Plasma Bicarbonate Research Articles

Association Between Serum Pregnancy-Associated Plasma Protein-A and Bicarbonate in Hemodialysis Patients

Acidosis is associated with protein-energy malnutrition, inflammation, and bone disease, and low bicarbonate levels have been implicated in higher mortality rates in chronic kidney disease. Recently, the concentration of serum pregnancy-associated plasma protein-A (PAPP-A) has become accepted as a prognostic marker in hemodialysis patients. This study determined the relationship between PAPP-A and bicarbonate levels in these patients. The study enrolled 65 hemodialysis patients (41 males, 24 females) and 26 control subjects (11 males, 15 females). Serum PAPP-A, intact parathormone (iPTH), calcium, phosphorus (P), and bicarbonate levels were measured. Correlations between PAPP-A and bicarbonate, iPTH, calcium, and phosphorus were evaluated. Median PAPP-A levels were significantly higher in hemodialysis patients [15.1 (<0.03-158.8) ng/ml] than in control subjects [6.6 (<0.03-16.4) ng/ml] (P < 0.05). There were statistically significant correlations between serum PAPP-A and bicarbonate, iPTH, and P in hemodialysis patients but not in control subjects. Elevation of serum PAPP-A has been found in hemodialysis patients and its significant correlation with bicarbonate suggests that it may be a prognostic factor.

Comparison of values of traditionally measured venous bicarbonate with calculated arterial bicarbonate in intensive care unit patients of a hospital in a third-world country

Background:Measurement of serum or plasma bicarbonate (HCO3−) from a sample of peripheral venous blood is routinely practiced in hospital patient managements. HCO3− status can also be obtained by a simple calculation during blood gas analysis requiring arterial blood as sample which is cumbersome for both patient and doctor. This study compared the measured bicarbonate levels with calculated arterial values in intensive care unit (ICU) patients to determine whether traditionally measured venous HCO3− and calculated HCO3− values [from arterial blood gas (ABG) analyzers] can be used interchangeably.Materials and Methods:This prospective study was carried out at a tertiary care teaching hospital in Dhaka, the capital of Bangladesh. A total of 56 adult patients with diverse medical conditions, presenting at the ICU of the health centre were enrolled in this study when deemed by the treating physician to have an ABG analysis. Arterial and venous samples were taken as close in time as possible for gas analysis and routine blood tests.Results:The HCO3− levels from ABG and traditionally measured serum showed acceptably narrow 95% limits of agreement using the Bland-Altman method.Conclusions:More widely prescribed venous HCO3− measurements can also be a useful substitute for an expensive ABG analyzer in resource-constrained health care sectors when required. However, accuracy of venous blood in assessment of additional ABG parameters is yet to be discovered.

Albuterol Administration Is Commonly Associated With Increases in Serum Lactate in Patients With Asthma Treated for Acute Exacerbation of Asthma

Controversy exists around the incidence and cause of hyperlactatemia during asthma exacerbations. We evaluated the incidence, potential causes, and adverse events of hyperlactatemia in patients with acute asthma exacerbation. This study was a subanalysis of subjects receiving placebo from a prospective, randomized trial evaluating an IV b -adrenergic agonist in acute asthma exacerbation. Plasma albuterol, serum lactate, and bicarbonate concentrations were measured at baseline and 1.25 h, and dyspnea score and spirometry were measured at baseline and hourly for 3 h. All subjects had a therapeutic trial comprising 5 to 15 mg nebulized albuterol, 0.5 to 1 mg nebulized ipratropium, and at least 50 mg oral prednisone or its equivalent prior to initiation of the study. Following randomization, subjects were treated with continued albuterol and IV magnesium at the discretion of their treating physician. Subjects were followed to hospital admission or discharge with follow-up at 24 h and 1 week. One hundred seventy-fi ve subjects were enrolled in the parent trial, with 84 in the placebo group. Sixty-fi ve had complete data. Mean SD albuterol administration prior to baseline was 12.3 5.3 mg. Mean baseline lactate was 18.5 8.4 mg/dL vs 26.5 11.8 mg/dL at 1.25 h ( P , .001). Forty-fi ve subjects (69.2%) had hyperlactatemia. Mean baseline bicarbonate level was 22.6 2.9 mEq/L vs 21.9 4.0 mEq/L at 1.25 h ( P 5 .11). Plasma albuterol concentration correlated with lactate concentration ( b 5 0.45, P , .001) and maintained a significant association after adjusting for asthma severity ( b 5 0.41, P 5 .001). Hyperlactatemia did not increase the risk of hospitalization or relapse ( P 5 .26) or was associated with lower FEV 1 % predicted at 3 h ( P 5 .54). Plasma albuterol was significantly correlated with serum lactate concentration after adjusting for asthma severity. Hyperlactatemia was not associated with poorer pulmonary function as measured by 3-h FEV 1 % predicted or increased hospitalization or relapse at 1 week.

