CLINICAL CHEMISTRY 2 BS MLS

LECTURE/PPT / PROF. GAIL ANN PAREL-PASCUAL, RMT, MPH 3rd Year

[TRANS] UNIT I: LIVER FUNCTION TESTS

OUTLINE
I Anatomy of the Liver
II Biochemical Functions of the Liver
A Excretory and Secretory
B Metabolism
C Detoxification and Drug Metabolism
III Liver Function Alterations during Disease
A Jaundice
i Pre-Hepatic Jaundice
ii Hepatic Jaundice
iii Posthepatic Jaundice
B Cirrhosis
C Tumors
D Reye Syndrome
E Drug – and Alcohol – Related Disorders
F Hepatitis
IV Assessment of the Liver Function
A Bilirubin
i Special Considerations  The excretory system of the liver
B Urobilinogen in Feces and Urine
o Secretions and excretions of the liver would have to be
i Determination of Urine Urobilinogen
ii Fecal Urobilinogen
drained
V Enzymes  Excretory system is associated to the organ
A Aminotransferases (ALT and AST) gallbladder; it begins in the bile canaliculi and
B Alkaline Phosphatase (ALP) would form to extrahepatic ducts and from this, will
C 5’ – Nucleotidase have right and left hepatic ducts, which drains the
D ϒ-Glutamyltransferase (GGT) secretions of the liver
E Lactate Dehydrogenase (LD)  Right and left will merge to form common
VI Tests Measuring Hepatic Synthetic Ability
hepatic duct, and this duct would eventually
A Serum Proteins
B Prothrombin time (Vitamin K Response Test) merge with the cystic duct of the gallbladder
VII Tests Measuring Nitrogen Ability o Understood that the secretions of the
A Ammonia gallbladder and liver will have to
transverse its way until the common bile
duct
ANATOMY OF THE LIVER  Secretions of both will have to travel
 Weighs 1.2 to 1.5 kg (healthy adult) the way down to the intestines or in
 Is located beneath and attached to the diaphragm and is the duodenum (upper portion of
protected by the lower rib cage small intestine)
o Seen in Figure 25-1
 Is divided unequally into two lobes (right and left) by the
falciform ligament
 Receives blood supply from 2 sources – hepatic artery and
portal vein
o Seen in Figure 25-2
o Hepatic Artery – provides nutrient rich blood; also
provides 25% of the total blood supply to the liver
o Portal Vein – provides nutrient rich blood from the
digestive tract; provides 75% of the total blood supply
to the liver
o These 2 sources would merge to form the hepatic
sinusoids
 Are spaces that line the hepatic cells/lines
between the hepatocytes
 Approximately 1500 mL of blood passes through the liver
per minute  Lobules – functional units of the liver; microscopic units
o Six sided structure
 Each lobule contains a central vein with portal triads at each
of the corners
o Hepatic artery, portal vein, bile duct
 Hepatic artery, portal vein – Provide blood supply
to the liver

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 Bile duct – helps in draining/releasing the o Major heme waste product: bilirubin
secretions coming from the liver  Comes from the degradation of hemoglobin, in
particular heme
 Bile
o Made up of bile acids or salts, bile pigments,
cholesterol, and other substances extracted from the
blood
o Body produces approximately 3 L of bile per day and
excretes 1 L of what is produced
 Bilirubin
o Principal pigment in bile
o Derived from the breakdown of RBCs/RBC destruction
o 200-300 mg of bilirubin is produced per day

 Contains 2 major cell types – Hepatocytes (hepatic cells)

and Kupffer cells
 Hepatocytes (hepatic cells) – 80% of the volume of the liver;
perform major functions of the liver; regenerative properties
(in some short term injury/damage)
o If the liver is damaged repeatedly for long period of
time, there is irreversible changes that would interfere
with the biochemical functions of the liver
 Kupffer cells – macrophages; active phagocytes
o Located in the hepatic sinusoids

