Hyponatremia and hypernatremia

A BRIEF OVERVIEW OF HYPONATREMIA & HYPERNATREMIA

1. HYPONATREMIA AND HYPERNATREMIA BY DR HASEN ALI MIA 1 st year PGT at NBMCH

2. SODIUM REGULATION:PHYSIOLOGICAL BASIS Most prevalent cation in ECF(normal level of around 135- 145 mmol /L). Intracellular concentration of around 10mmol/L. Responsible for 90% of total osmolality of ECF. Major function of sodium is to maintain ECF volume and thus BP. In normal individuals, the kidney strives to achieve Na +  balance – that is, to have Na +  excretion equal to Na +  ingestion. The long-term control of BP is achieved by the excretion or retention of Na +  (and hence plasma volume) in the kidney.

3. Serum sodium concentration regulation

4. Serum sodium concentration regulation

5. HYPONATREMIA Definition: Plasma Na + concentration <135 m Eq /L. Due to a relative excess of water in relation to sodium. Can result from excessive loss of sodium from excessive sweating, vomiting, diarrhoea, burns, and diuretics. It is a very common disorder, occurring in up to 22% of hospitalized patients. Result of an increase in circulating ADH and/or increased renal sensitivity to ADH, combined with any intake of free water.

6. Patients’ intravascular volume status must be evaluated to understand further the underlying problem leading to abnormalities in sodium physiology. Hyponatremia thus is subdivided diagnostically into three groups, depending on clinical history and volume status : hypovolemic, euvolemic , and hypervolemic .

7. TYPES: I- Hypo- osmolar hyponatremia (true hyponatremia ) Hypovolemic Hyponatremia Euvolemic Hyponatremia Hypervolemic Hyponatremia II- Pseudo hyponatremia Normal Osmolality High Osmolality

8. Hypovolemic Hyponatremia Patient dehydrated; reduction in total body sodium > reduction in total body water. NON RENAL LOSSES ( Urinary Sodium excretion < 20 mEq /L)- Vomiting, Diarrhea, Third space losses, Pancreatitis, Burns. RENAL LOSSES (Urinary Sodium excretion > 20 mEq /L)- The renal causes of hypovolemic hyponatremia share an inappropriate loss of Na + -Cl – in the urine. Volume depletion and an increase in circulating ADH. Causes : Reflux nephropathy, recovery phase of ATN, diuretics,mineralocorticoid deficiency, osmotic diuresis, ketonuria. ria .

9. “Cerebral salt wasting" : Rare cause of hypovolemic hyponatremia, and inappropriate natriuresis in association with intracranial disease. Associated disorders Subarachnoid hemorrhage , traumatic brain injury, craniotomy, encephalitis, and meningitis. Cerebral salt wasting typically responds to aggressive Na + -Cl – repletion.

10. Euvolemic Hyponatremia Patient has a normal store of sodium but an excess of total body water. The most common form seen in hospitalized patients.   The most common cause Inappropriate administration of hypotonic fluid. The syndrome of inappropriate antidiuresis is the most common condition causing euvolemic hyponatremia. Other causes : Glucocorticoid therapy , stress, hypothyroidism.

11. SIADH Most common cause of euvolemic hyponatremia. The secretion of ADH is not inhibited by either low serum osmolality or expanded intravascular volume. Child with SIADH is unable to excrete water. This results in dilution of the serum sodium and hyponatremia. Kidney increases sodium excretion in an effort to decrease intravascular volume to normal; thus, the patient has a mild decrease in body sodium.

12. Diagnostic Criteria for SIADH Absence of: Renal, adrenal, or thyroid insufficiency Heart failure, nephrotic syndrome, or cirrhosis Diuretic ingestion Dehydration Urine osmolality >100 mOsm /kg (usually > plasma) Serum osmolality <280 mOsm /kg and serum sodium <135 mEq /L Urine sodium >30 mEq /L Reversal of “sodium wasting” and correction of hyponatremia with water restriction

13. Hypervolemic Hyponatremia Increase in total body water > increase in total body sodium. Patients are edematous. RENAL CAUSES(urinary sodium > 20mEq/L): Acute or Chronic renal failure. NON RENAL CAUSES(urinary sodium < 20mEq/L) : CHF, Cirrhosis, Nephrotic syndrome.

14. Psuedo hyponatremia Normal Osmolarity Due to a measurement error which can result when the solid phase of plasma (that due to lipid and protein) is increased. Typically caused by hypertriglyceridaemia or paraproteinaemia .  

15. Psuedo hyponatremia…. High Osmolarity : Translocational hyponatraemia Occurs when an osmotically active solute that cannot cross the cell membrane is present in the plasma. In case of insulinopaenic diabetic patient, glucose cannot enter cells and hence water is displaced across the cell membrane, dehydrating the cells and “diluting” the sodium in the serum. This is also the cause of hyponatraemia seen in the TURP syndrome, in which glycine is inadvertently infused to the same effect.

