Osmotic Pressure Of Plasma Proteins Research Articles

Natriuretic Hormone

Until about 1957 it was generally accepted that the regulation of renal sodium excretion was dependent solely upon changes in(a) glomerular filtration rate (Factor 1) and(b) the activity of the renin-angiotensin-aldosterone system (Factor 2).coupled with the effect of changes in intrarenal haemodynamics and physical factors, such as hydrostatic pressure surrounding renal tubules, and plasma protein osmotic pressure in peritubular capillaries.Since that time, however, evidence has gradually been accumulated to suggest that these are not the only factors which are relevant in this context, and the existence of a humoral inhibitor of renal sodium reabsorption has therefore been postulated. This ‘third factor' has been given the name of natriuretic hormone, and indications of its presence have been found in two principal situations. These are(a) 'Sodium escape’ during chronic mineralocorticoid administration(b) Volume expansion with (i) isotonic saline (ii) blood

Case Scenario: Acute Postoperative Negative Pressure Pulmonary Edema

A 25-yr-old man (weight, 68 kg; height, 183 cm) presentedto the surgery center for excision of back and thigh schwan-nomas on the same day. The patient’s medical history wassignificant only for his history of multiple schwannoma re-sections and a history of smoking one pack of cigarettes perweek for the past 5 yr. He denied previous problems withgeneral anesthesia, and his baseline peripheral oxygen satu-ration was 99% on ambient air.Thepatientwaspremedicatedwith2mgmidazolam,andanesthesia was induced with 250 mg fentanyl, 500 mg thio-pental, and 8 mg vecuronium given for facilitation of tra-cheal intubation. He was atraumatically intubated with a7-mm ID endotracheal tube using a no. 3 Macintosh laryn-goscope (Teleflex Medical, Research Triangle Park, NC) onthe first attempt with direct visualization of the vocal cords.The patient was turned prone, bilateral breath sounds werereconfirmed, and schwannoma excisions were performed ontheleftthighandtheleftflank.Atotalof0.5mghydromor-phone was administered for analgesia. The intraoperativecoursewasunremarkable.Thepatientwashemodynamicallystable with minimal blood loss and was easily ventilated andoxygenated. A total of 500 ml lactated Ringer’s solution wasadministeredduringthe65-minsurgicalprocedure.Thepa-

Lung Fluid Balance During Development

After completing this article, readers should be able to: 1. Describe the major driving forces for liquid formation in and liquid removal from the lumen of the fetal lung. 2. Delineate the role of a normal volume of liquid within the lumen of the fetal lung for normal lung growth during development. 3. Describe the effects of labor on Na,K-ATPase activity in lung epithelial cells and clearance of lung liquid after birth. 4. Explain the route by which most residual liquid drains from the lung. 5. List the conditions associated with preterm birth that may contribute to delayed removal of fetal lung liquid. Curious students of mammalian development recognized more than a century ago that the lungs are filled with liquid during fetal life, (1) but the origin of that liquid remained obscure until 1948, when an unexpected discovery by two French scientists dispelled the prevailing view that fetal lung liquid derived from intrauterine inhalation of amniotic fluid. In studies designed to explore the ontogeny of the pituitary-adrenal axis, tracheal ligation of fetal rabbits for 9 days resulted in fluid distention of the lungs. (2) This serendipitous finding, subsequently confirmed and embellished by others, (3)(4)(5) established that the fetal lung itself, rather than the amniotic sac, is the source of the liquid that fills the lung during development. This liquid forms a slowly expanding structural template that prevents collapse and promotes growth of the fetal lung. Subsequent studies, conducted mostly with sheep, showed that liquid in the lumen of the fetal lung forms as a result of chloride secretion in the respiratory epithelium, (6)(7) a process that can be inhibited by diuretics that block Na,K-2Cl cotransport. (8)(9) In vitro experiments using cultured explants of lung tissue and monolayers of epithelial cells harvested from human fetal lung have …