 Chart is bilirubin metabolism

o Bilirubin comes from RBC destruction/breakdown of
RBC
 Under normal conditions, RBC’s life span is
approximately 120 days
 These RBCs are destroyed by the spleen and the
BIOCHEMICAL FUNCTIONS OF THE LIVER liver by the phagocytic cells of reticuloendothelial
 Excretory and Secretory system thereby releasing now hemoglobin
 Metabolism  Hemoglobin will be cleaved into heme, protein
 Detoxification (globin), and iron
 Storage o Iron is bound to transport protein
 Note: transferrin/siderophilin and it will be
o If the liver becomes nonfunctional, death will occur deposited/stored in the bone marrow or
within 24 hours due to hypoglycemia. liver for reuse of the body
 In relation to carbohydrate metabolism, liver works o Globin will be degraded to its constituent
in maintaining stable glucose concentration by amino acid for reuse of the body
storing glucose in the form of glycogen o Heme will be converted to bilirubin in 2
(glycogenesis) to 3 hours in the form of unconjugated
bilirubin (B1)
 Glycogenolysis: turning glycogen to glucose
 In other books, before conversion
o Liver converts stored glycogen when
heme will first undergo reactions,
there is decreased amount of glucose
so that before it becomes B1, heme
 Glucogenesis: Depleted supply of
will be first converted to biliverdin
carbohydrate in the body and cannot meet the
through the enzyme heme
energy requirement of the body
oxigenase and then biliverdin is
o Conversion of glucose from non
converted through the enzyme
carbohydrate sources like amino acid,
biliverdin reductase
lactate, pyruvate
o Unconjugated bilirubin (B1) is
o To abolish liver tissue function, more than 80% of the
insoluble in water it cannot be therefore
liver must be destroyed.
eliminated by the body until it has been
conjugated to B2
EXCRETORY AND SECRETORY  It needs transport protein, albumin
 Liver is the only organ that has the capacity to rid the body  B1 that is bound to albumin will
of heme waste products. have to enter the liver cell
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 Once at the liver cell, B1 will  When blood glucose levels is too low, the liver
have to be released from will perform its function
albumin in order for it to be o The stored glycogen will be converted in
picked up by another carrier to consumbale glucose units in the
protein, known as ligandin process of glycogenolysis
 Ligandin is localized and  Lipids
resides in the hepatocytes and o The liver is responsible for gathering free fatty acids
is responsible in transporting B1 from the diet, and those produced by the liver itself, and
in the endoplasmic reticulum of breaking them down to produce acetyl-CoA.
the liver where rapid o Acetyl-CoA can then enter several pathways to form
conjugation occurs triglycerides, phospholipids, or cholesterol.
 B1 will be converted into B2  Examples of lipids
(conjugation) only in the o 70% of the daily production of cholesterol (1.5-2.0 g) is
presence of enzyme UDPGT produced by the liver.
 B2 will move to the intestines  The greatest source of cholesterol in the body
and in the intestines, the comes from what is produced by the liver and not
gastrointestinal bacteria will directly from dietary sources
have to work on the B2 for it to  Common notion before is that the greatest
