It’s a Water Problem Sodium Emergencies Julia Creider, PGY4 Endocrine.

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It’s a Water ProblemSodium Emergencies

Julia Creider, PGY4 Endocrine

Objectives

Overview of sodium and water regulation

Understand the clinical manifestations, diagnosis, and causes of hypo- and hypernatremia

Review the management of hypo- and hypernatremia based on underlying cause

The Players: Water

Most abundant constituent in the body

50% of body weight in women, 60% in men

Two main compartments: Intracellular fluid (ICF), 55-75% Extracellular fluid (ECF), 25-45%

Intravascular Extravascular

The Players: Water

Osmolality = solute or particle concentration of a fluid (mosmol/kg)

Water easily diffuses across cell membranes to achieve osmotic equilibrium (ECF = ICF)

Main solutes of these compartments differ: ECF = Na+

ICF = K+

Determinant of the effective osmolality due to being restricted to their respective compartments

The Players: Sodium

Na+ is actively pumped out of cells by the Na+, K+-ATPase membrane pump

85-90% of body Na+ is extracellular

Hence, predominant ion in ECF and major determinant of ECF osmolality and volume

Regulation System: Antidiuretic Hormone

(ADH)

Peptide hormone consisting of a 6 amino acid ring with a cysteine to cysteine bridge and 3 amino acid tail

Synthesized as part of a precursor molecule consisting of a nonapeptide, a hormone-specific neurophysin, and an additional glycopeptide

Packaged in neurosecretory granules

Cleaved to the products during transport to posterior pituitary


(ADH) Main hormone involved in the regulation of water

homeostasis and osmolality

Half life in the circulation is 10-20min

Stimulation of release Increases in plasma osmolality Reductions in plasma volume


(ADH)


(ADH)


(ADH)

ADH LevelWater

Absorption

Urine Volume

Urine Osmo

Serum Osm

(Concentrated)

(Hypertoni

c)

(Dilute)

(Hypotoni

c)

Regulation System: Renin-Angiotensin-Aldosterone

System (RAAS)

Summary

Case

32F from home

Admitted to Neurology with decreased LOC and increase in frequency of seizures

Past Medical History: Glioblastoma, unresectable Seizures

Meds: Lamotrigine Etoposide

Case

Initial Investigations: Na+ 130 MRI – slight increase in size of tumor and increased edema EEG – + seizure activity

Initial Management: Neuro Observation Dilantin loaded Dexamethasone started for edema Due to decrease LOC and inability to eat, IV changed to

D5W/0.45NS

Case

End of the day: Patient condition not improving Team decides to recheck Na+

On call: Na+ 110

Hyponatremia: Definition

Plasma Na+ < 135 mmol

Very common, up to 30% of hospitalized patients

Disorder of water balance

Relative excess of body water compared to total body Na+

Usually associated with disturbance in ADH

Acute < 48hr

Chronic > 48hr

Hyponatremia: Clinical Manifestations

Wide spectrum of clinical symptoms

Mild and nonspecific severe and life threatening

Acute

Severity Symptom

Moderately severe

Nausea without vomitingConfusionHeadache

Severe VomitingCardiorespiratory distressAbnormal and deep somnolenceSeizuresComa

Chronic

Symptom

FatigueNauseaDizzinessGait disturbancesForgetfulnessConfusionLethargyMuscle crampsFractures

Hyponatremia: Severity

Brain cells start to swell due to difference in effective osmolality between brain and plasma

Usually occurs with acute hyponatremia

Chronic hyponatremia, the brain adapts by reducing the number of osmotically active particles within its cells

Hyponatremia: Chronic

Hyponatremia: Diagnosis

Measure serum osmolality: High Hypertonic hyponatremia Normal Pseudohyponatremia Low True hypotonic hyponatremia


Hypertonic hyponatremia occurs when the serum contains additional osmoles that increase the effective osmolality

Reduces the serum Na+ concentration by attracting water from the intracellular compartment

Causes Hyperglycemia Mannitol administration Glycine Sorbitol


Pseudohyponatremia is a laboratory artifact

Occurs when abnormally high concentrations of lipids or proteins in the blood interfere with the accurate measurement of Na+

Causes: Hyperlipidemia or hyperproteinemia



Hypotonic hyponatremia

Assess volume status Vital signs Orthostatic vitals JVP Skin turgor Mucous membranes Peripheral edema

Hypovolemic Hyponatremia: Causes

Hypervolemic Hyponatremia: Causes

Euvolemic Hyponatremia: Causes

Syndrome of Inappropriate Antidiuresis (SIADH)

