Since the blood coagulates spontaneously when removed from the body, the question now arises, How does it remain fluid in the blood vessels?

Though this question has long occupied much attention, it is still difficult to formulate a definite answer. Nor can we expect to find any adequate explanation until we are better acquainted with the exact details of the origin of the fibrin generators. It must be remembered that the blood may be regarded as a tissue, made up of living constituents requiring constant assimilation and elimination for the maintenance of its perfectly normal conditions and life. We can confidently say that coagulation is the outcome of certain chemical changes concomitant with the death of the blood, and that while it lives no such changes take place. But such an answer adds little to our knowledge of the matter.

Since constant chemical intercourse must be kept up between the blood and its surroundings in order to sustain the complex chemical integrity essential for its life, we cannot be surprised that its waste materials accumulate, and that it soon dies when shed, as other tissues do when deprived of their means of support. The formation of a solid and the separation of a liquid form of proteid is in no way unusual as a first step in the decline from exalted chemical construction, for similar changes occur in other tissues, and in protoplasm itself. The soft contractile substance of muscle probably tends during its contraction, and certainly at its death does undergo almost exactly the same kind of change as the blood in coagulation.

If we knew accurately the nutritive process taking place in the blood itself, and with which of its surroundings it keeps up chemical interchange, the answer would be much simplified. But we have in the blood three elements that probably have different modes of assimilation and elimination, viz., plasma, white cells and red discs. We practically know nothing of the changes they undergo during their nutrition; or whether their tissue-changes have a necessary relation to those of the neighboring tissues. We do know, however, that there exists some very intimate relation between the membrane lining the vessel walls and the contained blood. They seem to require frequently repeated contact one with the other in order that the normal condition of both may be maintained in perfect vital integrity. That fresh supplies of blood are-required by the vessel wall may be shown by the fact that when deprived of its nutriment by a stoppage of the blood flow, it soon loses its power of retaining the blood, and admits of extravasation. And that renewed contact with the vessel wall is equally necessary for the integrity of the blood, is seen from the fact that the cells congregate, the discs adhere together, and the plasma coagulates when stasis interferes with its intercourse with fresh parts of the intima. Probably the chemical changes going on in the one are useful for the nutrition of the other, and they mutually supply one another with some material essential for their life. This is apparent in those cases where coagulation takes place during life in the vessels. It never occurs so long as the intima of the vessel is perfect, and the blood flow constant, but it follows lesion of this delicate membrane, whether caused by injury or mal-nutrition.

The gradual occurrence of this impairment of function of the intima can be watched under the microscope in the small vessels of a transparent part during the initial stages of inflammation. Owing to the arrest of the flow of blood, the walls of the small vessels suffer from defective nutrition, and may be seen to allow some elements to escape, while the discs adhere together and the plasma coagulates.

In the larger vessels the same thing occurs when inflammation of their lining membrane destroys its capability of keeping up the necessary nutritive equilibrium. Thus clots form on the inner lining to the walls of an inflamed vein, often growing so as to fill the entire vessel, and give rise to a condition called thrombosis.

On the valves of the left side of the heart and in the arteries, where the delicate intima is subjected to great mechanical strain, it is common enough to find slight injuries of it covered over with thin clots. To the surgeon this mutual nutrition of intima and blood is of the utmost importance in attaining the occlusion of vessels, for it is upon this fact he has mainly to depend for the stoppage of hemorrhage from a wounded artery. A tightly-tied ligature either injures the inner coats mechanically, or starves the intima by checking the flow of blood through the vessel up to the next branch, and that portion of the vessel is filled with stationary blood, which soon clots and forms an adherent ping. But if the ligature be applied too loosely, a slight blood current passes through the point where the vessel is tied, and this suffices for the nutrition of the intima by the renewal of the blood's contact, so that no clot is formed, the vessel is not closed, and most probably, when the ligature has cut through the outer coat, "secondary hemorrhage" occurs.

