Silverstein and Hopper Chapter 56: Potassium Disorders

What is the most abdundant intracellular anion?

Potassium

What % of potassium is located in the intracellular compartment?

98-99%

What are the feedback mechanisms involved in potassium regulation?

• pH regulation

• Changes in osmolality

• Hormones including insulin, catecholamines, and aldosterone

How does the body maintain pH in metabolic alkalosis?

• In metabolic alkalosis, the body maintains pH by causing more potassium to move intracellularly in exchange for cellular H+ ions

  • Hyperosmolality causes the translocation of water from the cellular space, which drags cellular potassium into the extracellular fluid space

What substances transfer potassium from the extracellular space to the intracellular space?

• Insulin, catecholamines, and aldosterone

  • Any increase in extracellular fluid potassium concentration triggers aldosterone release

    • Aldosterone acts at the distal renal tubules to increase Na+/K+ ATPase activity -> promotes the transluminal transfer of potassium ions through the collecting duct principal cells into the renal tubular lumen, allowing for potassium excretion and sodium reabsorption

Kaliuretic Feedforward Control

•  Potassium control mechanism that responds to signals in the external environment and involves sensors in the stomach and the hepatic portal regions

  • Sensors detect local changes in potassium concentrations resulting from potassium ingestion and signal the kidney to alter potassium excretion to restore potassium balance

    • One without the influence of aldosterone

How does the body counteract hypokalemia?

Transfer of potassium from the intracellular space into the extracellular space

Hypokalemia

Occurs when the serum potassium concentration is less than 3.5 mEq/L

General Causes of Hypokalemia

Disorders of internal balance

Disorders of external balance

Causes of Hypokalemia - Disorders of Internal Balance (Redistribution)

Metabolic alkalosis

Insulin administration

Increased levels of catecholamines

B-adrenergic agonist therapy or intoxication

Refeeding syndrome

Causes of Hypokalemia - Disorders of External Balance (Depletion)

Renal potassium wasting

Prolonged inadequate intake

Diuretic drugs

Osmotic or postobstructive diuresis

Chronic liver failure

Inadequate parenteral fluid supplementation

Aldosterone-secreting tumor or any cause of hyperaldosteronism

Prolonged vomiting associated with pyloric outflow obstruction

Diabetic ketoacidosis

Renal tubular acidosis

Severe diarrhea

Ingestion of barium-containing party sparklers

Glucocorticoid drugs

Metabolic Consequences of Hypokalemia

Glucose intolerance

Neuromuscular Consequences of Hypokalemia

• Potassium necessary for maintenance of normal resting membrane potential

• Skeletal muscle weakness from hyperpolarized (less excitable) myocyte plasma membranes that may progress to hypopolarized membranes

  • Ventroflexion of the head and neck, a stiff stilted gaint, and a plantigrade stance may be evident

• Rhabdomyolysis which can have a toxic effect on renal tubules

• Smooth muscle impairment can occur and predispose to paralytic ileus and gastric atony

• Neuromuscular signs seldom present until potassium levels fall below 2.5 mEq/L

Cardiovascular Consequences of Hypokalemia

• In the myocardial cell, a high intracellular/extracellular potassium concentration ratio induces a state of electrical hyperpolarization leading to prolongation of the action potential

  • May predispose the patient to atrial and ventricular tachyarrhythimas, atrioventricular dissociation, and ventricular fibrillation

• ECG findings in hypokalemia are less reliable than hyperkalemia

  • Include depression of the ST segment and prolongation of the QT interval

  • Increased P wave amplitude, prolongation of the PR interval, and widening of the QRS complex may also occur

• Hypokalemia predisposes to digitalis-induced cardiac arrhythmias and causes the myocardium to become refractory to the effects of class I antiarrhythmic agents

Main Management Objectives of Hypokalemia

• Deterring continued potassium losses

• Replacing potassium deficits while considering the preparation type and route of administration

• Correcting the primary disease process

Treating Hypokalemia Associated with Metabolic Alkalosis

• Normalizing blood pH

• Replacing the potassium deficit

• Correcting the cause of the alkalosis

Treating Hypokalemia Associated with Primary Hyperaldosteronism

• Removing the cause of the excess aldosterone and/or counteracting the hormone's effect at the distal renal tubule by treating the patient with an aldosterone antagonist such as spironolactone

Treating Moderate to Severe Hypokalemia in the Anoretic or Vomiting Patient

• Parenteral administration of potassium chloride solution (or potassium phosphate in hypophosphatemic patients)