be converted into a clear source is from dietary sources
byproduct urobilinogen, but  Although, the diet that we have also affects
before it happens, B2 will have the concentration of cholesterol in the blood
to proceed to some pathways  Proteins
 B2 will first be converted to o Almost all proteins
mesobilirubin and then o E.g. albumin, hemoglobin, haptoglobin, a1-antitrypsin,
reduced to microglobulin, etc.
mesobilirubinogen and  Except immunoglobulins – produced by plasma
then to urobilinogen cells
 About 80% of the urobilinogen
form is oxidized to DETOXIFICATION AND DRUG METABOLISM
urobilin/stercobilin and is  The liver serves as a gatekeeper between substances
excreted to feces absorbed by the gastrointestinal tract (GIT) and those
 Reference value for released into systemic circulation.
urobilinogen: 50 – 250 mg is o “FIRST PASS” – every substance that is absorbed in
excreted per day the GIT must first pass through the liver
 20% will enter the extrahepatic  Liver acts as a barrier to prevent the entrance of
circulation and will be harmful substances from reaching the systemic
recirculated back to the liver circulation
and will be re excreted in feces  Take good care of liver as it performs crucial
 Small portion of urobilinogen functions
will enter the systemic o Liver have to allow the entry of important substances
circulation, bloodstream and is in the systemic circulation and is also capable of
excreted in urine preventing/impeding the entrance of toxic or harmful
 Reference value: 1-4 mg of substances from reaching the systemic circulation
urobilinogen is excreted in urine  Body’s 2 mechanisms for detoxification:
per day o Bind the material to inactivate the compound
o Chemically modify the compound
METABOLISM  So it can be released by the body
 Carbohydrates  Drug-metabolizing system of the liver - most important
o The liver can do 3 things mechanism
 (1) Use the glucose for its own cellular energy o Responsible for the detoxification of many drugs
requirements, o Takes place in the liver microsomes via the
 Enough amount of glucose should be cytochrome P-450 isoenzymes
considered in order for it to supply the  We have groups of enzymes which are needed for
necessary equipment that the body requires the drug metabolizing system of the liver
 (2) Circulate the glucose for use at the peripheral  In order for the drug detoxification to occur,
tissues, or we need the group of enzymes we have
 (3) Store glucose as glycogen (glycogenesis) (cytochrome P-450 isoenzymes)
within the liver itself or within other tissues
 Glycolysis, glycogenesis, glycogenolysis, and LIVER FUNCTION ALTERATIONS DURING DISEASE
gluconeogenesis
 When there is decreased blood glucose JAUNDICE
levels/fasting states, the liver will have to  French word jaune, which means “yellow”
convert this stored glycogen into consumable  Yellow discoloration of the skin, eyes, and mucous
glucose units (glycogenesis) membranes
 When the body detects high glucose levels,  Usually not noticeable to the naked eye (overt jaundice)
this extra glucose units will be until bilirubin levels reach 3.0-5.0 mg/dL
stored/deposited in the liver in the form of o Clinical signs appears only when bilirubin levels reach
glycogen (glycogenesis) 3.0-5.0 mg/dL
 3 Classifications:

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o Prehepatic, hepatic, and posthepatic jaundice the common hepatic duct and then
 Prehepatic and posthepatic are both abnormalities common bile duct
that reside outside the liver  There is a problem in secretion
 Prehepatic – abnormality occurs before liver  Hyperbilirubinemia (conjugated
metabolism hyperbilirubinemia or increased B2) and
 Posthepatic – abnormality occurs after liver bilirubinuria (presence of bilirubin in the urine)
metabolism  Unique feature: appearance of dark-stained
 Conjugation occurs but the problem is the granules on a liver biopsy sample
bilirubin in the form of B2 cannot be excreted  Rotor syndrome
in the bile canaliculi causing jaundice and  Clinical manifestation is the same with Dubin-
causing its leaking in the bloodstream Johnson
 ICTERUS - serum or plasma sample with a yellow  The defect causing this syndrome is not
discoloration due to an elevated bilirubin level known
 Liver biopsy does not show dark pigmented
PRE-HEPATIC JAUNDICE granules
 Before it reaches liver metabolism  4. Physiologic Jaundice of the Newborn
 May be referred to as unconjugated hyperbilirubinemia o Is a result of a deficiency in the enzyme UDPGT
o Elevated bilirubin concentration in the blood, in  No conjugation
particular in the unconjugated form or B1 o Lab result: Elevated B1
 Most commonly caused by an increased amount of bilirubin  B1 is deposited in the nuclei of brain and nerve
being presented to the liver cells, causing kernicterus
o Acute and chronic hemolytic anemias o Treatment: Ultraviolet radiation (phototherapy)
 In hemolytic anemia (in particular chronic), there is  Bilirubin is photosensitive, so when there is a
an increased or continuous destruction of RBCs request for such, you should protect the sample
so that, an increase in such causes now an from light because it is destroyed when is exposed
increased amount of bilirubin in the liver to light
 Lab result: Elevated B1  Lucey-Driscoll Syndrome
o Since it is before the metabolism o Form of unconjugated hyperbilirubinemia caused by a
circulating inhibitor of bilirubin conjugation
HEPATIC JAUNDICE o Lab result: Elevated B1
 When the primary problem causing the jaundice resides in
the liver POSTHEPATIC JAUNDICE
o There is an intrinsic defect/damage to the liver  Results from biliary obstructive disease (presence of
 Caused by disorders of bilirubin metabolism (conjugation) gallstones or tumors) that prevent the flow of conjugated
and transport defects (secretory functions of the liver) bilirubin into the bile canaliculi
 1. Crigler-Najjar syndrome o There’s conjugation but the problem lies the flow of B2
o Associated with conjugation deficit in the bile canaliculi for excretion
 B1 cannot be converted to B2  Bilirubin is unable to be properly excreted from the liver
o 2 types:  Stool becomes clay-colored
 Type 1 - complete absence of enzymatic bilirubin
conjugation CIRRHOSIS
 Type 2 - mutation causing a severe deficiency of  Scar tissue replaces normal, healthy liver tissue
the enzyme (UDPGT) responsible for bilirubin  Rarely causes signs and symptoms in its early stages
conjugation  As liver function deteriorates, the signs and symptoms
o Lab result: Elevated B1 appear
 2. Gilbert’s syndrome o Fatigue, nausea, unintended weight loss, jaundice,
o Is caused by a genetic mutation in the gene (UGT1A1) bleeding from the gastrointestinal tract, intense itching,
that produces UDPGT and swelling in the legs and abdomen
 UGT1A1 – Uridyldiphosphate  Most common cause (US) - chronic alcoholism
glucuronosyltransferase family 1 member A1 o Long term consumption of alcohol (ethanol)
 Codes for the enzyme UDPGT  Other causes: chronic hepatitis B, C, and D virus infection,
o Lab result: Elevated B1 autoimmune hepatitis, inherited disorders (a1-antitrypsin
 There is unconjugated hyperbilirubinemia deficiency, Wilson disease, hemochromatosis, and
 3. Dubin-Johnson syndrome and Rotor syndrome galactosemia); nonalcoholic steatohepatitis, blocked bile
o Bilirubin excretion deficit ducts, drugs, toxins, and infections
 There is conjugation but problem lies on the o Autoimmune hepatitis: adverse immune response
excretion of B2 in the bile canaliculi causing directed against the liver itself
leakage in the systemic circulation o a1-antitrypsin deficiency: plasma protein; deficient in
o Lab result: Elevated B2 patients with hepatic cirrhosis
o Dubin-Johnson syndrome VS Rotor syndrome o Wilson Disease: characterized by the accumulation of
 Dubin-Johnson syndrome copper in the brain, liver, and in other organs
 A rare inherited disorder caused by a  When there is excessive accumulation copper in
deficiency of the canalicular multidrug the liver, it could be a predisposing factor to the
resistance/multispecific organic anionic development of cirrhosis
transporter protein (MDR2/cMOAT) o Hemochromatosis: there is iron overload
o This protein is needed in the transport of  Excess iron will also accumulate in other organs to
B2 in the bile canaliculi to the include the liver
extrahepatic ducts into the right and left o Galactosemia: inborn error of carbohydrate
ducts into the common bile duct and into metabolism

