Liver infarction is a dangerous organ damage! Hepatic ischemia. Symptoms, treatment Cardiogenic ischemic hepatitis symptoms and treatment

Many people suffer from heart disease, therefore, in addition to drug therapy, treatment of coronary artery disease is allowed folk remedies. Anyone who has ischemia knows that this pathology requires the constant use of special medications, thanks to which it is possible to maintain the vessels in a normal state. Traditional methods will also be useful. The main thing is to exercise maximum caution when taking various infusions and decoctions.

Medicine from rosehip and hawthorn

Treatment of coronary heart disease with folk remedies involves the preparation of healing decoctions, teas and tinctures from such well-known plants as rose hips and hawthorn. By stocking up on their fruits, flowers and leaves, you can make a medicine that can significantly reduce the manifestations of the disease.

These plants are rich in potassium and magnesium with vitamin C, iron and calcium, and carotene.

Rosehip has a beneficial effect on vascular walls, strengthening them, and has the following properties:

• wound healing;
• anti-inflammatory;
• antimicrobial.

Hawthorn, in turn, promotes:

• strengthening immune forces;
• cleansing blood vessels;
• increase in hemoglobin;
• improving the functioning of the central nervous system.

You should not collect plant fruits in places where the level of environmental conditions leaves much to be desired, for example, near roads.

Treatment with folk remedies can be carried out as follows:

1. For the infusion, the fruits of hawthorn, rose hips, motherwort and chamomile are taken. You will need a teaspoon of each ingredient. The mixture poured with boiling water (1 liter) should sit for at least half an hour. Throughout the day, the drug must be drunk 20 minutes before meals, after dividing it into 3 parts.
2. Hawthorn and rosehip, a tablespoon each, are placed in a thermos, and boiling water is poured on top. After overnight infusion, it is drunk as tea all day. Berries also need to be consumed.
3. A decoction of hawthorn and motherwort is made to help people suffering from angina. The components in the amount of 6 tablespoons each need to be poured with boiling water (7 glasses) and left for the whole day, well wrapped. It is recommended to drink 3 glasses of the strained and cooled product before sitting down at the table.

Horseradish and garlic against ischemia

People have long used these products to combat many ailments. With the help of horseradish and garlic, IHD can be successfully treated. Patients suffering from heart disease should regularly eat horseradish, because it is considered a natural cardiotonic.

True, it is contraindicated for:

• inflammation of the gastrointestinal tract;
• liver lesions.

As for garlic, as numerous studies have shown, thanks to it:

• cardiac muscle tissue is restored;
• the smooth muscles of the vascular walls relax.

In order for the product to be as useful as possible, it should be ground beforehand. And long-term heat treatment makes it useless.

If coronary heart disease occurs, the following recipes will come in handy:

1. Place grated horseradish (5 g) in a thermos, add boiling water (250 ml) and leave for about 2 hours. Next, you can begin the inhalation procedure.
2. Mix crushed horseradish with honey (each component requires 1 tsp). For 1.5 months, the patient must eat a healing mixture, after which he can drink water.
3. Initially, grated horseradish (2 tbsp) is poured with boiling water and left to infuse for a day. Then add honey (1 glass) and freshly squeezed carrot juice(1 glass). If ischemia is diagnosed, you should drink a tablespoon of the prepared drug an hour before meals.
4. Garlic (50 g) is crushed, poured with vodka (1 glass) and infused for 3 days. Before use, the tincture must be diluted (8 drops of water per teaspoon). Three approaches are done per day.

Effective herbal infusions

Many patients treat coronary artery disease with folk remedies because medications have proven ineffective. But if you don’t know the properties of some herbs, you can seriously worsen your health. It is undesirable to engage in traditional therapy without the consent of a doctor.

You can cope with unpleasant symptoms using all kinds of preparations, for example:

1. Mix buckwheat flowers (2 tbsp) and mistletoe leaves (1 tbsp). The ingredients (1 tsp) are poured with a glass of boiling water, wrapped well and left overnight. It is recommended to drink 2 tablespoons at a time three times a day.
2. Corn roots (40 g) are crushed and mixed with lovage (40 g). The composition, filled with water, is placed on the fire and boiled for 8 minutes. Then it must be poured into a thermos, and after 40 minutes filtered. For 7 days, the infusion is drunk after eating 3 times a day, 0.5 cups.
3. Melissa with cumin, periwinkle, valerian (1 tbsp each) are mixed with hawthorn (flowers) and mistletoe (2 tbsp each). The ingredients must be thoroughly crumbled. A tablespoon of the resulting mixture is poured into a glass of boiled water and left to infuse for 2 hours. The drug is used in the morning and evening.
4. Finely chopped dill (or you can take seeds) in the amount of a tablespoon is poured into a glass of boiling water. It is recommended to drink the infused medicine on the day the attack occurred.
5. An excellent prophylactic remedy can be obtained from a drink for which you will need to stock up on elecampane root (70 g), honey (30 g) and oats (50 g). First, the oats should be sorted, washed, filled with water, boiled, and then left for 3-4 hours. Elecampane roots are crushed and poured with oat decoction. The mixture needs to be boiled and then left to steep for 2 hours. After straining, honey is added. Three times a day before meals, take half a glass of the drink.

If treatment of cardiac ischemia with traditional methods causes negative manifestations in the form of heaviness in the stomach, nausea with heartburn, the use of one or another remedy must be stopped immediately.

Whatever methods the patient uses, the results depend on the severity of the pathology. At the initial stage, the pathology is successfully treated through a combination of drug therapy and folk remedies.

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Types of coronary heart disease (CHD), symptoms and treatment

IHD occupies a strong leading position among the most common heart pathologies, often leads to partial or complete loss of ability to work, and has become a social problem for many developed countries of the world. A busy rhythm of life, constant stressful situations, adynamia, poor nutrition with consumption of large amounts of fat - all these reasons lead to a steady increase in the number of people suffering from this serious disease.

The term “coronary heart disease” combines a whole group of acute and chronic conditions that are caused by insufficient oxygen supply to the myocardium due to narrowing or blockage of the coronary vessels. Such oxygen starvation of muscle fibers leads to disturbances in the functioning of the heart, changes in hemodynamics and persistent structural changes in the heart muscle.

Most often, this disease is provoked by atherosclerosis of the coronary arteries, in which the inner wall of the vessels is covered with fatty deposits (atherosclerotic plaques). Subsequently, these deposits harden, and the vascular lumen narrows or becomes impassable, disrupting the normal delivery of blood to the myocardial fibers. From this article you will learn about the types of coronary heart disease, the principles of diagnosis and treatment of this pathology, the symptoms and what cardiologist patients need to know.

Types of IHD

Currently, thanks to the expansion of diagnostic capabilities, cardiologists distinguish the following clinical forms of IHD:

• primary cardiac arrest (sudden coronary death);
• angina pectoris and spontaneous angina pectoris;
• myocardial infarction;
• post-infarction cardiosclerosis;
• circulatory failure;
• heart rhythm disturbances (arrhythmias);
• painless ischemia of the heart muscle;
• distal (microvascular) ischemic heart disease;
• new ischemic syndromes (hibernation, stupefaction, metabolic adaptation of the myocardium).

The above classification of IHD refers to the system International classification diseases X.

Causes

In 90% of cases, IHD is provoked by a narrowing of the lumen of the coronary arteries, caused by atherosclerotic changes in the walls of blood vessels. In addition, disturbances in the correspondence of coronary blood flow and the metabolic needs of the heart muscle can be a consequence of:

• spasm of slightly changed or unchanged coronary vessels;
• tendency to thrombus formation due to disorders of the blood coagulation system;
• microcirculation disorders in the coronary vessels.

Risk factors for the development of such etiological causes of IHD may be:

• age over 40-50 years;
• smoking;
• heredity;
• arterial hypertension;
• diabetes;
• obesity;
• increased levels of total plasma cholesterol (more than 240 mg/dl) and LDL cholesterol (more than 160 mg/dl);
• physical inactivity;
• frequent stress;
• poor nutrition;
• chronic intoxication (alcoholism, work in toxic enterprises).

Symptoms

In most cases, IHD is diagnosed already at the stage when the patient has its characteristic signs. This disease develops slowly and gradually, and its first symptoms become apparent when the lumen of the coronary artery narrows by 70%.

Most often, IHD begins to manifest itself as symptoms of angina pectoris:

• a feeling of discomfort or chest pain that appears after physical, mental or psycho-emotional stress;
• the duration of the pain syndrome is no more than 10-15 minutes;
• pain causes anxiety or fear of death;
• pain can radiate to the left (sometimes to the right) half of the body: arm, neck, shoulder blade, lower jaw, etc.
• During an attack, the patient may experience: shortness of breath, a sharp feeling of lack of oxygen, tachycardia, increased blood pressure, nausea, increased sweating, arrhythmia;
• the pain may disappear on its own (after stopping the exercise) or after taking Nitroglycerin.

In some cases, angina pectoris can manifest itself with atypical symptoms: it occurs without pain, manifests itself only as shortness of breath or arrhythmia, pain in the upper abdomen, and a sharp decrease in blood pressure.

Over time and without treatment, coronary artery disease progresses, and the above symptoms may appear at a significantly lower intensity of exercise or at rest. The patient experiences an increase in attacks, they become more intense and longer lasting. This development of coronary artery disease can lead to myocardial infarction (in 60% of cases it first occurs after a prolonged angina attack), heart failure or sudden coronary death.

Diagnostics

Making a diagnosis of suspected coronary artery disease begins with a detailed consultation with a cardiologist. The doctor, after listening to the patient’s complaints, always asks questions about the history of the appearance of the first signs of myocardial ischemia, their nature, and the patient’s internal sensations. An anamnesis is also collected about previous diseases, family history and medications taken.

After interviewing the patient, the cardiologist conducts:

• measurement of pulse and blood pressure;
• listening to the heart with a stethoscope;
• tapping the borders of the heart and liver;
• general examination to identify swelling, changes in skin condition, the presence of venous pulsations, etc.

Based on the data obtained, the patient may be prescribed the following additional laboratory and instrumental examination methods:

• ECG (in the initial stages of the disease, an ECG with stress or pharmacological tests may be recommended);
• Holter ECG (24-hour monitoring);
• phonocardiography;
• radiography;
• biochemical and clinical blood test;
• Echo-CG;
• myocardial scintigraphy;
• transesophageal pacing;
• coronary angiography;
• catheterization of the heart and large vessels;
• magnetic resonance coronary angiography.

The scope of the diagnostic examination is determined individually for each patient and depends on the severity of symptoms.

Treatment of coronary artery disease is always complex and can be prescribed only after a comprehensive diagnosis and determination of the severity of myocardial ischemia and damage to the coronary vessels. These can be conservative (prescription of medications, diet, exercise therapy, spa treatment) or surgical techniques.

The need for hospitalization of a patient with coronary artery disease is determined individually depending on the severity of his condition. At the first sign of violation coronary circulation The patient is advised to give up bad habits and follow certain rules of balanced nutrition. When preparing your daily diet, a patient with coronary artery disease should adhere to the following principles:

• reducing the amount of foods containing animal fats;
• refusal or sharp limitation of the amount of table salt consumed;
• increasing the amount of plant fiber;
• introduction of vegetable oils into the diet.

Drug therapy for various forms of coronary artery disease is aimed at preventing angina attacks and may include various antianginal drugs. The treatment regimen may include the following groups of drugs:

In the initial stages of IHD, drug therapy can significantly improve health. Compliance with the doctor’s recommendations and constant medical observation in many cases can prevent the progression of the disease and the development of severe complications.

If conservative treatment is ineffective and there is extensive damage to the myocardium and coronary arteries, a patient with coronary artery disease may be recommended to undergo surgery. The decision on intervention tactics is always individualized. To eliminate the area of ​​myocardial ischemia, the following types of surgical operations can be performed:

• angioplasty of a coronary vessel with stenting: this technique is aimed at restoring the patency of a coronary vessel by introducing a special stent (mesh metal tube) into its affected area;
• coronary artery bypass grafting: this method allows you to create a bypass for blood to enter the area of ​​myocardial ischemia; for this, sections of the patient’s own veins or the internal mammary artery can be used as a shunt;
• transmyocardial laser revascularization of the myocardium: this operation can be performed if it is impossible to perform coronary artery bypass grafting; during the intervention, the doctor uses a laser to create many thin channels in the damaged area of ​​the myocardium that can be filled with blood from the left ventricle.

