Sodium Disorders - Hyponatremia And Hypernatremia - Harrisons 63

Front 1

Two key effectors in the defense of serum osmolality

Back 1

1. Water intake

2. Circulating AVP

Front 2

Definition of hyponatremia

Back 2

plasma Na+ concentration < 135 mM

Front 3

Hyponatremia: occurence in hospitalized patients, most common etiology, and the diagnostic subdivision into 3 groups

Back 3

Occurs in up to 22% of hospitalized patients.

This disorder is almost always the result of an increase in circulating AVP and/or increased renal sensitivity to AVP, combined with an intake of free water.

A notable exception is hyponatremia due to low solute intake.

The pathophysiology for the increased AVP response differs as a function of ECFV.

The subdiviion to 3 groups is based on clinical history and volume status:

* hypovolemic hyponatremia

* euvolemic hyponatremia

* hypervolemic hyponatremia

Front 4

Hypovolemic hyponatremia

Changes in total body water and total body sodium

Possible etiologies - divided by one important parameter...

Back 4

Total body water: decresed

Total body sodium: very decreased

U[Na] < 20: extrarenal losses

* Vomiting

* Diarrhea

* Third spacing of fluids

* Burns

* Pancreatitis

* Trauma

U[Na] > 20: renal losses

* Diuretic excess

* Mineral corticoid deficiency

* Salt-losing deficiency

* Bicarbonaturia with renal tubular acidosis and metabolic alkalosis

* Ketonuria

* Osmotic diuresis

* Cerebral salt wasting syndrome

Front 5

Euvolemic hyponatremia

Changes in total body water and total body sodium

What is the expected U[Na]?

Possible etiologies

Back 5

Total body water - increased

Total body sodium - no change

U[Na] > 20

Possible etiologies:

* Hypothyroidism

* Stress

* Drugs

* SIADH

Front 6

Hypervolemic hyponatremia

Changes in total body water and total body sodium

Possible etiologies - divided by one important parameter...

Back 6

Total body water - very increased

Total body sodium - increased

U[Na] < 20

* Nephrotic syndrome

* Cirrhosis

* Cardiac failure

U[Na] > 20

* Acute or chronic renal failure

Front 7

Beer potomania

Back 7

Hyponatremia can occur in patients with a very low intake of dietary solutes. Classically occurs in alcoholics (because beer is very low in protein and salt content), but not only.

The reduced urinary solte excretion limits water excretion such that hyponatremia ensues after relatively modest polydipsia.

These patients present with a very low urine osmolality (<100-200 mOsm/kg) with urine Na concentration <10-20 mM.

Resumption of normal diet and/or saline hydration will correct the causative deficit in urinary solute excretion.

Patients with beer potomania typically correct their plasma Na concentration promptly after admission to the hospital.

Front 8

There are a few gazillion reasons for SIADH.

How many can YOU tell?

Back 8

Malignant Diseases:

# Carcinoma

* Lung (small cell, mesothelioma)

* Oropharynx

* GIT (stomach, duodenum, pancreas)

* GUT (ureter, bladder, prostate, endometrium)

# Endocrine thymoma

# Lymphomas

# Sarcomas (Ewing's sarcoma)

Pulmonary disorders:

# Infections

* Bacterial pneumonia

* Viral pneumonia

* Pulmonary abscess

* Tuberculosis

* Aspergillosis

# Asthma

# Cystic fibrosis

# Respiratory failure associated with positive-pressure breathing

Disorders of the CNS:

# Infection

* Encephalitis

* Meningitis

* Brain abscess

* Rocky Mountain spotted fever

* AIDS

# Bleeding and masses

* Subdural hematoma

* Subarachnoid hemorrhage

* Cerebrovascular accident

* Brain tumors

* Head trauma

* Hydrocephalus

* Cavernous sinus thrombosis

# Multiple sclerosis

# Guillian-Barre syndrome

# Shy-Drager syndrome

# Delirium tremens

# Acute intermittent porphyria

Drugs:

# Chloropropamide

# SSRIs

# Tricyclic antodepressants

# Clofibrate

# Carbamezapine

# Vincristine

# Nicotine

# Narcotics

# Antipsychotic drugs

# Ifosfamide

# Cyclophosphamide

# NSAIDs

# MDMA

# AVP analogues

# Desmopressin

# Oxytocin

# Vasopressin

Other causes:

# Hereditary (gain of function mutations in the vasopressin V2 receptor)

# Idiopathic

# Transient

# Endurance exercise

# General anesthesia

# Nausea

# Pain

# Stress

Front 9

Clinical features of acute hyponatremia

Back 9

Hyponatremia induces generalized cellular swelling.

