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Metabolic acidosis is a common complication of chronic kidney disease and is believed to contribute to a number of sequelae, including bone disease, altered protein metabolism, skeletal muscle wasting, and progressive glomerular filtration rate loss. Small trials in animal models and humans suggest a role for alkali therapy to lessen these complications. Recent studies support this notion, although more definitive evidence is needed on the long-term benefits of alkali therapy and the optimal serum bicarbonate level. The role of dietary modification also should be given greater consideration. In addition, potential adverse effects of alkali treatment must be taken into consideration, including sodium retention and the theoretical concern of promoting vascular calcification. This teaching case summarizes the rationale for and benefits and complications of base therapy in patients with chronic kidney disease., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aims/hypothesis: The objective of this study was to evaluate the prospective relationship between dietary acid load, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and type 2 diabetes risk., Methods: A total of 66,485 women from the E3N-EPIC cohort were followed for incident diabetes over 14 years. PRAL and NEAP scores were derived from nutrient intakes. HRs for type 2 diabetes risk across quartiles of the baseline PRAL and NEAP scores were estimated with multivariate Cox regression models., Results: During follow-up, 1,372 cases of incident type 2 diabetes were validated. In the overall population, the highest PRAL quartile, reflecting a greater acid-forming potential, was associated with a significant increase in type 2 diabetes risk, compared with the first quartile (HR 1.56, 95% CI 1.29, 1.90). The association was stronger among women with BMI <25 kg/m2 (HR 1.96, 95% CI 1.43, 2.69) than in overweight women (HR 1.28, 95% CI 1.00, 1.64); statistically significant trends in risk across quartiles were observed in both groups (p trend < 0.0001 and p trend = 0.03, respectively). The NEAP score provided similar findings., Conclusions/interpretation: We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms.

Background and Purpose: Few studies have described the risk factors associated with the development of neurological pulmonary edema (NPE) after subarachnoid hemorrhage (SAH). We have hypothesized that acute-phase increases in serum lactate levels are associated with the early development of NPE following SAH. The aim of this study was to clarify the association between lactic acidosis and NPE in patients with nontraumatic SAH., Methods: We retrospectively evaluated 140 patients with nontraumatic SAH who were directly transported to the Nippon Medical School Hospital emergency room by the emergency medical services. We compared patients in whom NPE developed (NPE group) and those in whom it did not (non-NPE group)., Results: The median (quartiles 1-3) arrival time at the hospital was 32 minutes (28-38 minutes) after the emergency call was received. Although the characteristics of the NPE and non-NPE groups, including mean arterial pressure (121.3 [109.0-144.5] and 124.6 [108.7-142.6] mm Hg, respectively; P=0.96), were similar, the median pH and the bicarbonate ion (HCO3(-)) concentrations were significantly lower in the NPE group than in the non-NPE group (pH, 7.33 [7.28-7.37] vs. 7.39 [7.35-7.43]); P=0.002; HCO3(-), 20.8 [18.6-22.6] vs. 22.8 [20.9-24.7] mmol/L; P=0.01). The lactate concentration was significantly higher in the NPE group (54.0 [40.3-61.0] mg/dL) than in the non-NPE group (28.0 [17.0-37.5] mg/dL; P<0.001). Multivariable regression analysis indicated that younger age and higher glucose and lactate levels were significantly associated with the early onset of NPE in patients with SAH., Conclusion: The present findings indicate that an increased serum lactate level, occurring within 1 hour of the ictus, is an independent factor associated with the early onset of NPE. Multicenter prospective studies are required to confirm our results.

Renal tubular acidosis (RTAs) are a group of metabolic disorders characterized by metabolic acidosis with normal plasma anion gap. There are three main forms of RTA: a proximal RTA called type II and a distal RTA (type I and IV). The RTA type II is a consequence of the inability of the proximal tubule to reabsorb bicarbonate. The distal RTA is associated with the inability to excrete the daily acid load and may be associated with hyperkalaemia (type IV) or hypokalemia (type I). The most common etiology of RTA type IV is the hypoaldosteronism. The RTAs can be complicated by nephrocalcinosis and obstructive nephrolithiasis. Alkalinization is the cornerstone of treatment., (Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background/aims: Bone fracture is often complicated in hemodialysis (HD) patients. Metabolic acidosis is related to bone disease and muscle wasting, but it is not known whether acid-base disturbance is associated with the risk of bone fractures. The aim of this study was to clarify the association of serum bicarbonate level with bone fracture in HD patients., Methods: Using a subcohort of the Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D), 890 prevalent HD patients (age: 62 years old, male: 62.8%, duration of dialysis: 8.3 years) with secondary hyperparathyroidism were studied. After measuring predialysis serum bicarbonate at a 2-day interdialytic interval, we prospectively followed them every 3 months, and examined the occurrence of any type of bone fracture or hospitalization due to fracture over a 3-year observation period., Results: Seventy-four bone fractures and 47 hospitalizations due to fracture were observed during the follow-up period. HD patients with serum bicarbonate <20 mmol/l had a 1.93 (95% CI 1.01-3.71)-fold higher risk for all-cause fractures than those with serum bicarbonate of 20.0-21.9 mmol/l. A higher bicarbonate level (≥22 mmol/l) was also related to an increased risk of bone fracture. A restricted cubic regression spline disclosed that the higher or the lower than 21.0 mmol/l of serum bicarbonate, the greater the risk for bone fracture., Conclusion: Both a lower level and a higher level of predialysis bicarbonate concentration were associated with risk of bone fracture in HD patients with secondary hyperparathyroidism., (© 2014 S. Karger AG, Basel.)

Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated.

Background: Bleeding is the most frequent cause of preventable death after severe injury. Our purposes were to study the efficacy of tranexamic acid (TXA) and prothrombin complex concentrate (PCC) on a traumatic coagulopathy with a severe native metabolic acidosis and compare the efficacy of PCC versus fresh frozen plasma (FFP) to reverse a dilutional coagulopathy., Methods: In vitro effects of TXA and PCC were assessed with standard laboratory analysis (prothrombin time [PT]/international normalized ratio [INR]) and rotational thromboelastometry in a porcine hemorrhage with ischemia-reperfusion (H/I) model. FFP was used in comparison with PCC. In vitro doses were calculated to be the equivalent of 1-g TXA, 100-mg tissue plasminogen activator, 45-IU/kg PCC, and 4-U FFP. Agents were tested at baseline and then with severe metabolic acidosis after 6 hours of resuscitation., Results: Thirty-one swine were studied. Baseline hematocrit was 24%, pH was 7.56, INR was 1.0, and lactate level was 1.47. Six hours after H/I, the hematocrit was 15.9%, pH was 7.1, INR was 1.7, and lactate level was 10.26. Rotational thromboelastometry revealed that maximum clot firmness at baseline was 71.71 mm and decreased to 0.29 mm with tissue plasminogen activator, representing severe fibrinolysis. Following TXA dosing, the maximum clot firmness was immediately corrected to 69.06 mm. There was no difference (p = 0.48) between TXA function at baseline pH (mean, 7.56) or acidotic pH (mean, 7.11). The mean baseline PT was 13 ± 0.49 seconds (INR, 1). After H/I and resuscitation, the mean PT was 23.03 seconds (INR, 2.1). PCC reduced the PT to 20 (INR, 1.75; p = 0.001) and FFP to 17.44 (INR, 1.47; p = 0.001)., Conclusion: Both TXA and PCC seem to function well in reversing a traumatic coagulopathy in vitro, and TXA seems to have no loss of function in a severe metabolic acidosis. Further investigations are warranted.

