SG

CHAPTER 26

LIVER FUNCTION TESTS

1. FUNCTIONS OF THE LIVER

2. CAUSES OF HEPATOCELLULAR DAMAGE

3. INDICATIONS FOR LIVER FUNCTION TESTS

4. CLASSIFICATION OF LIVER FUNCTION TESTS

5. TESTS BASED ON EXCRETORY FUNCTION OF THE LIVER

6. TEST BASED ON CARBOHYDRATE METABOLISM

7. TESTS BASED ON SERUM PROTEINS

8. TEST BASED ON LIPID METABOLISM

9. TEST BASED ON DETOXICATING FUNCTION OF THE LIVER

10. TESTS BASED ON SYNTHETIC FUNCTION OF THE LIVER

11. TESTS BASED ON AMINO ACID CATABOLISM

12. TEST BASED ON DRUG METABOLISM

13. TESTS BASED ON SERUM ENZYMES

14. IMMUNOLOGICAL TESTS

15. LIVER FUNCTION TESTS IN HEPATITIS AND CIRRHOSIS

16. CHOICE OF LIVER FUNCTION TESTS

17. BIOCHEMICAL FEATURES OF ACUTE LIVER FAILURE

18. JAUNDICE

19. INTRAHEPATIC CHOLESTASIS OF PREGNANCY

20. PORTAL HYPERTENSION

21. ASCITES
 LIVER FUNCTION TESTS

FUNCTIONS OF THE LIVER

1. Liver is the key organ where metabolism of carbohydrates,

lipids and proteins takes place.

2. Liver is responsible for the formation and secretion of bile

in the intestine.

3. Certain dyes such as BSP are exclusively excreted through

the liver cells.

4. Liver cells are responsible for the formation of prothrombin

and fibrinogen.

5. Albumin is synthesised in the liver.

6. Kupfer cells of the liver remove foreign bodies from the

blood by phagocytosis.

7. Liver cells can detoxicate drugs and hormones.

8. Liver stores glycogen, vitamin B12 and vitamin A.

9. Liver is involved in blood formation in embryo.

10. Metabolism of nucleic acids takes place in the liver.

11. About 90% of the liver can be removed and still the
remaining liver cells divide, replacing the lost cells within
weeks.
CAUSES OF HEPATOCELULLAR DAMAGE

1. Viruses: HAV, HBV, HCV, herpes and adenovirus.

2. Alcohol.

3. Toxins: Carbon tetrachloride, chloroform, mushroom and

arsenic.

4. General diseases: Wilson disease, haemochromatosis, alpha-1

anti trypsin deficiency, porphyrias, sarcoidosis & amyloidosis.

5. Neoplasms: Hepatocellular carcinoma, metastatic liver disease

and lymphoma.

6. Bacterial infections: Tuberculosis, leptospirosis and brucella.

7. Parasites: Helminths, entamoeba, plasmodia and leishmania.

8. Drugs: Salicylate, tetracycline, methotrexate, isoniazid,

rifampicin, halothane, methyldopa and valproate.

INDICATIONS FOR LIVER FUNCTION TESTS

1. Jaundice.

2. Suspected liver metastasis.

3. Alcoholic liver disease.

4. Any undiagnosed chronic illness.

5. Annual checkup of diabetic patients.

6. Coagulation disorders.
CLASSIFICATION OF LIVER FUNCTION TESTS

1. Tests based on excretory function of the liver:

a) Bromo sulpha pthalein (BSP) test.

b) Tests based on bile pigment metabolism:

Serum bilirubin.

Urine bilirubin.

Urine urobilinogen.

Faecal urobilinogen.

Urine bile salts.

2. Test based on carbohydrate metabolism:

Galactose tolerance test.

3. Tests based on serum proteins:

a) Estimation of serum total protein.

b) Estimation of serum albumin.

c) Estimation of serum globulin.

d) Determination of A / G ratio.

e) Estimation of serum alpha feto protein.

f) Estimation of serum caeruloplasmin.

g) Estimation of serum ferritin.

4. Test based lipid metabolism:

Estimation of serum cholesterol.

5. Test based on detoxicating function of the liver:

Hippuric acid synthesis test.

6. Tests based on synthetic function of the liver:

a) Determination of prothrombin time.

b) Estimation of plasma fibrinogen.

c) Estimation of serum albumin.

