Aholia

A condition in which bile is not produced or passed into the small intestine is defined as acholia. In ICD-10, this violation is classified as a disease of the gallbladder - with the code K82.8. But, since bile acids and bile itself are synthesized in the liver, most specialists consider acholia syndrome as the result of pathological changes in the entire hepatobiliary system. [1]

Epidemiology

The statistics of pathologies of the hepatobiliary system leading to acholia are unknown.

The prevalence of a genetically determined disorder in the synthesis of bile acids is estimated at 1-2%, for example, Alagille syndrome occurs in about one newborn out of 100 thousand.

Causes acholia

The key causes of acholia lie in disorders of choleresis or cholekinesis - the formation of bile or its excretion. Both are functions of the hepatobiliary system, which consists of: the liver producing bile   (with the system of bile ducts and ducts), its accumulator - the  gallbladder  (in which bile becomes more concentrated), as well as the cystic and common excretory bile duct, through which bile enters the lumen of the duodenum.

Under what pathological changes is acholia syndrome observed? It develops if bile acids are not produced by hepatocytes (liver cells), and this can be when:

• dystrophic and  diffuse liver changes  in diabetes-related amyloidosis,  chronic hepatitis , obesity, alcoholism;
• necrosis or apoptosis of liver cells that occurs with  hepatitis A , B and C;
• damage to hepatocytes due to fibrosis and  cirrhosis of the liver ;
• fatty infiltration of the hepatic parenchyma or hepatic  steatosis .

In addition, acholia is observed in patients with bile secretion problems, which may be due to:

• dyskinesia of the gallbladder  and bile ducts, leading to extrahepatic  stasis of bile ;
• sclerosing cholangitis of  various etiologies;
• congenital anomalies of the biliary tract , for example, Alagil's syndrome - a genetically determined dysplasia of the intrahepatic bile ducts with chronic  cholestasis ; [2]
• immune-mediated destruction of the bile ducts in primary biliary cirrhosis, which is often combined with other autoimmune diseases.

Risk factors

Experts refer to the risk factors for the development of acholia:

• mutations of genes encoding liver enzymes necessary for the synthesis of bile acids;
• almost all diseases that in one way or another affect the functions of the hepatobiliary system;
• violations of the secretory function of the liver during its invasion by parasites (dysentery amoeba, lamblia, blood and liver flukes, bovine or pork tapeworm);
• gallstone disease ;
• metabolic disorders in endocrinopathies, in particular, diabetes mellitus and obesity;
• improper diet (with an excess of sweet and fat in the diet);
• chronic alcoholic liver intoxication;
• liver damage with various toxins, as well as the iatrogenic effect of drugs that can cause cholestasis and acute liver failure;
• a history of gallbladder fistulas and cholecystectomy (removal of the gallbladder);
• malignant neoplasms and liver metastases;
• immunodeficiency states.

Pathogenesis

Every day, an adult's liver produces on average 600-800 ml of bile, and this requires about 200 mg of primary bile acids - cholic and chenodeoxycholic, which are the basis of bile. They are synthesized by the agranular endoplasmic reticulum of the biliary part of hepatocytes - by oxidizing cholesterol (cholesterol), with further transfer to the membranes of the intrahepatic bile ducts. Also, the liver produces cholesterol - from blood lipoproteins, which capture special receptors in the vascular part of hepatocytes.

All these biochemical processes require enzymes of cytoplasmic membranes, microsomes, mitochondria and lysosomes of hepatocytes: cholesterol-7α-hydroxylase (CYP7A1), cholesterol-12α-hydroxylase (CYP8B1), sterol-27-hydroxylase (CYP27A1), acyl cholesterol acyl ACHAT), hydroxymethylglutaryl-CoA reductase (HMGR).

And the pathogenesis of acholia is associated with damage to liver cells - inflammatory, autoimmune, or under the influence of free radicals, which leads to dysfunctions of the cellular structures of hepatocytes and deficiency of enzymes that provide the synthesis of primary bile acids.

If bile from the gallbladder does not enter the intestine during the process of eating, then, in addition to obstruction of the biliary tract, the mechanism of development of acholia may consist in the lack of secretin and cholecystokinin - hormones produced by cells of the mucous membrane of the small intestine.

