Mechanisms of pathogenesis. General mechanisms of pathogenesis. Components of pathogenesis

DAMAGE TO THE NERVOUS SYSTEM IN DISEASES OF INTERNAL ORGANS

LECTURE 14

The pathogenesis of damage to the nervous system in somatic diseases is mainly due to metabolic, toxic, vascular and reflex disorders. Shifts in homeostasis that occur as a result of disturbances in protein, carbohydrate, fat, water-electrolyte, vitamin metabolism, hypoxemia and tissue hypoxia, the accumulation of various waste products that must be eliminated from the body, have a toxic effect on nervous tissue (neurons and glial cells, synapses, axons). Reflex disorders also play a certain role. Excessive release of neurotransmitters may occur, and then depletion of their tissue reserves, for example, norepinephrine activates the enzyme adenylate cyclase, which catalyzes the formation of cyclic adenosine monophosphate (cAMP) from ATP. The latter is necessary for the normal course of complex intracellular metabolic reactions, since with a decrease in cAMP, the activity of the genetic apparatus and enzyme systems decreases. Consequently, in most cases, a number of interrelated factors influence, one or two of which are the most significant. With pulmonary embolism, this is acute hypoxia and reflex disorders (shockoanoxic syndrome), with long-term nonspecific lung diseases - chronic hypoxia with severe changes in nerve cells and glia, kidney pathologies - metabolic disorders and toxicosis (hypo-, and later hyperkalemia, creatininemia, azotemia, the influence of the entire complex of metabolites accumulating in the blood with the development of cerebral edema), obstructive jaundice - bilirubinemia. Clinical manifestations depend, in addition, on heredity, the patient’s constitution, age, living and nutritional conditions, bad habits, previous pathology, and characteristics of the work performed. Somatogenously caused disorders of the regulatory influence of the nervous system on the activity of internal organs and endocrine glands create a vicious circle, contributing to the deepening of failure of both internal organs and the nervous system. The well-known common clinical picture of neuropsychic disorders in response to pathology of internal organs and endocrine glands confirms that they are based on similar pathogenetic mechanisms - a combination of the phenomena of irritation and loss at various levels of the nervous system (cortex, subcortex, trunk, spinal cord, etc. ) with some emphasis on one or the other of them.

It has been established that even relatively compensated insufficiency of the functions of an internal organ or endocrine gland with an increased predisposition can lead to clinically pronounced changes in the nervous system (fatigue, headache, dizziness, memory loss, etc.). Against the background of somatic disorders and accompanying shifts in hormonal-mediator-electrolyte balance and hypoxia, neuropsychic disorders develop earlier and more often due to infections, intoxications, injuries, chronic and acute cerebrovascular accidents, hereditary and chronically progressive diseases are more severe.

The first signs indicating involvement of the nervous system in somatic diseases are increased fatigue, irritability, headache, sleep disturbance, paresthesia and dysesthesia in the Zakharyin-Ged zones.

Thus, with damage to the heart, pain often spreads to the upper part of the chest and to the inner surface of the shoulder and forearm on the left (segment Cvп-Thi-Thiv), with damage to the lungs - to the area of the neck and shoulder girdle (Csh-Civ), liver - to the right hypochondrium (Thvш-Thix), stomach and pancreas - to the epigastric region (Thvп-Thix), kidneys and ureter - to the lower back and anterior upper surface of the thigh (Thxп-Li), small intestines - to the peri-umbilical region (Thx-Thxi). When the vagus nerve is involved, pain is often felt in the face (trigeminal nerve) and the back of the head (Sp segment); phrenic nerve - in the area of the shoulder girdle and neck (Csh-Civ).

All these symptoms are initially mild and inconsistent. In the future, if the dysfunction of one or another organ or endocrine gland increases, then organic disorders may gradually develop - nystagmus, symptoms of oral automatism, changes in reflexes, motor and sensory disorders. Sometimes an acute disease of an internal organ (pulmonary embolism, pancreatitis, obstructive jaundice, hepatitis) debuts with neuropsychic disorders: agitation, motor restlessness, hallucinations, meningeal phenomena, etc. Increased neuromuscular excitability, spasms and paresthesia in the extremities are the first signs of hypocalcemia due to insufficiency of the parathyroid glands and kidneys. Even in the presence of a clear picture of diseases of the liver, kidneys, lungs, pancreas, and pelvic organs, the establishment of a pathogenetic relationship between this disease and damage to the nervous system should be based on anamnesis, clinical data, and additional research methods. Neuropsychic disorders develop, as a rule, against the background of an already identified somatic or endocrine disease. The latter may precede the development of neuropsychiatric pathology by several years. Less often, the opposite relationship occurs: neuropsychic disorders outstrip the clinical manifestations of somatic ones. In this case, the interval between them is usually shorter - it rarely exceeds 2-3 months, sometimes six months to a year. During this period of time, the symptoms of a somatic disease, as a rule, become quite obvious. It is necessary to pay attention to the relationship between the severity and course of the underlying disease and existing disorders of the nervous system.

Diseases of the heart and great vessels. Diseases of the heart and large vessels - congenital and acquired defects, myocardial infarction, cardiac rhythm disorders, septic endocarditis, aneurysm and coarctation of the aorta, nonspecific aortoarteritis (Takayasu's disease), thromboangiitis obliterans and some others may be accompanied by a variety of neuropsychiatric disorders. The pathogenesis of these disorders is due to changes in blood and liquor circulation, vascular occlusion, embolism, reflex disorders, and sometimes the spread of the inflammatory process to the vessels of the brain (for example, with vasculitis, septic endocarditis).

The initial period of heart and vascular disease is most often characterized by asthenic vegetative-vascular disorders - general weakness, fatigue, sleep disturbance, sweating, instability of pulse and blood pressure (the so-called neurocirculatory asthenia). Cephalgic syndrome is manifested by paroxysmal or almost constant diffuse or more limited (temple, occipital) pain. With significant duration and severity of the disease, in addition to headache and other general cerebral symptoms (nausea, dizziness), small focal symptoms are noted - nystagmus, reflexes of oral automatism, hand tremors, pathological reflexes, etc.

The symptomatology of congenital heart defects manifests itself in childhood, with delays in physical and mental development, syncope or epileptiform seizures, paresis and other focal symptoms. Neurosis-like disorders are often observed - fear, anxiety, constant internal restlessness, sleep disorders, general weakness. The severity of symptoms depends on the severity of the underlying disease, premorbid personality characteristics, age and gender.

Extensive myocardial infarction can be complicated by various cerebral circulatory disorders (lethargy, lethargy, drowsiness or agitation, headache, meningeal symptoms, suppressed reflexes, etc.), sometimes developing into cardiogenic shock, cardiocerebral syndrome (dizziness, impaired consciousness, motor and sensory disorders, pathological reflexes) or cardiospinal syndrome (weakness in the limbs, changes in tendon and periosteal reflexes, conduction or segmental sensory disorders and pelvic disorders). One of the consequences of myocardial infarction may be reflex shoulder-hand syndrome, which is characterized by severe pain in the shoulder joint, arm, especially in the hand, swelling of soft tissues, and vasomotor disorders. Subsequently, trophic disorders are identified - atrophy of the muscles and skin of the hands, osteoporosis, etc.

Cerebrovascular accidents occur especially often against the background of hemodynamic disorders in children with congenital heart defects or in older patients suffering from acquired heart defects, hypertension or cerebral atherosclerosis.

Patients with congenital heart defects often experience paradoxical embolisms in the brain, the source of which is thrombosis of the veins of the lower extremities or hemorrhoidal veins. The development of acute cerebrovascular accidents in these cases is facilitated by both exogenous factors (physical stress, bending or turning the body, etc.) and compensatory polycythemia and increased blood viscosity observed in congenital heart defects. These patients often have early and late post-stroke pneumonia, which develop respectively in the first 3 days or 2-6 weeks after the stroke, as well as impaired carbohydrate metabolism (post-stroke diabetic syndrome).

The rapidity of development of early pneumonia, its occurrence mainly in large lesions affecting the hypothalamus and brain stem, its more frequent development on the side contralateral to the lesion in the brain, the presence in the lungs of signs of circulatory disorders in the form of plethora, hemorrhage and edema indicate the important role of central neurotrophic disorders in the pathogenesis of complications.

The hypostasis factor plays a lesser role in the development of early pneumonia, but a very important, and in some cases, decisive role in the development of later forms of the complication. In stroke patients, whose activation is delayed for one reason or another (cardiac pathology, thrombophlebitis), prolonged stay in bed almost always leads to impaired ventilation of the lungs.

In addition, the initial background of the patient’s health status is important for the development of both early and late forms of pneumonia. They occur more often in individuals with repeated cerebrovascular accidents and pseudobulbar and bulbar syndromes. Swallowing disorders in these patients contribute to the aspiration of saliva, pieces of food, mucus, and vomit into the respiratory tract.

An important provoking factor is coronary heart disease with small- and large-focal angiogenic cardiosclerosis, chronic lung diseases (bronchitis, bronchial asthma) resulting in pneumosclerosis (diffuse or limited) and emphysema, which leads to the development of pulmonary heart failure. The occurrence of a stroke in these patients further worsens the already impaired aeration of the lungs.

Disorders of carbohydrate metabolism in the acute period of stroke develop very often. They are characterized by lability and the absence of ketoacidosis. The severity of the disorders depends on the severity of the stroke, the size of the lesion and the nature of the process, as well as on the outcome of the condition of the pancreas. During the recovery period after a stroke, carbohydrate metabolism gradually normalizes, however, if there is compensated insufficiency of organs (primarily the pancreas) involved in the regulation of glycemia, then the risk of developing diabetes mellitus increases if the patient survives. A previous stroke is therefore one of the risk factors contributing to the onset of the disease, especially in older people.

Changes in heart rhythm (paroxysmal tachycardia, atrial fibrillation, bradycardia) are a common cause of fainting.

Fainting (syncope) occurs most often with atrioventricular block (Morgagni-Adams-Stokes syndrome) against the background of a decrease in heart rate to 30 - 10 beats/min. There is a feeling of lightheadedness, dizziness, general weakness, then loss of consciousness. Objectively - the face is pale, the pulse is very rare, weak filling. In severe cases, tonic and clonic convulsions and loss of urine develop. Frequent paroxysms gradually lead to the formation of encephalopathic syndrome.

The cerebral form of thromboangiitis obliterans is characterized by simultaneous involvement of the vessels of the brain, limbs and internal organs, while Takayasu's disease is characterized by obliteration of the vessels extending from the aortic arch. Both forms are manifested by symptoms of dyscirculatory encephalopathy and repeated transient ischemic attacks, accompanied by dizziness, disturbances of consciousness, speech, visual and motor disorders.

With septic endocarditis, damage to the nervous system is possible due to cerebral embolism. Entry of infected emboli into the vessels of the meninges can lead to the development of purulent meningitis, and into deep-lying vessels of the brain - single or multiple brain abscesses.

