The White Cell Trapping Hypothesis

The search for alternative mechanisms of skin damage in venous disease has resulted in investigation of the blood itself. Thomas investigated a series of patients and control subjects who were subjected to experimental venous hypertension by sitting with the legs dependent for a period of 60 minutes.12 Blood samples were taken from the great saphenous vein at the ankle. After 60 minutes patients with venous disease were trapping 30% of the white cells and control subjects were trapping 7%.

White cell margination is a normal event in the arterioles, capillaries, and venules. This phenomenon is thought to be important in the mechanism that results in tissue injury following ischemia. White blood cells are substantially larger than red cells and are responsible for many of the rheological properties of blood. White cells take 1000 times longer than red cells to deform on entering a capillary bed, and are responsible for about half the peripheral vascular resistance despite their small numbers in the circulation compared to red cells.13 In myocardial infarction they cause capillary occlusion, which can be prevented in experimental animals by first rendering the animal leukopenic.14,15 White blood cells have been implicated as the mediators of ischemia in many tissues including myocardium, brain, lung, and kidneys.1619 Polymorphonuclear leukocytes, particularly those attached to capillary endothelium, may become activated, in which cytoplasmic granules containing proteolytic enzymes are released.20 In addition, a nonmito-chondrial respiratory burst permits these cells to release free radicals, including the superoxide radical, which have nonspecific destructive effects on lipid membranes, proteins, and many connective tissue compounds.21 Leukotactic factors also are released, attracting more polymorphonuclear cells.

In conjunction with other authors I published a hypothesis suggesting that white cell trapping resulted in neutrophil activation, causing damage to the tissues (see Figure 6.1).22

Based on the literature on myocardial ischemia, we proposed that white cells might cause occlusion of capillaries. If some of the capillaries were occluded this might result in heterogeneous perfusion and therefore tissue hypoxia and ischemia. This seemed a reasonable suggestion at the time, since it predated our attempts to measure the severity of the diffusion block, and we included this to explain the hypoxia observed by transcutaneous oximetry. I subsequently have concluded that this part of the original hypothesis is not of major importance in producing skin damage in patients with venous disease.

White cell trapping hypothesis

Reduced blood flow on standing

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