This document discusses potassium balance and disorders of potassium levels. It begins by outlining the vital functions of potassium ions in the body and factors that influence potassium balance. It then details the causes, clinical features, diagnostic approaches, and therapies for hypokalemia and hyperkalemia. For hypokalemia, it discusses etiologies such as decreased intake, increased losses, and transcellular shifts. It outlines clinical consequences, diagnostic testing, and management including oral or IV potassium replacement. For hyperkalemia it similarly discusses etiologies, clinical consequences, and emergency, temporizing, and chelating therapy approaches.

1. Potassium balance and
clinical disorders
Mahmood Reza Khazaei
Pediatric nephrologist
Islamic Azad Mashhad Medical Sciences University

2. Objectives
• Vital functions of Potassium ion
• Potassium balance
• Factors influencing internal and external potassium balance
• Hypokalemia:
▫ Etiology
▫ Clinical features and diagnostic approach
▫ Therapy
• Hyperkalemia:
▫ Etiology
▫ Clinical features and diagnostic approach
▫ Therapy; urgent and non-urgent

3. Potassium ion vital functions
•Normal p.K+
: 3.5-5.5 mEq/L
•Vital functions:
▫ Maintains cell electro-neutrality
▫ Assists in conduction of nerve impulse
▫ Directly affects cardiac and skeletal muscle
contraction; repolarization phase of action
potential
▫ Plays a major role in acid-base balance

4. Distribution of potassium
ECF potassium is 24 mEq in 30 kg boy, compared to
total body potassium of 1950 mEq
Total Body water = 60%Wt
ECF (33%)
ICF (66%)
ECF (20%wt)
ICF (40%wt)
4
160

5. Distribution of potassium
• Clinical estimation of serum K represents only that
portion of K in the body ( 2 %), not total body K
• Occurrence of hyperkalemia or hypokalemia dose
not mean increase or decrease of total body
potassium; potassium depletion can occur despite
hyperkalemia ( DKA)

6. Routes of K excretion
•Fixed routes;
▫Sweat ( 2 % ); there is 200 ml of sweat
per day total K+
losses about 2 mEq/ day
▫Stool ( 10 % ); ～ 10 mEq/ day,
▫Increased in:
▫ diarrhea episodes, increase significantly,
▫ vomiting
▫ CRF; up to 50% of potassium intake

7. Routes of K excretion
•Variable route;
▫Renal K excretion; major route account for
78% of potassium excretion per day in
normal individuals, 60-80 mEq/ day
▫GFR of 150 L per day, 600 mEq of
potassium are filtered, only 60-80 mEq on
average excreted in urine, so 85% of
filtered potassium is reabsorbed

8. Potassium renal excretion
•The kidney is Major potassium regulator
•Healthy kidney can Excrete potassium as
low as 10 to up to 400 mEq/ day
depending upon potassium intake.

9. Potassium renal excretion
• Potassium secretion is dependent on the delivery
of sodium and water to the CCT and on the action
of the hormone aldosterone.
• Aldosterone increases sodium reabsorption from
the lumen and promotes potassium secretion into
the lumen, restoring electrical neutrality.

10. 600-700 mEq
70-80% 15-20%
60-90 mEq
10% of
filtered
load
(FEk～10%)
MAJOR SITE OF K+
SECRETION
Mediated by effect of
aldosterone on principal
cells of late DCT & CCD
A: Bulk Reabsorption
B: Fine Tuning Concentration Control

11. Factors influenced renal K excretion
• Increased
• Aldosterone
• Increased sodium delivery
to distal nephron;
• Diuretics
• Osmotic diuresis
• Saline infusion
• Presence of poorly
reabsorbed anion (HCO3,Cl)
• Insulin
• B2 adrenergic agonist
• Increase intracellular K
• Decreased
• Non-anion gap academia
• Decrease intracellular K
• Alpha adrenergic agonist

12. Renal potassium loss estimation
interpretation
Normal range
Indicator
<15 Extra-renal loss or
inadequate intake
20-40 mEq/Lit
Urine Potassium
Less than 20 mEq/day
24 hr. urine potassium
<1 renal K+. wasting
>1
Na+/K+ ratio
>30% renal K+. Wasting
<10%
FEk+
See next
TTKG

