9 Disorders of Water Homeostasis: Hyponatremia Flashcards Preview

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Flashcards in 9 Disorders of Water Homeostasis: Hyponatremia Deck (31):
1

Hyponatremia

  • Definition
  • Classification
    • Hypertonic hyponatremia
    • Isotonic hyponatremia
    • Hypotonic hyponatremia

  • Definition
    • PNa < 135 mEq/L
    • Most common electrolyte disorder
  • Classification
    • Hypertonic hyponatremia
      • Aka hyperglycemia
      • Plasma tonicity > 285 mOsm/kg
    • Isotonic hyponatremia
      • Aka pseudohyponatremia
      • Plasma tonicity 270 - 285 mOsm/kg
    • Hypotonic hyponatremia
      • Aka true hyponatremia
      • Plasma tonicity < 270 mOsm/kg

2

Hypertonic hyponatremia

  • Elevated serum conc of glucose or mannitol --> increase plasma tonicity
  • Hypertonicity drives water from intracellular --> extracellular compartment
    • Dilutes PNa
  • Situations of hyperglycemia
    • Katz conversion corrects PNa for the level of hyperglycemia
    • Add 1.6 mEq/L to PNa for every 100 mg/dl of Pglucose > 100 mg/dl

3

Isotonic hyponatremia

  • Pseudohyponatremia
  • Serum
  • Ion-selective electrode (ISE)
    • Direct ISE
    • Indirect ISE
  • When serum contains high proteins (multiple myeloma) or lipids (hypertriglyceridemia)
  • ISE in pathological circumstances

  • Pseudohyponatremia
    • Lab artifact
  • Serum
    • Composed of aqueous fractions (93%) & nonaqueous fractions (7%)
    • Aqueous fraction: where Na is located
    • Nonaqueous fraction: proteins + lipids
  • Ion-selective electrode (ISE)
    • Direct ISE: measures Na in plasma water
      • Normal Na in plasma water: 150 mEq/L
      • Normal PNa in total serum = 139.5 mEq/L
      • Ex. arterial blood gas machine
    • Indirect ISE: measures Na in total serum
      • Requires a fixed volume of diluent to be added to the serum sample before measuring
      • More commonly used
  • When serum contains high proteins (multiple myeloma) or lipids (hypertriglyceridemia)
    • Nonaqueous fraction volume increases & displaces water fraction
    • Total serum contains less water & Na per unit volume
  • ISE in pathological circumstances
    • Indirect ISE: any dilution by a fixed volume of diluent --> dilution error --> falsely low PNa
    • Direct ISE: this doesn't occur

4

Hypotonic hyponatremia

  • True hyponatremia
  • Term hyponatremia
  • Increased water intake
  • Decreased water excretion

  • True hyponatremia
    • Water input > water output --> dilute Na conc
  • Term hyponatremia
    • Misleading b/c altered PNa are primarily disorders of water homeostasis, not Na
    • Na conc ≠ Na content
  • Increased water intake
    • Kidney's capacity to excrete water is exceeded --> hyponatremia
    • Need to ingest > 18 L/day to maximally dilute urine & --> hyponatremia
      • Urine volume (L/day)
      • = (normal mOsm solute / day) / (lowest UOsm kidneys can generate)
      • = (900 mOsm/day) / (50 mOsm/L)
      • = 18 L/day
  • Decreased water excretion
    • Increased ADH activity
    • Decreased GFR
    • Decreased solute intake

5

Hypotonic hyponatremia: decreased water excretion due to increased ADH activity

  • General
  • Funciton
  • Main physiological stimuli for ADH release
  • TBW compartments
  • EABV
  • EABV vs. ECF volume
    • Normally
    • Certain diseases

  • General
    • Most common mech of hypotonic hyponatremia
  • Function
    • ADH increases AQP2 expression in the CD --> increases water reabsorption
    • ADH stimulation by baroreceptors can overcome inhibitory effects of hyponatremia (hypotonicity) on ADH secretion
  • Main physiological stimuli for ADH release
    • Plasma hypertonicity
      • Not applicable in hypotonic hyponatremia
      • Hypertonicity --> sensed by osmoreceptors --> trigger thirst & ADH release
      • Hypertonicity --> inhibits thirst & ADH release
    • Decreased effective arterial blood volume (EABV)
      • Common cause of hyponatremia
    • SIADH: ADH secreted autonomously when not needed
  • TBW compartments
    • ICF
    • ECF: water outside cells
      • ITF
      • IVF (plasma in veins & arteries)
  • EABV
    • Arterial blood volume that effectively perfuses organs
      • Inffered from other measruements (plasma renin, plasma aldo, urine Na, etc.)
    • Stretch-sensitive receptors in carotid sinus & aortic arch (baroreceptors) sense changes in EABV (not ECF volume)
      • Increase EABV --> Aff neural impulses inhibit ADH secretion from posterior pituitary
      • Decrease EABV --> decrease discharge rate of stretch receptors --> ADH secretion
  • EABV vs. ECF volume
    • Normally
      • Changes in EABV vary w/ changes in ECF volume
      • Ex. hypovolemia: both decreased
    • Certain diseases
      • ECF increases while EABV decreases
        • --> decreased organ perfusion ---> increased ADH release
      • Diseases
        • Pump failure (ex. CHF)
        • Decreased peripheral resistance (ex. liver cirrhosis)