• Rate of potassium infusion should seldom exceed 0.5 mEq/kg/hr for treatment of patients with mild to moderate hypokalemia

  • In profoundly hypokalemic patients (serum potassium <2.5 mEq/L) with normal or increased urine output, the rate can be increased to 1-1.5 mEq/kg/hr with ECG monitoring

Conditions that May Predispose an Animal to Adverse Effects of a Potassium Infusion

• Oliguria

• Anuria

• Hypoaldosteronism (Addison's disease)

• Coadministration of potassium-sparing drugs (spironolactone, triamterene)

Exception to the “Safe” Rate of Administration of Potassium

When marked hypokalemia causes apnea, under which circumstances an intravenous bolus of 0.01 ml/kg of a 2 mEq/ml solution can be live saving

Anticipated Complications of Treatment of Hypokalemia

• Hyperkalemia can occur from excessive potassium supplementation

• Hypokalemic neuromuscular dysfunction is worsened and refractoriness to therapy may be evident when metabolic alkalosis, hypomagnesemia, and hypocalcemia coexist

  • All acid-base disorders and electrolyte deficiencies must be corrected to attain normal neuromuscular function

Hyperkalemia

Occurs when the serum potassium concentration exceeds 5.5 mEq/L and is considered life threatening at serum concentrations greater than 7.5 mEq/L

What are the four basic disturbances that result in hyperkalemia?

Increased intake or administration

Translocation from the intracellular to extracellular fluid space

Decreased renal excretion

Artifactual or pseudohyperkalemia

Causes of Hyperkalemia - Increased Intake or Administration

• To avoid life-threatening neuromuscular side effects, the IV rate of potassium should not exceed 0.5 mEq/kg/hr

• Administration of packed red blood cells that are past the expiration date

• Certain medications such as ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics (e.g. spironolactone), or nonselective B-blocking drugs (e.g. propranolol), heparin, cyclosporine, and tacrolimus

Causes of Hyperkalemia - Translocation from the Intracellular to Extracellular Fluid Space

• Mineral acidosis (respiratory acidosis, uremia, or pharmacologic induction by ammonium chloride, hydrogen chloride, or calcium chloride infusions) causing potassium to move out of the intracellular space in exchange for hydrogen ions

  • Organic acids such as lactate and ketoacids rarely cause this effect because of their ability to maintain electroneutrality across the cell membrane

• Heat stroke

• Crushing injuries

• Tumor lysis syndrome associated with chemotherapy

• After radiation therapy in dogs with lymphosarcoma

• Cats treated with thrombolytic agents for aortic thromboemolism as a result of reperfusion of the affected limbs

• Occurs commonly during cardiopulmonary resuscitation and immediately following the return of spontaneous circulation due to ischemia induced cellular damage and release of large amounts of intracellular potassium

• Diabetic patients

  • Insulin deficiency that results in decreased cellular uptake of potassium

  • Hyperosmolality that potentiates potassium translocation with water due to "solute drag" effect

  • Decreased potassium excretion related to renal dysfunction

  • Insulin therapy normalizes the serum potassium concentration by correcting the insulin deficiency and hyperoasmolality, enabling relocation of potassium to the intracellular space, and decreasing the need for further protein catabolism

Causes of Hyperkalemia

• In animals with chronic renal disease, adaptation in the kidneys promotes an increase in fractional potassium excretion as well as adaptations in the GI system with increased fecal excretion

  • Distal tubule is dependent on adequate glomerular filtration rate and urine flow to excrete potassium

    • Until effective urine output and improvement of GFR return, any reduction of potassium levels can only occur with therapies such as hemodialysis or peritoneal dialysis

• Hyperkalemia may be due to dietary potassium exceeding renal excretion as well as ACE inhibitor therapy that may be used to treat hypertension and proteinuria

  • Feeding a potassium reduced diet can resolve hyperkalemia in these animals

• Other drug therapies such as nonspecific B-blockers, cardiac glycosides, ACE inhibitors, angiotensin receptor blockers, cyclosporine, tacrolimus heparin, and trimethoprim may also contribute to hyperkalemia in these patients with diminished renal function

• Patients with classic, severe hypoadrenocorticism typically have hyperkalemia and hyponatremia and a sodium:potassium ratio less than 27:1

  • An ACTH stimulation test is essential to differentiate this disease from AKI because these patients might also be azotemic and have resting serum cortisol values <1.0 ug/dL

