Qualification of the Stewart variables for the assessment of the acid-base status in healthy dogs and dogs with different diseases

Peter Stewart criticized the traditional theory of the acid-base status by Henderson-Hasselbalch as too simple and incomplete. He developed a new model with 3 independent variables: (1) pCO2, (2) SID (strong ion difference) and (3) Atot (Acid total). In healthy and ill dogs the diagnostic usefulness of both acid-base models were compared. This study included n=58 healthy dogs and 3 clinical cases of sick dogs.The age of the healthy dogs was 5.0 (2.0-7.0) years (= median (1.-3. quartil)).The 3 clinical cases included (1) a dog with septic shock, (2) with acute renal insufficiency, and (3) with hypovolaemic shock due to gastric torsion.Venous blood was taken of all dogs and the acid-base parameters were determined within < or =30 minutes. Electrolytes and albumin were determined in blood serum and used for calculation of the Stewart variables. Limits of reference intervals (x+/-1.96 - s) were determined for the healthy dogs yielding pCO2 = 3.6-6.5 kPa, [SID3] = 33.1-50.9 mmol/l resp. [SID4] = 31.8-49.6 mmol/l and [Al = 8.5-13.1 mmol/l. In Case 1 the Henderson-Hasselbalch parameters demonstrated the presence of a strong metabolic acidosis with mild respiratory influence (pH, [HCO3-], [BE] and PCO2 at upper range of normal). Analysis of the Stewart variables [SID3] resp. [SID4] revealed an electrolyte imbalance with [Cl-] and [lactate-] as the reason for metabolic acidosis. Case 2 showed a metabolic acidosis with respiratory compensation (pH, [HCO3-], [BE] and PCO2). Analysis of the Stewart variables with [SID3] resp. [SID4 caused by [K+], [Na+] and [lactate-]demonstrated the acidotic metabolism due to a renal malfunction. Case 3 had a metabolic acidosis (pH-value in the lower range) caused by electrolyte imbalances ([SID4]. The Stewart variables allow a better understanding of the causes of acid-base-disturbances in animals with implications for successful therapy via infusion.     

A Comparison of Simultaneously Collected Arterial, Mixed Venous, Jugular Venous and Cephalic Venous Blood Samples in the Assessment of Blood-Gas and Acid-Base Status in the Dog

Blood samples were collected simultaneously from the pulmonary artery, jugular vein, cephalic vein, and carotid artery in awake dogs. Blood-gas and acid-base values were measured from these blood samples in normal dogs and in dogs after production of metabolic acidosis and metabolic alkalosis. The values obtained from each of the venous sites were compared with those obtained from arterial blood to determine if venous blood from various sites accurately reflected acid-base balance and could therefore be used in the clinical patient. The results of this study demonstrated significant differences between the blood from various venous sites and the arterial site for PCO2 and pH in all acid-base states. Significant differences for standard bicarbonate (SHCO3) were found only when jugular and cephalic venous blood were compared with arterial blood in dogs with a metabolic acidosis. No significant differences were found for BE when blood from the venous sites was compared with arterial blood. The values for pH, HCO3, TCO2, BE, and SHCO3 measured on blood collected at the various venous sites were found to correlate well with those obtained from arterial blood, with a correlation coefficient of 0.99 for HCO3, TCO2, BE, and SHCO3. These correlation coefficients, together with similar values in BE at all collection sites, indicate that, in the dog with normal circulatory status, blood from any venous site will accurately reflect the acid-base status of the patient.     

