Medicine Nephrology

Renal function and acid-base balance

Description

This cluster of papers focuses on the diagnosis, management, and effects of metabolic acidosis, particularly in the context of chronic kidney disease. It explores the impact of bicarbonate therapy, dietary acid load, and renal function on acid-base balance, bone health, endothelin activity, and cardiovascular risk. The papers also discuss the potential benefits of nutritional interventions in addressing metabolic acidosis.

Keywords

Metabolic Acidosis; Chronic Kidney Disease; Bicarbonate Therapy; Dietary Acid Load; Renal Function; Acid-Base Balance; Bone Health; Endothelin Activity; Cardiovascular Risk; Nutritional Intervention

Volume 1 A history of renal physiology in 1950, Carl W. Gottschalk: general principles of electrolyte regulation - organization and control of body fluid compartments, molecular biology of transport organization … Volume 1 A history of renal physiology in 1950, Carl W. Gottschalk: general principles of electrolyte regulation - organization and control of body fluid compartments, molecular biology of transport organization of the kidney - structural organization, functional organization. Volume 2 Organization of the kidney - renal regulation of extrarenal function water and electrolyte exchanges - renal regulation of water balance - normal, renal regulation of water balance - deranged, renal regulation of sodium and chloride - normal, renal regulation of sodium and chloride - deranged, renal regulation of potassium - normal, renal regulation of potassium - deranged, renal regulation of magnesium - normal, renal regulation of magnesium - deranged, renal regulation of calcium - normal, renal regulation of calcium - deranged, renal regulation of phosphate - normal, renal regulation of phosphate - deranged, renal regulation of acid-base balance - normal, renal regulation of acid-base balance - deranged. Volume 3: Water and electrolyte exchanges - renal regulation of organic solutes and trace metals - normal, renal regulation of organic solutes and trace metals - deranged, renal regulation of proteins and macromolecules - normal, renal regulation of proteins and macromolecules - normal, renal regulation of proteins and macromolecules - deranged, extrinsic and intrinsic renal failure - failure of renal function, renal pharmacology.
A R Y Dole's titrimetric method for determination of the free fatty acide of plasma has been modified t o improve ita specificity.The fatty acid solution which is to be … A R Y Dole's titrimetric method for determination of the free fatty acide of plasma has been modified t o improve ita specificity.The fatty acid solution which is to be titrated ie first washed with 0.06 per cent H,SO, and thus freed of lactic acid and of an acetone-insoluble material which interferes.With this change, the Dole procedure yields results which agree well with those of Gordon's method.T w o titrimetric methods for determination of free fatty acids (FFA) of plasma, those of Dole (1) and Gordon (2), are now in wide use.Unlike the latter, the Dole method requires only moderate amounts of time, skill, and special apparatus, but it is not strictly specific for fatty acids (3).Specifically, plasma lactate interferes (2, 3), particularly at the high levels obtained with acute exercise.A procedure was devised to wash out interfering substances and to improve the specificity of the Dole method.In testing the modified procedure, efforts were made to account for the change in apparent FFA values observed with washing. M E T H O D SThe Modified Procedure.It is convenient (but not essential) to use twice the volumes of plasma and of reagents specified in the Dole procedure.Thus to 2 ml.heparinized plasma in a glass-stoppered test tube are added, with shaking, 10 ml."extraction" mixture (40 parts by volume of isopropanol, 10 parts heptane, and 1 part 1 N H2S04) ; then 6 ml.heptane and 4 ml.water are introduced, and the mixture is shaken for
The effect of alterations in extracellular pH on cellular and humoral immune function is reviewed. Because acidic pH predominates at inflammatory loci and other sites of immune activity, most studies … The effect of alterations in extracellular pH on cellular and humoral immune function is reviewed. Because acidic pH predominates at inflammatory loci and other sites of immune activity, most studies to date focus on the effect of acidic rather than alkaline pH. Investigations on polymorphonuclear leukocytes demonstrate mainly inhibition of chemotaxis, respiratory activity, and bactericidal capacity at reduced pH. Evidence of impaired lymphocyte cytotoxicity and proliferation at acidic pH is also beginning to emerge. Many of the clinical acidoses are accompanied similarly by immunodeficiency. Studies on macrophages and eosinophils are few and inconclusive. A small number of studies demonstrate acid-induced activation of complement proteins and the alternative complement pathway, plus increased antibody-binding to leukocytes at lowered pH. A differential effect of acidic pH on humoral and cellular immunity may, therefore, exist. Increasing recognition of the significance of extracellular pH in relation to immune function warrants further studies in this presently incomplete but rewarding field.
Of 78 comparative studies of plasma catecholamines in patients with essential hypertension and in normotensive controls, most reported higher catecholamine levels in the hypertensives, although only about 40% of the … Of 78 comparative studies of plasma catecholamines in patients with essential hypertension and in normotensive controls, most reported higher catecholamine levels in the hypertensives, although only about 40% of the studies were positive (reporting statistically significant hypertensive-normotensive differences). Although there was dramatic variability in catecholamine values within and across studies, virtually all studies of norepinephrine in young, consistently hypertensive patients were positive. The likelihood that a study was positive with respect to norepinephrine was independent of the likelihood with respect to epinephrine, so that total catecholamine values, or else the sum of norepinephrine plus epinephrine, differentiated hypertensives from normotensives to a greater extent than levels of either substance alone. The preponderance of literature on the subject supports the hypothesis that increased plasma catecholamine concentrations occur in some patients with essential hypertension. Elevated plasma norepinephrine in relatively young, established hypertensive patients is consistent with a pathophysiologic role for increased sympathetic neural activity in this subgroup.
In land mammals, a major task of the kidney is to reabsorb water to allow survival in a dry environment. Water conservation is enhanced by the renal medulla, which concentrates … In land mammals, a major task of the kidney is to reabsorb water to allow survival in a dry environment. Water conservation is enhanced by the renal medulla, which concentrates the urine to a level up to four times the osmolality of plasma. To produce this unique gradient of osmolality, the medulla has a countercurrent system of vessels and tubules that dictates active reabsorption of sodium in a milieu poor in oxygen (Figure 1).1 In this review, we describe how hypoxia of the medulla may relate to susceptibility to acute and chronic renal injury.The Renal Medullary Concentrating Mechanism as . . .
