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

What is cholestasis?

Cholestasis is also commonly referred to as «cholestasis syndrome». The morphology of the name of this disease is the presence of bile in the hepatocytes and hypertrophied Cooper cells (cell bilirubinostasis), which is manifested in particular in the form of small drops of bile concentrated in the area of ​​dilated canals (canal bilirubinostasis). In the case of extrahepatic cholestasis, the location of bile is concentrated in the region of interlobular dilated bile ducts (which determines ductular cholestasis), as well as in the liver parenchyma, where the bile has the appearance of so-called «bile lakes».

The existing cholestasis for several days provokes the emergence of potentially reversible ultrastructural changes. The unfolded phase of the disease is characterized by a number of histological changes in the form of enlargement of the bile capillaries, the formation of biliary thrombi, the disappearance of villous fibers from the canal membrane, and damage to cell membranes, which in turn provokes their permeability. In addition, among the changes in the enlarged phase, there is a violation of integrity in tight contacts and bilirubinostasis, the formation of hepatic outlet and periductal edema, sclerosis and biliary infarcts. At the same time, microabscesses, mesenchymal and periportal inflammations, etc are also formed, etc.

With the persistent form of cholestasis with the corresponding form of inflammation and the reaction in connective tissue, the disease becomes irreversible. After a certain time (in some cases calculated in months, in some years), a similar 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 conjunction with cholestasis. In some cases, the causes provoking liver damage are identified (alcohol, viruses, drugs), in some — not identified (primary biliary cirrhosis, sclerosing the primary cholangitis). A number of diseases (histiocytosis X, sclerosing cholangitis) leads to the destruction of both the intrahepatic ducts and the extrahepatic ducts simultaneously.

Main forms of the disease

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

  • Functional cholestasis. It is characterized by a decrease in the level of the biliary tubular current, as well as a decrease in organic anions (in the form of bile acids and bilirubin) and hepatic water excretion.
  • Morphological cholestasis. Characterized by the accumulation of bile components in bile ducts and hepatocytes
  • Clinical cholestasis. Determines the delay in the composition of blood components that are normally excreted in 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 the bile intrahepatic ducts and at the level of hepatocytes. On the basis of this, cholestasis is distinguished, which is caused by the defeat of hepatocytes, ductula and canal, and mixed cholestasis. In addition, acute cholestasis and chronic cholestasis are also determined, in icteric or jaundiced form.

Causes of cholestasis

The reasons for the appearance of the disease we are considering are extremely diverse. An important role in the study of the development of cholestasis is defined for bile acids, for which surface-active features are inherent in the extreme degree of their manifestations. It is bile acids that provoke cell damage to the liver with simultaneous strengthening of cholestasis. The toxicity of bile acids is determined by the degree of lipophilicity and hydrophobicity.

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

Bile-related disorders:

  • Alcoholic liver damage
  • Viral liver damage
  • Toxic liver disease;
  • Liver medication;
  • Benign form of recurrent cholestasis
  • Disorders in intestinal microecology
  • Liver cirrhosis
  • Cholestasis of pregnant women
  • Bacterial infections
  • Endotoxemia

Impaired bile flow:

  • Biliary primary cirrhosis;
  • Caroli’s disease
  • Sclerosing primary cholangitis
  • Biliary atresia
  • Tuberculosis
  • Sarcoidosis
  • Lymphogranulomatosis
  • Idaptopathy idiopathic.

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

These cancalicular and hepatocellular cholestasis lead mainly to lesions of transport membrane systems, extralobular cholestasis occurs when the epithelium of the bile ducts is affected.

Intrahepatic cholestasis is characterized by the entry into the blood, and accordingly, also in the tissues of various types of bile components (in the predominantly bile acids). In addition, there is a lack of either a deficit in the area of ​​the lumen of the duodenum, as well as in other intestinal departments.

Cholestasis symptoms

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

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

  1.  Redundancy in blood and bile tissue
  2.  Decreased volume of bile or its complete absence in the intestine;
  3.  The degree of exposure of the bile components, as well as the toxic metabolites of bile directly to tubules and liver cells.

The general severity of the symptoms, characteristic of cholestasis, is determined by the underlying disease, as well as hepatic-cell insufficiency and impaired excretory functions of the hepatitis.

Among the leading manifestations of the disease, as we have already noted above, regardless of the form of cholestasis (acute or chronic), it is determined by itching, as well as disturbances in digestion and absorption. Chronic forms of cholestasis are characterized by bone lesions (in the form of liver osteodystrophy), cholesterol deposits (in the form of xantham and xantelasm), as well as skin pigmentation resulting from the accumulation of melanin.

Rapid fatigue and weakness are not characteristic of the disease under consideration, in contrast to their relevance in hepatocellular lesions. The liver grows in size, its edge is smooth, its denseness and painlessness are noted. In the absence of portal hypertension and biliary cirrhosis, splenomegaly (enlarged spleen), as a symptom associated with the pathological process, is extremely rare.

