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What are the two main physiologic mechanisms that regulate body water?

Thirst. Antidiuretic Hormone (ADH)


How does thirst work?

Controlled by hypothalamus. Two stimuli are true thirst based on water need: 1) cellular dehydration caused by an increase in extracellular osmolality, 2) a decrease in blood volume, which may or may not be associated with a decrease in serum osmolality


What do Osmoreceptors do?

Sensory neurons which are located in or near the thirst center in the hypothalamus, respond to changes in extracellular osmolality by stimulating the sensation of thirst


Where is ADH stored?

Pituitary gland


Where is ADH made?

Its a hormone made in the hypothalamus, stored in the pituitary gland and released into the blood stream when necessary


What are ADH levels controlled by?

Extracellular volume and osmalality


How does ADH work?

ADH direct kidneys to concentrate the urine by reabsorbing the filtered water to the bloodstream --> less urine. When this system for regulating the kidney's handling of fluids is disrupted can cause diabetes insipidus


What is Diabetes Insipidus?

Deficiency of or a decreased response to ADH also known as arginine vasopressin (AVP). Unable to concentrate urine during periods of water restriction. Excrete large volumes of urine, usually 3-20 L/day


What are the similarities in signs and symptoms between DM and DI?

Excessive thirst and excessive urination


What are the signs and symptoms of DI?

Polyuria. Nocturia. Thrist. Mild daytime fatigue/somnolence


When monitoring urine output, what is considered polyuria?

> 50 ml/kg daily


What is urine osmolality like in DM?

A urine osmolality of 300 mOsmol/L or more plus a high serum glucose level


What is urine osmolality like in DI?

If the urine osmolality is less than 300 mOsmol/L in the presence of polyuria


What is urine osmolality like in Renal Disease?

High urine osmolality plus high serum uria


What are the two types of DI?

Neurogenic/Central (Defect in synthesis or release of ADH). Nephrogenic (Kidneys do not respond to ADH)


ADH normally promotes reabsorption of water in the collecting duct of nephrons. If urine osmolality does not increase after injection of exogenous ADH, what might the patient have?

Nephrogenic DI


Increased plasma osmolality normally stimulates release of ADH. If urine osmolality remains lower than plasma osmolality during fluid restriction, what might the patient have?

Central DI


When does Central DI occur?

In both sexes equally and affects all ages, with the most frequent age of onset between 10 and 20 years. Vasopressin (ADH) missing or very low level due to malfunction of hypothalamus or posterior pituitary gland (impaired synthesis, transport, and release of ADH)


What can Central DI be caused by?

Head injury. Tumors. Neurosurgical manipulations. Infections. Bleeding. There is usually a loss of 75-80% of ADH secretory neurons before polyuria becomes evident


What are the symptoms of Central DI?

Excessive thirst, fatigue, clear and odorless urine, dehydration


What is Nephrogenic DI caused by?

Kidney diseases, contributing to unresponsiveness to vasopressin (ADH). ADH receptors in kidney affected (side effect of lithium, electrolyte disorders (K depletion, chronic hypercalcemia))


What are the symptoms of Nephrogenic DI?

Excessive thirst, fatigue, clear and odorless urine, dehydration


What is a water deprivation test to differentiate types of DI?

Withholding all fluids to provide a potent stimulus for ADH secretion. 4-18 hours, with hourly measurements of body weight and urine osmolality, until two or three consecutive samples vary by less than 30 mOsm/kg or until the patient loses 5% body weight. Serum ADH level is measured, and then 5 units of ADH or 1ug of desmopressin (synthetic analog of ADH) is injected. Urine osmolality is then measured 30-60 minutes later. Plasma osmolality is also measured at various points during the test


What happens in Central DI with ADH injection?

Urine osmolality remains less than plasma osmolality after dehydration. After ADH injection, urine osmolality increases by MORE than 50%


What happens in Nephrogenic DI with ADH injection?

Urine osmolality remains less than plasma osmolality. After giving ADH, urine osmolality increases by LESS than 50%


How is Water and ADH used as treatment for Central DI?

Corrects metabolic abnormality due to excessive dilute urine. ADH replacement: Pitressin (vasopressin tannate in oil). Given IM Q2-4 days and provides relief for 24-72 hours


What is the current drug of choice for long-term therapy of Central DI?



How does Desmopressin work?

Acts selectively at V2 receptors to increase urine concentration and decrease urine flow in a dose dependent manner


How can Desmopressin be administered?

Parenterally, Intranasally, Orally


What are the contraindications for Desmopressin?

Hyponatremia. Renal impairment CrCl < 50


What should be remembered about Desmopressin Intranasal?

Delivers doses of 0.1 mL (10mcg) or multiples of 0.1 mL. Requires refrigeration. Primed prior to the first use


When should you consider an alternative route when using Desmopressin Intranasal?

If changes in nasal mucosa (scarring, edema) leads to unreliable absorption


What are the advantages to using Desmopressin Oral?

Extremes of age. Mentally/physically handicapped. Chronic allergic rhinitis. Nasal packing following transsphenoidal surgery


What is the Desmopressin Oral potency compared to Intranasal spray?

0.1mg tablet is equivalent to 2.5-5mcg of the nasal spray


How should Oral Desmopressin be taken?

Absorption decreased by 40-50% when taken with meals (take when fasting). Restrict fluid intake from 1 hour before to 8 hours after taking tablets


When should you consider IV or intranasal route when taking Oral Desmopressin?

If inadequate therapeutic response at maximum recommended oral doses


When is Parenteral Desmopressin used?

If cannot be administered intranasally or orally


How is Parenteral Desmopressin given?

1mcg SQ Q12h. If inadequate absorption --> 2mcg of desmopressin acetate given IV over two minutes


What are the ADRs associated with Desmopressin?

BP increased/decreased (IV). Facial flushing/HA. Dizziness. Chills. Hyponatremia. Water intoxication. Abdominal pain, nausea


What should patients report when taking Desmopressin?

Increased weight/swelling of extremities. Unresolved HA. Chest pain/palpitation. Respiratory difficulty. CNS change. Rash


What is the MOA of Chlorpropamide (Diabinese)?

Potentiates effect of small amounts of AVP or direct activation of V2 receptor (Antidiuretic effect enhanced by cotreatment with a thiazide diuretic)


What are the ADRs associated with Chlorpropamide?

Hypoglycemia. Disulfram like reaction to ethanol


What needs to be remembered about treatment of Nephrogenic DI?

Does not respond to ADH


What do you need to correct in Nephrogenic DI?

Hypokalemia and hypercalcemia


What is the treatment plan for Nephrogenic DI?

Discontinue any drugs that may be causing it. Thiazide diuretics and modest salt restriction is usually used (HCTZ 25mg QD or BID)


What are the complications when treating Nephrogenic DI?

Hypernatremia. Severe dehydration. Cardiovascular collapse. Death


What are the symptoms of Hypernatremia?

Weakness. Lethargy. Restlessness. Irritability. Twitching. Seizures. Coma. Death


What needs to be monitored when treating Nephrogenic DI?

Regular outpatient follow up. Treatment adjustments based on: Symptoms, Serum sodium level, Urine volume