Electrolyte Abnormalities: Eleni Kitsos, Md

Electrolyte Abnormalities Eleni Kitsos, MD

Sodium • Bulk cation of extracellular fluid  change in SNa reflects change in total body Na+ • Principle active solute for the maintenance of intravascular volume • Absorption: throughout the GI system via active Na,K-ATPase system • Excretion: urine, sweat & feces • Kidneys are the principal regulator

Sodium intake • Diet dependent • Infants receive ~7mEq/L from breast milk and 7-13 mEq/L for 20 calorie/oz formula. • Readily absorbed throughout the GI tract • Mineralocorticoid increase sodium transport • Glucose enhances absorption of sodium (cotransport system) • i.e. oral rehydration solution

Sodium Excretion • Kidneys are principal site of excretion and regulation sodium balance • Effective plasma volume determines amount of sodium in urine

• Excretion also occurs in stool and sweat • Minimal loss in stool UNLESS diarrhea • Sweat has 5-40 mEq/L of sodium • Increased in patients with cystic fibrosis, aldosterone deficiency, or psuedohypoaldosteronism

• Water balance determines sodium concentration • Volume depletion takes precedence over osmolality

Sodium regulation • Kidneys are the principal regulator • 2/3 of filtered Na+ is reabsorbed by the proximal convoluted tubule, increase with contraction of extracellular fluid • Countercurrent system at the Loop of Henle is responsible for Na+ (descending) & water (ascending) balance – active transport with Cl• Aldosterone stimulates further Na+ re-absorption at the distal convoluted tubules & the collecting ducts • <1% of filtered Na+ is normally excreted but can vary up to 10% if necessary

Hypernatremia: Sodium concentration >145mEq/L Excessive Intake

Water Deficit

Improperly mixed formula Central & nephrogenic DI Excess sodium bicarb Increased insensible loss (iatrogenic, baking soda) Inadequate intake Ingestion of hypertonic saline, seawater Intentional salt poisoning IV hypertonic saline Hyperaldosteronism

Water and Sodium Deficit GI losses (emesis/nasogastric suction, diarrhea, osmotic cathartics) Cutaneous losses Renal losses Osmotic diuresis: mannitol, diabetes mellitus Chronic kidney disease Polyuric ATN Post-obstructive diuresis

Increase sodium concentration

Increase in plasma osmolality

Increase ADH secretion and thirst

Renal conservation of water

Volume depletion takes precedence over osmolality Volume depletion stimulates ADH secretion even in setting of hyponatremia

Decrease sodium concentration

Decrease plasma osmolality

Stops secretion of ADH

Renal water excretion

Hypernatremia: Identify symptoms associated with hypernatremia • Dehydration • “Doughy” feel to skin • CNS symptoms: Irritability, lethargy, weakness • Parallel the degree of sodium elevation and acuity of increase

• High pitched cry and hyperpnea • Extreme thirst Hypernatremia due to severe Hyperaldosteronism sodium intoxication will have signs • Fever Hypernatremia is mild or absent of volume overload-pulmonary Associated with edema and mild hypocalcemia • Associated hyperglycemia edema, weight gain Hypertension • Hypokalemia Intracranialand hemorrhage metabolic alkalosis • Thrombosis: renal vein, dura sinu

Brain hemorrhage Extracellular osmolality increase

Water moves out of brain cells

Decrease brain volume

Tearing of Intracerebral veins and bridging vessels

Subarachnoid, subdural, and parenchymal hemorrhages

Seizures and coma

Diagnosis Work up

• BMP • Urinalysis • Fractional excretion of sodium • Elevated in salt poisoning • Low in hypernatremic dehydration

• Renal water loss (Diabetes insipidus): urine volume is low and dilute • Extrarenal water loss: urine volume is low and maximally concentrated • urine osm. >1000mOsm/kg

Diabetes insipidus

Combined sodium and water deficits

• ADH and water deprivation test • Desmopressin acetate

• Renal loss: urine volume is not appropriately low and now maximally concentrated

• Central DI: desmopressin increases urine osmolality above plasma osmolality • Nephrognic DI: no response to desmopressin

