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Hyponatremia and hyperkalemia
SMALL ANIMALS
associated with peritoneal effusion in four cats
Sally A. Bissett, BVSc, MVSc; Martin Lamb, BVetMed; Cynthia R. Ward, VMD, PhD, DACVIM
' Peritoneal effusions may cause concurrent
hyponatremia and hyperkalemia in cats.
' Hyponatremia and hyperkalemia may develop
despite normal adrenal gland function.
' Recognition of effusive states as a cause of
hyponatremia and hyperkalemia is important to
avoid an incorrect diagnosis of hypoadrenocorti-
cism and to avoid unnecessary ancillary tests.
A 14-year-old castrated male domestic shorthair cat
(cat 1) was referred to the Veterinary Hospital of
the University of Pennsylvania for evaluation of peri-
toneal effusion. The cat had a history of anorexia for
10 days and vomiting for 2 days. Hyperkalemia
(6.6 mEq/L; reference range 3.5 to 5.1 mmol/L) and
abdominal fluid, characterized as a modified transu-
date, were detected by the referring veterinarian 5
days prior to referral.
Physical examination revealed generalized muscle
wasting, a grade II/V systolic murmur, severe abdomi-
nal distension, and signs of pain on palpation of the
abdomen. A CBC and serum biochemical analysis were
performed; abnormal results included lymphopenia,
hyponatremia, hyperkalemia, mildly increased aspar-
tate aminotransferase activity, mild hyperbilirubine-
mia, and low total CO2 concentration (Table 1).
Results of venous blood gas analysis revealed mild
metabolic acidosis (pH 7.32; reference range, 7.36 to
7.47; base excess, –6.6; reference range, –4.0 to 4.0;
bicarbonate, 19.5; reference range, 22 to 28). Results of
peritoneal fluid analysis revealed a modified transudate
containing an abnormal population of cohesive epithe-
lial cells. The epithelial cells had severe anisocytosis
and anisokaryosis, suggestive of carcinoma.
Ultrasonography of the abdomen was performed and
revealed peritoneal effusion and masses within the cra-
nial portion of the mesentery. No evidence of heart dis-
ease was detected echocardiographically. On the basis
of cytologic and ultrasonographic findings, a tentative
diagnosis of abdominal carcinomatosis was made.
The electrolyte abnormalities detected in this cat
were strongly suggestive of hypoadrenocorticism
(Na:K ratio, 24.3; reference range, > 26); for this rea-
son, an ACTH stimulation test was performed. Blood
samples were collected for measurement of serum cor-
tisol and aldosterone concentrations before and 1 hour
after administration of ACTH gela (2.2 U/kg [1 U/lb] of
body weight, IM). Results of serum cortisol and
From the Departments of Clinical Studies (Bissett, Ward) and
Pathobiology (Lamb), School of Veterinary Medicine, The
University of Pennsylvania, Philadelphia, PA 19104.
Address correspondence to Dr. Ward.
1590 Scientific Reports: Clinical Report
aldosterone concentration measurements did not sup-
port a diagnosis of adrenal insufficiency (Table 2).
The owners decided against further diagnostic testing,
and the cat was euthanatized by the referring veteri-
narian 1 week later. A necropsy was not performed.
Medical records of 3 additional cats examined at
the Veterinary Hospital of the University of
Pennsylvania because of peritoneal effusion in conjunc-
tion with hyponatremia and hyperkalemia were
reviewed (cats 2, 3, and 4). These 3 cats were examined
between June 1992 and November 1998 and had either
an ACTH stimulation test or a necropsy performed in
an attempt to rule out hypoadrenocorticism. All 3 cats
were evaluated for weight loss and inappetence of 1 to
3 weeks’ duration, and 2 owners had noticed abdominal
enlargement (cats 3 and 4) prior to evaluation. Cats 2
and 3 were from multi-cat households, and 3 cats were
reported to have died from feline infectious peritonitis
(FIP) 3 years earlier in the same household as cat 3. On
physical examination, all cats had a severely distended
abdomen, and abdominal fluid was detected on abdom-
inal palpation. In addition, 1 cat (cat 2) had signs of
abdominal pain, an intermittent fever (103 to 105 F
[39.4 to 40.6 C]), and a grade II/V systolic murmur.
Results of CBC and serum biochemical analyses of
these 3 cats included leukocytosis, lymphopenia,
hyponatremia, hyperkalemia, hypochloremia, hypoal-
buminemia, increased aspartate aminotransferase activ-
ities, increased γ-glutamyltransferase activities, and
mild hyperbilirubinemia (Table 1). All 3 cats had severe
and repeatable hyponatremia and hyperkalemia, with
Na:K ratios < 23. Urinalysis was performed in cats 2
and 3 and revealed concentrated urine (urine specific
gravity, > 1.040) and mild bilirubinuria in both.
