Lesson3: Vascular Intima in Hemostasis

Blood Vessels (Vascularate)

• Serves as transporter of the blood

• Provides the interface between circulating blood and the body tissues

Blood Vessel 3 Layers:

1. Vascular Intima (inner layer)

2. Vascular Media (middle layer)

3. Vascular Adventitia (outer layer)

Vascular Intima

Layer that comes in contact with blood

Vascular Media

Composed of Muscular Cells/Muscle Cells

Vascular Adventitia

Contains Connective Tissues

Vascular Intima: Innermost Vascular Lining

Endothelial cells (endothelium)

Vascular Intima: Supporting the Endothelial

Internal elastic lamina composed of elastin and collagen

Vascular Intima: Subendothelial Connective Tissue

• Veins: collagen and fibroblasts

• Arteries: collagen, fibroblasts, and smooth muscle cells

Endothelial Cells

• Complex and heterogeneous cells

• Display unique structural and functional characteristic depending on the environment and physiologic requirements in the Blood Vessel:

• form a smooth, unbroken surface that eases the fluid passage of the blood

• Supported by a Basement membrane and Connective Tissue layer for additional support

Endothelial Cells are responsible for:

1. Immune Response

2. Vascular Permeability

3. Proliferation

4. Hemostasis

Endothelial cells: Immune Response

Regulates immune cell traffic

Endothelial cells: Vascular Permeability

Control of the endothelial cells in regards with the passage of molecules between blood and tissues

Endothelial cells: Proliferation

Participate in tissue repair

Endothelial cells: Hemostasis

Maintains blood fluidity and clot formation when necessary

Other organs with Endothelial Cells:

1. heart

2. brain

3. liver

4. lungs

5. kidney

Internal Elastic Lamina

• Add supportive structure

• Has elastin that provides elasticity to the blood vessel

Anticoagulation

Expressed when endothelial cells are intact

Pro-coagulation

Damaged endothelial cells

Anticoagulant Properties of Intact Vascular Endothelium

• it prevents thrombosis by:

  • Inhibiting platelet aggregation

  • Preventing coagulation activation and propagation

  • Enhancing fibrinolysis

    • Supporting anticoagulation

    • Contradict the clotting process

Structure of Blood Vessel wall: Rhomboid endothelial cell

• Present a smooth, contiguous surface (touching surface) that allows the vessel walls to be smooth

• Acts as physical barrier

Proteins Secreted in Vascular Endothelium

1. Prostacyclin (PGI2)

2. NO (Nitric Oxide)

3. Tissue Factor Pathway Inhibitor (TFPI)

4. Thrombomodulin

5. Heparan Sulfate

6. Tissue Plasminogen Activator (TPA)

Prostacyclin (PGI2)

• Also known as Prostaglandin I2

• Platelet inhibitor and vasodilator, prevents

  unnecessary platelet activation

NO (Nitric Oxide)

• Counteracts vasoconstriction/relaxes the blood

  vessel

• Causes vasodilation

  • Secreted by the smooth muscle, neutrophils, and macrophages

• Inhibits platelet activation

Tissue Factor Pathway Inhibitor (TFPI)

• Limits the activation of the Tissue Factor (TF): VIIa:Xa complex

• Sequence of the Tissue Factor Pathway or the Extrinsic Pathway

Thrombomodulin

Activates the protein C pathway

• Digests/Destruction of Factor Va and Factor VIIIa

  • Important coagulation factors in the common pathway and would affect to inhibit the formation of thrombin

  • Thrombin converts fibrinogen to fibrin

Heparan Sulfate

• Enhances the activity of anti-thrombin

• The target is thrombin

  • Activates fibrinogen to fibrin which is the stableclot

Tissue Plasminogen Activator (TPA)

• Activates the fibrinolytic system

• Activates plasminogen to plasmin in order to activate fibrinolysis

  • The action is the lysis of clot therefore, it is also a function that supports anticoagulation

Prostacyclin and Nitric Oxide

prevents unnecessary clotting

TFPI and Thrombomodulin

would affect the Secondary Hemostasis part of coagulation

Vascular endothelium is composed of rhomboid cells

Present a smooth, contiguous surface

ECs secrete prostacyclin

The eicosanoid platelet inhibitor

ECs secrete nitric oxide

A vascular “relaxing” factor

ECs secrete the glycosaminoglycan heparan sulfate

An anticoagulant that regulates thrombin generation

ECs secrete TFPI

A regulator of the extrinsic pathway of coagulation

ECs express the protein C receptor EPCR

An integral component of the protein C control system

ECs express cell membrane thrombomodulin

A protein C coagulation control system activator

ECs secrete TPA

Activates fibrinolysis

Procoagulant Properties of Damaged Endothelium

1. Smooth muscle cells

2. Collagen

3. Endothelial Cells

Smooth muscle cells

• induce vasoconstriction (initiatesprimary hemostasis)

• Reduces blood flow to avoid blood loss

Collagen

binds and activates platelets

Endothelial Cells

• secrete Von Willebrand Factor

• Von Willebrand Factor serve to aid in the adhesion of platelets in to the site of injury

• Platelet to Platelet and Platelet to Collagen adhesion

• secrete adhesion molecule that promotes platelet and leukocyte binding

  • P-selectin

  • ICAM’s

  • PECAM’s

Smooth muscle cells and Fibroblast

Exposes tissue factor (activator of clotting)

Endothelial Cells in inflammation

Tissue factor is induced by inflammation

Smooth muscle cells in arterioles and arteries

Induce vasoconstriction

Exposed subendothelial collagen

Binds VWF; binds to and

activates platelets

Damaged or activated ECs secrete VWF

Important for platelet binding to collagen at site of injury: platelet adhesion as a first line of defense against bleeding

Damaged or activated ECs secrete adhesion molecules: P-selectin, ICAMs, PECAMs

Promote platelet and leukocyte binding and activation at site of injury

Exposed smooth muscle cells and fibroblasts

Tissue factor exposed on cell membranes

ECs in inflammation

Tissue factor is induced by inflammation

Fibrinolytic Properties of Damaged Endothelium

1. Tissue Plasminogen Activator (TPA)

2. Plasminogen activator inhibitor 1 (PAI-1)

Tissue Plasminogen Activator (TPA)

Activates fibrin bound plasminogen to form

plasmin (plasmin digest thrombus and

restores blood flow)

Plasminogen activator inhibitor 1 (PAI-1)

Inhibits activation of fibrinolytic system