7. Tests based on amino acid catabolism:

a) Estimation of blood ammonia.

b) Estimation of CSF glutamine.

8. Test based on drug metabolism:

Antipyrine breath test.

9. Determination of serum enzyme activities:

a) Serum transaminases.

b) Serum alkaline phosphatase.

c) Serum 5’ nucleotidase.

d) Serum pseudocholinesterase.

e) Serum ornithine carbamoyl transferase.

f) Serum leucine amino peptidase.

g) Serum sorbitol dehydrogenase.

h) Serum gamma glutamyl transferase.

10. Immunological tests.

 TESTS BASED ON EXCRETORY FUNCTION OF THE LIVER

BSP TEST

1. The ability of the liver to excrete BSP (bromo sulpha pthalein)

dye is utilized in this test.

2. 5% BSP dye (5 mg BSP per kg body weight) is injected

intravenously.

3. Blood is collected after 45 minutes.

4. Normally only 5% dye remains in the blood at the end of 45

minutes.

5. In hepatic diseases, BSP removal is impaired, as the damaged

liver cells fail to conjugate the dye.

6. In liver cirrhosis, the removal of the dye is very slow and 50%
of the dye may be retained in the 45 minutes’ sample.
 TESTS BASED ON BILE PIGMENT METABOLISM

SERUM BILIRUBIN

VAN DEN BERGH REACTION

INTRODUCTION

1. Van Den Bergh reaction is a specific reaction to identify

increase in serum bilirubin.

2. Normal levels:

a) Serum total bilirubin: 0.3 to 1.1 mg/dl.

b) Serum unconjugated (indirect) bilirubin: 0.2 to 0.8 mg/dl.

c) Serum conjugated (direct) bilirubin: 0.1 to 0.3 mg/dl.

PRINCIPLE

1. Van den Bergh reagent is a mixture of equal volumes of

sulfanilic acid (in dilute HCL) and sodium nitrite.

2. Diazotized sulfanilic acid reacts with bilirubin to form

purple coloured azobilirubin.
 TYPES

1. Direct positive:

a) Conjugated bilirubin is soluble in water.

b) Van den Bergh reagent reacts with conjugated bilirubin

and gives purple colour immediately (normally within 30 seconds).

c) This is referred to as a direct positive van den Bergh

reaction.

2. Indirect positive:

a) Unconjugated bilirubin is insoluble in water.

b) Addition of methanol dissolves the unconjugated

bilirubin, which then gives the van den Bergh reaction
positive (normally within 30 minutes).

c) This is referred to as indirect positive van den Bergh

reaction.

3. Biphasic:

a) If the serum contains both unconjugated & conjugated

bilirubin in high concentration, purple colour is produced
immediately (direct positive) which is further intensified
by the addition of methanol (indirect positive).

b) This is known as biphasic van den Bergh reaction.

 SIGNIFICANCE

1. Van den Bergh reaction is highly useful in understanding the

nature of jaundice.

2. Jaundice is of three types:

a) Haemolytic jaundice: Increase in unconjugated bilirubin.

b) Obstructive jaundice: Increase in conjugated bilirubin.

c) Hepatic jaundice: Increase in both conjugated and

unconjugated bilirubin.

3. The response of van den Bergh reaction can differentiate

jaundice as follows:

a) Indirect positive: Haemolytic jaundice.

b) Direct positive: Obstructive jaundice.

c) Biphasic: Hepatic jaundice.

 BILIRUBIN IN URINE

1. Bilirubin is found in the urine in obstructive jaundice,

because conjugated bilirubin can pass through the glomerular
filter.

2. Urine is dark yellow in colour in obstructive jaundice

due to the presence of bilirubin.

3. Bilirubin is not present in the urine in prehepatic jaundice,

because unconjugated bilirubin is carried in the plasma attached to
albumin, hence it cannot pass through the glomerular filter.

4. Bilirubin in the urine is detected by Fouchet’s test.

5. Fouchet’s test:

a) 5 ml urine + 1 ml ammonium sulphate + 2 ml 10%

barium chloride. Filter and to the precipitate add a few drops
of Fouchet’s reagent (ferric chloride + trichloro acetic acid).

b) If bilirubin is present in the urine the colour changes

from yellow to green.

c) Ferric chloride oxidizes yellow bilirubin to green

biliverdin.
 UROBILINOGEN IN FAECES

1. Normal quantity of urobilinogen excreted in the faeces is

50 to 250 mg/day.