Ventilatory and Metabolic Compensation in Dogs With Acid-Base Disturbances

Ventilatory and metabolic compensation to acid-base disturbances is reviewed. The mechanisms for compensation as well as the values obtained from several studies using normal dogs and dogs with experimentally induced diseases are provided. Compensation is not the same in dogs and human beings. Dogs have a better ability to adapt to most respiratory disorders, and human beings adapt better to metabolic acidosis. In metabolic alkalosis and chronic respiratory acidosis there is no difference in compensation between these species. Ventilatory compensation for metabolic disorders in dogs is the same whether they have metabolic acidosis or metabolic alkalosis, whereas metabolic compensation in respiratory disturbances is less effective in acidosis. Values for the expected changes in PCO₂ in dogs with metabolic acidosis and metabolic alkalosis, and for bicarbonate concentration (HCO₃-) in dogs with acute and chronic respiratory alkalosis and acidosis are presented.     

Contemporary approach to acid-base balance and its disorders in dogs and cats

The issue of the acid-base balance (ABB) parameters and their disorders in pets is rarely raised and analysed, though it affects almost 30% of veterinary clinics patients. Traditionally, ABB is described by the Henderson-Hasselbach equation, where blood pH is the resultant of HCO3- and pCO2 concentrations. Changes in blood pH caused by an original increase or decrease in pCO2 are called respiratory acidosis or alkalosis, respectively. Metabolic acidosis or alkalosis are characterized by an original increase or decrease in HCO3- concentration in the blood. When comparing concentration of main cations with this of main anions in the blood serum, the apparent absence of anions, i.e., anion gap (AG), is observed. The AG value is used in the diagnostics of metabolic acidosis. In 1980s Stewart noted, that the analysis of: pCO2, difference between concentrations of strong cations and anions in serum (SID) and total concentration of nonvolatile weak acids (Atot), provides a reliable insight into the body ABB. The Stewart model analyses relationships between pH change and movement of ions across membranes. Six basic types of ABB disorders are distinguished. Respiratory acidosis and alkalosis, strong ion acidosis, strong ion alkalosis, nonvolatile buffer ion acidosis and nonvolatile buffer ion alkalosis. The Stewart model provides the concept of strong ions gap (SIG), which is an apparent difference between concentrations of all strong cations and all strong anions. Its diagnostic value is greater than AG, because it includes concentration of albumin and phosphate. The therapy of ABB disorders consists, first of all, of diagnosis and treatment of the main disease. However, it is sometimes necessary to administer sodium bicarbonate (NaHCO3) or tromethamine (THAM).     

Chloride Ion in Small Animal Practice: The Forgotten Ion

The Physiology of chioride ion and its relationship to clinical disorders in small animall practice is reviewed. Chioride is the major anion in the extracellular fluid and is important in the metabolic regulation of acid-base balance. A new clinical approach is used to assess chloride ion changes after accounting for changes in free water. Using this approach chloride disorders can be divided into corrected and artifactual. Changes in free water are solely responsible for the chioride ion changes in artifactual disorders, whereas in corrected chloride disorders, chloride ion itself changes. Corrected hypochioremia is associated with increases in the strong ion differece (SID) and metabolic alkalosis and is caused by administration of solution containing a high concentration of sodium relative to chioride (e.g., Sodium bicarbonate) or the excessive loss chioride relative to sodium (e.g., vomiting of stomach contents). Administration of chioride is correction of hypochioremic metabolic alkalosis. Corrected hyperchioremia is associated with a decreased SID and metabolic acidosis and is usually the result of excessive loss of sodium relative to chloride (e.g., diarrhea), chioride retention (e.g., renal tubular acidosis), or therapy with solutions containing a high concentration of chioride relative to sodium (e.g.,0.9% sodium chloride;3–24% hypertonic saline). Treatment with sodium bicarbonate should be attempted in patients with corrected hyperchioremia and a plasma pH beiow 7.2.     

Arterialized capillary blood used to determine the acid-base and blood gas status of dogs.

Blood samples were collected by microhematocrit tube from posterior medial margin of the shaved, but otherwise untreated, canine ear. Acid-base and blood gas values of these samples were compared with the values of samples obtained simultaneously from the carotid artery. The arterialized nature of capillary blood from the canine ear was demonstrated under various degrees of chemical restraint and during conditions of extreme hypoxic acidosis to hyperventilatory alkalosis. Once a week determinations of acid-base and blood gas status with such arterialized capillary blood from a group of awake dogs showed within-subject variance to be significantly less (P less than 0.05) than between-subject variance; thus, uniqueness of individual dogs was reliably revealed. This technique also was used to demonstrated breed differences for acid-base and blood gas characteristics.     