6

Hypotonic hyponatremia: decreased water excretion due to decreased GFR

  • Decrease GFR --> decrease water excretion
  • Pts w/ low GFR & limited renal water excretory capacity --> hyponatremic by ingesting the same amt of water that ppl w/ nromal GFR ingest

7

Hypotonic hyponatremia: decreased water excretion due to decreased solute intake

  • Normal solute intake
  • Main solutes in diet
  • Steady state
  • Urine volume vs. urine solute load
  • Effects of a low solute diet

  • Normal solute intake
    • 600-900 mOsm/day
  • Main solutes in diet
    • Urea from metabolism of proteins
    • Electrolytes (ex. salt)
  • Steady state
    • Solute intake = urine solute load = 600-900 mOsm/day
  • Urine volume vs. urine solute load
    • Urine volume & water excretion are dependent on urine solute load
      • Higher urine solute load --> higher urine volume
      • Lower urine solute load --> lower urine volume
    • Urine volume (L/day) = [urine solute load (mOsm/day)} / [UOsm (mOsm/L)]
  • Effects of a low solute diet
    • Reduce max capacity to excrete water
    • Drink a normal amt of water --> only able to excrete a little --> extra wtaer is retained --> diluted PNa --> hyponatremia

8

Etiology of hypotonic hyponatremia

  • Increased water intake
  • Decreased water excretion
    • Increased ADH activity
    • Decreased GFR
    • Decreased solute intake

  • Increased water intake
    • Psychogenic polydipsia
    • Marathon runners
    • Ecstasy
    • Water drinking contests
  • Decreased water excretion
    • Increased ADH activity
      • Decreased EABV w/ decreased ECF volume
      • Decreased EABV w/ increased ECF volume
      • Syndrome of Inappropriate ADH Secretion (SIADH)
    • Decreased GFR
      • AKI
      • CKD including pts w/ end-stage renal disease on chronic dialysis
    • Decreased solute intake
      • Beer potomania

9

Etiology of hypotonic hyponatremia:
Increased ADH activity

  • Decreased EABV w/ decreased ECF volume
  • Decreased EABV with increased ECF volume

  • Decreased EABV w/ decreased ECF volume
    • Hemorrhage
    • Vomiting
    • Secretory Diarrhea
    • Thiazide diuretics
    • Mineralocorticoid deficiency (e.g. primary adrenal insufficiency)
      • Causes of selective cortisol deficiency
        • Secondary adrenal insufficiency (pituitary)
        • Tertiary adrenal insufficiency (hypothalamus)
      • Primary adrenal insufficiency (adrenal gland) causes both aldo & cortisol deficiency
  • Decreased EABV with increased ECF volume
    • CHF
    • Liver cirrhosis
    • Nephrotic syndrome
      • Some pts with nephrotic syndrome actually have an increased EABV

10

Etiology of hypotonic hyponatremia: increased ADH activity:
Syndrome of Inappropriate ADH Secretion (SIADH)

  • General
  • Etiologies
  • Diagnostic criteria

  • General
    • ADH is secreted autonomously w/o physiological stimuli
  • Etiologies
    • Pulmonary causes
      • Infectious (pneumonia), tumors (lung cancer), etc.
    • CNS causes
      • Infectious (meningitis, encephalitis), tumors (craniopharyngioma), etc.
    • Drugs
      • Antidepressants (SSRIs), carbamazepine, cyclophophamide, etc.
    • Other causes
      • Nausea, pain
  • Diagnostic criteria
    • Hypotonic hyponatremia
    • Clinical euvolemia
    • UOsm > 100 mOsm/L
    • UNa > 30 mEq/L in the presence of normal salt and water intake
    • Serum uric acid < 4 mg/dL
    • Normal renal, thyroid, and adrenal function
    • Absence of diuretic use (particularly thiazides)

