Felipedia

Hypokalemic Myopathy in cats

Aetiology

Hypokalemic myopathy is a metabolic disorder of older cats that has been linked with chronic renal disease and excessive urinary potassium loss, although a similar, if not identical disease, was reported in 1984. Synonyms are feline kaliopenic polymyopathy-nephropathy syndrome, and sporadic feline hypokalemic polymyopathy. Low dietary potassium intake secondary to inadequate potassium levels in certain commercial rations has been associated with episodic hypokalemic myopathy. Additionally, potassium urinary loss may be exacerbated by some diets that are acidified to reduce development of crystalluria and urolithiasis. It has been suggested that increased potassium loss induced by renal dysfunction may represent a phenomenon peculiar to cats. Furthermore, chronic potassium depletion (e.g., from deficient rations) may lead to progressive renal disease (associated with renal ischemia, increased renal ammoniagenesis, activation of the alternate complement pathway, and tubulointerstitial injury) as well as sudden changes in muscle membrane sodium permeability. Decreased extracellular potassium levels will produce an increase in resting membrane potential, resulting in a greater difference between resting and threshold potential necessary for muscle contraction. This lessened state of electrical excitability underlies the muscle weakness. Additionally, hypokalemia may negatively affect insulin release and end-organ sensitivity to insulin. Other causes of hypokalemia include gastrointestinal loss of potassium, post-obstructive diuresis following relief of urethral obstruction in cats, administration of loop or thiazide diuretics, and rarely, mineralocorticoid excess.

Clinical signs

Clinical signs are characterized by acute onset of a stiff-stilted gait, reluctance to walk, exercise intolerance, ventroflexion of the neck (especially in cats), and muscle pain. Spinal reflexes may be depressed. Serum CK levels are moderately to markedly elevated, while serum potassium values are low (e.g., < 4.0 mEq/L). Serum creatinine levels may be markedly increased. In the hypokalemic cats fed a high-protein vegetarian diet, plasma taurine concentrations decreased and glutamic acid increased markedly. Mild, diffuse electromyographic changes (e.g., presence of positive sharp waves) have been recorded in various skeletal muscles. Light microscopic evaluation of muscle samples is usually normal, although myofibril vacuolation and mild myonecrosis may occasionally be observed. Ultrastructural changes in people indicate that the vacuoles are membrane-bound and reveal the frequent presence of tubular aggregates that selectively involve type 2 fibres. Rhabdomyolysis in severe hypokalemia might be related to osmotic expansion of cells due to increased intracellular sodium and chloride levels or reflect ischemic myonecrosis due to decreased muscle blood flow associated with impaired potassium metabolism during muscle contraction/exercise.

Prognosis is guarded to favourable and may depend upon the severity of the underlying renal disease, if present. Most cats reportedly show significant improvement in muscle strength within 2 to 3 days of initiation of treatment. Oral potassium supplementation (e.g., potassium gluconate - Tumil-Ktm, Daniels Pharmaceuticals), at 5 to 10 mEq/cat/day, divided bid, is recommended for severely hypokalemic cats. For less severely affected animals, 2 to 4 mEq/day is usually adequate. Permanent daily supplementation with regular re-evaluation of serum potassium, serum creatinine, and urinary potassium loss is recommended, since cats that are not supplemented have a tendency to become hypokalemic again.

Severe hypokalemia and generalized flaccid paralysis has been reported in a 6 year old female Miniature Poodle after furosemide administration for suspected congestive heart failure. In this case, hypokalemia presumably resulted from an increased flow rate in the distal tubules and increased secretion of aldosterone secondary to volume depletion caused by the thiazide diuretic. Muscle biopsies showed severe myonecrosis, phagocytosis, fibre splitting, internalised nuclei, and atrophy/hypertrophy. Peripheral nerve biopsy was normal. After treatment of the hypokalemia (intravenous fluids and potassium supplementation), the dog was clinically normal within 16 days of complete paralysis, while muscle biopsies were normal within 30 days.

Note that hypokalemia may also result from various metabolic and endocrine disorders. In one report, hypokalemic myopathy occurred in 9 cats as a result of severe diabetic ketoacidosis and its therapy (e.g., hypokalemic may result from the attendant osmotic diuresis, correction of the acidosis, or insulin-mediated cell uptake). In this study, normokalemia and the myopathy resolved within a few days of potassium supplementation. Acute onset of muscular weakness and ventroflexion of the neck have been reported in several hyperthyroid cats in association with hypokalemia, the cause of which was not determined. Cats responded quickly to potassium supplementation or following resolution of the hyperthyroidism. In humans, nonfamilial hypokalemic thyrotoxic periodic paralysis is commonly seen among Asians. It has been reported that sudden paralysis occurring while at rest after a large carbohydrate meal or strenuous exercise is a common presentation and that intracellular shifts of potassium triggered or facilitated by hyperthyroidism and hyperinsulinemia are the biochemical features. Correction of the hyperthyroidism is the definitive treatment in people. A periodic myopathy characterized by muscle stiffness, weakness, and pain secondary to persistent hypokalemia and metabolic alkalosis has been reported in a German Shepherd with an hepatic neuroendocrine carcinoma, thought to be a primary hepatic carcinoid [128]. Ectopic adrenocorticotrophin hormone secretion was suspected as the cause of hypercortisolism and hypokalemia (possibly associated with cortisol inactivation overload). Note that in most dogs with hyperadrenocorticism, hypokalemia is either not seen or is mild and clinically insignificant. Hypokalemia secondary to an aldosterone producing tumour of the adrenal gland (Conn’s syndrome) has been observed in cats. Aldosterone normally regulates electrolyte/fluid balance by facilitating sodium retention and potassium excretion. Clinical signs included intermittent muscle weakness and collapse that became progressively more severe. Blood biochemical studies revealed elevated aldosterone levels and high serum creatine kinase levels. Temporary improvement resulted from administration of spironolactone at 10 - 100 mg PO daily.

A second type of hypokalemic myopathy has been reported in young Burmese kittens, 2 to 6 months of age, although the disorder has also been reported in a 2 year old Burmese cat. This condition is considered to be a homozygote recessive hereditary disease and is characterized by periodic muscle weakness and ventroflexion of the neck associated with intermittent hypokalemia (e.g., < 3.0 mE/L) and increased serum creatine kinase values, sometimes reaching very high values, e.g., > 50,000 - 90,000 IU/L. The condition has also been termed periodic hypokalemic myopathy. Attacks occur suddenly and are transient and may be precipitated by stress or vigorous exercise. The variable clinical course is characterized by improvement followed by relapse, and there may be weeks between episodes. A head tremor is seen in some cats. Cats are reluctant to walk and tire easily, have a stiff, stilted gait with thoracic limb hypermetria, and a wide-based stance in the hind limbs. Carpal knuckling can be a distinctive clinical feature and some cats sink on their hocks. There are only minor electromyographic and histopathologic changes seen in muscle. Neither decreased potassium intake nor increased renal potassium loss have been found in affected Burmese cats. Continued dietary supplementation of oral potassium usually produces a favorable response (e.g., potassium gluconate solution at 2 to 4 mEq or mmol/cat PO daily, until serum potassium levels are stable). Some kittens improve without treatment. The periodic hypokalemic attacks in these cats are similar to those seen in humans with hypokalemic periodic paralysis, an inherited calcium channelopathy disorder associated with abnormal muscle membrane excitability and influx of potassium into the muscle fiber that causes muscle fiber depolarization and inexcitability. Patients have an increased sensitivity to insulin moving potassium into cells.