Term
| What are the protein spikes on serum electrophoresis? |
|
Definition
| lbumin then the globulins (alpha 1, alpha 2, beta, gamma) |
|
|
Term
| Which of the spikes on serum electrophoresis are due to proteins made by the liver? |
|
Definition
| albumin and most alpha and beta globulins are made by the liver |
|
|
Term
| Gamma globulins are synthesized by ____. |
|
Definition
|
|
Term
| How are serum proteins measured? |
|
Definition
| total serum proteins and albumin are measured directly and globulins are calculated as TP- albumin |
|
|
Term
| What is an appropriate albumin: globulin ratio? |
|
Definition
|
|
Term
| Which is more specific for liver injury/failure: total serum protein or serum albumin levels? |
|
Definition
| albumin because it is entirely produced by the liver |
|
|
Term
| What is the sensitivity and specificity of using albumin to test for liver failure? |
|
Definition
| low sensitivity (because of the high functional reserve of the liver) and low specificity |
|
|
Term
| What is the functional reserve of the liver? |
|
Definition
|
|
Term
| What else causes hypoalbuminemia besides liver disease? |
|
Definition
| malnutrition, debilitating illness, renal losses (nephrotic syndrome), skin losses (extensive burns, exfoliative dermatitides), intestinal loses (protein-losing enteropathies) |
|
|
Term
| Which coagulation factor is NOT synthesized in the liver? |
|
Definition
|
|
Term
| Which anticoagulants are synthesized in the liver? |
|
Definition
| antithrombin III, plasminogen, protein C, others |
|
|
Term
| How are fibrin degredation products gotten rid of? |
|
Definition
| they are catabolized in the liver |
|
|
Term
| Why would liver failure cause a DIC-like clinical picture? |
|
Definition
| low coagulation factors with low inhibitors of coagulation and high fibrin degredation products |
|
|
Term
| What vitamin should you give patients with cholestasis? |
|
Definition
| vitamin K because cholestasis prevents bile acids assisting in absorption of fat soluble vitamins like vitamin K |
|
|
Term
| What coagulation factors are tested for by the PTT? |
|
Definition
| factors XII, XI, IX, VIII, X, V, II, I |
|
|
Term
| What coagulation factors are tested for by the PT? |
|
Definition
| factor VII, X, V, II, and I |
|
|
Term
| Which coagulation factor has the shortest half life? |
|
Definition
|
|
Term
| Which test is used to monitor coagulopathy associated with acute liver failure or cholestasis? |
|
Definition
| prothrombin time because it is prolonged earlier than the partial thromboplastin time |
|
|
Term
| What is the half life of factor VII? |
|
Definition
|
|
Term
| What is the half life of albuin? |
|
Definition
|
|
Term
| In liver failure, which is affected FIRST, PT or albumin levels? |
|
Definition
| PT because of factor VII's short half life |
|
|
Term
| Where does the ammonia in our body come from? |
|
Definition
| most derives from deamination of amino acids; ammonia is also produced by intestinal bacteria which is then absorbed through the intestinal wall |
|
|
Term
| What happens to ammonia in our bodies? |
|
Definition
| urea cycle allows rapid conversion of ammonia into urea |
|
|
Term
| Because the urea cycle takes place primarily in the liver, patients in liver failure often have... |
|
Definition
|
|
Term
| What are the complications of hyperammonemia? |
|
Definition
|
|
Term
| What are the steps of the urea cycle? |
|
Definition
| ammonia combines with bicarbonate to produce carbamoyl phosphate --+ornithine--> citrulline---add aspartate---> arginosuccinate (+ fumarate)--> arginine --> urea (+ ornithine) |
|
|
Term
| What are the causes of hyperammonemia? |
|
Definition
| liver failure, excesive production (Gi bleeding, chemotherapy, cell death/turnover), bypass of liver circulation (portal hypertension, portosystemic shunts) |
|
|
Term
| How is an ammonia specimen collected? |
|
Definition
| specimens must be placed on ice and transported to the lab immediately; arterial blood is prefered because ammonia is higher in venous blood than in arterial blood |
|
|
Term
| What are the cytoplasmic liver enzymes? |
|
Definition
| aspartate aminotransferase and alanine aminotransferase; increase mostly with hepatocellular injury |
