Kidneys extracellular fluid volume

The integrity of mammalian kidneys is vital to body homeostasis, because the kidneys play the principal role in the excretion of metabolic wastes and the regulation of extracellular fluid volume, electrolyte balance, and acid-base... 

Diuretics are a group of therapeutic agents designed to reduce the volume of body fluids. Their mechanism of action is at the level of the kidney and involves an increase in the excretion of Na+ and Cl ions and, consequently, an increase in urine production. As discussed in Chapter 2, sodium is the predominant extracellular cation and, due to its osmotic effects, a primary determinant of extracellular fluid volume. Therefore, if more sodium is excreted in the urine, then more water is also lost, thus reducing the volume of extracellular fluids including the plasma. 

The primary function of the renal system is the elimination of waste products, derived either from endogenous metabolism or from the metabolism of xenobiotics. The latter function is discussed in detail in Chapter 10. The kidney also plays an important role in regulation of body homeostasis, regulating extracellular fluid volume, and electrolyte balance. 

The one-compartment model of distribution assumes that an administered drug is homogeneously distributed throughout the tissue fluids of the body. For instance, ethyl alcohol distributes uniformly throughout the body, and therefore any body fluid may be used to assess its concentration. The two-compartment model of distribution involves two or multiple central or peripheral compartments. The central compartment includes the blood and extracellular fluid volumes of the highly perfused organs (i.e., the brain, heart, liver, and kidney, which receive three fourths of the cardiac output) the peripheral compartment consists of relatively less perfused tissues such as muscle, skin, and fat deposits. When distributive equilibrium has occurred completely, the concentration of drug in the body will be uniform. 

The kidney and bladder are very important in toxicology because they are the main route of elimination of hydrophilic toxicant metabolites and because damage to them in the form of impaired kidney function or bladder cancer is one of the major adverse effects of toxicants. The kidney plays a key role in maintaining body homeostasis. The basic unit of the kidney, through which the organ performs its crucial blood filtration action, is the nephron. As the main organ through which fluid is lost from the body, it is vital in the maintenance of extracellular fluid volume. It acts to maintain... 

The kidneys play an important role in maintaining a proper environment for the cells in the body. By regulating the excretion of water, salts and metabolic end products, the kidneys control the plasma osmolality (i.e., the concentration of ions in the blood), the extracellular fluid volume, and the proportions of various blood solutes. The kidneys are also involved in the production of a set of hormones that make the blood vessels (arterioles) contract in the kidneys as well as in other parts of the body. These hormones can give rise to changes in the vascular structure, and... 

Figure 33-3. Summary of the renin-angiotensin-aldosterone system. Aldosterone secretion is controlled by several factors, including increased K+,ACTH, or angiotensin II.A1-dosterone acts to increase Na+ retention by both the kidney and colon.Aldosterone also promotes renal K+ excretion, which contributes to maintenance of Na+/K+ balance. In the absence of aldosterone, Na+ is lost, K+ is enhanced, the extracellular fluid volume is reduced, and mean arterial pressure and renal perfusion pressure are decreased. As a result, renin secretion is increased, leading to increased formation of angiotensin II, which promotes vasoconstriction and aldosterone secretion.

Because of its powerful action in the kidney, torasemide can rapidly deplete extracellular fluid volume and mobilize tissue oedema, particularly from the lung. This both improves the patient s breathing and improves their ability to exercise. 

Isotonicity of the extracellular space is regulated by (i.) thirst mechanism, (2.) ADH, and (S.) dilution and concentration potential of the kidneys. Maintenance of extracellular isovoiaemia is effected by a change in renal sodium excretion. For this reason, disturbances in the sodium supply primarily result in changes in the extracellular fluid volume. Isohydria is also continually regulated within the normal range. 

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... 

Edema is a common manifestation of volume overload and extracellular fluid volume expansion. Clinicians should evaluate patients for signs and symptoms of volume overload (e.g., pitting edema, rales, ascites, shortness of breath, and increased weight). Blood pressure monitoring in the clinic setting and at home if feasible to detect hypertension is also warranted. As kidney disease progresses dietary intervention and diuretic therapy (based on the degree of kidney function) will likely become necessary. 

Corticosteroids, CSA, TAC, and impaired kidney graft function may cause post-transplant hypertension. The primary mechanism of CI-associated hypertension in heart transplant recipients may be related to the Cl-induced stimulation of intact renal sympathetic nerves and the absence of reflex cardiac inhibition of the sympathetic nervous system, but a number of other mechanisms, including decreased prostacyclin and nitric oxide production, also have been proposed. " In addition to the propensity to cause peripheral vasoconstriction, CIs promote sodium retention, resulting in extracellular fluid volume expansion. TAC appears to have less potential to induce hypertension following transplantation than CSA. Most classes of antihypertensive medications effectively reduce blood pressure in transplant patients (see Chap. 13). ... 

These actions on electrolyte transport, in the kidney and in other tissues e.g., colon, salivary glands, and sweat glands), appear to account for the physiological and pharmacological activities that are characteristic of mineralocorticoids. Thus, the primary features of hyperaldosteronism are positive Na balance with consequent expansion of extracellular fluid volume, normal or slight increases in plasma Na+ concentration, hypokalemia, and alkalosis. Mineralocorticoid deficiency, in contrast, leads to Na+ wasting and contraction of the extracellular fluid volume, hyponatremia, hyperkalemia, and acidosis. Chronically, hyperaldosteronism can cause hypertension, whereas aldosterone deficiency can lead to hypotension and vascular collapse. 

Kidney dysfunction can lead to edema formation as a result of decreased formation of urine and the subsequent imbalance of water and electrolyte (e.g., sodium ion) homeostasis. Retention of salt and water results in an expansion of the extracellular fluid volume and, thus, edema formation. Thus, when salt intake exceeds salt excretion, edema can form. Edema formation also is associated with deceased protein levels in blood, as seen in nephrotic syndrome and liver disease. Cirrhosis of the liver leads to increased lymph in the space of Disse. Eventually, the increased lymph volume results in movement of fluid into the peritoneal cavity and ascites develops. 

Senekjian, H.O., Knight, T.F., Sansom, S.C., and Weinman, E.J. Effect of flow rate and the extracellular fluid volume on proximal urate and water absorption. Kidney Int. 17 155-161,... 

The volume of extracellular fluid is direcdy related to the Na" concentration which is closely controlled by the kidneys. Homeostatic control of Na" concentration depends on the hormone aldosterone. The kidney secretes a proteolytic enzyme, rennin, which is essential in the first of a series of reactions leading to aldosterone. In response to a decrease in plasma volume and Na" concentration, the secretion of rennin stimulates the production of aldosterone resulting in increased sodium retention and increased volume of extracellular fluid (51,55). 

The rate at which an equilibrium concentration of a drug is reached in the extracellular fluid of a particular tissue will depend on the tissue s perfusion rate the greater the blood flow the more rapid the distribution of the drug from the plasma into the interstitial fluid. Thus, a drug will appear in the interstitial fluid of liver, kidney, and brain more rapidly than it will in muscle and skin (Table 3.2). The pharmacokinetic concept of volume of distribution (a derived parameter that relates the amount of drug in the body to the plasma concentration) is discussed more fully in Chapter 5. 

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