Metabolic and electrolyte disturbances in acute canine babesiosis.

Arterial blood pH, PCO2, bicarbonate, base excess/deficit, and lactate, as well as serum sodium, potassium, and chloride were measured in clinically normal dogs and in dogs with acute canine babesiosis. Metabolic acidosis developed in dogs with fatal as well as nonfatal Babesia canis infection. In the fatal group, the acidosis was uncompensated; among survivors, base deficit and blood lactate were significantly lower, and pH, PCO2, and bicarbonate values were significantly higher. Serum potassium values were significantly lower, and serum chloride values were significantly higher in dogs with acute babesiosis than in clinically normal dogs. The shock resulting from acute canine babesiosis is best viewed as anemic shock. Treatment should include an alkalizing agent, a blood transfusion, fluid therapy, and a babesicidal drug.     

Simple acid-base disorders

The body regulates pH closely to maintain homeostasis. The pH of blood can be represented by the Henderson-Hasselbalch equation: pH = pK + log [HCO3-]/PCO2 Thus, pH is a function of the ratio between bicarbonate ion concentration [HCO3-] and carbon dioxide tension (PCO2). There are four simple acid base disorders: (1) Metabolic acidosis, (2) respiratory acidosis, (3) metabolic alkalosis, and (4) respiratory alkalosis. Metabolic acidosis is the most common disorder encountered in clinical practice. The respiratory contribution to a change in pH can be determined by measuring PCO2 and the metabolic component by measuring the base excess. Unless it is desirable to know the oxygenation status of a patient, venous blood samples will usually be sufficient. Metabolic acidosis can result from an increase of acid in the body or by excess loss of bicarbonate. Measurement of the "anion-gap" [(Na+ + K+) - (Cl- + HCO3-)], may help to diagnose the cause of the metabolic acidosis. Treatment of all acid-base disorders must be aimed at diagnosis and correction of the underlying disease process. Specific treatment may be required when changes in pH are severe (pH less than 7.2 or pH greater than 7.6). Treatment of severe metabolic acidosis requires the use of sodium bicarbonate, but blood pH and gases should be monitored closely to avoid an "overshoot" alkalosis. Changes in pH may be accompanied by alterations in plasma potassium concentrations, and it is recommended that plasma potassium be monitored closely during treatment of acid-base disturbances.     

Acid-base and electrolyte abnormalities in dogs with gastrointestinal foreign bodies

Gastrointestinal foreign bodies occur commonly in dogs. The objective of the study was to describe the acid-base and electrolyte abnormalities identified in dogs with gastrointestinal foreign bodies and determine if these abnormalities are related to the site or type of foreign body present. Medical records of 138 dogs were reviewed, and information on signalment, initial venous electrolyte and acid-base values, surgical findings, relevant historical information, imaging modalities used, cost of hospital visit, intra- or postoperative complications, and survival was obtained. The site of the foreign body was recorded in 94.9% of cases and the most common site was the stomach (50%), followed by the jejunum (27.5%). The foreign bodies were linear in 36.2% of cases. The most common electrolyte and acid-base abnormalities regardless of the site or type of foreign body were hypochloremia (51.2%), metabolic alkalosis (45.2%), hypokalemia (25%), and hyponatremia (20.5%). No significant association was found between electrolyte or acid-base abnormalities and the site of foreign body. Linear, as opposed to discrete, foreign bodies were more likely to be associated with a low serum sodium concentration (odds ratio, 0.85; 95% confidence interval, 0.75-0.95). Hyperlactatemia (> 2.4 mmol/L) was seen in 40.5% of dogs. A wide variety of electrolyte and acid-base derangements are found in dogs with gastrointestinal foreign bodies. Hypochloremia and metabolic alkalosis are common in these dogs. Hypochloremic, hypokalemic metabolic alkalosis is seen with both proximal and distal gastrointestinal foreign bodies.     