|
|
Term
| The cell membrane liver enzymes are AKA... |
|
Definition
|
|
Term
| What are the cell membrane liver enzymes? |
|
Definition
| alkaline phosphatase and gamma glutamyl transferase; mostly increase with hepatobiliary obstruction and injury |
|
|
Term
| Which liver enzyme is most SENSITIVE for hepatocellular injury? |
|
Definition
| AST; because AST concentration in hepatocytes is higher than ALT |
|
|
Term
| AST is preferred over ALT for monitoring... |
|
Definition
| early detection of liver injury as when monitoring for drug hepatotoxicity |
|
|
Term
| Which liver enzyme is most SPECIFIC for hepatocellular injury? |
|
Definition
|
|
Term
| What are the cytoplasmic enzymes like in chronic liver injury? |
|
Definition
| generally ALT is higher than AST because ALT has a longer half life; EXCEPT FOR ALCOHOLIC LIVER DISEASE |
|
|
Term
| Why is ALT not higher than AST in alcoholic liver disease? |
|
Definition
| AST is intra and extra mitochondrial while ALT is only extramitochondrial. Alcohol causes mitochondrial injury and MITOCHONDRIAL AST has a LONGER half life than ALT; as a result alcohol induces a disproportionate elevation of AST |
|
|
Term
| What liver enzyme findings are highly suggestive of alcoholic liver disease? |
|
Definition
| AST: ALT ratio of greater than or equal to 3:1 |
|
|
Term
| What types of biliary diseases can cause increase in ALP or GGT? |
|
Definition
| cholangitis, choledocolithiasis, carcinoma of the head of the pancreas, primary biliary cirrhosis, primary sclerosing cholangitis, space-occupying lesions in the liver (primary or metastatic) |
|
|
Term
| Where in the hepatocyte are ALP and GGT found? |
|
Definition
| in the cell membrane and also in microsomes (ER) |
|
|
Term
| Besides things that cause liver injury, what else can cause a rise in both GGT and ALP? |
|
Definition
| alcohol and drugs (phenytoin and carbamazepine) that induce microsomal enzyme synthesis |
|
|
Term
| What is ALP especially good at differentiating? |
|
Definition
| biliary tract injury from hepatocellular injury because it seldom increases significantly with hepatocellular injury |
|
|
Term
| Besides the liver, ALP is also found in what tissues? |
|
Definition
| bone, kidney, intestine, placenta |
|
|
Term
| Although ALP is found in many other tissues besides the liver, you can tell if ALP is from the liver because... |
|
Definition
| there are different isoenzymes from each type of tissue |
|
|
Term
| Most serum ALP is made up of which tissue isoenzymes? |
|
Definition
|
|
Term
| What causes increased bone ALP? |
|
Definition
| any condition associated with bone growth or turnover (adolescence, fractures, paget's disease, hyperparathyroidism) |
|
|
Term
| T/F Placental ALP is present during a normal pregnancy. |
|
Definition
|
|
Term
| T/F Gamma glutamyl transferase can increase significantly with hepatocellular injury. |
|
Definition
| true; unlike ALP it is less specific at distinguishing between hepatocellular from biliary tract disease |
|
|
Term
| What is the advantage to using GGT over ALP? |
|
Definition
| GGT is not present in significant concentration in tissues other than the liver |
|
|
Term
| What liver enzyme has a rough correlation to the amount of alcohol intake in alcoholic liver disease? |
|
Definition
| GGT is particularly elevated in chronic alcohol abuse because it is a microsomal enzyme) and may be used to monitor alcoholism |
|
|
Term
| Where does bilirubin come from? |
|
Definition
| 85% comes from hemoglobin of RBCs, other sources are myoglobin and cytochromes |
|
|
Term
| How is unconjugated bilirubin transported in the blood? |
|
Definition
| transported bound to albumin because it is insoluble in water |
|
|
Term
| What does the hepatocyte do to bilirubin to make it water soluble? |
|
Definition
| conjugates it with glucuronic acid |
|
|
Term
| How is bilirubin measured? |
|
Definition
| by a color reaction with diazotized sulfanilic acid (the diazo reaction) |
|
|
Term
| Where do the names "direct" and "indirect" bilirubin come from? |
|
Definition
