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Hypokalemia

Hypokalemia is defined as plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products concentration between 3.5–5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular Transcellular The movement of one cell into, through, and out of another cell. Tubular System shifts, or poor dietary intake. If minor in severity, hypokalemia is usually asymptomatic. However, acute reductions in K+ level or severe hypokalemia can lead to cardiac arrhythmias, muscle weakness, rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis, paralysis, and respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure. Diagnosis is by clinical history and lab testing. Management is guided by severity and includes treating urgent symptoms, replacing the K+ deficit, and treating the underlying cause.

Last updated: Oct 31, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Introduction

Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia (K+) is the main intracellular cation in all cells and is distributed unevenly between the intracellular fluid Intracellular fluid The fluid inside cells. Body Fluid Compartments (98%) and extracellular fluid Extracellular fluid The fluid of the body that is outside of cells. It is the external environment for the cells. Body Fluid Compartments (2%). The large disparity is necessary for maintaining the resting membrane potential Membrane potential The membrane potential is the difference in electric charge between the interior and the exterior of a cell. All living cells maintain a potential difference across the membrane thanks to the insulating properties of their plasma membranes (PMs) and the selective transport of ions across this membrane by transporters. Membrane Potential of cells.

  • The GI tract secretes 5%–10% of absorbed K+ daily.
  • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy are responsible for 90%–95% of the overall K+ regulation and will severely limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation the excretion of K+ if intake is low.

Definition

Hypokalemia is defined as plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products K+ concentration < 3.5 mEq/L.

Sites of action in the kidney

  • Glomerulus: K+ is freely filtered.
  • Proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System: 65%–70% of filtered K+ is reabsorbed.
  • Thick ascending limb Thick ascending limb Renal Sodium and Water Regulation of the loop of Henle Loop of Henle The U-shaped portion of the renal tubule in the kidney medulla, consisting of a descending limb and an ascending limb. It is situated between the proximal kidney tubule and the distal kidney tubule. Tubular System: 10%–25% of filtered K+ is reabsorbed.
  • Principal cell (cortical collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma): K+ is secreted.
  • 𝛼-intercalated cell ( collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma): K+ is reabsorbed.

Etiology

The etiologies of hypokalemia can be grouped by 4 distinct mechanisms: poor dietary K+ intake, transcellular Transcellular The movement of one cell into, through, and out of another cell. Tubular System shift, GI losses, and renal losses. 

