Overview

General considerations

K⁺is the main intracellular cation in all cells and is distributed unevenly between theintracellular fluidIntracellular fluidThe fluid inside cells.Body Fluid Compartments (98%) andextracellular fluidExtracellular fluidThe fluid of the body that is outside of cells. It is the external environment for the cells.Body Fluid Compartments (2%). 

• Disparity is necessary for maintaining theresting membrane potentialResting membrane potentialMembrane Potential of cells → K⁺ balance is tightly regulated
• Hyperkalemia causesdepolarizationDepolarizationMembrane Potential (i.e., decrease) of theresting membrane potentialResting membrane potentialMembrane Potential, leading to the inactivation of Na⁺channelsChannelsThe Cell: Cell Membrane → decreasedexcitabilityExcitabilitySkeletal Muscle Contraction of cardiac cells →  predisposition for arrhythmias 
• ThekidneysKidneysThe 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.
• The GI tract secretes 5%–10% of absorbed K⁺ daily.

Sites of action in the kidney

• Glomerulus: K⁺is freely filtered.
• Proximal tubuleProximal tubuleThe 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 limbThick ascending limbRenal Sodium and Water Regulation of theloop of HenleLoop of HenleThe 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 (corticalcollecting ductCollecting ductStraight 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 ductCollecting ductStraight 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 (final fine-tuning mechanism).

Normal response to ingested K⁺

A normal Western diet contains approximately 70–150 mmol of K⁺ per day. This diet is unlikely to lead to the development of hyperkalemia from increased intake only, owing to the following mechanisms:

1. Gut absorbs dietary K⁺ into the bloodstream.
2. Transcellular shift prevents excessive increase in extracellular fluid (ECF) K⁺ concentration.
   1. Insulin- and β₂-mediated
   2. K⁺ shifts primarily into muscle andliverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: Anatomy cells.
3. Increased ECF K⁺ concentration triggers mechanisms for renal K⁺ excretion.  
4. TranscellularTranscellularThe movement of one cell into, through, and out of another cell.Tubular System shifting into muscle/liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: Anatomy cells gradually reverses.
5. Remainder of ingested K⁺ load is renally excreted.

Etiology

The etiologies of hyperkalemia can be grouped into 5 categories:transcellularTranscellularThe movement of one cell into, through, and out of another cell.Tubular System shifts, tissue breakdown, inadequate renal excretion, drug-induced, and pseudohyperkalemia.

TranscellularTranscellularThe movement of one cell into, through, and out of another cell.Tubular System shifts

• Certain factors cause K⁺ to move transiently into or out of cells.
• The effect of this shift can be significant enough to decrease or increase the measured serum K⁺.
• The total body K⁺does not change.
• Factors that cause shifting out of the cell (→ raise ofplasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products K⁺):
  • AcidosisAcidosisA 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: H⁺/K⁺exchange maintains electroneutrality → moves H⁺ into cell to help balance extracellularpHpHThe quantitative measurement of the acidity or basicity of a solution.Acid-Base Balance in exchange for K⁺ moving out of the cell
  • Hyperosmolality (hyperglycemiaHyperglycemiaAbnormally high blood glucose level.Diabetes Mellitus, IV contrast,mannitolMannitolA 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):
    • High ECFosmolalityOsmolalityPlasma osmolality refers to the combined concentration of all solutes in the blood.Renal Sodium and Water Regulation → shift of water into ECF → decreases ECF K⁺ concentration → more favorable gradient fordiffusionDiffusionThe 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 of K⁺ out of cells
    • Solvent drag on K⁺ as water leaves the cell may also contribute.
    • Common mechanism inhyperglycemiaHyperglycemiaAbnormally high blood glucose level.Diabetes Mellitus (i.e., diabeticketoacidosisKetoacidosisA 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 (DKADKADiabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency.Hyperglycemic Crises))
  • Exercise: K⁺ is intentionally released by muscle cells to act as a local vasodilator.
• Factors that cause shifting into the cell (→ lowers theplasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products K⁺):
  • InsulinInsulinInsulin 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: stimulates Na⁺/K⁺ ATPase → 3 Na⁺ move out of cell, 2 K⁺ move into cell
  • β₂-Adrenergic agonist (i.e.,albuterolAlbuterolA short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat asthma.Sympathomimetic Drugs; stimulates Na⁺/K⁺ ATPase)
  • AlkalosisAlkalosisA pathological condition that removes acid or adds base to the body fluids.Respiratory Alkalosis: H⁺/K⁺exchanger moves H⁺ out of cell to help balance extracellularpHpHThe quantitative measurement of the acidity or basicity of a solution.Acid-Base Balance in exchange for K⁺ moving into cell