Microvascular Solute and Water Transport

This review evaluates (1) the regulation of water and solute transport across the endothelial barrier in terms of pore theory and the glycocalyx-junction-break model of capillary permeability; and (2) the mechanisms regulating permeability based on experiments using cultured endothelial cells and intact microvessels. The current form of the glycocalyx-junction-break model of capillary permeability describes the selectivity of the capillary wall (pore size) in terms of the space between the fibers of a quasi-periodic matrix on the endothelial cell surface, and the area for exchange (pore number) in terms of the length and frequency of breaks in the tight junction strands. An independent test of this model in a range of mammalian microvascular beds is new experimental evidence that the colloid osmotic pressure of plasma proteins is developed across the glycocalyx, not across the whole microvessel wall. We are beginning to understand that endothelial cells may change their phenotype in response to physical and chemical stresses. Such changes in phenotype may explain changes in the regulation of endothelial barrier function in intact microvessels that have previously been exposed to injury and differences in the regulation of contractile mechanisms between endothelial cells in vivo and in vitro.

On the active vascular absorption of plasma proteins from tissue: rethinking the role of the lymphatic system

According to Starling’s hypothesis, the osmotic pressure of plasma proteins in the capillary is the principal force for fluid absorption. The leakage of plasma proteins from capillaries to tissue during 24 h accounts for the total amount of plasma proteins in the vascular system. The same amount must therefore be reabsorbed by the lymphatic system, which is considered to be the sole absorber of proteins from tissue. However, it is a well-established routine in all kinds of organ transplantation to not restore the lymphatic system of the transplant. Experience has shown that this reconstruction is unnecessary, which consequently implies that the lymphatics are not of crucial importance for the survival of the organ. Inevitably, we must therefore question the vital role that the lymphatic system has been attributed in maintaining homeostasis as the sole absorber of proteins. Instead, it is proposed that the major part of plasma proteins in tissue is actively absorbed by the capillaries.

Drainage of plasma proteins from the renal medullary interstitium in rats.

1. Lymph vessels are scarce or lacking in the renal inner medulla, raising the question of whether plasma proteins entering the medullary interstitium are removed by diffusion through the interstitium to lymphatics in the outer medulla or cortex, or by convection into the vasa recta. 2. Using micropipettes, we infused 125I-albumin into the papilla of anaesthetized rats and watched its disappearance from the injection site as well as the uptake in the thoracic duct and plasma. 3. Tracer infused into the renal cortex appeared almost immediately in the thoracic duct lymph, and rose to a sevenfold higher concentration than in plasma, whereas tracer infused into the papilla appeared first and increased more sharply in plasma than in the lymph. No spread from the papillary injection site was observed. Tracer injected in renal hilar lymphatics was quantitatively recovered in the thoracic duct. 4. The plasma concentration pattern following papillary infusion was similar to that obtained by intravenous injection, indicating uptake in blood and subsequent distribution to extracellular fluid and lymph from all organs. 5. We conclude that plasma proteins normally diffusing out from the vasa recta are brought back through water flux (1) from the collecting ducts due to the high sodium chloride concentration in the papillary interstitium and (2) from the interstitium into the vasa recta driven by plasma protein osmotic pressure. Accordingly, there is no need for lymph vessels in the inner medulla.

Protein osmotic pressure gradients and microvascular reflection coefficients.

Microvascular membranes are heteroporous, so the mean osmotic reflection coefficient for a microvascular membrane (sigma d) is a function of the reflection coefficient for each pore. Investigators have derived equations for sigma d based on the assumption that the protein osmotic pressure gradient across the membrane (delta II) does not vary from pore to pore. However, for most microvascular membranes, delta II probably does vary from pore to pore. In this study, we derived a new equation for sigma d. According to our equation, pore-to-pore differences in delta II increase the effect of small pores and decrease the effect of large pores on the overall membrane osmotic reflection coefficient. Thus sigma d for a heteroporous membrane may be much higher than previously derived equations indicate. Furthermore, pore-to-pore delta II differences increase the effect of plasma protein osmotic pressure to oppose microvascular fluid filtration.

Pulmonary microvascular reflection coefficients estimated with modified lymphatic washdown technique.