11

Etiology of hypotonic hyponatremia: decreased solute intake:
Beer potomania

  • Normal solute intake
  • Steady state
  • Beer potomania
  • Other diet that causes decreased solute intake

  • Normal solute intake
    • 600-900 mOsm/day
  • Steady state
    • Solute intake = urine solute load
    • Urine water excretion depends on solute intake
  • Beer potomania
    • Pts w/ alcohol dependence drink large amts of beer & don't eat enough solutes
    • Poor solute intake --> limited amt of excretable water
    • Drink large amts of beer (90% water) --> ovewhelm limited kidney capacity for water excretion --> retain extra ingested water --> hyponatremia
  • Other diet that causes decreased solute intake
    • Tea & toast diet

12

Brain adaptation to hypotonic hyponatremia

  • Normal brain tonicity
  • Effect of decreased plasma tonicity on water in brain
  • Main way brain adapts to swelling
  • Regulatory volume decrease (RVD)
  • Acute hyponatremia (acute hypotonicity)
  • Chronic hyponatremia (chronic hypotonicity)
  • The more rapid the fall in PNa...

  • Normal brain tonicity
    • Brain cell tonicity & ECF tonicity are in equilibirum
    • No net water shift in or out of brain cells
  • Effect of decreased plasma tonicity on water in brain
    • Water moves into the brain along osmotic gradients --> brain edema
    • Astrocytes swell after hypotonic stress, neurons don't
  • Main way brain adapts to swelling
    • Lose solutes to decrease ICF osmolality & stop water movement into astrocytes
  • Regulatory volume decrease (RVD)
    • Astrocyte adaptation
    • Lose solutes --> decrease IC tonicity --> reestablish normal cellular volume
    • (1) astrocytes lose electrolytes (K, Cl)
      • 70% of solute loss
      • Peaks 3 hr after swelling, compete after 6-7 hr
    • (2) astrocytes lose organic osmolytes for osmoregulation
      • Mian osmolytes lost: glycerophosphorylcholine, phoscreatine, creatine, glutamate, glutamine, taurine, and myo-inositol
      • Occurs by 48 hr
  • Acute hyponatremia (acute hypotonicity)
    • Hyponatremia develops in
    • Little time for full adaptation to occur since it occurs rapidly
  • Chronic hyponatremia (chronic hypotonicity)
    • Hyponatremia develops gradually over >48 hr
    • Brain has more time to fully adapt
  • The more rapid the fall in PNa...
    • The more water will be accumulated before the brain is able to fully adapt & lose solute

13

Clinical manifestations (symptoms) of hyponatremia

  • Severe symptoms
  • Moderate symptoms
  • Mild symtpoms
  • "Asymptomatic"

  • Severe symptoms: hyponatremic encephalopathy
    • Seizures
    • Stupor
    • Coma
    • Significant cerebral edema
    • Death from brain herniation
  • Moderate symptoms: less cerebral edema
    • Lethargy
    • Disorientation
    • Confusion
    • Less cerebral edema
  • Mild symtpoms
    • Fatigue
    • Nausea
    • Headaches
    • Minimal cerebral edema
  • "Asymptomatic": no apparent symptoms (symptoms are very subtle)
    • Attention deficits
    • Gait disturbances
    • Falls
    • Fractures
    • Osteoporosis

14

Acute vs. chronic symptoms of hyponatremia

  • Acute hyponatremia (<48 hr)
  • Chronic hyponatremia (>48 hr)
    • Usual symptoms
    • Once the brain has enough time to volume-adapt via solute losses...
    • Glutamate
    • Osteoporosis

  • Acute hyponatremia (<48 hr)
    • Moderate or severe symptoms
  • Chronic hyponatremia (>48 hr)
    • Usual symptoms
      • Minimal or asymptomatic
      • Could cause moderate or severe when PNa is very low (<120 mEq/L)
      • Increased mortality
    • Once the brain has enough time to volume-adapt via solute losses...
      • Expanded brain volume decreases back toward normal
      • Reduces brain edema & symptoms
    • Glutamate
      • Neurotransmitter involved in cerebellar function
      • One of the most important osmolytes that brain cells lose to compensate for hypotonicity
      • Pts w/ chronic hyponatremia have brain glutamate deficiency
      • Deficiency --> ataxia & gait disturbances
    • Osteoporosis
      • 1/3 of our total body Na is in our bones
      • Increased bone resportio to mobilize stored Na into circulation --> osteoporosis, bone fractures, falls, & gait disturbances

15

Clinical features of different categories of hyponatremia according to their pathophysiological mechanism