2. Faecal urobilinogen is increased in haemolytic jaundice,

in which dark coloured faeces is passed.

3. Faecal urobilinogen is absent in obstructive jaundice in

which clay coloured faeces is passed.

UROBILINOGEN IN URINE

1. Normal excretion of urobilinogen in the urine is 1 to 4

mg/day.

2. Urine urobilinogen is increased in haemolytic jaundice,

in which dark coloured urine is passed.

3. Urine urobilinogen is absent in obstructive jaundice.

4. Urine urobilinogen is detected by Ehlrich’s test.

5. Ehlrich’s test:

a) To 10 ml of urine add 1 ml of Ehlrich’s reagent

(concentrated HCL + p dimethyl amino benzaldehyde). Mix
and let it stand for 10 minutes.

b) The colourless urobilinogen reacts with Ehlrich’s

reagent in acidic medium to form pink-red condensing products.
 BILE SALTS IN URINE

1. Bile salts are sodium or potassium salts of glycocholate

and taurocholate.

2. Bile salts are formed in the liver from cholesterol.

3. Bile salts reduce the surface tension & help in digestion

and absorption of fats.

4. Hay’s sulfur test is done for detection of bile salt in urine.

5. Hay’s sulfur test:

a) Urine is taken in a test tube and then sulfur powder is

sprinkled.

b) If the sulphur sinks to the bottom of the tube it indicates

presence of bile salts in the urine.

c) Bile salts lower surface tension and cause sulfur powder

to sink.

6. Bile salts are excreted in urine in obstructive jaundice.

 TEST BASED ON CARBOHYDRATE METABOLISM

GALACTOSE TOLERANCE TEST

1. The normal liver is able to convert galactose to glucose,

but this function is impaired in liver diseases and the amount of
blood galactose and galactose in the urine is increased.

2. The test is performed after an overnight fast.

3. 40 grams of galactose dissolved in a cup full of water is

given orally.

4. Four blood samples are collected at half hourly intervals

for 2 hours.

5. Normally 3 gms or less of galactose is excreted in the

urine within 3 hours and the blood galactose returns to normal
within one hour.

6. In hepatic diseases, the urinary excretion of galactose is

5 gms or more.

7. Galactose index is obtained by adding the four blood

galactose levels and the normal value is upto 160.

8. In hepatic diseases, very high values, even upto 500 may

be obtained, depending on the severity of the disease.

TESTS BASED ON SERUM PROTEINS

 ESTIMATION OF SERUM TOTAL PROTEIN, ALBUMIN,
GLOBULIN AND A/G RATIO

1. The normal levels are:

a) Serum total protein: 6 to 8.3 gm/dl.
b) Serum albumin: 3.7 to 5.3 gm/dl.
c) Serum globulin: 1.8 to 3.6 gm/dl.
d) A: G ratio: 2: 1.

2. Reversal of A: G ratio:

a) In liver cirrhosis, the A: G ratio is reversed.

b) Albumin is synthesised in the liver and its synthesis is

decreased in liver cirrhosis.

c) Immunoglobulins are significantly increased in liver

cirrhosis.

d) Hence, A: G ratio is reversed in liver cirrhosis.

3. In hypoalbuminemia (serum albumin < 2 gm/dl), plasma

osmotic pressure is decreased, leading to the flow of water
from plasma to interstitial compartment, leading to oedema.

4. A low serum albumin which fails to increase during

treatment is usually a poor prognostic sign.

ESTIMATION OF SERUM ALPHA FETO PROTEIN

1. Alpha feto protein is produced by the liver during foetal
development.

2. Circulatory AFP levels decrease after birth and stabilize

to normal range (serum level <5 ng/ml) within one year.

3. Elevated serum AFP levels are found in hepatocellular

carcinoma and metastatic cancers of liver.

ESTIMATION OF SERUM CAERULOPLASMIN

1. Caeruloplasmin is a copper containing protein.

2. Normal serum caeruloplasmin level is 18 to 35 mg/dl.

3. Serum caeruloplasmin level is increased in chronic active

hepatitis and biliary cirrhosis.

