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Biomedical subjects

S Cheema-Dhadli

Publications and source records attributed to S Cheema-Dhadli.

At least 19 recordsLinked to original sources
PubMed2005

Recurrent uric acid stones.

A 46-year-old female had a history of recurrent uric acid stone formation, but the reason why uric acid precipitated in her urine was not obvious, because the rate of urate excretion was not high, urine volume was not low, and the pH in her 24-h urine was not low enough. In his discussion of the case, Professor McCance provided new insights into the pathophysiology of uric acid stone formation. He illustrated that measuring the pH in a 24-h urine might obscure the fact that the urine pH was low enough to cause uric acid to precipitate during most of the day. Because he found a low rate of excretion of NH(4)(+) relative to that of sulphate anions, as well as a high rate of citrate excretion, he speculated that the low urine pH would be due to a more alkaline pH in proximal convoluted tubule cells. He went on to suspect that there was a problem in our understanding of the function of renal medullary NH(3) shunt pathway, and he suggested that its major function might be to ensure a urine pH close to 6.0 throughout the day, to minimize the likelihood of forming uric acid kidney stones.

Ammonia↗
PubMed2002

Hyponatraemia and hyperglycaemia during laproscopic surgery.

The aim of this masterclass is to develop a rational plan of therapy to deal with a severe degree of hyponatraemia (90 mmol/l) and hyperglycaemia (100 mmol/l) that occurred 100 min after the start of laproscopic surgery in a young woman. The lavage fluid used in this procedure was 10% dextrose.H(2)O in water (505 mmol glucose/l). To focus attention on specific issues, three questions are posed to the reader, as they were to a panel of 59 modern-day experts. Two imaginary consultants from the past were asked the same (and additional) questions. Their responses were restricted to knowledge available before the molecular era, to show the power of integrative physiology at the bedside. An analysis of intracellular events was helpful in answering the first question: 'Is an infusion of hypertonic saline required to treat her acute hyponatremia?' Similarly, a quantitative analysis of changes in the composition of the extracellular fluid compartment was helpful in answering the second question: 'Is an infusion of isotonic saline required to treat her hypotension?' A metabolic analysis was used to answer the third question, 'Should insulin be administered?'

Adult↗
PubMed1998

Hyperglycemia during normothermic cardiopulmonary bypass: the role of the kidney.

BACKGROUND: Hyperglycemia commonly occurs during cardiopulmonary bypass. We studied the quantitative impact of glucose input and its renal excretion on hyperglycemia during cardiopulmonary bypass. METHODS: The quantity of glucose infused and metabolite and hormone concentrations in plasma, as well as oxygen consumption, carbon dioxide production, and renal glucose excretion, were determined before, during, and after cardiopulmonary bypass in 8 patients. RESULTS: Hyperglycemia (14 to 29 mmol/L) was accompanied by an increase in plasma insulin levels. The degree of hyperglycemia was directly related to the amount of glucose infused. The rate of oxygen consumption did not decrease and the rate of urea appearance (gluconeogenesis) did not rise. Despite a very high filtered load of glucose, there was very little glucosuria, indicating a markedly enhanced renal absorption of glucose. CONCLUSIONS: Hormonal and metabolic factors permit the development of hyperglycemia during cardiopulmonary bypass but its severity depends on the quantity of glucose infused and, what appears to be a new finding, a markedly enhanced renal reabsorption of filtered glucose. Thus the kidney plays an important role in the development of severe hyperglycemia during cardiopulmonary bypass.

Absorption↗
PubMed1998

Minimum urine flow rate during water deprivation: importance of the permeability of urea in the inner medulla.

