Treatment of cholestasis. Intrahepatic cholestasis and its treatment

Cholestasis refers to a pathological condition in which there is a decrease in the production of bile and its entry into the intestine as a result of a violation of its production or excretion.

In medical practice, it is customary to talk about Cholestasis Syndrome, which does not occur by itself. This phenomenon is preceded by certain reasons. If the patient has constipation and pain on the right side, it is customary to talk about the occurrence of the disease. But to cure the disease, you need to contact an experienced specialist.

Diagnosis of pathology

To diagnose cholestasis for an experienced doctor is not difficult. During the reception of the patient, the first thing to do is interview and find out what symptoms haunt him. The main symptom of the onset of the disease is the occurrence of itching and rash on the skin. This process is due to the fact that bile does not enter the intestines in the right amount, and therefore food is poorly digested.

Also, the patient may complain of fatigue and constant weakness. To all this, the patient develops constipation. When defecating, you can find that the feces have acquired a colorless tint.

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With gradual damage to the liver and stagnation of bile in the gallbladder, the patient develops jaundice. It is characterized by a lack of absorption of important vitamins and fats from food.

To understand how to treat bile stasis, you need to examine the patient. Based on complaints, the doctor palpates the right area, where he detects a significant increase in the liver.

Ultrasound is used to make an accurate diagnosis. This will help to identify the cause of the development of the disease. If during the study an expansion of the ducts is detected, then cholangiography is prescribed.

To determine the exact symptoms and treatment, a liver biopsy should be performed. This method of examination allows you to evaluate the form of cholestasis. If you ignore this factor, then the patient may develop biliary peritonitis.

Treatment of cholestasis with medications

Treatment of cholestasis should be carried out under the strict supervision of the attending physician. It is strictly forbidden to self-medicate, since stagnation of bile can be caused by the formation of stones.

To identify and eliminate cholestasis, symptoms, treatment, you need to recognize the cause of the disease. If the stagnation of bile was caused by an inflammatory process, then the patient is prescribed antibacterial agents.

Also, the treatment of cholestasis includes the elimination of the main symptom of the disease, which is itching and rashes on the skin. The most effective way to stop skin manifestations is considered to be drainage of the biliary tract using an external or internal method. Two days after such treatment, skin itching and rash disappear.

If the patient has contraindications to performing drainage, then the doctor recommends using Cholestyramine. The action of the drug is aimed at eliminating skin itching. The duration of the treatment process is five days. During the process, the patient needs to take up to four grams of this remedy daily.

If the patient has hypoprothrombinemia, then Cholestyramine is replaced by Ursodeoxycholic acid. This medication will show an excellent result in those people who suffer from primary biliary cirrhosis.

In the absence of a result, these drugs are replaced with sedatives and glucocorticosteroid medications.

With intrahepatic cholestasis, hepatoprotective agents are prescribed. Heptral is most often prescribed. The duration of the treatment course for parenteral use is up to fourteen days. After that, the patient is transferred to the tablet form. The duration of this treatment is eight weeks.

Rifampicin may have the same effect. The drug is able to improve the acid microflora. You need to drink the remedy one hundred and fifty grams per day for twelve weeks.

With stagnation of bile in the gallbladder, they are prescribed in the form of Holosas, Magnesia.

Allohol is a cholikinetic and choleretic agent. Its action is aimed not only at stimulating the production of bile, but also at reducing the gallbladder.

So that the patient does not experience nausea and vomiting, Cerucal is prescribed in injections or tablets.

Treatment with folk methods

If cholestasis occurs, treatment may include the use of folk remedies. Their action is aimed at maintaining the health of the liver, stimulating the production of bile and its outflow from the gallbladder, expanding the biliary tract, crushing and removing stones.

Treatment with folk remedies includes several recipes:

Drink from birch leaves. To prepare it, you need to take a few dried birch leaves and pour them with two cups of boiled water. Then put on fire and let boil for ten minutes. After that, the drink must be filtered and taken in half a mug up to three times a day.
Herbal decoction. To prepare it, you should take St. John's wort, corn stigmas, immortelle flowers in equal proportions. Pour a cup of boiled water and put on fire for thirty to forty minutes. After cooking, the broth is filtered. You need to take a drink twenty minutes before eating up to three times a day.
A decoction of nettle and wild rose. To prepare the infusion, you need twenty grams of rose hips and ten grams of nettle leaves. The components are carefully crushed and poured with a cup of boiled water. The drink must be allowed to brew for forty minutes. Then strain and consume up to two times a day.
Oil remedy. To prepare it, you need to take a spoonful of honey and add three drops of mint oil there. You need to use this medicine up to three times a day for four weeks.
Lemon oil. In fruit drink, compote, tea or juice, you need to add one drop of lemon oil. This method should be used up to two times a day. The duration of the treatment course is four weeks.
Beet juice. To prepare the product, you need to take one beetroot, peel it and grate it on a fine grater. Then, using gauze, squeeze the juice and add the juice from the radish there. The ingredients are mixed in equal proportions. This medicine must be taken in the morning after sleep, one cup. The duration of the treatment course is twelve weeks.

Complementary Therapies

Stagnation of bile in the gallbladder can be for a variety of reasons. To identify them, you need to consult a doctor. He will conduct an examination and prescribe the appropriate treatment.

Physiotherapy can be used as additional methods. It includes performing a set of exercises in the form of a birch tree, a pose of inclination to the legs. Such exercises will improve the flow of bile.

Visceral therapy is also used. Its essence lies in exerting pressure on the gallbladder with a fist. With uniform pressure, an internal massage occurs. This process improves the flow of bile and leads to hepatofunction.

Nutrition during treatment

During the treatment process and after the removal of the gallbladder, the patient must follow the correct diet. It will improve the functioning of the digestive organs and reduce the risk of developing gallstone disease.

Food should be taken in small portions up to six times a day. In this case, hot and cold dishes should be excluded.

The diet should include fruit and vegetable dishes, whole grain bread, oatmeal, rice and buckwheat, lean meats in the form of chicken and beef, fish dishes.

Every evening at night, to have a laxative effect on the intestines, you need to drink kefir or fermented baked milk.
The diet for cholestasis excludes the use of alcoholic beverages and carbonated drinks, coffee, fatty broths, pastries and sweets, mushrooms and canned food, chocolate and cocoa.

So that bile does not stagnate in the gallbladder and enters the intestines in a timely manner, you need to drink plenty of fluids. Let it be water, fruit drinks, compotes and juices. But at least two liters of fluid should flow per day.

You should also cleanse the body in time with mineral water, sorbitol or magnesia.

Preventive actions

After the treatment process, the patient needs to pay attention to preventive measures. They will help maintain the health of the liver and gallbladder, avoid repeated relapses and stagnation of bile.

Preventive measures include:

In the timely treatment of chronic diseases in the organs of the biliary system.
In a constant examination by a doctor of the organs of the digestive function.
In the implementation of light jogging and walking in the morning.
On long walks in the fresh air.
In performing special exercises.
In swimming.
in therapeutic massage.

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We suggest that you read the article on the topic: “Symptoms and treatment of intrahepatic cholestasis” on our website dedicated to the treatment of the liver.

Cholestasis is a disease associated with stagnation of bile in the liver. The name comes from the Greek words chole and stasis, which are translated as “bile” and “stagnation”. Bile stagnates because there is some kind of obstruction in the way of its exit, a blockage that does not allow it to freely enter the intestines.

The obstruction occurs in any of the areas from the liver to the intestines. At the same time, bilirubin, still produced by the liver, is not released, but is carried through the bloodstream throughout the body. The main causes of cholestasis are a decrease or cessation of bile flow due to problems with the liver.

Signs of the disease are primarily itching, dark urine, clarified feces. The causes of the disease are viruses, alcohol, drugs, toxic damage and a number of diseases (histiocytosis, cholangitis, tuberculosis, cirrhosis, sarcoidosis, etc.), the main one is damage to liver cells by bile acid.

Cholestasis can accompany any pathology associated with the liver. Therefore, this disease requires urgent treatment.

Main symptoms

The very first symptoms of cholestasis are itching.(often begins in the liver, for a long time it may be the only sign of the disease). Usually itching is very disturbing at night, less during the day.

Then there are disturbances in the digestion of food, the patient loses his appetite, complains of abdominal pain, often vomiting. The main symptom is urine turns dark and feces light, steatorrhea begins - the release of excess fat with feces. Often diarrhea, which removes fluid from the body, the patient loses weight.

