Liver Function Tests Flashcards
1
Q
What are the roles of the liver?
A
- synthesis of protein, vitamins, and fats
- storage of glycogen, triglycerides, iron, copper, and lipid soluble vitamins (A, D, E, and K).
- glucose regulation (gluconeogenesis)
- detoxification
- excretory function (bile production/drainage).
2
Q
What are the common Liver Function Tests (LFTs) or sometimes called Hepatic Function Panel or Complete Metabolic Panel (CMP)?
A
Markers that indicate hepatic function:
- aspartate aminotransferase (AST)
- alanine aminotransferase (ALT)
- albumin
- alkaline phosphatase
- total protein
- total bilirubin
- direct bilirubin
3
Q
What are other labs that can be ordered for LFTs?
A
usually ordered in response to abnormal findings in your Hepatic Function Panel:
- lactate dehydrogenase (LDH)
- gamma glutamyl transpeptidase (GGT)
- 5’ nucleotidase
- coagulation factors (PT/PTT/INR)
- acute hepatitis panel
4
Q
What tests would you look at for hepatocellular injury (damage to the hepatocytes themselves)?
A
- AST
- ALT
- LDH
5
Q
What tests would you look at for cholestasis (flow of bile stops) or biliary excretory function?
A
- Bilirubin
- Alkaline phosphatase
- GGT
- 5’ nucleotidase
6
Q
What tests would you look at for hepatic synthetic function (cirrhosis)?
A
- albumin
- PT
- coagulation factors
7
Q
What is most important when evaluating a patient and interpreting LFTs?
A
HISTORY AND PHYSICAL!!!
*Never cut corners because that’s how people die. Sometimes LFTs can be normal in a disease state.
8
Q
What are important question to ask in your history and physical (H&P)?
A
- FMH (any issues with liver, bilirubin or anemia)
- Social Hx (occupation, travel, alcohol or illicit drug use, sexual activity).
- PMH/ PSH (home medications, surgeries)
9
Q
What are some things you would see on a physical exam if someone presented with liver disease?
A
- cachexia/temporal wasting
- spider nevi/palmar erythema, gynecomastia, caput medusa.
- ascites
- hepatic encephalopathy
- Virchow’s node/Sister Mary Joseph’s node
- Pleural effusion
- Neurologic issues
- JVD
- jaundice
- parotid gland enlargement
- asterixis
10
Q
What would cause aminotransferases (AST/ALT) to be released into the blood?
A
- toxins (EtOH, statins…)
- viral hepatitis
- ischemia/hypoperfusion
- malignancy
- Elevations in these enzymes indicate possible differentials.
11
Q
What is important about ASPARTATE aminotransferase (AST) and what is a normal value?
A
- NORMAL= 8-45 U/L
- formerly SGOT (serum glutamic-oxaloacetic transaminase).
- found in mitochondria and in multiple organs (liver, heart, muscle).
- In acute hepatitis, AST may elevate higher than ALT in the first 48 hours (half-life= 48 hours), then ALT will be higher after 48 hours.
12
Q
What is important about ALANINE aminotransferase (ALT) and what is a normal value?
A
- NORMAL= 7-55 U/L
- formerly SGPT (serum glutamic-pyruvic transaminase).
- unlike AST, it is PRIMARILY PRODUCED by the LIVER hepatocytes. Thus it is more specific to liver disease.
13
Q
Are AST elevations usually lower or higher than ALT elevations in the setting of hepatic injury?
A
lower (aka ALT is higher).
14
Q
If you see an AST:ALT ratio of 2:1, what should you think?
A
alcoholic liver disease
*higher levels indicate more damage
15
Q
What are the patterns of acute hepatic failure/fulminant (severe and sudden in onset) hepatic necrosis?
A
- LFTs usually 10x upper normal (in the 100s).
- hepatic encephalopathy= patient is lethargic, going in and out of consciousness, and/or can’t hold out their arms when asked to do so.
- prolonged PT
16
Q
What are some causes that would cause LFTs to be 15x GREATER than normal?
A
Consistent with acute hepatitis from:
- acute viral hepatitis
- alcoholic hepatitis
- toxins
- acetaminophen
- ischemia
- Wilson’s disease
- autoimmune
- Budd-Chiari syndrome
17
Q
What are some causes that would cause LFTs to be LESS than 15x normal?