Background Changes in acid-base balance caused by infusion of a 0.9% saline solution during anesthesia and surgery are poorly characterized. Therefore, the authors evaluated these phenomena in a dose-response study. … Background Changes in acid-base balance caused by infusion of a 0.9% saline solution during anesthesia and surgery are poorly characterized. Therefore, the authors evaluated these phenomena in a dose-response study. Methods Two groups of 12 patients each who were undergoing major intraabdominal gynecologic surgery were assigned randomly to receive 0.9% saline or lactated Ringer's solution in a dosage of 30 ml x kg(-1) x h(-1). The pH, arterial carbon dioxide tension, and serum concentrations of sodium, potassium, chloride, lactate, and total protein were measured in 30-min intervals. The serum bicarbonate concentration was calculated using the Henderson-Hasselbalch equation and also using the Stewart approach from the strong ion difference and the amount of weak plasma acid. The strong ion difference was calculated as serum sodium + serum potassium - serum chloride - serum lactate. The amount of weak plasma acid was calculated as the serum total protein concentration in g/dl x 2.43. Results Infusion of 0.9% saline, but not lactated Ringer's solution, caused a metabolic acidosis with hyperchloremia and a concomitant decrease in the strong ion difference. Calculating the serum bicarbonate concentration using the Henderson-Hasselbalch equation or the Stewart approach produced equivalent results. Conclusions Infusion of approximately 30 ml x kg(-1) x h(-1) saline during anesthesia and surgery inevitably leads to metabolic acidosis, which is not observed after administration of lactated Ringer's solution. The acidosis is associated with hyperchloremia.
Micropuncture studies have shown that glomerular filtration rate (GFR) falls in response to a rise in Na+ or Cl- concentrations in the loop of Henle, whereas studies in isolated kidneys … Micropuncture studies have shown that glomerular filtration rate (GFR) falls in response to a rise in Na+ or Cl- concentrations in the loop of Henle, whereas studies in isolated kidneys have shown that GFR falls in response to osmotic diuresis. To define the separate effects of an acute increase in plasma sodium (PNa), chloride (PCl) or osmolality (Posmol), changes in renal blood flow (RBF) and GFR were measured during intrarenal infusions of hypertonic NaCl, NaHCO3, Na acetate, dextrose, NH4Cl or NH4acetate to denervated kidneys. The infusions raised Posmol at the experimental kidney by 30-45 mosmol. RBF increased abruptly by 10-30% with all hypertonic infusions indicating that an acute increase in plasma tonicity causes renal vasodilatation. Renal vasodilatation persisted or increased further during infusion of dextrose, NaHCO3 and Na acetate, but GFR was unchanged. In contrast, during infusion of the two Cl-containing solutions, vasodilatation was reversed after 1-5 min and RBF and GFR decreased (P < 0.01) below preinfusion levels. Prior salt depletion doubled the vasoconstriction seen with hypertonic NaCl infusions. Overall, changes in RBF were unrelated to changes in PNa or fractional Na or fluid reabsorption but correlated with changes in PCl (r = -0.91) and fractional Cl- reabsorption (r = 0.94). The intrafemoral arterial infusion of the two Cl-containing solutions did not increase femoral vascular resistance. In conclusion, hyperchloremia produces a progressive renal vasoconstriction and fall in GFR that is independent of the renal nerves, is potentiated by prior salt depletion and is related to tubular Cl- reabsorption. Chloride-induced vasoconstriction appears specific for the renal vessels.
To establish normal reference ranges during pregnancy for common laboratory analytes.We conducted a comprehensive electronic database review using PUBMED and MEDLINE databases. We also reviewed textbooks of maternal laboratory studies … To establish normal reference ranges during pregnancy for common laboratory analytes.We conducted a comprehensive electronic database review using PUBMED and MEDLINE databases. We also reviewed textbooks of maternal laboratory studies during uncomplicated pregnancy.We searched the databases for studies investigating various laboratory analytes at various times during pregnancy. All abstracts were examined by two investigators and, if they were found relevant, the full text of the article was reviewed. Articles were included if the analyte studied was measured in pregnant women without major medical problems or confounding conditions and if the laboratory marker was measured and reported for a specified gestational age.For each laboratory marker, data were extracted from as many references as possible, and these data were combined to establish normal reference ranges in pregnancy. When possible, the 2.5 and 97.5 percentiles were reported as the normal range. In some of the reference articles, however, the reported range was based on the minimum and maximum value of the laboratory constituent. In those cases, the minimum to maximum range was used and combined with the 2.5 and 97.5 percentile range. We found that there is a substantial difference in normal values in some laboratory markers in the pregnant state when compared with the nonpregnant state.It is important to consider normal reference ranges specific to pregnancy when interpreting some laboratory results that may be altered by the normal changes of pregnancy.
(1960). A Micro Method for Determination of pH, Carbon Dioxide Tension, Base Excess and Standard Bicarbonate in Capillary Blood. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 12, No. 2, … (1960). A Micro Method for Determination of pH, Carbon Dioxide Tension, Base Excess and Standard Bicarbonate in Capillary Blood. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 12, No. 2, pp. 172-176.
Renal sodium and water retention and plasma volume expansion have been shown to precede ascites formation in experimental cirrhosis. The classical “underfilling” theory, in which ascites formation causes hypovolemia and … Renal sodium and water retention and plasma volume expansion have been shown to precede ascites formation in experimental cirrhosis. The classical “underfilling” theory, in which ascites formation causes hypovolemia and initiates secondary renal sodium and water retention, thus seems unlikely. While the occurrence of primary renal sodium and water retention and plasma volume expansion prior to ascites formation favors the “overflow” hypothesis, the stimulation of the renin-angiotensin-aldosterone system, vasopressin release and sympathetic nervous system associated with cirrhosis is not consonant with primary volume expansion. In this present article, the “Peripheral Arterial Vasodilation Hypothesis” is proposed as the initiator of sodium and water retention in cirrhosis. Peripheral arterial vasodilation is one of the earliest observations in the cirrhotic patient and experimental animals with cirrhosis. Arterial vasodilators and arteriovenous fistula are other examples in which renal sodium and water retention occur secondary to a decreased filling of the arterial vascular tree. An increase in cardiac output and hormonal stimulation are common features of cirrhosis, arteriovenous fistula and drug-induced peripheral arterial vasodilation. However, a predilection for the retained sodium and water to transudate into the abdominal cavity occurs with cirrhosis because of the presence of portal hypertension. The Peripheral Arterial Vasodilation Hypothesis also explains the continuum from compensated to decompensated cirrhosis to the hepatorenal syndrome.