In some cases, skin pigmentation changes, jaundice appears. Tumor-like spots form on the skin of the face, neck, and back due to lipid metabolism disorders. The temperature rises, mood swings begin, the patient is worried about fatigue.

Since cholestasis provokes a drop in the level of vitamins, such as A, D, K and others, in the body, signs of night blindness. For the same reason, the patient has increased bleeding.

Such a sign of liver disease as its increase in cholestasis without cirrhosis occurs in rare cases.

In the chronic course of the disease, due to prolonged jaundice, the skin becomes golden in color, fatty deposits on it also turn yellow, around the eyes (sometimes on other parts of the body) yellow formations develop, the so-called xanthomas, which appear as a result of the fact that fats are retained in the body. Often stones are formed in the gallbladder and bile ducts - cholelithiasis.

All of these symptoms appear as a result of a large volume of bile entering the blood (with its complete or almost complete absence in the intestine) and effects of bile on liver cells. If symptoms corresponding to cholestasis are detected, treatment should be started immediately, as soon as the doctor makes a diagnosis and determines the type of disease.

Types of cholestasis

By localization, the disease is divided into intrahepatic cholestasis and extrahepatic, according to the nature of the course, it can be acute and chronic, with jaundice (when the mucous membranes, sclera and skin are pigmented in yellow).

Intrahepatic cholestasis called the form in which stagnation of bile occurs in the intrahepatic bile ducts or in the cells of the liver, that is, it is formed inside the liver.
extrahepatic cholestasis the form is called when congestion is formed as a result of blockage of the extrahepatic bile ducts.

In acute cholestasis, the symptoms of the disease appear suddenly and are pronounced, in chronic cholestasis, the symptoms are weak, increasing over a long time (from weeks to months).

Also, intrahepatic cholestasis is divided into partial (with it the volume of secreted bile decreases), dissociative (the release of only some components of bile is delayed) and total (when the flow of bile into the duodenum is completely disrupted).

Causes of intrahepatic cholestasis

hepatitis;
alcoholic liver damage;
cirrhosis;
taking medications;
hormonal changes during pregnancy (pregnancy cholestasis);
endocrine pathologies (for example, hypothyroidism);
chromosomal disorders (trisomy 13,17 or 18 chromosomes);
congenital metabolic disorders (cystic fibrosis, etc.);
family syndromes.

Causes of extrahepatic cholestasis

the appearance of a stone or stones in the bile ducts;
bile duct;
thickening of bile;
pancreatitis;
malignant tumors of the bile duct and / or pancreas.

Diagnostics

If cholestasis is suspected, it is based on the history and symptoms characteristic of the disease. First of all, they turn to a general practitioner, then a consultation with a gastroenterologist is required, and the help of a surgeon and a hepatologist may be needed.

The doctor collects an anamnesis of diseases and complaints, an anamnesis of life, and conducts an examination. Further blood tests are ordered, including biochemical, urine, and also use ultrasound to accurately determine the localization of blockage in the biliary tract, since it is important to determine the form - extrahepatic or intrahepatic whether this disease. In addition, the patient may be prescribed a study using computed tomography and magnetic resonance imaging, which with high accuracy reveal pathological changes in the liver and gallbladder.

Another test method is endoscopic retrograde cholangiography(if this is not possible, it is replaced by percutaneous transhepatic cholangiography), which reveals the level of blockage.

Magnetic resonance cholangiography, which examines the bile ducts, is considered a promising method; this examination is highly informative.

In addition, a doctor with an intrahepatic form can be liver biopsy performed. But this examination is carried out only after the exclusion of the extrahepatic form, otherwise it can provoke the development of peritonitis.

The most effective treatment for both intrahepatic and extrahepatic cholestasis is considered etiotropic therapy, primarily aimed at eliminating the causes. Ursodeoxycholic acid also gives good results, including with cirrhosis of the liver caused by alcohol poisoning.

To eliminate pruritus in the treatment of the disease, plasmapheresis and opioid antagonists are used.

Since hypovitaminosis is noted in cholestasis, which entails side effects that require separate treatment, it is necessary to take vitamins K, D, E and fat-dissolving drugs.

If there is an obstruction in the bile duct mechanical or clogged bile ducts, then, in addition to conservative treatment, surgical intervention (conventional or endoscopic) is required.

Complications and consequences of cholestasis

With cholestasis in the body, the process of copper metabolism is disrupted. in a healthy state the body excretes 80% of copper with feces, but during cholestasis, copper remains in the body, causing pigmentation of the cornea of \u200b\u200bthe eye. Another consequence of cholestasis is a disruption in the functioning of the cardiovascular system, which leads to arterial hypotension, problems with blood clotting, increased bleeding and an increased risk of sepsis.

In addition, cholestasis provokes diseases such as:

osteoporosis;
hemeralopia (decreased vision at dusk, or night blindness);
the occurrence of stones in the gallbladder and / or bile ducts;
development of inflammation of the bile ducts (cholangitis);
liver failure;
cirrhosis.

cholestasis of pregnancy

Separately, it is worth mentioning such a pathology as intrahepatic cholestasis, which arose as a result of hormonal imbalance during pregnancy. Such the disease in pregnant women is relatively rare however, it can harm the body of both the mother and the fetus. The prognosis for a pregnant woman is usually favorable - cholestasis develops mainly in the third trimester and disappears almost immediately after childbirth. However, the risk of intrauterine fetal death increases to 15%.

The causes of the disease are still not exactly clear. Experts identify three potential groups:

excess estrogen, which during this period, in particular by the end of pregnancy, in a woman's body increases 1000 times;
compression of the gallbladder and the liver of the pregnant uterus (just in the last trimester it reaches its maximum size);
hereditary nature of the disease(more than half of the women in the family had such pathologies).

In addition, there are factors that also affect the development of cholestasis in pregnant women. If a woman has already had cholestasis of pregnancy, then the risk of recurrence during subsequent pregnancies increases to 70%. Liver disease before pregnancy increases the chance of cholestasis during pregnancy. In addition, the occurrence of cholestasis is higher in multiple pregnancy and pregnancy as a result of in vitro fertilization, as well as in the presence of close relatives who have suffered this disease.

Symptoms of cholestasis of pregnancy

severe itching, especially on the palms and feet;
dark urine and light feces;
jaundice.

Symptoms can appear all at once or one at a time, but most often the only symptom is itching.

Complications of cholestasis of pregnancy

The main complications of the disease in the mother are problems with absorption of fat-soluble vitamins (A, D, E, and K), unbearable itching and increased risk of recurrence during subsequent pregnancies.

There are many more complications for a child to be born. First of all, there is a risk of preterm birth for reasons that have not yet been clarified. Further, there is a possibility that the baby will inhale meconium during delivery, which there will be breathing problems. The risk of fetal death is also increased. Therefore, doctors often induce preterm labor to avoid complications for the baby.

Diagnosis and treatment of cholestasis of pregnancy

When making a diagnosis, doctors rely on the results of a survey of the pregnant woman about the presence of symptoms of the disease and personal and family medical history, a physical examination, blood tests, measurements of the level of bile in the blood, and ultrasound.

Treatment consists in relieving symptoms, especially itching, and preventing possible complications. Ursodeoxycholic acid preparations have been successfully used, as well as corticosteroids in the form of creams or lotions that relieve itching.

Prevention of cholestasis

To avoid the occurrence of cholestasis, it is necessary to prevent and treat diseases of the liver and biliary tract in time, as a result of which stagnation of bile develops. These include the timely removal of tumors and stones. In addition, regular deworming is necessary. Can support digestion with the help of herbal preparations, herbal preparations and herbal teas. To prevent stagnation of bile, it is necessary to maintain water balance, that is, drink clean water in sufficient quantities. In addition, it is required to abandon the use of alcohol, which has the most detrimental effect on liver cells, as well as adhere to a special diet low in fat.

diet for cholestasis

When sick, patients can eat soups in vegetable broth with the addition of vegetables, cereals and pasta; cereals; meat(lean beef, chicken, lean poultry), the preferred cooking method is boiling, baking after boiling.

Vegetables, herbs, fruits, non-acidic berries and juices from them, compotes, jelly, weak tea and coffee with milk are allowed; you can use sugar, jam, honey, wheat and rye bread, non-bread cookies, butter and vegetable oil, sour cream (a little), low-fat cheeses and low-fat cottage cheese.

