hyponatremia

harrison 19th

1. SODIUM METABOLISM Dr Kaleem Ahmad JR III Pulmonary Medicine

2. Water is the most abundant constituent in the body comprising approximately 50% of body weight in women and 60% in men. 55-75% is intracellular (intracellular fluid [ICF] ) and 25-45% is extracellular (extracellular fluid [ECF] ) . The ECF is further subdivided into intravascular (plasma water) and extravascular (interstitial) spaces in a ratio of 1 :3. The solute or particle concentration of a fluid is known as its osmolality expressed as milliosmoles per kilogram of water ( mOsm /kg) . The major ECF particles are Na+ and its accompanying anions Cl- and HCO 3 - whereas K+ and organic phosphate esters (ATP， creatinine phosphate and phospholipids) are the predominant ICF osmoles . ..

3. Vasopressin secretion water ingestion and renal water transport collaborate to maintain human body fluid osmolality between 280 and 295 mOsm /kg

4. SODIUM DISORDER Disorders of serum Na+ concentration are caused by abnormalities in water homeostasis leading to changes in the relative ratio of Na+ to body water. Water intake and circulating AVP constitute the two key. 85-90% of body Na+ is extracellular and the ECF volume (ECFV) is a function of total-body Na+ content 99.6% filtered Na+ is reabsorbed in kidney

5. HYPONATREMIA Hyponatremia is defined as a plasma Na+ concentration < 135 m.mol Very common disorder. Occurring in up to 22% of hospitalized patients. Depending on clinical history and volume status divided into Hypovolemic Hyponatremia Euvolumic Hyponatremia Hypervolemic Hyponatremia

6. HYPOVOLUMIC HYPONATREMIA Characterized by true deficiency of both Na+ and water Increase in circulating AVP level. Increased free water intake. GI loss (e.g. vomiting diarrhea tube drainage) Insensible loss (sweating, burns) Primary adrenal insufficiency Salt-losing nephropathies Phase of acute tubular necrosis. Thiazide diuretics

7. Glycosuria , Ketonuria , Bicarbonaturia Cerebral salt wasting

8. Hypovolumia Total body water decrease Total body sodium much decrease U Na GREATER THAN 20 Renal losses Diuretic excess Mineralocorticoides deficiency Salt losing deficiency Bicarbonaturia with renal tubular acidosis and metabolic alkalosis Ketonuria , osmotic diuresis Cerebral salt wasting syndrome U Na less than 20 Extra renal loss es Vomiting Diarrhea Third spacing of fluid Burns Pancreatitis Trauma

9. HYPERVOLUMIC HYPONATREMIA Patients with hypervolemic hyponatremia develop an increase in total-body Na+Cl - that is accompanied by a proportionately greater increase in total body water leading to a reduced plasma Na+ concentration:- Congestive heart failure [CHF] Cirrhosis Nephrotic syndrome Acute or chronic renal failure， Characterized by development of pitting edema (about 5 litres of excess water need to be retained to produce definite pitting edema in an avereged sized adult)

10. Hypervolumia Total body water much increase Total body sodium increase U Na greater than 20 Acute or chronic renal failure U Na less than 20 Nephrotic syndrome Cirrhosis Cardiac failure

11. EUVOLEMIC HYPONATREMIA Secondary adrenal insufficiency due to pituitary disease; Moderate to severe hypothyroidism, with correction after achieving euthyroid state. Syndrome of inappropriate antidiuresis (SIAD)

12. URINARY SODIUM GREATER THAN 20 Glucocorticoides deficiency Hypothyroidism Stress Drugs Syndrome of inappropriate antidiuretic harmone secretion (SIAD)

13. LOW SOLUTE INTAKE AND HYPONATREMIA Alcoholics (beer potomania ) Extreme vegetarian diets Tea toast diet PSEUDOHYPONATREMIA Expansion of extracellular fluid with isotonic fluids that do not contain Na There is no transcellular shift of water but the [Na+] decreases e.g. Hypertriglyceridemia Hyperproteinemia ( as in Multiple Myeloma) Rise in plasma lipids of 4.6 g/L or plasma protein concentrations greater than 10 g/ dL will decrease the sodium concentration by approximately 1 mEq /L.

