Sodium excretion and hyperfiltration during glucose infusion in man

The relations between renal hemodynamics (Inutest, CPAH) and sodium excretion were studied in 7 nondiabetics in whom a similar expansion was induced (1) with a 3-hour 5% glucose infusion and (2) with a 0.9% saline load. With both infusions the body weight increased, hematocrit fell, and the plasma renin activity was suppressed. During glucose infusion, blood glucose rose from 3.9 mmol/l to a plateau of around 13 mmol/l; glycosuria was absent during the 1st h, then appeared and stabilized during the following 2h. Glucose infusion caused a progressive increase in glomerular filtration rate and in renal blood flow in both absence and presence of glycosuria, without significant changes in sodium excretion despite volume expansion and increase of filtered sodium load. When saline was infused, there was a sustained increase of fractional sodium excretion, and no hemodynamic modifications were observed. We suggest that a primary glucose-induced metabolic stimulation of sodium reabsorption may play a role in the genesis of glucose-induced hyperfiltration.     

Splanchnic amino acid and glucose metabolism during amino acid infusion in dogs

With the organ-balance technique, we studied amino acid and glucose metabolism by hepatic and extrahepatic splanchnic tissues in awake dogs in the postabsorptive state and during a 3-h intravenous amino acid infusion. Dogs received a high (1.4 g/kg body wt, n = 5) or low (0.7 g/kg body wt, n = 8) dose of amino acids. In four of the latter dogs, the dose was delivered into a mesenteric vein. During the basal period there was a net removal of gluconeogenic amino acids (particularly alanine), but not branched-chain amino acids, and a net production of glucose by the liver in all dogs. During this time there was a net removal of glucose and production of alanine by the extrahepatic splanchnic tissues. During either high- or low-dose amino acid infusion, net hepatic glucose release increased; despite this, arterial plasma glucose declined due to an increase in tissue glucose uptake at extrasplanchnic sites. The net amount of glucogenic amino acids removed by the liver during high-dose (9.1 +/- 1.0 mmol.kg-1.3 h-1) and low-dose (4.8 +/- 0.6 mmol.kg-1.3 h-1) infusion equaled or exceeded the infused load of these amino acids. In addition, the liver contributed to the net disposal of branched-chain amino acids during high-dose (536 +/- 147 mumol.kg-1.3 h-1) and low-dose (341 +/- 70 mumol.kg-1.3 h-1) infusion. During high-dose infusion, extrahepatic splanchnic tissues participated in the net removal of branched-chain amino acids (436 +/- 162 mumol.kg-1.3 h-1) but not glucogenic amino acids, and net alanine production continued (410 +/- 91 mumol.kg-1.3 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute infusion of amphotericin B: Proximal tubular effects

Summary: Electron microprobe analysis (EMPX) was employed to determine the alterations in intracellular electrolyte concentrations in proximal tubular cells resulting from acute treatment with amphotericin B. Concurrent clearance data confirmed a drop in glomerular filtration rate (GFR) in the rats treated with amphotericin B infusion (1 mg/kg per h) compared to control animals infused with saline (0.69 ± 0.11 vs 1.27 ± 0.08 mL/min per 100 g; P < 0.001). Measurement of intracellular electrolytes in proximal tubular cells in mmol/kg wet weight by EMPX demonstrated no difference in Na (16.2 ± 0.6 vs 17.2 ± 0.5) or K (129.7 ± 2.1 vs 131.3 ± 2.0). Intracellular Rb accumulation following acute infusion was significantly reduced in the amphotericin B treated animals (3.9 ± 0.4 vs 6.6 ± 0.4; P < 0.0001), suggestive of a reduction in basolateral Na-K ATPase activity. These results do not support the tenet that amphotericin B causes a generalized increase in epithelial cell membrane ionic permeability, nor direct tubular toxicity in the doses and time frame studied. Rather, they suggest that a primary reduction in GFR results acutely in a load-dependent decrease in proximal tubular Na transport.     