As mentioned above, any alcoholic beverages are prohibited, as well as black coffee, cocoa. You can not eat sour fruits and berries, pickled vegetables, canned food, smoked foods, mustard, pepper, horseradish, chocolate, ice cream. Fatty meat and fish banned, soups on meat, fish, mushroom broths, cooking fats, lard; pastry products (pancakes, pancakes, cakes, fried pies, etc.). Sorrel, spinach, radish, green onion, radish should be excluded from the diet.

Liver diseases are extremely unpleasant, fraught with many consequences and require long and monotonous treatment. The sooner you seek help from a specialist, the more likely you are to stay healthy and reduce the risk of complications. Therefore, be sure to consult a doctor, especially during pregnancy, if itchy skin appears. If you feel severe pain in your right side, urgently call an ambulance and in no case postpone treatment if you have already been diagnosed with cholestasis.

Bile is produced in the body to perform very important functions. Without it, the processes of digestion and the removal of toxins from the body are impossible. When exposed to the liver of negative factors, bile formation, circulation and outflow of bile are disturbed. These dysfunctions can manifest themselves in different ways. One of the signs of a violation of the liver is the syndrome of intrahepatic cholestasis.

What it is

Intrahepatic cholestasis is a condition characterized by impaired circulation and flow of bile into the duodenum, not associated with mechanical damage or obstruction of the biliary tract. It can form at the level of intrahepatic bile ducts or hepatocytes.

Pathological processes occurring at the cellular level lead to excessive intake of bile elements into the blood, deficiency of bile in the intestine and the effect of its components on the hepatic tubules and cells.

According to the etiological factor, the syndrome is divided into:

damage to the canals;
damage to hepatocytes;
defeat of ductulas;
mixed type.

Downstream intrahepatic cholestasis happens:

sharp;
chronic.

The disease can take two forms:

icteric;
anicteric.

partial - characterized by a decrease in bile production;
dissociative - associated with a delay in the formation of some components of bile;
total - characterized by a violation of the transport of bile into the duodenum 12.

Causes

This syndrome is polyetiological. It can be provoked by both external negative effects on the body and diseases of internal organs.

Most often, the following reasons lead to a violation of bile formation:

toxic effect on the liver (drug, alcohol);
viral liver diseases;
intestinal dysbacteriosis;
cholestasis of pregnancy, benign recurrent cholestasis;
endotoxemia;
bacterial infections.

The following diseases lead to a violation of bile transport:

Caroli disease;
cirrhosis;
sclerosing cholangitis;
sarcoidosis;
biliary atresia;
lymphogranulomatosis;
tuberculosis;
transplant rejection.

Signs of cholestasis

Symptoms depend on the type of disease that provoked it. In addition, acute and chronic cholestasis manifest themselves in different ways. The main signs of an acute syndrome include:

fever;
abdominal pain;
loss of appetite;
jaundice;
discoloration of feces;
steatorrhea (excretion of a large amount of fat with feces);
dark urine;
osteoporosis due to malabsorption of calcium and vitamin D;
severe itching of the skin, and as a result of damage and scratching on it.

Symptoms of the chronic form:

as a result of prolonged jaundice, the skin becomes golden, yellow fat deposits form in it;
xanthomas - formations of a yellowish color, mainly around the eyes, developing due to the retention of fats in the body.
tuberous xanthomas - neoplasms in the form of tubercles on the buttocks, extensor surfaces of the arms, legs.
weight loss.

Xanthomas in the eye area

Tuberous xanthomas on the elbows

Complications of intrahepatic cholestasis

A neglected disease can have serious consequences, including:

bleeding due to vitamin K deficiency;
osteoporosis;
cholelithiasis;
cirrhosis;
liver failure;
decreased vision.

Diagnosis of pathology

Diagnosis and treatment of cholestasis is carried out by a surgeon or gastroenterologist. At the reception, the doctor examines the patient, collects an anamnesis of life and illness, and analyzes complaints. A number of measures are taken to confirm the diagnosis. The choice of a specific method depends on the indications and the patient's health status.

The following examinations are possible:

blood chemistry;
cholangography;
endoscopic retrograde cholangiopancreatography;
percutaneous transhepatic cholangiography.
magnetic resonance cholangiography.
liver biopsy.

How to treat intrahepatic cholestasis

Treatment is based on an integrated approach. The patient must adhere to a diet and receive etiotropic treatment.

Diet features:

restriction of neutral fats to 40 g / day;
enrichment of the diet with fat-soluble vitamins and calcium;
increasing the proportion of plant components in the diet.

Etiotropic treatment:

The treatment is based on agents that restore the structure of liver cells and their functions. These drugs include Heptral, Silimar, Ursodeoxycholic acid.
Detoxification therapy - a solution of glucose, sodium chloride or rheosorbilact intravenously.
Symptomatic therapy aimed at eliminating the clinical manifestations of the disease:

for the relief of skin itching - Nalmefene, Naloxone, Ondansetron;
to eliminate jaundice - cholestyramine;
to compensate for osteoporosis - vitamin D3 + calcium gluconate or Calcium D3 nycomed.
with bone pain - calcium gluconate intravenously.
vitamins - A, E;
with bleeding - Vikasol intramuscularly.

In severe cases, plasmapheresis, cryoplasmasorption, UVR of blood are performed.

Disease prevention

The basis for the prevention of intrahepatic cholestasis is the timely treatment of diseases that provoke it:

removal of liver tumors;
fight against gallstone disease;
anthelmintic treatment.

To reduce the risk of developing the syndrome, it is necessary to abandon bad habits and eliminate or minimize the toxic effect on the liver.

It is important to monitor nutrition, reduce the amount of fat in the diet, give up fried and spicy foods, and enrich the diet with plant components.

Itchy skin is the very first sign of cholestasis, which can occur months or years before jaundice and other symptoms of the disease appear. When itching occurs, it is important to first examine the liver in order to control the syndrome in time.
For patients, milk is useful, as it is a source of calcium. But it must be remembered that milk must be skimmed.

At the first sign of cholestasis, it is important to immediately contact a specialist. Ignoring the syndrome can lead to irreversible consequences, which include liver failure. Timely treatment can restore impaired liver function and eliminate the symptoms of pathology.

Cholestasis is a pathological condition characterized by a decrease in bile secretion into the duodenum, which occurs as a result of a violation of its formation, a change in composition, or a violation of excretion from the liver through the intrahepatic and extrahepatic bile ducts.

Bile is an enzyme that is involved in the process of digestion of fats that enter the gastrointestinal tract with food. The secretion of bile occurs in hepatocytes (liver cells) by filtering the blood coming from the unpaired organs of the abdominal cavity (stomach, pancreas and intestines).

1 - Hepatocyte
2 - Bile capillaries
3 - Hepatic sinusoids
4 - Interlobular bile duct
5 - Interlobular vein
6 - Interlobular artery

The hepatic sinusoids supply blood from the portal vein, which is then filtered by hepatocytes. All toxic substances and waste products of the body through the bile capillaries flow into the intrahepatic bile ducts, and pure blood through the hepatic veins returns to the bloodstream.

In the image, the numbers indicate:

1 - Duct of the gallbladder
2 - Common hepatic duct (consists of 2 intrahepatic ducts that collect bile from the right and left lobes of the liver)
3 - Choledoch (extrahepatic bile duct, which consists of the common hepatic and cystic duct)
4 - Pancreatic duct
5 - Connection of the bile duct with the pancreas
6 - Duodenum
7, 8, 9, 10, 11 - Gallbladder

General characteristics of intrahepatic and cystic bile:

	5.0 mmol/l	15.0 mmol/l
	165.0 mmol/l	280.0 mmol/l
	2.4 - 2.5 mmol/l	11.0 – 12.0 mmol/l
Bicarbonates	45 – 47 mmol/l	About 8 mmol/l
	90 mmol/l	14.5 – 15.0 mmol/l
Phospholipids	1.0 mmol/l	8.0 mmol/l
Cholesterol	3.0 mmol/l	25.0 – 26.0 mmol/l
Bile acids	35.0 mmol/l	310 mmol/l
bile pigments	0.8 – 1.0 mmol/l	3.1 - 3.2 mmol/l

A change in even one component of bile or a pathological process in the segment from the hepatocyte to the duodenum leads to the development of cholestasis.

The disease is common throughout the world and occurs in almost 60 - 65% of people suffering from liver diseases. Women get sick 3 times more often than men. Age does not affect the incidence of the disease.

