Interstitial Colloid Osmotic Pressure Research Articles

Pulmonary interstitial compliance: a function of the osmotic constituents of the interstitium.

We have attempted to dehydrate the lung interstitium to determine the nature of forces holding water in that compartment. We administered furosemide with and without bovine albumin intravenously to rabbits (n = 21) 18-24 h before they were anesthetized with pentobarbital sodium. Renal pedicels were ligated and 51Cr-labeled EDTA was injected to estimate lung interstitial water volume. After a period of equilibration the thorax was rapidly opened, and left atrial pressure was measured by direct puncture. 125I-labeled albumin was injected to label the lung vascular volume, and the rabbits were killed 3 min later. Lungs were removed and drained of blood, and extravascular water volume, interstitial volume, and dry weight were determined. Results from these rabbits were compared with a group of normal (n = 4) and overhydrated (n = 6) rabbits. We have found that lung interstitial water is removed in proportion to the change in intravascular forces. We estimate interstitial compliance to be 1.76% cmH2O-1. Our results are compatible with the hypothesis that removal of water is opposed by an increase in interstitial colloid osmotic pressure and not by a fall of hydrostatic pressure. This implies that in the normally hydrated state interstitial hydrostatic pressure is ambient.

Interstitial colloid osmotic and hydrostatic pressures in subcutaneous tissue of human thorax

Interstitial colloid osmotic pressure ( π i) of human subcutaneous tissue was measured simultaneously by three different techniques: in fluid collected by implanted nylon wicks or empty wick catheters, and by implantable colloid osmometers. Hydrostatic pressure in interstitial fluid ( P i) was measured by wick catheters and by wick-in-needle technique. The implantations were done at heart level on the side of the thorax in 15 healthy male subjects. They were divided in two groups, one for a direct comparison of the methods and one for a further investigation on the effect of suction in empty wick catheters. In nylon wicks implanted for 60 min, π i averaged about 16 mm Hg in both groups. In fluid sampled with empty wick catheters, a suction pressure of −10 cm H 2O, and 60-min implantation time, the mean π i was 10.5 and 12.9 mm Hg in the first and second group, respectively. Two factors contributed to lowering of π i in empty wick catheters: dilution of the samples by saline contained in the wick catheter before implantation, and a π i-lowering effect of suction. Measurements with implantable colloid osmometers averaged 9.8 mm Hg. Mean implantation time was 30 min. However, the π i value was positively correlated to implantation time and linear extrapolation to 60 min gives π i values similar to implanted nylon wicks. We therefore conclude that the three methods give the same π i in the same area of human subcutaneous tissue provided equal implantation time and little or no suction in empty wick catheters. P i was −0.2 mm Hg with both wick catheter and wick-in-needle technique.

The pulmonary interstitium in capillary exchange.

When capillaries filter excessive fluid, tissue fluid pressure increases, tissue colloid osmotic pressure decreases, and lymph flow increases. The change in tissue forces and flows have been termed edema safety factors since they act to oppose alterations in pulmonary capillary pressure. It is well known that pulmonary capillary pressure can be acutely increased by approximately 20 mm Hg before fluid enters the alveoli, and that the changes in the tissue forces are responsible for this phenomenon. The decrease in interstitial colloid osmotic pressure appears to account for approximately 50% of the tissue's ability to oppose increases in pulmonary capillary pressure. The tissue colloids change because the capillaries filter a protein-poor fluid, and the exclusion of plasma proteins decreases with increasing interstitial volume. Tissue pressure, at least in the perivascular regions, increases with tissue hydration and provides another major tissue force opposing capillary filtration. The contribution of lymph flow to the overall edema safety factor is difficult to estimate at the present time. However, it is possible that the pressure drop associated with the flow of interstitial fluid between the alveolar septal interstitium and the larger perivascular spaces could serve as an edema safety factor, rather than the standard lymphatic flow pressure drop across the capillary membrane. To calculate the standard lymph flow contribution to the total edema safety factor, total lymph flow [LF] and the filtration coefficient of the capillaries [Kf,c] must be known, i.e., Capillary Wall Drop = LF/Kf,c. For normal lung lymph flows and Kf,c's, it would appear that this factor is small. However, if the total pressure drop for fluid movement through the entire lung tissue is used to estimate the lymphatic factor, then it may represent a major portion of the edema safety factor, i.e., Total Pressure Drop = LF/[Kf,cKf,t]/Kf,c + Kf,t] where Kf,t is the filtration coefficient of the tissues. Tissue forces at different site within the lung tissue are presently under intense investigation in serveral laboratories. The next years should provide the necessary information to discuss fluid accumulation in lung tissue in terms of local transcapillary forces rather than the average forces that are now the "present state of the art."