In most cases, surgical treatment significantly improves the quality of life of a patient with coronary artery disease and reduces the risk of myocardial infarction, disability and death.

Educational film on the topic “Coronary heart disease”

Version: MedElement Disease Directory

Liver infarction (K76.3)

Gastroenterology

general information

Short description

Liver infarction- clinical and morphological syndrome characterized by acute damage (necrosis) of liver tissue due to acute hypoxia (ischemia).

Notes
This condition is also known under the names “ischemic (hypoxic) hepatitis”, “shock liver” and others. However, according to most authors, their use is inappropriate for the following reasons:
- there are no signs of inflammation corresponding to the meaning of the term hepatitis;
- shock (impaired perfusion due to decreased blood pressure) is not the only cause of liver infarction.

One should also distinguish between the terms “liver infarction” and “red atrophic liver infarction”. The latter is essentially a form (stage) of toxic liver dystrophy, characterized by the spread of foci of necrosis from the center of the lobules to the periphery, massive disintegration of liver tissue; the capillaries in the liver tissue that has lost its elasticity greatly expand and become filled with blood, which is why it turns red (“Toxic liver damage with hepatic necrosis” - K71.1).

Liver infarction is coded as a complication of the underlying disease or a concomitant disease (see section “Etiology and Pathogenesis”), since in most cases it occurs against the background of other diseases or in patients who have undergone surgical interventions.

Classification

Etiology and pathogenesis

Double blood supply (a. hepatica, v. porta) causes the rarity of infarctions in the liver.
Liver infarction can be caused by disruption of blood flow in the intrahepatic branches of one or both vessels. Objectively, liver infarction is most often spoken of in connection with a decrease in blood flow through a. hepatica, which provides 50-70% of the oxygen required by tissues. The portal vein is responsible for 65-75% of blood flow to the liver and 30-50% of tissue oxygenation. Arterial blood flow is closely linked to venous blood flow, so that the overall blood flow through the liver remains constant.
It is customary to talk about the equal participation of arteries and veins in the blood supply (oxygenation) of the liver, although in extreme conditions “load redistribution” is possible. The mechanism for regulating general blood flow is mediated only by the hepatic artery; the portal vein cannot regulate blood flow. Arterial blood flow is regulated by specific areas that release adenosine (a powerful vasodilator). When blood flow is high, adenosine is rapidly removed, resulting in arterial vasoconstriction. Conversely, when portal blood flow is low, an adenosine-mediated vasodilatory effect in the arterial vessels is required to increase total blood flow.

Causes Liver ischemia can be very diverse:

1. Systemic decrease in blood pressure:
- shock(in 50% of cases);
- celiac trunk compression syndrome.

2. Hepatic artery. Local decrease in blood flow:
- thrombosis (of any etiology);
- embolism (of any etiology);
- torsion of the accessory lobe of the liver;
- compression by a tumor (extremely rare);
- manipulations (surgical and diagnostic) both endoarterial (for example, angiography) and on the liver tissue itself (for example, radioablation of a tumor); the second cause of liver ischemia after shock;
- arterial injury (including rupture).

3. Hepatic portal vein:
- thrombosis and embolism (of any etiology);
- external compression.

To iatrogenic damage relate:
- arterial hypotension, causing insufficient perfusion of internal organs and a decrease in portal blood flow;
- the effect of anesthetics;
- right or left ventricular failure;
- severe hypoxemia;
- reperfusion injury to the liver.
- patients with liver cirrhosis are especially sensitive to the damaging effects of intraoperative ischemia, since liver tissue in this pathology is more dependent on blood flow through the hepatic artery.

Acute hepatic artery obstruction may occur as a result of thrombosis in patients with systemic vasculitis (periarteritis nodosa and others), myeloproliferative diseases (polycythemia, chronic myeloid leukemia). It occurs due to a tumor (compression, germination, embolism), atherosclerosis, inflammatory processes in neighboring organs, after injury, etc.

The cause of arterial blockage can be embolism due to infective endocarditis and other heart diseases (especially accompanied by atrial fibrillation), and aortic atheromatosis. Accidental ligation or injury to the hepatic artery during surgery is possible.

Pathogenesis
The arterial blood supply to the liver is variable: the branches of the hepatic artery themselves and numerous anastomoses vary. Therefore, the consequences of hepatic artery occlusion depend on its location, collateral circulation and the state of portal blood flow. Occlusion of the main trunk, as well as situations with simultaneous circulatory impairment in the portal vein system, are very dangerous.
Infarcts with occlusion of the terminal branches and insufficient collateral blood flow are segmental in nature; they rarely reach a diameter of 8 cm, although cases have been described when an entire lobe and even the gallbladder become necrotic.

Morphological picture. Liver infarction is always ischemic with a surrounding congestive hemorrhagic strip. The subcapsular fields are not affected due to the additional blood supply. Along the periphery of the infarction, the portal fields are preserved.

Portal vein thrombosis(pilethrombosis) is a rare disease, the idiopathic variant occurs in 13-61% of all portal vein thrombosis.

Etiology:
- taking contraceptives;
- compression of the portal vein from the outside by tumors, cysts;
- inflammatory changes in the wall of the portal vein (with peptic ulcer, appendicitis, injuries of the abdominal wall, abdomen);
- with cirrhosis of the liver;
- with intra-abdominal sepsis;
- when a vein is compressed by a tumor;
- for pancreatitis and other inflammatory processes in the abdominal cavity;
- as a postoperative complication;
- for injuries;
- with dehydration;
- in case of coagulation disorders.

Pathogenesis
Portal vein thrombosis is a common thrombosis that causes the veins to dilate in areas in front of the site where the clot forms. Possible fusion of the thrombus with the wall, its organization and recanalization.
In case of chronic disturbance of portal blood flow, shunts are opened and anastomoses are formed between the splenic and superior mesenteric veins on the one hand, and the liver on the other.
If portal vein thrombosis does not form against the background of cirrhosis (acute thrombosis), then there may be no changes in the liver. Thromboembolism of the liver veins is possible, as well as the spread of thrombosis to the branches of the portal vein with the development of hemorrhagic infarctions of the spleen and intestines.

Epidemiology

Sign of prevalence: Extremely rare

Prevalence unknown. A predominance of older patients is expected.

Risk factors and groups

- complicated hepatic artery aneurysm and other malformations Malformation is a developmental anomaly that entails gross changes in the structure and function of an organ or tissue.
liver vessels;
- vasculitis Vasculitis (syn. angiitis) - inflammation of the walls of blood vessels
;
- injuries;
- myeloproliferative diseases;
- operations on the abdominal organs, blood vessels, liver;
- atherosclerosis Atherosclerosis is a chronic disease characterized by lipoid infiltration of the inner lining of elastic and mixed arteries with subsequent development of connective tissue in their wall. Clinically manifested by general and (or) local circulatory disorders
;
- tumors.

Clinical picture

Clinical diagnostic criteria

Sudden pain in the liver area; nausea; vomit; fever

Symptoms, course

General provisions

1. Presumably, a certain number of cases of thrombosis of the branches of the hepatic artery go undetected, since small liver infarctions are asymptomatic.

2. Clinical picture liver infarction is scanty and variable. In most cases, a heart attack occurs against the background of other diseases or in patients who have undergone surgery, and is masked by the symptoms of these conditions.

The most common cause of liver infarction is cardiovascular diseases, which account for more than 70% of cases, followed by respiratory failure and sepsis, which together account for less than 15% of cases. Recently, due to the expansion of the range of interventions, intraoperative liver ischemia has come into second place.

Thus, in a typical picture of a liver infarction, there may be signs of heart disease (sometimes even a transient episode of arrhythmia), lung disease, or the fact of surgical intervention. The patient's mental status is also often altered due to decreased cerebral perfusion.

Most are common signs of liver infarction:
1. Sudden pain in the liver area, in the epigastrium Epigastrium is an area of ​​the abdomen bounded above by the diaphragm and below by a horizontal plane passing through a straight line connecting the lowest points of the tenth ribs.
or upper section belly. Pain may radiate Irradiation is the spread of pain beyond the affected area or organ.
in the scapular region, subclavian fossa, deltoid region. Subsequently, a friction noise may appear due to perihepatitis. Perihepatitis - inflammation of the peritoneum covering the liver and its fibrous membrane (capsule)
.
2. Pain on palpation without signs of peritoneal irritation.
3. Nausea, vomiting.
4. Fever (with large foci of ischemia Ischemia is a decrease in blood supply to an area of ​​the body, organ or tissue due to weakening or cessation of arterial blood flow.
and necrosis Necrosis (death) is the irreversible cessation of vital activity of cells, tissues or organs in a living organism.
).
5. Jaundice (extremely rare).

Diagnostics

The diagnosis is complex. Risk factors, etiologically significant causes, changes in laboratory parameters and the results of imaging methods are taken into account.

Ultrasound in case of liver infarction, it reveals a focus of low echogenicity, usually of a triangular type, located on the periphery of the organ, well demarcated from normal tissue.

At computed tomography In the abdominal cavity, liver infarction is detected as a focal, often wedge-shaped lesion of low attenuation.

Diagnosis of liver infarction also involves assessing the patency of the hepatic artery, since, for example, when performing cholecystectomy Cholecystectomy - surgery to remove the gallbladder
or interventions in the area of ​​the porta hepatis, anatomical resection of the liver, accidental ligation of the hepatic artery and its large branch is possible. In such cases, MRI, multiphase CT and Doppler ultrasound reveal areas of infarction and lack of hepatic blood flow.

The "gold standard" of diagnosis is considered High-resolution CT combined with Doppler ultrasound.
Superselective angiography is a good addition to vascular ultrasound and CT in doubtful cases, but can itself lead to liver ischemia.

Biopsy not recommended as a mandatory study. As a rule, it does not provide an idea of ​​the etiology of the disease and is often uninformative in the early stages. Examination of specimens reveals mild to moderate centrilobular necrosis with preservation of hepatic architecture.

Laboratory diagnostics

general information
1. There are no specific laboratory signs that confirm or reject the diagnosis of liver infarction.
2. Laboratory signs change over time.
3. The degree of change depends on the size of the liver infarction, the presence of concomitant (underlying) diseases, age, etiology and other reasons.

Tests:
1. Transaminases. Characteristic is a significant increase on days 1-3 with a drop in the level on days 7-10 when blood flow is restored.
2. LDH levels characterized by a wave-like course, depending on periods of ischemia and restoration of perfusion. As a rule, there is a significant increase in the first day (hours), with a drop and a subsequent brief increase after restoration of blood circulation. The level often significantly exceeds the ALT level in the first hours.
ALT/LDH ratio< 1,5 является более характерным для инфаркта печени, чем, например, для острого гепатита с синдромом цитолиза.

3. Prothrombin time may increase by 2-3 seconds.
4. Serum bilirubin levels are often slightly increased, with peak levels following peak aminotransferase levels.
5. Serum creatinine, urea, and nitrogen levels are often elevated due to acute tubular necrosis.

Differential diagnosis

Liver infarction must be differentiated from viral and drug-induced hepatitis if the activity of aminotransferases mainly increases. However, with hepatitis of this etiology, the activity of aminotransferases in the postoperative period increases at a later date, and both the increase and its subsequent decrease occur more gradually than with ischemic liver damage.

Complications

- liver failure Liver failure is a pathological condition characterized by impaired liver function and usually manifests itself as jaundice, hemorrhagic syndrome and neuropsychiatric disorders
;
- bleeding;
- formation of liver cirrhosis Liver cirrhosis is a chronic progressive disease characterized by degeneration and necrosis of the liver parenchyma, accompanied by its nodular regeneration, diffuse proliferation of connective tissue and deep restructuring of the liver architectonics.
;
- intestinal infarction;
- acute renal failure;
- spontaneous rupture of the spleen.

