, counteracts clot formation, ensuring balance.

Thrombus Characteristics

• Thrombus size and shape depend on origin and cause; arterial thrombi grow retrograde while venous thrombi follow blood flow.
• Thrombi show lines of Zahn, indicative of layered structure.
• Mural thrombi can occur in heart chambers and the aorta, often occlusive and composed of platelets and fibrin.

Clinical Correlations

• Venous thrombi lead to tissue congestion distal to blockages and can embolize to the lungs, posing a significant risk of death.
• Arterial thrombi are critical due to their potential to cause significant vascular obstruction, especially in coronary and cerebral vessels.
• Most venous thrombi occur in the legs, especially within deep veins, with superficial thrombi being less likely to embolize.

Embolism

• An embolus is a detached mass that travels through the bloodstream, often resulting from dislodged thrombi (thromboembolism).
• Other embolus types include fat droplets, air bubbles, cholesterol debris, and tumor fragments.
• Consequences of thromboembolism include tissue ischemia and necrosis (infarction).

Pulmonary Thromboembolism

• Incidence is 20 to 25 per 100,000 hospitalized patients, contributing to around 200,000 deaths annually in the U.S.
• Improvement noted in fatality rates from 6% to 2% over the past quarter century.