Assessment of Plasma Electrolytes, Urea and Creatinine of Patients for Adenotonsillectomy

Objective: Adenotonsillectomy is commonly performed for children with recurrent adenotonsillitis. Electrolyte derangement could be a source of complication or even mortality if not properly corrected. This study was therefore carried out to assess the plasma electrolytes, urea, and creatinine levels of patients for adenotonsillectomy in our hospital. Materials and Methods: This was a prospective study that was carried out at the Ear, Nose, Throat, Head, And Neck Surgery Clinic of the University of Benin Teaching Hospital, Benin City, between January 2009 and February 2012, of patients who underwent adenotonsillectomy. Both a thorough history, to ascertain relevant information, and a specific examination were done for the patients. The patients were tested for plasma sodium, potassium, chloride, bicarbonate, urea, and creatinine levels, using established standardized laboratory assay methods with reference intervals interpreted in accordance with established procedures. Results: 49 patients completed the study, made up of 33 males and 16 females, with a mean age of 6.62 years. 25 patients (51.02%) had normonatremia while 24 (48.97%) had hyponatremia. 41 patients (83.67%) had normokalemia, two (4.08%) had hyperkalemia while 6 (12.24%) had hypokalemia. 11 patients (22.45%) had acidosis, 37 (75.51%) had normal bicarbonate levels while only one (2.04%) had alkalosis. 45 patients (91.84%) had normochloremia, while one (2.04%) each had hyponatremia and another one (2.04%) had hyperchloremia. Low urea was seen in nine (18.37%) and normal urea in 40 (81.63%) patients. Normal creatinine levels were seen in 31 (63.27%) and low creatinine in 10 (20.41%) patients. Conclusion: Electrolytes, urea, and creatinine derangement; especially hyponatremia, exists in patients admitted for adenotonsillectomy, mainly due to their inability to feed properly. These electrolytes should be assessed and corrected before surgery, to avoid fatal complications.

The Importance of the Ionic Product for Water to Understand the Physiology of the Acid-Base Balance in Humans

Human plasma is an aqueous solution that has to abide by chemical rules such as the principle of electrical neutrality and the constancy of the ionic product for water. These rules define the acid-base balance in the human body. According to the electroneutrality principle, plasma has to be electrically neutral and the sum of its cations equals the sum of its anions. In addition, the ionic product for water has to be constant. Therefore, the plasma concentration of hydrogen ions depends on the plasma ionic composition. Variations in the concentration of plasma ions that alter the relative proportion of anions and cations predictably lead to a change in the plasma concentration of hydrogen ions by driving adaptive adjustments in water ionization that allow plasma electroneutrality while maintaining constant the ionic product for water. The accumulation of plasma anions out of proportion of cations induces an electrical imbalance compensated by a fall of hydroxide ions that brings about a rise in hydrogen ions (acidosis). By contrast, the deficiency of chloride relative to sodium generates plasma alkalosis by increasing hydroxide ions. The adjustment of plasma bicarbonate concentration to these changes is an important compensatory mechanism that protects plasma pH from severe deviations.

