Electrolyte Disorders - Jai Radhakrishnan, MD

Electrolyte Disorders

    Jai Radhakrishnan, MD

                            1

Objectives
„ Diagnostic and therapeutic principles of
  „ Disorders of osmolarity (Hypo/hypernatremia)
  „ Potassium
  „ Magnesium

                                                   2

Disorders of Osmolarity

                       Na Ξ Osmolality
Free Water Intake
                    „ Hyperosmolarity (Hypernatremia)
                    „ Hypoosmolarity (Hyponatremia)

         P. Na

Free Water Loss

                                                        3

Generation of Disorders of Osmolarity
                     „ Hypernatremia
                        „ If water intake is less than
 Free Water Intake        output

                     „ Hyponatremia
                        „ If free water intake is
          P. Na           greater than output

 Free Water Loss

                                                     4

Hyponatremia
„ Hypo-osmolar

„ Iso-osmolar
  „ lipid/protein

„ Hyper-osmolar
                    Osmotically active subs

                                              5

Case

27 year old male alcoholic is admitted with altered mental
status after a recent drinking spree.
P.E.: BP 100/70 HR=130 RR=40
Labs:   116|66|56 109
        5.0|15 |2.8
A.G.=35          Ketones=neg
Measured Osm= 350
Calculated Osm=156
Urine= +++ oxalate crystals
                                                             6

Hyperosmolar Hyponatremia:
 Osmolar Gap

„ Calculate:
2Na + Glucose/18 + BUN/2.8
„ Measure:
Freezing point depression (lab)
„ Gap: (Measured)-(Calculated)  10 presence of an osmotic substance that is not
   Na, glucose or BUN

                                                          7

Case: Hyperosmolar Hyponatremia

27 year old male alcoholic is admitted      „ Endogenous:
with altered mental status after a recent
                                               „ Acetone
drinking spree.
                                               „ Renal failure
P.E.: BP 100/70 HR=130 RR=40                   „ Lactate
Labs:   116|66|56 109                       „ Exogenous:
        5.0|15 |2.8                            „ Methanol
                                               „ Ethylene Glycol
A.G.=35          Ketones=neg
                                               „ Ethanol
Measured Osm= 350                              „ Glycine
Calculated Osm=156                             „ Mannitol

Urine= +++ oxalate crystals                                    8

Hypoosmolar Hyponatremia
                    „ Increased free water
                      supply
Free Water Intake
                    „ Decreased free water
                      excretion

         P. Na

Free Water Loss

                                             9

Hyponatremia:
1. Increased free water supply
                      „ Psychogenic polydipsia is the
                        only situation where this
  Free Water Intake
                        mechanism is solely responsible
                      „ Uosm low;

"Drink at least eight glasses of water a day." Really?
Is there scientific evidence for "8 × 8"?

                   Valtin H… Am J Physiol Regul Integr Comp   11

                   Physiol 283: R993-R1004, 2002

12
Sumit Kumar & Tomas Berl

Hyponatremia-
2. Impaired free water excretion by kidney

                     „   Too few nephrons
 Free Water Intake
                          „ renal failure

                     „   Too much ADH
                          „ Volume depletion

                               ƒ Real
          P. Na                ƒ Effective (edema states)
                          „   Endocrine
                               ƒ Thyroid
                               ƒ Adrenal
 Free Water Loss
                     „   INAPPROPRIATE ADH

                                                            13

Evaluation of Hyponatremia
                  „   Iso/hyperosmolar states
                       „   Measure plasma osmolarity (calculate osmolar gap)
                       „   Check Lipids/proteins
Free Water Intake„    Psychogenic polydipsia?
                       „   Urine Osm

Causes of SIADH
z   Tumours:     bronchogenic carcinoma, lymphoma,
                 pancreatic cancer, mesothelioma
z   Pulmonary:   pneumonia, TB, lung abscess, COPD
                 pneumothorax, HIV infection

z   CNS:         head injury, meningitis, subdural
                 haematoma, subarachnoid hge,
                 neurosurgery

z   Drugs:       carbamazepine, chlorpropamide,
                 cyclophosphamide, ‘ecstasy’, NSAID,
                 tricyclic antidepressants,
                 phenothiazines, SSRI

                                                       15

Case
     71 year old woman presented with fatigue and
     forgetfulness. PMHx: HTN on thiazides.
     Physical exam: Systolic BP drop of 20mmHg
     Plasma:          119|75| 4     UNa+=13
                      3.1|29|1.8    Uosm=422

 „   Hyperosmolar?
 „   Psychogenic polydipsia?
 „   Too few nephrons?
 „   Too much ADH?
      ‹ Volume depletion

      ‹ Edematous states

      ‹ Thyroid/Cortisol

      ‹ SIADH (by exclusion)                        16

Hyponatremia
Clinical Effects
                                                                460