It has also been shown that if any foreign substance, such as a thread, be introduced into the blood while circulating, a coagulum will form around it. From this it would appear that the presence of a substance which cannot carry on the necessary chemical intercourse with the blood will excite irritation in its elements, and so effect slight local death of the plasma and the production of fibrin.

The time required for the production of intra-vascular coagulation as a result of mere stasis is happily long, for it has been found that the blood current may be stopped in a limb, by pressure or otherwise, for many hours without coagulation occurring. Indeed, cases have occurred where a tight bandage has stopped the circulation for an entire day without injurious consequences. This is explained by the fact that so long as the intima lives, the blood remains fluid; in short, the tissues die before the blood clots in the vessels.

The tissues continue to live for some time after the animal is dead, and so we see the blood remains fluid in the vessels a considerable time, in fact, as long as the vessel wall can nourish itself and live. Thus it has been shown that the blood in a horse's jugular vein separated by ligature from the circulation, and removed from the animal, will remain fluid for fully twenty-four hours.

In cold-blooded animals the tissues live for even a longer time. The heart of the tortoise, if kept under suitable conditions, will beat for two days when removed from the body, and as Briicke has shown, blood contained in it will remain fluid until after the heart is dead.

If the details of the fibrin formation within the blood vessels be followed, it is found that the injured spot or foreign body first becomes covered over with white corpuscles, around which threads of fibrin appear attached to the rough surface. As more fibrin is formed and the layer thickens, only a few cells can be seen in its meshes, but a great number always exist on the surface of the new fibrin, forming a layer between it and the blood. It is further remarked that coagulation has some relation to the abundance of white cells in all spontaneously coagulated fluids. The more cells, the firmer the clot. In pathological exudations, also, and those acute serous collections which coagulate on removal from the body, fine granular threads of fibrin seem to start from the white cells, and radiate from them in a stellate manner. (Figs, 1oo and 109).

When white cells congregate at a point of a vessel from which the intima is stripped, their more active exertion possibly produces the ferment, etc. And at the same time they remain at the injured part of the vessel wall, and the removal of the fibrin factors cannot occur at the place of injury, since the intima is destroyed. Thus, local clots are formed which extend over the injured surface, and by a process of organization the repair of the denuded patch is accomplished.

Some believe that a great number of white blood cells undergo chemical disintegration the instant the blood is shed, and consider that the fibrin ferment, and probably other fibrin generators, are the result of the destruction of these weak cells, and exclude the red corpuscles from taking any share in the process.

There is some evidence, however, that the plasma and the discs can give rise to all the fibrin factors, and we know that in the circulation white cells must be destroyed and yet cause no coagulation.

If some fresh blood be allowed to flow into a fine capillary tube, the white cells can be seen to move away from the red discs, and the formation of the clot - a delicate fibrin network enclosing the discs - may be watched. Here some at least of the white cells exhibit manifestations of life for a considerable time after the clot has been formed, and their death could not have been the source of the fibrin factors.

In conclusion, then, we can only suppose that, as in other tissues, some chemical changes must go on in the elements of the blood in order to preserve its integrity. A cessation of these changes gives rise to new products which produce fibrin, and hence cause coagulation. But so long as the elements of the blood are frequently brought into close relationship with a healthy vessel wall, the fibrin factors are either produced in such small quantity as to be ineffectual, or they are altered, destroyed, or taken up by the intima and possibly utilized for its nutrition. When the blood is removed from the vessels, the production of the fibrin factors proceeds effectually, either on account of the blood elements undergoing destructive changes, the products of which accumulate; or owing to the impossibility of re-integration, the fibrin factors appear as a product of lethal chemical change or decomposition.

In accepting the first view, we only adopt the theory of John Hunter, who thought coagulation was an act of life. If we adopt the other view, we must needs say it is an act of death. But, after all, this is a mere difference in degree, for how can we distinguish between the unsuccessful attempt of a living tissue to re-integrate, or regain the chemical properties upon which its life depends, and the inevitable result of failure, which, if prolonged beyond a certain point, must cause its death?