Many investigators have used the lymphatic protein washdown technique to estimate the pulmonary microvascular membrane reflection coefficient to protein (sigma d). With that technique, the investigator causes a high microvascular filtration rate then estimates sigma d from the lymph and plasma protein concentrations. However the lymph may contain protein washed from the lung tissue, and the tissue protein may cause investigators to underestimate sigma d. Plasma protein osmotic pressure (IIc) may cause investigators to underestimate sigma d because IIc opposes fluid filtration. To minimize the effect of IIc, we decreased IIc to 5.6 +/- 1.1 mmHg in five anesthetized sheep. We increased the microvascular filtration rate by increasing pulmonary microvascular pressure to 22 +/- 3 mmHg. Then we tagged plasma protein with Evans blue dye and estimated sigma d from the lymph and plasma dye concentrations. Because tissue protein was not tagged, it did not interfere with our sigma d estimate. Our sigma d estimate (0.79 +/- 0.08) was much higher than previous estimates in anesthetized animals.

Hypoproteinemia slows lung liquid clearance in young lambs

To determine whether hypoproteinemia slows the rate at which liquid is cleared from the lung lumen, we studied 36 lambs, 18 of which underwent repeated plasmapheresis, reducing plasma protein concentration by 37% and plasma protein osmotic pressure by 39%. We killed 29 lambs (14 hypoproteinemic and 15 normoproteinemic) and removed their lungs 1, 2, or 6 h after intratracheal instillation of isotonic saline (6 ml/kg body wt). We measured extravascular lung water and determined the percentage of tracheally instilled liquid that was cleared from the lungs by comparison with control lambs that did not receive saline into their airways. The percent liquid cleared from the lungs after 1 and 2 h was significantly less in hypoproteinemic than in normoproteinemic lambs (37 vs. 65% at 1 h, 58 vs. 75% at 2 h, respectively). By 6 h nearly all the liquid (> 92%) was cleared from the lungs of all lambs. Thus hypoproteinemia slows the initial rate of clearance of liquid from the lungs of lambs. To determine whether reduced plasma protein osmotic pressure might redirect this liquid into lung lymphatics, we measured lung lymph flow (Q1) in five lambs (7.7 +/- 1.4 kg, 19 +/- 4 days old) for > or = 2 h before and 6 h after tracheal instillation of saline. In each lamb, paired studies were done 3-6 days apart; between studies the lambs underwent plasmapheresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of extracellular fluid volume expansion on avian lung fluid balance

We examined the effects of acute expansion of extracellular fluid volume (ECFV) on lung fluid balance and the ultrastructure of the pulmonary air-blood barrier in chickens ( Gallus domesticus). We compared changes in extravascular lung water content (EVLW) to the sum of mean pulmonary capillary blood pressure and plasma protein osmotic pressure (πc), as a measure of net intravascular filtration pressure (NIFP), produced by graded infusion of avian Ringer's solution. NIFP increased with each volume load largely as a result of decreased πc resulting in progressive increase in EVLW. Progressive interstitial edema occurred with fluid accumulation restricted to the inter air capillary septa, sparing the gas exchanging regions of the air-blood barrier. This was associated with increased thickness of the septa and increased pulmonary capillary endothelial vesiculation. The effect of increased ECFV on pulmonary hemodynamics and lung fluid balance in Gallus is similar to that in mammals.

Plasma protein osmotic pressure equations and nomogram for sheep

The equations developed by Landis and Pappenheimer (Handbook of Physiology. Circulation, 1963, p. 961-1034) for calculating the protein osmotic pressure of human plasma proteins have been frequently used for other animal species without regard to the fractional albumin concentration or correction for protein-protein interaction. Using an electronic osmometer, we remeasured the protein osmotic pressure of purified sheep albumin and sheep plasma partially depleted of albumin. We measured protein osmotic pressures of serial dilutions over the concentration range 0-180 g/l for albumin and 0-100 g/l for the albumin-depleted proteins at room temperature (26 degrees C). Using a nonlinear least squares parameter-fitting computer program, we obtained the equation of best fit for purified albumin, and then we used that equation together with the measured albumin fraction to obtain the best-fit equation for the nonalbumin proteins. The equation for albumin is IIcmH2O,39 degrees C = 0.382C + 0.0028C2 + 0.000013C3, where C is albumin concentration in g/l. The equation for the nonalbumin fraction is IIcmH2O,39 degrees C = 0.119C + 0.0016C2. Up to 200- and 100-g/l protein concentration, respectively, these equations give the least standard error of the estimate for each of the virial coefficients. The computed number-average molecular weight for the nonalbumin proteins is 222,000. Using the new equations, we constructed a nomogram, based on the one of Nitta and co-workers (Tohoku J. Exp. Med. 135: 43-49, 1981). We tested the nomogram using 144 random samples of sheep plasma and lymph from 31 sheep. We obtained a correlation coefficient of 0.99 between the measured and nomogram estimates of protein osmotic pressure.

