Electrolyte Imbalances
Alym Abdulla
CB Allard
Keith Barrett
Dr. Karen To
Electrolyte Imbalances
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Sodium
Potassium
Calcium
Phosphate
Magnesium
Sodium Imbalances
• Sodium Homeostasis
• Hyponatremia
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Etiology
Signs/Symptoms
Complications
Treatment
• Hypernatremia
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Etiology
Signs/Symptoms
Complications
Treatment
Na+ Homeostasis
• Na is main extracellular ion
• [Na] regulated by thirst, ADH, RAS
• Serum osmolarity >300mOsm/kg Æ
hypothalamic osmoreceptors Æ thirst, ADH
Na+ Homeostasis
• Na is main extracellular ion
• [Na] regulated by thirst, ADH, RAS
• Serum osmolarity >300mOsm/kg Æ
hypothalamic osmoreceptors Æ thirst, ADH
• ADH Æ free water reabsorption, low urine
volume, high urine osmolarity
Na+ Homeostasis
• Aldosterone Æ sodium reabsorption, low
urine Na
Na+ and ECFV
• Extracellular solutes (Na, glucose)
contribute to serum osmolality, affect
osmosis
– Increased ECF osmolality Æ H20 out of cells
– Decreased ECF osmolality Æ H20 into cells
– Clinical Sx due to cell shrinkage/swelling
• Hyper/hyponatremia are disorders of water
balance
Hyponatremia
• [Na] < 136mmol/L
• Approach
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Hypovolemic
Euvolemic
Hypervolemic
Redistributive
Hyponatremia
• Hypovolemic
– Loss of sodium and water, replaced by
hypotonic fluid
– Fluid losses, ARF/CRF, salt-wasting
nephropathy, cerebral salt-wasting syndrome
Hyponatremia
• Euvolemic
– Normal sodium stores, excess free water
– Psychogenic polydipsia, iatrogenic, SIADH
Hyponatremia
• Hypervolemic
– inappropriately high sodium stores
– ARF/CRF
– Decreased effective circulating volume
(cirrhosis, CHF)
– Uncorrected hypothyroidism or cortisol
deficiency (adrenal insufficiency)
Hyponatremia
• Redistributive
– Dilution of ECFV with proteins or lipids
• Hypertrigyceridemia
• Multiple myeloma
Hyponatremia
• Signs and Symptoms
– neurologic (cerebral edema)
• H/A, N/V, malaise, lethargy, weakness, muscle
cramps, anorexia, somnolence, disorientation,
personality changes, depressed reflexes, decreased
LOC
Hyponatremia
• Signs and Symptoms
– acute (<2 days) more likely symptomatic
– chronic; adaptation
• normalization of brain volume through loss of
cellular electrolytes (within hours) and organic
osmolytes (within days)
• adaptation creates risks associated with rapid
correction
Hyponatremia
• Complications
– seizures, coma, brainstem herniation, death
– rapid correction (>8mmol/L/d if chronic):
osmotic demyelination, central pontine
myelinolysis: cranial nerve palsies, paralysis,
decreased LOC
Hyponatremia
• Investigations
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ECF volume assessment
Serum lytes, glucose, Cr, osmolality
Urine osmolality, Na
Assess causes of SIADH (next slide), consider
CT chest
– TFTs, cortisol levels
Hyponatremia
• Treatment
– General measures
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water restrict (1L/day)
Treat cause
monitor Na frequently; do not rapidly correct
monitor U/O frequently; high output of dilute urine
is first sign of dangerously rapid correction
Hyponatremia
• Treatment
– Acute disorder
• if symptomatic, correct rapidly with 3% NaCl 12cc/kg/h up to Na = 125-135 +/- furosemide
• if asymptomatic, treatment depends on severity and
rapidity of onset
Hyponatremia
• Treatment
– Chronic/Unsure
• Asymptomatic
– general measures +/- IV 0.9% NS + lasix
• severe symptoms (seizures or decreased LOC)
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partially correct acutely
increase Na by 1-2mmol/L/hr for 4-6hrs
max increase 8mmol/L/d
correct with IV 3%NACl as above +/- furosemide
Hyponatremia
• If overly rapid correction
– Give free water (IV D5W) +/- DDAVP
• Impact of IV solution on plasma [Na]