Peritoneal fluid analysis revealed a modified transudate
with predominance of nondegenerate neutrophils and
macrophages in all cats. Massive peritoneal effusion
(cats 2, 3, and 4), diffusely hyperechoic liver with
rounded borders (cats 2 and 3), and hyperechoic renal
cortices (cats 2 and 3) were evident on ultrasonography
of the abdomen. Radiography of the thorax was per-
formed in 2 cats (cats 2 and 3); no abnormalities were
evident. Results of FeLV and feline immunodeficiency
virus serologic tests (cats 3 and 4) were negative. A cys-
tourethrogram was performed in cat 4 to exclude uri-
nary tract trauma or urinary obstruction as a cause of
the hyperkalemia; no abnormalities were detected. An
ACTH stimulation test was performed in 2 cats (cats 3
and 4) to exclude hypoadrenocorticism; serum cortisol
concentrations were within reference range (Table 2).
On the basis of history and results of peritoneal fluid
analysis and ultrasonography, a tentative diagnosis of FIP
was made in 2 cats (cats 2 and 3). Cat 2 was euthanatized
1 day after examination, and a necropsy was performed,
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Table 1—Summary of results of CBC, biochemical analysis, and The 4 cats in this report had considerable peri-

SMALL ANIMALS
Na:K ratio in 4 cats with peritoneal effusion toneal effusion that caused severe abdominal enlarge-
Cat No. ment, hyponatremia, and hyperkalemia. The Na:K
Variable Reference range 1 2 3 4 ratios were < 25 in all 4 cats, which was suggestive of
Na:K ratio ⬎ 26 24.3 18.9 23.0 16.9 adrenal insufficiency.10 However, the diagnoses for the
Lymphocytes
3
1.5–7.0 X 10 /ml
3
0.41 0 0.9 0.68 peritoneal effusion did not readily explain adrenal
Leukocytes 5.5–19.5 X 10 /ml N/A 25.9 N/A N/A gland dysfunction in any of the cats. Results of the
Sodium 148–157 mmol/L 146 140 132 122
Potassium 3.5–5.1 mmol/L 6.0 6.1 7.0 7.2 ACTH stimulation tests performed in 3 of the cats
Chloride 115–128 mmol/L N/A 109 103 97 revealed normal cortisol measurements, and an
Albumin 2.7–3.9 g/dl N/A 2.7 3.9 N/A increased aldosterone value was detected in the 1 cat in
AST 1–37 U/L 52 115 69 N/A
GGT 1–5 U/L N/A 17 73 N/A
which aldosterone was measured. In 1 cat, histologic
Bilirubin 0.1–0.05 mg/dl 0.8 1.4 0.6 N/A examination of the adrenal glands at necropsy also
CO2 16–25 mmol/L 13 N/A N/A N/A failed to support a diagnosis of hypoadrenocorticism.
N/A = Not available. AST = Aspartate transaminase. GGT = γ-glutamyl-
On the basis of these findings, and because hypona-
transferase. tremia and hyperkalemia could not be readily explained
by another cause, the electrolyte abnormalities were
Table 2—Cortisol and aldosterone concentrations after adminis- presumed to be secondary to the peritoneal effusion.
tration of ACTH in 3 cats with peritoneal effusion In dogs, the development of hyponatremia with
Cat No.
concurrent hyperkalemia has primarily been ascribed
Reference
Hormone range 1 3 4 to sodium loss via the gastrointestinal tract,1,2 skin,8
and pleural fluid drainage.6 However, in instances of
Cortisol (mg/dl)
Baseline 0.5–5.0 4.9 4.5 6.5
effusions in which drainage does not take place, it is
1 h post-ACTH 4.5–13.0 5.7 8.4 6.6 likely that hyponatremia develops secondary to sodi-
2 h post-ACTH 4.0–14.5 NP 11.1 NP um and water retention and impairment of free water
Aldosterone (pmol/L) excretion.11-13 Body cavity effusion can cause decreased
Baseline 194–388 2498 NP NP
1 h post-ACTH NA 2785 NP NP effective circulating volume (ECV) despite an increase
in total extracellular fluid volume (ECFV). This devel-
NP = Not performed. NA = No reference range available. ops when fluid is lost within the cavity and no longer
contributes to the ECV. The decrease in ECV causes
which revealed severe fibrinous peritonitis and con- nonosmotic antidiuretic hormone (ADH) release, acti-
firmed the diagnosis of FIP. Histologic examination of the vation of the renin-angiotensin-aldosterone system
adrenal glands revealed a normal corticomedullary ratio (RAAS), and stimulation of the sympathetic nervous
of 1:1 and periadrenal inflammation secondary to FIP. system. Sodium and water retention and ECFV expan-
Cat 3 was discharged from the hospital with instruc- sion develops in an attempt to increase the ECV.