Coarctation of the aorta due to increased blood supply to the upper half of the body and insufficient lower half leads to hypertrophy of the chest, shoulder girdle, hands and atrophy of the pelvic girdle and legs. Against this background, symptoms of discirculatory encephalopathy and acute cerebrovascular accidents - plethoric crises, parenchymal and subarachnoid hemorrhages usually develop. Symptoms of an aortic aneurysm are girdling pain at the level of its location, the intensity of which can vary depending on the position of the patient; subsequently, signs of ischemic myelopathy appear.

If the aneurysm is localized in the area of the aortic arch, nearby formations may be compressed - the left recurrent nerve (hoarseness of voice, coughing attacks, suffocation), the phrenic nerve (shortness of breath, hiccups), the borderline sympathetic trunk (Horner's symptom, burning pain in half of the face, lacrimation and redness of the eye, rhinorrhea).

The clinical picture of a dissecting aortic aneurysm is severe radicular pain in the chest or back with irradiation to the lower abdomen and legs, sometimes the development of collapse or shock.

Acute occlusion of the abdominal aorta and main arteries of the lower extremities is characterized by severe pallor of the legs and pain in them, the disappearance of pulsation of large vessels, the development of lower flaccid paralysis or paraplegia with dysfunction of the pelvic organs, as well as conduction-type sensitivity disorders.

Chronic obliteration of the abdominal aorta, aortic bifurcation and great vessels of the lower extremities is manifested by the gradual development of symptoms of discirculatory myelopathy. At the same time, vegetative-trophic, sensory and motor disorders are especially pronounced in the distal parts of the extremities (up to gangrene of the feet).

Treatment and prognosis. The most rational is a comprehensive treatment regimen, taking into account the characteristics of both the underlying disease and the existing complication. If neurological disorders develop against the background of myocardial infarction or congenital and acquired heart defects, then therapeutic measures should be aimed primarily at compensating for cardiovascular failure. For heart rhythm disturbances, antiarrhythmic drugs are indicated. Patients with a sharp decrease in pulse rate (atrioventricular block) are prescribed anticholinergics, and in cases of their insufficient effectiveness for appropriate indications, electrical stimulation. Septic endocarditis is treated with large doses of antibiotics.

Treatment of systemic diseases with impaired vascular patency (Takayasu's disease, atherosclerotic obliteration of the vessels of the extremities) at the initial stage is usually conservative with the use of antispasmodics, vasodilators, ganglion blockers, sympathetic blockades, oxygen therapy. For epileptic seizures - anticonvulsants, cerebrovascular accidents - treatment corresponding to the clinical picture of the stroke.

The prognosis is determined by the course of the underlying disease, the nature of the neuropsychic complication, the timeliness and volume of treatment measures. It is relatively less favorable for severe chronic diseases of the heart and great vessels, complicated by cardiogenic shock, cerebrovascular accident, and discirculatory encephalopathy of stages II-III.

Lung diseases. Neurological disorders can develop against the background of both acute lung diseases (thromboembolism of the main trunk, large, medium and small branches of the pulmonary artery, infarction pneumonia, severe bilateral pneumonia), and chronic nonspecific lung diseases (CNLD) (pulmonary emphysema, chronic bronchitis, bronchial asthma , pneumosclerosis).

Pathomorphologically, in the brain of patients who died from acute lung diseases, edema, diapedetic hemorrhages and plasmorrhages, foci of thrombotic and non-thrombotic softening, a combination of focal ischemia in the cortical sections with areas of congestion in the deeper areas, as well as venous stagnation with arterial ischemia are determined. Hyaline and ring-shaped thrombi are observed in the capillaries, dystrophic changes in nerve cells and glia, and areas of massive primary karyocytolysis.

Chronic hypoxia is manifested primarily by neurocellular pathology - a severe form of damage to nerve cells with a slowly increasing degenerative process in the nucleus and cytoplasm of neurons and glial cells.

In the pathogenesis of damage to the nervous system in lung diseases, the leading role is played by the influence of factors of hypercapnia and hypoxemia, which arise as a result of disorders of ventilation and gas exchange in the lungs. When examining the function of external respiration, depending on the nature and severity of the pathology, a decrease in vital capacity (VC) to 2400-1900 ml is noted; maximum pulmonary ventilation (MVV) up to 50-30 l and oxygen utilization coefficient (OK02) up to 30-28 ml; increase in minute volume of respiration (MOV) to 8-10 l and oxygen absorption per minute (POg) to 240-270 ml/min. The duration of breath holding (Stange-Gench test) is shortened to 10-15 s. The partial pressure of carbon dioxide (pCO2) increases to 50-60 mm Hg, the pH value shifts towards acidosis (up to 7.3). Arterial blood oxygen saturation (HbO2) gradually decreases (up to 80%), changing the level of standard bicarbonates (SB) and buffer bases (BB).

Deep metabolic disorders develop (the amount of fibrinogen increases, a - and g-globulins and amino acids, lactic acid, ammonia, inorganic phosphorus, the amount of ATP, phosphocreatine, etc. decreases. In thrombosis and embolism of the pulmonary artery, an important role is played by pronounced hemodynamic disturbances that arise as a result of blockage of the pulmonary vessel and widespread vascular spasm. Following this, arterial ischemia and venous congestion of the brain and spinal cord develop, the permeability of the vascular walls increases with the release of red blood cells per diapedesem into the subarachnoid space and brain matter, which causes massive primary karyocytolysis with the formation of extensive foci of neuronal loss in the cortex.

The complexity of the pathogenesis of brain disorders (hypoxemia, drop in blood pressure in the systemic circulation, vascular spasm, homeostasis disorders) leads to a greater frequency of focal brain lesions than with other types of hypoxia, and a variety of their nature (meningeal syndrome, encephalopathy with convulsive seizures, non-thrombotic softenings , hemorrhages, etc.).

The appearance of local neurological symptoms (often in the absence of a macroscopic focus in the brain) is explained by the phenomenon of capillary ischemia, which is uneven in nature, with massive primary karyocytolysis and areas of cell loss in the cortex. Glia are more resistant to the effects of hypoxia, although they exhibit a gross proliferative-dystrophic reaction, but basically retain their structure.

Clinic. Neurological disorders in the form of mild headache, photophobia, general hyperesthesia, and minor vegetative dystonic manifestations are usually included in the clinical picture of uncomplicated pneumonia and are present to one degree or another in almost all patients. More pronounced neurological symptoms, which should be regarded as neuropsychiatric complications, are observed in approximately 6-8% of inpatients with pneumonia. These complications are manifested by cerebral, meningeal, focal and autonomic symptoms, including severe headache, dizziness, psychomotor agitation, pain when moving the eyeballs, severe general hyperesthesia, epileptiform seizures, nystagmus, anisoreflexia, pathological symptoms, sensitivity disorders, changes in blood pressure, pulse, sweating, etc.

Encephalopathic and meningeal syndromes develop more often in severe forms of lobar pneumonia. Encephalopathic syndrome is manifested by polymorphic neuropsychic disorders: intense headache, a feeling of heaviness in the head and congestion in the ears, nausea, psychomotor agitation, mildly expressed focal symptoms - nystagmus, revitalization of tendon reflexes, anisoreflexia, increased muscle tone, as well as manifestations of vegetative-vascular dystonia in the form of blood pressure instability, pulse lability, acrocyanosis, etc. Often on the side of somatic pathology in the Zakharyin-Ged zones, hyperesthesia, hyperpathy or hypoesthesia are determined.

Meningeal syndrome is manifested by moderately severe headache, nausea, retching or vomiting, pain when moving the eyeballs, photophobia, general hyperesthesia, sometimes psychomotor agitation, tonic symptoms (stiffness of the neck muscles, zygomatic ankylosing spondylitis, etc.). In the cerebrospinal fluid, there is usually only an increase in pressure with unchanged cell and protein content. The course is short-lived (3-5 days). This symptom complex (meningeal syndrome with normal CSF) is called meningism. However, severe forms of pneumonia can be complicated by purulent meningitis due to dissemination of pathogens (most often pneumococci) into the subarachnoid space. In these cases, there is a sharp deterioration in the condition of the patients - a new rise in temperature to high numbers and pronounced cerebral, meningeal, and sometimes focal symptoms. Neutrophilic pleocytosis and hyperalbuminosis are observed in the cerebrospinal fluid. The course is longer (2-4 weeks), the prognosis, especially in the elderly, is not always favorable.

The clinical picture of pulmonary embolism is extremely polymorphic. It can be manifested by the following neurological syndromes - psychomotor agitation, meningeal, focal brain damage, epileptiform. It should be remembered that thromboembolism can cause acute coma.

Psychomotor agitation syndrome is especially common. Thromboembolism of the main trunk or large branches of the pulmonary artery is characterized by the acute development of pronounced psychomotor agitation: patients jump up, try to run, do not recognize relatives, hallucinate, and do not orient themselves in the environment. In prolonged forms of thrombosis and infarction pneumonia, such attacks occur periodically, more often at night. Typically, paroxysms of excitement are replaced by adynamia, decreased emotional reactions, lethargy, drowsiness, and lethargy. In some cases, periods of motor excitation are accompanied by the appearance of focal symptoms.

Meningeal syndrome is observed in subacute and acute forms of the disease. The more severe the pulmonary heart failure, the more usually the number of meningeal symptoms is detected. Meningeal syndrome in patients with pulmonary artery thrombosis and infarction pneumonia appears with increasing cerebral edema and serves as a poor prognostic sign.

Focal brain damage is observed in patients with predominantly prolonged forms of the disease. Of the transient symptoms of damage to the nervous system, the most common are nystagmus or nystagmoid twitching of the eyeballs, anisocoria, anisoreflexia, pathological reflexes, and intentional tremor when performing coordination tests. Often, against the background of deterioration of the patient’s condition, speech disorders such as sensory and motor aphasia, paresis, paralysis, etc. occur. General cerebral local symptoms in some cases appear several hours earlier than pronounced respiratory and cardiac disorders. It should be noted that the favorable dynamics of pulmonary pathology is accompanied by rapid complete or partial regression of neurological symptoms. If the increase in thrombosis in the pulmonary vessels is accompanied by a deepening of cerebral disorders, then in the event of death it is difficult to identify the immediate cause of death (cerebral circulatory disorder or a process in the pulmonary artery). Damage to the spinal cord develops less frequently and mainly in patients with subacute and protracted forms of the disease. There is depression or complete extinction of tendon reflexes in the lower extremities (especially often the knees) and sensitivity disorders of the segmental type. Characterized by positive dynamics of symptoms with normalization of the functions of the respiratory and cardiovascular systems. Torpidity of the knee reflexes is an important symptom, indicating the severity of the pulmonary process, even with a relatively satisfactory general condition of the patient. The progression of spinal disorders is a poor prognostic sign, as it usually indicates an increase in the thrombotic process in the pulmonary arteries.

Epileptic syndrome is characterized by the development of a generalized convulsive seizure. It can also complicate the course of pulmonary embolism (acute and subacute forms). Sometimes after an attack, patients experience the appearance or increase in focal neurological symptoms, which simulates an acute cerebrovascular accident. It is important to remember that post-ictal symptoms usually subside over the next 24 hours.

