7/9/2015

1

Are Electrolytes Really Important?

Jeff Giullian, MD, MBA

Lytes, Camera, Action

Jeff Giullian, MD, MBA

Around the World of ElectrolytesIn 80 Minutes

A Whirlwind Tour of Positively Charged Ions

Disclosures

• Otsuka Pharmaceuticals• Genentech Pharmaceuticals• DaVita Dialysis

Plan of Attack

• Ions, Ians, Eons & Aeons• Sodium: Highs and Lows• Potassium: Ups and Downs• Magnesium: Increases and Decreases• Calcium: Peaks and Valleys• Phosphorus: Heights and Depths• Other: If we have time

Ions, Ians, Eons and Aeons

7/9/2015

2

Ions, Ians, Eons and Aeons

• Name of Gaelic Origin• Top 10 name for boys born in England in 1960s

o Ranked 80th in US boys in 2014

Eons and Aeons

• Indefinite, prolonged period of timeo Geologic time divided into eras

o Time frame I will be speaking on electrolytes

• Aeon is also the name of:o A band

o A retail store

o A game

o A science fiction cartoon

Back to Ions (and Science)

• Dissolve in a solutiono Has a charge

o NaCl� Na+ Cl-

o Total number of electrons ≠ protons per atom

• Electrical currento Can light a bulb

o Foundation for batteries

• Glucose can dissolve in a solution but …Cannot light a bulb

No electrical current

Sodium

Hyponatremia: Quiz

• Which drug class is associated with low sodium

A. Diuretics

B. SSRI

C. Narcotics

D. NSAIDs

E. All the above

7/9/2015

3

Sodium

• 85% found in extracellular fluido Plasma

o Lymphatic fluid

• Important for osmotic pressureo Intra/Extracellular water balance

o Cellular swelling/shrinkage

• Sodium/Potassium/ATP pumpo Energy dependent

o Electrical current, muscle contraction

Sodium/Water Imbalance

• Water balanceo Dilution

o Concentration

�Solute balance

+ Solute loss

+ Solute gain

Osmolality

• 2 x Na+ +Glucose/18 + BUN/2.8o Normal is around 285-295

o Because normal sodium is around 140

• BUN is an ineffective osmoleo Easily crosses cell walls

o Does NOT easily cross blood brain barrier

• EtOH and other alcohols also contribute

Changes in Sodium/Water Balance

• Hypernatremiao Stimulates thirst (water intake)

o Release of ADH (Vasopressin)

• Vasopressino Sensitive to small (1-2%) changes in osmolality

o Sensitive to large (10-20%) changes in pressure

o Acts on 3 receptors to improve pressure and retain free water

Osmoregulation: ADH

7/9/2015

4

Vasopressin Receptors

• V1-alphaVasoconstriction

• V1-beta ACTH release

• V2 receptorCollecting ducts

Reabsorb water

Hyponatremia• Hypo-osmotic

o Salt depletion (Diarrhea, salt wasting, sweat, burns)

o Water excess

Euvolemic appearance (SIADH)

Edematous appearance (CHF, Cirrhosis, Nephrosis)

• Iso-osmotic

o Hyperlipidemia

• Hyper-osmotic

o Hyperglycemia, Mannitol

Hyponatremia: Signs & Symptoms

• Time Dependento Acute/Chronic

o CNS adaptation

o Loss of neurotransmitter

• Non-specifico Nausea

o Fatigue

o Attention/Executive

• Modesto Balance

o Cramps

o Muscle Weakness

• Severeo Seizures

o Resp compromise

o Coma

o Death

SIADH

• Euvolemic in appearanceo Excess ADH (Vasopressin) leads to fluid retention

o No edema, rales, JVP elevation

• Normal amount of sodium in the body• Pulmonary & Neuro issues are likely culprit

o COPD, Small cell lung cancer, PNAo CNS traumao Post surgical issues

• Acute on Chronic sodium drop is common

SIADH: Drugs

• HCTZ…1 in 8 patients on thiazide get low Na+

• Other diuretics (loop, aldactone)• Anti-Seizure• Anti-Depressant (SSRI, SNRI)• Anti-Psychotic• NSAIDs• Chemotherapy

