The most common disorder of purine metabolism is increased formation of uric acid with the development of hyperuricemia. A special feature is that the solubility of uric acid salts (urates) in blood plasma is low and when the solubility threshold in plasma is exceeded (about 0.7 mmol/l), they crystallize in peripheral zones with low temperature.
Depending on duration and severity hyperuricemia manifests itself:
- The appearance of tophi (Greek. tophus- porous stone, tuff) - deposition of urate crystals in the skin and subcutaneous layers, in small joints of the legs and arms, in tendons, cartilage, bones and muscles.
- Nephropathy as a result of crystallization of uric acid with damage to the renal tubules and urolithiasis disease.
- Gout is a lesion of small joints.
To diagnose disorders, determine the concentration of uric acid in the blood and urine.
Purine metabolism disorders
Gout
When hyperuricemia becomes chronic, we speak of the development of gout (Greek. poclos- leg, agra– capture, literally – “leg in a trap”).
In the blood, uric acid is in the form of its salts - sodium urates. Due to their low solubility, urate can settle in areas of low temperature, such as the small joints of the feet and toes. The urates that accumulate in the intercellular substance are phagocytosed for some time, but the phagocytes are not able to destroy the purine ring. As a result, this leads to the death of the phagocytes themselves, the release of lysosomal enzymes, the activation of free radical oxidation and the development of an acute inflammatory reaction - develops gouty arthritis. In 50-75% of cases, the first sign of the disease is excruciating night pain in the big toes.
For a long time, gout was considered a “gourmet disease,” but then the attention of researchers shifted to hereditary changes in the activity of purine metabolic enzymes:
- increased activity PRDF synthetases– leads to excess synthesis of purines,
- decrease in activity - because of this, PRDP is not used for the recycling of purine bases, but participates in the first reaction of their synthesis. As a result, the amount of destroyed purines increases and at the same time their formation increases.
Both enzymatic disorders are recessive and linked to the X chromosome. Gout affects 0.3-1.7% of the world's adult population, the ratio of affected men to women is 20:1.
Treatment Basics
Diet - reducing the intake of uric acid precursors from food and reducing its formation in the body. To do this, foods containing a lot of purine bases are excluded from the diet - beer, coffee, tea, chocolate, meat products, liver, red wine. Preference is given vegetarian diet with quantity clean water at least 2 liters per day.
TO medicines Treatments for gout include allopurinol, which is similar in structure to hypoxanthine. Xanthine oxidase oxidizes allopurinol to alloxanthin, and the latter remains tightly bound to the active site of the enzyme and inhibits it. The enzyme carries out, figuratively speaking, suicide catalysis. As a result, xanthine is not converted to uric acid, and since hypoxanthine and xanthine are more soluble in water, they are more easily excreted from the body in urine.
Urolithiasis disease
Urolithiasis is the formation salt crystals(stones) of different nature in the urinary tract. Direct education uric acid stones accounts for about 15% of all cases of this disease. Uric acid stones in the urinary tract are deposited at approximately half sick gout.
Most often, such stones are presented in the distal tubules and collecting ducts. Cause of deposition uric acid crystals is hyperuricemia and increased excretion of sodium urate in the urine. The main provoking factor for crystallization is increased urine acidity. When urine pH drops below 5.75, urates (enol form) become less soluble keto form and crystallize in the renal tubules.
Acidification of urine (normally 5.5-6.5) occurs for various reasons. This may be excess nutrition of meat products containing large amounts of nucleic acids. acids, amino acids and inorganic acids, which makes such foods “sour” and lowers the pH of urine. Also, the acidity of urine increases with acidosis of various origins (acid-base state).
Treatment Basics
Just as with gout, treatment comes down to purine-free diet and the use of allopurinol. In addition it is recommended plant based diet, leading to alkalinization of urine, which increases the proportion of more water-soluble substances in primary urine uric acid salts– urats. At the same time, existing crystals of uric acid (as well as oxalates) can dissolve when the urine is alkalinized.
Drug treatment must necessarily be accompanied by compliance purine-free diet With plenty of clean water, otherwise the appearance of xanthine crystals in tissues and xanthine stones in the kidneys.
Lesch-Nyhan syndrome
Disease L e sha-N And hana (frequency 1:300000) is a complete congenital lack of activity hypoxanthine guanine phosphoribosyl transferase, an enzyme responsible for the recycling of purine bases. The trait is recessive and linked to the X chromosome. It was first described in 1964 in the USA by medical student Michael Lesh and pediatrician William Nyhan.
Children are born clinically normal, only by 4-6 months are developmental abnormalities detected, namely, retarded physical development (difficulty holding up their head), increased excitability, vomiting, periodic increase temperature. The release of uric acid can be detected even earlier by the orange color of the diapers. By the end of the first year of life, symptoms increase, impaired coordination of movements, choreoathetosis, cortical paralysis, and leg muscle spasms develop. The most characteristic sign of the disease appears in the 2-3rd year of life - auto-aggression or self-mutilation - an irresistible desire of children to bite their lips, tongue, joints of fingers and toes.