                                Brain water g/100g dry weight
                                                                440
                                                                420
                                                                400
       PNa+=139:
                                                                380
       Baseline
                                                                360
                                                                340
                                                                320
       PNa+=119   in 2h                                               139   139-119   140-122   139-99
                                                                              (2h)     (3.5d)    (16d)

       PNa+=122 (3.5 days)
                                                                                       PNa+=140:
       PNa+= 99 (16 days)
                                                                                       Day 5
                   Correction                                                                        17

18
Sumit Kumar & Tomas Berl

Clinical Course of Treated
Hyponatremia

        Arieff A.. NEJM 1986;314(24):1529-35   19

20
Am J Med. 2006 Jan;119(1):71.e1-8

Hyponatremia-
Principles of Treatment
„ Treat vigorously if symptomatic/acute to
  reach a “safe” level
„ If vigorous treatment planned do not increase
  PNa+ by >0.5meq/h.
„ Use frequent monitoring of PNa+ to guide
  therapy.

                                              21

Treatment Modalities
                  All forms of hyponatremia will respond to water restriction.
                  „ Primary polydipsia
Free Water Intake „ Renal failure: Dialysis
                  „ True Volume depletion: Normal saline
                  „ Effective volume depletion: treat cause, loop diuretics.
                  „ Thyroid, cortisol: replacement
                  „ SIADH
         P. Na         „   Asymptomatic/chronic:
                            „   Water restrict
                            „   Salt tablets, high protein diet
                            „   Furosemide in divided doses
                            „   ADH Antagonists
Free Water Loss
                       „   Acute/Mental status change
                            „   Hypertonic saline until M.S. adequate (.5meq/hour)

                                                                                     22

Arginine Vasopressin

                       23

Tolvaptan (SALT-1 & SALT-2)

                              24

IV Conivaptan 40mg/d in
Hypervolemic Hyponatremia

                            25

Vasopressin v2-receptor blockade with tolvaptan in
patients with chronic heart failure

                Circulation. 2003 Jun 3;107(21):2690-6.   26

Case

    65 year old woman with no PMHx is admitted with
    unresponsiveness. Physical exam is normal.
    PNa+ = 115, Posm=240, Uosm=700, UNa+=70. Normal sugar/urea.

„   Hyperosmolar?
„   Psychogenic polydipsia?
„   Too few nephrons?
„   Too much ADH?
     ‹ Volume depletion

     ‹ Edematous states

     ‹ Thyroid/Cortisol

     ‹ SIADH (by exclusion)
                                „   How would you treat this
                                    patient?                   27

Hypertonic saline-
dose calculation
  Current PNa+ = 115 Target PNa+ = 120
„ Na+deficit = 5 meq/liter
  Total body Na+ deficit= 5 x total body water
                        = 5 x 0.5 x body wt (50kgs)
                        = 125meq
ƒ Amount of 3% NaCl needed (Na=513meq/L)              =
  125/513= 240ml
ƒ Rate of infusion=0.5meq/hour=10 hours
                =24ml/hour

                                                          28

HYPERNATREMIA

                29

Case

60 year old male with ARDS/intubated/pressors/TPN
PNa= 150. Urine output 150ml/hr. Normal hemodynamics.
Uosm=504 UNa=40meq
Urine dip=2+ glucose
Serum glucose 400.
‰What is the cause of hypernatremia ?
‰How would you treat him?

                                                        30

Pathogenesis of Hypernatremia

Free Water Intake   „ Decreased free water supply
                    „ Water loss
                      „ Osmotic diuresis, D.I.
                      „ Osmotic diarrhea
         P. Na
                      „ Insensible
                    „ Solute load

Free Water Loss

                                                    31

Workup of Hypernatremia
„ Why is the patient not drinking??
„ Is there increased free water loss:
  „   ?Polyuria
       „   Uosm: if 300 – solute diuresis
  „   ? GI (osmotic diarrhea)
„ Is the patient getting too much solute?

                                             32

Treatment of Hypernatremia
„ Provide free water
  „ Oral is optimal
  „ Rate of correction

Case

60 year old male with
                                   „   Why is the patient not drinking??
ARDS/intubated/pressors/TPN        „   Is there increased free water loss:
PNa= 150. Urine output 150ml/hr.         „ ?Polyuria
                                                 Uosm: if 300 – solute diuresis
Uosm=504 UNa=40meq                      „   ? GI (osmotic diarrhea)
                                   „   Is the patient getting too much
Urine dip=2+ glucose                   solute?

