Liver’s functions:

It is responsible for the production of bile which is stored in the gallbladder and released when required for the digestion of fats. The liver stores glucose in the form of glycogen which is converted back to glucose again when needed for energy. It also plays an important role in the metabolism of protein and fats.

It stores the vitamins A, D, K, B12 and folate and synthesizes blood clotting factors.Another important role is as a detoxifier, breaking down or transforming substances like ammonia, metabolic waste, drugs, alcohol and chemicals, so that they can be excreted. These may also be referred to as "xenobiotic" chemicals.

Role of the liver in carbohydrate metabolism.

From intestine glucose pass into the liver, where most part of it undergone the phosphorillation. Glucose-6-phosphate formed in result of this reaction, which catalyzed by two enzymes – hexokinase and glucokinase. When level of glucose in blood of v. porta and in the hepatocytes is normal activity of glucokinase is low. After eating activity of this enzyme increase and blood level of glucose decrease because glucose-6-phosphate cannot pass through membrane.

Fructose and galactose also transformed into glucose-6-phosphate in the liver.

Glucose-6-phosphate is a key product of carbohydrates metabolism. In the liver this substance can metabolized into different ways depend of liver’s and whole organism’s necessity.

1. Synthesis of glycogen. Content in the liver – 70-100g. After eating amount of glicogen in the liver increase up to 150g. After 24 hours of starvation content of glycogen in the liver decreases to zero and glukoneogenesis started.

2. Glucose-6-phosphatase catalize dephosphoryllation of glucose-6-phosphate and free glucose formed. This enzyme is present in the liver, kidney and small intestine. This process keep normal level of glucose in the blood.

3. Excess of glucose-6-phosphate, which is not used for synthesis of glycogen and forming of free glucose, decomposites in glycolysis for pyruvate and for acetyl-CoA, which are used for fatty acids synthesis.

4. Glucose-6-phosphate decomposites for H2O and CO2, and free energy for hepatocytes is formed.

5. Part of glucose-6-phosphate oxidized in pentosophosphate cycle. This way of glucose decomposition supplyes reducted NADPH, which is necessary in fatty acid synthesis, cholesterol synthesis, and also pentosophosphates for nucleic acids. Near 1/3 of glucose in liver  is used for this pathway, another 2/3 – for glycolysis.

Role of the liver in lipid metabolism


In the liver all processes of lipid metabolism take place. Most important of them are following:

1. Lipogenesis (synthesis of fatty acids and lipids). Substrate for this process – acetyl-CoA, formed from glucose and amino acids, which are not used for another purposes. This process is very active when the person eats a lot of carbohydrates. Liver more active than another tissues synthesizes saturated and monounsaturated fatty acids. Fatty acids then used for synthesis of lipids, phospholipids, cholesterol ethers. Glycerol-3-phosphate, which is necessary for lipids synthesis, formed in liver in result of two processes: from free glycerol under influence of glycerolkinase, or in reducing of dioxiacetone phosphate under influence of glycerolphosphate dehydrogenase. Active form of fatty acids interact with glycerol-3-phosphate and phosphatidic acid formed, which used for synthesis of triacylglycerines and glycerophospholipids.

2. Liver play a central role in synthesis of cholesterol, because near 80 % of its amount is synthesized there. Biosynthesis of cholesterol is regulated by negative feedback regulation. When the level of cholesterol in the meal increases, synthesis in the liver decreases.  Cholesterol  is using in the body for building cell membranes, synthesis of steroid hormones and vitamin D. Excess of cholesterol leads out in the bile to the intestine. Another part of cholesterol is  used for bile acids synthesis.

3. Liver is a place of ketone bodies synthesis. These substances are formed from fatty acids after their oxidation, and from liver are transported to another tissues, first of all to the heart, muscle, kidney and brain. These substances are main source of energy for many tissues of our organism excepting liver in normal conditions (heart) and during starvation (brain).

