Urine-Bile Salts in The Urine (Bile Acid Metabolism)

Sample

1. This is done in the urine.
2. This test can be done on the random sample after the meal.

Indications

1. Bile salts are detected in the urine to diagnose various conditions of liver diseases (Jaundice).
2. To diagnose obstructive jaundice.

Precaution

1. The postprandial sample is preferred that allows a more sensitive distinction between normal, abnormal results as compared to the fasting sample.
   1. Eating will stimulate secretion.

Pathophysiology

1. The liver assists intestinal digestion by secreting 700 to 1200 mL of bile acids per day.
   1. Bile is an alkaline, bitter taste, yellowish-green fluid.
      1. Gall bladder bile is more concentrated than hepatic bile.
         

         Bile acid metabolism

         Difference between hepatic and gall bladder bile:

         Constituents	Hepatic bile	Gall bladder bile
         Water	97%	85 to 92%
         Solids	2.2%	14.08%
         Bile acids	1.97%	9.14%
         Cholesterol	0.06%	0.26%
         Inorganic salts	0.84%	0.65%
         Fatty acids	0.14%	0.32%
         Specific gravity	1.01	1.04
         pH	7.1 to 7.3	6.9 to 7.7

   2. Primary bile acids are cholic and chenodexycholic acid, which constitute 60 to 95% of the bile.
      

      Primary bile acid conjugation

   3. Secondary bile acids are lithocholic acid and deoxycholic acid. This process takes place by the microflora of the intestine.
      

      Primary bile acid to secondary bile acid formation by the intestinal bacteria

   4. Bacterial 7-α-hydroxylase enzyme gives rise to secondary bile acids, deoxycholic acid, and lithocholic acids.
   5. In the liver, these secondary bile acids are conjugated with taurine and glycine and join the primary acid as the bile components and transform into bile salts.
   6. The average bile acid composition of normal bile is:
      1. Cholate conjugates = ∼38%.
      2. Chenodeoxycholate conjugate = ∼34%.
      3. Deoxycholate conjugate = ∼28%.
      4. Lithocholate conjugate = ∼1 to 2%.
   7. Control of bile acid secretion:
      1. The carrier-mediated active transport of bile acids into the bile canaliculi generates osmotic water flow and is the primary factor regulating bile formation and secretion.
      2. The influence of the bile acid secretion on biliary lipids excretion, in large part, due to the ability of bile acids to solubilize cholesterol and phospholipids in an aqueous medium in mixed micelles.
      3. Hepatic bile contains 5 to 15% solids, and major components are bile acids.
      4. Bile acids have a major role in regulating the bile flow.
      5. The hormone secretin increases bile flow without any increase in the bile flow output.
   8. Lithocholic acid is a secondary bile acid, and its properties are:
      1. It is water-insoluble.
      2. It precipitates in the colon.
      3. It is toxic to liver cells and RBCs.
      4. This may lead to cholestasis.
      5. When a small dose of lithocholic acid is injected, it may cause:
         1. Fever.
         2. Headache.
         3. Nausea.
         4. Malaise.
         5. Local inflammatory reaction.
         6. Its sulfated form is excreted in the feces.
      6. Instead of all these toxic injuries, it is found normally in the bile and the blood, so there must be some protective mechanism to protect from its toxic damage.
         

         Bile acids metabolism and formation of bile acids

3. Definition of bile salts:
   1. Bile acids are conjugated with taurine or glycine in the liver. Sodium or potassium conjugates of these bile acids are called bile salt.
      1. Primary bile acids are synthesized in the liver.
      2. Secondary bile acids are produced in the colon by bacterial action.
   2. Bile salts are formed when a base neutralizes an acid.
   3. Bile salt consists of:
      1. Bile salt contains:
         1. Conjugated bile acids.
         2. Cholesterol.
         3. Bilirubin.
         4. Electrolytes.
         5. Water
         6. Sodium glycocholate.
         7. Sodium taurocholate.
         8. Potassium and calcium bile salts are also common.
   4. Bile salts are needed for:
      1. 1. Facilitate fat absorption.
         2. Intestinal emulsification.
         3. Most of the bile salt is actively absorbed in the terminal ileum and return to the liver through the portal circulation for resecretion.
         4. The recycling of bile salts is termed the enterohepatic circulation.
4. Bile salts are made in the liver from cholesterol, and these help in fat absorption. They make them more soluble.

4. Mechanism of increased bile salts:
   4. Bile salts appear in the urine when there is an obstruction to the biliary tract, leading to an increase in the blood’s bile acids.
   5. Serum bile salts may rise even without the biliary obstruction if liver cell damage usually removes reabsorbed bile salts from the portal blood.
   6. Salts that are not removed from the enterohepatic cycle enter the enterohepatic circulation and give a sensitive hepatocellular dysfunction index.
   7. In many cases of jaundice, itching is caused by the bile salts in blood circulation.
5. Bile salts are positive in urine in other liver diseases.
6. Cholestasis, retention of bile, and bile salts lead to Itching (Pruritus).
   1. The biliary obstruction prevents the bile salts from entering the duodenum, leads to their accumulation in the blood.
   2. Serum bile salts may increase in liver diseases.
7. The level of bile salts correlates with itching.
8. This cholestatic itching may be seen in:
   1. Primary biliary cirrhosis.
   2. Primary sclerosing cholangitis.
   3. Intrahepatic cholestasis of pregnancy.
   4. Hereditary cholestatic syndrome.
9. Deficiency of bile salts:
   4. In the bile, deficiency of the bile salt allows cholesterol to precipitates as gall stones.
   5. Bile salts in the intestine emulsify the fat for absorption.
10. Excretion of the bile pigments: The bile pigments, including bilirubin, urobilinogen, and bile acids as bile salts, are excreted through kidneys and pass in the feces.
    

    Excretion of the bile pigments from kidneys and intestine (in feces)

Normal

• Typically bile salts are negative in the urine.

Procedure to detect bile salts in the urine:

1. Bile salts can be quantified by:
   1. Spectrophotometry.
   2. Chromatography.
   3. Radioimmunoassay.
2. Bile salts reduce the surface tension of liquids.
   1. The Scotch physician described this test (1885 to 1932).
3.  HAY’s test is done.
   1. Sulfur powder is sprinkled over the surface of urine, and it sinks if bile salts are present.
   2. Sulfur will remain (float) on the surface when bile salts are absent.
   3. Can run the control water where the sulfur granules will (float) remain over the surface.
      

      Urine bile salt test with sulfur granules

Positive bile salt test is seen in:

1. Obstructive jaundice.
2. Liver diseases with the appearance of jaundice.

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