In an earlier Statistics Note1 we commented on the analysis of paired data where there is more than one observation per subject, as shown in table I. We pointed out … In an earlier Statistics Note1 we commented on the analysis of paired data where there is more than one observation per subject, as shown in table I. We pointed out that it could be highly misleading to analyse such data by combining repeated observations from several subjects and then calculating the correlation coefficient as if the data were a simple sample. This note is a response to several letters about the appropriate analysis for such data. View this table: TABLE I Repeated measurements of intramural pH and PaCO2 for eight subjects2 The choice of analysis for the data in table I depends on the question we want to …
Quantitative analysis of ionic solutions in terms of physical and chemical principles has been effectively prohibited in the past by the overwhelming amount of calculation it required, but computers have … Quantitative analysis of ionic solutions in terms of physical and chemical principles has been effectively prohibited in the past by the overwhelming amount of calculation it required, but computers have suddenly eliminated that prohibition. The result is an approach to acid-base which revolutionizes our ability to understand, predict, and control what happens to hydrogen ions in living systems. This review outlines that approach and suggests some of its most useful implications. Quantitative understanding requires distinctions between independent variables (in body fluids: pCO2, net strong ion charge, and total weak acid, usually protein), and dependent variables [( HCO-3], [HA], [A-], [CO(2-)3], [OH-], and [H+] (or pH]. Dependent variables are determined by independent variables, and can be calculated from the defining equations for the specific system. Hydrogen ion movements between solutions can not affect hydrogen ion concentration; only changes in independent variables can. Many current models for ion movements through membranes will require modification on the basis of this quantitative analysis. Whole body acid-base balance can be understood quantitatively in terms of the three independent variables and their physiological regulation by the lungs, kidneys, gut, and liver. Quantitative analysis also shows that body fluids interact mainly by strong ion movements through the membranes separating them.
Department of Biological Chemistry, School of Medicine, Normal University, Boston 1 Fellow on the National Research Council in the Medical Sciences. Present address Department of Physiological Chemistry, School of Medicine, … Department of Biological Chemistry, School of Medicine, Normal University, Boston 1 Fellow on the National Research Council in the Medical Sciences. Present address Department of Physiological Chemistry, School of Medicine, University of Pennsylvania, Philadelphia.
Measurements have been made of cytoplasmic pH, (pHi) and free Mg2+ concentration, ( [Mg2+]i), in pig and mouse lymphocytes. pHi was measured in four ways: by a digitonin null-point technique; … Measurements have been made of cytoplasmic pH, (pHi) and free Mg2+ concentration, ( [Mg2+]i), in pig and mouse lymphocytes. pHi was measured in four ways: by a digitonin null-point technique; by direct measurement of the pH of freeze-thawed cell pellets; from the 31P nuclear magnetic resonance (NMR) spectrum of intracellular inorganic phosphate; and by the use of a newly synthesized, intracellularly-trappable fluorescent pH indicator. In HEPES buffered physiological saline with pH 7.4 at 37 degrees C, pHi was close to 7.0. Addition of physiological levels of HCO3- and CO2 transiently acidified the cells by approximately 0.1 U. Mitogenic concentrations of concanavalin A (Con A) had no measurable effect on pH in the first hour. [Mg2+]i was assessed in three ways: (a) from the external Mg2+ null-point at which the ionophore A23187 produced no net movement of Mg2+ or H+; (b) by Mg-sensitive electrode measurements in freeze-thawed pellets; and (c) from the 31P nuclear magnetic resonance spectrum of the gamma-phosphate of intracellular ATP. Total cell Mg2+ was approximately 12 mmol per liter cell water. The NMR data indicated [Mg2+]i greater than 0.5 mM. The null-point method gave [Mg2+]i approximately 0.9 nM. The electrode measurements gave 1.35 mM, which was thought to be an overestimate. Exposure to mitogenic doses of Con A for 1 h gave no detectable change in total or free Mg2+.
Plasma nitrite and nitrate determinations are increasingly being used in clinical chemistry as markers for the activity of nitric oxide synthase and the production of nitric oxide radicals. However, a … Plasma nitrite and nitrate determinations are increasingly being used in clinical chemistry as markers for the activity of nitric oxide synthase and the production of nitric oxide radicals. However, a systematic evaluation of the determination of nitrite and nitrate in plasma has not been performed. In this study the recovery and stability of nitrite and nitrate in whole blood and in plasma, the relation between nitrite and nitrate concentrations in plasma, and possible sources of artifacts were investigated. The main conclusions are: (a) Recovery of nitrite and nitrate from plasma is near-quantitative (87%) and reproducible; (b) nitrite and nitrate are stable in (frozen) plasma for at least 1 year; (c) nitrite in whole blood is very rapidly (> 95% in 1 h) oxidized to nitrate, and therefore plasma nitrite determination alone is meaningless; (d) the ranges of nitrite and nitrate concentrations in plasma samples of 26 healthy persons are 1.3-13 mumol/L (mean 4.2 mumol/L) and 4.0-45.3 mumol/L (mean 19.7 mumol/L), respectively; (e) plasma nitrite and nitrate concentrations were not correlated (nitrite as % of total nitrite + nitrate varied from 3.9% to 88% in plasma samples); and (f) plasma samples should be deproteinized, and background controls for each sample should be included in the assay, to avoid measuring artifactually high nitrite and nitrate concentrations in plasma.
