HyperHypo Na HyperHypo K

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Hyper/Hypo Na Hyper/Hypo K

• Friday, August 15th
• Pouneh Nouri MD
• Division of Nephrology and Hypertension

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Facts

• POSM 2 X Na glucose BUN 275-290
  mosmol/kg
• 18 2.8
• Na concentration Amount of Na 137-143 meq/L
• Volume of water
• Na concentration Plasma Osmolality
• Range of urine concentration ability 90-1200
  mOsm/Kg

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The Core principles in Sodium Balance

• Body senses and regulates serum Osmolality (not
  serum Na)
• Serum Osmolality is regulated by regulating water
  balance (not Na balance)
• Serum Na is a surrogate marker for serum
  osmolality

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Regulation of Serum Osmolality
Regulation of ECF Volume
ADH
ECV
POsm
-
-
Aldosterone
distal tubular sodium reabsorption
Thirst
UOsm
Non-osmolar stimuli to ADH secretion is the
interaction of the two system
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Facts

• Volume depletion override the effect of serum
  osmolality on ADH secretion.
• The osmoreceptors (which stimulate ADH secretion)
  are not triggered by hyperosmolality due to
  elevated urea (BUN), or blood sugar (BS), since
  they are ineffective osmole.

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Hypernatremia

• Symptoms
• Lethargy, Weakness, Irritability, Seizure,
  Coma,
• and Death
• Severity of symptoms depends on
• -The rate of rise in the POSM
• - Chronic hypernatremia is asymptomatic due to
  cerebral adaptation

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Etilogy of Hypernatremia

• Water Loss
• A - Insensible loss (fever, burns, tachypnea,
  exercise)
• B - Renal Loss (DI, osmotic diuresis)
• C - GI Loss (osmotic diarrhea)
• D - Hypothalamic disease (reset osmostat 2
  hyperaldo)
• E - Water loss into cells (seizure, rhabdo)
• Sodium ingestion or infusion

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Hypernatremia
U OSM
lt 800 mOsm/Kg
gt 800 mOsm/Kg
Extra-renal water loss
OR Sodium ingestion/infusion
Water intake
Renal water loss
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DDX of Renal Water Loss/Polyuria
Polyuria (UOP gt 3 L/d) UOSM lt 800 mOsm/Kg
Osmolar excretion rate ( UOP X Uosm)
gt 1000 mOsm/d
lt 1000 mOsm/d
Water diuresis DI Primary Polydipsia
Osmotic diuresis NaCl, Glucose, Urea,
Mannitol
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DDx of DI/polyuria
Water deprivation test
P OSM gt 295 mOsm/Kg
U OSM
300-800 mOsm/kg Partial DI Primary Polidipsia
lt 300 mOsm/Kg Complete DI
DDAVP
50 rise in UOSM Partial Central
DI 100-800 rise in UOSM Complete Central DI
No change in UOSM Nephrogenic DI Primary
Polydipsia
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Rx of Hypernatremia

• Free water deficit 0.6 X BW (Na /140) 1
• Quick calculation Deficit ? Na / 3
• Replace free water deficit (50 in first 24 h)
  ongoing free water loss
• Slow correction to prevent cerebral edema (0.5
  meq/L per hour or 12 meq/L per day)

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Specific Rx for Hypernatremia

• Desmopressin Central DI
• Salt and protein restriction DI
• Thiazides DI
• Amiloride Lithium induced Nephrogenic DI
• Chlorpropamide, Clofibrate, NSAIDs Central DI

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Why salt/Protein restriction in DI for Polyuria
and NOT water restriction?
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Hyponatremia

• Symptoms
• Nausea, malaise (120-125 meq/L)
• Headache, lethargy, obtundation ( 115-120 meq/L)
• Seizures, coma (lt115 meq/L)
• Chronic hyponatremia cause few if any symptoms