Acetonemic syndrome in children (AS), or cyclic acetonemic vomiting syndrome (non-diabetic ketosis, not diabetic ketoacidosis, acetonemic vomiting), is a set of symptoms that are caused by an increase in blood levels ketone bodies: acetone, acetoacetic acid and β-hydroxybutyric acid - breakdown products of fatty acids and ketogenic amines.
There are primary (idiopathic) and secondary (against the background of somatic, infectious, endocrine diseases, tumors and lesions of the central nervous system) acetonemic syndrome. Of greatest interest is the primary AS, which will be discussed further.
Prevalence
AS is a disease predominantly of childhood, manifested by stereotypical repeated episodes of vomiting, alternating with periods of complete well-being. More often occurs in children of the first years of life. The prevalence of AS is poorly understood. AS affects 2.3% of Austrians, 1.9% of residents of Scotland. In India, AS accounts for 0.51% of all hospitalizations in children's department. According to Russian literature, primary AS occurs in 4-6% of children aged 1 to 13 years. AS is more often registered in girls. The average age of onset of AS is 5 years. 50% of patients with this pathology require hospitalization and intravenous fluid administration. The average annual cost of examination and treatment of one patient with this pathology in the USA is 17 thousand dollars.
Etiology and pathogenesis
The main factor against which AS occurs is a constitutional abnormality—neuroarthritic diathesis (NAD). However, any stressful, toxic, nutritional, endocrine influences on energy metabolism, even in children without NAD, can cause the development of acetonemic vomiting.
Normally, the catabolic pathways of carbohydrate, protein and fat metabolism intersect in the Krebs cycle, a universal pathway for energy supply to the body.
The trigger for the development of ketosis is stress. comparative advantage counterinsular hormones and nutritional disorders in the form of fasting or excessive consumption of fatty and protein foods (ketogenic amino acids) with a lack of carbohydrates. An absolute or relative lack of carbohydrates causes lipolysis to be stimulated to meet the body's needs.
Ketosis causes a number of adverse effects on the baby's body. Firstly, with a significant increase in the level of ketone bodies, which are anion donors, metabolic acidosis occurs with an increased anion gap - ketoacidosis.
Its compensation is carried out due to hyperventilation, which leads to hypocapnia, causing vasoconstriction, including cerebral vessels. Secondly, excess ketone bodies have a narcotic effect on the central nervous system, up to the development of coma. Thirdly, acetone is a fat solvent and damages the lipid bilayer of cell membranes.
In addition, the utilization of ketone bodies requires additional amounts of oxygen, which can cause a discrepancy between oxygen delivery and oxygen consumption, that is, contributes to the development and maintenance of the pathological condition.
Excess ketone bodies irritate the mucous membrane gastrointestinal tract, which clinically manifests as vomiting and abdominal pain syndrome. The listed adverse effects of ketosis in combination with other disorders of water-electrolyte and acid-base balance (hypo-, iso- and hypertonic dehydration, metabolic acidosis due to bicarbonate loss and/or lactate accumulation) contribute to a more severe course of the disease and increase the length of stay in the intensive care unit therapy.
NAD is a polygenically inherited metabolic abnormality, which is based on a violation purine metabolism with excess production of uric acid and its precursors, instability of other types of metabolism (primarily carbohydrate and lipid) with a tendency to ketosis and mediator functions of the nervous system, which determine the characteristics of its reaction.
Genetic factors causing hyperuricemia include a number of enzyme defects: deficiency of hypoxynthine guanyl phosphoribosyltransferase; glucose-6-phosphatase deficiency; increasing the catalytic activity of the enzyme phosphoribosyl-pyrophosphate synthetase.
The hereditary factor of disorders of purine metabolism is confirmed by the results of family genetic studies of children with NAD: the frequency of detection of neuropsychiatric diseases in the pedigree of such children is up to 18%, gout is registered in 22% of cases. In first-degree relatives, urolithiasis, uric acid diathesis, and metabolic arthritis are 20 times more common than in the control group. Diseases of the circulatory system (coronary heart disease, hypertonic disease), diabetes.
Free purines and the compounds that form them are of particular importance in the life of the body; the synthesis of purine bases is the central link in the biosynthesis of nucleotides, which take part in almost all intracellular biochemical processes:
- they are activated precursors of DNA and RNA;
- nucleotide derivatives - activated intermediate products of many synthetic reactions;
- adenine nucleotide adenosine triphosphoric acid - a universal energy “currency” in biological systems;
- adenine nucleotides - components of three main coenzymes: NAD, FAD and SOA;
- purine nucleotides play a general regulatory role in the biological activity of cells, turning into cyclic nucleotides - cyclic adenosine monophosphate and cyclic guanosine monophosphate.
