Serum serotonin.

Reference values (norm) for serotonin concentration in blood serum in adults are 0.22-2.05 μmol/l (40-80 μg/l); in whole blood - 0.28-1.14 μmol/l (50-200 ng/ml).

Serotonin (oxytryptamine) is a biogenic amine found primarily in platelets. Up to 10 mg of serotonin circulates in the body at any given time. From 80 to 95% of the total amount of serotonin in the body is synthesized and stored in the enterochromaffin cells of the gastrointestinal tract. Serotonin is formed from tryptophan as a result of decarboxylation. In the enterochromaffin cells of the gastrointestinal tract, most of the serotonin is adsorbed by platelets and enters the bloodstream. This amine is localized in large quantities in a number of parts of the brain, there is a lot of it in mast cells of the skin, it is found in many internal organs, including various endocrine glands.

Serotonin causes platelet aggregation and polymerization of fibrin molecules; in thrombocytopenia, it can normalize blood clot retraction. It has a stimulating effect on the smooth muscles of blood vessels, bronchioles, and intestines. By stimulating the smooth muscles, serotonin narrows the bronchioles, causing increased intestinal peristalsis, and by vasoconstricting the renal vascular network, it leads to decreased diuresis. Serotonin deficiency underlies functional intestinal obstruction. Brain serotonin has a depressing effect on the function of the reproductive system involving the pineal gland.

The most studied pathway of serotonin metabolism is its conversion into 5-hydroxyindoleacetic acid by monoamine oxidase. This pathway metabolizes 20-52% of serotonin in the human body.

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Diseases and conditions in which the concentration of serotonin in the blood serum changes

Serotonin is elevated

• Metastases of abdominal carcinoma.
• Medullary thyroid cancer.
• Dumping syndrome.
• Acute intestinal obstruction.
• Cystic fibrosis.
• Myocardial infarction.

Carcinoid syndrome is a rare disease caused by increased secretion of serotonin by carcinoid, which in more than 95% of cases is localized in the gastrointestinal tract ( appendix - 45.9%, ileum - 27.9%, rectum - 16.7%), but can be located in the lungs, bladder, etc. Carcinoid develops from argyrophilic cells of intestinal crypts. Along with serotonin, carcinoid produces histamine, bradykinin and other amines, as well as prostaglandins. All carcinoids are potentially malignant. The risk of malignancy increases as the tumor size increases.

The concentration of serotonin in the blood in carcinoid syndrome increases by 5-10 times. In healthy people, only 1% of tryptophan is used to synthesize serotonin, while in patients with carcinoid - up to 60%. Increased synthesis of serotonin in a tumor leads to a decrease in the synthesis of nicotinic acid and the development of symptoms specific to vitamin PP deficiency (pellagra). A large number of serotonin metabolism products - 5-hydroxyindoleacetic and 5-hydroxyindoleaceturic acids - are detected in the urine of patients with malignant carcinoid. The excretion of 5-hydroxyindoleacetic acid in the urine, exceeding 785 μmol / day (the norm is 10.5-36.6 μmol / day), is considered a prognostically unfavorable sign. After radical surgical removal of the carcinoid, the concentration of serotonin in the blood and the excretion of its metabolic products with urine are normalized. The absence of normalization of excretion of serotonin metabolism products indicates that the operation was not radical or that metastases were present. Some increase in serotonin concentration in the blood may also occur with other gastrointestinal diseases.

Serotonin is reduced

• Down syndrome
• Untreated phenylketonuria

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The effect of serotonin on metabolism

In shock, the content of serotonin in all organs increases significantly, while the metabolism of the amine is disrupted and the content of its metabolites increases.