Treatment

There is no specific treatment for liver infarction.
Measures should be taken to eliminate hypoxemia and correct the causes that caused it - blood loss, heart failure, pulmonary embolism, sepsis.

In the case of idiopathic thrombosis, selective angiography with thrombolysis/thrombectomy is indicated. There is evidence of the successful use of non-selective thrombolysis in combination with anticoagulants.
In case of embolism, embolectomy and stenting of small branches of the artery can be performed.

Prevention of secondary infection with non-hepatotoxic antibiotics is carried out.

Forecast

The overwhelming majority of cases of liver infarction have a favorable outcome.
In the most severe patients, liver infarction is only one of the manifestations of multiple organ failure and indicates an unfavorable prognosis.
Fulminant liver failure due to liver infarction is rare and most likely occurs with chronic congestive heart failure or cirrhosis. Patients with this development option fall into a coma and usually die in the first 10 days.

Sometimes a secondary infection occurs. A sequestration of dead liver tissue may form and secondary bleeding may occur.

The overall prognosis depends primarily on the severity of the underlying predisposing condition rather than on the severity of liver damage.

Hospitalization

On an emergency basis.

Prevention

Not developed.

Information

Sources and literature

1. Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management /edited by Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, 9th ed., Saunders/Elsevier, 2009

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UDC 616.36-002.1:616-07:616-08

T.M. MURTAZALIEVA

Kazakh National Medical University named after S.D. Asfendiyarov

(Department of Internship and Residency in Therapy No. 3)

City Cardiology Center, Almaty

The literature review is devoted to one of the current problems of hepatology – the diagnosis and treatment of hypoxic hepatitis. The causes and mechanisms of hemodynamic disorders in the liver, leading to centrilobular necrosis of hepatocytes and a significant increase in the activity of blood aminotransferases, are outlined.

Keywords: hypoxic hepatitis, aminotransferasesserumblood, centrilobular necrosis of hepatocytes.

Hypoxic hepatitis (HH) is a liver injury caused by a discrepancy between oxygen delivery to the liver and its oxygen demand, characterized by a transient increase in the activity of serum aminotransferases caused by hypoxic necrosis of centrilobular liver cells. In some works, HS is referred to as “hypoxic liver damage”, “acute liver damage”, “ischemic hepatitis”, “shock liver”. In the ICD-X, this condition is classified as “liver infarction” (class XI - diseases of the digestive organs, block K70-K77 “Liver diseases”, code K76.3).

Until recently, it was believed that hepatic ischemia, that is, a decrease in hepatic blood flow, is fundamental in the development of the hemodynamic mechanisms observed in HH and that it represents a state of shock. In fact, shock occurs in only 50% of cases. A more important role in the mechanisms of development of HH is assigned to other hemodynamic mechanisms of hypoxia, such as congestion in the liver, arterial hypoxemia and dysoxia. Therefore, the use of the terms “liver ischemia” and “shock liver” is not accurate.

Among patients in intensive care units (ICU), the incidence of HH ranges from 0.9–22% or more. At cardiogenic shock its frequency reaches 22%, and with septic - 13.8%.

All conditions accompanied by a violation of the relationship between oxygen supply and demand can lead to hypoxic liver damage. Hemodynamic assessment, including measurement of blood pressure, central venous pressure and determination of the gas composition of arterial blood made it possible to identify groups of patients with different hemodynamic mechanisms responsible for the development of HS:

1. in congestive heart failure and acute cardiac arrest, liver hypoxia followed a decrease in hepatic blood flow (ischemia) due to left ventricular failure and venous stasis;

2. in chronic respiratory failure, liver hypoxia occurred mainly due to deep hypoxemia;

3. In toxic-septic shock, oxygen delivery to the liver was not reduced, but the organ's oxygen demand was increased, and the liver was unable to use oxygen properly.

There have been case reports of HH in specific conditions such as heat stroke, sickle cell anemia, acute blood loss, aortic aneurysm, acute lower limb ischemia, hereditary hemorrhagic telangiectasia, sleep apnea, anorexia, Budd-Chiari syndrome.

HH is often observed in patients with acute clinical situations: pulmonary edema, arrhythmias that occur against the background of progression of chronic congestive heart failure, myocardial infarction, pulmonary embolism and cardiac tamponade.

Decreased cardiac output, systemic hypotension, and systemic hypoxia can lead to the development of HH. Despite various causes, acute centrilobular necrosis (CLN) of hepatocytes is morphologically observed in HS.

A decrease in cardiac output and a critical drop in oxygen delivery to the liver are not the only hemodynamic mechanisms in the pathogenesis of HH. Another permissive factor is liver congestion, which is caused by left ventricular failure and can lead to secondary failure of the right heart, which leads to the spread of oxygen starvation throughout the patient's body. However, in cardiogenic shock, with severe hypotension and decreased cardiac output, the formation of GG may not be observed.

In approximately 15% of cases, the cause of HH is chronic respiratory failure, leading to severe hypoxemia. In this case, a very low level of partial pressure of oxygen (PaO 2) in arterial blood is usually observed.

In HH associated with toxic-septic shock, the increase in cardiac and hepatic blood flow is insufficient to compensate for the increased oxygen demand and the reduced ability of liver cells to use oxygen. However, this mechanism is not fully explained. Endotoxins and proinflammatory cytokines weaken the respiratory function of hepatocytes and disrupt microcirculation in the liver.

In some cases, patients with HH may have low blood pressure and central venous pressure, but cardiac output and oxygen saturation may be normal. However, hypoxia is not a consequence of a decrease in the supply of blood and oxygen to the liver. Liver hypoxia develops due to an increased demand for oxygen due to the inability of liver cells to use available oxygen. The latter phenomenon, sometimes referred to as “dysoxia,” has been demonstrated in studies assessing the relationship between splanchic blood flow and splanchic oxygen transport in patients with cardiogenic and septic shock. In cardiogenic shock, splanchial blood flow is reduced, but oxygen transport can reach up to 90%, while in septic shock, splanchial blood flow is increased, but liver cells are unable to extract oxygen.

Liver hypoxia alone is not sufficient for HH to develop. Reperfusion probably plays a role. Studies have shown that liver cell necrosis does not occur during ischemia, but rather during reperfusion. This situation, in which an organ was ischemic and then reperfused, was called “ischemic/reperfusion injury.” This mechanism includes “oxidative stress”, early activation of Kupffer cells, activation of polymorphonuclear cells (“neutrophilic hepatitis”) and impaired liver microcirculation.

The occurrence of CLN of hepatocytes explains the longer period of oxygen starvation of the liver. In light of a number of publications, it is more logical to propose that necrosis of liver cells most likely appears during transient periods of reperfusion before the death of the patient. Indeed, it is difficult to believe that patients who died after prolonged shock could live for so long without transient periods of hemodynamic recovery, allowing partial saturation of the liver with oxygen. Reperfusion appeared to be incomplete until death, limited to the periportal and mediolobular liver cells, while the centrilobular hepatocytes remained without oxygen. According to this scheme, periportal and centrilobular hepatocytes survived because oxygen delivery to them remained sufficient due to the lack of reperfusion, while mediolobular liver cells were killed by ischemic reperfusion.

Several dangerous complications can occur with HH, such as hypoglycemia, respiratory failure due to “hepatopulmonary” syndrome, and hyperammoniemia.

HH is typically observed in older adults with respiratory or congestive heart failure and low cardiac output. Risk factors include myocardial infarction, arrhythmias, pulmonary edema or sepsis. Clinical signs include weakness, shortness of breath, and pain in the right upper abdomen.

Liver damage in patients is obvious on the day of hospitalization. Serum aminotransferase and lactate dehydrogenase levels rise to extremely high levels. However, clinical symptoms liver damage remains in the background, in contrast to obvious signs of the cause that led to the development of HS. Painful hepatomegaly and swelling in the legs are observed in approximately only 50% of cases. There is no obvious jaundice. Some degree of encephalopytia (sleep disturbance or confusion) is common, but is the result of hemodynamic compromise and cerebral hypoxia rather than liver failure. After initial supportive treatment of the underlying disease in the ICU, the patient's condition quickly stabilizes.

Hypoxic liver injury may be suspected in patients with systemic hypoperfusion. Within a few hours, the level of serum aminotransferases increases (almost 200 times) along with LDH. The activity of alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH) in the blood serum increases rapidly, reaching amplitude values ​​within 24 hours. The peak of ACAT occurs earlier and is higher than the peak of ALAT, but this is not a constant feature and was observed only in 75% of cases. The activity of enzymes in the blood of patients decreases quickly and every other day is approximately half the peak level. After 2 or 3 days, the AST curve crosses the ALAT curve due to the shorter half-life. Normalization of aminotransferase activity is observed after 10–15 days. However, this is not a pathognomonic sign for HS. LDH activity reaches impressive numbers, which distinguishes it from the moderate increases observed in viral hepatitis (VH). This is important in the differential diagnosis of HH and VH. .

A moderate increase in serum bilirubin is typical for HH, but severe jaundice is rare. Higher bilirubin levels may be observed in patients with septic shock.

Another biological marker of HH is an early and sharp drop in prothrombin levels, the recovery of which is observed after 1 week. A sharp decrease in prothrombin levels is not typical for VH. .

Serum creatinine can also be one of the indicators of GG. An increase in serum creatinine is observed in 15% of patients. Renal failure, as a result of hemodynamic disorders (hepato-renal syndrome), worsens the course of HH and can be regarded as an additional diagnostic criterion, since kidney damage is not typical for drug-induced (PH) and CH.

Disorders of carbohydrate metabolism manifest themselves differently in patients with GG. Hypoglycemia has been regarded by some researchers as a hallmark of hypoxic liver injury. However, in clinical practice, hyperglycemia is more common than hypoglycemia, indicating metabolic disturbances in critically ill patients.

When the main causes of hemodynamic disorders of the hysterectomy are established, histological examination fades into the background, or there is no particular need for its implementation. However, when performing morphological studies, typical liver damage is revealed - CLI. Necrosis may be limited to a narrow zone around the central veins, but may also be extensive, leaving only a few healthy cells around the portal tracts. The area of ​​necrosis is filled with red blood cells and cellular destruction. At the border of the central lymphoma, fatty degeneration is detected. In most cases, CLN is associated with morphological signs of stagnation, characterized by dilation of sinusoids with edema of the spaces of Disse.

Ultrasound examination reveals hypoechoic foci, and computed tomography reveals foci of low density. They are mainly used for differential diagnosis. In the diagnosis of HS, ultrasonography is of greater importance, which makes it possible to detect the expansion of the inferior vena cava and hepatic veins.

Thus, three criteria are most often used to diagnose HH:

1. Situational history – heart failure, shock, respiratory failure or other conditions accompanied by impaired oxygen delivery to the organ;

2. A pronounced, and at the same time relatively quickly reversible increase in the activity of blood aminotransferases; with low aminotransferase activity, it is difficult to confirm HS without a biopsy and subsequent histological examination, which for a number of reasons is not very acceptable.

3) Exclusion of other causes of liver damage (VH, PH).

These criteria were developed in a large series of clinical studies, and are recommended to exclude liver biopsy when it is not required or, on the contrary, when it is necessary.

When verifying the diagnosis, it is necessary to exclude the fulminant course of acute hepatitis caused by toxic, drug, viral etiology. Detection of elevated serum aminotransferase levels is a fairly sensitive test for detecting liver disease. In this case, the specificity of the test depends on the level of hyperenzymemia. An increase in the level of aminotransferases less than 10 norms can occur in a number of diseases, and more than 10 norms - almost exclusively with liver damage: acute (viral, toxic, ischemic) and chronic (viral, autoimmune) hepatitis (Table 1).