In humans, the main sources of purine synthesis are phosphoribosyl monophosphate and glutamine, from which inosinic acid is formed - the main precursor of purine nucleotides, containing a fully prepared purine ring system.
From year to year, interest in the study of purine metabolism and its final product, uric acid, is growing, which is associated with a steady increase in the frequency of both asymptomatic and clinically manifest hyperuricemia, a biological abnormality unique to humans.
There are three main ways in which uric acid is formed in the body:
- from purines, which are released during tissue breakdown;
- from purines contained in food;
- from synthetically created purines.
Hyperuricemia can be detected in almost 38% of people, and the level of uric acid in the blood depends on age, gender, nationality, geographical area, level of urbanization, type of food.
Hyperuricemia can be primary or secondary. There are two ways of developing primary hyperuricemia - metabolic and excretory. The first is associated with a significant intake of purines into the body and their enhanced formation. Increased synthesis of uric acid, characteristic of NAD, can be caused by various enzyme defects, the main of which are:
- lack of glutaminase, which transforms glutamine into glutamic acid and ammonia;
— deficiency of hypoxynthine guanyl phosphoribosyltransferase, which ensures the synthesis of purine bases (hypoxanthine and guanine) and nucleotides (inosine monophosphate and guanosine monophosphate);
- hypoproduction of uricase, which converts uric acid into a more diluted allantoin;
- excess phosphoribosylpyrophosphate synthetase, which catalyzes the synthesis of phosphoribosylpyrophosphate from ATP and ribose-5-phosphate;
- hyperactivity of xanthine oxidase, which oxidizes hypoxanthine into xanthine and uric acid.
Clinic, diagnostics
Currently, NAD is considered an enzyme deficiency condition characterized by:
- increased excitability and rapid exhaustion of the nervous system at all levels of reception with the presence of a dominant focus of stagnant excitation in the hypothalamic-diencephalic region;
- deficiency of liver enzymes (glucose-6-phosphatase, hypoxanthine-guanine-phosphoribosylpyrophosphate synthetase);
- low acetylating ability of acetyl coenzyme A due to a deficiency of oxalic acid, necessary for the involvement of acetyl coenzyme A in the Krebs cycle;
— violation of the mechanism of reuse of uric and lactic acids;
- disorders of fat and carbohydrate metabolism;
- disruption of endocrine regulation of metabolism.
Children with NAD immediately after birth are characterized by increased excitability, emotional lability, sleep disturbance, and fearfulness. Aerophagia and pylorospasm are possible. By the age of one year, they usually lag significantly behind their peers in weight. Neuropsychic development, on the contrary, outstrips age standards. Children quickly master speech, show curiosity, interest in their surroundings, remember well and retell what they hear, but often show stubbornness and negativism in their behavior. Starting from 2-3 years of age, they experience equivalents of gouty attacks and crises in the form of transient night pain in the joints, abdominal pain of a spastic nature, biliary and gastric dyskinesias, odor intolerance, other types of idiosyncrasies, migraines, acetonemic crises. Sometimes persistent low-grade fever is observed. Possible tics, choreic and tic-like hyperkinesis, affective convulsions, logoneurosis, enuresis. Respiratory and cutaneous allergic manifestations in the form of atopic bronchial asthma, atopic dermatitis, urticaria, Quincke's edema, and under the age of 1 year allergic lesions skin lesions are extremely rare and usually appear after 2-3 years. In the pathogenesis of skin syndrome, not only allergic but also paraallergic (non-immune) reactions are important, caused by the release of biologically active substances, a decrease in the synthesis of cyclic nucleotides and a powerful inhibitory effect of uric acid on adenyl cyclase. One of the typical manifestations of NAD is saluria with predominant uraturia. Salt excretion is periodically observed simultaneously with dysuria not associated with infection. However, it is possible to develop pyelonephritis, which is often associated with nephrolithiasis. In children of prepubertal and pubertal age, an asthenoneurotic or psychasthenic type of accentuation is often detected. Girls exhibit hysterical character traits. Among neuroses, neurasthenia predominates. Vegetative-vascular dysfunction often occurs in the hyperkinetic type.
The most pronounced manifestation of metabolic disorders in children with NAD, requiring intensive medical care, is an acetonemic crisis. Its development can be facilitated by many factors that, under conditions of increased excitability of the nervous system, have a stressful effect: fear, pain, conflict, hyperinsolation, physical or psycho-emotional stress, changes in the microsocial environment, dietary errors (high content of proteins and fats) and even positive emotions “in excess” " Increased excitability of the autonomic centers of the hypothalamus, which occurs with NAD, under the influence of stress factors causes increased lipolysis and ketogenesis, resulting in the formation of a large number of ketone bodies. In this case, irritation of the vomiting center of the brain stem occurs, which causes vomiting.
Acetonemic crises occur suddenly or after precursors (auras), which include anorexia, lethargy, agitation, migraine-like headache, nausea, abdominal pain mainly in the umbilical region, acholic stool, smell of acetone from the mouth.
