Acholia

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

Epidemiology

Statistics of hepatobiliary system pathologies leading to acholia are unknown.

The prevalence of genetically determined disorders of bile acid synthesis is estimated at 1-2%, for example, Alagille syndrome occurs in approximately one newborn out of 100 thousand.

Causes acholia

The key causes of acholia are rooted in disorders of choleresis or cholekinesis – the formation of bile or its secretion. Both are functions of the hepatobiliary system, which consists of the bile-producing liver (with a system of bile canals and ducts), its storage site – the gallbladder (in which bile becomes more concentrated), as well as the cystic and common bile ducts, through which bile enters the lumen of the duodenum.

In what pathological changes is acholia syndrome observed? It develops if hepatocytes (liver cells) do not produce bile acids, and this can be the case:

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

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

• dyskinesia of the gallbladder and bile ducts, leading to extrahepatic bile stasis;
• sclerosing cholangitis of various etiologies;
• congenital anomalies of the biliary tract, such as Alagille 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 attribute the following to risk factors for the development of acholia:

• mutations in 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;
• disorders of the secretory function of the liver due to its invasion by parasites (dysentery amoeba, lamblia, blood and liver flukes, beef or pork tapeworm);
• cholelithiasis;
• metabolic disorders in endocrinopathies, in particular diabetes mellitus and obesity;
• poor nutrition (with an excess of sweets and fatty foods in the diet);
• chronic alcohol intoxication of the liver;
• liver damage by various toxins, as well as the iatrogenic effects of drugs that can cause cholestasis and acute liver failure;
• history of gallbladder fistulas and cholecystectomy (gallbladder removal);
• malignant neoplasms and metastases to the liver;
• immunodeficiency states.

Pathogenesis

On average, the adult liver produces 600-800 ml of bile daily, and this requires approximately 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 subsequent transfer to the membranes of the intrahepatic bile canals. The liver also produces cholesterol - from blood lipoproteins that capture special receptors of the vascular part of hepatocytes.

All these biochemical processes require enzymes of the cytoplasmic membranes, microsomes, mitochondria and lysosomes of hepatocytes: cholesterol 7α-hydroxylase (CYP7A1), cholesterol 12α-hydroxylase (CYP8B1), sterol 27-hydroxylase (CYP27A1), acyl-cholesterol acyltransferase (ACAT), 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 disruption of the functions of the cellular structures of hepatocytes and a deficiency of enzymes that ensure the synthesis of primary bile acids.

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

Read also – What causes biliary dyskinesia

Symptoms acholia

Characteristic symptoms of acholia include jaundice (due to stagnation of bile in the liver and disruption of the metabolism of the bile pigment, bilirubin), lighter stool (associated with the absence of stercobilinogen, which is formed during the breakdown of bilirubin), and choluria – dark yellow urine.

Etiologically associated with a disruption in the synthesis of bile acids by the liver, their accumulation in the blood is cholemia and acholia, which manifests itself as itching of the skin.

Occasionally, the temperature rises, and hemorrhages on the skin and mucous membranes are observed 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 disorders in acholia.

Complications and consequences

Bile ensures the digestive process, and its deficiency 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), weight loss, and general exhaustion.

The mechanism of lipid digestion disorder in acholia is explained by the fact that complete breakdown of fats in the gastrointestinal 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 enzymes of the intestine (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 the active enzyme trypsin (without which proteins coming with food are not digested).

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

In addition, many toxic substances, xenobiotics and metals are excreted in bile, and their accumulation in cholestasis-associated acholia 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, hepatic globin, cholesterol, bilirubin, bile acids, aminotransferases - that is, a blood test for liver function tests.

A general urine analysis and a coprogram (stool analysis) are also needed; analysis of bile obtained during duodenal intubation of the gallbladder. Sometimes a liver biopsy is necessary.

Instrumental diagnostics uses ultrasound of the liver and gallbladder, x-ray of the liver and bile ducts, cholescintigraphy and hepatobiliary scintigraphy. [ 3 ]

Read more:

• Liver and gallbladder diagnostics
• Additional methods of examination of the liver and gallbladder
• Diagnosis of biliary dyskinesia

Differential diagnosis

Due to the impressive list of diseases that lead to acholia or are accompanied by a violation of bile production, differential diagnosis is a complex 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 of eliminating the cause of acholia. Depending on the diagnosed disease, medications are prescribed:

• choleretic agents, such as Cholenzym or Febichol; drugs containing ursodeoxycholic acid – Ursonost or Ursomax;
• hepatoprotectors L'esfal, containing extracts of milk thistle Hepatofal planta, etc.

More information:

• Medicines for the treatment and restoration of the liver
• How to treat biliary dyskinesia

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

Physiotherapy for dyskinesia of the gallbladder and biliary tract

And herbal treatment is described in detail in the article - Folk remedies for liver treatment

Surgical treatment involves endoscopic interventions in cases of extrahepatic cholestasis, laser lithotripsy or laparoscopic removal of gallstones, closure of biliary fistula, stenting of bile ducts for their expansion, etc.

Prevention

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

The main measures to prevent diseases affecting the hepatobiliary system are considered to be a balanced diet, abstinence 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 efficiency of enterohepatic circulation of bile in its deficiency can be regulated by pharmacological agents.