  • Poor dietary K+ intake:
    • Western diet: approximately 70–150 mmol K+/day
    • Uncommon cause outside of chronic malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries states (e.g., alcoholism Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. Wernicke Encephalopathy and Korsakoff Syndrome)
  • Transcellular Transcellular The movement of one cell into, through, and out of another cell. Tubular System shift:
    • Intracellular shifting of K+ results in hypokalemia
    • Factors increasing the intracellular shift:
      • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin 
      • β2 adrenergic agonists Adrenergic agonists Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs (e.g., albuterol Albuterol A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat asthma. Sympathomimetic Drugs)
      • Alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis: H+/K+ exchanger moves H+ out of the cell to help balance extracellular pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance in exchange for K+ moving into the cell to maintain electroneutrality.
  • GI losses: hypokalemia develops due to downstream effects on the kidney:
    • Upper GI losses: HCl HCL Hairy cell leukemia (HCL) is a rare, chronic, B-cell leukemia characterized by the accumulation of small mature B lymphocytes that have “hair-like projections” visible on microscopy. The abnormal cells accumulate in the peripheral blood, bone marrow (causing fibrosis), and red pulp of the spleen, leading to cytopenias. Hairy Cell Leukemia is also in gastric fluid → metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis → contributes to hypokalemia via transcellular Transcellular The movement of one cell into, through, and out of another cell. Tubular System shifting:
    • Lower GI losses: 
      • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
      • Laxative abuse
      • Villous adenoma Villous adenoma An adenoma of the large intestine. It is usually a solitary, sessile, often large, tumor of colonic mucosa composed of mucinous epithelium covering delicate vascular projections. Hypersecretion and malignant changes occur frequently. Colorectal Cancer
  • Renal losses:
    • Metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis with high blood pressure:
      • Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia due to primary hyperaldosteronism Primary hyperaldosteronism Autonomous (renin-independent) secretion of aldosterone. Hyperaldosteronism, adrenal tumor Tumor Inflammation, bilateral adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation, or renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)
      • Cortisol Cortisol Glucocorticoids due to excessive ingestion of black licorice
      • Cortisol Cortisol Glucocorticoids due to genetic conditions ( congenital Congenital Chorioretinitis adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation)
      • Liddle syndrome Liddle syndrome Liddle syndrome, a type of pseudohyperaldosteronism, is a rare cause of secondary hypertension. Liddle syndrome results from autosomal dominant gain-of-function mutations in the genes that encode the epithelial sodium channel (ENaC) subunits, also known as the “collecting tubule sodium channel” or “amiloride-sensitive sodium channel.” The activity of ENAC is increased, leading to sodium and water retention. Liddle Syndrome 
    • Metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis with low or normal blood pressure:
      • Loop and thiazide diuretics Thiazide diuretics Thiazide and thiazide-like diuretics make up a group of highly important antihypertensive agents, with some drugs being 1st-line agents. The class includes hydrochlorothiazide, chlorothiazide, chlorthalidone, indapamide, and metolazone. Thiazide Diuretics: a significant cause of hypokalemia in outpatients and hospitalized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
      • Salt-wasting nephropathy Salt-wasting nephropathy Volume Depletion and Dehydration ( Bartter syndrome Bartter syndrome Bartter syndrome is a rare autosomal recessive disorder that affects the kidneys and presents either antenatally with severe or life-threatening manifestations or in childhood or adulthood with a milder course, depending on the genetic defect. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb of the loop of Henle. Bartter Syndrome, Gitelman syndrome Gitelman syndrome Gitelman syndrome is a rare genetic autosomal recessive disorder that affects the sodium-chloride cotransporter in the distal convoluted tubule of the nephron and causes electrolyte abnormalities. The syndrome presents clinically with symptoms of hypokalemia and hypomagnesemia. Gitelman Syndrome)
    • Metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis:
      • Type 1 Type 1 Spinal Muscular Atrophy (distal) or type 2 Type 2 Spinal Muscular Atrophy (proximal) renal tubular acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis ( RTA RTA Renal tubular acidosis (RTA) is an imbalance in physiologic pH caused by the kidney’s inability to acidify urine to maintain blood pH at physiologic levels. Renal tubular acidosis exist in multiple types, including distal RTA (type 1), proximal RTA (type 2), and hyperkalemic RTA (type 4). Renal Tubular Acidosis)
      • Nonreabsorbable anions Anions Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. Electrolytes (e.g., 𝛽-hydroxybutyrate (diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis) or toluene sniffing (drug of abuse))
    • Hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes:
      • Can directly cause hypokalemia
      • Can be due to diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea or diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
      • Uncorrected hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes can make hypokalemia correction due to any cause difficult.
Transcellular shift of k potassium

Transcellular Transcellular The movement of one cell into, through, and out of another cell. Tubular System shift of K+:
Extracellular shift of K+:
1. Acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis (increased H+) causes blockage of the Na+/H+ exchanger, which causes a decrease in intracellular Na+, in turn blocking Na+/K+ ATPase. On the other hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy, acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis activates the H+/K+ exchanger. Both cause an increase in extracellular K+.
2. Increased osmolarity Osmolarity The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Hypernatremia in extracellular space ( hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus, IV contrast, mannitol Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. Osmotic Diuretics) shifts water outside the cell, decreasing K+ concentration. Increased gradient causes K+ diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis outside.
Intracellular shift of K+:
1. Alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis (decreased H+) causes activation of the Na+/H+ exchanger, which causes an increase in intracellular Na+, in turn activating Na+/K+ ATPase. On the other hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy, alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis blocks the H+/K+ exchanger. Both cause a decrease in extracellular K+.
2. Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin and β2 adrenergic agonists Adrenergic agonists Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs activate Na+/K+ ATPase, lowering plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products K+ concentration.

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Clinical Presentation

Presentation of hypokalemia may include nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation, skeletal muscle manifestations, and cardiac manifestations, which are potentially very serious. Symptoms are more likely to appear as the severity of hypokalemia increases, but patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be asymptomatic even with relatively severe hypokalemia.

