Low Sodium: Potassium Ratios in Dogs and Cats
World Small Animal Veterinary Association World Congress Proceedings, 2003
J.A. Charles, BVSc, MVS, DACVP
Department of Veterinary Science, University of Melbourne
Werribee, Victoria, Australia

The classic electrolyte pattern of primary hypoadrenocorticism comprises hyponatraemia, hypochloraemia and hyperkalaemia. These abnormalities primarily reflect aldosterone deficiency, with impaired renal conservation of sodium (Na+) and excretion of potassium (K+) ions and depletion of the extracellular fluid (ECF) volume5-6. The normal serum sodium:potassium (Na+:K+) ratio in dogs and cats lies between 27:1 and 40:16. A low ratio (below 27:1) can be a valuable clue to the possibility of primary hypoadrenocorticism, especially if the ratio is greatly diminished6,12. However, a low ratio is neither pathognomonic of primary hypoadrenocorticism nor invariably present in affected animals.

In primary hypoadrenocorticism, insufficient aldosterone is secreted by the zona glomerulosa of the adrenal cortices. Aldosterone secretion is normally directly stimulated by hyperkalaemia and by angiotensin II which is produced in response to volume depletion. Aldosterone stimulates Na+ reabsorption and secretion of K+ and hydrogen (H+) ions in the distal nephrons. Its chief action is to increase the number of open Na+ channels in the luminal membranes of epithelial cells lining the distal tubules and collecting ducts. Sodium reabsorption via these channels generates electronegativity in the tubular lumen to promote K+ secretion. Electronegativity is dissipated by either passive reabsorption of chloride (Cl-) ions or by secretion of K+ or H+. Aldosterone also increases the number and activity of Na+-K+-ATPase pumps in the basolateral membranes of the tubular cells; this permits an increased intracellular K+ concentration to produce a chemical concentration gradient promoting K+ secretion into the tubular lumen3. High distal tubular flow rates also enhance K+ secretion by maintaining this concentration gradient between the tubular cells and the luminal fluid3,12. Aldosterone also promotes K+ secretion by increasing the number of open K+ channels in the luminal membranes of the tubular cells3.

In primary hypoadrenocorticism, hyponatraemia and hypochloraemia are chiefly a consequence of loss of Na+ and Cl- into urine5-6. Sodium loss leads to ECF volume depletion and often profound dehydration if fluid intake is inadequate6. Volume depletion is a strong non-osmotic stimulus for release of antidiuretic hormone (ADH or vasopressin). Impaired excretion of water loads due to ADH release may exacerbate the hyponatraemia by diluting ECF Na+5. Volume depletion also causes a decline in the glomerular filtration rate (GFR) and distal tubular flow rates and so contributes to both impaired water excretion and K+ retention5. Hyperkalaemia may also result from a shift in K+ from the intracellular to the extracellular compartment. This shift is enhanced by both aldosterone deficiency and by metabolic acidosis6.

Not all dogs and cats with primary hypoadrenocorticism have these electrolyte abnormalities3, 5-6, 12-13. Primary hypoadrenocorticism has a typically insidious onset and gradual course unless concurrent illness or other stress triggers an acute crisis by increasing the demand for mineralocorticoids6-7. Electrolyte levels may be normal or only hyponatraemia may be detectable early in the disease (when only glucocorticoid deficiency may be present) or if sampling occurs during a quiescent phase when clinical signs are minimal or absent5-6. Potassium balance may be preserved if Na+ intake is sufficient to maintain normal ECF volume and flow rates within the renal distal tubules3. Hyponatraemia developing in animals with glucocorticoid deficiency prior to the onset of mineralocorticoid deficiency is thought to result from volume depletion, activation of ADH, water retention and hence dilution of ECF Na+5-6. In these circumstances, hyponatraemia is not accompanied by hyperkalaemia6.