Read also -  What leads to biliary dyskinesia

Symptoms acholia

The characteristic symptoms of acholia are manifested by  jaundice  (with stagnation of bile in the liver and impaired metabolism of the bile pigment - bilirubin), clarification of feces (associated with the absence of stercobilinogen, which is formed during the breakdown of bilirubin), choluria - a dark yellow color of urine.

Etiologically associated with a violation of the synthesis of bile acids by the liver, their accumulation in the blood - cholemia and acholia, which is manifested by itching of the skin.

Occasionally, the temperature rises, and there are also hemorrhages on the skin and mucous membranes - due to insufficient synthesis of blood-clotting proteins in the liver.

In severe cases, cerebral conditions such as delirium and coma are possible.

But the very first signs of acholia are manifested by steatorrhea - fatty pale feces.

And constipation, diarrhea and flatulence are symptoms of digestive upset with acholia. 

Complications and consequences

Bile provides the digestive process, and its lack or complete absence has clinical consequences and complications in the form of decreased absorption of food (as well as fat-soluble vitamins A, E, D and K), loss of body weight, and general depletion.

The mechanism of impaired lipid digestion in acholia is explained by the fact that complete breakdown of fats in the digestive tract without bile is impossible, since for their digestion and assimilation they must be transformed into an emulsion. And the process of their emulsification in the lumen of the duodenum occurs under the influence of bile and hydrolytic intestinal enzymes (lipases), which are also activated by bile acids.

Without bile, the kinazogen secreted by the cells of the mucous epithelium of the duodenum and jejunum is not activated, and this, in turn, leads to a decrease in the level of enteropeptidase (enterokinase) - a digestive enzyme, as well as the activity of the proenzyme trypsinogen and its transformation into an active enzyme trypsin ( without which proteins from food are not digested).

The metabolic function of bile acids is also disrupted, which leads to an increase in blood cholesterol levels, deterioration of blood clotting, a decrease in bone mineral density (osteopenia) and their softening (osteomalacia).

In addition, many toxic substances, xenobiotics and metals are excreted in the bile, and their accumulation in acholia associated with cholestasis aggravates liver damage.

Diagnostics acholia

Diagnosis of acholia includes a complete history, physical examination, laboratory and imaging studies.

Blood tests are taken for albumin, fibronectin, hepatglobin, cholesterol, bilirubin, bile acids, aminotransferases - that is,  a blood test for liver function tests .

You also need a general urine test and a coprogram - feces analysis; analysis of bile obtained during  duodenal intubation of the gallbladder . Sometimes a liver biopsy is needed.

Instrumental diagnostics uses  ultrasound of the liver  and gallbladder,  x-ray of the liver and biliary tract , cholescintigraphy and  hepatobiliscintigraphy . [3]

More details:

• Diagnostics of the liver and gallbladder
• Additional methods for examining the liver and gallbladder  
• Diagnostics of the biliary dyskinesia

Differential diagnosis

Due to the impressive list of diseases leading to acholia or accompanied by impaired bile production, differential diagnosis is a difficult task. In case of digestive disorders, it is important to differentiate between a lack of bile and a decrease in the production of gastric juice and / or pancreatic digestive enzymes.

Treatment acholia

Treatment consists in eliminating the cause of acholia. Depending on the diagnosed disease, medications are prescribed:

• choleretic agents such as  Cholenzym  or  Febichol ; preparations containing ursodeoxycholic acid -  Ursonost  or  Ursomax ;
• hepatoprotectors  L'esfal , containing milk thistle extracts  Hepatofal plant  , etc.

More information:

• Medicines for the treatment and restoration of the liver
• How are biliary dyskinesias treated?

How physiotherapy treatment is carried out, read in the publication -

Physiotherapy for dyskinesia of the gallbladder and biliary tract

And herbal treatment is detailed in the article -  Alternative means of treating the liver

Surgical treatment involves endoscopic interventions in cases of extrahepatic cholestasis, laser lithotripsy or laparoscopic removal of stones in the gallbladder, closure of the bile fistula, stenting of the bile ducts to expand them, etc. 

Prevention

In many cases - with idiopathic conditions, autoimmune and congenital pathologies - prevention of acholia is impossible.

The main measures for the prevention of diseases affecting the hepatobiliary system are considered to be a balanced diet, refusal from alcohol, and a healthy lifestyle. [4]

Forecast

For most patients with acholia, the prognosis is favorable, since the level of bile acids and the effectiveness of enterohepatic circulation of bile in case of its lack can be regulated by pharmacological means.