Clinical picture of acetone crisis:
- repeated or uncontrollable vomiting for 1-5 days (trying to give water or feed the child provokes vomiting);
— dehydration and intoxication (pallor of the skin with a characteristic blush, physical inactivity, muscle hypotension);
- anxiety and excitement at the beginning of the crisis are replaced by lethargy, weakness, drowsiness, in rare cases, symptoms of meningism and convulsions are possible;
- hemodynamic disorders (hypovolemia, weakening of heart sounds, tachycardia, arrhythmia);
- spastic abdominal syndrome(cramping or persistent abdominal pain, nausea, stool retention);
- enlargement of the liver by 1-2 cm, persisting for 5-7 days after the crisis has stopped;
- increase in body temperature to 37.5-38.5 ° C;
- the presence of acetone in the urine, vomit, exhaled air, and an increased concentration of ketone bodies in the blood;
- hypochloremia, metabolic acidosis, hypoglycemia, hypercholesterolemia, beta-lipoproteinemia;
- V peripheral blood moderate leukocytosis, neutrophilia, moderate increase in ESR.
Diagnostics
Diagnosis of AS is based on the study of anamnesis, analysis of complaints, clinical symptoms and the results of certain instrumental and laboratory methods examinations. It is imperative to establish the nature of the AS: primary or secondary. The diagnosis must contain a decoding of the main syndromes that determine the severity of the child’s condition (dehydration, acidosis, hypovolemia, etc.).
The diagnostic criteria for cyclic acetonemic vomiting syndrome (primary AS) were determined by international consensus (1994).
Mandatory criteria:
- repeated, severe, isolated episodes of vomiting;
— of various durations intervals of normal health between episodes;
- duration of episodes of vomiting from several hours to days;
- negative laboratory, radiological and endoscopic examination results that could explain the etiology of vomiting as a manifestation of the pathology of the gastrointestinal tract.
Additional criteria:
- vomiting is characterized by stereotypy, and each episode is similar to the previous one in time, intensity and duration;
- attacks of vomiting can end spontaneously and without treatment;
- associated symptoms include nausea, abdominal pain, headache, weakness, photophobia, lethargy;
- associated signs include fever, pallor, diarrhea, dehydration, excessive salivation and social maladjustment;
- Vomit often contains bile, mucus and blood. Hematemesis is often a consequence of retrograde prolapse of the cardiac part of the stomach through the gastroesophageal sphincter (i.e., propulsive gastropathy), as in the classic Mallory-Weiss syndrome.
Differential diagnosis of primary AS
It is necessary to determine whether AS is primary or secondary. Require exceptions:
— diabetic ketoacidosis (determination of glycemic level);
— acute surgical pathology of the gastrointestinal tract;
— neurosurgical pathology (MRI, CT scan of the brain);
— infectious pathology(clinical picture, hyperleukocytosis, increased ESR);
- poisoning.
Treatment
Treatment of acetonemic syndrome can be divided into two stages: stopping the acetonemic crisis and carrying out measures in the interictal period aimed at preventing relapses.
Relief of acetonemic crisis
The objectives and directions of treatment of AS in children can be formulated as follows:
1) the diet is prescribed to all patients. It should contain easily digestible carbohydrates, be enriched with liquid, and limit fat intake;
2) the administration of prokinetics (domperidone, metoclopramide), enzymes and cofactors of carbohydrate metabolism (thiamine, cocarboxylase, pyridoxine) contributes to an earlier restoration of food tolerance and normalization of carbohydrate and fat metabolism;
3) infusion therapy must:
— quickly eliminate hypovolemia and extracellular fluid deficiency in order to improve perfusion and microcirculation;
4) in cases of moderate ketosis (urine acetone up to “++”), which is not accompanied by significant dehydration, water-electrolyte disorders and uncontrolled vomiting, diet therapy and oral rehydration are indicated in combination with the use of prokinetics in age-related doses and etiotropic therapy of the underlying disease.
At initial symptoms acetonemic crisis or its precursors, it is advisable to clean and rinse the intestines with a 1-2% solution of sodium bicarbonate and give the child every 10-15 minutes sweet tea with lemon, non-carbonated alkaline mineral water (Luzhanskaya, Borjomi, etc.), 1-2 % sodium bicarbonate solution, combined solutions for oral rehydration. Food should contain easily digestible carbohydrates and a minimum amount of fat (liquid semolina or oatmeal, mashed potatoes, milk, baked apples). Drug therapy includes antispasmodics (drotaverine for children from 1 to 6 years old - 10-20 mg 2-3 times a day, for children school age- 20-40 mg 2-3 times a day; papaverine bromide (after 5 years of age - 50-100 mg/day); enterosorbents (in age dosage). Due to stool retention in patients, the use of diosmectin is not advisable.
