Mechanisms underlying the volume regulation of interstitial fluid by capillaries: a simulation study

Abstract

BackgroundControl of the extracellular fluid volume is one of the most indispensable issues for homeostasis of the internal milieu. However, complex interdependence of the pressures involved in determination of fluid exchange makes it difficult to predict a steady-state tissue volume under various physiological conditions without mathematical approaches.MethodsHere, we developed a capillary model based on the Starling's principle, which allowed us to clarify the mechanisms of the interstitial-fluid volume regulation. Three well known safety factors against edema: (1) low tissue compliance in negative pressure ranges; (2) lymphatic flow driven by the tissue pressure; and (3) protein washout by the lymph, were incorporated into the model in sequence.ResultsAn increase in blood pressure at the venous end of the capillary induced an interstitial-fluid volume increase, which, in turn, reduced negative tissue pressure to prevent edema. The lymphatic flow alleviated the edema by both carrying fluid away from the tissue and decreasing the colloidal osmotic pressure. From the model incorporating all three factors, we found that the interstitial-fluid volume changed quickly after the blood pressure change, and that the protein movement towards a certain equilibrium point followed the volume change.ConclusionMathematical analyses revealed that the system of the capillary is stable near the equilibrium point at steady state and normal physiological capillary pressure. The time course of the tissue-volume change was determined by two kinetic mechanisms: rapid fluid exchange and slow protein fluxes.

Photoacoustic lymphangiography before and after lymphaticovenular anastomosis

“…However, it remains unclear what changes actually occur in the diameter of lymphatic vessels after edema is reduced. Either dilation or contraction of lymphatic vessels may appear during the process of edema reduction because the diameter of lymphatic vessels is affected by several factors, including lymphatic fibrosis, interstitial fluid pressure, and lymphatic flow [12,14]. The outcomes of cases 1 and 2 were likely caused by an increased flow of lymphatic fluid or improvement of lymphatic collector contraction, suggesting that the wall thickening was reduced after LVA, or that both of the above-discussed mechanisms may have been involved.…”

In silico model of the dilutional effects of conventional component therapy versus whole blood in the management of massively bleeding adult trauma patients

“…17 Briefly, the model comprised four interconnected modules: a hemostatic module, resuscitation module, body fluid compartment module, and dilutional coagulopathy module. The model was divided into five phases: an initial injury phase (minutes 1-10), a prehospital resuscitation phase (minutes [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30], an emergency department (ED) resuscitation phase (minutes 31-60), an operating room (OR) resuscitation phase (minutes 61-160), and a recovery phase (minutes 161-240). The duration of the initial injury phase and prehospital resuscitation phase were based on local experience and data from a randomized trial conducted at a Level 1 US civilian trauma center.…”

“…The model accounted for (1) changes in osmolarity and fluid volumes in the various compartments based on the osmolarity gradients between pairs of compartments, (2) metabolism of infused dextrose, (3) transcapillary diffusion of free water based on Starling's law for the transcapillary pressure gradient, 21 (4) solute-solvent coupling, whereby solute transfer from the PV to the ISF was accompanied by free water movement, 23 and (5) refilling of the PV from the ISF compartment via the lymphatic circulation. 24 Further details about the modeled changes in osmolarity and fluid volume in the body compartments are provided in Appendix S1, Methods, available as supporting information in the online version of this paper.…”

A step from the physiology to the physiome

“…The capillary exchange is not fixed but regulated by several factors such as hydrostatic and oncotic pressure in the vascular and extracellular compartments 1 . Himeno et al 2 tried to predict mathematically a steady state tissue volume and protein movement at capillary bed in response to change in blood pressure. By using a capillary model, which was based on Starling's principle, they concluded that the system of the capillary is stable near equilibrium at a normal physiological capillary pressure and the time course of tissue volume change is determined by the rapid fluid exchange and protein fluxes.…”