Experimental data indicate that hypercapnic adidosis has anti-inflammatory effects. These anti-inflammatory effects may even be a beneficial property in case of low tidal volume ventilation with consecutive hypercapnic acidosis. It is unclear whether these anti-inflammatory effects predominate in critically ill patients who suffer from multiple pro- and anti-inflammatory insults like extracorporeal organ support (pro-inflammatory), metabolic acidosis (pro- and anti-inflammatory), as well as hypoxia (pro-inflammatory). Eighteen pigs were randomized into three groups, mechanically ventilated and connected to a continuous veno-venous hemofiltration (CVVH) as pro-inflammatory insult. A reference group with normal acid-base state obtained normoventilation; a normoxemic acidemia group obtained normoxemic, mixed acidemia due to infusion of lactic and hyperchloremic acid and low tidal volume ventilation, and in a hypoxemic acidemia group the mixed acidemia was paralleled by hypoxemia. Lung histology including pulmonary leukocyte invasion, blood gases, blood cell counts, and hemodynamics were examined. The histological examination of the lungs of acidemic pigs showed a suppressed invasion of leukocytes and thinner alveolar walls compared with normoventilated and with hypoxemic pigs. Enhanced congestion and alveolar red blood cells (RBCs) combined with an increase of the pulmonary artery pressure were observed in acidemic pigs in comparison with the reference group. Normoxemic acidemia reduced the pro-inflammatory reaction to the CVVH and mechanical ventilation in the ventilated lung areas in the form of pulmonary leukocyte invasion. However, this did not result in reduced scores for lung injury. Instead, an increased score for criteria which represent lung injury (congestion and alveolar RBCs) was observed in acidemic pigs., (© 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.)

Introduction: Therapeutic Hypothermia (TH) has become a standard of care in improving neurological outcomes in cardiac arrest (CA) survivors. Previous studies have defined severe acidemia as plasma pH<7.20. We investigated the influence of severe acidemia at the time of initiation of TH on neurological outcome in CA survivors., Methods: A retrospective analysis was performed on 196 consecutive CA survivors (out-of-hospital CA and in-hospital CA) who underwent TH with endovascular cooling between January 2007 and October 2012. Arterial blood gas drawn prior to initiation of TH was utilized to measure pH in all patients. Shockable and non-shockable CA patients were divided into two sub-groups based on pH (pH<7.2 and pH≥7.2). The primary end-point was measured using the Pittsburgh Cerebral Performance Category (CPC) scale prior to discharge from the hospital: good (CPC 1 and 2) and poor (CPC 3 to 5) neurologic outcome., Results: Sixty-two percent of shockable CA patients with pH≥7.20 had good neurological outcome as compared to 34% patients with pH<7.20. Shockable CA patients with pH≥7.20 were 3.3 times more likely to have better neurological outcome when compared to those with pH <7.20 [p=0.013, OR 3.3, 95% CI (1.28-8.45)]. In comparison, non-shockable CA patients with p≥7.20 did not have a significantly different neurological outcome as compared to those with pH<7.20 [p=0.97, OR 1.02, 95% CI (0.31-3.3)]., Conclusion: Presence of severe acidemia at initiation of TH in shockable CA survivors is significantly associated with poor neurological outcomes. This effect was not observed in the non-shockable CA survivors., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Hypoxic-ischemic encephalopathy (HIE) occurring during the perinatal period is one of the primary causes of severe, long-term neurological deficits in children. Initial systemic supportive therapy remains a critical aspect of HIE management. In addition to support therapy, the widespread use of hypothermia has demonstrated a reduction in death and neurodevelopmental disability in infants with moderate to severe HIE. Neonates with HIE born outside of tertiary care centers must be rapidly identified as hypothermia candidates and have emergent transport arranged. While waiting for the transport team to arrive, these neonates often require intensive stabilization, including meticulous temperature management. This article examines the need for HIE outreach teaching programs, assists in the identification of a neonate for hypothermia therapy, and supplies evidence-based recommendations for the initial stabilization and care of neonates delivered at nontertiary care facilities. The guidelines and materials supplied represent the outreach model used by our regional hypothermia center and disseminated to the surrounding referral hospitals.

Background: The relationship between cord arterial pH (CA-pH) > 7.000 and the neonatal outcome is not clear., Aims: To evaluate if asymptomatic infants born with unexpected cord arterial pH (CA-pH) between 7.000 and 7.100 develop clinical, biochemical, and instrumental signs of hypoxic cerebral, renal, and heart failure more frequently than symptomatic infants., Study Design: Term infants with CA-pH of 7.000-7.100 and appropriate birth weight were prospectively and consecutively enrolled and classified as asymptomatic, when they had no resuscitation, early respiratory distress or early abnormal neurologic signs, and symptomatic infants. Clinical, biochemical, and instrumental signs of hypoxic cerebral, renal, and heart failure were evaluated in the two groups., Results: A total of 53 infants were enrolled. Twenty-eight (53%) were asymptomatic. CA-pH was similar in both the groups, while the cTnI serum concentration in the first day of life and the occurrence of poor feeding were higher in the symptomatic than in asymptomatic infants. An arterial lactate level of ≥ 4.1 mmol/l measured in the first hour of life was an independent risk factor for the development of a symptomatic course., Conclusions: In our population the majority of infants born with a CA-pH between 7.000 and 7.100 were asymptomatic and would not have needed immediate admission to the neonatal care unit. Symptomatic infants showed a higher occurrence of subclinical heart injury and poor feeding., (© 2013.)