Table 1 - Reasons for a significant increase in aminotransferase activity

	Transaminase activity	Bilirubin level	Comments
Liver ischemia			AST>ALT; rapid decrease in aminotransferase levels after the initial peak; ALT/LDG<1; наличие сопутствующих заболеваний
Toxic damage			The biochemical profile is similar to that of ischemic injury; instructions for taking toxic drugs
Acute viral hepatitis	From 5-10 to >10 norms		Slow decrease in aminotransferase levels; presence of risk factors
Acute biliary obstruction		From 5-10 to >10 norms	Increased aminotransferases precede cholestasis; usually rapid decline within 24-48 hours after obstruction
Alcoholic hepatitis		From 5-10 to >10 norms	AST/ALT>2

Sometimes Wilson-Konovalov disease and autoimmune hepatitis can manifest as acute hepatitis with increased levels of aminotransferases in the blood serum; much less often this is observed with liver lymphoma, Budd-Chiari syndrome, veno-occlusive disease and liver damage by certain viruses (herpes viruses). In most cases, ALT activity is higher than AST, with the exception of alcoholic liver disease and cirrhosis.

An AST/ALT ratio >2 in combination with an elevated GGT level most likely indicates an alcoholic etiology of liver damage. At the same time, an increase in ALT of more than 500 U/l, even despite the ratio of AST to ALT >2, indicates a non-alcoholic nature.

In chronic VH, as a rule, the AST/ALT ratio is 1. At the same time, an inverse ratio may indicate the development of liver cirrhosis.

Chronic organ ischemia, for example, in patients with chronic heart failure, shock leading to prolonged hypoxia, can also cause the development of fulminant hepatitis.

Budd-Chiari syndrome, Konovalov-Wilson disease, Reye syndrome, Sheehan syndrome are the most common reasons development of liver failure of non-viral etiology.

The clinical picture of fulminant hepatitis is growing rapidly; liver failure and hepatic encephalopathy determine the severity and, ultimately, the outcome of the disease. It is also characterized by massive necrosis of hepatocytes, leading to severe liver dysfunction. In this case, the unfavorable prognosis is due to the severity of the liver damage and the rapidity of development of characteristic morphological abnormalities, which do not leave time for the implementation of reparative processes. The pathogenetic basis for the formation of tissue hepatic and multiple organ damage is pro-inflammatory cytokines. Fulminant hepatitis is characterized by the early addition of symptoms of multiple organ failure, primarily cardiovascular, renal and respiratory. Complications often include bacterial sepsis and bleeding.

Treatment of patients with HH should be aimed at eliminating the underlying cause. At the liver level, therapeutic goals are to increase oxygen delivery and decrease oxygen exchange between the blood and liver cells. The main goal remains the restoration of systemic hemodynamics, which saturates the arterial blood with oxygen, increases cardiac output and increases blood pressure. Indeed, in case of circulatory failure, blood is redistributed to the main organs - the heart and brain, to the detriment of hepatosplanchic filling, and this redistribution can be regulated with the help of vasopressor drugs. It is necessary to ensure adequate systemic and organ blood flow, normalize the efficiency of alveolar-arterial oxygen transfer, and hemoglobin concentration. Clinical studies to find such drugs are ongoing.

The prognosis for GG is unfavorable. More than half of patients die during or shortly after their ICU stay. Hospital mortality is 56%. The 1-year survival rate is approximately 25%. Liver failure is not a direct cause of death. Most patients die from causes unrelated to HH.

To summarize a brief review of the literature, it should be noted that hypoxic hepatitis remains insufficiently studied. When establishing the main causes leading to hemodynamic disorders in the liver, significantly high activity of aminotransferases and serum LDH, hypoxic liver damage can be identified only in 50% of cases. However, high levels of aminotransferase and LDH activity are not specific criteria for GG. Difficulties in diagnosis also lie in the fact that due to the severity of the patient, due to the underlying disease, a histological examination is practically impossible to establish the morphological substrate of GG - centrilobular necrosis of the liver.

High prevalence of hypoxic liver damage among ICU patients, especially with cardiovascular pathology, contradictory and insufficiently studied data on pathogenetic mechanisms, lack of effective measures for therapeutic correction of impaired hemodynamic and metabolic processes in the patient’s body in general and, in particular, in the liver, high mortality among patients , designate GG as one of the pressing unsolved problems of modern hepatology, cardiology and resuscitation.

BIBLIOGRAPHY

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3 Fuhrmann V, Kneidinger N, Herkner H, et al. Hypoxic hepatitis: underlying conditions and risk factors of mortality in critically ill patients. //Intensive Care Med. – 2009. – 35. –P. 1397–13405.

4 Henrion J, Descamps O, Luwaert R, et al. Hypoxic hepatitis in patients with cardiac failure: incidence in a coronary care unit and measurement of hepatic blood flow. //J Hepatol 1994. – 21. – P. 696–703.

5 Raurich JM, Llompart-Pou JA, Ferreruela M, et al. Hypoxic hepatitis in critically ill patients: incidence, etiology and risk factors for mortality. //J Anesth 2011. – 25. – P. 50–56.

6 Henrion J, Schapira M, Luwaert R, Colin L, Delannoy A, Heller FR. Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. //Medicine (Baltimore). – 2003. – 82(6). – P.392-406.

7 Henrion J, Deltenre P, De Maeght S, Peny MO, Schapira M. Acute lower limb ischemia as a triggering condition in hypoxic hepatitis: a study of five cases. //J Clin Gastroenterol. – 2011. – 45(3). – P.274-277.

8 Birrer R, Takudan Y, Takara T. Hypoxic hepatopathy: pathophysiology and prognosis. //Intern Med. - 2007. - 46. - P. 1063–70.

9 Chang JP, Tan C-K. Serum albumin and male gender are independent predictors of mortality in patients with hypoxic hepatitis and can be used in a rognostic model to predict early in-patient mortality. //Hepatology 2008. - 48 (Suppl). – P. 447.

10 Henrion J, Minette P, Colin L, et al. Hypoxic hepatitis caused by acute exacerbation of chronic respiratory failure: a case-controlled, hemodynamic study of 17 cases. //Hepatology 1999. – 29. – P. 427–433.

11 Ucgun I, Ozakyol A, Metintas M, et al. Relationship between hypoxic hepatitis and cor pulmonale in patients treated in the respiratory ICU. //J Clin Pract 2005. - 59. - P. 1295 –1300.

12 Zhang H, Vincent J-L. Oxygen extraction is altered by endotoxin during tamponade-induced stagnant hypoxia in the dog. Circ Shock, 1993. - 40. - P. 168–176.;

13 Nelson DP, Samsel RW, Wood LD, Schumaker PT. Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia. //J Appl Physiol. – 1988. – 64. – P. 2410–2419.

14 Takala J, Ruokonen E. Blood flow and oxygen transport in septic shock.//Clin Intensive Care 1992; 3(Suppl to number 1): 24–27.

15 Edwards JD. Oxygen transport in cardiogenic and septic shock. //Crit Care Med. – 1991. – 19. – P. 658–663.

16 Jaeschke H, Farhood A. Neutrophils and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in the rat liver. // Am J Physiol. – 1991. – 260. – P. 355–362.

17 Henrion J. Ischemia/Reperfusion injury of the liver: pathophysiologic hypotheses and potential relevance to human hypoxic hepatitis. //Acta Gastroenterol Belg. - 2000. - 63. - P. 336–347.

18 Fuhrmann V, Jäger B, Zubkova A, Drolz A. Hypoxic hepatitis - epidemiology, pathophysiology and clinical management. //Wien Klin Wochenschr. – 2010. – 122(5-6). – P.129-139.

19 Ebert EC. Hypoxic liver injury. //Mayo Clin Proc. – 2006. – 81(9). – P.1232-1236.

20 Cassidy WM, Reynolds TB. Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury //J Clin Gastroenterol. - 1994. - 19. - P. 118–121.

21 Fuchs S, Bogomolski-Yahalom V, Paltiel O, Ackerman Z. Ischemic hepatitis. Clinical and laboratory observations of 34 patients. //J Clin Gastroenterol. – 1998. – 26. – P. 183–186.

22 Gitlin N, Serio KM. Ischemic hepatitis: widening horizons. //Am J Gastroenterol. - 1992. - 87. - P. 831–836.

23 Wallach HF, Popper H. Central necrosis of the liver. //Arch Pathol. – 1950. – 49. – P. 33–42.

24 Gore RM, Mathieu DG, White EM, et al. Passive hepatic congestion: cross-sectional imaging features. //A J R 1994. - 162. - P. 71–75.

25 Henriksson L, Hedman A, Johansson R, Lindstrom K. Ultrasound assessment of liver veins in congestive heart failure. //Acta Radiol. – 1982. – 23. – P. 361–363.

26 Karpov I.A., Yagovdik-Telezhnaya E.N. Fulminant hepatitis Medical news. – 2003. – No. 7. – pp. 64-66.

27 Henrion. Hypoxic hepatitis: the point of view of the clinician. //Acta Gastroenterol Belg. – 2007. -70(2). – P.214-216.

28 Dubin A, Estenssoro E, Murios G, et al. Effects of haemorrhage on gastrointestinal oxygenation.//Intensive Care Med. – 2001. – 27. – P. 1931–1936.

29 Deitch EA, Xu D, Kaise VL. Role of the gut in the development of injury and shock induced SIRS and MODS: the gut-lymph hypothesis, a review. //Front Biosci. – 2006. – 11. – P. 520–528.

30 Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. //Crit Care Med. – 2008. – 36. – P. 296–327.

31 Asfar P, De Bakker D, Meier-Hellemann A. et al. Clinical review: influence of Vasoactive and other therapies on intestinal and hepatic circulations in patients with septic shock. //Crit Care Med. – 2004. – 8. – P. 170–179.

B.S.ISKAKOV, S.G.ENOKYAN, A.M.KENZHEBAEV, B.S.TOKHTAROV,

T.M. MURTAZALIEVA

HYPOXYL HEPATITIS: DIAGNOSTICS

(adebi sholu)

Tү yin: Bul adebi sholu hepatology bir ozekti maselesine arnalgan - hypoxialyk hepatitis diagnosing samen emdeuine. Kan sary suyndagi aminetransferazalardyn belsendiliginin zhogarlauyna sepe bolatyn bauyrdyn orta boligi zhasushalaryn nekrozymen bauyrdyn hemodynamics based on the old mechanism of corsetilgen .

Tү withө zder: Hypoxial hepatitis, kan sarysunyn aminotransferases, bauyrdyn orta bolіgі zhasushalaryn necrosis.

B.ISKAKOV, S.ENOKYAN, A.KENZHEBAYEV, B.TOKHTAROV,

T.M.MURTASALIEVA

HYPOXEMIC HEPATITIS: DIFFICULTIES of DIAGNOSTICS AND TREATMENT PROBLEM

(literature review)

Resume: The review of literature is devoted to one of the actual problems of hepatology – to diagnostics and treatment of hypoxemic hepatitis. The reasons and mechanisms of haemo dynamic violations in a liver, bringing to a centrilobular liver cell necrosis and to essential increase of activity of aminotransferases of blood are stated.

Keywords: hypoxemic hepatitis, blood aminotransferases, centrilobular liver cell necrosis

"�_Vs-���me-font:minor-latin;mso-hansi-theme-font:minor-latin;font-weight: normal;mso-bidi-font-weight:bold'>bleeding from acute ulcers is often referred to , as for peptic ulcers, and the same treatment and tactical settings are applied to them. According to international clinical guidelines and expert consensus, in this situation it is more justified to replace, for example, ASA with clopidogrel or additionally prescribe proton pump inhibitors (PPIs). Thus, the center of the system for the prevention of gastrointestinal tract in patients with coronary artery disease who have been taking AAT for a long time is the prediction of possible EJP of GDZ by searching for predictors of a high risk of gastrointestinal tract bleeding, and, if they are identified, prescribing timely and adequate antisecretory therapy to patients.

It has been established that antisecretory therapy, which allows increasing the pH of the stomach contents to 5.0-7.0 units. during the period of active influence of risk factors, reduces the likelihood of gastrointestinal tract in patients by at least 50% and allows the initiation of active epithelization of the EJP of the gastrointestinal tract. Adequate antisecretory therapy allows you to solve the following problems:

stop active bleeding;

ü eliminate the symptoms of acute EP;

ü prevent recurrent bleeding.