  • Increased water intake
  • Decreased water excretion
    • Increased ADH activity
      • Decreased EABV w/ decreased ECF volume (low total body Na)
      • Decreased EABV w/ increased ECF volume (high total body Na)
      • SIADH
    • Decreased GFR
    • Decreased solute intake

  • Increased water intake
    • Euvolemic: total body Na remains normal
    • Excessive water intake --> decrease plasma tonicity --> inhibit ADH release --> diluted urine (UOsm < 100 mOsm/L)
  • Decreased water excretion
    • Increased ADH activity
      • ADH release despite low plasma tonicity --> concentrated urine (UOsm > 100 mosm/L) --> varied ECF volume status
      • Decreased EABV w/ decreased ECF volume (low total body Na)
        • Hypovolemia: HoTN, tachycardia, orthostatic HoTN, orthostatic tachycardia, flat jugular veins, clear lungs, no peripheral edema
      • Decreased EABV w/ increased ECF volume (high total body Na)
        • Hypervolemia: HTN, distended jugular veins, crackles, peripheral edema
      • SIADH
        • Euvolemia despite dilutional hyponatremia from excess water retention
        • Mild volume expansion --> increase weight
        • ADH --> initial water retention --> subsequent natriuresis --> regulate ECF volume toward normal
    • Decreased GFR
      • Expanded ECF volume w/ low UOsm
      • Low GFR --> inability to excrete Na --> hypervolemic
    • Decreased solute intake
      • Euvolemic since total body Na remains normal
      • Excessive water intake + limited ability to excrete water --> decrease plasma tonicity --> inhibit ADH release --> increase TBW
      • Decreased solute load --> low UOsm

16

Diagnostic approach to hyponatremia

  • Hypertonic
  • Isotonic
  • Hypotonic
    • Appropriately low UOsm
    • Inappropriately high UOsm
      • Low ECV
        • Low ECF
        • High ECF
      • Normal ECV & ECF

  • Hypertonic: plasma tonicity > 285 mOsm/kg
    • Hyperglycemia
  • Isotonic: plasma tonicity = 270-285 mOsm/kg
    • Pseudohyponatremia
  • Hypotonic: plasma tonicity < 270 mOsm/kg
    • Appropriately low UOsm (<100 mOsm/kg)
      • Psychogenic polydipsia
      • Beer potomania
    • Inappropriately high UOsm (>100 mOsm/kg)
      • Low ECV
        • Low ECF
          • True hypovolemia
        • High ECF
          • Heart failure
          • Liver cirrhosis
      • Normal ECV & ECF
        • SIADH

17

Treatment for hyponatremia

  • Severely symptomatic hyponatremia
    • Symptoms
    • Causes
    • Cerebral edema
    • Monitor setting
    • Treatment
    • Frequency of PNa checks
  • Moderately symptomatic hyponatremia
    • Symptoms
    • Cerebral edema
    • Monitor setting
    • Treatment
    • Frequency of PNa checks
  • Mildy symptomatic or "asymptomatic" hyponatremia
    • Symptoms
    • Cerebral edema
    • Monitor setting
    • Treatment
    • Frequency of PNa checks

  • Severely symptomatic hyponatremia
    • Symptoms: seizures, stupor, coma
    • Causes: acute or chronic hyponatremia w/ Na < 120 mEq/L
    • Cerebral edema: +++
    • Monitor setting: ICU (medical emergency)
    • Treatment: NaCl 3% 100 mL IV bolus immediately
    • Frequency of PNa checks: every 1-2 hr
  • Moderately symptomatic hyponatremia
    • Symptoms: confusion, disorientation, lethargy
    • Cerebral edema: ++
    • Monitor setting: ICU (medical emergency)
    • Treatment: Na3% IV slow infusion
    • Frequency of PNa checks: every 1-2 hr
  • Mildy symptomatic or "asymptomatic" hyponatremia
    • Symptoms: fatigue, nausea, headache / none detectable
    • Cerebral edema: +/-
    • Monitor setting: regular floor (not a medical emergency)
    • Treatment: target underlying pathophysiology
    • Frequency of PNa checks: every 8-12 hr

18

Pathophysiological targets of therapy in hyponatremia

  • Target underlying cause of increased ADH activity
    • Decreased EABV due to true hypovolemia
    • Decreased EABV due to heart failure or liver cirrhosis
    • SIADH
      • Reversible causes
      • Irreversible causes
  • Block ADH action
  • Decrease water intake
  • Decreased medullary gradient
  • Obligate renal water excretion by increasing solute intake