  • Cardiac manifestations:
    • ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) changes:
    • Arrhythmias:
      • Premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis atrial/ventricular contractions 
      • Atrioventricular block Atrioventricular block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular block (AV block), sinus bradycardia Sinus bradycardia Bradyarrhythmias
      • Ventricular tachycardia Ventricular tachycardia Ventricular tachycardia is any heart rhythm faster than 100 beats/min, with 3 or more irregular beats in a row, arising distal to the bundle of His. Ventricular tachycardia is the most common form of wide-complex tachycardia, and it is associated with a high mortality rate. Ventricular Tachycardia and/or ventricular fibrillation Ventricular fibrillation Ventricular fibrillation (VF or V-fib) is a type of ventricular tachyarrhythmia (> 300/min) often preceded by ventricular tachycardia. In this arrhythmia, the ventricle beats rapidly and sporadically. The ventricular contraction is uncoordinated, leading to a decrease in cardiac output and immediate hemodynamic collapse. Ventricular Fibrillation (V-fib) if severe
  • Muscular symptoms:
    • With mild-to-moderate hypokalemia:
    • With severe hypokalemia (< 2–2.5 mEq/L): 
      • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be asymptomatic even if severe hypokalemia is present.
      • Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis with an elevated serum CK level
      • Ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction
      • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure due to respiratory muscle weakness Respiratory muscle weakness Respiratory Acidosis (may require intubation Intubation Peritonsillar Abscess if severe)
Ecg changes seen in hypokalemia

ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) changes seen in hypokalemia

Image by Lecturio. License: CC BY-NC-SA 4.0

Diagnosis and Management

Diagnosis

  • Clinical history:
    • Identify the cause of hypokalemia (e.g., GI losses, diuretic use).
    • If the diagnosis is clear from history, no further testing is needed.
  • Lab testing: urine studies if the diagnosis is still unclear
  • Spot urine K+: frequently unreliable due to many possible confounding variables Confounding variables A confound is an additional variable other than the independent variable that has an effect on the dependent variable, causing an erroneous relationship to be inferred between them. Types of Biases:
    • > 15 mEq/L: renal loss
    • < 15 mEq/L: extrarenal loss
  • Urine potassium-creatinine ratio (more reliable than spot urine K+):
    • Adjusts for urine volume
    • Correlates better with the 24-hour urine collection (impractical)
    • < 15 mEq/g = extrarenal loss or transcellular Transcellular The movement of one cell into, through, and out of another cell. Tubular System shift:
      • If concurrent metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis → likely due to diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (including villous adenoma Villous adenoma An adenoma of the large intestine. It is usually a solitary, sessile, often large, tumor of colonic mucosa composed of mucinous epithelium covering delicate vascular projections. Hypersecretion and malignant changes occur frequently. Colorectal Cancer or laxative abuse)
      • If concurrent metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis → likely due to vomiting or diuretic use
    • > 15 mEq/g = renal loss:
      • If concurrent metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis RTA RTA Renal tubular acidosis (RTA) is an imbalance in physiologic pH caused by the kidney’s inability to acidify urine to maintain blood pH at physiologic levels. Renal tubular acidosis exist in multiple types, including distal RTA (type 1), proximal RTA (type 2), and hyperkalemic RTA (type 4). Renal Tubular Acidosis or nonreabsorbable anion
      • If concurrent metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis, low/normal blood pressure, and hypovolemia Hypovolemia Sepsis in Children → could be due to diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication, salt-wasting nephropathy Salt-wasting nephropathy Volume Depletion and Dehydration (Bartter or Gitelman syndrome Gitelman syndrome Gitelman syndrome is a rare genetic autosomal recessive disorder that affects the sodium-chloride cotransporter in the distal convoluted tubule of the nephron and causes electrolyte abnormalities. The syndrome presents clinically with symptoms of hypokalemia and hypomagnesemia. Gitelman Syndrome), or vomiting 
      • If concurrent metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis, high blood pressure, and hypervolemia Hypervolemia Renal Sodium and Water Regulation → may be due to mineralocorticoid excess Mineralocorticoid excess A hereditary disease characterized by childhood onset hypertension, hypokalemic alkalosis, and low renin and aldosterone secretion. It results from a defect in the activity of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which results in inadequate conversion of cortisol to cortisone. The build up of unprocessed cortisol to levels that stimulate mineralocorticoid receptors creates the appearance of having excessive mineralocorticoids. Metabolic Alkalosis, renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS), or Liddle syndrome Liddle syndrome Liddle syndrome, a type of pseudohyperaldosteronism, is a rare cause of secondary hypertension. Liddle syndrome results from autosomal dominant gain-of-function mutations in the genes that encode the epithelial sodium channel (ENaC) subunits, also known as the “collecting tubule sodium channel” or “amiloride-sensitive sodium channel.” The activity of ENAC is increased, leading to sodium and water retention. Liddle Syndrome

