TF=Tissue Factor

VWF= von Willebrand Factor

NO=Nitric Oxide

SNS=Sympathetic Nervous System

PNS=Parasympathetic Nervous System 

The tragedy of man is that he has developed an intelligence eager to uncover mysteries, but not strong enough to penetrate them. With minds but slightly evolved beyond those of our animal relations, we are tortured with precocious desires to pose questions which we are sometimes capable of asking, but rarely able to answer. ---Hans Zinsser

The vascular endothelium is a diaphanous layer of specialized cells, one cell thick, that lines the inner surface of all blood vessels and is the sole constituent of capillaries. It is the focus of MSM activity, because it controls the dynamic interaction of enzymatic Factors VII, VIII, IX and X that generates thrombin, soluble fibrin, and insoluble fibrin.

Endothelial cells respond to their immediate surroundings, communicate with one another via electrical signals, and produce substances essential for MSM activity including nitric oxide (NO), von Willebrand factor (VWF), fibronectin, tissue factor pathway inhibitor (TFPI), protein C, and tissue plasminogen activator (TPA).

Tissue factor is a glycoprotein produced by cells. It stabilizes labile factor VII enzyme to produce small amounts of thrombin. The "selectively permeable" vascular endothelium insulates tissue factor in extravascular tissues from Factor VII in flowing blood. It allows the slow "leakage" of tissue factor into flowing blood, and the slow "penetration" of factor VII into extravascular tissues. Factor VII thus interacts with tissue factor throughout the body to continuously generate small amounts of thrombin that sustain tissue maintenance and blood enzyme activity. Tissue damage disrupts the vascular endothelium, directly exposes blood enzymes to tissue factor, and activates the tissue repair mechanism that governs a predictable sequence of coagulation, inflammation, chemotaxis, mitosis, metabolism, immune activity and angiogenesis to enable tissue repair. 

Radiation and toxic chemicals cause "gap formation" between the cells of the vascular endothelium that makes it permeable to factor X, causing intense inflammation that explains sunburn. Coagulation does not occur in sunburn because gigantic factor VIII cannot penetrate the intact vascular endothelium.

The vascular endothelium releases nitric oxide (NO) and von Willebrand Factor (VWF) in accord with autonomic balance to regulate the capillary gate mechanism that governs hemodynamic physiology and determines cardiac output, cardiac efficiency, tissue perfusion, tissue oxygenation, organ function, organ protection, and arterial patency. 

 

In the brain, endothelial cells are bound tightly together to minimize penetration of blood proteins and pharmaceuticals into brain tissue. This is called the "blood-brain barrier." 

 

 

The loosely bound cells of the hepatic vascular endothelium facilitate glucuronidation of toxic substances and lipoprotein processing. 

 

 

 

 

 

The vascular endothelium is "selectively permeable" as shown in the green cells. It normally allows the penetration of factor VII from blood into extravascular tissues, where it reacts with tissue factor to generate small amounts of thrombin to energize tissue maintenance. Tissue factor in extravascular tissues slowly "leaks" through the vascular endothelium into flowing blood, where it activates factor VII to enable the continuous activities of factors VIII, IX, and X. 

Harmful radiation and toxic chemicals induce contraction of intracellular muscular elements, causing "gap formation" between cells as shown by the gray cells. This allows the passage of Factor X, which interacts with tissue factor and factor VII to generate thrombin to induce inflammation. Gigantic factor VIII cannot penetrate through these gaps, so coagulation does not occur.This explains the symptoms of sunburn.

Traumatic disruption as shown by the pink cells allows gigantic factor VIII to pass through the vascular endothelium and interact with tissue factor and factors VII, IX and X to initiate clot formation. The selectively permeable viscoelastic clot substitutes for the vascular endothelium and regulates the passage of factors VII and X to maintain optimal thrombin levels to energize tissue repair. It prevents excessive thrombin generation that invites malignancy. Gigantic factor VIII cannot penetrate the clot of its own making, which explains why clot formation is limited to the immediate area of tissue damage. 

Factor IX is a "co-factor" of factor VIII and does not interact with factors VII and X. 

 

 

 

 

 

 

 

 

 

 


 


 

 

  The cells of the vascular endothelium react to local conditions and communicate with one another via electrical signals, so that direct innervation of every cell is unnecessary.


 

 

 

 Direct dual autonomic innervation in the brain and internal organs causes the vascular endothelium to release von Willebrand Factor (VWF) in accord with sympathetic nervous activity and to release nitric oxide (NO) in accord with parasympathetic nervous activity. 

 Autonomic influence is extended to peripheral tissues, where direct innervation is absent, by epinephrine and insulin. Sympathetic tone releases epinephrine from the adrenal gland, and epinephrine releases VWF from the vascular endothelium to close the capillary gate mechanism. Parasympathetic tone releases insulin from the pancreas, and insulin releases NO from the vascular endothelium to open the capillary gate mechanism