This document discusses hyperkalemia, or high levels of potassium in the blood. It covers the normal physiology of potassium balance in the body, including intake through foods, absorption in the intestines, and excretion primarily through the kidneys under regulation of the hormone aldosterone. Causes of hyperkalemia include reduced kidney function, medications that interfere with potassium excretion, and conditions that cause a shift of potassium out of cells. The document provides details on evaluating, diagnosing, and classifying different severities of hyperkalemia based on serum potassium levels.

1. HYPERKALEMIAHYPERKALEMIA
Dr Niyaz Muhammed MDDr Niyaz Muhammed MD

2. Body content & physiologic functionBody content & physiologic function
Potassium is the most abundantPotassium is the most abundant
intracellular cationintracellular cation
major 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 Kout of and K++
into the cellinto the cell
in a 3:2 ratio (3Nain a 3:2 ratio (3Na++
:2K:2K++
).).

3. Necessary for electrical responsiveness ofNecessary 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 KRatio of intracellular to extracellular K
concentration determines the threshold ofconcentration determines the threshold of
a cell to generate an action potential.a cell to generate an action potential.

4. INTAKEINTAKE
Common potassium-rich foods includeCommon 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.

5. EXCRETIONEXCRETION
Approximately 10% of the daily potassiumApproximately 10% of the daily potassium
intake is cleared via the gastrointestinalintake is cleared via the gastrointestinal
tract.tract.
excretion of potassium mainly occurs inexcretion of potassium mainly occurs in
the kidneys.the kidneys.
Potassium is filtered in the glomerulus andPotassium is filtered in the glomerulus and
almost completely reabsorbed in thealmost completely reabsorbed in the
proximal tubule and the loop of Henle.proximal tubule and the loop of Henle.
Excretion mainly occurs in the corticalExcretion mainly occurs in the cortical
collecting duct.collecting duct.

6. Principal hormone regulating potassiumPrincipal hormone regulating potassium
secretion is aldosteronesecretion is aldosterone
Main 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 reabsorptionand water reabsorption
and secretion of Kand secretion of K++
into the urine.into the urine.
Glucocorticoids,ADH,high urinary flow rate, andGlucocorticoids,ADH,high urinary flow rate, and
high sodium delivery to the distal nephronhigh sodium delivery to the distal nephron
increase urinary potassium excretion.increase urinary potassium excretion.
Approx 10 -15 % of filtered load is exrcretedApprox 10 -15 % of filtered load is exrcreted

7. HyperkalemiaHyperkalemia
serum potassium exceeds 5.5 mmol/l.serum potassium exceeds 5.5 mmol/l.
Hyperkalemia may result from an increase inHyperkalemia may result from an increase in
total body potassium secondary to imbalance oftotal body potassium secondary to imbalance of
intake vs. excretionintake vs. excretion
or from maldistribution between intra- andor 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 slightespecially when GFR is <15 ml/min, a slight
increase in potassium intake can cause severeincrease in potassium intake can cause severe
hyperkalemia.hyperkalemia.

8. CAUSESCAUSES
SPURIOUS LAB VALUE-SPURIOUS LAB VALUE-
Hemolysis,Thrombocytosis,Leukocytosis,TissueHemolysis,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;; reducedreduced
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 theflow (and therefore low sodium delivery to the
distal tubule) lead to decreased renal excretion ofdistal tubule) lead to decreased renal excretion of
potassium.potassium.

9. HypoaldosteronismHypoaldosteronism
may either be primary (e.g. Addison disease) ormay either be primary (e.g. Addison disease) or
secondary (e.g. chronic renal failure), resulting insecondary (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)

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

11. 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) ,Inhibitionantagonist (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 chloridealdosterone biosynthesis , Induction of chloride
channel shunt, Increasing potassium efflux fromchannel 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

12. NSAIDsNSAIDs : Induction of hyporeninemic: Induction of hyporeninemic
hypoaldosteronism through inhibiting renalhypoaldosteronism through inhibiting renal
prostaglandin synthesisprostaglandin synthesis
ACE inhibitors, Angiotensin-II receptorACE inhibitors, Angiotensin-II receptor
antagonistsantagonists : Reduction in adrenal aldosterone: Reduction in adrenal aldosterone
biosynthesis through interrupting renin-biosynthesis through interrupting renin-
aldosterone axis.aldosterone axis.
Beta blockersBeta blockers : Inhibiting renin secretion: Inhibiting renin secretion
Heparin :Heparin : Inhibition of adrenal aldosteroneInhibition of adrenal aldosterone
biosynthesis , Decreasing number and affinity ofbiosynthesis , Decreasing number and affinity of
angiotensin-II receptorsangiotensin-II receptors

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

14. TRANSCELLULAR SHIFTTRANSCELLULAR SHIFT
Increased shift ofIncreased shift of potassiumpotassium from intra to extracellular spacefrom intra to extracellular space
 AcidosisAcidosis
 RhabdomyolysisRhabdomyolysis
 HemolysisHemolysis
 Tumor lysis syndromeTumor lysis syndrome
 increase in osmolality secondary to hyperglycemia orincrease in osmolality secondary to hyperglycemia or
mannitol infusionmannitol infusion
 digoxin and beta-blockersdigoxin and beta-blockers
 SuccinylcholineSuccinylcholine
 Hyperkalemic periodic paralysisHyperkalemic periodic paralysis
 Insulin deficiency,Malignant hyperthermia.Insulin deficiency,Malignant hyperthermia.