– Change serum [Na] (per L of infusate)
= (infusate [Na] – serum [Na]) / (TBW + 1L)
(TBW = 0.5 x wt (kg) in females or 0.6 x wt (kg) males)
Hypernatremia
• [Na] > 145 mmol/L
• relative water deficit
• usually net water loss, rarely hypertonic Na
gain
• problems with intake (access, thirst) and/or
increased water loss (renal [eg: DI],
extrarenal)
Hypernatremia
• Hypervolemic
• Non-hypervolemic
Hypernatremia
• Hypervolemic (rare)
– Iatrogenic
– Cushing’s syndrome
– Hyperaldosteronism
Hypernatremia
• Non-hypervolemic
– high urine osmolality and oliguria (appropriate
aldosterone response)
• water loss
• respiratory, skin, GI, osmotic, renal
Hypernatremia
• Non-hypervolemic
– high urine osmolality and oliguria (appropriate
aldosterone response)
• water loss
• respiratory, skin, GI, osmotic, renal
– high urine osmolality without oliguria
• diuretics, osmotic diuresis (hyperglycemia, uremia)
Hypernatremia
• Non-hypervolemic
– high urine osmolality and oliguria (appropriate
aldosterone response)
• water loss
• respiratory, skin, GI, osmotic, renal
– high urine osmolality without oliguria
• diuretics, osmotic diuresis (hyperglycemia, uremia)
– Low urine osmolality
• DI (nephrogenic, central)
Hypernatremia
• Signs and Symptoms
– depend on rapidity
– adaptive response: cells import and generate
osmotically active molecules to normalize size
– brain cell shrinkage: altered mental status,
weakness, neuromuscular irritability, focal
deficits, seizures, coma, polyuria, thirst, death
Hypernatremia
• Complications
– Vascular rupture (ICH)
– Rapid correction Æ cerebral edema
Hypernatremia
• Treatment
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Salt restrict, give free water (oral, IV)
Treat cause
Frequent monitoring Na
If HD unstable, correct volume deficit first with NS
H20 deficit = TBW x (serum Na – 140)/140
TBW = 0.6 x wt (kg) men or 0.5 x wt (kg) women
Hypernatremia
• Treatment
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H20 deficit = TBW x (serum Na – 140)/140
TBW = 0.6 x wt (kg) men or 0.5 x wt (kg) women
1L D5W = 1L “free water”
1L ½ NS = 500cc “free water”
Lower Na max 12mmol/L in 24hr
Change in [Na] = (infusate [Na] – serum [Na])/(TBW + 1L)
Don’t forget maintenance fluid
If hypervolemic
• Remove excess total body Na with diuresis or dialysis prior to
above
Potassium Imbalances
• Overview of potassium metabolism
• Hypokalemia
– Clinical manifestations
– Causes
– Management
• Hyperkalemia
– Clinical manifestations
– Causes
– Management
Potassium Metabolism
• Absorbed in the gut
• Majority of total body potassium sequestered
intracellularly (98%)
• Filtered by the glomerulus
Renal potassium handling
• Loop of Henle
– K reabsorbed along with Na and Cl
– Diuretics and salt wasting nephropathies interfere
• Collecting Duct
– Excretion: Principle cells, Aldosterone-mediated
– Reabsorption: intercalated cells; affected by acid/base
status
Hypokalemia
• < 3.5meq/L
• Symptoms
– unusual until K <3.0meq/L
– Severe rare until <2.5meq/L
– due to difficulties maintaining resting
membrane potential in nerves & muscle cells
→ difficulties generating action potentials
– resolve with the correction of low K
Clinical Manifestations
• Muscle weakness/cramps/rhabdomyolisis/
myoglobinuria/ileus
• ECG Abnormalities/Arrhythmias
Hypokalemia: ECG
Abnormalities
• Characteristic ECG changes
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Not seen in all pts
Do not correlate with severity of hypokalemia
Depression of ST segment
Decrease in amplitude of T wave
Increase in amplitude of U waves (occur after T wave; mostly
seen in V4-6)
Hypokalemia: Cardiac
Arrhythmias
– prolonged ventricular refractory period;
predisposes to re-entrant arrhythmias
– PAC/PVC
– Sinus bradycardia, AV block
– Paroxysmal artial or junctional tachycardias
– VT/VF