We evaluated whether altering the rate of excretion of sodium (Na) and chloride (Cl) when antidiuretic hormone (ADH) acts would cause urea to behave as an 'effective' or 'ineffective' urinary solute. Urine composition was compared to that in the excised papillary tip in rats treated with DDAVP while on a normal or a low electrolyte diet; half the rats were given a urea load. Studies were also carried out in humans who were water restricted for 12 to 16 hours and given DDAVP. One group had a high rate of NaCl excretion induced by a thiazide diuretic, while the other group consumed a low salt diet to decrease the rate of excretion of electrolytes. Urea (3 mmol/kg) was ingested after the control urine samples were collected. On the high salt protocols, the urine flow rate was directly proportional to the rate of excretion of electrolytes ('non-urea' osmoles) and there was no change in the 'non-urea' osmolality despite large changes in Na and Cl excretion rates. After urea was administered, there was no change in urine flow rate, 'non-urea' osmolality, or 'non-urea' osmole excretion rate, whereas the urinary urea concentration, urine osmolality and the rate of excretion of urea were higher. The papilla of the salt-loaded rats had a similar urea concentration to that in the urine. In contrast, in the low electrolyte excretion protocols, the sum of the concentrations of 'non-urea' osmoles in the urine was much lower than that in the excised papilla, and the converse applied to urea. Similar changes were observed in the composition of the urine in human subjects with high and low rates of excretion of electrolytes. We conclude that urea appears to be an 'ineffective' urine osmole when there is a high rate of salt excretion, whereas urea is an 'effective' osmole when there is a low rate of excretion of electrolytes.

Adolescent↗
PubMed1998

Physiological disposal of the potential alkali load in diet of the rat: steps to achieve acid-base balance.

The purpose of this study was to provide a better understanding of the physiological role of endogenous net organic acid production in rats consuming their usual diet. Balance studies were performed over 24 h, and urine was collected in the day and night portions of the diurnal cycle. A supplemented low-electrolyte diet(LED) was fed to determine whether urinary organic anions were identical to those in the diet. A titration procedure was developed to determine the pK of titratable groups in the urine of rats studied with and without an acid load. Although normal rats excreted net acid (NAE), the latter was inversely related to the amount of food consumed. The rates of excretion of bicarbonate (HCO3), citrate, unmeasured organic anions, and NH+4 were higher in the night portion of the diurnal cycle. NAE rose dramatically when alkali intake was decreased by consuming the LED. Dietary and urinary organic anions were not identical because rats fed the LED supplemented with potassium citrate excreted <10% of this alkali load as citrate and <25% as HCO3. In the 24 h after 3,000 ¿mol NH4Cl was given intraperitoneally, H+ did not appear to be retained, yet NAE rose by only close to 2,000 ¿eq. The rate of excretion of titratable groups with a pK in the 3 to 5 pH range fell by close to 1,000 ¿eq; most of these changes occurred in the first 7 h after NH4Cl was given. We conclude that rat chow provides a large net alkali load. There appear to be two types of endogenous acid production, a form associated with a rise in NAE (e.g., sulfuric acid) and dietary alkali-driven endogenous net acid production, which titrates this alkali. Renal excretion of organic anions makes these acids end products of metabolism.

Acid-Base Equilibrium↗
PubMed1998

Prevention of acute hyponatremia by mannitol: an unanticipated mechanism.

PURPOSE: To evaluate the effectiveness and mode of action of the osmotic diuretic mannitol to prevent the development of acute hyponatremia in a setting designed to mimic the acute hyponatremia observed on the day of surgery. RESULTS: Hyponatremia (129+/-1 mM, fall of 10+/-1 mM, p <0.01) was induced by the intraperitoneal administration of half-isotonic saline plus DDAVP to rats (n = 8); hyponatremia was due to a positive balance of electrolyte-free water (EFW). Rats given mannitol (10 mmol/kg body wt) in addition to the hypotonic saline plus DDAVP had only a minor degree of hyponatremia (plasma [Na+] 136+/-1 mM, fall 3+/-2 mM, p >0.05). All the mannitol given was excreted over the 16 h of observation, but the urine volume was not higher in these rats. The higher rate of excretion of EFW was due to a marked reduction in the rate excretion of Na+ with mannitol. This antinatriuresis was also present when mannitol was given intravenously. CONCLUSIONS: Although mannitol increased the excretion of EFW, the mechanism required an enhanced renal reabsorption of Na+ rather than an increase in the urine flow rate.

Animals↗
PubMed1997

Control of excretion of potassium: lessons from studies during prolonged total fasting in human subjects.

