15.1 BASIC CONSIDERATIONS

Aditi Dharap, Prachi S Karnik, Mukesh Agrawal

TABLE 15.1: Physiological functions of liver

Embryologically, liver develops from two sources: (a) Biliary tree and hepatocytes from ventral evagination of the primitive foregut (endoderm) into mesodermal septum transversus, and (b) Kupffer cells and supporting elements, e.g.

Anatomically, basic architecture of liver parenchyma may be broadly divided into two elements: (a) hepatic lobules, i.e. pentad arrangement of hepatocytes with a central vein and surrounding sinusoids, and (b) portal triads containing portal venules, hepatic arterioles and biliary canaliculi. A thick limiting plate of connective tissue separates hepatic lobules and portal triads from each other.

The biliary system includes biliary canaliculi, and ductules, hepatic ducts, gallbladder and common bile duct, which ultimately opens at ampulla of Vater in duodenum along with pancreatic duct.

Vascular supply: Liver is a highly vascular structure with dual blood supply—via portal circulation (75%) and via hepatic artery of systemic circulation (25%). Portal vein is formed by the fusion of splenic and superior mesenteric veins and carries most of the gastrointestinal blood flow to liver for metabolism of absorbed nutrients. It also supplies about half of the oxygen demand of liver, while remaining half is supplied by hepatic arteries. Branches of portal vein and hepatic artery are present in portal triad along with bile ducts, from where they traverse through limiting plates to enter venous sinusoids surrounding hepatocytes and drain into central hepatic vein. Liver does not have a capillary system (but sinusoids).

Physiologically liver plays a vital role in—(a) synthesis, storage and metabolism of various nutrients, (b) detoxification of metabolites, drugs and hormones and (c) excretion of certain substances in gut (Table 15.1).

Laboratory evaluation in liver disease aims to confirm the diagnosis of liver disease as well as to assess its

• Bilirubin metabolism (conjugation/excretion)

• Carbohydrate metabolism

- Glycogen storage (Glucose gt; Glycogen)

- Lipogenesis (Glucose gt; Lipids)

- Neoglucogenesis (Amino acids gt; Glucose)

- Glycogenolysis (Glycogen gt; Glucose)

• Protein metabolism

- Protein synthesis (Amino acids gt; Proteins)*

- De-amination (Amino acids gt; Ammonia gt; Urea)

• Lipid metabolism

- Formation and utilization of fatty acids

- Synthesis and esterification of cholesterol

- Synthesis of phospholipids and triglycerides

- Formation and conjugation of bile salts

• Hormone metabolism

- Detoxification of steroids

- Degradation of enzymatic proteins

• Drug metabolism and excretion

• Reticulo-endothelial function

- Phagocytosis via Kuppfer cells

- Immunoglobulin synthesis

*e.g. albumin, clotting factors, transport-proteins, etc.

course. Important components of hepatic evaluation include:

a. Imaging procedures for evaluation of anatomical lesions and excretory function:

• Ultrasonography is a baseline investigation for evaluation of hepatic size, focal lesions, e.g. abscesses, portal hypertension and biliary tract abnormalities. CT/MRI is more useful to delineate small focal lesions and tumors. MR cholangiography is valuable in assessment of pancreatico-biliary disorders.

• Radionucleotide liver scan is used for diagnosis of focal lesions (Tc⁹⁹ sulfur colloid scan) or assessment of excretory functions (Tc^99m iminodiacetic acid-IMIDA scan).

• Other imaging procedures, e.g. angiography, and endoscopic retrograde cholangiography (ERCP) are used in selected cases.

b. Liver function tests (LFTs): As the liver has large functional reserve, biochemical abnormalities usually precede clinical manifestations. Important liver function tests include:

• Tests for metabolic or synthetic dysfunction

- Serum bilirubin (unconjugated fraction)

- Prothrombin time and INR*

- Serum proteins, specially albumin.

- Serum ammonia (in acute cases)

• Tests for hepatocellular injury**

- Serum aspartate aminotransaminase (AST/ SGOT)

- Serum alanine aminotransferase (ALT/SGPT)

• Tests for cholestasis

- Serum alkaline phosphatise (ALP)

- Serum gamma-glutamyl transpeptidase (GGT)***

- Serum bilirubin (conjugated fraction)

• Tests for immune dysfunction

- Altered gammaglobulin levels

- Presence of antinuclear antibodies

*INR (International Normalized ratio) is the ratio of patient's prothrombtin time compared to control value, raised to the power international sensitivity index.

**AST and ALT are intracellular enzymes, released on cellular injury. ALT is mainly present in liver cells, while AST is also present in muscles and some other tissues. Hence, elevated ALT is more reliable indicator of hepatocellular injury than AST. ***GGT is more reliable indicator of cholestatic disease than ALP, which is also high in growing children due to bone isoenzyme fraction. GGT is normally high in newborns and infants lt; 6-9 months.

c. Liver biopsy is indicated in—(a) chronic liver disease or cirrhosis, (b) suspected metabolic or infiltrative disease, (c) unexplained, persistent icterus or abnormal liver function tests. However, it is contraindicated in—(i) acute liver failure, (ii) bleeding disorders, (iii) congestive hepatomegaly or vascular malformations of liver, and iv) suspected hydatid disease. Normal prothrombin time is an essential prerequisite for liver biopsy. (Ch 32.6)

15.2