Interstitial fluids

Transport in the blood is no longer a requisite for a hormonal response. Responses can occur after release of hormones into the interstitial fluid with binding to receptors in nearby ceUs, called paracrine control, or binding to receptors on the ceU that released the hormone, called autocrine control. A class of hormones shown to be synthesized by the tissue in which they act or to act in the local ceUular environment are the prostaglandins (qv). These ubiquitous compounds are derived from arachidonic acid [506-32-1] which is stored in the ceU membranes as part of phosphoHpids. Prostaglandins bind to specific ceUular receptors and act as important modulators of ceU activity in many tissues. 

Thus for the eapillary model, substituting for d and Hi, the interstitial fluid veloeity is given by... 

The basal metabolic rate for adults is 1 to 1.2 Calories/minute or 60 to 72 Calories/hour. This energy powers the movement of the chest during respiration and the beating of the heart—processes that are obviously necessary for life. However, a surprisingly large fraction of the BMR is used by cells to maintain ionic gradients between their interior and the fluid that surrnunds them (the interstitial fluid nr tissue fluid). 

Lipoprotein metabolism is the process by which hydrophobic lipids, namely triglycerides and cholesterol, are transported within the interstitial fluid and plasma. It includes the transport of energy in the form of triglycerides from intestine and liver to muscles and adipose, as well as the transport of cholesterol both from intestine and liver to peripheral tissues, as well as from peripheral tissues back to the liver. 

Oedema refers to an accumulation of interstitial fluid to a point where it is palpable or visible. In general this point is reached with a fluid volume of 2-3 liters. Oedema formation is the result of a shift of fluid into the interstitial space due to primary disturbances in the hydraulic forces governing transcapillary fluid transport and of subsequent excessive fluid reabsorption by the kidneys. Deranged capillary hydraulic pressures initiate oedema formation in congestive heart failure, and liver cirrhosis whereas a deranged plasma oncotic pressure... 

Moreover, a neighbouring cell will have a velocity equal but opposite in direction, giving a total surface velocity difference across the gap, b, between the two cells of AUj = Yavgd- The average interstitial fluid velocity gradient is proportional to ... 

The extracellular fluid (ECF) is the fluid outside the cell and is rich in sodium, chloride, and bicarbonate. O The ECF is approximately one-third of TBW (14 L in a 70-kg man or 12 Lin a 70-kg woman) and is subdivided into two compartments the interstitial fluid and the intravascular fluid. The interstitial fluid (also known as lymphatic fluid) represents the fluid occupying the spaces between cells, and is about 25% of TBW (10.5 L in a 70-kg man or 8.8 L in a 70-kg woman). The intravascular fluid (also known as plasma) represents the fluid within the blood vessels and is about 8% of TBW (3.4 L in a 70-kg man or 2.8 L in a 70-kg woman). The ECF is approximately one-third of TBW or 14 L in a 70-kg male. Because the exact percentages are cumbersome to recall, many clinicians accept that the ECF represents roughly 20% of body weight (regardless of gender) with 15% in the interstitial space and 5% in the intravascular space.6 Note that serum electrolytes are routinely measured from the ECF. 

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. 

Factors known to influence the clearance of drugs from interstitial sites, following extravasation or parenteral interstitial or transepithelial administration, include size and surface characteristics of particles, formulation medium, the composition and pH of the interstitial fluid, and disease within the interstitium. Studies indicate that soluble macromolecules smaller than 30 nm can enter the lymphatic system, whereas particulate materials larger than 50 nm are retained in the interstitial sites and serve as a sustained-release depot. The use of lipids or an oil in a formulation and the presence of a negative surface charge all appear to... 

The flux vector accounts for mass transport by both convection (i.e., blood flow, interstitial fluid flow) and conduction (i.e., molecular diffusion), whereas S describes membrane transport between adjacent compartments and irreversible elimination processes. For the three-subcompartment organ model presented in Figure 2, with concentration both space- and time-dependent, the conservation equations are... 

Neurons are very sensitive to changes in the pH of the interstitial fluid surrounding them. Normally, the pH of arterial blood is 7.4. Under conditions of alkalosis, in which pH increases, the excitability of neurons also increases, rendering them more likely to generate action potentials. This inappropriate stimulation of the nervous system may lead to seizures, particularly in epileptics predisposed to them. Under conditions of acidosis, in which pH decreases, the excitability of neurons is depressed, rendering them less likely to generate action potentials. This lack of nervous system stimulation may lead to a comatose state. Severe diabetic acidosis or acidosis associated with end-stage renal failure will often lead to coma. 

Embedded within the brain are four ventricles or chambers that form a continuous fluid-filled system. In the roof of each of these ventricles is a network of capillaries referred to as the choroid plexus. It is from the choroid plexuses of the two lateral ventricles (one in each cerebral hemisphere) that cerebrospinal fluid (CSF) is primarily derived. Due to the presence of the blood-brain barrier, the selective transport processes of the choroid plexus determine the composition of the CSF. Therefore, the composition of the CSF is markedly different from the composition of the plasma. However, the CSF is in equilibrium with the interstitial fluid of the brain and contributes to the maintenance of a consistent chemical environment for neurons, which serves to optimize their function. 

The adenohypophysis does not have a direct anatomical connection with the hypothalamus therefore, regulation of hormone secretion by way of neuronal signals is not possible. Instead, these two structures are associated by a specialized circulatory system and the secretion of hormones from the adenohypophysis is regulated by hormonal signals from the hypothalamus (see Figure 10.2). Systemic arterial blood is directed first to the hypothalamus. The exchange of materials between the blood and the interstitial fluid of the hypothalamus takes place at the primary capillary plexus. The blood then flows to the adenohypophysis through the hypothalamic-hypophyseal portal veins. Portal veins are blood vessels that connect two capillary beds. The second capillary bed in this system is the secondary capillary plexus located in the adenohypophysis. 

As metabolism increases, oxygen consumption and carbon dioxide production are enhanced. The concentration of hydrogen ions is also enhanced as more carbonic acid (formed from carbon dioxide) and lactic acid are produced by the working tissue. Furthermore, the concentration of potassium ions in the interstitial fluid is increased. The rate of potassium release from the cells due to repeated action potentials exceeds the rate of potassium... 

Capillaries are the site of exchange between blood and the interstitial fluid surrounding tissue cells. Tissues with a higher metabolic rate have a more extensive capillary network, that is, a greater number of capillaries per unit area. Because of extensive branching of these vessels, the cells of the body are typically within 20 pm of the nearest capillary. Consequently, the distance that substances must travel between blood and the cells is minimized. Capillaries are permeable to water and small water-soluble substances, such as glucose, amino acids, lactic acid, and urea, and impermeable to proteins. 

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 ... 

The lymphatic capillaries are close-ended vessels in close proximity to blood capillaries and, like blood capillaries, lymphatic capillaries are composed of a single layer of endothelial cells. However, large gaps in between these cells allow not only fluid, but also proteins and particulate matter to enter the lymphatic capillaries quite readily. Once the fluid has entered these capillaries, it is referred to as lymph. Not surprisingly, the composition of this fluid is similar to that of the interstitial fluid. 

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. 

---