Major operative trauma increases peripheral amino acid release during the steady-state infusion of total parenteral nutrition in man

The effect of major operative trauma on skeletal muscle metabolism was examined in nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acids/m2/day) for 5 days before and 4 days after an operation. Compared with the preoperative state, 72 hours after the operation there was a significant rise in arterial levels of glucagon, cortisol, norepinephrine, and inactive triiodothyronine and a drop in concentrations of insulin, active triiodothyronine, and amino acids. Forearm blood flow increased, as well as the efflux from forearm muscle of lactate, taurine, serine, glycine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, arginine, and total amino acid nitrogen (440%). This loss of muscle protein after trauma is associated with increased muscle proteolysis, as measured by increased urinary 3-methylhistidine excretion (83%), and accounts for increased nitrogen loss (54%) from the body. Increased activity of the sympathetic nervous system is manifested by increased levels of epinephrine and norepinephrine, a relative lack of insulin, and increased levels of glucagon. This hormonal milieu plays an important role in the production of hypoaminoacidemia, increased efflux of amino acids and lactate from muscle, and negative nitrogen balance observed in these traumatized patients.     

Effect of two regimens of intravenous amino acid infusion on renal haemodynamics, renal tubular function and sodium and water homeostatic hormones in healthy humans

The effect of two different regimens of intravenous infusion of amino acids on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and water handling judged from the clearance of lithium (CLi), and plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), arginine vasopressin (AVP), atrial natriuretic peptide (ANP), growth hormone (GH), and glucagon was investigated in healthy humans. In the first protocol (n = 11) the infusion lasted 90 min; both GFR and RPF increased significantly (median increase 7.1% and 9.1% respectively, P less than 0.05 both). In the second protocol (n = 13) the infusion lasted 30 min; both GFR and RPF tended to increase (median increase 3.5% and 7.4%) but the change did not reach significance. The changes in tubular sodium and water handling were similar in the two protocols. Absolute reabsorption rates in the proximal tubules were unaltered, resulting in an increased output into the distal tubules that was totally compensated for by an increased distal reabsorption. Thus no changes in urinary excretion of sodium and water were observed. Ang II, Aldo, AVP, ANP and GH were unchanged by amino acid infusion, but glucagon increased. It is suggested that the alterations in renal haemodynamics and distal tubular reabsorption may be mediated by glucagon.     

The prospects for amino acid infusion

Amino acid preparations for intravenous infusion are indispensable materials in parenteral nutrition. We have surveyed the progress and problems related to such preparations. In recent years, the necessity of various amino acid preparations suitable for different morbid states and/or ages has been the subject of much interest. In practice, several new amino acid preparations for specific uses have been proposed.     

Inhibition of urea tubular reabsorption by PGE1 infusion in man.

We have shown that the inhibition of prostaglandin (PG) synthesis in man decreases the fractional clearance of urea (FCurea). To understand the mechanism(s) by which PG affect the renal handling of urea, 6 normal volunteers were randomly studied in maximal antidiuresis (by water deprivation and by administering 1-desamino-8-D-arginine vasopressin) before and during PGE1 infusion, in two separate occasions: (A) after 7 days of normal protein (1 g/kg b.w./day) and water intake (10 ml/kg b.w./day), and (B) after 7 days of low protein intake (0.5 g/kg b.w./day) and high water intake (80 ml/kg b.w./day) to lower the corticomedullary osmotic gradient. During infusion of PGE1 at rates of 0.01, 0.05 and 0.1 micrograms/min/kg, randomly administered, the urinary fluid losses were replaced by infusing equal volumes of hypotonic NaCl (80 mmol/l). To evaluate the time effects of this protocol, control studies were performed in an other 8 subjects receiving vehicle infusion without PGE1. In study A, FCurea rose by 23% (p less than 0.01) at the lowest PGE1 infusion rate (0.01 micrograms/min/kg), in the absence of any simultaneous change in water and salt output, Uosm, PAH and inulin clearance. Higher PGE1 infusion rates (0.05 and 0.1 micrograms/min/kg) were associated with a progressive increase of FCurea (50%, p less than 0.001 and 91%, p less than 0.001, respectively), fractional clearance of water and salt output, inulin and PAH clearance and reduced Uosm from 1,005 (22 SEM; basal value) to 772 (38 SEM; minimum value) mosm/kg (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of preoperative amino acid infusion on thermoregulatory response during spinal anaesthesia