Relationship between depression score and acid-base status in Japanese Black calves with diarrhea

We evaluated the relationship between depression score and acid-base status in 84 purebred and crossbred Japanese Black calves. The bicarbonate (p<0.001) and base excess concentrations (p<0.001) were significantly and negatively correlated with the depression scores of the calves. The proposed diagnostic cutoff point for a depression score that indicates severe metabolic acidosis (BE < -10 mM) is 6.5 based on analysis of the ROC curve. The sensitivity and specificity were 88.4% and 81.2%, respectively. The depression scoring system is a useful tool for evaluation of the acid-base status of purebred and crossbred Japanese Black calves. In addition, a depression score of 6.5 suggests severe metabolic acidosis and that intravenous infusion of sodium bicarbonate solution is necessary.     

Prevalence and risk factors of hypoglycemia in virulent canine babesiosis

Hypoglycemia is a common complication of virulent canine babesiosis. A study was conducted to determine the prevalence of and potential risk factors for hypoglycemia in canine babesiosis from Babesia canis rossi. Plasma glucose concentration was measured at presentation in 250 dogs with babesiosis, of which 111 were admitted to hospital. The prevalence of hypoglycemia (<60 mg/dL) was 9% (23/250). Twenty-two hypoglycemic dogs required admission, making the prevalence of hypoglycemia in admitted dogs 19.8%. Sixteen dogs had severe hypoglycemia (<40 mg/dL), of which 5 had glucose < 18 mg/dL. Hyperglycemia (>100 mg/dL) was present in 38 dogs, of which 21 were admitted. Risk factors for hypoglycemia identified by univariate analysis were collapsed state (P < .00001), severe anemia (P = .0002), icterus (P = .003), age < 6 months (P = .02), and vomiting (P = .03). After logistic regression analysis, collapsed state (odds ratio [OR] = 18; 95% CI, 1.9-171; P = .01) and young age (OR = 2.8; 95% CI, 0.8-9.7; P = .1) remained significantly associated with hypoglycemia. Toy breeds and pregnant bitches were not at higher risk for hypoglycemia than other dogs. Blood glucose concentration should ideally be measured in all dogs requiring inpatient treatment for babesiosis but is mandatory in collapsed dogs; puppies; and dogs with severe anemia, vomiting, or icterus. Many dogs have probably been misdiagnosed with cerebral babesiosis in the past, and hypoglycemia should be suspected in any dog with coma or other neurological signs.     

A prospective, randomized comparison of Oxyglobin (HB-200) and packed red blood cell transfusion for canine babesiosis

Objective – To establish the efficacy of Oxyglobin (HB-200) in canine babesiosis and compare it to standard therapy, packed red blood cell transfusion (pRBCT) with respect to improvements in specific parameters of blood gas, acid-base, blood pressure, and subjective evaluations.
Design – Prospective, randomized, clinical trial.
Setting – Onderstepoort Veterinary Academic Hospital.
Animals – Twelve dogs (8–25 kg) naturally infected with Babesia rossi and a hematocrit of 0.1–0.2 L/L (10–20%).
Interventions – Treatment groups were randomized to receive either 20 mL/kg of Oxyglobin or pRBCT over 4 hours via a central venous catheter. Transfusions were followed by lactated Ringer's solution infusion. Rectal temperature, femoral arterial and mixed venous blood sampling, oscillometric blood pressure, and subjective assessment of patient status (habitus), and appetite were performed at time points 0, 1, 4, 8, 24, 48, and 72 hours.
Main Results – Dogs presented with a hypoalbuminemic alkalosis; hyperchloremic, dilutional acidosis; normotensive tachycardia; pyrexia; depression; and anorexia. Both treatments produced similar results, with the exception of significant differences in pH (4 h); PCO₂ (4 h); hemoglobin (8 h, 24 h); mean arterial pressure (48 h); albumin (4 h, 8 h); habitus (8 h, 48 h); and appetite (24 h). Arterial O₂ content was higher for pRBCT than Oxyglobin at 72 hours, but central venous PO₂ did not differ between groups or over time and was consistently subnormal.
Conclusions – Oxyglobin provides similar overall improvements to pRBCT in dogs with anemia from babesiosis, with respect to blood gas, acid-base and blood pressure, although patients receiving packed cells tended to have more rapid normalization of habitus and appetite.     