– Torsades de pointes (esp if low Mg)
Hypokalemia: Causes
• Decreased intake
– Rare as isolated cause
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Shift into Cells
GI Losses
Urinary Losses
Sweat Losses
Dialysis / Plasmapheresis
Shift into Cells
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Metabolic or respiratory alkalosis
Increased insulin
Increased beta-adrenergic activity
Significant increase in blood cell production
Hypothermia
Drugs
Urinary Losses
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Diuretics
Non-reabsorbable anions
Metabolic acidosis
Polyuria (DI)
Hypomagnesemia
– Up to 40% of hypokalemic patients
Management
• Goals
– Prevent serious complications
– Replace deficit
– Identify underlying cause(s)
Replace Deficit
• Potassium Deficit
– severity of hypokalemia varies with the degree
of total body deficit, except in cases where
significant intracellular shifting has occurred
Oral K Replacement
• Patients without significant complications
• Most will require multiple doses over hours-days
• Tablets
– slow K (8meq/tab, extended release)
– micro K (8meq/tab)
– K-dur (10 or 20meq/tab; 2 formulations)
• Liquid suspensions
– K elixir (40meq/dose)
– K lyte (potassium bicarb-potassium citrate;
25meq/effervescent tab)
IV Replacement
• Severe symptoms / can’t tolerate PO
• KCl
– Peripheral line (10meq in 100ml NS over 1h / dose)
– Central line (20meq in 100ml NS over 1h / dose)
• K Phos
– 22/15meq in 100ml NS over 1h / dose
• May cause phlebitis
Other
• Potassium Sparing Diuretics
– ongoing renal potassium wasting where replacement is
not sufficient
– diuretics acting distal to the principle cell
– amiloride, spironolactone
• Hypomagnesemia
– Cannot correct hypokalemia until magnesium deficit
replaced
– Ward: Magnesium Sulphate 1-2g over 2h
– ICU/CCU: Magnesium Sulphate 1-5g IV over 3h
Hyperkalemia
• >5.0meq/L
• Most commonly due to impairment in renal
potassium excretion
• Clinical manifestations relate to impaired ability to
generate action potentials in muscle and nervous
tissue
• Serious complications unusual below 7meq/L if
chronic
– may occur at much lower concentrations in the acute
setting
Clinical Manifestations
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Severe Muscle Weakness / Paralysis
ECG changes
Arrhythmias
Conduction Abnormalities
Metabolic Acidosis
Severe Muscle Weakness / Paralysis
• Ascending muscle weakness beginning in
the legs
• Can mimick Guillain-Barre
• Respiratory muscle weakness rare
ECG Abnormalities
• Classical progression
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Peaked T waves (not specific to hyperkalemia)
Lengthening of PR interval and QRS duration
Loss of P waves
QRS becomes sine wave
VF / asystole
ECG Abnormalities
Arrhythmias and Conduction
Abnormalities
• Sinus bradycardia, sinus arrest, VT, VF,
asystole
• RBBB, LBBB, bifascicular block, AV
blocks
Hyperkalemia: Causes
• Shift from Cells
• Reduced Potassium Excretion
Shift from Cells
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Metabolic acidosis
Insulin deficiency
Tissue catabolism
Beta-adrenergic blockade
Extreme exercise
Reduced Potassium Excretion
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Renal Failure
Hypoaldosteronism
Decreased Effective Circulating Volume
Ureterojejunostomy (urinary conduit)
Hyperkalemia: Management
• Urgency of therapy depends on severity and
presence of symptoms / ECG changes
• 3 Concepts in the approach to treatment
– antagonizing cardiac membrane effects with
calcium (transient)
– shifting K into cells (transient)
– eliminating excess K from the body (longer
lasting)
Hyperkalemia Management:
Calcium
– Directly antagonizes membrane effects of K
– Onset in minutes, duration 30-60min (may require
repeat dosing)
– Calcium gluconate 1g IV slow push over 2-3min
– Repeat after 5min if ECG changes persist