Most common cause of euvolemic hyponatremia

Inappropriate secretion of ADH independently from effective serum osmolality or circulating volume

Causes progressive hyponatremia until expression of vasopressin V2 receptors and aquaporin-2 water channels are down-regulated, called “vasopression escape”

A diagnosis of exclusion

SIADH: Diagnostic Criteria

SIADH: Causes

Physiologic

Malignancy

Pulmonary disorders

CNS disorders

Drugs

SIADH: Causes

Physiologic General anesthesia Nausea Pain Stress

SIADH: Causes

Malignancy Lung cancer Oropharynx GI tract – stomach, duodenum,

pancreas GU tract – ureter, bladder,

prostate, endometrium Lymphomas Sarcomas

SIADH: Causes

Pulmonary disorders Bacterial and viral pneumonia Pulmonary abscess TB Aspergillosis Asthma Cystic fibrosis Respiratory failure associated

with positive-pressure breathing

SIADH: Causes

CNS disorders Infection

Meningitis Brain abscess

Vascular and masses Subdural hematoma Subarachnoid hemorrhage Stroke Brain tumour Head trauma

Other Hydrocephalus Cavernous sinus thrombosis Multiple sclerosis Guillain-Barre syndrome Shy-Drager syndrome Delirium tremens

SIADH: Causes

Drugs Antidepressants

SSRIs Tricyclic MAOI Venlafaxine

Anticonvulsants Carbamazepine Valproate Lamotrigine

Anticancer drugs Platinum-based Cyclophospham

ide Methotrexate Vinca alkaloids

Vassopressin analogues Desmopressin Oxytocin Vasopressin

Miscellaneous Opiates MDMA Interferon NSAIDs Nicotine Amiodarone PPIs HCTZ

Cerebral Salt Wasting

Occurs in patients with CNS disease

Characterized by hyponatremia and extracellular fluid depletion due to inappropriate Na+ wasting in urine

Mechanism poorly understood Loss of sympathetic nervous system effect on

proximal tubule Release of circulating factor that impairs renal

tubular Na+ resorption

Similar to SIADH, except for hypovolemia

Cerebral Salt Wasting

Management: fluid resuscitation

Acute Hyponatremia: Causes

Hyponatremia: Diagnosis Summary

1. Measure serum osmolality

2. Volume status

3. Urine Osmolality and Na+

Hyponatremia: Management

Factors influencing management: Treatment based on underlying

cause Acute (<48hr) or chronic (>48hr) Severity of symptoms


Severe symptoms, initial management


Severe symptoms, now raised by 5mmol/l and symptoms improved


Severe symptoms, now raised by 5mmol/l and symptoms persist


Acute with moderately severe symptoms A single IV infusion of 150ml 3% hypertonic saline or equivalent

over 20 min. (2D)

Acute without severe or moderately severe symptoms If the acute decrease in serum sodium concentration exceeds

10mmol/l, we suggest a single IV infusion of 3% hypertonic saline (2D)

Chronic without severe or moderately severe symptoms In mild hyponatremia, we suggest against treatment with the sole

aim of increasing serum sodium (2C) Do not exceed > 10mmol/l in first 24hr or >8mmol/l during every

24hr after (1D) Follow serum sodium every 6hr (2D)


Correction calculation: Women TBW:

≈ 0.5 x body weight (young) ≈ 0.45 x body weight (elderly)

Men TBW: ≈ 0.6 x body weight (young) ≈ 0.5 x body weight (elderly)

Infusate Na+ content/L 3% Saline = 513 mmol/L 0.9% NS = 154 mmol/L 0.45% NS = 77 mmol/L Ringer’s = 130 mmol/L D5W = 0 mmol/L


Hypovolemic Hyponatremia: Volume repletion with 9% normal saline

Euvolemic Hyponatremia: Fluid restrict Treat underlying cause Salt tabs ADH receptor antagonists (conivaptan, tolvaptan)

Hypervolemic Hyponatremia: Fluid restrict Diuresis

Hyponatremia: Osmotic Demyelination Syndrome

Occurs with overly rapid correction of severe hyponatremia that has been present for more than 2-3 days

Cerebral adaptation occurs with loss of organic osmolites that take time to return, leading to a drop in brain volume

Mechanism of how decreased brain volume leads to demyelination is unknown

Risk Factors: Serum Na+ level at presentation Duration of hyponatremia Rate of correction

