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Review
. 2011 Dec;22(12):2166-81.
doi: 10.1681/ASN.2011080865. Epub 2011 Oct 27.

Body fluid dynamics: back to the future

Gautam Bhave  1 , Eric G Neilson
Affiliations
Review

Body fluid dynamics: back to the future

Gautam Bhave et al. J Am Soc Nephrol. 2011 Dec.

Abstract

Pioneering investigations conducted over a half century ago on tonicity, transcapillary fluid exchange, and the distribution of water and solute serve as a foundation for understanding the physiology of body fluid spaces. With passage of time, however, some of these concepts have lost their connectivity to more contemporary information. Here we examine the physical forces determining the compartmentalization of body fluid and its movement across capillary and cell membrane barriers, drawing particular attention to the interstitium operating as a dynamic interface for water and solute distribution rather than as a static reservoir. Newer work now supports an evolving model of body fluid dynamics that integrates exchangeable Na(+) stores and transcapillary dynamics with advances in interstitial matrix biology.

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Figures

Figure 1
Figure 1. Body Fluid Compartments
In the “average” adult man, ICF and ECF consist of about 57% and 43% of TBW. The ECF compartment is further subdivided into interstitial fluid/lymph (ISF), plasma, bone and connective tissue water, and transcellular water. Skeletal muscle predominates the ICF. Percentages are percent of TBW. Adapted from references and .
Figure 2
Figure 2. Double-Donnan Effect and Cell Volume Homeostasis
(A) Fixed intracellular anions (A-) create a large Donnan effect related osmotic pressure favoring untenable water entry. (B) The Na+/K+ ATPase essentially fixes Na+ ions extracellularly to create a Na+ related Donnan effect. The Na+ and fixed anion effects counteract one another to form a double-Donnan steady state with no transmembrane osmotic gradient. Adapted from reference.
Figure 3
Figure 3. Paradigm Shift in Transcapillary Fluid Exchange
(A, B) Classic view of transcapillary Starling forces with Πi and Pi ignored leading to predominant filtration on the arterial end giving way to absorption on the venous end. (C, D) Πi is a non-linear function of filtration rate (Jv). Filtration rate is the intersection of this function and Πi as a function of Starling forces. The Starling relationship is linear with a slope equal to 1/σKf and y-intercept of Πc + Pi/σ − Pc/σ. As Pc falls along the capillary, the linear Starling curve left shifts since the y-intercept increases. The left shift is blunted by a decrease in Pi. Πi increases with falling filtration and the relative steepness of the non-linear Πi (Jv) function maintains filtration along the capillary.
Figure 4
Figure 4. Triphasic Interstitial Model
Schematic representation of interstitial elements and their relationship to capillary forces and lymphatics. Interstitial Pi is a balance between GAG osmotic pressure (ΠGAG) and collagen hydrostatic pressure (Pcollagen). Net capillary filtration (JV) must equal lymphatic flow (JL) at steady state.
Figure 5
Figure 5. Effect of Local Interstitial Protein Gradients on Πi
(A) Schematic of two pore model where albumin primarily moves through large pores leading to high albumin concentration near large pores and low concentration near small pores. Local interstitial osmotic pressure will primarily reflect osmotic pressure in the vicinity of the small pore which is lower than bulk osmotic pressure. Increasing filtration rate will more steeply decrease local osmotic pressure as albumin wash-out increases around the small pore. (B) Qualitative interstitial osmotic pressure (Πi) versus filtration rate (Jv) curves. When Πi equals bulk Πi no interstitial protein concentration gradients exist leading to higher Πi and shallower dependence on Jv as albumin “washout” is less effective. When Πi reflects local Πi with a significant protein gradient between small and large pores, the effective Πi is lower and more steeply dependent on Jv as albumin washout occurs more efficiently in the vicinity of small pores.
Figure 6
Figure 6. Dynamics of Measured Interstitial Hydrostatic Pressure Pi
(A) Pi normally varies with interstitial volume (IFV). At low IFV, compliance is low and pressure rises significantly. Once IFV increases 20-50% above euvolemia, compliance increases dramatically and Pi essentially remains near constant allowing for edema formation. (B) Pi reflects a balance between Pcollagen and ΠGAG. Release of integrin mediated tension on collagen matrix decreases Pcollagen and right shifts the Pi-IFV curve leading to increased filtration until Pi rises with edema.
Figure 7
Figure 7. Transcapillary Dynamics in Hypovolemia and Nephrotic Syndrome
(A) Vasoconstriction with hypovolemia decreases Pc and left shifts the Starling Πi curve with an increased y-intercept. Transient interstitial fluid absorption occurs increasing Πi and restoring a lower level of steady-state filtration. Pi also decreases leading to a small right shift in linear Starling relationship (not shown). Transcapillary refill of plasma volume occurs with absorption, but may continue to occur if lymphatic flow is slow to match the lower steady state filtration rate. (B) Πc falls in nephrotic syndrome leading to a right shift of the Πi Starling curve and transiently increased filtration. The subsequent fall in Πi reduces filtration to a new steady state. Pi would increase slightly producing a left shift of the Starling linear curve to further minimize a rise in filtration (not shown).
Figure 8
Figure 8. Mechanisms of Excess Sodium Storage
(1) Na+ may be exchanged for K+ and the latter is excreted. Since total cation content is unchanged both cation content and tonicity remain constant. (2) Positive Na+ balance is matched by negative osmolyte (O) balance. (2a) O may be cationic (O+; e.g. choline) and undergo exchange with Na+. (2b) O may be a zwitterion (e.g. taurine, amino acids) or uncharged (e.g. sorbitol, inositol) and essentially exchange for NaCl. In both cases, cation content rises but total solute content is unchanged. (3) Intracellular anions (A-; e.g. sulfate) may be exchanged with chloride and incorporated into GAGs. Na+ associates with GAG sulfate moities via electrostatic interactions. Both total cation and solute content rise in this situation. Tonicity may or may not rise depending on the extent of osmole efficacy. For instance, Na+ salts with bone mineral matrix and possibly intracellular anions may be osmotically inactive; in this case, total body tonicity is unchanged.
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