9 Disorders of Water Homeostasis: Hyponatremia Flashcards

Question 1

Q

Hyponatremia

Definition
Classification
- Hypertonic hyponatremia
- Isotonic hyponatremia
- Hypotonic hyponatremia

Answer

A

Definition
- P_Na < 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

Question 2

Q

Hypertonic hyponatremia

Answer

A

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

Question 3

Q

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

Answer

A

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 P_Na 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 P_Na
- Direct ISE: this doesn’t occur

Question 4

Q

Hypotonic hyponatremia

True hyponatremia
Term hyponatremia
Increased water intake
Decreased water excretion

Answer

A

True hyponatremia
- Water input > water output –> dilute Na conc
Term hyponatremia
- Misleading b/c altered P_Na 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 U_Osm kidneys can generate)
  - = (900 mOsm/day) / (50 mOsm/L)
  - = 18 L/day
Decreased water excretion
- Increased ADH activity
- Decreased GFR
- Decreased solute intake

Question 5

Q

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

Answer

A

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)

Question 6

Q

Hypotonic hyponatremia: decreased water excretion due to decreased GFR

Answer

A

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

Question 7

Q

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

Answer

A

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)} / [U_Osm (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 P_Na –> hyponatremia

Question 8

Q

Etiology of hypotonic hyponatremia

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

Answer

A

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

Question 9

Q

Etiology of hypotonic hyponatremia:
Increased ADH activity

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

Answer

A

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

Question 10

Q

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

General
Etiologies
Diagnostic criteria

Answer

A

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
- U_Osm > 100 mOsm/L
- U_Na > 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)

Question 11

Q

Etiology of hypotonic hyponatremia: decreased solute intake:
Beer potomania

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

Answer

A

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

Question 12

Q

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 P_Na…

Answer

A

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 P_Na…
- The more water will be accumulated before the brain is able to fully adapt & lose solute

Question 13

Q

Clinical manifestations (symptoms) of hyponatremia

Severe symptoms
Moderate symptoms
Mild symtpoms
“Asymptomatic”

Answer

A

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

Question 14

Q

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

Answer

A

Acute hyponatremia (<48 hr)
- Moderate or severe symptoms
Chronic hyponatremia (_>_48 hr)
- Usual symptoms
  - Minimal or asymptomatic
  - Could cause moderate or severe when P_Na 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

Question 15

Q

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

Answer

A

Increased water intake
- Euvolemic: total body Na remains normal
- Excessive water intake –> decrease plasma tonicity –> inhibit ADH release –> diluted urine (U_Osm < 100 mOsm/L)
Decreased water excretion
- Increased ADH activity
  - ADH release despite low plasma tonicity –> concentrated urine (U_Osm > 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 U_Osm
  - 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 U_Osm

Question 16

Q

Diagnostic approach to hyponatremia

Hypertonic
Isotonic
Hypotonic
- Appropriately low U_Osm
- Inappropriately high U_Osm
  - Low ECV
    - Low ECF
    - High ECF
  - Normal ECV & ECF

Answer

A

Hypertonic: plasma tonicity > 285 mOsm/kg
- Hyperglycemia
Isotonic: plasma tonicity = 270-285 mOsm/kg
- Pseudohyponatremia
Hypotonic: plasma tonicity < 270 mOsm/kg
- Appropriately low U_Osm (<100 mOsm/kg)
  - Psychogenic polydipsia
  - Beer potomania
- Inappropriately high U_Osm (_>_100 mOsm/kg)
  - Low ECV
    - Low ECF
      - True hypovolemia
    - High ECF
      - Heart failure
      - Liver cirrhosis
  - Normal ECV & ECF
    - SIADH

Question 17

Q

Treatment for hyponatremia

Severely symptomatic hyponatremia
- Symptoms
- Causes
- Cerebral edema
- Monitor setting
- Treatment
- Frequency of P_Na checks
Moderately symptomatic hyponatremia
- Symptoms
- Cerebral edema
- Monitor setting
- Treatment
- Frequency of P_Na checks
Mildy symptomatic or “asymptomatic” hyponatremia
- Symptoms
- Cerebral edema
- Monitor setting
- Treatment
- Frequency of P_Na checks

Answer

A

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 P_Na 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 P_Na 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 P_Na checks: every 8-12 hr

Question 18

Q

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

Answer

A

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 P_Na 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)

Question 19

Q

Treatment of hyponatremia: summary

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

Answer

A

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

Question 20

Q

Correction of hyponatremia

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

Answer

A

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

Question 21

Q

Osmotic demyelination syndrome (ODS)

Aka
Pathogenesis
Other risk factors
Clinical Manifestations
Diagnosis
Treatment
Prevention
Prognosis

Answer

A

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

Question 22

Q

Hypernatremia

Definition
Pathophysiology
- Most cases
- Minority of cases

Answer

A

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

Question 23

Q

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
- P_Osm & Na
- Treatment

Answer

A

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
  - P_Osm & Na: increased
  - Treatment: D5W
- Hypovolemia
  - Loss of isotonic fluid
  - P_Osm & Na: unchanged
  - Treatment: 0.9% NS

Question 24

Q

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

Answer

A

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 U_Osm
    - 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

Question 25

Q

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)

Answer

A

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

Question 26

Q

Symptoms of hypernatremia

Mild symptoms
Moderate symptoms
Severe symptoms
Acute hypernatremia can cause…
Chronic hypernatremia usually cause…

Answer

A

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

Question 27

Q

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)

Answer

A

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

Question 28

Q

Diagnostic approach to hypernatremia

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

Answer

A

Hypoervolemic
- Salt tablets
- Hypertonic IV fluids
Not hypervolemic
- No polyuria
  - Thirsty
    - Increased skin loss
    - Increased GI loss
  - Not thirsty
    - Adipsia
    - Hypodipsia
- Polyuria
  - U_Osm = 300-600 mOsm/L & urine solute load > 1000 mOsm/day
    - Osmotic diuresis
  - U_Osm < 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)

Question 29

Q

Treatment for hypernatremia

Acute hypernatremia
Chronic hypernatremia

Answer

A

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

Question 30

Q

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

Answer

A

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 (C_eH20)
  - 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

Question 31

Q

Other therapies & complications of rapid correction of hypernatremia

Answer

A

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

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9 Disorders of Water Homeostasis: Hyponatremia Flashcards

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