To assess the association of 0.9% saline use versus a calcium-free physiologically balanced crystalloid solution with major morbidity and clinical resource use after abdominal surgery.0.9% saline, which results in a … To assess the association of 0.9% saline use versus a calcium-free physiologically balanced crystalloid solution with major morbidity and clinical resource use after abdominal surgery.0.9% saline, which results in a hyperchloremic acidosis after infusion, is frequently used to replace volume losses after major surgery.An observational study using the Premier Perspective Comparative Database was performed to evaluate adult patients undergoing major open abdominal surgery who received either 0.9% saline (30,994 patients) or a balanced crystalloid solution (926 patients) on the day of surgery. The primary outcome was major morbidity and secondary outcomes included minor complications and acidosis-related interventions. Outcomes were evaluated using multivariable logistic regression and propensity scoring models.For the entire cohort, the in-hospital mortality was 5.6% in the saline group and 2.9% in the balanced group (P < 0.001). One or more major complications occurred in 33.7% of the saline group and 23% of the balanced group (P < 0.001). In the 3:1 propensity-matched sample, treatment with balanced fluid was associated with fewer complications (odds ratio 0.79; 95% confidence interval 0.66-0.97). Postoperative infection (P = 0.006), renal failure requiring dialysis (P < 0.001), blood transfusion (P < 0.001), electrolyte disturbance (P = 0.046), acidosis investigation (P < 0.001), and intervention (P = 0.02) were all more frequent in patients receiving 0.9% saline.Among hospitals in the Premier Perspective Database, the use of a calcium-free balanced crystalloid for replacement of fluid losses on the day of major surgery was associated with less postoperative morbidity than 0.9% saline.
The serum creatinine concentration is widely interpreted as a measure of the glomerular filtration rate (GFR) and is used as an index of renal function in clinical practice. Glomerular filtration … The serum creatinine concentration is widely interpreted as a measure of the glomerular filtration rate (GFR) and is used as an index of renal function in clinical practice. Glomerular filtration of creatinine, however, is only one of the variables that determines its concentration in serum. Alterations in renal handling and metabolism of creatinine and methodological interferences in its measurement may have a profound impact on the serum concentration of creatinine. We review the fundamental principles of physiology, metabolism, and analytical chemistry that are necessary to correctly interpret the serum creatinine concentration. These principles are then applied to important clinical circumstances, including aging, pregnancy, diabetes mellitus, drug administration, and acute and chronic renal failure. Despite numerous limitations, serum creatinine remains a useful clinical tool, but more accurate measures of renal function are frequently necessary.
A simple, reliable, and reproducible fluorometric method for measuring thiobarbituric acid-reactive substances (TBARS) in serum is proposed, based on the reaction between malondialdehyde (MDA) and thiobarbituric acid. Formation of TBARS … A simple, reliable, and reproducible fluorometric method for measuring thiobarbituric acid-reactive substances (TBARS) in serum is proposed, based on the reaction between malondialdehyde (MDA) and thiobarbituric acid. Formation of TBARS was complete at pH 2.4-2.6, but extraction with n-butanol proved complete only at lower pH, i.e., 1.6-1.7. Analytical recoveries of MDA added to serum were 94%-101%; within- and between-run CVs were 2.4-3.6% and 4.6-5.5%; and the detection limit for TBARS in serum was 0.10 mumol/L. Optimized conditions included: (a) collection of either serum or heparinized plasma, (b) preservation from in vitro autoxidation by glutathione and EDTA, and (c) storage at -20 degrees C up to 35 days. The mean (+/- SD) TBARS concentration in 47 healthy adults was 1.01 (0.21) mumol/L; no sex-related difference was observed. Higher concentrations were measured in patients with renal insufficiency undergoing hemodialysis and in patients with insulin-dependent diabetes, chronic pancreatitis, or liver cirrhosis.
As a major component of uremic syndrome, cardiovascular disease is largely responsible for the high mortality observed in chronic kidney disease (CKD). Preclinical studies have evidenced an association between serum … As a major component of uremic syndrome, cardiovascular disease is largely responsible for the high mortality observed in chronic kidney disease (CKD). Preclinical studies have evidenced an association between serum levels of indoxyl sulfate (IS, a protein-bound uremic toxin) and vascular alterations. The aim of this study is to investigate the association between serum IS, vascular calcification, vascular stiffness, and mortality in a cohort of CKD patients.One-hundred and thirty-nine patients (mean +/- SD age: 67 +/- 12; 60% male) at different stages of CKD (8% at stage 2, 26.5% at stage 3, 26.5% at stage 4, 7% at stage 5, and 32% at stage 5D) were enrolled.Baseline IS levels presented an inverse relationship with renal function and a direct relationship with aortic calcification and pulse wave velocity. During the follow-up period (605 +/- 217 d), 25 patients died, mostly because of cardiovascular events (n = 18). In crude survival analyses, the highest IS tertile was a powerful predictor of overall and cardiovascular mortality (P = 0.001 and 0.012, respectively). The predictive power of IS for death was maintained after adjustment for age, gender, diabetes, albumin, hemoglobin, phosphate, and aortic calcification.The study presented here indicates that IS may have a significant role in the vascular disease and higher mortality observed in CKD patients.
Hill's equation can be slightly modified to fit the standard human blood O2 dissociation curve to within plus or minus 0.0055 fractional saturation (S) from O less than S less … Hill's equation can be slightly modified to fit the standard human blood O2 dissociation curve to within plus or minus 0.0055 fractional saturation (S) from O less than S less than 1. Other modifications of Hill's equation may be used to compute Po2 (Torr) from S (Eq. 2), and the temperature coefficient of Po2 (Eq. 3). Variations of the Bohr coefficient with Po2 are given by Eq. 4. S = (((Po2(3) + 150 Po2)(-1) x 23,400) + 1)(-1) (1) In Po2 = 0.385 In (S-1 - 1)(-1) + 3.32 - (72 S)(-1) - 0.17(S6) (2) DELTA In Po2/delta T = 0.058 ((0.243 X Po2/100)(3.88) + 1)(-1) + 0.013 (3) delta In Po2/delta pH = (Po2/26.6)(0.184) - 2.2 (4) Procedures are described to determine Po2 and S of blood iteratively after extraction or addition of a defined amount of O2 and to compute P50 of blood from a single sample after measuring Po2, pH, and S.
