Hyponatremia and ADH Release

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Questions and Answers

What is the characteristic of ADH release in some individuals with SIADH?

ADH secretion is erratic and independent of osmotic control (correct)

ADH levels vary appropriately with plasma osmolality

ADH is suppressed in the presence of high plasma osmolality

ADH is not released in response to low plasma osmolality

What is the consequence of a reset osmostat in SIADH?

ADH levels vary appropriately with plasma osmolality

The osmotic threshold for ADH release is abnormally low (correct)

ADH is suppressed in the presence of high plasma osmolality

ADH is not released in response to low plasma osmolality

What is the primary cause of hypovolemic hyponatremia?

Renal sodium loss (correct)

Excessive ADH secretion

Hepatic cirrhosis

Dilutional hyponatremia

Which of the following is a characteristic of euvolemic hyponatremia?

Normal blood volume Signup and view all the answers

What is the characteristic of ADH secretion in a small group of people with SIADH?

ADH is not suppressed in the presence of low plasma osmolality Signup and view all the answers

What is the plasma osmolality level at which symptoms of hyponatremia occur?

12 mg/dL Signup and view all the answers

What is the primary cause of hypervolemic hyponatremia?

Renal sodium retention Signup and view all the answers

What is the characteristic of hypovolemic hyponatremia?

Increased ADH secretion Signup and view all the answers

What is the primary mechanism of dilutional hyponatremia?

Excessive water intake Signup and view all the answers

What is the characteristic of euvolemic hyponatremia?

Increased ADH secretion Signup and view all the answers

Which of the following conditions is associated with nonosmotic ADH secretion?

All of the above Signup and view all the answers

What is the typical urine osmolality in SIADH?

Greater than 500 mOsm/kg Signup and view all the answers

What is the characteristic of dilutional hyponatremia?

Water intoxication Signup and view all the answers

What is the characteristic of nonosmotic ADH secretion?

ADH secretion is independent of osmotic control Signup and view all the answers

Which of the following is a common cause of hypovolemic hyponatremia?

Diuretic use Signup and view all the answers

What is the primary mechanism of hypovolemic hyponatremia due to diuretic use?

Renal sodium loss Signup and view all the answers

What is the primary mechanism leading to hyponatremia in hypovolemic hyponatremia?

Release of ADH, causing water retention by kidneys Signup and view all the answers

Which of the following conditions can cause dilutional hyponatremia?

Addison's disease Signup and view all the answers

What is the characteristic of hypervolemic hyponatremia in terms of total body water and sodium content?

Increase in total body water and total body sodium content Signup and view all the answers

Which of the following medications can cause nonosmotic ADH secretion leading to hyponatremia?

Chlorpropamide Signup and view all the answers

What is the primary difference between euvolemic hyponatremia and hypovolemic hyponatremia?

The volume of total body water Signup and view all the answers

Which of the following conditions can cause hypervolemic hyponatremia?

Liver failure Signup and view all the answers

What is the primary mechanism leading to hyponatremia in euvolemic hyponatremia?

Dilution of sodium content by excessive water intake Signup and view all the answers

Which of the following situations can cause nonosmotic ADH secretion leading to hyponatremia?

Postoperative period Signup and view all the answers

Which of the following can cause extrarenal losses leading to hypovolemic hyponatremia?

Diarrhea Signup and view all the answers

What is the underlying mechanism of hypertonic IV fluids causing hypernatremia?

Excess sodium infusion Signup and view all the answers

Which of the following can cause renal losses leading to hypovolemic hyponatremia?

Osmotic diuresis Signup and view all the answers

What is the underlying mechanism of TPN causing hypernatremia?

Excess sodium infusion Signup and view all the answers

What is a common cause of hypernatremia in the elderly?

All of the above Signup and view all the answers

What is the primary goal of treatment for hypernatremia?

H2O replacement Signup and view all the answers

Which of the following is a characteristic of hypervolemic hyponatremia?

Increased total body water and sodium content Signup and view all the answers

What is the underlying mechanism of excess sweating causing hypernatremia?

Water loss in excess of sodium loss Signup and view all the answers

What is a common sign of hypernatremia?

CNS Symptoms Signup and view all the answers

Which of the following can cause nonosmotic ADH secretion leading to hyponatremia?

