Hemodynamic Disorders and Thrombosis Quiz

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Questions and Answers

What physiological factor can influence local clotting events without physical disruption of the endothelium?

Loss of muscle tone

Formation of new blood vessels

Alterations in normal blood flow (correct)

Elevated blood pressure

Which condition is NOT classified as a condition leading to hypercoagulability?

High blood sugar (correct)

Prolonged bedrest

Cancer

Atrial fibrillation

Where can thrombi develop within the cardiovascular system?

In all parts including cardiac chambers, valves, and capillaries (correct)

Only in veins

Only in the aorta

Only in arteries

What characteristic is commonly associated with arterial thrombi?

Tendency to grow in a retrograde direction Signup and view all the answers

What term describes thrombi that are attached to the wall of the heart or aorta?

Mural thrombi Signup and view all the answers

How do venous thrombi primarily differ from arterial thrombi?

They contain more enmeshed erythrocytes Signup and view all the answers

What is the primary cause of stasis that contributes to venous thrombus formation?

Prolonged immobility Signup and view all the answers

Which of these describes a characteristic of thrombi that contain apparent laminations?

They are called lines of Zahn Signup and view all the answers

What can occur as a result of deep venous thrombosis in larger leg veins?

Embolization Signup and view all the answers

Which condition is most likely associated with cardiac mural thrombi?

Atrial fibrillation Signup and view all the answers

What mainly contributes to the formation of arterial thrombi?

Loss of endothelial integrity Signup and view all the answers

What characteristic distinguishes venous thrombi from arterial thrombi?

Venous thrombi are less significant in vascular obstruction. Signup and view all the answers

What is the definition of an embolus?

A solid or liquid mass carried by blood from a distant site Signup and view all the answers

In venous thrombosis, which type of vein is most commonly involved?

Saphenous vein Signup and view all the answers

What is the primary role of endothelial cells in hemostasis?

To prevent clot formation under normal conditions Signup and view all the answers

What is the primary concern regarding embolization from venous thrombi?

They can embolize to the lungs. Signup and view all the answers

Which of the following substances produced by endothelial cells has an antiplatelet effect?

Adenosine diphosphatase Signup and view all the answers

What role does atherosclerosis play in thrombosis?

It initiates thrombosis by affecting endothelial function. Signup and view all the answers

What triggers the procoagulant activities of endothelial cells?

Endothelial cell activation or injury Signup and view all the answers

What is the main function of tissue factor in hemostasis?

To activate the extrinsic clotting cascade Signup and view all the answers

How do endothelial cells contribute to fibrinolysis?

By synthesizing plasminogen activator (t-PA) Signup and view all the answers

What effect does an intact endothelium have on the immune response?

It inhibits platelet function and prevents inflammation. Signup and view all the answers

Which condition might lead to enhanced prothrombotic activities of endothelial cells?

Injury to the endothelial layer Signup and view all the answers

Which of the following is NOT a characteristic of normal hemostasis?

Inflammation at the site of injury Signup and view all the answers

What role do platelets play in hemostasis?

They centralize the formation of blood clots. Signup and view all the answers

Which mediator is primarily involved in platelet adhesion?

Von Willebrand factor (vWF) Signup and view all the answers

What is the purpose of ADP in platelet aggregation?

To promote enlargement of platelet aggregation. Signup and view all the answers

How does thrombin contribute to the stability of the hemostatic plug?

By converting fibrinogen into fibrin. Signup and view all the answers

What result does the interaction of thrombin with its receptor induce?

Irreversible platelet aggregation. Signup and view all the answers

What characterizes the primary platelet aggregation?

It is reversible. Signup and view all the answers

What describes the coagulation cascade?

It amplifies signals for local clot formation. Signup and view all the answers

What is the final product of the coagulation cascade?

Fibrin monomers Signup and view all the answers

What is the primary source of venous emboli in over 95% of cases?

Deep leg vein thrombi above the knee Signup and view all the answers

What is a common consequence of pulmonary embolism when 60% or more of the pulmonary circulation is obstructed?

Sudden death Signup and view all the answers

Which of the following conditions is NOT a predisposing factor for deep vein thrombosis (DVT)?

Frequent exercise Signup and view all the answers

What percentage of systemic thromboembolism is associated with left ventricular wall infarcts?

67% Signup and view all the answers

What treatment is commonly used for deep vein thrombosis?

Intravenous heparin Signup and view all the answers

What is the annual death toll attributed to pulmonary embolism in the United States?

200,000 deaths Signup and view all the answers

What is a common consequence of fat embolism from fractures of long bones?

Fat globules in circulation Signup and view all the answers

Which of the following is a major site affected by systemic thromboembolism?

Lower extremities Signup and view all the answers

What is the role of antithrombins in the clotting process?

They inhibit thrombin and other serine proteases. Signup and view all the answers

Which proteins are involved in the inactivation of cofactors Va and VIIIa?