Neutralization of the acidic contents of the stomach can be achieved by administering any antacids (magnesium and aluminum hydroxides), antisecretory drugs PPIs, histamine H2 receptor blockers or sucralfate, which block the lysis of fresh blood clots and provide complete vascular-platelet hemostasis,

Our patients received conventional therapy for AMI, including nitrates, cardioselective β-blockers, and calcium antagonists. In patients with EUP, depending on the severity of bleeding, antiplatelet agents, anticoagulants and angiotensin-converting enzyme (ACE) inhibitors, which can suppress the synthesis of erythropoietin in the kidneys and block its erythropoietic effect at the bone marrow level, were excluded (or doses were reduced).

The use of PPIs and antacids, along with generally accepted conservative hemostatic therapy, had a positive therapeutic effect and made it possible to stop bleeding in patients with AMI. However, it should be borne in mind that many PPIs inhibit the activity of “cardiac” drugs, which can lead to a decrease in the effectiveness of treatment of AMI. Preparations from the pantoprozole group, which can be used parenterally and in tablet forms, do not have these negative properties.

Conclusion

Thus, the high frequency of stressful EJP of gastrointestinal tract and gastrointestinal tract in patients with AMI requires obligatory early diagnosis and timely adequate treatment and preventive measures. Accurate assessment of gastrointestinal tract risk factors and timely clinical and endoscopic diagnosis of lesions of the gastrointestinal tract, adequate hemostatic and antisecretory therapy determine a favorable prognosis in patients with acute forms of coronary artery disease.

Risk factors for gastrointestinal tract in patients with AMI are elderly and senile age, male gender, ulcer history, use of AAT, interventional treatment methods (stenting of coronary vessels, CABG surgery).

BIBLIOGRAPHY

1 Kolobov S.V., Zayratiants O.V., Poputchikova E.A. Morphological features of acute erosions and gastric ulcers in patients with myocardial infarction during treatment with the drug Losek // Morphological Gazette. - 2002. - No. 3–4. – P.800–882.

2 Vertkin A.L., Zairatyants O.V., Vovk E.I. Damage to the stomach and duodenum in patients with acute coronary syndrome // Attending physician. – 2005. – No. 1. – P.66-70.

3 Sumarokov A.B., Buryachkovskaya L.I., Teacher I.A. Bleeding in patients with coronary heart disease during antiplatelet therapy // Cardio Somatics. — 2011. — No. 3. – P.29–35.

4 Shilov A.M., Osiya A.O. Coronary heart disease, gastrointestinal bleeding and Iron-deficiency anemia: principles of diagnosis and treatment // Attending physician. – 2012. – No. 5. – P.35-39.

5 Siluyanov S.V., Smirnova G.O., Luchinkin I.G. Bleeding from acute ulcers of the stomach and duodenum in clinical practice // Russian medical journal. - 2009. - No. 5. - P. 8.

6 Cook D.J., Reeve B.K. , Guyatt G.H. et al: Stress ulcer prophylaxis in critically ill patients: Resolving discordant meta–analyses. JAMA 1996. – 275. – P. 308–314.

7 Gelfand B.V., Guryanov V.A., Martynov A.N. and others. Prevention of stress damage to the gastrointestinal tract in patients in critical conditions // Consilium Medicum. - 2005. - No. 6. – P.464.

8 Vertkin A.L., Frolova Yu.V., Petrik E.A. and others. Prevention of gastrointestinal bleeding during exacerbation of coronary heart disease // Consilium Medicum. – 2008. – No. 2. – P.56.

B.S.ISKAKOV 1, K.A.SEITBEKOV 2, V.I.LAPIN 2, A.M.KENZHEBAEV 2, A.E.MAKHUAYUNOV 2

ZHEDEL MYOCARDIUM INFARCTIS BAR SCIENCE GASTRODUODENALDS KANG KETUDIN YKPALDARYN

Tү yin: Zhedel myocardial infarction bar science shiryshty kabatynyn erosivti zhane oyik zharala zakymdaluy gastroduodenals aimaktyn ischemia synonymous with microcirculation synonymous with old men baikalady. Bul naukastarda askazan-ishek zholdarynan kan ketudin qauipti ykpaldara: anamnesis of heat aura pain, anti-inflammatory therapy, invasive cardioversion.

Tү withө zder: myocardial infarction, erosive zhane oyyk zhary zakymdalu, as kazan-ishek zholdarynan kan ketu.

B.ISKAKOV 1, K.SEYTBEKOV 2, V.LAPIN 2, A.KENZHEBAYEV 2, A.E.MAKHUAYUNOV 2

ASSESSMENT OF RISK OF GASTRODUODENAL BLEEDING AT PATIENTS WITH THE ACUTE MYOCARDIAL INFARCTION

Resume: Patients with a sharp myocardial infarction have erosive and ulcer damages of a mucous membrane, are caused by ischemia and violation of microcirculation of a gastroduodenal zone. Risk factors of gastrointestinal bleedings at this category of patients are: “ulcer” anamnesis, antiaggregant therapy, invasive cardioversion.

Keywords: myocardial infarction, erosive and ulcer damages, gastrointestinal bleedings.

pport� 8ks>�`�yle='font-size:9.0pt;font-family:"Calibri","sans-serif";mso-ascii-theme-font: minor-latin;mso-hansi-theme-font :minor-latin;mso-bidi-font-family:Calibri; mso-bidi-theme-font:minor-latin;color:black;letter-spacing:.2pt’>5 Zolotarev Yu.G. Try to be healthy. – St. Petersburg: Dilya, 1999. – P.240.

A.ZULKHAZHI, A.K. KATARBAEV, I.Z. MAMBETOVA, A.B. SMAGULOVA, A.ZH. ZHADIKOVA

INFLUENCE OF HEALTH HARDENING ON CLINICAL AND IMMUNOLOGICAL INDICATORS IN PRESCHOOL CHILDREN

Summary: We studied the effect of health-improving hardening after 3, 6, 12 months on the clinical and immunological parameters of 32 children preschool age. Regular and long-term health hardening improved immunological parameters in children: the level of Ig G, IgA, IgM, total T-lymphocytes and phagocytosis increased, and the level of IgE decreased. When carrying out hardening measures, in the first 3 months children may experience an increase in respiratory morbidity, but later there is an improvement in physical development indicators and a decrease in the acute morbidity index.

Keywords: immunity, hardening, preschool children.

A.ZULKHAZHY, A.K.KATARBAYEV, I.Z.MAMBETOVA, A.B.SMAGULOVA, A.ZH.ZHADYKOVA

INFLUENCE OF IMPROVING HARDENING ON CLINIKO-IMMUNOLOGICAL INDICATORS AT CHILDREN OF PRESCHOOL AGE

Resume: We studied the influence of improving hardening through 3, 6, 12 months on clinical-immunological indicators of 32 children of preschool age. The regular and long improving hardening raised immunological indicators at children: the level of Ig G, IgA, IGM, the general T-lymphocytes and phagocytosis, the IgE level decreased. When tempering actions have been carried out, the first 3 months it seems the possibility of increasing respiratory incidence at children, but further improvement of physical indicators of development and decrease in an index of sharp incidence is noted.

Keywords: immunity, hardening, children of preschool age.

The close connection between cardiac and liver dysfunction has been studied by doctors of various specialties for more than two centuries. Nevertheless, the complexity and features of this association still attract active interest among scientists, and the results of the relatively few studies are often very contradictory, which can be explained by several reasons.

For example, the etiology of heart failure (HF) has changed over time. If previously HF was mainly associated with rheumatic valve disease, now it is mainly associated with ischemic cardiomyopathy. In addition, HF outcomes have improved dramatically due to the effectiveness of pharmacotherapy and the widespread availability of heart transplantation. Therefore, cardiac cirrhosis (LC), which was previously considered as a paradigm for the liver-HF association, is now rare.

Due to the fact that heart failure is systemic chronic disease, when present, it affects many organs, including the liver and kidneys. The characteristics of the liver vascular system and its high metabolic activity make it highly vulnerable to disturbances of systemic hemodynamics and initiate many molecular and hemodynamic changes.

Hepatic dysfunction (LD) is common in patients with HF (according to various authors, in 15-65% of cases) and closely correlates with hemodynamic parameters.

Currently, systematization of combined pathology of the heart and liver is carried out depending on the primary localization pathological process (Table 1).

In this review, we will focus on the main liver pathology caused by diseases of the cardiovascular system, primarily on congestive hepatopathy (CH) and cardiogenic ischemic hepatitis, as well as heart pathology formed against the background of liver diseases (cirrhotic cardiomyopathy).

Congestive cardiac hepatopathy

MH (“congestive liver”) includes a spectrum of clinical, biochemical, histological and hemodynamic abnormalities associated with chronic liver injury due to right ventricular/right atrial HF or any other cause of increased central venous pressure, including biventricular HF due to coronary artery disease or cardiomyopathy, severe pulmonary hypertension or cor pulmonale, constrictive pericarditis, and valvulopathies such as mitral stenosis and tricuspid regurgitation. This condition was first described in detail by the eminent hepatologist Sheila Sherlock in 1951.

The main mechanisms for the formation of MH are the overflow of blood into the central veins and the central part of the hepatic lobules, the development of local hypoxia in them, leading to the occurrence of dystrophic and atrophic changes, and subsequently to necrosis of hepatocytes, collagen synthesis and the development of fibrosis. In this case, the pressure in the portal vein does not exceed the pressure in the inferior and superior vena cava, as a result of which portocaval anastomoses develop extremely rarely. The severity and characteristics of liver injury depend on the vessels involved, the severity of venous stasis, and decreased perfusion. The first description of "nutmeg liver" was made by Kiernan and Mallory, who showed central congestion and focal necrosis of the liver associated with impaired blood circulation in the liver.

Clinical manifestations of MH depend on the rate of increase in heart failure: if venous congestion in the liver develops quickly, then the clinic will be dominated by complaints of acute pain in the right hypochondrium associated with stretching of the liver capsule, often simulating acute surgical pathology. If HF develops slowly, over several months or years, then its manifestations will dominate and mask the symptoms of MH. The latter option is much more common, therefore, in the vast majority of cases, MH is asymptomatic or oligosymptomatic. In such cases, patients complain of shortness of breath, orthopnea and cardialgia, practically ignoring the heaviness in the right hypochondrium and discoloration of the skin, since jaundice and pain are low-intensity. Objective signs of MH (an enlarged, dense and painful liver with a hard and smooth edge on palpation) are determined against the background of dilation of the jugular veins, the appearance of hepatojugular reflux and symptoms of HF.

A distinctive feature of MH is that the severity of its symptoms varies depending on the state of central hemodynamics and the effectiveness of treatment of the underlying cause of HF. Adequate therapy for HF leads to a rapid reduction in liver size and the elimination of clinical signs of MH. Another characteristic feature of MH is the absence of signs of portal hypertension (varicose veins of the esophagus and stomach, “caput medusa”) and the so-called minor signs of cirrhosis (palmar erythema, telangiectasia, “lacquered” tongue). In severe or refractory HF, MH symptoms progress, and cardiac cirrhosis gradually develops, accompanied by the appearance of ascites and splenomegaly. The liver becomes dense, its edge becomes sharp, and its size remains constant and does not depend on the effectiveness of treatment for heart failure.

In most cases with mild HF, the levels of serum transaminases (AlAt, AsAt) and bilirubin do not exceed normal indicators However, in severe heart failure, the activity of markers of cytolytic and cholestatic syndromes, as well as bilirubin levels, usually increase. In approximately 30% of patients with MH, transaminase levels are 2-3 times higher than normal. A significant decrease in ejection fraction (EF) is usually accompanied by a significant increase in serum transaminases due to secondary liver ischemia. Some patients have a cholestatic component, reflected in an increase in the level of γ-glutamyltransferase (GGT) and alkaline phosphatase, which are independent factors of venous stagnation and decreased perfusion.

