Hepatobiliary Flashcards
Enzyme tests for liver INFLAMMATION
- Tests for liver INFLAMMATION b/c elevation of these enzymes can be found in other tissues unrelated to liver
- ALT
- AST
- ALP
- GGT
Test for liver FUNCTION
- Bilirubin
- Albumin
- Ammonia
- Prothrombin
- AFP - alpha fetoprotein (AFP)
Indications for liver function tests
- Symptoms of liver disease
- Jaundice
- RUQ pain/swelling - protein and fluid imbalance
- Itchy skin - pruritus (toxin buildup)
- Dark (coca colored) urine - excreting bilirubin
- Pale stool - excreting bilirubin
- N/V
- Easy bruising - problems w/clotting
- Loss of appetite
- Chronic fatigue
- If patient has risk/concern for VIRAL hepatitis exposure or NAFLD/NASH
- Medication monitoring: APA, lamisil, fibrates, statins, niacin
- Disease monitoring
Which metabolic panel has LFTs included?
CMP - GGT, bilirubin and albumin left out
NOT BMP
Most specific liver enzyme test for hepatic injury
ALT
Causes for elevation of ALT
- Found in hepatocytes; also comes from kidney, less from skeletal and cardiac mm
- Hep A, B, C
- Acute drug injury
- EtOH and non-EtOH fatty liver
- Genetic + autoimmune liver problems
- Burns, skeletal trauma
- LOOK AT HOW MUCH HIGHER ABOVE NORMAL RANGE (2x, 3x, 4x, etc)
- Higher in infants than adults + children
AST present in which tissues?
- Liver
- Cardiac mm
- Skeletal mm
- Kidney
- Brain
Causes for elevation in AST
- Liver problems: hepatitis, cirrhosis, drug induced liver injury, metastasis, mononucleosis w/hepatitis
- Skeletal mm problems: Trauma, non-cardiac surgery, severe burns, muscular dystrophy, heat stroke
- Higher in infants + elderly vs adults
- MM wasting cause in elderly
normal ALT + ⇡AST suggestive of?
Cardiac or mm disease
As opposed to liver issue
Causes of ALP elevation
- Problem in hepatobiliary system
- Biliary disease: think biliary tract disease (stones) or infiltrative disease
- Pregnancy d/t placental synthesis
- Bone diseases
- Tumors, Paget’s, kids growing, hyperparathyroidism
⇡ALTs AND ⇡ ALP suggestive of?
Elevation of these suggest liver related issue
What to order next if elevation in ALP related to liver-biliary system?
GGT
BUT, no need to order if ALP and AST elevated
Causes of GGT elevation
- Not specific
- Liver problems: hepatitis, cirrhosis, liver tumors, hepatotoxic drugs
- MI
- EtOH ingestion
- Pancreatitis or pancreatic cancer
- EBV aka infectious mono
- NOT PRESENT IN BONE
↑ ALP, ↑ GGT, (-) hCG = _______
BILIARY ISSUE
Get a pregnancy test as ALP is elevated in pregnancy
↑ ALP, ↓ GGT = ________
BONE ISSUE
Remember: no GGT in bone!
↑ ALT, ↑ AST, normal ALP = ___________
Hepatocellular issue (LIVER)
↑ ALP, normal AST/ALT = __________
Biliary but related to bone and other sources w/GGT
Degree of elevation categories
- Borderline: < 2x ULN
- Mild: 2-5x ULN
- Start lab workup at this stage
- Moderate: 5-15x ULN
- Severe: > 15x ULN
- Massive AST or ALT > 10,000 IU/L
Causes of Mild-moderately elevated ALT/AST
- Common
- NAFLD + EtOH (get hx)
- Less common
- Meds: OTC, vitamins, etc
- Viral Hepatitis, B + C, A (acute s/s)
- Hemochromatosis = elevated iron levels
- Rare
- Alpha I antitrypsin deficiency
- Autoimmune disease (copper?)