Electrolyte abnormalities are not anticipated in other forms of hypoadrenocorticism. In secondary hypoadrenocorticism, decreased pituitary secretion of ACTH chiefly affects the glucocorticoid-secreting zonae fasciculata and reticularis of the adrenal cortices rather than the mineralocorticoid-secreting zona glomerulosa. Only rarely do these animals develop dilutional hyponatraemia as described above6. Abrupt discontinuation of corticosteroid therapy after long term administration is also expected to cause only glucocorticoid deficiency, with no effect on electrolytes. Overdosage of hyperadrenocorticoid dogs with o,p'-DDD (mitotane) may occasionally cause necrosis of all three adrenocortical layers to result in both mineralocorticoid and glucocorticoid deficiency but usually the zona glomerulosa is spared and electrolyte levels remain normal6.

Whereas electrolyte abnormalities and a low Na+:K+ ratio in primary hypoadrenocorticism primarily reflect aldosterone deficiency, comparable electrolyte patterns may develop in non-adrenal disorders (particularly renal and gastrointestinal disease) despite normal to increased plasma aldosterone concentrations1, 4, 8-11, 14, 16-18. Clinical signs in some of these disorders may mimic hypoadrenocorticism. The decline in the Na+:K+ ratio may reflect hyponatraemia alone, hyperkalaemia alone or concurrent hyponatraemia and hyperkalaemia12-13. In a retrospective study of 34 dogs with Na+:K+ ratios lower than 24:1, hyperkalaemia was invariably present but not all dogs had hyponatraemia12. In this study, renal or urinary tract disease was the most common underlying disorder (41%) and only 24% of affected dogs had primary hypoadrenocorticism. Hypoadrenocorticism was the most common cause of a ratio less than 15:1.

Electrolyte patterns suggestive of primary hypoadrenocorticism and Na+:K+ ratios as low as 14:1 have been documented in dogs with primary gastrointestinal disease. 4, 8, 11 Trichuriasis has been the most common underlying disorder4, 8, 11 but other conditions have included combined trichuriasis and ancylostomiasis4, combined trichuriasis and ascariasis12, combined trichuriasis and enteric salmonellosis, combined trichuriasis and gastric torsion, and perforating duodenal ulcers4. Comparable electrolyte patterns have also been observed in dogs with gastroenteric signs referable to parvoviral or canine distemper virus infection and in dogs with severe malabsorption syndromes6. A slight decrease in the Na+:K+ ratio in association with mild hyponatraemia and normokalaemia has also been described in a dog with lymphocytic gastritis17.

Severe loss of fluids (whether isotonic or hypotonic) in vomitus and/or diarrhoea is expected to cause depletion of ECF volume, a decline in GFR and distal tubular flow rates, activation of the renin-angiotensin-aldosterone system (RAAS) (to promote renal Na+ and water retention) and non-osmotic stimulation of ADH release (to promote renal water retention). Although direct loss of Na+ in gastroenteric fluids or decreased Na+ intake due to inappetence or anorexia may contribute, hyponatraemia chiefly results from dilution of ECF Na+ by retained water. This dilution is compounded by increased water consumption due to stimulation of thirst4-5, 8, 11.

Hyperkalaemia may develop if hypovolaemia and hyponatraemia persist. Hyperkalaemia is thought to be largely attributable to decreased renal excretion of K+ due to volume depletion and decreased distal tubular flow rates3. In hypovolaemic states, resorption of Na+ and hence water by proximal renal tubules is enhanced, leading to reduced luminal delivery of fluid to the distal nephron. Low distal tubular flow rates reduce the concentration gradient which normally promotes K+ secretion into the tubular lumen. If the concentration of Na+ in the lumina of distal tubules becomes very low, decreased uptake of Na+ into distal tubular cells may diminish the electrochemical gradient required for movement of K+ ions into the lumen, thereby exacerbating the hyperkalaemia1, 3, 10. Metabolic acidosis arising from loss of bicarbonate (HCO3 ) ions in diarrhoea may also promote hyperkalaemia via translocation of intracellular K+ into the ECF4,8, 11.

