HYPERKALEMIAHYPERKALEMIA

Dr Niyaz Muhammed MDDr Niyaz Muhammed MD

Body content & physiologic functionBody content & physiologic functionPotassium is the most abundant Potassium is the most abundant intracellular cationintracellular cationmajor key effector is the energy-major key effector is the energy-consuming enzyme Naconsuming enzyme Na++/K/K++-ATPase, -ATPase, located in the plasma membrane of cells, located in the plasma membrane of cells, which pumps Nawhich pumps Na++ out of and K out of and K++ into the into the cell in a 3:2 ratio (3Nacell in a 3:2 ratio (3Na++:2K:2K++).).

Necessary for electrical responsiveness of Necessary for electrical responsiveness of nerve and muscle cellsnerve and muscle cells..

NaNa++/K/K++-ATPase helps to maintain the resting -ATPase helps to maintain the resting potential.potential.

Ratio of intracellular to extracellular K Ratio of intracellular to extracellular K concentration determines the threshold of concentration determines the threshold of a cell to generate an action potential.a cell to generate an action potential.

INTAKEINTAKE

Common potassium-rich foods include Common potassium-rich foods include fruits, potatoes, beans, and grains.fruits, potatoes, beans, and grains.Recommended intake is 1-2 meq/kg.Recommended intake is 1-2 meq/kg.Absorption occcurs in small intestine.Absorption occcurs in small intestine.

EXCRETIONEXCRETIONApproximately 10% of the daily potassium Approximately 10% of the daily potassium intake is cleared via the gastrointestinal intake is cleared via the gastrointestinal tract.tract.excretion of potassium mainly occurs in excretion of potassium mainly occurs in the kidneys.the kidneys.Potassium is filtered in the glomerulus and Potassium is filtered in the glomerulus and almost completely reabsorbed in the almost completely reabsorbed in the proximal tubule and the loop of Henle. proximal tubule and the loop of Henle. Excretion mainly occurs in the cortical Excretion mainly occurs in the cortical collecting duct.collecting duct.

Principal hormone regulating potassium Principal hormone regulating potassium secretion is aldosteronesecretion is aldosteroneMain site of action is the cortical collecting duct.Main site of action is the cortical collecting duct.It activates the basolateral NaIt activates the basolateral Na++/K/K++-ATPase, -ATPase, thereby increasing Nathereby increasing Na++ and water reabsorption and water reabsorption and secretion of Kand secretion of K++ into the urine. into the urine.Glucocorticoids,ADH,high urinary flow rate, and Glucocorticoids,ADH,high urinary flow rate, and high sodium delivery to the distal nephron high sodium delivery to the distal nephron increase urinary potassium excretion.increase urinary potassium excretion.Approx 10 -15 % of filtered load is exrcreted Approx 10 -15 % of filtered load is exrcreted

HyperkalemiaHyperkalemiaserum potassium exceeds 5.5 mmol/l.serum potassium exceeds 5.5 mmol/l.Hyperkalemia may result from an increase in Hyperkalemia may result from an increase in total body potassium secondary to imbalance of total body potassium secondary to imbalance of intake vs. excretionintake vs. excretion

or from maldistribution between intra- and or from maldistribution between intra- and extracellular space.extracellular space.

In patients with impaired renal function, In patients with impaired renal function, especially when GFR is <15 ml/min, a slight especially when GFR is <15 ml/min, a slight increase in potassium intake can cause severe increase in potassium intake can cause severe hyperkalemia.hyperkalemia.

CAUSESCAUSES SPURIOUS LAB VALUE- SPURIOUS LAB VALUE-

Hemolysis,Thrombocytosis,Leukocytosis,Tissue Hemolysis,Thrombocytosis,Leukocytosis,Tissue ischemia during blood drawing. ischemia during blood drawing.

INCREASED INTAKE –INCREASED INTAKE – Intravenous or oral, blood transfusions.Intravenous or oral, blood transfusions.

DECREASED EXCRETION –DECREASED EXCRETION – Renal insufficiency acute or chronicRenal insufficiency acute or chronic;; reduced reduced

GFR (especially <15 ml/min/1.73 mGFR (especially <15 ml/min/1.73 m22) with low urine ) with low urine flow (and therefore low sodium delivery to the distal flow (and therefore low sodium delivery to the distal tubule) lead to decreased renal excretion of tubule) lead to decreased renal excretion of potassium.potassium.

