Antidiuretic hormone in the blood

Antidiuretic hormone is a peptide consisting of 9 amino acid residues. It is synthesized as a prohormone in hypothalamic neurons, the bodies of which are located in the supraoptic and paraventricular nuclei. The gene for antidiuretic hormone also codes for neurophysin II, a carrier protein that transports antidiuretic hormone along the axons of neurons that end in the posterior lobe of the pituitary gland, where antidiuretic hormone accumulates. Antidiuretic hormone has a daily secretion rhythm (its increase is observed at night). Secretion of the hormone decreases in the lying position, and its concentration increases when moving to a vertical position. All of the listed factors must be taken into account when evaluating the results of studies.

Reference values for plasma antidiuretic hormone concentrations

Plasma osmolarity, 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 release of antidiuretic hormone from storage vesicles is regulated primarily by plasma osmolarity. The average plasma osmolarity level is normally 282 mOsm/l with deviations in either direction of up to 1.8%. If plasma osmolarity rises above the critical level (threshold) of 287 mOsm/l, the release of antidiuretic hormone is sharply accelerated, which is associated with the activation of osmoreceptors located on the cell membrane of the supraoptic and paraventricular neurons of the hypothalamus and the cells of the carotid sinus on the carotid arteries. These receptors are capable of detecting changes in osmolarity in the blood plasma of about 3-5% above the average value, especially with sharp changes (more than 2% per hour). A rapid increase in plasma osmolarity by only 2% leads to a 4-fold increase in the secretion of antidiuretic hormone, whereas a decrease in osmolarity by 2% is accompanied by a complete cessation of the secretion of antidiuretic hormone.

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

The major biological effect of antidiuretic hormone is to increase the resorption of free water from the urine in the lumen of the distal renal tubules into the tubular cells. Antidiuretic hormone binds to specific V ₂ receptors on the outer membrane of these cells, causing activation of adenylate cyclase, which forms cAMP. cAMP activates protein kinase A. Protein kinase A phosphorylates proteins that stimulate expression of the gene for aquaporin-2, one of the proteins that creates channels for water. Aquaporin-2 migrates to the inner surface of the tubular cell membrane, where it is embedded in the membrane, forming pores or channels through which water from the lumen of the distal tubules freely diffuses into the tubular cell. Water then passes out of the cell through channels in the plasma membrane into the interstitial space, from where it enters the vascular bed.

Diabetes insipidus (antidiuretic hormone deficiency)

True diabetes insipidus is characterized by polyuria and polydipsia as a result of antidiuretic hormone deficiency. Persistent diabetes insipidus is caused by destruction of the supraoptic and periventricular nuclei or by transection of the supraoptic tract above the median eminence.

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

Diabetes insipidus that develops after surgical interventions on the pituitary gland or hypothalamus may be either transient or permanent. The course of the disease that occurs after an accidental injury is unpredictable; spontaneous recoveries may be observed several years after the injury.

In recent years, it has been shown that diabetes insipidus may have an autoimmune origin (the presence of antibodies to ADH-secreting cells). In rare cases, it may be hereditary. Diabetes insipidus may be a component of the rare Wolfram syndrome, in which it is combined with diabetes mellitus, optic atrophy, and sensorineural hearing loss.

Clinical signs of polyuria appear when the secretory capacity of hypothalamic neurons decreases by 85%. Deficiency of antidiuretic hormone can be complete or partial, which determines the degree of polydipsia and polyuria.

A 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 parameters quite accurately indicate the presence of insufficient secretion of antidiuretic hormone in the patient. The daily volume of urine reaches 4-10 liters or more, its density fluctuates within 1.001-1.005, osmolarity - within 50-200 mosm/l. During periods of severe dehydration, the urine density increases to 1.010, and osmolarity to 300 mosm/l. In children, the initial sign of the disease may be nocturia. In other respects, renal function is not impaired. Hyperosmolarity of plasma (above 300 mosm/l), hypernatremia (more than 155 mmol/l) and hypokalemia are often detected. When performing a water restriction test in patients with severe antidiuretic hormone deficiency, an increase in blood plasma osmolarity is observed, but urine osmolarity usually remains lower than blood plasma osmolarity.

When vasopressin is administered, urine osmolarity increases rapidly. In moderate ADH deficiency and polyuria, urine osmolarity during the test may be somewhat higher than plasma osmolarity, and the response to vasopressin is weakened.

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

Primary nocturnal enuresis (antidiuretic hormone deficiency)

Nocturnal enuresis is detected in every tenth child aged 5-7 years, and in every twentieth at the age of 10. Enuresis can be caused by many factors: stress, urogenital infections, nephrological disorders, etc. Quite often, nocturnal enuresis is only a consequence of another disease, but in some cases it is caused by primary nocturnal enuresis. This diagnosis is made in children over 5 years old who, in the absence of organic disorders and normal urination during the day, wet the bed at night more than 3 times a week. The physiological feature of the body 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 somewhat less often than boys.

