10/9- Jaundice and Biliary Disease Flashcards
How are liver labs denoted/reported (format)?
What are the Liver Function Tests (“LFTs”)?
- Where are these substances found in the body?
Aminotransferases
- Alanine aminotransferase (ALT)
- Aspartate aminotransferase (AST)
Bilirubin
- Total
- Direct
- Found in hepatocytes and bile ducts
Alkaline phosphatase (ALP, “alk phos”)
- Found in cells lining bile ducts
Describe bilirubin metabolism:
- Precursors
- Bound to ___ in serum
- Conjugation/transportation
- Bilirubin = end product of heme degradation
- Bound to albumin in serum
- Conjugated with UDP-glucuronic acid to become water soluble (enzyme mediated in hepatocyte)
- Transported into bile (small amt back into plasma -> urine)
- Deconjugated by bacterial enzymes to form urobilinogen -> excreted in feces
How is conjugated/unconjugated bilirubin differentiated in measurement?
Where is it measured?
Measured in serum: cleavage into measurable component
- Conjugated bilirubin cleaved rapidly
- Unconjugated bilirubin slowly cleaved >> needs accelerator
So basically:
- Direct bilirubin: amount measured without accelerator = conjugated bilirubin
- Total bilirubin: amount measured after accelerator added
- Indirect bilirubin = Total - Direct = unconjugated bilirubin
What is normal serum bilirubin?
1 - 1.5 mg/dL
What is jaundice?
At what bilirubin levels does this typically occur?
Yellow discoloration of skin, conjunctivae and mucous membranes by deposition of pigmented bilirubin
- Bilirubin > 3 mg/dL (unconjugated, conjugated, conjugated bound to albumin/delta fraction)
T/F: If someone is already jaundiced, their liver function tests should be abnormal
False
- Associated LFTs could be normal or abnormal
What are causes of jaundice?
Imbalance of formation and clearance of bilirubin
- Isolated Disorders of Bilirubin Metabolism
- Unconjugated hyperbilirubinemia
- Conjugated hyperbulirubinemia
- Liver Disease
- Acute hepatocellular injury
- Chronic hepatocellular disease
- Cholestatic disorders
- Biliary Obstruction
- Choledocholithiasis
- Inflammatory
- Neoplasm
- Extrinsic compression
In what causes of jaundice will you have normal LFTs? Abnormal?
Normal:
- Isolated disorders of bilirubin metabolism
Abnormal:
- Liver disease
- Biliary obstruction
For Isolated Disorders of Bilirubin Metabolism…
What can cause increased bilirubin production?
Hemolysis
- Sickle cell
- immune-mediated
- Parasitic
Ineffective erythropoiesis
- B12
- Folate
- Iron deficiencies
For Isolated Disorders of Bilirubin Metabolism…
What can cause decreased uptake?
Medication
- Rifampin competitively inhibits uptake transport protein
For Isolated Disorders of Bilirubin Metabolism… What can cause decreased conjugation?
Inherited disorders
What are some inherited disorders of bilirubin conjugation?
- Crigler-Najjar (type I, II)
- Gilbert’s
For the various inherited disorders of bilirubin conjugation, describe the:
- Mutation
- Conjugation amount
- Incidence
- Age group
- Serum bilirubin
- Treatment
What are key findings in the history that might help in the diagnosis of jaundice/liver problems?
- Abdominal pain, RUQ
- Fever, chills, rigors
- Anorexia, myalgias
- Duration of jaundice
Signs of liver obstruction:
- Pruritis (general itchiness)
- Darkening urine (urobilinogen)
What are exposures that might contribute to the jaundice/liver disorder?
- Viral sick contacts
- Blood transfusions, IVDU, sexual contacts
- Medications, supplements, alcohol
- Surgery
What are signs expected/looked for in physical exam for jaundice/liver diseases?