Estimation of the pulmonary microvascular reflection coefficient to protein in dogs

We used a new technique to estimate the pulmonary microvascular membrane reflection coefficient to plasma protein (sigma d) in anesthetized dogs. In five animals we continuously weighed the lower left lung lobe and used a left atrial balloon to increase the pulmonary microvascular pressure (Pc). We determined the relationship between the rate of edema formation (S) and Pc and estimated the fluid filtration coefficient (Kf) as delta S/delta Pc. From the S vs. Pc relationship and Kf, we estimated the Pc at which S/Kf = 10 mmHg for each dog. This pressure (P10) was 38.0 +/- 5.8 (SD) mmHg, and the plasma protein osmotic pressure (pi c) was 14.9 +/- 3.7 mmHg. In five additional dogs in which we decreased pi c to 2.9 +/- 1.7 mmHg, P10 = 27.2 +/- 2.6 mmHg. The P10 vs. pi c regression line fit to the data from all 10 dogs was P10 = 0.92 pi c +/- 24.4 mmHg (r = 0.88). We estimated sigma d from the slope of the regression line as sigma d = square root of delta P10/delta pi c. With this technique, we estimated that, with 95% probability, sigma d lies between 0.72 and unity. This is higher than most previous sigma d estimates.

Physiological effects of pH changes on colloid osmotic pressures

Our purpose was to explore the effects of variations in pH, particularly in the physiological range, on the colloid osmotic pressure (COP) of the body's fluids. Theoretically, changing pH would alter the electrical charge density on plasma proteins and the interstitial ground substance, thereby altering plasma and interstitial protein osmotic pressure as well as interstitial fluid pressure. We found that the COP of human plasma, human albumin, bovine albumin, and Wharton's jelly from human umbilical cords increased linearly as pH increased over the range of 6.0-8.0. COP of plasma and the albumins all displayed essentially the same sensitivity to pH. At equal concentrations, hyaluronate in umbilical cords was approximately 16 times more sensitive to pH than was plasma. Dextran 70 displayed no COP dependency on pH. For plasma, the albumins, and hyaluronate the pH dependence of COP on pH also decreased linearly with concentration (C in g/dl). For plasma and the albumins over the physiological range of pH, COP = COPpH 7.4 [1.00 + 0.01C (pH -7.40)] at 37 degrees C. The data suggest that, relative to the normal net transcapillary pressure gradient, physiological variations in pH affect plasma COP as well as interstitial fluid pressure and thus may play a significant role in regulating the body's fluid distribution.

Edema formation in the lungs and its relationship to neonatal respiratory distress.

Pulmonary edema is an important feature of many newborn lung diseases, including respiratory distress from severe perinatal asphyxia, heart failure, hyaline membrane disease, pneumonitis from group B beta-hemolytic streptococcus, and chronic lung disease (bronchopulmonary dysplasia). Neonatal pulmonary edema often results from increased filtration pressure in the microcirculation of the lungs. This occurs during sustained hypoxia, in left ventricular failure associated with congenital heart disease or myocardial dysfunction, following excessive intravascular infusions of blood, colloid, fat, or electrolyte solution, and in conditions that increase pulmonary blood flow. Low intravascular protein osmotic pressure from hypoproteinemia may predispose infants to pulmonary edema. Hypoproteinemia is common in infants who are born prematurely. Large intravascular infusions of protein-free fluid further decrease the concentration of protein in plasma and thereby facilitate edema formation. Lymphatic obstruction by air (pulmonary interstitial emphysema) or fibrosis (long-standing lung disease) also may contribute to the development of edema. Bacteremia, endotoxemia, and prolonged oxygen breathing injure the pulmonary microvascular endothelium and cause protein-rich fluid to accumulate in the lungs. The risk of neonatal pulmonary edema can be reduced by several therapeutic measures designed to lessen filtration pressure, increase plasma protein osmotic pressure, and prevent or reduce the severity of lung injury.