Osmoregulation: ADH

7/9/2015

5

Osmoregulation: SIADH SIADH: Lab Values

• Low Sodium, low plasma osmolarity• High urine sodium (>40)• Urine Osmolarity >100

o Not maximally dilute urine

o But, does not have to be “concentrated” urine

• Low uric acid, low BUN• Not responsive to Normal Saline

o Pee out all the salt in <1 liter of water

To fluid Restrict or Not

• (Urine Sodium + Urine Potassium) / Serum sodiumo If ratio < 0.5Lots of free water in urine. Free water Restriction will work

o If ratio > 1.0Minimal free water in urine. Free water Restriction will not work

o If ratio 0.5-1.0Grey zoneOK to try fluid restriction, but may not work

SIADH: Treatment

• Fluid restrictiono NOT FREE (Length of Stay)

• Add Soluteo NaCl tabs (+ loop diuretic)

o 3% SalineStart at 25ml/hr, measure q4-6hr, increase by 5ml/hr

Urine Osm can be predictive of response rate

• Demeclocycline: Damage to V2 Receptor• Vasopressin antagonist

Hyponatremia: Overcorrection

• Acute treatmento Get Na+ up 4-6mEq/L�Into temporary safe zone

o Can push 3% Saline (100cc at a time)

• Chronic treatmento Loss of organic osmoles

o Replace K+ first (if indicated)

o Risk of demyelination (ODS, CPM)

o 8-12mEq change in 24 hours (shoot for 4-6mEq)

o 6-8mEq next 24 hours

o Re-lower with D5W if needed

Hyponatremia: Volume Overload

• CHF, Cirrhosis, Nephrosis• Dilutional

o Sodium Overload

o But…too much water

• Low sodium is an independent RF foro Rehospitalization (think 30 day rule!)

o Other morbidity

o Death

7/9/2015

6

Hyponatremia: Heart Failure Hypernatremia

• Think Shrinkage…

Cellular Shrinkage

Hyponatremia Hypernatremia

• Mostly Dehydration (water deficit)• Sodium overload

o Sea water ingestiono Salt tablet overdose (It actually has happened!)

• RF: Elderly, Ill, DI, AMS, Heat stroke, Diarrhea• Give Free Water

o D5Wo Dilute IVFs in Abxo NG tube, PO fluids, etc

Sodium Points

• Hyponatremia is imbalance of sodium and water molecules

• Vasopressin is often elevated• Treatment: Add solute or Remove water• Do NOT treat too aggressively

Potassium

7/9/2015

7

Potassium Quiz

• Medications that affect potassium levels include:

A. Loop diuretics

B. Aldosterone blocking diuretics

C. ACE inhibtitors

D. Beta Blockers

E. A, B, C but not D

Potassium

• Mostly found intracellular (98%)• Chiefly found in muscle, including cardiac• Resting membrane potential of cells:

o Ratio of intracellular:extracellular potassium

o HypoK+ increases this potential in skeletal muscle

o HypoK+ lowers this potential in cardiac muscle making cardiac cells more excitable

o HyperK+ can also increase cardiac excitability

Hypokalemia: Loss vs Movement

• Losseso Reduced intake (rare)

o GI losses (lower GI mostly)

o Renal

o Sweat

• Translocation (increased activity of ATP pump)o Insulin (endogenous, exogenous)

o Alkalosis (upper GI losses)

o B-Adrenergic

o Leukocytosis/Leukemia

o Hypothermia

Urinary Potassium Losses

• Increased mineralocorticoid activityo Aldosterone (from adrenal gland)

o Reabsorb Sodium, Release Potassium

o Good for volume depletion as water follows salt

• High Distal sodium deliveryo Diuretics!

• Non-reabsorbable Anionso Toluene

o Penicillin

Hypokalemia: Other Causes

• RTA: Stay tuned• Hypomagnesemia

o Increases urine K+ losses

• Ampho Bo Increases cell wall permeability

• Genetic: Bartter’s, Gitelman’s, Liddle’s

7/9/2015

8

Hypokalemia: Symptoms

• Typically only below 3.0 mEq/L• Weakness (Similar to hyperkalemia)• Muscle cramps�Rhabdo• Cardiac arrhythmias• Impaired renal bicarbreabsorption�alkalosis

Potassium Release Exercise

• During strenuous activity, potassium is released from muscle cells

• Dilation of blood vessels, increase in blood flow to muscles

• Hypokalemia can blunt this response leading to micro-ischemia

U waves Hypokalemia: Replacement

• Pain and phlebitis if IV >10mEq/hour• Can be faster if central line• Typically requires 10-50mEq per 0.1• Oral preparations: KCl is best absorbed• K+ sparing diuretics

