Interstitial Fluid Pressure in Control of Interstitial Fluid Volume During Normal Conditions, Injury and Inflammation

1992 ◽  
pp. 475-485
Author(s):  
R. K. Reed ◽  
H. Wiig ◽  
T. Lund ◽  
S. Å. Rodt ◽  
M.-E. Roller ◽  
...  
2009 ◽  
Vol 297 (1) ◽  
pp. R6-R16 ◽  
Author(s):  
R. M. Dongaonkar ◽  
G. A. Laine ◽  
R. H. Stewart ◽  
C. M. Quick

The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure ( P i) and protein concentrations ( C i) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P i and C i as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P i and C i arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P i and C i result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P i is unaffected by interstitial compliance. These simple algebraic solutions predict P i and C i that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.


1992 ◽  
Vol 72 (1) ◽  
pp. 53-57 ◽  
Author(s):  
M. E. Koller ◽  
R. K. Reed

This study shows that, in rat trachea, dextran anaphylaxis is associated with increased negativity of interstitial fluid pressure (Pif) as measured with sharpened glass capillaries (tip diameter 3–7 microns) connected to a servo-controlled counterpressure system. Experiments were carried out in pentobarbital-anesthetized Wistar-Moller rats. Pif in the control situation was -2.5 +/- 0.38 (SD) mmHg. The mean pressure in animals killed 2 min after initiation of the anaphylactic reaction by injection of 1 ml of 10% Dextran 70 in 0.9% NaCl was -10.3 +/- 2.6 mmHg. In another experimental series, interstitial fluid volume was measured after dextran administration but without inducing circulatory arrest. Interstitial fluid volume increased from 0.94 +/- 0.16 to 1.56 +/- 0.42 ml/g dry wt after 10 min to 1.57 +/- 0.30 and 1.10 +/- 0.27 ml/g dry wt after 30 and 60 min, respectively. The increased negativity in Pif in tracheal mucosa in the early phase of dextran anaphylaxis will markedly increase the transcapillary net filtration pressure in the initial phase of edema development.


2001 ◽  
Vol 281 (3) ◽  
pp. H1085-H1092 ◽  
Author(s):  
Helge Wiig ◽  
Tjøstolv Lund

There is clinical and experimental evidence that lack of thyroid hormones may affect the composition and structure of the interstitium. This can influence the relationship between volume and pressure during changes in hydration. Hypothyrosis was induced in rats by thyroidectomy 8 wk before the experiments. Overhydration was induced by infusion of acetated Ringer, 5, 10, and 20% of the body weight, while fluid was withdrawn by peritoneal dialysis with hypertonic glucose. Interstitial fluid pressure (Pi) in euvolemia (euvolemic control situation) and experimental situation was measured with micropipettes connected to a servocontrolled counterpressure system. The corresponding interstitial fluid volume (Vi) was found as the difference between extracellular fluid volume measured as the distribution volume of 51Cr-labeled EDTA and plasma volume measured using125I-labeled human serum albumin. In euvolemia, Vi was similar or lower in the skin and higher in skeletal muscle of hypothyroid than in euthyroid control rats, whereas the corresponding Pi was higher in all tissues. During overhydration, Pi rose to the same absolute level in both types of rats, whereas during peritoneal dialysis there was a linear relationship between volume and pressure in all tissues and types of rats. Interstitial compliance (Ci), calculated as the inverse value of the slope of the curve relating changes in volume and pressure in dehydration, did not differ significantly in the hindlimb skin of hypothyroid and euthyroid rats. However, in skeletal muscle, Ci was 1.3 and 2.0 ml · 100 g−1 · mmHg−1 in hypothyroid and euthyroid rats ( P < 0.01), with corresponding numbers for the back skin of 2.7 and 5.0 ml · 100 g−1 · mmHg−1 ( P < 0.01). These experiments suggest that lack of thyroid hormones in rats changes the interstitial matrix, again leading to reduced Ci and reduced ability to mobilize fluid from the interstitium.


2008 ◽  
Vol 294 (2) ◽  
pp. R651-R659 ◽  
Author(s):  
R. M. Dongaonkar ◽  
C. M. Quick ◽  
R. H. Stewart ◽  
R. E. Drake ◽  
C. S. Cox ◽  
...  

