A Q u i c k R e f e ren c e o n

Hypokalemia
a, b
Márcia Mery Kogika, DVM, MS, PhD *, Helio Autran de Morais, DVM, PhD

KEYWORDS

Hypokalemia
Dog
Cat
Fractional excretion
Potassium

KEY POINTS

Hypokalemia is usually caused by excessive losses of potassium in the urine or in the
gastrointestinal tract.

Iatrogenic hypokalemia is common with use of diuretics and insulin or glucose-containing
fluids.

Clinical signs are observed when hypokalemia is moderate or severe; life-threatening car-
diac arrhythmias may occur.

INTRODUCTION

In mammalian cells, potassium is the major intracellular cation, representing
approximately 90% to 95% of the total body potassium. The remaining 5% to
10% is extracellular, being close to three-quarters in bone and one-quarter in
plasma and interstitial fluid.1–3

One of the most important functions of intracellular potassium is generation of
normal resting cell membrane potential. Hypokalemia hyperpolarizes the cell
decreasing its membrane excitability. This effect is noticed mostly in cardiac
and skeletal muscles.1–3

Potassium is removed primarily by the kidneys; 90% to 95% is excreted in urine.1–3

Hypokalemia is more common than hyperkalemia in dogs and cats.1,4–6

ANALYSIS

Reference values for dogs and cats range from 4.0 to 5.5 mEq/L and may vary
slightly among laboratories owing to the methodology and type of sample
(plasma, blood, or serum).1,4,7

The authors have nothing to disclose.

a
Department of Internal Medicine, School of Veterinary Medicine and Animal Science, Univer-
sity of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, São Paulo 05508-270, São Paulo,
Brazil; b Department of Clinical Sciences, Veterinary Teaching Hospital, College of Veterinary
Medicine, Oregon State University, Magruder Hall, 700 Southwest 30th Street, Corvallis, OR
97331, USA
* Corresponding author.
E-mail address: mmkogika@usp.br

Vet Clin Small Anim - (2016) -–-

http://dx.doi.org/10.1016/j.cvsm.2016.10.010 vetsmall.theclinics.com
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2 Kogika & de Morais

Potassium concentration in plasma or blood is lower (0.5 mEq/L) than in

serum because potassium is released from platelets during the clotting
process.1,4,7

Methodology: most laboratories and point-of-care testing devices use ion-
selective electrode methods; unlike with flame photometry, hyperlipemia and hy-
perproteinemia do not interfere with potassium measurement when ion-selective
electrode methods are used.1,4

Artifacts: pseudohypokalemia is an in vitro decrease in potassium concentration;
it occurs infrequently in samples with hyperlipemia or hyperproteinemia if the po-
tassium concentration is measured by flame photometry.1,4

Indications: serum potassium should be measured in patients developing
chronic or frequent vomiting or diarrhea, marked polyuria, muscle weakness,
or unexpected cardiac arrhythmias, as well as in those being treated with insulin,
diuretics, or receiving total parenteral nutrition.1

Danger values: clinical signs are associated with potassium serum concentrations
of less than 3.5 mEq/L (moderate hypokalemia is defined as 2.5–3.0 mEq/L and
severe as <2.5 mEq/L). Muscle weakness, cardiac arrhythmias, and polyuria
may occur when serum potassium is less than 3.0 mEq/L, whereas rhabdomyol-
ysis and respiratory muscle paralysis may be observed if potassium concentration
is below 2.0 mEq/L.1,4

Hypokalemia does not cause metabolic alkalosis in dogs and cats.1

Drug effect/iatrogenic: hypokalemia may occur in patients receiving diuretics, in-
sulin, mineralocorticoid analogs (eg, fludrocortisone), potassium-free fluids, and
sodium bicarbonate.1

Fractional urinary excretion of potassium (FEK) can be used to help localize the
source of potassium loss, whether renal loss or not.1 It is calculated as:

UK =SK
FEK 5  100 ð%Þ
Ucr =Scr
Where UK is the urine concentration of potassium (mEq/L); SK is the serum concen-
tration of potassium (mEq/L); Ucr is the urine concentration of creatinine (mg/dL),
and Scr is the serum concentration of creatinine (mg/dL) The FEK should be less
than 6% for nonrenal sources of potassium loss. Increased values are difficult to
interpret and do not necessarily mean that the kidneys are the source of potassium
losses.

Complementary examinations: an electrocardiogram helps to characterize ar-
rhythmias associated with hypokalemia and monitor its resolution after potas-
sium supplementation.

