General pathogenesis

The radiosensitivity of cells depends on the amount of genetic material, the activity of power station systems intensity metabolic enzyme activity and ratio providing repair cells, the stability of biological membranes and their reparation, as well as the presence in the cell radiotoxins precursors. At the core of radiation damage to cells are a violation of the ultrastructure of organelles and related metabolic changes.

Small doses of ionizing radiation cause reversible, nonlethal changes cells. They appear immediately or within a few minutes after exposure (inhibition of nucleic acid metabolism, changes in the permeability of cell membranes, occurrence of stickiness of chromosomes, formation of grains and lumps in the nuclear matter, the delay of mitosis) and over time disappear.

At high doses of radiation in cells occur lethal changes that lead to their death before the entry into mitosis (interphase death) or at the time of mitotic division (mitotic or reproductive, death). Interphase death is preceded by changes in the permeability of nuclear, cytoplasmic and mitochondrial membranes. Changing the membranes of lysosomes results in the release and activation of DNase, RNase, cathepsins, phosphatase enzyme hydrolysis of mucopolysaccharides, and others. Inhibits the cellular respiration, there is degradation of deoxyribonucleic complex in the nucleus. The main reason for the death of reproductive cells are structural chromosomal damage (structural aberrations) occurring under the influence of radiation.

It is believed that significantly higher radiosensitivity nucleus than cytoplasm. It also plays a crucial role in the outcome of cell irradiation. Cell death leads to the devastation of tissue disruption of their structure and function.

The effect of ionizing radiation on the body

The effect of ionizing radiation can be local (radiation burns, necrosis, cataracts) and common (radiation sickness).

Local effects of ionizing radiation (exposure of tissues during radiation therapy, dermal radioactive isotopes) most often manifested in the form of radiation burns. Soft X and p-radiation penetrating the tissue at a small depth to cause burns to the skin; high-energy bremsstrahlung and neutrons, which have a greater penetrating power, can affect and deep-lying tissue. Course radiation burns characterized by the development in series of successive periods (early radiation reaction, latent, acute inflammation, restoration), the duration and severity of symptoms depend on the severity of the lesion (1 degree - 8-12 Gy - light; II degree - 12-20 Gy - moderate severity ; III degree - more than 20 Gy - severe). When irradiated with doses of 20 Gy kills not only the skin but also the subcutaneous tissue, fascia, muscles and even bones. Patients develop fever, high leukocytosis, severe pain.

Radiation sickness. When an external uniform irradiation of the body, depending on the dose of ionizing radiation arise from lesions subtle reactions of the individual systems to the acute form of radiation sickness. Upon irradiation at doses of 1-10 Gy develops the typical form of acute radiation sickness in which most clearly manifested major pathogenetic patterns of clinical formation of its individual periods, there is a preferential bone marrow (bone marrow syndrome). In the dose range 10-20 Gy there is intestinal, at doses of 20-80 Gy - toxemic (vascular) and at doses above 80 Gy - cerebral form of radiation sickness.

A typical form of acute radiation sickness on the severity of determined by the absorbed radiation dose, divided into four groups: I - mild (1-2 Gy); II - moderate (2-4 Gy); III - severe (4-6 Gy); IV - extremely severe (more than 6 Gy). In its current is divided into four phases: 1) initial acute reaction; 2) an imaginary clinical well-being (latent phase); 3) the height of the disease; 4) Recovery.

Initial acute phase response in the human body develops a dose dependent manner in the first minutes or hours after the irradiation. There are some agitation, headache, general weakness. Then come dyspepsia (nausea, vomiting, loss of appetite), in the blood - a short-term leukocytosis with a left shift, the absolute lymphocytopenia. The clinical manifestations of the disease are a consequence of both the direct damaging effects of ionizing radiation, and indirectly (through the neurohumoral regulation violations). Observed an increase in the excitability of the nervous system, vegetative lability functions - blood pressure fluctuations. heart rate, etc. Activation of the pituitary-adrenal system leads to increased secretion of adrenal hormones, which in this situation may have adaptive value. At doses of 8-10 Gy observed the development of shock-like state with a fall in blood pressure, transient loss of consciousness, fever, development of diarrhea.