– Calcium chloride has 3x the dose of calcium as calcium
gluconate
– DO NOT GIVE in digitalis overdose (potentiates the
cardiotoxic effects of digitalis)
Hyperkalemia Management:
Insulin and Dextrose
– Shifts K into cells; concurrent dextrose to
prevent hypoglycemia
– Common regiment
• Humulin R 10units IV push
• D50 ½ amp IV push
• Effect begins in 10-20min and peaks 30-60min
– Lasts approx 4-6 hours
– Will lower serum K by 0.5-1.2meq/L
Hyperkalemia Management:
Beta-2 Adrenergic Agonists
– Shifts K into cells
– Not used as commonly as insulin, should not be used as
monotherapy
– Albuterol / salbutamol 10-20mg in 4ml NS by nebulizer
over 10min
• 4-8x the bronchodilator dose
– Expect to lower serum K by approx 0.5-1.5meq/L
– Additive effect with insulin
– Side effects include tachycardia and angina
• Avoid in patients with known CAD
Hyperkalemia Management:
Eliminate Potassium
• Diuretics
– No proven role in acute setting
• Cation Exchange Resin
• Dialysis
Hyperkalemia Management:
Cation Exchange Resin
– Kayexalate 15-30g po
– Requires multiple doses to achieve significant
effect (usually bid/tid dosing)
– Can lower serum K by 0.4meq/L in 24h
– Major complication reported is intestinal
necrosis
• Very rare
Hyperkalemia Management:
Dialysis
– Most effective way to remove excess K
– Reserve for patients with severe hyperkalemia
or significant complications
– Ideal when etiology is expected to persist
(tumor lysis, trauma)
Address Underlying Cause
• Ensure not receiving K
• Hold drugs that may be causing
hyperkalemia
– most commonly ACEI, ARB, potassium
sparing diuretics, NSAIDS
• Address possible causes of renal failure
The Rest
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Calcium
Phosphate
Magnesium
Chloride
Bicarbonate
Calcium
• Membrane excitability in muscle/nervous
tissue.
• Skeletal Structure
• Intracellular Signal Cascades
Calcium
• Total Serum 2.375mmol/L
– 1.125mmol/L protein bound
– 0.125mmol/L insoluble complexes
– 1.125mmol/L ionized calcium
Calcium - Homeostasis
• Intestine
• Kidneys
• Skeletal System
Intestine
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Intake: 1000mg/day
300mg absorbed – duodenum and jejunum
150mg/day secreted by liver, pancreas, gut.
Net gain of 150mg/day or 15%
Absorption influenced by intake and by
Vitamin D effect on enterocytes.
Kidney
• Filters 10,000mg/day
• 9,000mg reabsorbed “proximally” and not
influenced by parathyroid hormone (PTH)
• 1,000mg/day reaches “distally” and this is
influenced by PTH
• PTH release tightly regulated by calcium
sensors on parathyroid cells. (0.1mg/dL)
Skeletal System
• Contains approximately 1.2kg of Calcium
• Large reservoir for adding and removing
Calcium.
• PTH plays a critical role in mobilizing
Calcium from these stores.
Parathyroid Hormone
• Kidney:
– Stimulates Vitamin D production
– Stimulates Calcium re-absorption
– Inhibits Phosphate re-absorption
• Bone:
– Acutely, osteoclastic resorption
– Chronically, osteoblastic bone formation
• Intestine:
– Indirect activation of Calcium transport
Hypercalcemia
• 90% of cases related to malignancy or primary
hyperparathyroidism
• Usually mild, 2.65 – 2.875mmol/L, symptoms
generally present at > 3.25mmol/L
• Presents as muscle weakness, smooth muscle
hypoactivity, confusion, deep coma, renal failure,
shortened QTc interval
Malignancy
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Humoral hypercalcemia of malignancy
Vitamin D secreting lymphomas
Direct skeletal invasion
True ectopic hyperparathyroidism
Treatment:
– Treat maligancy
– IV saline with a loop diuretic
Primary Hyperparathyroidism
• Parathyroid adenoma
• Elevated serum PTH, hypercalcemia,
hypophosphatemia, increased plasma
calcitriol
• Most are asymptomatic, or may present
with calcium nephrolithiasis, osteopenia,
reduced renal function.