CAUSES AND CLINICAL SIGNS

Tables 1 and 2 list potential causes of hypokalemia in dogs and cats.
 The main mechanism leading to hypokalemia is increase in potassium losses
through the gastrointestinal tract (vomiting or diarrhea) or the kidneys. Kidney
losses can occur owing to intrinsic renal disease (impairment of tubular potas-
sium absorption, tubular acidosis, increased losses through polyuria) or from
drugs that affect sodium, chloride, and potassium handling in renal tubular
cells (diuretics and potassium-free fluids).1–3,5
 Potassium translocation from extracellular fluid to intracellular fluid can occur
with use of insulin or glucose-containing fluids.1
 A Quick Reference on Hypokalemia 3

Table 1
Causes of hypokalemia – extrarenal conditions and translocations

Extrarenal Observation
Decreased Rare - can be associated with prolonged anorexia or severely
intake of potassium-deficient diet.
potassium Common and important - fluid therapy with potassium free
fluids (eg, 0.9% NaCl, 5% dextrose in water, lactated Ringer’s
solution over several days).
Increased Common and important.
loss (normal FEK <6%) Chronic or frequent vomiting / potassium concentration in
gastric juice is not high, however loss of HCl may cause
alkalosis, bicarbonaturia and renal tubular secretion of
potassium (FEK could be >6%).
Vomiting associated with dehydration / loss of potassium
from gastric contents; dehydration may activate renin–
angiotensin–aldosterone system (renal loss of potassium;
FEK could be >6%).
Diarrhea (acute or chronic) causes intestinal loss of potassium,
and activation of renin–angiotensin–aldosterone system
occur if hypovolemia/dehydration.

Translocation (ECF to ICF) Observation

Glucose-containing fluid
with or without insulin
TPN solutions
Catecholamines
Hypokalemic periodic
paralysis
Other uncommon or rare
conditions
Common and important. Shift of potassium from plasma to
intracellular compartment. Insulin promotes uptake of
glucose and potassium by hepatic and skeletal muscle cells.
Uncommon but important. Glycogenesis during TPN or enteral
hyperalimentation stimulates insulin release (refeeding
syndrome).
Rare, and can be associated to stress of the illness or
pheochromocytoma; excess of catecholamines stimulates b2
receptors and potassium shifts to intracellular space.
Rare. In Burmese cats, a familial disorder characterized by
sudden translocation of potassium to intracellular space
owing to possible anomalous activation of Na1, K1-ATPase.
Albuterol overdose / b2 –adrenergic agonist, which may
increase cellular uptake of potassium by liver and muscle
cells.
Hypothermia / shift of potassium into cells.

Abbreviations: ECF, extracellular fluid; FEK, fractional potassium excretion; ICF, intracellular fluid;
TPN, total parenteral nutrition.
Data from Refs.1–4

 Prolonged anorexia, decrease in potassium ingestion, or intravenous use of

potassium-free fluids may also lead to hypokalemia.1–3

Clinical signs may vary depending on the degree of potassium deficit and acute-
ness of potassium depletion. Clinical signs do not always correlate well with the
degree of hypokalemia because they are related to the ratio of intracellular to
extracellular potassium concentration. Common signs of hypokalemia include
anorexia, muscular weakness (generalized or mild), and polyuria. Flaccid ventro-
flexion of the neck, forelimb hypermetria, and a broad-based hind limb stance
can be seen in cats with polymyopathy, in Burmese cats with hypokalemic peri-
odic paralysis, and in cases of severe hypokalemia. Hypokalemia may cause life-
threatening ventricular or supraventricular tachyarrhythmias.1–3,5,6
4 Kogika & de Morais