Journal Article THE EXCRETION OF ACID IN RENAL DISEASE Get access OLIVER WRONG, OLIVER WRONG University Department of Medicine, Manchester Royal Infirmary, and the Medical Unit, Cardiff Royal Infirmary Search … Journal Article THE EXCRETION OF ACID IN RENAL DISEASE Get access OLIVER WRONG, OLIVER WRONG University Department of Medicine, Manchester Royal Infirmary, and the Medical Unit, Cardiff Royal Infirmary Search for other works by this author on: Oxford Academic PubMed Google Scholar H. E. F. DAVIES H. E. F. DAVIES University Department of Medicine, Manchester Royal Infirmary, and the Medical Unit, Cardiff Royal Infirmary Search for other works by this author on: Oxford Academic PubMed Google Scholar QJM: An International Journal of Medicine, Volume 28, Issue 2, April 1959, Pages 259–313, https://doi.org/10.1093/oxfordjournals.qjmed.a066844 Published: 01 April 1959 Article history Received: 19 June 1958 Published: 01 April 1959
The 10-point Apgar score has been used to assess the condition and prognosis of newborn infants throughout the world for almost 50 years. Some investigators have proposed that measurement of … The 10-point Apgar score has been used to assess the condition and prognosis of newborn infants throughout the world for almost 50 years. Some investigators have proposed that measurement of pH in umbilical-artery blood is a more objective method of assessing newborn infants.
The syndrome of renal tubular acidosis has been categorized into three physiologic types that have different clinical findings and prognostic and therapeutic implications. We reviewed radiographs of the skeleton and … The syndrome of renal tubular acidosis has been categorized into three physiologic types that have different clinical findings and prognostic and therapeutic implications. We reviewed radiographs of the skeleton and kidneys in 92 patients (56 children and 36 adults) with renal tubular acidosis in order to determine whether the radiologic findings could be related to the type of syndrome. Forty-four patients had Type 1 renal tubular acidosis, 18 had Type 2, and 30 had Type 4. Evidence of skeletal abnormalities was uncommon (17 per cent) and was confined to patients who had the Type 2 disorder or azotemia. The children with Type 2 and skeletal abnormalities had rickets; the adults had osteopenia without pseudofractures. Nephrocalcinosis was evident in approximately one fourth of the group (29 per cent) and was restricted to patients with the Type 1 syndrome. In patients with Type 4, osteopenia was evident in 12 per cent, all of whom were azotemic. Our observations indicate that the radiographic manifestations of renal tubular acidosis are influenced by the physiologic type of renal tubular acidosis.
Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU).
When lactic acidosis accompanies low-flow states or sepsis, mortality rates increase sharply. This review summarizes our current understanding of the pathophysiological aspects of lactic acidosis, as well as the approaches … When lactic acidosis accompanies low-flow states or sepsis, mortality rates increase sharply. This review summarizes our current understanding of the pathophysiological aspects of lactic acidosis, as well as the approaches to its diagnosis and management.
Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes.
The eighth edition of the<i>Textbook of Medical Physiology</i>by Arthur C. Guyton, MD, is similar to the seventh edition with few changes or rearrangements. It is shorter by 67 pages (6.6%). … The eighth edition of the<i>Textbook of Medical Physiology</i>by Arthur C. Guyton, MD, is similar to the seventh edition with few changes or rearrangements. It is shorter by 67 pages (6.6%). The former Unit II discussion of blood cells, immunity, and blood clotting has been moved to Unit VI, where it follows the description of cardiovascular, renal, and acid-base physiology. Chapters 11 and 12, which deal with normal and abnormal electrocardiograms, have been significantly improved. Unit IV, which describes the circulation of blood, has been rearranged and updated. The nervous system material has been rearranged and ends with chapter 61 describing cerebral flow, cerebrospinal fluid, and brain metabolism. Dr Guyton continues to present physiological principles in molecular and physical terms and introduces a new feature—two print sizes. Large print describes fundamental physiological information that medical students need to know. Smaller print represents nonbasic physiological information such as anatomy, chemistry,
Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue
Background The research on the impact of dynamic corrected anion gap (cAG) on prognosis is scarce. Objective This study aimed to investigate the relationship between changes in cAG (ΔcAG) during … Background The research on the impact of dynamic corrected anion gap (cAG) on prognosis is scarce. Objective This study aimed to investigate the relationship between changes in cAG (ΔcAG) during intensive care unit (ICU) hospitalization and mortality. Methods In this multicenter, retrospective cohort study, patients with both initial and final records of serum sodium, potassium, chloride, bicarbonate, and albumin were recruited from the eICU Collaborative Research Database. Two cohorts were included in the study: cohort A (final cAG &amp;gt; initial cAG) and cohort B (final cAG &amp;lt; initial cAG). Multivariable logistic regression was utilized to assess the association between mortality and ΔcAG in each cohort. ΔcAG was calculated as shown as follows: <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m1"><mml:mrow><mml:mo>Δ</mml:mo><mml:mi>c</mml:mi><mml:mi>A</mml:mi><mml:mi>G</mml:mi><mml:mo>=</mml:mo><mml:mfrac><mml:mrow><mml:mo>|</mml:mo><mml:mi>f</mml:mi><mml:mi>i</mml:mi><mml:mi>n</mml:mi><mml:mi>a</mml:mi><mml:mi>l</mml:mi><mml:mtext> </mml:mtext><mml:mi>c</mml:mi><mml:mi>A</mml:mi><mml:mi>G</mml:mi><mml:mtext> </mml:mtext><mml:mo>‐</mml:mo><mml:mtext> </mml:mtext><mml:mi>i</mml:mi><mml:mi>n</mml:mi><mml:mi>i</mml:mi><mml:mi>t</mml:mi><mml:mi>i</mml:mi><mml:mi>a</mml:mi><mml:mi>l</mml:mi><mml:mtext> </mml:mtext><mml:mi>c</mml:mi><mml:mi>A</mml:mi><mml:mi>G</mml:mi><mml:mo>|</mml:mo></mml:mrow><mml:mrow><mml:mi>i</mml:mi><mml:mi>n</mml:mi><mml:mi>i</mml:mi><mml:mi>t</mml:mi><mml:mi>i</mml:mi><mml:mi>a</mml:mi><mml:mi>l</mml:mi><mml:mtext> </mml:mtext><mml:mi>c</mml:mi><mml:mi>A</mml:mi><mml:mi>G</mml:mi></mml:mrow></mml:mfrac><mml:mo>×</mml:mo><mml:mn>100</mml:mn><mml:mo>%</mml:mo></mml:mrow></mml:math> . Results Among the 11,216 enrolled patients, 4,147 (37%) individuals were classified into cohort A, while 7,069 (63%) patients were assigned to cohort B. In cohort A, for every 10% increase in ΔcAG, ICU and hospital mortalities increased by 46.1% (odds ratio: 1.461, 95% confidence interval [1.378, 1.548]) and 55.5% (1.555 [1.467, 1.648]), respectively. Interaction and subgroup analyses demonstrated consistent results among patients with different Acute Physiology and Chronic Health Evaluation Ⅳ (APACHE Ⅳ) scores (≤58 vs. &amp;gt;58), time interval (≤97 h vs. &amp;gt;97 h) and initial cAG (≤16 mEq/L vs. &amp;gt;16 mEq/L). Meanwhile, in cohort B, ICU and hospital mortalities decreased by 31.4% (0.686 [0.619, 0.759]) and 29.4% (0.706 [0.651, 0.764]), respectively, with each 10% increase in ΔcAG, especially among patients with higher APACHE IV scores (&amp;gt;62) and initial cAG (&amp;gt;16 mEq/L). When analyzed categorically, the ΔcAG still exhibited a significant risk gradient across quartiles. Conclusion Further elevated cAG after ICU admission demonstrates a robust association with an increased mortality risk in critically ill patients. ICU patients with higher APACHE Ⅳ scores or initial cAG may benefit from measures aimed at reducing cAG.