14. Clinical diagnosis Symptoms due to hyponatremia depends on its severity and the rate at which it evolves. The symptoms primarily neurologic, due to development of cerebral edema within a rigid skull. Symptoms are : Headache, lethargy, Confusion, gait disorder, Nausea, vomiting In severe hyponatremia seizures, coma, brain-stem herniation , permanent brain damage or death. Hypo- natremia < 135 mmol /lit mild < 130 mmol /lit moderate < 120 mmol /lit severe

15. Severe and Acute Hyponatremia Severe hyponatremia (Na+<120meq/l) and rapid development of hyponatremia (<48 hours) A key complication is normocapnic or hypercapnic respiratory failure. Normocapnic respiratory failure is noncardiogenic , neurogenic pulmonary edema , with a normal pulmonary capillary wedge pressure.

16. Causes of acute hyponatremia Iatrogenic Postoperative premenopausal women Hypotonic fluids with cause of ↑ vasopressin Glycine irrigation: TURP, uterine surgery Colonoscopy preparation Recent institution of thiazides Polydipsia Exercise induced Multifactorial , e.g., thiazide and polydipsia

17. Persistent chronic hyponatremia Pathogenesis: Efflux of organic osmolytes ( creatine , betaine , glutamate, myo -inositol , and taurine ) from brain cells,decrease intracellular osmolality decrease water entry.(compensation) Complete within 48 h , time period defines chronic hyponatremia. Symptom: Vomiting, nausea Confusion and seizures Subtle gait and cognitive defects Increases risk of falls Risk of bony fractures (hyponatremia associated reduction in bone density)

18. Diagnostic Evaluation of Hyponatremia Clinical assessment Underlying cause Detailed drug history Drugs that stimulate release of AVP or enhance its action on vasopressin V2 receptor Chlorpropamide Cyclophosphamide SSRls NSAIDS Tricyclic antidepressants AVP analogues Clofibrate Desmopressin Carbamazepine Vasopressin Nicotine Ifosfamide Antipsychotic drugs MDMA“ecstasy ” (3,4-methylenedioxymethamphetamine)

19. Multifactorial , Consider all the possible causes In case of true salt and water depletion Dehydration Shock Thrist Severa cramps in the legs thigh and abdomen Metabolic alkalosis in case of vomiting and metabolic acidosis in diarrhoea .

20. Features of low volume status Diminished skinTurgor Dry oral mucous membranes More reliable signs of hypovolemia Decreased jugular venous pressure (JVP) Orthostatic tachycardia (an increase of > 15-20 beats/min upon standing) Orthostatic hypotension (a >10-20 mmHg drop in blood pressure on standing) . More severe fluid loss leads to hypovolemic shock Patients may exhibit peripheral cyanosis cold Extremities oliguria and altered mental status

21. LABORATORY TEST Serum osmolality To exclude pseudohyponatremia which is defined as the coexistence of hyponatremia with a normal or increased plasma tonicity. In hyponatremia plasma osmolality is generally less than 275 mOsm /kg Serum Na K Hyperkalemia may suggest adrenal insufficiency or hypoaldosteronism Urine Na K To differentiate various causes of water loss

22. Serum glucose Plasma Na+ concentration falls by 1.6-2.4 mM for every 100 mg/ dL increase in glucose due to glucose-induced water efflux from cells. Serum uric acid Patients with SIAD-type physiology will typically be hypouricemic (serum uric acid <4 mg/ dL )， Volume-depleted patients will often be hyperuricemic .

23. Urine Osmolality A urine osmolality <100 mOsm /kg is suggestive of polydipsia Urine osmolality >400 mOsm /kg indicates that AVP excess is playing a more dominant role Whereas intermediate values are more consistent with multifactorial pathophysiology Serum protein & lipid profile To exclude causes of pseudo-hyponatremia

24. THYROID， ADRENAL， AND PITUITARY FUNCTION Hypothyroidism and secondary adrenal failure due to pituitary insufficiency are important causes of euvolemic hyponatremia. Whereas primary adrenal failure causes hypovolemic hyponatremia . RADIOLOGY Chest XRay - PA view CT of Thorax & Brain

25. MANAGEMENT Three major considerations to guide therapy for hyponatremia. 1. Severity of symptoms 2. Risk for ODS (osmotic demylenation syndrome) It occurs, if plasma Na+ concentration is corrected, by > 8-10 mM within the first 24h and/or by >18 mM within the first 48h. 3. Highly unpredictable response Once the urgency in correcting the plasma Na + concentration has been established and appropriate therapy instituted, the focus should be on treatment or withdrawal of the underlying cause .

