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M L Halperin

Publications and source records attributed to M L Halperin.

At least 127 records · Page 7Linked to original sources
PubMed1990

Effect of metabolic acidosis on glucose reabsorption in rats with acute hyperglycemia.

The rate of reabsorption of glucose in the kidney is a factor to consider with respect to the degree of hyperglycemia in poorly controlled diabetics. The rate of reabsorption of glucose in the proximal tubule is driven by the electrochemical gradient for sodium across the luminal membrane. This gradient in the proximal tubule is also used to reabsorb a number of other substances, quantitatively the most important being bicarbonate. We wished to explore the hypothesis that acidosis, by reducing the filtered load of bicarbonate and therefore the reabsorption of bicarbonate in the proximal tubule, might permit an increased rate of reabsorption of glucose. Hyperglycemia was induced in rats by the infusion of hypertonic glucose. Reabsorption of glucose was measured by clearance methods and factored for glomerular filtration rate (GFR), which has a direct effect on the reabsorption of glucose. The reabsorption of glucose was increased in the kidney when the reabsorption of bicarbonate in the proximal tubule was decreased by either HCl-induced acidosis or the administration of a carbonic anhydrase inhibitor. This effect was independent of a change in GFR and the fractional excretion of Na, factors that may also lead to changes in the reabsorption of glucose by the kidney.

Acidosis↗
PubMed1990

Influence of acute hyponatremia on renal ammoniagenesis in dogs with chronic metabolic acidosis.

The purpose of this study was to determine how acute hyponatremia might augment the excretion of ammonium in dogs with chronic metabolic acidosis. The excretion of ammonium was higher during hyponatremia because the proportion of ammonium produced that was excreted in the urine increased from 66% in controls to 77%. Effects on the production of ammonium are more complex. The rate of renal ammoniagenesis was not increased during hyponatremia in absolute terms nor when expressed per millimole of oxygen consumption. In contrast, this rate was somewhat higher during hyponatremia if expressed per millimole of sodium reabsorbed (9.8 vs. 10.3 mumol). The rate of oxygen consumption by the kidney did not fall, as anticipated, during hyponatremia; when this rate was expressed per millimole of sodium reabsorbed it rose from 46 to 55 mumol. There was no significant change in the rate of extraction of glutamine by the kidney, but there was a significant decrease in the rate of release of alanine during hyponatremia. Hence there appears to be more oxidation (yielding more ammonium) and less transamination of glutamine. We conclude that the renal events which led to a higher rate of excretion of ammonium during hyponatremia were a larger than expected rate of ammonium production owing to a greater rate of oxygen consumption together with lesser rate of transamination of the glutamine extracted by the kidney. In addition, more of the ammonium produced was transferred to the urine.

Acidosis↗
PubMed1990

Urine electrolytes and osmolality: when and how to use them.

The purpose of this review is to provide an update on the use of the urine electrolyte and osmolality measurements in patients with disorders of fluid, electrolytes, and/or acid-base metabolism. It is critical to appreciate that there are no 'normal values' for these parameters, only 'expected values' relative to clinical situations. Pitfalls in the interpretation of each electrolyte in the urine are also provided. To detect a mild to moderate degree of reduction of the 'effective' intravascular volume, both urine sodium (Na) and chloride (Cl) concentrations should be measured. Pitfalls in this assessment are abnormal renal and adrenal function and the use of diuretics. Insights into the etiology of the low 'effective' intravascular volume can be deduced by comparing the urine Na, potassium (K), and Cl concentrations. The urine net charge (Cl vs. Na + K) is the most reliable way to estimate the urine ammonium concentration short of its direct measurement, an assay that is not provided by most laboratories. This measurement is important in the differential diagnosis of hyperchloremic metabolic acidosis. To examine the renal response to hypokalemia or hyperkalemia, the two components of K excretion (K secretion and urine flow rate) should be examined separately. The former is evaluated using the transtubular K, concentration gradient. The urine osmolality is used to assess antidiuretic hormone action and the osmolality of the renal medulla and to determine the etiology of polyuria and/or hypernatremia. The urine osmolality can also be used to assess the ammonium concentration, using the urine osmolal gap, and to detect unusual urine osmoles.

Acid-Base Imbalance↗
PubMed1990

Ammonium metabolism: emphasis on energy considerations.