In the case of the development of an acetonemic crisis, accompanied by repeated or uncontrollable vomiting, treatment is aimed at correcting acidosis, ketosis, dehydration and dyselectrolythemia. It is advisable to re-cleanse the intestines and then rinse it with a 1-2% solution of sodium bicarbonate 1-2 times a day.
Indications for prescribing infusion therapy:
1. Persistent and repeated vomiting, which does not stop after the administration of prokinetics.
2. The presence of moderate (up to 10% of body weight) and/or severe (up to 15% of body weight) dehydration.
3. Presence of decompensated metabolic acidosis with an increased anion gap.
4. Presence of hemodynamic and microcirculatory disorders.
5. Signs of disorders of consciousness (stupor, ketoacidotic coma).
The presence of anatomical and functional difficulties for oral rehydration (malformations of the facial skeleton and oral cavity), neurological disorders (bulbar and pseudobulbar disorders).
Before starting infusion therapy, it is necessary to ensure reliable venous access (mainly peripheral), using catheters such as Venflon or analogues, to determine hemodynamics, acid-base and water-electrolyte conditions.
The main objectives for initial infusion therapy are:
- in the correction of hypoglycemia, if it exists;
— elimination of hypovolemia;
- restoration of satisfactory microcirculation.
As infusion solutions, 5-10% glucose solution with insulin and crystalloid sodium-containing solutions (0.9% sodium chloride solution, Ringer's solution) are used in a ratio of 1: 1 or 2: 1, taking into account indicators of water-electrolyte metabolism. The total volume of administered fluid is 50-60 ml/kg/day. To combat hypovolemia and peripheral hypoperfusion, rheopolyglucin (10-20 mg/kg) is used. In complex infusion therapy, cocarboxylase (50-100 mg/day), 5% solution is used ascorbic acid(2-3 ml/day). For hypokalemia - correction of potassium levels (potassium chloride 5% solution 1-3 ml/kg in 100 ml of 5% glucose solution intravenously).
Given the available data regarding the limited capabilities of the most common crystalloid solutions ( saline solutions and glucose solutions) quickly and effectively eliminate ketosis and its pathophysiological consequences, there are serious theoretical and practical prerequisites for the use of sugar alcohol solutions as an alternative means of treating ketotic conditions. The main difference between sugar alcohols (sorbitol, xylitol) is the peculiarities of their metabolism, namely its independence from insulin, and a significantly greater anti-ketogenic effect.
If the child drinks willingly sufficient quantity liquids, parenteral administration infusion solutions can be completely or partially replaced by oral rehydration, which is carried out with combination drugs. For persistent, indomitable vomiting, parenteral metoclopramide is indicated (for children under 6 years of age). single dose 0.1 mg/kg, children from 6 to 14 years old - 0.5-1.0 ml). Considering possible undesirable side effects from the nervous system (dizziness, extrapyramidal disorders, convulsions), administration of metoclopramide more than 1-2 times is not recommended.
In case of severe abdominal spastic syndrome, antispasmodics (papaverine, platyphylline, drotaverine in an age-specific dosage) are administered parenterally. If the child is excited, restless, hyperesthesia is expressed, tranquilizers are used - diazepam drugs in average-age dosages. After stopping vomiting, it is necessary to give the child a sufficient amount of liquid: dried fruit compote, sweet fruit juices, tea with lemon, low-mineralized alkaline mineral waters. A diet with a sharp limitation of fats, proteins and other ketogenic foods is indicated.
Therapeutic measures during the interictal period
Activities during the interictal period are aimed at preventing relapses of acetonemic crises and include a number of areas, the main of which is nutritional therapy.
Diet therapy for NAD is aimed at:
- limiting the consumption of foods rich in purines;
- increased excretion of uric acid by the kidneys due to increased diuresis;
- decreased excitability of the autonomic nervous system;
- promoting alkalinization of urine;
— elimination of food allergens and allergenic substances.
— proteins (purines) contribute to the endogenous formation of uric acid;
- fats negatively affect the excretion of urates from the body;
- carbohydrates have a sensitizing effect.
However, given the high need child's body in plastic material, in a diet with NAD it is dangerous to reduce the proportion of animal protein, although it is necessary to limit intake as much as possible:
- meat of young animals, poultry and offal (kidneys, heart, liver, lungs, brain, blood and liver sausage), since they contain a large amount of purines. Preference is given to the meat of adult animals and birds (beef, lean pork, rabbit, chicken, turkey) in boiled form;
— legumes (peas, soybeans, beans, beans);
— some types of fish (sprats, sardines, sprat, cod, pike perch, pike);
— mushrooms (ceps);
- salt, since it retains fluid in the tissues and prevents the excretion of uric acid compounds through the kidneys.