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Hyponatremia
POSM
lt 275 mOsm/Kg
gt 290 mOsm/Kg
Normal pseudohyponatremia
True hypo-osmolar hyponatremia
Glucose Mannitol
Lipid (High TG) Protein (multiple myeloma)
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Hypo-osmolar hyponatremia
Excess water intake Primary Polydipsia
Effective POSM ( BUN, uremia, CKD)
ADH
Appropriate ADH (in response to non-osmolar
Stimuli, i.e. ECF volume)
Inappropriate ADH
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Hypo-osmolar Hyponatremia
Volume Status
Hypovolemic Dehydration Addisons Diuretics
Edematous CHF Cirrhosis Nephrotic Synd. CKD
Isovolemic
UOSM
gt100 mOsm/Kg SIADH Hypothyroidism
lt100 mOsm/Kg Primary Polydipsia
UNa gt 20 meq/L Una lt 20 meq/L

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Rx of severe Hyponatremia

• Na deficit 0.6 X BW 120-Na
• Volume of 3 saline required Deficit/500
• To rise sodium 1 meq/L, we need 70cc hypertonic
  saline
• Rate of correction
• Acute (lt48 h) or symptomatic 1-2 meq/L/hr
• Chronic (gt48 h) or asymptomatic 0.5 meq/L/hr
• Do not exceed 12 meq/L rise on the first day

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Cerebral Demyelination Syndrome

• Central and extrapontine Myelinosis (CPM)
• Caused by excessive rate or amount of correction
  of serum Na
• Presents with Dysphagia, Quadriparesis, Locked-in
  Sundrome
• Can be permanent or fatal

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Rx of Hyponatremia

• Hypovolemia Isotonic Saline
• Polydipsia Water Restriction
• SIADH Water Restriction
• Furosemide
• Demeclocycline ( toxicity)
• V1 V2 R antagonist (Conivaptan)

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Rx of Hyponatremia

• When choosing a solution to correct hyponatremia,
  aim for negative free water balance, i.e. the
  calculated osmolality of the urine 2X (UNaUK)
  should be lower than the chosen solutions
  Osmolality.
• IVF osmolality (2 X Na concentration in IVF)
• 3 saline 2 x 513 1026 mOsm/L
• NS 2 x 154 308 mOsm/L
• ½ NS 2 x 75 150
• ¼ NS 2 x 37.5 75

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NS for Rx of Hyponatremia
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Vasopressin Receptor Antagonists
SALT I and SALT II Trials.
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Vasopressin Receptor Antagonists

• Conivaptan is the only FDA approved one for
• Hyponatremia due to SIADH and CHF
• V1aR antagonist can cause
• Splanchnic vasodilation and variceal bleeding in
  cirrhosis.
• Hypotension and decrease in PCWP
• V1aR blockade can potentially add to the effect
  of beta-adrenergic, RAS, and aldosterone blockade
  in CHF.
• PureV2R antagonists can theoretically be
  deleterious in CHF, as the V1aR remains unblocked
  in face of high ADH level.

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Hyperkalemia

• Worrisome if serum K gt 5.8 meq/L in
  non-dialysis, non-cardiac patients
• Worrisome if serum K gt 6 meq/L in dialysis
  patients.
• Pseudohyperkalemia
• Hemolysed Blood Sample
• Leukocytosis/Thrombocytosis
• Check out ECG, and plasma potassium (in
  heparinized tube)

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Hyperkalemia
intake
Cell shift Metabolic acidosis Hyperglycemia B-bloc
kers Cell Lysis Digitalis Hyperkalemic periodic
paralysis
Decreased urinary K excretion 24 hr urine K lt 40
mEq
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Tubular flow
COX2
Renin Angiotensin
AA PGE2
Aldosterone
MCR
Na
Na
Cortisol Cortisone
K
ß-HSD
K
K
H
CCD/CNT
Tubular lumen
Blood
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Tubular flow
Type IV RTA
ACEi/ARB
NSAIDS COX2I
COX2
Renin Angiotensin
GFR ECV
AA PGE2
Addisons Heparin
Aldosterone
MCR
Na
ENaC Block Amiloride Trimetoprim pentamidine
Na
Spironolactone
K
K
K
H
CCD/CNT
Tubular lumen
Blood
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TTKG (Trans Tubular K Gradient)

