Antidiuretic hormone in the blood

Antidiuretic hormone is a peptide consisting of 9 amino acid residues. It is synthesized as prohormone in hypothalamic neurons, whose bodies are located in supraoptic and paraventricular nuclei. The gene for the antidiuretic hormone also encodes neurofizin II, a carrier protein transporting an antidiuretic hormone along the axons of neurons that terminate in the posterior lobe of the pituitary gland, where an accumulation of antidiuretic hormone occurs. Antidiuretic hormone 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. All these factors should be taken into account when evaluating the results of research.

Reference values of the concentration of antidiuretic hormone in the blood plasma

Osmolarity of plasma, mosm / l	ADH, pg / ml
270-280	<1.5
280-285	<2.5
285-290	1-5
290-295	2-7
295-300	4-12

The yield of the antidiuretic hormone from the storage vesicles is regulated primarily by plasma osmolality. 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 the antidiuretic hormone is sharply accelerated, which is associated with the 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 secretion of the antidiuretic hormone 4 times, whereas a decrease in osmolarity by 2% is accompanied by a complete cessation of the secretion of the antidiuretic hormone.

Hemodynamic factors also have a pronounced regulatory effect on the secretion of antidiuretic hormone. 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, the pulses from the "stretched" baroreceptors transmit information to the neurons of the supraoptic and paraventricular nuclei of the hypothalamus, which stimulate the release of the antidiuretic hormone.

The main biological effect of antidiuretic hormone is to increase the resorption of free water from the urine, located in the lumen of the distal part of the renal tubules, into the cells of the tubules. Antidiuretic hormone binds to specific V ₂ receptors in the outer membrane of these cells, inducing 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 (insufficiency of antidiuretic hormone). True diabetes insipidus is characterized by polyuria and polydipsia as a result of insufficiency of the antidiuretic hormone. 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 can serve as a 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 antibodies 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%. Insufficient antidiuretic hormone is complete or partial, which determines the degree of polydipsia and polyuria.

The study of the concentration of antidiuretic hormone in the 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 secretion of antidiuretic hormone. 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. When the water limited test is performed in patients with severe antidiuretic hormone deficiency, the blood plasma osmolality is increased, but the osmolarity of the urine usually remains below the osmolarity of the blood plasma.

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

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

Primary nocturnal enuresis (insufficiency of antidiuretic hormone). 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. The physiological feature of the organism of such patients is a low concentration of antidiuretic hormone in the blood. 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 antidiuretic hormone. His level in the body constantly fluctuates. In a healthy child at night, the concentration of antidiuretic hormone in the blood is higher than in the day, and with a primary night enuresis, this level is already quite low, at night it decreases even more, resulting in a large amount of unconsolidated 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 the night portions when carrying out the Zimnitsky sample. Osmolarity of urine in night portions is lower than in daytime. The concentration of antidiuretic hormone 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 antidiuretic hormone in the blood plasma is more often detected in the evening and night hours. The appointment of patients with primary nocturnal enuresis of synthetic analogues of antidiuretic hormone leads to a cure in 70-80% of patients.

Nephrogenic diabetes insipidus (diabetes insipidus, not sensitive to antidiuretic hormone). At the heart of the disease is the lack of sensitivity of the epithelium of the renal tubules to the antidiuretic hormone. When the antidiuretic hormone interacts with the renal tubular receptors, cAMP is not formed, so protein kinase A is not activated and the intracellular effect of the antidiuretic hormone 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 in diabetes insipidus. For nephrogenic diabetes insipidus is normal or elevated concentration of antidiuretic hormone 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.

With nephrogenic diabetes insipidus, the use of antidiuretic hormone 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 the disruption of the secretion of antidiuretic hormone. Characterized by oliguria, (constant or periodic), lack of thirst, the presence of common edema, increased body weight and high concentration of antidiuretic hormone in the blood plasma, inadequate to the level of osmolarity.