ESTIMATION OF SERUM FERRITIN

1. Ferritin (storage form of iron) is stored in the liver cells.

2. Normal serum ferritin level is 20 to 300 ng/ml.

3. With liver damage from any cause, ferritin leaks into the
blood; therefore, serum ferritin can be an indirect
indicator of liver necrosis.

4. Serum ferritin is a surrogate marker for viral hepatitis.

5. In hemochromatosis, an elevated serum ferritin is

related to iron overload.

TEST BASED ON LIPID METABOLISM

 ESTIMATION OF SERUM CHOLESTEROL

1. The liver plays an important role in the synthesis,

esterification, oxidation & excretion of cholesterol.

2. Normal serum cholesterol level is 150 to 200 mg/dl.

3. In obstructive jaundice, the serum cholesterol level is

increased.

4. In hepatic diseases’, the serum cholesterol level is

decreased.

QUESTIONS

1. Functions of the liver.

2. Classify liver function tests.

3. Liver function tests based on excretory function.

4. Liver function tests based on serum proteins.

5. Galactose tolerance test.

6. Estimation of serum cholesterol as a liver function test.

 TEST BASED ON DETOXICATING FUNCTION OF
THE LIVER

HIPPURIC ACID TEST OF QUICK

1. Liver detoxicates benzoic acid by combining it with

glycine to form hippuric acid.

2. The patient is given 6 gms of sodium benzoate dissolved

in 200 ml of water to drink.

3. The urine is collected for 4 hours.

4. Normally at least 3 gms of hippuric acid should be

excreted in the urine in 4 hours.

5. Smaller amounts are excreted in hepatic diseases.

TESTS BASED ON SYNTHETIC FUNCTION OF THE

LIVER

DETERMINATION OF PROTHROMBIN TIME

1. Prothrombin is formed in the liver from inactive pre-

prothrombin, in the presence of vitamin K.

2. Normal prothrombin time is 11 to 13.5 seconds.

3. Prothrombin time indicates the functional status of the

liver.

4. In liver diseases, depending on the degree of liver damage,

prothrombin time is increased from 20 to as much as 150 seconds.
 5. In obstructive jaundice, due to absence of bile salts, there
may be defective absorption of vit K; hence prothrombin time
is increased, as prothrombin formation suffers.

6. Internationalized normalized ratio (INR):

a) INR is the preferred test of choice for patients taking

vit K antagonists.

b) INR = Patient PT / Control PT.

c) Normal INR value is 2 to 3.

ESTIMATION OF PLASMA FIBRINOGEN

1. Fibrinogen is synthesised in the liver.

2. Normal plasma fibrinogen level is 200 to 400 mg/dl.

3. Plasma fibrinogen is decreased in acute hepatic necrosis,

liver cirrhosis and carbon tetrachloride poisoning.

ESTIMATION OF SERUM ALBUMIN

1. Albumin is synthesized in the liver.

2. Normal level of serum albumin is 3.7 to 5.3 gm/dl.

3. Decrease in serum albumin level indicates liver

cirrhosis.
 TESTS BASED ON AMINO ACID CATABOLISM

ESTIMATION OF BLOOD AMMONIA

1. Ammonia is formed by transdeamination of amino acids.

2. Ammonia is converted to urea only in the liver.

3. Normal blood ammonia level is 15 to 45 micrograms/dl.

4. In hepatic diseases and liver cirrhosis the blood ammonia

level is increased.

ESTIMATION OF CSF GLUTAMINE

1. Glutamic acid combines with ammonia to form glutamine.

2. Normal CSF glutamine level is 6 to 14 mg/dl.

3. CSF glutamine level is increased in liver cirrhosis and

infectious hepatitis.
TEST BASED ON DRUG METABOLISM

ANTIPYRINE BREATH TEST

1. Antipyrine is metabolised by cytochrome P450 system.

2. When given orally it is absorbed from the intestine

completely, not bound to plasma proteins and metabolized
only by the liver.

3. 2 microcurie of C14 labelled dimethyl amino antipyrine

is given orally.

4. Breath samples are collected for 2 hours and analyzed.

5. Normal subjects excrete 8% of the administered dose

in 2 hours.