Serum glucose 400.
‰What is the cause of
hypernatremia ?
‰How would you treat him?
                                                                          34

Calculation of water deficit
„ Calculate Amount of Water
   ƒ 0.4 x body weight x (PNa/140 – 1)
     0.4 x 50 x (150/140 – 1) =          1.4 liters
   ƒ Insensible losses=            +     1 liter/24h
   ƒ                   Total volume=     2.4 liters
„ Rate (0.5meq/hour)
   „ For Na to go from 150->140=20 hours
„ Prescription: Rate of water repletion
       = 2400/20=120ml/hr.

                                                       35

Hyper- and
Hypokalemia

              36

Hyperkalemia- Etiology

                   „ Intake (never alone)

                   „ Shift (Acute)
                        „   Acidosis
       ICF   ECF        „   Insulin lack
                        „   Tissue Lysis
                        „   Beta blockade
                        „   Digitalis o.d.
                        „   Succinylcholine

                   „ Excretion (Chronic)
                        „   Advanced renal failure
                        „   Hypoaldosteronism
                        „   Volume depletion
                                                     37

Hyperkalemia: Case
    50 year old male with NIDDM/ CRI has been prescribed a low Na
       diet for HTN. He presents to the ER with marked weakness.
    Labs: 130|98|50 280
             8.0 |17| 2.7

„Is this pseudohyperkalemia ?
„What is causing the hyperkalemia?

„How would you treat ?

                                                                    38

Treatment of Hyperkalemia
„ Antagonism of membrane action
   „ Intravenous calcium
„ Shift
   „ Insulin (Dextrose)
   „ NaHCO3
   „ ß-2 agonists
„ Removal
   „ Diuretics
   „ Cation exchange resin
   „ Dialysis

                                  39

Hypokalemia- Etiology

                   „ Intake (never alone)

                   „ Shift
                       „   Treatment with insulin
                       „   Alkalosis
       ICF   ECF       „   ß-2 stimulation
                       „   Periodic paralysis
                       „   Treatment of anemia

                   „ Increased Excretion
                       „   GI
                       „   Renal
                             „   Hyperaldosteronism
                             „   Diuresis
                             „   Ampho-B
                             „   Hypomagnesemia
                                                      40

Hypokalemia-
Clinical Consequences
„ Cardiac arrhythmias
„ Muscle weakness
„ Rhabdomyolysis
„ Renal dysfunction
„ Glucose intolerance

                        41

Hypokalemia-Treatment
„ Estimate of deficit is difficult
   ƒ   ~100-200 meq for 1 meq/liter
„ PO therapy usually adequate
„ IV therapy if severe/symptomatic
   ƒ   Max conc. 40meq/liter
   ƒ   Max rate 20meq/hour
   ƒ   Use in saline (not dextrose)

                                      42

Hypokalemia-case
„ 58 yr old cirrhotic is admitted with worsening ascites
„ Meds: Lasix 40mg bid, Lactulose
„ EKG: Unifocal VPC’s, prominent U waves
„ Admission labs:      125|87|32 80
                       2.2 |20|2.0
How would you treat her hypokalemia ?

                                                           43

Disorders of
Magnesium

               44

Hypomagnesemia:Etiology

            „ Intake
               „   Malnutrition
               „   GI malabsorption
            „ Shift
               „   Pancreatitis
               „   Insulin administration
ICF   ECF      „   Post-parathyroidectomy (hungry bone syndrome)
            „ Excretion (Renal)
               „   Post-obstructive, Post ATN
               „   Post-renal transplant
               „   Bartter’s/Gitelman’s syndromes
               „   Drugs: Diuretics, aminoglycosides, cisplatinum,
                   amphotericin
               „   Alcohol (decreased intake contributing)

                                                                     45

Hypomagnesemia:Clinical Effects
„ Cardiovascular
  „ Arrhythmia (prolonged QT)
„ Metabolic
  „ Hypocalcemia
  „ Hypokalemia
„ Neurological
  „ Tetany
  „ Seizures

                                  46

Hypomagnesemia: Treatment
„ Oral
   „ MgO
   „ Mg-containing antacids
   „ Milk of Magnesia
   „ Mg citrate, sulfate, lactate
„ Intravenous (avoid IM)
   „ Bolus
   „ Infusion

                                    47

Hypermagnesemia:Etiology

            „ INTAKE
              „ Mg-containing
                antacids/laxatives
ICF   ECF     „ IV magnesium replacement
            „ SHIFT
              „ DKA
              „ Tissue injury
            „ EXCRETION

                                           48

Hypermagnesemia:
Clinical Consequences
„ >4mEq/L
   „ Inhibition of neuromuscular transmission
   „ Inhibition of cardiac conduction
„ > 7 mEq/L
   „ Lethargy
   „ PR, QT and QRS prolongation
„ >10mEq/L
   „ Respiratory failure/voluntary muscle paralysis
   „ CHB/Asystole

                                                      49

Hypermagnesemia
Treatment
„ IV calcium
„ Dialysis

                  50

END

      51