| conjugated bilirubin is also known as direct bilirubin because it is not bound to albumin and reacts promptly with diazotized sulfanilic acid. Unconjugated=indirect because it is bound to albumin, reacts slowly and requires an accelerant that seperates it from albumin. |
|
|
Term
| How is indirect bilirubin measured? |
|
Definition
| bilirubin from reaction with accelerant (-) bilirubin from reaction without accelerant |
|
|
Term
| What would cause a prolonged jaundice after resolution of an acute liver injury? |
|
Definition
| delta-bilirubin or biliprotein, which is when bilirubin becomes covalently attached to albumin an has a half life of 20 days |
|
|
Term
| What are the prehpatic causes of indirect hyperbilirubinemia? |
|
Definition
| excessive production (intenral bleeding, hemolytic anemia), drugs athat displace bilirubin from albumin) |
|
|
Term
| What are the hepatic causes of indirect hyperbilirubinemia? |
|
Definition
| reduced hepatocyte uptake (hepatocellular injury or drugs), impaired conjugation (hepatocellular injury, hereditary hyperbilirubinemias, physiologic jaundice of the newborn) |
|
|
Term
| What are the hepatic causes of direct hyperbilirubinemia? |
|
Definition
| impaired excretion into canaliculi (hepatocellular injury, drugs, hereditary hyperbilirubinemias), intrahepatic biliary injury/obstruction (primary biliary cirrhosis, primary sclerosing cholangitis, space occupying lesions) |
|
|
Term
| Which hereditary hyperbilirubinemias cause an increase in direct hyperbilirubinemia? |
|
Definition
|
|
Term
| Which hereditary hyperbilirubinemias cause in increase in indirect hyperbilirubinemia? |
|
Definition
|
|
Term
| What lab values would you expect for excessive bilirubin production (pre-hepatic)? |
|
Definition
| predominant elevation of indirect bilirubin, AST may increase (not specific for liver disease), not so much ALT or ALP |
|
|
Term
| What lab values would you expect in hepatocellular injury (e.g. hepatitis)? |
|
Definition
| variable elevation of direct and indirect bilirubin; both ALT and AST increased (not so much ALP) |
|
|
Term
| What lab values would you expect in biliary tract injury (e.g. choledocolithiasis)? |
|
Definition
| predominant elevation of direct bilirubin; ALP is increased, not so much AST or ALT |
|
|
Term
| When is alpha-fetoprotein normally produced? |
|
Definition
| produced by the hepatocytes and yolk sac of the fetus; highest concentration by 12 to 14 weeks of gestation, adult level by age 1; maternal serum levels mirror the fetal AFP levels |
|
|
Term
| When are AFP levels abnormally high? |
|
Definition
| pregnancy with open fetal neural tube defects (anencephaly, spina bifida), germ cell tumors, hepatocellular injury (minor increase), hepatocellular carcinoma |
|
|
Term
| What percent of patients with HCC have markedly elevated levels of AFP? |
|
Definition
|
|
Term
| What level of AFP suggests a strong liklihood of HCC? |
|
Definition
|
|
Term
| T/F AFP is useful for screening for HCC. |
|
Definition
| false; tumors are often widespread by the time the AFP is elevated; used instead to monitor response to therapy |
|
|
Term
| Why are maternal serum AFP screened? |
|
Definition
| increase in AFP indicates open neural tube defect; decreae in AFP indicates down syndrome |
|
|
Term
| What is the function of alpha-1-antitrypsin? |
|
Definition
| the most important protease inhibitor in the blood; also an acute phase reactant (levels increase with inflamation of any cause) |
|
|
Term
| What is the gene that codesfor A1AT? |
|
Definition
|
|
Term
| How many alleles of A1AT are there? |
|
Definition
| >75, the most commmon allele variant in the US is "M" |
|
|
Term
| What do you see on liver biopsy of a patient with A1AT deficiency? |
|
Definition
| eosinophilic globs signifiying improperly folded A1AT that is stuck in hepatocytes |
|
|
Term
| What are the findings on serum protein electrophoresis in patients with A1AT def? |
|
Definition
|
|
Term
| What are the most common deficiency alleles that can cause A1AT deficiency? |
|
Definition
|
|
Term
| Compared with the MM phenotype, ZZ is ___ of normal levels of A1AT. |
|
Definition
|
|
Term
| Compared with the MM phenotype, MZ is ___ of normal levels of A1AT. |
|
Definition
|
|
Term
