Abstract
Increases in the volume of the interstitial space are readily recognized clinically as interstitial edema formation in the loose connective tissue of skin, mucosa, and lung. However, the contents and the hydrostatic pressure of this interstitial fluid can be very difficult to determine even in experimental settings. These difficulties have long obscured what we are beginning to appreciate is a dynamic milieu that is subject to both intrinsic and extrinsic regulation. This review examines current concepts regarding regulation of interstitial volume, pressure, and flow and utilizes that background to address three major topics of interest that impact IV fluid administration. The first of these started with the discovery that excess dietary salt can be stored non-osmotically in the interstitial space with minimal impact on vascular volume and pressures. This led to the hypothesis that, along with the kidney, the interstitial space plays an active role in the long-term regulation of blood pressure. Second, it now appears that hypovolemic shock leads to systemic inflammatory response syndrome principally through the entry of digestive enzymes into the intestinal interstitial space and the subsequent progression of enzymes and inflammatory agents through the mesenteric lymphatic system to the general circulation. Lastly, current evidence strongly supports the non-intuitive view that the primary factor leading to inflammatory edema formation is a decrease in interstitial hydrostatic pressure that dramatically increases microvascular filtration.
Highlights
The traditional view that the interstitial space is a relatively static and, frankly, uninteresting region is being reassessed in light of new research showing that the interstitium plays an active role in the regulation of interstitial volume and content and is a key participant in the pathogenesis of inflammation and shock
A comparable effect is seen in the extracellular matrix of loose connective tissue found throughout the body, where fibroblasts attach to multiple collagen fibers via integrin connections and compact the matrix [15,16,17,18]
The lymphatic system drains interstitial fluid first through blindend initial lymphatic capillaries located within the interstitial space [49]
Summary
The traditional view that the interstitial space is a relatively static and, frankly, uninteresting region is being reassessed in light of new research showing that the interstitium plays an active role in the regulation of interstitial volume and content and is a key participant in the pathogenesis of inflammation and shock. That the generally predictable relationship between interstitial volume and interstitial pressure can change markedly and that these transitional episodes can occur within minutes. On another front, recent investigations have revealed that the interstitial space plays an active role, in addition to the kidney, in the regulation of salt and water balance in the body including blood pressure. Insights on the Interstitial Space volume, pressure and flow and, utilizing that background, addresses topics of interest that impact IV fluid administration
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