1. Look for signs of acute biliary obstruction (often associated with infection/cholangitis)
- Fever
- Tachycardia
- Hypotension
2. Look for clues of chronic liver disease
- Spider nevi
- Palmar erythema
- Gynecomastia
- Caput medusae
- Splenomegaly
Also:
- RUQ tenderness: Murphy’s sign (of cholecystitis)- respiratory arrest on inspiration Cirrhosis:
- Ascites
- Asterixis
What cells/conditions align with:
- ALT/AST
- Alkaline phosphatase
- ALT/AST: hepatocellular
- Alkaline phosphatase: cholestasis
How do the following relate to liver-related disease:
- WBC
- Hgb
- Platelets
- Prothrombin time
- WBC: elevated with infection, inflammation
- Hgb: reduced in hemolysis, chronic liver disease
- Platelets: reduced in chronic liver disease
- Prothrombin time: msmt of Vit K dependent factors; elevated either due to:
- Impaired Vit K activity in the liver (not producing it) OR
- Impaired Vit K absorption form the gut (bile salt dependent; requires intact biliary system– could indicate obstruction)
How does the history differ in liver disease vs. biliary obstruction?
Liver disease (feels more systemic)
- Anorexia
- Myalgias
- High risk exposures: blood, IV, sexual
- Toxic exposrue: med, alcohol
Biliary Obstruction (feels more like surgery issue)
- Abdominal pain (RUQ)
- Fevers, rigors
- Prior hepatobiliary surgery
- Older age
- Weight loss
How does the physical exam differ in liver disease vs. biliary obstruction?
Liver disease
Stigmata of chronic liver disease
- Asterixis
- Ascites
- Splenomegaly
Biliary obstruction:
- Fever
- Tachycardia
- RUQ tenderness
- Palpable mass
- Surgical scars
How do the lab tests differ in liver disease vs. biliary obstruction?
Liver disease:
- AST/ALT: ^^^
- Alk phos: normal/^
- PT: ^^ with no correction with Vit K
- Low platelets
Biliary obstruction:
- AST/ALT: normal/^
- Alk phos: ^^^
- PT: ^^ with correction with Vit K
- WBC: ^^
- Lipase/amylase: ^^
What is the mechanism of hepatocellular liver diseases?
Hepatocyte or bile duct injury leading to impaired conjugation and regurgitation of bilirubin
What are causes of acute liver disease?
- Viral hepatitis
- Drug induced liver injury
- Hepatic ischemia
- Wilson’s disease
What are causes of chronic liver disease?
- Chronic viral hepatitis
- Hemochromatosis
- Alpha 1 anti-trypsin deficiency
- Autoimmune hepatitis
What are causes of cholestatic liver disease?
- Primary biliary cirrhosis
- Med induced
- Pregnancy
- Total parenteral nutrition
- Paraneoplastic syndrome: lymphoma
What is choledocholithiasis?
Gallstones in the bile duct
What may cause malignant obstruction of the bile system?
Intrinsic: cholangiocarcinoma
Extrinsic:
- Pancreatic head CA
- Ampullary CA
- Peri-ductal lymphadenopathy
What is the composition of gallstones?
Solid mix of:
- Cholesterol crystals
- Mucin
- Calcium bilirubinate
- Glycoproteins
- Pigments
Two main types:
- Cholesterol (more yellow)
- Pigment (darker)
- Mixed
What causes gallstone formation
Imbalance in content of bile
Cholesterol stones are __% of Western stones
- Bile = ___ + ___ + ___
- What is the process of formation?
Cholesterol stones are 80-90% of Western stones
- Bile = cholesterol + bile + phospholipids
Process:
- Cholesterol supersaturation → precipitation of monohydrate microcrystal
- Stasis and coalescence of microcrystals in gallbladder → gallstone
Pigment stones are composed primarily of ___
- Different colors/their meaning
Pigment stones are composed primarily of polymerized calcium bilirubinate
Excessive unconjugated bilirubin
- Black = outside of bile duct
- Hemolysis (increased production)
- Cirrhosis (impaired conjugation)
- Ileal disease (increased re-circulation)
- Brown = within the bile duct
- Chronic biliary infections (bacterial deconjugation of bilirubin)
What are risk factors for gallstone formation
- Modifiable
- Non-modifiable
Modifiable
- Pregnancy
- Weight loss
- Drugs
- Gallbladder dismotility
Non-modifiable
- Age
- Gender
- Ethnicity
- Genetics
What causes choledocholithiasis?