The prognosis for cholestasis is doubtful, the process of liver damage in this disease proceeds slowly (from 3 to 10 years - without eliminating the cause that caused the pathological process), but, one way or another, leads to the development of hepatocellular insufficiency and hepatic coma, followed by death.

Causes

Intrahepatic cholestasis is associated with a violation of the processes of bile formation and its entry into the bile capillaries. This is facilitated by the following conditions and diseases:

sepsis;
intrauterine infection;
hypothyroidism;
chromosomal diseases (trisomy 13 pairs of chromosomes - Patau syndrome, trisomy 18 pairs of chromosomes - Edwards syndrome);
family syndromes (Alagille syndrome);
congenital storage and metabolic diseases (cystic fibrosis, galactosemia, alpha-1 antitrypsin deficiency);
alcoholic liver damage;
viral hepatitis;
toxic and drug damage to the liver;
cirrhosis of the liver;
congestive heart failure.

Extrahepatic cholestasis develops due to impaired patency of the biliary tract. This condition is facilitated by:

obstruction of the biliary tract by an enlarged liver, pancreas, pregnant uterus, neoplasm in the abdominal cavity, etc .;
atresia (underdevelopment or complete absence) of the biliary tract;
choledochal cyst;
choledocholithiasis (blockage of the bile duct by a stone from the gallbladder);
Caroli's disease (congenital dilation of the bile duct and impaired contractility);
biliary dyskinesia.

Classification

According to the location of the pathological process, cholestasis is divided into:

Intrahepatic - stagnation of bile is localized inside the liver;
Extrahepatic - bile stasis occurs outside the liver.

According to the mechanism of occurrence, they distinguish:

Partial cholestasis - a decrease in the amount of bile secreted;
Dissociative cholestasis - a decrease in the release of certain components of bile (for example, cholesterol, phospholipids, bile acids, etc.);
Total cholestasis is a violation of the flow of bile into the duodenum.

By the presence of jaundice, there are:

Anicteric cholestasis;
Icteric cholestasis.

According to the severity of symptoms, they are divided into:

Acute cholestasis (symptoms of the disease are pronounced, develop suddenly);
Chronic cholestasis (symptoms develop gradually, are mild).

Forms of cholestasis:

Functional cholestasis - a decrease in the amount of some components of bile (bilirubin, bile acids, water), which is combined with a slowdown in the flow of bile through the intrahepatic bile ducts;
Morphological cholestasis - the accumulation of bile in the intrahepatic bile ducts, which leads to an increase in the liver and the destruction of hepatocytes;
Clinical cholestasis - bile components that normally enter the gastrointestinal tract accumulate in the blood.

By the presence of cytolysis syndrome (cell destruction), cholestasis occurs:

With the presence of cytolysis;
No cytolysis.

Symptoms of cholestasis

The complex of symptoms depends on the degree of liver dysfunction and absorption of fats and fat-soluble vitamins into the body.

General manifestations of the disease:

headache;
dizziness;
general weakness;
increased fatigue;
irritability;
depression;
visual impairment;
drowsiness.

Respiratory manifestations:

shortness of breath with minimal exertion.

Manifestations from the cardiovascular system:

pain in the region of the heart;
increased heart rate;
lowering blood pressure;
bleeding.

Gastrointestinal manifestations:

belching with air;
heartburn;
nausea;
vomiting of intestinal contents;
pain in the right hypochondrium and in the stomach;
pancreatitis (inflammation of the pancreas);
flatulence;
lack of appetite;
stool disorder;
steatorrhea (the presence in the feces of a large amount of undigested fat);
discoloration of feces.

Manifestations from the urinary system:

pain in the lumbar region;
swelling of the lower extremities;
pain when urinating;
darkening of the urine.

Manifestation from the musculoskeletal system:

myalgia (pain in the muscles);
arthralgia (pain in the joints);
bone pain;
rarely - spontaneous fractures of the upper and lower extremities.

Diagnostics

Diagnosis of the disease is based on the examination of the patient, the implementation of laboratory and instrumental examination methods, consultations of related specialists:

When examining patients with cholestasis, the following changes can be detected:

intense yellowing of the skin and visible mucous membranes (jaundice);
the presence of scratches on the skin due to itching;
formations of xanthoma and xanthelasma - subcutaneous small inclusions of yellow color, which are located more often in the area of \u200b\u200bthe eyelids, nose, chest and back;
an increase in the size of the liver and the occurrence of dull pain with pressure in the region of the right hypochondrium.

Laboratory methods of examination

General blood analysis:

General urine analysis:

Biochemical blood test:

Liver tests:

total bilirubin	8.6 - 20.5 µmol/l	30.5 - 200.0 µm/l and above
direct bilirubin	8.6 µmol/l	20.0 - 300.0 µmol/l and above
ALT (alanine aminotransferase)	5 – 30 IU/l	30 - 180 IU/l and above
AST (aspartate aminotransferase)	7 – 40 IU/l	50 - 140 IU/l and above
Alkaline phosphatase	50 – 120 IU/l	130 - 180 IU / l and above
LDH (lactate dehydrogenase)	0.8 – 4.0 pyruvite/ml-h	5.0 – 7.0 pyruvate/ml-h
Thymol test		4 units and more

Coagulogram (blood clotting):

Lipidogram (the amount of cholesterol and its fractions in the blood):

Instrumental examination methods

Ultrasound of the abdominal organs reveals an increase in the liver, pathology of the gallbladder and extrahepatic bile ducts.
CT (computed tomography) and MRI (magnetic resonance imaging) can more accurately identify the pathological process in the liver, intrahepatic and extrahepatic bile ducts, gallbladder and nearby organs.
Retrograde cholangiopancreatography is an examination method based on the injection of a contrast agent into the bile ducts through the duodenum using a fibrogastroscope. This examination allows you to identify the pathological condition of the extrahepatic biliary tract.
Percutaneous transhepatic cholangiography reveals pathology of the intrahepatic bile duct, extrahepatic bile duct, and gallbladder.
A liver biopsy is a study of organ tissue to identify the causes of bile stasis.

Expert advice

therapist;
gastroenterologist;
surgeon;
traumatologist;
hematologist.

Treatment of cholestasis

The treatment of the disease is complex and includes the appointment of medications, surgical, alternative treatment and diet.

Medical treatment

Ursodeoxycholic acid (ursosan, ursochol) 13-15 mg per 1 kg of body weight at night daily. If cholestasis occurs due to cystic fibrosis, the dosage of the drug is increased to 20-30 mg per 1 kg of body weight per day. The course of treatment is long.
Glucocorticosteroids (methylpred, medrol, solumedrol) daily in the morning on an empty stomach. The dose of the drug is prescribed individually in each case and depends on the weight of the patient and the severity of the pathological process.
When itching occurs, it is recommended:
- cholestyramine 4 g 4 times a day (bile acid sequestrants);
- rifampicin 150-300 mg per day, the maximum daily dose of the drug should not exceed 600 mg (antibacterial agent);
- naltrexone 500 mg once a day (opiate antagonist);
- sertraline 57 - 100 mg 1 time per day;
- ultraviolet irradiation of the skin for 10 - 12 minutes daily.
Hepatoprotectors - heptral 400 mg - 5 ml in an ampoule intramuscularly or 800 - 10 ml in an ampoule intravenously for 2 weeks, then taking the drug in tablets of 400 mg per day for 2 - 2.5 months.
Multivitamin complex with a high content of fat-soluble vitamins (A, D, K, E) 1 tablet 1-2 times a day for 2-3 months.
For bleeding - vitamin K (Vikasol) 10 mg 1 time per day.
For pain in the bones - calcium gluconate 15 mg per 1 kg of body weight dissolved in 500 ml of 5% glucose solution intravenously drip 1 time per day. The course of treatment is 1 week.
Sessions of plasmapheresis and hemosorption to cleanse the blood of toxins.

Surgery

In case of intrahepatic cholestasis, in case of ineffectiveness of the conservative treatment and the progression of the symptom of the disease, the only surgical method of treatment is liver transplantation.

Products that are allowed for consumption:

non-fatty meat (beef, veal) boiled, baked or stewed;
poultry (chicken fillet, turkey) boiled, baked or stewed;
non-fatty fish;
soups on vegetable broths;
baked or boiled vegetables and herbs;
cereals (buckwheat, rice, millet);
pasta from durum wheat;
non-fat dairy products (kefir, sour cream, cottage cheese, cheese);
no more than one egg per day;
fruits and berries in the form of compotes, fruit drinks, juices;
jam;
sugar;
white dried bread, crackers, drying.