In addition, among the symptoms, feces are discolored. Steatorrhea (excessive secretion with fatty fatty masses due to intestinal absorption) is caused by a lack of bile salts in the lumen of the intestine, which are required to ensure the absorption of fat-soluble vitamins and fats. This, in turn, corresponds to pronounced manifestations of jaundice.

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

Short-lived cholestasis leads to a deficiency in the body of vitamin K. A prolonged course of this disease provokes a lowering of the level in the body of vitamin A, which is manifested in «chicken 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 fairly severe pain syndrome arising in the lumbar or thoracic region. Against this background, spontaneity of fractures that occur even with minor injuries is also noted.

Changes in the level of bone tissue are also complicated by the actual impairment that occurs during the absorption of calcium. In addition to vitamin D deficiency, the appearance 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).

Thus, due to the characteristic deficiency of bile in the disease, digestion is disrupted, as, in fact, the absorption of edible fats. Diarrhea, a companion of steatorrhea, provokes loss of fluid, fat-soluble vitamins and electrolytes. For this reason, malabsorption develops, followed by a decrease in weight.

As markers of cholestasis (in particular its chronic form) xanthomas (yellow tumor-like spots on the skin appearing as a result of disturbances in the lipid metabolism of the body) act. Advantageously, the area of ​​concentration of these spots is localized in the area around the eyes, on the chest, back, neck, and also in the region of the palmar creases and under the mammary glands. Preceding the appearance of xanthus hypercholesterolemia, which can last for three months or more. It is noteworthy that xanthomas are an education prone to reverse development, which in particular occurs in the case of a decrease in cholesterol levels. Another species of xanthom are such formations as xanthelasm (yellowish plaques, centered around the eyes and directly on the eyelids).

The characteristic manifestation of cholestasis is also a violation in the exchange of copper, which contributes to the development of processes of collagenogenesis. About 80% of the total volume of aspirated copper is normally excreted in the intestine with bile in a healthy person, after which it is removed along with the feces. In the case of cholestasis, the accumulation of copper in the body occurs in significant concentrations (by analogy with Wilson-Konovalov’s disease). A number of cases indicate the detection of a pigmentary corneal ring.

The accumulation of copper in liver tissues occurs in cholangiocytes, hepatocytes and in the system cells of mononuclear phagocytes. The localization of excess content in copper cells is due to etiological factors.

It occurs among patients with cholestasis in its chronic form and such manifestation as dehydration changes the activity of the cardiovascular system. Violation of vascular reactions occurs due to arterial hypotension, in addition there is a violation in the regeneration of tissues, increased bleeding. Increased risk of sepsis.

The prolonged course of cholestasis is often complicated by the formation of pigmentary stones in the biliary system, which, in turn, is complicated by bacterial cholangitis. The formation of biliary cirrhosis determines the relevance of signs of hepatic-cell insufficiency and portal hypertension.

Anorexia, fever, vomiting and abdominal pain can be symptoms of a disease that provoked cholestasis, but they are not symptoms of cholestasis itself.

Diagnosis of cholestasis

Cholestasis is determined based on the patient’s history and the presence of characteristic symptoms along with palpation of the relevant areas. As an algorithm for diagnostic research, ultrasound is provided, with the help of which it becomes possible to determine the mechanical blockage formed in the biliary tract. Cholangiography is used to detect an expansion in the ducts.

In case of suspicion of the relevance of intrahepatic cholestasis, a liver biopsy can be performed, for which, however, it is necessary to completely exclude the possibility of an extrahepatic form of cholestasis in the patient. Otherwise, ignoring this factor can lead to the development of bile peritonitis.

Localization of the level of damage (extrahepatic or intrahepatic cholestasis) can be performed using cholestcentography, in which iminodiacetic acid is labeled with technetium.

Treatment of cholestasis

The intrahepatic form of the disease indicates the effectiveness of etiotropic therapy. That is, it implies a specific treatment, focused on eliminating the causes that caused the particular disease in question. This may involve removing the stone, de-worming, resection of the tumor, etc. Based on a number of studies, a high degree of efficacy in the use of ursodeoxycholic acid in the case of cholestasis with topical biliary cirrhosis, as well as sclerosing primary cholangitis, alcoholic liver disease, etc. has been determined.

Plasmapheresis, colestipol, cholestyramine, opioid antagonists, etc. are used to treat skin pruritus. In addition, a diet is recommended with the exception of eating neutral fat while reducing its volume to a daily norm of less than 40 g. In addition, fat-soluble vitamins are prescribed to compensate for their deficiency (K, A, E, D), as well as calcium. In the event of a mechanical obstruction in the outflow of bile, endoscopic or surgical treatment is performed.

If you suspect a cholestasis with the actual symptoms for him, you should consult a gastroenterologist. Additionally, a surgeon’s consultation may be needed.