13. Transtubular K gradient ( TTKG)
• TTKG used to assess renal handling of potassium
(aldosterone activity/ effect on late DCT & CCD).
• TTKG calculation will done if:
• Urine potassium level is >20 mEq/L but <40 mEq/L,
• Urine Na+ level should be greater than 10 mEq/L Urine
• Urine osmolality should be greater than or equal to serum
osmolality.
Urine K+ × serum osmolality/serum K+ × urine osmolality

14. Transtubular K gradient ( TTKG)
Condition TTKG Result
Hypokalemia <3 No renal loss (normal kidney function)
Hypokalemia >7 (>4) mineralocorticoid excess
Hyperkalemia >10 normal aldosterone activity
Hyperkalemia <5 aldosterone deficiency/resistance
…………………………………………………………………………………………………………………………………
Hypokalemia + high TTKG;
Hyperaldosteronism
pseudohyperaldosteronism (e.g. Cushing's syndrome, Liddle's syndrome)
Hyperkalemia + low TTKG:
RTA-IV,
CAH,
potassium sparing diuretics; triamterene , Amiloride, spironolactone

15. HYPOKALEMIA
Hypokalemia is defined as a plasma potassium level less than 3.5 mEq/L.
Serum potassium (mEq/L) Severity
3.0 - 3.4 Mild
2.5 - 3.0 Moderate
2.0 - 2.4 Severe
<2.0 Critical

16. Decreased
intake
Increased losses Transcellular
shifts
Medicines Spurious
Illness
Fasting
Prolonged
IV fluids
not
containing
potassium
Eating
disorder
Gastrointestinal
• Vomiting
• Diarrhoea
• Fistula
Renal
• Diuretics
• Osmotic diuresis
• Aldosterone
excess
• Mineralocorticoid
excess
• Congenital
disorders
• Renal artery
stenosis
Alkalosis
Hypomagnesaemia
Hypernatraemia
Glucose/insulin
infusion
Diabetic
ketoacidosis
Refeeding
syndrome
Loop diuretics
(eg frusemide)
Thiazide
diuretics
Amphotericin
Cisplatin
Insulin
Salbutamol
Adrenaline
Sampling error
• Recent
line flush
• IV fluids
near
sampling
site
Hypokalemia; etiology

17. Hypokalemia; diagnosis
•History; renal or extra-renal losses, diabetes
mellitus, thyroid disease, family history, drug
history.
•O/E; Growth pattern, body weight, pulse, HTN,
respiratory pattern
•Investigations; WBC, ABG, anion gap, urine
potassium excretion per 24 hours, TTKG, Ser. Mg

18. Hypokalemia; Clinical consequences
• muscle weakness, cramps, paralysis
• hyporeflexia
• constipation, ileus
• lethargy, confusion
• rhabdomyolysis (rare)
• Nephrogenic diabetes insipidus
• ECG changes in hypokalemia
• Flattened T waves and prominent U waves (apparent QT
prolongation)
• Prominent U waves combined with depressed ST segments and
flattened T waves
• widening of QRS complex
• fibrillation

19. Pull and push effect” of potassium on T wave of ECG

20. Urine K+ excretion
DKA
RTA-I
RTA-II
Amphotricin
> 15 mEq/L
Assess acid –base status
Hypertension?
TTKG<3
Assess K + secretion
TTKG>4
Met. Alkalosis
< 15 mEq/L
Met. Acidosis
Lower GI K+ loss
Diuretic
vomiting
Sweet K + loss
Assess acid –base status
Met. Alkalosis Met. Acidosis
Vomiting
Barter/Gitelman
Hypomagnesemia
Diuretic abuse
Renal vascular stenosis
Hyperaldostronism
Liddle’s synd.
Na+ wasting
nephropathy
Osmotic diuresis
Diuretics
(+)
(-)
Lab. data
1- RFT
2- ABG, FBS, s.Mg+2
3- Urine K & Cl
4- PRA &
Aldosterone
5- TTKG

21. Hypokalemia; management
•Is there acid base imbalance?
•Consider the degree and source of potassium
losses.
•Check the serum magnesium level in complicated,
severe and chronic hypokalaemia.

