Extracellular and Intracellular Compartments

Table 5.1 The concentrations of some ions in the extracellular and intracellular compartments...

The most common molecules in the body are water and inorganic molecules such as sodium, potassium and chloride ions. A feature that is common among all living cells is that the concentrations of these ions are different in the extracellular and intracellular compartments. The extracellular fluid is high in sodium (Na+) and chloride (CT) ions, but low in potassium (K" ) ions (Figure 10.1). In contrast, the intracellular solution is... 

Abstract Cyclosporine A (CsA) therapy is associated with side effects related to oxidative stress. We characterized the reactive oxygen and nitrogen species produced in the extracellular and intracellular compartments of bovine aortic endothelial cells (BAEC) exposed to CsA. CsA induced a dose-dependent increase of the intracellular oxidation of the NO-sensitive fluorescent probe DAF-2/DA. In agreement with this, CsA produced a dose-dependent accumulation of nitrites in the supernatants of BAEC. In contrast, in BAEC treated with CsA, the presence of superoxide anion could only be detected in the intracellular compartment, as measured by the oxidation of dihydroethidium. The formation of peroxynitrite was assessed in the intracellular compartment, by flow cytometry with... 

Solutes that cannot freely cross cell membranes, such as sodium, are referred to as effective osmoles. The concentration of effective os-moles in the ECF determines the tonicity of the ECF, which directly affects the distribution of water between the extra- and intracellular compartments. Addition of an isotonic solution to the ECF will result in no change in intracellular volume because there will be no change in the effective osmolality of the ECF. Addition of a hypertonic solution to the ECF, however, will result in a decrease in cell volume, whereas addition of a hypotonic solution to the ECF will result in an increase in cell volume. Table 49-1 summarizes the composition of commonly used intravenous solutions and their respective distribution into extracellular and intracellular compartments following infusion. 

Water distributes between the different fluid compartments according to the concentration of solutes, or osmolality, of each compartment. The osmolality of a fluid is proportionate to the total concentration of all dissolved molecules, including ions, organic metabolites, and proteins (usually expressed as milliosmoles (mOsm)/kg water). The semipermeable cellular membrane that separates the extracellular and intracellular compartments contains a number of ion channels through which water can freely move, but other molecules cannot. Likewise, water can freely move through the capillaries separating the interstitial fluid and the plasma. As a result, water will move from a compartment with a low concentration of solutes (lower osmolality) to one with a higher concentration to achieve an equal osmolality on both sides of the membrane. The force it would take to keep the same amount of water on both sides of the membrane is called the osmotic pressure. 

Identify the electrolytes primarily found in the extracellular and intracellular fluid compartments. 

The barium ion is a physical antagonist of potassium, and it appears that the symptoms of barium poisoning are attributable to Ba -induced hypokalemia. The effect is probably due to a transfer of potassium from extracellular to intracellular compartments rather than to urinary or gastrointestinal losses. Signs and symptoms are relieved by intravenous infusion ofKh ... 

In this theory, calcium enters the cell down the enormous electrochemical gradient that normally exists between the extracellular and intracellular fluid compartments. In doing so, it actually reverses the calcium pump and synthesizes ATP in a similar way as the reversal of the sarcoplasmic calcium pumps617 (Fig. 7). There is however, no evidence to support this theory and it has a number of unlikely features. It stresses the need for relevant data rather than circumstantial evidence, and this is particularly necessary in considering intracellular theories. 

Several studies of animals exposed to barium by parenteral routes indicate that barium decreases in serum potassium (Foster et al. 1977 Jaklinski et al. 1967 Roza and Berman 1971 Schott and McArdle 1974). In one study, dogs intravenously administered barium chloride demonstrated a decrease in serum potassium accompanied by an increase in red blood cell potassium concentration (Roza and Berman 1971). The authors concluded that the observed hypokalemia was due to a shift of potassium from extracellular to intracellular compartments and not to excretion. Additional intravenous studies have linked the observed hypokalemia to muscle paralysis in rats (Schott and McArdle 1974) and cardiac arrhythmias in dogs (Foster et al. 1977). These experiments in animals strongly support the suggestive human case study evidence indicating hypokalemia is an important effect of acute barium toxicity. 