Products that are prohibited for consumption:

meat (pork, lamb);
bird (goose, duck);
fatty fish (beluga, sturgeon, catfish);
borscht, cabbage soup;
soups on meat, fish, mushroom broths;
salo;
whole milk, cream, fermented baked milk;
pickled vegetables;
canned food;
caviar;
smoked meats;
sauces (mayonnaise, ketchup, mustard, horseradish);
some vegetables (radish, radish, sorrel, spinach, onion);
alcohol;
coffee, sweet sparkling water, cocoa;
ice cream;
chocolate;
products with cream;
delicious pastries.

Complications

osteoporosis (destruction of bones due to a violation of their density);
hemerolopia (reduced vision at dusk due to malabsorption of fat-soluble vitamin A);
bleeding caused by malabsorption of fat-soluble vitamin K in the gastrointestinal tract;
cholelithiasis (formation of stones in the gallbladder);
cholangitis (inflammation of the intrahepatic and extrahepatic bile ducts);
hepatic encephalopathy;
liver failure;
hepatic coma;
cirrhosis of the liver;
fatal outcome.

Prevention

active lifestyle;
playing sports;
balanced diet;
rejection of bad habits;
timely treatment of diseases of the liver and organs of the gastrointestinal tract;
annual preventive examinations with laboratory blood tests and ultrasound of the abdominal organs.

Cholestasis is a disease characterized by a decrease in the flow of bile into the duodenum due to a violation of its excretion, formation or excretion. Cholestasis, the symptoms of which are manifested primarily in skin itching, dark urine and light-colored feces, depending on the characteristics of the etiology, can be extrahepatic or intrahepatic, depending on the nature of the course, acute or chronic, with or without jaundice.

general description

Cholestasis is also commonly referred to as "the cholestasis syndrome". Morphologists name this disease determines the presence of bile in hepatocytes and in hypertrophied Cooper cells (cellular bilirubinostasis), which in particular manifests itself in the form of small drops of bile concentrated in the area of dilated canals (canalicular bilirubinostasis). In the case of extrahepatic cholestasis, the location of bile is concentrated in the region of the interlobular dilated bile ducts (which determines ductular cholestasis), as well as in the liver parenchyma, where the bile looks like the so-called "bile lakes".

Cholestasis existing for several days provokes the occurrence of potentially reversible ultrastructural changes. The extended phase of the disease is characterized by a number of histological changes in the form of expansion of the bile capillaries, the formation of bile clots, the disappearance of villi from the canalicular membrane, and damage to cell membranes, which, in turn, provokes their permeability. In addition, among the changes in the extended phase, integrity violations in tight junctions and bilirubinostasis, the formation of hepatic rosettes and periductal edema, sclerosis and biliary infarcts are distinguished. At the same time, microabscesses, mesenchymal and periportal inflammation, etc. are also formed.

With a persistent form of cholestasis with a corresponding form of inflammation and a reaction in the connective tissue, the disease becomes irreversible. After a certain time (in some cases, calculated in months, in some - years), such a course of the disease leads to the development of a biliary form of fibrosis and to primary / secondary biliary cirrhosis.

It should be noted that any pathology associated with the liver can occur in combination with cholestasis. In some cases, the causes that provoke liver damage have been identified (alcohol, viruses, drugs), in some cases they have not been identified (primary biliary cirrhosis, sclerosing primary cholangitis). A number of diseases (histiocytosis X, sclerosing cholangitis) lead to the defeat of both intrahepatic ducts and extrahepatic ducts.

The main forms of the disease

Cholestasis can manifest itself as an intrahepatic or extrahepatic form. Intrahepatic cholestasis, the symptoms of which occur depending on their own forms of separation, determines the following varieties:

functional cholestasis. It is characterized by a decrease in the level of bile tubular current, as well as a decrease in organic anions (in the form of bile acids and bilirubin) and hepatic excretion of water.
Morphological cholestasis. It is characterized by the accumulation of bile components in the bile ducts and hepatocytes.
clinical cholestasis. Determines the delay in the composition of the blood components that are normally excreted in the bile.

As for extrahepatic cholestasis, it develops during extrahepatic obstruction in the bile ducts.

Returning to intrahepatic cholestasis, we note that it occurs as a result of the absence of obstruction in the main bile ducts, while its development can be carried out both at the level of intrahepatic bile ducts and at the level of hepatocytes. Based on this, cholestasis is isolated, which is caused by damage to hepatocytes, ductules and canals, as well as mixed cholestasis. In addition, acute cholestasis and chronic cholestasis are also determined, in its icteric or anicteric form.

Causes of cholestasis

The causes of the appearance of the disease we are considering are extremely diverse. An important role in considering the development of cholestasis is determined for bile acids, which are characterized by surface-active features in the extreme severity of their manifestations. It is bile acids that provoke cellular damage to the liver while increasing cholestasis. The toxicity of bile acids is determined based on the degree of their lipophilicity and hydrophobicity.

In general, cholestasis syndrome can occur in a variety of conditions, each of which can be defined in one of two groups of disorders:

Bile disorders:
Alcoholic liver damage;
Viral damage to the liver;
Toxic damage to the liver;
Drug damage to the liver;
Benign form of recurrent cholestasis;
Violations in the intestinal microecology;
Cirrhosis of the liver;
Cholestasis of pregnancy;
bacterial infections;
Endotoxemia.

Bile flow disorders:

Biliary primary cirrhosis;
Caroli disease;
Sclerosing primary cholangitis;
Biliary atresia;
Tuberculosis;
Sarcoidosis;
Lymphogranulomatosis;
Ductopenia is idiopathic.

Canalicular and hepatocellular cholestasis can be triggered by alcoholic, drug, viral or toxic liver damage, as well as endogenous disorders (cholestasis in pregnant women) and heart failure. Ductular (or extralobular) cholestasis occurs in the case of diseases such as cirrhosis of the liver.

The listed canalicular and hepatocellular cholestasis lead mainly to damage to the transport membrane systems, extralobular cholestasis occurs when the epithelium of the bile ducts is damaged.

Intrahepatic cholestasis is characterized by the entry into the blood, and, accordingly, also into the tissues of various types of bile components (mainly bile acids). In addition, their absence or deficiency is noted in the lumen of the duodenum, as well as in other intestinal sections.

Cholestasis: symptoms

Cholestasis due to excessive concentration of bile components in the liver, as well as in body tissues, provokes the occurrence of hepatic and systemic pathological processes, which, in turn, cause the corresponding laboratory and clinical manifestations of this disease.

The basis of the formation of clinical symptoms is based on the following three factors:

Excessive entry into the blood and bile tissues;
Decrease in the volume of bile or its complete absence in the intestine;
The degree of impact of bile components, as well as toxic bile metabolites directly on the tubules and liver cells.

The general severity of symptoms characteristic of cholestasis is determined by the underlying disease, as well as hepatocellular insufficiency and impaired excretory functions of hepatocytes.

Among the leading manifestations of the disease, as we have already noted above, regardless of the form of cholestasis (acute or chronic), skin itching is determined, as well as disturbances in digestion and absorption. For the chronic form of cholestasis, characteristic manifestations are bone lesions (in the form of hepatic osteodystrophy), cholesterol deposits (in the form of xanthoma and xanthelasma), as well as skin pigmentation due to the accumulation of melanin.

Fatigue and weakness are not typical symptoms of the disease under consideration, in contrast to their relevance in hepatocellular damage. The liver increases in size, its edge is smooth, its compaction and painlessness are noted. In the absence of portal hypertension and biliary cirrhosis, splenomegaly (enlarged spleen), as a symptom accompanying the pathological process, is extremely rare.

In addition, discoloration of the feces is among the symptoms. Steatorrhea (excess excretion of fat in the feces due to impaired intestinal absorption) is caused by a lack of content in the intestinal lumen of bile salts, which are required to ensure the absorption of fat-soluble vitamins and fats. This, in turn, corresponds to the pronounced manifestations of jaundice.

The stool becomes offensive, becomes liquid and voluminous. The color of the feces allows you to determine the dynamics in the process of obstruction of the biliary tract, which can be, respectively, complete, intermittent or resolving.