Influence of body posture on transcapillary pressures in human subcutaneous tissue

Capillary pressure in the human circulation varies within a wide range depending on the height difference between the capillary and the heart. To study the influence of body posture on transcapillary pressures in subcutaneous tissue, 28 healthy volunteers were examined. Interstitial colloid osmotic pressure (IIi) was measured in fluid collected by implantation of multi-filamentous nylon wicks. Interstitial fluid hydrostatic pressure (Pi) was measured by a 'wick-in-needle' method. Samples for determination of plasma colloid osmotic pressure (IIp) were obtained by venipuncture. In the upright position IIi was 15.2 (SD 2.1) mmHg on the thorax and 10.4 (SD 2.1) mmHg at the ankle. Similar values were obtained in subjects examined after 2 h in a horizontal position. During sustained rest in bed (40 h) IIi on thorax was practically unchanged, while IIi at the ankle rose from 10.1 (SD 2.9) mmHg to 12.2 (SD 2.8) mmHg. Pi averaged -1.3 (SD 1.6) mmHg on the thorax and -0.4 (SD 2.5) mmHg at the ankle, but the difference was not statistically significant. Altogether the body-posture dependent variations in IIi and Pi are small, and can compensate for only a fraction of the changes in capillary pressure.

Interstitial fluid colloid osmotic and hydrostatic pressures in subcutaneous tissue of patients with nephrotic syndrome

Colloid osmotic pressure in plasma (IIp) and in interstitial fluid from subcutaneous tissue (IIi) was measured in 13 patients with nephrotic syndrome and in 20 healthy volunteers. Interstitial fluid was sampled by nylon wicks, and interstitial fluid pressure was measured by the 'wick-in-needle' technique. In the persons with normal plasma proteins we found a mean IIp of 26.9 mmHg, a mean IIi of 15.8 mmHg on the thorax, and a mean IIi of 11.1 mmHg on the lower leg. A fall of IIp from normal values to 16.5 mmHg caused a fall in IIi of about 8 mmHg on the thorax and about 7 mmHg on the leg without oedema formation. In patients with IIp from 16.0 mmHg down to 8.0 mmHg, IIi did not change very much, and was about 5.5 mmHg on the thorax and 2.6 mmHg on the leg. These results support the view that reduction of IIi plays an important role as an oedema preventing factor in patients with hypoproteinaemia.

Interstitial fluid volume, colloid osmotic and hydrostatic pressures in rat skeletal muscle. Effect of hypoproteinemia.

Colloid osmotic pressures in plasma (COPp) and interstitial fluid (COPi), interstitial fluid pressure (Pi) as well as interstitial fluid volume (IFV) was measured in rat skeletal muscle during development of hypoproteinemia. The hypoproteinemia was induced with intraperitoneal injections of aminonucleoside puromucin causing a renal lesion similar to that in human nephrotic syndrome with renal loss of plasma protein and subsequent fall in COPp. When COPp fell from control values (about 20 mmHg) to about 10 mmHg, the fall was accompanied by an identical fall in COPi (in mmHg) while Pi did not change. Provided the pre- to postcapillary resistance ratio was unchanged, the pressure imbalance in the Starling forces (net filtration pressure) was similar to the control situation at this stage of the hypoproteinemia. With further fall in COPi, the absolute fall in COPi was less, - leading to increased net filtration pressure, and finally edema appeared. In presence of edema, Pi rose from average control values of -0.20 mmHg to an average of +1.5 mmHg. Interstitial fluid volume in hypoproteinemic rats without edema was similar to that of controls (about 0.30 ml/g dry tissue), and increases to 3 to 4 times this value in the presence of edema. Comparing the fall in COPi to IFV in the nephrotic rats without edema show that the fall in COPi must have been brought about by a lymphatic washout of interstitial proteins since IFV was similar to the controls when COPi had fallen to 1/3 that of control.

