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Pathophysiology assignment by
- James-MSCN
- Gloria -MSCN **Topic: DIABETES INSIPIDUS Objectives
- Define diabetes insipidus
- Describe the etiology and pathogenesis
- Describe the types of the diseases resulting from ADH insufficiency
- Pathophysiology of the disease
- Outline the clinical manifestations
- Be able to compare signs and symptoms of Diabetes Insipidus (DI) and Syndrome of inappropriate antidiuretic hormone (SIADH) secretion**
Etiology and pathogenesis
Diabetes insipidus (DI) is a disorder of insufficient ADH (vasopressin) which is secreted from the posterior pituitary gland in response to changes in blood osmolality. It is characterized by excessive loss of water in the urine. ADH acts directly on the renal collecting ducts and distal tubules, increasing membrane permeability to and reabsorption of water. Damage to the ADH- producing cells in the hypothalamus can occur with closed head trauma, intracranial tumors, and neurosurgery. Some pharmacologic agents can lead to abnormalities in ADH secretion. For example, the diuresis that follows alcohol ingestion occurs because of decreased ADH secretion. DI is a term meaning a large diuresis of inappropriately dilute urine. In adults with DI, 30% of cases are idiopathic, 20% are caused by the surgical treatment of brain tumors, and 16% result from nonsurgical brain trauma, 25% hypophysectomy. ADH deficiency may be accompanied by other hypothalamic-pituitary hormone deficiencies. Damage to the posterior pituitary gland may cause temporary or permanent deficiency of ADH. The two forms of DI are as follows:
1. Neurogenic or central DI. Caused by the insufficient secretion of ADH, it occurs when any organic lesion of the hypothalamus, pituitary stalk, or posterior pituitary interferes with ADH synthesis, transport, or
release. Causative lesions include primary brain tumors, hypophysectomy, aneurysms, thrombosis, infections, and immunologic disorders. Central DI is a well-recognized complication of traumatic brain injury. It can also be caused by hereditary disorders that affect ADH genes or result in structural changes in the pituitary gland.
2. Nephrogenic DI. Caused by inadequate response of the renal tubules to ADH, nephrogenic DI is usually acquired or may be genetic. Acquired nephrogenic DI is generally related to disorders and drugs that damage the renal tubules or inhibit the generation of cAMP in the tubules. These disorders include pyelonephritis, amyloidosis, destructive uropathies, and polycystic kidney disease, all of which lead to irreversible diabetes insipidus. Drugs that may induce a reversible form of nephrogenic diabetes insipidus include lithium carbonate, colchicines, amphotericin B, loop diuretics, general anesthetics (such as methoxyflurane), and demeclocycline. Several genetic causes of nephrogenic DI have been identified. One of the best described is a mutation in the gene that codes for aquaporin-2, which is one of the four water transport channels in the renal tubule. NB There is a rare form of DI associated with pregnancy. In gestational DI, the level of the vasopressin-degrading enzyme vasopressinase is increased. Clinical manifestations are usually mild and do not require treatment. Dipsogenic or primary polydipsia may be confused with diabetes insipidus. It is caused by the chronic ingestion of extremely large quantities of fluid that wash out the renal medullary concentration gradient, which results in a partial resistance to ADH. This condition resolves with decreased fluid ingestion. Psychogenic causes of polydipsia must be differentiated from true DI because administering an ADH analog to an individual with psychogenic DI will result in severe hypoosmolality. Agents that enhance release of ADH include :β- adrenergic agents, barbiturates, carbamazepine, clofibrate, cyclophosphamide, histamine, carbon dioxide, morphine and narcotic analogs, nicotine, prostaglandin E2 and vincristine Agents that suppress release include: α- adrenergic agents, alcohol and phenytoin.
needed, as is a urine specific gravity measurement. Dilute urine in the presence of water deficit and hypernatremia along with abnormally low serum ADH levels are diagnostic of central DI. A water deprivation test may be used to confirm the diagnosis. Water intake is restricted, and the urine osmolality is measured hourly. When are secondary to brain tumors, and 9% follow a plateau in urine osmolality is reached, vasopressin is administered. With central DI, urine concentration increases after vasopressin administration. Polyuria and polydipsia also resolve. In the case of nephrogenic DI, little or no response to vasopressin occurs. Individuals with long-standing diabetes insipidus develop a large bladder capacity and hydronephrosis. Neurogenic diabetes insipidus usually has an abrupt onset and many individuals can specifically recall the date of onset of their symptoms. Nephrogenic DI usually has a more gradual onset
Treatment
Daily replacement of ADH is needed for the management of DI. DDAVP (1-deamino-8-d- arginine vasopressin), a synthetic analog of ADH, can be given to replace vasopressin deficiency. Free access to fluids is necessary, and home testing of urine specific gravity may be useful for some individuals to allow them to adjust their dose independently. Signs and Symptoms of Diabetes Insipidus (DI) and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion Sig ns and Symptoms DI SIADH) Urine output High Low (no hypovolemia) Urine osmolality Low (<100-200 mOsm/L) High (>800 mOsm/L) Urine specific gravity Low (<1.010) High (>1.020) Serum sodium Hypernatremia (>145 mEq/L) Hyponatremia (<135 mEq/L) Serum osmolality Hyperosmolar (>300 mOsm/L) Hypoosmolar (<285 mOsm/L) Symptoms Polyuria, thirst, high urine output, signs of dehydration Water retention, low urine output, nausea, vomiting, mental changes
KEY POINTS
- Antidiuretic hormone (ADH) secretion is regulated primarily by osmoreceptors in the hypothalamus that respond to changes in extracellular osmolality. An increase in serum osmolality stimulates secretion of ADH. Renal distal and collecting tubules respond to ADH by becoming more permeable to water. In the presence of ADH, water is reabsorbed from the urine filtrate, resulting in concentrated urine.
- Central diabetes insipidus (DI) is due to lack of production of ADH by the hypothalamus or release by the posterior pituitary gland. Central DI may be idiopathic or related to brain surgery, trauma, or tumor.
- Nephrogenic DI is caused by lack of renal collecting tubule responsiveness to ADH. Nephrogenic DI may be caused by receptor abnormalities, renal disease, medications, or electrolyte imbalance.
- Most commonly, DI causes polydipsia accompanied by thirst, polyuria, increased serum sodium level, and increased osmolality. Increased osmolality may cause cellular shrinkage with neurologic signs and symptoms. The diagnosis is confirmed when dilute urine is formed during water deprivation, which is promptly corrected with administration of vasopressin.
- DI is treated with ADH hormone replacement therapy and fluid therapy. REFERENCES
- Huether, Sue E., McCance, Kathryn L. (2017) Understanding Pathophysiology 6 th^ ed. St. Louis, Missouri USA: Elsevier Inc.
- Banasik, Jacquelyn L. & Copstead, Lee-Ellen C. (2019) Pathophysiology , 6 th^ ed. St. Louis, Missouri USA: Elsevier Inc.
