Metabolic alkalosis in the rat. Evidence that reduced glomerular filtration rather than enhanced tubular bicarbonate reabsorption is responsible for maintaining the alkalotic state.

Abstract

A B S T R A C T Maintenance of chronic metabolic alkalosis might occur by a reduction in glomerular filtration rate (GFR) without increased bicarbonate reabsorption or, alternatively, by augmentation of bicarbonate reabsorption with a normal GFR. To differentiate these possibilities, free-flow micropuncture was performed in alkalotic Munich-Wistar rats with a glomerular ultrafiltrate total CO2 concentration of 46.5±0.9 mM (vs. 27.7±0.9 mM in controls). Alkalotic animals had a markedly reduced single nephron GFR compared with controls (27.4±1.5 vs. 51.6±1.6 nl/min) and consequently unchanged filtered load of bicarbonate. Absolute proximal bicarbonate reabsorption in alkalotic animals was similar to controls (981±49 vs. 1,081±57 pmol/min), despite a higher luminal bicarbonate concentration, contracted extracellular volume, and potassium depletion. When single nephron GFR during alkalosis was increased toward normal by isohydric volume expansion or in another group by isotonic bicarbonate loading, absolute proximal bicarbonate reabsorption was not substantially augmented and bicarbonaturia developed. To confirm that a fall in GFR occurs during metabolic alkalosis, additional clearance studies were performed. Awake rats were studied before and after induction of metabolic alkalosis associated with varying amounts of potassium Portions of this work were presented at the National Meet-

Mechanosensory function of microvilli of the kidney proximal tubule

“…When Na ϩ reabsorption (with the control perfusate) is plotted as a function of the estimated microvillous torque, the relation is strikingly linear, with no suggestion of a transport maximum. Such linearity of reabsorption, over a broad range of delivery rates, has been a consistent finding in studies of HCO 3 Ϫ transport in the proximal tubules of rat kidneys (6,26,27). Note, however, that in the dextran perfusions, the effect of microvillous torque on reabsorption is not linear (3.6-fold torque increase in viscosity resulting in a 1.2-fold increase in reabsorption).…”

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

“…This augmented death risk might be a reflection of the presence of higher comorbid conditions (especially heart failure and COPD) in this population (Table 2), or due to the harmful effects of metabolic alkalosis per se on the myocardium (mediated through electrolyte disturbances), skeletal muscle, and the central nervous system (9). Experimental evidence suggests that lower GFR might maintain an alkalotic state, thereby conferring a persistent risk for these patients (24).…”

Chronic hypercapnia stimulates proximal bicarbonate reabsorption in the rat.

“…Calculations of filtration and reabsorptive rates were also as previous outlined (1,4,5). Results are presented as mean±SEM, and significance was assessed by the paired or unpaired t test as appropriate.…”

“…Relatively normal rates of tubular hydrogen ion secretion would then suffice to prevent bicarbonate from appearing in the urine. This mechanism has been proposed to be the one that maintains the other major hyperbicarbonatemic acid-base disorder, chronic metabolic alkalosis (1). On the other hand, if glomerular filtration remained normal, enhanced tubular bicarbonate reabsorption, predominantly in the proximal nephron, would be needed to prevent bicarbonaturia.…”

“…Acute hypercapnia has also been found to have only a small effect on free-flow proximal bicarbonate reabsorption (4). In fact, no factor has yet been reported to reliably increase proximal bicarbonate reabsorption above the mean level found in the normal euvolemic state (1,5).…”