HypoaldosteronismHypoaldosteronism may either be primary (e.g. Addison disease) or may either be primary (e.g. Addison disease) or

secondary (e.g. chronic renal failure), resulting in secondary (e.g. chronic renal failure), resulting in hyperkalemia accompanied by urinary salt wasting, hyperkalemia accompanied by urinary salt wasting, leading to volume depletion and hypotension.leading to volume depletion and hypotension.congenital adrenal hyperplasia;(CAH)congenital adrenal hyperplasia;(CAH)Hyporeninemic hypoaldosteronismHyporeninemic hypoaldosteronism::

Urinary tract obstruction, Sickle cell disease, Urinary tract obstruction, Sickle cell disease, Lupus nephritis, Kidney transplant.Lupus nephritis, Kidney transplant.Renal tubular disordersRenal tubular disorders::

Pseudohypoaldosteronism type 1Pseudohypoaldosteronism type 1 Psuedohypoaldosteronism type2(Gordon syndrome)Psuedohypoaldosteronism type2(Gordon syndrome)

PHA type I caused by autosomal dominant PHA type I caused by autosomal dominant mutations in the human mineralocorticoid mutations in the human mineralocorticoid receptor (receptor (MRMR) gene in the kidney.) gene in the kidney.PHA-II (also known as Gordon’s syndrome) is a PHA-II (also known as Gordon’s syndrome) is a rare familial renal tubular defect . Gordon’s rare familial renal tubular defect . Gordon’s syndrome is characterized by volume syndrome is characterized by volume expansion, suppressed renin, and reduced expansion, suppressed renin, and reduced mineralocorticoid-induced renal clearance of mineralocorticoid-induced renal clearance of potassium leading to hypertension and potassium leading to hypertension and hyperkalemia, and hyperchloremic acidosis with hyperkalemia, and hyperchloremic acidosis with normal glomerular filtration rate normal glomerular filtration rate

medicationsmedications AmilorideAmiloride : Blocking sodium channels of luminal : Blocking sodium channels of luminal membrane of principal cells.membrane of principal cells. SpironolactoneSpironolactone : Mineralocorticoid receptor : Mineralocorticoid receptor antagonist (competing with aldosterone) ,Inhibition antagonist (competing with aldosterone) ,Inhibition of adrenal aldosterone biosynthesis.of adrenal aldosterone biosynthesis.Cyclosporine, TacrolimusCyclosporine, Tacrolimus : Inhibition of adrenal : Inhibition of adrenal aldosterone biosynthesis , Induction of chloride aldosterone biosynthesis , Induction of chloride channel shunt, Increasing potassium efflux from channel shunt, Increasing potassium efflux from cells.cells.Trimetoprim, PentamidineTrimetoprim, Pentamidine : Blocking of sodium : Blocking of sodium channels in the luminal membrane of principal cellschannels in the luminal membrane of principal cells

NSAIDsNSAIDs : Induction of hyporeninemic : Induction of hyporeninemic hypoaldosteronism through inhibiting renal hypoaldosteronism through inhibiting renal prostaglandin synthesisprostaglandin synthesisACE inhibitors, Angiotensin-II receptor ACE inhibitors, Angiotensin-II receptor antagonists antagonists : Reduction in adrenal aldosterone : Reduction in adrenal aldosterone biosynthesis through interrupting renin-biosynthesis through interrupting renin-aldosterone axis.aldosterone axis.Beta blockers Beta blockers : Inhibiting renin secretion: Inhibiting renin secretionHeparin :Heparin : Inhibition of adrenal aldosterone Inhibition of adrenal aldosterone biosynthesis , Decreasing number and affinity of biosynthesis , Decreasing number and affinity of angiotensin-II receptorsangiotensin-II receptors

Calcium channels blockers (Nifedipine, Calcium channels blockers (Nifedipine, Amlodipine) Amlodipine) : Inhibition of adrenal aldosterone : Inhibition of adrenal aldosterone biosynthesis , Reduction in aldosterone biosynthesis , Reduction in aldosterone secretionsecretionSuccinylcholineSuccinylcholine : Leakage of potassium out of : Leakage of potassium out of cells through depolarization of cell membranescells through depolarization of cell membranesDigoxin :Digoxin : Inhibition of Na Inhibition of Na++/K/K++-ATPase-ATPaseMannitol : Mannitol : “Solvent drag phenomena” whereby “Solvent drag phenomena” whereby potassium shifts out of cells due to the body’s potassium shifts out of cells due to the body’s attempt to maintain isotonicity while undergoing attempt to maintain isotonicity while undergoing a hypertonic infusiona hypertonic infusion

TRANSCELLULAR SHIFTTRANSCELLULAR SHIFTIncreased shift of Increased shift of potassiumpotassium from intra to extracellular space from intra to extracellular space AcidosisAcidosis RhabdomyolysisRhabdomyolysis HemolysisHemolysis Tumor lysis syndromeTumor lysis syndrome increase in osmolality secondary to hyperglycemia or increase in osmolality secondary to hyperglycemia or

mannitol infusionmannitol infusion digoxin and beta-blockers digoxin and beta-blockers SuccinylcholineSuccinylcholine Hyperkalemic periodic paralysisHyperkalemic periodic paralysis Insulin deficiency,Malignant hyperthermia.Insulin deficiency,Malignant hyperthermia.