Table 2
Causes of hypokalemia – renal conditions

Renal Observation
CKD More common in cats than in dogs with CKD.
Polyuria and specific renal diseases may decrease renal reabsorption
or increase renal potassium excretion.
Distal (type I) renal Rare. Hypokalemia is usually present before treatment of acidosis;
tubular acidosis increased aldosterone secretion may contribute to urinary
potassium loss.
Proximal (type II) Rare. Hypokalemia usually develops during therapy with NaHCO3
renal tubular that leads to an increase in tubular flow, lumen electronegativity,
acidosis and intracellular shift of potassium.
Diet-induced Rare. Diets low in potassium and with urinary acidifiers induce
hypokalemic chronic tubulointerstitial nephritis.
nephropathy
in cats
Postobstructive Common and important. Hypokalemia follows relief of urethral
diuresis obstruction mainly in cats.
Osmotic diuresis Common and important. In ketoacidotics in dogs and cats; glucosuria
and ketonuria cause osmotic diuresis leading to renal loss of
potassium.
Drug induced Common and important.
Loop diuretics (eg, furosemide) cause high luminal flow and increase
NaCl delivery to the distal nephron, increasing renal potassium
excretion.
Thiazide diuretics (eg, chlorothiazide, hydrochlorothiazide) / loss of
potassium in urine, similar mechanism as observed for loop
diuretics.
Amphotericin B / binds to sterol in renal tubular collecting duct cells
causing development of pores that leads to the leakage of
potassium.
Hyperadrenocorticism More common in dogs with adrenal-dependent disease than with
pituitary-dependent disease.
Primary Uncommon, for example, adrenal adenoma or hyperplasia.
hyperaldosteronism Aldosterone increases renal tubular (distal and collecting tubules)
potassium secretion.
Hyperthyroidism Important. Polyuria results in renal potassium wasting via losses from
proximal and distal nephrons.
Other uncommon Peritoneal dialysis / potassium-free dialysate over an extended
or rare conditions period of time.
Synthetic mineralocorticoid (fludrocortisone) excess / urinary
potassium loss owing to increased renal tubular secretion of
potassium.
Penicillins derivates in high doses and carbenicillin / it may act as
nonresorbable anions in the distal tubule increasing secretion of
potassium.
High sodium intake / increased delivery of sodium to the distal
nephron increases activity of Na1, K1-ATPase and tubular (distal
and collecting) leading to loss of potassium.

Abbreviation: CKD, chronic kidney disease.

 A Quick Reference on Hypokalemia 5

Fig. 1. Algorithm for clinical approach to hypokalemia. ECF, extracellular fluid; FEK, frac-
tional potassium excretion; ICF, intracellular fluid; PD, polidipsia; PU, poliuria. (From DiBar-
tola SP, de Morais HA. Disorders of potassium: hypokalemia and hyperkalemia. In: DiBartola
SP, editor. Fluid, electrolyte, and acid-base disorders. 3rd edition. St Louis (MO): Elsevier;
2006. p. 102; with permission.)

STEPWISE APPROACH

An algorithm for the differential diagnosis of hypokalemia is showed in Fig.1.

SUMMARY

Hypokalemia occurs as a consequence of potassium depletion mainly because of in-

crease in losses or redistribution. Inadequate potassium intake can occasionally lead
to hypokalemia. Clinical sings develop in moderate (potassium concentration between
2.5 and 3.0 mEq/L) and severe hypokalemia (potassium concentration <2.5 mEq/L.)
Serum potassium should be investigated in dogs and cats developing chronic or
frequent vomiting or diarrhea, marked polyuria, muscle weakness, or unexpected car-
diac arrhythmias, as well as in those under therapy with insulin, diuretics, or receiving
total parenteral nutrition. Hypokalemia can also occur after relieve of urethral obstruc-
tion, mainly in cats. The FEK may help to identify the source of potassium loss; an FEK
of less than 6% occurs mostly with extrarenal losses of potassium.

REFERENCES

1. DiBartola SP, de Morais HA. Disorders of potassium: hypokalemia and hyperkale-

mia. In: DiBartola SP, editor. Fluid, electrolyte, and acid-base disorders. 4th edi-
tion. St Louis (MO): Elsevier; 2012. p. 92–119.
6 Kogika & de Morais

2. Sahni V, Gmurcyk A, Rosa RM. Extrarenal potassium metabolism. In: Alpem RJ,
Moe OW, Caplan M, editors. Seldin and Giebisch’s the kidney, vol. 1, 5th edition.
San Diego (CA): Elsevier; 2013. p. 1629–57.
3. Kemel KS, Halperin ML, Steigerwalt SP, et al. Disorders of potassium balance. In:
Brenner BM, editor. Brenner & Rector’s the kidney, vol. 1, 5th edition. Philadelphia:
W.B. Saunders Company; 1996. p. 999–1037.
4. DiBartola SP, Green RA, de Morais HA, et al. Electrolyte and acid base abnormal-
ities. In: Willard MD, Tvedten H, editors. Small animal clinical diagnosis by labora-
tory methods. 4th edition. St Louis (MO): WB Saunders; 2004. p. 117–34.
5. Chew DJ, DiBartola SP, Schenck PA. Chronic renal failure. In: Canine and feline
nephrology and urology. 2nd Edition. St Louis (MO): Elsevier Saunders; 2011.
p. 145–96.
6. Dow SW, Fettman MJ, Curtis CR, et al. Hypokalemia in cats: 186 cases
(1984-1987). J Am Vet Med Assoc 1989;194:1604–8.
7. Giovaninni LH, Kogika MM, Lustoza MD, et al. Serum and blood comparison of
ionized calcium, sodium, potassium and chloride in cats, by ion-selective elec-
trode method. Arquivo Brasileiro de Medicina Veterinária e Zootecnia 2007;59:
821–3.