Hyperkalemia: Etiology

• Reduced excretion• Hypoaldosteronism• Potassium loads (or K+ sparing diuretics)• Metabolic Acidosis • Medications

o ACEi, ARB, B-Blockers, Spironolactone, Amiloride

• Pseudo-hyperkalemia (blood draws)

Blood Draw Induced HyperK+

• Cell lysis from small needle/shear stress• K+ movement out of cell from fist pumping + tourniquet

• Thrombocytosis: K+ moves out of platelets after clotting

• Hereditary due to passive movement out of certain RBCs

7/9/2015

9

HyperK+ in CKD/ESRD

• Reduced renal excretion• Metabolic Acidosis• Meds (ACEi, ARB, B-Blocker, Aldactone)• Reduced distal sodium delivery in patients with CHF, volume depletion

• Insulin deficiency

Hyperkalemia: Cardiac Risk

Hyperkalemia: Treatment

• Move K+ into cells (temporary)o Insulin (give with glucose)

o B-agonists (It takes A LOT of albuterol)

o Bicarbonate (Only works if acidotic)

• Stabilize the myocardiumo Calcium gluconate, Calcium Chloride

o (Requires central line but 3x more potent)

o Antagonizes membrane action

Hyperkalemia: Treatment

• Diuretics: Minimally effective acutely• Kayexelate: Sodium Polystyrene

o Exchanges Na+ for K+

o Oral or rectal

o Avoid in patients with ileus, GI surgery

• Zirconium (ZS-9): Not yet FDA approvedo Exchanges Na+ and H+ for K+

• Patiromer: Not yet FDA approvedo Exchanges Ca++ for K+

Hyperkalemia

• Dialysis is ultimate treatment if needed• Post-dialysis rebound

o 0.5mEq/L 30-60 min post HD

o Greater in patients that received pre-HD Rx

• Small molecule• Acid removal (bicarb bath) helps as well

Renal Tubular Acidosis

• Type I is DISTAL• Type II is Proximal• Type III is non-existant• Type IV is due to low mineralocorticoid

7/9/2015

10

Renal Acid Handling

• Acid comes from food, changes in respiration

• Kidney excretes excess hydrogen load daily

• Filtered bicarb is reclaimed by proximal tubule

• Ammonium (NH3 + H+ � NH4+

Distal RTA (Type I)

• Defect in Hydrogen ion excretion• Impairs distal acidification• Plasma bicarb usually quite low (10 mEq/L)

• Typically leads to hypokalemia• Improves with bicarb therapy

Distal RTA (Type I)

• Familial• Autoimmune disorders (Sjogrens, SLE, RA)

• Ampho B, Lithium• Hypercalcemia (Sarcoid, Vit D, HyperPTH)• Obstruction

Proximal RTA (Type I)

• Inability to reclaim filtered bicarbonate• Carbonic anhydrase inhibitors• Rarely causes much acidosis as Ammonium can be generated distally

• Serum bicarb modestly depressed• Aminoglycosides, Heavy metals, Fanconi’s

Type 4 RTA

• Hyperkalemia• Mineralocorticoid deficiency

o Potassium and Hydrogen reabsorption

o Sodium losses

• NSAIDs, CNI, Heparin, Bactrim• Sickle Cell Anemia• Occasionally DM

Electrolytes and Blood Pressure

7/9/2015

11

HTN Quiz

• Which of the following is correctA. Low sodium diet always lowers blood pressure

B. Low sodium diet when coupled with low chloride and high potassium lowers blood pressure more than low sodium alone

C. Low potassium diet lowers blood pressure

D. Sodium in the diet only affects Caucasians

Salt Sensitivity

• HTN is rare in societies with low dietary sodium

• Low salt diet takes 4-5 weeks to work• Modest effect overall

o Greater effect in salt sensitive individuals

• Sodium leads to water retention• Increases with Age• AA > Caucasion

Salt Sensitivity

• Sodium may inhibit vasodilation• HCTZ certainly works initially to lower salt/water

• Longer term effects on vasoconstriction• High sodium diet may limit effectiveness of ACEi, ARB and CCB