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o Nonalcoholic steatohepatitis: there is liver inflammation  Ethanol causes hepatic toxicity (most common)
and there will be presence of infiltrates in the liver o Approximately 90% of the alcohol absorbed from the
 The predisposing factor is due to the excessive stomach and small intestines is transported to the liver
consumption of fatty rich foods which can lead to for metabolism.
development of cirrhosis o Alcohol dehydrogenase and aldehyde dehydrogenase
o Blocked bile ducts, drugs, toxins, and infections:  Enzymes playing pivotal role in alcohol
predisposing factor for the development of liver metabolism
cirrhosis  Alcohol dehydrogenase is an isoenzyme of lactate
 Treatment: dehydrogenase (LD 6)
o Abstaining from alcohol o Alcohol -> acetaldehyde -> acetate -> water and
o Medications – hepatitis-related cirrhosis carbon dioxide
 Interferon – viral hepatitis  There are people who have low concentrations of
 Corticosteroids – autoimmune hepatitis alcohol dehydrogenase and aldehyde
dehydrogenase
TUMORS  Prone to hepatic toxicity
 Classification:  Long-term excessive consumption of alcohol
o Primary o There are abnormalities that can occur in the liver
 Begins in the liver cells o 3 stages: alcoholic fatty liver -> alcoholic hepatitis (liver
o Metastatic cells become affected/damaged) -> alcoholic cirrhosis
 Tumors from other parts of the body spread to the (most severe stage)
liver  Alcoholic fatty liver
 More common; 90-95% of all hepatic malignancies o Lab results: slight elevations in AST, ALT, and GGT;
 Colon, lung, and breast cancers – spread to the biopsy shows fatty infiltrates in the vacuoles of the liver
liver  Alcoholic hepatitis
 Other classification: o Lab results: moderately elevated AST, ALT, GGT, and
o Benign - hepatocellular adenoma, hemangiomas ALP; total bilirubin (> 30 mg/dL); AST/ALT ratio > 2;
 Hemangiomas: masses of blood vessels formed decreased serum albumin; prolonged PT
but etiology is unknown  Albumin is a negative acute phase reaction
o Malignant - hepatocellular carcinoma (most common)  Concentration of bilirubin will be
and bile duct carcinoma decreased/reduced
 Hepatocellular carcinoma’s most common cause  Prothrombin time (PT) is ordered to determine the
is the occurrence of hepatitis B and C viral risk of bleeding
infections  Alcoholic cirrhosis
 Whether primary or metastatic, any malignant tumor in the o Lab results: increased liver function tests (AST, ALT,
liver is a serious finding with survival times measured in GGT, ALP, total bilirubin); decreased serum albumin;
months. prolonged PT
o Liver biopsy – only definitive diagnosis
REYE SYNDROME
 Associated with elevated ammonia HEPATITIS
 A group of disorders caused by infectious, metabolic, toxic,  Implies injury to the liver characterized by the presence of
or drug-induced disease found almost exclusively in inflammation in the liver tissue
children  Viral infections account for the majority of hepatitis cases
 Is often preceded by a viral syndrome o Subtypes: HAV, HBV, HCV, HDV, and HEV
o Etiology is unknown but is believed that it is often  Symptoms - jaundice, dark urine, fatigue, nausea,
preceded by a viral syndrome just like varicella, vomiting, and abdominal pain
influenza, and upper respiratory tract infections or even o HBV and HCV - prolonged elevation of serum
a gastroenteritis which is caused by a virus transaminase (ALP, AST, etc.) level (longer than 6
 Epidemiologic association between ingestion of aspirin months – chronic hepatitis)
(acetaminophen) during a viral syndrome and the o Routes of transmission
development of Reye syndrome  HAV and HEV – fecal-oral
 An acute illness characterized by noninflammatory  HBV, HCV, HDV – parenteral; sexual
encephalopathy (there is brain involvement) and fatty
degeneration of the liver ASSESSMENT OF THE LIVER FUNCTION
o In the liver metabolism/liver biopsy sample, you can
see fatty infiltrates BILIRUBIN
 Lab results: mild hyperbilirubinemia; elevated levels of  Classic diazo reaction
ammonia and aminotransferases (AST and ALT) o Basis of commonly used methods today
o Bilirubin + diazotized sulfanilic acid -> colored product
DRUG-AND ALCOHOL-RELATED DISORDERS (urine sample)
 Drug induced liver injuries  Van Den Burgh – found that the diazo reaction may be
o Caused by drugs applied to serum samples only in the presence of an
o Most common: alcohol accelerator (solubilizer)
 Most common cause of drug toxicity: immune-mediated o B2 does not need solubilizer, while B1 needs it
injury to the hepatocytes  Evelyn and Malloy - the first clinically useful methodology
o There is an adverse immune response that is directed for the quantitation of bilirubin in serum samples
against the hepatic cells of the liver/hepatocytes o Accelerator: 50% methanol (solubilizer)
 Hepatocytes: perform major functions of the liver; o Diazo A: 0.1% Sulfanilic Acid + HCl
when attacked will have alterations in the functions o Diazo B: 0.5% Sodium Nitrite
of the liver o Diazo Blank: 1.5% HCl