Decreased Weight Renal Losses Nephropathy Diuretic use Diabetes insipidus Postobstructive diuresis Diuretic phase of ATN LABORATORY DATA + ↑ Urine Na ↑ Urine volume ↓ Specific gravity

Increased Weight Extrarenal Losses GI losses Skin losses Respiratory *

+

↓ Urine Na ↓ Urine volume ↑ Specific gravity

+

Exogenous Na Mineralocorticoid excess Hyperaldosteronism

+†

Relative ↓ urine Na Relative ↓ urine volume Relative ↑ specific gravity

CLINICAL MANIFESTATIONS Predominantly neurologic symptoms: lethargy, weakness, altered mental status, irritability, and 1819 seizures. Additional symptoms may include muscle cramps, depressed deep tendon reflexes, and respiratory failure. MANAGEMENT Replace free water losses based on the calculations in the text, and treat cause. Consider a natriuretic agent if there is increased weight.

Treatment Na+

• Rate of correction for 0.5 mEq/L/hr; <12 mEq/L hours • If hypernatremic dehydration:

Frequent monitoring every 24 of Na+ to adjust as needed to assure appropriate correction

1. Restore intravascular volume with isotonic fluid 2. Repeat bolus if hypotension, tachycardia, or poor perfusion

• Calculate water deficit

• Water deficit = Body weight x 0.6(1-145/current sodium) • Rate of correction for calculated water deficit • 50% first 12-24 hrs • Remaining next 24 hrs

Identify symptoms associated with rapid rehydration Rapid fall in serum osmolality

Water movement from serum into cells

• Gradual development of hypernatremia generates idiogenic osmoles (prevent loss of brain water)

Brain swelling manifest as seizures or coma

Management if brain edema occurs secondary to rapid correction • If patient developes seizure as a result of brain edema: 1. STOP hypotonic fluids 2. Infuse 3% saline  acutely increase the serum sodium reversing cerebral edema

Hyponatremia • <135 mEq/L • Low plasma osmolality

Common electrolyte abnormality ~25 % hospitalized patients

• TBW and total body sodium determine serumPseudohyponatremia: sodium Lab artifact if very high concentration concentration of protein or lipid or with hyperglycemia • Increase in ratio of water to sodium Normal or high plasma • Deficit in sodium or excess free water osmolality • Evaluation of hyponatremia should start with assessment of Solution: point of care testing volume status i-stat, ABG (ion selective electrode)

Hyponatremia: Classification based on volume status • Hypervolemic • CHF • Nephrotic syndrome • Septic capillary leak

Cirrhosis Hypoalbuminemia

• Hypovolemic • Renal losses • Extra-renal losses • GI losses • Third spacing

Cerebral salt wasting aldosterone effect

Hyponatremia: Classification based on volume status • Euvolemic hyponatremia • • • •

SIADH Glucocorticoid deficiency Hypothyroidism Water intoxication • Psychogenic polydipsia • Diluted formula • Beer potomania

Pseudohyponatremia (1) Hyperglycemia: Na + decreased 1.6 mEq/L for each 100mg/dL rise in glucose (2) Hyperlipidemia: Na + decreased by 0.002 × lipid (mg/dL) (3) Hyperproteinemia: Na + decreased by 0.25 × [protein (g/dL) − 8]

Hyponatremia: Clinical manifestations • Cellular swelling due to water shifts into cells • Very dangerous for the brain Brain cells swell

Increase ICP

Impaired cerebral blood flow

Brainstem herniation

• Anorexia, nausea, emesis, malaise, lethargy, confusion, agitation, headache, seizures, coma • Hypothermia and Cheyne-stokes respiration • Muscle cramps and weakness; rhabdomyolysis with water intoxication • Chronic hyponatremia: better tolerated

Hyponatremia management Acute (water intoxication) or if hypotonic seizures occur

Chronic

• Small, rapid increase in sodium with hypertonic saline

• Rapid correction  central pontine myelinolysis

• 4-6 mL/kg of 3% NaCl

• Hyponatremic seizures • Poorly responsive to anticonvulsants

• Consequences of brain edema > small risk of CPM

• More common in chronic hyponatremia

• Goal 12 mEq/L/24 hours or 18 mEq/L/48 hours • Desmopressin may be given if increase is to rapid

