Intracellular fluid volume

Regulation of the osmolarity of extracellular fluid, including that of the plasma, is necessary in order to avoid osmotically induced changes in intracellular fluid volume. If the extracellular fluid were to become hypertonic (too concentrated), water would be pulled out of the cells if it were to become hypotonic (too dilute), water would enter the cells. The osmolarity of extracellular fluid is maintained at 290 mOsm/1 by way of the physiological regulation of water excretion. As with sodium, water balance in the body is achieved when water intake is equal to water output. Sources of water input include ... 

The intravenous administration of isotonic saline (0.9% NaCl) should be used to restore ECF and intracellular fluid volumes. Infusion of isotonic saline restores the extracellular volume deficit. Isotonic saline also restore intracellular volume deficits in patients with DKA and hypotonicity. Aggressive hydration itself... 

Mannitol can cause both acute expansion of extracellular fluid volume and a rapid reduction of intracellular fluid volume with retention of brain electrolytes these may have been the mechanisms in this case. 

A decreased accumulation in terms of enhanced efflux of the antibiotics accounts for the resistance mechanism to erythromycin in PMS- or MS-resistant staphylococci, but the amount of erythromycin (EM) accumulated in induced or constitutive EM-resistant cells, nevertheless, was about 8 pmol/0.76 pi (assuming 76% intracellular fluid volume [7]) per bacterium 11 x 10 M. At an external erythromycin concentration of 1 pg/ml (1.36 x 10 M), even the resistant bacteria take up 11 X 10 M of EM. The accumulation of the drug in resistant S. aureus cells is 8 times greater than the extracellular level. The accumulation of the drug in... 

V2 = intracellular fluid volume = 40.6 percent of total body weight... 

ECF, respectively). The ECF comprises interstitial fluid (15%) and plasma (5%). The total blood volume (TBV) is 8% of body water, the 3% of the body water associated with red cells being counted as part of the intracellular fluid volume. The localisation of a drug into blood cells is often studied since it provides a measure of how the compound will distribute into other tissues. Apart from water, the overall body composition is made up (approximately ) as follows water G0%, protein 18%, fat 15% and minerals 7%. 

AletabolicFunctions. The chlorides are essential in the homeostatic processes maintaining fluid volume, osmotic pressure, and acid—base equihbria (11). Most chloride is present in body fluids a Htde is in bone salts. Chloride is the principal anion accompanying Na" in the extracellular fluid. Less than 15 wt % of the CF is associated with K" in the intracellular fluid. Chloride passively and freely diffuses between intra- and extracellular fluids through the cell membrane. If chloride diffuses freely, but most CF remains in the extracellular fluid, it follows that there is some restriction on the diffusion of phosphate. As of this writing (ca 1994), the nature of this restriction has not been conclusively estabUshed. There may be a transport device (60), or cell membranes may not be very permeable to phosphate ions minimising the loss of HPO from intracellular fluid (61). 

FIGURE 10-2. Distribution of body fluids showing the extracellular fluid volume, intracellular body fluid volume, and total body fluids in a 70 kg adult. Extracellular volume (ECV) comprises 14 liters of total body fluid (42 liters). Plasma volume makes up approximately 3 liters of the 14 liters of ECV. Intracellular volume accounts for the remaining 28 liters of total body fluids with roughly 2 liters being located within the red blood cells. Blood volume (approximately 5 liters) is also depicted and is made up of primarily red blood cells and plasma. (Reprinted from Guyton AC, Hall JE. Textbook of Medical Physiology. 8th ed. Philadelphia Saunders, 1991 275, with permission.)... 

The volume ratio interstitial intracellular water varies with age and body weight On a percentage basis, interstitial fluid volume is large in premature or normal neonates (up to 50% of body water), and smaller in the obese and the aged. 

The concentration (c) of a solution corresponds to the amount (D) of substance dissolved in a volume (V) thus, c = D/V. If the dose of drug (D) and its plasma concentration (c) are known, a volume of distribution (V) can be calculated from V = D/c. However, this represents an apparent volume of distribution (Vapp), because an even distribution in the body is assumed in its calculation. Homogeneous distribution will not occur if drugs are bound to cell membranes (5) or to membranes of intracellular organelles (6) or are stored within the latter (7). In these cases, Vapp can exceed the actual size of the available fluid volume. The significance of Vapp as a pharmacokinetic parameter is discussed on p. 44. 

The total volume of the fluid compartments of the body into which drugs may be distributed is approximately 40 L in a 70-kg adult. These compartments include plasma water (approximately 10 L), interstitial fluid (10 L), and the intracellular fluid (20 L). Total extracellular water is the sum of the plasma and the interstitial water. Factors such as sex, age, edema, pregnancy, and body fat can influence the volume of these various compartments. 

In a dilute medium, synthesis of water results with production of ATP, whereas in a concentrated medium, synthesis of amino acid occurs. In both cases the process leads to the isosmotic regulation of intracellular fluid and therefore the maintenance of a constant cell volume.9... 

Furosemide rarely causes the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (although it has been found useful in treating some patients with SIADH who cannot tolerate water restriction (428)). In furosemide-induced cases (SEDA-7, 246), serum ADH concentrations were raised, total body sodium was normal, total body potassium greatly reduced, and intracellular water raised at the expense of extracellular fluid volume. However, such cases are rare, and no new cases have been published since this complication was reported in SEDA-7. 