15. Diagnostic algorithm based on GFR andDiagnostic algorithm based on GFR and
aldosterone levelsaldosterone levels..

16. Diagnosis of hyperkalemiaDiagnosis of hyperkalemia
can be classified according to serum potassiumcan 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 withHyperkalemia is rarely associated with
symptoms, occasionally patients complain ofsymptoms, occasionally patients complain of
palpitations, nausea, muscle pain, orpalpitations, nausea, muscle pain, or
paresthesia. moderate and especially severeparesthesia. moderate and especially severe
hyperkalemia can lead to disturbances ofhyperkalemia can lead to disturbances of
cardiac rhythm.cardiac rhythm.

17. 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 wavesPeaking of the T waves
ST segment depressionST 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

21. DiagnosisDiagnosis
History of potassium intakeHistory of potassium intake
Risk factors for transcellular shifts ofRisk factors for transcellular shifts of
potassiumpotassium
Medications that cause hyperkalemiaMedications that cause hyperkalemia
Symptoms of renal insufficiency-Symptoms of renal insufficiency-
Oliguria,Oedema.Oliguria,Oedema.

22. 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

23. 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.

24. Renin, angiotensin, aldosteroneRenin, angiotensin, aldosterone
Hyporeninemic hypoaldosteronism,Hyporeninemic hypoaldosteronism,
pseudohypoaldosteronismpseudohypoaldosteronism
Cortisol, 11-beta hydroxylase or 21-Cortisol, 11-beta hydroxylase or 21-
hydroxylase or 17-OH progesterone inhydroxylase or 17-OH progesterone in
plasmaplasma
Reduced enzyme activities in congenitalReduced enzyme activities in congenital
adrenal hyperplasiaadrenal hyperplasia
AlbuminAlbumin
ProteinuriaProteinuria

25. TTKG – transtubular potassium gradientTTKG – transtubular potassium gradient
Serum osmolalitySerum osmolality ** Urine potassiumUrine potassium
Urine osmolality * Serum PotassiumUrine osmolality * Serum Potassium
 evaluate the renal response to hyperkalemiaevaluate the renal response to hyperkalemia
TTKG expected to be high (usually >10) inTTKG expected to be high (usually >10) in
hyperkalemia when renal response is intact. Anhyperkalemia when renal response is intact. An
inappropriately low TTKG in a hyperkalemicinappropriately low TTKG in a hyperkalemic
patient suggests hypoaldosteronism or a renalpatient suggests hypoaldosteronism or a renal
tubule defect.tubule defect.

26. Index of potassium secretory activity in theIndex of potassium secretory activity in the
distal tubuledistal tubule
Test is most useful in distinguishingTest is most useful in distinguishing
patients who have mineralocorticoidpatients who have mineralocorticoid
deficiency versus resistance by observingdeficiency versus resistance by observing
a change in TTKG values aftera 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 resistantdeficient but not aldosterone resistant
statesstates

27. TREATMENTTREATMENT
2 Basic goals2 Basic goals
1) to stabilise the heart to prevent life1) 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.

28. Step 1Step 1: Evaluate patient for potential: Evaluate patient for potential
toxicities and initiate ECG monitoringtoxicities and initiate ECG monitoring
Ca-Gluconate 10%Ca-Gluconate 10%
To stabilise the cell membrane of heartTo stabilise the cell membrane of heart
cells to prevent arrhythmiascells to prevent arrhythmias
0.5–1 ml/kg over 5-10 min, preferably0.5–1 ml/kg over 5-10 min, preferably
administered via central venous accessadministered via central venous access
Should be given over 30 mins in patientsShould be given over 30 mins in patients
taking digoxin.taking digoxin.
Step 2:Step 2: Identify and immediately eliminateIdentify and immediately eliminate
sources of potassium intakesources of potassium intake

29. Step 3Step 3:: Increase potassium shift fromIncrease potassium shift from
extra- to intracellular spaceextra- to intracellular space
Dextrose and insulin infusion.Dextrose and insulin infusion.
0.1 U/kg of insulin in 0.5g/kg(2ml/kg) of0.1 U/kg of insulin in 0.5g/kg(2ml/kg) of
25 % dextrose solution over 15 to 30 mins.25 % dextrose solution over 15 to 30 mins.
Beta-adrenergic agonists (salbutamol,Beta-adrenergic agonists (salbutamol,
reproterolreproterol))
Salbutamol can be applied via nebulizerSalbutamol can be applied via nebulizer
or given intravenouslyor given intravenously
Nebulized: 2.5 mg if <25 kg and 5 mg ifNebulized: 2.5 mg if <25 kg and 5 mg if
>25 kg>25 kg

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

31. Can be given orally or as a retentionCan be given orally or as a retention
enema. Dose is 1g/kg.enema. Dose is 1g/kg.
More effective if given orally. EnemasMore 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 theis the
ultimate measure in severe hyperkalemia.ultimate measure in severe hyperkalemia.
Hemodialysis (HD)Hemodialysis (HD) provides aprovides a
substantially higher potassium clearancesubstantially higher potassium clearance
Continuous veno-venous hemofiltrationContinuous veno-venous hemofiltration
(CVVH) can more satisfactorily provide(CVVH) can more satisfactorily provide
long-term control of potassium.long-term control of potassium.

32. ReferencesReferences
Nelson text book of paediatrics-19Nelson text book of paediatrics-19thth
editionedition
page no:219-222.page no:219-222.
Webb NJ, Postlethwaite RJ (2003) ClinicalWebb NJ, Postlethwaite RJ (2003) Clinical
Paediatric Nephrology, 3rd edn. OxfordPaediatric Nephrology, 3rd edn. Oxford
University PressUniversity Press
Anja Lehnhart and Markus J. KemperAnja 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 thTextbook of pediatric nephrology :5 th
edition.Aravind baggaedition.Aravind bagga