Polyneuropathic syndrome is rarely observed in patients with a prolonged form of pulmonary embolism. These disorders are transient and regress relatively well under the influence of treatment aimed at normalizing blood gas composition and hemodynamics.

The syndrome of “decompensation of the old focus” develops in patients with subacute and protracted forms of pulmonary embolism who have previously suffered a stroke or transient cerebrovascular accident. The damage to the nervous system is completely compensated and does not appear until the onset of pulmonary disease. The sudden development of focal neurological symptoms (paresis, sensitivity disorders, speech, etc.) simulates a recurrent cerebrovascular accident. The differential diagnosis is based on medical history and clinical data (thrombophlebitis, shortness of breath, cyanosis, tachycardia, etc.) and the presence of symptoms indicating the localization of the lesion in the basin of the same vessel. The diagnosis of decompensation of the blood supply to the brain against the background of the presence of a cyst in the brain from a previous stroke is confirmed by the rapid favorable dynamics of neurological symptoms when the pulmonary insufficiency is relieved. In patients suffering from atherosclerosis or hypertension, increasing pulmonary insufficiency can result in cerebrovascular accident - ischemic softening or hemorrhage.

Chronic encephalopathy syndrome develops in patients with COPD with long-term pulmonary insufficiency and is characterized by diffuse dull headache, especially intense in the morning, with physical stress, cough, increased fatigue, irritability, irascibility and slight scattered focal symptoms (hyperreflexia, anisoreflexia, ataxia, trembling of outstretched fingers hands). Sometimes syncope and paroxysms of the type of cough and fainting syndrome (betolepsy) are observed.

Inflammatory lung diseases with the presence of a purulent focus (empyema, bronchiectasis, etc.) can lead to the formation of a metastatic abscess (single or multiple) in the brain, which is expressed by an increase in general cerebral and focal symptoms, epileptic seizures, etc.

Pulmonary tuberculosis is usually manifested by symptoms of general intoxication and autonomic dysfunction: headache, weakness, sweating, tachycardia, and blood pressure instability. Tuberculosis intoxication can lead to meningism (severe headache, photophobia, nausea). In the case of generalization of tuberculosis infection, the development of tuberculous meningitis, tuberculoma of the brain or spinal cord, and tuberculous spondylitis is possible.

Diagnosis of the diseases in question presents certain difficulties, especially in the initial stages of the disease or its atypical course. The reaction of the nervous system to some extent can be proactive, for example, with prolonged thrombosis of the pulmonary vessels, in some cases neuropsychic disorders (headache, nausea, vomiting, psychomotor agitation, meningeal symptoms, paresis) may come to the fore. and pulmonary-cardiac disorders (shortness of breath, cyanosis, tachycardia, decreased blood pressure) become pronounced in a more advanced stage of the disease.

The appearance of general cerebral and focal disorders against the background of pulmonary failure following psychomotor agitation syndrome (a typical sign of pulmonary embolism or infarction pneumonia), instability of symptoms and their dependence on the dynamics of pulmonary heart failure are the main diagnostic signs of hypoxic encephalopathy. When examining the cerebrospinal fluid, only an increase in cerebrospinal fluid pressure is noted (up to 200-300 mm H2O or more) without cytosis and hyperalbuminosis.

Treatment of neuropsychiatric disorders in patients with pulmonary embolism is inextricably linked with the treatment of the underlying disease. Extremely severe thromboembolism of the trunk and main branches of the pulmonary artery is treated surgically (emergency embolectomy). The presence of neuropsychic disorders is not a contraindication to surgery, since it usually contributes to their regression. Severe thromboembolism of the pulmonary artery, as well as embolism of its intermediate and lobar branches, are indications for thrombolytic therapy with simultaneous correction of the hemostatic system (fibrinolysin or activators of endogenous fibrinolysis, disaggregants, thrombolytics, anticoagulants).

Conservative treatment can be combined with surgical prevention of recurrent pulmonary embolism (installation of a filter in the inferior vena cava). Along with drugs aimed at treating pulmonary disease, drugs that normalize the functions of the nervous system (metabolics, vitamins, vasotropic drugs) should also be recommended.

Antipsychotics are most often used to relieve psychomotor agitation. Symptomatic treatment of other cerebral disorders is carried out - vomiting (droperidol, triftazine), hiccups (metoclopramide, torecan, etaprazine), pain syndromes (analgesics or lytic mixtures consisting of aminazine or tizercin, diphenhydramine or pipolfen and promedol).

The prognosis of neuropsychic disorders in pulmonary embolism and infarction pneumonia is always serious.

Only favorable dynamics of the underlying disease prevent the transition of transient disorders into persistent organic brain lesions. Neuropsychiatric disorders in chronic pneumonia, emphysema, bronchitis, and pulmonary tuberculosis are usually moderate, and with systematic treatment and compliance with the recommendations for the regimen, most patients remain able to work.

Liver diseases. Diseases of the liver and biliary tract are often complicated by neuropsychiatric disorders. The clinical manifestations of the latter are determined by the form, severity and duration of the underlying disease - cholecystitis, cholelithiasis, cholangitis, cholepancreatitis, obstructive jaundice, liver cirrhosis, etc.

The most commonly observed are asthenic manifestations and diffuse damage to the brain and spinal cord, and sometimes to individual peripheral nerves, i.e., the syndromes of encephalopathy, encephalomyelopathy and polyradiculoneuropathy.

Liver disease can be one of the causes of optic neuritis.

Pathogenesis Damage to the nervous system is caused by disturbances in the detoxification function of the liver and various types of metabolism - protein, lipid, carbohydrate, water-electrolyte, vitamin. Hyperglobulinemia develops, the formation of fibrinogen, prothrombin, and vitamin metabolism (in particular, vitamins C and K) are disrupted, which causes a change in the coagulating properties of the blood and the development of hemorrhagic syndrome. The acid-base state of the blood shifts towards acidosis, and the alkaline reserve of the blood decreases. Water-salt metabolism and the course of all redox processes in the nervous system are upset. In case of jaundice, a toxic effect is caused by the accumulation of bilirubin and bile acids in the blood, and ammonia in hepatoportal disorders. One of the links in the pathogenesis may be dysfunction of other organs, which is confirmed by the frequent development of hepatocardial, hepatolienal, or hepatorenal syndromes.

Neurosthenic-like syndrome occurs in two variants - hypersthenic (irritability, increased excitability, emotional lability, incontinence, anger, excessive mobility) and asthenic (physical and mental fatigue, resentment, suspiciousness). The mood is unstable. The sleep is superficial and disturbing. Usually complaints of headache, a feeling of heaviness in the head, dizziness, as well as discomfort in the heart, palpitations, sexual disorders (impotence, menstrual irregularities, etc.). Some patients with sensitive character traits with mechanical or parenchymal jaundice experience severe itching and a burning sensation in any part of the body, causing a desire to “take everything off”, sensations of electric current and hot waves passing through the body, “twitching and gurgling in the area abdomen”, “vibration in the spine”, etc.

Hepatogenic encephalopathy is manifested by headache, dizziness, sometimes nausea and minor diffuse symptoms (nystagmus, cranial nerve paresis, coordination disorders, hyperkinesis, anisoreflexia, pathological reflexes). In the advanced stage of liver cirrhosis (ascites, splenomegaly), more severe forms of portal encephalopathy with impaired consciousness are observed. Due to the formation of anastomoses between the system of the cava and portal veins, ammonia and other toxic products from the gastrointestinal tract enter the blood (normally they pass through the liver filter and undergo detoxification). Against the background of polymorphic neurological symptoms, psychomotor agitation, as well as hyperkinesis (usually choreoathetosis or fluttering tremor), are often observed. Psychomotor agitation can progress to stupor, stupor and then coma. With an acute increase in the difficulty of blood flow from the portal vein to the liver, the likelihood of neurological disorders increases. The formation of ammonia is proportional to the content of proteins in the intestine, therefore, with bleeding from varicose veins of the esophagus, portal encephalopathy develops especially often.

The cause of the development of acute toxic-dyscirculatory encephalopathy (ATDE) is often obstructive jaundice. In milder cases, OTDE is manifested by severe apathy, adynamia, headache, and a diffuse decrease in muscle tone. With moderately severe OTDE, focal neurological symptoms (anisoreflexia, pathological reflexes, impaired cranial innervation, oral automatism reflexes, meningeal signs) are added, and with severe OTDE, in addition to an increase in organic cerebral symptoms, signs of spinal cord damage appear (paresis of the legs, decreased muscle tone, plantar and Achilles reflexes). There is a certain correspondence between the severity and duration of bilirubin autointoxication, on the one hand, and the depth of neurological disorders, on the other.

The symptoms of polyradiculoneuropathies associated with liver pathology have the following features: at the beginning of the disease, there is typically limited damage to one or two roots or one nerve, and only after a few weeks or months the process spreads to other nerves and gradually affects all limbs - a polyneuropathic syndrome occurs. Depending on the clinical manifestations, sensitive, motor and mixed forms are distinguished.

The most common is the sensitive (sensory) form, which is characterized by pain, paresthesia, a disorder of surface sensitivity in the distal parts of the extremities and vegetative-vascular disorders (coldness of the hands and feet, hyperkeratosis, hyperhidrosis, discoloration of the skin). The degree of movement disorders varies - from mild weakness to relatively deep paresis. On the arms, there is a predominant lesion of the radial nerve, on the legs - the peroneal nerves.

Sometimes, with diseases of the liver and biliary tract, various visceral disorders develop - hepatocholecystocardial and hepatorenal syndromes. Most often, cholecystocoronary Botkin syndrome is observed, which manifests itself as recurrent cardialgia against the background of a diet disorder, dyspeptic symptoms, jaundice, etc. In elderly patients suffering from atherosclerosis involving the vessels of the brain and heart, pathology of the liver and biliary tract may be a risk factor for stroke or myocardial infarction.

Diagnosis is based on clinical data and additional research methods, among which the most important indicators are EEG (the appearance of triphasic waves is one of the early signs of the transition of hepatogenic encephalopathy to a coma) and EMG (decreased amplitude of myopotentials, rare fibrillations, changes in nerve conduction velocity are detected in subclinical forms of hepatogenic polyneuropathies). An increase in pressure is detected in the cerebrospinal fluid. CT and MRI are important for assessing the condition of the brain and liver.

Treatment. Prescribe detoxification, dehydration, lipotropic and restorative agents - rheopolyglucin, diacarb, cerebrolysin, retabolil, glutamic acid, methionine, pancreatin, intravenous infusions of glucose with insulin, isotonic sodium chloride solution, blood, plasma or blood substitutes (polyglucin, etc.), as well as diet with limited salt and protein. To reduce the activity of the intestinal bacterial flora, which produces ammonia, short courses of antibiotics or sulfa drugs are sometimes prescribed. Excitement and motor restlessness can be relieved by the administration of antipsychotics. When bleeding occurs, ascorutin, vikasol, calcium gluconate, dicinone, etc. are prescribed. A number of diseases of the liver and biliary tract are treated promptly (cholecystitis, cholelithiasis, cirrhosis of the liver, etc.). The appearance of neuropsychic disorders, as a rule, should not serve as a contraindication to surgical intervention.