The metabolism of a typical North American diet yields a net acid load. Hydrogen ions are removed from the body after combining with bicarbonate to form CO2. This leaves the body with a deficit of bicarbonate. The role of the kidney is to add 'new' bicarbonate to the body. It does so primarily by synthesizing NH4+ plus bicarbonate while making NH4+ an end-product of metabolism (excreting it in the urine). Production of NH4+ occurs primarily in proximal convoluted tubule cells. Although several possible pathways can do this, the primary one stimulated by chronic metabolic acidosis is the glutaminase/glutamate dehydrogenase one. The upper limit on this pathway is set by energy turnover considerations. This, in effect, means control by renal work (sodium reabsorption) and fuel competitions (availability of fat-derived fuels).

Acidosis, Renal Tubular↗
PubMed1989

Renal and hepatic aspects of ketoacidosis: a quantitative analysis based on energy turnover.

The central theme explored is that the rate of ATP production cannot exceed its rate of use in any organ or compartment. Thus the rate of ATP turnover exerts an absolute control over the rates in pathways that synthesize it. This is manifested in two major ways: substrate competition for oxidation and the influence of changes in oxygen consumption rate on the rate of fuel oxidation. By direct measurement, the rate of ketogenesis in the liver is as high as 1500 mmol/day during chronic ketoacidosis of fasting. Given the limited ate of hepatic oxygen consumption, ketogenesis and glucose synthesis from amino acids compete as precursors for hepatic ATP synthesis. Thus There is little room to increase the rate of ketoacid production further in these subjects. Energy turnover considerations in the kidney during chronic fasting seem to limit renal NH4+ production. In this case, there is competition between glutamine and ketone bodies as ATP precursors. This aspect may be important in the regulation of lean body mass catabolism of fasting. There is a "trade-off" in maintaining high circulating ketone body concentrations during fasting. The benefit is primarily for the CNS, and the cost is small loss of lean body mass owing to the need for high rates of NH4+ excretion.

Acidosis↗
PubMed1989

Ammonium excretion in chronic metabolic acidosis: benefits and risks.

The expected renal response to a chronic acid load is an enhanced rate of ammonium production and excretion. Notwithstanding, high rates of ammonium production and/or excretion on a chronic basis may have detrimental consequences to patients. Examples discussed include the loss of extra lean body mass during chronic fasting, an accelerated rate of progression of renal insufficiency and possibly destruction of the medullary area of the kidney owing to local alkalinization.

Acidosis↗
PubMed1989

Effects of chronic hypokalaemia and adrenalectomy on potassium transport by the medullary collecting duct of the rat.

1. The purpose of this study was to evaluate the roles of chronic hypokalaemia and of aldosterone in K+ transport in the medullary collecting duct. Renal clearance and duct transport measurements were made before and after KCl infusion in three groups of animals: normal rats on a regular K+ diet (group I), and sham-operated (II) or adrenalectomized rats (group III), both on a low K+ diet. 2. Only the sham-operated animals on the low K+ diet became hypokalaemic. They also had the lowest rate of K+ excretion at the time of study. Adrenalectomized rats were normokalaemic, and had an intermediate rate of K+ excretion. After the acute KCl infusion, kaliuresis remained significantly depressed in the rats which were previously hypokalaemic. In contrast, K+ excretion rates in response to K+ infusion were high and not significantly different in both previously normokalaemic groups, independent of the presence of the adrenal glands. 3. In the medullary collecting duct, before the KCl infusion there was no net K+ transport in either normokalaemic group (I and III). However, after the KCl infusion there was significant K+ secretion in both of these groups (32% and 22% of total urinary excretion, respectively). In contrast, the sham-operated hypokalaemic rats on the low K+ diet had a small absolute, but large fractional K+ reabsorption (64% of delivered load) in the medullary collecting duct. With KCl infusion in this group, K+ delivery to the medullary duct increased, but absolute reabsorption along the duct was maintained, resulting in a fractional reabsorption of 28% of delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1989

What is the underlying defect in patients with isolated, proximal renal tubular acidosis?

Our aim in this article is to propose a new hypothesis concerning the etiology of renal tubular acidosis (RTA) in that subgroup of patients who have the isolated, primary type of proximal RTA. We suggest that their underlying disorder is a more alkaline intracellular pH of the proximal convoluted tubule. Increased alkalinity of proximal tubular cells would explain the low rate of bicarbonate reabsorption per liter glomerular filtration and the decreased rate of ammonium excretion despite a low urine pH and the presence of chronic metabolic acidosis. Additional diagnostic tests to evaluate this hypothesis in this specific subgroup of patients with proximal RTA are also outlined.