Diagnostic algorithm based on GFR and Diagnostic algorithm based on GFR and

aldosterone levelsaldosterone levels..

Diagnosis of Diagnosis of hyperkalemiahyperkalemia

can be classified according to serum potassium can be classified according to serum potassium into mild (5.5–6.5 mmol/l), moderate (6.5–into mild (5.5–6.5 mmol/l), moderate (6.5–7.5 mmol/l) and severe (>7.5 mmol/l) 7.5 mmol/l) and severe (>7.5 mmol/l) hyperkalemia.hyperkalemia.Hyperkalemia is rarely associated with Hyperkalemia is rarely associated with symptoms, occasionally patients complain of symptoms, occasionally patients complain of palpitations, nausea, muscle pain, or palpitations, nausea, muscle pain, or paresthesia. moderate and especially severe paresthesia. moderate and especially severe hyperkalemia can lead to disturbances of hyperkalemia can lead to disturbances of cardiac rhythm.cardiac rhythm.

ECG changes may present as non-ECG changes may present as non-specific repolarization abnormalities.specific repolarization abnormalities.ECG changes begin withECG changes begin with

Peaking of the T waves Peaking of the T waves ST segment depression ST segment depression Increased PR intervalIncreased PR interval Flattening of the P waveFlattening of the P wave Widening of the QRS complexWidening of the QRS complex.. Ventricular fibrillation , AsystoleVentricular fibrillation , Asystole

DiagnosisDiagnosis History of potassium intakeHistory of potassium intakeRisk factors for transcellular shifts of Risk factors for transcellular shifts of potassiumpotassiumMedications that cause hyperkalemiaMedications that cause hyperkalemiaSymptoms of renal insufficiency-Symptoms of renal insufficiency-Oliguria,Oedema.Oliguria,Oedema.

InvestigationsInvestigations  Full blood count

Hemolytic anemiaHemolytic anemia HUSHUS ThrombocytosisThrombocytosis Infection & sepsisInfection & sepsis

  Blood gas analysisBlood gas analysis AcidosisAcidosis

  Serum osmolalitySerum osmolality Calculation of TTKGCalculation of TTKG

S Creatinine, Blood urea –S Creatinine, Blood urea – Acute and chronic renal insufficiencyAcute and chronic renal insufficiency

   CKCK RhabdomyolysisRhabdomyolysis

  LDHLDH Hemolysis, tumor lysis syndrome.Hemolysis, tumor lysis syndrome.

  Renin, angiotensin, aldosteroneRenin, angiotensin, aldosterone Hyporeninemic hypoaldosteronism, Hyporeninemic hypoaldosteronism,

pseudohypoaldosteronism pseudohypoaldosteronism   Cortisol, 11-beta hydroxylase or 21-Cortisol, 11-beta hydroxylase or 21-hydroxylase or 17-OH progesterone in hydroxylase or 17-OH progesterone in plasmaplasma

Reduced enzyme activities in congenital Reduced enzyme activities in congenital adrenal hyperplasiaadrenal hyperplasia  AlbuminAlbumin

ProteinuriaProteinuria

  TTKG – transtubular potassium gradientTTKG – transtubular potassium gradient Serum osmolality Serum osmolality ** Urine potassium Urine potassium Urine osmolality * Serum PotassiumUrine osmolality * Serum Potassium evaluate the renal response to hyperkalemia evaluate the renal response to hyperkalemia

TTKG expected to be high (usually >10) in TTKG expected to be high (usually >10) in hyperkalemia when renal response is intact. An hyperkalemia when renal response is intact. An inappropriately low TTKG in a hyperkalemic inappropriately low TTKG in a hyperkalemic patient suggests hypoaldosteronism or a renal patient suggests hypoaldosteronism or a renal tubule defect. tubule defect.