Acid-base and electrolyte alterations associated with salivary loss in the pony

Esophageal fistulas were made in 6 ponies to evaluate whole blood acid-base values and serum and salivary electrolyte alterations associated with salivary depletion. Acid-base and electrolyte values remained within normal ranges for 15 days in 3 control ponies fed a pelleted diet through nasogastric tubes. In 6 ponies with esophageal fistulas that were fed the same diet through esophagostomy tubes, hypochloremia and hyponatremia developed during the same period. Serum K concentrations were only marginally depleted, probably because of dietary replacement. Salivary depletion resulted in transient metabolic acidosis from bicarbonate lost in saliva followed by progressive metabolic alkalosis. The alkalosis probably resulted from renal compensation of electrolyte imbalances. Salivary electrolytes were in high concentrations, probably because of increased salivary flow rates. Initial saliva was rich in Na, Cl, and K, but progressive reduction in salivary Na and Cl concentrations occurred during the 5-day collection period. These electrolyte savings could be explained by dietary influences and hormonal control of electrolyte transport in salivary ducts. Therapy for correction of acid-base and electrolyte alterations was also discussed.     

Evaluation of acid-base disturbances in calf diarrhoea

The severity of acid-base disturbances in diarrhoeic calves was investigated and a simple, inexpensive method of monitoring them was evaluated. The Harleco apparatus measures the 'total carbon dioxide' in a blood sample, mostly generated from the bicarbonate present, and any abnormalities are mainly due to metabolic acidosis or alkalosis. Its performance was tested against a standard blood gas analyser by comparing the results obtained by both methods with nearly 2000 blood samples from healthy or diarrhoeic calves. After technical modifications, the technique gave excellent precision and accuracy for the clinical evaluation of acid-base balance, using venous whole blood. The samples were very stable, especially at 0 degrees C, but also at room temperature. The normal range (mean +/- 1.96 sd) for total carbon dioxide in whole blood from calves was 21 to 28 mmol/litre. For samples corresponding to mild, moderate or severe acidosis, 79 per cent were correctly classified by the Harleco apparatus and only 0.1 per cent were beyond the adjacent degree of severity. After four days of diarrhoea, the calves which later died had twice the deficit in plasma bicarbonate of those which survived. As death approached, the deficit was almost three times that in surviving calves and the blood pH shortly before death was as low as 6.79 +/- 0.08. The Harleco apparatus was less successful with alkalotic samples, but metabolic alkalosis is less common and usually less severe.     

Experimental determination of net protein charge and A(tot) and K(a) of nonvolatile buffers in canine plasma

