Common

Electrolyte disorders
Vittawin Sawangduan, MD

Renal Division
Department of Internal Medicine
Lampang Hospital

20/01/66
Outline
• Hyponatremia and hypernatremia
• Hypokalemia and hyperkalemia
Dysnatremia
Disorders of Sodium = Disorders of Water
• Edelman’s equation

• A simplified version

Na
• Plasma [Na+] = mmo/L
water

• Normal range 135-145 mmol/L

• Total body sodium reflects volume status

Thirst center Water homeostasis

Osmoregulation

• Regulate via ECF osmolality

• Prevent changes in cell volume

Baroregulation

• Regulate via ECF volume

Arginine • Also stimulate RAS pathway
Vasopressin • Maintain blood pressure
Baroregulation

Osmoregulation
Sensitivity of AVP secretion

AVP release in similar amount

• 1% rise in plasma osmolality
• large reductions in effective
circulating volume (5% to 10%)

Verbalis JG, et al. Best Pract Res Clin Endocrinol Metab. 2003 Dec;17(4):471-503.
Hyponatremia
Hyponatremia
• Plasma [Na+] level < 135 mmol/L

Na Na
• Plasma [Na+] = mmo/L → ↓Plasma [Na+] = mmol/L
water ↑ water
• Hyponatremia is usually a disorder of water excess (AVP-/Not AVP-
mediated)

+ BUN glucose
• Plasma osmolality (mOsm/kg H2O) : 2Na + 2.8
+
18
• Hyponatremia -> hypotonicity -> water shift into the cell -> cell swelling
-> problematic for the brain in the nondistensible cranium
N Engl J Med 2000; 342:1581-1589
Clinical manifestations
• The severity of symptoms correlates with the acuity of hyponatremia
onset and its magnitude
• Acute onset < 48 hours
• Postoperative phase, post-resection of the prostate or endoscopic uterine
surgery, polydipsia, exercise, MDMA, oxytocin, recently started desmopressin,
terlipressin, vasopressin or thiazide
• Chronic onset ≥ 48 hours or unknown onset
• Mild hyponatremia: plasma [Na+] > 129 mmol/L
Moderate hyponatremia: plasma [Na+] 125-129 mmol/L
Severe hyponatremia: plasma [Na+] < 125 mmol/L
Clinical manifestations
• Symptoms
• Moderately severe : nausea without vomiting, confusion, headache
• Severe : vomiting, cardiorespiratory distress, abnormal and deep
somnolence, seizures, coma (GCS ≤ 8)

• Adverse outcomes of chronic mild to moderate Hyponatremia

Cognitive impairment, falls, fractures and osteoporosis, gait instability
and mortality

Am J Kidney Dis. 2020 Feb;75(2):272-286.

 Diagnostic approach to hyponatremia
Hyponatremia
(PNa+ < 135 mmol/L)

+ BUN glucose
1 True hyponatremia? Posm = 2Na + 2.8
+
18

Measure plasma osmolality, glucose, BUN

Hypotonic (true) Isotonic Hypertonic

hyponatremia hyponatremia hyponatremia
Posm < 275 mOsm/kg H2O Posm 275-295 mOsm/kg H2O Posm > 295 mOsm/kg H2O
Hypotonic (true) Isotonic Hypertonic
hyponatremia (Pseudo) (translocational)
hyponatremia hyponatremia
Hyperlipidemia Hyperglycemia
Paraproteinemia Mannitol
Glycine
IVIg Corrected PNa+
glucose−100
= PNa+ + (1.6 x )
100
if blood glucose < 400 mg/dL

glucose−100
= PNa+ + (2.4 x )
100
if blood glucose > 400 mg/dL

Henry DA. Ann Intern Med, 2015;163(3):ITC1-190

Goce Spasovski, et al. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47
 Hypotonic (true)
hyponatremia