Hypovolemic hyponatremia Restore IV volume with isotonic saline

ADH suppression

Excretion of excess water

Hypervolemic hyponatremia

• Water and sodium restriction • Diuretics may help (excreting both Na and water) • If heart failure or cirrhosis give vasopressin antagonist

Fill in the blank Urine Output

DI

SIADH

CSW

Serum Na

Urine Na

Serum Osm

Urine Osm

Decreased Weight Renal Losses +

Increased or Normal Weight Extrarenal Losses

Na -losing nephropathy

GI losses

Nephrotic syndrome

Diuretics

Skin losses

Congestive heart failure

Adrenal insufficiency

Third spacing

SIADH

Cerebral salt-wasting syndrome Cystic fibrosis

Acute/chronic renal failure

Water intoxication Cirrhosis Excess salt-free infusions LABORATORY DATA ↑ Urine Na

+

↓ Urine Na

+

↓ Urine Na

+†

↑ Urine volume

↓ Urine volume

↓ Urine volume

↓ Specific gravity

↑ Specific gravity

↑ Specific gravity

↓ Urine osmolality ↑ Urine osmolality ↑ Urine osmolality MANAGEMENT (IN ADDITION TO TREATING UNDERLYING CAUSE) Replace losses

Replace losses

Restrict fluids

Plan appropriate lab evaluation of hyponatremia

Differential Diagnosis of Hyponatremia

DISORDER Systemic dehydration Decreased effective plasma volume Primary salt loss (nonrenal) Primary salt loss (renal) SIADH Cerebral salt wasting Decreased free water clearance Primary polydipsia Runner's hyponatremia NSIAD Pseudohyponatremia Factitious hyponatremia

INTRAVASCULAR VOLUME STATUS Low Low

URINE SODIUM

Low Low High Low Normal or high

Low High High Very high Normal or high

Normal or high Low High Normal Normal

Normal Low High Normal Normal

Low Low

Table 55-2 Causes of Hyponatremia HYPOVOLEMIC HYPONATREMIA EXTRARENAL LOSSES

Burns cause massive **Gastrointestinal (emesis, diarrhea) losses of isotonic Skin (sweating or burns) fluid and resultant MCC of ThirdDiarrhea space losses (bowel obstruction, peritonitis, sepsis)volume depletion hypovolemic RENAL LOSSES hyponatremia Thiazide or loop diuretics Emesis will usually cause Osmotic diuresis hypernatremia or normal Postobstructive diuresis sodium unless receiving Polyuric phasefluids of acute tubular hypotonic

If given hypotonic fluid HYPONATREMIA will defelop

necrosis Juvenile nephronophthisis (OMIM 256100/606966/602088/604387/61 1498) ADH production Autosomal recessive polycystic kidney disease (OMIM 263200) and water Third space Tubulointerstitial nephritis retention esp. if losses are Volume depletion receiving Obstructive uropathy isotonic hypotonic Cerebral salt wasting solutions Proximal (type II) renal tubular acidosis (OMIM 604278)* Lack of aldosterone effect (high serum potassium): Absence of aldosterone (e.g., 21-hydroxylase deficiency [OMIM 201910]) Pseudohypoaldosteronism type I (OMIM 264350/177735)

EUVOLEMIC HYPONATREMIA

Syndrome of inappropriate antidiuretic hormone secretion Nephrogenic syndrome of inappropriate antidiuresis (OMIM 304800) Desmopressin acetate Glucocorticoid deficiency Hypothyroidism Water intoxication: Iatrogenic (excess hypotonic intravenous fluids) Feeding infants excessive water products Swimming lessons Tap water enema Child abuse Psychogenic polydipsia Diluted formula Beer potomania Exercise-induced hyponatremia

HYPERVOLEMIC HYPONATREMIA Heart failure Cirrhosis Nephrotic syndrome Acute, chronic kidney injury Capillary leak caused by sepsis Hypoalbuminemia caused by gastrointestinal disease (protein- losing enteropathy)

