Water total body

This compartment constimtes two-thirds of total body water and provides the environment for the cell (1) to make, store, and utilize energy (2) to repair itself (3) to replicate and (4) to perform special functions. 

This compartment contains about one-third of total body water and is distributed between the plasma and interstitial compartments. The extracellular fluid is a delivery system. It brings to the cells nutrients (eg, glucose, fatty acids, amino acids), oxygen, various ions and trace minerals, and a variety of regulatory molecules (hormones) that coordinate the functions of widely separated cells. Extracellular fluid removes COj, waste... 

Fluid restriction is generally unnecessary as long as sodium intake is controlled. The thirst mechanism remains intact in CKD to maintain total body water and plasma osmolality near normal levels. Fluid intake should be maintained at the rate of urine output to replace urine losses, usually fixed at approximately 2 L/day as urine concentrating ability is lost. Significant increases in free water intake orally or intravenously can precipitate volume overload and hyponatremia. Patients with stage 5 CKD require renal replacement therapy to maintain normal volume status. Fluid intake is often limited in patients receiving hemodialysis to prevent fluid overload between dialysis sessions. 

Describe the unique relationship between serum sodium concentration and total body water. 

O Total body water (TBW) is approximately 50% of lean body weight in the normal female and 60% of lean body weight in males. TBW is comprised of the intracellular fluid (two-thirds of TBW) and the extracellular fluid (one-third of TBW). The extracellular fluid is made up of two major fluid subcompartments the interstitial space and the intravascular space. 

The most fundamental concept to grasp is an assessment of total body water (TBW), which is directly related to body... 

Osmotic diuretics such as mannitol act on the proximal tubule and, in particular, the descending limb of the Loop of Henle — portions of the tubule permeable to water. These drugs are freely filtered at the glomerulus, but not reabsorbed therefore, the drug remains in the tubular filtrate, increasing the osmolarity of this fluid. This increase in osmolarity keeps the water within the tubule, causing water diuresis. Because they primarily affect water and not sodium, the net effect is a reduction in total body water content more than cation content. Osmotic diuretics are poorly absorbed and must be administered intravenously. These drugs may be used to treat patients in acute renal failure and with dialysis disequilibrium syndrome. The latter disorder is caused by the excessively rapid removal of solutes from the extracellular fluid by hemodialysis. 

Estimation of total body water (virtual tritium space) in the rat, cat, rabbit, guinea-pig, and man, and of the biological half-life of tritium in man,... 

After oral ingestion, ethanol pharmacokinetics must take into account (1) Absorption from the gastrointestinal tract. Since ethanol is absorbed most efficiently from the small intestines, the rate of gastric emptying is an important factor that governs the rate of rise of blood alcohol concentration (BAC), i.e., the slope of the ascending limb of the BAC-time curve, and the extent of first pass metabolism of ethanol by the liver and stomach. (2) Distribution of ethanol in the body. Ethanol distributes equally in total body water, which is related to the lean body mass of the person, and (3) the elimination of ethanol from the body, which occurs primarily by metabolism in the liver, first to acetaldehyde and then to acetate [7]. 

Albumin 5% and 25% concentrations are available. It takes approximately three to four times as much lactated Ringer s or normal saline solution to yield the same volume expansion as 5% albumin solution. However, albumin is much more costly than crystalloid solutions. The 5% albumin solution is relatively iso-oncotic, whereas 25% albumin is hyperoncotic and tends to pull fluid into the compartment containing the albumin molecules. In general, 5% albumin is used for hypovolemic states. The 25% solution should not be used for acute circulatory insufficiency unless diluted with other fluids or unless it is being used in patients with excess total body water but intravascular depletion, as a means of pulling fluid into the intravascular space. 

The volume of distribution of many drugs is significantly increased or decreased in patients with CKD. Changes result from altered protein or tissue binding, or pathophysiologic alterations in body composition (e.g., fractional contribution of total body water to total body weight). 

Sixty percent of total body water is distributed intracellularly, and 40% is contained in the extracellular space. 

Euvolemic hyponatremia is associated with a normal or slightly decreased ECF sodium content and increased total body water and ECF volume. 