The intial CNS response to acute hyponatremia is an increase in interstitial pressure, leading to shunting of ECF and solutes from the interstitial space into the CSF and then into the systemic circulation. This is accompanied by an efflux of the major intracellular ions (Na, K, Cl) from brain cells.

The symptoms are primarly neurologic, reflecting the development of cerebral edema within a rigid skull.

Early symptoms can include nausea, headache, and vomiting.

Severe complications can rapidly involve, including seizure activity, brainstem herniation, coma and death.

Front 10

Acute symptomatic hyponatremia

Back 10

A medical emergency.

Women, particularily before menopause, are much more than men likely to develop encephalopathy and severe neurologic sequelae.

Occuring in a number of specific settings:

# Itarogenic

* Postoperative: premenopausal women

* Hypotonic fluids given to postoperative patient with an increase in circulating AVP

* Glycine irrigation: TURP, uterine surgery

* Colonoscopy preparation

# Recent instituion of thiazides

# Polydipsia

# MDMA ingestion

# Exercise induced - increase in circulating AVP and excessive free water intake

# Multifactorial (meaning - combination of any of the above)

Front 11

Chronic hyponatermia

Back 11

Defined clinically as >48 hours.

Results in an efflux of organic osmolytes (creatine, betaine, glutamate, myoinositol, taurine) from brain cells. This response reduces intracellular osmolality and the osmotic gradient favoring water entry.

There can still be symptoms, such as vomiting, nausea, confusion, and seizures, usually at Na concentration < 125 mM.

Even patients who are judged "asymptomatic" can manifest subtle gait and cognitive defects that reverse with the correction of hyponatremia.

Chronic hyponatremia increases the risk of bony fractures, because of neurologic dysfunction and reduction in bone density.

Therefore every attempt should be made to correct safely the plasma Na concentration, even in the absence of overt symtpoms.

Front 12

Pseudohyponatremia

Back 12

Defined as the coexistence of hyponatremia with a normal or increased plasma tonicity.

Most clinical laboratories measure plasma Na concentration by testing diluted sample and then correcting for this dilution by assuming that plasma is 93% water.

This correction factor can be inaccurate in patients with pseudohyponatremia, due to extreme hyperlipidemia and/or hyperproteinemia.

To rule this out, laboratory investigation of hyponatremia should include a measurement of serum osmolality.

The measured osmolality should also be converted to the effective osmolality (tonicity) by subtracting the measured concentration of urea (if in mg/dL: divided by 2.8).

Patients with real hyponatremia should have an effective osmolality of <275 mOsm/kg.

Front 13

Laboratory investigation of hyponatremia

What needs to be measured, and why?

Back 13

* Measured serum osmolality - to rule out pseudohyponatremia.

* BUN and creatinine - if elevated, can indicate renal dysfunction as a potential cause.

* Serum K - hyperkalemia can indicate adrenal insufficiency or hypoaldosteronism.

* Serum glucose - Na concentration falls by 1.6-2.4 mM for every 100 mg/dL increase in glucose.

This situation is not defined as pseudohyponatremia, but this "real" hyponatremia will resolve after correction of hyperglycemia.

* Serum uric acid - patients with SIAD-type physiology will typically be hypouricemic (<4 mg/dL), and volume-depleted patients will often be hyperuricemic.

* Urine electrolytes and osmolality - crucial tests in the intial evaluation of hyponatremia.

Urine Na concentration <20-30 mM is consistent with hypovolemic hyponatremia, or hypervolemic hyponatremia - but not euvolemic.