22. Choice of dosing route
• Oral is the preferred route of administration
• Oral potassium is well absorbed from the GI tract.
• Taken with or soon after food to reduce GI irritation.
• Consider intravenous replacement if:
• child is unable to tolerate oral medication,
• serum potassium <2.5 mEq/L, or
• ECG changes present

23. Oral/enteral dosing
• Acute replacement dose
• 1 - 2 mEq/kg/dose orally (maximum 20 mEq per dose)
• Dose may be repeated, after checking serum potassium level, to a
maximum of 5 mEq/kg/DAY (maximum daily dose 50 mEq)
• Maintenance dose(if required)
• 2 - 5 mEq/kg/DAY orally in divided doses (maximum 20 mEq per dose)
• Hypokalemia + high urine Cl: Oral Potassium Chloride
• Hypokalemia + Met. Acidosis: K. citrate salt
• Magnesium deficiency should be corrected if refractory
hypokalemia

24. Medication Forms:
• Vial KCl 15% 2mEq/ml
• Vial KCl 10% 1.33 mEq/ml
• Tab. Eff K. 1gr 14 mEq/Tab
• EC Tab 600 mg 8 mEq/tab
• Tab potassium Citrate 5 & 10 mEq/tab

25. Potassium replacement therapy
IV potassium indicated in:
severe hypokalemia
symptomatic hypokalemia (cardiac/respiratory)
Oral potassium cannot be tolerated
Malabsorption syndrome is suspected
- IV potassium preparation:
should normally be diluted in saline solution
maximum concentration:
peripheral lines up to 40 mEq/L
central lines more than 40 mEq/L
1 meq/kg of K+ → ser K+ 1mEq ↑

26. Potassium replacement therapy
- cardiac monitoring is necessary
in patients with profound hypokalemia (< 2.5 mEq/L)
if cardiac arrhythmias are present,
if IV potassium is going to be rapidly administered
- rapid IV bolus administration of potassium is usually contra-indicated
- rapid IV administration of potassium (5 - 10 mEq over 10 minutes) in:
respiratory muscle paralysis
hypokalemia-induced malignant arrhythmias
Consideration:
1. IV administration via a central line
2. physician-supervised,
3. Cardiac monitoring
4. repeat serum K+ level q 30 minutes

27. K+ supplementation therapy for hypokalemia
5 - 10 meq/hour If heart block or renal insufficiency exists
10 - 20 meq/hour Standard IV replacement rate
20 - 40 meq/hour Serum potassium < 2.5 mEq/L or moderate-severe symptoms
> 40 meq/hour Serum potassium < 2.0 mEq/L or life-threatening symptoms
Ser K+: 3-3.5 Oral→1-2 mEq/kg/day (max 40-120 mEq/day)
2.5-3 Oral-iv → 40-60 mEq/lit
2 – 2.5 iv → 0.5-1 mEq/kg/hr (max 10 mEq/hr)
< 2 iv →2-3 mEq/kg/hr
IV infusion rate for severe or symptomatic hypokalemia
• Maximum potassium concentration for peripheral IV access is 40 mEq/Lit
• Maximum potassium replacement should not exceed 100 mEq/ day, or even
lower if there is oliguria, or renal dysfunction exist.
• Maximum potassium concentration for peripheral IV access is 40 mEq/Lit
• Maximum potassium replacement should not exceed 100 mEq/ day, or even
lower if there is oliguria, or renal dysfunction exist.

28. HYPERKALEMIA
Hyperkalemia is defined as a plasma potassium level less than 5.5 mEq/L.
Serum potassium (mEq/L)
Severity
5.5 - 6.0
Mild
6.0 - 6.5
Moderate
> 6.5
Severe

29. Hyperkalemia
• Spurious (pseudohyperkalemia)
• Marked leuckocytosis ( >100000/ mm),
• Sever thrombocytosis,
• Hemolysis,
• Tumor lysis syndrome,
• Rhabdomyolysis
• Redistribution ( potassium shift out cells)
• Acidemia
• Hyperkalemic periodic paralysis
• B2 adrenergic blockers
• miscellaneous
• Renal failure
• Aldosterone deficiency
• Drugs:
• ACEI, ARBS, cyclosporine, Spironolactone, NSAID, Digoxin, B2 agonists,
Most common: Renal Failure, Drugs and potassium shift

30. Hyperkalemia; Clinical consequences
• Usually occur when potassium conc. > 6.5 mEq/ L,
• Neuromuscular; weakness, ascending paralysis, and
respiratory failure
• progressive ECG changes; peaked T Wave, fattened
P wave, prologned PR interval, idioventricular rhythm,
and widened QRS complex, and deep S wave, followed
by ventricular fibrittation.
• These cardiac changes may occur suddenly without
warning