Tissue breakdown

• Similar totranscellularTranscellularThe movement of one cell into, through, and out of another cell.Tubular System shift, but the shift is not reversible
• Damage to cell results in release of the highly concentrated intracellular K⁺:
  • Tumor lysisTumor LysisTumor Lysis Syndrome syndrome (high-volume malignantcell deathCell deathInjurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects.Cell Injury and Death afterchemotherapyChemotherapyOsteosarcoma)
  • RhabdomyolysisRhabdomyolysisRhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation.Rhabdomyolysis (muscle cells; trauma, crush injuries, prolongedimmobilizationImmobilizationDelirium)
  • RBC transfusion (if multiple units or old bloodRBCsRBCsErythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production.Erythrocytes: Histology lyse over time in storage)
  • GI bleeding (RBC metabolized by GI tract → intracellular K⁺ released)
  • LargehematomaHematomaA collection of blood outside the blood vessels. Hematoma can be localized in an organ, space, or tissue.Intussusception (RBC reabsorbed and metabolized → intracellular K⁺ released)
  • BurnsBurnsA burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns.Burns (skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions cells)

Inadequate renal excretion

Renal failureRenal failureConditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate.Crush Syndrome:

• OliguriaOliguriaDecreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age.Renal Potassium Regulation → ↓ distalflow rateFlow ratemaximum flow the ventilator will deliver a set tidal volume in liters per minuteInvasive Mechanical Ventilation → ↓ K⁺secretionSecretionCoagulation Studies 
• OliguriaOliguriaDecreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age.Renal Potassium Regulation plus excess K⁺ load or aldosterone blocker (ACEiACEiA class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Renin-Angiotensin-Aldosterone System Inhibitors/ARB) will result in hyperkalemia.
• OliguriaOliguriaDecreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age.Renal Potassium Regulation by itself may not cause hyperkalemia.

Volume depletionVolume depletionVolume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids.Volume Depletion and Dehydration:

• HypovolemiaHypovolemiaSepsis in Children → ↓ distal Na⁺ delivery → ↓ K⁺secretionSecretionCoagulation Studies 
• Also occurs in states of total body fluid overload, but witheffective arterial blood volumeEffective arterial blood volumeRenal Sodium and Water Regulation depletion (congestiveheart failureHeart FailureA heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction.Total Anomalous Pulmonary Venous Return (TAPVR),cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome.Cirrhosis)
• Volume depletionVolume depletionVolume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids.Volume Depletion and Dehydration can also causeAKIAKIAcute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine.Acute Kidney Injury → hyperkalemia fromoliguriaOliguriaDecreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age.Renal Potassium Regulation

FunctionalhypoaldosteronismHypoaldosteronismHypoaldosteronism is a hormonal disorder characterized by low levels of aldosterone. These low levels can be caused by decreased aldosterone production or a peripheral resistance to aldosterone. When hypoaldosteronism occurs as a result of an acquired decrease in renin production, the condition is more commonly referred to as renal tubular acidosis (RTA) type 4.Hypoaldosteronism:

• Mineralocorticoid deficiency:
  • Primary adrenal insufficiencyPrimary adrenal insufficiencyAn adrenal disease characterized by the progressive destruction of the adrenal cortex, resulting in insufficient production of aldosterone and hydrocortisone. Clinical symptoms include anorexia; nausea; weight loss; muscle weakness; and hyperpigmentation of the skin due to increase in circulating levels of acth precursor hormone which stimulates melanocytes.Adrenal Insufficiency and Addison Disease
  • Hyporeninemic hypoaldosteronismHyporeninemic hypoaldosteronismReduced aldosterone synthesis due to decreased stimulation of Renin-angiotensin-aldosterone system.Hypoaldosteronism
• Tubulointerstitial disease:sickle cell diseaseSickle cell diseaseSickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage.Sickle Cell Disease,urinary tractUrinary tractThe urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra.Urinary Tract: Anatomy obstruction
• Drugs (see table below) 

Drug-induced hyperkalemia

Drugs are a very common cause of hyperkalemia and cause it by a variety of the previously mentioned mechanisms. A key part of the diagnosis of hyperkalemia is to review all the recent drugs and medications that a patient has received.

Pseudohyperkalemia

• False positiveFalse positiveAn FP test result indicates that a person has the disease when they do not.Epidemiological Values of Diagnostic Tests hyperkalemia, due to process of drawing and/or processing of a blood sample
• Related to blood draw:
  • DamagedRBCsRBCsErythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production.Erythrocytes: Histology lyse and release their intracellular K⁺.
  • Prolonged tourniquet
  • Excessive fist clenching
  • Venipuncture trauma
• Related to blood sample processing:
  • Severe thrombocytosis orleukocytosisLeukocytosisA transient increase in the number of leukocytes in a body fluid.West Nile Virus 
  • More likely if blood sample analysis is delayed
  • Intracellular K⁺ is released fromplateletsPlateletsPlatelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm.Platelets: Histology after clotting in the test tube.
  • WBCs lyse and release intracellular K⁺

Clinical Presentation

The most severe symptoms of hyperkalemia are impaired electrical conduction in the heart. Cardiac symptoms are more likely to occur with increasing severity and acuity of hyperkalemia; however, even relatively severe hyperkalemia can be asymptomatic. Muscular symptoms may be observed, and these include weakness and paralysis. 

Cardiac symptoms

Cardiac symptoms are the most important symptoms of hyperkalemia, as they can be rapidly fatal.

• ECGECGAn 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 follow a characteristic progression with increasing K⁺:
  • Peaked T waves and shortQT intervalQT intervalElectrocardiogram (ECG) →PR intervalPR intervalElectrocardiogram (ECG) prolongation and QRS widening → loss of P waves → QRS widens to sine wave →asystoleAsystoleNo discernible electrical activity, flatline on electrocardiogram (P waves and QRS complexes are not present).Cardiac Arrest
  • This classic progression is often not observed clinically.
  • ECGECGAn 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) findings are helpful if present but are not sensitive for hyperkalemia overall.
• Arrhythmias:
  • Advancedatrioventricular blockAtrioventricular blockAtrioventricular (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 bradycardiaSinus bradycardiaBradyarrhythmias
  • Sinus arrestSinus arrestThe omission of atrial activation that is caused by transient cessation of impulse generation at the sinoatrial node. It is characterized by a prolonged pause without P wave in an electrocardiogram. Sinus arrest has been associated with sleep apnea (rem sleep-related sinus arrest).Bradyarrhythmias
  • Slow idioventricular rhythm
  • VentriculartachycardiaTachycardiaAbnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.Sepsis in Children,ventricular fibrillationVentricular fibrillationVentricular 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), and/orasystoleAsystoleNo discernible electrical activity, flatline on electrocardiogram (P waves and QRS complexes are not present).Cardiac Arrest if severe
• Monitoring:
  • Important at all levels of hyperkalemia
  • Can be done with repeat ECGs and/or continuous cardiac monitoring 

SomepatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship will not haveECGECGAn 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 or arrhythmias, even with severe hyperkalemia.

