Disorders of water and sodium homeostasis Prof A. Pomeranz 2017
Pediatric (Nephrology) Tool Box Disorders of water and sodium homeostasis
Pediatric Nephrology Tool Box Hyponatremiaand and Hypernatremia = Hospital outpatient clinic
How to interpret the tests? Serum Osmolality Can differentiate between true hyponatremia, pseudohyponatremia and hypertonic hyponatremia Urine Osmolality Can differentiate between primary polydipsiaand impaired free water excretion Urine Sodium concentration Can differentiate between hypovolemia hyponatremia and SIADH Assess volume status
Hyponatremiaand Hypernatremia
Hyponatremia Defined as sodium concentration < 135 meq/l Generally considered a disorder of wateras opposed to disorder of salt Results from increased water retention Normal physiologic measures allow a person to excrete up to 10 liters of water per day which protects against hyponatremia Thus, in most cases, some impairment of renal excretion of water is present
Causes Normal ADH response to low sodium is to be suppressed to allow maximally dilute urine to be excreted thereby raising serum sodium level Psuedohyponatremia High blood sugar (DKA) or protein level (triglycerides, multiple myeloma) can cause falsely depressed sodium levels Causes of Hyponatremiacan be classified based on either volume status or ADH level Hypovolemic, Euvolemic or Hypervolemic ADH inappropriately elevated or appropriately suppressed
ADH suppresion Conditions which ADH is suppressed Primary Polydipsia Low dietary solute intake Tea and Toast syndrome or Beer Potomania Advanced Renal Failure
ADH elevation Conditions which ADH is elevated Volume Depletion True volume depletion (i.e. bleeding) Effective circulating volume depletion (i.e. heart failure, NS and cirrhosis) Exercised induced hyponatremia Thiazide Diuretics Adrenal insufficiency SIADH
First step in Assessment: Are symptoms present? Hyponatremia can be asymptomatic and found by routine lab testing It may present with mild symptoms such as nausea and malaise (earliest) or headache and lethargy Or it may present with more severe symptoms such as seizures, coma or respiratory arrest
Presentation determines if immediate action is needed If severe symptoms are present, hypertonic saline needs to be administered to prevent further decline If severe symptoms are not present, can start by initiating fluid restriction and determining cause of hyponatremia Oral fluid restriction is good first step as it will prevent further drop in sodium NOTE: This does not mean that you can t give isotonic fluids to someone who is truly volume depleted
WHAT NEXT? With no severe symptoms and fluid restriction started, next step is to assess volume status to help determine cause Hypovolemic urine output, dry mucous membranes, sunken eyes Euvolemic normal appearing Hypervolemic Edema, past medical history, Jaundice (cirrhosis), NS, S3 (CHF)
Volume status helps predict cause Hypovolemia True Volume Depletion Adrenal insufficiency Thiazide overdose Exercised induced hyponatremia Euvolemia SIADH Primary Polydipsia Hypervolemia Cirrhosis, NS and CHF
Workup for Hyponatremia 3 mandatory lab tests (blood) Serum Osmolality Urine Osmolality Urine Sodium Concentration Additional labs depending on clinical suspicion TSH, cortisol(hypothryoidism or Adrenal insufficiency) Albumin, triglycerides and Serum Protein Electrophoresis (SPEP) (psuedohyponatremia).
How to interpret the tests? Serum Osmolality Can differentiate between true hyponatremia, pseudohyponatremiaand hypertonic hyponatremia Urine Osmolality Can differentiate between primary polydipsia and impaired free water excretion Urine Sodium concentration Can differentiate between hypovolemia hyponatremia and SIADH Assess volume status (help to determine the cause)
Additional Tests TSH high in hypothyroidism Cortisol low in adrenal insufficiency, though may be inappropriately normal in infection/stressful state, therefore should get Corti-Stim test to confirm Head CT and Chest Xray May see evidence of cerebral salt wasting or pulmonary disease which can both cause hyponatremia
And of course the not so common Iatrogenic infusion of hypotonic fluids ( Surgeon sign ) Ecstasy use increased water intake with inappropriate ADH secretion Underlying infections NSIAD Nephrogenic syndrome of inappropriate antidiuresis Hereditary disorder that presents with low sodium levels in newborn males with undetectable ADH levels (gain of function of the vasopressin receptor (V2R gene)) Reset Osmostat Occurs in children and pregnancy where regulated sodium set point is lowered
SIADH: Important concept to understand Caused by various etiologies CNS disease tumor, infection, CVA, Subarachnoid hemorrhage (SAH) Pulmonary disease TB, pneumonia, positive pressure ventilation Cancer Lung, pancreas, thymoma, ovary, lymphoma Drugs NSAIDs, SSRIs, diuretics, TCAs Surgery Postoperative Idopathic most common
Main diagnostic criteria for SIADH Clinical Euvolemia Hypotonic Hyponatremia Normal hepatic, renal and cardiac function Normal thyroid and adrenal function Urine osmolality greater than 100 mosm/kg though generally greater than 400-500 mosm/kg in setting of low serum osmolality (inappropriate) Urine sodium level greater than 20 meq/l
Treatment is based on symptoms Patients with serum sodium above 120 are generally asymptomatic Symptoms tend to occur at serum sodium levels lower than 120 or when a rapid decline in sodium levels occur Patients can have mild symptoms at sodium concentrations of 110-115 meq/l when this level is reached gradually