- Wilson disease (copper?)
AST : ALT > 2 indicative of?
Which lab elevation makes it even more suggestive of this issue?
ALCOHOLIC LIVER DISEASE (still get hx)
GGT > 2x ULN
Common causes of ALT/AST elevation in ASYMPTOMATIC patients
- Autoimmune
- (B) Hep
- (C) Hep
- Drugs, toxins
- EtOH
- Fatty liver
- Growths (TUMOR)
- Hemodynamic disorder (CHF)
- Iron (hemochromatosis), Copper (Wilson’s), alpha-1 antitrypsin deficiency
- Muscle injury
Work-up of mildly elevated transaminases
First confirm by either repeating labs or performing clarifying test (GGT)
Only go through algorithm if acutely ill. Repeat in 3-4 weeks to see trend
Fatty liver disease RFs: high cholesterol, abd obesity, HTN, etc
Viral Hep RFs: IV drug use, high risk sexual activity (no protection), etc
Check iron panel - ferritin level - hemochromatosis
Albumin, Hep B, C; Abd U/S
Why is having excess fat in liver a problem?
Makes it more difficult for liver to function
Fat → inflammation
NAFLD
- Non-alcoholic fatty liver disease
- Has little to no inflammation
- Signs + Symptoms
- Metabolic syndrome (HTN, lipids, high TG level + low HDL, elevated BG) → need to be well-controlled to manage liver inflammation
- NAFLD fibrosis score = HIGH → GI referral → biopsy
- Inflammation → scarring → fibrosis
- Can progress to fibrosis and cirrhosis
NASH
- Non-alcoholic steatohepatitis
- Inflammation present
- See LFTs elevation → see CHRONIC damage
Liver disease progression
Hepatitis → Fibrosis → Cirrhosis → Cacner
Inflammation → scarring → severe scarring leaving irreversible damage → cancer
Fibrosis
Cirrhosis
ESLD
Liver failure
Fibrosis: Inflammation starts to scar. Scar tissue replaces the normal, healthy tissue. It is difficult for blood to flow through a scared, stiff liver. Healthy liver has to compensate for the inflamed, scared liver.
Cirrhosis is scared liver. Scared tissue replacing healthy tissue, can’t function well, eventually will not function (fail).
- Complications of cirrhosis: bleeding, edema, jaundice, itchy, diabetes, sensitivity to medications (ie liver not processing), toxin build up in brain, varices
- Chronic liver failure, cause death if no transplant to replace
- Not all end w/end stage liver disease, but put pt at risk more for cancer and disease
End stage liver disease: DECOMPENSATION, ex: hepatic encephalopathy, variceal bleed, ascites, kidney failure, lung transplant
Cancer: transplant.
Liver failure: loss of function, confusion, disorientation, coma
Bilirubin transport (picture)
- Bilirubin byproduct of RBCs breakdown
- SPLEEN → breakdown of heme → unconjugated bilirubin needs attachment to albumin → LIVER → unconjugated biliubin > conjugated bilirubin (via GBT) → INTESTINES → urobilinogen > stercobilin
- Stercobilin gives stool brown color
- Pool pale = bilirubin not able to get into intestines!
- Unconjugated NOT excreted in urine, only conjugated bilirubin
Conjugated bilirubin in liver suggests a problem in…
Something wrong POST-HEPATIC
High levels of unconjugated bilirubin suggests a problem in…
INTRAHEPATIC
Direct bilirubin
Looks for water soluble (conjugated) bilirubin
Indirect bilirubin
Total bilirubin - direct bilirubin
Total bilirubin =
What does this tell you?