• Possible direct role in LVH

NaCl and Hypertension

• Primary hypertension (Essential hypertension

• Primarily in societies with average sodium intakes above 2.3 g/day

• Rare with average sodium less than 1.2 g/day

• Chloride appears to be a major component

Sodium and Hypertension

7/9/2015

12

Hypertension

• Low sodium diet (<2 grams) help in salt sensitive individuals

o African Americans > Whites

o Na-K-2Cl in Loop � Low renin HTN

• Higher potassium diet increases vasodilation• Sodium-to-Potassium ratio assoc with HTN• Chloride may increase HTN, so NaCl and KClnot optimal. Dietary Potassium is different

Magnesium

Magnesium Quiz

• Low Magnesium is often associated with:A. Hyperkalemia

B. Changes in parathyroid hormone

C. Hyponatremia

D. Hypokalemia

Magnesium

• Both GI absorption and excretion• Bulk of renal reabsorption is in the loop of Henle

• Paracellular route as opposed to directly through the TAL cells

• Unlike all other ion, no hormonal regulation

Thick Ascending Limb of LOH Hypomagnesemia

• Exacerbated by alkalosis, hypokalemia• Neuromuscular complications

o Hyperexcitability

o Tetany

o ??Migraines

• Cardiovascular complicationso Widening of QRS, AV arrhythmias

o Torsades de Pointes (Polymorphic VT)

7/9/2015

13

Torsade de Pointes Hypomag: Etiology

• Renal or GI losseso Loop diuretics > Thiazides

• PPI: Omeprazole is biggest culprit• Alcohol abuse

o Very common, 30%

o Defect in urinary excretion

• Abx: Aminoglycosides, Ampho B, Pentamadine

Hypomag: Treatment

• Check K+ and Ca++ levelso Often associated with either hypoK+ or hypoCa++

o If HypoCa++, check PTH

• Oral replacement OK, but can cause diarrheao Milk of Magnesia! (MgOH)o Mag Citrateo Slo Mag: Mag Chloride

• IV Mag Sulfate 2-4 grams is usually sufficient

Hypermagnesemia

• Rarely an issue other than OB patients• Iatrogenic or other excess dosing

o Decrease neuromuscular excitability

o Used to reduce preterm labor

• Magnesium Enemaso Large amount of absorption in GI tract

Disorders of Calcium & Phos

• Not going to address this issue in terms of advanced CKD and ESRD

• This is a HUGE topic covered elsewhere• Inextricably linked in CKD but not necessarily linked in normal renal function

Hormonal Involvement

• PTH and Vitamin D help control Calcium Levels

• Low PTH leads to low bone turnover• Vitamin D (sun�liver�kidney) leads to increased GI calcium absorption

• Sarcoid, TB and Small Cell lung cancero Ectopic Vitamin D

o PTH related protein

7/9/2015

14

Calcium

Hypocalcemia

• Calcium is bound to proteinso Hypoalbuminemia leads to low Calcium lab testo Correct Calcium for albumin or check ionized Ca++

• Leads to Hypotension in ICU patients• Parasthesias• Leads to tetany at very low levels

o Trousseau’s sign: Hand contracture with BP cuff x 3 min

o Chvostek’s sign: Hyperexcitability of facial nerve

Hypocalcemia: Cardiac Effects• Bradycardia• Impaired contractility• Narrowing of QRS and Prolongation of QT

Hypocalcemia Effect on PTH

7/9/2015

15

Vitamin D Supplements

• Nutritional Vitamin Do 25-OH Vitamin D2: Ergocalciferol

o 25-OH Vitmain D3: Cholecalciferol

o Increase Calcium and Phos levels, Decrease PTH

• Activated Vitamin Do 1, 25-OH Vitamin D: Calcitriol (Rocaltrol)

o Increase Calcium and Decrease PTH, may increase Phos

Vitamin D Analogs

• Paracalcitol (Zemplar)• Doxercalciferol (Hecterol)• May improve PTH without causing as much hyperphosphatemia

Hypercalcemia: CHIMPANZEES

• Calcium Intake• Hyperparathyroid• Immobility • (Iatrogenic)• Milk Alkali• Paget’s Dz of Bone

�Acromegaly

�Neoplasia

�Zollinger-Ellison

�Excess Vitamin D

�Excess Vitamin A

�Sarcoidosis

Hungary Bone Syndrome

• Post parathyroidectomy• Bones avidly take up calcium• Recalcitrant hypocalcemia• Hypophosphatemia and Hypomagnesemia• Hyperkalemia: Common but unclear etiology

• May need oral calcium, IV calcium, nutritional Vitamin D, activated Vitamin D