The duration of the primary phase of acute reaction 1-3 days.

Phase imaginary clinical well-being characterized by the inclusion of a protection-compensatory reactions. Therefore patients feel becomes satisfactory tested clinically visible signs of illness. The duration of the latent phase depends on the radiation dose and ranges from 10-15 days to 4-5 weeks.

With a relatively small doses (up to 1 Gy) initial light functional responses not go into a detailed clinical picture of the disease is limited and damped phenomena initial reactions. In very severe defeat latent phase is absent.

However, at that time loss increases blood system: peripheral blood lymphocytopenia progressing against the background of leukopenia lowered content reticulocytes and platelets. In the bone marrow develops devastation (aplasia). There may be atrophy of the gonads, the suppression of the early stages of spermatogenesis, atrophic changes in the small intestine and skin. Neurological symptoms gradually smoothed out.

The phase height of the disease is characterized by the fact that the health of patients once again deteriorating sharply, growing weakness, increased body temperature, there is bleeding and hemorrhages in the skin, mucous membranes, gastrointestinal tract, brain, heart and lungs. As a result of metabolic disturbances and dyspeptic disorders (anorexia and diarrhea) is sharply reduced body weight.

In total irradiation at a dose of 1 Gy, acute radiation sickness occurs in typical form, which is sometimes called bone marrow.

Bone marrow form of acute radiation sickness occurs in four clinical periods: the primary reactions, the latent period, the period of extensive clinical evidence, the outcome of the disease.

The first period, the duration of which varies from a few hours to a day or two, is a reaction of the nervous system to irradiation: agitation, headache, instability of autonomic functions, labile blood pressure and pulse rate, functional disorders of the internal organs ("X-hangover»). Dysmotility alimentary canal manifested by vomiting and diarrhea. Body temperature may rise as a result of the central thermoregulation disorders. There intermittent leukocytosis, accompanied by lymphopenia. In severe cases, this period of possible radiation shock.

The second period got clinicians called "period of imaginary well-being." The phenomena associated with overexcitation nervous system, disappear, and other painful symptoms appear later. There is still some signs of the progression of the disease: leukopenia and lymphopenia progression.

The third period is characterized by severe symptoms of radiation sickness. From the blood - a significant leukopenia, thrombocytopenia and anemia. Inevitably there are infectious complications, which constitute the main cause of the patient's suffering. Typically the development of auto-infection in the oral cavity (inflammation of the tongue and gums, necrotic angina). Eating is difficult. A common complication of radiation disease is pneumonia, which is against the background of reduction of immunological reactivity proceeds very seriously and may result in death of the patient. The appearance of the patient is characteristic - the skin is covered with numerous punctate hemorrhages. It appears in the urine, feces, sputum.

Signs of recovery are feeling better, the normalization of the blood picture, the emergence of young blood formed elements. However, long after the disease can persist residual effects - fatigue, tiredness, weakness, instability of hematopoiesis, sexual dysfunction, hair loss, weakening of the immune system, trophic disorders, leading to premature aging.

The intestinal form of acute radiation sickness occurs when irradiated laboratory animals at doses of 10-20 Gy, causing death 3-5 days after exposure. At autopsy the animals always ascertain the death of the bulk of the intestinal epithelium, denudation of villi, their flattening and destruction.

In humans, at an irradiation dose of 10-20 Gy in death bowl comes on the 7-10th day. The main signs of illness are nausea, vomiting, bloody diarrhea, fever, can be observed complete paralytic ileus and bloating. Develop a deep hemorrhage and leukopenia with a complete absence of lymphocytes in peripheral blood, as well as a picture of sepsis.

The cause of death in the intestinal form of acute radiation sickness is dehydration, accompanied by a loss of electrolytes and protein, the development of irreversible shock associated with the action of microbial toxins and tissue origin.

Toxemic form is characterized by severe hemodynamic disturbances mainly in the intestine and liver, vascular paresis, tachycardia, hemorrhage, severe intoxication and meningeal symptoms (swelling of the brain). Observed and hyperasotemia oliguria due to renal disease. Death occurs in the 4-7 th day.