OBJECTIVES: Acidemia frequently evolves in pediatric critical care patients, especially with congenital heart defects. Worsening acidemia secondary to inadequate systemic oxygen delivery can be detrimental to patients’ outcomes and the … OBJECTIVES: Acidemia frequently evolves in pediatric critical care patients, especially with congenital heart defects. Worsening acidemia secondary to inadequate systemic oxygen delivery can be detrimental to patients’ outcomes and the ability to predict it has the potential to prompt early interventions to improve the clinical state. We aimed to evaluate the association of a novel near real-time predictive analytics algorithm with acidemia (ACD) (arterial pH &lt; 7.25) in pediatric patients admitted to a critical care unit. STUDY DESIGN: Retrospective observational study in nine tertiary institutions in the United States. SETTING: Majority of patients were admitted to the cardiac ICU. Using Etiometry platform data (Etiometry, Boston, MA), acidemia (ACD) index was validated. PATIENTS: Patients 12 years old or younger were admitted to an ICU between February 1, 2018, and November 31, 2020. INTERVENTION: A total of 24,431 arterial blood pH measurements from 1858 patients were included in the validation dataset. The ACD index was calculated using a physiologic algorithm that incorporates patients’ variables including laboratory and clinical data. Based on the previous assessment of the physiologic state of the patient, the physiologic algorithm interprets the new data in a real-time manner using Bayes’ theorem. MEASUREMENT AND MAIN RESULTS: Based on a complete dataset, the area under the receiver operating characteristic curve of the ACD index was 0.93. As the index value increased, the likelihood of having acidemia increased ( p &lt; 0.01). The relative risk of having acidemia when the ACD index is less than 1 was 0.11 (95% CI, 0.07–0.15), and the relative risk of not having acidemia when the ACD index was greater than 99 was 0.38 (95% CI, 0.32–0.46). CONCLUSIONS: In this large pediatric cohort, higher ACD index values were associated with a higher likelihood of having acidemia. Consequently, this novel index has the potential to identify severe changes in clinical status. Prospective analysis of the ACD index is important to understand its utility in the management of pediatric critical illness.
During a secondary data analysis toward the preparation of an additional manuscript, the authors identified an error in Figure 1 in the original publication [...] During a secondary data analysis toward the preparation of an additional manuscript, the authors identified an error in Figure 1 in the original publication [...]
Objective: To determine whether high anion gap levels predict increased serum lactate &gt;2 mmol/L, and to determine the best AG cut-off point for predicting serum lactate levels greater than 2 … Objective: To determine whether high anion gap levels predict increased serum lactate &gt;2 mmol/L, and to determine the best AG cut-off point for predicting serum lactate levels greater than 2 mmol/L and greater than 4 mmol/L.Material and Methods: This is a retrospective study among patients with sepsis without shock admitted to the emergency department of a tertiary care, university hospital. Anion gap and serum lactate were collected. Patients’ baseline characteristics and laboratory results were also incorporated to calculate the Sequential (sepsis-related) Organ Failure Assessment (SOFA) score. Analysis of diagnostic accuracy and Receiver Operator Characteristics (ROC) was used to demonstrate the appropriate cut-off point of the anion gap for predicting serum lactate &gt;2 mmol/L.Results: The study included 236 patients. Anion gap &gt;12 mmol/L had a sensitivity of 93.3% (95%CI 88.2-96.6%) and a specificity of 13.7% (95%CI 6.8-23.8%) for predicting serum lactate &gt;2 mmol/L. There was poor discriminative performance of the anion gap to predict serum lactate &gt;2 mmol/L (area under ROC is 0.65; 95%CI 0.58-0.72). In contrast, there was good discriminative performance of the anion gap to predict serum lactate &gt;4 mmol/L (area under ROC 0.83; 95%CI 0.77-0.88). The optimal cut-off point was anion gap &gt; 18 mmol/L, which was good for predicting serum lactate &gt;4 mmol/L.Conclusion: An anion gap &gt;12 mmol/L is not suitable for assessing lactate &gt;2 mmol/L; however, an anion gap &gt;18 mmol/L can predict serum lactate &gt;4 mmol/L in patients with sepsis who had mean arterial pressure (MAP) &gt;65 mmHg.
