Hyponatremia and ADH Release

SIADH Pathogenesis

• SIADH is characterized by sustained ADH release, which can be erratic and independent of osmotic control in some individuals.
• In others, ADH levels vary appropriately with plasma osmolality, but the osmotic threshold for ADH release is abnormally low (reset osmostat).
• A small group of people have low levels of ADH, and when plasma becomes hypoosmotic, ADH is not suppressed.

Diagnosing SIADH

• Symptoms of hyponatremia occur when plasma osmolality falls to 120 mmol/dL.
• Ionized calcium levels are almost equal to heart failure.
• Causes of SIADH include:
  • Central nervous system disorders
  • Pulmonary disorders
  • Cancer
  • Infections
  • Pain
  • Emotional stress
  • Postoperative state
  • Narcotics
  • Hepatic cirrhosis
  • Renal disorders
  • Nephrotic syndrome
  • Acute renal failure
  • Chronic renal failure
  • Hypothyroidism
  • Glucocorticoid deficiency
  • Primary polydipsia
  • Diuretics
  • Osmotic diuresis (glucose, urea, mannitol)
  • Mineralocorticoid deficiency
  • Salt-losing nephropathies

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

• SIADH is characterized by less than maximally dilute urine in the presence of plasma hypoosmolality.
• The etiology of SIADH is often unknown, but it involves sustained ADH secretion.

Hyponatremia

• Hyponatremia occurs when plasma sodium levels drop below 135 mmol/L.
• Causes of hyponatremia include:
  • Protracted vomiting
  • Severe diarrhea
  • Sequestration of fluid in the 3rd space replaced with free H2O or treated with hypovolemic IVF
  • Significant ECF loss resulting in ADH release, causing H2O retention by kidneys and hyponatremia

Euvolemic Hyponatremia

• Euvolemic hyponatremia occurs when total body water (TBW) is increased, but there is no significant change in total body sodium content.
• Causes of euvolemic hyponatremia include:
  • Dilutional hyponatremia due to increased H2O intake without Na+ retention in renal failure, Addison's disease, myxedema, or non-osmotic ADH secretion (stress, post-op, and certain drugs)
  • Certain medications, such as:
    • Chlorpropamide
    • Tolbutamide
    • Opioids
    • Barbiturates
    • Vincristine
    • Clofibrate
    • Carbamazepine

Hypervolemic Hyponatremia

• Hypervolemic hyponatremia occurs when total body water (TBW) and total body sodium content are increased.
• Causes of hypervolemic hyponatremia include:
  • Congestive heart failure (CHF)
  • Liver failure
  • Decrease in effective circulating volume causing release of ADH and angiotensin II, leading to hyponatremia.

Na+ Regulation and Imbalance

• Na+ regulation occurs through renal and extrarenal mechanisms
• Normal Na+ levels in the body (TBW) can be affected by various factors, including extrarenal losses (vomiting, diarrhea, burns, excessive sweating), renal losses (intrinsic renal disease, osmotic diuresis, loop diuretics), and hyper-tonic IV fluids

Causes of Hyponatremia

• Extrarenal losses: vomiting, diarrhea, burns, excessive sweating
• Renal losses: intrinsic renal disease, osmotic diuresis, loop diuretics
• Heart failure, pancreatitis, peritonitis, small bowel obstruction, rhabdomyolysis, burns
• SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion), hypothyroidism, glucocorticoid deficiency, primary polydipsia, salt-losing nephropathies

SIADH

• Characterized by less than maximally dilute urine in the presence of plasma hypoosmolality
• Often caused by unknown factors
• Low PO4- levels may indicate hyperparathyroidism

Hyperparathyroidism

• Primary hyperparathyroidism: increased serum Ca+, normal PO4- levels
• Secondary hyperparathyroidism: increased serum Ca+, decreased PO4- levels
• Humoral Hypercalcemia of Malignancy: diagnosed by presence of PTH-related peptide
• Alkaline phosphatase levels are increased in hyperparathyroidism with increased bone turnover

Diagnostic Tests for Hyperparathyroidism

• Parathyroid Hormone Assays (PTH) by IRMA (immunoradiometric assays) for improved sensitivity
• Rule out malignancy and impaired renal status
• Check urinary excretion of calcium
• Benign familial hypercalcemia from parathyroid hyperplasia does not have hypercalciuria or other complications of hypercalcemia

Treatment of Hyperparathyroidism

• Mild symptoms and Ca+ levels < 15 mg/dL: conservative approach
• Asymptomatic patients: conservative approach, but watch for psychiatric and neuromuscular disturbances
• Prominent symptoms: anxiety, nervousness, daytime sleepiness, loss of energy, crying easily, excessive worry, irritability, lack of interest
• Surgical vs conservative therapy: based on complicating problems, such as nephrolithiasis, cystic bone disease, overt neuromuscular disease, decreased cortical bone density, and reduced renal function

Hypermagnesemia

• Rare, often due to deficient excretion of magnesium in urine (renal disease or failure) or chronic ingestion of laxatives or antacids
• Signs and symptoms: EKG shows prolonged PR interval, widening of QRS, and increased T wave amplitude if plasma level is 5-10 mEq/L; DTRs decrease or disappear, hypotension, respiratory depression, and cardiac arrest when Magnesium >12-15 mEq/L

This quiz is about hyponatremia, a condition where the sodium levels in the blood are too low, and how it affects the release of antidiuretic hormone (ADH) in the body.