The prognosis is more favorable with the development of neuropsychic disorders against the background of cholecystitis, cholangitis and cholelithiasis, less so against the background of cirrhosis of the liver, with portocaval anastomosis, splenomegaly, ascites, bleeding from the veins of the esophagus.

Diseases of the pancreas. In hyperglycemic conditions due to diabetes mellitus, various symptoms are observed: headache, dizziness, general weakness, memory loss, itching, sensory disturbances, and motor disorders. The following syndromes are distinguished: neurasthenic, encephalopathic, polyneuropathic, autonomic polyneuropathy, neuralgia and neuropathy of individual nerves, most often the facial one, as well as hyperglycemic (diabetic) coma.

Diabetic encephalopathy is characterized by headache, decreased memory and attention, nystagmus, impaired pupillary reactions to light and convergence, paresis of the facial and oculomotor nerves, etc. Severe forms of diabetes, especially in the elderly, can be complicated by stroke. Pathomorphological studies suggest that in the pathogenesis of encephalopathy and strokes in diabetes, an important role belongs to the macroangiopathy inherent in diabetes mellitus, i.e. damage to arterioles, precapillaries, vascularizing the cortex, subcortical formations and the brain stem.

It should be emphasized the frequency of nonthrombotic softenings, which is explained by excessive accumulation of carbon dioxide. The latter, dilating the cerebral vessels, causes a regional drop in blood pressure, which, in the presence of an increased need for oxygen in the brain tissue of diabetic patients, leads to softening without the formation of a blood clot in the brain vessel.

Diagnosis of strokes occurring against the background of diabetes mellitus has certain difficulties. The neurological picture is masked by adynamia, peripheral sensitivity disorders, anisoreflexia, areflexia, etc., which accompany diabetes. In many patients in the acute period of stroke, the course of diabetes also worsens: the blood sugar level rises to values unusual for the patient, acetonuria appears, etc. Comatose states in these patients are characterized by a long duration (from 1 to 3-5-8 and more than 20 days).

Cerebrovascular disease may be complicated by the development of hyperglycemic coma. All this in cases of stroke with loss of consciousness, stupor, and stupor complicates the differential diagnosis with diabetic (hyperglycemic) coma.

Hemorrhagic stroke in patients with diabetes mellitus develops more often when combined with hypertension or as a complication of diabetic coma, apparently as a result of the toxic effect of products of impaired metabolism, in particular ketone bodies, on the cerebral vessels.

In people suffering from diabetes mellitus, polyneuropathic disorders are common, which occur with a predominance of sensory, autonomic and motor symptoms. The sensitive form is manifested by paresthesia, pain and a slight decrease in surface sensitivity, impaired coordination of movements, the motor form is manifested by mild flaccid paresis of the limbs and muscle atrophy, more pronounced in the proximal parts. Diabetic polyneuropathies are highly characterized by peripheral autonomic failure. The most common manifestations of PVN are orthostatic hypotension, fixed tachycardia, nocturnal diarrhea, and pelvic disorders. There are also neuropathies and neuralgia of individual nerves, especially the facial one.

Hyperglycemic diabetic coma often develops gradually - over several hours or days. Headache, dizziness, thirst, and polyuria appear. Patients become lethargic, drowsy, apathetic, and indifferent. There is dry skin with traces of scratching. If left untreated, the precomatose state turns into a coma: consciousness is completely lost, blood pressure drops, the pulse becomes weak and frequent, and there is a smell of acetone from the mouth. The pupils are narrow, corneal, abdominal and tendon reflexes gradually decrease. In coma of degrees 1-11, pathological reflexes are usually detected.

Treatment. In the acute period of a stroke against the background of diabetes mellitus, insulin should be prescribed: by normalizing carbohydrate metabolism and reducing hypoxia, it improves the nutrition of brain tissue. To avoid hypoglycemia, it is better to administer insulin in fractional doses. Dysfunction of the blood coagulation and anticoagulation systems, the frequency of non-thrombotic softenings and the presence of foci combined in the nature of the pathological process require caution when prescribing anticoagulants to patients with diabetes mellitus. In cases of diabetic coma, immediate intravenous administration of insulin is indicated, and hypoglycemic - glucose. Surgical interventions are used for purulent pancreatitis, pancreatic necrosis, pancreatic tumors (insulinoma).

The course of the syndromes of diabetic polyneuropathy, diabetic and hypoglycemic encephalopathy is often recurrent with improvement under the influence of complex treatment.

Kidney diseases. Acute renal failure (acute glomerulonephritis, post-abortion sepsis, poisoning, trauma, etc.) and long-term kidney diseases (chronic glomerulonephritis, pyelonephritis, urolithiasis) in the stage of subcompensation and especially decompensation can cause a variety of neuropsychic disorders - polyneuropathy, encephalopathy, dyskalemic paralysis, uremic coma, etc.

Pathomorphologically, the brain reveals a typical picture of toxic encephalopathy with a combination of vascular and parenchymal-cellular changes (edema, angioonecrosis, diapedetic hemorrhages, degenerative cell changes, etc.).

The pathogenesis of neurological disorders in kidney diseases in the stage of decompensation is mainly due to intoxication caused by azotemia.

However, syndromes such as asthenic-like, renovisceral, and moderate encephalopathy can complicate subcompensated renal failure when there are no signs of azotemia yet. Loss of sodium and chlorides, slight hypo- and hyperkalemia and hypoalbuminemia lead to a decrease in the colloid-osmotic pressure of the blood, an increase in vascular permeability with the development of edema, diapedetic hemorrhages and plasmorrhages in the brain, spinal cord and peripheral nerves, and subsequently to changes in nerve cells and conductors , nerve plexuses and peripheral nerves, as well as impaired contractile function of muscles.

Toxic damage or mechanical compression of the branches of the autonomic plexus of the kidneys by stones can lead to pathological irritation of the pain impulse into the spinal nodes and segmental apparatus of the spinal cord and the appearance of pain and hyperesthesia in the renal zones of Zakharyin-Ged, pain in the heart (renocardial syndrome), abdomen (renovisceral syndrome) ) or exacerbation of lumbosacral radiculitis. In an advanced stage of renal failure, the combined toxic effects of azotemia and the entire complex of metabolites of average molecular weight, metabolic acidosis, protein and water-electrolyte imbalance, especially hyperkalemia and hypercreatininemia, as well as arterial hypertension, become of primary importance.

Neurosthenia-like syndrome in the initial period of kidney disease is manifested by symptoms of hypersthenia (irritability, irascibility, mood instability, sleep disorders), later (stage of subcompensation and decompensation) symptoms of hyposthenia (increased fatigue, absent-mindedness, touchiness, tearfulness) begin to predominate. All disorders usually develop against the background of lower back pain, edema, dysuric disorders, etc.

Algic syndrome is characterized by pain that is localized in the lower back at the level of the Tmx-Li segments on one (renal colic) or both (nephritis) sides, is constant or paroxysmal in nature, does not always subside in the supine position and can spread to the inner surface of the thigh and groin fold

When studying sensitivity, hyperesthesia or hyperpathy is most often determined in the area of the affected segments. The severity of symptoms of tension in the nerve trunks is insignificant. Symptoms of prolapse in the motor and reflex spheres are usually absent.

It should be taken into account that kidney pathology can cause exacerbation of lumboischialgic syndrome in patients suffering from spondylosis deformans and osteochondrosis of the spine, which accordingly changes the clinical picture of the disease.

With polyneuropathic syndrome, moderate sensory, autonomic and reflex disorders are observed: pain, burning, numbness, acrocyanosis, hypoesthesia or hyperesthesia in the distal arms and legs (mainly in the feet), sometimes decreased Achilles reflexes. Severe forms with paralysis and paresis of the limbs are now rarely observed due to improved treatment of renal failure.

Renocardial syndrome is characterized by prolonged aching pain in the left half of the chest, which is combined with lower back pain and is poorly relieved by nitroglycerin. Electrocardiographic examination does not reveal significant deviations from the norm. The pain regresses as renal failure resolves. At the same time, in patients suffering from coronary heart disease, paroxysm of renal pain can provoke attacks of angina pectoris.

Renoabdominal syndrome develops at the height of an attack of urolithiasis and is manifested by epigastric pain, nausea, belching, heartburn (not associated with food intake), hiccups, loss of appetite and other dyspeptic disorders. Can imitate diseases such as cholecystitis, appendicitis, pancreatitis, gastritis, peptic ulcer.

Acute encephalopathic disorders usually occur against the background of a sharp increase in renal failure. Patients develop general cerebral (headache, dizziness, apathy or, conversely, agitation), as well as meningeal and minor focal symptoms (anisocoria, horizontal nystagmus, muscle hypotonia, increased reflexes, etc.). The most severe disorders are observed in the oligoanuric stage of the disease, when severe psychomotor agitation can be replaced by somnolence, and later by a soporous or comatose state. In the fundus, dilated veins or even congestive nipples are observed. In the cerebrospinal fluid there is an increase in pressure (up to 250-300 mmH2O) with normal composition or slight pleocytosis and hyperalbuminosis.

With a significant increase in hypo- or hyperkalemia, dyskalemic paralysis often develops - weakness of the muscles of the arms, legs and torso, which can reach the degree of complete immobility, as well as respiratory and cardiac disorders (shortness of breath, bradycardia, arterial hypotension, etc.). Tendon reflexes and muscle tone are reduced. Hypokalemic paralysis is more pronounced in the proximal parts of the arms and legs, rarely affecting the muscles of the face, hyperkalemic paralysis usually spreads to the muscles of the face, pharynx and larynx.

Clinical manifestations of acute encephalopathy and dyskalemic paralysis usually gradually disappear as renal failure is compensated. But in cases of long-term and severe renal disease, neuropsychic disorders (headache, general weakness, decreased memory and attention, increased oral automatism reflexes, revitalized tendon reflexes, pathological reflexes, etc.) become persistent, i.e. develop chronic dysmetabolic encephalopathy. Sometimes it can occur as a pseudotumor syndrome (headache, nausea, epileptic seizures, aspontaneity, workload).

Cerebrovascular accidents (crises, transient disorders, strokes) are most often observed in chronic nephritis complicated by arterial hypertension.

Uremic coma is characterized by itching, scratching on the skin, ammonia-like breath, hiccups, vomiting, myoclonus, and often convulsive paroxysms. In the shallow stage of coma, all tendon reflexes are animated, and the corneal and pharyngeal reflexes are usually already reduced. Bilateral pathological pyramidal reflexes are evoked.

It should be taken into account that the course of chronic renal failure (CRF) has changed somewhat over the past two decades due to the development of effective treatment methods. This largely applies to the terminal stage of chronic renal failure - uremia. Hemodialysis and kidney transplantation can prolong the life of patients for many years.