Background. Intravenous amino acid infusion during general anaesthesiaprevents decreases in core temperature resulting from increasedenergy expenditure and heat accumulation. Methods. We investigated whether such stimulation also occursduring spinal anaesthesia, which blocks sympathetic nervousactivity. We examined the effect of i.v. amino acid infusionon changes in core temperature during spinal anaesthesia. Thirty-fivepatients were divided into two groups: an i.v. amino acid infusiongroup (4 kJ kg^–1 h^–1 starting 2 hbefore surgery); and a saline infusion group. Tympanic membranecore temperature, forearm–fingertip temperature gradient(an index of peripheral vasoconstriction) and mean skin temperaturewere measured for 90 min after the onset of spinal anaesthesia. Results. Changes in mean arterial pressure and heart rate didnot differ significantly between the groups during the studyperiod. Mean final core temperature 90 min after inductionof spinal anaesthesia was 35.8 (SEM 0.1)°C in the salinegroup and 36.6 (0.1)°C in the amino acid group (P<0.05).The increased level of oxygen consumption in the amino acidgroup compared with the saline group was preserved even afterthe onset of spinal anaesthesia. The thermal vasoconstrictionthreshold, defined as the tympanic membrane temperature thattriggered a rapid increase in forearm–fingertip temperaturegradient, was increased in the amino acid group [36.8 (0.1)°C]compared with the saline group [36.5 (0.1)°C] (P<0.05). Conclusions. Preoperative infusion of amino acids effectivelyprevents spinal anaesthesia-induced hypothermia by maintaininga higher metabolic rate and increasing the threshold core temperaturefor thermal vasoconstriction. Br J Anaesth 2003; 90: 58–61     

Effect of amino acid infusion for prevention of intraoperative hypothermia during laparotomy

BACKGROUND: Amino acid infusion prevents intraoperative hypothermia. The purpose of this study is to examine the effect of amino acid infusion on intraoperative core temperature of patients during laparotomy. METHODS: Forty-two patients (duration of surgery of 180 min or more) and 32 patients (duration of surgery less than 180 min) scheduled for open gastrectomy under sevoflurane anesthesia combined with epidural anesthesia were randomly allocated to receive either amino acid solution (A group) or electrolyte solution (S group) intravenously. Each solution was started at anesthesia induction. The levels of tympanic temperature were recorded after induction, during surgery and at extubation. RESULTS: Patients in each of the two groups (A group vs. S group) were comparable with their characteristics and anesthetic management. Amino acid infusion prevented intraoperative hypothermia for cases of 180 min or more. The number of patients with temperature of less than 35.5 degrees C in A group was less those that in S group for cases shorter than 180 min. CONCLUSIONS: Amino acid infusion has more preventive effect on intraoperative hypothermia than electrolyte solution.     

Kinetic study during amino acid infusion in catabolic patients. Comparison between two solutions

The equilibrium kinetic of two different amino acid solutions was investigated in ten catabolic patients (Parentamin, Pierrel; HBC, Baxter). Plasma amino acid pattern was determined on arterial samples before TPN and several times over 48 hours of TPN. Nitrogen balance was measured from 24 hours urine collection. Three different cinetic trends were found: a fast modification (diminution or increase), a slow adaptation, or no modification of plasmatic levels, however each amino acid reached a steady state plateau. The adequacy of the infusion of each amino acid was evaluated comparing its steady-state plasma level to the after lunch level in healthy man. This made possible to approximate metabolic needs of each of the infused amino acids and to identify the inadequacy of some metabolic pathways to synthetized non essential amino acids lacking in solutions. This made possible to identify amino acids infused in excess or in defect, and those infused in dose adapt to the metabolic needs of such patients.     

Proximal renal tubular dysfunction in primary distal renal tubular acidosis

Low-molecular-weight (LMW) proteinuria has been described in patients with primary distal renal tubular acidosis (dRTA). However, other proximal renal tubular dysfunctions have rarely been reported. In this report we describe reversible and multiple proximal renal tubular cell dysfunctions in a patient with dRTA. A 4-year-old girl was admitted to our hospital for investigation of short stature and proteinuria. Laboratory studies revealed a hyperchloremic metabolic acidosis without aciduria, hypokalemia, hypouricemia with uricosuria, hypercalciuria, LMW proteinuria, phosphaturia, and generalized aminoaciduria. The patient was diagnosed as having dRTA with multiple proximal renal tubular dysfunctions. All proximal renal tubular dysfunction subsided 1.5 years after starting alkali therapy. The precise pathogenic mechanisms underlying the development of multiple proximal renal tubular dysfunctions in dRTA remained unclear. However, proximal renal tubular endosomal dysfunction resulting from a profound intracellular acidosis caused by vacuolar H⁺-ATPase dysfunction or hypokalemic nephropathy might contribute to the development of proximal renal tubular dysfunctions in patients with dRTA.     