Under physiological conditions, interstitial fluid volume is tightly regulated by balancing microvascular filtration and lymphatic return to the central venous circulation. Even though microvascular filtration and lymphatic return are governed by conservation of mass, their interaction can result in exceedingly complex behavior. Without making simplifying assumptions, investigators must solve the fluid balance equations numerically, which limits the generality of the results. We thus made critical simplifying assumptions to develop a simple solution to the standard fluid balance equations that is expressed as an algebraic formula. Using a classical approach to describe systems with negative feedback, we formulated our solution as a “gain” relating the change in interstitial fluid volume to a change in effective microvascular driving pressure. The resulting “edemagenic gain” is a function of microvascular filtration coefficient ( K f), effective lymphatic resistance ( R L), and interstitial compliance ( C). This formulation suggests two types of gain: “multivariate” dependent on C, R L, and K f, and “compliance-dominated” approximately equal to C. The latter forms a basis of a novel method to estimate C without measuring interstitial fluid pressure. Data from ovine experiments illustrate how edemagenic gain is altered with pulmonary edema induced by venous hypertension, histamine, and endotoxin. Reformulation of the classical equations governing fluid balance in terms of edemagenic gain thus yields new insight into the factors affecting an organ's susceptibility to edema.


2006 ◽  
Vol 85 (5) ◽  
pp. 442-446 ◽  
Author(s):  
A. Bletsa ◽  
T. Nedrebø ◽  
K.J. Heyeraas ◽  
E. Berggreen

Lowering of interstitial fluid pressure (Pif) is an important factor that explains the rapid edema formation in acute inflammation in loose connective tissues. Lipopolysaccharide (LPS) and the pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) are pathogenetic in gingivitis. To test if these substances induce lowering of Pif in rat oral mucosa, we measured Pif with a micropuncture technique. IL-1β and TNF-α caused lowering of Pif, whereas LPS induced an immediate increase in Pif, followed by lowering after 40 min. Measurements of fluid volume distribution showed a significant change in interstitial fluid volume (Vi) 1.5 hr after LPS exposure as Vi changed from 0.41 ± 0.02 to 0.51 ± 0.03 mL/g wet weight ( p < 0.05), confirming edema. These findings show that LPS, IL-1β, and TNF-α induce lowering of Pif in the rat oral mucosa and contribute to edema formation in LPS-induced gingivitis.


2000 ◽  
Vol 278 (5) ◽  
pp. H1627-H1639 ◽  
Author(s):  
Helge Wiig ◽  
Rolf K. Reed ◽  
Olav Tenstad

Lack of thyroid hormones may affect the composition and structure of the interstitium. Hypothyrosis was induced in rats by thyroidectomy 4–12 wk before the experiments. In hypothyroid rats ( n = 16), interstitial fluid pressure measured with micropipettes in hindlimb skin and muscle averaged +0.1 ± 0.2 and +0.5 ± 0.2 mmHg, respectively, with corresponding pressures in control rats ( n = 16) of −1.5 ± 0.1 ( P < 0.001) and −0.8 ± 0.1 mmHg ( P < 0.001). Interstitial fluid volume, measured as the difference between the distribution volumes of 51Cr-EDTA and125I-labeled BSA, was similar or lower in skin and higher in hypothyroid muscle. Total protein and albumin concentration in plasma and interstitial fluid (isolated from implanted wicks) was lower in hypothyroid compared with control rats. Hyaluronan content ( n = 9) in rat hindlimb skin was 2.05 ± 0.15 and 1.92 ± 0.09 mg/g dry wt ( P > 0.05) in hypothyroid and control rats, respectively, with corresponding content in hindlimb skeletal muscle of 0.35 ± 0.07 and 0.23 ± 0.01 mg/g dry wt ( P < 0.01). Interstitial exclusion of albumin in skin and muscle was measured after 125I-labeled rat serum albumin infusion for 120–168 h with an implanted osmotic pump. Relative excluded volume for albumin (Ve/Vi) was calculated as 1 − Va/Vi, and averaged 28 and 28% in hindlimb muscle ( P > 0.05), 44 and 45% in hindlimb skin ( P > 0.05), and 19 and 32% in back skin ( P < 0.05) in hypothyroid and control rats, respectively. Albumin mass was higher in back skin in spite of a lower interstitial fluid albumin concentration, a finding explained by a reduced Ve/Vi in back skin in hypothyroid rats. These experiments suggest that lack of thyroid hormones in rats changes the interstitial matrix again leading to reduced interstitial compliance and changes in the transcapillary fluid balance.


1993 ◽  
Vol 74 (5) ◽  
pp. 2135-2139 ◽  
Author(s):  
M. E. Koller ◽  
K. Woie ◽  
R. K. Reed

The present study was performed to investigate whether the increased negativity of interstitial fluid pressure (Pif) observed after intravenous injection of dextran could be mediated via mast cell degranulation induced by C48/80 and polymyxin B sulfate. Increased negativity of Pif, concomitant with edema formation and increased albumin extravasation, was seen with both substances. However, the two substances differed in that polymyxin B sulfate induced less negativity in Pif and a larger but transient increase in capillary albumin extravasation and interstitial fluid volume. Total tissue water (TTW) increased from 2.11 to 2.71 ml/g dry wt 10 min after polymyxin B and returned to control level at 30 and 60 min. Injection of C48/80 increased TTW to 2.68 ml/g dry wt at 30 min, and TTW was still elevated at 60 min. Albumin extravasation followed a similar pattern; polymyxin B sulfate increased albumin extravasation from < 0.08 to 1.18 ml/g dry wt during the first 5 min after administration. C48/80 was less potent, and maximal albumin leakage was seen after 10–25 min (0.25 ml/g dry wt). The observations demonstrate the importance of the interstitium and the loose connective tissues as "active" participants in the edema-generating process and suggest an interaction with the structural components of the interstitium, as well as an important role for the mast cells in the chain of events creating increased negativity of Pif.