Role of the liver in protein metabolism


Liver has full set of enzymes, which are necessary for amino acids metabolism. Amino acids from food are used in the liver for following pathways:

1. Protein synthesis.

2. Decomposition for the final products.

3. Transformation to the carbohydrates and lipids.

4. Interaction between amino acids.

5. Transformation to the different substances with amino group.

6. Release to the blood and transport to another organs and tissues.

The high speed of protein synthesis and decomposition is typical for the liver. Hepatocytes catch different protein from blood (from hemolysated RBC, denaturated plasma proteins, protein and peptide hormones) and decomposite them to the free amino acids which are used for new synthesis. When organism does not get necessary quantity of amino acids from food, liver synthesizes only high necessary proteins (enzymes, receptors).

Liver syntesizes 100 % of albumines, 90 % of α1-globulines, 75 % of α2-globulines, 50 % of β-globulines, blood clotting factors, fibrinogen, protein part of blood lipoproteins, such enzyme as cholinesterase. The speed of these processes is enough high, for example, liver synthesizes 12-16g of albumine per day.

Amino acids, which are not used for protein synthesis are transformed to another substances. Oxidative decomposition of amino acids is main source of energy for liver in normal conditions.

Liver can synthesize non-essential amino acids. Liver synthesizes purine and pyrimidine nucleotides.


Liver function tests

Most laboratories perform a standard group of tests (Table), which do not assess genuine liver function but are useful for:

1  . Detecting the presence of liver disease;

2  . Placing the liver disease in the appropriate broad diagnostic category. This then allows the selection of further, more expensive and time-consuming inves­tigations such as ultrasound, computed tomography (CT) scanning, endoscopy and liver biopsy;

3  . Following the progress of liver disease.

Routine liver function tests

Standard group of test

Property being assessed

Plasma albumin or total protein

Protein synthesis

Plasma bilirubin total

Hepatic anion transport


Hepatocellular integrity


Presence of cholestasis


Hepatic anion transport: bilirubin

Measurements of bilirubin in blood and urine are usually used to assess hepatic anion transport, although many other anions, including bile salts, are also transported by the liver. Understanding the mechanisms by which bilirubin is formed and removed is essential for the diagnosis of patients with jaundice or liver disease, since abnormal lev­els of bilirubin in blood can occur in patients in whom there is no liver disease.

Bilirubin production and metabolism

The body usually produces about 300 mg of bilirubin per day as a breakdown product of haem. About 80% arises from red cells with the remainder coming from red cell precursors destroyed in the bone marrov ('ineffective erythropoiesis'), and from other haem proteins such as myoglobin and the cytochromes.

After a life span of about 120 days the erythrocytes die. The dead erythrocytes are taken up by the phagocytes of the reticuloendothelial system of the body. About 7 gram of Hb is released daily from these phagocytosed erythrocytes. The Hb molecule is broken down into 3 parts:

(i) The protein (globin) part is utilized partly as such or along with other body proteins.

(ii) The iron is stored in the reticuloendothelial cells and is reused for the synthesis of Hb and other iron containing substances of the body.

(iii) The porphyrin part is converted to bile pigment, i.e. bilirubin which is excreted in bile.

The several stages, which are involved in the formation of bile pigment from Hb and the farther fate of this pigment, are given below:

1. Hemoglobin dissociates into heme and globin.

2. Heme in the presence of the enzyme, heme oxygenase, loses one molecule of CO and one atom of iron in Fe3+ form producing biliverdin. In this reaction, the porphyrin ring is cleaved by oxidation of the alpha methenyl bridge between pyrrole rings. The enzyme needs NADPH+H+ and O2.

Biliverdin which is green in color is the first bile pigment to be produced; it is reduced to the yellow-colored bilirubin, the main bile pigment, by the enzyme biliverdin reductase requiring NADPH+H+.

Bilirubin is non-polar, lipid soluble but water insoluble. Bilirubin is a very toxic compound. For example, it is known to inhibit RNA and protein synthesis and carbohydrate metabolism in brain. Mitochondria appear to be especially sensitive to its effect. Bilirubin formed in reticuloendothelial cells then is associated with plasma protein albumin to protect cells from the toxic effects. As this bilirubin is in complex with plasma proteins, therefore it cannot pass into the glomerular filtrate in the kidney; thus it does not appear in urine, even when its level in the blood plasma is very high. However, being lipid soluble, it readily gets deposited in lipid-rich tissues specially the brain.

This bilirubin is called indirect bilirubin or free bilirubin or unconjugated bilirubin.