Effect of albumin infusion on pulmonary microvascular fluid and protein transport

The effect of human albumin infusion on the dynamics of fluid and protein transport across the pulmonary microcirculation was studied. Lung lymph flow ( Q ̇ L ) from a chronic lung lymph fistula in unanesthetized sheep was used as a reliable indicator of transvascular fluid filtration rate ( Q ̇ L ). Lymph protein content was considered equal to interstitial protein content. Pulmonary vascular pressures, Q ̇ L , lymph and plasma proteins were continuously monitored. After a 4-hr baseline period, 50g of human, salt-poor albumin (400 cc) was infused over 0.5-hr. A hypersensitivity reaction occurred, in four studies, reflected in a large increase in pulmonary artery pressure and Q ̇ L . Mean data for the remaining six studies are summarized for baseline, after albumin infusion and 2 and 4 hr postinfusion. Microvascular pressure ( P mr, mm Hg) for the four periods was 8, 12, 8, and 8, while plasma colloid osmotic pressure ( π mv, mm Hg) was 21, 27, 24, and 24, respectively. Interstitial colloid osmotic pressure ( π mv) was 11, 11, 13, and 14 mm Hg. Q ̇ L was unchanged over the entire study period. We found that albumin infusion produced an immediate increase in plasma oncotic pressure and a transient increase in P mv. However, the colloid osmotic gradient between the interstitium and plasma returned to baseline by 4 hr despite a continued increase in plasma proteins as interstitial protein content increased in an equal manner. These data suggest a very transient, if any, decrease in lung extravascular fluid after albumin infusion.

Relation between Pulmonary Transvascular Fluid Filtration Rate and Measured Starling's Forces after Major Burn

Our purpose was to determine the reliability of the currently used measurements of pulmonary vascular hydrostatic and oncotic pressures in monitoring pulmonary water after a major burn. The flow of pulmonary lymph, a reliable indicator of the rate of filtration of pulmonary transvascular fluid (Qf), was measured before and for 72 hours after a third-degree burn over 40 to 55 percent of the total body surface in sheep. Changes in Qf were correlated with measured changes in pulmonary microvascular (Pmv), plasma colloid osmotic pressure (pi p), and interstitial colloid osmotic pressure (pi i), as measured in the pulmonary lymph. The periods from 0 to 24 hours (resuscitation), from 24 to 48 hours (early mobilization of fluid), and from 48 to 72 hours (early recovery) were compared with baseline. Regression equations and correlation coefficients for Qf vs Pmv, Qf vs Pmv minus pi p, and Qf vs Pmv minus (pi p -ph i), the oncotic gradient, were calculated. There were significant differences in slopes between the periods of time, with all three comparisons indicating that the response of the microcirculation to the same changes in pressure was different in each of the periods. The correlation between Qf and the comparisons of pressures was clearly best in the period from 48 to 72 hours. The comparison of Pmv minus pi p was not better than Pmv alone, while the comparison of Pmv minus the gradient (pi p -- pi i) was significantly better than either of the other comparisons in predicting Qf.

Plasma water shifts during thermal dehydration.

Changes in body water compartments during acute dehydration before and after acclimation to heat and the role of plasma proteins in body fluid dynamics were studied in the rat. Compartment volumes, plasma and interstitial protein concentrations, and colloid osmotic pressures (COP) were measured in anesthetized (with thiopental sodium) and, if necessary, nephrectomized rats. Albumin outfluxes, total protein mass (TPM), and total albumin mass (TAM) were calculated. Nonacclimated rats conserved plasma volume (PV) as long as dehydration did not exceed 15-16% body weight loss (18.6% total body water loss). This was associated with decreased albumin outflux, elevated plasma COP, and reduced subcutaneous COP. When water loss reached 25,5%, PV and extracellular fluid volume decreased by 45 and 34%, respectively. Albumin outflux recovered, TPM and TAM decreased, and plasma COP remained high. In acclimated dehydrated rats PV remained unchanged, albumin outflux decreased, TPM and COP increased, and interstitial COP decreased. Most of the water loss was intracellular in origin. It was concluded that PV changes during dehydration are related to changes in plasma protein distribution. PV conservation rate is different in rats as compared to desert PV conservers.

Lymph and pulmonary response to isobaric reduction in plasma oncotic pressure in baboons.

