#48: Hyponatremia Deconstructed

July 17, 2017 | By Matthew Watto, MD

Step up your salt game. We deconstruct hyponatremia with our Chief of Nephrology, Dr. Joel Topf aka @kidney_boy aka The Salt Whisperer. Learn the correct steps to diagnose and manage this common and dangerous condition. Topics covered include: true versus false hyponatremia, SIADH, tea and toast hyponatremia, beer potomania, safe rates of sodium correction, IV fluid choice, and more.

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Case: 85yo F with anxiety, asthma, HTN (on a CCB), hypothyroidism with TSH of 3 on therapy. Na+ was 128 from previous values 134-137 mg/dL. She is more fatigued than usual.

Background:

1. Tonicity and sodium generally move in same direction (i.e. up or down), but NOT ALWAYS.
2. Plasma is liquid component of blood (includes clotting factors). Serum is the liquid component of blood after blood has clotted.
3. Osmolality: the number of particles contained in one liter of water. Typically measured in mmol/L (or mOsm/kg). Plasma osmolality (normal range 285-295 mmol/L) is the concentration of all solutes in plasma, both electrolytes (e.g. Na+, Cl-) and nonelectrolytes (e.g. urea, albumin).
4. Antidiuretic hormone (ADH): AKA vasopressin. “Adds hydration to the body hormone”. Released if hypovolemia, or elevated plasma osmolality. Hypovolemia trumps plasma osmolality.
5. Volume status: History is key. Physical exam can help for grossly hypo- or hypervolemic patients, but euvolemia can be difficult to differentiate from mild hypovolemia, or hypervolemia. Elevated specific gravity, or low urine sodium (<30 mmol/L) suggest either true hypovolemia, or low effective arterial volume (e.g.h heart failure).
6. Solute ingested each day (aka solute load) = Solute excreted under normal conditions. 1 mmol/L = 1 mOsm/kg. Solute is excreted via urine, which can be diluted to minimum of 50 mmol/L (minimum urinary concentration), or concentrated to maximum 1200 mmol/L (or 1200 mOsm/kg). E.g. 60 kg person ingests about 10 mOsm/kg/day = solute load of 600 mOsm/day that must be excreted. So, a solute load of 600 mmol divided by minimum urine concentration of 50 mmol/L = 12 L urine output. Thus if this person ingest 13 L water then 1 L cannot be excreted and sodium will fall.

Clinical Pearls:

1. First step, repeat serum sodium measurement! Then check plasma osmolality to determine if true or false hyponatremia.
2. False hyponatremia aka “pseudohyponatremia”: Sodium is low, but plasma osmolality is normal (e.g. multiple myeloma, IVIG administration, hyperlipidemia), or high (e.g. mannitol, glucose).
3. False hyponatremia w/normal osmolality:  A lab error due to the way sodium is measured. Excess protein or lipid in the plasma cause over dilution of the sample → falsely low sodium measurement.
4. False hyponatremia w/high osmolality: Increased concentration of osmotically active particles (e.g. mannitol or glucose) in blood draw out intracellular water → dilution of plasma sodium concentration.
5. True hyponatremia: Both sodium and plasma osmolality are low. Water intake exceeds water output → dilution of plasma sodium concentration by free water. Can be ADH independent or ADH dependent (see below). Check urine osmolality, and specific gravity. If ADH independent, specific gravity is 1.005-1.010 and urine <100-200 mOsm/kg. If ADH dependent, then urine >200-300 mOsm/kg.
6. ADH independent causes: Psychogenic (primary) polydipsia; renal failure (can’t get rid of water); If low solute intake like “tea and toast”, or beer potomania → not enough solute intake to make urine and excrete free water
7. If tea and toast diet or beer drinker eating 100 mmol/day solute and minimum urinary concentration of 50 mmol/L, then max urine output is 100 mmol/day divided by 50 mmol/L = 2 L/day maximum water excretion. If this person ingests >2 L/day then sodium will fall.
8. Psychogenic polydipsia: Average person with normal renal function must drink more than 18L per day to drop sodium, or more than 2L in an hour (e.g. fraternity hazing).
9. Acute renal failure or CKD: Not producing urine, thus water intake can easily exceed output. Dialysis patients hyponatremic predialysis.
10. SIADH: Diagnosis of exclusion. Urine osmolality >300 mmol/L. Check thyroid panel, cortisol. Patients have very low urine outputs. ADH dramatically lowers water excretion → thus, water intake easily exceeds water output. Often transient and due to stressors e.g. lung disease, surgery, trauma. If persistent, then look for causes like CNS or lung disease, and consider imaging. Treatment is fluid restriction, increased solute load (with salt tabs, or Ure-Na), and low dose loop diuretic (blunts action of ADH by altering medullary concentration gradient for water).
11. Meds that cause SIADH: SSRIs, anti-seizure medications, sulfonylureas, opioid narcotics
12. Urine sodium is low in volume depletion, heart failure, and cirrhosis. If on diuretic, then urine sodium falsely elevated.
13. Uric acid: In cases of decreased renal perfusion (e.g. heart failure and hypovolemia) uric acid increases. In SIADH uric acid is suppressed and drops below normal.
14. Vaptans: Antagonize action of ADH in the kidney. Risk for liver toxicity/acute hepatic failure.
15. Rate of fluid correction: If severe and symptomatic hyponatremia (usually Na+ <115), then consider DDAVP clamp (administration of ADH) with IV hypertonic saline. Goal 5 mEq rise in sodium immediately and 10 mEq in first 24 hours. Should be done in ICU. If mild and asymptomatic hyponatremia, then goal 6 mEq rise in sodium per day (Max is 12 per day or 0.5mEq per hour). Shooting for 6 mEq gives a buffer.

