Interstitial fluid hydrostatic pressure

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 ... 

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 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).

Bulk flow plays only a minor role in the exchange of specific solutes between blood and tissue cells. A far more important function of bulk flow is to regulate distribution of extracellular fluid between the vascular compartment (plasma) and the interstitial space. Maintenance of an appropriate circulating volume of blood is an important factor in the maintenance of blood pressure. For example, dehydration and hemorrhage will cause a decrease in blood pressure leading to a decrease in capillary hydrostatic pressure. As a result, net filtration decreases and net reabsorption increases, causing movement, or bulk flow, of extracellular fluid from interstitial space into the vascular compartment. This fluid shift expands the plasma volume and compensates for the fall in blood pressure. 

Increased capillary hydrostatic pressure promotes filtration and inhibits reabsorption. As a result, excess fluid is forced out of the capillary into the interstitial space. An increase in capillary pressure is generally caused by an... 

Pulmonary surfactant decreases surface tension of alveolar fluid. Reduced surface tension leads to a decrease in the collapsing pressure of the alveoli, an increase in pulmonary compliance (less elastic recoil), and a decrease in the work required to inflate the lungs with each breath. Also, pulmonary surfactant promotes the stability of the alveoli. Because the surface tension is reduced, the tendency for small alveoli to empty into larger ones is decreased (see Figure 17.2, panel b). Finally, surfactant inhibits the transudation cf fluid out of the pulmonary capillaries into the alveoli. Excessive surface tension would tend to reduce the hydrostatic pressure in the tissue outside the capillaries. As a result, capillary filtration would be promoted. The movement of water out of the capillaries may result in interstitial edema formation and excess fluid in the alveoli. 

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). 

Fluid shifts during exercise occur mainly as a result of increased capillary filtration from the vascular compartment to the interstitial space caused by the increases in hydrostatic and systemic blood pressures (13,21,22), with assistance from the increased tissue osmolality (14,23) resulting from elevated muscle metabolism. The latter would tend to draw interstitial fluid into the muscle cells (13) and, in conjunction with the shift of water from inactive muscle, would increase tissue total pressure (Figure 1). 

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. 

The filtration pressure (= difference between hydrostatic capillary pressure and tissue pressure) furthers the discharge of plasma fluid from the arterioles as a result of the higher protein content of the plasma, the coUoidosmotic pressure promotes the backflow of interstitial fluid into the venules. In the arteriole, the hydrostatic pressure is 40 - 45 mm Hg it drops down to 10-15 mm Hg in the direction of the venous capillary loop. Both the coUoidosmotic pressure and the tissue pressure remain unchanged at -25 to -30 mm Hg or —2 to —5 mm Hg along the arterial and venous parts of the capillaries. Consequently, an effective filtration pressure of 10—15 mm Hg is generated in the arterial capillary loop and of -10 to —15 mm Hg in the venous loop. (s. fig. 16.3)... 

In liver diseases involving elevated hydrostatic pressure (e.g. as a result of portal hypertension), the inflow of fluid into the interstitium is increased, whereas the return of fluid into the vascular bed is decreased due to the depressed colloidosmotic pressure (e.g. as a result of hypalbuminaemia). Likewise, a boost in capillary permeability leads to an outflow of fluid into the interstitial tissue. (2, 5, 8, 12)... 

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. 

The hydrostatic pressure in an arteriole is the force that "pushes" fluid out of the capillary and into the interstitial spaces. The plasma protein osmotic pressure, plus the tissue pressure, is the force that "pulls" water from interstitial spaces into the venular side of the capillary. Thus, if the hydrostatic pressure is greater than the osmotic pressure, fluid will leave the circulation if it is less, fluid will enter the circulation. 

As the arterial blood enters the capillaries, fluid moves from the intravascular space into the interstitial space (that surrounding the capillaries) because of what are known as Starling s forces. The hydrostatic pressure in the arteriolar end of the capillaries ( 37 mm Hg) exceeds the sum of the tissue pressure ( 1 mm Hg) and the osmotic pressure of the plasma proteins ( 25 mm Hg). Thus, water tends to leave the capillaries and enter extravascular spaces. At the venous end of the capillaries, the hydrostatic pressure falls to approximately 17 mm Hg while the osmotic pressure and the tissue pressure remain constant, resulting in movement of fluid back from the extravascular (interstitial) spaces and into the blood. Thus, most of the force bringing water back from the tissues is the osmotic pressure mediated by the presence of proteins in the plasma. 

Increased vascular permeability has been demonstrated, with extravasation of blood plasma expanding the interstitial fluid space and— because of the lack of functional lymphatics— drastically increasing the hydrostatic pressure in the tumor interstitium. 

After seeping copiously out of the highly permeable tumor microvessels—an equilibrium is reached when the hydrostatic and oncotic pressures within the microvessels and the respective interstitial pressures become equal—fluid accumulates in the tumor extracellular matrix and a high interstitial fluid pressure (IFP) builds up in sohd tumors (Young et al. 1950 Gutmann et al. 1992 Less et al. 1992 Milosevic et al. 2001,2004). 

Edema results from the abnormal accumulation of fluid in the interstitial tissue. Edema may be localized, resulting from local changes in vascular permeability or hydrostatic pressure. Systemic edema is associated with changes in protein or electrolyte content of the body fluids. (The causes of allergic and inflammatory edema are discussed in separate sections.) Obstruction of the lumina of the veins or lymphatics induces changes in capillary hydrostatic pressure or prevents lymphatic drainage [52]. 

Hydrostatic and colloid osmotic pressures within the blood and interstitial fluid primarily govern transcapillary fluid shifts (Figure 61.1). Although input arterial pressure averages about 100 mmHg at heart level, capillary blood pressure Pc is significantly reduced due to resistance R, according to the Poiseuille s equation ... 

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