Muscular symptoms

• Muscle weakness
• Ascending flaccid paralysis (can resemble Guillain–Barré syndrome)
• Unlikely to haverespiratory failureRespiratory failureRespiratory 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 torespiratory muscle weaknessRespiratory muscle weaknessRespiratory Acidosis

Management and Diagnosis

The management of hyperkalemia often takes precedence over the diagnosis because of the possibility of life-threatening arrhythmias and is guided by determining the level of urgency needed for treatment. Usually, the etiology of hyperkalemia is not difficult to determine and is not impeded by treating it first.

Management

1. Hyperkalemic emergency?
   • ECGECGAn 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, arrhythmia, or severe muscle weakness/paralysis
   • Serum K⁺ usually > 6.5 mEq/L 
   • Options for emergency treatment:
     • IVcalciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes to stabilizemyocardiumMyocardiumThe muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow.Heart: Anatomy
     • InsulinInsulinInsulin 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/glucoseGlucoseA 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 +/–sodiumSodiumA member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23.HyponatremiabicarbonateBicarbonateInorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.Electrolytes +/– β₂ agonist, to shift K⁺ into cells
     • Cation exchange resin +/– loop diuretic to remove K⁺
     • HemodialysisHemodialysisProcedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys.Crush Syndrome
   • Monitor serum K⁺ frequently
   • Continuous cardiac monitoring and/or repeatECGECGAn 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) while treating
   • Consult nephrology early
2. Lab result accurate?
   • Hemolyzed specimen?
     • Very common type of pseudohyperkalemia
     • Most labs will routinely indicate if specimen is hemolyzed.  
     • Redraw lab prior to making treatment decisions.
   • Less common causes of pseudohyperkalemia?
     • Severe thrombocytosis (i.e., > 1000 × 10⁹/L)
     • SevereleukocytosisLeukocytosisA transient increase in the number of leukocytes in a body fluid.West Nile Virus (i.e., > 50,000 × 10⁹/L)
     • MeasureplasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products K⁺(rather than routine serum K⁺) to obtain accurate level.
3. Moderate hyperkalemia with high risk?
   • Generally asymptomatic and withoutECGECGAn 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
   • Serum K⁺ 5.5–6.5 mEq/L with high-risk factor:
     • Sudden increase (e.g., 3.7 mEq/L to 6 mEq/L overnight) 
     • Ongoing K⁺ release (e.g.,tumor lysisTumor LysisTumor Lysis Syndrome,rhabdomyolysisRhabdomyolysisRhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation.Rhabdomyolysis)
     • Ongoing K⁺absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption (e.g., GI bleeding) 
     • Kidney dysfunction
     • MetabolicacidosisAcidosisA 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
   • Treat similarly to hyperkalemic emergency, but no need for IVcalciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes.
4. Moderate hyperkalemia without high risk?
   • Generally asymptomatic and withoutECGECGAn 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
   • Serum K⁺ 5.5–6.5 mEq/L without any of the above risk factors
   • Treat urgently:
     • Cation exchange resin +/– loop diuretic +/–hemodialysisHemodialysisProcedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys.Crush Syndrome to remove K⁺
     • Differences with emergent treatment:
       • Do not need IVcalciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes 
       • Do not necessarily need shifting measures
   • Monitor serum K⁺ frequently
   • Continuous cardiac monitoring and/or repeatECGECGAn 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) while treating
5. Mild hyperkalemia?
   • Generally asymptomatic and withoutECGECGAn 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
   • Serum K⁺ < 5.5 mEq/L 
   • Does not require urgent treatment
   • Management is primarily risk-factor modification:
     • Dietary K⁺ restriction if renal dysfunction
     • Stop/adjust offending medications (e.g.,ACEiACEiA class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Renin-Angiotensin-Aldosterone System Inhibitors/ARB,NSAIDsNSAIDSPrimary vs Secondary Headaches,etcETCThe electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP).Electron Transport Chain (ETC).).
     • Start/adjust loop orthiazideThiazideHeterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics.HyponatremiadiureticsDiureticsAgents that promote the excretion of urine through their effects on kidney function.Heart Failure and Chronic Coronary Syndrome Medication.
     • Start/adjust oralsodiumSodiumA member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23.HyponatremiabicarbonateBicarbonateInorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.Electrolytes.
     • Start/adjust cation exchange resin.
6. Identify and treat any contributing underlying diseases.

