Nutrition 445
Case Study 1
Due September 18, 2013
Case:
A 36-year old man was admitted to a hospital following episodes of nausea, vomiting,
and general malaise. His urine was darker than usual. Upon examination it was
discovered that his liver was enlarged and tender to palpation. Liver function tests were
abnormal; plasma ALT was 1500 IU/L; AST was 400 IU/L. During the next 24 hours the
man developed jaundice, and his plasma total bilirubin was 9.0 mg/dL (154 mmol/L). A
diagnosis of hepatitis was made.
The UL of the normal ranges in this lab are LD 300 IU/L, ALT, and AST 40 IU/L
Questions:
1) Define hepatitis and discuss the major causes of hepatitis.
Hepatitis is a disease of the liver where the liver becomes inflamed preventing
proper function of the organ; and, there are five types of hepatitis, with the most
common forms being Hepatitis A, B, and C. Hepatitis A is spread through
contaminated food through the oral-fecal rout, by someone who prepared your food
who has the virus, or by drinking contaminated water in parts of the world with
poor sanitation. Hepatitis B and C are both spread by contact with an infected
person’s blood, semen or bodily fluid.
2) What reactions are catalyzed by AST and ALT? and what coenzyme is required?
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) become
elevated when the hepatitis virus has affected the liver since the liver is the main site
for the catabolism of amino acids (the transfer or removal of amino acids). This
process occurs through transamination reactions, which involve the transfer of an
amino group from one amino acid to an amino acid carbon skeleton, which are
catalyzed by aminotransferases.
(See written reaction below)
(Smith, Grooper, 2013)
AST, found in higher concentrations in the heart, and ALT, found in higher
concentrations of the liver, catalyze the two most important aminotransferases
reactions, which are both revisable reactions. ALT catalyzes the transfer of the
amino group alanine to an –ketogluterate, producing pyruvate and glutamate,
while AST transfers amino groups from aspartate to an –ketogluterate, producing
oxaloacetate and glutamate.
(See Figures 1 and 2 below)
(Advanced Nutrition and Human Metabolism, 2013)
Figure 1
Figure 2
3) What conditions are important to maintain in performing the enzyme assays?
Enzyme assays are laboratory methods used for measuring enzymatic activity and
measuring the loss of a substrate that should be measured under steady-state
conditions and should also be tested under steady-state conditions. Problems that
arise are due to lack of attention to detail, so it is crucial to ensure that the enzymes,
substrates, buffers, etc. have been fully evaluated and characterized. The addition
of an acidic solution to a basic solution, or vice versa, otherwise known as a titration,
is the way to determine the concentration of an active site in the assay; likewise,
multiple concentrations of the substrate should be tested in order to distinguish
noncompetitive inhibition from uncompetitive inhibition. To distinguish a
competitive inhibitor from a noncompetitive inhibitor or uncompetitive inhibitor is
increased at concentrations of substrate above its own Km value, the velocity should
be measured and it is recommended that less than 10% of the substrate should be
converted into the product. Measuring the rate of the product formation should be
liner to time, meaning, measuring the rate of product formation at the concentration
of the substrate using the assay and equipment that will be used in the final assay
and the linear part should be evaluated from the data. High and low controls of the
substrate should be included in the final assay with the high control having the
maximum enzyme activity at each substrate showing the substrate titration without
the inhibitor and the low control has the substrate titration with the enzyme,
substrate, or the inhibitor, which reflects the signal expected for there to be no
enzyme activity at each substrate concentration.
(Mechanism of Action Assays for Enzymes, 2008)
4) Which other enzymes might have been elevated in the plasma?
Excluding aspartate aninotransferase and alanine aminotransferases, other enzymes
that may be elevated in the plasma is alkaline phosphate, gamma-glutamyl
transferase (GGT), and bilirubin. Elevations of these enzymes can be detected by
doing a liver panel, which is a way to screen for damage; these results do not detect
a specific condition but instead they indicate that there may be a liver dysfunction.