Hemodialysis: Core Curriculum 2014

From the Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN. Received May 1, 2013. Accepted in revised form July 1, 2013. Originally published online November 21, 2013. Address correspondence to Thomas A. Golper, MD, S3303 Medical Center North, Vanderbilt University Medical Center, 21st Ave S, Nashville, TN 37232. E-mail: thomas.golper@vanderbilt. edu 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.07.028 PRINCIPLES OF DIALYSIS AND HOW MODALITIES DIFFER

Two rare cases of osteomyelitis

circulatory collapse, severe hypoglycemia, metabolic acidosis, severe anemia or hemolysis, renal failure, hemoglobinuria, liver failure, coagulopathy. Patients with complicated or severe malaria may have hyperparasitemia (≥100,000 parasites/μL of blood; ≥5 to 10% of parasitized RBCs) and/ormajor signs of organ dysfunction. The criteria for complicated malaria are acidemia/acidosis (arterial pH b 7.25; plasma bicarbonate b15 mmol/L); venous lactate (N5 mmol/L); severe anemia (Hct b 15% parasitemia levels N 100.000/μL); kidney failure with serum creatinine N 3.0 mg/dL; pulmonary edema/ARDS; hypoglycemia (plasma glucose b 40 mg/dL); hypotension/shock; hemorrhage/CID; convulsions; hemoglobinuria not associated with drug effects oxidizing or enzymatic deficits. Hyperparasitism increases mortality. Case report: Male 61 years old. In December/2010, the patient presented a clinical condition characterized by fever, chills, myalgias, arthralgias, frontal headache, asthenia, and anorexia. At the emergency room, the clinical examination revealed sub-jaundiced; sweaty skin, painful hepatomegaly, without palpable lymphadenopathy; hypotension and tachycardia fever (40 °C). Analytically: normal peripheral blood leukocyte count, Hb 16.5 g/dL, leukocytes 7800 (g/L), creatinine 1.80 mg/dL; hyperbilirubinemia and Plasmodium positive (P. falciparum parasitemia 7.2%). Hewas admitted in the intensive care unit due to severity criteria. The patient developed multiorganic dysfunction — MODS: pulmonary (mechanical ventilation); hematologic with thrombocytopenia and severe anemia requiring transfusional support, liver dysfunction (total bilirubin up to maximum 3.9 g/dL); renal dysfunction (AKI stage I) and cardiovascular dysfunction. The treament was initiated with doxycycline 100 mg 8/8 h and quinine sulfate 600 mg 8/8 h for 7 days. He had favorable clinical course with total recovery of all disorders. Conclusion: According to the WHO, malaria is by far the tropical and parasitic disease that causes more social and economic problems in the world and is only surpassed in number of deaths by AIDS. Severe malaria can progress extremely rapidly and cause death within hours or days. The authors emphasize that timely diagnosis and organ support in intensive care unit allowed the favorable outcome of this case report. More studies are needed to combat the disease.

Contribution of Unmeasured Anions to Acid–Base Disorders and its Association with Altered Demeanor in 264 Calves with Neonatal Diarrhea

BackgroundThe quantitative effect of strong electrolytes, unmeasured anions (UAs), p CO 2, and plasma protein concentrations in determining plasma pH and bicarbonate (HCO 3 −) can be demonstrated using the physicochemical approach. Demeanor of calves with diarrhea is associated with acidemia, dehydration, and hyper‐d‐lactatemia.HypothesisUnmeasured anions are a major factor influencing changes in plasma pH and HCO 3 − of calves with diarrhea and UAs and strong UAs, estimated by anion gap (AG) and strong ion gap (SIG), respectively, are more strongly associated with alteration of demeanor compared to other acid–base variables.AnimalsA total of 264 calves with diarrhea from two data sets (DS1 and DS2).MethodsRetrospective study. Forward stepwise regression was performed to determine the relationship between measured pH or HCO 3 −, and physicochemical variables. A two‐way ANOVA was performed to investigate the association between acid–base variables and attitude (bright, obtunded, and stuporous), posture (standing, sternal or lateral recumbency), and strength of suckling reflex (strong, weak, or absent).ResultsIncreased strong UAs estimated by SIG was the most important contributor to changes in measured pH and HCO 3 − (DS1: r 2 66 and 59%, DS2: 39 and 42%, P < .0001). SIG and AG were correlated to deteriorating calf demeanor for all three clinical scoring categories: attitude, posture, and suckle reflex (P < .0001).Conclusion and Clinical RelevanceElevated concentrations of strong UAs were the primary cause of acidemia and had an important influence on the demeanor of calves with diarrhea. These findings emphasize the importance of the calculation of UAs when evaluating acid–base abnormalities in calves.

