Transcript It’s a Water Problem

It’s a Water Problem
Sodium Emergencies
Julia Creider, PGY4 Endocrine
S
Objectives
S Overview of sodium and water regulation
S Understand the clinical manifestations, diagnosis, and
causes of hypo- and hypernatremia
S Review the management of hypo- and hypernatremia based
on underlying cause
The Players: Water
S Most abundant constituent in the body
S 50% of body weight in women, 60% in men
S Two main compartments:
S Intracellular fluid (ICF), 55-75%
S Extracellular fluid (ECF), 25-45%
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Intravascular
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Extravascular
The Players: Water
S Osmolality = solute or particle concentration of a fluid
(mosmol/kg)
S Water easily diffuses across cell membranes to achieve
osmotic equilibrium (ECF = ICF)
S Main solutes of these compartments differ:
S ECF = Na+
S ICF = K+
S Determinant of the effective osmolality due to being
restricted to their respective compartments
The Players: Sodium
S Na+ is actively pumped out of cells by
the Na+, K+-ATPase membrane
pump
S 85-90% of body Na+ is extracellular
S Hence, predominant ion in ECF and
major determinant of ECF osmolality
and volume
Regulation System: Antidiuretic
Hormone (ADH)
S Peptide hormone consisting of a 6 amino acid ring with a
cysteine to cysteine bridge and 3 amino acid tail
S Synthesized as part of a precursor molecule consisting of a
nonapeptide, a hormone-specific neurophysin, and an
additional glycopeptide
S Packaged in neurosecretory granules
S Cleaved to the products during transport to posterior
pituitary
Regulation System: Antidiuretic
Hormone (ADH)
S Main hormone involved in the regulation of water
homeostasis and osmolality
S Half life in the circulation is 10-20min
S Stimulation of release
S Increases in plasma osmolality
S Reductions in plasma volume
Regulation System: Antidiuretic
Hormone (ADH)
Regulation System: Antidiuretic
Hormone (ADH)
Regulation System: Antidiuretic
Hormone (ADH)
ADH Level
Water
Absorption
Urine Volume Urine Osmo
Serum Osm




(Concentrated) (Hypertonic)




(Dilute)

(Hypotonic)