6. Patients with hepatitis and cirrhosis excrete only 2%.

 SERUM ENZYMES IN LIVER DISEASES

SERUM TRANSAMINASES

1. Transaminases carry out transamination reactions.

2. The normal levels of transaminases are:

a) Serum aspartate transaminase (AST) /

Serum glutamate oxaloacetate transaminase (SGOT)
- 5 to 40 IU/L.

b) Serum alanine transaminase (ALT) /

Serum glutamate pyruvate transaminase (SGPT)
- 5 to 45 IU/L.

3. Increase in both transaminases is found in liver diseases.

4. Most causes of liver cell injury are associated with a

greater increase in ALT than AST.

5. Serum ALT levels are greatly increased in viral hepatitis

and estimation of serum ALT helps in the diagnosis of acute
viral hepatitis.

AST: ALT RATIO / DE RITIS RATIO

1. Normal AST: ALT ratio is 0.8.

2. A high ratio (AST is higher) is seen in:

a) Alcoholics.

b) Liver cirrhosis.
 c) Non-alcoholic steato hepatitis (NASH).

d) Liver metastases.

3. A low ratio (ALT is higher) is seen in:

a) Acute viral hepatitis.

b) Acute hepatocellular injury.

c) Extra hepatic obstruction of bile duct.

SERUM ALKALINE PHOSPHATASE

1. Alkaline phosphatase breaks down organic phosphate

esters.

2. Normal serum alkaline phosphatase level is 40 to 125

IU/L.

3. Serum alkaline phosphatase level is greatly increased

in obstructive jaundice and helps in diagnosis of this
condition.

4. In bile duct obstruction, bile salts accumulate in the bile

duct. Bile salts cause emulsification of the membrane. Alkaline
phosphatase is a membrane bound enzyme. Alkaline
phosphatase is emulsified from the membrane and gets into
the circulation. Whenever there is bile
duct obstruction, alkaline phosphatase (membrane bound
enzyme) level is elevated.
5’ nucleotidase level is also elevated in obstructive
jaundice for the same reason.
 5. Bile duct obstruction results in increased synthesis of
ALP by bile duct epithelial cells and releases ALP
into the serum.

6. Serum ALP level is also increased in bone diseases.

SERUM 5’ NUCLEOTIDASE

1. 5’ nucleotidase enzyme hydrolyses nucleotides.

2. Its normal serum level is 2 to 17 IU/L.

3. Its level is greatly increased in obstructive jaundice

and it helps in the diagnosis of this condition.

4. 5’ nucleotidase has advantage over serum ALP in

that it is not affected in bone diseases.

SERUM PSEUDOCHOLINESTERASE

1. Pseudocholinesterase is a serine hydrolase enzyme that

catalyzes the hydrolysis of choline esters in the body.

2. Acetylcholine esterase hydrolyzes acetylcholine more

quickly, while pseudocholinesterase hydrolyzes
butyrylcholine more quickly.

3. Normal level of serum pseudocholinesterase is 8 to 18

U/ML.

4. Pseudocholinesterase is formed in the liver and its

serum level is reduced in hepatic diseases.
 SERUM ORNITHINE CARBAMOYL TRANSFERASE

1. OCT (ornithine carbamoyl transferase) is an enzyme of

the urea cycle.

2. Its normal serum level is 8 to 20 IU/L.

3. This enzyme is exclusively found in the liver and has

no activity in other tissues.

4. The level of serum OCT is greatly increased in acute

viral hepatitis.

SERUM LEUCINE AMINOPEPTIDASE

1. LAP (leucine aminopeptidase) is a proteolytic enzyme.

2. Its normal range is 15 to 55 IU/L.

3. Its level is greatly increased in obstructive jaundice.

4. Its advantage over ALP is that leucine amino peptidase

is not increased in bone diseases.

5. LAP level is also increased in liver cancer.

 SERUM SORBITOL DEHYDROGENASE

1. Sorbitol dehydrogenase converts sorbitol to fructose.

2. Its normal serum level is 1 to 2 IU/L.

3. Its level is increased in acute viral hepatitis & carbon

tetrachloride poisoning.

4. Sorbitol dehydrogenase is found in highest concentration

in the liver; it is a very specific indicator of liver disease.

