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Liver Function Tests

Liver Diseases
 Classification
 Cholestatic – primary interference with metabolism or secretion of bile
 Failure of bile to reach GI (decrease synthesis or secretion)
 Hepatocellular – damage to the liver (viral or drug-induced hepatitis)
 Aminotransferases
 Normal:
 Alanine Aminotransferase (ALT): (0-35 IU/L)
 Aspartate Aminotransferase: (0 to 35 units/L)
Alanine Aminotransferase (ALT): (0-35 IU/L)
 Alanine aminotransferase (ALT) is a cytoplasmic enzyme in liver
 It is present in a higher concentration in the liver than in other tissues
 More specific for liver damage.
 Formerly called “serum glutamic pyruvic transaminase, SGPT”
 ALT: interpretation

 ALT is more specific for liver disease than AST

 In acute viral hepatitis without extensive necrosis, ALT exceeds AST,
whereas AST exceeds ALT in alcoholic hepatitis owing to release of
mitochondrial AST
 Elevation lasting 6 months or more indicate chronic active or persistent
hepatitis
Aspartate Aminotransferase (0 to 35 units/L)

 Also present in high concentration in cardiac and skeletal muscle, kidney,

pancreas and red cells.
 Is abundant in heart and liver tissue and moderately present in skeletal
muscle, the kidney, and the pancreas
 In cases of acute cellular injury to the heart or liver, the enzyme is released
into the blood from the damaged cells.
Asparate Aminotransferase (AST)

 Measuring AST activity is useful for identifying inflammation and necrosis

of the liver
 Ethanol induces liver cell necrosis, result in the release of AST.
 Viral hepatitis usually causes release of only microsomal enzyme, but
fulminant viral hepatitis also may cause hepatic cell mitochondrial necrosis
similar to alcoholic hepatitis
 Increase ratio AST/ALT may be useful in alcoholic liver disease
 AST: interpretation

 An abnormal serum AST result is associated with an acute abnormality of the

heart, liver, or skeletal muscle
 In viral hepatitis, serum AST activity is typically 10-20 times the upper limit
of the reference range, ALT still greater than AST
 In contrast to viral hepatitis, serum AST exceeds ALT in extensive necrotic
injury such as occurs in alcoholic hepatitis
 Alkaline Phosphatase (AP)

 Normal: 30 to 120 units/L

 is present as a number of isoenzymes and is found in the highest
concentrations in bone, liver, kidney, intestine and placenta.
 80% in liver and bones
 This enzyme is secreted into the bile, and substantially elevated ALP serum
concentrations can be seen with mild intrahepatic or extrahepatic biliary
obstruction.
 Lactated Dehydrogenase (LDH)

 Normal: 100 to 190 units/L

 Has 5 isoenzymes (LDH 1-5)
 LDH1 – Cardiac
 Mostly used in cardiac disease (MI)
 LDH5 - liver (less sensitive than AST/ALT)
 Gamma-Glutamyl Transferase (GGT)

 Normal: 0 to 70 units/L
 The enzyme GGT is found in the kidney, liver, and pancreas
 To evaluate of hepatobiliary disease.
 Increased ALP in the presence of a normal GGT is more suggestive of
muscular or bone-related issues.
 As GGT is a hepatic microsomal enzyme, tissue concentrations increase in
response to microsomal enzyme induction by alcohol and other drugs (e.g.,
carbamazepine, phenobarbital, phenytoin).
 As a result, GGT is a sensitive indicator of recent or chronic alcohol
exposure.
 Bilirubin

 Normal
 Total Bilirubin: 0.1 to 1.0 mg/dL

 Direct (conjugated) Bilirubin: 0 to 0.2 mg/dL

Bilirubin is primarily a breakdown product of Hgb (Hgb  bilirubin + Iron
+ Globin) in the RES

 It is then transferred into the blood, where it is almost completely bound to

serum albumin.
 Hyperbilirubinemia
 Increases in serum bilirubin
 Three primary causes:
1. Hepatocellular injury:
 Interference with the ability of the liver to conjugate bilirubin, leading to a
disproportional increase of total bilirubin relative to the direct bilirubin (i.e., the
indirect bilirubin will be increased)
 Increase in AST and ALT values
2. Cholestatic or obstructive (posthepatic):
 Cholelithiasis (gallstone) or tumor
 Increase conjugated (direct) bilirubin
 Mild elevations in AST and ALT, as well as marked increase in ALP and
GGT
 Dark brown–colored urine
3. Hemolysis (prehepatic):
 Erythrocytes are rapidly hemolyzed (sickle cell disease, drug-induced
hemolysis)
 Indirect bilirubin increases
 Case

