Introduction
Diabetes insipidus is a type of diabetes that is characterized by a reduced production of the ADH (antidiuretic hormone) also known as vasopressin in the body. This type of diabetes is manifested in the form of water metabolism disorders. This means that a patient experiences excessive thirst and excretes a lot of severely diluted urine. There are two main types of diabetes insipidus. The first one is characterized by reduced secretion of vasopressin, and it is known as cranial diabetes insipidus. The second type is known as nephrogenic diabetes insipidus (Babey, Kopp & Robertson, 2011). This type is caused by the failure by the kidneys to respond to vasopressin. These are the most common types of diabetes. This essay will look into the pathophysiology, diagnosis, and treatment of these two conditions.
Pathophysiology of Nephrogenic Diabetes Insipidus
In this condition, the kidneys become insensitive to the antidiuretic effects of vasopressin. This may result in excessive production of dilute urine. Loss of body water prompts increased plasma osmolality. This triggers the thirst mechanism thereby increasing a patient’s water intake to compensate for the lost amount. Because of this, the plasma osmolality is stabilized at a higher level prompting the body to increase the thirst threshold. Polydisia and polyuria levels vary depending on various factors. These might include differences in solute load, thirst sensitivity, and vasopressin osmostats. For polyuria to occur, renal insensitivity does not have to be complete.
This is because the effects only need to be enough to hamper concentration of urine at vasopressin plasma levels. This level is achieved under normal conditions of water intake. In this case, the plasma osmolality is almost at the osmotic thirst threshold. According to vasopressin deficiency calculations, this level can only be reached after sensitivity to vasopressin has been reduced by tenfold. Practically, the levels of vasopressin in urine concentration have to be more than 5pg/mL. (Uyeki, Barry, Rosenthal & Mathias, 1993).
Urine osmolality and levels of plasma vasopressin are the main determinants of the severity of nephrogenic diabetes insipidus. Insensitivity to the vasopressin can be incomplete at times. This means patients suffering from this condition have the ability to concentrate their urine if they do not take much water. This may also occur when large doses of vasopressin are administered.
Pathophysiology of Cranial Diabetes Insipidus
When it comes to cranial diabetes insipidus, the main defect is lack of osmoregulated vasopressin production (Majzoub & Srivatsa, 2006). This means that the excreted renal water is solute free. To maintain a water and normonatraemia balance, a lot of fluid intake is required. In case a patient does not access water or he/she is not thirst sensitive, he/she develops hypernatraemia. High water intake makes plasma osmolality stabilize at higher levels. This is necessary for maintaining normal water balance.
Diagnosis
The first step in diagnosing diabetes insipidus is making sure that a patient’s urine volume is tracked in the course of a twenty-four hour period. This can positively indentify polyuria. Subsequent tests include blood tests to measure serum, glucose, calcium, and potassium levels. These tests are meant to rule out conditions that enable nephrogenic insipidus. Osmolality in urine samples is best determined from early morning samples. However, concomitant serum samples provide the best results.
One can also diagnose this condition by measuring plasma vasopressin in response to plasma osmolality (Ball, Vaidja & Baylis, 1997). A hypertonic saline is induced over a time of two hours for this to be accomplished. This continues until plasma osmolality of about 300mmol/kg is achieved.
Administering low dosage desmopressin can also be used as a diagnosis tool. This is particularly important in cases where there is no equipment to measure plasma vasopressin. In this diagnosis, the patient’s urine osmolality and volume, weight, and plasma sodium are recorded for the first three days. Then a small dose of intramuscular desmopressin is administered for the next eight to ten days. If there is a reduction of thirst indentified and reduced urine volumes within this period, then the patient may be suffering from nephrogenic insipidus.
Treatment
Cranial diabetes insipidus is mostly treated by introducing a synthetic hormone known as arginine vasopressin into the body. The drug’s vasopressin molecule prolongs its antidiuretic ability. For diuresis to be fully controlled, several dosages are required. Daily oral doses vary from 100 to 1000μg for two or three times a day. Sometimes, treatment may result in erratic changes in osmolality (Makaryus & McFarlane, 2006). This usually happens in the initial stages of treatment before the correct dosage has been figured out.
Nephrogenic diabetes inspidus is harder to treat than cranial diabetes. Other than drug induced or metabolic related disorders, the rest involves lengthy treatments. Treatment involves salt restriction together with the administration of a thiazide diuretic. A potassium-sparing drug like amiloride should accompany this medication. Lately, the condition is being treated using a combination of indomethacin, thiazide, and desmopressin.
References
Babey, M., Kopp, P. & Robertson, G.L. (2011). Familial forms of diabetes insipidus: clinical and molecular characteristics. Nature reviews. Endocrinology, 7(12), 701-14.
Ball, S.G., Vaidja, B. & Baylis, P.H. (1997). Hypothalamic adipsic syndrome: diagnosis and management. Clin Endocrinol, 47,405–409.
Makaryus, A.N. & McFarlane, S.I. (2006). Diabetes insipidus: diagnosis and treatment of a complex disease. Cleveland Clinic journal of medicine, 73(1), 65-71.
Majzoub, J.A. & Srivatsa, A. (2006). Diabetes insipidus: clinical and basic aspects. Pediatric endocrinology reviews, 1, 60-65.
Uyeki, M., Barry, F.L., Rosenthal, S.M. & Mathias, R.S. (1993). Successful treatment with hydrochlorothiazide and amiloride in an infant with congenital nephrogenic diabetes insipidus. Pediatr Nephrol, 7, 554–556.