Extracellular fluid renal regulation

Around 99% of calcium is contained in the bones, whereas the other 1% resides in the extracellular fluid. Of this extracellular calcium, approximately 40% is bound to albumin, and the remainder is in the ionized, physiologically active form. Normal calcium levels are maintained by three primary factors parathyroid hormone, 1,25-dihydroxyvitamin D, and calcitonin. Parathyroid hormone increases renal tubular calcium resorption and promotes bone resorption. The active form of vitamin D, 1,25-dihydroxyvitamin D, regulates absorption of calcium from the GI tract. Calcitonin serves as an inhibitory factor by suppressing osteoclast activity and stimulating calcium deposition into the bones. 

No specific antidote has been shown to be effective in treating 1,2-dibromoethane intoxication once absorption into the bloodstream has occurred (Ellenhorn and Barceloux 1988). Intravenous infusions of glucose may limit the hepatotoxicity of 1,2-dibromoethane (ERA 1989b). During the recovery phase, a diet rich in vitamin B and carbohydrates may limit liver damage (Dreisbach and Robertson 1987 Lawrence and Michaels 1984). Hemodialysis may be needed to regulate extracellular fluid and electrolyte balance and to remove metabolic waste products if renal failure occurs (ERA 1989b). 

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. 

Vasopressin, also called antidiuretic hormone (ADH), is a cyclic nonapeptide hormone, which is released from the posterior pituitary. Its primary function in the body is to regulate extracellular fluid volume by affecting renal handling of water. Specific actions include inhibition of... 

Cystatin refers to a diverse family of protein cysteine protease inhibitors. There are three general types of cystatins Type 1 (stefens), which are primarily found in the cytoplasm but can appear in extracellular fluids Type 2, which are secreted and found in most extracellular fluids and Type 3, which are multidomain protease inhibitors containing carbohydrates and that include the kininogens. Cystatin 3 is used to measure renal function in clinical chemistry. See Barrett, A.J., The cystatins a diverse superfamily of cysteine peptidase inhibitors, Biomed. Biochim. Acta 45,1363-1374,1986 Katunuma, N., Mechanisms and regulation of lysosomal proteolysis, Revis. Biol. Cellular 20, 35-61, 1989 Gauthier, F., Lalmanach, G., Moeau, T. et al., Cystatin mimicry by synthetic peptides, Biol Chem. Hoppe Seyler 373, 465-470, 1992 Bobek, L.A. and Levine,... 

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. 

Among the catecholamines, dopamine has long been of interest to both chemists and neuroscientists. It is one of the most important neurotransmitters and is ubiquitous in the mammalian central nervous system[5]. It modulates many aspects of brain circuitry in a major system of the brain including the extra pyramidal and mesolimbic system, as well as the hypothalamic pituitary axis[6]. It also plays a crucial role in the functioning of the central nervous, cardiovascular, renal and hormonal systems[4], A loss of dopamine containing neurons or its transmission is also related to a number of illnesses and conditions including Parkinson s disease, schizophrenia, motivational habit, reward mechanisms and the regulation of motor functions and in the function of the central nervous, hormonal and cardiovascular system[5,18,19]. It is therefore of interest to measure dopamine in the extracellular fluid in animals to order to monitor neurotransmission processes and correlate neurochemistry with behavior[19]. 

The pH of extracellular fluid is kept within very narrow limits (7.35-7.45) by buffering mechanisms (see also Chapter 1), the lungs, and the kidneys. These three systems do not act independently. For example, in acute blood loss release of ADH and aldosterone restores the blood volume and renal regulation of the pH leads to shifts in K+ and Na+ levels. 

Serum phosphorus concentration is so closely regulated by the kidneys that it is unusual for hyperphosphatemia (serum phosphorus concentration >4.5 mg/dL) to develop in patients with normal renal function. The most frequent causes of hyperphosphatemia are decreases in urinary phosphorus excretion, and increases in phosphate entrance into the extracellular fluid via either exogenous administration or endogenous intracellular phosphate release. 

The parathyroid hormone regulates ionic calcium homeostasis in extracellular fluids by a direct action on the skeleton. It also promotes the renal excretion of phosphorus and produces other physiological effects which are not obviously related to its calcemic action. 

PHYSIOLOGICAL FUNCTIONS The primary function of PTH is to maintain a constant concentration of Ca in the extracellular fluid. The principal processes regulated are renal Ca reabsorption and mobdization of bone Ca + (Figure 61-3). The actions of PTH on tissues are mediated by at least two GPCRs that couple to G and G in cell-specific manners. 

---