2 Uosm
AVP effect? (mOsm/kg H2O)

< 100 100-200 > 200

No AVP effect +/- AVP effect AVP effect

Polydipsia Polydipsia Volume status

Low solute intake Low solute intake
Beer potomania Beer potomania 3
Tea & toast diet Tea & toast diet
SIAD
Reset osmostat :
variable UOsm Henry DA. Ann Intern Med, 2015;163(3):ITC1-190
Best Pract Res Clin Endocrinol Metab. 2003 Dec;17(4):471-503
Goce Spasovski, et al. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47
 Hypotonic hyponatremia & Uosm > 200

3 Volume status Physical exam + lab

Hypovolumia Euvolumia Hypervolumia

4
UNa < 30 UNa > 30 UNa 20-40 UNa > 40 UNa < 30 UNa > 30

Dehydration Diuretics (thiazide) Hypothyroidism Heart failure CKD

Diarrhea Salt-losing 2o AI Liver disease (can also be
Vomiting nephropathy SIAD Nephrotic euvolemic)
3rd space loss Addison’s disease syndrome
Cerebral salt ? Hypo-/euvolumia
wasting !! If patient is receiving diuretics,
Try NSS iv + F/U PNa
UNa can be > 30 mmol/L
Henry DA. Ann Intern Med, 2015;163(3):ITC1-190 Goce Spasovski, et al. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47
Diagnostic criteria for the SIAD

10

Goce Spasovski, et al. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47.

 Common
causes of SIAD

Goce Spasovski, et al. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47.

Common
causes of SIAD

Goce Spasovski, et al. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47.

Management of hyponatremia

Goce Spasovski, et al. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47.

Osmotic demyelinating syndrome (ODS)
• Neurologic symptoms (dysarthria, dysphagia, paraparesis or quadriparesis,
confusion, obtundation, and coma) typically occur 2-6 days after correction
• Excessive correction results from water diuresis
• High risk of ODS : [Na+] ≤ 105, hypokalemia, alcoholism, malnutrition,
advanced liver disease, Thiazide diuretic in elderly woman
• Management:
• Discontinue active treatment
• Administer 5% D/W (2-3 ml/kg/hr) and desmopressin (2-4 μg q 8 hr IV)
until [Na+] is less than the limits
• Monitor [Na+] q 2 hr until it corrects, then q 4-6 hr for the first 48 hr

Henry DA. Ann Intern Med, 2015;163(3):ITC1-190

Am J Kidney Dis. 2020 Feb;75(2):272-286.
 Management according to causes of hyponatremia
Hypovolumia Euvolumia Hypervolumia
(SIAD)
• Isotonic saline • Restrict water and salt
• Gid rid of cause • Loop diuretics
• Required Na = TBW x ΔPNa • Restrict water
• ΔPNa of gaining 1 L of any • NaCl tablet (5-15 g/d)
infusate = • Furosemide + NaCl tablet
infusate Na + K − PNa • Vaptans (V2R antagonist)
TBW + 1
UNa + UK Restricted water Predictors of failure from
TBW = correction factor x BW PNa (ml/d) fluid restriction:
Correction factors: > 1.0 < 500 • Uosm > 500 mOsm/kg
0.45 → elderly women, • UNa + UK > PNa
0.5 → non-elderly women, elderly men = 1.0 500-1,000 • 24-hour urine volume
0.6 → non-elderly men < 1.0 1,000 < 1,500 mL/day
Management according to causes of hyponatremia
• Addison disease : Isotonic saline
glucocorticoid and mineralocorticoid replacement
• Glucocorticoid insufficiency : Glucocorticoid replacement
• Primary polydipsia* : Restrict water
• Decreased solute intake* : Restrict water, increase electrolytes and protein in diet

*if volume-depleted or decreased solute excretion, cautiously administer isotonic

saline and consider desmopressin (if no access to fluids) initially or if there is a
rapid increase in urine output and/or plasma sodium
Hypernatremia
 Hypernatremia
• Plasma [Na+] level > 145 mmol/L