Jellied meat, sauces, meat and fish broths should be excluded from the diet, because 50% of purines pass into the broth when boiled. You should not abuse foods that have a stimulating effect on the nervous system (coffee, cocoa, strong tea, spicy snacks, spices). Even small doses of alcohol can impair the excretion of uric acid, and low levels of the enzyme alcohol dehydrogenase in children with NAD increases the risk of developing alcohol dependence.
— milk and dairy products;
- vegetables (potatoes, White cabbage, cucumbers, carrots, tomatoes);
— fruits, berries (apples, except Antonovka, watermelon, grapes, apricot, peach, pear, plum, cherries, oranges);
- forest and walnuts;
— flour products;
— cereals (except oatmeal and polished rice);
- sugar and honey;
- products enriched with niacin, retinol, riboflavin and vitamin C;
— large quantity liquids (up to 1.5-2.5 liters depending on age) in the form of citrus and citrate mixtures, carrot drinks, mint and linden teas, vegetable, berry and fruit juices, rosehip and berry decoctions, alkaline mineral waters. Low-mineralized mineral waters act diuretically, stimulate glomerular filtration processes, and normalize water-salt metabolism. Mineral waters are prescribed at the rate of 3-5 ml/kg per dose three times a day for a month in 3-4 courses per year. Alkalinization of urine increases the solubility of uric acid in urine and prevents the formation of urate stones. Vegetables and fruits are consumed for the same purpose. Their positive effect is that they contain a large amount of potassium ions, which have a diuretic effect and increase the excretion of urate in the urine.
Treatment of AS during the interictal period is carried out in courses at least 2 times a year, usually in the off-season. Hepatoprotectors are prescribed. For frequent and severe acetonemic crises, ursodeoxycholic acid derivatives are prescribed for prevention. In addition to hepatoprotectors, the function of hepatocytes is optimized by lipotropic drugs, the use of which is recommended 1-2 times a year. If the exocrine function of the pancreas decreases, treatment with pancreatic enzyme preparations is carried out for 1-1.5 months until the coprogram indicators are completely normalized. To treat saluria, a decoction of juniper fruits, horsetail extract, decoction and infusion of lingonberry leaves are used. Sedatives from medicinal plants: soothing tea, decoction of valerian root, decoction of hawthorn fruits and flowers, passionflower extract, as well as Pavlov’s mixture. The duration of use of sedatives is determined by the presence of a syndrome of increased neuro-reflex excitability.
Children with NAD must always follow some rules regarding the regimen. First of all, sufficient stay fresh air, regular, strictly dosed physical exercise(do not overwork), mandatory water treatments(swimming, cold and hot shower, dousing), prolonged sleep (at least 8 hours). Hyperinsolation should be avoided. It is advisable to reduce the time spent watching TV and working with the computer. Due to the restriction of many foods in the diet of children, it is recommended to conduct courses of vitamin therapy in the winter and spring. Spa treatment shown in the conditions of a drinking balneological resort.
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Along with other pathologies, a disorder of purine metabolism is also considered serious illness, the treatment of which should be given attention. First of all, these are disruptions in the metabolism of useful substances, which provoke the occurrence of other diseases, such as gout, nephropathy or renal failure.
As a rule, a disorder of purine metabolism occurs in children, but adults are also susceptible to this pathology. Only usually patients in adulthood are faced with a number of concomitant diseases and complications.
General information
Violation of purine metabolism according to ICD-10 has code E79. Usually this disease is chronic in nature and is directly related to the deposition of acid salts in the tissues of the kidneys and joints. Symptoms of purine metabolism disorders are quite specific and manifest themselves as repeated exacerbations of arthritis, accompanied by pain.
An undetected and untreated problem in time can lead to more serious consequences: for example, the development of urolithiasis and kidney failure. All therapeutic measures in such a situation, the aim is usually to relieve unpleasant symptoms, reduce the severity of the clinical picture, prevent the development of complications and normalize the metabolism of useful substances.
Causes of pathology
A prerequisite for the development of the disease is the excessive formation of purine bases or their too slow excretion with uric acid.
The primary form of the pathology is explained by hereditary predisposition. But the secondary type of the disease may be associated with regular use of diuretics, anti-inflammatory drugs and other medications.
Violations of purine metabolism provoke:
- alcohol;
- severe hypothermia;
- some pharmaceuticals;
- products containing relevant formations;
- pathologies of an infectious nature;
- psycho-emotional and physical stress.
Symptoms
Signs of purine metabolism disorders resemble typical manifestations of metabolic failures. Pathology is characteristic increased level creatinine kinase, which appears in almost all patients. Other nonspecific signs of the disease can be detected using an electromyographic examination.
In patients with disorders of purine metabolism, extremely low production of ammonia is observed, due to which performance is significantly reduced and appetite is almost completely absent. Patients feel general malaise, lethargy, depression. In some cases, pronounced weakness develops.
Children who suffer from disorders of purine metabolism for a long time often remain mentally underdeveloped and have an increased tendency to autism. In more rare cases, small and adult patients experience seizures resembling epileptic seizures, as well as convulsions. Among other things, the psychomotor development of a sick person slows down or stops altogether.
