HYPONATREMIA [1]
[Figure] "Evaluation of Hyponatremia"
A. ECF (Extracellular Fluid) Volume Depletion

1. Renal Losses (Urinary Na+ >20mM)
   1. Diuretics
   2. Mineralocorticoid Excess
   3. Salt-Losing Nephritis
   4. Diabetic Ketoacidosis
   5. Osmotic Diuresis
2. Extrarenal Losses (Urinary Na+ < 20mM)
   1. Vomiting
   2. Diarrhea
   3. Burns
   4. Pancreatitis
   5. Rhabdomyolysis

B. ECF Volume Slight Excess

1. Urinary Na+ >20mM
2. Glucocorticoid Deficiency
3. Hypothyroidism
4. SIADH (syndrome of inappropriate antidiuretic hormone)

C. ECF Volume Excess

1. Renal Failure (Urinary Na+ >20mM)
2. Non-Renal Failure (Urinary Na+ >20mM)
   1. Nephrotic Syndrome (Ur Na+ <10mM)
   2. Congestive Heart Failure
   3. Cirrhosis with portal congestion
   4. Hepatorenal Syndrome

1. Dehydration (Inadequate Fluid Intake)
2. Drugs
   1. Infusion of hypertonic Sodium Salts
   2. Hypertonic saline, sodium bicarbonate
3. Hyperaldosteronism - rare cause of hypernatremia
4. Diabetes Insipidus (DI)
   1. Failure to make (adequate) ADH (central or neurogenic DI)
   2. Failure to respond to ADH (nephrogenic DI)
   3. Lithium - ~50% of patients, likely via down regulation of AQP2 channels
   4. Amphotericin - direct tubular toxicity
   5. Foscarnet - direct tubular toxicity
   6. Demeclocycline - reduces adenyl cyclase activity in renal medulla, decreases ADH
   7. Other: methoxyflurane, vasopressin analogs
5. Renal Failure (inability to filter Na+)
6. Coma (disordered ADH regulation; absence of thirst mechanism)

1. Diuretic Use
2. Metabolic / Respiratory Alkalosis
3. Hyperaldosteronism
4. Diabetic Ketoacidosis with Osmotic Diuresis
5. Other renal losses - such as various renal tubular acidoses

1. Drugs
   1. K+ salts
   2. ACE inhibitors
   3. K+ sparing diuretics (eg. Spironolactone, Triampterene)
   4. High dose TMP/SMX (Bactrim®)
   5. Non-steroidal anti-inflammatory drugs (PG-1 synthase inhibitors)
2. Acidosis: acid pH shifts cause K+ to exit cells, basic shifts cause K+ to enter cells.
3. Renal Tubular Acidosis Type IV
4. Addison's Disease
5. Tumor lysis syndrome

1. Medications
   1. Hypoglycemics: insulin, oral agents
   2. Pentamidine intravenous
   3. Quinine and quinidine
   4. Salicylates
   5. ß-adrenergic blocking agents (ß-blockers)
2. Severe Liver Disease
3. Alcohol (EtOH) intoxication
4. Adrenocortical Insufficiency
5. Thyroid or Growth Hormone Deficiency
6. Malnutrition and Starvation
7. Renal Failure
8. Insulinoma
9. Shock
10. Familial hypoglycemic hyperinsulinemia of childhood [2]

1. Endocrinopathy: Hypoparathyroidism (permanent or transient)
2. Vitamin D Deficiency or Resistance
3. Renal Losses
4. Pancreatitis - usually severe

1. Endocrine
   1. Primary Hyperparathyroidism (70-80%)
   2. Renal Osteodystrophy: secondary hyperparathyroidism (often with hypocalcemia)
   3. Hyperthyroidism
   4. Pheochromocytoma
   5. Hypervitaminosis D
   6. Milk-Alkali Syndrome
2. Inflammatory
   1. Granulomatous Disease: sarcoidosis, tuberculosis, fungal diseases
   2. Lymphomas
3. Neoplastic
   1. Carcinoma: ectopic PTH-like production (especially squamous tumors)
   2. Multiple Myeloma (Ca2+ often >15mM)
   3. Lymphomas
4. Drugs
   1. Increased calcium intake, particularly with vitamin D
   2. Calcitriol
   3. Thiazide Diuretics

