Unit 1: Liver Function Teest Flashcards
Yellow discoloration of the skin, eyes, and mucous
membranes
Jaundice
3 Classifications of Jaundice
Pre hepatic
Hepatic
Post hepatic
abnormality occurs before liver
metabolism
Pre hepatic jaundice
abnormality occurs after liver
metabolism
Post hepatic
Conjugation occurs but the problem is the
bilirubin in the form of B2 cannot be excreted
in the bile canaliculi causing jaundice and
causing its leaking in the bloodstream
Post hepatic jaundice
serum or plasma sample with a yellow
discoloration due to an elevated bilirubin level
Icterus
unconjugated hyperbilirubinemia
Pre hepatic jaundice
Most commonly caused by an increased amount of bilirubin
being presented to the liver
Pre hepatic
increased or continuous destruction of RBCs
so that, an increase in such causes now an
increased amount of bilirubin in the liver
Acute and chronic hemolytic anemias
Pre hepatic lab results
Lab result: Elevated B1
primary problem causing the jaundice resides in
the liver
Hepatic
Caused by disorders of bilirubin metabolism (conjugation)
and transport defects (secretory functions of the liver)
Hepatic
Syndrome of Chronic Nonhemolytic
Unconjugated Hyperbilirubinemia
Crigler-Najjar syndrome
Associated with conjugation deficit
Crigler-Najjar syndrome
complete absence of enzymatic bilirubin
conjugation
Crigler-Najjar syndrome type 1
mutation causing a severe deficiency of
the enzyme (UDPGT) responsible for bilirubin
conjugation
Crigler-Najjar syndrome type 2
Crigler-Najjar Syndrome lab result
Lab result: elevated B1
Is caused by a genetic mutation in the gene
(UGT1A1) that produces UDPGT
Gilbert’s syndrome
Gilbert’s syndrome Lab results
Lab result: Elevated B1
Bilirubin excretion deficit
Dubin-Johnson syndrome and Rotor syndrome
Dubin-Johnson syndrome and Rotor syndrome lab result
Lab result: Elevated B2
A rare inherited disorder caused by a
deficiency of the canalicular multidrug
resistance/multispecific organic anionic
transporter protein (MDR2/cMOAT)
Dubin-Johnson syndrome
Unique feature: appearance of dark-stained
granules on a liver biopsy sample
Dubin Johnson syndrome
caused by mutations in SLCO181 and
SLCO1B3 genes (solute carrier organic
anion transporter fomily member 183/183
genes)
Rotor syndrome (Rotor hyperbilirubinemia)
Neonatal hyperbilirubinemia
a result of a deficiency in the enzyme UDPGT
B1 is deposited in the nuclei of brain and nerve
cells, causing kernicterus
Physiologic Jaundice of the Newborn
Treatment for Physiologic Jaundice of the Newborn
Phototherapy
exchange transfusion
pharmacological treatment
Baby is exposed to fluorescent lamp to
convert B1 to water-soluble fragment ready
for elimination
Conventional phototherapy
Applies a blanket (bili-blanket) ilagay sa
likod ng baby to convert B1 into a double
by-product for elimination.
Extensive phototherapy
Aliquot of blood from the baby and
exchange with donors blood to solve
hyperbilirubinemia.
Exchange transfusion
Will induce the activity of UDPGT
Phenobarbitone
Slow down the rate of hemolysis.
IV Immunoglobulins
Potent inhibitors of heme oxygenase.
Competitive inhibitors.
Metalloporphyrins
Form of unconjugated hyperbilirubinemia caused by a
circulating inhibitor of bilirubin conjugation
Lucey-Driscoll Syndrome
Lucey-Driscoll Syndrome lab result
Lab result: Elevated B1
o Occurs in breast-feed neonates (4-7th day of life).
o Milk component inhibits enzyme UDPGT.
Breast Milk Jaundice Syndrome
Results from biliary obstructive disease (presence of
gallstones or tumors) that prevent the flow of conjugated
bilirubin into the bile canaliculi
Post hepatic
Stool becomes clay-colored
Post hepatic
Last stage of liver failure
Cirrhosis
adverse immune response
directed against the liver itself
Autoimmune hepatitis
plasma protein; deficient
in patients with hepatic cirrhosis
a1-antitrypsin deficiency
characterized by the accumulation
of copper in the brain, liver, and in other organs
Wilson Disease
there is iron overload
Hemochromatosis
inborn error of carbohydrate
metabolism
Galactosemia
there is
liver inflammation and there will be presence of
infiltrates in the liver not associated with alcohol
Nonalcoholic steatohepatitis (NASH)
Treatment of cirrhosis
o Abstaining from alcohol
o Medications – hepatitis-related cirrhosis
▪ Interferon – viral hepatitis
▪ Corticosteroids – autoimmune hepatitis
Classification of tumors
Primary
Metastatic
Benign
Malignant
Begins in the liver cells
Primary tumor
Tumors from other parts of the body spread to the
liver
Metastatic tumor
hepatocellular adenoma, hemangiomas
Benign tumor
o is also known as Hepatic adenoma
o Caused by massive oral contraceptive pill intake.
Hepatocellular adenoma
o Cavernous hemangiomas
o Tangled blood vessels.
Hemangiomas
hepatocellular carcinoma (most
common; 90% of primary liver cancers) and bile duct
carcinoma
Malignant
Associated with elevated ammonia
Reye’s syndrome
Lab results of Reye’s syndrome
Lab results: mild hyperbilirubinemia; elevated levels of
ammonia and aminotransferases (AST and ALT)
Most common caused of hepatic toxicity.