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 There are manufacturers that will create their own o Unprotected from light - bilirubin values may reduce by
blanks 30%–50% per hour
 Blanks can be distilled water; also possible o Proper storage of sample - stable for 2 days at RT, 1
that they have specific blanks to be used week at 4°C, and indefinitely at - 20°C
o Final reaction: pink to purple azobilirubin (red-purple)
 pH 1.2 ; 560 nm
 Analytes could only be measured at specific
wavelengths
 Jendrassik and Grof
o Most commonly used method
o More sensitive than Evelyn and Malloy method
 Requires the addition of buffer
o Accelerator: caffeine sodium benzoate
o Buffer: Sodium Acetate
o Final reaction: pink to blue azobilirubin (blue)
 600 nm: required wavelength
 Bilirubinometry (neonatal population): POCT
o Involves the measurement of reflected light from the
skin using two wavelengths that provide a numerical
index
 Numerical index is reflection of the amount of UROBILINOGEN IN FECES AND URINE
bilirubin present in the body of the  Increased levels of urinary urobilinogen
newborn/neonate o Hemolytic disease and in defective liver cell function
o Looks like glucometer (hepatitis)
 Absence of urobilinogen from the urine and stool
o Complete biliary obstruction

DETERMINATION OF URINE UROBILINOGEN

 Principle:
o Urobilinogen reacts with p-
dimethylaminobenzaldehyde (Ehrlich’s reagent) to
form a red color, which is then measured
spectrophotometrically.
o Specimen: fresh 2-hour urine specimen
 During the collection of sample, you have to
refrigerate the sample until the sample is
completely collected
 When using the several methods described earlier, B1 and o Reference Range: 0.1 - 1.0 Ehrlich unit every 2 hours ;
B2 are identified. 0.5 – 4.0 Ehrlich units per day (0.86-8 mmol/d)
o B1 will only react with the diazotized sulfanilic acid in  1 Ehrlich unit = 1 mg of urobilinogen
the presence of an accelerator.
o B2 can react directly (without an accelerator).
FECAL UROBILINOGEN
o 3rd fraction – Delta bilirubin (B2 that is bound to
albumin)  Visual inspection of the feces
 Seen in hepatic obstruction  Semiquantitative method (same principle with urine
 B2 that is bound to albumin is large to be filtered urobilinogen)
by albumin causing elevation of delta bilirubin in o Specimen: aqueous extract of fresh feces
blood o Any urobilin present is reduced to urobilinogen by
 Total Bilirubin – 3 fractions: Unconjugated, Conjugated, and treatment with alkaline ferrous hydroxide before
Delta bilirubin Ehrlich’s reagent is added.
 Nomenclature  Reference Range: 75 – 275 Ehrlich units per 100 g of fresh
o Indirect and direct bilirubin – outdated feces; 75 to 400 Ehrlich units per 24-hour
o Unconjugated and conjugated bilirubin
 Proper naming as of today ENZYMES
 Liver enzymes: localized in the liver
SPECIAL CONSIDERATIONS o Aminotransferases (ALT and AST)
 Sample: Serum or Plasma  ALT: most liver specific enzyme
o Evelyn and Malloy method – serum is preferred o Alkaline Phosphatase (ALP)
o 5’-nucleotidase (5NT)
 Fasting sample
o ϒ-glutamyltransferase (GGT)
o Lipemia increases the bilirubin concentration, so that,
o Lactate dehydrogenase (LD)
when processing a lipemic sample, the bilirubin
concentration is falsely elevated
 Hemolysed sample should be avoided
AMINOTRANSFERASES (ALT AND AST)
o The hemolyzed sample can decrease the reaction of  Are most useful in the detection of hepatocellular damage
bilirubin with diazotide sulfanilic acid, results to falsely to the liver
decreased bilirubin concentration  Serum activity of both transaminases rises rapidly in almost
 Specimens must be protected from light all diseases of the liver and may remain elevated for up to
o Bilirubin is photosensitive 2-6 weeks
 Properly protect the sample from the collection  Highest levels of AST and ALT:

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o Acute conditions (viral hepatitis, drug- and toxin- o Ig G and Ig M - elevated in chronic active hepatitis
induced liver necrosis, and hepatic ischemia) o Ig M - primary biliary cirrhosis
 Also elevated in: o Ig A- alcoholic cirrhosis
o Acute myocardial infarction, renal infarction,
progressive muscular dystrophy PROTHROMBIN TIME (VITAMIN K RESPONSE TEST)
 Special test in hematology section
ALKALINE PHOSPHATASE (ALP)  Commonly increased in liver disease
 Found in very high concentrations in cases of extrahepatic  Not routinely used to aid in the diagnosis of liver disease
obstruction (may be due to presence of gallstones, tumors  May be useful in following the progression of disease and
or toxins) with only slight to moderate increases seen in the assessment of the risk of bleeding
those with hepatocellular disorders such as hepatitis and o Doctors include PT in the test to determine risk of
cirrhosis bleeding
 Also elevated in:  Prolonged PT - Severe Diffuse Liver Disease
o Bone-related disorders such as Paget’s disease o Hepatocytes are damaged and liver function
(osteitis deformans), bony metastases, diseases decreases
associated with an increase in osteoblastic activity, and o Infections, fatty infiltration, liver fibrosis
rapid bone growth during puberty
TESTS MEASURING NITROGEN METABOLISM
5’ - NUCLEOTIDASE
 Serum levels become significantly elevated in hepatobiliary AMMONIA
disease  The liver converts ammonia to urea.
 Levels of both 5NT and ALP are elevated in liver disease o Ammonia is toxic in the body but small amount is
o In primary bone disease - ALP level is elevated, 5NT present in the body
level is usually normal or only slightly elevated  In liver failure, ammonia and other toxins increase in the
 5NT has no bone source bloodstream and may ultimately cause hepatic coma.
o May ultimately cause unconsciousness to the patient
Y-GLUTAMYLTRANSFERASE (GGT)  Neurologic development may also occur
 Highest levels of GGT are seen in biliary obstruction  Specimen: Plasma collected in EDTA, lithium heparin, or
 Elevated GGT: potassium oxalate; placed on ice/water slurry
o Ingestion of alcohol or certain drugs (barbiturates,  Delay in testing: Plasma must be removed and placed on
tricyclic antidepressants, and anticonvulsants) ice or frozen( - 70ᵒC)
o It is a sensitive test for cholestasis (blockage of the bile
flow from the liver) caused by chronic alcohol or drug
ingestion.

LACTATE DEHYDROGENASE
 High serum levels may be found in metastatic carcinoma of
the liver.
 Moderate elevations of total serum LD levels are common
in acute viral hepatitis and in cirrhosis REFERENCES
 Slight elevations in biliary tract disease
 NOTE: Discussed enzymes (6 enzymes) are elevated in Notes from the discussion by Prof. Gail Ann Parel - Pascual,
hepatic alterations (liver disorders) RMT, MPH
o Determine the methods of determination (Carmen
Method for AST, Oliver-Rosalki, etc.)

TEST MEASURING HEPATIC SYNTHETIC ABILITY It’s been years since you thought of taking this course, we
thought to have a memorable 4 years stay, but then, things
SERUM PROTEINS happen, well, at some point we can consider it as the worst thing
that happened. We all lost the opportunity to learn what we
 Known as plasma proteins
dream to learn for more than 2 years.
 Useful in quantitating the severity of hepatic dysfunction
 ALBUMIN – low due to decreased protein synthesis But on the other hand, we can say that we have learned things
o Low/reduced in case of alcoholic cirrhosis, alcoholic we thought we cannot do, like this, and like the bond we had
hepatitis with our classmates.
 α-GLOBULIN – decreased in chronic liver disease
o Low or absent α-globulin – α1-antitrypsin deficiency Hoping this reviewer can help you more even though the skills
 Deficient in patients with hepatic cirrhosis are not that matching.
 ϒ-GLOBULIN - transiently increased in acute liver disease
and remain elevated in chronic liver disease God Bless fRMT!

LEAP OF FAITH, HARDWORK, DILIGENCE AND TRUST, GO AHEAD AND BELIEVE YOU CAN DO THINGS! 7