Vegetarian diet is a very old practice that is liable to confer some health benefits. Recent studies have demonstrated that modification of the dietary pattern with a reduction of animal protein intake and increased consumption of plant-based foods could influence cardiovascular risk profile and mortality rate. Moreover, phosphate bioavailability from plant proteins is reduced. These statements could lead to some benefits for chronic kidney disease (CKD) patients. This review summarizes the characteristics and benefits of vegetarian diets in the general population and the potential beneficial effects of such a diet on phosphate balance, insulin sensitivity, and the control of metabolic acidosis in CKD patients. Potential drawbacks exist when a vegetarian diet is associated with protein intake that is too restrictive and/or insufficient energy intake, justifying an early and regular nutritional follow-up jointly assumed by a nephrologist and a renal dietitian., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The article presents information on the nature and dynamics of metabolic changes in oral fluid in women during gestation. It is shown that dystrophic-inflammatory processes of periodontal tissues grow backed by the progression of metabolic acidosis. High content of sulfhydryl groups and disulfide ties in soluble proteins and low molecular weight compounds of oral fluid during pregnancy and activation of enzymatic antioxidant defense system periodontal tissues are found.

Background: Heavy alcohol consumption during pregnancy negatively impacts the physical growth of the fetus. Although the deleterious effects of alcohol exposure during late gestation on fetal brain development are well documented, little is known about the effect on fetal bone mechanical properties or the underlying mechanisms. The purpose of this study was to investigate the effects of late gestational chronic binge alcohol consumption and alcohol-induced acidemia, a critical regulator of bone health, on functional properties of the fetal skeletal system., Methods: Suffolk ewes were mated and received intravenous infusions of saline or alcohol (1.75 g/kg) over 1 hour on 3 consecutive days per week followed by 4 days without treatment beginning on gestational day (GD) 109 and concluding on GD 132 (term = 147 days). The acidemia group was exposed to increased inspired fractional concentrations of CO2 to closely mimic the alcohol-induced decreases in maternal arterial pH seen in the alcohol group., Results: Fetal femurs and tibias from the alcohol and acidemia groups were ~3 to 7% shorter in length compared with the control groups (p < 0.05). Three-point bending procedure demonstrated that fetal femoral ultimate strength (MPa) for the alcohol group was decreased (p < 0.05) by ~24 and 29%, while the acidemia group exhibited a similar decrease (p < 0.05) of ~32 and 37% compared with the normal control and saline control groups, respectively. Bone extrinsic and intrinsic mechanical properties including maximum breaking force (N) and normalized breaking force (N/kg) of fetal bones from the alcohol and acidemia groups were significantly decreased (p < 0.05) compared with both control groups., Conclusions: We conclude that late gestational chronic binge alcohol exposure reduces growth and impairs functional properties of the fetal skeletal system and that the repeated episodes of alcohol-induced maternal acidemia may be at least partially responsible for these effects., (Copyright © 2013 by the Research Society on Alcoholism.)

Postacidotic arrhythmias have been associated to increased sarcoplasmic reticulum (SR) Ca(2+) load and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation. However, the molecular mechanisms underlying these arrhythmias are still unclear. To better understand this process, acidosis produced by CO2 increase from 5% to 30%, resulting in intracellular pH (pHi) change from 7.15 to 6.7, was incorporated into a myocyte model of excitation-contraction coupling and contractility, including acidotic inhibition of L-type Ca(2+) channel (I(CaL)), Na(+)-Ca(2+) exchanger, Ca(2+) release through the SR ryanodine receptor (RyR2) (I(rel)), Ca(2+) reuptake by the SR Ca(2+) ATPase2a (I(up)), Na(+)-K(+) pump, K(+) efflux through the inward rectifier K(+) channel and the transient outward K(+) flow (I(to)) together with increased activity of the Na(+)-H(+) exchanger (I(NHE)). Simulated CaMKII regulation affecting I(rel), I(up), I(CaL), I(NHE) and I(to) was introduced in the model to partially compensate the acidosis outcome. Late Na(+) current increase by CaMKII was also incorporated. Using this scheme and assuming that diastolic Ca(2+) leak through the RyR2 was modulated by the resting state of this channel and the difference between SR and dyadic cleft [Ca(2+)], postacidotic delayed after depolarizations (DADs) were triggered upon returning to normal pHi after 6 min acidosis. The model showed that DADs depend on SR Ca(2+) load and on increased Ca(2+) leak through RyR2. This postacidotic arrhythmogenic pattern relies mainly on CaMKII effect on I(CaL) and I(up), since its individual elimination produced the highest DAD reduction. The model further revealed that during the return to normal pHi, DADs are fully determined by SR Ca(2+) load at the end of acidosis. Thereafter, DADs are maintained by SR Ca(2+) reloading by Ca(2+) influx through the reverse NCX mode during the time period in which [Na(+)]i is elevated., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Acute pancreatitis recently became the most common cause for hospitalization among gastrointestinal diseases. There is no specific therapy against the disease due to insufficient understanding of pathogenesis. Animal and in vitro models indicated that reduced pancreatic ductal bicarbonate secretion and consequent intraductal acidosis is an early event in acute pancreatitis, but human data are lacking. Therefore, our aim was to determine the luminal pH in the main pancreatic duct during acute pancreatitis in humans. Intraductal pH was measured in patients with acute biliary pancreatitis (n = 6) during endoscopic retrograde cholangio-pancreatography. Patients with common bile stones without pancreatitis (n = 5) and a patient with an adenoma of the papilla of Vater served as controls. The luminal pH was significantly lower in the group of acute biliary pancreatitis vs. controls (6.97 ± 0.13 vs. 7.79 ± 0.20). Our brief report shows for the first time that there is marked intraductal acidosis in acute biliary pancreatitis, which seems to worsen with time. Further clinical trials are needed to determine the exact roles of reduced intraductal pH in ABP., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Hypoxia represents the lack of oxygen below the basic level, and the range of known channels related to hypoxia is continually increasing. Since abnormal hypoxia initiates pathological processes in numerous diseases via, to a great degree, producing acidic microenvironment, the significance of these channels in this environment has, until now, remained completely unknown. However, recent discovery of acid-sensing ion channels (ASICs) have enhanced our understanding of the hypoxic channelome. They belong to the degenerin/epithelial Na (+) channel family and function once extracellular pH decreases to a certain level. So does the ratiocination emerge that ASICs participate in many hypoxia-induced pathological processes, including pain, apoptosis, malignancy, which all appear to involve them. Since evidence suggests that activity of ASICs is altered under pathological hypoxia, future studies are needed to deeply explore the relationship between ASICs and hypoxia, which may provide a progressive understanding of hypoxic effects in cancer, arthritis, intervertebral disc degeneration, ischemic brain injury and so on.