Acidosis, Renal Tubular↗
PubMed1989

Urine electrolytes in the assessment of extracellular fluid volume contraction.

The purpose of this study was to determine which urine electrolytes should be measured to confirm that the extracellular fluid (ECF) volume is depleted. ECF volume contraction was induced by furosemide administration to rats consuming an electrolyte-free diet. An external potassium balance was achieved by replacing potassium losses with KHCO3 and KCl so that the sodium and chloride deficits were comparable (equivalent to a 30% reduction in ECF volume). As expected, the urine sodium and chloride concentrations fell to 2 +/- 0.3 mmol/l and 3 +/- 0.3 mmol/l, respectively. Rats were then randomized to receive 50-75% of their sodium or chloride deficit as either: NaCl (control group), NH4Cl or NaHCO3 to mimic clinical situations associated with ECF volume contraction. In the NaCl group, the urine sodium and chloride concentrations remained low (6 +/- 2 mmol/l and 7 +/- 2 mmol/l), consistent with persistent ECF volume contraction. Although the NH4Cl group continued to have a low urine sodium concentration (2 +/- 0.2 mmol/l), there was now a marked increase in the urine chloride concentration (51 +/- 7 mmol/l; p less than 0.01 vs. NaCl group). In contrast, although the NaHCO3 group continued to have a low urine chloride concentration (2 +/- 1 mmol/l), there was a significant increase in the urine sodium concentration (19 +/- 3 mmol/l; p less than 0.01 vs. NaCl group). We conclude that the clinical assessment of ECF volume by urine electrolytes requires an evaluation of both the urine sodium and chloride concentrations.

Ammonium Chloride↗
PubMed1988

The plasma potassium concentration in metabolic acidosis: a re-evaluation.

The purpose of these investigations was to describe the mechanisms responsible for the change in the plasma [K] during the development and maintenance of hyperchloremic metabolic acidosis. Acute metabolic acidosis produced by HCI infusion resulted in a prompt rise in the plasma [K], whereas no change was observed during acute respiratory acidosis in the dog. After 3 to 5 days of acidosis due to NH4Cl feeding, dogs became hypokalemic; this fall in the plasma [K] was due largely to increased urine K excretion. Despite hypokalemia, aldosterone levels were not low, and the calculated transtubular [K] gradient was relatively high, suggesting renal aldosterone action. Thus, rather than anticipating hyperkalemia in patients with chronic metabolic acidosis due to a HCl load, the finding of hyperkalemia should suggest that the rate of urinary K excretion is lower than expected (ie, there are low aldosterone levels or failure of the kidney to respond to this hormone).

Acidosis↗
PubMed1988

Effect of anaesthesia on insulin-induced hypoglycemia in rabbits.

The aim of this study was to determine how anaesthetized rabbits survive much longer than awake rabbits after receiving an insulin overdose. Insulin appeared to act in both groups of rabbits because there was a prompt fall in circulating glucose, free fatty acids, and beta-hydroxybutyrate concentrations. Carbohydrate appeared to be the principal energy source for anaesthetized rabbits because their respiratory quotient approached unity. Although the fall in glycemia was similar in both groups of rabbits, the circulating lactate concentration rose only in the anaesthetized group. This rise in lactate in the initial 60 min after insulin was given could account for most of the fall in glycemia if the source of lactate was the glucose pool. The decline in hepatic glycogen was close to 100 mumol/g liver; this would account for about one-third of the total energy turnover and close to one-half of the measured glucose appearance in these anaesthetized rabbits. As judged from the rate of oxygen consumption, muscle glycogen seemed to supply two-thirds of the fuel to be oxidized in these rabbits. However, only one-third of the lactate released from muscle was first converted to glucose and the remainder was oxidized directly to CO2. Although insulin provided the metabolic setting for a rapid rate of glucose oxidation, this rate appeared to be diminished when the overall rate of oxygen consumption was lower during anaesthesia.

3-Hydroxybutyric Acid↗
PubMed1988

A renal mechanism limiting the degree of potassium loss in severely hyperglycemic patients.