16. CLINICAL FEATURES Severity of symptoms depends upon the severity of hyponatremia and the rate at which the sodium concentration is lowered. Acute: develops in 48 hours or less. Subjected to more severe degrees of cerebral edema. Chronic: develops over 48 hours and brain edema is less and is well tolerated. The signs and symptoms are due to increase in volume of ICF and increase in volume of brain cells rather than decrease in serum sodium.

17. SIGNS AND SYMPTOMS OF HYPONATREMIA

18. DIAGNOSIS History and physical examination- to identify hypovolemic hyponatremia ( diarrhoea , vomitting , burns). Radiologic imaging - to assess whether patient has a pulmonary or CNS cause for hyponatremia.

19. DIAGNOSIS…. Laboratory tests - Provide important initial clue in the differential diagnosis Plasma Osmolality Urine Osmolality Urine Sodium concentration Uric acid level Serum potassium Serum glucose

20. Plasma Osmolality- Normal plasma osmolality is 275-290 mEq /l . >290 mEq /L- hyperglycemia or administration of mannitol 275-290 mEq /L- Hyperlipidemia or hyperproteinemia <275 mEq /L- Evaluate volume status 1. Increased Volume- CHF, Cirrhosis, Nephrotic syndrome 2. Euvolemic - SIADH, Hypothyroidism, psychogenic polydipsia 3. Decreased Volume- GI and 3 rd space loss, renal losses Urine Osmolality- Normal value is > 100 mosmol /kg Normal to high : Hyperlipidemia, hyperproteinemia, hyperglycemia, SIADH < 100 mosmol /kg Hypo- osmolar hyponatremia - Excessive sweating, Burns,Vomiting , Diarrhea , Urinary loss

21. Urine Sodium >20 mEq /L SIADH, diuretics <20 mEq /L cirrhosis, nephrosis, congestive heart failure, GI loss, skin, 3 rd spacing, psychogenic polydipsia Uric Acid Level < 4 mg/dl consider SIADH FeNa (Fractional Excretion of Sodium) Help to determine pre-renal from renal causes Serum glucose - also should be measured; plasma Na + concentration falls by 1.6 to 2.4 m M for every 100-mg/dl increase in glucose due to glucose-induced water efflux from cells; this "true" hyponatremia resolves after correction of hyperglycemia Serum Potassium : Hyperkalemia - Renal insufficiency or Adrenal insufficiency with hypoaldosteronism Hypokalemia - with metabolic acidosis suggests vomiting or diuretic therapy

22. TREATMENT Individualized considering etiology, rate of development, severity and clinical signs and symptoms. Hyponatremia which developed quickly needs to be treated fast whereas slow developing hyponatremia should be corrected slowly. GOALS of THERAPY: 1. To raise the plasma sodium concentration at a slow rate. 2. To replace sodium or potassium deficit or both. 3. To correct underlying etiology. BASIC PRINCIPLES OF CORRECTION: Rapid correction is indicated in acute (<48hours) symptomatic or severe hyponatremia.(serum Na <120 mEq /L). In chronic cases patients are at little risk, however rapid correction can lead to demyelination. Use slower acting therapies like water restriction.

23. Hypovolemic hyponatremia will respond to intravenous hydration with isotonic normal saline, with a rapid reduction in circulating AVP and a brisk water diuresis. Diuretics induced hyponatremia is treated with saline and potassium supplementation. Hypervolemic hyponatremia responds to salt, water restriction (intake < urine output), and loop diuretics . Euvolemic hyponatremia will respond to successful treatment of the underlying cause, with an increase in plasma Na + concentration. Regardless of the initial rate of correction, chosen acute treatment is stopped once- 1. patient’s symptoms are abolished 2. A safe plasma sodium ( >125 mEq /L) is achieved.

24. SPECIFIC THERAPY: 1. Removal of responsible drugs- diuretics, chlorproamide etc 2. Management of physical stress or post operative pain. 3. Specific treatment of underlying cause. 4. Vasopressin antagonists ( vaptans ) highly effective in treating SIADH and hypervolemic hyponatremia, reliably increasing plasma Na + concentration as a result of their aquaretic effects (augmentation of free-water clearance). Most of these agents specifically antagonize the V 2 vasopressin receptor. TO CALCULATE NEED OF REPLACEMENT SODIUM CONTAINING FLUID: 0.9% saline (154mEq/L) and 3% NaCl - hypertonic saline (513 mEq /L) are the only two routinely used I.V. fluids . However 0.9% NS is not used to correct hyponatremia in SIADH

25. Symptomatic Hyponatremia GOAL : Quickly raise the sodium level but only as much as necessary to ensure that the pt has normal respiration , seizure free and is alert. Initial therapy – with 3% NaCl @ 4-6 ml/kg over 30-60 mints. If no clinical improvement –another 3-4 ml/kg Therapy stopped once child is asymptomatic or serum sodium is 125 meq /lit Once pt is asymptomatic, remaining deficit corrected by NS. Total body sodium defict is approximated as : Na + deficit( meq /lit)=(130 - serum Na + ) x 0.6 x BW(kg) Rate of rise of serum should not exceed 0.5-1 meq /lit/hr. Rate of rise of sodium can be predicted as follows: Rise of serum Na+/lit of fluid infused=(Inf Na + - plasma Na + )/(0.6 x BW+ 1)