Objective: To evaluate if acidemia in vigorous infants is a useful variable in the assessment of intrapartum care with regard to cardiotocographic (CTG) patterns during the second stage., Methods: Cases (n = 241) were infants with an umbilical artery pH < 7.05, controls (n = 482) were infants with pH ≥ 7.05. Apgar score was ≥ 7 at 5 min in both groups. CTGs during the last two hours of labor were assessed and neonatal outcomes compared. A sub-analysis of cases with metabolic acidemia: pH < 7.00 and base deficit ≥ 12 mmol/L and acidemia: 7.00 < pH < 7.05 was performed., Results: 63% of cases had a pathological CTG versus 26% of controls (p < 0.001). Patterns with severe variable decelerations had a significantly longer duration in cases. Metabolic acidemia was significantly associated with severe variable decelerations and decreased variability. Infants to cases were admitted to neonatal care in 19% versus 2% of controls (p < 0.001). With metabolic acidemia, 32% were admitted., Conclusion: An umbilical artery pH < 7.05 at birth of vigorous infants may be a useful variable for quality control of intrapartum management with regard to the assessment of second-stage CTGs. Differences in duration of pathological patterns indicate passiveness in academic cases.

It is important to understand the unique aspects vis-à-vis protein-energy wasting for patients undergoing PD. As a result of obligatory protein losses with the therapy, the serum albumin levels of patients undergoing PD are lower, as is the threshold serum albumin at which the risk for death is increased. Consequently, it is prudent to consider a lower threshold for serum albumin for the diagnosis of protein-energy wasting for patients undergoing PD. Likewise, it is important to consider the energy intake from obligatory nutrient absorption in the form of carbohydrates when estimating total energy intake (diet and dialysate) when evaluating patients for protein-energy wasting. The continuous nature of PD also has important therapeutic implications for protein-energy wasting. Such patients are more likely to have a complete correction of metabolic acidosis, and glucose absorption from the peritoneal dialysate has a protein-sparing effect, allowing some patients to maintain neutral nitrogen balances in the face of suboptimal protein intake. In contrast, clinical trials of amino-acid-based PD solutions have not met expectations and cannot be recommended for routine use for treatment of protein-energy wasting. In conclusion, it is important to consider these unique nutritional considerations when providing care to patients undergoing PD., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Disorders of fatty acid oxidation are rare but can be fatal. Hypoglycaemia with acidosis is a cardinal feature. Cases may present during early childhood or can be delayed into adolescence or beyond. We present a case of multiple acyl-coenzyme A dehydrogenase deficiency (MADD), an extremely rare disorder of fatty acid oxidation. Our 20-year-old patient presented with cardiovascular collapse, raised anion gap metabolic acidosis and non-ketotic hypoglycaemia. She subsequently developed multi-organ failure and sadly died. She had a previous diagnosis of cyclic vomiting syndrome (CVS) for more than 10 years, warranting frequent hospital admissions. The association between CVS and MADD has been made before though the exact relationship is unclear. All patients with persistent severe CVS should have metabolic investigations to exclude disorders of fatty acid oxidation. In case of non-ketotic hypoglycaemia with acidosis, the patient should be urgently referred to a specialist in metabolic diseases. All practitioners should be aware of these rare disorders as a cause of unexplained acidosis.

Following a propofol anesthetic, a 5-year-old girl with lower extremity spasticity seized and developed hypertriglyceridemia, hyperkalemia, and metabolic acidosis. A presumed diagnosis of propofol infusion syndrome (PRIS) was made, but further investigation revealed neonatal adrenoleukodystrophy. PRIS should be considered with this constellation of symptoms, but other neurometabolic disorders must always be ruled out., (© 2013 Blackwell Publishing Ltd.)

Purpose: In acute kidney injury patients, metabolic acidosis is common. Its severity, duration, and associated changes in mean arterial pressure (MAP) and vasopressor therapy may be affected by the intensity of continuous renal replacement therapy (CRRT). We aimed to compare key aspects of acidosis and MAP and vasopressor therapy in patients treated with two different CRRT intensities., Methods: We studied a nested cohort of 115 patients from two tertiary intensive care units (ICUs) within a large multicenter randomized controlled trial treated with lower intensity (LI) or higher intensity (HI) CRRT., Results: Levels of metabolic acidosis at randomization were similar [base excess (BE) of -8 ± 8 vs. -8 ± 7 mEq/l; p = 0.76]. Speed of BE correction did not differ between the two groups. However, the HI group had a greater increase in MAP from baseline to 24 h (7 ± 3 vs. 0 ± 3 mmHg; p < 0.01) and a greater decrease in norepinephrine dose (from 12.5 to 3.5 vs. 5 to 2.5 μg/min; p < 0.05). The correlation (r) coefficients between absolute change in MAP and norepinephrine (NE) dose versus change in BE were 0.05 and -0.37, respectively., Conclusions: Overall, LI and HI CRRT have similar acid-base effects in patients with acidosis. However, HI was associated with greater improvements in MAP and vasopressor requirements (clinical trial no. NCT00221013).

Aim: To examine concentrations of three cardiovascular propeptides in umbilical cord plasma of neonates born to mothers with Type 1, Type 2 and gestational diabetes. Measurement of cardiovascular markers in umbilical cord plasma may potentially help identify neonates at risk of postnatal complications. Neonates born to mothers with diabetes have an increased risk of neonatal morbidity and mortality, and measurement of these new biomarkers may potentially help identify neonates at risk of these complications., Subjects & Methods: Copeptin, midregional proadrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) were measured in cord plasma of neonates (n = 63) born to mothers with the three types of diabetes. Associations with maternal glycemic control, mode of delivery and neonatal metabolic acidosis were examined., Results: Umbilical cord plasma copeptin concentrations were lowest in neonates after elective cesarean sections (6.1 pmol/l; interquartile range [IQR]: 4.5-9.1) compared with emergency cesarean sections (156 pmol/l; IQR: 9.6-311; p = 0.019) and vaginal delivery (831 pmol/l; IQR: 107-2407; p < 0.0001). MR-proADM was also affected by mode of delivery; however, this seemed more likely to be caused by an inverse association with the acid-base balance. In this population, only MR-proANP plasma concentrations were related to type of diabetes. Neonates born to mothers with Type 1 diabetes had higher concentrations (median 260 pmol/l; IQR: 222-318) compared with Type 2 diabetes (175 pmol/l; IQR: 169-200; p = 0.003) and gestational diabetes (200 pmol/l; IQR: 149-276; p = 0.009)., Conclusion: Umbilical cord plasma copeptin and MR-proADM concentrations primarily reflect perinatal stress associated with mode of delivery and the degree of fetal acidosis, whereas MR-proANP concentrations are higher in neonates born to mothers with Type 1 diabetes.