Conjugated + unconjugated
If it’s hyperbilirubinemia
Prehepatic: dysfunction of and condition
- Unconjugated bilirubinemia issue
- Typically second to hemolysis
- Something is going wrong in breakdown of RBCs
- Hemolytic anemia
Intrahepatic conditions
- Unconjugated bilirubinemia
- Disorders of enzyme metabolism impending conjugation (Gilbert syndrome)
- Conjugated bilirubinemia
-
Intrahepatic choleestasis or hepatocellular damage from inflammation
- Flow of bile impaired from liver cells where it is produced to small intestine
-
Intrahepatic choleestasis or hepatocellular damage from inflammation
Posthepatic condition
- Conjugated bilirubinemia
- Blockage in biliary system keeps bilirubin from being transported (stones, tumor)
- Will often see pale stools and dark urine → d/t inability to excrete through biliary, goes into urine instead
Indications for Hepatic panel
- Acute jaundice
- Elevated bilirubin in asymptomatic patient
- Direct/Indirect bilirubin included: ALT, albumin, ALP, AST, +/- GGT
Urobilinogen indication for decreased levels
- Biliary disease - POSTHEPATIC
- Prevention of moving from biliary system into bowels
- Obstruction of conjugated bilirubin to bowel → less urobilinogen → PALE STOOLS
Urobilinogen indication for increased levels
- Increased in hemolytic process, hepatic disease
- Some goes back to liver, can’t be re-processed by liver and sent to gut… so “extra” goes to kidney
Bilirubinuria
- Conjugated bilirubin in urine (coca-colar urine)
- Unconjugated bilirubin is albumin bound (NOT WATER SOLUBLE = NOT IN URINE)
- Not in hyperbliirubinemia
Urine testing chart
Hemolytic disease, hepatic disease, and biliary obstruction
Albumin
What, function, decreased levels indication
- Protein made in liver
- Helps keep fluid in blood stream and not leak out of blood stream into tissues → edema, ascites
- Helps carry nutrients and hormones throughout body
- Bound to unconjugated bilirubin
-
Low levels = severe liver disease (late finding)
- Edema, ascites, trouble with drug metabolism/excretion
Ammonia
High levels indicate…
- Waste product of intestinal bacteria
- Broken down in liver → urea + glutamine
- If liver damaged → ammonia buildup → hepatic encephalopathy
- Lethargy, agitation, disorientation → coma if untreated
- Give lactulose to bind to ammonia and excrete in stool
Prothrombin time (PT)
Longer PT indication
- Measures time required for prothrombin to be converted to thrombin
- Dependent on Vitamin K which is stored in liver
- Non-functioning liver cannot carry out this process leading to prolonged PT and bleeding risk and clotting irregularities
Alpha fetoprotein (AFP)
- Tumor marker in adults…should only exist in small amounts
- Made in fetus liver and yolk sac (decreases after age 1)
- Increased in hepatocellular carcincoma
- Get serial levels to follow cirrhosis patients
- Increase should raise suspicion for HCC - cancer!!
- Not a screening tool for hepatocellular carcinoma but should get aFP if have cirrhosis
Ultrasound liver
Indications
- First line - low cost
- Can differentiate fatty changes vs cystic lesion vs solid lesion
- Fatty liver
- Screen for lesion
- BEST FOR GALLSTONES
- Gallbladder polyps
- Not invasive
- Can do in pts w/o s/s
- Abnormal → MRI
Fibro scan (Elastography)
Indication
- U/S of liver that detects fibrosis
- Used as surveillance in those with known fibrosis (degree of)
Liver MRI
Indications
- Gold standard imaging for the liver
- Indications
- Fatty liver
- Cyst, lesion
- Biliary duct dilation
- Choledocholithiasis
- Angioma, tumor
Liver CT
Indications
- Best if need image of entire abdomen
- Generalized abd pain
- Pelvic CT - appendicitis, gyn abnormality
- Indications
- Fatty liver
- Cyst, lesion
- Biliary duct dilation
- Choledocholithiasis
- Angioma, tumor
Gallbladder function and process
- Stores bile made from liver → releases bile to cystic duct → common bile duct → small intestine to aid in digestion
Gallstone conditions
- Result of too much cholesterol or too few bile salts
- Cholelithiasis - presence of too much gallstones
- Cholecystitis - inflammation of gallbladder
- Biliary colic - intermittent symptoms fo cholecystitis
Gallbladder workup + tx
- RUQ pain? Associated with fatty food?