Potassium (K) secretion in the cortical 'distal nephron' was assessed in vivo in 29 consecutive patients presenting with diabetic ketoacidosis (DKA) or the hyperglycemic hyperosmolar syndrome (HHS). The only selection criteria applied were that the electrolytes and osmolality be measured in the urine on admission. Five patients with DKA and 3 patients with HHS were reported in detail as plasma aldosterone levels were also measured in these patients on admission. K secretion in the 'cortical distal nephron' was assessed by a semiquantitative index, the transtubular K concentration gradient (TTKG). TTKG values less than 6.0, consistent with less than maximal renal K secretion, were found in 28 of 29 patients despite the presence of hyperkalemia and/or stimuli for renin and aldosterone release. Plasma aldosterone levels on admission were very elevated in 4 patients, at the upper end of the usual normal range in 3 and in the low part of the normal range in 1 patient. Treatment with intravenous saline, KCl and insulin corrected the fluid and electrolyte abnormalities in the plasma over 24-48 h. Concurrently, plasma aldosterone levels fell, but the TTKG rose; this suggest that there was an increased renal tubular response to aldosterone after initial therapy. The mechanism responsible for this reversible impairment of renal K secretion is unknown. It may limit total body K depletion in patients presenting with DKA and HHS by diminishing renal K excretion.

Aldosterone↗
PubMed1988

Severe metabolic acidosis induced in a patient during fasting by KCl administration.

The purpose of this study was to determine the cause of an acute metabolic acidosis of the normal anion gap type which developed during a 3 day period when 64 mmol of KCl was administered daily to an obese but otherwise healthy subject fasted for 2 weeks (called the index case). She had typical ketoacidosis of fasting for the first 13 days of fasting; since the plasma [K] was 3.6 mmol/l, she was given 64 mmol of KCl daily for 3 days. On day 3 of KCl treatment, the plasma [HCO3] was 13 mmol/l with no change in the plasma anion gap or 3-hydroxybutyrate concentration; the plasma [K] had risen to 4.3 mmol/l. The cause of the acidosis was a reduction of urine ammonium excretion by 42 mmol/day without a parallel fall in the rate of 3-hydroxybutyrate excretion. Since renal ammonium production can be inhibited by K administration, 5 other obese subjects were studied in a similar fashion to gain insight into the problem. They had a similar reduction in the daily rate of ammonium excretion (41 mmol) after KCl; however, their daily 3-hydroxybutyrate excretions declined by a similar amount (47 mmol) and thus metabolic acidosis did not develop.

3-Hydroxybutyric Acid↗
PubMed1988

The urine osmolal gap: a clue to estimate urine ammonium in "hybrid" types of metabolic acidosis.

The urine osmolal gap is defined as the difference between measured urine osmolality and the sum of the concentrations of sodium, potassium, chloride, bicarbonate, urea and glucose. Normally, this gap is 80-100 mosmol/kg H2O. A determination of the urine osmolal gap may be useful to ascertain the etiology of metabolic acidosis which is of the mixed wide and normal plasma anion gap type ("hybrid" metabolic acidosis). For example, with "hybrid" metabolic acidosis, a low urine osmolal gap will suggest the absence of excessive organic aciduria (ketoacidosis) and the basis of the normal anion gap type of acidosis will be determined by the urine anion gap or "net charge". Where "hybrid" metabolic acidosis has occurred due to wide anion gap metabolic acidosis with loss of organic acid anion in the urine, the urine osmolal gap will be high and can be used in a semi-quantitative fashion to estimate the sum of urinary ammonium plus ketone body anion concentrations.

Ammonia↗
PubMed1987

Accelerated loss of lean body mass in fasting rats due to activation of pyruvate dehydrogenase by dichloroacetate.

In order to test the hypothesis that increased pyruvate dehydrogenase (PDH) activity during fasting will result in accelerated loss of lean body mass, we administered sodium dichloroacetate (DCA) intraperitoneally to eight rats during the last three days of a six-day fast, while fasting control rats were given normal saline. DCA treatment resulted in an increased proportion of PDH in the active form in liver (26.5 +/- 4.3% v 13.4 +/- 0.5%, P less than 0.01). During the three-day period of administration, DCA treated rats lost more weight than control animals (42 +/- 2 v 25 +/- 1 g, P less than 0.001) and excreted more nitrogen in the urine (18.1 +/- 1.0 v 6.8 +/- 0.6 mmol/d, P less than 0.001). Calculations from nitrogen balance data suggest that 85% of the increase in weight loss of DCA treated rats over that of control animals was attributable to loss of lean body mass. We conclude that increased flux of pyruvate through the PDH reaction in the DCA-treated animals resulted in increased protein catabolism.

Acetates↗