Bicarbonate, resorption

Kidneys Dysfunction of the proximal tubule may occur as a late manifestation of Wilson s disease. Epithelial flattening, a loss of the brush-border membrane, mitochondrial anomalies and fatty cellular changes can be observed. These findings are, in turn, responsible for proteinuria with a predominance of hyperaminoaciduria (L. UzMAN et al., 1948). Enhanced calciuria and phosphat-uria may cause osteomalacia as well as hypoparathyroidism. (329, 344) Glucosuria and uricosuria, if present, are without clinical relevance. Due to decreased bicarbonate resorption, tubular acidosis may occur, with a tendency towards osteomalacia as well as the development of nephrocalcinosis and renal stones (in some 15% of cases). (344, 356, 392) The intensity of the copper deposits in the kidneys correlates closely with the cellular changes and functional disorders. The glomerular function is not compromised, with the result that substances normally excreted in the urine are not retained. 

FIGURE 10.12 Sodiuin bicarbonate resorption by cells of the proximal renal tubule. (1) Sodium enters through the apical membrane via the Na-H exchanger. (2) The resorbed sodium passes out of the celJ into the interstitial space by way of the Na-HCOj COtrans-porter. f3) The bicarbonate in the filtrate accepts a proton to become carbonic acid. Steps that ate catalyzed by carbonic anhydrase are indicated by (CA). 

The kidney regulates the acid-base balance of the body by control over resorption of sodium ions, which may exchange for hydrogen ions in the kidney tubule. Since most dietaries are of acid-ash, the urine is usually more acid than the original plasma filtrate and much of the phosphate excreted is thus changed to the acid monosodium salt, Within the range of normal variability, with an alkaline ash diet, the urine may become alkaline, and in extreme instances, some sodium bicarbonate may be excreted. 

About 70% of the filtered Na and K is resorbed in the proximal tubule. Sodium is cotransported with glucose and the amino adds, resulting in the resorption of over 99% of these nutrients. Cotransport of Na with bicarbonate results in resorption of 80 to 90% of the filtered bicarbonate. The uptake of these nutrients at the apical membrane occurs by Na mino acid and Na-glucose cotransport systems. One of two sodium ions are cotransported with each glucose. Seven Na-amino acid cotransport systems have been found in the renal tubule. These include systems specific for acidic amino acids, basic amino acids, glycine, neutral amino acids, cysteine, and cystine. One or more sodium ions are cotransported with each amino acid. 

Most of the filtered sodium is resorbed, not by the distal tubule, but by more proximal segments of the renal tubule. Sodium resorption in these regions can be regulated, though the adjustments that occur are not as important to maintaining Na balance as those occurring in the distal tubule. The transport systems to be described involve the resorption of glucose, amino acids, bicarbonate, potassium, and chloride. Sodium ions are resorbed, or cotransported, with all of these nutrients. 

The thiazide diuretics, also called sulfonamide or ben-zothiadiazide diuretics, vary in their actions. For instance, the potency of hydrochlorothiazide (Hydro-Diuril and Esidrix) is ten times greater than that of chlorothiazide (Diuril), but the drugs have equal efficacy. The duration of action of hydrochlorothiazide, which is 6 to 12 hours, equals that of chlorothiazide. On the other hand, chlorthalidone (Hygroton) has a duration of action lasting 48 hours. Some thiazide derivatives inhibit carbonic anhydrase, which is unrelated to their diuretic activity. Those that are active in this respect may, at sufficient doses, have the same effect on bicarbonate excretion as does acetazola-mide. They cause a moderate loss of sodium (5 to 10% of the filtered load), chloride, and water, and the clearance of free water is impaired. They may cause metabolic alkalosis (resorption of bicarbonate and loss of hydrogen ions), hyperuricemia (enhanced resorption of uric acid), or hyperglycemia (due to directly inhibited insulin release and to hypokalemia). 

Epidemiologic studies have consistently documented that increased potassium intake is associated with greater bone mineral density. In trials, supplemental potassium bicarbonate reduced bone turnover as manifest by less urinary calcium excretion and by biochemical evidence of greater bone formation and reduced bone resorption. However, no trial has tested the effect of increased potassium or diets rich in potassium on bone mineral density or clinical outcomes related to osteoporosis. 

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