 A.R., a 42-year-old man with a 2-year history of hypertension controlled

with hydrochlorothiazide and a 1-year history of Parkinson disease
controlled by carbidopa/levodopa, is hospitalized after an episode of
orthostatic hypotension. Admitting laboratory results show a hematocrit
(Hct) of 27% (normal, 39–49). Because A.R. had a long history of
alcoholism, additional laboratory tests were obtained.
 His results were as follows: total bilirubin, 3.5 mg/dL (normal, 0.1–1.0);
direct bilirubin, 0.5 mg/dL (normal, <0.2); ALP, 40 units/L (normal, 30–
120); AST, 32 units/L (normal, <35); and ALT, 27 units/L (normal, <35).
Based on this inform’n what are three major causes of increased bilirubin
in adults, and what might be the most logical cause of increased bilirubin in
A.R.?
 Albumin (3.5 – 5 g/day)

 Albumin, the most abundant protein in blood, is synthesized almost

entirely by the liver
 Hypoalbuminemia is commonly associated with edema and transudation
of ECF
 Low means the liver’s ability to produce albumin and other proteins is
diminished
 Low serum albumin in the absence of liver disease is seen in
malnutrition, renal or intestinal albumin loss, severe infections, and
severe burns

Amylase and Lipase
 Normal
 Amylase (35–120 units/L) and
 Lipase (0–160 units/L)
 Produced in the pancreas and secreted into the duodenum to assist in
the digestive process
 Amylase is responsible for breaking down complex carbohydrates into
simple sugars and is also found in the saliva.
 Significant elevations in serum amylase are observed in patients with acute
pancreatitis or pancreatic duct obstruction.
 Amylase levels tend to rise 6 to 48 hours after onset of the disease and
usually return to normal 3 days after the acute event.
 In chronic pancreatitis or obstruction, amylase levels may remain elevated
for longer periods.
 Lipase is responsible for breaking down triglycerides into fatty acids.
 Elevated serum lipase levels are also suggestive of pancreatic disease and
tend to be more specific for pancreatic disease than amylase.
 The onset of lipase elevation is similar to amylase; however, lipase typically
remains elevated for 5 to 7 days and can be useful in diagnosing patients in
later stages of pancreatic disease.
 Narcotics (e.g., morphine) can increase serum concentrations of amylase
and lipase.
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ENDOCRINE TESTS
Glucose
 Normal: 70–110 mg/dL
Hypoglycemia
 5 Causes
 Too much insulin
 Not enough food
 Increased physical activity
 Illness
 Injury
 Early signs: Headache, Hunger, Mild agitation
 Blood sugar below 50-70 mg/dL
 Hallucinations or nervousness or outright hostility
 Cold sweat and tachycardia common but not required
 Blood sugar below 20 - 50 mg/dL
 Convulsions and loss of consciousness
 As sugar drops the convulsions stop but coma persists
 Hyperglycemic Syndromes
 Diabetic ketoacidosis (DKA)
 Hyperglycemic hyperosmolar state (HHS)
 Manifestations – dehydration, polyuria/
polydipsia, altered mental status, nausea, emesis, abdominal pain
 Drugs that Affect Blood Glucose
 Beta blockers:
 Decrease glycogenolysis & gluconeogenesis
 Increase or impair insulin secretion
 Also mask hypoglycemic symptoms
 Phenytoin: suppress insulin secretion
 Diuretics: cause hyperglycemia
 Estrogen: contraceptives cause 43-61% increase; Progestron only – no
effect
 Glucose – lab assessment
Initial diagnosis and short-term monitoring
 Fasting BG

 Two hrs Post Prandial

 Oral Glucose Tolerance Test (OGTT)