Understanding Vd requires knowledge of the types of fluids into which a drug can distribute. A standard patient (70 kg, or 154 lbs) can be used to demonstrate key ideas. A 70-kg patient has approximately 5.0 L of blood. Because not every patient weighs 70 kg, blood volume is often expressed on a per mass basis as 0.071 L/kg (5 L/70 kg). Multiplication by patient mass gives that patient s approximate blood volume. Whole blood is 54% plasma by volume, so the amount of plasma in a 70-kg patient is 2.7 L. Other sources of fluid in the body include interstitial fluid and lymph ( 10 L) and intracellular fluids (—25 L). The total body water of a 70-kg male patient is approximately 38 L, or 55% of the body s mass. The value is closer to 50% for females. Total body volume for a 70-kg patient is around 70 L. 

Considerable losses of body water may occur rather suddenly via hemorrhage or more slowly via severe diarrhea or vomiting. Excessive losses of blood volume cause shock, which may set in when 25-30% of the blood volume is lost. The physiologic mechanism to correct for blood loss involves the rapid movement of interstitial fluid into the circulatory system, into which as much as 50% of the interstitial fluid may thus be transferred within a matter of a few hours. The interstitial fluid is, in turn, partially replaced by intracellular fluid however, this is a much slower process, and 1 or 2 days is required to reestablish a fluid equilibrium in the organism. The lost fluids and electrolytes must eventually be replaced through diet or intravenous feeding. 

Total body water If the drug has a low molecular weight and is hydrophobic, it can not only move into the interstitium through the slit junctions, but can also move through the cell membranes into the intracellular fluid. The drug therefore distributes into a volume of about 60% of body weight, or about 42 L in a 70-kg individual. 

A sweat rate of one liter per hour, as occurs with continuous moderate exercise, would lead to the loss of about 40 mmol of Na per hour. A 5-hour running marathon would result in the loss of 200 mmol of sodium. This loss represents depletion of about 12% of the sodium in the ECF. This loss does not, however, result in a drop in plasma sodium concentrations. Plasma sodium is maintained during prolonged exercise by the loss of plasma water, resulting in a drop in plasma volume. Experiments involving human subjects exercising on a stationary bicycle for 3 hours in a warm humid room suggested that about 10% of the water lost in sweat comes from plasma, 38% from interstitial fluid, and about 52% from intracellular fluids (Table 10.9). 

Crystalloid solutions consist of electrolytes in water. Crystalloid solutions may be isotonic, hypertonic or hypotonic. Isotonic solutions have approximately the same osmolality as plasma and, therefore, may be given rapidly in large volumes into peripheral veins. Hypertonic solutions act to draw water into the extracellular fluid (ECF) from the intracellular fluid and represent a method of rapidly restoring circulating volume at the expense of tissue hydration. Hypotonic solutions are usually only used to correct plasma hypertonicity. Because true hypotonic solutions (e.g. sterile water) cause erythrolysis (Krumbhaar 1914), they can only be given slowly via a central vein (Worthley 1986). For this reason, isotonic solutions containing a metabolizable substrate, such as dextrose, and no electrolytes are usually used. 

Hypertonic saline (2-4 ml/kg of 7-7.5% sodium chloride) has been advocated as a method of quickly restoring circulating volume in shock (Table 17.5). Its use results in an increase in the ECF of four to five times the infused volume for at least 60 min after it is infused (Onarheim 1995). Hypertonic saline draws fluid into the ECF from the intracellular fluid, principally from muscle and liver cells (Onarheim 1995) without providing significant fluid replacement. Administration of hypertonic saline should always be followed (within 2.5 h of administration the point in experimental studies when cardiac output begins to... 

The mineralocorticoids have a main action on the distal tubules in the kidney to increase sodium absorption, with concomitant increased excretion of K and H. Aldosterone is the main endogenous mineralocorticoid. It is produced in the outermost layer of the adrenal cortex (the zona glomerulosa). An excessive secretion of mineralocorticoids (e.g. in Conn s syndrome) causes marked salt and water retention, with a resultant increase in the volume of extracellular fluid, alkalosis, hyperkalaemia and often hypertension. A decrease in secretion (e.g. Addison s disease) causes a disproportional loss of Na compared to fluid loss, so osmotic pressure of the extracellular fluid is reduced. This results in an increase in intracellular compared to extracellular fluid volume. The concomitant decrease in excretion of K results in hyperkalaemia with some decrease in bicarbonate. The control of synthesis and release of aldosterone is complex and involves both the renin-angiotensin system and the electrolyte composition of the blood. As with other... 

The symptoms of hypernatremia are primarily caused by a decrease in neuronal cell volume, and may include weakness, restlessness, confusion, and coma. Hypernatremia results in movement of water from the intracellular space to the extracellular fluid. Neurons can adapt to hypertonicity in the ECF by generating intracellular organic osmolytes within 24 hours of onset. This increase in intracellular fluid tonicity then draws water into the neurons, thus limiting the decrease in cell volume. Patients with chronic hypernatremia are less likely to present with symptoms caused by this cerebral adaptation. 

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). 

The major body constituent is water. An average person, weighing 70 kg. contains about 42 litres of water in total. The intracellular fluid compartment (ICF) is the volume of lluid inside the cells (28 I), and the extracellular fluid compartment (ECF) is that volume of fluid which lies outside cells (14 I). The ECF can be further subdivided into plasma (3.5 I) and interstitial lluid (lO.. I). 

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