Hyponatremia

Debra Bynum,MDDivision of Geriatric Medicine

Clinical Case An 82 y/o woman is admitted from a nursing

home with confusion. She has had a poor appetite over the past year with significant weight loss. Two weeks ago HCTZ was added. Over the past few days, the nurses note some n/v, no diarrhea, fever or other complaints.

On exam, she has some dry oral mucosa but she is not orthostatic. There is no evidence of CHF, ascites or edema. She is awake, but lethargic. Neuro exam is nonfocal. Labs: Na 121 (last 130 4 weeks ago), normal renal/liver function. Serum osm 250, urine osm 280, urine Na 30.

Pretest 1. What are the potential Causes of

hyponatremia in this patient? 2. Does her urine osm of under 300 rule out

SIADH? 3. What other laboratory data is needed? 4. How might her diet be contributing to her

hyponatremia? 5. How is the urine Na helpful? What in this case

would limit its usefulness? 6. How does water intake or relatively

hypotonic fluid intake worsen hyponatremia with SIADH?

The Forces Behind Na and water Intracellular volume maintained by regulation of

plasma osmolality (changes in water balance) sensed by hypothalamic osmoreceptors and affected by ADH and the thirst mechanism via changes in water intake and urine osmolality

Plasma volume ultimate goal; maintained by regulation of Na balance;sensed by afferent arteriole, carotid sinus, cardiac atria and effected by renin-angio-aldo system, sympathetic nervous system, ADH and atrial natriuretic peptide acting on urine na excretion

Overview

n orm a lm easu re lip id s , p ro te in s

vo lu m e exp an d edC H F

C irrh os isn ep h ro tic

V o lu m e D ep le tedad ren a l in su ff

extra ren a l lossesren a l sa lt w as tin g

E u vo lem icp o lyd ip s ia

S IA D H

low (< 2 8 0 )A ssess E C F C lin ica lly

H ig h (> > 2 8 0 )g lu cose

m an n ito l, so rb ito l, g lyc in e

seru m osm (m easu red )

Hyponatremia Euvolemic

SIADH Relatively high urine

osm (>100, often >300)

High/normal urine Na (>40)

hypouricemia/urinary urea wasting

Hypothyroidism ADH Like compounds

(prolactinoma, HCG, waldenstrom’s)

Primary Polydipsia Low urine Osm (<100) Intake over 10 L/day

Hypovolemic appropriate ADH urine na <20 (unless

diuretic use) high urine osm (ADH) hyperuricemia/ dec urinary

uric acid Hypervolemic

CHF, cirrhosis, nephrotic syndrome

“appropriate ADH” low urine Na high urine osm (ADH) poor prognostic factor

ADH

“antidiuretic” central role in most all causes of

hyponatremia; must just determined whether ADH is appropriate, “semi appropriate”, or inappropriate

Stimulation of release: nausea/vomiting, pain, volume depletion

SIADH

Does not in itself cause edema (activation of volume receptors leads to release of urine na and water)

Symptoms relate to rapidity of change 115-120: headache, lethargy, obtundation 110-115: coma, seizures

SIADH Causes:

CNS: neoplasms, bleed, guillain-barre, SIP, sarcoidosis (hypothalamic involvement), pituitary surgery, nausea

Drugs: SSRI, thiazide diuretics, carbamazepine, haloperidol, amitriptyline, bromocriptine…

Pneumonia, TB, ARDS, malignancy Ectopic ADH: carcinomas (small cell),

pancreatic or duodenal ca, thymic ca ADH like compounds: prolactinoma,

Waldenstrom’s

SIADH: Persistent Hyponatremia Increased ADH> renal

water retention> increased body water

Body fluid dilution hyponatremia dec urine osm over

time with new steady state for water

hyponatremia persists until water restricted and excess water dissipated

Water intake> renal water retention > increased body water

increased ECF volume increased output,

renal blood flow and decreased tubular reabsorption of na (maintain normal volume!)

increase na excretion (stretch receptors – inc natriuretic peptides…)

hyponatremia new steady state for

na

SIADH: Treatment Water restriction Aggressive treatment (3% saline, +/-

furosemide) not indicated unless symptomatic, acute, or na <110

no faster than .5 meq/L per hour correction (to avoid risk of central pontine myelinolysis)

once na reaches 120, water restriction only

Volume Depletion

True volume depletion due to vomiting, diarrhea, bleeding, urinary losses

n/v also stimulate ADH release (to maintain circulating volume)

Adrenal Insufficiency (lack of cortisol resulting in decreased na reabsorption plus volume depletion)