Proteins C and S Signup and view all the answers

What initiates the generation of plasmin from plasminogen?

Enzymatic degradation by activators Signup and view all the answers

What prevents free plasmin from indiscriminate lysing of thrombi in the body?

α2-antiplasmin Signup and view all the answers

What are the primary influences on thrombus formation known as Virchow's triad?

Endothelial injury, stasis or turbulence of blood flow, and blood hypercoagulability Signup and view all the answers

What is the primary function of fibrinolysis?

To break down fibrin and moderate clot size Signup and view all the answers

How is plasminogen activated to plasmin?

By plasminogen activators Signup and view all the answers

What is the function of tissue factor pathway inhibitor (TFPI)?

To inhibit the clotting cascade Signup and view all the answers

Study Notes

Hemodynamic Disorders, Thrombosis, and Shock

The health of cells and tissues depends on an intact circulation to deliver oxygen and remove wastes, and on normal fluid homeostasis. Normal fluid homeostasis means maintaining blood as a liquid until clot formation is essential.
Normal hemostasis results from tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels, while inducing rapid formation of a localized hemostatic plug at the site of vascular injury.
Hemostasis and thrombosis both involve three components: the vascular wall, platelets, and the coagulation cascade.

Hemostasis and Thrombosis: Vasoconstriction

Vasoconstriction: Endothelin release causes vasoconstriction.
This reduces blood flow to the injured area, limiting blood loss

Hemostasis and Thrombosis: Primary Hemostasis

Platelet adhesion: Platelets adhere to the exposed collagen in the vascular wall. Von Willebrand factor facilitates this.
Shape change: Platelets change shape, becoming stickier.
Granule release: Platelets release ADP and TXA₂, promoting further platelet aggregation.
Recruitment: Platelets aggregate (clump together) forming a hemostatic plug.
This plug stops or slows blood loss.

Hemostasis and Thrombosis: Secondary Hemostasis

Tissue factor expression: Tissue factor is exposed when the endothelium is damaged.
Phospholipid complex expression: This enhances interactions between clotting factors.
Thrombin activation: Thrombin activation leads to fibrin polymerization.
Fibrin polymerization: Fibrin forms a meshwork, further strengthening the hemostatic plug.

Thrombus and Antithrombotic Events

Release of t-PA (tissue plasminogen activator): Fibrinolysis(breaking down fibrin) is initiated.
Thrombomodulin: Blocks coagulation cascade
Trapped neutrophils & red blood cells: The thrombus becomes visible.
Polymerized fibrin: The blood clot's final stage

Endothelium

Endothelial cells modulate (influence and regulate) the opposing aspects of normal hemostasis.
Anti- and prothrombotic activities of endothelial cells regulate thrombus formation, propagation, or dissolution.
Endothelial cells have antiplatelet, anticoagulant, and fibrinolytic properties at baseline that can become procoagulant after injury or activation.

Antithrombotic Properties

Endothelial cells maintain a liquid blood flow environment under most circumstances by blocking platelet adhesion and aggregation, inhibiting the coagulation cascade, and lysing blood clots.
Antiplatelet effects, anticoagulant effects, and fibrinolytic effects are critical.

Antiplatelets

In the presence of an intact endothelium, platelets and coagulation factors don't interact with the highly thrombogenic subendothelial ECM.
Prostacyclin (PGI₂) and nitric oxide.
Adenosine diphosphatase.
Heparin-like molecules and thrombomodulin.

Fibrinolytic Properties

Plasminogen Activator (tPA).
The Extrinsic coagulation sequence and the tissue factor sequence lead to favoring thrombosis.
There is also an inhibitory pathway to limit thrombosis.

Prothrombotic Properties

Endothelial injury leads to platelet adhesion. This is facilitated by von Willebrand factor (vWF).
Endothelial cells can produce procoagulant effects in response to injury or activation by bacterial endotoxin or cytokines (e.g., TNF, IL-1). Tissue factor is synthesized in these cases.
Endothelial cells can have antifibrinolytic effects by secreting inhibitors of plasminogen activator (PAIs).

Platelets

Platelets play a central role in normal hemostasis
Platelet adhesion to the ECM is primarily mediated by interactions with vWF, acting as a bridge between platelet surface receptors (e.g., Gplb) and exposed collagen.
Platelet activation increases the expression of phospholipid complexes.
Dense body contents such as ADP and ATP, calcium, histamine, serotonin, and epinephrine are released.

Platelet Aggregation

Platelet aggregation follows adhesion and granule release.
ADP and thromboxane A2 promotes platelet aggregation which forms the primary hemostatic plug.
This primary aggregation, is reversible.
Thrombin binding to platelet surface receptors (PARs) leads to irreversible aggregation and platelet contraction, leading to the secondary hemostatic plug. Fibrinogen is converted to fibrin.

