Acidosis defense mechanisms in the preimplantation stages of embryos in BALB/c strain mice.

Regulation of intracellular pH (pHi) is an important homeostatic function of cells. There are three major pHi regulatory mechanisms: the HCO3-/Cl- exchanger (AE), which alleviates alkalosis, and the Na+/H+ exchanger (NHE) and Na+,HCO3-/Cl- exchanger (NDBCE), both of which counteract acidosis. NHE activity, which is high at the germinal vesicle stage of oocyte, is inhibited during meiotic maturation, while this inhibition is abolished when the oocyte reaches the pronuclear (PN) stage of the zygote. On the other hand, we have previously found that NDBCE performs complementary regulation against acidosis during meiotic maturation. Additionally, we found that AE activity, which is a defense mechanism against alkalosis, gradually decreases during preimplantation period of embryonic development. Considering that NHE activity is inhibited during meiotic maturation and AE activity gradually decreases during embryonic development stages, we investigated whether NHE and NDBCE activities, both of which act against acidosis, functionally change from the PN zygote to the blastocyst stage of the embryo and identified these pH-regulating proteins at the molecular level in mice of the Balb/c strain. PN zygotes, two-cell (2-c), four-cell (4-c), morula and blastocyst stage embryos were obtained from 5-8-week-old, sexually mature female Balb/c mice by using the classical superovulation procedure. pHi was recorded by using the microspectrofluorometric technique on zygotes and embryos simultaneously loaded with the pH-sensitive fluorophore, 2',7'-Bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). The activities of NHE and NDBCE were determined from the recovery curve of induced-acidosis in bicarbonate-free and bicarbonate-containing media, respectively. Specific inhibitors such as cariporide (1 µM), S3226 (1 and 10 µM), EIPA (1, 5, and 25 µM), and amiloride (1 mM) were used to functionally identify NHE isoforms, and the nonspecific inhibitor 4,4'-diisocyanatostilbene-2,2' disulphonic acid, disodium salt (DIDS) was used to confirm NDBCE activity. The isoforms of the pHi-regulatory proteins were also identified by molecular biology using real-time PCR. We found that NHE activity was high at all embryonic stages, and differences between stages were not significant. Functional and molecular findings indicated that isoforms of NHE 1 and 5 are present in the blastocyst, whereas isoforms of NHE 1, 3, and 4 are functional at earlier embryonic stages. Although the contribution of NDBCE activity to recovery from induced-acidosis was detected at all embryonic stages, it was significant only in the PN zygote and the 2-c embryo. This finding was confirmed by molecular analysis, which detected the expression of SLC4A8 encoding NDBCE at all embryonic stages. In conclusion, NHE is an active and important defense mechanism against acidosis and is encoded by at least two protein isoforms in all stages of the Balb/c strain of mice. NDBCE has a supportive function in all embryonic stages, especially in the PN zygote and the 2-c embryo. Preimplantation stage embryos have effective mechanisms to defend against acidosis in response to their metabolic end products (increased acid load) and the acidic environment in utero.

Acid-base and electrolyte evaluation in dogs with upper GI obstruction: 115 dogs (2015-2021).