Management

  • Treat urgent complications if present:
    • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
    • Arrhythmia: increased risk occurs with:
      • Increasing severity of hypokalemia (particularly < 2.5 mEq/L)
      • Concurrent hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes
      • Concurrent coronary artery disease Coronary artery disease Pathological processes of coronary arteries that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause. Stable and Unstable Angina
      • Concurrent digoxin Digoxin A cardiotonic glycoside obtained mainly from digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. Cardiac Glycosides or antiarrhythmic drug 
      • Older age
  • Replace K+:
    • Mild to moderately severe: oral KCl or potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia citrate
    • Severe (< 3 mEq/L, urgent symptoms, or if unable to take by mouth): IV K+
    • Maximal rate of infusion: 
      • 10 mEq/hr through peripheral IV
      • 20 mEq/hr through a central line
      • Fast rates of infusion can cause pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and irritation to the peripheral veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology.
    • KCl should not be mixed in 5% dextrose Dextrose Intravenous Fluids in water (causes insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology transcellular Transcellular The movement of one cell into, through, and out of another cell. Tubular System shift).
  • Replace magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes if low
  • Monitoring is important at all levels of hypokalemia:
    • Cardiac monitoring:
      • Serial ECGs and/or continuous cardiac monitoring (i.e., telemetry Telemetry Transmission of the readings of instruments to a remote location by means of wires, radio waves, or other means. Crush Syndrome)
      • Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will not have signs of arrhythmia or ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) changes even with severe hypokalemia.
    • Lab monitoring:
      • Repeat serum K+ frequently based on the severity of hypokalemia and the clinical situation.
      • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance monitoring for hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
  • Treat the underlying disease (potassium-sparing diuretic may be required):
    • Bartter syndrome Bartter syndrome Bartter syndrome is a rare autosomal recessive disorder that affects the kidneys and presents either antenatally with severe or life-threatening manifestations or in childhood or adulthood with a milder course, depending on the genetic defect. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb of the loop of Henle. Bartter Syndrome or Gitelman syndrome Gitelman syndrome Gitelman syndrome is a rare genetic autosomal recessive disorder that affects the sodium-chloride cotransporter in the distal convoluted tubule of the nephron and causes electrolyte abnormalities. The syndrome presents clinically with symptoms of hypokalemia and hypomagnesemia. Gitelman Syndrome: amiloride Amiloride A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. Liddle Syndrome
    • Primary aldosteronism: spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics
    • Chronic diuretic use