Renal effects of amino acid infusion in cardiac surgery

OBJECTIVE: To evaluate effects of amino acids on renal function and oxygen consumption and the role of individual amino acids on renal blood flow (RBF) changes. DESIGN: Prospective, randomized, controlled study. SETTING: Operating room in cardiothoracic surgery department, university hospital. PARTICIPANTS: Twenty-two male patients submitted to elective first-time coronary artery bypass surgery. INTERVENTIONS: A catheter was placed in the left renal vein for thermodilution RBF measurements and blood sampling. In 11 patients, a balanced mixed amino acid infusion was infused (200 mL/hr) for 30 minutes immediately after the operation. MEASUREMENTS AND MAIN RESULTS: RBF and glomerular filtration rate increased during amino acid infusion compared with the control group. Renal oxygen consumption increased in the amino acid group and correlated with the increase in RBF (r = 0.70, p<0.001). Amino acid infusion induced two- to fourfold increases in plasma concentrations of individual amino acid concentrations and promoted renal extraction of aspartate, glutamate, glycine, and histidine. No correlation was observed between arterial concentration or uptake of individual amino acids and RBF. CONCLUSIONS: The increase in RBF from a mixed amino acid infusion was associated with increased glomerular filtration rate and renal consumption of oxygen. Changes in RBF of a mixed amino acid infusion could not be linked to plasma level or renal uptake of any individual amino acids.     

Glucagon secretion is essential for aminoacid-induced hyperfiltration in man

The role of glucagon as a mediator of aminoacid-induced alteration of renal haemodynamics was evaluated in man in three different protocols. In the first it was shown that the increase in glomerular filtration rate (GFR) and renal plasma flow (RPF) observed during an aminoacid infusion was prevented by the additional infusion of somatostatin (SRIF), but reproduced by a glucagon infusion in the presence of SRIF. In the second protocol it was shown that, at variance with normal subjects, six totally pancreatectomised patients, thus deprived of pancreatic glucagon secretion, did not increase their GFR and RPF when infused with amino-acids, whereas they exhibited the expected hyperfiltration when infused with glucagon. In the third protocol it was shown that glucagon infusion in a renal artery did not alter the homolateral renal haemodynamics. It is concluded that glucagon secretion is a mandatory step in the cascade of events linking the infusion of aminoacids to the renal hyperfiltration. Other steps beyond glucagon secretion are necessarily involved because glucagon has no direct renal effect.     

Proximal renal tubular dysfunction in severe burns

Proximal renal tubular function was studied in 11 patients with severe burn injury. Creatinine clearance was normal or increased in ten patients. Fractional excretion of sodium was less than 1% in ten. Fractional excretion of uric acid and amylase were increased in all but four and two cases, respectively, while absolute clearances of lysozyme and beta 2-microglobulin were increased in all but one patient. Renal threshold phosphate concentration was reduced in four patients. Twenty-four-hour urine glucose excretion exceeded 1 g in five patients, aminoaciduria was noted in eight, and proteinuria, predominantly globulinuria, was present consistently. Metabolic acidosis was seen in one patient, and transient hypokalemia occurred in two. Abnormalities of proximal tubular function were more marked in the five patients with the greatest extent of third-degree burns who died. The cause of proximal tubular dysfunction is not clear and may be related to an adaptive response to severe injury.     

Proximal interphalangeal articulation in man]

A report is presented on microdissections of the proximal interphalangeal joint, in particular the proximal attachments of volar plate and tendon sheath. The proximal anchorage of the joint capsule is assured by three components, occurring bilaterally. A. Laterobasal and retrochlear fibres. B. An internal cord which inserts along the inner side of the line of attachment of the osteofibrous sheath of phalanx I; C. The cruciform ligament of the sheath which is inserted at the outer side of the osteofibrous sheath of phalanx I.