Plasma Bicarbonate and Odds of Incident Hypertension

Several biomarkers of metabolic acidosis, including lower plasma bicarbonate, have been associated with prevalent hypertension in cross-sectional studies. We sought to examine prospectively whether lower plasma bicarbonate is associated with incident hypertension. We conducted a prospective case-control study nested within the Nurses' Health Study II. Plasma bicarbonate was measured in 695 nonobese women without hypertension at time of blood draw who subsequently developed hypertension during 6 years of follow-up. Control subjects were matched to case subjects according to age, race, time and day of blood draw, and day of menstrual cycle. We used unconditional logistic regression to generate odds ratios (ORs) for development of hypertension by quintile of baseline plasma bicarbonate. After adjusting for matching factors, body mass index, family history of hypertension, plasma creatinine, and dietary and lifestyle factors, higher plasma bicarbonate was associated with lower odds of developing hypertension across quintiles (P for linear trend = 0.04). Those in the highest compared with the lowest quintile of plasma bicarbonate had 31% lower odds of developing hypertension (OR = 0.69; 95% confidence interval = 0.48-0.99). Further adjustment for diet-estimated net endogenous acid production, plasma insulin, 25-hydroxyvitamin D, and uric acid did not alter these findings. Our case-control study is consistent with a modest association between higher plasma bicarbonate and reduced odds of developing hypertension among nonobese women, although our findings are of borderline statistical significance. Further research is required to confirm this finding as part of a larger prospective cohort study and to elucidate the mechanism for this relation.

Acute Gastrointestinal Bleeding

Acid-base balance has been studied in 21 patients with acute upper gastrointestinal bleeding. A low plasma bicarbonate concentration was found in nine patients, accompanied in each case by a base deficit of more than 3 mEq/litre, indicating a metabolic acidosis. Three patients had a low blood pH. Hyperlactataemia appeared to be a major cause of the acidosis. This was not accompanied by a raised blood pyruvate concentration. The hyperlactataemia could not be accounted for on the basis of hyperventilation, intravenous infusion of dextrose, or arterial hypoxaemia. Before blood transfusion it was most pronounced in patients who were clinically shocked, suggesting that it may have resulted from poor tissue perfusion and anaerobic glycolysis. Blood transfusion resulted in a rise in lactate concentration in seven patients who were not clinically shocked, and failed to reverse a severe uncompensated acidosis in a patient who was clinically shocked. These effects of blood transfusion are probably due to the fact that red blood cells in stored bank blood, with added acid-citratedextrose solution, metabolize the dextrose anaerobically to lactic acid. Monitoring of acid-base balance is recommended in patients with acute gastrointestinal bleeding who are clinically shocked. A metabolic acidosis can then be corrected with intravenous sodium bicarbonate. one a probable Mallory-Weiss lesion, one a small-bowel reticulosis, and one had thrombocytopenia. In four patients the cause of bleeding was not identified. Arterial blood samples were taken within 36 hours of hospital admission, with the patients breathing air. No patient received any drugs known to cause a lactic acidosis. Though patients were supine at rest when the blood samples were taken, conditions were iiOt truly basal, as some of them were anxious and not all were fasting. In 14 patients an arterial blood sample was taken before blood transfusion, and in seven the first sample was taken during blood transfusion. The blood samples were analysed immediately for pH, carbon dioxide tension (Pco.), and oxygen tension (Poe) with a Radiometer electrode system at 37°C. Plasma bicarbonate concentration and base deficit were derived from pH and Pco2 by use of Siggaard-Andersen's (1963) nomogram. An aliquot of the blood sample was deproteinized at the bedside with icecold perchloric acid. Blood lactate and pyruvate concentrations were measured by means of a lactate dehydrogenase enzyme assay, the reagent kits supplied by Biochemica Test Combination being used as specified by the manufacturers (Boehringer und Soehne, 1967). For the purpose of this study arterial hypoxaemia has been defined as an arterial oxygen tension of less than 80 mm Hg, and clinical shock as the presence of cold, sweaty extremities in combination with a systolic blood pressure of less than 100 mm Hg.

