Normally, water, alcohol, electrolytes are absorbed in the stomach. In case of accidental or deliberate use, toxic agents can be absorbed. With destructive changes in the stomach wall (including with violations of the barrier function), it is possible for protein to enter the internal environment of the body, which is fraught with the development of immunopathological processes: allergic reactions and states of immune autoaggression . Disruption of the barrier and protective function of the stomach The mucous- bicarbonate barrier protects the mucous membrane from the action of acid, pepsin and other potential damaging agents. • Components of the stomach barrier. – Slime. It is constantly secreted to the surface of the epithelium. – Bicarbonate (HCO3- ions). It is secreted by superficial mucous cells, has a neutralizing effect. – pH… The mucus layer has a pH gradient. On the surface of the mucus layer, the pH is 2.0, and in the near-membrane part it is more than 7.0. – H +. The permeability of the plasmolemma of gastric mucous cells for H + is different. It is insignificant in the membrane facing the lumen of the organ (apical), and rather high in the basal part. With mechanical damage to the mucous membrane, when exposed to oxidation products, alcohol, weak acids or bile, the concentration of H + in the cells increases, which leads to their death and destruction of the barrier. – Tight contacts. Formed between superficial epithelial cells. If their integrity is violated, the function of the barrier is violated.
Regulation of the stomach. The secretion of bicarbonate and mucus is enhanced by glucagon, PgE , gastrin , epidermal growth factor (EGF). To prevent damage and restore the barrier, antisecretory agents (for example, blockers of histamine receptors), PG , gastrin , sugar analogues (for example, sucralfate ) are used. • Disruption of the stomach barrier. – Under unfavorable conditions, the barrier is destroyed within a few minutes, death of epithelial cells, edema and hemorrhages in the own layer of the mucous membrane occur. There are factors that are unfavorable for maintaining the barrier, for example, non-steroidal anti-inflammatory drugs (aspirin, indomethacin ), ethanol, bile salts. – Helicobacter pylori is a gram-negative bacterium that survives in the acidic environment of the stomach. H. pylori attacks the surface epithelium of the stomach and destroys the barrier, contributing to the development of gastritis and gastric ulcer. This microorganism is isolated in 70% of patients with gastric ulcer and 90% of patients with duodenal ulcer or antral gastritis. – A decrease in acidity in the stomach creates favorable conditions for the life and reproduction of many microbes, for example, cholera vibrio, shigella , amoeba. So, patients with gastric achilia are more likely to get infB (transmitted by the oral-fecal route), are exposed to intoxication, and have a higher risk of developing stomach neoplasms.
In the clinical laboratory, any clotting factor deficiency can be determined using plasma deficient in a known clotting factor. To determine the deficiency of most factors, their activity is compared with the activity of this factor in normal or standard plasma, where it is taken as 100%, that is, it corresponds to 100 U / dl. Severe deficiency of factor VIII or factor IX corresponds to less than 1 U / dl of normal plasma (less than 1%), moderate deficiency – 1-5 U / dl , mild deficiency – in the range from 5 U / dl to the lower limit of normal. For most clotting factors, the normal range is 50-150 U / dL (50-150%). Patients with hemophilia A or B may develop factor VIII or factor IX inhibitors after replacement therapy. The amount of inhibitor present is determined using a standardized clinical assay called the Bethesda assay . One Betsda unit is defined as the amount that inhibits coagulation factor 50 in normal plasma. Determination of platelet aggregation . If a qualitative defect in platelet function is suspected , a platelet aggregation test is usually performed. For this, the patient’s platelet-rich plasma is activated by one of the agonists (ADP, adrenaline, collagen, thrombin or thrombin-receptor peptide, ristocetin ). Retesting or testing other symptomatic family members can help determine if the defect is inherited. Many medications, especially aspirin and other NSAIDs, valproic acid, skew platelet function tests. There are aggregometers that measure the specific release of ADP by platelets in the form of luminescence ( lumiagregometer ) and, with a higher sensitivity, determine abnormalities in the release reaction from platelet granules.
Tests for susceptibility to thrombotic disorders. A hereditary predisposition to thrombosis is associated with a decrease in anticoagulant function (proteins C and S, AT-III), with the presence of a factor V molecule resistant to inactivation by protein C (factor V Leiden), with an increased number of procoagulants (mutation of the gene encoding prothrombin) or with fibrinolysis deficiency ( plasminogen deficiency ). In severe clinical condition and a positive history of thrombosis, specific tests are performed to determine natural anticoagulants.At present, both immunological and functional tests are performed, but the most informative are clinically functional analyzes of proteins C and S, AT-III. Factor V Leiden is a common factor V mutation that is associated with a significant risk of thrombosis. A point mutation of the factor V molecule prevents the inactivation of activated factor V by protein C and thus permits the persistence of activated factor V. This defect is also called resistance to activated protein C and is easily diagnosed by DNA testing. A mutation of the prothrombin gene (G20210A) occurs in the non-coding region of the prothrombin gene with the replacement of G at position 20210 by A. This mutation increases the amount of prothrombin mRNA , which leads to an increase in the amount of prothrombin and predisposes to thrombosis. This abnormality is easily diagnosed with a molecular diagnostic test (DNA). Elevated homocysteine levels . Homocysteine levels can be elevated as a result of genetic mutations. Elevated homocysteine levels lead to homocystinuria . Such patients are prone to both arterial and venous thrombosis, as well as the progression of arteriosclerosis. Fibrinolytic system tests . The lysis time of the euglobulin clot is used to assess the decline in fibrinolysis function . Most laboratories conduct more specific tests to determine the level of plasminogen , plasminogen activator and fibrinolysis inhibitors . An increase in fibrinolysis can be associated with hemorrhagic symptoms, and its slowdown – with thrombosis.