Patients with primary nocturnal enuresis produce 2-3 times more urine at night than healthy children. The antidiuretic hormone plays a key role in this process. Its level in the body constantly fluctuates. In a healthy child, the concentration of antidiuretic hormone in the blood is higher at night than during the day, and with primary nocturnal enuresis, this level, already quite low, decreases even more at night, resulting in the formation of a large amount of dilute urine. Usually, by four o'clock in the morning, much earlier than in healthy children, the bladder of patients is filled to the limit. Sleep at this time is very deep, so children wet the bed.

Patients with primary nocturnal enuresis are characterized by nocturia, low specific gravity of urine in night portions when performing the Zimnitsky test. Urine osmolarity in night portions is lower than in daytime portions. The concentration of antidiuretic hormone in blood plasma, when examined during the daytime, is quite often within the normal range, and if its decrease is detected, it is insignificant. Reduced concentration of antidiuretic hormone in blood plasma is more often detected in the evening and night hours. Prescription of synthetic analogs of antidiuretic hormone to patients with primary nocturnal enuresis leads to recovery in 70-80% of patients.

Nephrogenic diabetes insipidus (diabetes insipidus not sensitive to antidiuretic hormone)

The disease is based on the lack of sensitivity of the renal tubular epithelium to antidiuretic hormone. When antidiuretic hormone interacts with renal tubular receptors, cAMP is not formed, so protein kinase A is not activated and the intracellular effect of antidiuretic hormone is not realized. Mostly males are affected. The disease is inherited as an X-linked trait. Changes in laboratory parameters and functional tests are similar to those found in diabetes insipidus. Nephrogenic diabetes insipidus is characterized by normal or increased concentrations of antidiuretic hormone in the blood plasma. When conducting a test with vasopressin, there is no increase in the level of cAMP in the urine after its administration.

In nephrogenic diabetes insipidus, the use of antidiuretic hormone drugs is ineffective. Thiazide diuretics in combination with long-term restriction of table salt in the 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 inappropriate secretion of vasoporessin (Parchon syndrome)

The most common variant of antidiuretic hormone secretion disorder. Characterized by oliguria (constant or periodic), lack of thirst, presence of general edema, weight gain and high concentration of antidiuretic hormone in blood plasma, inadequate to the level of osmolarity.

This syndrome may develop in case of CNS pathology, in particular in case of meningitis, encephalitis, brain tumors and abscesses, subarachnoid hemorrhages, traumatic brain injury, and may also be caused by pneumonia, tuberculosis, acute renal failure, psychosis, and some medications (vincristine, carbamazepine, etc.). In some cases, inadequate secretion of antidiuretic hormone is possible with hypothyroidism. The mechanism of impaired secretion of antidiuretic hormone is caused by direct damage to the hypothalamus. Sometimes the cause of inadequate secretion of antidiuretic hormone cannot be determined. A decrease in sodium concentration (less than 120 mmol/l) is detected in blood plasma; if it falls below 110 mmol/l, neurological symptoms develop - stupor, seizures are possible. Plasma osmolarity is low (less than 270 mOsm/l), hypoosmolar coma may develop. When examining daily urine, increased excretion of sodium from the body is noted. Increased levels of antidiuretic hormone in blood plasma in relation to its osmolarity, decreased aldosterone concentration, and decreased response to the antidiuretic hormone secretion suppression test by water loading are detected.

Ectopic secretion of antidiuretic hormone is possible with a wide variety of tumors. Most often, ectopic secretion of antidiuretic hormone accompanies bronchogenic lung cancer, malignant tumors of the pancreas, thymus glands, and duodenum. Changes in laboratory parameters are similar to those in the syndrome of inappropriate vasoporesin secretion.

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 blood vessels and the level of tissue perfusion. This cascade [enzyme (renin) - peptide hormone ( angiotensin II ) - steroid hormone (aldosterone)] performs its important function due to its specific ability to detect and return to normal even the slightest increase or decrease in the volume of sodium and water in the body.

The functioning of the renin-angiotensin-aldosterone system can be summarized by its response to reductions in the volume of sodium and water in the body (for example, in the case of bleeding, which leads to a decrease in the volume of circulating blood).

As a result of bleeding, blood pressure in the afferent arterioles of the glomerular glomeruli of the kidneys decreases. Juxtaglomerular cells located in the wall of these arterioles detect the weakening of the tension of the arteriole wall, resulting in the release of renin into the glomerular capillary blood.

Renin released into the blood affects angiotensinogen, a plasma protein belonging to the α2-globulin group _. Angiotensinogen is synthesized and secreted by the liver. Renin cleaves a decapeptide (angiotensin I) from it in the kidneys. Angiotensin I (AI) is a substrate for ACE, which cleaves 2 amino acids from it, forming an octapeptide - angiotensin II (AII). Angiotensin II has several effects aimed at correcting the reduced volume of extracellular fluid. One of these actions 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 to 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 reabsorption of sodium and water in the distal tubules of the kidneys (as well as in the distal colon, sweat glands, and salivary glands). This action is aimed at restoring the reduced volume of extracellular fluid. Aldosterone exerts its effects through receptors that are found not only in the kidneys, but also in the heart and blood vessels.

Angiotensin II causes a direct increase in tubular reabsorption of sodium and water in the kidneys, and also has direct vasoconstrictor 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 the feeling of thirst.

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

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