Transcapillary Starling pressures in the fetus, newborn, adult, and pregnant adult.

We used the method of membrane osmometry to determine capillary pressure (Pc), plasma protein osmotic pressure (IIp), interstitial protein osmotic pressure (IIif), and interstitial free fluid pressure (Pif) in subcutaneous tissue. These pressures were measured in the sheep and guinea pig fetus, newborn, adult, and pregnant adult. Although there were some similarities, we found major species differences. 1) IIp was a minimum in the fetus and gradually increased to a maximum with adulthood in the guinea pig, whereas IIp attained adult values in the newborn lamb. 2) IIp and Pc did not change with pregnancy in sheep, but, in the guinea pig, IIp and Pc decreased by approximately 30% during pregnancy. 3) The maximum and minimum IIif occurred in the fetal and adult guinea pig, respectively, whereas this was reversed in the sheep. 4) IIif decreased with pregnancy in the guinea pig but not in the sheep. 5) The minimum Pif was found in the newborn of both species. These data suggest that the forces that determine the intravascular-interstitial fluid distribution are different in the fetus, newborn, and adult and also vary among species.

Fluid exchanges through capillary walls: A modification of the starling hypothesis

In textbooks of physiology it is usually stated that fluids are extravasated from the arterial ends of capillaries, because, there, the outward transmural pressure of the blood exceeds its net inward osmotic pressure. At the venous ends, however, the position is reversed. The fluids are, therefore, reabsorbed. In this paper it is argued that this is not a true picture of what must really happen. For, having once become equal there is no reason why the pressures should ever cease to be so. Instead, fluids are absorbed at exactly that rate which just keeps pace with falling hydraulic pressure, as the blood proceeds along the capillary loop. Moreover, the forces are indeed shown to be equal at the extreme venous ends of the capillaries. It is further argued that, though this mechanism might operate anywhere in the horizontal position, it could not possibly work in the feet of a standing man. For here the hydraulic blood pressure everywhere greatly exceeds the osmotic pressure of plasma proteins. An addition to Starling's hypothesis is therefore suggested to adapt it to dependent tissues. An experiment by which the validity of this addition might be tested is described.

Effect of ischemia on capillary pressure and equivalent pore radius in capillaries of the isolated dog hind limb.

Measurements were made of filtration coefficients ( L p ), area per unit path length ( A /Δ x ), and equivalent pore radius ( r p ) in the control state and following severe ischemia (arrested blood flow) for periods of 30 minutes, 1 hour, and 3 hours. The value of A s /Δ x for diffusion of all lipid-insoluble substances was not changed after 30 minutes of ischemia, but it was increased after 1 and 3 hours of ischemia. The value of r p calculated from the theory of restricted diffusion yielded values of 34-35 Å for both the control period and after all three periods of ischemia. Combination of hydrodynamic data ( L p ) and diffusion data ( A ω /Δ x ) yielded values for r p of 23 Å for control and ischemic periods. Measurements of plasma-protein osmotic pressure, tissue-protein osmotic pressure, tissue hydrostatic pressure, and capillary hydrostatic pressure supported the conclusion that extended periods of arrested blood flow did not affect muscle capillary membrane porosity. In 5 of 16 hind limbs, there appeared to be a porosity change following 3 hours of arrested blood flow. This change was demonstrated by a net decrease in plasma-protein osmotic pressure and an increase in r p from 34 Å to 54 Å. L p was not changed after 30 minutes but was increased after 1 hour of ischemia; the increase was associated solely with an increase in capillary surface area. After 3 hours of ischemia, the primary change in 11 of 16 hind limbs was an increase in capillary surface area, although an increase in the size of the pores per unit membrane area could not be rigorously excluded. In 5 hind limbs after 3 hours of ischemia, an increase in r p was the primary change and an increase in capillary surface area was of secondary importance. The data indicate that the edema which occurs subsequent to reperfusion of the vasculature after moderately long periods of severe ischemia results from an increase in capillary hydrostatic pressure augmented by an increase in capillary surface area not associated with an increase in membrane porosity. The rise in capillary pressure for any given arterial or venous pressure involves a decrease in precapillary resistance, but postcapillary resistance does not change for any given flow.