Hyponatremia: Osmotic Demyelination Syndrome

Clinical Manifestations: Typically delayed for 2-6 days after correction Often irreversible Dysarthria Dysphagia Paraparesis or quadriparesis Behaviour changes Confusion, lethargy and coma

Overcorrection: Can re-lower Na+ by giving free water +/- DDAVP


Principals: Severe symptoms aim for a quicker initial rise in Na+

Treat the underlying cause Do not over correct

~10 mmol in first 24hr than ~ 8mmol following 24hr intervals

Monitor serum Na+ levels frequently Allows for adjustments in treatment Ensures not over correcting

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Hypernatremia

Case

21 M

Post car accident and traumatic brain injury

Received mannitol and hypertonic saline for raised ICP

Serum Na+ 160

Hypernatremia

Serum Na+ > 145 mmol/L

Water deficit

Usually loss of hypotonic fluid AND impaired access to free water

Hypernatremia is a powerful thirst stimulus

Thus usually develops in patients without access to water Impaired mental status (eg elderly or critically ill) Infants

Hypernatremia: Clinical Manifestations

Acute Hypernatremia: Rapid decrease in brain volume Leads to rupture of cerebral veins Causing focal intracerebral and subarachnoid

hemorrhages Also demyelinating brain lesions

Symptoms: Lethargy, weakness, irritability Twitching, seizures, coma

Chronic Hypernatremia: Less likely to have neurological sysmptoms

Hypernatremia: Causes

Unreplaced Water Loss

•Insensible and sweat losses•Gastrointestinal losses•Central or nephrogenic diabetes insipidus•Osmotic diuresis•Hypothalamic lesions impairing thirst or osmoreceptor function

Water Loss into Cells •Severe exercise or seizures

Sodium Overload•Intake or administration of hypertonic sodium solutions

Hypernatremia: Diagnosis

Diabetes Insipidus (DI)

ADH deficiency (central) or resistance (nephrogenic)

Central: hypothalamic or posterior pituitary disease Congenital, trauma/surgery, tumors, infiltrative Idiopathic, hypoxic encephalopathy, anorexia, EtOH

Nephrogenic: Congenital: ADH receptor V2 mutation, aquaporin-2

mutation Drugs: Lithium, amphotericin, demeclocycline, cidofovir Metabolic: hypercalcemia, severe hypokalemia Tubulointerstitial: postobstruction, recovery phase of

ATN, amyloid, pregnancy (placental vasopressinase)

Hypernatremia: Management

Replace free water deficit

Volume of infusate (L/day) = target change/change in Na+

Limitations: inaccurate lean body weight, not account for ongoing fluid loss, not include isoosmotic fluid deficit


Calculate and replace ongoing free water loss Obligatory water output from sweat and stool (30-

40ml/hr) Ongoing urinary and/or GI losses that have Na+ and

K+ concentrations below the serum Na+ concentration

Eg. if 100ml/h of urine excreted, with urine Na+ and K+ concentration that is ½ of serum Na+

concentration, the free water clearance would be 50ml/h


Treat underlying cause

Restore access to water

Replace free water deficit

Check serum Na+ frequently

If central DI give DDAVP

If chronic avoid rapid correction, no more than 10mmol/L per day

Summary

Hypo- and hypernatremia are water handling problems

Many different causes

Treatment must target underlying cause

Frequent Na+ monitoring required

Rate of correction is important to prevent neurological sequela

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Questions?

References

Longo, D.L. et al. Harrison’s principles of internal medicine 18th edition. Boston: McGraw-Hill Professional. 2011. Print.

Melmed, S. et al. Williams textbook of endocrinology 12th edition. Saunders. 2011. Print.

Sabatine, M.S. et al. Pocke Medicine 4th edition. Philadelphia: Lippincott Williams & Wilkins. 2011. Print.

Spasovski, G. et al. Clinical practice guidelines on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014: 170, G1-G47.

Sterns, R. Etiology and evaluation of hypernatremia. Uptodate. Oct 2013. Accessed Sept 2014.

Sterns, R. Manifestations of hyponatremia and hypernatremia. Uptodate. July 2013. Accessed Sept 2014.

Sterns, R. Treatment of hypernatremia. Uptodate. July 2013. Accessed Sept 2014.

It’s a Water Problem Sodium Emergencies Julia Creider, PGY4 Endocrine.

Documents

hr slide

summary slide

ns slide

antidiuretic hormone

water regulation

plasma volume slide

water osmolality

pgy4 endocrine slide