  • Target underlying cause of increased ADH activity
    • Decreased EABV due to true hypovolemia
      • Volume expansion (ex. NaCl 0.9%)
    • Decreased EABV due to heart failure or liver cirrhosis
      • Block ADH action in kidneys
      • Usually irreversible & impossible to stop ADH release
    • SIADH
      • Reversible causes: stop SSRI, treat penumonia or meningitis, treat pain
      • Irreversible causes (ex. advanced lung cancer): block ADH action in kidneys
  • Block ADH action
    • V2 receptor antagonists ("Vaptans"): treat hypervolemic (CHF, cirrhosis) or euvolemic (SIADH) hyponatremia
      • Must be initiated in an inpatient setting w/ frequent PNa monitoring
    • Avoid fluid restriction in first 24 hr
    • Expensive
  • Decrease water intake
    • Fluid restriction so water input < water output (negative water balance)
    • Amt of fluid restriction require dto create a state of negative water balance (from ingested water & food)
      • Should be less than the sum of urine & insensible losses
    • Worst case scenario (ex. SIADH): restrict fluid to <800 mL/day
  • Decreased medullary gradient
    • Water is reabsorbed in the IMCD
      • Mian driver: hypertonic medulla (1200 mOsm/kg at the renal papilla)
      • Hypertonicity: 50% Na, 50% urea
    • NaCl transport
      • Na/K/2Cl in the apical TkAL transports Na to the medulla
    • Loop diuretics
      • Reduce medullar gradient --> increase free wtaer excretion
      • Produce hypotonic urine
    • In euvolemic pts: administer w/ 0.9% NaCl to avoid hypovolemia & create an extra stimulus for ADH release
  • Obligate renal water excretion by increasing solute intake
    • Na tablets
    • Increaes dietary solute (i.e. salt & protein)

19

Treatment of hyponatremia: summary

  • Primary polydipsia
  • Hypovolemia
  • Heart failure or liver cirrhosis
  • SIADH
  • Renal insufficiency
  • Beer potomania

  • Primary polydipsia
    • Fluid restriction
  • Hypovolemia
    • Volume expansion
  • Heart failure or liver cirrhosis
    • Fluid restriction
    • Loop diuretics
    • V2 receptor antagonists (not in liver cirrhosis)
  • SIADH
    • Treat underlying cause if possible
    • Fluid restriction
    • Loop diuretics
    • Salt tablets
    • Increase dietary solute intake
    • V2 receptor antagonists
  • Renal insufficiency
    • Fluid restriction
  • Beer potomania
    • Increase dietary solute intake

20

Correction of hyponatremia

  • Goals
    • Severely symptomatic hyponatremia
    • Moderately symptomatic, midly symptomatic, and “asymptomatic” hyponatremia
  • Max limits of correction

  • Goals
    • Severely symptomatic hyponatremia
      • Raise serum sodium concentration by 6 mEq/L in first 6 hours and postpone any further correction for next day
      • Increasing serum sodium by 6 mEq/L is usually enough to stop symptoms
    • Moderately symptomatic, midly symptomatic, and “asymptomatic” hyponatremia
      • Raise serum sodium concentration by 6 mEq/L in any 24h period
  • Max limits of correction
    • 10 – 12 mEq/L in first 24h
    • 18 mEq/L in first 48h
    • These are limits one should not cross to avoid risk of osmotic demyelination syndrome

21

Osmotic demyelination syndrome (ODS)

  • Aka
  • Pathogenesis
  • Other risk factors
  • Clinical Manifestations
  • Diagnosis
  • Treatment
  • Prevention
  • Prognosis

  • Aka
    • Central pontine myelinolysis (CPM)
  • Pathogenesis
    • Rapid correction of chronic hyponatremia
    • --> acute brain shrinking --> astrocyte death --> loss of cell/cell interactions b/n astrocytes & oligodendrocytes
    • Dying astrocytes --> demyelination via cytokines, inflammatory mediators, T cells, microglia, & macrophages
  • Other risk factors
    • [Na+] < 105 mEq/L
    • Alcoholism
    • Malnutrition
    • Advanced liver disease
    • Liver transplantation
    • Hypokalemia
  • Clinical Manifestations
    • Onset of symptoms typically is delayed several days (up to 1 week) after overcorrection of hyponatremia
    • Altered mental status, quadriparesis, dysphagia and dysarthria
  • Diagnosis
    • Based on the clinical presentation of new-onset neurological symptoms in a patient with a recent overcorrection of hyponatremia
    • MRI may be useful to detect demylinating lesions but may not be (+) for up to 4 weeks after symptom onset
  • Treatment
    • No effective treatment
    • Could be a benefit from relowering serum sodium concentration, corticosteroids, or plasmapheresis
  • Prevention
    • Avoid overcorrection of hyponatremia
    • Recognize early overcorrection and act promptly by relowering serum sodium concentration so serum sodium concentration does not cross maximal limits of correction
  • Prognosis
    • 40% of patients experience full recovery
    • 25% of patients develop persistent neurological deficits
    • 6% succumb to the disease