26. Hypovolemic hyponatremia will respond to intravenous hydration with isotonic normal saline with a rapid reduction in circulating AVP and a brisk water diuresis Hypervolemic hyponatremia due to CHF will often respond to improved therapy of the underlying cardiomyopathy e.g. following the institution or intensification of angiotensin -converting enzyme (ACE) inhibiter. Finally patients with hyponatremia due to beer potomania and low solute intake will respond very rapidly to intravenous saline and the resumption of a normal diet. Notably patients with beer potomania have a very high risk of developing ODS due to the associated hypokalemia alcoholism malnutrition and high risk of overcorrecting the plasma Na+ concentration

27. Water deprivation has long been cornerstone of the therapy of chronic hyponatremia The urine-to-plasma electrolyte ratio , (urinary [Na+]+[K+]/plasma [Na+]) can be exploited as a quick indicator of electrolyte-free water excretion Patients with a ratio of >1 should be more aggressively restricted (<500 mL /d)， those with a ratio of ~1 should be restricted to 500-700 mL /d and those with a ratio <1 should be restricted to <1L/d Hypokalemia should be corrected.

28. PHARMACOTHERAPY Many patients with SIAD respond to combined therapy with oral furose mide 20 mg twice a day and oral salt tablets. Demeclocycline AVP antagonists (vaptans ) are highly effective in SIAD and in hypervolemic hyponatremia due to heart failure or cirrhosis increasing plasma Na+ concentration due to their aquarectic effects (augmentation of free water clearance) . Antagonize V 2 AVP recepter

29. Treatment of acute symptomatic hyponatremia should include hypertonic 3% saline (513 mM ) to acutely increase plasma Na+ concentration by 1-2 mM /h to a total of 4-6 mM . The traditional approach to calculate Na+ deficit = 0.6 x body weight x (target plasmaNa + concentration - starting plasma Na+ concentration) ， Followed by a calculation of the required rate. A widely used formula is the Adrogue-Madias formula. Change in serum Na+ with infusing solution ( mM /l/h) = [ infusate (Na + K)]-serum Na/ (total body water +1)

30. Plasma Na+ concentration should be monitored every 2-4 h during treatment. In patients with severe symptomatic hyponatremia, the rate of sodium correction should be 6 to 12 mEq per L in the first 24 hours and 18 mEq per L or less in 48 hours. A bolus of 100 to 150 mL of hypertonic 3% saline can be given to correct severe hyponatremia. Chronic hypernatremia should be corrected at a rate of 0.5 mEq per L per hour , with a maximum change of 8 to 10 mEq per L in a 24-hour period.

31. WE MUST KNOW FLUID COMPOSITION COMMONLY USED: 154meq/l in 0.9%NS 513meq/l in 3%NS 77meq/l in 0.45%NS zero meq /l in D5W, D10W, D25W

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33. HYPERNATREMIA Hypernatremia is defined as an increase in the plasma Na+concentration to>145mM. less common than hyponattremiai Mortality rate as high as 40% is reported with hypernatremia , though it is uncommonly identified as the primary cause of death. ETIOLOGY Usually the result of a combined water and electrolyte deficit with losses of water in excess of Na+. Elderly individuals and neonates are more susceptible. hypernatremia may rarely have a central defect in hypothalamic osmoreceptor function， with a mixture of both decreased thirst and reduced A VP secretion.