The detoxication of indirect bilirubin takes place in the membranes of endoplasmatic reticulum of hepatocytes. Here bilirubin interact with UDP-glucuronic acid and is converted to the water soluble form -bilirubin mono- and diglucoronids. Another name of bilirubin mono- and diglucoronids is conjugated bilirubin or direct bilirubin or bound bilirubin. This reaction is catalized by UDP-glucoroniltransferase.

Conjugated bilirubin is water soluble and is excreted by hepatocytes to the bile. Conjugated (bound) bilirubin undergoes degradation in the intestine through the action of intestinal microorganisms. Bilirubin is reduced and, mesobilirubin is formed. Then mesobilirubin is reduced again and mesobilinogen is formed. The reduction of mesobilinogen results in the formation of stercobilinogen (in a colon). Stercobilinogen is oxidized and the chief pigment (brown color) of feces stercobilin is formed. A part of mesobilinogen is reabsorbed by the mucous of intestine and via the vessels of vena porta system enter liver. In hepatocytes mesobilinogen is splitted to pyrol compounds which are excreted from the organism with bile. If the liver has undergone degeneration mesobilinogen enter the blood and is excreted by the kidneys. This mesobilinogen in urine is called urobilin, or true urobilin. Thus, true urobilin can be detected in urine only in liver parenchyma disease.

Another bile pigment that can be reabsorbed in intestine is stercobolinogen. Stercobolinogen is partially reabsorbed in the lower part of colon into the haemorroidal veins. From the blood stercobolinogen pass via the kidneys into the urine where it is oxidized to stercobilin. Another name of urine stercobilin is false urobilin.

As mentioned above, the conversion of bilirubin to mesobilirubin occurs under the influence of intestinal bacteria. These bacteria are killed or modified when broad-spectrum antibiotics are administered. The gut is sterile in the newborn babies. Under these circumstances, bilirubin is not-converted to urobilinogen, and the feces are colored yellow due to bilirubin. The feces may even become green because some bilirubin is reconverted to green-colored biliverdin by oxidation.

The total bilirubin content in the blood serum is 1,7-20,5 micromol/l, indirect (unconjugated) bilirubin content is 1,7-17,1 micromol/l and direct (conjugated) bilirubin content is 0,86-4,3 micromol/l.




Hepatocellular damage: aminotransferase measurements

Soluble cytoplasmic enzymes and, to a lesser extent, mitochondrial enzymes are released into plasma in hepatocellular damage. The measurement of the activity of ALT or AST in plasma provides a sensitive index of hepatocellular damage. Plasma ALT measurements are more liver-specific than AST. Cytoplasmic and mitochondrial isoenzymes of AST exist and in chronic hepatocellular disease (e.g. cirrhosis), serum AST tends to be increased to a greater extent than ALT. The aminotransferases are mainly located in the periportal hepatocytes, and they do not give a reliable indication of centrilobular liver damage. As with all tests based on the release of enzymes from damaged tissue, there is a lag period of some 24 h from the initiation of tissue damage to the first appearance of increased enzyme levels in the plasma.

AST- 8-40 U/L or (0,1-0,45 mmol/(hour´L))

ALT- 5-30 U/L or (0,1-0,68 mmol/(hour´L))

Cholestasis: alkaline phosphatase (ALP) and -γ-glutamyltransferase (GGT)

Some enzymes, such as ALP and GGT, are normally attached, or 'anchored', to the biliary canalicular and sinusoidal membranes of the hepatocyte. For this reason, ALP and GGT tend to be released into plasma in only small amounts following hepato­cellular damage. However, they are released in much greater amounts when there is cholestasis, since their synthesis is induced and they are ren­dered soluble - due, at least in part, to the presence of high hepatic concentrations of bile acids.

Changes in the activities of GGT and ALP often parallel each other in cholestatic liver disease. Plasma GGT has the advantage of being more liver-specific, as plasma ALP may also be increased due to release from bone in bone disease. However, alcohol and many drugs such as anticonvulsants may induce the expression of GGT without caus­ing cholestasis. An isolated increase in GGT should thus be interpreted with caution.

ALP – 40-125 U/L or  0,5-1,3 mmol/(hour´ L)

GGT – 6-45 U/L in male and 5-30 U/L in female.


Hepatic protein synthesis

The measurement of certain plasma proteins pro­vides an index of the liver's ability to synthesise protein.


