Intra hepatic cholestasia

Description:

Any pathological process in a liver can be followed by a cholestasia syndrome – reduction of intake of bile in a duodenum owing to disturbance of its education, excretion and/or removal. At a cholestasia reduction of canalicular current of bile, hepatic excretion of water and/or organic anions (bilirubin, bile acids), accumulation of bile in hepatocytes and biliary tract, a delay of components of bile in blood (bile acids, lipids, bilirubin) are observed. It is long the remaining cholestasia (within months or years) leads to development of biliary cirrhosis.

The cholestasia is divided on out of - and intra hepatic, acute and chronic, icteric and anicteric. The extrahepatic cholestasia arises at mechanical obstruction of the main extrahepatic or main intra hepatic channels. Stones of the general bilious channel are the most frequent reason of an extrahepatic cholestasia. The intra hepatic cholestasia develops in the absence of obstruction of the main bilious channels (that is confirmed at a holangiografiya). Any pathological process within a liver (with damage of hepatocytes and/or bilious tubules) can be followed by a cholestasia (hepatocellular or canalicular). In one cases etiological factors of damage of a liver are known (drugs, viruses, alcohol), in others – no (primary biliary cirrhosis – PBTs, primary sclerosing cholangitis – PSH). At a number of diseases (a sclerosing cholangitis, a Christian's disease) are surprised as out of - and intra hepatic channels.

Symptoms of the Intra hepatic cholestasia:

The main clinical manifestations of a cholestasia (both acute, and chronic) – a skin itch, jaundice and disturbance of absorption of fats.
The skin itch, jaundice are observed at considerable disturbance of excretory function of hepatocytes (> 80%) and are not precursory symptoms of a disease. The itch considerably worsens quality of life of patients, its nature is finally not found out. Possibly, the connections causing an itch (pruritogena) are synthesized in a liver (in favor of it disappearance of an itch in an end-stage of a liver failure testifies). Traditionally the itch of skin is connected with a delay of bile acids in skin and irritation of nerve terminations of a derma, epidermis. At the same time direct correlation between expressiveness of an itch and level of bile acids in blood serum does not manage to reveal.
Markers of a chronic cholestasia – the xanthomas (the flat or towering educations, soft, yellow color, usually around eyes, and also in palmar folds, under mammary glands, on a neck, a breast or a back) reflecting a delay of lipids in an organism. Tuberous xanthomas (in the form of hillocks) are found on extensor surfaces in large joints, buttocks, in the places which are exposed to pressure, cicatricial changes of skin.
Insufficient content of bile acids in a gleam of intestines is followed by disturbance of absorption of fats, development of a steatorrhea, weight loss, deficit of fat-soluble vitamins (And, D, K, E). Expressiveness of a steatorrhea, as a rule, corresponds to jaundice degree.
The long cholestasia is complicated by formation of stones in bilious system. In the presence of stones or after operations on bilious channels, especially at patients with a hepatoenteric anastomosis, the bacterial cholangitis often joins (a classical triad pains in right hypochondrium, fever from oznoba, jaundice make).
Synthetic and detoksikatsionny functions of a liver at a cholestasia long time remain safe, at long cholestatic jaundice (3-5 years) hepatocellular insufficiency develops.

Reasons of the Intra hepatic cholestasia:

Bilification includes a number of volatile transport processes: capture of components of bile from blood (bile acids, other organic and inorganic ions), their transfer through a sinusoidal membrane in a cell, further through a canalicular membrane in a bilious capillary. Transport of components of bile depends on functioning of proteins – the carriers which are built in sinusoidal and canalicular membranes (including Na+-, K+-Atfazy, carriers for bile acids, organic anions, etc.). Development of a cholestasia is the cornerstone of disturbance of these transport processes.
At mechanical obstruction of the main channels major importance in development of a syndrome of a cholestasia has increase in pressure in bilious channels (bilious hypertensia more than 15-25 cm w.g. leads to suppression of biliary secretion).
Some bile acids having the expressed surface-active properties, collecting at a cholestasia, can cause damages of cells of a liver and strengthen a cholestasia. The main link in development of a necrosis of hepatocytes consider damage by bile acids of membranes of mitochondrions that reduces synthesis of ATP in a cell, increases intracellular concentration of calcium, stimulates the kaltsiyzavisimy hydrolases injuring a hepatocyte cytoskeleton.
Connect with influence of bile acids also apoptosis of hepatocytes – the programmed cell death (there is an increase in intracellular concentration of magnesium to the subsequent activation of magniyzavisimy nuclear proteases, endonucleases and DNA degradation), and also the expression of HLA I antigens of a class which is not observed normal on hepatocytes, a HLA II class on epithelial cells of bilious channels which can be factors of development of autoimmune reactions against hepatocytes and bilious channels.

Treatment of the Intra hepatic cholestasia:

If the causative factor of a cholestasia is known, carry out etiological treatment: removal of a stone, tumor resection, timely cancellation of drugs, deworming, etc. In the presence of mechanical obstruction of a bilious path and impossibility of radical treatment recovery of a drainage of bile (balloon dilatation of strictures, endoprosthesis replacement, a biliodigestivny anastomosis) is necessary.
Dietary restrictions include reduction of animal fats in a diet (in the presence of a steatorrhea), the use of the margarine containing triglycerides with an average length of a chain (their absorption happens without participation of bile acids). At development of hypovitaminoses replacement therapy by vitamins orally or parenterally is necessary. At impossibility of determination of level of vitamins B to serum treatment is appointed empirically, especially at jaundice.
Means of the choice at not obstructive cholestasia in many cases – ursodeoksikholovy acid (UDHK) – safety of use of which and efficiency concerning clinical and laboratory symptoms of a cholestasia are proved. UDHK represents the tertiary bile acid which is formed in intestines and a liver, making 0,1-5% of a common pool of bile acids. Drug is non-toxical owing to hydrophily of a molecule. At treatment of UDHK there is a shift of proportions of components of bile towards sharp dominance of UDHK over other bile acids. UDHK forces out toxic bile acids from enterogepatichesky circulation (by competitive inhibition of absorption in an ileal gut), preventing their damaging action on membranes. Besides, UDHK is capable to be built in membranes of hepatocytes, having the cytoprotective effect (it is shown in experiments on the isolated membranes of hepatocytes, erythrocytes, cells mucous a stomach), reducing products by the surfaces of hepatocytes of HLA I antigens of a class, preventing development of autoimmune reactions (immunomodulatory action). UDHK has cholagogue effect owing to the holegepatichesky shunt. The optimum dose of UDHK makes 10-15 mg/kg a day. Drug is accepted it is long (constantly).
For treatment of an itch of skin use phenobarbital, холестирамин, колестипол, at a refractory itch – a plasma exchange, phototherapy (ultra-violet radiation).