Neurological disorders in chronic renal failure should be considered as part of the body's overall response to impaired renal function. The influence of a complex of intoxication factors, including anemia, can manifest itself at different times depending on the sensitivity of certain parts of the nervous system. This underlies a certain stage in the development of neurological disorders in end-stage chronic renal failure. The clinical dynamics are as follows. Initially, brainstem symptoms appear, then tendon reflexes and leg muscle strength gradually decrease; in the hands, tendon reflexes remain elevated for some time, sometimes with the presence of pathological signs; then weakness and depression of tendon reflexes in the arms are added against the background of even greater damage to the lower extremities - the appearance of deep lower atrophic paresis and paralysis with the absence of tendon reflexes and distal-type sensory disorders. This process occurs against the background of progressive encephalopathy, as evidenced by increasing changes in the emotional and mental sphere, asterixis, multiple myoclonus.

It is known that phylogenetically younger parts of the nervous system are more sensitive to both hypoxia and intoxication. Therefore, with a mild degree of intoxication, the cortical level is primarily affected, and the functional state of the limbic-reticular complex also changes. In this case, symptoms of encephalopathy are revealed. As intoxication increases, the initial excitement is replaced by severe weakness, increased fatigue, lethargy, apathy, forgetfulness, and drowsiness. With a further increase in intoxication, spinal symptoms are increasingly revealed - a decrease in muscle strength, muscle tone and tendon reflexes and sensory disorders in the legs. These symptoms may depend both on a violation of the descending influences of the reticular formation, and on the direct effect of intoxication on the spinal cord and peripheral nerves, which leads to a decrease in pyramidal symptoms and an increase in atrophic paresis.

The widespread introduction of chronic dialysis has led to the identification of a new form of neurological pathology - dialysis encephalopathy, the leading manifestation of which is dementia. To date, the pathogenesis of brain damage in such cases remains unclear; Excess aluminum in the water used for dialysis has been cited as a possible cause. The presence of a permanent shunt sometimes leads to the development of median nerve tunnel neuropathy in the carpal tunnel.

The pattern of regression of symptoms of focal damage to the nervous system after successful kidney transplantation is the opposite of the dynamics of their increase: initially the symptoms of damage to the peripheral nerves and spinal cord disappear, then the symptoms of renal encephalopathy regress. The duration of the restoration process is up to 2-3 years. The symptoms remaining after this period are hardly reversible and must be classified as persistent residual disorders. It should be remembered that cytomegalovirus infection sometimes occurs in patients with a kidney transplant.

Treatment. Therapy should be carried out taking into account the form and stage of the renal disease, clinical manifestations and pathogenesis. Usually it is aimed primarily at compensating for renal failure. Uremia with hypercreatininemia and hyperkalemia and an increase in cerebral, meningeal and general focal symptoms requires the mandatory use of hemodialysis (peritoneal dialysis) or hemosorption (which are often preparations for a kidney transplant). In case of urolithiasis, pyelonephritis, hydronephrosis, kidney injuries, according to indications (ineffectiveness of conservative therapy, etc.), surgical intervention is used, after which complete or partial regression of neuropsychic disorders is noted. Treatment of emotional and mental disorders in the structure of encephalopathic syndrome is carried out using tranquilizers, antidepressants, nootropics, restorative drugs, etc. The prescription of any medications should be carried out only after consultation with a nephrologist, taking into account the presence of severe renal failure in some patients.

The prognosis is determined by the form and severity of the underlying disease and partly by the characteristics of the complication. Persistent compensation of neurological symptoms can only be achieved by eliminating renal failure. Neurosthenic-like, polyneuropathic, renocardial, renovisceral, encephalopathic disorders can completely regress if they are caused by acute and relatively mild kidney diseases or long-term diseases in the stage of subcompensation or compensation. An increasing or recurrent course of these syndromes is observed in patients with chronic glomerulonephritis or pyelonephritis in the stage of decompensation.

Connective tissue lesions. Lupus erythematosus, polymyositis, dermatomyositis, periarteritis nodosa, scleroderma, temporal arteritis, thromboangiitis obliterans are often accompanied by neuropsychiatric disorders - encephalopathic, polyneuropathic, myasthenic, myopathic syndromes and some others.

The pathogenesis of these disorders is due to autoimmune degenerative-inflammatory changes in the membranes of the brain and spinal cord and blood vessels.

Rheumatism can be complicated by cerebral disorders with predominant damage to the subcortical nodes - minor chorea. Essentially, rheumatic brain damage is limited to chorea minor. The previously existing concept of “cerebral rheumovasculitis” as an everyday cause of damage to the nervous system turned out to be untenable. Damage to cerebral vessels in rheumatism is a rarity.

Among the causes of cerebral strokes, both primary vasculitis and vasculitis in connective tissue diseases occupy a prominent place. Particular attention is drawn to Snedonna's syndrome, associated with antiphospholipid factor - perhaps the most common cause of ischemic strokes in young patients.

Temporal arteritis (Horton's disease) is characterized by sharp local pain in the temporal region, which may be accompanied by trismus. The pathomorphological basis of the disease is giant cell arteritis of the temporal artery. Palpation reveals a thickened and painful temporal artery. Sometimes it is visible upon examination. Often the optic nerve is involved in the process on the affected side (decreased visual acuity; in the fundus there is a picture of ischemic neuritis). A sharp increase in ESR is characteristic.

Neurolupus- neurological manifestations of systemic lupus erythematosus. Most often, against the background of general malaise, fever, headache, dizziness, damage to the peripheral nervous system is observed (neuropathy, polyneuropathy, etc.), but sometimes other levels of the nervous system are also involved with the development of the syndrome of encephalopathy, myelopathy, encephalomyelopathy.

Periarteritis nodosa is pathomorphologically characterized by damage to small arteries with the gradual development of dense nodules. Since the process can involve vessels of almost all organs and tissues, including the nervous system, the clinical manifestations of the disease are extremely diverse. It occurs at any age, but is somewhat more common in men 30-50 years old. At the onset of the disease, fever, diffuse pain and polymorphic skin rashes are usually observed. Along the vessels, dense, painful nodules are felt. Already at an early stage of the disease, internal organs are involved - the spleen, liver, kidneys, gastrointestinal tract, which is manifested by abdominal pain, hematuria, intestinal bleeding and other symptoms. Over time, patients acquire a characteristic appearance - an earthy-pale color of the skin against the background of general exhaustion. In almost all cases, a variety of neurological disorders are observed - neuropathies, polyneuropathy, encephalopathy, myelopathy, acute vascular disorders (subarachnoid, subdural, parenchymal hemorrhages). Most often, the peripheral nervous system is affected in the form of multiple mononeuropathies.

Diagnosis is based on the clinical picture (a combination of fever, skin disorders, kidney and peripheral nerve damage) and data from additional studies (hypergammaglobulinemia, leukocytosis with a left shift, high ESR).

With polymyositis, edema, lymphoid cell accumulations, destruction of fibers, etc. are detected in muscle tissue.

The clinical picture is characterized by the appearance of diffuse or limited muscle pain, mainly in the proximal limbs, low-grade fever, and general fatigue. The muscles are slightly swollen and painful on palpation. Changes gradually develop in the internal organs (heart, lungs, gastrointestinal tract), skin (depigmentation, swelling), nervous system (peripheral nerves, membranes, spinal cord, brain stem, etc. are involved) and muscles. Therefore, the disease can occur with the syndromes of polyneuropathy, radiculoneuropathy, myelopathy, encephalopathy, myopathy, and myasthenia. In the blood - leukocytosis, hyperglobulinemia, increased ESR, as well as the activity of aminotransferases and aldolase.

Differential diagnosis is most often carried out with other forms of polyneuropathies and myopathy. In unclear cases, muscle biopsy data can help establish the diagnosis.

Treatment. All forms of collagenosis are treated with long-term repeated courses of anti-inflammatory (indomethacin, voltaren, brufen, reopirin, delagil), antihistamines (suprastin, pipolfen, diazolin) and hormonal (prednisolone, urbazone, dexamethasone) drugs in various combinations. The inclusion of corticosteroids is mandatory in severe cases of the disease.

EPILEPSY.

According to WHO experts, epilepsy is a chronic brain disease of various etiologies, which is characterized by repeated epileptic seizures resulting from excessive neural discharges and is accompanied by a variety of clinical and paraclinical symptoms.

It is necessary to strictly distinguish between an epileptic seizure and epilepsy as a disease. Single, or, according to the terminological dictionary of epilepsy, random epileptic seizures or epileptic reaction, according to the terminology of domestic researchers, having arisen in a certain situation, do not recur in the future. An example is some cases of febrile seizures in children. Recurrent epileptic seizures in acute cerebral diseases, for example, cerebrovascular accidents, meningitis, encephalitis, should not be classified as epilepsy. According to the proposal of S.N. Davidenkov, in such cases it is advisable to use the term “epileptic syndrome”.

Etiology. For the development of epilepsy, there must be a persistent focus of epileptic activity caused by organic damage to the brain. At the same time, epileptization of neurons, i.e., a special state of neurons that determines the “convulsive readiness” of the brain in the foci of its organic damage and the degree of epileptic influence of these foci on brain structures, depends on the premorbid characteristics of the organism and, in particular, on the epileptic genetic predisposition or acquired nature, which determines a greater likelihood of an epileptic seizure in a patient with brain damage.

The significance of the genetic factor is most clearly seen in typical absence seizures (short-term loss of consciousness followed by amnesia), inherited in an autosomal dominant manner with incomplete gene penetrance, in primary generalized epilepsy beginning in childhood; The role of the genetic factor in partial seizures is less pronounced, however, as noted, even in this case, among the close relatives of patients, seizures are more common than the population average.

Exogenous factors influencing the development of the disease include perinatal and postnatal neuroinfections, neurotoxicosis and traumatic brain injury, which are of greatest importance. This does not exclude the role of other factors - intrauterine, vascular, toxic. As for perinatal pathology (from the 27th week of fetal life to the 7th day of newborn life), the greatest role here is played by traumatic factors (discrepancy between the sizes of the fetal head and pelvis, the use of obstetric aids, etc.) and anoxic (fetal asphyxia during prolonged labor, entanglement of the fetal neck with the umbilical cord, etc.).

Pathogenesis. In the pathogenesis of epilepsy, both changes in the functional state of some neurons in the area of the epileptogenic lesion (epileptogenic focus), the totality of which constitutes the epileptic focus, and the peculiarities of the interaction of the population of epileptic neurons are important. The electrical activity of epileptic neurons is characterized by the occurrence of paroxysmal

And its individual manifestations. It is considered at various levels - from molecular disorders to the organism as a whole. By studying pathogenesis, doctors identify how the disease develops.

The evolution of the doctrine of pathogenesis is an extremely important part of the development of medicine as a whole. It was the presence of a description of pathogenetic processes at various levels that made it possible to penetrate deeper into the causes of the development of diseases and select more and more effective therapy for them. Issues of pathogenesis are studied by pathological physiology, pathological anatomy, histology and biochemistry; any medical specialty cannot do without consideration of issues of pathogenesis. And although the number of typical pathogenetic processes is limited, their combinations and the ratio of the severity of their course form unique clinical pictures for many known diseases.

