Interstitial osmotic pressure

In arterioles, the hydrostatic pressure is about 37 mm Hg, with an interstitial (tissue) pressure of 1 mm Hg opposing it. The osmotic pressure (oncotic pressure) exerted by the plasma proteins is approximately 25 mm Hg. Thus, a net outward force of about 11 mm Hg drives fluid out into the interstitial spaces. In venules, the hydrostatic pressure is about 17 mm Hg, with the oncotic and interstitial pressures as described above thus, a net force of about 9 mm Hg attracts water back into the circulation. The above pressures are often referred to as the Starling forces. If the concentration of plasma proteins is markedly diminished (eg, due to severe protein malnutrition), fluid is not attracted back into the intravascular compartment and accumulates in the extravascular tissue spaces, a condition known as edema. Edema has many causes protein deficiency is one of them. 

Understanding the effects of colloid administration on circulating blood volume necessitates a review of those physiologic forces that determine fluid movement between capillaries and the interstitial space throughout the circulation (Fig. 10—5).4 Relative hydrostatic pressure between the capillary lumen and the interstitial space is one of the major determinants of net fluid flow into or out of the circulation. The other major determinant is the relative colloid osmotic pressure between the two spaces. Administration of exogenous colloids results in an increase in the intravascular colloid osmotic pressure. In the case of isosomotic colloids (5% albumin, 6% hetastarch, and dextran products), initial expansion of the intravascular space is essentially that of the volume of colloid administered. In the case of hyperoncotic solutions such as 25% albumin, fluid is pulled from the interstitial space into the vasculature... 

FIGURE 10-5. Operative forces at the capillary membrane tending to move fluid either outward or inward through the capillary membrane. In hypovolemic shock, one therapeutic strategy is the administration of colloids that can sustain and/or draw fluid from the interstitial space by increasing the plasma colloid osmotic pressure. (Reprinted from Guyton AC, Hall JE. Textbook of Medical Physiology. 8th ed. Philadelphia Saunders,... 

The body s normal daily sodium requirement is 1.0 to 1.5 mEq/kg (80 to 130 mEq, which is 80 to 130 mmol) to maintain a normal serum sodium concentration of 136 to 145 mEq/L (136 to 145 mmol/L).15 Sodium is the predominant cation of the ECF and largely determines ECF volume. Sodium is also the primary factor in establishing the osmotic pressure relationship between the ICF and ECF. All body fluids are in osmotic equilibrium and changes in serum sodium concentration are associated with shifts of water into and out of body fluid compartments. When sodium is added to the intravascular fluid compartment, fluid is pulled intravascularly from the interstitial fluid and the ICF until osmotic balance is restored. As such, a patient s measured sodium level should not be viewed as an index of sodium need because this parameter reflects the balance between total body sodium content and TBW. Disturbances in the sodium level most often represent disturbances of TBW. Sodium imbalances cannot be properly assessed without first assessing the body fluid status. 

Plasma colloid osmotic pressure is generated by proteins in the plasma that cannot cross the capillary wall. These proteins exert an osmotic force, pulling fluid into the capillary. In fact, the plasma colloid osmotic pressure, which is about 28 mmHg, is the only force holding fluid within the capillaries. Interstitial fluid colloid osmotic pressure is generated by the small amount of plasma proteins that leaks into the interstitial space. Because these proteins... 

Figure 15.7 Starling principle a summary of forces determining the bulk flow of fluid across the wall of a capillary. Hydrostatic forces include capillary pressure (Pc) and interstitial fluid pressure (PJ. Capillary pressure pushes fluid out of the capillary. Interstitial fluid pressure is negative and acts as a suction pulling fluid out of the capillary. Osmotic forces include plasma colloid osmotic pressure (np) and interstitial fluid colloid osmotic pressure (n,). These forces are caused by proteins that pull fluid toward them. The sum of these four forces results in net filtration of fluid at the arteriolar end of the capillary (where Pc is high) and net reabsorption of fluid at the venular end of the capillary (where Pc is low).

Although the interstitial fluid hydrostatic pressure is "negative," it causes fluid to be pulled out of the capillary, so this pressure is "added" to the other outward forces. The only force pulling fluid into the capillary is the plasma colloid osmotic pressure ... 