Na
• Plasma [Na+]= mmo/L
water
+ ↑Na
↑Plasma [Na ] = mmol/L
↓ water

• Causes
• Na gain
• Net water loss (renal/non-renal)
+ Impaired thirst or lack of access to
water
 Approach to hypernatremia
Likely
Hypovolumia to be
Uosm > Posm Euvolumia Hypervolumia
Uosm > 600 Uosm 300-600 Uosm < Posm Uosm > 600 UNa > 20
Likely to be
Inadequate Extrarenal Renal Uosm < 300 Na gain
water intake loss loss → Diabetes insipidus (DI) • IV NaHCO3
• Central DI • IV NSS, 3% NaCl
UNa < 20 UNa < 20 UNa > 20
• Nephrogenic DI
• Immobility • GI loss • Loop diuretics • Adipsic DI • Stop causative IV
• ETT • Burn • Osmotic diuresis • Furosemide + free water
• Excess Fluid deprivation test replacement
• Impaired (hyperglycemia,
sensorium sweating mannitol) Insensible loss
• No insensible
• Cushing syndrome
• Post-ATN/ • Fever
loss in fluid obstruction • Hyperaldosteronism
prescription • Mechanical ventilation
Rx U/D
Correct cause + free water replacement Free water replacement
Am Fam Physician. 2015;91(5):299-307 Am J Kidney Dis. 2020 Feb;75(2):272-286 Comprehensive nephrology 6th ed
Management of hypernatremia
• Identification of cause and its correction
• Hypotension → NSS iv load as resuscitation
• Acute vs chronic
• Acute onset (< 48 hours) : rapid correction to normal over 24 hour
• Chronic (> 48 hours) or unknown : usually ↓PNa < 10 mmol/L/day
PNa
• Calculate water deficit = TBW x −1
140
• Calculate ongoing loss
• Insensible loss: ~ 10 ml/kg/day or 30–50 ml/hr; + 3.5 ml/ kg/day/1°C of fever
UNa+UK
• Renal water loss: Free water clearance = V x 1 −
PNa
• Fluid selection : water (preferred) , 5%DW, NSS/2
Dyskalemia
Potassium homeostasis
• The distribution of K + in the body differs strikingly from that of Na + .
• Whereas Na + is largely extracellular, K + is the most abundant
intracellular cation.
• Some 98% of the total-body K + content (~50 mmol/kg body weight) is
inside cells, most in muscle (70%)
• Only 2% is in the extracellular fluid (ECF)

ICF 98% ECF 2%

[K+] = 150 meq/L [K+] = 3.5-5.0meq/L
K+ homeostasis
External K+ balance
• Dietary intake
60-80 mmol/day
• Excretion
kidneys 90% -95%
colon 5%-10%
Internal K+ balance
• Distribution between
ICF (98%) and ECF (2%)
Cellular potassium shifts

Comprehensive Nephrology, 6th ed. Clin J Am Soc Nephrol 10: 1050–1060, 2015
Renal potassium handling

Brenner & Rector’s the kidney, 10th edition.

Principal cell Lumen Interstitium

Na+ 3Na+
ENaC
2K+
K+
ROMK K+
MR

Aldosterone
Hypokalemia
Consequences of hypokalemia (K+ < 3.5 mmol/L)
• Cardiovascular: hypertension, ventricular arrhythmias
• Hormonal: glucose intolerance
• GI: constipation, ileus
• Muscular: proximal muscle weakness, rhabdomyolysis, cramps
• Renal:
• Tubulointerstitial fibrosis, intrarenal vasoconstriction
• Metabolic alkalosis – ↑NH4 + secretion at collecting duct
• Nephrogenic diabetes insipidus
• Hepatic encephalopathy – ↑ NH3 at proximal tubule
Approach to hypokalemia
• Acid-base status : normal, metabolic acidosis or metabolic alkalosis
• Evaluate response of kidney due to hypokalemia