Cerebral form of acute radiation sickness occurs when irradiated with doses above 80 Gy. Death in this case comes in 1-3 days after exposure, and the action of very high doses (150-200 Gr) death may occur even during the actual irradiation (death under the ray), or in a few minutes - hours after exposure, as well as local irradiation of the head at doses of 100-300 Gy.

This form of radiation injury is characterized by the development of convulsive, paralytic syndromes, disorders of blood and lymph circulation in the central nervous system, vascular tone and thermoregulation. Later, there are functional disorders of the digestive and urinary systems, there is a progressive decrease in blood pressure.

The cause of death in cerebral form of acute radiation sickness is severe and irreversible damage of the central nervous system, characterized by significant structural changes, the death of cells of the cerebral cortex and hypothalamus neurons. The defeat of the nervous system plays a major role directly damaging effects of ionizing radiation on the fabric, as well as primary radiotoxins as H2O2 and other substances produced by oxidation of unsaturated fatty acids and phenols. Individual monitoring the effects of human exposure to doses exceeding 100 Gy indicate the occurrence of disorders in which the regulation of higher nervous activity, blood circulation and respiration.

Chronic radiation sickness occurs when the body's long-term exposure to low, but higher than the permissible dose. There are two main variants of the disease:

- Due to external irradiation (general or local);

- Due to internal exposure (due to intake of radioactive nuclides).

The disease is characterized by the gradual development of a long and undulating course, the timing of the origin and nature of the changes at the same time determined by the intensity and the total radiation dose.

The initial period of the disease is characterized by unstable development of leukopenia, symptoms of asthenia, vegetative-vascular instability, and others.

Open period of the disease characterized by failure of physiological regeneration of the most radiosensitive tissues in combination with functional changes in the nervous and cardiovascular systems.

The recovery period is characterized by smoothing destructive and distinct predominance of reparative processes in the most radiosensitive tissues.

According to the severity of chronic radiation sickness caused by common external irradiation, divided into three groups: mild (I), medium (II) and severe (III) degree.

Chronic radiation sickness 1 degree (mild) characterized by mild pronounced neuro-regulatory disturbances in the activity of various organs and systems, unstable moderate leukopenia and thrombocytopenia.

In chronic radiation sickness II degree (middle) joined gravity functional disorders of the nervous, cardiovascular and digestive systems. Progressing leukopenia and lymphopenia, reduced platelet count; in the bone marrow - the phenomena of hypoplasia of hematopoiesis.

In chronic radiation sickness III degree (severe) anemia, the phenomena of severe hypoplasia of hematopoiesis, atrophic processes in the mucosa of the gastrointestinal tract, joining infectious-septic complications, hemorrhagic syndrome and circulatory disorders. Extremely uncommon severe, with patients developing diarrhea and cachexia.

The clinical picture of chronic radiation sickness caused by internal exposure, generates a loss of one or more critical organs, which are deposited in the body received radioactive nuclides.

Long-term effects of radiation may develop after the general and local exposure of the body after a number of years and are non-tumor or tumor character.

For non-tumor forms in the first place include a reduction in life expectancy, hypoplastic state in hematopoietic tissue, the mucous membranes of the digestive system, the respiratory tract, the skin and other organs; sclerotic processes (cirrhosis, nephrosclerosis, arteriosclerosis, cataracts, and other radiation.) and dishormonal state (obesity, hypophysial cachexia, diabetes insipidus).

One of the most common forms of long-term consequences of radiation injury is the development of tumors in critical organs during irradiation incorporated emitters (a- and radiation), a radiation and leukemia.
The action of chemical factors

Human Environment contains a large number of chemical factors, which may cause a pathological condition. Among these industrial poisons, pesticides used in agriculture, household poisons, and so on. D. Medications taken in large doses or in case of intolerance, could also lead to poisoning.

In the clinical picture of poisoning distinguish the following groups of poisons - suffocating, irritating (cauterizing), blister agents, narcotics, seizure, blood, cardiac, vascular (capillary), renal, hepatic, psychotomimetic and others.

