Antidiuretic hormone in the blood plasma

ADH is a peptide consisting of 9 amino acid residues. It is synthesized as a prohormone in hypothalamic neurons, whose bodies are located in supraoptic and paraventricular nuclei. The gene for ADH also encodes neurofizin II, a carrier protein transporting ADH via axons of neurons that terminate in the posterior lobe of the pituitary where accumulation of ADH occurs. ADH has a daily rhythm of secretion( its increase is observed at night).The secretion of the hormone decreases in the lying position, when it moves to a vertical position its concentration rises. Dependence of the level of ADH in the blood from osmolarity is shown in Table. All of these factors should be taken into account when evaluating the results of studies.

Table Reference values ​​for plasma concentration of ADH [Tiz U., 1997]

Table Reference values ​​for plasma concentration of ADH [Tits U., 1997]

The release of ADH from storage vesicles is regulated primarily by the osmolarity of the plasma. The average plasma osmolality level is normal at 282 mosm / L with deviations in one direction or another up to 1.8%.If the osmolality of the plasma rises above the critical level( threshold) of 287 mosm / L, the yield of ADH is sharply accelerated, which is associated with activation of osmoreceptors located on the cellular membrane of the supraoptic and paraventricular neurons of the hypothalamus and carotid sinus cells in the carotid arteries. These receptors are able to detect changes in osmolality in the blood plasma of 3-5% higher than the average, especially with abrupt changes( more than 2% per hour).A rapid increase in osmolality of the plasma by only 2% leads to an increase in ADH secretion by 4 times, whereas a decrease in osmolarity by 2% is accompanied by a complete cessation of ADH secretion.

Hemodynamic factors also have a pronounced regulatory effect on the secretion of ADH.Reduction of mean arterial pressure and / or "effective" plasma volume by less than 10% can be detected by baroreceptors located in cells of the left atrium and, to a lesser extent, in the carotid sinus. On the multisynaptic afferent path, pulses from the "stretched" baroreceptors transmit information to the neurons of the supraoptic and paraventricular nuclei of the hypothalamus, which stimulate the release of ADH.

The main biological effect of ADH is the increase in the resorption of free water from the urine, located in the lumen of the distal part of the renal tubules, into the tubule cells. ADH binds to specific V2-receptors on the outer membrane of these cells, triggering the activation of adenylate cyclase, which forms cAMP.cAMP activates

protein kinase A. Protein kinase A phosphorylates proteins that stimulate the expression of the aquaporin-2 gene, one of the proteins that create channels for water. Aquaporin-2 migrates to the inner surface of the membrane of the tubular cells, where it is embedded in the membrane, forming pores or canals through which water from the lumen of the distal tubules diffuses freely inside the tubular cell. Then, water passes from the cell through the channels in the plasma membrane to the interstitial space, where it enters the vascular bed.

Non-diabetes mellitus( ADH deficiency).True diabetes insipidus is characterized by polyuria and polydipsia due to ADH deficiency. To persistent diabetes insipidus lead destruction of the surveillance and peripheral nuclei or cutting of the surveillance path above the median elevation.

The cause of the disease may be the defeat of the neurohypophysis of any genesis. Most often these are tumors - craniopharyngomas and gliomas of the optic nerve. In patients with histiocytosis, insipid diabetes develops in 25-50% of cases. Occasionally, the cause of diabetes insipidus is encephalitis, sarcoidosis, tuberculosis, actinomycosis, brucellosis, malaria, syphilis, influenza, tonsillitis, all kinds of typhus, septic conditions, rheumatism, leukemia. Non-diabetes mellitus can develop after a traumatic brain injury, especially if it is accompanied by a fracture of the base of the skull.

Non-diabetes, which develops after surgery on the pituitary or hypothalamus, can be either transient or permanent. The course of the disease that occurs after accidental trauma is unpredictable;Spontaneous recovery may occur several years after the injury.

In recent years, it has been shown that diabetes insipidus can have an autoimmune origin( the presence of AT to ADH-secreting cells).In rare cases, it can be hereditary. Non-diabetes mellitus can be a component of a rare occurrence of Tungsten syndrome, in which it combines with diabetes, atrophy of the optic nerves and sensorineural hearing loss.

Clinical signs of polyuria appear when the secretory capacity of hypothalamic neurons is reduced by 85% [Dedov II, 1995].ADH deficiency is complete or partial, which determines the degree of polydipsia and polyuria.

The study of the concentration of ADH in blood plasma is not always necessary for the diagnosis of diabetes insipidus. A number of laboratory indicators quite accurately indicate the patient's lack of ADH secretion. The daily volume of urine reaches 4-10 liters and more, its density varies within the range of 1,001-1,005, osmolarity - within 50-200 mosm / l. During periods of severe dehydration, the urine density rises to 1.010, and osmolality to 300 mOsm / l. In children, the initial sign of the disease can be nocturia. In other respects, the kidney function is not impaired. Often, hyperosmolarity of plasma( above 300 mosm / L), hypernatremia( more than 155 mmol / l) and hypokalemia are revealed. In the water limited test, patients with severe ADH deficiency have an increase in blood plasma osmolality, but urine osmolality usually remains below the osmolality of the blood plasma.