Background: Hypothermia and acidosis have been suggested as key initiators of trauma-induced coagulopathy, and severe bleeding caused by hyperfibrinolysis (HF) predicts mortality. We tested in vitro (1) whether clinically relevant grades of hypothermia, acidosis, and their combination impact on recombinant tissue-type plasminogen activator (r-tPA)-evoked HF and assessed (2) the efficacy of tranexamic acid (TA) in inhibiting fibrinolysis under such conditions., Methods: To assess the effects of r-tPA-evoked HF, venous blood (3,000 μL) from healthy volunteers was incubated with r-tPA (final concentration, 100 ng/mL) or saline (control) for 30 minutes at the final measurement temperature. Before thromboelastometric measurements, samples were acidified (addition of 40 μL of 0.5 or 1N hydrochloric acid, respectively) to achieve a pH (alpha-stat) of approximately 7.1 or 6.9, respectively. To assess effects of hypothermia, tests were performed at blood/thromboelastometer temperatures of 33°C and 37°C, respectively. Coagulation was analyzed using rotational thromboelastometry (ROTEM), particularly assessing the Clot Lysis Index (CLI) after 45 minutes (CLI45) in extrinsically activated assays (EXTEM)., Results: Addition of r-tPA evoked fibrinolysis (CLI45: median, 64; 25th/75th percentile, 48/80) compared with saline controls (CLI45: median, 93; 25th/75th percentile, 91/96). Moderate acidosis (pH [mean ± SD], 7.12 ± 0.03) did not affect r-tPA-induced fibrinolysis. However, severe acidosis (pH, 6.91 ± 0.02) significantly aggravated r-tPA-induced fibrinolysis (CLI45: median, 49; 25th/75th percentile, 26/71; p = 0.0039) compared with fibrinolysis with normal pH and normothermia (median, 77; 25th/75th percentile, 65.5/83). In contrast, hypothermia (33°C) at normal pH (median ± SD, 7.37 ± 0.02) markedly mitigated fibrinolysis (CLI45: median, 94; 25th/75th percentile, 88/96; p = 0.0156) compared with normothermia (CLI45: median, 64; 25th/75th percentile, 48/80). TA (final concentration, 0.33 mg/mL) abolished r-tPA-evoked fibrinolysis even during severe acidosis (CLI45: median, 92; 25th/75th percentile, 86.5/94; p = 0.0039)., Conclusion: Severe acidosis significantly increases r-tPA-evoked fibrinolysis, whereas hypothermia markedly mitigates HF. The latter finding may imply that rapid rewarming of trauma patients might aggravate fibrinolysis. TA reliably abolished fibrinolysis also under these conditions, supporting its role in trauma-induced coagulopathy.

This article outlines the challenges of identification and management of tissue hypoperfusion as a consequence of haemorrhagic shock in civilian polytrauma cases. It also describes damage resuscitation, but does not cover specific trauma cases such as pregnancy, burns, head injuries, children and elderly trauma.

Aim: To determine whether a relationship exists between the markers of severe acidemia (SA) and the developmental, verbal, and behavioral characteristics of children with SA born at term 5 years previously, without apparent neurological impairment., Methods: A cohort of 76 children-38 with SA (pH < 7, base deficit ≥12 mmol/L) and 38 non-SA (pH ≥ 7.20)-were evaluated using the Battelle Developmental Inventory, McCarthy's Verbal Scale, the Token Test for Children, and the Conners 3rd Edition-Parent. The relationships between markers of SA and verbal and behavioral scores were analyzed with parametric correlations. Multiple regression analysis was used to determine the possible effect of these markers on verbal abilities, verbal memory, and attention., Results: Although none of the scores were in the "impaired" range, the SA group scored lower in verbal index (p = .000) and verbal memory (p = .004) on the McCarthy's Scales and in verbal comprehension (p = .001) on the Token Test for Children-2, and higher on the inattention (p = .003) and hyperactivity-impulsivity domains of the Conners Scales (p = .009) compared with the control group. There were no differences between the groups in the motor, personal-social, or cognitive domains on the Battelle Developmental Inventory. The SA markers were found to be predictors, accounting for 61.6% of verbal variability., Conclusions: SA markers reflect mild long-term consequences regarding verbal abilities and inattentiveness among children born at term without apparent neurological impairment on discharge but do not suggest severe impairment to the 5-year development of children. The authors recommend that these children should be monitored to determine whether they need or might benefit from an early intervention program.

We present a case of early coma, metabolic acidosis and methemoglobinemia after substantial acetaminophen toxicity in the absence of hepatic failure. A 77-year-old female presented to the emergency department with a decreased level of consciousness. She was found unresponsive by a family member in her bed, and was reported to be acting normally when she was last seen eight hours earlier. Laboratory results on arrival were: pH 7.19, sodium 139 mmol/L, chloride 106 mmol/L, potassium 3.3 mmol/L, CO2 8 mmol/L, and an anion gap of 25. Both venous lactate (10.2 mmol/L) and methemoglobin (9.4 %) were elevated. The patient's acetaminophen concentration was markedly elevated at 7138 µmol/L (1078 µg/ml). Hepatic enzymes and coagulation tests were normal [alanine transaminase (ALT) 8 U/L, international normalized ratio (INR) 1.0]. Intravenous N-acetylcysteine (NAC) was initiated at a dose of 150 mg/kg over 15 minutes, followed by 50 mg/kg over the next four hours, followed by 100 mg/kg over the next 16 hours. Twenty-four hours after admission, the anion gap metabolic acidosis had resolved, and the methemoglobin was 2.1%. Aminotransferases peaked at 44 U/L and INR peaked at 1.9. A urine 5-oxoproline assay performed five days after admission was negative, suggesting no evidence of a 5-oxoprolinase deficiency. We describe the pathophysiology and discuss the literature on acetaminophen-induced coma and metabolic acidosis in the absence of hepatic injury; and propose mechanisms for associated methemoglobinemia.