Regulation System: ReninAngiotensin-Aldosterone
System (RAAS)
Summary
Case
S 32F from home
S Admitted to Neurology with decreased LOC and increase in
frequency of seizures
S Past Medical History:
S Glioblastoma, unresectable
S Seizures
S Meds:
S Lamotrigine
S Etoposide
Case
S Initial Investigations:
S Na+ 130
S MRI – slight increase in size of tumor and increased edema
S EEG – + seizure activity
S Initial Management:
S Neuro Observation
S Dilantin loaded
S Dexamethasone started for edema
S Due to decrease LOC and inability to eat, IV changed to
D5W/0.45NS
Case
S End of the day:
S Patient condition not improving
S Team decides to recheck Na+
S On call:
S Na+ 110
Hyponatremia: Definition
S Plasma Na+ < 135 mmol
S Very common, up to 30% of hospitalized patients
S Disorder of water balance
S Relative excess of body water compared to total body Na+
S Usually associated with disturbance in ADH
S Acute < 48hr
S Chronic > 48hr
Hyponatremia: Clinical
Manifestations
S Wide spectrum of clinical symptoms
S Mild and nonspecific  severe and life threatening
Acute
Chronic
Severity
Symptom
Symptom
Moderately
severe
Nausea without vomiting
Confusion
Headache
Severe
Vomiting
Cardiorespiratory distress
Abnormal and deep somnolence
Seizures
Coma
Fatigue
Nausea
Dizziness
Gait disturbances
Forgetfulness
Confusion
Lethargy
Muscle cramps
Fractures
Hyponatremia: Severity
S Brain cells start to swell due to
difference in effective osmolality
between brain and plasma
S Usually occurs with acute
hyponatremia
S Chronic hyponatremia, the brain
adapts by reducing the number of
osmotically active particles
within its cells
Hyponatremia: Chronic
Hyponatremia: Diagnosis
S Measure serum osmolality:
S High  Hypertonic hyponatremia
S Normal  Pseudohyponatremia
S Low  True hypotonic hyponatremia
Hyponatremia: Diagnosis
S Hypertonic hyponatremia occurs when the serum contains
additional osmoles that increase the effective osmolality
S Reduces the serum Na+ concentration by attracting water
from the intracellular compartment
S Causes
S Hyperglycemia
S Mannitol administration
S Glycine
S Sorbitol
Hyponatremia: Diagnosis
S Pseudohyponatremia is a laboratory artifact
S Occurs when abnormally high concentrations of lipids or
proteins in the blood interfere with the accurate
measurement of Na+
S Causes: Hyperlipidemia or hyperproteinemia
Hyponatremia: Diagnosis
Hyponatremia: Diagnosis
S Hypotonic hyponatremia
S Assess volume status
S Vital signs
S Orthostatic vitals
S JVP
S Skin turgor
S Mucous membranes
S Peripheral edema
Hypovolemic Hyponatremia:
Causes
Hypervolemic Hyponatremia:
Causes
Euvolemic Hyponatremia:
Causes
Syndrome of Inappropriate
Antidiuresis (SIADH)
S Most common cause of euvolemic hyponatremia
S Inappropriate secretion of ADH independently from
effective serum osmolality or circulating volume
S Causes progressive hyponatremia until expression of
vasopressin V2 receptors and aquaporin-2 water channels
are down-regulated, called “vasopression escape”
S A diagnosis of exclusion
SIADH: Diagnostic Criteria
SIADH: Causes
S Physiologic
S Malignancy
S Pulmonary disorders
S CNS disorders
S Drugs
SIADH: Causes
S Physiologic
S General anesthesia
S Nausea
S Pain
S Stress
SIADH: Causes
S Malignancy
S Lung cancer
S Oropharynx
S GI tract – stomach, duodenum,
pancreas
S GU tract – ureter, bladder, prostate,
endometrium
S Lymphomas
S Sarcomas
SIADH: Causes
S Pulmonary disorders
S Bacterial and viral pneumonia
S Pulmonary abscess
S TB
S Aspergillosis
S Asthma
S Cystic fibrosis
S Respiratory failure associated with
positive-pressure breathing
SIADH: Causes
S CNS disorders
S Infection
S Other
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Meningitis
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Hydrocephalus
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Brain abscess
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Cavernous sinus thrombosis
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Multiple sclerosis
S Vascular and masses
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Subdural hematoma
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Guillain-Barre syndrome
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Subarachnoid hemorrhage
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Shy-Drager syndrome
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Stroke
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Delirium tremens
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Brain tumour
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Head trauma
SIADH: Causes
S Drugs
S Antidepressants
S Anticancer drugs
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Miscellaneous
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SSRIs
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Platinum-based
S Opiates
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Tricyclic
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Cyclophosphamide
S MDMA
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MAOI
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Methotrexate
S Interferon
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Venlafaxine
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Vinca alkaloids
S NSAIDs
S Anticonvulsants
S Vassopressin
S Nicotine
S Amiodarone
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Carbamazepine
analogues
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Valproate
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Desmopressin
S PPIs
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Lamotrigine
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Oxytocin
S HCTZ
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Vasopressin
Cerebral Salt Wasting
S Occurs in patients with CNS disease
S Characterized by hyponatremia and extracellular fluid
depletion due to inappropriate Na+ wasting in urine
S Mechanism poorly understood
S Loss of sympathetic nervous system effect on proximal tubule
S Release of circulating factor that impairs renal tubular Na+
resorption
S Similar to SIADH, except for hypovolemia
Cerebral Salt Wasting
S Management: fluid resuscitation
Acute Hyponatremia: Causes
Hyponatremia: Diagnosis
Summary
1.
Measure serum osmolality
2.