Fig. The secretion and effects of ADH

Fig. Secretion and effects of ADH

With the introduction of vasopressin, the osmolarity of urine increases rapidly. With moderately severe ADH and polyuria deficiency, the osmolarity of the urine during the test may be slightly higher than the osmolarity of the plasma, and the response to vasopressin is weakened.

Constantly low concentrations of ADH in the blood plasma( less than 0.5 pg / l) indicate a marked neurogenic diabetes insipidus, subnormal levels( 0.5-1 pg / L) in combination with plasma hyperosmolarity - about partial neurogenic diabetes insipidus. Determination of the concentration of ADH in blood plasma is the main criterion that allows to differentiate partial diabetes insipidus from primary polydipsia.

Primary nocturnal enuresis( ADH deficiency).Nocturnal enuresis is detected in every tenth child aged 5-7 years, and at the age of 10 years - every twentieth. The cause of enuresis can be many factors: stress, urogenital infections, nephrologic disorders, etc. Quite often, bedwetting is only a consequence of another disease, but in some cases it is caused by a primary nocturnal enuresis. This diagnosis is given in children older than 5 years who, in the absence of organic disorders and normal urination during the day, urinate in bed at night more often 3 times a week. Physiological feature of the organism of such patients is a low concentration in the blood of ADH.There is a hereditary predisposition to the development of primary nocturnal enuresis. Girls get sick less often than boys.

In patients with primary nocturnal enuresis at night, 2-3 times more urine is formed than in healthy children. The most important role in this process is played by ADH.His level in the body constantly fluctuates. A healthy child at night has a higher concentration of ADH in the blood than during the day, and with a primary nocturnal enuresis, this level is already quite low, decreases even more at night, resulting in a large amount of unconcentrated urine. Usually by four o'clock in the morning, much earlier than in healthy children, the bladder in patients is filled to the limit. Sleep at this time is very deep, so children urinate in bed.

For patients with primary nocturnal enuresis, nocturia is characteristic, and a low specific gravity of urine in night portions when carrying out a Zimnitsky sample. Osmolarity of urine in night portions is lower than in daytime. The concentration of ADH in the blood plasma, when tested in the daytime hours, is often within normal limits, and if its decrease is detected, it is insignificant. Reduced concentration of ADH in the blood plasma is more often detected in the evening and night hours. The appointment of synthetic analogues of ADH to patients with primary nocturnal enuresis leads to a cure in 70-80% of patients [Temerina EA, 1998].

Nephrogenic diabetes insipidus( diabetes insipidus, not sensitive to ADH).At the heart of the disease is the lack of sensitivity of the epithelium of renal tubules to ADH.When ADH interacts with the renal tubular receptors, cAMP is not formed, so protein kinase A is not activated and the intracellular effect of ADH is not realized. Mostly males are ill. The disease is inherited as a trait linked to the X chromosome. Changes in laboratory indicators and functional tests are similar to those detected with diabetes insipidus

.For nephrogenic diabetes insipidus is normal or elevated concentration of ADH in the blood plasma. When carrying out the test with vasopressin, there is no increase in the level of cAMP in the urine after its introduction.

In patients with nephrogenic diabetes insipidus, the use of ADH drugs is ineffective. Thiazide diuretics combined with prolonged restriction of table salt in a diet can give a good clinical result. It is necessary to correct hypokalemia and hypercalcemia under the control of the concentration of potassium and calcium in the blood serum.

Syndrome of inadequate secretion of vasopressin( Parkhon syndrome) is the most frequent variant of ADH secretion violation. Characterized oligurie,( constant or periodic), lack of thirst, the presence of common edema, increased body weight and high concentration of ADH in blood plasma, inadequate level of osmolarity.

This syndrome can develop with CNS pathology, particularly in meningitis, encephalitis, tumors and abscesses of the brain, subarachnoid hemorrhages, craniocerebral trauma, and can also be caused by pneumonia, tuberculosis, OPP, psychoses, some drugs( vin-cystine, carbamazepineand etc.).In some cases, inadequate secretion of ADH is possible with hypothyroidism. The mechanism of violation of ADH secretion is caused by direct damage to the hypothalamus. Sometimes the cause of inadequate secretion of ADH can not be established. In blood plasma, a decrease in the concentration of sodium( less than 120 mmol / l) is detected;if it becomes below 110 mmol / l, neurological symptoms develop - stupor, cramps are possible. Osmolarity of the plasma is low( less than 270 mosm / L), hypoosmolar coma may develop. In the study of 24-hour urine, increased excretion of sodium from the body is noted. There is an increased content of ADH in the blood plasma in relation to its osmolarity, a reduced concentration of aldosterone, a reduced response in the test of oppression of ADH secretion by the water load.

Ectopic secretion of ADH is possible for a variety of tumors. Most often ectopic secretion of ADH accompanies bronchogenic lung cancer, malignant tumors of the pancreas, thymus gland, duodenum. Changes in laboratory parameters are similar to those in the syndrome of inadequate secretion of vasopressin.

A comprehensive assessment of the results of laboratory studies in patients with various forms of polyuria is presented in the table.

Table Evaluation of laboratory indicators in patients with polyuria

Table Evaluation of laboratory indicators in patients with polyuria

End of Table.

Test of stimulation of ADH by restriction of water intake before administration of vasopressin

End of Table.