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Physiology of Diuretic Action
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PHYSIOLOGY OF DIURETIC ACTION
O B J E C T I V E S Upon completion of this chapter, the student should be able to answer the following questions: 1. What effects do diuretics have on Na+ handling by the kidneys? 2. What effects do aquaretics have on water handling by the kidneys? 3. Why do diuretics decrease the volume of the extracellular fluid? 4. What mechanisms are involved in delivering diuretics to their sites of action along the nephron?
D
iuretics, as the name implies, are drugs that cause an increase in urine output. It is important, however, to distinguish this diuresis from that which occurs after the ingestion of large volumes of water. In the latter case, the urine is primarily made up of water, and solute excretion is not increased. In contrast, diuretics result in the enhanced excretion of both solute and water. All diuretics (with the exception of aquaretics, which will be discussed) have as their common mode of action the primary inhibition of Na+ reabsorption by the nephron. Consequently, they cause an increase in the excretion of Na+, termed natriuresis. However, the effects of diuretics are not limited to Na+ handling.
5. What is the primary nephron site where each class of diuretics acts, and what is the specific membrane transport protein affected? 6. How do nephrons alter their function in response to diuretics, and how does this affect the action of diuretics? 7. What are the effects of the various classes of diuretics on the renal handling of K+, Ca++, bicarbonate (HCO−3), inorganic phosphate (Pi), and solute-free water?
The renal handling of many other solutes also is influenced, usually as a consequence of alterations in Na+ transport. Recently, drugs have been developed that block the action of arginine vasopressin (AVP) on the distal tubule and collecting duct. These drugs, called aquaretics, cause a water diuresis. This chapter reviews the cellular mechanisms of action of various diuretics and the nephron sites at which these diuretics act. In addition to their effects on Na+ handling by the nephron, their effects on the renal handling of other solutes (e.g., K+, Ca++, inorganic phosphate [Pi], and bicarbonate [HCO−3 ]) and of water are considered. The effects of aquaretics on water excretion also are discussed. 167
PHYSIOLOGY OF DIURETIC ACTION
O B J E C T I V E S Upon completion of this chapter, the student should be able to answer the following questions: 1. What effects do diuretics have on Na+ handling by the kidneys? 2. What effects do aquaretics have on water handling by the kidneys? 3. Why do diuretics decrease the volume of the extracellular fluid? 4. What mechanisms are involved in delivering diuretics to their sites of action along the nephron?
D
iuretics, as the name implies, are drugs that cause an increase in urine output. It is important, however, to distinguish this diuresis from that which occurs after the ingestion of large volumes of water. In the latter case, the urine is primarily made up of water, and solute excretion is not increased. In contrast, diuretics result in the enhanced excretion of both solute and water. All diuretics (with the exception of aquaretics, which will be discussed) have as their common mode of action the primary inhibition of Na+ reabsorption by the nephron. Consequently, they cause an increase in the excretion of Na+, termed natriuresis. However, the effects of diuretics are not limited to Na+ handling.
5. What is the primary nephron site where each class of diuretics acts, and what is the specific membrane transport protein affected? 6. How do nephrons alter their function in response to diuretics, and how does this affect the action of diuretics? 7. What are the effects of the various classes of diuretics on the renal handling of K+, Ca++, bicarbonate (HCO−3), inorganic phosphate (Pi), and solute-free water?
The renal handling of many other solutes also is influenced, usually as a consequence of alterations in Na+ transport. Recently, drugs have been developed that block the action of arginine vasopressin (AVP) on the distal tubule and collecting duct. These drugs, called aquaretics, cause a water diuresis. This chapter reviews the cellular mechanisms of action of various diuretics and the nephron sites at which these diuretics act. In addition to their effects on Na+ handling by the nephron, their effects on the renal handling of other solutes (e.g., K+, Ca++, inorganic phosphate [Pi], and bicarbonate [HCO−3 ]) and of water are considered. The effects of aquaretics on water excretion also are discussed. 167