• TTKG Urine K Plasma Osm
• Plasma K Urine Osm
• Valid if Uosm gt P Osm
• Normal renal response to Hyperkalemia TTKG gt 6
• Normal renal response to Hypokalemia TTKG lt 3

X
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Decreased urinary K Excretion
TTKG
gt6
lt6
Decreased CCD K secretion
Decreased tubular flow
Renal failure ( GFR)
ECV
Adrenal Insufficiency Addisons 1 hypoaldo
Hyporenin Hypoaldo (Type IV RTA) DM SLE Obstructi
on Myeloma/Amyloid HIV NSAIDs
Meds NSAIDs ACEi/ARB Heparin Spironolactone Cyclos
porine Amiloride Triamterene Trimethoprim Pentami
dine
RAAS Blockade
Na channel Blockade
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Signs and Symptoms of Hyperkalemia

• Muscle weakness (rare)
• ECG changes
• Peaked T waves
• Shortened ST interval
• Widened QRS
• Loss of P wave
• Sine wave idioventricular rythm
• Cardiac arrythmia

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Treatment of Hyperkalemia

• Stabilize membrane excitability (if ECG changes)
• Calcium chloride or Gluconate, 1 g IV
• Increase K entry into cells (rapid but
  transient)
• Glucose 25 g and Insulin 10 U
• ß2-adrenergic agonist (Albuterol)
• NaHCO3 in non-dialysis patients
• Removal of excess K (slow but definitive)
• Cation exchange resin (Kayexalate)
• diuretics
• Dialysis
• Dietry K restriction (chronically helpful)

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Hypokalemia
Cell shift Metabolic Alkalosis Insulin
excess ß-agonist Hypokalemic periodic paralysis
GI loss Vomiting Diarrhea
Urinary K wasting 24 h urine K gt 25 mEq
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Tubular flow
Reninoma RAS
Na delivery Bartter Gitelman Loop
diuretics Thiazides
Renin Angiotensin

Osmotic diuresis
1 Hyperaldo GRA
Aldosterone
MCR
Na
Liddle Synd
Na
Cushing
Nonabsorbable anion
Cortisol
K
K
ß-HSD
K
Cortisone
Amphotericin
Licorice AME
Classic distal RTA
H
CCD/CNT
Tubular lumen
Blood
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Hypokalemia
TTKG
lt3
gt3
Tubular flow Osmotic diuresis
CCD K Secretion/Excretion
Normal or low BP
High BP
Distal Na delivery Thiazide Loop diuretics
bartter Synd Gitelman synd Drugs
Non-reabsorbable anions HCO3- Hippurate
(Glue sniffing) Penicillin Cisplatin
Aminoglycosides Amphotericin RTA
Proximal or Classic distal
Aldosterone
high
low
Renin
Cushing Liddle Synd Licorice ingestion AME
high
low
Renal Artery Stenosis Malignant HTN Reninoma
Primary Hyperaldo GRA
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Sings and Symptoms of Hypokalemia

• Muscle weakness
• Polyuria/Polydipsia (acquired nephrogenic DI)
• Rhabdomyolysis
• ECG changes
• Depressed ST segment
• Flat T wave
• Prolonged QT interval
• U waves
• Cardiac arrythmia

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Treatment of Hypokalemia

• Oral KCl supplements
• IV KCl (no more than 10 mEq/hr through peripheral
  line, 40 mEq/hr through central line)
• Amiloride or spironolactone may be useful in
  patients with hyperaldosteronism

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The End

• Thank you