This study explored the associations between triglyceride glucose (TyG), TyG with body mass index (TyG-BMI), triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for insulin resistance (METS-IR) and the effects … This study explored the associations between triglyceride glucose (TyG), TyG with body mass index (TyG-BMI), triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for insulin resistance (METS-IR) and the effects of dietary acid-base load in patients with chronic kidney disease (CKD). Methods A total of 288 patients with CKD were included in this study. Four non-insulin-based insulin resistance (IR) markers were used to assess IR levels in patients with CKD; dietary intake – 24-h dietary recall; and diet-based acidity – potential renal acid load (PRAL), net endogenous acid production (NEAP), and dietary acid load (DAL). Multiple linear regression analysis correlated dietary acid-base load and non-insulin-based IR markers. Results Spearman’s correlation indicated DAL was significantly associated with TyG-BMI (r = 0.251, P &amp;lt; 0.001) and METS-IR (r = 0.274, P &amp;lt; 0.001), but weakly correlated with the TG/HDL-C ratio (r = 0.14, P = 0.018). After adjusting for sex, age, energy, hypertension (HTN), diabetes, and estimated glomerular filtration rate, multiple linear regression analysis showed that DAL was associated with TyG-BMI (β = 0.336; P = 0.008) and METS-IR (β = 0.091; P = 0.007). Conclusions Patients with the highest DAL scores had the highest TyG-BMI, TyG, TG/HDL-C ratio, and METS-IR. After adjusting for confounders, there was a significant positive association between DAL and TyG-BMI and METS-IR.
The purpose of this secondary analysis was to assess the potential role of dietary acid load in people with type 1 diabetes. Participants were randomly assigned to either a vegan … The purpose of this secondary analysis was to assess the potential role of dietary acid load in people with type 1 diabetes. Participants were randomly assigned to either a vegan or a portion-controlled diet group for 12 weeks, and 3-day dietary records were analyzed. Potential renal acid load and net endogenous acid production—both markers of dietary acid load—decreased significantly in the vegan group, but not in the portion-controlled group. Body weight decreased by 5.2 kg in the vegan group, compared with a nonsignificant change in weight in the portion-controlled group. Changes in dietary acid load correlated positively with changes in body weight. The reduction in dietary acid load may partly explain the observed weight loss on a vegan diet.
| Cambridge University Press eBooks
Bromism is a syndrome that results from bromide intoxication. It is difficult to diagnose since it mimics a myriad of psychiatric and dermatological disturbances. Historically, the most common sources have … Bromism is a syndrome that results from bromide intoxication. It is difficult to diagnose since it mimics a myriad of psychiatric and dermatological disturbances. Historically, the most common sources have been drug ingestion or contaminated drinks. This work aims to thoroughly review all the state-of-the-art aspects of bromism and bromoderma, including its pathophysiology, diagnosis, treatment, and other relevant clinical and forensic features. In this context, a comprehensive search was conducted in PubMed (U.S. National Library of Medicine) without time restrictions. Bromism may occur in individuals of any age or gender, but it is more frequent in women. In children, it usually occurs under therapy for resistant epilepsy or is breastfed by mothers who ingested bromide and may manifest as bromoderma. In adults, bromism manifests with psychiatric and neurological signs such as hallucinations, delusions, or ataxia. Pseudohyperchloremia with a negative anion gap is highly suggestive of the diagnosis. Treatment requires the removal of bromide, which is achieved by per os or intravenous saline administration or even hemodialysis.Although bromism is not usually observed in clinical and forensic practice, it is still related to the administration of controlled or immediate-release formulations, mainly analgesics or antiepileptic drugs, as well as internet-purchased supplements.
| Cambridge University Press eBooks
ABSTRACT Background Patient‐based real‐time quality control (PBRTQC) has garnered increasing attention, yet false positive alerts are common in practical applications. In patients undergoing dialysis, serum potassium (K + ) levels … ABSTRACT Background Patient‐based real‐time quality control (PBRTQC) has garnered increasing attention, yet false positive alerts are common in practical applications. In patients undergoing dialysis, serum potassium (K + ) levels exhibit large fluctuations before and after dialysis, often leading to false positive quality control alerts in routine PBRTQC applications. We aimed to reduce false positive alerts in PBRTQC applications by distinguishing between the test results of dialysis and non‐dialysis patients and constructing separate PBRTQC models. Methods We collected K + test results from 362,077 patients at our center from September 2023 to September 2024. The data were divided into dialysis, physical examination, and non‐dialysis groups, with data from September 2023 to February 2024 comprising the training set. We constructed PBRTQC models for dialysis patients ( n = 3217), those undergoing physical examination ( n = 7339), and non‐dialysis patients ( n = 153,565) using four statistical methods: moving median, moving average, weighted moving average, and exponentially weighted moving average. We validated the three models using data from the dialysis group (validation set 1) from March to September 2024 and the non‐dialysis group (validation set 2) from March to April 2024. By comparing false positive rates, the average number of patient results affected prior to error detection or median number of patient results affected prior to error detection, and the average probability of error detection in the three models, we evaluated whether the pre‐classified PBRTQC model can reduce the false positive rate of K + . Results Statistical analysis revealed significant differences among the dialysis, physical examination, and non‐dialysis groups ( p &lt; 0.001). Based on the minimum sum of the false positive rate, false negative rate, and average number of patient results affected prior to error detection, the models for the dialysis and non‐dialysis groups used the exponentially weighted moving average; the MM method was used in the physical examination group. Validation set 1 showed false positive rates of 69.257% for the physical examination group, 1.143% for the dialysis group, and 35.675% for the non‐dialysis group. According to the total allowable error (TEA), the median number of patient results affected prior to error detection in the dialysis group (1/2TEA, positive: 307.30, negative: 795.20) was higher than that in the physical examination group (1/2TEA, positive: 10.57, negative: 4.67) and non‐dialysis group (1/2TEA, positive: 24.57, negative: 29.57). The average probability of error detection in the dialysis group (1/2TEA, positive: 2.83%, negative: 0.67%) was lower than that in the physical examination group (1/2TEA, positive: 41.47%, negative: 45.11%) and non‐dialysis group (1/2TEA, positive: 16.00%, negative: 18.00%). In validation sets 2 and 3, the false positive rate for the non‐dialysis group and physical examination group was 1.906% and 2.83%, respectively. This indicates that pre‐classifying dialysis specimens can significantly reduce the occurrence of false positives. Additionally, K + results in the non‐dialysis group exhibited notable seasonal variations. Conclusions Establishing PBRTQC models through pre‐classification of dialysis patients can significantly lower the false positive rate of K + , enhancing the accuracy of real‐time monitoring for laboratory testing systems.
