Potassium renal tubular reabsorption

An 18-year-old woman presented with new onset seizures and polydipsia. She had a hyponatremia of 117 mmol/1, polyuria for several hours, renal glycosuria with urine glucose of over 55 mmol/1, a blood glucose of 6.6 mmol/1, and solute diuresis. She had low tubular reabsorption of phosphorus, with an appropriate transtubular potassium gradient of 3.0 and a serum potassium of 3.7 mmol/1. After medical treatment and gradual correction of her hyponatremia, her tubular... 

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. 

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. 

Aldosterone maintains the sodium levels of the body by stimulating the reabsorption of sodium in the renal tubules. In adrenalectomized dogs and in patients with Addison s disease, sodium excretion is proportional, but not equal, to glomerular filtration. Aldosterone acts in the distal tubule at the site of sodium reabsorption and potassium excretion, but much of the information on aldosterone s mode of action and on renal tubular cells has been obtained indirectly by studying the effect of the hormone on simpler systems. Aldosterone stimulates active sodium transport across the bladder and skin of toads. This effect of aldosterone is manifest only after a lag period. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

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... 

Mineralocorticoids are believed to increase sodium reabsorption by affecting sodium channels and sodium pumps on the epithelial cells lining the renal tubules.18,58 Mineralocorticoids ability to increase the expression of sodium channels is illustrated in Figure 29-5. These hormones enter the tubular epithelial cell, bind to receptors in the cell, and create an activated hormone-receptor complex.18 This complex then travels to the nucleus to initiate transcription of messenger RNA units, which are translated into specific membrane-related proteins.27,58 These proteins in some way either create or help open sodium pores on the cell membrane, thus allowing sodium to leave the tubule and enter the epithelial cell by passive diffusion.27,83 Sodium is then actively transported out of the cell and reabsorbed into the bloodstream. Water reabsorption is increased as water follows the sodium movement back into the bloodstream. As sodium is reabsorbed, potassium is secreted by a sodium-potassium exchange, thus increasing potassium excretion (see Fig. 29-5). 

Cell death due to apoptosis or necrosis is not the only form of tubular injury in AKI. There is also sub-lethal injury causing cell dysfunction. For example, alterations in proximal tubular cell polarity occur during renal ischemia. Tubule polarity is essential for its primary function of selective reabsorption of ions from the tubular fluid. Sodium-potassium-ATPase (NaK-ATPase), the enzyme, normally localized to the basolateral membrane, maintains tubular polarity by regulation of cellular transport sodium and potassium in proximal tubules. NaK-ATPase is hnked to the cytoskeleton/ membrane complex by a variety of proteins including spectrin. It has been demonstrated that in early reperfusion period spectrin dissociates from the cytosleleton and NaK-ATPase moves from the basolateral membrane into the cytoplasm and apical membrane [54-58]. 

---