Liver enzymes Flashcards
Bilirubin is a breakdown product of heme (ferroprotoporphyrin IX).
The initial steps of bilirubin metabolism occur in reticuloendothelial cells, predominantly in the spleen.
normal values of total serum bilirubin
are between 1.0 and 1.5 mg/dL, with 95% of a normal population falling between 0.2 and 0.9 mg/dL.
Normal values for the indirect component are
between 0.8 and 1.2 mg/dL.
The most frequently reported upper limit
of normal for conjugated bilirubin is 0.3 mg/dL.
The presence of conjunctival icterus
suggests a total serum bilirubin level of at least 3.0 mg/dL but does not allow differentiation between conjugated and unconjugated hyperbilirubinemia.
Tea- or cola-colored urine may indicate the presence of bilirubinuria and thus conjugated hyperbilirubinemia.
the most sensitive markers of acute hepatocellular injury,
The serum aminotransferases (also called transaminases),
ALT (formerly serum glutamic pyruvic transaminase, or SGPT)
AST (formerly serum glutamic oxaloacetic transaminase, or SGOT) catalyze the transfer of the α-amino groups of alanine and l-aspartic acid, respectively, to the α-keto group of ketoglutaric acid.
a cytosolic enzyme also found in many organs, is present in greatest concentration by far in the liver and is, therefore, a more specific indicator
ALT
The differential diagnosis of marked elevations of aminotransferase levels (>1000 U/L)
includes viral hepatitis (A to E), toxin- induced liver injury, DILI, ischemic hepatitis, and less commonly, autoimmune hepatitis, acute Budd-Chiari syndrome, ALF caused by Wilson disease, and acute obstruction of the biliary tract.
If the AST level is less than 300 U/L, a ratio of AST to ALT of more than 2 suggests
alcohol- associated liver disease, and a ratio of more than 3 is highly suggestive of alcohol-associated liver disease
ratio results from a deficiency of pyridoxal 5′-phosphate in patients with alcohol- associated liver disease;
ALT synthesis in the liver requires pyridoxal phosphate
When a patient with chronic alcohol-associated liver disease sustains a superimposed liver injury, particularly acetaminophen hepatotoxicity,
the aminotransferase levels can be strikingly elevated, yet the AST/ ALT ratio is maintained.
CHRONIC, MILD ELEVATIONS, ALT > AST (<150 U/L OR 5 × NORMAL)
Hepatic α1-Antitrypsin deficiency Autoimmune hepatitis Chronic viral hepatitis (B, C, and D) Hemochromatosis Medications and toxins Steatosis and steatohepatitis Wilson disease
Nonhepatic
Celiac disease
Hyperthyroidism
SEVERE, ACUTE ELEVATIONS, ALT > AST (>1000 U/L OR > 20-25 × NORMAL)
Hepatic
Acute bile duct obstruction
Acute Budd-Chiari syndrome Acute viral hepatitis Autoimmune hepatitis
Drugs and toxins
Hepatic artery ligation Ischemic hepatitis Wilson disease
SEVERE, ACUTE ELEVATIONS, AST > ALT (>1000 U/L OR >20-25 × NORMAL)
Hepatic
Medications or toxins in a patient with underlying alcohol-associated liver injury
Nonhepatic
Acute rhabdomyolysis
Chronic, mild elevations, AST > ALT (<150 U/L, <5 × normal)
Hepatic
Alcohol-associated liver injury (AST/ALT >2:1, AST nearly always <300 U/L)
Cirrhosis
Nonhepatic
Hypothyroidism
Macro-AST Myopathy Strenuous exercise
The first step in the evaluation of mildly elevated serum aminotransferase levels
is to repeat the test to confirm persistence of the elevated value.
The clinical onset of Wilson disease
is usually between 3 and 55 years of age; the diagnosis should be considered initially in all patients age 40 or younger and those older than age 40 with aminotransferase elevations that remain unexplained after other causes are excluded
has a serum half-life of approximately 7 days, and although the sites of degradation are unknown,
ALP
clearance of ALP from serum is independent of either patency of the biliary tract or functional capacity of the liver
In a person with isolated elevation of the serum ALP level,
the serum GGTP or 5′NT is used to distinguish a liver from a bone origin of the ALP elevation
elevated serum GGTP level
has high sensitivity for hepatobiliary disease, its lack of specificity limits its clinical utility
GGTP is elevated in patients
taking antiepileptics, including phenytoin, carbamazepine, valproic acid, and barbiturates, as well as some drugs used in antiretroviral therapy, such as non-nucleoside reverse transcriptase inhibitors and the protease inhibitor abacavir.
PBC is a classic autoimmune disease.
immunologic injury is characterized by T cell–mediated destruction of the intrahepatic bile ducts.
Although predominantly a disease of middle- aged women, with a median age at diagnosis of approximately 50 years, 5% to 10% of affected patients are men.
Albumin
The average adult pro- duces approximately 15 g/day and has 300 to 500 g of albumin distributed in body fluids.
The liver has the ability to double the rate of synthesis in the setting of rapid albumin loss or a dilutional decrease in the serum albumin concentration
half-life of albumin is 14 to 21 days; there are multiple sites of degradation, including skin, muscle, liver, and kidney, as well as leakage in the gut.