Long-term monitoring
 Glycosylated hemoglobin (A )
1C

 Fructosamine
Fasting Plasma Glucose (FPG):
 Normal: 80 – 110 mg/dl
 Prediabetes (impaired fasting glucose)
 110 < FPG < 126 mg/dl
 Diagnosis of DM:
 FPG > 126 mg/dl (at two occasions)
 FPG done after 8 hrs of fasting (before BF)
 ADA recommend Q3 years screening (>30 yrs of age if have risk
factors)
Oral Glucose Tolerance (OGTT)
 Normal:
 < 140 mg/dL
 Prediabetes
 2-hr post prandial glucose: 140 – 200 mg/dL
 DM:
 2-hr post prandial glucose ≥200 mg/dL
 Commonly used to diagnosis gestational DM (pregnancy)
 75 G glucose solution given over 5 min following overnight fasting and
blood drown at 0, 0-2 hr, and at 2 hrs.
 No alcohol 3 days before the test, coffee and tea, not permitted drug the
test.
Glycosylated Hemoglobin (HgbA1C)
 Normal: 4-6%
 DM poorly controlled: >8%
 Bound glucose to RBC irreversibly (over 120 days life span) is measured
 Hgb A1c reflects a patient's average blood glucose concentration over the
life span of circulating RBCs
 Fasting is not required
 not reliable in pregnancy
 Case: Glucose
 T.C., a 68-year-old male, visits his physician to assess control of his type
2 diabetes. T.C.'s Hgb A1c was 9%. What is average glucose
concentration for the last four months? Is T.C.’s blood glucose
controlled?
 Thyroid-Stimulating Hormone
 Normal: 2 to 10 µ units/L
 used to monitor individuals diagnosed with primary hypothyroidism.
 Secondary Hypothyroidism:
 Due to damage or trauma or tumors to the hypothalamus or pituitary gland
 Secretion of thyroid-releasing hormone (TRH) and TSH are impaired or absent
due to this damage.
 Primary Hypothyroidism:
 low levels of T3 and T4.
 Stimulate TRH and TSH release
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 Cardiac Function Tests

 Creatine Kinase (CK)

 Normal: 0 to 150 units/L

 catalyzes the transfer of high-energy phosphate groups in tissues that
consume large amounts of energy (e.g., skeletal muscle, myocardium, brain).
 The serum concentration of CK can be increased by:
 strenuous exercise,
 intramuscular injections of drugs that are irritating to tissue (e.g.,

diazepam, phenytoin)
 acute psychotic episodes
 crush injuries
 myocardial damage.
 CK is composed of M and B subunits, which are further divided into three
isoenzymes: MM, BB, and MB.
 The CK-MM isoenzyme is found predominantly in skeletal muscle, the
CK-BB in the brain, and the CK-MB in the myocardium.
 Myocardial damage appears to correlate with the amount of CK-MB
released into the serum (i.e., the higher the amount of CK-MB, the more
extensive the myocardial injury
 CK-MB typically begins to increase 3 to 6 hours after an acute myocardial
infarction (MI), peaks at 12 to 24 hours
 Remains elevated only for 2- to 3-days
 CK is released from any damaged cell in which it is stored so conditions
that affect the brain, heart, or skeletal muscle and cause cellular destruction
demonstrate elevated CK levels and correlating isoenzyme source CK-BB,
CK-MB, CK-MM
 Raise in CK-MB:
 Congestive heart failure, MI, Myocarditis, Tachycardia
 Raise I CK-MM
 Alcoholism, Hypoxic shock , Dermatomyositis, Hypothyroidism, GI infarction,
Muscular dystrophies, neoplasma ofprostate, bladder or GIT, pumonary edema,
surgery,
 Raise in CK-BB
 Reye’s syndrome, Brain infarction, Head injury
 CK decreased in:
 Small stature (Related to lower muscle mass than average
stature)
 Sedentary lifestyle (Related to decreased muscle mass)
 Case: cardiac markers
 S.G., a 44-year-old woman, appears at the ED of a local hospital, with
complaints of sudden-onset chest pain, diaphoresis, and nausea that began
about 1 hour ago. S.G describes her pain as severe and not relieved by
position change, antacids, or nitroglycerin. An electrocardiogram (ECG)
reveals changes consistent with an acute MI. The total CK serum
concentration is 118 units/L (normal, <150) and the CK-MB is 5 units/L
(normal, <12). S.G. was admitted to the coronary care unit to rule out an
acute MI. Why are the total CK and CK-MB serum concentrations within
the normal range in S.G., despite clear evidence supporting an acute MI?
 Troponin
 Troponins are proteins that mediate the calcium-mediated interaction of
actin and myosin within muscles.
 There are two cardiac-specific troponins, cardiac troponin I (cTnI) and
cardiac troponin T (cTnT).
 Whereas cTnT is present in cardiac and skeletal muscle cells, cTnI is
present only in cardiac muscle
 Compared with the detection of CK-MB, the presence of troponin I is a
more specific and sensitive indicator of myocardial damage
 the concentration of cTnI increases within 2 to 4 hours of an acute MI,
enabling clinicians to quickly initiate appropriate therapy.
 Troponin also remains elevated for about 10 days compared to the 2- to 3-
day elevation typically observed with CK-MB
 The use of troponin as a primary diagnostic test for acute MI is
becoming widely accepted as a standard
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