In chronic hepatocellular damage, there is impaired albumin synthesis with an accompanying fall in plasma [albumin]. Albumin measurements provide a fairly good index of the progress of chronic liver disease. In acute liver disease, however, there may be little or no reduction in plasma [albumin], as the biological half-life of albumin is about 20 days and the fractional clearance rate is therefore low. Factors other than impaired hepatic synthesis may lead to a decreased plasma [albumin]. These include loss of albumin into the extravascular compartment, ascites, increased degradation and poor nutritional status.

Ascites Increased portal venous pressure, a low plasma colloid oncotic pressure and Na+ retention due to secondary hyperaldosteronism combine to cause ascites in cirrhotic patients. This often devel­ops when plasma [albumin] falls below 30 g/L.

Coagulation factors

In liver disease, the synthesis of prothrombin and other clotting factors is diminished, leading to an increased PT. This may be one of the earliest abnormalities seen in patients with hepatocellular damage, since prothrombin has a short half-life (approximately 6 h). The PT is often expressed as a ratio to a control value (the international nor­malised ratio, INR).

Deficiency of fat-soluble vitamin K, due to failure of absorption of lipids, may also cause a prolonged PT. In vitamin K deficiency, the coagulation defect can often be corrected by parenteral administra­tion of vitamin K, but this has no effect in patients with hepatocellular damage.



Plasma Ig measurements are of little value in liver disease because the changes are of low specificity. In most types of cirrhosis, plasma [IgA] is often increased, while in primary biliary cirrhosis plasma [IgM] increases greatly. In chronic active hepatitis, plasma [IgG] tends to be most increased.

Serological tests

Anti-mitochondrial antibodies are present in over 95% of patients with primary biliary cirrhosis, and anti-smooth muscle and anti-nuclear factor antibodies are found in about 50 % of patients with chronic active hepatitis. Viral antigens and antibody measurements are also important in detecting infective causes of liver disease.

Marker of fibrosis

A variety of markers have been described that may be of help in the assessment of hepatic fibrosis. Procollagen type III terminal peptide and hyaluronic acid (hyluronin) are the most commonly used tests.

Other liver function tests

A number of liver function tests have been described that give an indication of the functional liver mass. These tests are not often used but include the

aminopyrine breath tests, the galactose elimination test and the monoethylglycinexylidide (MEGX) test.

Disordered metabolism

Patients with severe liver disease may have

1. significant decreases in plasma [urea], due to fail­ure of the liver to convert amino acids and NH3 to urea.

2. hypoglycaemia due to impaired gluconeogenesis or glycogen breakdown, or both;

3. raised concentrations of all the plasma lipid fractions, if cholestasis is present. An abnormal lipoprotein that contains high concentrations of phospholipid, lipoprotein X, is present in plasma in nearly all the cases of cholestasis.

The place of chemical tests in the diagnosis of liver disease

The jaundiced patient

Jaundice or icterus is the orange-yellow discoloration of body tissues which is best seen in the skin and conjunctivae.

 Jaundice   is   due   to   hyperbilirubinaemia   and becomes clinically apparent when the plasma bilirubin exceeds about 40-50 μmol/l.



Pre-hepatic hyperbilirubinaemia:

 This is due to overproduction of bilirubin. It occurs in:

·         haemolytic anemia

·         haemolytic disease of newborn, due to rhesus incompatibility

·         ineffective erythropoiesis (e.g. pernicious anemia)

·         Rhabdomyolysis

Hepatocellular hyperbilirubinaemia

This can arise from:

Hepatocellular damage caused by infective agents, drugs and toxins


Low activity of  bilirubin UDP-glucuronyltransferase in congenital deficiency, premature infants or competitive inhibition of the enzyme by drugs (novobiocin).

Cholestatic hyperbilirubinaemia

Cholestasis may be intrahepatic or extrahepatic. In both, there is conjugated hyperbilirubinaemia and bilirubinuria.

Cholestasis commonly occurs in:

  • Acute hepatocellular damage (e.g. due to infectious hepatitis)

·         Cirrhosis

·         Intrahepatic carcinoma (most commonly secondary)

·         Primary biliary cirrhosis

·         Drugs (e.g. methyltestosterone, phenothiazines).

