Page 609 - Textbook of Pathology, 6th Edition

The hepatocytes are polygonal cells with a round single synthesis and elimination of bilirubin pigment, urobilino- 593
nucleus and a prominent nucleolus. The liver cells have a gen and bile acids are as follows:
remarkable capability to undergo mitosis and regeneration. 1. BILIRUBIN. Bilirubin pigment can be detected in serum,
Thus it is not uncommon to find liver cells containing more faeces and urine.
than one nuclei and having polyploidy up to octoploidy. A
hepatocyte has 3 surfaces: one facing the sinusoid and the i) Serum bilirubin estimation is based on van den Bergh
space of Disse, the second facing the canaliculus, and the third diazo reaction by spectrophotometric method. Diazo reagent
facing neighbouring hepatocytes. consists of diazotised sulfanilic acid. Water-soluble conjugated
The blood-containing sinusoids between cords of hepato- bilirubin gives direct van den Bergh reaction with diazo
cytes are lined by discontinuous endothelial cells and scatte- reagent within one minute, whereas alcohol-soluble
red flat Kupffer cells belonging to the reticuloendothelial unconjugated bilirubin is determined by indirect van den
system. Bergh reaction. Addition of alcohol to the reaction mixture
The space of Disse is the space between hepatocytes and gives positive test for both conjugated and unconjugated
sinusoidal lining endothelial cells. A few scattered fat storing bilirubin pigment. The unconjugated bilirubin level is then
Ito cells lie within the space of Disse. estimated by subtracting direct bilirubin value from this total
The portal triad or tract besides containing portal vein value. The serum of normal adults contains less than 1 mg/
radicle, the hepatic arteriole and bile duct, has a few dl of total bilirubin, out of which less than 0.25 mg/dl is
mononuclear cells and a scanty connective tissue considered conjugated bilirubin. Bilirubin level rises in diseases of
to be extension of Glisson’s capsule. The portal triads are hepatocytes, obstruction to biliary excretion into the
surrounded by a limiting plate of hepatocytes. duodenum, in haemolysis, and defects of hepatic uptake and
The intrahepatic biliary system begins with the bile conjugation of bilirubin pigment such as in Gilbert’s disease.
canaliculi interposed between the adjacent hepatocytes. The ii) In faeces, excretion of bilirubin is assessed by inspection
bile canaliculi are simply grooves between the contact of stools. Clay-coloured stool due to absence of faecal
surfaces of the liver cells and are covered by microvilli. These excretion of the pigment indicates obstructive jaundice.
canaliculi join at the periphery of the lobule to drain iii) In urine, conjugated bilirubin can be detected by
eventually into terminal bile ducts or ductules (canal of commercially available ‘dipsticks’, Fouchet’s test, foam test CHAPTER 21
Hering) which are lined by cuboidal epithelium. or ictotest tablet method. Bilirubinuria does not occur in
FUNCTIONS. The liver performs multifold functions. These normal subjects nor is unconjugated bilirubin excreted in the
are briefly listed below: urine. Bilirubinuria occurs only when there is raised level of
1. Manufacture and excretion of bile. conjugated bilirubin (filterable). Its excretion depends upon
2. Manufacture of several major plasma proteins such as the level of conjugated bilirubin in plasma that is not protein-
albumin, fibrinogen and prothrombin. bound and is therefore available for glomerular filtration.
3. Metabolism of proteins, carbohydrates and lipids. Bilirubinuria appears in patients of hepatitis before the
4. Storage of vitamins (A, D and B ) and iron. patient becomes jaundiced.
12
5. Detoxification of toxic substances such as alcohol and 2. UROBILINOGEN. Urobilinogen is normally excreted in
drugs. the urine. Its semiquantitative estimation in the urine can be
done by preparing dilutions with Ehrlich’s aldehyde reagent
LIVER FUNCTION TESTS or by ‘dipstick’ method. An increase in urobilinogen in the

In view of multiplicity and complexity of the liver functions, urine is found in hepatocellular dysfunctions such as in
it is obvious that no single test can establish the disturbance alcoholic liver disease, cirrhosis and malignancy of the liver.
in liver function. Thus a battery of liver function tests are It is also raised in haemolytic disease and in pyrexia. In The Liver, Biliary Tract and Exocrine Pancreas
employed for accurate diagnosis, to assess the severity of cholestatic jaundice due to complete biliary obstruction,
damage, to judge prognosis and to evaluate therapy. These urobilinogen disappears from the urine.
tests are described below in relation to major liver functions. 3. BROMSULPHALEIN EXCRETION. Bromsulphalein
A summary of various liver function tests is given in (BSP) is a dye which is removed from circulation by the same
Table 21.1. mechanisms of binding, conjugation and excretion as
bilirubin. BSP is injected intravenously and a sample of
I. TESTS FOR MANUFACTURE AND venous blood 45 minutes later is tested for percentage of
EXCRETION OF BILE injected dye remaining in the blood. The test is rarely
performed nowadays because of the availability of enzyme
Bile is produced by the liver, stored in the gallbladder and
secreted via biliary ducts into the duodenum. Bile consists estimations which are better indicators of hepatic
of biliary phospholipids and primary and secondary bile dysfunction. Presently, the only value of BSP excretion test
acids. To understand the mechanisms underlying biliary is in the diagnosis of Dubin-Johnson’s syndrome (page 601).
pathology, it is important to understand normal bilirubin 4. BILE ACIDS (BILE SALTS). The primary bile acids
metabolism (page 596). In brief, jaundice will develop if (cholic acid and cheno-deoxycholic acid) are formed from
bilirubin is excessively produced, or there is impaired hepatic cholesterol in the hepatocytes. These bile acids on secretion
uptake and conjugation of bilirubin, or it is insufficiently into the gut come in contact with colonic bacteria and
excreted into the duodenum. Tests employed to assess the undergo deconjugation with the production of secondary bile