A short cholestasis leads to a deficiency in the body of vitamin K. The long course of this disease provokes a decrease in the level of vitamin A in the body, which manifests itself in "night blindness", that is, in violation of adaptation to the darkness of vision. In addition, there is also a deficiency of vitamins E and D. The latter, in turn, acts as one of the main links in hepatic osteodystrophy (in the form of osteoporosis or osteomalacia), manifesting itself in a rather severe pain syndrome that occurs in the lumbar or thoracic region. Against this background, there is also a spontaneity of fractures that occur even with minor injuries.

Changes at the level of bone tissue are also complicated by the actual violation that occurs in the process of calcium absorption. In addition to vitamin D deficiency, the occurrence of osteoporosis in cholestasis is determined by calcitonin, growth hormone, parathyroid hormone, sex hormones, as well as a number of external factors (malnutrition, immobility, decreased muscle mass).

The pathological process in which the excretion, synthesis and flow of bile into the duodenum is disturbed is characterized in medicine as cholestasis of the liver (Greek - cholestasis). With cholestasis, it is possible both to partially slow down the flow of bile, and to completely stop it.

A wide category of people, including pregnant women and newborns, is at risk of the disease.

Despite the fact that this syndrome is not so common, it can be quite difficult to identify it at an early stage. However, untimely diagnosis and treatment of cholestasis can cause a number of irreversible changes in the body, the main of which is acute liver failure. This indicates a high degree of danger of this disease.

Causes cholestasis

In view of the extensive classification of known forms of cholestasis syndrome, the causes of its occurrence are very diverse. Bile acids play an important role in pathogenesis. It is because of their toxic properties (namely, hydrophobicity and lyophilicity) that damage to liver tissues occurs and, as a result, the further development of the disease.

Two groups of causes of the development of the disease

Violation of the secretion and flow of bile:

Caroli disease (a rare disease in which the bile ducts dilate);
biliary atresia;
various forms of tuberculosis;
lymphogranulomatosis.

Violation of the formation of bile:

intoxication of the body with poisons or salts of heavy metals;
taking medications that adversely affect the functioning of the liver;
benign recurrence of cholestatic syndrome;
heart failure;
alcoholism;
violation of the intestinal microflora;
cholestasis during pregnancy;
hepatitis;
sepsis.

Classification

Depending on the location, cholestasis is divided into the following types:

intrahepatic;
extrahepatic.

The intrahepatic form develops at the level of the internal bile ducts and the hepatocyte level and is associated with impaired bile synthesis, as well as its entry into the bile capillaries.

Types of intrahepatic cholestasis

Functional (decrease in bile tubular current and the level of secreted hepatic fluid).
Morphological (accumulation of bile in the ducts and hepatocytes).
Clinical (delay of bile-forming components contained in the blood).

Extrahepatic cholestasis is associated with the patency of the bile ducts, which is caused by functional and structural disorders of the biliary system.

Divisions of cholestasis

Acute and chronic (depending on the nature of the disease).
Icteric and anicteric (based on the presence of jaundice as a symptom).
Partial and dissocial.

Why is cholestasis of the liver dangerous?

Left untreated, cholestasis can cause serious complications. Within a few days of the disease, a number of structural changes occur that are reversible at an early stage.

Expanded form:

bile capillaries expand;
increases the permeability of cell membranes;
biliary clots form.

At this stage, there may be:

microabscesses;
inflammation;
hepatic sockets;
biliary infarcts.

The most dangerous form is persistent. Occurs at a later date, after months and years of illness. In this case, pathological changes become irreversible, develop:

biliary form of fibrosis;
biliary cirrhosis.

Advanced forms of cholestatic syndrome can cause serious complications, such as:

Internal bleeding.
"Night blindness".
Osteoporosis.
Cirrhosis of the liver.
Liver failure.

Signs and symptoms of cholestasis

Excess bile caused by cholestasis provokes the appearance in the body of a functional pathology of the liver and internal organs, which is expressed in the laboratory and clinical manifestations of this syndrome.

In laboratory conditions, with cholestasis, the following markers are detected, usually associated with changes in the blood structure:

An increase in cholesterol levels.
An increase in the level of bilirubin.
Increased activity of alkaline phosphatase.
Increased levels of bile acids.
Increasing the level of copper.
Abundance of urobilinogen in the urine.

Standard biochemical methods of research allow revealing signs only at the later stages of the development of the disease, when the level of incoming bile decreases by more than 20%. At the same time, it is important to consider the identified changes in the aggregate, since their isolated interpretation can cause an erroneous diagnosis.

Clinical symptoms, depending on the form of the disease, can vary from latent to pronounced. The severity of certain symptoms is determined by three factors:

Excess bile in the blood and tissues.
Deficiency of bile in the intestines.
Toxic effect of bile mass on channels and cells of the liver.

Regardless of the form of cholestasis, the symptoms and signs of the disease are of a general clinical nature:

The occurrence of itching.
Change in the color of urine and feces (light feces, urine "beer" color).
Enlargement of the liver.
Cholestasis of the gallbladder (cholecystitis).
Biliary colic.
Constipation.
Bitterness in the mouth.
Jaundice.

Chronic cholestasis can cause organic damage to bone tissue (hepatic osteodystrophy), which leads to bone fragility even with minor injuries.

Methods for diagnosing cholestasis

Signs of cholestatic syndrome are detected on the basis of data:

history;
palpation;
characteristic symptoms of the disease, detected as a result of testing.

With cholestasis, the symptoms of the disease will be indicated by:

alkaline phosphatase;

Palpation is carried out by feeling the area of the liver to establish it:

volume;
density;
soreness.

Ultrasound examination allows to establish stagnation of bile in the channels, and cholanginography reveals the expansion of the bile ducts. Localization of tissue damage is determined by cholescintigraphy, where technetium-labeled iminodiacetic acid is used.
Photo: Differential diagnosis Having ruled out the possibility of extrahepatic cholestasis, a liver biopsy can be performed to establish the intrahepatic form of the disease.

Treatment of cholestasis

If there is the slightest suspicion of a disease, the patient should immediately contact a gastroenterologist who will prescribe a diet and course of treatment.

Cholestasis can accompany any pathology associated with the liver. Therefore, this disease requires urgent treatment.

Main symptoms

Since cholestasis provokes a drop in the level of vitamins, such as A, D, K and others, in the body, signs of night blindness. For the same reason, the patient has increased bleeding.

Such a sign of liver disease as its increase in cholestasis without cirrhosis occurs in rare cases.

Types of cholestasis

Intrahepatic cholestasis called the form in which stagnation of bile occurs in the intrahepatic bile ducts or in the cells of the liver, that is, it is formed inside the liver.
extrahepatic cholestasis the form is called when congestion is formed as a result of blockage of the extrahepatic bile ducts.

In acute cholestasis, the symptoms of the disease appear suddenly and are pronounced, in chronic cholestasis, the symptoms are weak, increasing over a long time (from weeks to months).

Causes of intrahepatic cholestasis

Causes of extrahepatic cholestasis

the appearance of a stone or stones in the bile ducts;
bile duct;
thickening of bile;
pancreatitis;
malignant tumors of the bile duct and / or pancreas.

Diagnostics

Another test method is endoscopic retrograde cholangiography(if this is not possible, it is replaced by percutaneous transhepatic cholangiography), which reveals the level of blockage.

Magnetic resonance cholangiography, which examines the bile ducts, is considered a promising method; this examination is highly informative.

Treatment

To eliminate pruritus in the treatment of the disease, plasmapheresis and opioid antagonists are used.

Since hypovitaminosis is noted in cholestasis, which entails side effects that require separate treatment, it is necessary to take vitamins K, D, E and fat-dissolving drugs.

If there is an obstruction in the bile duct mechanical or clogged bile ducts, then, in addition to conservative treatment, surgical intervention (conventional or endoscopic) is required.

Complications and consequences of cholestasis

In addition, cholestasis provokes diseases such as:

osteoporosis;
hemeralopia (decreased vision at dusk, or night blindness);
the occurrence of stones in the gallbladder and / or bile ducts;
development of inflammation of the bile ducts (cholangitis);
liver failure;
cirrhosis.

cholestasis of pregnancy

The causes of the disease are still not exactly clear. Experts identify three potential groups:

excess estrogen, which during this period, in particular by the end of pregnancy, in a woman's body increases 1000 times;
compression of the gallbladder and the liver of the pregnant uterus (just in the last trimester it reaches its maximum size);
hereditary nature of the disease(more than half of the women in the family had such pathologies).

Symptoms of cholestasis of pregnancy

Symptoms can appear all at once or one at a time, but most often the only symptom is itching.