Diagnosis

1. AKIAKIAcute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine.Acute Kidney Injury orCKDCKDChronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities.Chronic Kidney Disease present?
2. Recent process that could causetranscellularTranscellularThe movement of one cell into, through, and out of another cell.Tubular System shift?
   • New or worsening metabolicacidosisAcidosisA 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 (includingDKADKADiabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency.Hyperglycemic Crises)
   • Recent intense exercise
   • Recent surgery
3. Other predisposing disease process present?
   • HypovolemiaHypovolemiaSepsis in Children or other states of decreasedeffective arterial blood volumeEffective arterial blood volumeRenal Sodium and Water Regulation (congestiveheart failureHeart FailureA heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction.Total Anomalous Pulmonary Venous Return (TAPVR),cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome.Cirrhosis)
   • High cell turnover (tumor lysisTumor LysisTumor Lysis Syndrome syndrome,rhabdomyolysisRhabdomyolysisRhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation.Rhabdomyolysis,burnsBurnsA burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns.Burns)
   • RBCabsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption (RBC transfusion, GI bleeding, largehematomaHematomaA collection of blood outside the blood vessels. Hematoma can be localized in an organ, space, or tissue.Intussusception reabsorption) 
4. Review medication list carefully.
5. Checkplasma renin activityPlasma renin activityRenal Artery Stenosis and aldosterone if etiology is still not identified.