Plasma colloid osmotic pressure was reduced by 76% (from 19.6 +/- 0.6 to 4.7 +/- 1.5 mm Hg) in five baboons while pulmonary capillary hydrostatic pressure was maintained at a normal level. This resulted in fluid retention, weight gain, peripheral edema and ascites, but no pulmonary edema. Thoracic duct lymph flow increased 6-fold and pulmonary lymph flow 7-fold. Thoracic duct lymph had a lower colloid osmotic pressure (2.0 +/- 0.7 mm Hg) than plasma (4.7 +/- 1.5 mm Hg), whereas the colloid osmotic pressure of pulmonary lymph (4.7 +/- 0.7 mm Hg) was the same as that of plasma. The lymph-plasma ratio for albumin fell in thoracic duct lymph but remained unchanged in pulmonary lymph. The difference between plasma colloid osmotic pressure and pulmonary artery wedge pressure decreased from 15.3 +/- 1.9 to -0.7 +/- 2.9 mm Hg. Despite this increase in filtration force, the lungs were protected from edema formation by a decrease of 11 mm Hg in pulmonary interstitial colloid osmotic pressure and a 7-fold increase in lymph flow.

Interaction of transcapillary Starling forces in the isolated dog forelimb.

Three of the four Starling forces were measured in the intact dog forelimb after anesthetization and all four of the Starling forces were measured in the same forelimb which was surgically isolated yet innervated. In the isolated forelimb, isogravimetric capillary pressure (Pci) averaged 15.6 mmHg; colloid osmotic pressure of the plasma proteins (IIp) averaged 19.9 mmHg; mean interstitial fluid pressure (Pif) was +0.4 mmHg, and the average value of interstitial colloid osmotic pressure (IIif) was 4.9 mmHg. Thus the net imbalance in the Starling forces, i.e., (Pci - Pif) - (IIp - IIif), averaged 0.3 mmHg. Furthermore, the value of IIif was consistently decreased after isolation (average decrease of 1.2 mmHg) while Pif was always increased following isolation (average increase of 4.3 mmHg). In addition, it was found that if the forelimb was denervated during isolation, then Pif was increased by an average of 2 mmHg above Pif in the innervated, isolated forelimb. In summary, these studies show that the differences between the intact and isolated forelimb are that Pci averages 10-11 mmHg in the intact forelimb and 15-16 mmHg in the isolated innervated forelimb while interstitial fluid pressure is negative in the intact limb and positive in the isolated limb.

Effect of Vibrio cholera toxin on vascular and extravascular spaces of rat intestine.

SummaryThe addition of cholera toxin to closed loops of proximal small intestine resulted in an increase in the extravascular space of serum albumin. It did not alter the tissue red blood cell, dextran or urea spaces while causing a decrease in the inulin space. The increase in the albumin space suggests that the interstitial colloid osmotic pressure was elevated.

Comparative analysis of the protein content of local subcutaneous tissue fluid and plasma

Local subcutaneous tissue fluid from rabbits was sampled with a liquid paraffin cavity method. The albumin, globulin, and total protein content of the nanoliter samples of the fluid obtained by this method were determined by electrophoretic separation on cellulose acetate strips and polyacrylamide gels. The total protein, albumin, and globulin content was quantitated from microdensitometer scannings after different staining procedures. Plasma samples were treated identically and ran simultaneously. The average protein content of tissue fluid was 32% of the plasma protein content. The albumin:globulin ratio of tissue fluid, 2.67, was significantly higher than the corresponding plasma ratio of 1.64. Direct injury (local burn) increased the protein content of local tissue fluid and decreased the albumin:globulin ratio. The results imply that there is normally a marked difference between the extravasation of albumin and globulins to the interstitial fluid compartment. The effect of the sampling procedure and direct local injury (burn) on capillary permeability was also evaluated by determining the exchange of radioactively labeled albumin from plasma to the tissue fluid. Two and a half hours after the intravenous injection of the labeled protein, the tissue fluid activity was only 8% of that of plasma. The locally sampled subcutaneous tissue fluid thus has a low plasma protein content, a high albumin:globulin ratio, and the exchange rate of intravenously injected albumin to the fluid is low. The effect of the found tissue fluid protein content on interstitial colloidosmotic pressure is considered.