Goal: Listeners will recall the pathophysiology of hyponatremia and develop a systematized approach to identifying the type and cause of hyponatremia, as well as how to safely manage hyponatremia.

Learning objectives:
By the end of this podcast listeners will:

1. Differentiate true and false hyponatremia
2. Recall the pathophysiology true and false hyponatremia
3. Interpret blood and urine tests to identify the cause of hyponatremia
4. Recall the limitations of volume status exam
5. List ADH dependent causes of hyponatremia
6. List ADH independent causes of hyponatremia
7. Explain the pathophysiology of beer drinker’s potomania, “tea and toast”
8. Utilize uric acid to differentiate SIADH other causes of hyponatremia
9. Employ basic therapy for SIADH
10. Recall safe rates of correction in hyponatremia
11. Become familiar with the concept of a DDAVP clamp

Disclosures:
Dr. Topf’s disclosures as listed on his blog Precious Bodily Fluids: “I am on the speakers bureau for Astute Medical. I have an ownership stake in four Davita run dialysis clinics and one vascular access center. Astellas paid for my trip to Australia (Feb ’15) for me to speak at one meeting and three hospitals. Takeda Oncology made a donation to MM4MM the program that is taking me to Mount Everest in 2018.”

Time Stamps
00:00 Intro
03:00 Guest interview
06:45 Pick of the week w/Dr. Topf
15:50 Clinical case of hyponatremia
17:18 False hyponatremia normal osmolality
19:04 False hyponatremia high osmolality
20:06 Understanding why osmolality matters
22:58 Workup false hyponatremia
24:15 Recap of discussion so far
25:10 ADH dependent vs independent hyponatremia
26:30 Psychogenic polydipsia
28:45 Renal failure and hyponatremia
29:33 Tea and toast, and Beer Drinker’s potomania
34:42 ADH dependent hyponatremia
37:45 Volume versus osmolality
39:30 Volume status exam
44:44 Additional testing with urine lytes and uric acid
47:00 Treatment for SIADH
52:12 Discussion of the vaptans
57:51 Additional testing in SIADH
62:20 When to admit patient for hyponatremia
63:29 Clinical case of hyponatremia complications
68:26 Fluids and rate of correction
73:06 DDAVP clamp
76:00 Moderate hyponatremia
78:05 Diuretic dosing DOES matter!
81:29 Loop diuretics for SIADH
83:55 Take home points
86:55 Outro

Links from the show:

1. #VisualAbstracts (Twitter)
2. Tartine (cookbook) by Elizabeth M. Prueitt
3. I Hate You, Don’t Leave Me (book) by Hal Strauss
4. Intentional Parenting (book) by Sissy Goff
5. Mindset (book) by Carol Dweck
6. 8.0 Bit techno – The Curbsiders Theme Song by Stuart Kent Brigham
7. Precious Bodily Fluids: Musing of a Salt Whisperer blog by Dr. Joel Topf
8. Check out @kidney_boy on Twitter Dr. Topf’s feed
9. Free PDF of The Fluid, Electrolyte And Acid-base Companion by Sarah Faubel and Joel Topf
10. Evidence Based Physical Diagnosis (book) by Steve McGee
11. Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med 1987.
12. Urea-Na pills for hyponatremia
13. SALT 1 and SALT2  trials of tolvaptan for hyponatremia NEJM Robert Schrier
14. TEMPO 3:4 Trial ADPKD Liver toxicity NEJM 2012
15. Clinical practice guideline on diagnosis and treatment of hyponatraemia Eur J Endo 2014