TESTS OF EXCRETION BY THE LIVER

Bile Pigment

Serum bilirubin concentration depends on the rate of

removal of bilirubin from destruction of hemoglobin.

Normal removal of bilirubin from the body is shown in

Figure 18.1.

Types of Bilirubin

In the plasma, bilirubin is present as ‘indirect’ reacting

bilirubin, which is not water-soluble; and ‘direct’-reacting

esterified bilirubin (bilirubin glucuronide), which is water

soluble. In the van den Bergh reaction, the water soluble

ester reacts readily with diazo reagent (‘direct reaction’),

the addition of alcohol renders the unesterified bilirubin

soluble so that diazotization may occur (‘indirect reaction’).

Jaundice: is a term used in clinical medicine to describe a

visible yellow discoloration of the skin and sclera.

Classification of the Causes of Jaundice

Unconjugated Bilirubin

Prehepatic (hemolytic retention jaundice) (Fig. 18.2)

1. Excessive red cell hemolysis

FIG. 18.1: Urine urobilinogen 0–4 mg/24 h; bilirubin absent;

fecal urobilinogen 40–280 mg/24 h

Normal

Bilirubin-Urobilinogen Cycle (Solid arrows = conjugated bilirubin;

dotted arrows = urobilinogen)

FIG. 18.2: Urine urobilinogen increased; bilirubin absent;

fecal urobilinogen increased

Hemolytic jaundice

Bilirubin formation increased

Liver Function Tests 455

a. Familial: e.g. spherocytosis, enzyme defects in

red cell.

b. Acquired

• Traumatic, e.g. hematomas

• Toxic, e.g. phenylhydrazine

• Infective, e.g. malaria

• Neoplastic, e.g. Hodgkin’s disease.

2. Excessive “shunt” production.

Hepatic (Fig. 18.3)

1. Nonhemolytic retention jaundice (defect of transport

into cell or microsomes).

a. Familial:

• UDP glucuronyl transferase deficiency (Types

I and II)

• Gilbert’s disease

• Crigler-Najjar syndrome.

b. Acquired or uncertain inheritance

 Neonatal jaundice, e.g. physiological breast milk,

or serum factor.

Conjugated Bilirubin

Intrahepatic Cholestasis (regurgitation jaundice)

A. Hepatocellular injury

• Toxic, e.g. carbon tetrachloride necrosis

• Infective, e.g. viral hepatitis

• Neoplastic, e.g. primary or secondary carcinoma

of liver

• Cirrhosis, e.g. familial or acquired.

B. Bile duct injury

• Familial, e.g. Dubin-Johnson syndrome. Rotor

syndrome, recurrent familial cholestasis

• Toxic, e.g. drugs (phenothiazines, steroids)

• Inflammatory, e.g. sclerosing cholangitis

• Neoplastic, e.g. cholangiocarcinoma

• Others, e.g. primary biliary cirrhosis, pregnancy,

intrahepatic atresias.

C. Posthepatic (extrahepatic cholestasis): Various causes

are (Fig. 18.4):

1. Intramural: e.g. stones, parasites.

2. Mural:

• Congenital, e.g. extrahepatic biliary atresia

• Inflammatory, e.g. acute cholangitis

• Neoplastic, e.g. cholangiocarcinoma, carcinoma of ampulla of Vater.

3. Extramural:

• Inflammatory, e.g. acute pancreatitis

• Neoplastic, e.g. carcinoma of pancreas,

lymphoma.

Hyperbilirubinemia

Various causes have been discussed, rise in conjugated or

unconjugated bilirubin in blood/serum has been indicated.

Urine Urobilinogen

Urobilinogen is normally formed from bilirubin by

bacterial action in the bowel. Normally, all urobilinogen

FIG. 18.3: Urine urobilinogen increased; bilirubin present;

bilirubin excretion decreased; fecal urobilinogen decreased

Hepatitis

Bilirubin--Urobilinogen Cycle

(Solid arrows = Conjugated bilirubin; dotted arrows = urobilinogen)

FIG. 18.4: COMPLETE Urine Fecal

Tumor urobilinogen urobilinogen

Stricture Absent Trace to

Severe Absent

hepatitis (rarely)

INTERMITTENT Fluctuates Fluctuates

Stone

Obstruction

Bilirubin present

456 Concise Book of Medical Laboratory Technology: Methods and Interpretations absorbed from the gut is excreted by the liver, only up to 4

mg appearing in urine in 24 hours.

Urine urobilinogen increased (> 4 mg/24 h);

A. Impaired liver function or partial duct obstruction.

B. ‘Overloading’ of the liver as a result of increased

urobilinogen production following hemolytic disease.

Urine Urobilinogen Absent

If biliary duct obstruction is complete, no bilirubin enters

the gut, no urobilinogen is formed, and none is found in

the urine or feces.