Knowing the typical pathogenetic reactions, their course and interaction with each other, it becomes possible to prescribe adequate therapy, even in cases where the diagnosis of the disease has not yet been established, but the pathological changes occurring in the body are clearly defined. Thus, it became possible to stabilize the patient’s condition until the diagnosis was established and etiotropic therapy began.

General information

The main link

This is the process necessary for the development of the rest and determines the specificity of the disease. Pathogenetic treatment is based on its timely elimination, since in this case the disease will not develop.

Periods

Etiopathogenesis

Due to the relationship between etiology and pathogenesis, the term “etiopathogenesis” (aetiopathogenesis, from the Greek. αἰτία - cause), defining a set of ideas about the causes and mechanisms of disease development, but since it contributed to the confusion of the concepts of cause and effect in pathology, it was not widely used. However, there are 3 generally accepted options for the relationship between etiology and pathogenesis:

The etiological factor initiates pathogenesis, while disappearing itself (burn);
The etiological factor and pathogenesis coexist (most infections);
The etiological factor persists, periodically initiating pathogenesis (malaria).

In addition, the dependence of pathogenesis on etiology can be demonstrated by the example of cause-and-effect relationships:

“Straight line”: consumption of large amounts of fat → atherosclerosis → coronary circulatory failure → myocardial infarction → cardiogenic shock → death.
Branched types (divergence and convergence).

Specific and nonspecific mechanisms

Local and general phenomena

Literature

Zaichik A. Sh., Churilov L. P. Mechanisms of development of diseases and syndromes // Pathophysiology. - St. Petersburg: ELBI-SPb, 2002. - T. I. - pp. 63-79. - 240 s. - 90,000 copies.;
Ataman A.V. Mechanisms of development of diseases and syndromes // Pathological physiology in questions and answers. - 2nd, expanded and revised. - Vinnitsa: Nova Book (Ukrainian) Russian , 2008. - pp. 27-31. - 544 p. - 2000 copies. - ISBN 978-966-382-121-4;
Vorobyov A. I., Moroz B. B., Smirnov A. N. Pathogenesis// Great Soviet Encyclopedia .

Notes

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Synonyms:

See what “Pathogenesis” is in other dictionaries:

Pathogenesis… Spelling dictionary-reference book

PATHOGENESIS- PATHOGENESIS. Contents: General characteristics of pathogenetic mechanisms and their occurrence......... 96 The significance of pathogenesis data for therapy and prevention................... 98 The problem of “local and general" and pathogenesis.... 99... ... Great Medical Encyclopedia

Origin, causes of diseases. Dictionary of foreign words included in the Russian language. Chudinov A.N., 1910. pathogenesis (gr. pathos suffering + ... genesis) a section of pathology that studies all biological (physiological, biochemical, etc.)… … Dictionary of foreign words of the Russian language

AND PATHOGENESIS, pathogenesis, many. no, husband (from Greek pathos disease and genesis birth) (med.). Sequence in the development of some pathological (painful) process. Pathogenesis of typhoid fever. Ushakov's explanatory dictionary. D.N. Ushakov... ... Ushakov's Explanatory Dictionary Technical Translator's Guide

pathogenesis- pathological genesis

The term " pathogenesis" comes from two words: Greek pathos - suffering (according to Aristotle, pathos - damage) and genesis - origin, development. Pathogenesis is the doctrine of the mechanisms of development, course and outcome of diseases, pathological processes and pathological conditions.

Pathogenesis – This is a set of mechanisms that are activated in the body when harmful (pathogenic) factors act on it and are manifested in the dynamic stereotypical deployment of a number of functional, biochemical and morphological reactions of the body that determine the occurrence, development and outcome of the disease.

classification of pathogenesis:

A) private pathogenesis, which studies the mechanisms of individual pathological reactions, processes, conditions and diseases (nosological units). Clinicians study particular pathogenesis, revealing the mechanism of specific diseases in specific patients (for example, the pathogenesis of diabetes mellitus, pneumonia, gastric ulcer, etc.). Particular pathogenesis refers to specific nosological forms.

b) general pathogenesis involves the study of mechanisms, the most general patterns underlying typical pathological processes or certain categories of diseases (hereditary, oncological, infectious, endocrine, etc.). General pathogenesis deals with the study of mechanisms leading to functional failure of any organ or system. For example, general pathogenesis studies the mechanisms of development of heart failure in patients with pathologies of the cardiovascular system: heart defects, myocardial infarction, coronary heart disease, lung diseases with pulmonary hypertension.

The study of pathogenesis comes down to the study of the so-called pathogenetic factors, those. those changes in the body that occur in response to the influence of an etiological factor and subsequently play the role of cause in the development of the disease. The pathogenetic factor causes the appearance of new life disorders in the development of the pathological process, disease.

The trigger mechanism (link) of any pathological process or disease is damage, arising under the influence of a harmful factor.

Damage may be:primary; they are caused by the direct action of a pathogenic factor on the body - these are damages at the molecular level, secondary; they are a consequence of the influence of primary damage on tissues and organs, accompanied by the release of biologically active substances (BAS), proteolysis, acidosis, hypoxia, impaired microcirculation, microthrombosis, etc.

The nature of the damage depends on the nature of the stimulus (pathogenic factor), the species and individual properties of the living organism. The levels of damage can be different: molecular, cellular, tissue, organ and organismal. The same irritant can cause damage at many different levels.

Simultaneously with the damage, protective and compensatory processes are activated at the same levels - molecular, cellular, tissue, organ and organismal.

The primary link in this long chain is damage that occurs under the influence of a pathogenic factor, and which becomes the cause of secondary damage, causing tertiary damage, etc. (Impact of a mechanical factor - injury - blood loss - centralization of blood circulation - hypoxia - acidosis - toxemia, septicemia - etc.).

In this complex chain of cause-and-effect relationships, we always distinguish basic(synonyms: main, leading) link Under main (main) link in pathogenesis understand a phenomenon that determines the development of a process with its characteristic specific features. For example, the basis of arterial hyperemia is the dilation of arterioles (this is the main link), which causes acceleration of blood flow, redness, an increase in the temperature of the hyperemic area, an increase in its volume and an increase in metabolism. The main link in the pathogenesis of acute blood loss is a deficit in circulating blood volume (CBV), which causes a decrease in blood pressure, centralization of blood circulation, shunting of blood flow, acidosis, hypoxia, etc. When the main link is eliminated, recovery occurs.

Untimely elimination of the main link leads to disruption of homeostasis and the formation vicious circles pathogenesis. They arise when the emerging deviation in the level of functioning of an organ or system begins to support and strengthen itself as a result of the formation positive feedback.

Regarding such a section of pathogenesis as flow diseases, the question of acute And chronic processes. Traditionally, one of the criteria for acute or chronic course is temporary. If a pathogenic agent (or information about it recorded by the immune or nervous system) persists in the body, the disease takes on a protracted course, which is clinically called subacute, and after a certain period - chronic.

Remission- this is a temporary improvement in the patient’s condition, manifested in slowing down or stopping the progression of the disease, partial reverse development or disappearance of clinical manifestations of the pathological process.

Relapse- this is a new manifestation of the disease after its apparent or incomplete cessation.

Complication- this is a pathological process secondary to an existing disease, arising in connection with the characteristics of the pathogenesis of the primary (main) disease or as an unforeseen consequence of diagnostic and therapeutic measures.

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Hypoxia – oxygen deficiency – a condition that occurs when there is insufficient supply of oxygen to the body’s tissues or a violation of its use in the process of biological oxidation. The body's compensatory reaction is to increase the level of hemoglobin in the blood. The trigger for the development of hypoxia is associated with hypoxemia - a decrease in the oxygen content in arterial blood.
A healthy body may find itself in a state of hypoxia if the need for oxygen (oxygen demand) is higher than the ability to satisfy it. The most common causes of this condition are:

2. temporary cessation or weakening of pulmonary ventilation when diving to different depths;

3. increasing oxygen demand when performing muscular work.

Short term adaptation mechanisms can only be effective at relatively low altitudes and for short periods of time. The increased load on the heart and respiratory muscles requires additional energy consumption, that is, it increases oxygen demand. Due to intense breathing (hyperventilation), CO2 is intensively removed from the body. A drop in its concentration in arterial blood leads to a weakening of breathing, since CO2 is the main stimulator of the respiratory reflex. Acidic products of anaerobic glycolysis accumulate in tissues.
D long-term adaptation is a shift in the main field of activity from transport mechanisms to oxygen utilization mechanisms, to increasing the efficiency of using the resources available to the body. This is achieved primarily by stimulating biosynthetic processes in transport, regulation and energy supply systems, which increases their structural potential and reserve power. In transport systems, this is the growth of the vascular network (angiogenesis) in the lungs, heart, brain, growth of lung tissue, and an increase in the number of red blood cells in the blood. In regulatory systems, this is, on the one hand, an increase in the activity of enzymes responsible for the synthesis of mediators and hormones, and on the other, an increase in the number of receptors for them in tissues. Finally, in energy supply systems - an increase in the number of mitochondria and oxidation and phosphorylation enzymes, the synthesis of glycolytic enzymes.

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Arterial hypertension is a persistent increase in blood pressure in the arteries of the systemic circulation, when the upper pressure is equal to or exceeds 140 mm Hg. Art., lower pressure equals or exceeds 90 mm Hg. Art.

Arterial hypertension can be divided into two stages:

systolic pressure – 140-159 mm Hg. Art., or diastolic pressure – 90-99 mm Hg. Art.
systolic pressure – from 160 mm Hg. Art., or diastolic pressure - from 100 mm Hg. Art.

In almost 95% of patients, the causes of increased blood pressure remain unclear, and such a disorder is classified as primary or essential arterial hypertension (EAH).

In hypertension, the causes of which are clearly established, they speak of secondary(or symptomatic) arterial hypertension (AH). VAH is much less common than EAH, but identifying the causes of VAH often allows patients to be completely cured of high blood pressure.

Criteria for the diagnosis of hypertension established when DBP and/or SBP is equal to or greater than 90 and 140 mm Hg. Art., respectively.

The term “pathogenesis” comes from two words: Greek. pathos - suffering and genesis - origin, development. Pathogenesis is the study of the mechanisms of development, course and outcome of diseases, pathological

processes and pathological conditions. By studying pathogenesis, we elucidate the mechanisms of disease development and deal primarily with internal factors.

Pathogenesis is a set of mechanisms that are activated in the body when harmful (pathogenic) factors act on it and are manifested in the dynamic stereotypical deployment of a number of functional, biochemical and morphological reactions of the body that determine the occurrence, development and outcome of the disease. The scope of the concept is revealed through the classification of pathogenesis.

Particular pathogenesis studies the mechanisms of individual pathological reactions, processes, conditions and diseases (nosological units). Clinicians study particular pathogenesis, revealing the mechanism of specific diseases in specific patients (for example, the pathogenesis of diabetes mellitus, pneumonia, gastric ulcer, etc.).