Status of some selected renal function indicators in cigarette smokers.

In recent years, it has become apparent that smoking has a negative impact on renal function, being one of the most important avoidable renal risk factors. This study was aimed at assessing the renal function of cigarette smokers. The study was carried out on one hundred and sixty (160) subjects comprising of one hundred (100) cigarette smokers and sixty (60) apparently healthy non-smokers serving as control. Renal function was assessed by measuring the levels of plasma urea, creatinine, sodium, potassium, chloride and bicarbonate using standard colorimetric methods as indicators. In this study, it was observed that there was no significant difference in the levels of urea, creatinine, chloride and bicarbonate when compared with control. There was significant increase (p < 0.05) in sodium level (143.76±5.45) when compared with control (139.85±4.03) (p<0.05). There was a significant decrease in potassium level (3.86±0.54) when compared with control (4.08±0.49) (p<0.05). Conclusively, Smoking has an acute increasing effect on plasma sodium levels and at the same time decreasing the plasma potassium level. We therefore suggest that clearance test be done on smokers for more detail assessment of their renal function.

Successful correction of D-lactic acid neurotoxicity (drunken lamb syndrome) by bolus administration of oral sodium bicarbonate

Drunken lamb syndrome (DLS) has recently been described as lamb D-lactic acidosis syndrome (LDLAS). In 2012, 18 lambs aged between 7 days and 28 days with LDLAS were identified. Biochemically,...

Acute Coagulopathy of Trauma in the Rat

Acute coagulopathy of trauma (aCOT) is a state of disordered coagulation developing soon after severe injury and blood loss and has been defined in the clinical literature as an elevation in prothrombin time (PT) and activated partial thromboplastin time (aPTT). The purpose of this study was to develop a rat model of aCOT resulting from polytrauma and hemorrhage and showing an elevation in PT and aPTT. Sprague-Dawley rats (300-400 g) were anesthetized with isoflurane. Polytrauma was induced by damaging 10 cm of small intestines, the right and medial liver lobes, the right leg skeletal muscle, and fracture of the right femur. Rats were hemorrhaged 40% of their estimated blood volume. No resuscitation was given. Venous and arterial blood samples were taken at times up to 4 h. Polytrauma and hemorrhage resulted in a significant rise in PT, aPTT, potassium, lactate, and glucose. There was a significant decrease in plasma bicarbonate, base excess, and sodium. Blood urea nitrogen and creatinine rose steadily throughout the 4 h indicative of progressive renal failure. Hematocrit decreased significantly immediately after hemorrhage and trauma indicating a movement of fluid into the vascular space from extravascular sources, which was mirrored by a decrease in plasma fibrinogen concentration. In contrast, platelet count initially decreased, rose at 2 h, and decreased again at 3 to 4 h, indicating that platelets were released into the vascular space. The change in platelet count was mirrored by the changes in thrombin-antithrombin and plasmin-antiplasmin complexes. Rotational thromboelastometry showed complex changes. Clotting firmness fell initially, rose at 2 h, and fell again at 3 to 4 h similar to the changes in platelet count. α Angle was elevated, and clotting time was shortened over the 4 h. Treatment with cytochalasin D (platelet function inhibitor) eliminated the increases in clotting firmness and thrombin generation seen at 2 h with rising platelet count. This model of aCOT in rats showed complex changes in clotting parameters over 4 h that included a rise in PT and aPTT. At 4 h, there was a decrease in clotting firmness, even though the clot formation was faster (elevated α angle and decrease in clotting time). The decrease in clotting firmness correlated with falling fibrinogen and platelet count. This model affords an opportunity to evaluate interventions in the treatment of aCOT.