Mechanisms for increasing the content of serotonin and histamine in tissues

Mechanism	Factors that cause them
Degranulation of mast cells, intestinal enterochromaffin cells; release of amines	Low molecular weight (monoamines, diamines, aromatic amines), macromolecular (poisons, toxins, antigen-antibody complex, peptone, anaphylactin) substances
Intensification of catabolism, proteolysis, autolysis	Alteration, excess of glucocorticoids, thyroid hormones, increased activity of proteolytic enzymes, hypoxia
Increased activity of bacterial tissue mitochondrial tryptophan and histidine decarboxylase	Mineralocorticoid excess, glucocorticoid deficiency, adrenaline excess, and noradrenaline deficiency
Decreased activity of mitochondrial mono- and diamine oxidases	Excess corticosteroids, increased concentration of biogenic amines (substrate inhibition), impaired acid-base balance, hypoxia, hypothermia
Redistribution from depot bodies	Disruption of microcirculation in the skin, lungs, gastrointestinal tract

Serotonin affects various types of metabolism, but mainly bioenergetic processes, which are significantly disrupted in shock. Serotonin causes the following changes in carbohydrate metabolism: increased activity of liver, myocardium and skeletal muscle phosphorylases, decreased glycogen content in them, hyperglycemia, stimulation of glycolysis, gluconeogenesis and oxidation of glucose in the pentose phosphate cycle.

Serotonin increases the oxygen tension in the blood and its consumption by tissues. Depending on the concentration, it either inhibits respiration and oxidative phosphorylation in the mitochondria of the heart and brain, or stimulates them. A significant (2-20 times) increase in the serotonin content in tissues leads to a decrease in the intensity of oxidative processes. In a number of organs (kidneys and liver), the bioenergetic processes in which are most impaired in shock, the serotonin content is especially significantly increased (16-24 times). The serotonin content in the brain is increased to a lesser extent (2-4 times) and the energy processes in it remain at a high level for a long time. The effect of serotonin on the activity of individual links of the respiratory chain system in shock is not the same in different organs. If in the brain it increases the activity of NADH2 and reduces the activity of succinate dehydrogenase (SDH), then in the liver it increases the activity of SDH and cytochrome oxidase. The mechanism of enzyme activation is explained by the effect of serotonin on adenylate cyclase with subsequent formation of cAMP from ATP. It is believed that cAMP is an intracellular mediator of serotonin action. The content of serotonin in tissues correlates with the level of activity of energy enzymes (especially with SDH and liver ATPase). Activation of SDH by serotonin in shock is of a compensatory nature. However, excessive accumulation of serotonin leads to the fact that the nature of this relationship becomes inverse, while the activity of SDH decreases. Limitation of the use of succinic acid as an oxidation product significantly depletes the energy capabilities of the kidneys in shock. As shock develops, a relationship appears between the amount of serotonin in the kidneys and the activity of LDH, this indicates a switch in the activating effect of serotonin from the use of succinate (under physiological conditions) to the consumption of lactate due to inhibition of SDH, which is an adaptive reaction.

In addition, serotonin affects the content and metabolism of purine nucleotides, the increase in the level of which in mitochondria stimulates the rate of ATP turnover. Serotonin forms a reversibly dissociating micellar complex with ATP. A decrease in the content of serotonin in cells correlates with a decrease in the level of ATP in them.

The accumulation of serotonin during shock is to a certain extent associated with changes in the ATP content. At the same time, the presence of other forms of intracellular serotonin connection with proteins, lipids, polysaccharides and divalent cations, the level of which in tissues also changes during shock, cannot be ruled out.

Serotonin's participation in intracellular energy processes consists not only in the formation of energy, but also in its release with the participation of ATP hydrolases. Serotonin activates Mg-ATPase. Increased activity of liver mitochondria ATPase in shock may also be the result of increased serotonin levels.

Thus, the accumulation of serotonin in the body tissues during shock can actively influence the metabolism of carbohydrates in the glycolytic and pentose cycles, respiration and associated phosphorylation, accumulation and use of energy in cells. The molecular mechanism of serotonin action is mediated by the movement of ions along the membrane.