• Parathyroidectomy
Hypocalcemia
• Majority of cases are related to inadequate intake,
deficiencies in Vitamin D and/or
hypoparathyroidism.
• Hypomagnesemia
• Present with parasthesias, tetany, prolonged QTc
interval, and in rare cases hypocontractility of
myocardium and CHF.
Vitamin D Deficiency
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Inadequate intake or exposure to sunlight
Fat malabsorption
Chronic Renal Failure
Hepatic Failure
Renal 1-alpha-hydroxylase deficiency
1,25-vitamin D receptor defects
Hypoparathyroidism
• Surgical
• Idiopathic/Autoimmune
• Infiltrative Diseases
• Congenital
Phosphate
• Integral to many biological processes
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DNA double-helix
Energy via ATP
2nd messenger systems IP3 and cAMP
Skeletal System
Phosphate
• 0.97 – 1.45mmol/L
• Not as tightly regulated as Calcium
• On average 67% of ingested phosphate is
absorbed by the duodenum and jejunum
• 90% of Phosphate seen by the kidney is
reabsorbed
Hyperphosphatemia
• No obvious signs and symptoms per se.
• Causes Include:
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Artefactual
Increased GI Intake
IV Phosphate Loads
Endogeouns Phosphate Loads
Reduced Renal Clearance
Hyperphosphatemia
• Treatment
– Limit exogenous intake if that is the culprit
– Limit PO intake in renal failure and use
Phosphate binders
– Endogenous Phosphate responds to forced
saline diuresis +/- a loop diuretic
Hypophosphatemia
• Signs and symptoms are non-specific.
• If chronic, leads to defects in skeletal
mineralization, or osteomalacia.
• Causes Include:
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Inadequate Intake
Renal Losses – HPT, Medications
Excessive Skeletal Mineralization
Phosphate Shifts into ECF
Hypophosphatemia
• Treatment
– Best accomplished via the oral route.
– 2000 - 4000mg/day divided into 2-4 doses
Magnesium
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DNA replication and transcription
Translation of RNA
Use of ATP as energy source
Regulates peptide hormone secretion
Incorporated into the hydroxyapatite crystal
of skeletal structure.
Magnesium
• 1.5 – 2.0 mg/dL
• Like Phosphate, predominates
intracellularly and is not as tightly regulated
as Calcium.
• 33% of the ingested Magnesium is absorbed
and it is abundant in our diets.
• No independent regulatory system.
Hypermagnesemia
• Clinically significant levels are uncommon.
• Symptoms include drowsiness and signs are
hyporeflexia and eventual neuromuscular,
respiratory, and cardiovascular collapse.
• Causes
– Renal Failure accompanied by antacid use
– Parenteral Magnesium Sulfate for eclampsia
Hypomagnesemia
• Non-specific symptoms weakness, respirator
dependence, seizures and cardiovascular collapse.
• Causes are limited to:
– Inadequate Intake: alcoholics, malabsorption sydrome,
continuous vomiting, NG suctioning.
– Excessive Renal Losses: diuretics, saline infusions,
hyperaldosteronism, diuresis secondary to diabetes,
hypokalemia, hypercalcemia, hypercalciuria,
aminoglycosides, cisplatin.
Hypomagnesemia
• Treatment
– IM or IV Magnesium replacement
– 24 – 48mEq of Magnesium Sulfate over 24
hours is sufficient
– Oral Magnesium difficult to administer because
of it cathartic effects.
The END
• Thank you to Dr. Karen To
• In loving memory of Keith Barrett