Bicarbonate renal tubular reabsorption

Sodium bicarbonate increases renal tubular reabsorption of amphetamine, resulting in a prolonged amphetamine elimination half-life be aware of this combination. 

The answer is a. (Hardman, pp 16-20.) Sodium bicarbonate is excreted principally in the urine and alkalinizes it. Increasing urinary pH interferes with the passive renal tubular reabsorption of organic acids (such as aspirin and phenobarbital) by increasing the ionic form of the drug in the tubular filtrate. This would increase their excretion. Excretion of organic bases (such as amphetamine, cocaine, phencyclidine, and morphine) would be enhanced by acidifying the urine. 

Vaupshas H J, Levy M 1990 Distribution of saline following acute volume loading postural effects. Clinical and Investigative Medicine 13 165-177 Velanovich V 1989 Crystalloid versus colloid fluid resuscitation a meta-analysis of mortality. Surgery 105 65-71 Vukmir R B, Bircher N G, Radovsky A et al 1995 Sodium bicarbonate may improve outcome in dogs with brief or prolonged cardiac arrest. Critical Care Medicine 23 515-522 Walton R J 1979 Effect of intravenous sodium lactate on renal tubular reabsorption of phosphate in man. Clinical Science 57 125-127... 

The low plasma PCO2 leads to decreased renal tubular reabsorption of bicarbonate and increased renal excretion ofNa , K, and water. Water also is lost by salicylate-induced sweating (especially in the presence of hyperthermia) and hyperventilation dehydration, which can be profound, particularly in children, rapidly occurs. Because more water than electrolyte is lost through the lungs and by sweating, the dehydration is associated with hypernatremia. Prolonged exposure to high doses of salicylate also causes depletion ofK due to both renal and extrarenal factors. 

Renal Tubular Acidoses, Types I and II These syndromes are predominantly characterized by loss of bicarbonate because of decreased tubular secretion of (distal or type I RTA) or decreased reabsorption of HCO3 (proximal or type II RTA). Because the major urine-acidifying power of the kidneys rests in the distal tubules, the proximal and distal RTAs may be differentiated by measurement of urine pH. In proximal RTA, urine pH becomes <5.5, whereas in distal RTA the distal tubules are compromised and urine pH is >5.5. When distal RTA is associated with obstructive nephropathy, sickle cell disease, or systemic lupus erythematosus, hyperkalemia may... 

Besides hypoglycemia, D-fructose-induced renal acidification in the HFI defect involves a lowered hydrogen-ion secretory capacity of the proximal nephron, as evidenced by a 20 to 30% diminution in renal-tubular (T) reabsorption of bicarbonate (THCO3) and simultaneous occurrence, and persistence throughout D-fructose administration, of impaired tubular reabsorption of phosphate, cc-amino nitrogen, and uric acid. This abnormality of renal metabolism affects the renal cortex, which contains aldolase B, but does not affect the renal medulla. Thus, the abnormality may result from accumulation of D-fructose 1-phosphate in the renal cortex. The intimate, biochemical mechanism for renal, tubular acidosis is still unknown.164... 

In type II renal tubular acidosis there is a defect in the secretion of hydrogen ions by the proximal tubule. Because the proximal tubule is the major site of bicarbonate reabsorption (4000 mEq of bicarbonate per day as compared to 70 mEq in the distal tubule), the defect in secretion of hydrogen ions in this condition leads to the flooding of the distal tubule with bicarbonate. The capacity of hydrogen ions secreted by the distal tubule to buffer this massive efflux of bicarbonate is soon overwhelmed and, as a result, large quantities of bicarbonate are excreted in the urine. Much more bicarbonate needs to be administered in this condition to correct the acidosis than is necessary in type I renal tubular acidosis. In general, in renal tubular acidosis the impairment in hydrogen ion secretion leads to excretion of potassium ions in urine. 

Tubular acidosis is primary (an isolated inherited metabolic disorder) or secondary (a metabolic disorder associated with inherited or acquired lesions). It is characterized by the inability to maintain normal blood pH as a result of interference with bicarbonate reabsorption or a defect in renal hydrogen excretion. By definition, glomerular filtration is not altered in renal tubular acidosis. 