33. Therapy of hyperkalemia
• Medication Overview: Mechanism of action
• Emergency treatment: Antagonism of membrane actions of potassium
• Calcium chloride
• Calcium gluconate 10%
• Temporizing treatment: Shift potassium intracellularly
• Glucose / insulin
• Alkalinize ( Sodium bicarbonate IV)
• Inhaled 2 adrenergic agonist (albuterol)
• Chelating therapy: Removal of potassium from the body
• Loop / thiazide diuretics
• Cation exchange resin: sodium polstyrene sulfonate (Kayexelate®)
• Dialysis

34. Control of underline disease
Stop Potassium retaining drugs
Diet modification
Monitor potassium level
Control of underline disease
Stop Potassium retaining drugs
Diet modification
Monitor potassium level
Mild (K+=5.4-5.9) Moderate (K+=6.0-6.4) severe(K+>6.5)
ECG; Are ECG changes presents?
ECG; Are ECG changes presents?
Emergency treatment
Calcium Gluconate
Repeat after 5 min if persisted ECG findings
Emergency treatment
Calcium Gluconate
Repeat after 5 min if persisted ECG findings
Temporizing treatment
albuterol
Glucose/Insulin
Bicarbonate
Temporizing treatment
albuterol
Glucose/Insulin
Bicarbonate
Chelating therapy
Loop / thiazide diuretics
Cation exchange resin (Kayexelate®)
Dialysis
Chelating therapy
Loop / thiazide diuretics
Cation exchange resin (Kayexelate®)
Dialysis
yes
No

36. Calcium:
2 solutions :
•Calcium gluconate 10%: 0.5 mL/kg slow IV injection
• 2-5 minutes if unstable, over 15-20 min if stable (Max: 20 mL)
• Preferable if only peripheral line available
OR
•Calcium Chloride 10% : 0.1-0.2 mL/kg slow IV injection (as above) (Max: 10 mL)
Note: Give under cardiac monitoring, discontinue if HR dropping significantly
Avoid extravasations
NOT to be given simultaneously with bicarbonate
NOT to be given if digoxin toxicity
Onset of Action: <3 minutes, should see normalization of ECG. If not: repeat dose
(twice)
Duration: ~30 minutes

37. Salbutamol (Albuterol):
o Salbutamol: nebulization
▪ Less than 25 kg : 2.5 mg neb 1-2 hourly
▪ More than 25 kg : 5 mg neb (Adu max 10-20 mg) 1-2
hourly
o Salbutamol : IV *Only if severe hyperkalemia under
supervision by physician on tertiary center with monitoring for
tachycardia
Onset of Action: 30 minutes
Duration: 2-3 hours

38. Insulin/glucose, to be given at the same time
If severe hyperkalemia:
o Dextrose 10% : 5 mL/kg IV bolus (if no hyponatremia)
o Insulin short action: 0.1 U/kg IV bolus (max 10 units)
Then followed by infusion insulin/glucose (see below)
If moderate hyperklemia:
o Dextrose 10% IV at maintenance with 0.9% sodium chloride (normal
saline)
o Insulin short action infusion : 0.1 U/kg/h IV
Note: Close monitoring of glucose every 30-60 minutes
Onset of Action: 15 minutes
Duration: peak 60 minutes, 2-3 hours

39. Bicarbonate
In metabolic acidosis only
Severe hyperkalemia and metabolic acidosis
o Sodium Bicarbonate 8.4% 1 mEq/mL : 1-3ml/kg IV over 5
minutes
Mild to moderate hyperkalemia and metabolic acidosis:
o Sodium Bicarbonate 8.4% 1 mEq/mL : 1 mL/kg slow IV infusion
over 30 minutes
Note: Do NOT give simultaneously with Calcium
Onset of Action: 30-60 minutes
Duration: 2-3 hours

40. Polystyrene sulfonate (Kayexalate)
Mild effect, multiple doses necessary, may be used as long term
agent
Dose: 0.3-1 g/kg 6 hourly (max 15-30 g) PR or oral (with lactulose)
Note: NOT to be used if ileus, recent abdominal surgery,
perforation, hypernatremia
Onset of Action: 1 hour PR, 4-6 hours oral
Duration: variable

42. Hyperkalemia;non-urgent manangement
• Any underlying causes should be diagnosed and
treated:
• Offending drugs discontinued
• Low potassium diet considered (CKD)
• Metabolic acidosis
• Fludrocortisone may be useful in the setting of
hypoaldosteronism.

43. Hyperkalemia;non-urgent manangement
• Increased renal potassium elimination may be
achieved by
• volume expansion with normal saline
• Judicious use of loop diuretics to improve the distal
delivery of sodium and water.