Background: Normally, end-tidal CO(2) is within 2 mm Hg of arterial PO(2) (PaCO(2)). However, if dead space in the lungs increases owing to shock with poor lung perfusion, the arterial-end tidal PCO(2) difference [P(a-ET)CO(2)] increases. We have found that in severely injured patients, P(a-ET)CO(2) of less than 10 mm Hg is associated with survival and P(a-ET)CO(2) of greater than 16 mm Hg is usually fatal. Our initial studies suggested that intravenously administered bicarbonate increases P(a-ET)CO(2)., Methods: This retrospective therapeutic study evaluated the effects of intravenously administered bicarbonate in a cohort of 225 severely acidotic (arterial pH ≤ 7.10) trauma patients who underwent emergency surgery from 1989 through 2011. Patients were divided into groups: early deaths (<48 hours), deaths in the operating room, deaths within 48 hours, and survivors. Winter's formula was defined as PaCO(2) = (HCO(3)) (1.5) + 8 ± 4., Results: Of the 225 patients, the mean (SD) initial arterial pH was 6.92 (0.16) with HCO(3) of 11.0 (3.5) mEq/L. According to the Winter's formula, PaCO(2) should have been 24 (4) mm Hg but actually was 50 (14) mm Hg. In 73 patients, the effect of an average of two to eight vials of bicarbonate increased HCO(3) from 10.5 (3.1) mEq/L to 16.8 (4.0) mEq/L. In addition, PaCO(2) increased from 44 (9) mm Hg to 51 (11) mm Hg and end-tidal CO(2) stayed relatively constant (26 [6] to 25 [5]). This resulted in a increase in P(a-ET)CO(2) from 17 (9) mm Hg to 24 (13) mm Hg, affecting survival. In the final values after resuscitation, the P(a-ET)CO(2) in the 75 patients who survived was 10 (6) mm Hg, while the 103 patients who died in the operating room or within 48 hours of surgery had a P(a-ET)CO(2) of 23 (10) mm Hg (p < 0.001)., Conclusion: In severely acidotic, critically injured patients, reducing the PaCO(2) to less than 40 mm Hg and decreasing the P(a-ET)CO(2) to 10 (6) mm Hg should be attempted, using as little HCO(3) therapy as possible. Bicarbonate should be given only if severe acidosis persists despite resuscitation and if PaCO(2) levels near those which are appropriate can be obtained., Level of Evidence: Therapeutic study, level IV.

Background: Various cytokines are increased in hemodialysis (HD) patients, and are considered prognostic markers. Metabolic acidosis is common among chronic HD patients and is associated with survival. The relationship between acidosis and cytokines in HD patients has not been fully explored. The study aim was to measure pro- and anti-inflammatory cytokines in HD patients, with relation to bicarbonate levels., Methods: Forty-seven stable HD patients were included (male/female 28/19, mean age 70.4 ± 14.5 years). Blood tests were taken before a midweek dialysis session. Cytokine secretion from peripheral blood mononuclear cells was measured., Results: Acidosis versus no acidosis (serum HCO3 – 21.5 ± 0.2 vs. 24.9 ± 0.3 mEq/l, p < 0.001) was associated with decreased secretion of the anti-inflammatory interleukin-10 (IL-10, 1.16 ± 0.11 vs. 1.71 ± 0.20 ng/ml, p = 0.023). Patients with acidosis had higher parathyroid hormone (PTH), calcium-phosphate product, protein intake and transferrin. Higher IL-10 was associated with increased IL-6 secretion, higher bicarbonate, younger age and lower PTH., Conclusions: In stable chronic HD patients, a possible direct relation exists between metabolic acidosis and IL-10.

Background/aims: Severe acute pancreatitis can result in acute lung injury. This study aims to investigate the clinical characteristics and possible prediction index of acute lung injury in severe acute pancreatitis., Materials and Methods: We retrospectively evaluated 184 patients with severe acute pancreatitis admitted between April 2007 and July 2010. There were 51 patients who developed acute lung injury with a rate of 27.7% (51/184). Clinical data of the acute lung injury and non-acute lung injury patients were compared, and the characteristics of acute lung injury were also analyzed. Meanwhile, we validated a few possible prediction indexes to identify the patients at high risk for acute lung injury at the time of hospital admission., Results: The severity index, hospital day, and the incidence of infectious complications were significantly higher in the acute lung injury patients than in the nonacute lung injury patients (p<0.05). The differences between the non-acute lung injury and acute lung injury groups in mortality (3% vs. 11.8%, p<0.05), operation (5.3% vs. 15.7%, p<0.05), and incidence of renal failure (15.8% vs. 33.3%, p<0.05), cardiovascular failure (3.8% vs. 15.7%, p<0.05), and pancreatic cyst (18% vs. 37.3%, p<0.05) were statistically significant. The patients with higher level of severity index score, acidosis, tachypnea, smoking history, and obesity were prone to develop acute lung injury. conclusion: Acute lung injury occurrence in patients with severe acute pancreatitis varies according to predisposing conditions and independently carries poor prognosis.

In this paper, we concluded that transient acidosis reperfusion conferred cardioprotection against myocardial ischemia reperfusion injury in isolated rat hearts through activating PI3K-Akt-eNOS pathway.

Purpose: The aim was to assess whether impaired cardiac function contributes to symptoms of severe malaria in general or to metabolic acidosis in particular in children living in endemic regions., Methods: In a prospective observational investigation, 183 children with severe malaria were investigated for hemodynamic status and cardiac function upon admission (day 0) and after recovery (day 42). Cardiac function parameters were assessed by cardiac ultrasonography. Blood gas analyses and cardiac enzymes were measured at hospitalization and follow-up. Differences in subgroups with and without metabolic acidosis as well as other severe malaria-defining symptoms and conditions were assessed., Results: Cardiac index (CI) was significantly increased on day 0 compared to day 42 (5.8 ml/m(2), SD ± 1.8 ml/m(2), versus 4.7 ml/m(2), SD ± 1.4 ml/m(2); P < 0.001). CI correlated negatively with hemoglobin levels but not with parameters indicating impaired tissue perfusion or metabolic acidosis. Parasite levels had a significant influence on metabolic acidosis but not on CI. Alterations related to cardiac function, hemoglobin levels and metabolic acidosis were most prominent in children younger than 2 years., Conclusion: Increased CI reflecting high output status is associated with low hemoglobin levels while metabolic acidosis is linked to parasite levels.

Introduction: Severe hyperkalemia, with potassium (K+) levels ≥ 6.5 mEq/L, is a potentially life-threatening electrolyte imbalance. For prompt and effective treatment, it is important to know its risk factors, clinical manifestations, and predictors of mortality., Methods: An observational cohort study was performed at 2 medical centers. A total of 923 consecutive Korean patients were analyzed. All were 19 years of age or older and were hospitalized with severe hyperkalemia between August 2007 and July 2010; the diagnosis of severe hyperkalemia was made either at the time of admission to the hospital or during the period of hospitalization. Demographic and baseline clinical characteristics at the time of hyperkalemia diagnosis were assessed, and clinical outcomes such as in-hospital mortality were reviewed, using the institutions' electronic medical record systems., Results: Chronic kidney disease (CKD) was the most common underlying medical condition, and the most common precipitating factor of hyperkalemia was metabolic acidosis. Emergent admission was indicated in 68.6% of patients, 36.7% had electrocardiogram findings typical of hyperkalemia, 24.5% had multi-organ failure (MOF) at the time of hyperkalemia diagnosis, and 20.3% were diagnosed with severe hyperkalemia at the time of cardiac arrest. The in-hospital mortality rate was 30.7%; the rate was strongly correlated with the difference between serum K+ levels at admission and at their highest point, and with severe medical conditions such as malignancy, infection, and bleeding. Furthermore, a higher in-hospital mortality rate was significantly associated with the presence of cardiac arrest and/or MOF at the time of diagnosis, emergent admission, and intensive care unit treatment during hospitalization. More importantly, acute kidney injury (AKI) in patients with normal baseline renal function was a strong predictor of mortality, compared with AKI superimposed on CKD., Conclusions: Severe hyperkalemia occurs in various medical conditions; the precipitating factors are similarly diverse. The mortality rate is especially high in patients with severe underlying disease, coexisting medical conditions, and those with normal baseline renal function.

