Hepatic/Biliary Flashcards
fWhat is physiological jaundice of the newborn?
occurs if the liver is immature and doesn’t have enough conjugating enzymes.
This results in high blood levels of unconjugated bilirubin, which can cross the blood brain barrier and deposit in the brain cells, causing encephalopathy (kernicterus).
Where is jaundice easily seen?
Sclera of the eyes
(sclera ictus)
At what level of bilirubin is jaundice recognized?
> 2.5 mg/dL
What is jaundice and how does it occur?
Jaundice is the yellow discoloration of body tissues due to high levels of bilirubin
Jaundice results from defect in normal metabolism or excretion of bilirubin
Explain how conjugated (direct) bilirubin is formed and the pathway to excretion in the bowel
In the liver, unconjugated bilirubin is conjugated with glucuronide molecule resulting in conjugated (direct) bilirubin. This is then excreted from the liver and into the intrahepatic canaliculi, which lead to the hepatic ducts, the common bile duct, and the bowel
What is the Bilirubin test used for? What are the normal and critical ranges?
Used to evaluate liver function
Part of the evaluation of adult patients with hemolytic anemias and newborns with jaundice
Normal range
Adult: Total 0.3-1.0 mg/dL
Indirect 0.2-0.8 mg/dL
Direct 0.1-0.3 mg/dL
Newborn: Total 1.0-12.0 mg/dL
Critical values: Adult > 12 mg/dL, Newborn > 15 mg/dL
Jaundice caused by hepatocellular dysfunction results in?
elevated indirect bilirubin and usually cannot be repaired surgically
Jaundice from extrahepatic dysfunction (gallstones, tumor blocking bile ducts) results in?
elevated direct bilirubin and usually can be repaired surgically
What is conjugated hyperbilirubinemia and what causes it?
Defect in metabolism that occurs after addition of glucuronide.
Caused by Obstruction of bile duct by a gallstone.
What is total bilirubin?
Total bilirubin = direct + indirect
Indirect is 70-85% of the total.
When is direct hyperbilirubinemia diagnosed?
With jaundice, when more than 50% is direct, it is considered direct hyperbilirubinemia from gallstones, tumor, inflammation, scarring, or obstruction of extrahepatic ducts.
When is Indirect hyperbilirubinemia diagnosed?
Indirect hyperbilirubinemia is diagnosed when less than 15-20% of the total is direct and is caused by accelerated RBC hemolysis, hepatitis, or drugs.
What does bilirubin in the urine suggest?
Direct bilirubin is water soluble and can be excreted in the urine
Bilirubin in the urine suggests disease affecting metabolism after conjugation or defects in excretion (gallstones)
Interfering factors of bilirubin?
Blood hemolysis and lipemia can produce inaccurate results
Drugs can cause increased blood level of total bilirubin – antibiotics, ascorbic acid, codeine, epinephrine, methotrexate, morphine, oral contraceptives, salicylates, steroids, sulfonamides, and vitamin A.
Drugs causing increased urine bilirubin levels include antibiotics, barbiturates, diuretics, oral contraceptives, steroids, sulfonamides, phenazopyridine
Drugs causing decreased blood levels of total bilirubin include barbiturates, caffeine, penicillin, and high dose salicylates
Drugs causing false negative results in the urine include vitamin C and indomethacin
Drugs causing false positive results in the urine include pyridium-like drugs that color the urine yellow or orange.
What can cause increased blood levels of indirect bilirubin?
Erythroblastosis fetalis, transfusion reaction, sickle cell anemia, hemolytic anemia, hemolytic jaundice, pernicious anemia, large volume blood transfusion, resolution of large hematoma – RBC destruction occurs, so large amounts of heme are available for catabolism into bilirubin, which exceeds the liver’s capability to conjugate bilirubin, so indirect bilirubin levels rise
Hepatitis, cirrhosis, sepsis, neonatal hyperbilirubinemia – diseased, injured, or immature liver cannot conjugate the bilirubin presented to it
Crigler-Najjar syndrome, Gilbert syndrome – congenital enzyme deficiencies interrupt conjugation of bilirubin
What causes increased blood levels of direct bilirubin?
Gallstones, extrahepatic duct obstruction (tumor, inflammation, gallstone, scarring, surgical trauma) – blockage of bile ducts
Extensive liver metastasis – intrahepatic ducts or hepatic ducts become obstructed
Cholestasis from drugs – some drugs inhibit excretion of bile from hepatocyte into the bile canaliculi
Dubin-Johnson syndrome, Rotor syndrome – congenital defects in enzyme quantity inhibit metabolism and excretion of bilirubin
What causes increased urine levels of bilirubin?