Extrahepatic cholestasis is most often due to:

·         gallstones

·         carcinoma of the head of the pancreas

·         carcinoma of the biliary tree

·         bile duct compression from other causes.

Hemolytic jaundice is characterized by

  1. Increase mainly of unconjugated bilirubin in the blood serum.

  2. Increased excretion of urobilinogen with urine.

  3. Dark brown colour of feces due to high content of stercobilinogen.


Hepatic jaundice is characterized by

1.Increased levels of conjugated and unconjugated bilirubin in serum.

2.Dark coloured urine due to the excessive excretion of bilirubin and urobilinogen.

3.Pale, clay coloured stools due to the absence of  stercobilinogen.

4.Increased activities of alanine and aspartate transaminases.




Obstructive (post hepatic ) jaundice is characterized by

1.Increased concentration mainly of conjugated bilirubin in serum.

2.Dark coloured urine due to elevated excretion of bilirubin and clay coloured feces due to absence of stercobilinogen.



The congenital hyperbilirubinaemias

These are all due to inherited defects in the mechanism of bilirubin transport and metabolism.

Gilbert's syndrome

This familial autosomal dominant trait is probably present in 2-3% of men; it is 2-7 times more common in men than women. The unconjugated hyperbilirubinaemia is usually asymptomatic, and plasma [bilirubin] fluctuates, higher levels tending to occur during intercurrent illness. Most patients have a plasma [bilirubin] less than 50 μmol/L, but higher levels are not uncommon. Other com­monly performed tests of 'liver function' are normal, and there is no bilirubinuria.

Gilbert's syndrome is caused by decreased expres­sion of bilirubin UDP-glucuronyltransferase 1A1, due to a mutation in the promoter portion of the gene.

Gilbert's syndrome can most easily be differenti­ated from the mild degree of hyperbilirubinaemia in haemolytic anaemia by haematological investi­gations. Confirmatory tests for Gilbert's syndrome include monitoring the effects on plasma [bilirubin] of a reduced energy intake (1.67 MJ/day; 400 kcal/day), particularly a reduction in the intake of lipids, for 72 h. This results in at least a doubling of plasma [unconjugated bilirubin] in patients with Gilbert's syndrome, whereas in normal individuals it does not rise above 25 μmol/L. Diagnosis by genotyping is possible but is rarely performed at present although it is likely to be increasingly performed in the future.

Fasting plasma [bile acids] are normal in Gilbert's syndrome, but raised in hyperbilirubinaemia due to liver disease.

Crigler-Najjar syndrome

This rare condition, due to low activity of biliru­bin UDP-glucuronyltransferase, gives rise to severe hyperbilirubinaemia in neonates, leading to kernicterus and often to early death.

Dubin-Johnson syndrome and Rotor's syndrome

These rare disorders are characterised by a benign conjugated hyperbilirubinaemia, accompanied by bilirubinuria. In both, there is a defect in the transfer of conjugated bilirubin into the biliary canaliculus. Urinary coproporphyrins are normal in patients with Dubin-Johnson syndrome, but increased in Rotor's syndrome.

Acute hepatitis

This is usually caused by viruses (hepatitis A, B, C, D and E, cytomegalovirus or Epstein-Barr). Toxins such as ethanol and paracetamol can also damage the liver. There is often a pre-icteric phase when increases in ALT and AST activities and in urobilinogen in urine occur. By the time clinical jaun­dice appears, plasma ALT and AST activities are usually more than 6 times, and occasionally more than 100 times, the upper reference value. The stools may be very pale, due to impaired biliary excretion of bilirubin, and urobilinogen then disappears more or less completely from the urine. ALP activity is usually only slightly increased, up

to about twice the upper reference value, but it may be considerably raised in cases (relatively uncommon) in which there is a marked cholestatic element, as occurs in acute alcoholic hepatitis. Acute viral hepatitis usually resolves quickly and chemical indices of abnormality revert to normal within a few weeks.

Poisoning and drugs

Findings similar to those in acute viral hepatis are observed in patients with hepatocellular toxicity due to drugs (e.g. paracetamol overdose, halothane jaundice, carbon tetrachloride poisoning). Drugs such as chlorpromazine may produce cholestasis, with increased plasma ALT and GGT, while phenytoin, barbiturates and ethanol induce GGT synthesis without necessarilv causing liver damage. Certain herbal remedies and recreational drugs such as ecstasy may also induce liver damage.