1999 ◽  
Vol 10 (3) ◽  
pp. 328-336 ◽  
Author(s):  
K.J. Heyeraas ◽  
E. Berggreen

Tissue pressure is the hydrostatic pressure in the interstitial fluid which surrounds the pulpal cells. This pressure outside the vessels is normally considerably lower than the blood pressure inside the vessels. The dental pulp has a relatively low interstitial compliance due to its enclosure between rigid dentin walls. Accordingly, even a modest increase in pulpal fluid volume will raise the tissue pressure, which may compress blood vessels, leading to ischemia and necrosis. Inflammation may lead to an increase in both interstitial fluid volume and blood volume in the low-compliant pulp and thereby increase the tissue pressure. However, the increased tissue pressure may, in turn, initiate increased lymph flow and absorption of fluid into capillaries in nearby non-inflamed tissue. Both of these latter factors will transport fluid out of the affected area and subsequently out of the tooth and consequently lower the tissue pressure. Increased tissue pressure, whether caused by increased blood volume or increased capillary filtration, will promote outward flow of fluid through exposed dentin tubules and thereby help to protect the pulp against entry of harmful substances. It seems physiologically beneficial, therefore, for the pulp to have a high tissue pressure, which promptly increases when blood flow increases due to its low compliance.


2001 ◽  
Vol 280 (4) ◽  
pp. H1807-H1813 ◽  
Author(s):  
Per Ole Iversen ◽  
Ellen Berggreen ◽  
Gunnar Nicolaysen ◽  
Karin Heyeraas

The volume and fluid pressure characteristics of the intact bone marrow is incompletely understood. We used microspheres and lipoproteins for measurements of intravascular volume (IVV) and EDTA for interstitial fluid volume (IFV) within the rat bone marrow. Interstitial fluid pressure (IFP) was determined with micropipettes connected to a servo-controlled counter-pressure system. Both the microspheres and the lipoproteins yielded estimates of IVV of ∼1 ml/100 g. After a brief reactive hyperemia, IVV increased to 2.5 ml/100 g, whereas IFV decreased with ∼1.5 ml/100 g, so that total extracellular volume did not change. Baseline bone marrow IFP was 9.7 mmHg. The hyperemia led to a transient twofold increase in IFP, whereas a marked blood loss decreased IFP by almost one-half. These novel data suggest that extracellular volume and IFP within the bone marrow can be measured with tracer methods and the micropuncture technique. The responses of IVV, IFV, and IFP during changes in blood flow to the bone marrow suggest a tight regulation and are thus compatible with those for a low-compliant tissue.


1996 ◽  
Vol 271 (6) ◽  
pp. R1465-R1469 ◽  
Author(s):  
R. H. Stewart ◽  
D. A. Rohn ◽  
U. Mehlhorn ◽  
K. L. Davis ◽  
S. J. Allen ◽  
...  

We hypothesized that myocardial microvascular filtration rate (Jv) could be manipulated by varying end-diastolic myocardial interstitial hydrostatic (P(int)) pressure. Dogs under general anesthesia were instrumented with intramyocardial capsules to measure P(int) and with prenodal myocardial lymphatic trunk cannulas and superior vena caval balloon-tipped catheters to manipulate myocardial lymph flow. Because, for a given surface area, the lymph-to-plasma protein concentration ration (CL/CP) varies inversely with JV, CL/CP was utilized as an index of changes in JV. When lymphatic outflow pressure (P0) was elevated to abolish lymph flow and force myocardial interstitial fluid volume to expand, P(int) rose significantly from 15.0 +/- 0.8 to 27.6 +/- 1.0 mmHg and CL/CP increased significantly from 0.75 +/- 0.04 to 0.85 +/- 0.04, indicating a decrease in JV. When P0 was lowered and lymph flow resumed, P(int) and CL/CP decreased significantly to 15.3 +/- 0.9 mmHg and 0.75 +/- 0.04, respectively, indicating an increase in JV. We conclude that myocardial microvascular filtration rate may be modulated by changes in P(int) resulting from alterations in myocardial interstitial fluid volume secondary to variations in lymph flow from the heart.


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