In particular, elevated GGT levels are not only associated with more severe HF class, lower EF, and increased B-type natriuretic hormone levels, but are also an independent predictor of death and heart transplantation. Hyperbilirubinemia is not typical for MH, but in severe HF there may be a slight increase in the level of total and indirect bilirubin, which is considered an unfavorable prognostic sign. With the development of cardiac cirrhosis, dysproteinemia appears (decrease in the concentration of total protein and albumin, increase in the level of α 2 - and γ-globulins), in 75% of cases the prothrombin time increases. Characteristic features Ascites developing as a result of MH and cardiac cirrhosis are a high protein content in the ascitic fluid (>2.5 g/dl) and an increase in the value of the serum-ascitic albumin gradient (>1.1 g/dl). Many patients, especially those with severe HF, have elevated uric acid levels, which are now considered a marker of inflammation, metabolic disorders, oxidative stress, endothelial dysfunction and possibly myocardial damage. Hyperuricemia may result from decreased renal perfusion and urate excretion and correlates well with higher pulmonary artery and right ventricular pressures and clinical signs of congestive heart failure.

To confirm the diagnosis of MH, it is necessary to exclude other causes of liver damage, in particular, to exclude the presence of viral hepatitis B and C using enzyme immunoassay or polymerase chain reaction, as well as alcoholic liver disease, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and drug-induced liver injury. It should be remembered that many medications used to treat cardiovascular pathology are metabolized in the liver and may adversely affect it (Table 2).

All patients undergo echocardiography and ultrasound with Dopplerography of the liver vessels, which clearly reveals venous congestion (dilated hepatic veins merging into the dilated inferior vena cava), usually in the absence of portal hypertension (portal vein diameter<13 мм), а также отек стенки желчного пузыря (при развитии кардиального цирроза). Кроме того, допплерография сосудов печени позволяет исключить альтернативные диагнозы, такие как синдром Бадда-Киари.

In severe diagnostic cases, laparoscopy is performed to verify MH, during which an enlarged liver with a rounded edge and a thickened capsule is visualized, and the surface of the liver has a characteristic “nutmeg” appearance with the presence of dark red and brown-yellow areas.

Routine liver biopsy is not indicated; it is mainly performed in candidates for heart transplantation in the presence of ascites to exclude cirrhosis. Histologically, MH is characterized by venous congestion in the sinusoid region, congestion of the central parts of the lobule, expansion of the spaces of Disse, atrophy and necrosis of the centrilobular zone. A characteristic sign of MH is the absence of pathological changes at the periphery of the lobule, since venous congestion does not reach this zone, and the influx of arterial blood from the hepatic artery protects hepatocytes from damage and leads to their hypertrophy. Also a characteristic feature of MH is the reversibility of venous congestion, and sometimes fibrosis, provided that HF ​​is adequately treated.

The cornerstone of MH treatment is effective etiotropic and pathogenetic treatment of concomitant cardiovascular pathology and pulmonary heart failure, which is accompanied by rapid regression of the clinical and biochemical manifestations of MH, which was first described by Jolliffe et al. back in the early 1930s. When prescribing ACE inhibitors, which are first-line drugs for the treatment of heart failure, it should be remembered that almost all of them (with the exception of lisinopril) are metabolized in the liver, and in the presence of MH and PD, delayed transformation of the prodrug into the active substance and inactivation of the active drug may occur, which requires frequent dosage monitoring. This also applies to angiotensin II receptor inhibitors, with the exception of valsartan and irbesartan, as well as most non-selective and selective beta-blockers. Loop diuretics (furosemide, torsemide) in most cases effectively reduce venous congestion in the liver, helping to reduce and eliminate ascites and jaundice. However, these drugs in MH should be used with caution to avoid dehydration, hypotension and liver ischemia, including necrosis of the 3rd zone of the hepatic lobule. If it is necessary to use digoxin, it should also be prescribed carefully and in a low dose, since in patients with MH the likelihood of its toxic effects increases.

Anticoagulants should also be used with extreme caution, since patients with MH have an increased prothrombin time and often have increased sensitivity to warfarin. If it is necessary to prescribe amiodarone, despite the fact that it undergoes extensive hepatic metabolism, a dose reduction is usually not required. Statins themselves can cause hypertransaminasemia, but they are contraindicated only when AST and ALT levels increase more than 3 times.

In refractory cases, laparocentesis is used, but it should be remembered that it is accompanied by protein loss and can worsen the nutritional status of patients with HF, which is already impaired. Transjugular intrahepatic shunting or peritoneal-vascular shunting is contraindicated in such patients, since it always leads to worsening of the HF class.

Patients refractory to medical treatment are candidates for heart transplantation or implantation of a left ventricular (LV) assist device.
Prescribing hepatoprotectors to patients with MH may be advisable only in cases of severe cytolytic syndrome and the development of cardiac cirrhosis.

MH itself rarely progresses to classic liver failure and is the immediate cause of death. In the vast majority of cases, death occurs due to underlying cardiovascular pathology.
In some cases, in patients with MH, it may be advisable to prescribe hepatoprotectors.

Hepatoprotectors that affect the structure and function of hepatocyte cells are the basis of pathogenetic therapy for liver pathology. The action of hepatoprotectors is aimed at restoring homeostasis in the liver, increasing its resistance to the action of pathogenic factors, normalizing functional activity and stimulating regeneration processes in the liver. There are currently a large number of drugs on the pharmaceutical market presented as hepatoprotectors, and there is an opinion that any of them is a priori effective and safe. In fact, the clinical effectiveness of many well-known and long-used hepatoprotectors has not been proven. Moreover, some of them are potentially harmful and can have a hepatotoxic effect. This is especially true for hepatoprotectors of plant origin and numerous widely advertised nutritional supplements.

For many hepatoprotectors, only a few randomized clinical trials have been conducted (or none at all), and these studies have found the absence or weak effect of such drugs on important parameters (disappearance of viremia, histological picture and survival), despite a slight decrease in the activity of liver enzymes and improvement subjective indicators. Hepatoprotectors such as ursodeoxycholic acid (UDCA), essential phospholipids, and amino acid preparations (ademetionine, ornithine aspartate) have been proven to be effective to varying degrees. Silymarin preparations should be considered as hepatoprotectors with supposed but unproven effectiveness that can be used for certain conditions. Other herbal hepatoprotectors cannot yet be recommended for widespread use in chronic liver diseases, since their effectiveness has not been proven and requires further study in carefully designed randomized trials.

In the treatment of liver diseases, UDCA, a hydrophilic non-toxic tertiary bile acid formed under the action of bacterial enzymes from 7-keto-lithocholic acid, which enters the liver from the small intestine, is of great importance from drugs that have an evidence base of effectiveness and safety.

The mechanisms of action of UDCA are diverse and have not yet been fully studied. Experimental and clinical data accumulated to date indicate that UDCA has hepatoprotective, anticholestatic, immunomodulatory, hypocholesterolemic, litholytic and antiapoptotic effects. UDCA is used for acute and chronic hepatitis of various etiologies, non-alcoholic steatohepatitis, primary biliary cirrhosis, hepatopathy of pregnant women, liver diseases accompanied or caused by cholestasis.

Given the topic addressed in this article, it is interesting to note that UDCA has a positive effect on the ratio of serum markers of fibrogenesis and fibrolysis. Thus, in a study by Holoman (2000), the use of UDCA decreased the serum concentration of N-terminal peptide of type 3 collagen and matrix metalloproteinases and simultaneously increased the level of their tissue inhibitors. Long-term administration of UDCA at a dose of 12-15 mg/kg/day for 6-12 months was accompanied by a significant improvement in the histological picture and biochemical liver parameters.

Thus, the decision to choose a hepatoprotector should be made based on the same principles as when selecting cardiac drugs, that is, on the principles of evidence-based medicine.

Cardiogenic ischemic hepatitis

Cardiogenic ischemic hepatitis (CAH), or “shock liver,” is a hypoxic liver injury that develops with inadequate liver perfusion and leads to necrosis of hepatocytes in the centrilobular zone. The formation of CAG is possible only with a combination of several pathological factors (significant hypoperfusion, impaired functioning of vascular collaterals, inability of the liver to increase oxygen consumption), since the peculiarities of the blood supply to the liver initially prevent the development of its ischemic damage. A combination of these factors occurs in acute heart failure, predominantly right ventricular, induced by acute myocardial infarction, acute rhythm disturbances, pulmonary embolism, acute cor pulmonale, as well as blood loss, dissecting aortic aneurysm, prolonged compartment syndrome, septic or burn shock, heat stroke, carbon dioxide poisoning, etc. The incidence of CAG in intensive care patients ranges from 11 to 22%. In 70% of cases, the main cause of CAH is cardiovascular pathology, in 30% - acute respiratory failure, sepsis and other rarer conditions.

The diagnosis of CAG is based on three main criteria: 1) rapid development of liver pathology against the background of typical manifestations of cardiogenic or circulatory shock; 2) a significant (>20 normal), but quickly reversible increase in the level of serum transaminases; 3) the absence of other possible causes of liver damage. Clinically, CAG manifests itself by the appearance of severe shortness of breath, pain in the right hypochondrium, and an increase in the size of the liver. In rare cases, jaundice, oliguria, signs of hepatic encephalopathy, up to hepatic coma. Characteristic changes in liver function tests appear 12-24 hours after an acute cardiovascular event and are manifested by a sharp (20 times or more) increase in the levels of AST, ALT and lactate dehydrogenase, less often - hyperbilirubinemia and coagulopathy (extension of prothrombin time, decrease in fibrinogen levels, thrombocytopenia). When the provoking factor is eliminated, the indicators return to normal within 5-10 days.

The main treatment strategy for CAG is to restore adequate liver perfusion through anti-shock measures and mandatory administration of drugs that have a positive inotropic effect, such as dopamine. With the development of hepatic encephalopathy, L-arginine, L-ornithine-L-aspartate, and antibiotics are used. The prognosis for coronary angiography is determined by the patient's cardiovascular status, since mortality in this disease is determined by the underlying disease.

Cirrhotic cardiomyopathy

The term “cirrhotic cardiomyopathy” (CD) is commonly understood as a decrease in the contractile function of the heart, which is observed in some patients with cirrhosis. Initial studies in the early 1950s documented the existence of a hyperdynamic hemodynamic pattern in cirrhosis, manifested by increased cardiac output and decreased systemic vascular resistance. H.J. Kowalski was the first to report that patients with Laennec's cirrhosis had abnormal cardiovascular function and QT interval prolongation. Early histologic studies demonstrated myocardial hypertrophy and ultrastructural changes, including cardiomyocyte edema, fibrosis, exudation, nuclear vacuolization, and unusual pigmentation.

The size of the left atrium and LV in patients with cirrhosis is normal or slightly enlarged, which is associated with hemodynamic dysfunction. Many patients with cirrhosis experience shortness of breath, fluid retention, and limited physical activity.

The main mechanisms for the development of CD are chronic alcoholism and hyperdynamic type of hemodynamics. Due to alcohol abuse, the synthesis of contractile proteins and the formation of the bond of cardiac proteins with toxic acetaldehyde deteriorate, which contributes to the deterioration of cardiac function. With the hyperdynamic type of hemodynamics, the heart is constantly overloaded due to increased cardiac output and circulating blood volume, which also leads to disruption of its contractile function. Other potential mechanisms for the deterioration of cardiac function in cirrhosis are increased production of cardiodepressive substances such as endotoxins, endothelins, cytokines and bile acids, as well as disruption of the regulatory function of β-receptors, the functioning of membrane potassium and calcium channels, and activation of the cannabinoid system.