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The effect of serotonin on organ functions

The action of serotonin at the systemic level consists in its specific influence on the functional state of many organs. Intraventricular administration of serotonin in doses close to shock doses and intravenous administration of b-oxytryptophan (easily penetrating the blood-brain barrier and converting into serotonin in the brain) causes phase changes in the bioelectrical activity of the brain, characteristic of the activation reaction in the cortex, hypothalamus and mesencephalic reticular formation. Similar changes in the brain have been established in the dynamics of shock development, which indirectly indicates a significant role of serotonin in changing the function of the central nervous system during shock. Serotonin is involved in the occurrence of membrane potential and the organization of synaptic transmission of nerve impulses. Adaptation of the body to extreme effects is accompanied by an increase in the serotonin content in the brain due to an increase in the power of serotonergic neurons. An increase in the serotonin content in the hypothalamus activates neurosecretion and enhances the function of the pituitary gland. However, significant accumulation of serotonin in the brain may play an important role in the development of its edema.

Serotonin has a significant multifaceted effect on the cardiovascular system. Large doses (10 mg or more) cause cardiac arrest in various types of experimental animals. Direct effects of serotonin on the myocardium cause systemic and coronary hypertension, as well as severe circulatory disorders in the heart muscle, accompanied by its necrosis ("serotonin" infarction). In this case, changes in the oxidative and carbohydrate-phosphorus metabolism of the myocardium are close to those that occur in coronary circulation disorders. The ECG in shock shows very significant changes: an increase followed by a slowdown in heart rate, extrasystole, a gradual shift in the electrical axis of the heart to the left, and deformation of the ventricular complex, which may be the result of coronary circulation disorders.

The effect of serotonin on blood pressure depends on the rate, dose, and method of administration, as well as on the type of experimental animals. Thus, in cats, rabbits, and rats, intravenous administration of serotonin causes hypotension in most cases. In humans and dogs, it initiates phase changes: short hypotension, followed by hypertension and subsequent hypotension. The carotid artery is highly sensitive even to small doses of serotonin. It is assumed that there are two types of receptors through which the pressor and depressor effects of serotonin are mediated by the parasympathetic nervous system and the carotid glomerulus. Intravenous administration of serotonin in a dose approximately corresponding to its content in the circulating blood volume in shock causes a decrease in systemic blood pressure, cardiac output, and peripheral vascular resistance. A decrease in the amount of serotonin in the intestinal wall and lung tissues is probably associated with the mobilization of this amine from the depot. The effect of serotonin on the respiratory organs can be both local and reflexive, causing bronchiolospasm and increased respiratory rate in rats.

The kidneys contain a small amount of serotonin, but its metabolism changes significantly during their ischemia. Large doses of serotonin cause persistent pathological vascular spasm, ischemia, foci of necrosis in the cortex, desolation, degeneration and necrosis of the tubular apparatus. Such a morphological picture resembles microscopic changes in the kidneys during shock. A significant (10-20 times) and persistent increase in the serotonin level in the kidney tissue during shock can cause a long-term spasm of their vessels. Particularly high serotonin levels are observed during dysuric disorders. In acute renal failure, the concentration of serotonin in the blood is elevated in the stage of oliguria and anuria, begins to decrease during the period of diuresis recovery and normalizes in the polyuria phase, and becomes below physiological values during recovery. Serotonin reduces renal plasma flow, glomerular filtration rate, diuresis, and excretion of sodium and chlorides in urine. The mechanism of these disorders is due to a decrease in intraglomerular hydrostatic pressure and filtration, as well as an increase in the osmotic gradient of sodium content in the medulla and distal tubules, which leads to increased reabsorption. Serotonin is important in the mechanism of renal failure in shock.

Thus, moderate accumulation of serotonin in the brain and its central effect in shock may be useful, especially in terms of activation of the HPAS. Activation of energy enzymes by serotonin should also be regarded as a positive, compensatory phenomenon in shock. However, excessively high accumulation of serotonin in the myocardium and kidneys creates the possibility of direct excess influence of the amine on coronary and renal circulation, disruption of its metabolism and the occurrence of cardiac and renal failure.

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