22

Hypernatremia

  • Definition
  • Pathophysiology
    • Most cases
    • Minority of cases

  • Definition
    • Serum sodium concentration of greater than 145 mEq/L
    • Always implies plasma hypertonicity
    • Much less common than hyponatremia
  • Pathophysiology
    • Most cases
      • Water input < water output
        • --> negative water balance --> increase Na conc
      • Due to...
        • Decreased water intake
        • Increased water excretion + decreased water intake
    • Minority of cases
      • Na excess
      • Ex. salt tablets or hypertonic sol'ns (ex. Na bicarbonate)
      • Pts are usually also hypervolemic due to increased total body Na

23

Pathophysiology of hypernatremia

  • Decreased water intake
  • Increased water excretion + decreased water intake
    • Increased water excretion by itself
    • Increased water excretion due to extrarenal water loss
    • Increased water excretion due to renal water loss (i.e. polyuria)
  • Dehydration vs. hypovolemia
    • Definition
    • POsm & Na
    • Treatment

  • Decreased water intake
    • Water is unavailable
    • Unconsciousness
      • Water is available but patient is not awake to drink water
    • Altered thirst mechanism
      • Water is available, pt is awake, but he or she just doesn’t feel thirsty because of problems with his/her neural thirst pathways
  • Increased water excretion + decreased water intake
    • ​Increased water excretion by itself usually doesn't result in significant hypernatremia
      • For increased water excretion to cause hypernatremia, it must be accompanied by decreased water intake
      • Hypernatremia caused solely by increased water excretion will also increase plasma tonicity
        • --> stimulate thirst and water intake --> minimize any increase in serum sodium concentration
      • Thirst: defense mechanism against hypernatremia
        • Unless water intake is compromised (e.g. decrease thirst response), hypernatremia won't develop
    • Increased water excretion due to extrarenal water loss
      • GI tract (ex. diarrhea, fistula, ostomy)
      • Skin (ex. sweating)
    • Increased water excretion due to renal water loss (i.e. polyuria)
      • Decreased ADH activity --> decreased water reabsorption --> water diuresis
      • Increased urine solute load (opp of beer potomania)
        • Need to excrete large amts of solutes in urine w/ large amts of water excretion
        • Increased urine solute --> solute diuresis (osmotic diuresis)
  • Dehydration vs. hypovolemia
    • Dehydration
      • Loss of pure water or hypotonic fluid
      • POsm & Na: increased
      • Treatment: D5W
    • Hypovolemia
      • Loss of isotonic fluid
      • POsm & Na: unchanged
      • Treatment: 0.9% NS

24

Hypernatremia etiology

  • Decreased water intake
  • Increased water excretion + decreased water intake
    • Extra-renal water loss
    • Renal water loss
      • Solute diuresis
      • Water diuresis
        • Central
          • Idiopathic
          • Genetic
          • Acquired
        • Nephrogenic
          • Genetic
          • Acquired

  • Decreased water intake
    • ​Water is unavailable
      • E.g. lost in desert w/ no water
    • Unconsciousness or altered mental status
      • E.g. pt intubated & sedated in ICU
    • Altered thirst mechanism
      • Adipsia (complete lack of thirst) or hypodipsia (decreased thirst sensation)
      • Caused by CNS disorders that comprise thirst neurla pathways (e.g. brain tumor)
  • Increased water excretion + decreased water intake
    • ​Extra-renal water loss
      • Increased GI losses
        • Vomiting
        • Nasogastric drainage
        • Non-secretory Diarrhea (e.g. inflammatory diarrhea, osmotic diarrhea, malabsorption)
        • Ileostomy
        • Pancreatobiliary fistula
      • Increased skin losses
        • Excessive sweating
    • Renal water loss
      • ​Solute diuresis
        • ​Glucose (ex. hyperglycemia)
        • Urea (ex. post-ATN diuresis, post-obstructive diuresis, high protein intake)
        • Electrolytes: electrolyte-containing IV fluids (ex. 0.9% NaCl)
      • Water diuresis: diabetes insipidus (DI) --> decreased ADH --> low UOsm
        • Central
          • ​Idiopathic
            • Most common
          • Genetic
            • ​Familial Central DI: mutation in ADH gene causing misfolding of ADH protein --> ADH protein is not functional
            • Wolfran syndrome
            • Congenital hypopituitarism
          • Acquired
            • Neurosurgery
            • Head trauma
            • Brain tumors
            • Infiltrative disorders: e.g. Langerhans cell histiocytosis, sarcoidosis
        • Nephrogenic
          • ​Genetic
            • ​Inactivating mutation of V2 receptor gene (most common)
            • Inactivating mutation of Aquaporin 2 gene
          • Acquired
            • ​Renal disease: post-ATN, bilateral urinary tract obstruction, sickle cell disease, autosomal dominant polycystic kidney disease
            • Electrolyte abnormalities: hypercalcemia, hypokalemia
            • Drugs: lithium, amphotericin, demeclocycline, V2 receptor antagonists, ifosfamid