Common bile duct stones
- Migration from gallbaldder
- Secondary formation
Detected in 3-20% of cholecystectomy pts
What is the natural course of choledocholithiasis? T
reatment?
Spontaneous migration (20%)
Complications (50%):
- Colic jaundice
- Cholangitis
- Pancreatitis
All operable candidates should have a cholecystectomy to prevent recurrence
When do you suspect CBD stone?
- Numerous testing methods, all influenced by the pre-test probability
- First Line: Liver Function Tests + Transabdominal
Ultrasound
- Results of LFTs and USG + Clinical factors determine further evaluation (AST/ALT raised because of obstruction, not liver disease, so those may rise/fall rapidly)
What do you expect to see on ultrasound of CBD stone?
CBD > 6-7 mm or 1 mm/decade
- You’re really looking for dilation (specificity of seeing a stone is only 50%)
What signs/findings put someone at low risk (0-5%) of having CBD stone? Plan of action?
- Normal liver tests
- Normal CBD size on US
Need to:
- No further evaluation
- Consider intraoperative cholangiogram
What signs/findings put someone at intermediate risk (5-50%) of having CBD stone? Plan of action?
- Age >55 y
- Cholecystitis
- Dilated CBD: >6 mm
- Bilirubin: 1.8-4 mg/dL
- Abnormal LFTs other than bilirubin
- Pancreatitis
Need to:
- First line EUS/MRCP
- Followed by ERCP if CBD stone found
What signs/findings put someone at high risk (>50%) of having CBD stone? Plan of action?
- Cholangitis
- Dilated CBD: >6 mm
- CBD stone on US
- Bilirubin: >4 mg/dL
Need to:
- First line ERCP
What is ERCP?
Endoscopic Retrograde CholangioPancreatography
- Endoscopic access of the pancreatic and biliary ductal system
- Diagnostic and therapeutic (although limited to mostly therapeutic)
Limitations:
- Altered anatomy
- Requires sedation
Risks:
- Pancreatitis: 0-25%
- Bleeding
- Infection
- Perforation
Describe endoscopic ultrasound
- Equipment
- Imaging of what
- Endoscope equipped with ultrasound transducer at tip
- Radial (360) or Curve Linear Arrary
- Imaging of subepithelial layers of the GI lumen and surrounding structures
- Most GI structures imaged from within the stomach or duodenum
What is MRCP?
- Method
- Pros
- Limitations
Magnetic Resonance Cholangiopancreato-graphy
- Heavily T2 weighted images highlight still fluids (i.e. bile and pancreatic secretions, allowing outlining of biliary and pancreatic ducts)
Pros:
- Non-invasive
- No contrast required
Limitations:
- Contraindications to MRI
- Insensitive in non-dilated ducts and for stones under 6mm
Pros/Cons of TUS?
Pros
- Inexpensive
- Safe
- Widely available
- Portable
Cons:
- Low sensitivity
- Operator dependent
Pros/Cons of CT?
Pros
- Detection of concomitant intrahepatic duct stones, liver parenchymal lesions, and pancreatic lesions
Cons
- Radiation exposure
- Contrast allergy
- Renal impairment
Pros/Cons of MRC?
Pros:
- High accuracy for duct stone detection
- Noninvasive intrahepatic and extrahepatic duct evaluation
Cons:
- Expensive
- Time consuming
- Limited value in stones 10 mm
- Claustrophobia
- Ferromagnetic implant
- Artifact interference
Pros/Cons of EUS?