Nutritional interventions that might influence sarcopenia, as indicated by literature reporting on sarcopenia per se as well as dynapenia and frailty, are reviewed in relation to potential physiological aetiological factors, i.e. inactivity, anabolic resistance, inflammation, acidosis and vitamin D deficiency. As sarcopenia occurs in physically active and presumably well-nourished populations, it is argued that a simple nutritional aetiology is unlikely and unequivocal evidence for any nutritional influence is extremely limited. Dietary protein is probably the most widely researched nutrient but only for frailty is there one study showing evidence of an aetiological influence and most intervention studies with protein or amino acids have proved ineffective with only a very few exceptions. Fish oil has been shown to attenuate anabolic resistance of muscle protein synthesis in one study. There is limited evidence for a protective influence of antioxidants and inducers of phase 2 proteins on sarcopenia, dynapenia and anabolic resistance in human and animal studies. Also fruit and vegetables may protect against acidosis-induced sarcopenia through their provision of dietary potassium. While severe vitamin D deficiency is associated with dynapenia and sarcopenia, the evidence for a beneficial influence of increasing vitamin D status above the severe deficiency level is limited and controversial, especially in men. On this basis there is insufficient evidence for any more specific nutritional advice than that contained in the general healthy lifestyle-healthy diet message: i.e. avoiding inactivity and low intakes of food energy and nutrients and maintain an active lifestyle with a diet providing a rich supply of fruit and vegetables and frequent oily fish.

Introduction: Combat Gauze (CG) is currently the most widely used hemostatic dressing in combat. The testing of CG was initially performed in healthy and physiologically normal animals. The goal this study was to assess the efficacy in a model of severe acidosis and coagulopathy., Methods: To obtain an acidotic and coagulopathic model, Yorkshire swine sustained 35% blood volume hemorrhage followed by a 50-min supraceliac aortic ischemia-reperfusion injury with 6-h resuscitation (epinephrine to keep mean arterial pressure >40 and intravenous fluids to keep central venous pressure >4). We created a femoral artery injury and randomized the animals to CG versus a standard gauze (SG) dressing. We performed rotational thromboelastography with both CG and SG., Results: Using our model, 17 anesthetized Yorkshire swine developed appropriately significant coagulopathy, acidosis, and anemia. The SG failure rate was 100% on the first application and worked once on the second application. Combat Gauze was successful in achieving hemostasis 93% of the time on the first application and had 100% success with the second application. Rotational thromboelastography demonstrated that the only difference was a decreased clotting time with CG compared with SG (P = 0.012)., Conclusions: Combat Gauze significantly outperforms standard gauze dressings in a model of major vascular hemorrhage in acidotic and coagulopathic conditions. This effect appears to result from a decreased time lag between activation and first detectable clotting. Combat Gauze appears to maintain its efficacy even in the setting of severe acidosis and coagulopathy for the control of hemorrhage from vascular injury., (Published by Elsevier Inc.)

Ultrasound-guided cannulation of a large-bore catheter into the internal jugular vein was performed to provide temporary hemodialysis vascular access for uremia in a 65-yr-old woman with acute renal failure and sepsis superimposed on chronic renal failure. Despite the absence of any clinical evidence such as bleeding or hematoma during the procedure, a chest x-ray and computed tomographic angiogram of the neck showed that the catheter had inadvertently been inserted into the subclavian artery. Without immediately removing the catheter and applying manual external compression, the arterial misplacement of the hemodialysis catheter was successfully managed by open surgical repair. The present case suggests that attention needs to be paid to preventing iatrogenic arterial cannulation during central vein catheterization with a large-bore catheter and to the management of its potentially devastating complications, since central vein catheterization is frequently performed by nephrologists as a common clinical procedure to provide temporary hemodialysis vascular access.

Introduction: The use of recombinant factor VIIa (rFVIIa) in trauma patients is usually part of rescue therapy when haemorrhage and coagulopathy have not responded to conventional treatment. In this scenario, trauma patients are likely to have one or more components of the 'triad of death' (coagulopathy, acidosis and hypothermia). The aim of this study was to report on the outcome of trauma patients with the 'triad of death' immediately prior to receiving rFVIIa., Materials and Methods: Trauma patients receiving rFVIIa with the 'triad of death' were identified from the Australia and New Zealand Haemostasis Registry (ANZHR) and included in the study. The 'triad of death' was defined as an INR of >1.5, serum pH of <7.2 and a core temperature of <35 °C. Pre-dose clinical signs, investigations, adverse events and outcomes were analysed., Results: There were 2792 patients in the ANZHR, of which 386 were trauma patients and 45 patients had the 'triad of death'. Patients with the 'triad of death' were significantly older and had higher injury severity scores than other trauma patients, with a mortality of 68.9%. Survivors were significantly less acidaemic (p<0.001) and had significantly less packed red blood cell (PRBC) transfusion prior to rFVIIa administration (p=0.041) than non-survivors with the triad of death., Discussion: In the face of refractory bleeding, coagulopathy, acidosis and hypothermia following conventional resuscitation, the use of rFVIIa in trauma patients was associated with survival in 31% of patients and may be considered as a management option. Administration of rFVIIa in patients with a pH of <6.91 appears futile., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To examine the relationship between umbilical cord pH at term and serious neonatal outcomes., Design: Observational cohort study., Settings: Deliveries within the Oxford Radcliffe Hospital NHS Trust between 1991 and 2009., Population: In all, 51,519 singleton, term, nonanomalous live neonates with validated umbilical cord arterial pH values., Methods: Absolute risks, relative risks with 95% confidence intervals, and numbers needed to harm were calculated for different levels of arterial pH across the entire range., Main Outcome Measures: Neonatal encephalopathy with seizures and/or death, encephalopathy within 24 hours of birth, 5-minute Apgar scores and neonatal unit admission., Results: The median arterial pH was 7.22, interquartile range 7.17-7.27. The absolute risk of an adverse neurological outcome was significantly increased below 7.10 (0.36%) and was lowest between 7.26 and 7.30 (0.16%). Even below 7.00, the risk was only 2.95%. However, more than 75% of neonates with neurological outcomes examined, including seizures within 24 hours of birth, had a pH above 7.10. A small increase in risk was evident at higher pH levels., Conclusion: The threshold pH for adverse neurological outcomes is 7.10 and the 'ideal' cord pH is 7.26-7.30. Above 7.00, however, neonatal acidaemia is weakly associated with adverse outcomes. Most neonates with neurological morbidity have normal cord pH values. Other variables must influence adverse outcomes and account for more of these than acidaemia. A better understanding of these is required before intrapartum fetal monitoring can improve., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Background: Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP)., Design: The analyses included 2241 participants aged ≥55 y who were free of hypertension at baseline (1990-1993) and who had complete dietary and BP data. Dietary data were obtained from a 170-item food-frequency questionnaire. We used 2 measures to characterize dietary acid load: (1) potential renal acid load (PRAL) by using an algorithm including protein, phosphorus, potassium, calcium, and magnesium, and (2) estimated net endogenous acid production (NEAP) based on protein and potassium. HRs for 6-y incidence of hypertension were obtained in tertiles of PRAL and NEAP with adjustment for age, sex, BMI, smoking, education, and intakes of alcohol, fiber, and total energy., Results: We identified 1113 incident cases of hypertension during 8707 person-years of follow-up. The median dietary acid load ranged from -14.6 to 19.9 mEq/d across categories of PRAL. Hypertension risk was not significantly associated with dietary acid load. The multivariate HRs (95% CIs) in consecutive tertiles of PRAL were 1.00 (reference), 1.01 (0.87, 1.17), and 1.02 (0.88, 1.18) (P trend = 0.83). The median dietary acid loads were 30.4, 36.7, and 43.7 mEq/d, respectively, in consecutive tertiles of NEAP. Corresponding HRs for NEAP were 1.00 (reference), 0.92 (0.80, 1.07), and 0.94 (0.81, 1.10) (P-trend = 0.46)., Conclusion: The findings from this prospective cohort study provided no evidence of an association between dietary acid load and risk of hypertension in older adults.