A deficit of K+ of close to 300 mmol develops in the first 2 wk of fasting, but little further excretion of K+ occurs, despite high levels of aldosterone and the delivery of ketoacid anions that are not reabsorbed in the distal nephron. Our purpose was to evaluate how aldosterone could have primarily NaCl-retaining, rather than kaliuretic, properties in this setting. To evaluate the role of distal delivery of Na+, four fasted subjects received an acute infusion of NaCl to induce a natriuresis. To assess the role of distal delivery of HCO3-, five fasted subjects were given an infusion containing NaHCO3. The natriuresis induced by an infusion of NaCl caused only a small rise in the rate of excretion of K+ (0.8 +/- 0.1 to 1.9 +/- 0.3 mmol/h); in contrast, when HCO3- replaced Cl- in the infusate, K+ excretion rose to 8.3 +/- 2.2 mmol/h, despite little excretion of HCO3- (urine, pH 5.8) and similar rates of excretion of Na+. The transtubular K+ concentration gradient was 19 +/- 3 with HCO3- and 6 +/- 2 with NaCl. We conclude that the infusion of NaHCO3 led to an increase in K+ excretion, likely reflecting an increased rate of distal K+ secretion. With a low distal delivery of HCO3-, aldosterone acts as a NaCl-retaining, rather than a kaliuretic, hormone.

Adult↗
PubMed1997

Hyponatremia in the rat in the absence of positive water balance.

The purpose of this report is to determine the mechanisms that lead to hyponatremia when isotonic saline was the only fluid infused into rats given antidiuretic hormone (ADH), and what might minimize the degree of this hyponatremia. Normal rats were deprived of food and water for the 24-hr study period. They received an infusion of isotonic saline to expand their extracellular fluid (ECF) volume with and without exogenous ADH administration (N = 8 in each of the four groups). Similar studies were also carried out in 32 rats fed a low electrolyte diet for 72 hr before the experiment. An additional control group was fed the low electrolyte diet supplemented with sodium (Na), potassium (K), and chloride (Cl). Hyponatremia developed over 24 hr in rats fed their usual diet if treated with ADH and isotonic saline (fall, 13 +/- 2 mM, P < 0.01). The hyponatremia was caused by negative balance for Na + K salts. Hyponatremia did not develop after the saline + ADH treatment if rats were pretreated for 3 days with a low electrolyte diet. Two factors were required to develop this hyponatremia--generation of electrolyte-free water as a result of the excretion of a large quantity of Na + K salts at a high concentration in the urine, and prevention of the excretion of this electrolyte-free water by ADH. Increasing the avidity for Na reabsorption by the kidney prevented this type of hyponatremia from developing.

Animals↗
PubMed1997

Minimum urine flow rate during water deprivation: importance of the nonurea versus total osmolality in the inner medulla.

Antidiuretic hormone leads to an increase in the permeability for water and urea in the inner medullary collecting duct. Hence, urea may not be an "effective" osmole in the inner medulla during maximal renal water conservation. Accordingly, the purpose of this study was to evaluate whether differences in the rate of urea excretion would influence maximum renal water conservation in humans. In water-deprived rats, the concentration of urea and total osmolality were somewhat higher in the urine exiting the inner medullary collecting duct than in interstitial fluid obtained from the entire papillary tip. Nevertheless, the "nonurea" (total osmolality minus urea in millimolar terms) osmolality was virtually identical in both locations. Chronically fasted human subjects that were water-deprived for 16 h had a lower rate of urea excretion (71 +/- 7 versus 225 +/- 14 mumol/min) and a somewhat lower urine osmolality (745 +/- 53 versus 918 +/- 20 mosmol/kg H2O). Nevertheless, they had identical urine flow rates (0.5 +/- 0.01 and 0.5 +/- 0.02 ml/min, respectively), and their nonurea osmolality also was similar (587 +/- 25 and 475 +/- 14 mosmol/kg H2O, respectively) to the water-deprived normal subjects. The composition of their urine differed in that the principal nonurea osmoles became NH4+ and beta-hydroxybutyrate rather than Na and C1. During water deprivation in normal subjects, the ingestion of urea caused a twofold rise in urine flow rate, a fall in the nonurea osmolality, and a rise in the rate of excretion of nonurea osmoles. The nonurea osmolality of the urine, and presumably the medullary interstitial fluid as well, was inversely related to the urea excretion rate. In chronic fasting, the nature, but not the quantity, of nonurea osmoles changed. The similar minimum urine volume was predictable from an analysis based on nonurea osmole considerations.