Physicochemical Interpretation of Acid‐Base Abnormalities in 54 Adult Horses with Acute Severe Colitis and Diarrhea

The quantitative effect of strong electrolytes, pCO2 , and plasma protein concentration in determining plasma pH and bicarbonate concentrations can be demonstrated with the physicochemical approach. Plasma anion gap (AG) and strong ion gap (SIG) are used to assess the presence or absence of unmeasured anions. The physicochemical approach is useful for detection and explanation of acid-base disorders in horses with colitis. AG and SIG accurately predict hyperlactatemia in horses with colitis. Fifty-four horses with acute colitis and diarrhea. Retrospective study. Physicochemical variables were calculated for each patient. ROC curves were generated to analyze sensitivity and specificity of AG and SIG for predicting hyperlactatemia. Physicochemical interpretation of acid-base events indicated that strong ion metabolic acidosis was present in 39 (72%) horses. Mixed strong ion acidosis and decreased weak acid (hypoproteinemia) alkalosis was concomitantly present in 17 (30%) patients. The sensitivity and specificity of AG and SIG to predict hyperlactatemia (L-lactate > 5 mEq/L) were 100% (95% CI, 66.4-100; P < .0001) and 84.4% (95% CI, 70.5-93.5 P < .0001). Area under the ROC curve for AG and SIG for predicting hyperlactatemia was 0.95 (95% CI, 0.86-0.99) and 0.93 (95% CI, 0.83-0.99), respectively. These results emphasize the importance of strong ions and proteins in the maintenance of the acid-base equilibria. AG and SIG were considered good predictors of clinically relevant hyperlactatemia.

Effect of Beta-Alanine With and Without Sodium Bicarbonate on 2,000-m Rowing Performance

To examine the effect of beta-alanine only and beta-alanine with sodium bicarbonate supplementation on 2,000-m rowing performance. Twenty well-trained rowers (age 23 ± 4 y; height 1.85 ± 0.08 m; body mass 82.5 ± 8.9 kg) were assigned to either a placebo or beta-alanine (6.4 g · d(-1) for 4 weeks) group. A 2,000-m rowing time trial (TT) was performed before supplementation (Baseline) and after 28 and 30 days of supplementation. The post supplementation trials involved supplementation with either maltodextrin or sodium bicarbonate in a double-blind, crossover design, creating four study conditions (placebo with maltodextrin; placebo with sodium bicarbonate; beta-alanine with maltodextrin; beta-alanine with sodium bicarbonate). Blood lactate, pH, bicarbonate, and base excess were measured pre-TT, immediately post-TT and at TT+5 min. Performance data were analyzed using magnitude based inferences. Beta-alanine supplementation was very likely to be beneficial to 2,000-m rowing performance (6.4 ± 8.1 s effect compared with placebo), with the effect of sodium bicarbonate having a likely benefit (3.2 ± 8.8 s). There was a small (1.1 ± 5.6 s) but possibly beneficial additional effect when combining chronic beta-alanine supplementation with acute sodium bicarbonate supplementation compared with chronic beta-alanine supplementation alone. Sodium bicarbonate ingestion led to increases in plasma pH, base excess, bicarbonate, and lactate concentrations. Both chronic beta-alanine and acute sodium bicarbonate supplementation alone had positive effects on 2,000-m rowing performance. The addition of acute sodium bicarbonate to chronic beta-alanine supplementation may further enhance rowing performance.