Decreased urinary excretion of K+ is the usual mechanism responsible for hyperkalaemia in small animals3. Common non-adrenal causes include urethral obstruction, anuric or oliguric renal failure (especially acute renal failure but also terminal chronic renal failure) and bladder 6 rupture with uroperitoneum2-3. Affected animals are expected to have renal azotaemia and they may also have hyponatraemia, hypochloraemia, hypovolaemia, metabolic acidosis and a low Na+:K+ ratio2-3, 12, 17. Both hypovolaemia and metabolic acidosis may contribute to hyperkalaemia, the former by reducing GFR and hence distal tubular flow rates and the latter by promoting translocation of intracellular K+ into the ECF3. Hyponatraemia and hypochloraemia may largely reflect decreased dietary intake and gastrointestinal losses (especially via vomiting). However, in uroperitoneum, loss of fluid into the peritoneal cavity causes a reduced effective circulating volume, stimulation of RAAS, non-osmotic ADH release and stimulation of thirst so that dilution of ECF Na+ and Cl-ions by retained water occurs2,5.

There have been multiple reports of hyponatraemia, hyperkalaemia and low Na+:K+ ratios in dogs with body cavity effusions. Examples have included idiopathic and experimentally induced chylothorax16-17, pleural effusion associated with partial lung lobe torsion18 or metastatic mammary neoplasia12, abdominal effusion associated with congestive heart failure, pancreatitis or haemangiosarcoma12 and ascites secondary to peliosis hepatis and portal hypertension9. In some of these cases, electrolyte disturbances only emerged after repeated drainage of fluid16.

Almost all reported cases of electrolyte disorders associated with body cavity effusions have involved dogs. However, hyponatraemia, hyperkalaemia and a decreased Na+:K+ ratio below 25:1 have been recently described in four cats with peritoneal effusions1. One cat had peritoneal carcinomatosis and another feline infectious peritonitis; the cause of effusion was not established in the two other cats.

Development of hyponatraemia in some animals with cavity effusions may be explained simply by direct loss of isotonic fluid into the cavity12, 16, 18. Sodium loss into the subcutis and into a pleural effusion was postulated as the cause of hyponatraemia and hypovolaemia in a dog with a cutaneous/subcutaneous lymphangiosarcoma and suspected intrathoracic spread, with hyponatraemia being compounded by repeated drainage of fluid from both sites and by reduced Na+ intake due to inappetence10. However, many animals with body cavity effusions have a decreased effective circulating volume despite an increased total ECF volume1,5 . Decreased effective circulating volume would be expected to cause non-osmotic secretion of ADH, activation of RAAS and stimulation of thirst. Dilution of ECF Na+ by retained water would therefore be expected to contribute to hyponatraemia1,5. Consistent with retention of water, elevated plasma aldosterone and renin concentrations and decreased urine fractional excretion of Na+ were demonstrated in the dog with peliosis and ascites9. Similarly, an elevated serum aldosterone concentration was documented in one cat with a peritoneal effusion and two cats with peritoneal effusions were shown to be producing concentrated urine1.

Irrespective of the mechanism responsible for hyponatraemia, development of hyperkalaemia in animals with body cavity effusions is thought to chiefly reflect impaired renal K+ excretion due to hypovolaemia anddecreased distal tubular flow rates1,3, 5, 10, 16. An, inappropriately low urine fractional excretion of K+ despite an appropriate increase in aldosterone concentration and appropriate renal Na+ retention was demonstrated in a dog with pleural effusion due to lung lobe torsion18 and a dog with chylothorax16.

Repetitive episodes of external haemorrhage may cause hyponatraemia by direct Na+ loss. Daily phlebotomy over 14 consecutive days caused severe hyponatraemia in dogs fed low salt diets15. Affected dogs had impaired renal concentrating ability which was thought to be referable to hypo-osmolality, impaired ADH release and depletion of Na+ and Cl- from the renal medullary interstitium15. Some phlebotomised dogs also developed hyperkalaemia with impaired renal K+ excretion15, probably as a consequence of hypovolaemia and reduced distal tubular flow rates.