Pain or stress Signup and view all the answers

What type of hypernatremia is characterized by [ TBW and Na+; greater  TBW]

Hypernatremia with Hypovolemia Signup and view all the answers

What is the treatment approach for a patient with hypernatremia who cannot drink?

IV H2O replacement with D5W Signup and view all the answers

What is the underlying mechanism of mineralocorticoid excess causing hypernatremia?

Excess sodium reabsorption Signup and view all the answers

What is a complication of untreated hypernatremia?

Both A and B Signup and view all the answers

What is a characteristic of hypernatremia in the elderly?

Both A and B Signup and view all the answers

What is the primary mechanism of hypernatremia in the elderly?

Inadequate H2O intake Signup and view all the answers

What is the primary cause of hypernatremia?

Deficit of H2O relative to solute Signup and view all the answers

What is the consequence of hypernatremia on intracellular spaces?

H2O moving out of intracellular spaces Signup and view all the answers

What is the mortality rate associated with hypernatremia?

40-60% Signup and view all the answers

What is the primary cause of hypernatremia in a patient with diabetes?

Hyperglycemia Signup and view all the answers

Which of the following is a risk factor for hypernatremia?

Vomiting Signup and view all the answers

What is the characteristic of hypernatremia in terms of plasma osmolality?

Hypertonic Signup and view all the answers

What is the consequence of a water deficit in the body?

Hypernatremia Signup and view all the answers

What is the primary mechanism of hypernatremia?

Deficit of H2O relative to solute Signup and view all the answers

What is the characteristic of a patient with diabetes insipidus?

Cannot secrete a concentrated urine Signup and view all the answers

What is the effect of renal insufficiency on urine concentration?

Prevents maximally concentrated urine Signup and view all the answers

What is the consequence of hypernatremia on cellular tonicity?

Cellular tonicity equal to ECF Signup and view all the answers

What is the pathogenesis of hypernatremia?

Excess water loss Signup and view all the answers

What is the relationship between hypernatremia and hyperosmolality?

Hypernatremia implies hyperosmolality Signup and view all the answers

What is the relationship between hypernatremia and Na+ balance?

Hypernatremia can occur with or without a disturbance in Na+ balance Signup and view all the answers

What is the effect of excess sweating on the body?

Leads to hypernatremia Signup and view all the answers

What is the consequence of uncontrolled diabetes on sodium levels?

Hypernatremia Signup and view all the answers

What is the primary indicator for surgical therapy in hyperparathyroidism?

Calcium > 12 mg Signup and view all the answers

What is the primary cause of hypermagnesemia?

All of the above Signup and view all the answers

What is the effect of hypermagnesemia on the nervous system?

Decreased deep tendon reflexes or disappearance Signup and view all the answers

At what level of magnesium does cardiac arrest occur?

Magnesium >12-15 mEq/L Signup and view all the answers

What is the effect of hypermagnesemia on the EKG?

Prolonged PR interval Signup and view all the answers

What is the effect of hypermagnesemia on blood pressure?

Hypotension Signup and view all the answers

What is a common cause of deficient excretion of magnesium in urine?

Both A and B Signup and view all the answers

At what level of magnesium do symptoms typically occur?

Magnesium >5-10 mEq/L Signup and view all the answers

What is the treatment for severe hypermagnesemia?

IV of 10% Calcium Gluconate [10-20 cc] Signup and view all the answers

How can magnesium levels be decreased if renal function is okay?

IV Lasix Signup and view all the answers

What is a recommended treatment for hypomagnesemia?

Plasma magnesium Signup and view all the answers

What should patients and families be advised against if they have hypermagnesemia?

Do not take Magnesium containing laxatives or antacids Signup and view all the answers

What is the mortality rate associated with hypernatremia?

40-60% Signup and view all the answers

Which of the following are risk factors for hypernatremia? (Select all that apply)

Excessive sweating Signup and view all the answers

What is the primary goal of treatment for hypernatremia?

Replacing water Signup and view all the answers

True or False: Diabetes insipidus is a defect in the production or release of ADH by the posterior pituitary.

True Signup and view all the answers

What is the syndrome characterized by less than maximally dilute urine in the presence of plasma hypoosmolality and hyponatremia?

SIADH Signup and view all the answers

Which of the following is a common etiology of SIADH?

Sustained ADH release Signup and view all the answers

Symptoms of hyponatremia occur when plasma osmolality falls to 12 mg/dL.

False Signup and view all the answers

In primary hyperparathyroidism, high serum Ca+, normal ______.