Volume Depletion: Treatment Carefully monitor sodium as fluids given to

prevent overly rapid correction goal .5 meq/L per hour correction Degree that 1 L fluid will raise plasma Na conc:

Increase PNa= (infusate [Na] -Pna) / (TBW +1) Isotonic saline:

raises plasma sodium by 1-2 meq/L for every liter of fluid infused since saline has higher Na concentration (154 meq/L) than hyponatremic plasma

volume repletion removes stimulation of ADH

Thiazide Diuretics

Elderly women at higher risk Element of volume depletion Not seen as often with loop diuretics

(inhibition of NaCl transport in loop of Henle prevents generation of countercurrent gradient and limits ability of ADH to induce water retention)

May result in normal/increased urine Na, even though underlying volume depletion;

CHF, Cirrhosis, Nephrotic syndrome CHF/Cirrhosis: pressure sensed at

carotid sinus baroreceptors reduced due to poor cardiac output or peripheral vasodilation/poor circulating volume; associated with higher mortality; degree of hyponatremia as prognostic marker

Nephrotic syndrome: usually due to renal disease rather than poor circulating volume

Primary Polydipsia

Psychiatric disorder, often complicated by increased thirst with antipsychotic meds

can occur with hypothalemic lesions (sarcoid or other infiltrative processes)

Usually no hyponatremia unless intake over 10-15 L/day, or acute 3-4 L water load

Urine osm below 100 (NOT ADH problem!) Increased problems if other ADH stimulus

(n/v, anxiety)

Low Dietary Solute Intake “Tea and Toast” Diet Beer drinkers: Beer Potomania Normally excrete 600-900 mosmol/kg solute

daily (if minimum urine osm is 60 mosmol/kg, max urine output will be 10-15L/day: 900mosm/day / 60 mosmol/kg = 15)

If daily intake poor, daily solute excretion may fall below 250 mosmol/kg, reducing the maximum urine output to below 4 L day; Hyponatremia develops if greater than 4 L consumed in day

Urine appears dilute (osm of 100)

Pseudohyponatremia

Plasma osmolality that is normal or elevated

usually not at risk for hypoosmolality induced cerebral edema

Lipids, proteins Not a problem with labs that

directly measure na

High plasma osmolality Hyperglycemia mannitol IVIG with maltose retention in patients with

renal failure Glycine: TURP; exception to rule that patients

with hyperosm hyponatremia do not get into trouble; complicated by urinary retention, n/v, postsurgical state; severe hyponatremia after urological procedure should be treated acutely with saline/furosemide!

Back to the Case... 1. What are the potential causes of

hyponatremia in this patient? Thiazide diuretic (complicating urine na) underlying SIADH (suggested by

inappropriately high urine osm) recent n/v and volume loss (although not

orthostatic) poor solute intake/ “tea and toast” diet ( may

be reason that urine osm is not as high as would be expected with SIADH alone)

?CNS event (stroke, subdural)

Case...

2. Does her urine osm of under 300 rule out SIADH? No; classically urine osmolality is 300

or greater, but the urine osm of 220 in the setting of a serum na of 121 is inappropriately elevated (over 100 really is inappropriate)

Case... 3. What other laboratory data

would be needed? TSH Cortisol level (although not orthostatic) probably neuroimaging given underlying

dementia and risk for CVA, subdural, etc consider uric acid to help differentiate

hypovolemia from SIADH (hypouricemia in SIADH, elevated/normal uric acid if dehydrated)

Case...

4. How might her diet be contributing to her hyponatremia? Poor solute intake could result in

dilute urine and hyponatremia as discussed previously

Case...

5. How is the urine Na helpful in differentiating SIADH from hypovolemia? What in this case would limit its usefulness? Urine Na should be normal/elevated with

SIADH and should be low with hypovolemia

thiazide diuretic use may elevated urine na temporarily

Case... 6. How does water intake or hypotonic fluid

intake worsen the hyponatremia with SIADH? Example: patient with SIADH, urine osmolality of 616

mosmol/kg; 1 liter of NS has 308 mosmol of NaCl, 1000 cc H2O;

Isotonic Saline NaCl H2O In 308 1000 ml Out 308 500 ml (conc

616) Net 0 +500 of free H2O!

Case... 7. How would you manage this patient?

Water restriction? Need to address amount of intake she has had

Avoid rapid correction (osmotic demylination) Discontinuation of Thiazide Would probably not give IVF initially as most

may be due to thiazide, SIADH, poor diet, although may be complicating element of hypovolemia; if n/v persisted after holding thiazide, consider small amount of normal saline (relatively hypertonic with urine osm of 220)