OBJECTIVES: Metabolic alkalosis, although uncommon in small animals, has been previously associated with gastrointestinal obstructions. Depending on the population and disease process evaluated, previous prevalence of metabolic alkalosis is reported as ranging from 2% to 45% in canine patients. The objective of this study was to determine the prevalence of metabolic alkalosis and other acid-base and electrolyte disorders in a cohort of dogs with a confirmed upper gastrointestinal obstruction. MATERIALS AND METHODS: Electronic medical records were reviewed to identify dogs who presented for vomiting with evidence of an upper gastrointestinal obstruction from January 2015 to October 2021. Patients were enrolled only if a preoperative venous blood gas was obtained and analysed in house. Traditional acid-base analysis was utilised to determine an acid-base status before relieving the obstruction. When available, post-operative venous acid-base status was determined within 24 hours after surgery, and compared to preoperative results. RESULTS: A total of 115 dogs were included in the study. Twenty-five out of 115 (22%) dogs displayed either a simple metabolic alkalosis or a mixed acid-base disturbance before surgery. Twenty-seven out of 115 dogs (37%) had a normal acid-base status at entry. Seventy-one dogs had pre- and post-operative venous blood gas results available. Metabolic alkalosis was resolved in nearly all patients post-operatively, with no patients displaying a simple metabolic alkalosis. A mixed metabolic acidosis and respiratory alkalosis was the most common condition post-operatively, found in 25 of 71 (35%) dogs. Severe derangements of electrolytes were infrequent preoperatively (3/115; 2.6%). A majority of patients in this study exhibited hypokalaemia (64.4%), hypochloraemia (72.8%) and hyponatraemia (77.4%) on preoperative venous blood gases. Venous pH, Pv CO2 , bicarbonate and base excess were significantly higher preoperatively when compared to the post-operative results. CLINICAL SIGNIFICANCE: This study found the prevalence of pre-operative metabolic alkalosis in dogs with a documented upper gastrointestinal obstruction to be lower than previously reported. Surgical or endoscopic alleviation of the upper gastrointestinal obstruction resulted in resolution of metabolic alkalosis in nearly all patients.

Cardiorespiratory effects of isoflurane and medetomidine-tiletamine-zolazepam in 12 bonobos (Pan paniscus).

BACKGROUND: Cardiovascular disease is a significant cause of mortality in captive great apes. However, data from bonobos are lacking due to a paucity of collections in Europe. Comprehensive preventive screening is required to understand the aetiopathogenesis of cardiovascular disease, but the provision of a stable and predictable anaesthetic protocol with minimal cardiovascular effects is challenging. METHODS: This prospective, observational case series reports anaesthesia of 12 bonobos using hand-injected medetomidine and tiletamine-zolazepam followed by maintenance with isoflurane in oxygen. Comprehensive clinical examinations, including arterial blood gases and echocardiography were undertaken. RESULTS: Induction of anaesthesia with hand injection was successful in all but one individual. Respiratory acidosis with metabolic alkalosis and respiratory alkalosis with metabolic acidosis were documented. Hypochloraemia may have contributed to non-respiratory alkalosis in one individual. Ten bonobos experienced hypotension and required haemodynamic support. Both N-terminal pro b-type natriuretic peptide and troponin I cardiac biomarkers correlated with left ventricular ejection fraction (percentage). Recovery was smooth, rapid and uneventful in all animals. LIMITATIONS: The effects of the anaesthetic must be considered during echocardiographical interpretation. CONCLUSIONS: The anaesthesia protocol provided a safe, predictable induction and recovery, facilitating diagnostics (including echocardiography) and minor surgical procedures. Comprehensive monitoring, including invasive blood pressure monitoring and haemodynamic support, is highly recommended.

Acid-Base.

In clinical medicine, evaluation of acid-base balance can be a valuable diagnostic and monitoring tool. Blood gas machines need very small volumes of blood and provide immediate results, making them ideal for use in the emergency room and intensive care setting. This review outlines the stepwise approach to assessment of acid-base balance in dogs, common causes of acid-base abnormalities, and the general approach to treatment.

Metabolic alkalosis following mitral valvuloplasty in a dog with preoperative acute kidney injury.

CASE DESCRIPTION: An 11-year-old sexually intact male Shih Tzu diagnosed with acute kidney injury and left-sided congestive heart failure that had nonelective mitral valve surgery. CLINICAL FINDINGS: Metabolic alkalosis developed postoperatively, and plasma bicarbonate concentration peaked 2 days after surgery (40.2 mmol/L; pH, 7.550). TREATMENT AND OUTCOME: Acetazolamide administration increased the urinary excretion of bicarbonate and contributed to the improvement of the dog's acid-base status and oxygenation capacity. Metabolic alkalosis persisted for 4 days after surgery, and no treatment was required after resolution. Plasma urea nitrogen and creatinine concentrations normalized 2 days after surgery. CLINICAL RELEVANCE: Severe metabolic alkalosis can occur as a complication following mitral valve surgery. Acetazolamide may be suitable for the treatment of severe metabolic alkalosis.