Volume status
3.
Urine Osmolality and Na+
Hyponatremia: Management
S Factors influencing management:
S Treatment based on underlying cause
S Acute (<48hr) or chronic (>48hr)
S Severity of symptoms
Hyponatremia: Management
S Severe symptoms, initial management
Hyponatremia: Management
S Severe symptoms, now raised by 5mmol/l and symptoms improved
Hyponatremia: Management
S Severe symptoms, now raised by 5mmol/l and symptoms persist
Hyponatremia: Management
S Acute with moderately severe symptoms
S A single IV infusion of 150ml 3% hypertonic saline or equivalent over 20
min. (2D)
S Acute without severe or moderately severe symptoms
S If the acute decrease in serum sodium concentration exceeds 10mmol/l,
we suggest a single IV infusion of 3% hypertonic saline (2D)
S Chronic without severe or moderately severe symptoms
S In mild hyponatremia, we suggest against treatment with the sole aim of
increasing serum sodium (2C)
S Do not exceed > 10mmol/l in first 24hr or >8mmol/l during every 24hr
after (1D)
S Follow serum sodium every 6hr (2D)
Hyponatremia: Management
S Correction calculation:
S Infusate Na+ content/L
S Women TBW:
S 3% Saline = 513 mmol/L
S ≈ 0.5 x body weight (young)
S 0.9% NS = 154 mmol/L
S ≈ 0.45 x body weight (elderly)
S 0.45% NS = 77 mmol/L
S Men TBW:
S ≈ 0.6 x body weight (young)
S Ringer’s = 130 mmol/L
S ≈ 0.5 x body weight (elderly)
S D5W = 0 mmol/L
Hyponatremia: Management
S Hypovolemic Hyponatremia:
S Volume repletion with 9% normal saline
S Euvolemic Hyponatremia:
S Fluid restrict
S Treat underlying cause
S Salt tabs
S ADH receptor antagonists (conivaptan, tolvaptan)
S Hypervolemic Hyponatremia:
S Fluid restrict
S Diuresis
Hyponatremia: Osmotic
Demyelination Syndrome
S Occurs with overly rapid correction of severe hyponatremia
that has been present for more than 2-3 days
S Cerebral adaptation occurs with loss of organic osmolites
that take time to return, leading to a drop in brain volume
S Mechanism of how decreased brain volume leads to
demyelination is unknown
S Risk Factors:
S Serum Na+ level at presentation
S Duration of hyponatremia
S Rate of correction
Hyponatremia: Osmotic
Demyelination Syndrome
S Clinical Manifestations:
S Typically delayed for 2-6 days after correction
S Often irreversible
S Dysarthria
S Dysphagia
S Paraparesis or quadriparesis
S Behaviour changes
S Confusion, lethargy and coma
S Overcorrection:
S Can re-lower Na+ by giving free water +/- DDAVP
Hyponatremia: Management
S Principals:
S Severe symptoms aim for a quicker initial rise in Na+
S Treat the underlying cause
S Do not over correct
S
~10 mmol in first 24hr than ~ 8mmol following 24hr intervals
S Monitor serum Na+ levels frequently
S
Allows for adjustments in treatment
S
Ensures not over correcting
Hypernatremia
S
Case
S 21 M
S Post car accident and traumatic brain injury
S Received mannitol and hypertonic saline for raised ICP
S Serum Na+ 160
Hypernatremia
S Serum Na+ > 145 mmol/L
S Water deficit
S Usually loss of hypotonic fluid AND impaired access to free
water
S Hypernatremia is a powerful thirst stimulus
S Thus usually develops in patients without access to water
S Impaired mental status (eg elderly or critically ill)
S Infants
Hypernatremia: Clinical
Manifestations
S Acute Hypernatremia:
S Rapid decrease in brain volume
S Leads to rupture of cerebral veins
S Causing focal intracerebral and subarachnoid
hemorrhages
S Also demyelinating brain lesions
S Symptoms:
S Lethargy, weakness, irritability
S Twitching, seizures, coma
S Chronic Hypernatremia:
S 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)
S ADH deficiency (central) or resistance (nephrogenic)
S Central:
S hypothalamic or posterior pituitary disease
S Congenital, trauma/surgery, tumors, infiltrative
S Idiopathic, hypoxic encephalopathy, anorexia, EtOH
S Nephrogenic:
S Congenital: ADH receptor V2 mutation, aquaporin-2 mutation
S Drugs: Lithium, amphotericin, demeclocycline, cidofovir
S Metabolic: hypercalcemia, severe hypokalemia
S Tubulointerstitial: postobstruction, recovery phase of ATN,
amyloid, pregnancy (placental vasopressinase)
Hypernatremia: Management
S Replace free water deficit
S Volume of infusate (L/day) = target change/change in Na+
S Limitations: inaccurate lean body weight, not account for
ongoing fluid loss, not include isoosmotic fluid deficit
Hypernatremia: Management
S Calculate and replace ongoing free water loss
S Obligatory water output from sweat and stool (30-40ml/hr)
S Ongoing urinary and/or GI losses that have Na+ and K+
concentrations below the serum Na+ concentration
S 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
Hypernatremia: Management
S Treat underlying cause
S Restore access to water
S Replace free water deficit
S Check serum Na+ frequently
S If central DI give DDAVP
S If chronic avoid rapid correction, no more than 10mmol/L per day
Summary
S Hypo- and hypernatremia are water handling problems
S Many different causes
S Treatment must target underlying cause
S Frequent Na+ monitoring required
S Rate of correction is important to prevent neurological sequela
Questions?
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References
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Longo, D.L. et al. Harrison’s principles of internal medicine 18th edition.
Boston: McGraw-Hill Professional. 2011. Print.
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Melmed, S. et al. Williams textbook of endocrinology 12th edition. Saunders.
2011. Print.
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Sabatine, M.S. et al. Pocke Medicine 4th edition. Philadelphia: Lippincott
Williams & Wilkins. 2011. Print.
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Spasovski, G. et al. Clinical practice guidelines on diagnosis and treatment of
hyponatraemia. Eur J Endocrinol. 2014: 170, G1-G47.
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Sterns, R. Etiology and evaluation of hypernatremia. Uptodate. Oct 2013.
Accessed Sept 2014.
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Sterns, R. Manifestations of hyponatremia and hypernatremia. Uptodate. July
2013. Accessed Sept 2014.
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Sterns, R. Treatment of hypernatremia. Uptodate. July 2013. Accessed Sept
2014.