Hyponatremia: Identify various etiologies

PSEUDOHYPONATREMIA •Hyperlipidemia •Hyperproteinemia HYPEROSMOLALITY •Hyperglycemia •Iatrogenic (mannitol, sucrose, glycine) HYPOVOLEMIC HYPONATREMIA EXTRARENAL LOSSES •Gastrointestinal (emesis, diarrhea) •Skin (sweating or burns) •Third space losses (bowel obstruction, peritonitis, sepsis) RENAL LOSSES •Thiazide or loop diuretics •Osmotic diuresis •Postobstructive diuresis •Polyuric phase of acute tubular necrosis •Juvenile nephronophthisis (OMIM 256100/606966/602088/604387/611498) •Autosomal recessive polycystic kidney disease (OMIM 263200) •Tubulointerstitial nephritis •Obstructive uropathy •Cerebral salt wasting •Proximal (type II) renal tubular acidosis (OMIM 604278) * •Lack of aldosterone effect (high serum potassium): • Absence of aldosterone (e.g., 21-hydroxylase deficiency [OMIM 201910]) • Pseudohypoaldosteronism type I (OMIM 264350/177735) • Urinary tract obstruction and/or infection

EUVOLEMIC HYPONATREMIA •Syndrome of inappropriate antidiuretic hormone secretion •Nephrogenic syndrome of inappropriate antidiuresis (OMIM 304800) •Desmopressin acetate •Glucocorticoid deficiency •Hypothyroidism •Water intoxication: • Iatrogenic (excess hypotonic intravenous fluids) • Feeding infants excessive water products • Swimming lessons • Tap water enema • Child abuse • Psychogenic polydipsia • Diluted formula • Beer potomania • Exercise-induced hyponatremia HYPERVOLEMIC HYPONATREMIA •Heart failure •Cirrhosis •Nephrotic syndrome •Acute, chronic kidney injury •Capillary leak caused by sepsis •Hypoalbuminemia caused by gastrointestinal disease (protein-losing enteropathy)

Distinguish between dilutional and total body deficit of sodium

Recognize clinical findings associated with water intoxication in patients of various ages

Potassium • Normal range: 3.5-4.5 • Largely contained intra-cellular  SK does not reflect total body K • Important roles: contractility of muscle cells, electrical responsiveness • Principal regulator: kidneys Age Premature infant Newborn Infant Child >1 year old

Range (mEq/L or mmol/L) 4 to 6.5 3.7 to 5.9 4.1 to 5.3 3.5 to 5

Potassium • Daily requirement 1-2 mEq/kg • Complete absorption in the upper GI tract • Kidneys regulate balance • 10-15% filtered is excreted

• Aldosterone: increase K+ & decrease Na+ excretion • Mineralocorticoid & glucocorticoid  increase K+ & decrease Na+ excretion in stool

Potassium • Solvent drag • Increase in Sosmo  water moves out of cells  K+ follows • 0.6 SK / 10 of Sosmo • Evidence of solvent drag in diabetic ketoacidosis

• Acidosis • Low pH  shifts K+ out of cells (into serum) • High pH  shifts K+ into cells • 0.3-1.3 mEq/L K+ change / 0.1 unit change in pH in the opposite direction

Increased Stores Increased Urine K

Normal Stores +

Transfusion with aged blood

Decreased Urine K

+

Renal failure

Tumor lysis syndrome

Exogenous K (e.g., salt substitutes)

Hypoaldosteronism

Leukocytosis (>100 K/µL)

Spitzer syndrome

Aldosterone insensitivity

Thrombocytosis (>750 K/µL)

↓ Insulin

Metabolic acidosis *

+

+

K -sparing diuretics

Type IV RTA

Congenital adrenal hyperplasia Blood drawing (hemolyzed sample) Rhabdomyolysis/crush injury Malignant hyperthermia Theophylline intoxication

Hyperkalemia: Etiology • Spurious • Difficult blood draw  hemolysis  false reading

• Increase intake • Iatrogenic: IV or oral • Blood transfusions

• Decrease excretion • • • • • • •

Renal failure Adrenal insufficiency or CAH Hypoaldosteronism Urinary tract obstruction Renal tubular disease ACE inhibitors Potassium sparing diuretics