Complications of cholestasis of pregnancy

Prevention of cholestasis

diet for cholestasis

cholestasis- This is a pathological condition in which there is a decrease in the release of bile into the small intestine, resulting from a violation of its production or excretion. Depending on the etiopathogenetic mechanisms of development of disturbances in the flow of bile into the duodenum, extrahepatic cholestasis and its intrahepatic form are distinguished, which have fundamental differences in clinical manifestations.

In most situations, specialists use the term "cholestasis syndrome", since this pathological condition is not an independent nosological form. Pathologically, this pathology manifests itself as the appearance of bile droplets in the liver cells and around dilated canals (intrahepatic cholestasis). If there is an extrahepatic variant of cholestasis, bile droplets accumulate mainly around the dilated bile ducts, and also in a small amount directly in the hepatic parenchyma.

Cholestasis of the liver with a long course provokes the development of structural disorders of the structure of the liver of a reversible and irreversible nature. In the advanced phase of the pathological process, there is an expansion of the bile capillary network, the formation of thrombotic masses in the vessels, the disappearance of the villous cover in the projection of the canacular membranes and an increase in the permeability of cell membranes, which is a histological criterion for cholestasis.

Chronic cholestasis, in addition to the above changes, is characterized by the formation of irreversible disorders in the form of the development of biliary infarcts, sclerosis zones and the formation of microabscesses. Gastroenterological specialists are of the opinion that almost any form of liver damage, as a structural unit, inevitably provokes the pathogenetic mechanisms of cholestasis. In addition, there are a number of pathologies accompanied by damage to the ducts of both intrahepatic and extrahepatic localization.

Causes of cholestasis

Among the pathological conditions that can provoke the development of cholestasis, there is a wide range of diseases, but all these etiological factors are united by a single etiopathogenetic mechanism for the development of cholestasis. Thus, the main link in pathogenesis is the damaging effect of bile acids on liver cells. All diseases and pathological conditions that are the background for the development of cholestasis are usually divided into two pathogenetic categories: diseases accompanied by impaired bile production in the required amount and pathological conditions that disrupt the normal flow of bile.

Violation of the bile-forming function of the liver is observed with alcoholic damage to the hepatic parenchyma, viral and toxic effects on the body with a predominant localization of toxic agents in the liver. In addition, the process of bile formation is negatively affected by disturbed microflora in the intestine, cirrhotic changes in the liver and endotoxemic conditions. This etiopathogenetic category also includes intrahepatic cholestasis of pregnant women.

The normal process of bile outflow is negatively affected by pathological changes in the bile ducts (cholangitis, ductopathy, Caroli's disease), congenital anomalies of the bile duct system, as well as systemic biliary. Such systemic diseases as, and inevitably provoke changes in the normal functioning of the structures of the hepato-biliary system, but these disorders develop mainly in the late stages of the underlying disease.

Intrahepatic cholestasis in all situations is accompanied by an excessive accumulation of bile acids not only in the circulating blood, but also in tissues of various types with a simultaneous insufficient content in the lumen of the duodenal section of the small intestine. Hepatic cholestasis can occur in several forms. So, with its functional variant, there is a significant slowdown in the tubular bile flow, and morphological cholestasis is accompanied by a significant deposition of bile components in the projection of hepatocytes and bile ducts. The clinical form of intrahepatic cholestasis is observed when bile components are retained in the circulating blood, while under normal conditions bile acids are excreted into bile.

The development of intrahepatic cholestasis becomes possible even in the absence of obstruction of the lumen of the main bile duct. However, the existing obstruction of the bile ducts of the intrahepatic order inevitably provokes the development of cholestasis syndrome.

Symptoms and signs of cholestasis

Cholestatic syndrome, caused by excessive excretion of bile acids and other components of bile in the liver and other tissues of the human body, is inevitably accompanied by the development of pathological structural changes in target organs that have specific clinical and laboratory manifestations.

The development of clinical variants of the course of cholestasis and their intensity is based on three main mechanisms: excessive deposition of bile components in the circulating blood and tissues, a significant decrease in the concentration of bile in the duodenum, and the toxic damaging effect of bile acids on hepatocytes. The intensity of the manifestation of certain clinical symptoms directly depends on the underlying disease, the severity of hepatocellular insufficiency and the severity of the violation of the excretory function of hepatocytes.

A feature of cholestasis is that the development of manifestations of asthenic syndrome occurs only with concomitant hepatocellular damage and manifests itself in the form of the appearance of unmotivated weakness, dizziness, and the inability to perform the usual physical activity. With the existing intrahepatic cholestasis, there is a change in the shape and size of the liver in the direction of its significant increase, provided that there is no pain syndrome and a violation of the structure of the hepatic parenchyma. An increase in the parameters of the spleen occurs only as a concomitant pathology of biliary cirrhotic liver damage, which is extremely rare.

One of the most specific manifestations of cholestasis, which allows an experienced specialist to establish a preliminary diagnosis without conducting a specific laboratory examination of the patient, is a change in the stool in the form of an increase in its daily amount, malodor, discoloration and structural disturbance. Due to the fact that with cholestasis there is a restriction of the flow of bile acids into the duodenal section of the small intestine, a large concentration of unsplit fats accumulates in the feces.

Violations of the absorption function of the intestine inevitably affect the vitamin balance in the body. So, even a short course of cholestasis provokes the development of vitamin K deficiency in the body, manifested by excessive bleeding of the mucous membranes. Chronic cholestasis in all situations is accompanied by signs of group A.

The result of a violation of the digestive and absorption function of the intestine, which is observed in all pathogenetic variants of cholestasis, is a long debilitating. Abundant diarrhea syndrome provokes the development of dehydration and the release of large amounts of electrolytes and other nutrients. The outcome of this condition is the development of malabsorption syndrome and progressive weight loss of the patient, even with normal nutrition.

The most important clinical criterion for chronic cholestasis is a pathognomonic lesion of the skin in the form of yellow tumor-like spots resulting from a violation of lipid metabolism. The favorite localization of these changes are the skin of the upper half of the body, as well as the area of natural skin folds. The appearance and disappearance of xanthomas can be regarded as a diagnostic sign that reflects the level of cholesterol in the blood. In a situation where the patient's age spots are localized exclusively paraorbitally, experts use the term "xanthelasma".

Also, cholestasis is accompanied by manifestations characteristic of a violation of copper metabolism in the body, since under normal conditions, the excretion and absorption of copper in the small intestine occurs together with bile. Prolonged cholestasis is accompanied by a significant increase in the concentration of copper and its deposition in target organs of the type.

The main complication of cholestasis, observed in 70% of cases with a long course, is the formation of pigment stones in the structures of the biliary system and concomitant signs of bacterial cholangitis. In addition, the clinical picture in each patient may differ, depending on the manifestation of the underlying disease.

In addition to the characteristic clinical manifestations that allow an experienced specialist to correctly diagnose already during the initial contact with a patient with cholestasis, there is a certain algorithm for examining this category of patients. All laboratory and instrumental techniques used in this situation are aimed not so much at diagnosing cholestasis as at identifying the cause of its occurrence. Thus, an ultrasound examination or cholangiography in most cases allows you to establish the exact localization of the mechanical blockade in the lumen of the structures of the hepato-biliary system. If a patient is suspected of having an intrahepatic variant of cholestasis, provided that there is no information content during other instrumental research methods, a needle biopsy is recommended.

cholestasis in pregnancy

The prevalence of this pathology among the general population of pregnant women is 1:500 and such a high rate is due to the family type of inheritance. In addition, cholestasis during pregnancy is prone to recurrent course, so the subsequent one in 80-90% of cases also proceeds with signs of cholestasis. The level of fetal mortality in cholestasis in a pregnant woman is no more than 10% and in the priority majority of cases is caused by massive uterine bleeding due to vitamin K deficiency.

The pathogenetic mechanisms of the development of cholestasis in a woman during pregnancy are explained by a violation of the metabolism of estrogens, which have an inhibitory effect on the formation and secretion of bile. In a situation where there is a significant deposition of bile acids and other components of bile in the placenta, the risk of provocation in the early stages of fetal development, incompatible with life, is significantly increased. Among gastroenterologists, there is an opinion that pregnancy acts as a provoking factor in the development of genetic product defects present from birth and bile secretion.