Ketoacidotic diabetes mellitus is another potential cause of hyperkalaemia, hyponatraemia, hypovolaemia and a low Na+:K+ ratio in dogs12. Hyponatraemia in diabetes chiefly results from excessive urinary loss of Na+ due to glycosuric osmotic diuresis6. Hyperosmolality due to hyperglycaemia may contribute to hyponatraemia by causing water to shift from intracellular to extracellular compartments5-6. Gastrointestinal loss of Na+ and reduced Na+ intake may also contribute. Insulin deficiency and hyperosmolality may both promote hyperkalaemia3,12 but ketoacidosis usually does not3. However, most diabetic patients have total body depletion of K+ because of urinary loss, loss of muscle mass, anorexia and vomiting, and hypokalaemia is more commonly detected than hyperkalaemia3.

Metabolic acidosis, prerenal azotaemia, hyperphosphataemia, hyponatraemia, hyperkalaemia and a low Na+:K+ ratio (as low as 14:1) despite normal adrenocortical function have been documented in three greyhound bitches presenting in late pregnancy with lethargy, muscle weakness, depression and vomiting. Two of these dogs had evidence of gastrointestinal haemorrhage but the gastrointestinal signs in all three were either of delayed onset or considered too mild to afford an explanation for the severity of the electrolyte changes. One bitch was found to have a uterine tear. A satisfactory explanation for the electrolyte pattern was not identified but the authors speculated that, as in women, progesterone may competitively inhibit aldosterone in bitches during pregnancy14.

Low Na+:K+ ratios associated with hyperkalaemia alone or with both hyperkalaemia and hyponatraemia have also been observed in individual dogs with mushroom poisoning, a behavioural disorder and a thyroid carcinoma12. The mechanisms responsible for the electrolyte disorders in these animals were not established. Pyometra and pancreatitis have also been diagnosed in individual dogs with low Na+:K+ ratios, severe hyponatraemia, milder hyperkalaemia and severe polyuria and polydipsia12. Renal Na+ loss and dilutional hyponatraemia were suspected to have contributed to the electrolyte abnormalities12.

Ultimately, accurate distinction of primary hypoadrenocorticism from other conditions causing hyponatraemia, hyperkalaemia and/or a low Na+:K+ ratio requires an ACTH stimulation test, with assays of pre and post-ACTH serum cortisol and/or plasma aldosterone 1, 4, 7-8, 10, 16-17. Animals with non-adrenal disorders may have normal to elevated baseline levels of cortisol and aldosterone and are expected to have a normal to exaggerated response of these hormones to ACTH 1, 4, 8, 10-11, 14, 16-18


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11. Malik R, Hunt GB, Hinchliffe JM, Church DB. Severe whipworm infection in the dog. J Sm Anim Pract 1990; 31:185-188.

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14. Schaer M, Halling KB, Collins KE, Grant DC. Combined hyponatremia and hyperkalemia mimicking acute hypoadrenocorticism in three pregnant dogs. J Am Vet Med Assoc 2001; 218:897-899.

15. Tyler RD, Qualls CW, Heald RD et al. Renal concentrating ability in dehydrated hyponatremic dogs. J Am Vet Med Assoc 1987; 191:1095-1100.

16. Willard MD, Fossum TW, Torrance A, Lippert A. Hyponatremia and hyperkalemia associated with idiopathic or experimentally induced chylothorax in four dogs. J Am Vet Med Assoc 1991; 199:353-358.

17. Willard MD, Refsal K, Thacker E. Evaluation of plasma aldosterone concentrations before and after ACTH administration in clinically normal dogs and in dogs with various diseases. Am J Vet Res 1987; 48:1713-1718.

18. Zenger E. Persistent hyperkalemia associated with nonchylous pleural effusion in a dog. J Am Anim Hosp Assoc 1992; 28:411-413.

Speaker Information
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J. A. Charles, BVSc, MVS, DACVP
Department of Veterinary Science, University of Melbourne
Werribee, Victoria, Australia

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