Tools Non-renal K+ loss or shift Renal K+ loss

Spot UK+ (mmol/L) < 20 > 20
24 hour UK+ (mmol/L) < 20 > 20
Uk UCr < 5% > 5%
FEK+ / x100%
Sk SCr
+ Uk UCr <2 >4
TTKG /
Sk SCr
*UNa > 25 and Uosm > Posm
 Pseudohypokalemia Hypokalemia
Ex. Leukocytosis in AML

Acute Chronic

Acute Loss Shift Renal K loss Non-Renal K loss

TTKG > 4 UK > 20 TTKG < 2 UK < 20
• Diarrhea • Periodic paralysis
• Vomiting • ẞ2-agonist, stress HypoMg Diarrhea
• Diuretics • Insulin Laxative abuse
met alkalosis met alkalosis
• Refeeding syndrome BP ↔ BP↑, PAC/PRA Normal gap
Not necessary • Vit B12/folic Rx in met acidosis
to W/U urine K Diuretics RAS
megaloblastic anemia
Vomiting Aldosteronism
Normal acid-base Bartter Cushing
TTKG < 2 UK < 20 Gitelman Liddle

RTA Normal gap met acidosis

 Periodic paralysis
Familial hypokalemic periodic Thyrotoxic periodic paralysis
paralysis (FHPP) (TPP)
Age at onset Childhood to 3rd decade >20 years

Attack duration Hours to days Hours to days

Precipitants Exercise, stress, carbohydrate load Exercise, stress, carbohydrate load

Associated features Hypokalemia between paralytic episodes Symptoms of thyrotoxicosis may be

suggests other causes subtle
Etiology AD (2/3 transmission) inherited defect in Negative family history
Ca2+ (or Na+) channel on muscle
membrane
Epidemiology Men > women Highest incidence in Asian men > women

Preventive Carbonic anhydrase inhibitors Euthyroid state

treatment Potassium-sparing diuretics Propranolol
Management of hypokalemia
• Correct cause
• Potassium replacement

• ↓PK+ 4 to 3 mEq/L
• deficit of 100 to 200 mEq

• ↓PK+ 3 to 2 mEq/L
• deficit of 400 to 600 mEq/L.
Management of hypokalemia
• Serum K >2.5 mmol/L and asymptomatic → oral
• No acidosis: KCl (Ped KCl, 1 mEq/ml; Elixer KCl 40 meq/30ml)
• Acidosis: K citrate solution (9.3 mEq/15 ml) K citrate tablet, Shohl’s
solution (K 0.5, Na 0.5, citrate 3 mEq/ml)
• Hypophosphatemia: K phosphate (1 mEq/ml)
• Parenteral – serum K <2.5 mmol/L, arrhythmia, weakness, hepatic
encephalopathy, digoxin
• Avoid IV with dextrose
• Peripheral vein: max. 60 mEq/L → NSS 1,000 ml + KCl 30 ml (6 mEq / 100 ml)
• Central vein: max. 200 mEq/L → NSS 450 ml + KCl 50 ml (1 mEq / 5 ml)
• Monitor ECG if >10 mEq/hr
Hyperkalemia
Consequences of hyperkalemia (K ≥ 5.5 mmol/L)
• Muscle and heart : Increased resting membrane potential

• Muscle - weakness or paralysis

• Heart- conduction abnormalities and arrhythmias
Comprehensive Nephrology, 6th ed
Ingested K + moves transiently into cells for storage
before excretion by the kidney
Approach to hyperkalemia
1. Pseudohyperkalemia
2. Excess intake of potassium and tissue necrosis
3. Redistribution
4. Reduced renal potassium excretion
5. Medication-related hyperkalemia
❶Pseudohyperkalemia
• K+ release from cell during or after venipuncture
Etiologies
• Forearm contraction, fist clenching, tourniquet use
• Correct technique
• Thrombocytosis, leukocytosis, erythrocytosis
• Rapid send specimen to laboratory room

Brenner & Rector’s the kidney, 10th edition.