SERUM GAMMA GLUTAMYL TRANSFERASE

1. GGT (gamma glutamyl transferase) transfers gamma

glutamyl residues from one peptide to another.

2. Its normal level is 10 to 50 IU/L.

3. GGT level is increased in alcoholic liver cirrhosis.

4. Sudden increase in GGT level in chronic alcoholics

suggests recent bouts of alcohol drinking.
 ENZYME ASSAYS IN LIVER DISEASES

Liver Disorder Enzyme Assays

1. Hepatocellular damage Alanine transaminase

Ornithine carbamoyl transferase

Sorbitol dehydrogenase

2. Intra-hepatic / Extra-hepatic bile Alkaline phosphatase

duct obstruction 5’ nucleotidase

Leucine aminopeptidase

3. Alcoholic liver cirrhosis Gamma glutamyl transferase

Aspartate transaminase
 IMMUNOLOGICAL TESTS

1. IgG level is increased in viral hepatitis, alcoholic

hepatitis and autoimmune hepatitis.

2. IgM shows marked increase in primary biliary cirrhosis

and moderate increase in viral hepatitis & liver cirrhosis.

3. Autoantibodies:

a) Primary biliary cirrhosis is associated with anti-

mitochondrial antibodies (AMA).

b) Primary sclerosing cholangitis is associated with

anti-nuclear cytoplasmic antibodies (ANCA).

c) Autoimmune hepatitis is associated with anti-

smooth muscle antibodies (ASMA) and anti-liver/
kidney microsomal antibodies type-1 (ALKMA1).

d) Hepatocellular carcinoma is associated with

rheumatoid factor (RF) and anti-smooth muscle
antibodies (ASMA).

e) Chronic hepatitis is associated with rheumatoid

factor (RF), anti-smooth muscle antibodies (ASMA)
and anti-liver/kidney microsomal antibodies type-1
(ALKMA1).
 LIVER FUNCTION TESTS IN HEPATITIS AND CIRRHOSIS

Liver Functions Tests Hepatitis Cirrhosis

1. Serum total protein Normal Decreased
2. Serum albumin Normal Decreased
3. Serum globulin Normal Increased
4. A: G ratio Normal Reversed
5. Serum alkaline Marginal increase Elevated one to two times
phosphatase normal
6. Serum alanine Value increased into Value increased upto
transaminase thousands maximum of 300 IU/L
7. AST: ALT ratio Low High
 CHOICE OF LIVER FUNCTION TESTS

1. Liver function tests are the most common group of

biochemical tests done to diagnose and monitor the course
of liver disease.

2. The increased incidence of infectious diseases like viral

hepatitis and leptospirosis requires these tests to be done in all
patients with unexplained illness.

3. The choice of biochemical tests to measure liver functions,

mostly depends on the purpose of the investigation; the
clinical history of the subject is often a guiding factor in this
regard.

4. A single test in isolation may have little diagnostic value,

frequently a combination of lab investigations is employed in
liver function tests; these include serum bilirubin, ALT, AST, ALP,
GGT, proteins & cholesterol.

5. In general, ALT and ALP distinguish the pattern of liver

disease.

6. Albumin determines the chronicity & prothrombin time

determines the severity of liver dysfunction.

BIOCHEMICAL FEATURES OF ACUTE LIVER FAILURE

1. Decreased gluconeogenesis leading to hypoglycaemia.

2. Decreased lactate clearance leading to lactic acidosis.

3. Decreased ammonia clearance leading to hyperammonemia.

4. Decreased synthetic capacity leading to coagulopathy.

QUESTIONS

1. Liver function tests based on enzymes.

2. Liver function test based on detoxicating function.

3. Liver function tests based on synthetic function.

4. Antipyrine breath test.

5. De Ritis ratio and its significance.

6. Liver function tests in hepatitis & cirrhosis.

7. Tests based on amino acid catabolism.

CLINICAL MANIFESTATIONS OF LIVER DYSFUNCTION

1. Jaundice.

2. Intrahepatic cholestasis of pregnancy.

3. Portal hypertension.

4. Ascites.
 JAUNDICE

1. The word jaundice is from the French ‘jaunisse’ (yellow

disease).

2. Jaundice is yellow colouration of the sclera, mucous

membrane & skin due to increase in the serum bilirubin level.