Acute liver failure

This rare condition is usually caused by paraceta­mol poisoning or hepatitis virus and the prognosis is often poor. It is accompanied by major meta­bolic disturbances including hyponatraemia, hypocalcaemia, hypoglycaemia and lactic acidosis often masked by respiratory alkalosis. The levels of the aminotransferases do not correlate well with the severity of the disease.

Chronic hepatitis

Hepatic inflammation that persists for more than 6 months is regarded as 'chronic hepatitis'. It may be due to chronic infection with hepatitis virus, alcohol abuse or be autoimmune in origin. Usually such patients have an isolated elevation in serum aminotransferase unless the disease has progressed to cirrhosis. Autoimmune hepatitis is frequently treated with azathioprine. The thera­peutic action of the azathioprine depends on the production of active metabolites. Toxicity can occur in patients who have low activities of the enzyme thiopurine methyl transferase (TPMT).

Cholestatic liver disease

Both extrahepatic (e.g. gallstones) and intrahepatic (e.g. tumours, certain drugs) causes of obstruc­tion cause cholestasis. The distinction between the two is often clinically important from the point of view of further investigation and treat­ment, but it can rarely be made by chemical tests.

Plasma [bilirubin] is often greatly increased, and there is marked bilirubinuria; urobilinogen often becomes undetectable in urine. Plasma ALP and GGT activities are considerably increased, often to more than three times the upper reference values, but plasma ALT and AST activities are usually only moderately raised. In long-standing cholestatic jaundice, hepatic protein synthesis may be impaired and plasma ALP activity may start to fall 15 a result, and even return to normal; this emphasises the importance of performing a baseline set of investigations as early as possible in patients with liver disease.

Plasma ALP and GGT activities may be markedly increased in patients with partial biliary obstruc­tion, due to local obstruction in one of the smaller biliary ducts, such as often occurs in both primary and secondary carcinoma of the liver. Partial bil­iary obstruction may have little or no effect on the capacity of the liver to excrete bilirubin, so there may be no evidence of jaundice in these patients, at least initially; bilirubin excretion in the other parts of the liver may be capable of fully compen­sating for the sector affected by the local biliary obstruction.

Chemical features that may help to distinguish cholestasis from hepatocellular damage are sum­marised in Table 7.3. These are 'typical' findings, and many cases do not follow these patterns exactly. The distinction between intrahepatic and extrahepatic cholestasis is usually made by radio­logical investigations - for example, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound or CT scanning - or by liver biopsy.

Infiltrations of the liver

The liver parenchyma may be progressively disor­ganised and destroyed in patients with primary or secondary carcinoma, lymphoma, amyloidosis, reticuloses, tuberculosis, sarcoidosis and abscesses. These diseases often lead to partial biliary obstruc­tion, with the associated chemical changes described above. Plasma [α1-fetoprotein] (AFP) is often greatly increased in hepatoma  but it can be moder­ately increased in chronic hepatitis and cirrhosis. Plasma AFP measurements are also useful for moni­toring patients who are at increased risk of develop­ing hepatoma. Patients with liver tumours may often have elevated ALP and GGT as the only abnor­mality due to localised obstruction.

Cirrhosis of the liver

Alcoholism, viral hepatitis, autoimmune disease and prolonged cholestasis are the most frequent known causes of cirrhosis in Britain, although in half the cases no obvious cause is found. Less often, cirrhosis is associated with metabolic disorders such as Wilson's disease, cystic fibrosis, API deficiency, haemochromatosis, or galactosaemia.

Mild cirrhosis.  In mild cases, no clinical abnormali­ties may be apparent, due to the reserve functional capacity of the liver. Plasma GGT measurements provide a sensitive means of detecting mild cir­rhosis, but most heavy drinkers (many of whom do not have cirrhosis of the liver) have raised plasma GGT activities; these usually fall within 2 months of stopping drinking. Marked abnor­malities in liver function tests are rarely present.