Increased capillary permeability may allow plasma proteins to leak into the interstitial spaces of a tissue. The presence of excess protein in these spaces causes an increase in interstitial fluid colloid osmotic pressure and pulls more fluid out of the capillaries. Mediators of inflammation such as histamine and bradykinin, which are active following tissue injury and during allergic reactions, increase capillary permeability and cause swelling. 

Mechanism of Action An osmotic diuretic, antiglaucoma, and antihemolytic agent that elevates osmotic pressure of theglomerular filtrate, inhibiting tubular reabsorption of water and electrolytes, resulting in increased flow of water into interstitial fluid and plasma. Therapeutic Effect Produces diuresis reduces lOP reduces iCP and cerebral edema. 

Several mechanisms have evolved to prevent this catastrophe. In bacteria and plants, the plasma membrane is surrounded by a nonexpandable cell wall of sufficient rigidity and strength to resist osmotic pressure and prevent osmotic lysis. Certain freshwater protists that live in a highly hypotonic medium have an organelle (contractile vacuole) that pumps water out of the cell. In multicellular animals, blood plasma and interstitial fluid (the extracellular fluid of tissues) are maintained at an osmolarity close to that of the cytosol. The high concentration of albumin and other proteins in blood plasma contributes to its osmolarity. Cells also actively pump out ions such as Na+ into the interstitial fluid to stay in osmotic balance with their surroundings. 

Interstitial fluid flow, ion diffusion and osmotic pressure... 

Permeation of mAbs across the cells or tissues is accomplished by transcellular or paracellular transport, involving the processes of diffusion, convection, and cellular uptake. Due to their physico-chemical properties, the extent of passive diffusion of classical mAbs across cell membranes in transcellular transport is minimal. Convection as the transport of molecules within a fluid movement is the major means of paracellular passage. The driving forces of the moving fluid containing mAbs from (1) the blood to the interstitial space of tissue or (2) the interstitial space to the blood via the lymphatic system, are gradients in hydrostatic pressure and/or osmotic pressure. In addition, the size and nature of the paracellular pores determine the rate and extent of paracellular transport. The pores of the lymphatic system are larger than those in the vascular endothelium. Convection is also affected by tortuosity, which is a measure of hindrance posed to the diffusion process, and defined as the additional distance a molecule must travel in a particular human fluid (i. e., in vivo) compared to an aqueous solution (i. e., in vitro). 

It is essential that there is a balance between intracellular (within cells) and interstitial fluids (between cells) so that they have the same balanced osmotic pressure. Both over- and under-hydration can result in some drastic and serious body and neurological abnormalities due to abnormal flow of the ions between the inter-and intra-cellular fluids. 

The reverse flux of fluid from the interstitial to the vascular space (14) is caused by increased interstitial fluid pressure (12) and increased plasma protein concentration (oncotic pressure), hyperosmotemia, or both depending upon the intensity (above or below 50 -peak capacity) and duration of the exercise. Increased interstitial hydrostatic pressure and increased plasma osmotic pressures retard the fluid shift from plasma to the interstitium. Equilibrium is reached when interstitial pressure balances capillary filtration pressure (24). After cessation of exercise, restitution of plasma volume takes 40-60 minutes (21,22) unless significant dehydration is present. The immediate post-exercise hyperosmotemia, the relative hyperproteinemia, and the reduction in systemic blood pressure contribute to the restoration of plasma volume. The reduction in blood pressure, which produces a fall in local hydrostatic pressure within the capillaries of the previously active muscle, is probably the single most important factor. 

Whether an increase in vascular permeability results in mucosal edema depends on the balance between the amount of leakage into the mucosa and the rate of clearance from the mucosa, either through the lymphatics or across the epithelium into the airway lumen. The increase of vascular permeability produced by inflammatory stimuli can result in the bulk flow of plasma into the airway mucosa (Renkin, 1992). The amount of plasma leakage depends upon the number of gaps that form in the endothelium of the leaky vessels, the duration of the gaps and the intravascular pressure that drives the extravasation (Clough, 1991 Taylor and Ballard, 1992). The movement of plasma proteins and other osmotically active solutes into the mucosa can increase the interstitial oncotic pressure, which favors the net movement of fluid out of vessels and further increases the amount of leakage (Taylor and Ballard, 1992). 