Severe symptoms present As stated earlier, symptoms dictate treatment If severe symptoms are present, starting bolus of 1ml/Kg (70-100 ml) of 3% hypertonic saline (5meq/ml, which generally raise serum sodium level by 2-3 meq/l) Goals for correction: 1.5 to 2 meq/l per hour for first 3-4 hours until symptoms resolve Increase by no more than 10 meq/l in first 24 hrs Increase by no more than 18 meq/l in first 48 hrs
What if little to no symptoms are present? Oral fluid restriction is the first step NOTE: This only pertains to oral fluid, isotonic IV fluids do not count towards fluid intake If volume depletion is present, isotonic (0.9%) saline can be given intravenously Careful monitoring should be used whether symptoms are present or not Serum sodium levels should be drawn every 4-6 hours or more frequently if hypertonic saline is used
Formulas that may help: How much sodium does the patient need? Sodium deficit = Total body water x (desired Na actual Na) Total body water is estimated as lean body weight x 0.6 for children (0.5 for women or 0.6 for men)
How about an example: 30 kg girl with sodium level of 116 meq/l How much sodium will bring him up to 124 in the next 24 hours? Sodium needed = 0.6 x 30 x (124-116) = 144 meq/l Hypertonic saline contains 500 meq/l of sodium Normal saline contains 154 meq/l of sodium
Example (continued) The patient needs 144 meqin next 24 hours That averages to 6 meqper hour (6x24=144) However, this will only raise the serum sodium by 0.33 per hour therefore, increasing the rate 30 ml to 45 ml will produce the desired rate of serum sodium increase of 1.0 to 1.5 meqper hour until symptoms resolve
What if the sodium increases too fast? The dreaded complication of increasing sodium too fast is Central Pontine Myelinolysis which is a form of osmotic demyelination Symptoms generally occur 2-6 days after elevation of sodium and usually either irreversible or only partially reversible Symptoms include: dysarthria, dysphagia, paraparesis, quadriparesis, lethargy, coma or even seizures
Risk Factors for demyelination Rate of correction over 24 hours more important than rate of correction in any one particular hour More common if sodium increases by more than 20 meq/l in 24 hours Very uncommon if sodium increases by 12 meq/l or less in 24 hours CT but preferably MRI to diagnose demyelinationif suspected, though imaging studies may not be positive for up to 4 weeks after initial correction
Treatment Options for demyelination CPM (Central Pontine Myelinolysis) is associated with poor prognosis Prevention is key Small studies have shown that plasmapharesisdone immediately after diagnosis may improve clinical outcomes
Summary of Hyponatremia Hyponatremia has variety of causes Treatment is based on symptoms Severe symptoms = Hypertonic Saline Mild or no symptoms = Fluid restriction Overcorrection, more than 12 meqincrease in 24 hours must be avoided with monitoring Serum Osmolality, Urine Osmolality and Urine sodium concentration are initial tests to order
Moving on to Hypernatremia Produced by either administration of hypertonic fluids or much more frequently, loss of thirst Because of extremely efficient regulatory mechanisms such as ADH and thirst, hypernatremiagenerally occurs only in people with prolonged lack of thirst mechanism Patients with loss of ADH (Diabetes Insipidus) usually can compensate with increased fluid intake
Causes of Hypernatremia Insensible and sweat losses GI losses Diabetes Insipidus(both central and nephrogenic) Osmotic Diuresis DKA or hyperglycemic hyperosmolar nonketotic state (HHNK) Hypothalamic lesions which affect thirst function Causes include tumors, granulomatous diseases or vascular disease Sodium Overload Infusion of Hypertonic sodium bicarbonate for metabolic acidosis
Symptoms of Hypernatremia Initial symptoms include lethargy, weakness and irritability Can progress to twitching, seizures or coma Resulting decrease in brain volume can lead to rupture of cerebral veins leading to hemorrhage Severe symptoms usually occur with rapid increase to sodium concentration of 158 meq or more Sodium concentration greater than 180 meqare associated with high mortality
Diagnosis of Hypernatremia Same labs as workup for hyponatremia: Serum osmolality, urine osmolality and urine sodium Urine sodium should be lower than 25 meq/l if and water and volume loss are cause. It can be greater than 100 meq/l when hypertonic solutions are infused or ingested If urine osmolalityis lower than serum osmolalitythen DI is present Administration of DDAVP will differentiate Urine osmolality will increase in central DI, no response in nephrogenic DI
Treatment of Hypernatremia First, calculate water deficit Water deficit = CBW x ((plasma Na/desired Na level)-1) CBW = current body water assumed to be 60% of body weight in children (50% of body weight in men and 40% in women) Sample (calculation): 30 kg girl with 168 meq/l How much water will it take to reduce her sodium to 140 meq/l
Calculation continued Water deficit = 0.6 x 30 ([168/140]-1) = 3.6 L But how fast should I correct it? Same as hyponatremia, sodium should not be lowered by more than 12 meq/l in 24 hours Overcorrection can lead to cerebral edema which can lead to encephalopathy, seizures or death So what does that mean for our patient? The 3.6 L which will lower the sodium level by 28 should be given over 56-60 hours, or at a rate of 60 ml/hr Typical fluids given in form of D5 water
Summary of Hypernatremia Loss of thirst usually has to occur to produce hypernatremia Rate of correction same as hyponatremia D5 water infusion is typically used to lower sodium level Same diagnostic labs used: Serum osmolality, Urine osmolalityand Urine sodium Beware of overcorrection as cerebral edema may develop
Questions?