If the hepatobiliary system is functioning, fecal
urobilinogen varies directly with rate of red cell hemolysis.
In case of hemolysis, the daily excretion is related to
the existing total body hemoglobin mass. If there is a
reduced total body hemoglobin mass, accelerated rates
of hemolysis may only yield an amount of urobilinogen
that would be within normal limits for an individual with
Fecal urobilinogen absent occurs with exclusion of
bilirubin from the gut in complete biliary tract obstruction
and in extreme cases of hepatocellular disease. Absence
of urobilinogen in feces is important in indicating biliary
tract obstruction, persistent absence is a strong indication
of malignant obstructive disease. Decreased fecal
urobilinogen excretion may occur when antibiotics which
alter intestinal flora are used (tetracyclines, streptomycin,
Bromsulphalein (Sulfobromophthalein) Excretion
Sulfobromophthalein sodium (Bromsulphalein, BSP, is
a dye which is bound avidly by albumin, the complex is
picked up by the liver cell, and the BSP is transported into
the microsomes, conjugated and excreted in the bile, in a
manner analogous to bilirubin.
BSP is given intravenously and its amount present in the
blood after 30, 45 or 60 minutes indicate hepatic function.
The greater the liver function loss, greater the amount
BSP present in blood (this test is of no significant value in
differential diagnosis). BSP retention in blood conjugated/
unconjugated runs parallel to bilirubin related disorders.
In the presence of fevers, administration of anabolic
steroids, Tele-paque, Dubin-Johnson syndrome and in
Gilbert’s disease, BSP retention is increased. In the latter
two disorders the uptake by liver cells is normal (so normal
retention at 45 minutes) but after getting conjugated it
regurgitates back into blood (so BSP retention is marked at
1. Lipemic/jaundiced sera may cause interference. In any
case one should not perform the test in the presence
of acute liver/gallbladder disease.
2. Know the patient’s weight, inject 5 mg BSP/kg body
weight intravenously, over a period of 60 seconds.
Having injected set the time to 45 minutes.
3. After 45 minutes withdraw 8–10 mL blood from the
other arm, let it clot, remove serum after centrifuging.
4. Take 2 test tubes marked test and blank:
The full reddish color develops in the alkaline solution,
and the dye is colorless in acid solution.
5. Read the absorbance of test at 575 nm (or 590 nm)
setting the zero with the blank.
6. Refer the absorbance reading to the calibration curve
to obtain the percentage of the dye dose remaining
in the blood after the 45 minutes interval. Report as
percentage of dye retention afterminutes,” giving
the dose used. Normal retention is up to 4% (average
Calibration: Into a 1 liter volumetric flask pipette very
accurately 2.0 mL of 5% BSP. Dilute to the mark with
distilled water and mix well. Into 4 clean test tubes pipette
accurately the following amounts of the diluted dye: 0.25,
0.50, 0.75, and 1.0 mL. Make each to 1.0 mL with distilled
water. To each tube add exactly 4.0 mL of N/10 NaOH.
Mix by inversion and read the absorbance at 575/590 nm.
These standards correspond to values of 25, 50, 75 and
100% retention in the test. Plotted on graph paper, the
readings should fall on a straight line passing through the
Conditions Associated with Increased BSP Retention
¾ Jaundice from any cause except Gilbert’s syndrome
¾ Lymphomatous or leukemic infiltration
¾ Prolonged fasting or malnutrition
¾ Contrast media used for gallbladder examination.
• Spuriously high retention because excessive weight
• Spuriously low retention because binding is reduced
• Spuriously low retention because the dye enters the
• Spuriously low retention because albumin bound dye
EVALUATION OF SYNTHESIS IN LIVER
Serum Proteins (Albumin Especially)
Since serum albumin and a small fraction of globulin
are synthesized in liver, serum proteins are affected both
quantitatively and qualitatively in liver disease. In any
disease causing hepatocellular damage, the concentration
of serum albumin decreases. In many liver disorders,
serum globulins may rise to such a level so as to maintain
normal or increased total protein concentration even
when there is severe albumin depletion.
The changing levels of serum albumin thus provide
valuable indices of severity, progress, and prognosis
in hepatic disease. Decreased albumin and elevated
globulins in serum indicate hepatocellular origin of
jaundice or liver disease. In obstructive jaundice, serum
protein changes occur late, after secondary hepatocellular
damage has occurred. Cholangitis and biliary cirrhosis,
changes may return to normal before convalescence from
hepatitis is complete. However, liver disease is not the only
cause of serum protein alterations.
