Mona D. Doshi, MD Director, Renal Transplant Program Associate Professor Wayne State University School of Medicine Disorders of water & salt balance
Agenda • Clinical relevance of hyponatremia • Water handling • Pathophysiology • Approach • Clinical Vignettes • Treatment
Body Fluid Compartments Total Body Water=0.60*body weight 1/3 Extra-Cellular Fluid 1/4th plasma 2/3 Intra-Cellular Fluid
In a 70 kg man • TBW • ICF • ECF • Plasma Volume
In a 70 kg man • TBW=0.6*70 kg=42kg or 42 Liters • ICF=2/3*42=28 Liters • ECF=1/3*42=14 Liters • Plasma Volume=1/4*14=3.5 Liters Water moves freely from one compartment to another to maintain similar osmolality in each compartment
What is Osmolality? • Osmolality is number of solutes per kg of water • # of solute =wt/gm mol wt of the solute • POSM=2Na + Glc/18 +BUN/2.8 • Normal: 285-290mOsm/kg • Effective POSM=2Na
Instantaneous regulation of osm ECF Water ICF ECF ICF Water Na=160 Osm=320 Osm=280 Na=120 Osm=240 Osm=280 ICF expands with hyponatremia ICF shrinks with hypernatremia Disturbance in osmolality Change Cell Volume very harmful to brain cells & can affect cellular function
What does sodium concentration tell you? 1 Litre of water 140 meq of sodium 1/2 Litre of water 70 meq of sodium SERUM SODIUM TELLS YOU RATIO OF SALT TO WATER
Clinically….. HYPONATREMIA HYPERNATREMIA Gain of sodium alone Hard to eat, unless TPN Loss of too much water • Loss of sodium alone • Hard • Gain of too much water • Loss of sodium + water • Replacing with water 99% of hypo- or hyper- natremia disorders are due to water balance
Water balance • Water intake=Water losses • Maintain serum osm of 285-290 mOsm/kg • Ability of the kidney to excrete dilute and concentrated urine is enormous • Water loading can have the kidney dilute urine and excrete up to 25 liters per day • And when water deprivation 0.5 liter per day
Following are needed to maintain water balance • GFR • Loop of Henle • Collecting tubules • Anti-Diuretic Hormone (Vasopressin)
Vasopressin • Stimuli for secretion: • Plasma Osmolality • Posm ↑=ADH ↑=Uosm↑ • Posm ↓=ADH↓=Uosm↓ • Non osmotic stimuli are • Volume depletion-diarrhea • Effective volume depletion-CHF DO NOT WANT TO DIE WITH PERFECT OSM
Comparison of ADH secretion-Osmotic and volume stimuli True decrease in effective volume can cause much higher vasopressin levels than osmolar changes
Hyponatremia i.e. S. Na <135 meq/L • Defined as serum sodium < 135 meq/L • Due to net gain of water • Plasma Osmolality: POSM = 2 (Na) + glucose + urea Normal = 2 (140) + 5 + 5 = 290 (275-290 mM) Associated with low POSM
Too much water in ECF+ICF POSM is low Represents relative excessive water than sodium • ↑ Water Intake • Volume depletion-both salt & water are lost but replaced by hypotonic fluids • Habit-Primary polydipsia • ↑ Water Re-absorption ( due to excessive ADH) • Appropriate-Volume depletion low volume>>>osm • Inappropriate-SIADH
Gain of water in ECF only POSM is high • Shift of water from ICF to ECF compartment with Hyperglycemia ECF Na= Glc=600 BUN=10 Posm=↑ ICF ICFosm=280 Water movement For every 100mg/dL increase in Glc, sodium decreases by1.6meq/L
Gain of water in ECF only POSM is normal • Addition of non-sodium, isotonic solution like Glycine or sorbitol ECF Na=140 Glc=90 BUN=10 Posm=280 ECF ICFosm=280 NO WATER MOVT 1 L of glycine
Approach Check Serum Osmolality History & Assess volume status Check for ADH Urine Osmolality Need to r/o thyroid, adrenal & renal insufficiency
Approach Volume replete Volume deplete Is the ADH appropriate or inappropriate? NEED TO EXAMINE THE PATIENT
True Volume Depletion • History of GI loss, diuretic use, blood loss • Examination: • low BP • Increased HR • Dry mucous membranes
Effective Volume Depletion • History: heart failure, liver disease, nephrotic syndrome • Exam: • Low BP • Increased heart rate • Edema, pleural effusions, ascites
Euvolemic- SIADH • TOO MUCH ADH IN ABSENCE OF PHYSIOLOGICAL NEED • Intracranial disease • Pulmonary disease • Chest wall disorder (surgery, VZV) • Severe pain or emotional distress • Severe N/V • Ectopic ADH: Small cell lung cancer • Drugs: opiods, carbamazepine, chlorpropamide, cyclophosphamide, cisplatin, vincristine, vinblastine, amitriptylline, SSRI, neuroleptics, bromocriptine, ecstasy (MDMA)
Case 1: • A 30 year old woman is admitted for an increase in edema and worsening jaundice. She is a known alcoholic and has had several admissions for jaundice and ascites. She stopped taking her diuretic approximately 10 days ago. • Physical examination: blood pressure 80/60, heart rate 76 supine. No orthostatic change in BP noted. She has icteric sclera, ascites, sacral and pedal edema. Her liver span is 10 cm. • Na 125, K 3.2, HCO3 28, BUN 5, Cr 0.8 & Gluc 80 • Bilirubin 12 mg/dL, albumin 2.5 g/dL • Usodium 1 meq/L U osm 900 osm/kg water
Approach-Case 1 • POSM = 2(125) + 80/18 + 5/2.8=256 • True OR hypo-osmolar/hyponatremia • What is her volume status? • What is her effective circulatory volume? • With so much edema, why is her UNa low?