This syndrome can develop in the pathology of the central nervous system, in particular with meningitis, encephalitis, tumors and abscesses of the brain, subarachnoid hemorrhages, craniocerebral trauma, and can also be caused by pneumonia, tuberculosis, acute renal failure, psychoses, certain drugs (vincristine, carbamazepine and other). In some cases, inadequate secretion of antidiuretic hormone is possible with hypothyroidism. The mechanism of the disruption of the secretion of the antidiuretic hormone is due to direct damage to the hypothalamus. Sometimes the cause of inadequate secretion of antidiuretic hormone 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, neurologic 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. Detect an increased content of antidiuretic hormone in the blood plasma in relation to its osmolarity, a reduced concentration of aldosterone, a reduced response in the test of inhibition of the secretion of the antidiuretic hormone by the water load.

Ectopic secretion of antidiuretic hormone is possible with a variety of tumors. Most often, the ectopic secretion of the antidiuretic hormone 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.

Functional state of the renin-angiotensin-aldosterone system

The renin-angiotensin-aldosterone system determines the constancy of the volume and osmolarity of the extracellular fluid. It plays the same role in determining the diameter of the vessels and the level of tissue perfusion. This cascade [enzyme (renin) - peptide hormone (angiotensin II) - steroid hormone (aldosterone)] fulfills its important function due to the specific ability to detect and return to normal even the smallest increase or decrease in the volume of sodium and water in the body.

Functioning of the renin-angiotensin-aldosterone system can be briefly described in the example of its reaction to the reduction of the volume of sodium and water in the body (for example, in case of bleeding, resulting in a decrease in the volume of circulating blood).

As a result of bleeding, blood pressure in the leading arterioles of the glomerular glomeruli of the kidneys decreases. Yuxtaglomerular cells located in the wall of these arterioles catch the weakening of the tension of the wall of arterioles, as a result of which renin is released into the glomerular capillary blood.

The renin released into the blood acts on the angiotensinogen, a plasma protein belonging to the α ₂ -globulin group. Angiotensinogen is synthesized and secreted by the liver. Renin cleaves off decapeptide (angiotensin I) in the kidneys. Angiotensin I (AI) is a substrate for ACE, which cleaves 2 amino acids from it, forming octapeptide-angiotensin II (AII). Angiotensin II has several effects aimed at correcting the contracted volume of extracellular fluid. One such action is an increase in the synthesis and secretion of aldosterone in the adrenal glands. Another effect is vasoconstriction of blood vessels. Angiotensin II can be converted into angiotensin III - a heptapeptide that stimulates the secretion of aldosterone by the adrenal glands, and, like angiotensin II, inhibits the secretion of renin.

Aldosterone causes the reabsorption of sodium and water in the distal tubules of the kidneys (as well as in the distal part of the colon, sweat and salivary glands). This action is aimed at restoring the reduced volume of extracellular fluid. Aldosterone realizes its effects through receptors, which are found not only in the kidneys, but also in the heart and blood vessels.

Angiotensin II causes a direct increase in the tubular reabsorption of sodium and water in the kidneys, and also has direct vasoconstrictive activity, thereby reducing the volume of the vascular bed, adapting it to the reduced volume of blood plasma. As a result, blood pressure and tissue perfusion are maintained at the desired level. Angiotensin II also activates the adrenergic (sympathetic) nervous system, which quickly releases norepinephrine. Norepinephrine also causes vasoconstriction and prevents tissue hypoperfusion. Finally, angiotensin II stimulates a feeling of thirst.

The main function of the renin-angiotensin-aldosterone system is to maintain a constant volume of circulating blood. At the same time, this system plays a leading role in the pathogenesis of renal arterial hypertension, therefore, in such patients, the study of the indices of the renin-angiotensin-aldosterone system is of paramount importance in establishing a diagnosis and in conducting proper treatment. Renin, angiotensin and aldosterone are functionally closely interrelated in the human body, therefore it is recommended to simultaneously determine all three indicators.

[1], [2], [3], [4], [5], [6], [7], [8], [9]