Physical exercise, pharmacological stress and therapeutic measures can affect changes in pressure in the cavities of the heart. In particular, in patients with cirrhosis, end-diastolic pressure increases and ejection fraction decreases during exercise, indicating an abnormal ventricular response to increased ventricular filling pressure. Aerobic exercise and maximum heart rate should be lower in most patients with cirrhosis than in patients without cirrhosis. Abnormal LV diastolic function, caused by decreased LV relaxation, is reflected in impaired ventricular filling. Transmitral blood flow changes, with an increased contribution of the atria to the late phase of LV filling. The pathophysiological basis of diastolic dysfunction in cirrhosis is increased myocardial wall stiffness, most likely due to a combination of mild myocardial hypertrophy, fibrosis, and subendothelial edema.

The main electrocardiographic change in cirrhosis is the prolongation of the QT interval, corrected for heart rate, which is observed in approximately every second patient with cirrhosis and does not depend on its etiology. In patients with alcoholic cirrhosis, prolongation of the QT interval is associated with an increased risk of sudden cardiac death. Prolongation of the QT interval in cirrhosis is also associated with the presence of cardiac autonomic dysfunction, primarily decreased baroreceptor sensitivity, and is partially reversible after liver transplantation.

There is currently no specific treatment for LV dysfunction associated with cirrhosis. Therefore, therapy is carried out according to general rules by limiting salt, taking diuretics and reducing afterload. The administration of cardiac glycosides does not significantly improve the contractile function of the heart in CD, and therefore they are not considered as significant drugs for its treatment. Particular caution should be exercised during and after stressful events, most notably surgery, including transjugular intrahepatic bypass and liver transplantation. The effect of a prolonged QT interval on mortality in patients with cirrhosis is the subject of future research. Fundamentally new methods of treating CD, such as anti-cytokine therapy, are also of great interest.

In conclusion, we note that the issues discussed in this article have important clinical significance both for gastroenterologists and cardiologists. In particular, gastroenterologists consulting patients with “unexplained” elevated transaminases or so-called idiopathic cirrhosis should always be aware of the potential role of heart failure, even latent heart failure, and order appropriate cardiac evaluation. In turn, cardiologists monitoring patients with HF who have concomitant PD should consider the latter as a group increased risk and treat more aggressively. We hope that further research and increased identification of PD in HF will help improve the overall understanding of the disease process, as well as treatment and clinical outcomes in this disease.

The list of references is in the editorial office

MORPHOLOGY, PATHOLOGY

UDC 616.342-008.1

PATHOGENESIS OF LIVER ISCHEMIA-REPERFUSION

(literature review)

I.F. Yaroshenko, T.Yu. Kalanchina

Department of Pathological Physiology VolSMU

For radical treatment of severe liver damage, liver transplantation and partial liver resection are increasingly used in world practice. During surgical operations, temporary compression of the hepatoduodenal ligament with the blood vessels passing through it is possible. In all these cases, liver ischemia occurs for some duration. Impaired blood supply to the liver also occurs during shocks of various etiologies, including hemorrhagic, burn, etc. At various intervals, blood supply to the liver is restored due to reperfusion. However, ischemia-reperfusion (IR) leads to severe complications: graft rejection, inflammatory processes and even necrotic damage to hepatocytes, ultimately deciding the fate of the affected organ.

Liver ischemia and subsequent reperfusion were modeled in various animals (rats, rabbits, pigs) and studied in humans during surgery. The methods and duration of ischemia and reperfusion varied. So, V.V. Zinchuk et al. (2003) the hepatic artery in rabbits was ligated for 30 min, while the reperfusion period lasted 120 min; P. Liu et al. (2000) ischemicized the left and middle lobes of the liver for 30 minutes, followed by reperfusion for 4 hours; A. Morisue et al.

(2003) liver ischemia was induced in Wistar rats for 30 min followed by reperfusion; M.Y. Seo and S.M. Lee (2002) modeled ischemia for 60 min and reperfusion for 5 h in rats; H. Yuzawa et al. (2005) clamped the porcine hepatic artery and portal vein for 45 min, followed by reperfusion; R.S. Koti et al. (2005) subjected rats to 45 min of lobar liver ischemia followed by 2-h reperfusion; J.C. Yang et al.

(2004) induced hepatic artery occlusion in rats for 30 min, followed by 2- and 6-hour reperfusion; M. Ohmori et al. (2005) performed occlusion of the hepatic artery and portal vein for 60 minutes followed by reperfusion; A. Hirakawa et al. (2003) caused 30 and 120 min ischemia

liver followed by 6-hour reperfusion; S. Hyu^j a1. (2000) clamped the afferent vessels of the rat liver for 20, 40, 60, 90 min. Restoration of blood flow occurred after removal of the terminal; I.8. Coy a1. (2005) subjected rats to 45 minutes of lobar ischemia of the liver followed by 2 hours of reperfusion; O. Erdogan e! a1. (2001) used 30- and 45-minute liver ischemia in rats followed by 60-minute reperfusion; I. LaShep e! a1. (2003) performed occlusion of the portal vein and hepatic artery for 30 minutes, followed by reperfusion; B. 01akoshSH18 e! a1. (2003) reproduced 60-minute total liver ischemia and 120-minute reperfusion.

K. Yamagami e! a1. (2002) studied the mechanisms of impairment in IR using warm ischemia. All rats were exposed to 42°C for 30 min followed by reperfusion. A. Khandoga e! a1. (2003) studied disturbances in thermal IR in mice.

When the afferent vessels of the liver were clamped for 20, 40, 60, and 90 minutes, blood flow was restored after removal of the clamp. At the same time, ultrastructural changes occurred in sinusoidal endothelial cells. After 20 or 40 min of ischemia, fenestration of endothelial cells increased and became honeycomb-like. However, reperfusion after 120 min led to restoration of cell structure. After 60 or 90 min of ischemia, endothelial cells were destroyed and the perikaryon tended to desquamate. Reperfusion after 120 min did not lead to cell recovery, but caused increased damage and irreversible changes. The hepatic sinusoids were filled with large numbers of blood cells and vesicles derived from hepatocytes. Mitochondrial edema and hepatocellular vesicles were noted. Severe circulatory disorders were observed.

The consequence of damage to hepatocytes is dysfunction of mitochondria. Such studies were conducted to study warm ischemia in rats. Warm ischemia was reproduced under

general anesthesia of animals by immersing them in a water bath at a temperature of 42 ° C for 15 minutes, followed by reperfusion for 60 minutes. The authors recorded a violation of the integrity of mitochondrial membranes and the loss of their ability to produce energy.

Markers of liver damage in IR are alanine transaminase, aspartate transaminase, hyaluronic acid, glutathione S-transferase, γ-glutamyl transpeptidase, pseudocholinesterase, a-glutathione-8-transferase, reducing and oxygenating glutathione, released into the blood during the destruction of hepatocytes. procalcitonin, IL-6.

The pathogenesis of damage in liver IR is a multifactorial process. It includes: 1) disturbance of calcium homeostasis; 2) generation of reactive oxygen and nitrogen substances; 3) microcirculation disorders; 4) activation of Kupffer cells.

Liver damage in IR consists of two phases: intracellular and extracellular. Ca2-dependent reactions play an important role as a triggering factor in the first phase, while in the late phase the generation of biologically active substances plays a predominant role.

During the early period of reperfusion, the content of oxygen free radicals and cytokines increases, the generation of which occurs in Kupffer cells. Generation of superoxide anion radical occurs 6 and 24 hours after reperfusion. This leads to the expression of inducible forms of nitric oxide synthase through the activation of nuclear transcription of factor kappa B in hepatocytes and Kupffer cells. Reactive oxygen substances in liver IR are generated with the participation of xanthine oxidase. Free oxygen radicals are removed by antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase. It has been proven that an increase in free radicals in the liver leads to an increase in the blood levels of alanine aminotransferase, aspartate aminotransferase, malondialdehyde (MDA), an increase in inflammatory infiltrates in the sinusoids, nuclear fragmentation, cell shrinkage and chromatin mass with the formation of apoptotic bodies in apoptotic cells. It has been shown that impaired liver protection against oxidative stress is associated with a loss of glutathione-synthesizing capacity of the liver. After 4 and 6 hours from the start of reperfusion, the production of nitric oxide increases.

A large number of cytokines are involved in the process of cell damage in liver IR. In liver IR, cytokines are produced by Kupffer cells. They also produce chemokines, i.e. cytokines with chemoattractant properties, important for the destruction of neutrophils and partial damage to hepatocytes. IL-beta production by Kupffer cells increases 6.48-72 hours after reperfusion. Protein-1 plays a major role in the attraction and activation of neutrophils in liver IR, which is

acting as a chemoattractant for monocytes. Among cytokines, IL-12 plays an important role in liver damage. The critical role of tumor necrosis factor (TNF-a) in the development of the pathological process in liver IR has been proven. Its action is associated with the activation of neutrophils, as well as with an increase in microthrombosis in the vessels of the liver. TNF production increases within 6-24 hours after liver ischemia. During ischemia followed by reperfusion, an increase in IL-6 was detected in arterial and venous blood. An important regulator of the inflammatory response of the liver in IR is the proinflammatory cytokine Peroxime proliferator, which activates a-receptors. At the same time, the degree of damage to hepatocytes is reduced by IL-18 and IL-13, a cytokine that causes suppression of the production of proinflammatory mediators by macrophages. In experiments on mice, it was shown that after 90 minutes of ischemia followed by liver reperfusion, IL-13 reduced the expression of TNF-a, the production of inflammatory protein-2 leading to the transport of neutrophils to the liver, hepatocellular edema and damage to hepatocytes. Colony-stimulating factor and macrophage colony-stimulating factor are involved in the pathogenesis of IR liver damage. In this case, cytokines and hyaluronic acid can be indicators of the early phase of liver damage during hepatectomy in humans. The cytokine, hepatocyte growth factor, has a cytoprotective effect. It prevents leukocyte infiltration and activates hepatocyte proliferation.

Impaired microcirculation is the main target of liver damage in IR. The consequence of impaired microcirculation is the pathology of the liver parenchyma, a lack of microcirculatory perfusion, leading to no-reflow and an inflammatory response associated with reperfusion, which includes activation and dysfunction of leukocytes and Kupffer cells (reperfusion paradox). No-reflow in sinusoids is caused by swelling of endothelial cells and intravascular hemoconcentration, as well as a deterioration in the balance between endothelin and NO. The reperfusion paradox is associated 1) with the release and action of pro-inflammatory cytokines (TNF-a, IL-1) and oxygen radicals; 2) increased regulation of endothelial and leukocyte adhesion molecules (selectin, ß-integrin, ICAM-1); 3) interaction of leukocytes with endothelium in the microvessels of the liver. Of course, impaired microcirculation is associated with a shift in hemocoagulation.

As already indicated, endothelin plays an important role in microcirculatory disorders in liver IR. The role of endothelin in this process was clarified using non-selective blockade of endothelin receptors - bosentan. Blockade of the endothelin system during IR has been assessed by various methods. It has been shown that the release of endothelin leads to microcirculatory disorders and local hypoxia, and thus to liver damage. Blockade of endo-receptors

Telina protects hepatic microcirculation, increases the supply of oxygen to cells and reduces hepatocellular damage. Thromboxan A2 is involved in platelet aggregation in IR, which was discovered by K. Napa7aI e! a1. (2000).

It is assumed that NO has a cytoprotective effect on microcirculation. In experiments on rats using an NO synthase inhibitor and a control test - serum transaminase - this property of NO was confirmed.

Platelets play an important role in microcirculation disorders in IR. A. Khandoga e! a1. (2003) conducted an intravital study using fluorescence microscopy of the interaction of platelets with endothelial cells after 20–40 min of reperfusion after liver ischemia. At the same time, rolling and adhesion of platelets were detected in terminal arterioles and postsinusoidal venules. In this case, platelet accumulation in the sinusoids occurred within 20 minutes after reperfusion. When ischemia was prolonged from 30 to 60 and 90 minutes, the number of platelets interacting with the endothelium increased significantly. Postischemic platelet adhesion has been associated with increased thrombin activity and release of platelets from the systemic circulation. In addition, platelet adhesion was linearly correlated with worsening sinus perfusion. Prolonged reperfusion up to 4 hours did not increase the interaction of platelets and endothelium. Thus, endothelial cells in arterioles, venules and sinusoids interact with platelets already in the early period of reperfusion. The extent of their interaction depends on the duration of ischemia, but not on the time of reperfusion.