It is also believed that a fraction of HCO3 is reabsorbed independently of any form of excretion, whether it be carbonic anhydrase dependent or independent. Thus, proximal tubular acidosis could result from low carbonic anhydrase activity, ineffective diffusion of hydrogen ions, or a defect in the -independent reabsorption of bicarbonate. It is not known which distortion is responsible for proximal renal tubular acidosis. 

If tubular reabsorption does not meet physiological requirements, a renal tubular mechanism for generating bicarbonate is called into play this mechanism is shown in outline in Figure 1.4B. Carbon dioxide from metabolism reacts with water to yield hydrogen ions, which are actively pumped into the tubular fluid rendering the urine acid, and bicarbonate ions, which diffuse into the renal interstitial fluid and hence into the general extracellular fluid of the body. The tubules continually add bicarbonate to the body by this mechanism. 

These results suggest acute renal failure (ARF) due to tubular necrosis caused by phenol. Plasma sodium is low due mainly to impaired reabsorption in the nephron, although the slightly low albumin suggests haemodilution possibly as a result of excessive i.v. fluids. Potassium is raised due to poor exchange with sodium in the distal tubule and the acidosis (low pH and low bicarbonate concentration) arises from defective acidification of the glomerular filtrate acidosis is often associated with hyperkalaemia (raised plasma... 

The mechanism for the renal toxicity observed in cases of adult exposure to uranium is believed to be due to the retention of uranium in the kidney. This is the result of the reabsorption of bicarbonate from the ultrafiltrate in the proximal tubule and the resulting release of the U02 ion from a bicarbonate complex. Newborn humans have relahvely inefficient tubular secretion and reabsorption compared to older children or adults, and whether this would increase or decrease the susceptibility of newborns to uranium toxicity is not known. 

Major functions of the distal nephron include the regeneration of bicarbonate, the excretion of acid (hydrogen ion), the secretion of potassium, and the reabsorption of water. Damage to this portion of the nephron may present as significant acidemia and either hypo-or hyperkalemia, depending on the mechanism of injury. For example, amphotericin B produces small pores in the luminal membrane of distal tubular cells. These pores allow small molecules such as potassium to leak out the molecules are then wasted in the urine. Consequently, amphotericin B nephrotoxicity is characterized by hypokalemia secondary to renal potassium wasting. ATN is associated with urinary sediment characterized by the presence of tubular cells, coarse granular casts, and rarely, RBC casts. 

Mineralocorticoid excess also plays a significant role in the maintenance of metabolic alkalosis. In patients with volume-responsive metabolic alkalosis, intravascular volume depletion stimulates aldosterone secretion. As discussed earlier, excess mineralocorticoid activity may also underlie the generation of metabolic alkalosis. In either situation, the increased mineralocorticoid effect stimulates collecting duct H+ secretion. Metabolic alkalosis may also be maintained by persistent hypokalemia. Hypokalemia has a multitude of effects on renal acid-base homeostasis, enhancing proximal tubular bicarbonate reabsorption, stimulating ammoniagenesis and increasing distal tubular H secretion. ... 

Metabolic compensation occurs when respiratory alkalosis persists for more than 6 to 12 hours. In response to the alkalemia, proximal tubular bicarbonate reabsorption is inhibited and the serum bicarbonate concentration falls. Renal compensation is usually complete within 1 to 2 days. The renal bicarbonaturia, as well as decreased NH4+ and titratable acid excretion, are direct effects of the reduced PaC02 and pH on renal reabsorption of chloride and bicarbonate. The... 

In this condition, all metabolic functions of the kidney are depressed these functions include tubular secretion of hydrogen ions, reabsorption of bicarbonate ions and production of ammonia. In a subject with impaired renal function, the urine can scarcely be concentrated or diluted by comparison with plasma, its pH can be only slightly lowered below or raised above the pH of plasma and, because of lack of ammonia synthesis, the excretion of acid is profoundly depressed. The kidney can no longer perform its homeostatic regulatory role. Such a patient consuming a normal diet becomes progressively more acidotic because of the release of acid resulting from the metabolism of protein (Chapter 5). 

B. Bicarbonate ions entering renal venous blood as a result of reabsorption in the proximal convoluted tubule are the same ions that were in the tubular fluid. 

---