A
- possible improving etiology of acute hepatitis. More chronic issue: - chronic Hep C - Chronic Hep B - Wilson disease - Viruses (EBV, HIV, CMV) - primary biliary cirrhosis - hemochromatosis primary sclerosing cholangitis - alpha-1 antitrypsin - anorexia nervosa - nonalcoholic fatty liver disease
18
Q
What is important about alkaline phosphatase and what is a normal value?
A
- NORMAL= 45-115 U/L
- derived from liver and bones
19
Q
How do you determine if an elevated alkaline phosphatase is coming from the liver or bones?
A
Order GGT:
- if 4x ELEVATED then this is consistent with cholestasis; aka the biliary tree).
- if not elevated, then think bone fracture, abnormal bone formation (Paget’s disease), 3rd trimester of pregnancy, or just youth.
20
Q
What is important about gamma glutamyl transpeptidase (GGT) and what is a normal value?
A
- NORMAL= 9-48 U/L
- mainly located in hepatocytes and biliary epithelial cells.
- Again, elevation with elevated ALT leads to a cholestasis picture.
21
Q
What is 5’ nucleotidase?
A
- found in multiple organs (liver, brain, and intestines), but is released into serum from ONLY HEPATOBILIARY tissue.
- found near the bile canalicular membrane of hepatocytes.
22
Q
Is 5’ nucleotidase ever elevated in conditions other than liver disease?
A
Rarely
23
Q
What is important about lactate dehydrogenase (LDH) and what is a normal value?
A
- NORMAL= 122-222 U/L
- found in multiple areas of the body and used mostly for MI, or hemolysis.
24
Q
What is important to know about ammonia?
A
- it is produced in the body during normal protein metabolism and by intestinal bacteria (primarily those in the colon).
- if the liver is functioning properly, it will clear the ammonia (by converting it to urea for the kidneys to excrete). If it is not, then you will see a rise in ammonia levels leading to HEPATIC ENCEPHALOPATHY (disconnect in motor functions due to effects on nervous tissue in the brain).
- poor correlation of blood serum ammonia and hepatic function however, because everyone reacts to ammonia levels differently.
25
What is important to know about PT (Prothrombin Time)/INR (International Normalized Ratio)?
- PT assesses EXtrinsic pathway of clotting. This will INCREASE in liver disease due to decreased synthesis of both vitamin K-dependent and -independent clotting factors; mostly factor 7.
- In severe and/or chronic liver disease (both the PT and aPTT may be prolonged).
- INR will be elevated due to vitamin K dependent coagulation factors 2, 7, 9 and 10.
26
What is the MELD score?
score calculated from 3 components: total bilirubin, creatinine, and INR to prioritize patients for liver transplant.
27
Again what labs would point you to a Hepatocellular pattern?
- AST/ALT greater than alkaline phosphatase
- possible elevation of serum bilirubin
- possible abnormal tests of synthetic function
28
Again what labs would point you to a Cholestasis pattern?
We are now lower in that biliary tree so think:
- elevation of ALKALINE PHOSPHATASE out of proportion to AST/ALT.
- serum bilirubin may be abnormal
- GGT abnormality (elevated).
- synthetic function tests can be abnormal
29
What is important about albumin and what is a normal value?
- NORMAL= 3.5-5 g/dL
- low levels point to chronic disorder of the liver.
* not accurate if malnourished in last 24-48 hours.
30
What is important about PT/INR and what are normal values?
- NORMAL PT= 9.5-13.8 seconds
- NORMAL INR= 0.9-1.1
- prolongation suggests vitamin K deficiency that may be related to malabsorption or hepatocellular dysfunction.
31
What is bilirubin?
end product of heme degradation
32
What is important about hyperbilirubinema and what is a normal value of total serum bilirubin?
- NORMAL= 0.2-1.2 mg/dL
- fractionate to direct (conjugated) and indirect (unconjugated) to help with Dx.
- level >2.5 mg/dL is required to produce jaundice.
- if elevated with normal alkaline phosphatase, then likely genetic disorder or hemolysis.
33
What is important about DIRECT (conjugated) bilirubin and what is a normal value?
- NORMAL= 0-0.3 mg/dL
- job of the liver is to make non-water soluble (unconjugated) bilirubin, water soluble by conjugating it (direct bilirubin), so that it can be excreted in bile.
- values >1.0 mg/dL always abnormal in infants (so do something).