A major role in liver damage in IR is played by the activation of Kupffer cells with the subsequent release of pro-inflammatory mediators, including Tn-a. These mediators stimulate a cascade of events including an increase in chemokines and adhesion molecules to the vascular endothelium, leading to the transport of neutrophils into the liver and tissue damage. Superoxide anion radical generation in Kupffer cells was unregulated 6–24 h after reperfusion. TiN-a production increased in both lobes after reperfusion. IL-R increased at later times of reperfusion.

Activation of polymorphonuclear leukocytes plays a critical role in liver injury in IR. Transport of neutrophils into Kupffer cells of the liver occurs with the participation of P-selectin. Subsequently, activation of neutrophils is observed, resulting in dysfunction of the RES. Activated neutrophils infiltrate the diseased liver with a parallel increase in the expression of adhesion molecules on endothelial cells. The heme oxygenase system is the most important cytoprotective mechanism activated by

cellular stress and including antioxidant and anti-inflammatory functions, regulating cell cycle and supporting microcirculation. Selectin plays a major role in polymorphonuclear infiltration of the liver, which also promotes platelet adhesion to the vascular wall. Neutrophils damage hepatocytes with the help of enzymes, in particular neutrophil elastase plays an important role. The use of an elastase inhibitor smooths out liver damage.

Regulation of neutrophil-dependent damage to hepatocytes in liver IR occurs under the influence of CD4+ lymphocytes. In liver IR, CD4+ lymphocytes quickly enter the liver and, through IL17, promote the transport of neutrophils.

Activation of the NF-kappa B gene, localized in DNA, plays an important role in the development of the inflammatory process in hepatocytes during liver IR. It has now been found that protein 1 kappa B alpha and protein 1 kappa B beta, localized in DNA, are of primary importance in its regulation. In the early stages of IR, rapid activation of the genes p38, p44/42, stress-activating protein kinase and c-Jun N - terminal kinase of mitogen-activating protein kinase occurs, the transduction signal and transcription activator-3 increase, and nuclear translocation of activator protein-1 occurs. , activation of the receptor to increase the end product of glycogenolysis, which is a key signaling pathway linking inflammation and cell death.

The death of hepatocytes in liver IR occurs either as a result of necrosis or apoptosis. Using a model of an isolated perfused liver, it was found that after thermal reperfusion (10 min) necrosis of hepatocytes was observed. It remained stable up to 120 min. After 30 minutes, apoptosis sharply increased. Only after 42 hours did hepatocyte necrosis develop in the area of ​​the blood-filled sinusoids.

Since many aspects of the pathogenesis of lesions in liver IR have been clarified, the attention of researchers is currently directed to finding ways to prevent disorders following liver ischemia-reperfusion.

One of these methods is to carry out a kind of ischemic preparation for the upcoming liver IR. Its essence boils down to the fact that on the eve of the upcoming liver IR, short-term ischemia is carried out with an equally short-term reperfusion. Thus, in the work of W.Y. Lee et al. (2005) the rat liver was subjected to ischemia for 10 min and reperfusion for 10 min. This was immediately followed by prolonged liver ischemia for 90 minutes, followed by 5 hours of reperfusion. It was shown that ischemic preparation decreased the activity of aminotransferase in the blood, alanine aminotransferase, α-glutathione-8-transferase, platelet aggregation, and the content of cyclic adenosine-5 monophosphate. Lipid peroxidation in mitochondria is significantly reduced by oxide-

BULLETIN OF THE VOLGOGRAD SCIENTIFIC CENTER OF THE RAMS

tive stress. In studies by A. Barrier et al. (2005) the same preparation for liver IR led to an increase in the amount of anti-apoptotic protein Bcl-2 and an increase in inducible nitric oxide synthase. M. Glanman et al. (2003) showed that preparation reduced the activation of Kupffer cells and sinusoidal perfusion lesions, while maintaining adequate oxidative

recovery processes in mitochondria. According to C. Peralta et al. (2003), the mechanisms responsible for the endogenous protective effect in preparing the liver for IR include: 1) transient production of NO during preparation; 2) reduction of toxic substances formed during perfusion; 3) long-term effect on extrahepatic organs, such as the lungs; 4) preservation of energy metabolism during ischemia; 5) decrease in nuclear transcription factor. In the process of preparing the liver for IR, damage to cellular proteins and DNA is prevented. The preparation blocks the xanthine oxidase pathway to generate reactive oxygen species. After preparation, NOS2 transcription and expression increases, which has a protective effect. A. Chouker et al. (2005) showed that preparation moderates portal vein purine concentrations during thermal liver IR in humans. According to R.S. Koti (2005), the protective effect in preparing the liver for IR was associated with an increase in L-arginine. Thus, there is no doubt that preparing the liver for IR significantly reduces the damage to hepatocytes during long-term liver IR.

Another direction in research on the prevention of hepatocyte damage in liver IR was an attempt to use chemical compounds that affect various aspects of the pathogenesis underlying the pathological process.

Based on the main link in the pathogenesis of the formation of free oxygen radicals, the pathogenetic method of treatment is antioxidant therapy. Ascorbic acid as an antioxidant can be used to prevent hepatocyte damage in liver IR.

Another direction in the correction of liver dysfunction in IR is the use of receptor antagonists for damaging cytokines. Thus, with the help of an endothelin A receptor antagonist in liver IR, the content of endothelin and the interaction of platelets with the endothelium were reduced. In experiments by S. Zeng et al. (2004) showed that when the receptor is blocked to increase the end product of glycolysis, the activation of nuclear factor kappa B remains increased, but the transcription of the pro-regulatory cytokine TNF-a increases. The authors suggested that blockade of this pathway may represent a new strategy for reducing liver damage and improving regeneration. Administration of an A2A receptor agonist before ischemia may attenuate post-ischemic apoptosis in liver cells and thus minimize damage

liver, which is associated with a decrease in caspase-3 activity. B. Cavalieri et al. (2005) proposed a new non-competitive allosteric blocker of IL-8 receptors, repertaxin, which, by binding CXCRI/R2 in an inactive structure, prevents the signal from the receptor and the chemotaxis of polymorphonuclear leukocytes. It has been shown that CD 13 inhibits Kupffer cells and protects the liver from damage during IR through mechanisms that reduce lipid peroxidation.

Experiments have shown that inhibitors of cytokine enzymes are able to correlate liver dysfunction in IR. In particular, the liver thromboxane synthase inhibitor FK506 has a protective effect in IR. An inhibitor of a selective cyclooxygenase enzyme involved in the conversion of prostaglandins into thromboxane A2, significantly mitigates microcirculatory and hepatocellular damage in liver IR. Y.I. Kim et al. (2002) used a protease inhibitor to prevent liver damage in IR. Apoptosis in IR can be inhibited by a specific inhibitor of caspases and prevent liver damage.

A number of hormones can be used to treat lesions in liver IR. Thus, prostaglandin E1 is a cytoprotector; it reduces the content of thromboxane A2 in liver IR, normalizes the NO content and prevents the formation of superoxide anion radical. D. Giakoustidis et al. (2002) successfully used high doses of α-tocopherol, which mitigated damage to hepatocytes in IR.

Anticoagulants and fibrinolytics can reduce damage in liver IR. Thus, anitrombin increases the release of prostacyclin from endothelial cells and reduces damage to hepatocytes in IR. Heparin improves liver function in liver IR, affecting microcirculation disorders in the liver sinusoids and partly through inhibition of endothelin-1. Plasminogen activator has a positive effect on the degree of hepatocyte damage in liver IR.

A number of cytokines have a positive effect on liver damage in IR. It was found that some cytokines mitigate the damage to hepatocytes in liver IR. Thus, hepatocyte growth factor causes depression of oxidative stress and inhibition of the ICAM-1 molecule, thereby helping to reduce the severity of damage in IR. Y.J. Lee and Y.K. Song (2002) used IL-10 in combination with galectin-3 to prevent cell damage in IR.

The immunosuppressant cyclosporine improves the condition of hepatocytes during thermal IR of the liver.

It was found that the abundance of intracellular glycogen can reduce liver IR. In this connection, the authors believe that before a complex of liver operations, it is useful for patients to be given a large amount of glucose. L.N. Lin (2004) showed that

propofol prevented liver damage in IR by reducing the level of free radicals and inhibiting lipid peroxidation in patients after surgery for liver cancer. B.H. Heijnen et al. (2003) and A. Khandoga et al. (2003) successfully used hypothermia up to 10-15°C to prevent damage in IR. The use of oxybaric oxygenation reduces the adhesion of neutrophils in venules, and also blocks vasoconstriction of arterioles and thereby reduces liver dysfunction.

Biliverdin was successfully used for cold liver IR and liver transplantation in rats.

Some amino acids may have a protective effect in liver IR. In particular, B. Nilsson et al. (2000) used adenosine for this purpose. Certain doses of ethanol have a positive effect on hepatocytes in IR. Pyruvate plays a limiting role in the damage of hepatocytes in IR. Glycine can effectively prevent liver rejection in rats after IR by suppressing the expression of CD1 4b NF-kappa B, binding Kupffer cell activity, and inhibiting the activity of TNF-a and IL-1. Melanotonin reduces mitochondrial oxidative stress and improves liver metabolism in IR. L-arginine and L-cacnavanine - NO synthase inhibitors - improve liver function after IR. At the same time, L-arginine increases NO, reduces MDA and corrects TXA (2) / PGI (2). L-arginine also reduces platelet aggregation.

To prevent damage in IR, some authors use gene therapy.

So, A.J. Coito et al. (2002) successfully used heme oxygenase, a cytoprotective protein, by transplanting the adenoviral heme oxygenase-1 gene. Jaeschke H. (2002) proposed antioxidant gene therapy for the treatment of lesions in IR.

H. Jiang et al. (2005) and F.Q. Meng et al. (2005) used the drug “oxymatrine” for liver IR. In doing so, they found that the drug inhibits cell apoptosis, which is associated with dysregulation of fas and fas-ligand polymorphonuclear leukocytes. Repertaxin prevents postischemic hepatocellular necrosis in rats (80%) and polymorphonuclear leukocyte infiltration (96%) within 254 hours of reperfusion. Sener G. et al. (2005) used 2-mercaptoethan sulfonate to treat the consequences of liver IR.

In the literature there are isolated studies on damage to other organs in liver IR. So, H.M. Wang et al. (2005) reported lung damage in liver IR, and J.C. Yang et al. (2004) determined an increase in the content of MDA, ALT, AST and a decrease in the activity of SOD and ATPase in the lungs, liver, kidneys, pancreas and heart. According to X.L. Wang et al. (2003), protease has a protective effect in acute lung injury after IR re-

In the literature available to us, we have not found data on the participation of the lymphatic system in the processes of liver damage in IR, with the exception of the mention of a decrease in lymph flow in one work. At the same time, given the important role of the lymphatic system in the transport of tissue destruction products and excess amounts of interstitial fluid - factors that support the inflammatory process, clarification of this issue is absolutely necessary. Even more important is the fact that the lymphatic system is involved in the spread of the pathological process from the source of damage through the organ lymph, thoracic lymphatic duct, right heart to the lungs. The consequence of this, undoubtedly, is the occurrence of a pathological process in the lungs, and, possibly, in other organs.

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UDC: 616.36 - 089.166

effects of radiofrequency thermal ablation

ON THE STRUCTURE OF INTACT AND ISCHEMIZED

A.A. Dolzhikov, V.F. Kulikovsky, D.I. Naberezhnev, V.D. Lutsenko

Belgorod Regional Clinical Hospital, Belgorod State University

Radiofrequency thermal ablation (RFA) is currently considered one of the most promising methods for treating primary and metastatic liver tumors in unresectable cases. The emergence of the method, the development of its technical support and

principles of use go back a little over 10 years. During the introduction and use of RFA, ideas have developed about its advantages, limitations and individual factors influencing the result. However, in a number of studies performed