Peculiarities
The most striking disorders of purine metabolism include excessive formation and further accumulation of uric acid, which is observed in gout and Lesch-Nyhan syndrome. The latter lies in the hereditary deficiency of a certain enzyme, which leads to the non-use of re-released purines. As a result, they oxidize, transforming into uric acid.
Diagnostics
Detection of the disease is extremely difficult and does not always give exact result, since this pathology has many symptoms similar to other disorders in homeostasis. However, with long-term monitoring of the patient’s condition and his tests in general outline, it is quite possible to detect disruptions in purine metabolism and the reasons for its occurrence.
The diagnosis can be made based primarily on complete absence indicators of the functioning of renal enzymes, active substances of the liver and skeletal muscles. With help laboratory research partial deficiency can be detected in lymphocytes and fibroblasts.
Special treatment that would be aimed at eliminating enzyme dysfunction has not yet been developed, so you can only rely on complex therapy.
Treatment
Disorders of purine metabolism require complex treatment, which is based primarily on a strict diet, including foods with low content uric acid, and drug therapy.
Pharmacological methods include several stages:
- balance and normalization of metabolic processes with the help of vitaminization;
- establishing metabolic acidosis and controlling the acidic environment in the urine;
- establishment and constant maintenance of normal levels of hyperlipidemia;
- control and normalization of the patient’s blood pressure during the day;
- therapy probable complications pathology.
Treatment of consequences
Gout is a disorder of purine metabolism that was not diagnosed and treated in time. These diseases are very closely related to each other. That is why the signs and treatment of gout are not much different from those with metabolic failures. In general, the treatment of this pathology comes down to the correction of purine metabolism. To do this, the patient is recommended:
- limit physical activity during exacerbations;
- following a certain diet;
- drinking regimen, including 2 liters of water daily;
- the use of local compresses using "Dimexide";
- use of prescribed doses of non-steroidal anti-inflammatory drugs.
Treatment of purine metabolism disorders can be carried out as follows: inpatient conditions, and at home. However, the latter option is permissible only after consultation with a specialist and confirmation of the diagnosis.
Drug therapy
Basic treatment is based on the long-term use of drugs that normalize the amount of uric acid in the blood. Medicines can only be used during remission. Depending on the effect, there are several types of recommended drugs:
- agents that reduce the production of uric acid, for example, Allopurinol;
- medications containing etebenecid increase the rate of elimination of uric acid from the body;
- mixed-action drugs.
Long-term drug therapy is advisable for frequent attacks, severe clinical picture of the disease, formation of tophi and kidney injury.
During periods of remission, patients are also shown a variety of physiotherapeutic procedures: massage, paraffin baths, ultrasound.
In almost all treatment regimens for pathology, doctors mention adherence to a certain diet. A special diet helps the patient effectively eliminate Negative consequences metabolic disorders. Usually, the first complications that a balanced diet can effectively cope with are a disorder in fat metabolism. Against the background of this pathology, the patient rapidly gains weight, and sometimes faces atherosclerosis, coronary heart disease, as well as a steady increase in blood pressure.
In all the situations described, specialists prescribe diets to patients that limit the amount or completely eliminate foods rich in purines. These include: mushrooms, meat, legumes, fish. In addition, patients are shown fasting days with a vegetable, dairy or fruit menu.
It is worth saying that the diet for purine metabolism disorders should be used for quite a long time. The patient's diet includes split meals 4-5 times throughout the day.
The menu also excludes purines and has certain restrictions regarding salt, proteins, fats and carbohydrates. The energy value of the daily diet should range between 2700-2800 calories. Daily menu provides for the consumption of 80 g of protein, 90 g of fat, 400 g of carbohydrates.
- low-fat varieties meat and fish;
- dairy components;
- bread made from first grade flour;
- all kinds of cereals;
- vegetables and fruits in any form.
Should be excluded:
- fatty types fish and meat;
- raspberries;
- strong tea and coffee;
- chocolate;
- cocoa powder;
- legumes;
- cranberries;
- sorrel.
A variety of cooking fats are also prohibited.
By following a properly selected diet and other components of complex treatment, the patient feels significant relief in just a few weeks.
Acetone syndrome in children is a dysfunction of the metabolic system. The condition of a sick child is characterized by a high content of ketone bodies in the blood. During metabolism, they break down into acetone substances. This can trigger episodic attacks with abdominal pain. IN severe cases the child develops a coma.
Acetonemic syndrome can be secondary when the disease develops against the background of other disorders of carbohydrate, fat or protein metabolism. Primary idiopathic acetonemic syndrome also occurs in children. In this case, the main provoking mechanism is the hereditary factor. IN Lately the incidence of acetonemic syndrome has increased in newborns whose mothers suffered from insufficiency during pregnancy renal function. If the urine of a pregnant woman is periodically detected, and she suffers from constant edema, then the risk of developing intrauterine acetonemic syndrome in the fetus increases many times over.