  Index of potassium secretory activity in the Index of potassium secretory activity in the distal tubuledistal tubule

Test is most useful in distinguishing Test is most useful in distinguishing patients who have mineralocorticoid patients who have mineralocorticoid deficiency versus resistance by observing deficiency versus resistance by observing a change in TTKG values after a change in TTKG values after administration of mineralocorticoid: administration of mineralocorticoid: increase in TTKG in mineralocorticoid-increase in TTKG in mineralocorticoid-deficient but not aldosterone resistant deficient but not aldosterone resistant statesstates

TREATMENTTREATMENT

2 Basic goals2 Basic goals1) to stabilise the heart to prevent life 1) to stabilise the heart to prevent life threatening arrhythmias. threatening arrhythmias.

2) to remove potassium from the body.2) to remove potassium from the body.

Step 1Step 1: Evaluate patient for potential : Evaluate patient for potential toxicities and initiate ECG monitoring toxicities and initiate ECG monitoring Ca-Gluconate 10%Ca-Gluconate 10%To stabilise the cell membrane of heart To stabilise the cell membrane of heart cells to prevent arrhythmiascells to prevent arrhythmias0.5–1 ml/kg over 5-10 min, preferably 0.5–1 ml/kg over 5-10 min, preferably administered via central venous accessadministered via central venous accessShould be given over 30 mins in patients Should be given over 30 mins in patients taking digoxin.taking digoxin.Step 2:Step 2: Identify and immediately eliminate Identify and immediately eliminate sources of potassium intake sources of potassium intake

Step 3Step 3:: Increase potassium shift from Increase potassium shift from extra- to intracellular space extra- to intracellular space Dextrose and insulin infusion.Dextrose and insulin infusion.

0.1 U/kg of insulin in 0.5g/kg(2ml/kg) of 25 0.1 U/kg of insulin in 0.5g/kg(2ml/kg) of 25 % dextrose solution over 15 to 30 mins.% dextrose solution over 15 to 30 mins.Beta-adrenergic agonists (salbutamol, Beta-adrenergic agonists (salbutamol, reproterolreproterol) ) Salbutamol can be applied via nebulizer Salbutamol can be applied via nebulizer or given intravenouslyor given intravenouslyNebulized: 2.5 mg if <25 kg and 5 mg if Nebulized: 2.5 mg if <25 kg and 5 mg if >25 kg>25 kg

Sodium bicarbonate:Sodium bicarbonate:1-2 meq/kg over 5-10 mins1-2 meq/kg over 5-10 minspreferably given to patients who are preferably given to patients who are acidotic.acidotic.Step 4:Step 4: Increase potassium excretion Increase potassium excretion Loop diuretics (furosemide) Loop diuretics (furosemide) Ion-exchange resins-sodium polystyrene Ion-exchange resins-sodium polystyrene sulfonate(kayexalate).sulfonate(kayexalate).Sodium in the resin is exchanged for body Sodium in the resin is exchanged for body potassium .potassium .

Can be given orally or as a retention Can be given orally or as a retention enema. Dose is 1g/kg.enema. Dose is 1g/kg.More effective if given orally. Enemas More effective if given orally. Enemas should be retained at least 30-60 min. should be retained at least 30-60 min. Onset within 1-2 h, lasting 4-6 h.Onset within 1-2 h, lasting 4-6 h.Renal replacement therapy (RRT) Renal replacement therapy (RRT) is the is the ultimate measure in severe hyperkalemia. ultimate measure in severe hyperkalemia. Hemodialysis (HD) Hemodialysis (HD) provides a provides a substantially higher potassium clearancesubstantially higher potassium clearanceContinuous veno-venous hemofiltration Continuous veno-venous hemofiltration (CVVH) can more satisfactorily provide (CVVH) can more satisfactorily provide long-term control of potassium.long-term control of potassium.

ReferencesReferences

Nelson text book of paediatrics-19Nelson text book of paediatrics-19thth edition edition page no:219-222.page no:219-222.Webb NJ, Postlethwaite RJ (2003) Clinical Webb NJ, Postlethwaite RJ (2003) Clinical Paediatric Nephrology, 3rd edn. Oxford Paediatric Nephrology, 3rd edn. Oxford University PressUniversity PressAnja Lehnhart and Markus J. Kemper Anja Lehnhart and Markus J. Kemper

Pediatr Nephrol. Mar 2011; 26(3): 377–Pediatr Nephrol. Mar 2011; 26(3): 377–384.Pubmed.384.Pubmed.

Textbook of pediatric nephrology :5 th Textbook of pediatric nephrology :5 th edition.Aravind baggaedition.Aravind bagga