The risk group for the development of this pathology is women who are in the third trimester of pregnancy and in most cases the only clinical manifestation of cholestasis is excruciating widespread skin itching. The predominant localization of skin manifestations of cholestasis during pregnancy is the upper half of the body and especially the palms of the hands. In most situations, pruritus is self-leveled after the delivery of a woman no later than two weeks later.

The most informative in relation to the diagnosis of cholestatic syndrome during pregnancy is a biochemical blood test, in the study of which there is a significant increase in the direct fraction of bilirubin and alkaline phosphatase activity, provided that ALT and AST are normal. When conducting a specific analysis of the content of bile acid fractions in the blood of a pregnant woman with cholestasis, there is a significant increase in their concentration, exceeding normal values by 100 or more times.

Despite the fact that cholestasis during late pregnancy is a common pathology even in absolutely healthy women, when its signs are detected, it is necessary to carefully examine the patient for the presence of other diseases that have a similar clinical and laboratory picture (parenchymatous and obstructive jaundice, hereditary diseases with metabolic disorders, acute).

Under the condition of slightly pronounced clinical and laboratory criteria for cholestasis, the treatment of a pregnant woman consists exclusively in the use of symptomatic drugs (Promethazine at a daily dose of 75 mg, Phenobarbital at a daily dose of 45 mg orally). In a situation where a pregnant woman has a significant excess of the level of bile acids and there are no indications for a planned delivery, it is recommended to use drugs whose action is aimed at lowering the level of serum bile acids (Cholestyramine in a daily dose of 12 g) with the simultaneous use of Phytomenadione according to 10 mg subcutaneously once a week and Folic acid at a daily dose of 1 mg.

Due to the increased risk of uterine bleeding, the diet for cholestasis of pregnancy is of great importance. A woman should consume enough foods containing a high concentration of vitamin K, as well as limit the intake of fatty foods.

Cholestasis in children

The incidence of cholestasis in children during the neonatal period and in the infancy varies significantly in the population of different countries and regions, however, there is some tendency towards an increase in the incidence of cholestasis of extrahepatic origin in this category of patients. Transient variants of the course of the cholestatic syndrome of newborns should also not be overlooked, even though it does not bring significant harm to the health and development of the child.

Determining the etiopathogenetic variant of cholestasis in children is of paramount importance, since the further tactics of treating the patient depend on it. Currently, most variants of extrahepatic cholestasis in infants are an absolute indication for the use of surgical intervention, since modern methods of surgical treatment of extrahepatic biliary atresia can achieve good results in eliminating signs of cholestasis.

Common signs characteristic of both etiopathogenetic variants of cholestasis is the appearance of clinical and laboratory signs of impaired bile outflow. Clinical criteria in this case are the appearance of icteric staining of the skin and mucous membranes, discoloration of the feces and darkening of the urine. The most important diagnostic sign of cholestasis in the neonatal period is the color of feces, since its change allows us to assess the dynamics of the development of cholestasis. For newborns, the appearance of pronounced skin itching is not typical, and at an older age, a pronounced one is observed with an intrahepatic variant of cholestasis. It should be borne in mind that during the neonatal period, cholestasis always occurs with jaundice, which is a specific pathognomonic clinical marker of this pathology.

In children, in addition to severe clinical symptoms, cholestasis is accompanied by significant changes in laboratory parameters in the form of an increase in conjugated bilirubin, an increased total cholesterol and an increase in alkaline phosphatase activity.

The most common cause of the development of an extrahepatic variant of cholestasis in a child during the neonatal period is extrahepatic atresia of the biliary tract, which is observed in one case in 10,000 newborns. The intrahepatic variant of the development of cholestasis in children occurs with direct viral, metabolic and immunological hepatocellular damage to the hepatic parenchyma.

Drug correction of cholestasis consists in prescribing drugs that improve the outflow of bile and normalize the levels of bile acids in the blood serum, and the choice of the drug directly depends on the degree of clinical and laboratory manifestations of cholestasis (Phenobarbital at an estimated dose of 5 mg per 1 kg of a child's weight, Cholestyramine at a daily dose of 4 G). The appointment of glucocorticosteroid drugs is considered unjustified for infants due to the complete lack of effectiveness and an increased risk of developing infectious complications.

Treatment of cholestasis

Since cholestasis is not an independent nosological form and is a clinical and laboratory accompaniment of the underlying underlying disease, all options for therapeutic measures used in this pathology are classified as symptomatic or etiopathogenetic.

The main goal of the symptomatic component of the treatment of cholestasis is to eliminate the main clinical signs of the disease, namely pruritus. The most effective method of stopping the skin manifestations of cholestasis is the drainage of the biliary tract by external or internal methods, after which, skin itching stops within two days. If there are contraindications to the use of drainage of the bile ducts, Cholestyramine should be used, the use of which allows leveling skin itching for five days. The optimal single dosage of Cholestyramine is considered to be 4 g with the preferred intake together with breakfast, lunch and dinner. The appearance of signs of hypoprothrombinemia is an indication for the transition to the parenteral route of administration of Cholestyramine in the minimum effective dose.

Another drug that has an effective antipruritic effect is Ursodeoxycholic acid. This drug is especially effective in the treatment of patients suffering from primary biliary cirrhosis at a calculated dose of 10 mg per 1 kg of patient weight. If there is no effect from the use of the above drugs, you should resort to the appointment of sedative drugs in a short course (Phenobarbital 0.05 g twice a day). Glucocorticosteroid preparations have a good antipruritic effect, however, due to the wide range of negative reactions in the form of deterioration of the bone tissue and an increase in the risk of infectious complications, this treatment is used extremely rarely.

If the patient has refractory itching, combined with critical values of cholesterol in the blood and xanthomatous neuropathy, plasmapheresis should be used for a short course. However, in most cases, the only method to eliminate refractory pruritus in cholestasis is liver transplantation.

The use of drugs with a pronounced hepatoprotective effect is indicated for intrahepatic cholestasis, and the drug of choice in this situation is Heptral. The course of hepatoprotective therapy consists in the parenteral administration of Heptral at a dose of 5 ml for two weeks and the subsequent transition to a tablet intake of the drug at a daily dosage of 800 mg for at least two months. Rifampicin has a similar effect, which improves the acid microflora necessary for the normal metabolism of bile acids. The regimen of Rifampicin is oral administration of 150 mg per day for three months.

The patient's biliary compression is the basis for the use of surgical intervention techniques. Currently, the calculus present in a patient with cholestasis in the projection of the common bile duct is successfully eliminated by endoscopic papillosphincterotomy. In a situation where the obstruction of the bile ducts is due to the existing tumor substrate, the primary task of the operating oncologist is to assess the resectability of the tumor. If the tumor process is at an inoperable stage, the surgeon should make a decision to drain the biliary tract by endoscopic access.

The use of any surgical aid for cholestasis requires a careful approach to the issue of preparing the patient for surgery, given the high risk of developing infectious and hemorrhagic complications. In order to prevent possible bleeding, preoperative preparation of a patient suffering from cholestasis provides for parenteral administration of vitamin K in a daily dose of 0.03 g. To reduce the risk of infectious complications, an adequate antibiotic therapy regimen should be used in the patient in the preoperative and postoperative period.

The fundamental link in the treatment of chronic cholestasis is the correction of eating behavior and beriberi. Nutrition correction consists in enriching the daily menu with products containing vegetable fat and sharply limiting the use of neutral fats. In the event that a patient has minimal manifestations of vitamin A deficiency in the form of a decrease in twilight vision, it is recommended to use a course of parenteral administration of an oil solution at a dose of 10,000 IU.

In addition, the chronic course of cholestasis is always accompanied by a violation of the process of bone formation, which is expressed in the development of progressive osteoporosis and the consequences of this pathological condition. If the initial manifestations of osteoporosis are detected in a patient with cholestasis, it is necessary to use vitamin D replacement therapy according to the scheme: once a month, intramuscular injection of 100,000 IU or orally 3 times a week, 50,000 IU. The appointment of vitamin D is justified even in the absence of signs of bone tissue damage as a prophylactic for patients with a long course of icteric syndrome.

In some situations, the cholestatic syndrome in a patient may occur with the appearance of a pronounced pain syndrome in the projection of the bones, therefore, in this case, it is justified to prescribe intravenous calcium gluconate at a calculated dose of 15 mg per 1 kg of body weight with 5% glucose solution in a volume of 500 ml. Also, the appointment of replacement therapy with calcium and vitamin D preparations is necessarily carried out in the postoperative period after liver transplantation.