Severe cirrhosis The following clinical features may occur, either alone or in combination: haematemesis, ascites and acute hepatic decompensa­tion, often fatal. Jaundice may develop, plasma [albumin] falls and the PT becomes abnormal. Clinical deterioration accompanied by prolonged PT, a generalised amino aciduria, increased plasma [NH3] and reduced plasma [urea] may herald the development of acute hepatic failure.

Hyaluronan (also known as hyaluronic acid) is a glucosaminoglycan synthesised by the mesenchymal cells and degraded by hepatic sinusoidal endothelial cells by a specific receptor-mediated process. Elevated levels are associated with sinusoidal capilliarisation that is seen in cirrhosis. Hyaluronan levels are significantly higher in patients with liver cirrhosis compared with hepatic fibrosis, chronic hepatitis and fatty liver. Measurement of fasting serum hyaluronan can reliably differentiate cirrhotic from non-cirrhotic liver disease and can be regarded as a useful test in the diagnosis of liver cirrhosis, particularly when a liver biopsy is contraindicated. There appears to be no significant difference in hyaluronan levels between cirrhosis caused by different aetiologies but hyaluronan levels are increased proportionally to the severity of cirrhosis.

Copper in liver disease

The liver is the principal organ involved in copper metabolism. The amount it contains is main­tained at normal levels by excretion of copper in bile and by incorporation into ceruloplasmin. The liver's copper content is increased in Wilson's disease, primary biliary cirrhosis, pro­longed extrahepatic cholestasis, and intrahepatic bile duct atresia in the neonate.

Wilson's disease (hepatolenticular degeneration) is a rare, hereditary, autosomal recessive disorder with a prevalence of about 1 in 30 000. The defective gene encodes a protein involved in the hepatobiliary excretion and renal reabsorption of copper. Copper is deposited in many tissues, including the liver, brain, eyes and kidney. Symptoms are mainly due to liver disease and to degenerative changes in the basal ganglia. Plasma [ceruloplas­min] is nearly always low, but it is not clear how this relates to the aetiology of Wilson's disease.

The diagnosis may be suspected from the family history or on clinical grounds, such as liver disease in patients less than 20 years old, or characteristic neurological disease. Kayser-Fleischer rings, due to the deposition of copper in the cornea, can be detected in most patients. The following chemical tests may be valuable:

·         Plasma [ceruloplasmin] This is usually less than 200 mg/L (reference range 250-450 mg/L).

·         Plasma   [copper] This   is   usually   less   than 12 μmol/L (reference range 12-26 (μmol/L).

·         Urinary copper output This is always more than 1. 0 μmol//24 h (normally below 0.5 μmol/24 h).

·         Liver [copper] is always greater than 250 μg/g dry weight (reference range 50-250 μg/g dry weight).
This is the most sensitive test, but it involves liver biopsy.

These tests are not 100 % specific for Wilson's disease. For example, plasma [ceruloplasmin] may occasionally be low in severe cirrhosis, and uri­nary copper output and liver [copper] may be raised in biliary cirrhosis. However, urinary copper output is valuable for case-finding among rela­tives, since a normal result virtually excludes Wilson's disease.

Abnormalities of other chemical tests are often present in Wilson's disease. There is usually evidence of renal tubular damage, with a generalised

(overflow) amino aciduria, glycosuria and phosphaturia and, in advanced cases, renal tubular acidosis.


Liver disease is the commonest cause of ascites. If a diagnostic paracentesis is performed, the appearance of the fluid (blood-stained, bile-stained, milky,  etc.)  should be noted, and fluid [total protein] should be determined.

Transudates and exudates

Ascites with a fluid [protein] less than 30 g/L is called a transudate. It is usually associated with non-infective causes such as uncomplicated cirrhosis, in which there is a combination of back-pressure effects and low plasma [albumin]. However, fluid [protein] may be greater in some of these patients, and 30 g/L is not a reliable diagnostic cut-off point.

Ascites with a fluid [protein] much in excess of 30 g/L is called an exudate. It usually indicates the presence of infective conditions such as tubercu­lous peritonitis, or malignant disease or pancreatic disease. If pancreatic disease is thought to be the cause, fluid amylase activity should be measured; a serosanguinous fluid with a high amylase activ­ity will help to confirm the diagnosis. If hepatoma is suspected, plasma and ascitic fluid [AFP] may both be considerably increased.




Oddsei - What are the odds of anything.