Clinical Relevance

  • Rhabdomyolysis: potassium may be normal or high on presentation due to the release of intracellular K+ as muscle cells die. Because many causes of rhabdomyolysis exist other than hypokalemia and the risk of hyperkalemia with overaggressive K+ replacement is significant, only replace K+ if and when plasma levels are low. Diagnosis is made by history and CK levels, and management of the underlying cause is needed.
  • Diabetic ketoacidosis (DKA): presents with K+ deficit of the total body (urinary losses from osmotic diuresis/polyuria); however, plasma K+ is normal or high due to severe transcellular shifting from insulin deficiency. Diagnosis is made by history and lab testing, which include glucose and serum ketones. Treatment includes starting an insulin drip and replacing K+ once the plasma level falls to 4.5 mEq/L since the intracellular shift will cause hypokalemia. 
  • Hypokalemic periodic paralysis: characterized by acute attacks of muscle weakness and/or paralysis precipitated by rest after exercise, stress, and/or a high-carbohydrate meal. Hypokalemic periodic paralysis can be genetic or acquired (associated with hyperthyroidism/thyrotoxicosis). Hypokalemic periodic paralysis is the prototypical disease due to severe transcellular shifting of K+. The presentation includes a plasma K+ decrease to 1.5–2.5 mEq/L. Supplemental K+ should only be replaced if symptomatic and done cautiously given the risk for rebound hyperkalemia once the transcellular shifting is corrected. 
  • Chronic hypokalemia: can have long-term adverse effects, including worsening hypertension, chronic kidney disease, and polyuria. Chronic hypokalemia may increase the risk of developing diabetes in conjunction with thiazide diuretics.
  • False-positive hypokalemia: a common occurrence in hospital settings, usually caused by blood drawn from an IV nearby a hypotonic fluid infusion. Cells in the blood can also have significant uptake of K+ if the blood sample is left in warm temperatures for a prolonged period of time, or if the WBC is very high (e.g., > 100,000/mL in leukemia).
  • Salt-wasting nephropathies: Bartter syndrome and Gitelman syndrome with a clinical presentation of metabolic alkalosis, low or normal blood pressure, and hypokalemia from renal losses. Both are rare, autosomal recessive syndromes; however, the mechanism of Bartter syndrome resembles a loop diuretic and the mechanism of Gitelman syndrome resembles a thiazide diuretic. Treatment includes a potassium-sparing diuretic (spironolactone or amiloride) and NSAIDs.
  • Liddle syndrome: a rare, autosomal dominant disease presenting clinically with metabolic alkalosis, high blood pressure, and hypokalemia from renal losses. Treatment includes a potassium-sparing diuretic (amiloride or triamterene).
  • Type 1 RTA (also known as distal RTA): the condition results in systemic metabolic acidosis due to impaired distal acidification in the kidney. Distal RTA can be genetic or acquired (due to drugs or autoimmune disease). Diagnosis is made on history and lab testing. Treatment is oral bicarbonate, usually in the form of sodium bicarbonate or potassium citrate.
  • Type 2 RTA (also known as proximal RTA): the condition results in systemic metabolic acidosis due to impaired reabsorption of filtered bicarbonate in the proximal tubule. Proximal RTA can be genetic or acquired (i.e. due to drugs or multiple myeloma). Diagnosis is made on history and lab testing. Treatment is more complicated than type 1 RTA and involves a combination of oral bicarbonate, oral K+ supplementation, hydrochlorothiazide, and a potassium-sparing diuretic (amiloride or spironolactone).
  • Nonreabsorbable anions: anions (e.g., 𝛽-hydroxybutyrate, hippurate) associated with metabolic acidosis cause hypokalemia from increased renal excretion of K+. Ketoacidosis can result from uncontrolled diabetes, starvation, or alcoholism and is associated with high 𝛽-hydroxybutyrate levels. Hippurate is a metabolite of toluene, which is found in paint thinner, and inhaled as a drug of abuse (“huffing”). 

References

  1. Emmett, M. & Ellison, D.H. (2019). Bartter and Gitelman syndromes. UpToDate. Retrieved March 15, 2021, from https://www.uptodate.com/contents/bartter-and-gitelman-syndromes
  2. Emmett, M. & Palmer, B.F. (2020). Treatment of distal (type 1) and proximal (type 2) renal tubular acidosis. UpToDate. Retrieved March 15, 2021, from https://www.uptodate.com/contents/treatment-of-distal-type-1-and-proximal-type-2-renal-tubular-acidosis
  3. Liamis, G., Liberopoulos, E., Barkas, F., & Elisaf, M. (2013). Spurious electrolyte disorders: A diagnostic challenge for clinicians. American Journal of Nephrology. 38(1), 50–57. https://doi.org/10.1159/000351804
  4. Mount, D. (2020). Causes of hypokalemia in adults. UpToDate. Retrieved March 1, 2021, from https://www.uptodate.com/contents/causes-of-hypokalemia-in-adults
  5. Mount, D. (2019). Clinical manifestations and treatment of hypokalemia in adults. UpToDate. Retrieved March 1, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-treatment-of-hypokalemia-in-adults
  6. Mount, D. (2020). Evaluation of the adult patient with hypokalemia. UpToDate. Retrieved March 1, 2021, from https://www.uptodate.com/contents/evaluation-of-the-adult-patient-with-hypokalemia

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