Purpose: Urinary excretion of chloride corrects metabolic acidosis, but this may be hampered in patients with impaired renal function. We explored the effects of renal function on acid-base characteristics and urinary strong ion excretion using the Stewart approach in critically ill patients with metabolic acidosis., Materials and Methods: We examined the plasma and urine chemistry in 65 critically ill (mixed medical and surgical) patients with metabolic acidosis. The apparent strong ion difference, effective strong ion difference, strong ion gap, and urinary simplified strong ion difference (urinary SID) were calculated. Linear regression analyses were used (1) to assess whether plasma creatinine concentrations were related to urinary SIDs values, adjusted for blood pH levels, and (2) to determine whether urinary SID values were associated with blood pH levels., Results: Creatinine concentrations were positively and significantly (P < .001) associated with urinary SIDs values, adjusted for pH levels. Urinary simplified strong ion difference values were inversely and significantly (P < .001) related to pH levels., Conclusions: In critically ill patients with metabolic acidosis, impaired renal function was associated with greater urinary SIDs. Subsequently, the higher urinary SIDs values were related to lower pH levels, illustrating the importance of renal chloride excretion to correct for acidosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Falls are an important health problem and the risk of falling increases with age. The costs due to falls are related to the progressive decline of patients' clinical conditions, with functional inability inducing increasing social costs, morbidity and mortality. Renal dysfunction is mostly present in elderly people who often have several comorbidities. Risk factors for falls have been classified as intrinsic and extrinsic, and renal dysfunction is included among the former. Chronic kidney disease per se is an important risk factor for falls, and the risk correlates negatively with creatinine clearance. Vitamin D deficiency, dysfunction of muscles and bones, nerve degeneration, cognitive decline, electrolyte imbalance, anemia, and metabolic acidosis have been reported to be associated with falls. Falls seem to be very frequent in dialysis patients: 44% of subjects on hemodialysis fall at least once a year with a 1-year mortality due to fractures of 64%. Male sex, comorbidities, predialysis hypotension, and a history of previous falls are the main risk factors, together with events directly related to renal replacement therapy such as biocompatibility of the dialysis membrane, arrhythmias, fluid overload and length of dialysis treatment. Peripheral nerve degeneration and demyelination as well as altered nerve conduction resulting in muscular weakness and loss of peripheral sensitivity are frequent when the glomerular filtration rate is less than 12 mL/min. Moreover, depression and sleep disorders can also increase the risk of falls. Kidney function is an important parameter to consider when evaluating the risk of falls in the elderly, and the development of specific guidelines for preventing falls in the uremic population should be considered.

Background: Mitochondrial cytopathies are a diverse group of disorders characterized by impaired mitochondrial energy production. Disease manifestations are protean and may include seemingly disparate findings., Case Diagnosis/treatment: Here we report a 5-year-old girl with the uncommon pairing of bilateral corneal dystrophy requiring corneal transplantation and severe Fanconi syndrome recalcitrant to oral bicarbonate therapy necessitating intravenous supplementation. Etiological work-up included qualitative urine organic acid testing, which demonstrated abnormalities in lactate, pyruvate, and ketoacids suggestive of a mitochondrial etiology. Confirmatory genetic testing in blood leukocytes revealed a large, novel, heteroplasmic, de novo mitochondrial DNA deletion at nt 8648-16072., Conclusion: The finding of Fanconi syndrome with disease processes in other, seemingly unrelated, organ systems should raise clinical suspicion for mitochondrial disease. Early assessment of urine organic acids in the etiological work-up of Fanconi syndrome may assist in the identification of respiratory chain disorders.

Background: Spectral analysis of fetal heart rate (FHR) variability is a useful method to assess fetal condition. There have been several studies involving the change in spectral power related to fetal acidemia, but the results have been inconsistent., Aims: To determine the change in spectral power related to fetal umbilical arterial pH at birth, dividing cases into preterm (31-36 weeks) and term (≥37 weeks) gestations., Study Design: Case-control study. The 514 cases of deliveries were divided into a low-pH group (an umbilical arterial pH <7.2) and a control group (pH≥7.2)., Subjects: FHR recorded on cardiotocography during the last 2h of labor., Outcome Measures: The spectral powers in various bands of FHR variability., Results: In preterm fetuses, the total, low (LF), and movement (MF) frequency spectral powers and LF/HF ratio were significantly lower in the low-pH group than the control group (all P<0.05). In contrast, in term fetuses, the total frequency, LF, and MF powers were significantly higher in the low-pH group than the control group (all P<0.05). The area under the receiver operating characteristic of LF power to detect a low pH at birth was 0.794 in preterm fetuses and 0.595 in term fetuses. The specificity was 86.8% and 93.3% in preterm and term fetuses, respectively., Conclusions: The changes in spectral power responding to a low pH are different between term and preterm fetuses. Spectral analysis of FHR variability may be useful fetal monitoring for early detection of fetal acidemia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)