Dfureties In broadest terms a diuretic is something that produces a dfuresis or increased urine formation.Thus 1 litre of water drunk surplus to normal requirements is a powerful diuretic,as demonstrated by generations of students in their physiology practical classes.Bowever,in medical terms a diuretic usually refers to a drug which causes a diuresis in someome who would otherwise pass much less urine.In practice the definition is even more restricted since,in general,diuretics act by causing a loss of excess sodium,chloride and water (though other ioas are often lost in excess too)thereby reducing the extracellofar fluid volue,which is the dominant site of sodiun and chloride. Sodiun has heen described as the skeleton of the extracellular fluid.The intracellular sodium level is relatively low and fixed,so extra sodium taken into the hody is added to the extracellular fluid,and sodiun lost fron the body is lost from the extracellular fluid.Given a certain amount of sodium in the extracellular fluid,electrical neutrality demands an equal amount of amion.Thus chloride is retained to balance the sodiun ions.To maintain pormal osmolality,an equivalent amount of water is retained.Thus the extracellular fluid clothes the sodium skeleton. In normal circumstances the body tolerates moderate fluctuations in extracellular fluid volume.Whem we eat a salty meal and are compelled by the acconpanying thirst to drink more fluid.our extracellular volune may go up by a litre or more without disturbing body function.The extra fluid is excreted in a leisurely fashion over a day or two under the influence of reduced aldosterone and increased natriuretic hormone.Both these hormones act primarily by regulating body sodiun. Bowever,in sone diseases there are gross changes in body sodfun and consequently extracellular fluid.In heart failure the volume may rise froa around 10-15 litres (depending on body size)by several litres in mild cases and by 5-10 litres in severe cases.Similar changes can occur in lfver and renal failure.The excessive
Diuretics In broadest terms a diuretic is something that produces a diuresis or increased urine formation. Thus 1 litre of water drunk surplus to normal requirements is a powerful diuretic, as demonstrated by generations of students in their physiology practical classes. However, in medical terms a diuretic usually refers to a drug which causes a diuresis in someone who would otherwise pass much less urine. In practice the definition is even more restricted since, in general, diuretics act by causing a loss of excess sodium, chloride and water (though other ions are often lost in excess too) thereby reducing the extracellular fluid volume, which is the dominant site of sodium and chloride. Sodium has been described as the skeleton of the extracellular fluid. The intracellular sodium level is relatively low and fixed, so extra sodium taken into the body is added to the extracellular fluid, and sodium lost from the body is lost from the extracellular fluid. Given a certain amount of sodium in the extracellular fluid, electrical neutrality demands an equal amount of anion. Thus chloride is retained to balance the sodium ions. To maintain normal osmolality, an equivalent amount of water is retained. Thus the extracellular fluid clothes the sodium skeleton. In normal circumstances the body tolerates moderate fluctuations in extracellular fluid volume. When we eat a salty meal and are compelled by the accompanying thirst to drink more fluid, our extracellular volume may go up by a litre or more without disturbing body function. The extra fluid is excreted in a leisurely fashion over a day or two under the influence of reduced aldosterone and increased natriuretic hormone. Both these hormones act primarily by regulating body sodium. However, in some diseases there are gross changes in body sodium and consequently extracellular fluid. In heart failure the volume may rise from around 10-15 litres (depending on body size) by several litres in mild cases and by 5-10 litres in severe cases. Similar changes can occur in liver and renal failure. The excessive