| Compared with the MM phenotype, SS is ___ of normal levels of A1AT. |
|
Definition
|
|
Term
| Compared with the MM phenotype, MS is ___ of normal levels of A1AT. |
|
Definition
|
|
Term
| Which alleles for A1AT deficiency are associated with liver pathology? |
|
Definition
| Z allele (particularly the ZZ genotype) |
|
|
Term
| What lab tests are used to diagnose A1AT? |
|
Definition
| serum A1AT is used to screen for AAT deficiency; AAT typing is needed to confirm the diagnosis of the deficiency |
|
|
Term
| How do you diagnose the specific type of deficiency of A1AT? |
|
Definition
| DNA is isolated and amplified by PCR; amplicons are fragmented with a restriction enzyme; fragments are seperated by electrophoresis; M, Z, and S have specific banding patterns (RRLPs) |
|
|
Term
| How do you determine phenotype for A1AT variants. |
|
Definition
| electrophoresis of A1AT protein in a gel with a pH gradient; A1AT protein will migrate to different isoelectric points |
|
|
Term
| How do you diagnose primary biliary cirrhosis with lab values? |
|
Definition
| get a serum anti-mitochondrial antibody (AMA); AMA type M2 are more specific for PBC than other types; other AMA types can occur in other collagen vascular disease |
|
|
Term
| What is the most common variant of autoimmune hepatitis in the US? |
|
Definition
|
|
Term
| What antibodies are associated with type 1 autoimmune hepatitis? |
|
Definition
| anti smooth muscle antibodies (ASMA), anti actin antibodies, anti nuclear antibodies (ANA) |
|
|
Term
| Which antibodies are present in type 2 autoimmune hepatitis? |
|
Definition
| anti-liver kidney microsomal antibodies (anti-LKM) |
|
|
Term
| Which antibody is present in type 3 autoimmune hepatitis? |
|
Definition
| anti-soluble liver antigen antibodies (anti-SLA) |
|
|
Term
| What does an antibody test for hepatitis a or e mean? |
|
Definition
| IgM antibodies indicate acute disease (within a few months), IgG or toal antibodies indicate past infection and immunity |
|
|
Term
| Besides testing for antibodies to hepatitis E and A, you can also test for _____ although this is not done routinely. |
|
Definition
| HAV and HEV RNA can be detected in feces and blood |
|
|
Term
| What is the first laboratory marker to become positive in acute hep B infection? |
|
Definition
| HBsAg; present before symptoms |
|
|
Term
| What is the significance of a positive HBsAg test? |
|
Definition
| patient has an acute or chronic hepatitis B infection; patients who recover will become negative |
|
|
Term
| What is the significance of a positive IgM anti-HBcAg? |
|
Definition
| generally detectable at the onset of symptoms, no longer detectable within 6-8 months |
|
|
Term
| Why are HBsAg and IgM anti-HBcAg used in comination with each other? |
|
Definition
| HBsAg is more sensitive as it appears earlier while IgM anti0HBcAg is more specific as it is only present in acute hepatitis (not present in chronic hepatitis) |
|
|
Term
| What are the lab values of someone who has recovered from hepatitis B? |
|
Definition
| disppearance of HBsAg, appearance of anti-HBsAg (total) antibodies, persistence of total (IgG) anti-HBcAg antibodies |
|
|
Term
| What is the "window period" of hepatitis B infection? |
|
Definition
| period between the disapperance of HbsAg and the apperance of anti-HBsAg antibodies where the only evidence of recent infection is the present of (total) HBcAg antibodies |
|
|
Term
| How do you diagnose chronic hepatitis B? |
|
Definition
| take two samples, 6 months apart, and see if they are positive for HBsAg both times OR take a single sample and see if they are positive for HBsAg AND negative for IgM anti-HBcAg antibodies |
|
|
Term
| What are the markers of active hepatitis B infection? |
|
Definition
| hepatitis B e antigen (HBeAg), hepatitis B DNA (HBV DNA) |
|
|
Term
| What are the lab results in a patient who is chronically infected wiht hepatitis B but has an inactive disease? |
|
Definition
| HBeAg is characteristically negative, hybridization test for HBV DNA, often negative (requires more than a million viral copies/mL), PCR test for HBV DNA, often positive (detects down to 250 viral copies/mL) |
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