Body composition 1 Total body water 1 Lean body mass T Body fat or i Serum albumin <-> or T -Acid glycoprotein (T by several disease states)... 

For a drug that is confined solely to the circulation (blood volume is 80 mb kg ) the volume of distribution will be 0.08 L kg . Distribution into total body water (800 mb kg ) results in a volume of distribution of 0.8 b kg . Beyond these values the number has only a mathematical importance. For instance a volume of distribution of 2 b kg means only, that less than 5 % of the dmg is present in the circulation. The drug may be generally distributed to many tissues and organs or concentrated in only a few. 

It is easiest to understand how clearance relates to the rate of decline of drug concentrahon (half-life) if we consider the model depicted in Figure 2.9. When a dose (D) is administered intravenously then the inihal free concentrahon achieved in plasma Cp(fo) is dependant on the volume of extracellular or total body water minus plasma water and the amount of drug bound to hssues and proteins. 

Caicuiation of sodium deficit-To calculate the amount of sodium that must be administered to raise serum sodium to the desired level, use the following equation (TBW = total body water) Na deficit (mEq) = TBW (desired - observed plasma Na). 

Peak plasma concentrations (Cmax) fasted healthy volunteers occur between 1 and 2 hours with a terminal plasma elimination half-life of approximately 30 hours (range, 20 to 50 hours) after oral administration. Steady-state concentrations are reached within 5 to 10 days following oral doses of 50 to 400 mg given once daily. The apparent volume of distribution approximates that of total body water. Plasma protein binding is low (11 % to 12%). 

Stir with a pencil or pen and discuss the change in color as a response to increased dose of food color in each glass. Discuss how some chemicals, caffeine being one, distribute throughout total body water. 

This is a bit of a surprise as the patient only weighs 62 kg and therefore has a total body water content of around 40 1 at most. How can an apparent volume of distribution be so much bigger than any physiological volume ... 

During development, marked changes in body composition occur. Alterations in the total body water (TBW), extracellular water (ECW) and body fat pools are illustrated in Fig. 1. The most dynamic changes occur in the first year of life with the exception of total body fat which in males is reduced by approximately 50% between 10 and 20 years of life. 

Total body water Increased Increased Near adult pattern... 

Reduced total body water reduced lean body mass increased body fat... 

The total body water of prematures, newborns, and infants is significantly greater than it is for older children and adults. This increased total body water increases the volume of drug distribution for water-soluble compounds. As a consequence, there is a need to administer... 

Drug distribution in elderly patients may be altered by hypoalbuminemia, qualitative changes in drug-binding sites, reductions in relative muscle mass, increases in the proportion of body fat, and decreases in total body water. The plasma level of free, active drug is often a direct function of the extent of drug binding to plasma proteins. There is a well-documented age-dependent decline (about 20%) in plasma albumin concentration in humans due to a reduced rate of hepatic albumin... 

Body fluids are partitioned between the intracellular fluids (ICF), which constitute two-thirds of total body water, and extracellular fluids (ECF), which constitute one-third of total body water. The ECF consists of plasma and interstitial fluid plus lymph. The ionic composition differs substantially between ECF and ICF (Table 21.1). Sodium is the primary cation in ECF, whereas potassium is the principal intracellular cation. 

The elimination half-life of Li+ is estimated at 24 hours, and more than 90% of the dose of Li+ is excreted into the urine. Renal clearance, however, is only 20%, since Li+ is actively reabsorbed in the proximal tubule at sites normally used for the conservation of Na. Thus, competition between Li+ and Na for uptake sites can alter the elimination of Li+ and its concentration in total body water. Na+ loading enhances Li+ clearance, while Na+ depletion promotes Li+ retention. This important relationship explains the appearance of Li+ toxicity (discussed later) associated with diet (low Na ),... 

Pharmacokinetics Protein binding low. Rapidly distributes to total body water after IV infusion. Extensively metabolized by the liver. Minimal excretion in the urine. Removed by hemodialysis. Half-life 5 hr. 

Distribution Decreased total body water Higher concentration of drugs that... 

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