❷Excess intake of K+ and tissue necrosis
External sources of K+ in susceptible patients (CKD, AKI, Dialysis)
• Potassium-rich diet
• Salt substitutes
• Alternative medicines, alternative diets
• Pica (geophagia)
• K+-containing medication (K+-penicillin)
• Red cell transfusion : rate and volume, central venous infusion,
irradiated blood, age of blood infused
(23 mmol/l in 7-day-old blood→ 50 mmol/l in 42-day-old blood)

Brenner & Rector’s the kidney, 10th edition.

❷Excess intake of K+ and tissue necrosis
Internal sources of K+
• Cellular injury : rhabdomyolysis, hemolysis, tumor lysis syndrome,
hypercatabolic state
• UGIH, large hematoma

Brenner & Rector’s the kidney, 10th edition.

❸Redistribution
• Metabolic acidosis
• Non-organic metabolic acidosis
↓pH 0.1 == ↑K+ 0.24-1.7
• Organic metabolic acidosis : less effect
• Insulin deficiency
• Hypertonicity: hyperglycemia, mannitol (solvent drag)
• Drugs/toxins/herbs
• Digoxin overdose, bufotoxin : inhibit Na+-K+-ATPase
• Β-blocker
• Succinylcholine
• α- agonist Brenner & Rector’s the kidney, 10th edition.
 Na

❹Reduced renal potassium excretion

• Decreased GFR : AKI, CKD (GFR < 20 ml/min/1.73 m2) MR Aldosterone
• Defect in renal tubular secretion
• Disturbance in RAAS axis
→ Hypoaldosteronism
• Tubular resistance to action of
aldosterone

Hyperkalemic RTA (type IV)

TTKG < 6 FEK+ < 10%

24 hrs urine K+ < 20 meq
Brenner & Rector’s the kidney, 10th edition.
 ❹Reduced renal potassium excretion
Disturbance in RAAS axis : Mineralocorticoid deficiency
Primary
• Combined deficiency of aldosterone,
desoxycorticosterone, and cortisol
Addison’s disease
Bilateral adrenal destruction,
adrenalectomy, hemorrhage or CA
• Congenital enzymatic defects
21-Hydroxylase deficiency
3β-Hydroxydehydrogenase deficiency
• Isolated aldosterone deficiency
Critically ill patients
Secondary
• Hyporeninemic hypoaldosteronism
Diabetic nephropathy
Lupus nephritis
Tubulointerstitial nephropathies
Nephrosclerosis
NSAIDs agents
Acquired immunodeficiency syndrome
Immunoglobulin M monoclonal
gammopathy
Obstructive uropathy
Hyporeninemic Hypoaldosteronism
Typical Clinical Features
• Mean age 65 yr
• Asymptomatic hyperkalemia (75%), Weakness (25%), Arrhythmia (25%)
• Hyperchloremic metabolic acidosis (>50%)
• Renal insufficiency (70%)
• Diabetes mellitus (50%) Rx
• Thiazides or loop diuretics
• Cardiac disorders
• Fludocortisone 0.2-1 mg/day
• Arrhythmia (25%)
• Hypertension (75%) (beware of HT, edema)
• Congestive heart failure (50%) • Low K diet, K-exchange resin
Brenner & Rector’s the kidney, 10th edition.
❺Drug-induced
hyperKalemia

Kidney International (2020) 97, 42–61

Acute treatment of hyperkalemia

Comprehensive Nephrology, 6th ed

Am J Kidney Dis. 74(5): 682-695
Mayo
MayoClin
ClinProc.
Proc.2021;96(3):744-762
2021;96(3):744-762
Thank you for your attention