Administration, Oral↗
PubMed1996

Alkali therapy extends the period of survival during hypoxia: studies in rats.

The goal of this study was to evaluate whether sodium bicarbonate might be a useful form of therapy for hypoxic L-lactic acidosis; our aim was to determine if alkali could extend the time of survival in this setting. Hypoxia was induced in anesthetized, paralyzed, artificially ventilated rats by lowering inspired O2 to 5.5%, an amount sufficient to develop a severe degree of L-lactic acidosis. Measuring arterial blood gases frequently permitted maintenance of a near-constant arterial O2 content. Three groups of hypoxic rats were studied: first, no infusions (n = 10); second, sodium bicarbonate at a rate equal to H+ production in the no-infusion group (n = 12); and third, a control for the Na load in the second group as NaCl (n = 17). Survival was close to twofold longer in the sodium bicarbonate group. Part of this beneficial effect seemed to be increased anaerobic glycolysis, producing ATP along with L-lactic acid. In addition, there was a large decrease in the metabolic demand (consumption of O2) in the 7- to 15-min period in the sodium bicarbonate group. Rats exposed to hypoxia and infused with NaCl for 15 min or alkali for 15, 27, or 40 min were then returned to room air; all survived for the subsequent experimental period of 150 min. We found that there is both a rationale and experimental evidence for giving sodium bicarbonate to prolong survival during hypoxia.

Acidosis, Lactic↗
PubMed1994

Potassium excretion: a story that is easy to digest.

The aim of this article is to consider how a large quantity of potassium (K+) can be excreted without the development of hyperkalemia. The hypothesis will focus on interactions between K+ and HCO3- primarily within the kidneys. It is speculated that the absorption of K+ from the gastrointestinal tract is accompanied by an initial addition of HCO3- to the body; this in turn could, via intrarenal events, promote the delivery of HCO3- to the cortical collecting duct (CCD), where interactions may permit the development of a very high rate of excretion of K+. To test one portion of this hypothesis, studies were performed in sheep because they normally consume approximately 10-fold more K+ per kilogram body weight than do humans. In the absence of a significant degree of anabolism, there is only a limited potential to shift K+ acutely into cells. Hence, an extremely large capacity to excrete K+ is required to avoid a severe degree of hyperkalemia. The excretion of K+ depends primarily on the ability to have a sustained rise in the (K) in each liter of luminal fluid exiting the CCD to very high levels and to have a large number of liters of fluid exit the terminal CCD while antidiuretic hormone is acting. A reasonable approximation of this CCD flow rate can be obtained by examining the osmole excretion rate when ADH acts. Because these sheep excreted 1,650 mosmol (2 L x 827 mosm/kg H2O) per day, a minimum estimate for volume delivery out of the CCD is 5 to 6 L/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Does saline "correct" the abnormal mass balance in metabolic alkalosis associated with chloride depletion in the rat?

An elevated plasma pH and bicarbonate are the clinical hallmarks of metabolic alkalosis. Nevertheless, to fully define its pathophysiology, one needs a quantitative interpretation of events in 3 areas - the ECF, ICF, and urine. Accordingly, our purpose was to study mass balance in Cl--depletion metabolic alkalosis with normal initial balance for Na+ and K+. In the 20 h following the "exchange" of Cl- (loss, 2455 mumol) and HCO(3-) (gain, 2455 mumol), only 334 mumol HCO(3-) remained in the ECF and 337 mumol were excreted. The remaining 1784 mumol disappeared primarily via titration because 3051 mueq of endogenous anions were produced and excreted largely with K+. Accordingly, metabolic alkalosis was associated with a deficit rather than a surplus of HCO(3-). To reflect the shift of H+ into cells driven by the exit of K+, the cumulative deficit of Cl- was replaced as KCl or NaCl. The fall in plasma [HCO(3-)] was larger in the KCl group (13.2 vs. 9.4 mmol/L); it was largely due to H+ exit from cells; in contrast, disappearance of HCO(3-) from the ECF was due to new endogenous acid production in the NaCl group. Thus, there was an overall deficit of HCO(3-) in metabolic alkalosis associated with KCl depletion (extracellular alkalosis and intracellular acidosis); processes in the ICF were not corrected by NaCl.

Alkalosis↗
PubMed1993

Kaliuretic response to aldosterone: influence of the content of potassium in the diet.