Hyperkalemia: Etiology • Trans-cellular shifts • • • •

Acidemia Rhadomyolysis; Tumor lysis syndrome; Tissue necrosis Succinylcholine Malignant hyperthermia

Hyperkalemia: recognize associated clinical and lab features • EKG changes • • • • •

~6: peak T waves ~7: increased PR interval ~8-9: absent P wave with widening QRS complex Ventricular fibrillation Asystole

• Neuromuscular effects • Delayed repolarization, faster depolarization, slowing of conduction velocity • Paresthesias  weakness  flaccid paralysis

Manage hyperkalemia Lower K + temporarily • Calcium gluconate 100mg/kg IV • Bicarb: 1-2 mEq/kg IV • Insulin & glucose • Insulin 0.05 u/kg IV + D10W 2ml/kg then • Insulin 0.1 u/kg/hr + D10W 24 ml/kg/hr

• Salbutamol (β2 selective agonist) nebulizer

Increase elimination • Hemodialysis or hemofiltration • Kayexalate via feces • Furosemide via urine

Goals of hyperkalemia management 1. Stabilize the heart to prevent life-threatening arrhythmia 2. Remove potassium from the body

Recognize clinical and lab features with hypokalemia • Hypokalemia • <2.5: life threatening • Common in severe gastroenteritis

Hypokalemia: etiology • Distribution from ECF • Hypokalemic periodic paralysis • Insulin, Β-agonists, catecholamines, xanthine

• Decrease intake • Extra-renal losses • Diarrhea • Laxative abuse • Perspiration

• Excessive colas consumption

Hypokalemia: Etiology • Renal losses • • • • • • • •

DKA Diuretics: thiazide, loop diuretics Drugs: amphotericin B, Cisplastin Hypomagnesemia Alkalosis Hyperaldosteronism Licorice ingestion Gitelman & Bartter syndrome

Hypokalemia: presentation ECG changes Flattened or inverted T-wave • U wave: prolonged repolarization of the Purkinje fibers • Depressed ST segment and widen PR interval • Ventricular fibrillation can happen

• • • •

Usually asymptomatic Skeletal muscle: weakness & cramps; respiratory failure Flaccid paralysis & hyporeflexia Smooth muscle: constipation, urinary retention

Decreased Stores Hypertension

Normal Stores * Normal Blood Pressure Renal

Extrarenal

Renovascular disease

RTA

Skin losses

Metabolic alkalosis

Excess renin

Fanconi syndrome

GI losses

Hyperinsulinemia

Excess mineralocorticoid

Bartter syndrome

High CHO diet

Leukemia

Cushing's syndrome

DKA

Enema abuse

β 2 -Catecholamines

Antibiotics

Laxative abuse

Diuretics

Anorexia nervosa

Familial hypokalemic periodic paralysis

Amphotericin B

Malnutrition

Familial

LABORATORY DATA ↑ Urine K

+

↑ Urine K

+

↓ Urine K

+

↑ Urine K

+

hypokalemia • Diagnostic studies: • (1) Blood: Electrolytes, blood urea nitrogen/creatinine (BUN/Cr), creatine kinase (CK), glucose, renin, arterial blood gas (ABG) • (2) Urine: Urinalysis, K + , Na + , Cl − , osmolality, 17ketosteroids • (3) Other: ECG, consider evaluation for Cushing's syndrome

Hypokalemia Management • The rapidity of treatment should depend on the symptom severity. See Formulary for dosage information: • Acute: Calculate deficit, and replace with potassium acetate or potassium chloride. Enteral replacement is safer when feasible, with less risk for iatrogenic hyperkalemia. Closely follow serum K + . • Chronic: Determine daily requirement and replace with potassium chloride or potassium gluconate.

SIADH: clinical and lab features

SIADH management

Differentiate SIADH from hyponatremic dehydration

Recognize disease conditions and medication associated with SIADH

Recognize the role of head trauma in development of SIADH

Pyloric Stenosis: recognize associated acid-base changes

Manage pyloric stenosis appropriately