- if elevated, means decreased excretion from bile ductules.
34
What are 3 possible problems that you should consider if DIRECT bilirubin in elevated (past 0.3 mg/dL)?
1. extrahepatic/biliary obstruction
2. intrahepatic cholestasis
3. hepatocellular injury
35
How does the liver conjugate bilirubin from the blood?
via UDP-glucuronyltransferase (UGT1A1 gene is most important). Conjugation is necessary for excretion of bilirubin across the bile canalicular membrane into bile.
36
What is normal for INDIRECT (unconjugated) bilirubin?
- NORMAL= 96% of total bilirubin is in unconjugated form.
37
What are some possible problems that you should consider if INDIRECT (unconjugated) bilirubin in elevated?
- Bilirubin overproduction from hemolysis, hematoma, or ineffective erythropoiesis.
- Reduced uptake from cirrhosis or Gilbert's syndrome.
- Impaired conjugation from impaired UDP-glucuronosyltransferase, Crigler-Najjar syndrome, or Gilbert's syndrome.
38
What is Gilbert's syndrome?
- most common inherited impairment of conjugated bilirubin excretion.
- you will have a transient elevation of UNCONJUGATED bilirubin due to UGT1A1 reduction in activity, preventing the unconjugated bilirubin from entering the hepatocytes.
- serum bilirubin is usually
39
When is Gilbert's syndrome most often diagnosed?
at or shortly after puberty or in adult life during routine examination.
40
Is Gilbert's syndrome often symptomatic?
NO, but may become intermittently jaundiced with acute illness/stress.
*Remember 2.5 mg/dL is the minimum you need to become jaundiced.
41
What is Crigler-Najjar Syndrome?
- RARE inherited (autosomal recessive) disorder of UDP-glucuronosyltransferase causing COMPLETE failure of bilirubin-glucuronide conjugation.
- causes jaundice/kernicterus (bilirubin encephalopathy).
- Types 1 and 2
42
What is Type 1 Crigler-Najjar syndrome?
- more severe of the 2 causing elevated unconjugated (indirect) bilirubin (20-45 mg/dL) with no detectable constitutive expression of UGT1A1 activity in hepatic tissue.
- usually LFTs are normal otherwise.
- Dx in infancy
43
What is Type 2 Crigler-Najjar syndrome?
- lower average unconjugated bilirubin, normal LFTs, less kernicterus, some UGT1A1 activity (aka less severe).
- may not be Dx until later in life.
44
What is Dubin-Johnson syndrome?
- RARE inherited metabolic disorder causing an inability to transport bilirubin-glucuronide through hepatocytes into canaliculi.
- causes elevated CONJUGATED (direct) bilirubin with normal LFTs.
- usually asymptomatic benign process.
- may see jaundice/icterus with an illness.
45
What is the cardinal feature of Dubin-Johnson syndrome?
- grossly dark/black liver.
46
What is Rotor syndrome?
- RARE benign, autosomal recessive disorder causing impaired excretion of conjugated bilirubin.
- only abnormality seen on lab tests is an elevation of total serum bilirubin, mainly due to predominant rise in CONJUGATED (direct) bilirubin.
- liver is NOT pigmented like it is in Dubin-Johnson's
47
What is Hereditary Hemochromatosis?
- autosomal recessive mutation of HFE gene (classic or Type 1) causing impaired iron homeostasis and thus increased intestinal iron, leading to fibrosis and cirrhosis of liver.
48
What is the "bronze diabetic" or classic triad of hereditary hemochromatosis?
cirrhosis, DM, and skin pigmentation
| *most pts will be asymptomatic.
49
What la elevations will you see with hereditary hemochromatosis?
- elevated iron studies
- elevated AST/ALT or serum ferritin (>1000 ug/L)= do liver biopsy, which will show iron deposition in a periportal distribution.
50
How do you treat hereditary hemochromatosis?
phlebotomy to reduce iron stores and then once stabilized, do maintenance phlebotomy every 2-3 months.
*check family members also
51
What is alpha-1 antitrypsin (AAT) deficiency?
- autosomal recessive most common cause of liver disease in children, due to lack of alpha-1 antitrypsin, which is produced by the hepatocytes to inhibit proteolytic elastase in the lungs and other organ systems.
- affects lungs, liver, and skin
52
What are the 2 alleles that we need to know for alpha-1 antitrypsin (AAT) deficiency?