34. causea Insensible losses fever exercise heat exposure severe burns mechanicalventilation . iatrogenic administration of excess Na+ can be causative， for example after IV administration of excessive hypertonic Na+ -Cl- or Na+ -HC03- Diarrhea is in turn the most common gastrointestinal cause of hypernatremia . Notably osmotic diarrhea and viral gastroenteritides typically generate stools with Na+ and K+ < 1 00 mM ， thus leading to water loss and hypernatremia . In contrast secretory diarrhea typically results in isotonic stool and thus hypovolemia with or without hypovolemic hyponatremia.

35. osmotic diuresis secondary to hyperglycemia， excess urea， postobstructive diuresis ， or mannitol ; diabetes insipidus (DI) Central Nephrogenic (renal resistance to AVP) Hypercalcemia hypokalemia lithium ifosfamide and several antiviral agents gestational DI ( due to circulating placental protease with vasopressinase activity)

36. linical Features Hypernatremia increases osmolality of the ECF generating an osmotic gradient between the ECF and ICF, an eff1ux of intracellular water, and cellular shrinkage. predominantly neurologic. Altered mental status is the most frequent manifestation ranging from mild confusion and lethargy to deep coma. The sudden shrinkage of brain cells in acute hypernatremia may lead to parenchymal or subarachnoid hemorrhages and/or subdural hematomas. hypernatremic rhabdomyolysis (Osmotic damage to muscle membranes)

37. Diagnostic Approach history should focus on presence or absence of thirst polyuria extrarenal source for water loss The physical examination should include a detailed neurologic exam and an assessment of the ECF volume status.

38. Laboratory investigation measurement of serum ( >295 mOsm /kg ) and urine osmolality (>800 mOsm /kg) urine electrolytes circulating AVP level Urinary and serum glucose a excretion of low volumes (<500 mL!d ) of maximally concentrated urine， i.e.， urine with osmolality >800 mOsm /kg; water loss is primarily responsible for the generation of hypernatremia

39. NEPHROGENIC VERSUS CENTRAL DIABETES INSIPIDUS Patients with NDI will fail to respond to DDAVP with a urine osmolality that increases by<50% or < 150 mOsm /kg from baseline in combination with a normal or high circulating AVP level . patients with central DI will respond to DDAVP， with a reduced circulating AVP level.

40. The underlying cause of hypernatremia should be identified and corrected，be it drugs，hyperglycemia，hypercalcemia，hypokalemia，or diarrhea. It is imperative to correct hypernatremia slowly to avoid cerebral edema， typically replacing the calculated free water deficit over 48 h . Notably， the plasma Na+ concentration should be corrected by no more than 10 mM /d， which may take longer than 48 h in patients with severe hypernatremia (> 160 mM ). A rare exception is patients with acute hypernatremia (<48 h) due to sodium loading who can safely be corrected rapidly at a rate of 1 mM /h. Water should ideally be administered by mouth or by nasogastric tube

41. patients can receive free water in dextrose-containin g IV solutions， such as 5% dextrose (DsW); blood glucose should be monitored it may be appropriate to initially treat with hypotonic saline solu tions (1/4or1/2 normal saline); normal saline is usualy inappropriate in the absence of very severe hypernatremia where normal saline is proportionally more hypotonic relative to plasma or frank

42. Intravenous intranasal or oral DDAVP. Amiloride (2.5-10 mg/d) Thiazides NSAIDs

43. MANAGEMENT OF HVPERNATREMIA Water Deficit 1 . Estimate tota l-body water ( TßW ): 50% of body weight in women and 60% in men 2. Ca lculate free-water deficit [(N 扩 1 40)/ 1 40} x TßW 3. Administer deficit over 48-72 h without decrease in plasma Na+ concentration by > 1 0 mM /24 h Ongoing Water Losses 4. Ca lculate free-water clearance， C，H，o r u. + U I C H_Q = V x 门一半一 - 一 --'- 1 1 P J .'ò where V is urinary 、 口lume ， UNe is urinary [ Na可 ， UK is urinary [ K可 ， and PNe is plasma [Na 吁 Insensible Losses 5. - 1 0 mL /kg per day: less if、巳ntilated ， more if febril巳 Total 6. Add com ponents to determine water de有ζit and ongoing water loss; ζorrect the water de白cit over 48-72 h and replace daily water loss. Avoid correction of plasma [ Na+J by > 1 0 mM /d