Incidence of hypochloremic metabolic alkalosis in dogs and cats with and without nasogastric tubes over a period of up to 36 hours in the intensive care unit.

OBJECTIVE: To evaluate the incidence of hypochloremic metabolic alkalosis (HCMA) in dogs and cats in the ICU that had intermittent nasogastric tube (NGT) aspiration for up to 36 hours. DESIGN: Prospective cohort study (December 2013 to October 2014). SETTING: Privately owned emergency and referral teaching hospital. ANIMALS: Forty-nine client-owned dogs and 16 client-owned cats. INTERVENTIONS: Patients wherein NGT placement was recommended and client consent was obtained were included in the interventional group. Those with an NGT placed (NGT group) had the NGT aspirated every 4 hours. Patients for whom placement of a NGT was declined by the owner served as a reference group (NoNGT). Venous blood gas and electrolyte values were obtained every 12 hours. MEASUREMENTS AND MAIN RESULTS: Thirty-five dogs and cats had an NGT placed. Thirty dogs and cats did not have an NGT placed. The serum venous blood gas and electrolyte changes were compared over time within the NGT group and between the NGT and NoNGT groups. No cases developed HCMA. In the NGT group, blood pH increased over time. There was no significant difference between the NGT and the NoNGT group in the average value of pH, HCO3- , base excess, chloride, or corrected chloride. Serum venous blood gas, chloride, and corrected chloride changes were not associated with the volumes of gastric fluid aspirated over time. CONCLUSIONS: In this small population of dogs and cats, intermittent NGT aspiration was not associated with the development of HCMA over a period of up to 36 hours after NGT placement.

Food engorgement in 35 dogs (2009-2013) compared with 36 dogs with gastric dilation and volvulus.

The clinical features and management of food engorgement (FE) in dogs have not been previously described. This retrospective observational study describes characteristics and outcome of 35 dogs with FE, and compares features on presentation to 36 dogs with gastric dilation and volvulus (GDV). Cases were retrospectively reviewed for history, clinical findings and outcome. Gastric distension was measured by caudal gastric margin (CGM), level with lumbar vertebrae, on a lateral abdominal radiograph. Frequent characteristics of dogs with FE included tachycardia, tachypnoea, hyperproteinaemia, increased base excess (BE), mild hypernatraemia and hyperlactataemia. There was overlap in CGM between dogs with GDV (CGM range L3 to >L6) and dogs with FE (CGM range

A Quick Reference on Metabolic Alkalosis.

Metabolic alkalemia is characterized by an increase in bicarbonate concentration and base excess, an increase in pH, and a compensatory increase in carbon dioxide pressure. This article outlines indications for analysis, reference ranges, causes, and clinical signs of metabolic alkalosis. Algorithms for evaluation of patients with acid-base disorders and metabolic alkalosis are included.

[Blood gas analysis in dogs in veterinary practice. A review]. / Blutgasanalyse beim Hund in der tierärztlichen Praxis--eine Übersicht.

Blood gas analysis is useful to obtain information about acid-base state and gas exchange of the lung. Interpretation is based on the Henderson-Hasselbalch equation. This approach has its limitations especially in interpretation of complex disturbances of acid-base status and has been complemented by base excess and anion gap. Peter Stewart described a model of quantitative approach to the acid-base disturbances which has been further developed and is known as the strong ion approach. This model differs from the traditional approach in the assessment of metabolic disorders of acid base status. Both models complement each other but also have their advantages and disadvantages. For simple disorders of the acid-base state the Henderson-Hasselbalch approach can be used, however in complex disturbances of acid-base balance, especially with abnormalities of serum albumin and phosphate concentrations, the strong ion approach is recommended. With the understanding of both models and of the clinical presentation of blood gas abnormalities, optimal case management and therapy can be provided.

