Respiratory adjustment to chronic metabolic alkalosis in man.

This study examined the ventilatory adjustment to chronic metabolic alkalosis induced under controlled conditions in normal human volunteers. Metabolic alkalosis induced by buffers (sodium bicarbonate, trishydroxymethylamine methane) or ethacrynic acid was associated with alveolar hypoventilation, as evidenced by a rise in arterial Pco(2), a fall in arterial Po(2), a reduced resting tidal volume, and a diminished ventilatory response to CO(2) inhalation. Alveolar hypoventilation did not occur when metabolic alkalosis was induced in the same subjects by thiazide diuretics or aldosterone despite comparable elevations of the arterial blood pH and bicarbonate concentration.The different ventilatory responses of the two groups could not be ascribed to differences among individuals comprising each group, pharmacological effects of the alkalinizing agents, differences in the composition of the lumber spinal fluid, changes in extracellular fluid volume, or sodium and chloride balance.The differences in ventilatory adjustments were associated with differences in the patterns of hydrogen and potassium ion balance during the induction of alkalosis. Alveolar hypoventilation occurred when hydrogen ions were buffered (sodium bicarbonate, trishydroxymethylamine methane) or when renal hydrogen ion excretion was increased (ethacrynic acid). Alveolar hypoventilation did not occur when induction of similar degrees of extracellular alkalosis was accompanied by marked potassium loss and no demonstrable increase in external hydrogen loss (thiazides and aldosterone).These observations suggest that respiratory depression does not necessarily accompany extracellular alkalosis but depends on the effect of the mode of induction of the alkalosis on the tissues involved in the control of ventilation.

Parathyroid hormone and the regulation of acid-base balance.

Parathormone (PTH) excess limits renal bicarbonate reabsorption. This may aggravate the acidosis in patients with renal insufficiency and secondary hyperparathyroidism. Why parathormone, the primary action of which is thought to be stabilization of the inonized fraction of calcium, affects acid-base balance remains uncertain. Parathormone not only promotes the release of calcium from bone but also mobilizes salts, including bicarbonate and phosphate. Accumulation of these anions in the extracellular fluid would limit the ionization of calcium. Teleologically it is not unexpected to find that, coincident with evolution of a mechanism which permits rapid mobilization of calcium from bone, a system had to develop which removed the byproducts of bone dissolution. If this concept is valid, parathormone-induced depression of renal bicarbonate reabsorption in uremia represents an undesired side effect of an adaptive mechanism. This would extend Bricker's "trade-off" hypothesis which ascribes metabolic bone disease due to PTH-induced phosphate loss to include metabolic acidosis resulting from diminished renal bicarbonate regeneration. Parathyroidectomy or phosphate restriction have been proposed for correction of the side effects of secondary hyperparathyroidism. These therapeutic manipulations cannot be recommended for general use. A more rational apprach for prevention of secondary hyperparathyroidism is the combined use of phosphate restriction with a short-acting vitamin D derivative.

Effect of ethanol on phospholipid metabolism by the rat lung.

Prefeeding of alcohol shows the in vivo incorporation of orally administered palmitic acid into phosphatidylcholine of the lung. This impairment is also demonstrable in vitro utilizing lung slices and 14C-labeled palmitate or cytidine 5'-diphosphocholine as precursors. It is concluded that alcohol ingestion affects the utilization of precursors needed for phospholipid formation in the lung.

Effect of potassium on utilization of (1-14C)palmitic acid in renal cortex of the rat.

The renal cortex has an unusually high rate of palmitic acid utilization. The uptake, oxidation, and distribution of this fatty acid in the cortex, unlike other tissues, responds to variations in medium and tissue potassium content. This potassium dependency is mimicked and amplified by rubidium. These observations indicate that in the renal cortex, both potassium and rubidium promote the accumulation, oxidation, and esterification of palmitic acid.

Palmitate incorporation in the lungs of dogs with granulomatous disease.

Moderate hypoxia did not influence the pulmonary incorporation of an intravenous dose of [1-14C]palmitate either in dogs with experimentally produced granulomatous disease or in normal controls. The lung weight in the diseased animals, was, on the average, double that of the controls. There was a proportionate increase in uptake of the radioactive label at 1 hr after infusion in the diseased lungs, hence the specific activity of labeled palmitate (counts per minute per gram of phospholipid) was no different in the two groups. Moreover, half the radioactivity of the phospholipids was recovered in palmitate separated from the phosphatidyl choline fraction in both diseased and normal lungs. Anatomic studies demonstrated increased numbers of Type II pneumocytes lining all alveolar air spaces in the diseased lung. Autoradiographic studies indicated the presence of labeled palmitate in the Type II cells, but not in the inflammatory cells of the granulomata. We conclude that the increased palmitate uptake in this disease is accounted for by the metabolic activity of the Type II pneumocytes.

The effect of DL-2-bromopalmitate on the utilization of palmitic acid by rat granular pneumocytes.

The effect of DL-2-bromopalmitate (BrPA), an analogue of palmitic acid (PA), on the utilization of this fatty acid by rat lungs was investigated by a combination of anatomic and biochemical methods. The experiments were performed in vitro on two types of preparations, isolated perfused lungs and lung slices. In the isolated lung preparation the substrate reached the lung via the capillaries, in lung slices via the alveolar epithelium. Electron microscope autoradiography showed that BrPA depressed uptake of PA by granular pneumocytes. Radioactivity recovered by tissue analysis and capture of CO2 established that PA oxidation and incorporation into phospholipids and triglycerides was depressed by BrPA. A close correlation was found between the reduction in radioactivity in phospholipids and the grain density over lamellar bodies. The study shows that BrPA reversibly interferes with the uptake and utilization of long chain fatty by granular pneumocytes. BrPA appears as a useful tool to study palmitate metabolism and surfactant production by the lung.

Urea transport in the dogfish kidney.

There is increasing evidence that urea movement across many epithelia involves more than passive diffusion. Of particular interest is the observation that urea transport across the erythrocyte membrane and across the vasopressin-stimulated urinary bladder of the toad occurs by facilitated diffusion, and can be selectively inhibited by phloretin and chromate. These inhibitory agents have been employed in studies of renal urea reabsorption by the spiny dogfish Squalus acanthias. Both agents inhibit urea reabsorption; the effect of chromate is of particular interest, since it blocks urea reabsorption to a proportionately greater extent than sodium reabsorption, and does so irreversibly.