The excretion of potassium (K+) decreased by 50% (30 v 63 mEq/d, P < .01) when subjects consumed a diet that was low in K+ for 3 days. Although part of this conservation of K+ was achieved in part by suppressing the release of aldosterone, nevertheless providing exogenous mineralocorticoids did not lead to a large kaliuresis when there was a modest degree of K+ depletion. Accordingly, the purpose of this study was to evaluate possible mechanisms for this antikaliuretic response to mineralocorticoids. The renal handling of K+ was examined by independent analysis of the two factors that influence its excretion, the driving force to secrete K+ and the urine volume. This driving force is reflected in a noninvasive fashion by the transtubular [K+] gradient (TTKG). Stimuli to increase the rate of excretion of K+ in subjects on a normal and a low-K+ diet included the administration of 200 micrograms fludrocortisone (9 alpha F), the induction of a high urine flow rate (9 alpha F+furosemide), the induction of bicarbonaturia (9 alpha F+acetazolamide), and the excretion of Cl(-)-poor urine (< 15 mEq/L). On the low-K+ diet, the peak value for the TTKG 3 to 4 hours after 9 alpha F was less than half that while on the normal diet (6.4 v 14, P < 0.01). In contrast, the TTKG was not significantly different on either diet when there was bicarbonaturia or the excretion of a Cl(-)-poor urine (18 v 17 and 17 v 16, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1993

Relative rates of appearance of nitrogen and sulphur: implications for postprandial synthesis of proteins.

The purpose of this study was to gain insights on the temporal fate of proteins based on the rate of appearance of waste products of nitrogen (urea) and sulphur (sulphate) metabolism. Urine was collected every 2 h from 25 normal subjects to measure the rates of excretion of urea, creatinine, and sulphate throughout the 24-h cycle. Samples of blood and urine were also obtained over a 4-h period from 10 subjects who consumed a mixed meal containing 0.4 g protein/kg body weight to obtain information on the relative rates of degradation of amino acids with and without sulphur in a noninvasive fashion. The daily excretion (mean +/- SEM) of urea, creatinine, and sulphate was 396 +/- 28, 14 +/- 0.4, and 15 +/- 0.6 mmol, respectively; the molar sulphate/nitrogen (S/N) ratio was 2.0 +/- 0.1%. There were relatively minor (< 20%) excursions in the rate of excretion of urea and creatinine in any 2-h period as compared with the corresponding 24-h rate; the concentrations of urea and creatinine in plasma also varied < 20% throughout the day. Only 23% of the nitrogen in protein in the standard meal appeared as urea in the 210 min after this meal was consumed. The small changes in the rate of appearance of urea and creatinine imply that the oxidation of amino acids was spread out over the day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Is accelerated oxidation of lactate required for dichloroacetate to lower the level of lactate in blood?

We examined mechanisms by which dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), led to a decrease in the concentration of lactate in blood in a unique "metabolic setting," where the concentration of lactate in blood was 5.4 +/- 0.5 mmol/L. Elevated levels of lactate were induced in anaesthetized rabbits by the administration of a large dose of insulin. The rate of consumption of oxygen was 1.2 +/- 0.1 mmol/min, the respiratory quotient was close to unity, and close to half of the PDH was in its active form; therefore, virtually all ATP synthesis should require flux through PDH. Hence, we predicted that DCA should not cause a significant decrease in the concentration of lactate in blood in this model. In contrast, if DCA was effective, new insights could be obtained into its mechanisms of action, at least in this setting. During steady-state hyperlactatemia, DCA was given as its sodium salt, 2 mmol/kg (n = 10); a control group (n = 5) received equimolar NaCl. Forty minutes later, the level of lactate in blood in the DCA group was 1.3 +/- 0.2 mmol/L, significantly lower than in the NaCl group (4.2 +/- 0.6 mmol/L). To determine the organ(s) responsible for removing lactate, arteriovenous differences were measured in organs drained by the jugular, femoral, and hepatic veins. There was no net uptake of lactate in these drainage beds after DCA was administered. From a quantitative analysis of the rate of removal of lactate and the rate of consumption of oxygen, it seems unlikely that the majority of the decrease in lactate could be directly attributed to an increase in its oxidation.

Animals↗