tions to the owner to administer prednisone (5 mg, PO, Activation of these systems also stimulates thirst and
q 12 h), but had no signs of improvement and died at impairs free water excretion as well as a decrease in
home 2 weeks later. A necropsy was not performed. renal distal tubular flow. These factors, combined with
There was no clear diagnosis for the cause of the peri- decreased sodium intake, most likely explain the
toneal effusion in the fourth cat (cat 4). This cat was hyponatremia of the 4 cats described in this report. In
discharged from the hospital with instructions to the support of this theory, ADH secretion and RAAS stim-
owner to administer prednisone (5 mg, PO, q 24 h); ulation was evidenced by the formation of concentrat-
infection with FIP was considered possible given the ed urine in 2 cats in which a urinalysis was performed
cytologic findings of the peritoneal fluid. This cat was and increased serum aldosterone concentration that
lost to follow-up. was measured in 1 cat. Evidence of decreased urinary
There are several reports in the veterinary litera- sodium excretion would further support this theory,
ture of concurrent hyponatremia and hyperkalemia but this was not performed in these cats. However,
despite normal adrenal function. All of these reports increased plasma aldosterone and renin concentra-
are of dogs and describe hyponatremia and hyper- tions, as well as decreased urine fractional excretion of
kalemia secondary to various disorders, including sodium, have been reported in a dog with hypona-
gastrointestinal tract disease (predominantly whip- tremia, hyperkalemia, and peritoneal effusion.9
worm infestation),1-3 acute renal failure,4 external Decreased ECV can also predispose animals to
blood loss,5 chylothorax associated with repeated hyperkalemia by decreasing renal distal tubular flow
drainage,4,6 pleural effusion secondary to lung lobe rate.14-17 Potassium secretion within the renal distal
torsion,7 and cutaneous lymphangiosarcoma associat- tubule cells depends on the serum potassium concen-
ed with pleural effusion.8 In addition, 1 recent report tration, the cellular Na-K-ATPase activity induced by
described concurrent hyponatremia and hyper- aldosterone, the luminal electronegativity created by
kalemia in a dog with portal hypertension and peri- sodium reabsorption (electrochemical gradient), and
toneal effusion secondary to peliosis hepatitis associ- the luminal potassium concentration (concentration
ated with infection with Bartonella spp.9 To the gradient). Decreased distal tubular flow rate, especial-
authors’ knowledge, concurrent hyponatremia and ly in conjunction with hyponatremia, impairs potassi-
hyperkalemia in the absence of hypoadrenocorticism um secretion because of poor sodium delivery
has not been previously reported in cats or in associ- (decreased electrochemical gradient) and potassium
ation with effusive states in cats. saturation of the luminal fluid (decreased concentra-

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tion gradient), despite normal or increased concentra-
SMALL ANIMALS
tions of aldosterone. In dogs with gastrointestinal tract
disease, hyperkalemia may be caused by hypovolemia
and movement of potassium extracellularly, secondary
to metabolic acidosis.1,2 Hyperkalemia may be exacer-
bated in patients with metabolic acidosis; however, this
was most likely not the cause of hyperkalemia in the
cats of this report, because only 1 cat had mild meta-
bolic acidosis. A primary renal tubular potassium
secretory defect, often referred to as aldosterone resis-
tance, would be an alternate cause of hyperkalemia in
the cats of this report.15 True aldosterone resistance is a
sodium chloride wasting syndrome that develops sec-
ondary to nephropathy; it is an inheritable condition in
infants and an acquired defect in adult humans.15,18,19
Although unlikely, detection of decreased urinary sodi-
um excretion would be necessary to exclude this dif-
ferential in the cats reported here. Other renal tubular
potassium defects are associated with a variety of dis-
eases in humans (predominantly nephropathies), and
the underlying mechanism is often thought to involve
an immunologic reaction directed at renal tubular
cells.15 These diseases are characterized by an inability
to increase renal potassium excretion in response to
increased distal tubular sodium concentration and flow
rate (eg, treatment with furosemide or sodium sulfate).
Because these treatments were not assessed in the cats
of this report, a primary renal potassium secretary
defect cannot be excluded as the cause of the hyper-
kalemia.
Although none of the cats in this report appeared
to have adverse effects caused by the hyponatremia and
hyperkalemia, it is important to recognize that peri-
toneal effusions (and potentially other body cavity
effusions) may cause concurrent hyponatremia and
hyperkalemia. Recognition of effusive states as a cause
of hyponatremia and hyperkalemia is important to
avoid false diagnoses of hypoadrenocorticism and to
avoid unnecessary ancillary tests. Although the
authors propose that decreased sodium intake and the
effects of decreased ECV promote the formation of
concurrent hyponatremia and hyperkalemia, further
investigation of urine sodium and potassium excretion
and the response of the kidneys to increased distal
tubular sodium concentration and flow rate is needed
to confirm this theory.
a 19. Komesaroff P. Pseudohypoaldosteronism: options for con-
Acthar Gel, Armour Pharmaceuticals, King of Prussia, Pa.
1592 Scientific Reports: Clinical Report
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