Urine Na concentration >30 mM is typical for patients with SIAD.

It is not always accurate!

* Thyroid, adrenal, and pituitary function - should be tested in the appropriate clinical setting.

Front 14

"Gold standard" for the diagnosis of hypovolemic hyponatremia

Back 14

Demonstration that plasma Na concentration corrects after hydration with normal saline.

Front 15

Three major considerations guide the therapy of hyponatremia

Back 15

1. The presence and/or severity of symptoms determine the urgency and goals of therapy.

2. Patients with chronic hyponatremia are at risk for ODS - Osmotic Demyelination Syndrome.

3. Frequent monitoring of plasma Na concentration during corrective therapy is imperative, because the response to interventions such as hypertonic saline, isotonic saline, or AVP antagonists can be highly unpredictable.

Front 16

ODS - Osmotic Demyelination Syndrome

Back 16

A result of overly rapid correction of hyponatremia.

This is a result of attenuated and delayed reaccumulation of osmolytes by brain cells after the correction.

Rapid correction is also associated with a disruption of the BBB, allowing the entry of immune mediators that may contribute to the demyelination.

The lesions of ODS classically affect the pons.

Clinically, patients with central pontine myelinolysis can present 1 or more days after overcorrection of hyponatremia with paraparesis or quadriparesis, dysphagia, dysarthria, diplopia, a "locked-in syndrome", and/or loss of consciousness.

Relowering of plasma Na+ concentration after overly rapid correctioncan prevent or attenuate ODS.

Even appropriately slow correction canbe associated with ODS, particularly in patients with additional risk factors, like alcoholism, malnutrition, hypokalemia, and liver transplantation.

Front 17

Treatment of euvolemic hyponatremia

Back 17

Euvolemic hyponatremia due to SIAD, hypothyroidism, or secondary adrenal failure will respond to successful treatment of the underlying cause.

Not all causes of SIAD are immediately reversible, necessitating pharmacologic therapy to increase the plasma Na+concentration.

Front 18

Treatment of hypovolemic hyponatremia

Back 18

Hypovolemic hyponatremia will respond to IV hydration with isotonic normal saline, with a rapid reduction in circulating AVP and a brisk water diuresis.

It may be necessary to reduce the rate of correction if the history suggests thathyponatremia has been chronic.

Front 19

Treatment of hypervolemic hyponatremia

Back 19

Hypervolemic hyponatremia due to CHF will often respond to improved therapy of the underlying cardiomyopathy.

Front 20

Treatment of hyponatremia due to beer potomania (and low solute intake)

Back 20

Beer potomania will respond very rapidly to IV saline and the resumption of a normal diet.

Patients with beer potomania have a very high risk of developing ODS, due to the associated hypokalemia, alcoholism, malnutrition,and high risk of overcorrecting the plasma Na+ concentration.

Front 21

Water restriction and potassium replacement in treatment of chronic hyponatremia

And a possible treatment if of all the above failed

Back 21

Aggressive fluid restriction can be difficult for SIAD to tolerate, because their thirst is inappropriately stimulated.

The urine-to-plasma electrolyte ratio is a quick indicator of electrolyte-free water excretion.

It is calculated: (urinary[Na] + [K]) / plasma[Na]

ratio > 1: aggressive restriction, <500 mL/day

ratio ~ 1: restriction of 500-700 mL/day

ratio < 1: restriction of <1 L/day

In hypokalemic patients, potassium replacement will serve to increase Na concentration. Potassium might overcorrect Na.

Oral urea and/or salt tablets are generally not practical or well tolerated.

If all that failed - many patients with SIAD respond to combined therapy with oral furosemide and oral salt tablets.

Front 22

AVP antagonists (vaptans)

Back 22

Highly effective in SIAD and inhypervolemic hyponatremia due to heart failure or cirrhosis.

Front 23

Treatment of acute symptomatic hyponatremia

Back 23

Treatment should include hypertonic 3% saline (513 mM) to acutely increase plasma Na+ concentrationby 1–2 mM/h to a total of 4–6 mM.