25

Brain adaptation to hypernatremia (hypertonicity)

  • Increase plasma tonicity -->
  • Main way the brain fully adapts
  • Regulatory volume increase (RVI)
  • Acute hypernatremia (acute hypertonicity)
  • Chronic hypernatremia (chronic hypertonicity)

  • Increase plasma tonicity -->
    • Water moves out of the brain along osmotic gradients --> brain shrinks
  • Main way the brain fully adapts to shrinking
    • Gains solutes to increase ICF osmolality and stop water movement out of astrocytes
  • Regulatory volume increase (RVI)
    • Astrocyte adaptation
    • Gain solutes to increase intracellular osmolality and reestablish normal cellular volume
    • (1) astrocytes gain sodium and chloride
    • (2) accumulation of organic osmolytes similar to hyponatremia
  • Acute hypernatremia (acute hypertonicity)
    • Hypernatremia that develops in
    • Little time for full adaptation to occur since hypernatremia occurs rapidly
    • Rare
  • Chronic hypernatremia (chronic hypertonicity)
    • Hypernatremia that develops gradually (>48h)
    • Most common type of hypernatremia
    • When hypertonicity occurs gradually the brain has more time to fully adapt to it

26

Symptoms of hypernatremia

  • Mild symptoms
  • Moderate symptoms
  • Severe symptoms
  • Acute hypernatremia can cause...
  • Chronic hypernatremia usually cause...

  • Mild symptoms
    • Irritability
    • Restlessness
  • Moderate symptoms
    • Stupor
    • Muscular twitching
    • Hyperreflexia
    • Spasticity
  • Severe symptoms
    • Seizures
    • Coma
    • Death
  • Acute hypernatremia can cause...
    • Moderate to severe symptoms as a result of rapid brain shrinking
  • Chronic hypernatremia usually cause...
    • Mild or no symptoms

27

Clinical features of different categories of hypernatremia according to their pathophysiological mechanism

  • Decrease in water intake
  • Increase in water excretion and decrease in water intake
    • Extra-renal water loss
    • Renal water loss
      • Decreased ADH activity (water diuresis)
      • Increased urine solute load (solute or osmotic diuresis)

  • Decrease in water intake
    • Clinically euvolemic since total body sodium remains normal
    • Since plasma osmolality is elevated, ADH release is increased and UOsm is appropriately high (> 600 mOsm/L)
  • Increase in water excretion and decrease in water intake
    • Extra-renal water loss
      • Euvolemic if losing pure water
      • Hypovolemic if losing water associated with significant amounts of sodium
      • Most patients will lose water and sodium
      • Since plasma osmolality is elevated, ADH release is increased and UOsm is appropriately high (> 600 mOsm/L)
    • Renal water loss
      • Decreased ADH activity (water diuresis)
        • Euvolemic since they lose pure water without sodium
        • Even though plasma osmolality is elevated, ADH activity is decreased --> UOsm is low (< 300 mOsm/L)
        • Urine solute load
          • Product of multiplying UOsm x daily urine volume
          • Within normal limits (600 – 900 mOsm/day)
      • Increased urine solute load (solute or osmotic diuresis)
        • Euvolemic if losing pure water
        • Hypovolemic if losing water associated with significant amounts of sodium
        • Plasma osmolality is elevated --> ADH activity is increased --> UOsm is moderately elevated (300 - 600 mOsm/L)
        • Urine solute load is high (> 1000 mOsm/day) due to the presence of the osmotic solute in urine

28

Diagnostic approach to hypernatremia

  • Hypervolemic
  • Not hypervolemic
    • No polyuria
      • Thirsty
      • Not thirsty
    • Polyuria
      • UOsm = 300-600 mOsm/L & urine solute load > 1000 mOsm/day
      • UOsm < 300 mOsm/L & urine solute load = 600-900 mOsm/day
        • Response to DDAVP
        • No response to DDAVP