1. Z allele= most common resulting in emphysema and eventual cirrhosis or hepatocellular carcinoma.
2. null allele= rare, worst= no AAT, so no liver issues but really bad lung issues.
53
How does AAT deficiency present?
- in childhood= jaundice, ascites, poor nutrition
| - adolescence or adulthood= anorexia, ascites, peripheral edema.
54
How do you Dx AAT deficiency?
- serum alpha-1 antitrypsin level with a PCR based of of that for the Z (severe), S (mild), or null (worst) alleles.
55
What is the treatment for AAT deficiency?
- no cure
| - just symptomatic relief: diuretics for edema, vitamin support, and phenobarb for jaundice.
56
What is primary biliary cirrhosis?
- T cell mediated autoimmune intra-lobular bile duct damage, leading to cholestatic pattern of LFTs (AST/ALT elevations and alkaline phos elevation).
* 95% cases are female.
57
What are the primary symptoms of primary biliary cirrhosis?
- pruritus
- fatigue
- hyperpigmented skin (jaundice)
- hepatosplenomegaly
- weight loss
- RUQ discomfort
- xanthomas
58
**** What is the classic test for primary biliary cirrhosis? (BOARD QUESTION)
- ANTIMITOCHONDRIAL ANTIBODIES (AMA)
59
What other labs will you see with primary biliary cirrhosis?
- elevated ESR
- elevated serum lipids
- elevated ceruloplasmin
- elevated alkaline phos
60
*** What is primary sclerosing cholangitis? (BOARD QUESTION)
- fibrosis of biliary ducts (both intra and extrahepatic) and associated with ULCERATIVE COLITIS.
61
What labs will you see with primary sclerosing cholangitis?
- cholestatic pattern of LFTs (AST/ALT elevations and alkaline phos elevation).
62
What is nonalcoholic fatty liver disease?
- hepatic steatosis without secondary cause (alcohol).
- etiology unclear but most likely due to insulin resistance.
- LFTs usually mildly elevated, bilirubin and albumin usually normal.
63
What are the 2 types of nonalcoholic fatty liver disease?
1. Nonalcoholic fatty liver (NAFL)= no inflammation
| 2. Nonalcoholic steatohepatitis (NASH)= infllammation
64
What is Wilson's disease?
- autosomal recessive that causes abnormal copper excretion leading to cirrhosis and neurological deficits (dysarthria, ataxia, dystonia).
65
What will you classically see with Wilson's disease?
- Kayser-Fleischer rings (corneal deposits).
| - ceruloplasmin levels=
66
How is the liver related to thyroid function?
it produces thyroxine-binding globulin, which is required for conversion of T4 to T3.
67
What is the first and easiest imaging modality we should consider?
- ultrasound= will show cirrhosis, what common bile duct looks like (dilation...), Hep C, helps distinguish between solid and cystic masses, and helps direct percutaneous biopsies for interventional radiology.
68
What is the second imaging modality we should consider?
CT scan for visualizing hepatomegaly, intrahepatic tumors, portal hypertension, or biliary tree dilatation.
*more expensive
69
What is the third imaging modality we should consider?
MRI= most accurate technique for identification of liver LESIONS (hemangiomas, fatty infiltrates, or tumors).
*high cost and any implantable metal devices CANNOT get an MRI (BIG MAGNET=BADNESS).
70
For what is positron emmission tomography (PET) scan used?
smaller lesions or metastatic disease
| *shows bright colors
71
What is cholescintigraphy (HIDA scan)?
nuclear medicine exam useful in cholecystitis or evaluation of cystic duct/common bile duct/ampulla.
*takes a couple hours (long time).
72
What is magnetic resonance cholangiography (MRCP)?
noninvasive test used to look at intrahepatic and extrahepatic bile ducts, stones, structures, or dilation.
73
What is endoscopic retrograde cholangiopancreatography (ERCP)?
INVASIVE procedure, but more reliable than MRCP to evaluate malignant vs benign stricture, can extract stones, or insert stents.
*risk of pancreatitis post-exam.
74
What is percutaneous transhepatic cholangiography (PTC)?
| *What I saw at the Cleveland Clinic
INVASIVE procedure that helps evaluate anatomy of biliary tree. Can find site of obstruction and clarifies inconclusive scans.
*risk of fever, bacteremia, peritonitis, intraperitoneal hemorrhage