In terms of biochemistry, chemical poisons can be divided for electoral effects on enzyme systems (oxidative phosphorylation poisons, toxins that block the functional groups of proteins and enzymes, enzyme inhibitors, biosynthesis, and so on. D.). Chemical poisons have both local and general effect.

In terms of pathophysiology, we can speak of hypoxic poisons with different mechanisms of action; poisons predominantly central or peripheral action; poisons selectively affecting choline - and adrenergic transmission, and so forth.

The study of the mechanism of poisoning is extremely important for the development of the most effective means of pathogenetic therapy.

In the pathogenesis of poisoning has a number of specific features, due to the chemical characteristics of the poison. The study and identification of these features help to formulation of a differential diagnosis and the use of specific therapies. Furthermore, as a trigger, chemical poisons include pathophysiological complex system shifts up to allergic condition, shock, collapse, coma, hypoxia. For example, if a chemical poison effect accompanied by severe pain, the clinical picture of poisoning takes the form of a painful shock, and that is what is dictated by the medical tactic. Hemolytic poisons give a picture of acute oxygen starvation, capillary - collapse. Kidney and liver poisons in severe cases, cause a coma. The substances of protein nature, plant and animal origin, and certain medications can cause anaphylactic shock.

Furthermore exogenous toxins, causes poisoning substance can be endogenous, ie. E. Natural metabolic products accumulated in excess. This is very important violation of neutralizing function of the liver and a violation of renal excretion of metabolic products. The intestines are home to removal of metabolic products and the formation of rotting food, it accumulates intestinal microflora and digestive enzymes are active. In violation of gut mucosal barrier function, such as ileus occurs severe poisoning organism intestinal contents.

Poisoning caused by chemical poisons are content specific area of medicine - Toxicology.
The action of biological factors

The flora and fauna surrounding the person, contains a large number of pathogenic biological agents.

Many plants and their fruits are poisonous to humans (mushrooms, ergot, henbane, wolfberries). Some substances of plant origin are allergens, causing severe disease (asthma, dermatitis, etc.).

Poisonous to humans are also representatives of the animal world (poisonous snakes, insects, etc.).

The most extensive group of pathogenic biological agents comprise microorganisms - bacteria, viruses, rickettsia, protozoa. Penetrating into the body and multiply, they cause it to different pathological processes.

In the occurrence of infectious diseases in addition to pathogen often have value and other biological objects-vectors (flies, mosquitoes, lice, ticks, etc.).

Worms, multiply in the human body, poisoning it with their decay products and waste. In addition, worms contribute to sensitization of the organism. Parasites, even if they themselves do not cause severe pathological changes, can contribute to the implementation of the body other, more pathogenic agents.

Microorganisms, parasites on the skin and mucous membranes of man and does not cause him any harm normal conditions are called saprophytes. However, in the case of reducing the barrier properties of the tissues, and the general immunological reactivity saprophytes can cause pathological changes.

As a source of toxic substances, plants and products of animal origin may have a therapeutic effect and (ergot, a snake venom).
The role of psychogenic factors in the pathology

Diseases in which the occurrence of the leading role played by emotional stress or other disturbances of higher nervous activity, called neurogenic or psychogenic.

Any trauma is accompanied by pronounced autonomic disorders, which in severe cases may be in the nature of psychogenic shock. Much more often than acute trauma, it is a chronic overstrain of nervous activity. This is usually less noticeable, but the consequences will inevitably appear. Trauma and mental fatigue reduces the ability of the nervous system to mobilize the defense mechanisms, violate her functional mobility, limit its flexibility to adapt to ever-changing environmental conditions and internal environment. Chronic trauma of the nervous system decreases the body's resistance to disease. Emotional stress can become unfavorable background against which any pathological stimulus causes the disease. The emotional state can determine the outcome of the pathological process.

It should be said about the meaning of words. By definition, Pavlov, is "strongly conditioned stimulus is not included in any quantitative and qualitative comparisons with other stimuli." We describe the facts of sudden death from posts, joyful or tragic. Particularly exposed to sick people words. The authoritative word of the doctor should be, so it is particularly careful. Section of medicine dealing with the influence of psychogenic factors in the course of the disease, called the medical deontology.