General pathogenesis involves the study of mechanisms, the most general patterns underlying typical pathological processes or certain categories of diseases (hereditary, oncological, infectious, endocrine, etc.). General pathogenesis deals with the study of mechanisms leading to functional failure of any organ or system. For example, general pathogenesis studies the mechanisms of the development of heart failure in patients with pathologies of the cardiovascular system: heart defects, myocardial infarction, coronary heart disease, lung diseases with pulmonary hypertension.

The study of pathogenesis comes down to the study of so-called pathogenetic factors, i.e. those changes in the body that occur in response to the influence of an etiological factor and subsequently play the role of cause in the development of the disease. The pathogenetic factor causes the appearance of new life disorders in the development of the pathological process, disease.

1.Damage as the initial link in pathogenesis. Levels of damage and their manifestation

The trigger mechanism (link) of any pathological process or disease is damage that occurs under the influence of a harmful factor.

Damage may be:

Primary; they are caused by the direct action of a pathogenic factor on the body - these are damages at the molecular level,

Secondary; they are a consequence of the influence of primary damage on tissues and organs, accompanied by the release of biologically active substances, proteolysis, acidosis, hypoxia, impaired microcirculation, microthrombosis, etc. The nature of the damage depends on the nature of the stimulus (pathogenic factor), the species and individual properties of the living organism. The levels of damage can be different: molecular, cellular, tissue, organ and organismal. The same irritant can cause damage at many different levels.

Simultaneously with the damage, protective and compensatory processes are activated at the same levels - molecular, cellular, tissue, organ and organismal. Damage at the molecular level is local in nature and is manifested by the rupture of molecules, intramolecular rearrangements, which leads to the appearance of individual ions, radicals, and the formation of new molecules and new substances that have a pathogenic effect on the body. Intermolecular rearrangements contribute to the emergence of substances with new antigenic properties. But simultaneously with the damage, protective and compensatory processes at the molecular level are also activated. Damage at the cellular level is characterized by structural and metabolic disorders, accompanied by the synthesis and secretion of biologically active substances: histamine, serotonin, heparin, bradykinin, etc. Many of them have a pathogenic effect, increasing permeability of microvasculature vessels, increasing extravasation and, as a consequence,

Thickening of the blood, an increase in its viscosity, a tendency to sludge and microthrombosis, i.e. disruption of microcirculation. Damage at the cellular level is accompanied by a violation of enzymatic activity: inhibition of Krebs cycle enzymes and activation of glycolytic and lysosomal enzymes are noted, which causes disruption of metabolic processes in the cell.
Damage at the tissue level is characterized by a violation of its basic functional properties (decreased functional mobility, decreased functional lability), the development of pathological parabiosis, tissue degeneration. Protective-compensatory processes at the tissue level are manifested by the inclusion of previously non-functioning alveoli and capillaries, the formation of new microvessels, which improves trophism damaged tissues. Damage at the organ level is characterized by a decrease, distortion or loss of specific functions of the organ, a decrease in the share of participation of the damaged organ in the general reactions of the body. For example, with myocardial infarction and valvular heart defects, the function of the heart and its share in adequate hemodynamic support of functioning organs and systems are disrupted. Compensatory reactions and processes are formed at the level of an organ, system and even the body as a whole, which leads, for example, to hypertrophy of the corresponding part of the heart, a change in its regulation, which affects hemodynamics - as a result, compensation for impaired functions occurs. The pathogenic effect of damaging factors is realized at the functional element level. Functional element according to A.M. Chernukha is a combination of cell parenchyma, microcirculatory unit, nerve fibers and connective tissue. Each functional element of tissue consists of: - parenchyma cells,
-arterioles, precapillaries, capillaries, postcapillaries, venules, lymphatic capillaries, arteriole-venular anastomoses;
- nerve fibers with receptors;
- connective tissue.
16. Cause-and-effect relationships in pathogenesis. The leading link in pathogenesis, “vicious circles”. Categories of local and general, structural and functional, specific and nonspecific reactions in pathogenesis.

Each pathological process or disease is considered as a long chain of cause-and-effect relationships, which spreads like a chain reaction. The primary link in this long chain is damage that occurs under the influence of a pathogenic factor, which causes secondary damage, causing tertiary damage, etc. (impact of a mechanical factor - injury - blood loss - centralization of blood circulation > hypoxia > acidosis > toxemia, septicemia, etc.).

In this complex chain of cause-and-effect relationships, the main link is always identified (synonyms: main, leading). The main (main) link of pathogenesis is understood as a phenomenon that determines the development of a process with its characteristic specific features. For example, the basis of arterial hyperemia is the dilation of arterioles (this is the main link), which causes acceleration of blood flow, redness, an increase in the temperature of the hyperemic area, an increase in its volume and an increase in metabolism. The main link in the pathogenesis of acute blood loss is a deficit in circulating blood volume (CBV), which causes a decrease in blood pressure, centralization of blood circulation, shunting of blood flow, acidosis, hypoxia, etc. When the main link is eliminated, recovery occurs. Untimely elimination of the main link leads to disruption of homeostasis and the formation of vicious circles of pathogenesis. They arise when the emerging deviation in the level of functioning of an organ or system begins to maintain and strengthen itself as a result of the formation of positive feedback. For example, blood loss is accompanied by pathological deposition of blood ® with the release of its liquid part from the vascular bed ® with a further increase in BCC deficiency ® with deepening arterial hypotension, which through baroreceptors activates the sympathoadrenal system, which enhances vasoconstriction and centralization of blood circulation - ultimately, pathological deposition of blood increases and further decrease in BCC; As a result, the pathological process progresses. The formation of vicious circles aggravates the course of the disease. Timely diagnosis of the initial stages of the formation of vicious circles and prevention of their formation and elimination of the main link is the key to successful treatment of the patient. In a complex chain of cause-and-effect relationships, local and general changes are distinguished. The question of the relationship between local and general phenomena in the pathogenesis of the disease and pathological process remains quite complex. There are no absolutely local processes in a whole organism. The entire body is involved in the pathological process, the disease. As you know, with any pathology: pulpitis, stomatitis, local burn, boil, pituitary adenoma, the entire body suffers. With the development of any disease, as a rule, nonspecific and specific mechanisms are detected. Nonspecific mechanisms are determined by the inclusion in the pathogenesis of typical pathological processes, which are characterized by a natural, stereotypical and genetically determined development of various processes over time: inflammation, fever, changes in microcirculation, thrombosis, etc. , as well as increasing the permeability of biological membranes, generating reactive oxygen species, etc. Then the system of cellular and humoral immunity is activated, providing specific protection and fight against a foreign object that has entered the body. However, there is no clear distinction between specific and nonspecific mechanisms. The pathogenic effect of etiological factors is realized through three mechanisms of pathogenesis: direct, humoral and neurogenic. Direct damaging effects are exerted by physical and mechanical factors that have a large supply of kinetic energy, thermal (burns), chemical (burns).

Humoral mechanisms of pathogenesis are mediated by body fluids: blood, lymph, intercellular fluid. This mechanism plays a special role in the generalization of pathology (metastasis, sepsis, etc.).

The neurogenic mechanism of pathogenesis is mediated through the nervous system due to disruption of regulatory processes.
17. Body reactivity: definition of the concept. Types of reactivity. The most important factors determining reactivity.

Ideas about the reactivity and resistance of the body began to take shape back in the days of ancient medicine, reaching its greatest development in ancient Greek medicine. Even then, doctors saw that people have different resistance to diseases and tolerate them differently.

1. Reactivity (re + lat. as1zush - effective, active) - the property of a living organism to react in a certain way to the influence of any environmental factors (ESMT).

2. Reactivity is the ability of the body to respond by changing its life activity to the influence of the environment (A.D. Ado).

Reactivity is inherent in all living organisms, along with such manifestations as development, growth, reproduction, heredity, metabolism. The formation of reactivity is carried out on the basis of such properties inherent in living organisms as: irritability, sensitivity, resistance.

Taking into account the biological properties of the organism, they distinguish between species (or biological), group and individual reactivity. The main one is species reactivity - a set of reactivity features characteristic of a given species of living beings. For example, animals are indifferent to pathogens that cause whooping cough and scarlet fever, and humans are indifferent to pathogens that cause swine fever. Diseases such as atherosclerosis and myocardial infarction in humans differ significantly from similar pathologies in rabbits, etc. Sometimes this reactivity is called primary. It is aimed at preserving the species and the individual.

Group reactivity is formed on the basis of species and is divided into age, gender and constitutional. Age-related reactivity determines the specificity of reactions to stimuli characteristic of a given age. In particular, newborns, compared to adults, have a greater ability to maintain bioenergetics through anaerobic glycolysis; adults do not get whooping cough. In old age, there are features of the response to infectious agents, which may be associated with a decrease in the function of barrier formations, a reduced ability to produce antibodies and a decrease in phagocytic activity.

Sexual reactivity is determined by the reactive characteristics inherent in a given gender: for example, women are more resistant to blood loss and pain, and men are more resistant to physical activity.

Constitutional reactivity is determined by heredity and the long-term influence of environmental factors that form stable morpho-functional characteristics of the body. In particular, normosthenics and hypersthenics are more resistant to prolonged and increased physical and psycho-emotional stress compared to asthenics. Hippocrates, based on the constitutionally determined reactions of the nervous system, identified the main types of temperaments: sanguine, choleric, melancholic and phlegmatic, believing that each type is predisposed to certain diseases.

Individual reactivity is determined by inherited information, individual variability and constitutional characteristics of each organism, which determine the nature of its course of both physiological reactions and pathological processes. A typical example of the manifestation of individual reactivity is allergic reactions in individuals.

Taking into account the degree of specificity of the body's responses, specific and nonspecific reactivity are distinguished. Specific reactivity is manifested by the development of immunity to antigenic exposure. Specific reactions form in the patient a characteristic clinical picture of each nosological form (for example, damage to the hematopoietic organs in radiation sickness; spasm of arterioles in hypertension). Nonspecific reactivity is manifested by general reactions characteristic of many diseases (development of fever, hypoxia, activation of phagocytosis and the complement system, etc.).

Reactivity can manifest itself in an unchanged form (this is primary, or hereditarily determined reactivity) and in a modified form under the influence of external and internal conditions (this is secondary or acquired reactivity).

Depending on the biological significance of the body's response to the action of a particular agent, physiological and pathological reactivity are distinguished.

Physiological reactivity is reactivity in relation to physiological stimuli in adequate conditions of existence of the organism. It is protective and adaptive in nature and is aimed at maintaining the dynamic constancy of the internal environment of the body and at the full interaction of the body with the environment.

Pathological (painfully altered) reactivity is reactivity that occurs as a result of the action of a pathogenic irritant on the body and is characterized by reduced adaptability of the body to the environment (for example, allergic reactions). Shock of any origin sharply affects the body's reactivity, inhibiting it, as a result of which the body's resistance to infection weakens, and after shock, conditions are created for the development of wound infection, as phagocytosis weakens and the bactericidal activity of leukocytes decreases. Anesthesia inhibits the phagocytic activity of leukocytes and inhibits the production of antibodies.