Acid-base abnormalities frequently are present in sick dogs. The mechanism for an acid-base disturbance can be determined with the simplified strong ion approach, which requires accurate values for the total concentration of plasma nonvolatile buffers (A(tot)) and the effective dissociation constant for plasma weak acids (K(a)). The aims of this study were to experimentally determine A(tot) and K(a) values for canine plasma. Plasma was harvested from 10 healthy dogs; the concentrations of quantitatively important strong ions (Na+, K+, Ca2+, Mg2+, Cl-, L-lactate) and nonvolatile buffer ions (total protein, albumin, phosphate) were determined; and the plasma was tonometered with CO2 at 37 degrees C. Strong ion difference (SID) was calculated from the measured strong ion concentrations, and nonlinear regression was used to estimate values for A(tot) and K(a), which were validated with data from an in vitro and in vivo study. Mean (+/- SD) values for canine plasma were A(tot) = (17.4 +/- 8.6) mM (equivalent to 0.273 mmol/g of total protein or 0.469 mmol/g of albumin); K(a) = (0.17 +/- 0.11) x 10(-7); pK(a) = 7.77. The calculated SID for normal canine plasma (pH = 7.40; P(CO2) = 37 mm Hg; [total protein] = 64 g/L) was 27 mEq/L. The net protein charge for normal canine plasma was 0.25 mEq/g of total protein or 0.42 mEq/g of albumin. Application of the experimentally determined values for A(tot), K(a), and net protein charge should improve understanding of the mechanism for complex acid-base disturbances in dogs.     

Clinical signs, diagnosis, and treatment of alkalemia in dogs: 20 cases (1982-1984)

Alkalemia (pH greater than 7.50) was measured in 20 dogs admitted over a 3-year period for various clinical disorders. Alkalemia was detected in only 2.08% of all dogs in which blood pH and blood-gas estimations were made. Thirteen dogs had metabolic alkalosis (HCO3- greater than 24 mEq/L, PCO2 greater than 30 mm of Hg), of which 8 had uncompensated metabolic alkalosis, and of which 5 had partially compensated metabolic alkalosis. Seven dogs had respiratory alkalosis (PCO2 less than 30 mm of Hg, HCO3- less than 24 mEq/L); 4 of these had uncompensated respiratory alkalosis and 3 had partially compensated respiratory alkalosis. Ten dogs had double or triple acid-base abnormalities. Dogs with metabolic alkalosis had a preponderance of clinical signs associated with gastrointestinal disorders (10 dogs). Overzealous administration of sodium bicarbonate or diuretics, in addition to anorexia, polyuria, or hyperbilirubinemia may have contributed to metabolic alkalosis in 8 of the dogs. Most of the dogs in this group had low serum K+ and Cl- values. Two dogs with metabolic alkalosis had PCO2 values greater than 60 mm of Hg, and 1 of these had arterial hypoxemia (PaO2 less than 80 mm of Hg). Treatments included replacement of fluid and electrolytes (Na+, K+, and Cl-), and surgery as indicated (8 dogs). Six dogs with respiratory alkalosis had a variety of airway, pulmonary, or cardiac disorders, and 3 of these had arterial hypoxemia. Two other dogs were excessively ventilated during surgery, and 1 dog had apparent postoperative pain that may have contributed to the respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical Applications of Quantitative Acid-Base Chemistry

Stewart used physicochemical principles of aqueous solutions to develop an understanding of variables that control hydrogen ion concentration (H+) in body fluids. He proposed that H+ concentration in body fluids was determined by PCO₂, strong ion difference (SID = sum of strong positive ion concentrations minus the sum of the strong anion concentrations) and the total concentration of nonvolatile weak acid (A_tot) under normal circumstances. Albumin is the major weak acid in plasma and represents the majority of A_tot. These 3 variables were defined as independent variables, which determined the values of all other relevant variables (dependent) in plasma, including H+. The major strong ions in plasma are sodium and chloride. The difference between Na+ and Cl^- may be used as an estimation of SID. A decrease in SID below normal results in acidosis (increase in H+) and an increase in SID above normal results in alkalosis (decrease in H+). Unidentified strong anions such as lactate will decrease the SID, if present. Equations developed by Fencl allow Stewart's work to be easily applied clinically for evaluating the metabolic (nonrespiratory) contribution to acid-base balance. This approach separates the net metabolic abnormality into components, and allows one to easily detect mixed metabolic acid-base abnormalities. The Fencl approach provides insight into the nature and severity of the disturbances that exist in the patient. Sodium, chloride, protein, and unidentified anion derangements may contribute to the observed metabolic acid-base imbalance.     

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.