Differential Diagnosis

• RhabdomyolysisRhabdomyolysisRhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation.Rhabdomyolysis: large-scale musclecell deathCell deathInjurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects.Cell Injury and Death, which can result from many possible etiologies (trauma, drugs, toxins,infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease): Serum K⁺ can increase suddenly ifrhabdomyolysisRhabdomyolysisRhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation.Rhabdomyolysis is unrecognized or inadequately treated or ifAKIAKIAcute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine.Acute Kidney Injury develops (common complication).RhabdomyolysisRhabdomyolysisRhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation.Rhabdomyolysis is diagnosed by a serum CK level > 5 times the upperlimitLimitA value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lungInvasive Mechanical Ventilation of normal and treated withIV fluidsIV fluidsIntravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids.Intravenous Fluids.
• Tumor lysisTumor LysisTumor Lysis Syndrome syndrome:large-scale malignantcell deathCell deathInjurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects.Cell Injury and Death, often sudden and brought on by the initiation ofchemotherapyChemotherapyOsteosarcoma: Large amounts of intracellular K⁺,phosphatePhosphateInorganic salts of phosphoric acid.Electrolytes, anduric acidUric acidAn oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin.Nephrolithiasis are released when malignant cells die. Treated withrasburicaseRasburicaseGout Drugs (forhyperuricemiaHyperuricemiaExcessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women.Gout),calciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes supplementation, anddialysisDialysisRenal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD).Peritoneal Dialysis and Hemodialysis, if necessary.
• Digoxin toxicityDigoxin ToxicityCardiac Glycosides:DigoxinDigoxinA 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 is the only commonly used cardiac glycoside.ToxicityToxicityDosage Calculation is common, as thetherapeutic windowTherapeutic WindowDosage Calculation is narrow and excretion is renal. Clinical presentation includes arrhythmias, hyperkalemia, and characteristicvisionVisionOphthalmic Exam changes, including increased yellow colors invisionVisionOphthalmic Exam (xanthopsia). Treated with digoxin-specific antibody (FabFabUnivalent antigen-binding fragments composed of one entire immunoglobulin light chain and the amino terminal end of one of the immunoglobulin heavy chains from the hinge region, linked to each other by disulfide bonds. Fab contains the immunoglobulin variable regions, which are part of the antigen-binding site, and the first immunoglobulin constant regions. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme papain.Immunoglobulins: Types and Functions) fragments, whichbindBINDHyperbilirubinemia of the Newborn to and thereby inactivate the circulating drug. 
• Malignant hyperthermiaMalignant hyperthermiaAn important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis.Malignant Hyperthermia:a life-threatening syndrome characterized by hyperthermia,muscle rigidityMuscle rigidityContinuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.Motor Neuron Lesions, and hyperkalemia (viarhabdomyolysisRhabdomyolysisRhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation.Rhabdomyolysis):Malignant hyperthermiaMalignant hyperthermiaAn important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis.Malignant Hyperthermia is triggered by perioperative volatile anesthetic use in genetically predisposedpatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship. Treatment includesdantroleneDantroleneSkeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants.Spasmolytics (skeletal muscle reluctant) and supportive care.
• Primary adrenal insufficiencyPrimary adrenal insufficiencyAn adrenal disease characterized by the progressive destruction of the adrenal cortex, resulting in insufficient production of aldosterone and hydrocortisone. Clinical symptoms include anorexia; nausea; weight loss; muscle weakness; and hyperpigmentation of the skin due to increase in circulating levels of acth precursor hormone which stimulates melanocytes.Adrenal Insufficiency and Addison Disease (Addison disease): a rare, autoimmune type of destruction of theadrenal glandsAdrenal GlandsThe adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response.Adrenal Glands: Anatomy: Addison disease is diagnosed by measuring aldosterone (low),reninReninA highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system.Renal Sodium and Water Regulation (high), serumcortisolCortisolGlucocorticoids (low), and ACTH (low) and ACTH stimulation test. Addison disease leads to hyperkalemia primarily throughhypoaldosteronismHypoaldosteronismHypoaldosteronism is a hormonal disorder characterized by low levels of aldosterone. These low levels can be caused by decreased aldosterone production or a peripheral resistance to aldosterone. When hypoaldosteronism occurs as a result of an acquired decrease in renin production, the condition is more commonly referred to as renal tubular acidosis (RTA) type 4.Hypoaldosteronism. The disease manifests acutely asadrenal crisisAdrenal crisisAdrenal crisis is the acute decompensation of adrenal function that can be triggered by another disease, surgery, stress, or increased glucocorticoid inactivation.Adrenal Insufficiency and Addison Disease, which is an emergency because of circulatoryshockShockShock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed.Types of Shock. Acute treatment is high-doseglucocorticoidsGlucocorticoidsGlucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs.Glucocorticoids and supportive care. Long-term treatment is by substitutingglucocorticoidsGlucocorticoidsGlucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs.Glucocorticoids (hydrocortisoneHydrocortisoneThe main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Immunosuppressants) andmineralocorticoidsMineralocorticoidsMineralocorticoids are a drug class within the corticosteroid family and fludrocortisone is the primary medication within this class. Fludrocortisone is a fluorinated analog of cortisone. The fluorine moiety protects the drug from isoenzyme inactivation in the kidney, allowing it to exert its mineralocorticoid effect.Mineralocorticoids (fludrocortisoneFludrocortisoneA synthetic mineralocorticoid with anti-inflammatory activity.Mineralocorticoids).  
• DiabeticketoacidosisKetoacidosisA 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 (DKADKADiabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency.Hyperglycemic Crises):severeacidosisAcidosisA 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 caused byinsulinInsulinInsulin 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 deficiency, usually in the setting oftype 1Type 1Spinal Muscular AtrophydiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus: Presents with total body K⁺ deficit (urinary losses fromosmotic diuresisOsmotic diuresisVolume Depletion and Dehydration/polyuriaPolyuriaUrination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes.Renal Potassium Regulation); however, serum K⁺ will be normal or high. Treatment is byinsulinInsulinInsulin 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 replacement followed by K⁺ supplementation once theplasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products level falls. If there is even mildhypokalemiaHypokalemiaHypokalemia is defined as plasma potassium (K+) concentration< 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake.Hypokalemia on presentation, this represents severe total body K⁺ deficit, and theplasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products K⁺ will decrease even further once aninsulinInsulinInsulin 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 drip is started. In this situation, K⁺ must be replaced until theplasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products level is at least 3.3 mEq/L prior to startinginsulinInsulinInsulin 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. 
• Hyperkalemic periodic paralysisHyperkalemic Periodic ParalysisIon Channel Myopathy: a rare genetic disease withautosomal dominant inheritanceAutosomal dominant inheritanceAutosomal Recessive and Autosomal Dominant Inheritance:Hyperkalemic periodic paralysisHyperkalemic Periodic ParalysisIon Channel Myopathy is characterized by acute attacks of muscle weakness and/or paralysis due to hyperkalemia from severetranscellularTranscellularThe movement of one cell into, through, and out of another cell.Tubular System shifting of K⁺. Attacks are precipitated by cold temperatures, rest after exercise, and/or K⁺ ingestion. If recovery is not spontaneous, treatment is with inhaled β₂ agonists and K⁺-removing therapies (e.g.,furosemideFurosemideA benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency.Loop Diuretics, cation exchange resins,dialysisDialysisRenal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD).Peritoneal Dialysis and Hemodialysis).
• Type IV renal tubularacidosisAcidosisA 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 (RTARTARenal 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): a syndrome of decreased urinarysecretionSecretionCoagulation Studies of K⁺ and H⁺ at the principal cell, resulting in a non–anion gapAnion gapMetabolic Acidosis metabolicacidosisAcidosisA 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 and hyperkalemia: Common causes includediabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus,NSAIDsNSAIDSPrimary vs Secondary Headaches,calcineurin inhibitorsCalcineurin InhibitorsCompounds that inhibit or block the phosphatase activity of calcineurin.Immunosuppressants, heparin, and Addison disease. Diagnosed by history and measuring serumcortisolCortisolGlucocorticoids,reninReninA highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system.Renal Sodium and Water Regulation, and aldosterone. Treatment is by mineralocorticoid replacement (e.g.,fludrocortisoneFludrocortisoneA synthetic mineralocorticoid with anti-inflammatory activity.Mineralocorticoids). Hyperkalemia is usually not severe unless concurrent predisposing factors are present.