Alkaline phosphatase (ALP) is a source of the bone and liver and when ALP is
elevated you want to check GGT to help locate the source because high levels can
indicate cholestasis or hepatocellular injury. Both ALP and GGT will be elevated
within the bile duct if the damage to the liver was caused by alcohol, GGT is not a
source of the bone and is the most sensitive enzyme to detect liver damage.
Bilirubin is elevated within the blood when too much of the enzyme is being
produced which indicated less is being removed due to obstructions within the bile
duct or issues processing bilirubin, levels of bilirubin are variable depending on the
severity of jaundice or alcohol consumption.
(Hepatitis, 2003)
(Hepatic Function Panel, 2013)
5) How does “total” bilirubin relate to “direct” and “indirect” bilirubin?
The result of the breakdown of Haemoglobin is bilirubin, and bilirubin is the
principle pigment in bile, which then gets excreted from the body via feces.
Bilirubin circulates throughout the blood stream in two forms, direct and indirect.
Indirect bilirubin is insoluble and travels through the bloodstream to the liver
where is it then changed to the soluble direct form. Direct bilirubin is soluble and is
made by the liver from indirect bilirubin. Total bilirubin is the sum of direct
bilirubin and indirect bilirubin and total bilirubin levels, along with direct bilirubin
levels, are measured in the blood while indirect bilirubin levels are derived from the
total and direct bilirubin measurements by subtracting the direct bilirubin value
from the total value. We can measure the amount of bilirubin by collecting a blood
sample and this test is used for liver moderation by checking if the liver is
functioning properly as well as watching for any signs of liver dysfunction/disease
such as hepatitis. Blood samples are also a way to find out if the bile ducts are
blocked, and to monitor the presence and progression of jaundice.
(Total and Direct Bilirubin)
6) What other diagnostic tests need to be done for this patient before a treatment plan
can be recommended?
The patient has hepatitis symptoms and was diagnosed with hepatitis, so his doctor
should perform a blood test to check for the presence of the antibody to determine
the type of hepatitis and possibly perform a liver biopsy to determine the extent of
the liver damage. Other diagnostic tests that need to be done for this patient before
a treatment plan can be recommended would be narrowing the hepatitis down to an
acute or chronic form, then decide which one of the five forms of hepatitis, so the
patient can be properly treated. Hepatitis A, B, and C are viral forms of hepatitis
and can be diagnosed by a physical exam, blood tests, liver biopsy, and imaging
studies like a CAT scan or a sonogram. No matter what type of hepatitis this man
has he should avoid alcohol consumption because that can further damage the liver.
Works Cited
Alter, HJ: Hepatitis. Semin Liver Dis. 6:1, 1986.
Cassidy, WM, Reynolds, TB: Serum lactate dehydrogenase in the differential diagnosis
of acute hepatocellular injury. J Clin Gastroenterol. 19(2); 118, 1994.
Chames, Frances. "Hepatitis." Presented at the E. Lansing CHM Campus. 14 Feb. 2003.
Lecture.
Jacobson, IM, Dienstag, JL.: The delta hepatitis agent: viral hepatitis, type D.
Gastroenterology. 86: 1614, 1985.
Liver Function Tests; LFTs." Hepatic Function Panel (n.d.): n. pag. Lab Tests Online. 6
Mar. 2013. Web. 15 Sept. 2013.
National Digestive Diseases Information Clearinghouse 2007, NIH publication, Volume
no. 07-6190
Smith, Grooper: Advanced Nutrition and Human Metabolism. 6: 2005, 2009, 2013
Strelow, John, Walthere Dewe, Phillip W. Iversen, Harold B. Brooks, Jeffrey A.
Radding, James McGee, and Jeffrey Weidner: Mechanism of Action Assays for
Enzymes. Assay Guidance Manual. National Center for BioTechnology Information,
1 May 2008. Web. 12 Sept. 2013.
Total and Direct Bilirubin: Clinical Chemistry Lab Manual. F113-122.