3. Slight increase in serum bilirubin is best detected by

examining the sclera, which has a particular affinity for
bilirubin due to its high elastin content.

4. Jaundice is visible when the serum bilirubin level exceeds

2.4 mg/dl.

5. Jaundice is of three types:

a) Haemolytic or pre-hepatic jaundice.

b) Hepatic jaundice.

c) Obstructive or post-hepatic jaundice.

6. Haemolytic jaundice:

a) Pre-hepatic jaundice is caused due to increased breakdown

of haemoglobin, so the liver cells are unable to conjugate the increased
bilirubin formed.

b) There is increase in serum unconjugated bilirubin.

c) Increased excretion of urine urobilinogen and faecal

stercobilinogen (dark urine and faeces).

d) The causes of pre-hepatic jaundice are incompatible blood

transfusion, haemolytic disease of the newborn, haemolytic
anaemia and malaria.
 7. Hepatic jaundice:

a) In hepatocellular jaundice, there is dysfunction of the hepatic

cells.

b) Cell necrosis reduces the ability of the liver to metabolize

and excrete bilirubin, leading to a buildup of unconjugated
bilirubin in the blood.

c) As the disease progresses, swelling of cells and oedema due

to inflammation cause mechanical obstruction of intrahepatic
biliary tree; this may cause rise in conjugated bilirubin.

d) In hepatic jaundice, there may be an increase in both serum

conjugated and unconjugated bilirubin (mixed picture).

e) Decreased faecal stercobilinogen (clay coloured faeces).

f) Urine may be dark yellow (due to increased excretion of

urobilinogen - defective enterohepatic circulation or presence of
bilirubin in the urine - intra-hepatic bile duct obstruction).

g) The causes of hepatic jaundice are hepatitis, hepatotoxicity,

cirrhosis, drug induced hepatitis and alcoholic liver disease.

8. Obstructive jaundice:

a) It is caused due to obstruction to the flow of bile in the

extra-hepatic bile duct.

b) There is increase in conjugated bilirubin.

c) Absence of faecal stercobilinogen (clay coloured faeces)

and increased urine bilirubin (dark yellow urine).

d) The causes of obstructive jaundice are gallstones and

cancer of head of pancreas.
 9. Jaundice is commonly associated with pruritis.

10. Treatment of jaundice is typically determined by the

underlying cause.

INTRAHEPATIC CHOLESTASIS OF PREGNANCY

1. ICP (intrahepatic cholestasis of pregnancy) is a reversible type

of hormonally influenced cholestasis.

2. ICP most often presents in the late second or early third trimester
of pregnancy.

3. ICP is characterized by generalized itching, often commencing

with pruritis of the palms of hands and soles of feet.

4. Affected women have a defect involving the excretion of bile

salts, which leads to increased serum bile salts; these are deposited
within the skin, causing intense pruritis.

5. Sex hormone levels are increased in pregnancy; sex hormones

exert cholestatic effect via inhibition of the hepatocellular bile salt
export pump.

6. Selenium plays a role in bile secretion and selenium deficiency

may be a causative factor in ICP.

7. Jaundice may occur in 20 to 75% of cases of ICP and typically

develops 1 to 4 weeks after the onset of pruritis.

8. Ursodeoxycholic acid (UDCA) is the drug of choice for the

treatment of ICP; UDCA improves bile export from the liver.
 9. Anti-histamines are administered with UDCA to alleviate the
pruritis symptoms.

10. Phenobarbital, cholestyramine and dexamethasone may also

be used.

PORTAL HYPERTENSION

INTRODUCTION AND CAUSE

1. The portal vein carries approximately 1500 ml of blood

per minute from the small and large intestine, spleen and
the stomach to the liver.

2. The normal portal pressure is 5 to 10 mm Hg.

3. Obstruction of the portal venous flow results in rise in

the portal venous pressure (portal hypertension).

4. The major cause of portal hypertension is liver cirrhosis.

5. The response to increased venous pressure is the

development of collateral circulation that diverts the obstructed
blood flow to the systemic veins.

6. These porto-systemic collaterals form by opening and

dilatation of pre-existing vascular channels connecting
the portal venous system and the superior and inferior vena
cava.
CLINICAL FEATURES

1. Weakness, anorexia, sudden massive bleeding, vomiting,

weight loss and abdominal pain.