Other processes that lead to nonlinear compartmental models are processes dealing with transport of materials across cell membranes that represent the transfers between compartments. The amounts of various metabolites in the extracellular and intracellular spaces separated by membranes may be sufficiently distinct kinetically to act like compartments. It should be mentioned here that Michaelis-Menten kinetics also apply to the transfer of many solutes across cell membranes. This transfer is called facilitated diffusion or in some cases active transport (cf. Chapter 2). In facilitated diffusion, the substrate combines with a membrane component called a carrier to form a carrier-substrate complex. The carrier-substrate complex undergoes a change in conformation that allows dissociation and release of the unchanged substrate on the opposite side of the membrane. In active transport processes not only is there a carrier to facilitate crossing of the membrane, but the carrier mechanism is somehow coupled to energy dissipation so as to move the transported material up its concentration gradient. 

The superoxide anion can initiate a series of radical chain reactions in the extracellular and intracellular spaces [47-54], For simplicity, we have schematically represented these reactions as a two-compartment model as shown in Fig. 1. This simple model illustrates the site-specific characteristics of free radical reactions. 

In a study of the absorption of inorganic mercury by the rat jejunum, Foulkes and Bergman (1993) found that while tissue mercury could not be rigorously separated into membrane-bound and intracellular compartments (as can the heavy metal cadmium), its uptake into the jejunum includes a relatively temperature-insensitive and rapid influx into a pool readily accessible to suitable extracellular chelators. A separate, slower and more temperature-sensitive component, however, leads to the filling of a relatively chelation-resistant compartment. Nonspecific membrane properties, such as surface charge or membrane fluidity, might account for mucosal mercury uptake (Foulkes and Bergman 1993). 

Physiological fluids within the human body can be divided into human intracellular fluid (hICF, with a volume of 271 for a 70 kg person) and human extracellular fluid (hECF, 131). Extracellular fluid can further be subdivided into two sub-compartments, that is human interstitial fluid (hISF, 9.51) and the liquid component of blood (plasma, 3.51 for a 70 kg person) (Tas, 2014). While the extracellular fluid represents the fluid outside cells, and intracellular fluid the fluid within cells, the interstitial fluid is the tissue fluid found between cells. There is a striking difference between the compositions of extracellular and intracellular fluids as presented in Table 7.7. Since the composition of blood plasma is close to that of hECF (Krebs, 1950), synthetic SBFs developed by various research groups frequently attempt to emulate these compositions (Table 7.8). 

In biological tissues, water molecules encounter a number of complex semipermeable structures in the intracellular, extracellular, and vascular compartments. As a result, water diffusion through such structures exhibits directionality in the orientation of preferred motion. The measured diffusion is thus greater parallel to the barriers (Fig. 7.1b) than perpendicular to them. This directional dependence is known as anisotropy [1]. 

Patients with acute hyperkalemia usually require other therapies to manage hyperkalemia until dialysis can be initiated. Patients who present with cardiac abnormalities caused by hyperkalemia should receive calcium gluconate or chloride (1 g intravenously) to reverse the cardiac effects. Temporary measures can be employed to shift extracellular potassium into the intracellular compartment to stabilize cellular membrane effects of excessive serum potassium levels. Such measures include the use of regular insulin (5 to 10 units intravenously) and dextrose (5% to 50% intravenously), or nebulized albuterol (10 to 20 mg). Sodium bicarbonate should not be used to shift extracellular potassium intracellularly in patients with CKD unless severe metabolic acidosis (pH less than 7.2) is present. These measures will decrease serum potassium levels within 30 to 60 minutes after treatment, but potassium must still be removed from the body. Shifting potassium to the intracellular compartment, however, decreases potassium removal by dialysis. Often, multiple dialysis sessions are required to remove potassium that is redistributed from the intracellular space back into the serum. 

Volumes of the intracellular and extracellular body fluid compartments are kept constant by the osmotic pressure, which is created by the concentration of dissolved ions (electrolytes) in each compartment. The normal osmotic concentration is in the range of 280-310 mOsm/L. 

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