Chemical methods and electrophoretic methods are
available for serum proteins estimation. Electrophoresis is
most precise and specific way of assessing serum proteins.
The flocculation and turbidity methods crudely estimate
globulins and hence are not specific and obsolete in
Deficiency of prothrombin may occur as a result of:
1. Inadequate absorption of bile from the intestinal tract,
2. Inability of a damaged liver to convert vitamin K to
A normal prothrombin concentration does not rule out
Low Prothrombin in Presence of Jaundice
When a low prothrombin level is found in a jaundice
patient, give 2–4 mg vitamin K, IV or IM, and measure
prothrombin concentration later.
1. Return to normalcy of prothrombin concentration
(85–100% of normal) indicates that the capacity of liver
cells to synthesize prothrombin is good.
2. A poor response implies hepatocellular disease, either
primary or following prolonged obstructive disease.
Low Prothrombin in the Absence of Jaundice
In the absence of jaundice, a low prothrombin level usually
indicates serious liver damage, and no response to large
doses (60–70 mg) of parenteral water-soluble vitamin K
confirms it. This is true if jaundice is also present.
Associated with extensive destruction of liver parenchyma
is reduction in serum levels of cholesterol and cholesterol
esters, extremely low concentration implies a poor
prognosis. Persistently low cholesterol ester concentration
or ester/total cholesterol ratio indicates continuing
hepatocellular damage, a rise in cholesterol ester is
considered as a good sign and heralds improvement.
Increase of Total but Decrease of Esters
Accompanying biliary obstruction is usually a rise in total
cholesterol, but the cholesterol ester concentration is
often unaffected. The determination of cholesterol ester,
however, is not a fruitful exercise clinically.
The liver removes noxious materials or renders them
harmless by conjugation of toxic substances with amino
oxidation or reduction, by excretion, etc.
This test depends upon conjugation by liver of sodium
benzoate with glycine to produce hippuric acid, which
is excreted in the urine. It is preferrable to give sodium
benzoate-1.77 g-IV (instead of orally in which case the
absorption may be irregular), one hour later at least
0.7 g of hippuric acid should be excreted in the urine.
Consideration of low values is permissible only if impaired
renal function is ruled out for retention of hippuric acid.
Liver and muscles are rich in enzymes of Kreb’s cycle.
Among such enzymes is a group responsible for transfer of
NH2 groups from amino acids to keto acids, thus, providing
for metabolism of amino acids. Destruction of muscle or
of liver cells releases the enzymes, with consequent rise in
their values in plasma. In obstructive jaundice and more
so in acute hepatitis, the serum levels of SGOT and SGPT
rise to very high levels (300-1500 units, normal being 5-40
units), as does LDH concentration (normal concentration,
200-450 units). Chronic hepatitis may produce
moderate elevations of serum transaminases. Liver cell
destruction incident to neoplastic disease metastatic to
the liver produces moderate elevation of transaminases
In many cases, there seems to be a correlation between
the differences in the degree of elevation of SGOT and
SGPT and the cause of jaundice. Rise of SGPT is greater
than elevation of SGOT in extrahepatic obstruction, acute
hepatitis and toxic hepatitis, the reverse is true in cirrhosis
of liver, intrahepatic neoplasm, and hemolytic jaundice.
The concentration of this enzyme often increases in the
plasma of an icteric patient. It is normally present in the
liver and excreted in the bile so that elevation of serum
alkaline phosphatase may be a manifestation of retention;
this is a convenient explanation for the observation that
serum alkaline phosphatase concentration increases in
obstructive jaundice. In acute and chronic hepatocellular
disease, serum alkaline phosphatase is raised, but not to
the extent typical of obstructive jaundice. In hemolytic
rise in the absence of jaundice. It should be kept in mind
that phosphatase levels may be normal early in obstructive
disease and with relief of obstruction. Pregnancy and such
diseases as Paget’s disease of bone, hyperparathyroidism,
and rickets/osteomalacia, are also associated with
elevated serum alkaline phosphatase concentration and
SUGGESTED LIVER FUNCTION TESTS
Urine bilirubin, urine urobilinogen, serum bilirubin, BSP
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