Term
| Nonspec clues to liver disease |
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Definition
| anorexia, fatigue, nausea, vomiting, mental confusion |
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Term
| More specific (late findings – no good early signs |
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Definition
jaundice, dark urine, abdominal swelling/ascites, peripheral edema
Unforunately none of these are specific markers of liver disease and for many pts these are late findings |
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Term
| What and where are the transaminases, alanine amino transferase (ALT), aspartate amino transferase (AST) |
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Definition
o Transaminases are enzymes that catalyze the transfer of alpha-amino groups from Aas to alpha-keto acids. These enzymes are important in gluconeogenesis and other biochemical functions of liver: lots of these in hepatocytes
• ALT: in liver only, in cytosol
• AST: in many tissues, in cytosol and mitochondria |
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Term
| T/F: Tests to determine enzyme levels look at the concentration |
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Definition
F • Measures enzyme activity
o Patient serum + substrate enzymes produces a colored product (from the substrate) absorbance of colored product converted to enzyme activity (spectrophotometry) |
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Term
| What information do transaminase levels tell us? Acute/chronic? |
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Definition
• Transaminases are useful: convenient to measure, present in liver cells in large amounts, direct release of enzymes into blood through fenestrated endothelium allows rapid “quantitative” assessment of ongoing hepatocyte necrosis, blood level roughly proportional to the number of hepatocytes that died recently (hours-days, since otherwise they are degraded by RES)
o Look at patterns of AST and ALT: acute diseases will have high AST/ALT, milder/chronic diseases will have only slightly elevated AST/ALT
Normally, ALT slightly higher than AST |
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Term
| What are some limitations to transaminase use in diagnostics? |
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Definition
o Patterns: looking at ratio between AST/ALT can give you a clue if alcohol is playing a role. AST/ALT will not be as elevated in someone equally sick (underestimate liver damage)
High AST:ALT ratio suggests alcohol! |
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Term
| Alcoholic liver dz and transaminases? |
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Definition
• Require pydidoxal 5’-phosphate (a B vitamin) as an essential cofactor of AST/ALT
o AST and ALT require P5P (Vit B6) as an enzymatic cofactor
o Alcoholics are often deficient in P5P as their major calorie source is alcohol
o P5P deficiency results in lower synthesis of AST/ALT (less in hepatocytes) and very low enzymatic activity (ALT worse than AST) less AST/ALT released into blood and it isn’t measured by lab assays (even if they’re being released)
o Mitochondrial AST and alcohol: alcohol shifts mAST from mitochondria to plasma membrane where it readily enters blood – thus AST easier to remove from hepatocytes |
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Term
| What are AST/ALT levels in alcoholic liver dz and what's a limitation? |
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Definition
AST >>ALT is released into blood from damaged hepatocytes
Enzymatic activity in blood for both AST/ALT are lower than expected from the extent of liver dysfunction
o Patterns: looking at ratio between AST/ALT can give you a clue if alcohol is playing a role. AST/ALT will not be as elevated in someone equally sick (underestimate liver damage)
High AST:ALT ratio suggests alcohol! |
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Term
| Your patient has been dx with decreased bile flow. What is the basis of the lab test that you've done to determine this and why is it that you can detect the levels? |
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Definition
• Alkaline phosphatase:
o Located at canalicular (apical) membrane of hepatocytes and bile duct cells (not inside of hepatocytes)
o Very sensitive to any changes in bile flow, obstruction of large or small bile ducts
o Amplified by bile acid retention
o Easily released into blood as it is a GPI-anchored protein solubilized from membrane by detergents (bile acids)
Bile acids build up in hepatocytes during bile flow problems
Accumulated bile acids solubilize membranes – blebbed hepatocytes (bile-acid induced injury)
o Easily measured spectrophotometrically
o Purpose: still trying to work out physiologic purpose
Know that it detoxifies LPS from bacteria
o The degree of elevation of AP is highly variable depending on duration and extent of cholestasis and other unknown factors |
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Term
| What other things can be detected from dec bile flow? |
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Definition
| 5’-nucleotidase, leucine aminopeptidase, gamma-glutamyl transpeptidase |
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Term
| What causes elevation of AP? |
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Definition
Cholestasis (especially in extrahepatic obstruction) – problems of bile flow
Infiltrative diseases (granulomas) – probably squashing small bile ducts
Neoplastic disease infiltrating liver |
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Term
| T/F: AP is a very sensitive test of dec bile flow |
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Definition
o This is a sensitive test as it will go up if only some small ducts are obstructed and/or if there is only partial obstruction of major ducts
o Disadvantages: not completely specific because of isoenzymes in other organs (bone, intestine, placenta)
E.g. bone disease, intestinal obstruction, pregnancy |
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Term
| T/F: Build up of serum bilirubin can result from extra-hepatic organ disease |
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Definition
False: Rationale: liver is virtually the only mech for excretion and cholestasis from any cuase results in “back-up” of these compounds in blood