26. Asymptomatic or Chronic Hyponatremia Rate of correction should be comparatively slow . <8–10 m M in the first 24 h and <18 m M in the first 48 h SIADH Response to isotonic saline is different in the SIADH In hypovolemia both the sodium and water are retained Sodium handling is intact in SIADH Administered sodium will be excreted in the urine, while some of the water may be retained possibly worsening the hyponatremia Water restriction 0.5-1 liter/day Salt tablets Demeclocycline Inhibits the effects of ADH Onset of action may require up to one week

27. HYPERNATREMIA Defined as an increase in the plasma Na + concentration to >145 m M . Considerably less common than hyponatremia. Associated with mortality rates as high as 40–60%. Caused by a relative deficit of water in relation to sodium which can result from Net water loss : A ccounts for majority of cases Pure water loss Hypotonic fluid loss Hypertonic gain : Results from iatrogenic sodium loading

28. Causes of Hypernatremia Net water loss Pure water loss Unreplaced insensible losses (dermal and respiratory) Hypodipsia Neurogenic diabetes insipidus Post-traumatic tumors, cysts, histiocytosis , tuberculosis, sarcoidosis Idiopathic aneurysms, meningitis, encephalitis, Guillain-Barre´ syndrome Congenital nephrogenic diabetes insipidus Acquired nephrogenic diabetes insipidus Renal disease (e.g. medullary cystic disease) Hypercalcemia or hypokalemia Drugs (lithium, methoxyflurane , amphotericin B, vasopressin V 2 -receptor antagonists )

29. Hypotonic fluid loss Renal causes Loop diuretics Osmotic diuresis (glucose, urea, mannitol) Post obstructive diuresis Polyuric phase of acute tubular necrosis Gastrointestinal causes Vomiting Nasogastric drainage Entero cutaneous fistula Diarrhea Use of osmotic cathartic agents (e.g., lactulose) Cutaneous causes Burns Excessive sweating

30. Hypertonic sodium gain Hypertonic sodium bicarbonate infusion Ingestion of sodium chloride Ingestion of sea water Hypertonic sodium chloride infusion Primary hyper- aldosteronism Cushing’s syndrome

31. Clinical Features The symptoms of hypernatremia are predominantly neurologic. Altered mental status is the most common 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 haemorrhages and/or subdural hematomas. Osmotic damage to muscle membranes also can lead to hypernatremic rhabdomyolysis.

32. DIAGNOSIS HISTORY AND PHYSICAL EXAMINATION: History Should focus on the presence / absence of thirst, polyuria, and/or an extrarenal source for water loss, such as diarrhoea. The physical examination should include a detailed neurologic exam and an assessment of the ECFV; patients may be hypovolemic, with reduced JVP and orthostasis . Accurate documentation of daily fluid intake and daily urine output. LAB INVESTIGATIONS: Measurement of serum and urine osmolality in addition to urine electrolytes. - The appropriate response to hypernatremia and a serum osmolality >295 mosmol /kg is an increase in circulating ADH and the excretion of low volumes (<500 mL/d) of maximally concentrated urine, i.e., urine with osmolality >800 mosmol /kg

33. MANAGEMENT A two-pronged approach : Addressing the underlying cause. Correcting the prevailing hypertonicity. RATE OF CORRECTION : Hypernatremia that developed over a period of hours (accidental loading) Rapid correction improves prognosis without cerebral edema. Reducing Na + by 1 mmol /L/ hr appropriate. Hypernatremia of prolonged or unknown duration A slow pace of correction prudent. Maximum rate 0.5 mmol /L/ hr to prevent cerebral edema. A targeted fall in Na + of 10 mmol /L/24 hr ,

34. Goal of Treatment Reduce serum sodium concentration to 145 mmol /L. Make allowance for ongoing obligatory or incidental losses of hypotonic fluids that will aggravate the hypernatremia. In patients with seizures, prompt anticonvulsant therapy and adequate ventilation. Administration of Fluids Water ideally should be administered by mouth or by nasogastric tube as the most direct way to provide free water, i.e., water without electrolytes. Alternatively, patients can receive free water in dextrose-containing IV solutions such as 5% dextrose.

35. Hypernatremia with ECF volume contraction: Isotonic saline is given initially till ECF vol is restored. Subsequently water deficit can be replaced with water by mouth or I.V. 5% dextrose or 0.45% NaCl Hypernatremia with increased ECF volume: Since hypernatremia is secondary to solute administration, it can be rapidly corrected . Patients are volume overloaded- loop diuretic is given along with water to remove excess sodium