Point-of-care (POC) tests for blood ammonia (BA) measurement have not been well evaluated in veterinary species. This cross-sectional study sought to establish an inferred reference interval for BA using a … Point-of-care (POC) tests for blood ammonia (BA) measurement have not been well evaluated in veterinary species. This cross-sectional study sought to establish an inferred reference interval for BA using a POC analyser in dogs and cats. Blood ammonia was measured in 175 dogs and 63 cats for which relevant clinical history and laboratory data was available. Reference values were inferred based on comparisons between patients with and without disease pathologies reported to cause BA elevation. Descriptive statistics, Pearson Chi2, and Mann-Whitney U testing were used to assess for associations between clinical parameters and BA concentration. Seventy-one percent (124/175) of dogs and forty-six percent (29/63) of cats had undetectable BA. Following the exclusion of dogs with potential causes of hyperammonaemia, all remaining dogs had BA < 30 µg/dL. With one exception, all dogs with BA > 30 µg/dL had liver disease. All dogs with a clinical suspicion of hepatic encephalopathy (HE) had BA > 40 µg/dL. Following the exclusion of cats with potential causes of hyperammonaemia, all remaining cats had BA < 25 µg/dL. Only 50% of cats with BA > 25 µg/dL had liver disease. All cats with a clinical suspicion of HE had BA > 30 µg/dL. Based on this study population, BA < 30 µg/dL and <25 µg/dL should be considered normal in dogs and cats, respectively. Additionally, dogs with BA > 30 µg/dL are likely to have liver disease, while cats with BA > 25 µg/dL appear to exhibit a wider variety of disease pathologies.
Abstract Neonatal shock has a high mortality rate in neonates. New treatment approaches are being researched. Methylene blue (MB) may have the ability to enhance blood pressure but is rarely … Abstract Neonatal shock has a high mortality rate in neonates. New treatment approaches are being researched. Methylene blue (MB) may have the ability to enhance blood pressure but is rarely used on newborns. MB usage in a newborn with catecholamine-resistant shock who needed renal replacement therapy (RRT) due to hyperammonemia from an underlying urea cycle defect is presented here. A 3050-g female neonate, born at 38 weeks' gestation, was admitted to our neonatal intensive care unit on the fourth postnatal day due to hyperammonemia and encephalopathy. She was in shock but did not have sepsis, and her cardiological evaluation was normal. Upon detection of severe hyperammonemia, protein intake was ceased and ammonia-reducing medications were initiated. She required RRT due to persistent severe hyperammonemia, but despite receiving fluid resuscitation, vasopressors, and hydrocortisone, her blood pressure remained low until starting MB. Afterwards, RRT waseffectively performed. After continuous RRT, the patient's ammonia level decreased. Unfortunately, the patient died on the tenth day following delivery due to multiple organ failure. Catecholamine-resistant shock is a significant factor in neonatal mortality. In neonates with decompensated catecholamine-resistant shock and normal cardiac function, MB might be a novel therapeutic alternative. However, more studies are required to examine the efficacy, dose, and use.
A 67-year-old man with a history of severe chronic obstructive pulmonary disease (COPD) and multiple medical problems presented to the emergency department (ED) with worsening shortness of breath for one … A 67-year-old man with a history of severe chronic obstructive pulmonary disease (COPD) and multiple medical problems presented to the emergency department (ED) with worsening shortness of breath for one to two days. He was initially treated with bilevel positive airway pressure (BIPAP) but required intubation approximately 4 hours after presentation. Multiple doses of nebulized albuterol (total of 21 mg) were given both before and after intubation. The patient’s initial lactate level was 2.3 mmol/L, with rapid elevation to a maximum of 11.3 mmol/L. In combination with the markedly elevated lactate, the patient had abdominal distention and nonspecific abdominal pain in the setting of chronic CO2 retention and acute hypercapnic respiratory failure, transient hypotension, an elevated peripheral white blood cell (WBC) count with neutrophil predominance, and an increased anion gap. The clinical presentation, elevated lactate level, and other laboratory abnormalities prompted a concern for severe sepsis and possible bowel ischemia. The patient was treated with intravenous fluids and broad-spectrum antibiotics, but at the same time, albuterol was held. Lactate decreased rapidly after albuterol was discontinued. A computed tomography (CT) scan of the abdomen did not show signs of ischemia, and abdominal distention improved with an orogastric tube. With mechanical ventilation and steroids, the patient’s respiratory status improved, and he was extubated on hospital day six. Final blood cultures were negative, and in retrospect, the patient did not have severe sepsis. The timeline of lactate increase and decrease suggests that the markedly elevated lactate levels in this patient were due to a Type B lactic acidosis related to albuterol.
| Cambridge University Press eBooks
| Cambridge University Press eBooks
Purposes of review The inflammatory response in sepsis raises circulatory levels of gaseous transmitters (gasotransmitters) nitric oxide (NO) and hydrogen sulfide (H 2 S), both of which generate and sustain … Purposes of review The inflammatory response in sepsis raises circulatory levels of gaseous transmitters (gasotransmitters) nitric oxide (NO) and hydrogen sulfide (H 2 S), both of which generate and sustain septic shock. Current best practices, including early intravenous fluid, early antibiotics, and vasopressor support, do not target gasotransmitters. A single 5-g dose of intravenous hydroxocobalamin (high-dose HOC) is a safe intervention that targets circulating gasotransmitters. In this review, we provide an overview of the role of gasotransmitters in septic shock, outline the rationale for high-dose HOC in septic shock, and summarize clinical evidence for high-dose HOC in septic shock. Recent findings NO and H 2 S are elevated early in septic shock, activate inflammatory pathways, and higher levels correlate with greater severity of illness. Preclinical evidence demonstrates high-dose HOC improves outcomes in models of septic shock by scavenging circulating NO and H 2 S. Multiple case series and a Phase IIa trial show that high-dose HOC is a safe intervention that reduces vasopressor dose in adults with septic shock. Without high-level evidence, clinicians across the United States are using high-dose HOC for adults with septic shock. Summary High-dose HOC is a promising, nontoxic intervention that targets the pathophysiologic pathway of septic shock. Despite compelling observational and Phase IIa trial data, a pivotal phase III trial testing high-dose HOC in adults with septic shock is required before widespread use can be recommended.