Paracetamol (acetaminophen)
Lab results: slight elevations in AST, ALT, and GGT;
biopsy shows fatty infiltrates in the vacuoles of the
liver
Alcoholic fatty liver
Lab results: moderately elevated AST, ALT, GGT,
and ALP; total bilirubin (> 30 mg/dL); AST/ALT ratio
> 2; decreased serum albumin; prolonged PT
Alcoholic hepatitis
Lab results: increased liver function tests (AST, ALT,
GGT, ALP, total bilirubin); decreased serum albumin;
prolonged PT
Alcoholic cirrhosis
Implies injury to the liver characterized by the presence of
inflammation in the liver tissue
Hepatitis
prolonged elevation of serum
transaminase (ALP, AST, etc.) level (longer than 6
months – chronic hepatitis)
HBV and HCV
Routes of transmission
Fecal-oral
HAV
HEV
Route of transmission
Parenteral sexual
HBV, HCV, HDV
Basis of commonly used methods today
CLASSIC DIAZO REACTION
Bilirubin + diazotized sulfanilic acid -> colored
product (urine sample)
CLASSIC DIAZO REACTION
found that the diazo reaction may be applied to serum
samples only in the presence of an accelerator (solubilizer)
VAN DEN BURGH
first clinically useful methodology for the quantitation of
bilirubin in serum samples
EVELYN AND MALLOY
Evelyn and malloy
o Accelerator:
o Diazo A:
o Diazo B:
o Diazo Blank:
o Accelerator: 50% methanol (solubilizer)
o Diazo A: 0.1% Sulfanilic Acid + HCl
o Diazo B: 0.5% Sodium Nitrite
o Diazo Blank: 1.5% HCl
pink to purple azobilirubin (red-purple)
▪ pH 1.2 ; 560 nm
Final reaction
Evelyn and Malloy
candidate reference method for total bilirubin
Requires the addition of buffer
JENDRASSIK AND GROF
Jendrassik and Grof
Accelerator
caffeine sodium benzoate
Buffer of Jendrassik and Grof
Sodium Acetate
Jendrassik and Grof
Final reaction:
pink to blue azobilirubin
Jendrassik and Grof
required wavelength
600 nm
Involves the measurement of reflected light from the skin
using two wavelengths that provide a numerical index
BILIRUBINOMETRY
Bilirubin found in Dubin-Jonnson
Delta bilirubin (measured as B2)
Total bilirubin 3 fractions:
Unconjugated, Conjugated, and
Delta bilirubin
serum is preferred in this method
Evelyn and Malloy
Bilirubin conversion factor
17.1
Absence of urobilinogen from the urine and stool
Complete biliary obstruction
Urobilinogen reacts with p-
dimethylaminobenzaldehyde (Ehrlich’s reagent) to
form a ____ color, which is then measured
spectrophotometrically.
Red
Spx for urine urobilinogen
fresh 2-hour urine specimen
most liver specific enzyme
Alanine amino transferase
Method AST
Karmen Method
Karmen method indicator
Malate dehydrogenase
Karmen Method
Optimal pH
7.3 to 7.8
Karmen method wavelength
340 nm
METHOD: ALT
Coupled enzymatic reaction
Indicator method ALT
Lactate dehydrogenase
Ph 7.3 to 7.8
340 nm
Found in very high concentrations in cases of extrahepatic
obstruction
Alkaline phospatase
Is considered the most useful single technique for ALP
isoenzyme analysis
ELECTROPHORESIS
ALP activity is measured before and after heating the serum
at 56°C for 10 minutes.
HEAT FRACTIONATION / STABILITY TEST / HEAT
DENATURATION
A continuous-monitoring technique which allows calculation
of ALP activity based on the molar absorptivity of p-
nitrophenol
BOWERS AND MCCOMB
Serum levels become significantly elevated in hepatobiliary
disease
5’ - NUCLEOTIDASE
Highest levels of GGT are seen in biliary obstruction
Y-GLUTAMYLTRANSFERASE (GGT)
GGT substrate
: y-glutamyl-p-nitroaninide
High serum levels may be found in metastatic carcinoma of
the liver.
Lactate dehydrogenase
L → P reaction (Lactate to pyruvate
WACKER METHOD (FORWARD/ DIRECT)
P → L reaction (Pyruvate to lactate)
WROBLEUSKI LA DUE (REVERSE/INDIRECT)
May be useful in following the progression of disease and
the assessment of the risk of bleeding
Prothrombin time (Vit. K response test)
Prolonged PT
Severe Diffuse Liver Disease
Useful in quantitating the severity of hepatic dysfunction
SERUM PROTEINS
low due to decreased protein synthesis
o Low/reduced in case of alcoholic cirrhosis, alcoholic
hepatitis
Albumin
decreased in chronic liver disease
o Low or absent α-globulin – α1-antitrypsin deficiency
▪ Deficient in patients with hepatic cirrhosis
a- Globulin
transiently increased in acute liver disease
and remain elevated in chronic liver disease
Y-globulin
elevated in chronic active hepatitis
IgG and IgM
primary biliary cirrhosis
IgM
alcoholic cirrhosis
IgA
Fasting sample
Lipemic
Bilirubin conc. Falsely ⬆️
Hemolysed sample
Bilirubin conc. falsely ⬇️
Fecal urobilonogen Spx
Aqueous extract of fresh feces
Any urobilin present is reduced to urobilinogen by treatment with ——- before Ehrlich’s reagent is added
alkaline ferrous
hydroxide