  • In the absence of aldosterone, the resulting natriuresis causes a reduced effective circulating volume, which further impairs distal tubule potassium excretion

  • Decreased volume also leads to reduced renal perfusion, prerenal azotemia, and further potassium retention

  • Initial therapy should include restoration of the effective circulating volume

ECG Changes in Patients with Hyperkalemia

• Peaked, narrow T waves

• Prolonged QRS complex and interval

• Depressed ST segment

• Depressed P wave

• Atrial standstill

• Ventricular flutter/fibrillation

Balanced Electrolyte Solutions vs NaCl for Hyperkalemia

• Balanced electrolyte solutions that contain potassium can be used to stabilize these patients

  • A study found no difference in rate to normalization of potassium between a balanced electrolyte IV fluid containing potassium and 0.9% NaCl, however the balanced solutions led to a more rapid correction in acid base status

Pseudohyperkalemia

• Artifactual increase in potassium from potassium released from increased numbers of circulating blood cells, especially platelets and leukocytes

  • Typically occurs with significantly elevated counts (>1,000,000 platelets and >100,000 leukocytes)

• Confirmation can be made by determining the plasma potassium concentration because this should not be affected by changes in platelet or white blood cell numbers

Consequences of Hyperkalemia

• Hyperkalemia results in changes in the cell membrane excitability, causing changes in cardiac myocyte excitation and conduction

• Muscle weakness can occur when the serum potassium concentration exceeds 7.5 mEq/L

• Ratio of intracellular to extracellular potassium is the main factor in determining the cardiac resting membrane potential

  • In hyperkalemic patients, the concentration gradient across the cardiac cell membranes is reduced, leading to a less negative resting membrane potential

    • Makes these cardiac cell membranes more excitable

• Elevated potassium also inactivates some of the sodium-potassium channels during the resting phase, making these cells slower to reach threshold potential

• An overall decrease in potassium permeability means that efflux of potassium in repolarization is delayed, slowing the cell's recovery

• Acidemia results in extracellular shift in potassium as well as decreasing the B-adrenergic receptors in cardiac tissues

• Atrial standstill, ventricular flutter, and asystole are reported effects

• Sinus tachycardia, third degree heart block, ventricular premature complexes, and atrioventricular dissociation have also been reported

Treatment of Hyperkalemia

• ECG and blood pressure monitoring recommended

• Exogenous potassium supplementation discontinued

• Evaluate for urinary tract abnormalities (uroabdomen, ureteral obstruction, urinary stones)

• In asymptomatic animals with normal urine output, serum potassium concentrations between 5.5 and 6.5 mEq/L rarely require immediate therapy

• Replacement fluids can be used to rehydrate the patient and correct for prerenal azotemia and promote diuresis

• Loop diuretics or thiazide diuretics can increase urinary potassium excretion, but use must follow rehydration

Treatment of Hyperkalemia in Patients with Potassium >7.5 mEq/L

• 10% calcium gluconate or calcium chloride can be administered to antagonize the cardiotoxic effects of hyperkalemia, but this has no effect on serum potassium concentration

  • Calcium functions by increasing the threshold potential to maintain the gradient between that and the resting membrane potentials

  • Reduces membrane excitability

  • Give slowly over 15-20 minutes with ECG monitoring

• B-adrenergic agonists (terbutaline, albuterol, epinephrine), sodium bicarbonate, and dextrose with or without insulin can be administered to reduce serum potassium concentrations

  • Shift potassium intracellularly, lowering serum potassium

• Use caution with sodium bicarbonate because of need for slow administration and potential to cause severe alkalosis and paradoxical cerebral acidosis

  • Rarely used

• Calcium gluconate, dextrose/insulin, and B-adrenergic agonists are first-line therapies for management of hyperkalemia treatment

How do you reduce total body potassium in the oliguric or anuric patient?

Extracorporeal therapy

MOA of 10% Calcium Gluconate in Hyperkalemia

Increases threshold voltage but will not lower serum potassium

MOA of Sodium Bicarbonate in Hyperkalemia

Causes metabolic alkalosis allowing for potassium to move intracellularly, paradoxical CNS acidosis with rapid administration

MOA of 50% Dextrose in Hyperkalemia

Allows for translocation of potassium into the intracellular space in the presence of endogenous insulin

• Add exogenous insulin if needed

MOA of Terbutaline for Hyperkalemia

Stimulates Na+/K+ to cause translocation of potassium into the cell