Acid-base assessment: when and how to apply the Henderson-Hasselbalch equation and strong ion difference theory.

The Henderson-Hasselbalch equation is probably the most famous equation in biology but is more descriptive than mechanistic. The traditional approach to acid-base assessment using the Henderson-Hasselbalch equation provides a clinically useful and accurate method when plasma protein concentrations are within the reference range. The simplified strong ion approach is a mechanistic acid-base model that can provide new insight into complicated acid-base disturbances. The simplified strong ion approach should be used to evaluate acid-base balance whenever plasma protein concentrations are abnormal.

Efficacy of oral potassium chloride administration in treating lactating dairy cows with experimentally induced hypokalemia, hypochloremia, and alkalemia.

Hypokalemia occurs commonly in lactating dairy cows. The objectives of this study were to determine (1) whether a 24-h oral KCl dose of 0.4 g/kg of body weight (BW) was effective and safe in hypokalemic cattle; (2) whether potassium was best administered as 2 large doses or multiple smaller doses over a 24-h period; and (3) the effect of oral KCl administration on plasma Mg concentration and urine Mg excretion in fasted lactating dairy cattle. Plasma K and Cl concentrations were decreased, and blood pH increased, in 15 lactating Holstein-Friesian cows by administering 2 intramuscular (i.m.) 10-mg injections of isoflupredone acetate 24h apart followed by 2 i.m. injections of furosemide (1mg/kg of BW) 8h apart and by decreasing feed intake. Cows were randomly assigned to 1 of 3 treatment groups with 5 cows/group: untreated control (group C); oral administration of KCl at 0.05 g/kg of BW 8 times at 3-h intervals (group K3); and oral administration of KCl at 0.2g/kg of BW twice at 12-h intervals (group K12). A 24-h KCl dose rate of 0.4 g/kg of BW increased plasma and milk K concentration and plasma Cl concentration, and corrected the metabolic alkalosis and alkalemia, with no clinically significant difference between 2 large doses (group K12) or multiple small doses (group K3) of KCl over 24 h. Oral KCl administration decreased peripheral fat mobilization in cattle with experimentally induced hypokalemia, as measured by changes in plasma nonesterified fatty acid concentration, and slightly augmented the fasting-induced decrease in plasma Mg concentration. Our findings support recommendations for a 24-h oral KCl dose of 0.4 g/kg of BW for treating moderately hypokalemic cattle. Additional Mg may need to be administered to inappetant lactating dairy cattle being treated with oral KCl to minimize K-induced decreases in magnesium absorption.

Incidence, nature, and etiology of metabolic alkalosis in dogs and cats.

BACKGROUND: The incidence and causes of metabolic alkalosis in dogs and cats have not been fully investigated. OBJECTIVES: To describe the incidence, nature, and etiology of metabolic alkalosis in dogs and cats undergoing blood gas analysis at a veterinary teaching hospital. ANIMALS: Dogs and cats at a veterinary medical teaching hospital. METHODS: Acid-base and electrolyte results for dogs and cats measured during a 13-month period were retrospectively collected from a computer database. Only the first measured (venous or arterial) blood gas analyzed in a single hospitalization period was included. Animals with a base excess above the reference range for the species were included. RESULTS: A total of 1,805 dogs and cats were included. Of these, 349 (19%) were identified as having an increased standardized base excess, 319 dogs and 30 cats. The mixed acid-base disorder of metabolic alkalosis with respiratory acidosis was the most common abnormality identified in both dogs and cats. Hypokalemia and hypochloremia were more common in animals with metabolic alkalosis compared to animals without metabolic alkalosis. The 4 most commonly identified underlying diseases were respiratory disease, gastrointestinal tract obstruction, furosemide administration, and renal disease. CONCLUSIONS AND CLINICAL IMPORTANCE: Metabolic alkalosis was less common than metabolic acidosis in the same population of animals. Evidence of contraction alkalosis was present in many patients in this study. Hypokalemia and hypochloremia were more frequent in patients with metabolic alkalosis and suggest the importance of evaluation of acid-base status in conjunction with serum electrolyte concentrations.