This modest increaseis typically sufficient to alleviate severe acute symptoms, after whichcorrective guidelines for chronic hyponatremia are appropriate.

The increase in plasma Na+concentration can be highly unpredictable during treatment withhypertonic saline, due to rapid changes in the underlying physiology;plasma Na+ concentration should be monitored every 2–4 hduring treatment, with appropriate changes in therapy based on theobserved rate of change.

Intravenous loop diuretics will help treatacute pulmonary edema and will also increase free water excretion.

AVP antagonists do not have an approved role in the management of acute hyponatremia.

Front 24

Correction of Na in chronic hyponatremia

Back 24

The rate of correction should be relatively slow to avoid ODS: <8–10 mM in the first 24 h and <18 mM in the first 48h.

Lower target rates are appropriate in patientsat particular risk for ODS, such as alcoholics or hypokalemic patients.

Front 25

Hypernatremia: definition, etiology

Back 25

Hypernatremia is defined as Na concentration > 145 mM.

It is considerably less common than hyponatremia, and is associated with high mortality rates (40-60%), mostly due to the severity of the underlying disease processes.

Front 26

Diagnostic approach to hypernatremia

Back 26

If ECF volume increased: administration of hypertonic NaCl / NaHCO3

Else...

If minimum volume of maximally concentrated urine:

* Insensible water loss

* GI water loss

* Remote renal water loss

Else...

If urine osmole excretion rate > 750 mOsm/d: diuretic, or osmotic diureses (can be secondary to hyperglycemia, excess urea, postobstructive diuresis, or mannitol).

Else...

We are talking about diabetes insipidus.

Now if there is renal response to desmopressin - urine osmolality increased: central diabetes insipidus.

If there is not renal response: nephrogenic diabetes insipidus.

Front 27

Clinical features of hypernatremia

Back 27

Thesymptoms of hypernatremia are predominantly neurologic.

Alteredmental status is the most frequent manifestation, ranging from mildconfusion and lethargy to deep coma.

The sudden shrinkage of braincells in acute hypernatremia may lead to parenchymal or subarachnoidhemorrhages and/or subdural hematomas - mostly in pediatric and neonatal patients.

Osmotic damage to muscle membranes can also lead tohypernatremic rhabdomyolysis.

Patients with chronic hypernatremiaare less likely to develop severe neurologic compromise, but the cellular response to chronic hypernatremia predisposes these patients to developing cerebral edema and seizures during overly rapid hydration.

Front 28

Diagnostic approach - history, physical examination, laboratory

Back 28

History: presence or absence of thirst, polyuria, and/or an extrarenal source for water loss (like diarrhea).

Physical examination: detailed neurologic exam, assessment of ECFV.

Accurate documentation of daily fluid intake and daily urine outputis also critical for the diagnosis and management of hypernatremia.

Laboratory: serum and urine osmolality, urine electrolytes.

Front 29

Treatment of hypernatremia - correction rate

Back 29

It is imperative to correct hypernatremia slowlyto avoid cerebral edema, typically replacing the calculated free waterdeficit over 48 h.

The plasma Na+ concentration should becorrected by no more than 10 mM/d, which may take longer than 48 hin patients with severe hypernatremia (>160 mM).

A rare exceptionis patients with acute hypernatremia (<48 h) due to sodium loading,who can safely be corrected rapidly at a rate of 1 mM/h.

Front 30

Treatment of hypernatremia - calculations

Back 30

Water deficit

1. Estimate total-body water (TBW): 50% of body weight in women and 60% in men.

2. Calculate free-water deficit: [(Na - 140)/140] x TBW

3. Administer deficit over 48-72 h, without decrease in plasma Na concentration by >10 mM/24h

Ongoing water losses

4. Calculate free-water clearance:

V x {1 - (U[Na] + U[K])/P[Na]}

V is urinary volume

Insensible losses

5. ~10 mL/kg per day: less if ventilated, more if febrile.

Total

6. Add components to determine water deficit and ongoing water loss; correct the water deficit over 48-72 h and replace daily water loss.

Avoid correction of plasma Na by >10 mM/d.