1. Most causes are iatrogenic
2. Particularly common in hospitalized (sick) patients
   1. Gastrointestinal Losses
   2. Renal Losses
   3. Drug Induced Losses
3. Gastrointestinal Losses
   1. Prolonged nasogastric suction
   2. Diarrhea
   3. Malabsorption syndromes
   4. Steatorrhea
   5. Short bowel syndrome
   6. Acute pancreatitis
   7. Severe malnutrition
   8. Intestinal fistulae
4. Renal Losses
   1. Parenteral fluid therapy
   2. Volume expanded conditions: heart failure, cirrhosis, nephrotic syndrome
   3. Hypercalcemia, hypercalciuria
   4. Osmotic diuresis: diabetes, mannitol
   5. Phosphate depletion
   6. Hungry-bone syndrome
   7. Correction of chronic systemic alkalosis
   8. Postobstructive Nephropathy (with diuresis)
   9. Kidney transplantation
   10. Primary renal tubular magnesium wasting
5. Drugs
   1. Diuretics: thiazide or loop diuretics
   2. Aminoglycosides
   3. Antibiotics
   4. Amphotericin B
   5. Cisplatinum
   6. Cyclosporine
   7. Foscarnet
   8. Pentamidine

1. Decreased intestinal absorption
   1. Antacids containing aluminum or magnesium
   2. Steatorrhea and chronic diarrhea
   3. Inadequate intake
   4. Vitamin D deficiency or resistance
2. Increased urinary excretion
   1. Proximally acting diuretics
   2. Osmotic diuresis - especially with hyperglycemia
   3. Hyperparathyroidism - primary and secondary
   4. Disorders of Vitamin D - deficiency or resistance
   5. Renal Tubular Defects including Fanconi syndrome
   6. Acute volume expansion
   7. Kidney Transplantation
   8. Alcohol Abuse
   9. Carbonic Anhydrase Inhibition
   10. Acidosis: Metabolic or Respiratory
3. Internal redistribution
   1. Increased insulin, particularly during refeeding
   2. Acute respiratory alkalosis (pain, anxiety, salicylate poisoning, sepsis, heat stroke)
   3. Recovery from malnutrition (refeeding syndrome)
   4. Sepsis
   5. Hungry Bone Syndrome
   6. Intravenous IGF-1 administration causes acute hypophosphatemia also [3]
   7. Insulin, glucagon, epinephrine, cortisol

1. Reduced Urinary Excretion
   1. Hypoparathyroidism
   2. Renal Failure: acute or chronic
   3. Acromegaly
   4. Tumoral calcinosis
   5. Vitamin D intoxication / overdose
   6. Bisphosphonate therapy
   7. Magnesium deficiency
2. Increased Endogenous Load
   1. Tumor lysis syndrome
   2. Rhabdomyolysis
   3. Bowel infarction
   4. Malignant hyperthermia
   5. Hemolysis
   6. Acid-base abnormalities
3. Increased Exogenous Load
   1. Overingestion of phosphates
   2. Intravenous infusion
   3. Cow's milk feeding to premature babies
   4. Phosphate-containing enemas
   5. Acute phosphate poisoning
4. Pseudohyperphosphatemia
   1. Multiple myeloma
   2. Hemolysis in vitro
   3. Hypertriglyceridemia

References

1. Service FJ. 1995. NEJM. 332(17):1144
2. Herbert SC. 1998. Am J Med. 104(1):87
3. Le Roith D. 1997. NEJM. 336(9):633
4. Weisinger JR and Bellorin-Font E. 1998. Lancet. 352(9125):391