Dietary electrolyte balance affects the nutrient digestibility and maintenance energy expenditure of Nile tilapia.

Acid-base disturbances caused by environmental factors and physiological events including feeding have been well documented in several fish species, but little is known about the impact of dietary electrolyte balance (dEB). In the present study, we investigated the effect of feeding diets differing in dEB (-100, 200, 500 or 800 mEq/kg diet) on the growth, nutrient digestibility and energy balance of Nile tilapia. After 5 weeks on the test diet, the growth of the fish was linearly affected by the dEB levels (P< 0·001), with the lowest growth being observed in the fish fed the 800 dEB diet. The apparent digestibility coefficient (ADC) of fat was unaffected by dEB, whereas the ADC of DM and protein were curvilinearly related to the dEB levels, being lowest and highest in the 200 and 800 dEB diets, respectively. Stomach chyme pH at 3 h after feeding was linearly related to the dEB levels (P< 0·05). At the same time, blood pH of the heart (P< 0·05) and caudal vein (P< 0·01) was curvilinearly related to the dEB levels, suggesting the influence of dEB on postprandial metabolic alkalosis. Consequently, maintenance energy expenditure (MEm) was curvilinearly related to the dEB levels (P< 0·001), being 54 % higher in the 800 dEB group (88 kJ/kg(0·8) per d) than in the 200 dEB group (57 kJ/kg(0·8) per d). These results suggest that varying dEB levels in a diet have both positive and negative effects on fish. On the one hand, they improve nutrient digestibility; on the other hand, they challenge the acid-base homeostasis (pH) of fish, causing an increase in MEm, and thereby reduce the energy required for growth.

Comparison of the utility of the classic model (the Henderson-Hasselbach equation) and the Stewart model (Strong Ion Approach) for the diagnostics of acid-base balance disorders in dogs with right sided heart failure.

Classically, the acid-base balance (ABB) is described by the Henderson-Hasselbach equation, where the blood pH is a result of a metabolic components--the HCO3(-) concentration and a respiratory component--pCO2. The Stewart model assumes that the proper understanding of the organisms ABB is based on an analysis of: pCO2, Strong Ion difference (SID)--the difference strong cation and anion concentrations in the blood serum, and the Acid total (Atot)--the total concentration of nonvolatile weak acids. Right sided heart failure in dogs causes serious haemodynamic disorders in the form of peripheral stasis leading to formation of transudates in body cavities, which in turn causes ABB respiratory and metabolic disorders. The study was aimed at analysing the ABB parameters with the use of the classic method and the Stewart model in dogs with the right sided heart failure and a comparison of both methods for the purpose of their diagnostic and therapeutic utility. The study was conducted on 10 dogs with diagnosed right sided heart failure. Arterial and venous blood was drawn from the animals. Analysis of pH, pCO2 and HCO3(-) was performed from samples of arterial blood. Concentrations of Na+, K+, Cl(-), P(inorganic), albumins and lactate were determined from venous blood samples and values of Strong Ion difference of Na+, K+ and Cl(-) (SID3), Strong Ion difference of Na+, K+, Cl(-) and lactate (SID4), Atot, Strong Ion difference effective (SIDe) and Strong Ion Gap (SIG4) were calculated. The conclusions are as follows: 1) diagnosis of ABB disorders on the basis of the Stewart model showed metabolic alkalosis in all dogs examined, 2) in cases of circulatory system diseases, methodology based on the Stewart model should be applied for ABB disorder diagnosis, 3) if a diagnosis of ABB disorders is necessary, determination of pH, pCO2 and HCO3(-) as well as concentrations of albumins and P(inorganic) should be determined on a routine basis, 4) for ABB disorder diagnosis, the classic model should be used only when the concentrations of albumins and P(inorganic) are normal.

Metabolic alkalosis due to feeding chicks in breeding Adélie penguins Pygoscelis adeliae under natural conditions.

