Most ideas about the pathogenesis of deep venous thrombosis (DVT) are dominated by a 'consensus model' first articulated around 1962. This model invokes Virchow's triad' and attributes thrombo-genesis in veins to some combination of 'hypercoagulability', 'stasis' and 'intimal injury'. This arose as a by-product of studies on the mechanisms of haemostasis and bleeding diatheses that were at best only indirectly relevant to thrombosis, and there are reasons for doubting the causal significance of 'hypercoagulability' and 'stasis' in the aetiology of DVT. Proponents of the consensus model make little reference to a substantial literature, mostly historical, that: (a) emphasizes the significance of the venous valve pockets (VVP) and blood rheology in DVT pathogenesis;,and (b) describes morphological features specific to venous thrombi that a valid aetiological model must explain. This literature provides the basis for an alternative hypothesis of DVT aetiology, published some 30 years ago, which has been experimentally corroborated and is compatible with recent cell and molecular biological studies of the venous endothelium. We review this alternative hypothesis, considering its potential value for future research on DVT and embolism, and its significance for clinical practice.

It is argued that Brownian motion makes a less significant contribution to the movements of molecules and particles inside cells than is commonly believed, and that the numbers of similar molecules and particles within any near-homogeneous subcompartment of the cell internum are insufficient to justify the statistical assumptions implicit in the derivation of the diffusion equation. For these reasons, it is contended that, contrary to accepted opinion, diffusion theory cannot provide an explanation for intracellular transport at the molecular level. Although attempts have been made to adapt diffusion theory to complex media, the conclusion is that none satisfactorily overcomes the problem of applying the theory to cell biology. However, the heuristic influence of the theory on cellular biophysics and physiology is noted, and possible alternative frameworks for interpreting the valuable experimental data obtained from such studies are outlined.

Intestinal Ileus is Gut Shock caused by Bowel Hypoxia.

Publisher Summary Since life is based on protein chemistry, it follows that there is probably some “primitive” or basic mechanism, common to all organisms, by which amino acids have been obtained since the origin of life on earth. Different life forms may subsequently have made modifications in the manner by which they accumulate or store amino acids, but similarities in dealing with amino acids should still be more striking than differences in the diversity of organisms which have been studied. As protocols for the preparation and extraction of pools vary significantly from laboratory to laboratory, it is difficult to compare and draw conclusions from the artificial end points that they provide. Furthermore, pools of amino acids are often referred to as if they are distinct and individual entities in their own right. It has been accepted for a long time that amino acids experience difficulty in entering cells because they are virtually insoluble in lipid, and membrane theory predicts, (but does not demonstrate, that they will be excluded. We shall not cease from exploration And the end of all our exploring Will be to arrive where we started And know the place for the first time. T. S. ELIOT (“Four Quartets”)

The hypothesis that our tissues are oxygenated by ‘pure’ diffusion is rejected because diffusion is never ‘pure’ in living tissues—it is everywhere contaminated by the ‘impurity’ of convective or agitative ‘flow’. The suggested alternative hypothesis is that tissue cells breathe by ‘convection + diffusion’ like all other aquatic organisms and that all aquatic respiration is identical. This change alters the interrelationship between Cell Theory, Membrane Theory, and Diffusion Theory: it also invalidates the premises of Krogh's tissue oxygenation model (Krogh's Cylinder), and his conclusions. The presumption that cell respiration is active (rather than passive, as is implicit in classical theory) has wideranging consequences: the following are only a few: —Cells must work to procure oxygen, and—the ratio of work done to oxygen procured must depend on the oxygen content of the ECF.—since pO2 is only one of many factors determining oxygen content, it cannot be more than one of many factors determining the adequacy or efficiency of cell oxygenation: etc.

The Cell Theory is criticised and an alternative version proposed. It is suggested that the notion of a sponge-like, spongioform, cell (7) might be preferable to the classical notion of a membrane-bound cell. This would allow consideration of the probability that cells behave like sponges and procure their material and metabolite requirements entrained in a convected flow of water past their internal membrane systems. I shall consider some deductive consequences of this alternative in a companion article (1). The Cell Theory, however, formulated on the basis of a membrane-bound cell, specifically excludes the possibility of convective flow in and out of cells. For that reason, the metaphysical and historical foundations of Cell Theory are re-examined, the cases for the physicochemical viewpoint as against the teleological viewpoint further discussed, and the relationship of them to the notions of 'cell', 'membrane', and 'diffusion' looked into all over again. It is concluded that there is more evidence, from light and electron microscopy, for a spongioform cell than for a balloon cell.

The historical background against which a new hypothesis must be discussed is presented, and the main threads of thinking about thrombosis are isolated so far as they can be. The interplay between such ideas as pus, white thrombus, white blood corpuscles, platelets, fibrin, and red blood cells, is traced: the origins of our concepts of blood circulation, stasis and slow blood flow, and vessel wall damage, are likewise dug up. The new hypothesis rearranges concepts which are not themselves actually or entirely new: instead of postulating that reduced blood flow results in ‘silting’ of presumably lifeless blood cells, it proposes that slow flow is more likely to injure venous endothelium by metabolic deprivation: and, in place of ‘passive’ silting, it postulates attachment of while blood cells and platelets to the damaged endothelium by virtue of their phagocytic or reparative function/s. This implies that thrombi are likely to form wherever living blood cells pass through veins whose endothelium is dying or dead from impaired nutrition (or other cause). The death of endothelium may be widespread, as in the agonal state, or, very limited, as in venous valve pockets when stasis is prolonged. The hypothesis is novel in that it seeks to explain thrombogenesis in functional or physiological terms, rather than in terms of purely biochemical pathogenesis.