Bland cholestasis
Anabolic steroids
Estrogens
Cholestatic hepatitis
Angiotensin-converting enzyme inhibitors: captopril, enalapril Antimicrobials: amoxicillin-clavulanic acid, ketoconazole Azathioprine
Chlorpromazine
NSAIDs: sulindac, piroxicam
Granulomatous hepatitis
Allopurinol
Antibiotics: sulfonamides
Antiepileptics: carbamazepine, phenytoin
Cardiovascular agents: hydralazine, procainamide, quinidine Phenylbutazone
Vanishing bile duct syndrome
Amoxicillin-clavulanic acid Chlorpromazine Dicloxacillin Flucloxacillin Macrolides
Extrahepatic Causes of Cholestatic Liver Enzymes in Adults
INTRINSIC
AIDS cholangiopathy Ampullary cancer Ascariasis
Autoimmune pancreatitis Cholangiocarcinoma Choledocholithiasis CMV
Cryptosporidiosis Immune-mediated duct injury Infections
Malignancy
Microsporidiosis Parasitic infections PSC
EXTRINSIC
Gallbladder cancer Malignancy Metastases, including portal adenopathy from metastases Mirizzi syndrome Pancreatic cancer Pancreatic pseudocyst Pancreatitis
Serum albumin levels less than 3 g/dL in a patient with newly diagnosed hepatitis
should raise suspicion of a chronic process.
Serum albumin is an excellent marker of hepatic synthetic function in patients with chronic liver disease and cirrhosis
___ is the end result of a complex series of enzymatic reactions involving clotting factors, all of which are produced in the liver except factor VIII, which is produced by vascular endothelial cells
Clotting
Factors involved in the synthesis of prothrombin
include II, V, VII, and X.
used to express the degree of anticoagulation on warfarin therapy.
The INR
A prolonged prothrombin time can be caused by a number of conditions besides reduced hepatic synthetic function:
congenital deficiency of clotting factors, vitamin K deficiency (vitamin K is required for normal functioning of factors II, VII, IX, and X), and DIC.
can be identified by measuring a factor VIII level in serum;
DIC
the level is decreased in DIC and normal or increased in liver disease.
allows an assessment of current hepatic synthetic function;
factor VII has the shortest serum half-life (6 hours) of all the clotting factors.
The prothrombin time
Used to allocate donor organs for LT
The INR, along with total serum bilirubin and creatinine levels, are components of the MELD score
is not an accurate measure of bleeding risk in patients with cirrhosis, because it assesses only the activity of procoagulant clotting factors, not anticoagulant factors such as protein C and antithrombin, the production of which is also reduced in cirrhosis.
The prothrombin time
a glucosaminoglycan produced in mesenchymal cells and widely distributed in the extracellular space.
Hyaluronic acid
A fasting hyaluronic acid level greater than 100 mg/L had a sensitivity of 83% and specificity of 78% for the detection of cirrhosis in patients with a variety of chronic liver diseases
Indocyanine Green Clearance
Indocyanine green (ICG) is a nontoxic dye that is cleared exclusively by the liver; 97% of an administered dose (0.5 mg/kg given as an IV bolus) is excreted unchanged into bile.
can be measured directly by spectrophotometry.
Possible uses of ICG
include the assessment
of hepatic dysfunction, measurement of hepatic blood flow, and
prediction of clinical outcomes in patients with liver disease.
has been studied as a
measure of functional hepatic mass.
Galactose Elimination Capacity
given as a single IV bolus (0.5 g/kg)
Caffeine clearance tests
quantify functional hepatic capacity by assessing the activity of cytochrome P450 1A2, N-acetyltransferase,and xanthine oxidase
given orally (200 to 366 mg), and levels are measured in blood, urine, saliva, breath, or scalp hair.
Lidocaine Metabolite Formation
Lidocaine is metabolized to its major metabolite monoethyl-glycinexylidide (MEGX) by the hepatic cytochrome P450 sys-
tem.
BILE ACIDS
synthesized from cholesterol in hepatocytes, conjugated to glycine or taurine, and secreted into bile
are sensitive but nonspecific indicators of hepatic
dysfunction and allow some quantification of functional hepatic
reserve.
Serum bile acids
Acetaminophen Toxicity
The dose of acetaminophen exceeds 15 g, almost 4 times the recommended daily dose, in 80% of cases.
Acetaminophen doses within the therapeutic range (≤4 g/day) can be sufficient to cause liver injury in susceptible persons, such as those who use ethanol chronically.
The King’s College criteria
identify patients with a poor prognosis from acetaminophen-induced liver injury:
those with an arterial pH below 7.3 or those with an INR above 6.5
serum creatinine level above 3.4 g/dL
stage 3 to 4 hepatic encephalopathy
The score has subsequently been validated as an accurate predictor of survival in patients with advanced liver disease.
The MELD score incorporates 3 objective variables into a mathematical formula: 9.57 × loge(creatinine) + 3.78 × loge(total bilirubin) + 11.2 × loge(INR) + 6.43.
The working range is 6 to 40, and the score has been shown to correlate with mortality in patients undergoing surgery other than LT, including hepatic resection, other abdominal procedures, and cardiac surgery