Disorders of purine metabolism, which provokes the development of acetonemic syndrome, may be associated with the use of medicines containing artificial purines.
Symptoms of acetone syndrome in children
Mechanism pathological changes biochemical reactions begin in the renal structures. Blood enriched with purines enters here. Renal glomeruli unable to adequately process large amounts of purine substances. With the blood flow, they return to the bloodstream in the form of ketone bodies. In the future, these substances require:
- increased oxygen supply for their oxidation;
- increasing blood volume to reduce their concentration;
- reducing blood glucose levels to utilize acetone.
All these processes form the corresponding clinical picture:
- develops - increased ventilation of the lungs;
- the child's breathing quickens;
- heart rate increases;
- against the background of all this, the child becomes lethargic and apathetic;
- An acetone coma may develop under the narcotic influence of acetone and ketone bodies on brain structures.
But the main symptom of acetone syndrome in children is periodic uncontrollable vomiting with severe pain in the abdominal area. It is repeated with a certain frequency and is distinguished by the constancy of such parameters as duration, amount of vomit and the condition of the child.
Acetonemic syndrome in children is a typical alternation of periods of absolute well-being in the child’s condition with attacks of acetonemic crises. Their clinical picture is described above. The reasons for their occurrence are the accumulation of a critical amount of ketone bodies in the child’s blood.
Treatment of acetone syndrome and prognosis
Treatment of acetone syndrome in children comes down to two aspects:
- relief of acetone crisis;
- prolongation of the remission period, in which there is a tendency to reduce the incidence of crisis cases under the influence of acetone substances.
To relieve a crisis, prokinetics and cofactors (involved in the metabolic process) are used in combination with enzymatic replacement therapy. In severe cases, intravenous infusion therapy is prescribed. Thus, the electrolyte composition of the blood is restored, fluid losses are replenished, and the level of ketone bodies is reduced. For intravenous infusion, drugs with an alkaline reaction are used. During the remission period, the focus is on the child's diet and lifestyle.
Acetonemic syndrome in children is often accompanied by increased nervous excitability, which provokes the release of purines and ketone bodies into the blood. may provoke a crisis. Attention should be paid to reducing stress load and avoiding critical physical activity.
Diet for acetone syndrome
A constant diet for acetone syndrome is the basis successful treatment and preventing the risk of crises. Foods that are sources of large amounts of purines should be excluded from the child’s diet. These are meat products, rice, offal, mushrooms, beans, peas, fatty fish.
Introduce easily digestible foods into your child's diet. These are eggs, dairy products, vegetables and fruits. Be sure to let your child drink at least 2 glasses of mineral water with a weak alkaline reaction (Borjomi, Essentuki) during the day. Useful fresh juices from fruits and vegetables.
If necessary, you can use enzyme preparations to improve digestion processes. But this can only be done after consulting with your doctor.
Violations and their causes in alphabetical order:
disorder of purine metabolism -
Purine metabolism is a set of processes of synthesis and breakdown of purine nucleotides. Purine nucleotides consist of a nitrogenous purine base residue, a ribose carbohydrate (deoxyribose) linked by a b-glycosidic bond to the nitrogen atom of the purine base, and one or more phosphoric acid residues attached by an ester bond to the carbon atom of the carbohydrate component.
What diseases cause purine metabolism disorders:
The most important disorders of purine metabolism include excessive formation and accumulation of uric acid, for example in gout and Lesch-Nyhan syndrome.
The latter is based on a hereditary deficiency of the enzyme hypoxanthine phosphatidyltransferase, as a result of which free purines are not reused, but are oxidized into uric acid.
Children with Lesha-Nyhan syndrome have inflammatory and dystrophic changes. caused by the deposition of uric acid crystals in tissues: the disease is characterized by delayed mental and physical development.
Disturbances in purine metabolism are accompanied by disturbances in fat (lipid) metabolism. Therefore, in many patients, body weight increases, atherosclerosis of the aorta and coronary arteries progresses, coronary heart disease develops, and persistently increased arterial pressure.
Gout is often accompanied by diabetes mellitus, cholelithiasis, significant changes occur in the kidneys.
Attacks of gout are provoked by alcohol intake, hypothermia, physical and mental stress, and usually begin at night with severe pain.
Which doctors should you contact if a purine metabolism disorder occurs:
Have you noticed a disorder in purine metabolism? Do you want to know more detailed information or do you need an inspection? You can make an appointment with a doctor– clinic Eurolab always at your service! The best doctors will examine you and study you external signs and will help you identify the disease by symptoms, advise you and provide necessary help. you also can call a doctor at home. Clinic Eurolab open for you around the clock.
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If you have previously performed any research, Be sure to take their results to a doctor for consultation. If the studies have not been performed, we will do everything necessary in our clinic or with our colleagues in other clinics.
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