- RUQ U/S
- LFTs
- Lipase
- CBC
- Surgery? gallbladder removal as there were too many stones
- Infection? more urgent!!!
Gallbladder workup + tx
- RUQ pain? Associated with food? What types of food? (fatty)
- RUQ U/S
- LFTs
- Lipase
- CBC
- Surgery? gallbladder removal as there were too many stones
- Infection? more urgent!!!
No gallbladder?
Difficulty digesting fats. Bile released into small intestine → bile salt diarrhea
Pancreatitis causes and acute symptoms
- Gallstones, choledocholithiasis (stones in common bile duct)
- Heavy EtOH use (acute or chronic)
- High TGs
- Acute?
- Acute LUQ, epigastric or periumbilical pain, starts intermittent → constant → N/V + worse after eating and w/lying down
Pancreatitis lab workup
- Labs: CBC, CMP, UA, lipase, LDH, TGs
- Lipase: pancreatic enzyme, more sensitive and specific than amylase
Pancreatitis imaging
U/S 1st line → Abd CT
Hepatitis A testing
HAV IgM, HAV IgG, Total
- Test for anti-HAV immunoglobulin
- HAV IgM (+) = acute infection - should only be ordered if symptoms acute
- Presents 3-4 weeks after exposure, normalize within 8 weeks
- HAV IgG (+) = past infection or immunity (develop 2 weeks post infection after IgM increases and last 10 years post infection)
- Total HAV antibody - does not distinguish between IgG and IgM
- HAV IgM (+) = acute infection - should only be ordered if symptoms acute
Hepatitis A pathology
Transmitted via fecal-oral route or through contaminated food or water - contagious
Symptoms: fatigue, N/V, upper abd pain jaundice, dark urine, itching
Not chronic - only acute
Vaccine - after 2006 - get one if traveling to underdeveloped country
Hepatitis B pathology
Vaccine
Transmitted through blood and bodily fluids, needles, sexual contact
More asymptomatic, contributing to silent spread
- Can be mild and resolve or become chronic
- If not cleared after ∼6 months = chronic
- Vaccine
- Given to all infants at birth
- At risk pops: healthcare workers, ESRD, DM, Hep C, HIV…
- 3 dose series
- Antibody titers confirm immunity/response to vaccine
Hepatitis B markers
what do each indicate?
- Hep B surface antigen
- Presence implies acute or chronic infection
- Person is infectious → able to spread virus as it’s in system
- Hep B surface antibody
- Indicates recovery and immunity from Hep B infection
- Develops after vaccination
- Does not develop in chronic carries - ACUTE
- Hep B core antibody
- Appear 4 weeks after infection and persist for life
- Only present if prior infection, will not develop post vaccination
- Implies prior or chronic infection
- Hep B IgM antibody (IgM andti-HBc)
- Occurs with acute infection
- Lasts for 6 months
- Positive implies infection within last 6 months
Hepatitis B scenarios (slide 5)
Hepatitis C pathology
Screening
- Transmitted through blood/bodily fluids
- No vaccine available
-
1x lifetime screen for all adults aged ≥ 18 years
- Screening for all pregnant women during each delivery
Hepatitis C markers
HCV antibody test + HCV RNA + Viral genotyping
- HCV antibody test
- Reactive or non-reactive
- Can take 4-10 weeks to become positive - be sure to retest
- Remains positive for life - can develop it again
- Will be positive in person who had it already in past
- If someone has no hx of Hep C infection - use this test to confirm
- HCV RNA
- Ordered to confirm (+) HCV antibody test
- Once infection tx/resolved → negative
- Viral genotyping ordered for + HCV RNA
- Determine type and length of tx