References

1. Gutmann, L., Conwit, R. (2025). Hyperkalemic periodic paralysis. UpToDate. Retrieved June 19, 2025, fromhttps://www.uptodate.com/contents/hyperkalemic-periodic-paralysis
2. Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., Loscalzo, J. (2015).Harrison’s principles of internal medicine (19th ed..). New York: McGraw Hill Education.
3. Levine, M.D., O’Connar A. (2025). Digitalis (cardiac glycoside) poisoning. UpToDate. Retrieved June 19, 2025, fromhttps://www.uptodate.com/contents/digitalis-cardiac-glycoside-poisoning
4. Mount, D.B. (2025). Causes and evaluation of hyperkalemia in adults. UpToDate. Retrieved June 19, 2025, fromhttps://www.uptodate.com/contents/causes-and-evaluation-of-hyperkalemia-in-adults
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6. Mount, D.B. (2025). Treatment and prevention of hyperkalemia in adults. UpToDate. Retrieved June 19, 2025, fromhttps://www.uptodate.com/contents/treatment-and-prevention-of-hyperkalemia-in-adults
7. Nieman, L. K. (2025). Causes of primary adrenal insufficiency (Addison’s disease). UpToDate.  Retrieved June 19, 2025, from https://www.uptodate.com/contents/causes-of-primary-adrenal-insufficiency-addisons-disease
8. Nieman, LK. (2025). Treatment of adrenal insufficiency in adults. UpToDate. Retrieved June 19, 2025, fromhttps://www.uptodate.com/contents/treatment-of-adrenal-insufficiency-in-adults
9. Young, W. F., Jr. (2025). Etiology, diagnosis, and treatment of hypoaldosteronism (type 4 RTA). UpToDate. Retrieved June 19, 2025, fromhttps://www.uptodate.com/contents/etiology-diagnosis-and-treatment-of-hypoaldosteronism-type-4-rta