The compensation of post-traumatic oedema in the rabbit at different ages.

1. The compensation of fluid loss from the circulation after an LD(50) period of bilateral hind-limb ischaemia in a thermoneutral environment has been studied in the rabbit from birth until young adulthood.2. The fluid loss from the circulation was calculated from the increase in the great vessel haematocrit value as the red cell volume and F(cells) were unchanged after limb ischaemia. This ;apparent' fluid loss was compared with the ;actual' fluid loss calculated from the increase in water content of the injured limbs.3. The 0- to 1-day-old rabbit was better able to restore fluid, and protein, to the circulation than the older animal and suffered a smaller percentage reduction in arterial blood pressure after an LD(50) period of ischaemia.4. The better compensation of post-traumatic fluid loss during the first 48 hr of life may be explained by the high capillary filtration coefficient and the post-traumatic increase in plasma protein osmotic pressure found at that age.5. The more efficient restoration of the plasma volume by the 0- to 1-day-old rabbit may account for the increased ability to withstand post-traumatic fluid loss at that age.

Effect of histamine on equivalent pore radius in capillaries of isolated dog hindlimb

Measurements were made of filtration coefficients ( L p ), area per unit path length ( A Δx ) and of equivalent pore radius ( R p ) in the control state and during continuous intraarterial infusion of histamine (20–60 μg/min per kg limb weight) in the isolated dog hindlimb. The osmotic transient procedure was utilized with lipid-insoluble molecules: urea, glucose, sucrose, raffinose, inulin and Dextran 10 (Pharmacia), employed to produce transient osmotic-pressure effects. The net flux of these substances across the capillary membrane was determined from the arterial-venous concentration difference by chemical analysis. Independent of the absolute value of the reflection coefficient (σ), the A s Δx for diffusion of all substances but Dextran 10 was increased during histamine infusion. R p calculated from the theory of restricted diffusion yielded values of 39 Ångstroms (Å) for control and 38 Å during histamine infusion. Combination of hydrodynamic data ( L p ) with diffusion data A w Δx yielded values for R p of 31 Å for control and 29 Å for histamine. Measurements of plasma-protein osmotic pressure, tissue-protein osmotic pressure, tissue hydrostatic pressure and capillary hydrostatic pressure support the conclusion that histamine (20–60 μg/min per kg limb weight) when administered intraarterially does not affect capillary-membrane porosity. The transient increase in fluid movement across the capillary produced by histamine could result from a change in capillary surface area, an increase in the number of pores per unit surface area, or both. Whatever the mechanism, the increase in fluid movement was not persistent in this preparation and L p reverted to control value 10–20 min after beginning histamine infusion even though the agent continued to be infused.

Single proximal tubules of Necturus kidney. IV. Dependence of H20 movement on osmotic gradients.

The relationship between net water flux and osmotic gradients across the Necturus kidney proximal tubule was studied with stopped flow microperfusion technique. To minimize water movement induced by Na transport, perfusion solutions contained 62.5 mm/l. NaCl; at this concentration no net water movement is observed with isosmolar solutions. Mannitol was added to prepare perfusion solutions with gradients ±70 mOs/l. relative to plasma. With these gradients, water movement was symmetrical in both directions across the membrane: tubular volume decreased 46% with hypoosmolar perfusion fluid, and increased 51% with hyperosmolar fluid. The membrane water permeability coefficient, Pf, is 0.15 x 10–8 ml/(cm2 sec. cm H2O). This coefficient permits calculation of net water movement ascribable to plasma protein osmotic pressure. The calculated value is approximately 1% of the fluid normally absorbed by the tubule. This conclusion was confirmed in separate experiments in which albumin was added to perfusion fluid to produce a protein concentration 67% higher than in plasma. Under these conditions, water was still absorbed from the tubule, indicating that proteins do not play a major role in water absorption.