2. Ascites, rectal hemorrhoids, para-umbilical hernia,

jaundice, edema, gynaecomastia, Dupuytren’s contracture,
asterixis (liver flap), palmar erythema, testicular atrophy
and splenomegaly.

3. Pallor, dyspnea, telangiectasis, foetor hepaticus, venous

hums and tarry stools.

4. Caput medusa:

a) Caput medusa, also known as palm tree sign, is the

appearance of distended and engorged superficial
epigastric veins, which are seen radiating from the
umbilicus across the abdomen.

b) The name caput medusa (Latin for ‘head of Medusa’)

originates from the apparent similarity to Medusa’s head,
which had venomous snakes in place of hair.

c) It is caused by dilation of the para-umbilical veins,

which carry oxygenated blood from mother to foetus in
utero and normally close within one week of birth.

d) The veins become re-canalised due to portal

hypertension caused by liver failure.

5. Features of encephalopathy:

a) Disturbance of sleep-wake cycle and memory loss.

b) Personality changes and bizarre behaviour.

INVESTIGATIONS

1. Ultrasound, CT scan, MRI, angiography, endoscopy

and liver biopsy.

2. Complete blood count: Anemia, leukopenia and

thrombocytopenia.

3. Increase in serum AST, ALT and ALP.

4. Increase in prothrombin time.

5. Decrease in serum albumin.

6. Arterial blood gas analysis.

TREATMENT

1. Beta blockers: Propranolol / Nadolol.

2. Simvastatin.

2. Sclerotherapy and variceal ligation.

3. Decompressive shunts & de-vascularization

procedures.

4. Liver transplantation.
ASCITES

INTRODUCTION

1. Ascites is defined as the accumulation of more than

25 ml of fluid in the peritoneal cavity.

2. The word ascites is of Greek origin and means bag

or sac.

CAUSES

1. Liver diseases:

Cirrhosis, hepatitis, fulminant hepatic failure & hepatic

metastasis.

2. Hypoalbuminemia:

Nephrotic syndrome, protein losing enteropathy and

severe malnutrition.

3. Heart diseases:

Congestive cardiac failure & constrictive pericarditis.

4. Miscellaneous:

Bacterial / fungal peritonitis & peritoneal carcinomatosis.

PATHOPHYSIOLOGY

1. Hypoalbuminemia & reduced plasma osmotic pressure

favour the extravasation of fluid form the plasma into the
intra-peritoneal space.

2. Due to portal hypertension, there is decrease in the

effective circulating blood volume; decreased renal
perfusion leads to activation of the renin angiotensin
system resulting in sodium and water retention.

CLINICAL FEATURES

1. Features of liver disease:

a) Increased abdominal size, weight gain, early satiety,

abdominal discomfort and dyspnea.

b) Jaundice, palmar erythema, spider angiomata,

muscle wasting and gynaecomastia.

2. Features of cardiac failure:

Orthopnea, peripheral edema, pulmonary congestion

and elevated JVP.

3. Sister Mary-Joseph nodule:

Sister Mary-Joseph nodule is a palpable nodule bulging

into the umbilicus as a result of malignant cancer in the
abdomen, which may be a cause of ascites.
 INVESTIGATIONS

1. Ascites is detected on physical examination by visible

bulging of the flanks, shifting dullness or fluid thrill (in
massive ascites).

2. X-ray, ultrasound and abdominal CT scan.

3. Diagnostic paracentesis and laparoscopy.

4. Blood cell count and bacterial culture of the ascitic fluid.

5. Serum albumin ascites gradient (SAAG):

a) SAAG = Albumin concentration in serum – Albumin

concentration in ascitic fluid.

b) SAAG > 1.1 gm/dl indicates ascites due to portal

hypertension.

c) SAAG < 1.1 gm/dl indicates non-portal hypertensive

ascites.
TREATMENT

1. Abstinence from alcohol.

2. Restricting dietary sodium to 2 grams/day.

3. Diuretics: Spironolactone and furosemide.

4. Vasopressin receptor antagonist: Tolvaptan

5. Therapeutic paracentesis.

6. Liver transplantation.

QUESTIONS

1. Jaundice.

2. Portal hypertension.

3. Ascites.

4. Intrahepatic cholestasis of pregnancy.