PO4- Signup and view all the answers

Match the following treatments to their corresponding conditions:

Estrogens = Mild hypercalcemia in postmenopausal women Prednisone = Vitamin D excess IV of 0.9% NS with KCL and Lasix = Patients with normal renal function Bisphosphonates plus NS and Lasix = Patients with malignancy Signup and view all the answers

Study Notes

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.

Advanced Laboratory Evaluation

Disorders of Sodium

Hypernatremia: plasma Na+ >145 mEq/L, caused by a deficit of H2O relative to solute, with a mortality rate of 40-60%
Hypernatremia implies hyperosmolality of ECF, resulting in H2O moving out of intracellular spaces until cellular tonicity is equal to that of ECF
Risk factors for hypernatremia: vomiting, diarrhea, renal disease, taking loop diuretics, burns, and excessive sweating
Pathogenesis of hypernatremia: usually caused by excess loss of H2O from the body that is not adequately replaced, leading to hyperosmolality of ECF

Pathogenesis of Hypernatremia (continued)

Osmotic diuresis, commonly caused by hyperglycemia, can lead to hypernatremia
Renal insufficiency can prevent maximally concentrated urine, predisposing to hypernatremia
Diabetes insipidus, a defect in production or release of ADH, can cause hypernatremia
In the elderly, hypernatremia can occur due to inability to access H2O, impaired thirst, impaired renal concentrating ability, and increased insensible H2O loss

Diagnosis and Treatment of Hypernatremia

Diagnosis: signs and symptoms include thirst, CNS symptoms (brain stem shrinkage, confusion, neuromuscular irritability, seizures, and coma)
Treatment: primary goal is H2O replacement, with IV fluids with D5W if patient cannot drink

Principle Causes of Hypernatremia

Hypernatremia with hypovolemia: extrarenal losses (vomiting, diarrhea, burns, excessive sweating) and renal losses (intrinsic renal disease, osmotic diuresis, loop diuretics)
Hypernatremia with euvolemia: extrarenal losses (tachypnea, fever) and renal losses (central DI, nephrogenic DI)
Hypernatremia with hypervolemia: hyper-tonic IV fluids, mineralocorticoid excess, and adrenal tumor secreting deoxycorticosterone

Surgical vs Conservative Therapy

Guidelines for surgery: calcium > 12 mg, hypercalciuria >400 mg/24 hrs, nephrolithiasis, cystic bone disease, overt neuromuscular disease, decreased cortical bone density, reduced renal function, and age 2.1 mEq/L

Hypermagnesemia

Etiology: rare, deficient excretion of magnesium in urine due to renal disease or renal failure, or chronic ingestion of magnesium-containing antacids
Signs/Symptoms: if plasma level is 5-10 mEq/L, EKG shows prolonged PR interval, widening of QRS and increased T wave amplitude, decreased DTRs, hypotension, respiratory depression, and cardiac arrest when Magnesium >12-15 mEq/L

Advanced Laboratory Evaluation

Disorders of Sodium

Hypernatremia: plasma Na+ >145 mEq/L, caused by a deficit of H2O relative to solute, with a mortality rate of 40-60%.
Risk factors: vomiting, diarrhea, renal disease, taking loop diuretics, burns, and excessive sweating.
Pathogenesis: usually caused by excess loss of H2O from the body that is not adequately replaced, leading to hyperosmolality of ECF, which results in H2O moving out of intracellular spaces until cellular tonicity equals that of ECF.
Most common cause of hypernatremia from osmotic diuresis is hyperglycemia, seen in nonketotic hyperosmolar hyperglycemic coma of diabetes.
Renal insufficiency can prevent maximally concentrated urine, predisposing to hypernatremia.
Diabetes insipidus is a defect in production or release of ADH by the posterior pituitary, leading to an inability to secrete a concentrated urine.
Common in the elderly, related to inability to access H2O, impaired thirst, impaired renal concentrating ability, and increased insensible H2O loss.
Diagnosis: based on signs and symptoms, including thirst, CNS symptoms, and neuromuscular irritability.
Treatment: H2O replacement is the primary goal; if the patient cannot drink, IV with D5W.

Principle Causes of Hypernatremia

Hypernatremia with hypovolemia: extrarenal losses, vomiting, diarrhea, burns, excess sweating, and intrinsic renal disease.
Hypernatremia with euvolemia: central DI, nephrogenic DI, and inability to access H2O.
Hypernatremia with hypervolemia: hypertonic IV fluids, saline, NaHCO3, and TPN.