Elevates osmotic pressure of glomerular filtrate, increases flow of water into interstitial fluid and plasma, inhibiting renal tubular reabsorption of sodium, chloride, producing diuresis. Enhances flow of water from eye into plasma, reducing intraocular pressure (IOP)... 

The fibroblasts and other cells of the stroma are surrounded by a dense layer of secreted materials through which nutrients must reach the cells and waste must be excreted. The arteriolar ends of blood capillaries have tiny junctions between the endothelial cells so that small molecules leak out under hydrostatic pressure. This fluid, interstitial fluid, feeds the stroma and then drains back into the venous end of capillaries under the influence of increased capillary osmotic pressure and reduced hydrostatic pressure. It contains glucose, amino acids, some metabolites such as citrate, pyrophosphate, and extracellular ATP (Sect. 9.1.4) as well as vitamins and inorganic ions. It is free of the proteins and other large molecules present in blood plasma, but it receives soluble proteins that are secreted into it by matrix cells such as fibroblasts. 

Pulmonary edema may result from the failure of any of a number of homeostatic mechanisms. The most common cause of pulmonary edema is an increase in capillary hydrostatic pressure because of left ventricular failure. Excessive fluid administration in compensated and decompensated heart failure patients is the most frequent cause of iatrogenic pulmonary edema. Besides hydrostatic forces, other homeostatic mechanisms that may be disrupted include the osmotic and oncotic pressures in the vasculature, the integrity of the alveolar epithelium, interstitial pulmonary pressure, and the interstitial lymph flow. The edema fluid in cardiogenic pulmonary edema contains a low amount of protein, whereas noncardiogenic pulmonary edema fluid has a high protein concentration. This indicates that noncardiogenic pulmonary edema results primarily from disruption of the alveolar epithehum. The reader is referred to Chap. 28 for a detailed discussion of this topic. 

What are the components of the safety factor There are in fact three key components the negative interstitial pressure, the capacity of the lymphatic system to transport more fluid than it does under normal circumstances and the fact that increased lymph drainage tends to wash protein out of the interstitial spaces, thus reducing perimicrovascular osmotic pressure. 

Fig. 6. (a) Interstitial pressure gradients in the mammary adenocarcinoma R3230AC as a function of radial position. The circles ( ) represent data points (Boucher et al., 1990), and the solid line represents the theoretical profile based on our previously developed mathematical model (Jain and Baxter, 1988 Baxter and Jain, 1989). Note that the pressure is nearly uniform in most of the tumor, but drops precipitously to normal tissue values in the periphery. Elevated pressure in the central region retards the extravasation of fluid and macromolecules. In addition, the pressure drop from the center to the periphery leads to an experimentally verifiable, radially outward fluid flow. (Reproduced from Boucher et al., 1990, with permission.) (b) Microvascular pressure (MVP) in the peripheral vessels of the mammary adenocarcinoma R3230AC is comparable to the central interstitial fluid pressure (IFP) (adapted from Boucher and Jain, 1992). These results suggest that osmotic pressure difference across vessel walls is small in this tumor. 

The fluid spaces in the body occupy about 60% of the total body mass. The two main spaces are the intracellular fluid (ICF) and the extracellular fluid (ECF), with the ECF subdivided into the intravascular space (plasma), the interstitial space (lymph), and transcellular fluids such as pleural, cerebrospinal, pericardial, peritoneal, and gastrointestinal fluids. The ECF and ICF spaces are normally in an osmotic equilibrium in which body water moves under osmotic pressure between ICF and ECF, governed by the osmotically active molecules in each space. The electrolyte constituents of ICF and ECF are different, particularly for sodium, which is higher in ECF than ICF, and potassium, which is higher in ICF compared to ECF. 

Oncotic pressure (or colloid osmotic pressure) is the osmotic pressure that results from the difference between the protein (mainly albumin) concentrations of plasma and the interstitial fluid. Water is lost from the body via feces, urine, salivation, insensible respiration, and through the skin, with sensible perspiration of sweat occurring in a few species. Although the movement of proteins between spaces is restricted, water and small ions can move across permeable membranes between the spaces. The volume of ECF is highly dependent on its sodium concentration and, under physiological conditions, the sodium ion concentrations of plasma and interstitial fluids are similar. 

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