Pros:
- High accuracy for duct stone detection
- Less invasive than ERC
- Detects small stones in a nondilated duct
Cons:
- Operator dependent
- High cost of equipment
- Insensitive for proximal common hepatic duct /intrahepatic duct stones
Pros/Cons of ERC?
Pros:
- High accuracy
- Therapeutic potential
Cons:
- Higher risk than EUS
- False positives (air bubbles)
- False negatives with small stones in dilated duct
- Unsuccessful cannulation
How is choledocholithiasis treated?
Endoscopic:
- ERCP with sphincterotomy and stone extraction
Surgical
- Laprascopic bile duct exploration at time of cholecystectomy
What can cause malignant biliary obstruction?
- Primary bile duct tumor: cholangiocarcinoma
- Extrinsic compression or invasion of bile duct
- Pancreatic head adenoCA
- Gallbladder CA
- Ampullary CA
- Porta hepatis lymphadeonopathy
How should malignant biliary obstruction be managed?
- Depending on overall management of the underlying malignancy, biliary drainage may be required
- Percutaneous vs. endoscopic drainage/stent placement
What is acute cholangitis/how does it develop?
- Ascending bacterial entry into bile duct from duodenum
- Biliary obstruction
- Stones
- Prior biliary surgery >> stricture, stent
- Malignant obstruction - Biliary stasis and bacterial growth
- Increased intraductal pressure >> translocation of bacteria into bloodstream (may cause sepsis, not simple infection; emergency!)
What are symptoms of acute cholangitis?
Charcot’s Triad:
- Fever (90%)
- RUQ pain
- Jaundice
Also:
- Elevated WBC
- Abnormal LFTs
Often positive blood cultures (50%)
- Enteric Gm (-): E. coli, Klebsiella, Enterococcus
- Gm (+), anaerobes
- Prior intervention: VRE, Pseudomonas, MRSA
What is therapy for acute cholangitis: mild disease?
Empiric Antibiotics : 80% will resolve
- Biliary excretion: ampicillin/sulbactam, piperacillin/tazobactam, quinolones
- Anaerobe +/- resistant organisms
Biliary drainage within 24-48 hours
What is therapy for acute cholangitis: severe disease (SIRS, shock, unstable)?
Urgent biliary drainage
What is biliary decompression?
- Method
- Goal
- Risks
Endoscopic: ERCP
- Upon cannulation, aspirate to lower pressures, send for bile culture
- Limited contrast injection
- Goal is drainage :
- Sphincterotomy + stone extraction
- Sphincterotomy + stent placement
- Stent placement alone - Increased risk of post sphincterotomy bleeding
What are alternate options for biliary drainage?
ERRCP: ↓ morbidity and mortality compared to percutaneous or surgery
If ERCP not possible:
- Altered anatomy
- Unstable for sedation
- Failed cannulation
Percutaneous Transhepatic Cholangiography (PTC)
- Image guided placement of drainage catheter into the intrahepatic duct and then advanced
- Risks: Bleeding, infection, peritonitis
Surgery : Common Bile Duct Exploration
- Open or Laprascopic
- T-tube placement
What is chronic pancreatitis?
Benign stricture of the intra-pancreatic CBD
What is primary sclerosing cholangitis (PSC)
- Associations
- Inflammatory disorder with multiple intra- and extra-hepatic strictures
- Associated with IBD
What is AIDS cholangiopathy?
Focal narrowings of bile duct due to infection
What is Mirizzi’s syndrome?
Impaction of gallstone in cystic duct causing CBD obstruction
What is ischemic stricture? (what causes it)
- Hepatic artery injury
- Liver transplantation
Summary
- Bilirubin metabolism is a fine balance between production and excretion
- Jaundice develops as a result of an imbalance
- Basic history, physical exam and laboratory tests can identify cause of jaundice
- Diagnostic +/- therapeutic modalities chosen based on suspected condition
- Biliary disorders are common and varied