Clinicopathologic variables associated with hypokalemia in lactating dairy cows with abomasal displacement or volvulus

To identify potential mechanisms for hypokalemia in dairy cows with left-displaced abomasum (LDA), right-displaced abomasum (RDA), or abomasal volvulus (AV). Retrospective analysis of clinicopathologic data from 2 convenience samples of cows. 112 lactating dairy cows with AV (group 1); 1,332 lactating dairy cows (group 2) with LDA (n = 1,160) or RDA or AV (172). Data were analyzed via Spearman ρ and multivariate stepwise regression. 78 of 112 (70%) group 1 cows were hypokalemic (mean serum potassium concentration, 3.5 mEq/L; reference range, 3.9 to 5.8 mEq/L). For group 1 cows, serum chloride concentration had the strongest positive association with serum potassium concentration, and serum potassium concentration was negatively associated with plasma bicarbonate and serum glucose, creatinine, and urea concentrations. Six hundred thirty-six of 1,160 (55%) of group 2 cows with LDA were hypokalemic (mean serum potassium concentration, 3.7 mEq/L). Ninety-two of 172 (53%) group 2 cows with RDA or AV were hypokalemic (mean serum potassium concentration, 3.8 mEq/L). For group 2 cows, serum chloride concentration had the strongest positive association with serum potassium concentration, and serum potassium concentration was negatively associated with indices of feed intake (serum bilirubin concentration) and hydration status. Results suggested hypokalemia was associated with hypochloremia, alkalemia, low feed intake with high amount of milk produced, hypovolemia, and hyperglycemia in lactating dairy cows. Treatment of hypokalemia should include surgical correction of abomasal displacement, increased dietary potassium intake via dietary dry matter intake or oral administration of KCl, and correction of hypochloremia, alkalemia, metabolic alkalosis, and dehydration.

Evaluation of the potassium channel activator levcromakalim (BRL38227) on the lipid profile, electrolytes and blood glucose levels of streptozotocin‐diabetic rats (评估钾通道激活剂左克罗卡林（BRL38227）对链脲霉素‐糖尿病大鼠血脂谱、电解质以及血糖水平的影响)

Levcromakalim is a vasorelaxant used in the management of hypertension in diabetes mellitus. Thus, the effects of levcromakalim were investigated in streptozotocin (STZ)-diabetic rats. Diabetes was induced in Wistar albino rats with a single injection of STZ (60 mg/kg, i.p.) following chronic (4 weeks) treatment with levcromakalim (75 μg/kg per day). Rats were then divided into the following groups (n = 5 in each group): (i) a normal saline (2 mL/kg)-treated group; (ii) a 5 mg/kg glibenclamide-treated group; (iii) 350 mg/kg metformin-treated group; and (iv) 5, 10, 20 and 40 IU/kg insulin-treated groups. Rats were transferred to metabolic cages and the lipid profile, plasma and urine electrolytes and blood glucose levels were determined 24 h after drug administration. Levcromakalim treatment significantly reduced total cholesterol, low-density lipoprotein (LDL), and triglyceride levels in diabetic rats (all P < 0.05 compared with untreated diabetic rats). In addition, levcromakalim reduced plasma sodium, bicarbonate, and chloride levels, but increased urinary bicarbonate and chloride levels, in diabetic rats (all P < 0.05 compared with untreated diabetic rats). Levcromakalim significantly inhibited the effects of glibenclamide, metformin, and low-dose (20 IU/kg) insulin treatment in diabetic rats (all P < 0.05). Only 40 IU/kg insulin produced significant reductions in hyperglycemia in levcromakalim-treated diabetic rats. Levcromakalim induced resistance to glibenclamide, metformin, and low-dose insulin treatment in diabetic rats, leading to persistent hyperglycemia. However, reductions in LDL, total cholesterol and triglyceride levels following chronic levcromokalim treatment may decrease the risk of cardiovascular disease in diabetic rats.

Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage

Introduction:This study was designed to evaluate the ameliorative and hypocholesterolemic effects of dietary supplementation of Cnidoscolus aconitifolius leaf meal (CALM) on hepatic injury and kidney injury associated with protein energy malnutrition (PEM).Materials and Methods:In this study, PEM was induced in weaning male Wistar albino rats by feeding them with low protein diet for 2 weeks. The effects of several recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed were assessed in PEM rats. Plasma biochemical parameters were assessed as well.Results:After the induction of PEM, results obtained showed significant increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total proteins (T.P), total bilirubin (T.Bil), triglycerides, total cholesterol, low density lipoproteins (LDL), blood urea nitrogen (BUN), and creatinine with significant reduction in plasma high density lipoproteins (HDL), albumin, sodium (Na+), potassium (K+), chloride (Cl−), bicarbonate (HC03−), and phosphate (P042−) in PEM rats. Upon introduction of recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed for 4 weeks caused significant (P < 0.05) reduction in plasma values of ALP, ALT, AST, T.bil, T.P., LDL, total cholesterol, triglycerides, BUN, creatinine, and significant increase in HDL and complete restoration of plasma electrolytes.Conclusions:C. aconitifolius in protein deficient diets has a protective role against hepatic injury and renal damage associated with PEM.

History of Medical Understanding and Misunderstanding of Acid Base Balance

To establish how controversies in understanding acid base balance arose, the literature on acid base balance was reviewed from 1909, when Henderson described how the neutral reaction of blood is determined by carbonic and organic acids being in equilibrium with an excess of mineral bases over mineral acids. From 1914 to 1930, Van Slyke and others established our acid base principles. They recognised that carbonic acid converts into bicarbonate all non-volatile mineral bases not bound by mineral acids and determined therefore that bicarbonate represents the alkaline reserve of the body and should be a physiological constant. They showed that standard bicarbonate is a good measure of acidosis caused by increased production or decreased elimination of organic acids. However, they recognised that bicarbonate improved low plasma bicarbonate but not high urine acid excretion in diabetic ketoacidosis, and that increasing pCO2 caused chloride to shift into cells raising plasma titratable alkali. Both indicate that minerals influence pH. In 1945 Darrow showed that hyperchloraemic metabolic acidosis in preterm infants fed milk with 5.7 mmol of chloride and 2.0 mmol of sodium per 100 kcal was caused by retention of chloride in excess of sodium. Similar findings were made but not recognised in later studies of metabolic acidosis in preterm infants. Shohl in 1921 and Kildeberg in 1978 presented the theory that carbonic and organic acids are neutralised by mineral base, where mineral base is the excess of mineral cations over anions and organic acid is the difference between mineral base, bicarbonate and protein anion. The degree of metabolic acidosis measured as base excess is determined by deviation in both mineral base and organic acid from normal.

Respiratory compensation to a primary metabolic alkalosis in humans

There is limited and disparate information about the extent of the respiratory compensation (hypoventilation) that occurs in response to a primary metabolic alkalosis in humans. Our aim was to examine the influence of the plasma bicarbonate concentration, the plasma base excess, and the arterial pH on the arterial carbon dioxide tension in 52 adult patients with primary metabolic alkalosis, mostly due to diuretic use or vomiting. Linear regression analysis was used to correlate degrees of alkalosis with arterial carbon dioxide tensions. In this alkalotic cohort, whose arterial plasma bicarbonate averaged 31.6 mEq/l, plasma base excess averaged 7.8 mEq/l, and pH averaged 7.48, both plasma bicarbonate and base excess correlated closely with arterial carbon dioxide tensions (r = 0.97 and 0.96, respectively; p < 0.0001), while there was little relationship between arterial pH and arterial carbon dioxide tensions (p = 0.08). The arterial carbon dioxide tension increased 1.2 torr for each 1.0 mEq/l increment in plasma bicarbonate or base excess (95% confidence interval, 1.1 - 1.3 torr). This 1.2 torr increase amounts to a ~ 50% greater degree of respiratory compensation (hypoventilation) to primary metabolic alkalosis than has been reported in prior smaller studies.