Gallstones, extrahepatic duct obstruction (tumor, inflammation, gallstone, scarring, surgical trauma), extensive liver metastasis, cholestasis from drugs, Dubin-Johnson syndrome, Rotor syndrome – defects in bilirubin metabolism and excretion inhibit intestinal excretion of bilirubin.
Above are associated with direct hyperbilirubinemia, which is water soluble and is excreted.
What is Aspartate Aminotransferase (AST) used to evaluate and what are the normal ranges?
Used in evaluation of patients with suspected hepatocellular disease
Normal: 0-35 units/L
Where are high levels of AST found in the body?
Found in high concentration within highly metabolic tissue, such as heart muscle, liver cells, skeletal muscle cells, and lesser in the kidneys, pancreas, and RBCs.
When cells of a tissure containing high levels of AST are injured, what happens?
When cells of these tissues are injured, the cells lyse and AST is released and picked up in the blood, and the level rises
Amount of elevation is directly related to the number of cells affected by the disease or injury
AST is cleared from the blood in a few days
What is the time period for the rise and fall of AST after an injury?
Levels become elevated 8 hours after cell injury, peak at 24-36 hours, and return to normal in 3-7 days.
If injury is chronic, levels will remain elevated.
What common type of disease will cause elevations in AST
Diseases affecting hepatocytes will cause elevations
In acute hepatitis, levels can rise 20 times the normal value
In acute extrahepatic obstruction, levels quickly rise to 10 times the norm and swiftly fall
In cirrhosis, the level depends on the amount of active inflammation
When is the AST/ALT ratio usually > 1?
usually greater than 1 with alcoholic cirrhosis, liver congestion, and metastatic tumors of the liver.
The ratio is less accurate if AST > 10 times normal
When is the AST/ALT ratio < 1?
A ratio < 1 is seen with acute hepatitis, viral hepatitis, or infectious mononucleosis
AST interfering factors?
Pregnancy may decrease AST
Exercise may increase levels
Levels may be falsely decreased with pyridoxine deficiency (beriberi, pregnancy), severe chronic liver disease, uremia, or diabetic ketoacidosis
Drugs may increase levels – antihypertensives, coumadin, digitalis, erythromycin, hepatotoxic meds, isoniazid, oral contraceptives, opiates, salicylates, statins
What causes increased levels of AST?
Liver diseases (hepatitis, hepatic cirrhosis, drug induced liver injury, hepatic metastasis, hepatic necrosis (early stages only), hepatic surgery, infectious mononucleosis with hepatitis, hepatic infiltrative process (tumor) – liver cell injury causes cell death and lysis, releasing AST
Skeletal muscle diseases (trauma, recent noncardiac surgery, multiple traumas, severe deep burns, progressive muscular dystrophy, recent convulsions, heat stroke, primary muscle diseases (myopathy, myositis)) – cause muscle cell injury with cell death and lysis and release of AST
Other diseases (acute hemolytic anemia, acute pancreatitis) – cell injury leading to cell death and lysis and release of AST
What causes decreased levels of AST?
Acute renal disease
Beriberi
DKA
Pregnancy
Chronic renal dialysis
What is Alanine Aminotransferase (ALT) used for and what are the normal ranges?
Used in evaluation of patients with suspected hepatocellular disease as well as monitoring of improvement or worsening of these diseases
Normal: 4-36 international units/L
What will an abnormal ALT point to in jaundiced patients?
In jaundiced patients an abnormal ALT will point to the liver rather than RBC hemolysis as the source
Where is ALT found in the body?
Enzyme mainly found in the liver with lesser quantities in the heart muscle, skeletal muscle cells, and kidneys
Most ALT elevations are caused by?
Most ALT elevations are caused by liver dysfunction, so ALT is not only sensitive but also specific for liver disease.
Injury or disease in the liver will cause a release of ALT into the bloodstream.
In viral hepatitis the AST/ALT ratio is?
in viral hepatitis AST/ALT < 1
In hepatocellular disease (other than viral) AST/ALT is?
ALT/AST ratio is > 1
ALT interfering factors
Previous IM injections may cause elevated levels
Numerous drugs can cause increased ALT levels including acetaminophen, salicylates, codeine, contraceptives….
Causes of significant increases in ALT
Significantly increased levels – hepatitis, hepatic necrosis, hepatic ischemia