  • Hypoervolemic
    • Salt tablets
    • Hypertonic IV fluids
  • Not hypervolemic
    • ​No polyuria
      • ​Thirsty
        • Increased skin loss
        • Increased GI loss
      • Not thirsty
        • Adipsia
        • Hypodipsia
    • Polyuria
      • ​​UOsm = 300-600 mOsm/L & urine solute load > 1000 mOsm/day
        • Osmotic diuresis
      • UOsm < 300 mOsm/L & urine solute load = 600-900 mOsm/day
        • Response to DDAVP
          • Central diabetes insipidus (DI)
        • No response to DDAVP
          • Nephrogenic diabetes insipidus (DI)

29

Treatment for hypernatremia

  • Acute hypernatremia
  • Chronic hypernatremia

  • Acute hypernatremia
    • Usually associated with moderate to severe neurological symptoms
      • Ex. seizures
      • When serum sodium concentration is greater than 158 mEq/L
    • Medical emergency
    • Treatment: D5W IV
      • Goal: normalizing serum sodium concentration by 24h
  • Chronic hypernatremia
    • Usually asymptomatic or associated with minimal symptoms
    • Correction of chronic hypernatremia involves targeting the underlying disorder
      • Ex. surgery for a brain tumor causing Central DI
    • Administration of water or hypotonic fluids corrects both the water deficit and replaces ongoing water losses
    • Goal: correct the serum sodium concentration by 10 mEq/L in 24h

30

Example

  • 58 year-old woman is brought to the ER after a head injury during an unrestrained motor vehicle crash
  • CT head showed epidural hematoma with associated skull fracture
  • Over the following 24h, patient develops polyuria with a urine output of 3.1 L/24h
  • On exam: BP=120/76 mmHg, HR=67 bpm, RR=18 resp/min. Weight=75 kg. No JVD. Lungs are clear to auscultation. No peripheral edema. Patient is alert and oriented. No focal neurological deficits.
  • Laboratory data: Na=167 mEq/L, K=3.6 mEq/L, Cl=112 mEq/L, BUN=10 mg/dL, Cr=0.8 mg/dL, Glucose=151 mg/dL. UOsm=116 mOsm/kg, UNa=30 mEq/L, UK=15 mEq/L.

 

  • Calculate free water deficit
  • Calculate the amount of time required to correct the free water deficit
  • Calculate the rate of correction of the free water deficit
  • Calculate obligatory water losses
  • Calculate the final rate of correction

  • Calculate free water deficit
    • TBW * [ (Na / 140) - 1] * 0.5 (for a woman)
    • 70 * [ (167 / 140) - 1] * 0.5
  • Calculate the amount of time required to correct the free water deficit
    • Amt to correct = 167 - 140 = 27 mEq/L
    • Goal: correct serum sodium concentration by no more than 10 mEq/L in 24h
    • Rule of three: 10 mEq/L / 24h = 27 mEq/L / X
  • Calculate the rate of correction of the free water deficit
    • Volume / time
    • 6750 mL / 64.8 h
  • Calculate obligatory water losses
    • Skin & stool: 40 mL/h
    • Respiratory insensible losses match metabolic water production and therefore are not taken into account
    • Urine: electrolyte-free water clearance (CeH20)
      • V * { 1 - [ (Una + Uk) / Pna ] }
      • 3.1 * {1 - [ (30 + 15) / 167 ] }
    • Since patient losses 2.26 L of water in the urine in 24h, we need to replace this in the same amount of time
      • Rate of correction = 2260 mL / 24 h
  • Calculate the final rate of correction
    • Free water deficit + skin & stool + urine
    • Since patients with hypernatremia usually cannot drink on their own, these can be administered either intravenously as D5W or enterally as pure water using a feeding tube

31

Other therapies & complications of rapid correction of hypernatremia

  • Other therapies
    • Main goal
      • Improve associated symptoms (i.e. polyuria)
    • Central DI
      • Desmopressin (dDAVP): intranasal or subcutaneous
    • Nephrogenic DI
      • Low solute diet
        • Low solute intake will limit the amount of water excretion in the urine
      • Thiazide diuretics
        • Thiazides induce hypovolemia
        • --> increase proximal tubular reabsorption of sodium and water
        • --> decrease in distal delivery of water to the ADH-sensitive sites in the collecting tubules
        • --> reduce the urine output improving polyuria
  • Complications of rapid correction
    • Water moving into astrocytes --> cerebral edema
    • Goal: correct no more than 10 mEq/L / 24 hr