Coagulation Cascade

The coagulation cascade is a series of enzymatic reactions that amplify the activation process.
Inactive proenzymes are proteolytically cleaved, leading to activated enzymes, eventually resulting in thrombin.
Thrombin converts soluble fibrinogen into insoluble fibrin, which forms a meshwork entrapping platelets and other cells, creating the secondary hemostatic plug.
To prevent runaway clotting, the coagulation cascade must be restricted to the injury site with natural anticoagulants.

Antithrombins

Antithrombins, such as antithrombin III, inhibit thrombin and other serine proteases (factors IXa, Xa, Xla, and XIla).
Proteins C and S are vitamin K-dependent proteins and inactivate cofactors Va and VIIIa.
Tissue factor pathway inhibitor (TFPI) limits clotting.

Fibrinolysis

Activation of the clotting cascade initiates a fibrinolytic cascade that limits the size of the clot.
Plasmin breaks down fibrin and interferes with polymerization
Plasmin is generated by enzymatic degradation of plasminogen, activated by factor XII-dependent pathways or by plasminogen activators (t-PA being most important).

Thrombosis

Three primary influences (Virchow's triad) affect thrombus formation: endothelial injury, abnormal blood flow (stasis or turbulence), and hypercoagulability.

Thrombosis: Endothelial Injury

Endothelial injury is important in thrombus formation in the heart or arterial circulation.
Any disturbance of prothrombotic and antithrombotic activity of endothelium can influence local clotting.

Thrombosis: Abnormal Blood Flow

Turbulence causes endothelial injury and dysfunction leading to arterial or cardiac thrombosis.
Stasis is a major factor in venous thrombosis.

Thrombosis: Hypercoagulability

Hypercoagulability is any alteration of the coagulation pathways that predisposes to thrombosis.
Can be primary (genetic) or secondary (acquired).
Examples include factor V Leiden, prothrombin gene mutation, and antithrombin III deficiency
Secondary examples include prolonged bed rest, myocardial infarction, atrial fibrillation, cancer, disseminated intravascular coagulation etc.

Thrombosis: Morphology

Thrombi can develop anywhere in the cardiovascular system, influence location & form of thrombus.
Arterial thrombi typically propagate retrograde, while venous thrombi extend in the direction of blood flow.
Thrombi can have grossly or microscopically visible laminations called lines of Zahn.
Mural thrombi refer to thrombi in the heart chambers or the aorta lumen.

Thrombosis: Arterial Thrombi

Arterial thrombi are frequently occlusive and consist of a friable meshwork of platelets, fibrin, erythrocytes and altered leukocytes.
Thrombosis in the major arteries is clinically significant.

Thrombosis: Venous Thrombi

Venous thrombi, largely the result of coagulation cascade activation, are usually occlusive.
Platelets play a secondary role.
Venous thrombi contain more enmeshed erythrocytes, often called "red" or "stasis" thrombi.
Venous thrombi are frequently associated with slow or sluggish blood flow.

Fate of the Thrombus

Propagation
Embolisation
Dissolution
Organization and recanalization

Emboli

An embolus is a detached intravascular solid, liquid, or gaseous mass carried by the blood to a distant site of origin.
A majority (99%) of emboli originate as dislodged thrombi (thromboembolism).

Pulmonary Thromboembolism

Has incidence rate of 20 to 25 cases per 100,000 hospitalized patients.
Deep leg vein thrombi above the knee are the source.
Most pulmonary emboli (60%–80%) are clinically silent.
Consequences include ischemic necrosis of downstream tissue and sudden death/right ventricular failure.

Systemic Thromboembolism

Systemic thromboembolism refers to emboli in the arterial circulation.
Most (80%) originate from intracardiac mural thrombi.
Common sites for arterial embolization include lower extremities and brain.

Predisposing Factors for Deep Vein Thrombosis

Immobility
Pregnancy
Post-operative
Severe burns
Heart failure
Cancer

Prophylaxis & Treatment for Deep Vein Thrombosis (DVT)

High-risk patients should undergo prophylaxis (Heparin, leg compression).
Treatment involves intravenous heparin and warfarin.

Other Types of Emboli

Fat embolism (fat globules in the circulation, after fractures or trauma)
Air embolism (air bubbles obstructing vascular flow, during obstetric procedures or chest wall injuries).
Amniotic fluid embolism (a rare, serious complication of labor and postpartum).

Clinical Correlations (Venous vs. Arterial Thrombosis)

Venous thrombi obstruct distal blood vessels and can embolize to the lungs.
Arterial thrombi are more clinically relevant due to their ability to produce tissue infarction at critical sites like coronary and cerebral vessels.

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Description

Test your knowledge on hemodynamic disorders, thrombosis, and shock. This quiz covers the critical processes of hemostasis, including vasoconstriction and primary hemostasis involving platelets and coagulation. Dive into the mechanisms that keep blood flowing and the conditions leading to clot formation.