Species, sex and age types of reactivity are physiological. They determine the body’s normal reaction to stimuli. These types of reactivity cannot in principle be pathological, otherwise, in the process of evolution, the species, sex, age, possessing pathological reactivity would inevitably disappear from the face of the Earth. At the same time, individual reactivity, depending on hereditary and constitutional properties, age, gender and environmental influences, can be both physiological and pathological.
The reactivity of the body depends on the influence of external factors and the functional state of the body itself. Any impact of environmental factors affects the reactivity of the body.

Ambient temperature also has a significant impact on the body's reactivity.

The time of year and weather conditions affect the body's reactivity. In particular, people with rheumatism are very sensitive to changes in barometric pressure, high humidity and low temperature. Under these conditions, they are more likely to experience exacerbations or relapses of the disease.

Psychogenic factors and stress change the body's reactivity, predisposing to cardiovascular diseases or contribute to the manifestation of diseases with a hereditary predisposition (diabetes mellitus, hypertension, etc.).

Internal factors also influence the body's reactivity. Among these factors, the nervous system occupies a special place. Practical medicine has long attached great importance to a person’s mood in his resistance to various diseases. Avicenna believed that in order to be healthy, you need to be vigorous. N.I. Pirogov argued that negative emotional disturbances facilitate the onset of the disease, and a good state of mind contributes to the healing of wounds. S.P. Botkin believed that fever could occur under the influence of psychogenic causes.

All parts of the nervous system are involved in the formation of reactivity: receptors, spinal and medulla oblongata, subcortical formations and cerebral cortex.

I.P. attached exceptional importance to the role of the central nervous system in the reactivity of the body. Pavlov. While studying the types of higher nervous activity in dogs, he found that reactivity depends on the strength, mobility and balance of the basic nervous processes - excitation and inhibition in the cerebral cortex. According to the strength of the basic nervous processes, he identified two types: strong and weak; according to the balance of the basic nervous processes: balanced and unbalanced; and according to mobility - stagnant and mobile. These types of higher nervous activity according to I.P. Pavlov corresponds to the human temperaments described in his time by Hippocrates. People with extreme types of higher nervous activity are more often susceptible to diseases (for example, neuroses).

Hereditary human diseases: general characteristics, classifications. Comparison of the concepts hereditary diseases, congenital diseases, phenocopies. Typical congenital anomalies of the head and neck.

Hereditary human diseases are studied by medical genetics - this is a branch of human genetics that studies hereditarily determined morphological and functional disorders in human ontogenesis, the patterns of their inheritance, phenotypic implementation and distribution, as well as developing methods for the diagnosis, prevention and treatment of these disorders.

The term “hereditary diseases” is sometimes identified with the term “congenital diseases”. Congenital diseases are understood as such

conditions that already exist at birth. Congenital diseases can be caused by hereditary and non-hereditary factors. These include congenital malformations of a non-hereditary nature, which are phenocopies of hereditary malformations. At the same time, not all hereditary diseases are congenital - many diseases manifest themselves at a much later age.

Phenocopy is a non-hereditary change in any characteristics of an organism under the influence of the environment, copying the phenotypic manifestation of mutations that are absent in the genotype of a given individual. For example:

1. Congenital infections (toxoplasmosis, rubella, syphilis, etc.) can induce phenocopies of pathological mutations in several siblings (siblings

These are children of the same parental pair: brothers and sisters) and thereby raise suspicion of a hereditary disease.

2. Phenocopies caused by external factors of a chemical and physical nature can occur with a certain frequency not only in the proband, but also in his siblings, if the factors continue to operate after the birth of a sick child.

1. Hereditary diseases. The manifestation of the pathogenic effect of mutation as an etiological factor is practically independent of the external environment. It can only change the severity of the symptoms of the disease. Heredity plays a decisive role here. Diseases in this group include all chromosomal and genetic hereditary diseases with full manifestation: Down's disease, hemophilia, phenylketonuria, achondroplasia, etc.

2. Diseases with a hereditary predisposition. For these diseases, heredity is an etiological factor, but for the penetrance of mutated genes, a corresponding state of the body is necessary, due to the harmful influence of the environment (gout, some forms of diabetes - their manifestation depends on excessive nutrition). Such diseases usually appear with age under the influence of external factors: overwork, overeating, cold, etc.

3. In this group of diseases, the etiological factors are environmental influences, however, the frequency of occurrence and severity of the disease significantly depends on the hereditary predisposition. This group includes atherosclerosis, hypertension, tuberculosis, eczema, and peptic ulcer. They arise under the influence of external factors (sometimes not even one, but a combination of many factors - these are multifactorial diseases), but much more often in individuals with a hereditary predisposition. Like diseases of the 2nd group, they belong to diseases with a hereditary predisposition, and there is no sharp boundary between them.

4. Heredity does not play any role in the origin of diseases of this group. Etiological factors are only external (environmental) factors. This includes most injuries, infectious diseases, burns, etc. Genetic factors can only influence the course of pathological processes (recovery, restoration processes, compensation of impaired functions).

Hereditary diseases make up a significant part in the structure of general human pathology. More than 2000 of them are already known, and this list is constantly updated with new forms. They have a significant impact on morbidity and mortality. 40% of child mortality is partially or completely due to hereditary pathology, at least 40% of spontaneous abortions are associated with chromosomal abnormalities.

10.5% of the population suffers from hereditary diseases or diseases with a hereditary predisposition. 5% of newborns have certain hereditary defects. Moreover, in children's hospitals, about 30% of beds are occupied by patients with hereditary diseases.

Hereditary diseases are classified from a clinical and genetic point of view. The clinical classification is based on the systemic and organ principle, since all hereditary diseases are the same in etiology (they are based on a mutation):

1. Metabolic diseases - phenylketonuria, galactosemia, gout, glycogenosis, homocystinuria, porphyria, etc.

2. Connective tissue diseases - Marfan syndrome, chondrodystrophy, achondroplasia, etc.

3. Blood diseases - hemoglobinopathies, membranopathy, enzymopathies, etc.

4.Mental illnesses - schizophrenia, manic-depressive psychosis, etc.

5. Diseases of the gastrointestinal tract - celiac disease, peptic ulcer, hereditary hyperbilirubinemia, etc.

6. Kidney diseases - hereditary nephritis, cystinuria, cystinosis, polycystic kidney disease, tuberous sclerosis, etc.

From a genetic point of view, hereditary diseases are classified as mutations, since they are the etiological factor of diseases. Depending on the level of organization (amount of damage) of hereditary structures, gene, chromosomal and genomic mutations are distinguished, and in this regard, hereditary diseases are divided into 2 large groups:

1. Genetic - diseases caused by gene mutations that are passed on from generation to generation.

2. Chromosomal - diseases caused by chromosomal and genomic mutations.

There is another group of diseases associated with heredity - these are diseases that arise when mother and fetus are incompatible with antigens and develop on the basis of an immunological reaction in mothers. The most typical and well-studied disease of this group is hemolytic disease of the newborn. It occurs when a Rh-positive fetus develops in the body of a Rh-negative mother. According to pathogenesis, congenital diseases are divided into hereditary diseases and hereditarily predisposed ones, which is caused by damage to the hereditary apparatus of the reproductive or somatic cell.
19. Etiology and pathogenesis of hereditary diseases. Examples of molecular and chromosomal hereditary human diseases.

The cause of hereditary diseases is mutations. Mutation is the process of changing hereditary structures. It is more correct to call a mutant organism a “mutant.” Mutations in germ cells lead to the development of a mutant organism. They are characteristic of all cells and are passed on from generation to generation. There are spontaneous and induced mutagenesis. This division is to a certain extent arbitrary.

Spontaneous mutagenesis is the occurrence of a mutation under normal physiological conditions of the body without additional exposure to any factors external to the body. It is determined by a number of chemical substances formed during the metabolic process, natural background radiation, replication errors, etc. The mutation process in humans occurs continuously and intensively, constantly leading to new mutations. According to the literature, the frequency of gene mutations in humans is 1-2 per 100,000 gametes or less. The frequency of chromosomal and genomic mutations is much higher than that of gene mutations. For example, the frequency of nondisjunction of sex chromosomes and the 21st pair of chromosomes in humans is approximately 1% for each pair, and taking into account the occurrence of nondisjunction for other pairs of chromosomes, the total frequency of nondisjunction exceeds 20%. The frequency of spontaneous mutations may depend on the physiological state of the organism, age, genotype and other factors. The dependence of the occurrence of new mutations of achondroplasia and Marfan syndrome on the age of the fathers was noted. The older a man is, the more likely it is that his germ cells carry mutant alleles.
The most important characteristics of chemical mutagenesis:

Dependence of the effect on the concentration of the substance and the time of action,

The likelihood of chromosome damage due to the action of chemicals depends on the stage of the cell cycle (for example, for alkylating mutagens, the stage of DNA synthesis is the most sensitive),

The absence of a threshold for the action of alkylating mutagens on human chromosomes, although the action of two mutagen molecules or two damaging centers in one molecule is necessary for a break to occur,

The basis for the interaction of a chemical mutagen with a chromosome is an enzymatic reaction,

The mechanism of interaction of a certain mutagen is the same for all stages of the cell cycle and includes three stages: penetration into the cell, activation or inactivation of the substance in the cell before contact with the chromosome and interaction of activated molecules with the chromosome,

Independence of the action of chemical mutagens under combined influence (lack of synergism and antagonism),

The reaction of the cell's chromosomal apparatus to mutagen is determined by many factors, the contribution of each of which is relatively small.

Both chemical and radiation mutagenesis are dangerous when large populations are involved.

Major human chromosomal diseases Chromosomal diseases are a large group of clinically different pathological conditions, the etiological factor of which is chromosomal or genomic mutations. The classification of chromosomal diseases is based on the types of mutations (polyploidy, aneuploidy, translocation, deletion, inversion, duplication) and the chromosomes involved. All forms of chromosomal and genomic mutations are found in humans. Full forms of tetraploidy and triploidy were found only in spontaneous abortions, which indicates their lethal effect in the early stages of development. The lethal effect of other forms of chromosomal and genomic mutations depends on the type of chromosome involved and the nature of the disorder. The following groups and types of well-recognized chromosomal syndromes are distinguished:

1. Monosomy syndromes (XO - Shereshevsky-Turner syndrome).

2. Trisomy syndromes: 8+, 9+, 13+ (Patau syndrome), 18+ (Edwards syndrome), 21+ (Down syndrome). In addition, there is trisomy on the X chromosome.

3. Syndromes caused by deletions.

4. Partial trisomy syndromes.

Pathogenesis of chromosomal diseases. The nature and severity of manifestations of chromosomal diseases varies depending on the type of anomaly and the chromosome. Common to all forms of chromosomal diseases is the multiplicity of lesions:

Craniofacial dysmorphia,

Congenital malformations of internal and external organs,
-slow growth and development
-impaired mental function
- dysfunctions of the nervous and endocrine systems.