Hyponatremia

Plasma Na+ <135 mEq/L, caused by an excess of H2O relative to solute.
Causes: protracted vomiting, severe diarrhea, and sequestration of fluid in 3rd space replaced with free H2O or treated with hypovolemic IVF.
Euvolemic hyponatremia: dilutional hyponatremia can occur from excess H2O intake without Na+ retention in the presence of renal failure, Addison's disease, myxedema, or nonosmotic ADH secretion.
Hypervolemic hyponatremia: increase in TBW and total body Na+ content, common in CHF and liver failure.

Principle Causes of Hyponatremia

Hyponatremia with hypovolemia: GI losses, vomiting, diarrhea, and 3rd spacing.
Hyponatremia with euvolemia: syndrome of inappropriate ADH secretion, hypothyroidism, glucocorticoid deficiency, and primary polydipsia.
Hyponatremia with hypervolemia: congestive heart failure, hepatic cirrhosis, and nephrotic syndrome.

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

SIADH is characterized by a less than maximally dilute urine in the presence of plasma hypoosmolality and hyponatremia.
Etiology: often unknown, but sustained ADH release or erratic ADH secretion independent of osmotic control.
Pathogenesis: in some, ADH secretion is erratic and apparently independent of osmotic control, while in others, ADH levels vary appropriately with plasma osmolality, but the osmotic threshold for ADH is abnormally low.

Diagnosing SIADH

Symptoms of hyponatremia occur when plasma osmolality falls to 250 mg/dL, ionized Ca+ is almost always low, and PO4- is often low.
In primary hyperparathyroidism, serum Ca+ is high, and PO4- is normal; if PO4- is low, it is a 2nd disease.

Diagnostic Tests

Parathyroid hormone assays: recently, PTH by IRMA has improved sensitivity to detect hyperparathyroidism.

Further Evaluation

Once hypercalcemia and elevated PTH are established, rule out malignancy and impaired renal status.
Check urinary excretion of calcium.

Treatment

If symptoms are mild and Ca+ is 15 mg/dL, conservative approach is appropriate.
Patients with benign familial hypercalcemia from parathyroid hyperplasia do not have hypercalciuria or other complications of hypercalcemia and do not need surgery.

The So-Called Asymptomatic Patient

If patient is asymptomatic, a conservative approach is appropriate.
Most cases are associated with psychiatric and neuromuscular disturbances that are not articulated.
Prominent symptoms include anxiety, nervousness, daytime sleepiness, loss of energy, crying easily, excessive worry, irritability, and lack of interest.

Therapy

Rate of complications is low in the asymptomatic patient with the exception of nephrolithiasis.
Decision for or against surgery is based on complicating problems.### Mild Hypercalcemia Treatment
Estrogens may be used to treat mild hypercalcemia in postmenopausal women
Prednisone (20-40 mg/day PO) is usually effective in controlling calcium levels in cases of Vitamin D excess

Hypercalcemia Treatment

With normal renal function, IV of 0.9% NS with KCL and Lasix can be used to increase renal excretion of calcium
Goal of treatment is to have the patient void at least 3 liters/day
In patients with malignancy, bisphosphonates plus NS and Lasix can be used to inhibit osteoclasts from absorbing bone

Hyperparathyroidism Treatment

Symptomatic and progressive hyperparathyroidism requires surgical intervention
99m Tc Sestamibi, a radionuclide agent, is used to "map" the tumor prior to surgery
Patients should only be referred to a surgeon experienced in parathyroid exploration

Surgical vs Conservative Therapy

Guidelines for surgery include:
- Calcium > 12 mg
- Hypercalciuria >400 mg/24 hrs
- Nephrolithiasis
- Cystic bone disease
- Overt neuromuscular disease
- Decreased cortical bone density
- Reduced renal function
- Age 2.1 mEq/L

Hypermagnesemia

Rare, due to deficient excretion of magnesium in urine (2nd to renal disease or renal failure)
Signs/symptoms include:
- EKG shows prolonged PR interval, widening of QRS and increased T wave amplitude (if plasma level is 5-10 mEq/L)
- Decreased or absent DTRs
- Hypotension
- Respiratory depression
- Cardiac arrest (when magnesium >12-15 mEq/L)