o Interpretation: cholestasis (extrahepatic or intrahepatic) |
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Term
| Big disadv to using bilirubin as a marker of liver dz |
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Definition
| o Disadvantages: does not distinguish hepatocellular disease (in which hepatocytes don’t make bile – e.g. viral hepatitis) from true bile duct obstruction |
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Term
| What does jaundice tell you about a px? |
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Definition
| o Blood levels go up if any steps in production or hepatocyte excretion are altered. However obstruction at the level of bile ducts must be complete or virtually complete for bilirubin levels in blood to change (unlike alk phos) – jaundice is a good marker for liver disease, but if you see it is non-specific (i.e. doesn’t tell you where the problem is) |
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Term
| Conj vs. Unconj hyperbilirubinemia? |
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Definition
o Interpretation of elevated serum bili
Conjugated hyperbilirubinemia: bili reached liver and was conjugated but not excreted in bile
• Cholestasis/biliary obstruction (must be essentially complete)
• Hepatocellular damage (collateral damage to all liver functions)
o Bile formation impaired >> conjugated impaired
• Rare disorders of canalicular secretion of conjugated bili
Unconjugated hyperbilirubinemia: bili didn’t reach liver efficiently or was not conjugated
• Massive overproduction – acute hemolysis
• Impaired conjugation
o Common: Gilbert’s syndrome (mild and benign)
o Rare: Crigler-Najjar syndrome (severe) |
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Term
| Conj bilirubin goes a non-enzymatic reaction with albumin...What's the problem and what's the result? |
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Definition
o If obstruction, conjugated bilirubin spontaneously undergoes non-enzymatic reaction with albumin – forms covalent bond into a bili-albumin conjugate (delta bilirubin)
This is not of interest during liver disease since bili-albumin is measured as conjugated bili
However, after resolution of cholestasis/liver disease, bili-albumin is cleared like albumin
• Albumin has long half-life (several weeks) compared to conj. bili (hours to days) resolution of jaundice is often SLOW ocmparied to improvement of other liver functions |
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Term
| Decreased albumin causes? Limitation of albumin measurements... |
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Definition
o Rationale: liver is the sole source of albumin
o Interpretation of decreased level
Decrease liver production
Increased renal/GI loss (nephrotic syndrome; protein losing enteropathy in IBD)
Protein malnutrition
o Disadvantages: prolonged half-life (good for long-term picture, bad for monitoring function day-to-day), no unique interpretation |
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Term
Prothrombin time increases why? What's the factor with the short half-life?
What does inc in PT mean? |
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Definition
o Rationale:
Liver is sole source of Vit K-dependent clotting factors, including those critical for PT
Factor VII has very short half-life (hours)
o Interpretation of increased PT
Hepatocyte protein synthesis impaired
Vit K deficiency/Coumadin therapy
DIC
o Advantages: rapidly reflects changes in liver function |
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Term
| What does abnormal albumin or PT mean? |
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Definition
o Liver markedly diseased – reserve function of liver is gone!
o Albumin: monitor slow changes in liver function (months to years), reflects long-term liver dysfunction
o PT: monitors rapid changes in liver function (hours to days/weeks), reflects short or long-term liver dysfunction |
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Term
| • Other clues to globally impaired liver function |
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Definition
o Bilirubin: goes up with any disease that globally impairs liver function (OR blocks bile flow)
o Glucose: hypoglycemia (late finding; indicates very poor liver function)
o BUN: low BUN is a late and poorly specific finding in liver dysfunction due to poor urea synthesis |
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Term
| T/F: Blood levels of elimination products are useful in diagnosing liver function disease |
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Definition
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Term
| • Clues to cholestatic vs. hepatocellular dz |
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Definition
think about how many fold the upper limit of normal (5x, 10x upper limit etc.) – i.e. it’s relative!
o Hepatocellular:
Major: AST/ALT
Minor: bilirubin, PT/albumin
o Cholestasis
Major: Alkaline phosphatase
Minor: bilirubin, AST/ALT, PT (Vit K deficiency) |
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Term
| Abnormalities of PT vs. albumin |
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Definition
o Abnormalities of PT vs. albumin (chronic)
o Known duration of abnormal liver tests
o History of exposure to potential causative agents
o Clinical signs of consequences of long-standing liver disease
o Tempo of subsequent changes in AST/ALT, bili, PT
Chronic tends to change slowly, acute tends to change quickly |
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Term
| Liver dysfunction severity tests: |
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Definition
o PT
o Albumin
o (Bilirubin, glucose)
o (Clinical signs of consequences of severe liver dysfunction such as hepatic encephalopathy)
o Time course: clues to severity of liver damage, and potentially, to severity of liver dysfunction may come from the temporal sequence of changes in readily available liver tests
E.g. rapid fall in ASST/ALT in severe hepatitis may not be a good sign |
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Term
| T/F: Fulminant – AST/ALT goes up really fast and comes down crashing. |
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Definition
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