Prolonged abnormal vomiting causes metabolic alkalosis. Many seabirds are known to feed their chicks by regurgitation. We hypothesized that metabolic alkalosis occurs in seabirds even under natural conditions during the breeding season. Adélie penguins Pygoscelis adeliae feed their chicks by regurgitating food for 50-60 d until the chicks fledge. In this study, the concentrations of Cl(-), HCO(3)(-), Na+, K+, pH, and PCO2 in the blood of breeding Adélie penguins were measured throughout the chick-rearing season. The pH of penguin venous blood shifted from 7.54 in the guarding period to 7.47 in the crèche period. Decreasing Cl(-) and increasing HCO(3)(-) blood concentrations in parents were associated with increasing mass of their brood in the guarding period, the early phase of the rearing season, indicating that regurgitating to feed chicks causes loss of gastric acid and results in relative metabolic alkalosis. The inverse trend was observed during the crèche period, the latter phase of the rearing season, when parents spent more time at sea and have fewer opportunities for gastric acid loss. This was assumed to be the recovery phase. These results indicate that regurgitation might cause metabolic alkalosis in breeding Adélie penguins. To our knowledge, this is the first report to indicate that seabirds exhibit metabolic alkalosis due to regurgitation to feed chicks under natural conditions.

High dietary calcium causes metabolic alkalosis in egg-type pullets.

One hundred sixty healthy egg-type pullets were randomly divided into 2 groups at 35 d of age. The groups were fed either with a normal-calcium (control, 8.5 g of Ca/kg) diet or with a high-calcium (HC, 36.3 g of Ca/kg) diet, respectively. The experiment lasted for 32 d. The healthy situations of the egg-type pullets were observed. Blood gas values and serum and urine electrolyte content were determined. The HC diet caused watery excreta in pullets. The pullets raised on the HC diet had significantly higher blood pH, bicarbonate, base excess, and significantly lower blood partial pressure of oxygen, partial pressure of carbon dioxide, and oxygen saturation than the pullets raised on the control diet. Phosphorus and potassium decreased; meanwhile, calcium increased in the HC group as compared with the control group. Sodium, magnesium, and chloride in serum had no significant difference between the HC group and the control. The pullets raised on the HC diet had significantly higher urine pH than the pullets raised on the control diet. For HC pullets, urinary concentration and 24-h urinary excretion of calcium and chloride was significantly higher, and magnesium, inorganic phosphorus, and sodium was significantly lower than that of the control pullets. It is concluded that some metabolic disorders associated with high dietary calcium in egg-type pullets may be related to a state of metabolic alkalosis.

Ultrasonographic findings in 2 cows with duodenal obstruction.

Two cases where clinical findings suggestive of proximal ileus resulting in hypokalemic and hypochloremic alkalosis are presented. Ultrasonographs showed distension of the sigmoid flexure along the ventral border of the liver and between the serosal lamellae of the greater omentum in the flank, allowing exact preoperative obstruction localization.

Metabolic alkalosis: a quick reference.

This article serves as a quick reference for metabolic alkalosis. Guidelines for analysis and causes, signs, and a stepwise approach are presented.

Making sense of blood gas results.

Recent technologic advances have allowed the production and marketing of cage-side blood gas analyzers to private practitioners. The widespread use of cage-side portable blood gas analyzers in veterinary practices has increased the need to develop the basic skills of blood gas analysis as part of a tool kit for practicing veterinarians. Rapid expansion of emergency and critical care medicine as a specialty and increased numbers of veterinary emergency and veterinary specialty practices have occurred concurrently with the availability of blood gas analyzers that are affordable for private practitioners. As a result, evaluation of blood gas results is no longer an activity confined to academic institutions and has become a daily part of many practicing veterinarians' activities.

Metabolic acid-base disorders in the critical care unit.

The recognition and management of acid-base disorders is a commonplace activity in the critical care unit, and the role of weak and strong acids in the genesis of metabolic acid-base disorders is reviewed. The clinical approach to patients with metabolic alkalosis and metabolic acidosis is discussed in this article.