extracellular fluid is distributed between the interstitial compartment,where several extra litres are manifested as oedema.and the intravascular compartnent, where increased blood volune leads to venous congestion and cardiac strain.In these circunstances.diuretics can improve the situation draratically. Essentially diuretics are selective poisons of the kidney's ability to reabsorb sodiun fron the glonerular filtrate.They do not affect the obligatory reabsorption in the proximal convoluted tubule,but act on the distal convoluted tubule.and in the case of the highly potent loop diuretics on the cells of the ascending limb of the loop of Henle.By reducing sodiun reabsorption,diuretics increase sodiun loss in the urine.and this is accompanied by loss of chloride and of water.The benefits can be imediate and dramatic in the case of heart failure.In advanced heart failure excessive extracellular fluid leads to severe dependent oedema (which is mainly an inconvenience),and an increased intravascular volune which places a severe burden on the failing heart and favours the developeent of life-threatening pulmonary oedems.Intravenous administration of a powerful diuretic can relieve the pulmonary oedens and improve the cardiac state within the hour,with continuing improvenent in the next few days.The loss of fluid is apparent in the huge quantities of urine passed,e.g.5 litres in the first few hours.It can also be monitored by the simple measure of weighing the patient.Loss of,say,7 litres of surplus extracellular fluid in a week results in a loss of weight of 7 kg.since each litre of urine or extracellular fluid weighs very close to I kg.Nutritional changes over this period of time would normally produce little change in weight. Diuretics are also used in the treatnent of hypertension,particularly as an initial treatment of mild hypertension.Their action is complex,but at least part of the effeet is due to loss of extracellular fluid,leading to a reduced plasma volune,a fall in stroke volune and hence a fall in arterial blood pressure.Excessive diuretic therapy can sometines lead to inappropriately low blood pressure,by excessively reducing cireulating blood volume. Diuretics vary in their effects on electrolytes other than sodiun and chloride. In general,a diuresis tends to reduce the opportunity for reabsorption of other
extracellular fluid is distributed between the interstitial compartment, where several extra litres are manifested as oedema, and the intravascular compartment, where increased blood volume leads to venous congestion and cardiac strain. In these circumstances, diuretics can improve the situation dramatically. Essentially diuretics are selective poisons of the kidney's ability to reabsorb sodium from the glomerular filtrate. They do not affect the obligatory reabsorption in the proximal convoluted tubule, but act on the distal convoluted tubule, and in the case of the highly potent loop diuretics on the cells of the ascending limb of the loop of Henle. By reducing sodium reabsorption, diuretics increase sodium loss in the urine, and this is accompanied by loss of chloride and of water. The benefits can be immediate and dramatic in the case of heart failure. In advanced heart failure excessive extracellular fluid leads to severe dependent oedema (which is mainly an inconvenience), and an increased intravascular volume which places a severe burden on the failing heart and favours the development of life-threatening pulmonary oedema. Intravenous administration of a powerful diuretic can relieve the pulmonary oedema and improve the cardiac state within the hour, with continuing improvement in the next few days. The loss of fluid is apparent in the huge quantities of urine passed, e.g. 5 litres in the first few hours. It can also be monitored by the simple measure of weighing the patient. Loss of, say, 7 litres of surplus extracellular fluid in a week results in a loss of weight of 7 kg, since each litre of urine or extracellular fluid weighs very close to 1 kg. Nutritional changes over this period of time would normally produce little change in weight. Diuretics are also used in the treatment of hypertension, particularly as an initial treatment of mild hypertension. Their action is complex, but at least part of the effect is due to loss of extracellular fluid, leading to a reduced plasma volume, a fall in stroke volume and hence a fall in arterial blood pressure. Excessive diuretic therapy can sometimes lead to inappropriately low blood pressure, by excessively reducing circulating blood volume. Diuretics vary in their effects on electrolytes other than sodium and chloride. In general, a diuresis tends to reduce the opportunity for reabsorption of other
ions such as potassium,and so potassium depletion is a risk.requfring in some cases potassiun supplememts.In contrast,diuretics which antagonize the actions of aldosterone tend to raise body potassium by antagonizing aldosterone's promotion of potassium excretion In exchange for sodium reabsorption
ions such as potassium, and so potassium depletion is a risk, requiring in some cases potassium supplements. In contrast, diuretics which antagonize the actions of aldosterone tend to raise body potassium by antagonizing aldosterone's promotion of potassium excretion in exchange for sodium reabsorption