Case 1 • What is mechanism of hyponatremia? • Can you tell if ADH is being secreted? How? • Why is her ADH the way it is?
Approach-Case 1 • What is her volume status? hypervolemic • What is her effective circulatory volume? Low from third spacing, low alb & vasodilation • With so much edema, why is her UNa low? Effective circulatory volume is low and therefore kidney hangs on to salt.
Case 1 • What is mechanism of hyponatremia? Low effective circulatory volume leading to renal retention of water, daily water intake > water loss via urine • Can you tell if ADH is being secreted? How? Uosm > Sosm • Why is her ADH the way it is? Low circulatory volume
Case 2 • 73 y/o lady with BP 170/90 was started on thiazide diuretic. She returns to clinic c/o dryness of mouth, weakness & dizziness. • Sitting her BP is 130/90 and P is 90/min. Standing her BP is 100/60 and P 120/min. Mucous membranes are dry. • Labs: Na 107, K 2, BUN 20, Cr 0.9, glc 108, Sosm 220 Una 3, Uosm 880
Approach-Case 2 • POSM = 2(107) + 108/18 + 20/2.8=227 • True OR hypo-osmolar/hyponatremia • What is her volume status? • Why is her UNa low?
Case 2 • What is mechanism of hyponatremia? • Can you tell if ADH is being secreted? How? • Why is her ADH the way it is?
Approach-Case 2 • What is her volume status? Low • Why is her UNa low? Increased sodium reabsorption via proximal tubules • What is mechanism of hyponatremia? Volume depletion leading to increased water intake via thirst & increased water reabsorption via the kidney to maintain plasma volume. Thiazide diuretic related loss of diluting capacity
Case 2 • Can you tell if ADH is being secreted? How?Uosm>>Sosm • Is the ADH appropriate? Yes
Case 3 • Jake is a 22 y/o man who developed headache 5 days ago. Exam is unremarkable. • Labs: Na 117, K 4.0, BUN 10, Glc 50, Posm 245 • Una 50 mq/L, Uosm 500 mosm/kg
Approach-Case 3 • POSM = 245 • True OR hypo-osmolar/hyponatremia • What is his volume status? • Can you tell if ADH is being secreted? How? • Is the ADH appropriate or inappropriate?
Approach-Case 3 • What is his volume status? Euvolemic • Can you tell if ADH is being secreted? How? Uosm>>Sosm • Is the ADH appropriate or inappropriate? Inappropriate-no osmotic or volume stimuli
Symptoms of Hyponatremia • Related to underlying cause: • Diuretic/ vomiting/diarrhea: dryness of mouth • CHF/NS/ Cirrhosis: swelling of legs, SOB, ascites • Related to low osmolality & increased brain cell volume: • Seizures • Coma • jerks
Treatmtent • Four Issues: • Asmyptomatic vs. symptomatic • acute (within 48 hours) • chronic (>48 hours) • Volume status • Underlying cause
Why does duration & rate matter so much? Takes up to 48 hours
Correction Rate • When do you need to Rx quickly? • Acute (<24h) severe Hyponatremia (< 120 mEq/L) • Prevent brain swelling or Rx brain swelling • Symptomatic Hyponatremia (Seizures, coma, etc.) • Alleviate symptoms • “Quickly”: 3% NS, 1-2 mEq/L/h until: • Symptoms stop • 3-4h elapsed and/or Serum Na has reached 120 mEq/L • Then SLOW down correction to 0.5 mEq/L/h with 0.9% NS or simply fluid restriction. Aim for overall 24h correction to be < 10-12 mEq/L/d to prevent myelinolysis
Rx of asymptomatic hyponatremia • Treat the cause • Fluid restriction & Diuretics in all • Tolvaptan or V2 rec antagonist is now available • EXCEPT, VOLUME DEPLETION
Hypernatremia i.e. S. Na > 145 meq/L • Defined as serum sodium > 145 meq/L • Due to net loss of water • Plasma Osmolality: POSM = 2 (Na) + glucose + urea Normal = 2 (135) + 5 + 5 = 290 (275-290 mM) Associated with high POSM
Too little water in ECF+ICF POSM is high Represents relative less water than sodium • Water Intake • Lack of access to water- Intubated, ICU, NH, babies • Rarely-increased salt: TPN • Water Re-absorption ( due to lack or resistant to ADH) • Lack-Central DI • Corrected with ADH • Resistant-NDI • Not corrected with ADH
Case 1: • 80 year old gentleman is admitted with stroke. He is awaiting swallow study to get allow oral feeding vs. TPN. • Labs: Sodium 150, S. Osm 305, Uosm 600 • What is the cause of hypernatremia
Case 2: • Mr. Case underwent resection of brain tumor. His serum sodium is 160, S osm is 330, Uosm 800 • What is the possible cause? • Lack of free water • Lack of ADH • Resistance to ADH