According to Clark and Schneider, after parenteral administration of reserpine, there is a significant increase in the amount and acidity of gastric juice, which most authors explain by the parasympathomimetic effect due to the sympatholytic effect of the drug. With the direct effect of reserpine on the gastric mucosa, as well as with the activation of the pituitary-adrenal system, a number of researchers associate stomach disorders with it . The mechanism of the ulcerogenic action of aspirin and other salicylic drugs is explained from different points of view, among which there are supporters of an increase in the acidity of gastric juice, others are associated with an increase in the anticoagulant properties of blood and the resulting gastrointestinal bleeding; number of researchers suggest weakening the protective properties of the gastric mucosa due to inhibition of secretion glyukoproteidov gastric mucus, and also increase mucosal barrier permeability for ions of Na and H + ions, using Aspira Zion gastrobiopsy revealed dystrophic changes of surface epithelial cells, a Pfeiffer and Weibel (1973) using electronic microscopic technique, found changes in the parietal and main cells of the gastric glands; observed alterative changes and hemorrhages in the gastric mucosa. At the same time, no significant changes were found in the morphological state of the gastric mucosa under the influence of aspirin. Most researchers associate gastric damage with the use of glucocorticoids with an increase in the digestive capacity of gastric juice, a violation of the mucous barrier, a decrease in tissue resistance and a deterioration in regeneration processes. At the same time, a number of researchers find that medications alone cannot cause serious lesions on the part of the stomach; additional conditions must play a role here. According to the literature, long-term use of diuretics such as novurit , diamox causes inhibition of gastric secretion by affecting the blood flow of the gastric mucosa, and also changes the electrolyte composition of blood and.
Investigations carried out by us in 50 patients with atherosclerotic cardiosclerosis A H II phase, showed that already a single administration of a therapeutic dose novurita (1 ml) reduced the gastric secretory and excretory functions [Beloborodo- Island , 1975]. Under the influence of novurite , the ionic composition of gastric juice also changed with a decrease in sodium concentration in it. It can be assumed that the secretion of water and ions of hydrogen, sodium and potassium is largely due to changes in vascular tissue permeability and microcirculation in the stomach, which can occur under the influence of diuretics. This is supported by a parallel violation of electrolyte metabolism, i.e., a decrease in sodium content in erythrocytes under the action of diuretics. It can be assumed that novurite , used for a longer time in patients with atherosclerotic cardiosclerosis with congestive heart failure, can cause gastric digestion disorders , which should be taken into account in the therapy. Given the widespread use in cardiological practice of a fast-acting and rather strong diuretic ( saluretic ) agent like furosemide, it was of undoubted interest to study its effect on gastric acid production. Moreover, it does not cause a noticeable inhibition of carbonic anhydrase, and the latter is found in large quantities in the gastric mucosa. There are conflicting opinions on this issue in the literature. Thus, in clinical [ Merz , Poppe , 1968] and experimental studies, no noticeable effect of furosemide on gastric secretion was noted, while the use of this saluretic in patients with peptic ulcer caused a decrease in the concentration of hydrochloric acid in the gastric contents. Studies carried out by us in 10 patients with atheroeclerotic cardiosclerosis with stage HIIA showed that a single administration of lasix (1 ml IV) does not have regular changes in the secretory activity of the stomach, which should be taken into account when. the choice of diuretics.
In the occurrence of acute ulcers, a certain importance is attached to reflex mechanisms, strong stimuli play a role that alters hemodynamics and metabolic processes in the gastrointestinal tract. In the mechanism of development of acute ulcers and erosions of the stomach in cardiac pathology, great importance is attached to stress. The significance of stress influences is evidenced by the data of Selye (1953), indicating ulceration of the gastric mucosa as one of the characteristic manifestations of stress reactions. There is no doubt that the impact of stress plays a role in the occurrence of acute destructive changes in the stomach in patients with acute cardiovascular diseases, such as acute myocardial infarction. It is known that stress reactions are realized in the body through the pituitary- adrenal system. In this regard, attention is drawn to the increased secretion of 17 hydroxycorticosteroids in heart attack. An important role in the development of gastric ulcers is played by such biogenic amines as histamine and serotonin. The monograph indicates that with a significant increase in histamine in the organ, it turns into a damage factor, which causes increased vascular permeability and tissue edema, as well as local circulatory hypoxia. According to the data , there was an increase in the amount of histamine in the lungs in chronic pulmonary pathology, the degree of which is parallel to the degree of pulmonary and pulmonary heart failure.
This is confirmed especially in those persons who had a concomitant disease with peptic ulcer disease. And research has shown the effect of histamine on vascular pathology in experimental ulcers . This is confirmed by those who noted in experimental histamioid ulcers the phenomenon of pronounced mucoid edema and necrotic changes in the vascular wall, which aggravates ulceration , attaches importance to the increased level of serotonin in the ulcer formation , studying its dynamics and the pathological picture of the state of the enterochromaffin apparatus of the stomach in patients with acute infarction. Summarizing the foregoing, we note that in patients suffering from diseases of the cardiovascular system, especially complicated by circulatory insufficiency, there are violations of both the functional state of the stomach, mainly in the direction of oppression of its main functions, and structural changes in the gastric mucosa up to ulceration . A number of factors, such as hypoxemia, hypercapnia, venous stasis, atherosclerosis of the mesenteric arteries, increased histamine levels, should be given great importance in the pathogenesis of these complications. Various drugs used in the treatment of patients with cardiovascular disease can increase these disorders.