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MS2 GI > 10/9- Jaundice and Biliary Disease > Flashcards

10/9- Jaundice and Biliary Disease Flashcards

1
Q

How are liver labs denoted/reported (format)?

A
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2
Q

What are the Liver Function Tests (“LFTs”)?

  • Where are these substances found in the body?
A

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
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3
Q

Describe bilirubin metabolism:

  • Precursors
  • Bound to ___ in serum
  • Conjugation/transportation
A
  • 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
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4
Q

How is conjugated/unconjugated bilirubin differentiated in measurement?

Where is it measured?

A

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
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5
Q

What is normal serum bilirubin?

A

1 - 1.5 mg/dL

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6
Q

What is jaundice?

At what bilirubin levels does this typically occur?

A

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)
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7
Q

T/F: If someone is already jaundiced, their liver function tests should be abnormal

A

False

  • Associated LFTs could be normal or abnormal
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8
Q

What are causes of jaundice?

A

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
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9
Q

In what causes of jaundice will you have normal LFTs? Abnormal?

A

Normal:

  • Isolated disorders of bilirubin metabolism

Abnormal:

  • Liver disease
  • Biliary obstruction
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10
Q

For Isolated Disorders of Bilirubin Metabolism…

What can cause increased bilirubin production?

A

Hemolysis

  • Sickle cell
  • immune-mediated
  • Parasitic

Ineffective erythropoiesis

  • B12
  • Folate
  • Iron deficiencies
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11
Q

For Isolated Disorders of Bilirubin Metabolism…

What can cause decreased uptake?

A

Medication

  • Rifampin competitively inhibits uptake transport protein
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12
Q

For Isolated Disorders of Bilirubin Metabolism… What can cause decreased conjugation?

A

Inherited disorders

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13
Q

What are some inherited disorders of bilirubin conjugation?

A
  • Crigler-Najjar (type I, II)
  • Gilbert’s
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14
Q

For the various inherited disorders of bilirubin conjugation, describe the:

  • Mutation
  • Conjugation amount
  • Incidence
  • Age group
  • Serum bilirubin
  • Treatment
A
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15
Q

What are key findings in the history that might help in the diagnosis of jaundice/liver problems?

A
  • Abdominal pain, RUQ
  • Fever, chills, rigors
  • Anorexia, myalgias
  • Duration of jaundice

Signs of liver obstruction:

  • Pruritis (general itchiness)
  • Darkening urine (urobilinogen)
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16
Q

What are exposures that might contribute to the jaundice/liver disorder?

A
  • Viral sick contacts
  • Blood transfusions, IVDU, sexual contacts
  • Medications, supplements, alcohol
  • Surgery
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17
Q

What are signs expected/looked for in physical exam for jaundice/liver diseases?

A

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
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18
Q

What cells/conditions align with:

  • ALT/AST
  • Alkaline phosphatase
A
  • ALT/AST: hepatocellular
  • Alkaline phosphatase: cholestasis
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19
Q

How do the following relate to liver-related disease:

  • WBC
  • Hgb
  • Platelets
  • Prothrombin time
A
  • 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)
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20
Q

How does the history differ in liver disease vs. biliary obstruction?

A

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
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21
Q

How does the physical exam differ in liver disease vs. biliary obstruction?

A

Liver disease

Stigmata of chronic liver disease

  • Asterixis
  • Ascites
  • Splenomegaly

Biliary obstruction:

  • Fever
  • Tachycardia
  • RUQ tenderness
  • Palpable mass
  • Surgical scars
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22
Q

How do the lab tests differ in liver disease vs. biliary obstruction?

A

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: ^^
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23
Q

What is the mechanism of hepatocellular liver diseases?

A

Hepatocyte or bile duct injury leading to impaired conjugation and regurgitation of bilirubin

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24
Q

What are causes of acute liver disease?

A
  • Viral hepatitis
  • Drug induced liver injury
  • Hepatic ischemia
  • Wilson’s disease
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25
Q

What are causes of chronic liver disease?

A
  • Chronic viral hepatitis
  • Hemochromatosis
  • Alpha 1 anti-trypsin deficiency
  • Autoimmune hepatitis
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26
Q

What are causes of cholestatic liver disease?

A
  • Primary biliary cirrhosis
  • Med induced
  • Pregnancy
  • Total parenteral nutrition
  • Paraneoplastic syndrome: lymphoma
27
Q

What is choledocholithiasis?

A

Gallstones in the bile duct

28
Q

What may cause malignant obstruction of the bile system?

A

Intrinsic: cholangiocarcinoma

Extrinsic:

  • Pancreatic head CA
  • Ampullary CA
  • Peri-ductal lymphadenopathy
29
Q

What is the composition of gallstones?

A

Solid mix of:

  • Cholesterol crystals
  • Mucin
  • Calcium bilirubinate
  • Glycoproteins
  • Pigments

Two main types:

  • Cholesterol (more yellow)
  • Pigment (darker)
  • Mixed
30
Q

What causes gallstone formation

A

Imbalance in content of bile

31
Q

Cholesterol stones are __% of Western stones

  • Bile = ___ + ___ + ___
  • What is the process of formation?
A

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
32
Q

Pigment stones are composed primarily of ___

  • Different colors/their meaning
A

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)
33
Q

What are risk factors for gallstone formation

  • Modifiable
  • Non-modifiable
A

Modifiable

  • Pregnancy
  • Weight loss
  • Drugs
  • Gallbladder dismotility

Non-modifiable

  • Age
  • Gender
  • Ethnicity
  • Genetics
34
Q

What causes choledocholithiasis?

A

Common bile duct stones

  • Migration from gallbaldder
  • Secondary formation

Detected in 3-20% of cholecystectomy pts

35
Q

What is the natural course of choledocholithiasis? T

reatment?

A

Spontaneous migration (20%)

Complications (50%):

  • Colic jaundice
  • Cholangitis
  • Pancreatitis

All operable candidates should have a cholecystectomy to prevent recurrence

36
Q

When do you suspect CBD stone?

A
  • 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)
37
Q

What do you expect to see on ultrasound of CBD stone?

A

CBD > 6-7 mm or 1 mm/decade

  • You’re really looking for dilation (specificity of seeing a stone is only 50%)
38
Q

What signs/findings put someone at low risk (0-5%) of having CBD stone? Plan of action?

A
  • Normal liver tests
  • Normal CBD size on US

Need to:

  • No further evaluation
  • Consider intraoperative cholangiogram
39
Q

What signs/findings put someone at intermediate risk (5-50%) of having CBD stone? Plan of action?

A
  • 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
40
Q

What signs/findings put someone at high risk (>50%) of having CBD stone? Plan of action?

A
  • Cholangitis
  • Dilated CBD: >6 mm
  • CBD stone on US
  • Bilirubin: >4 mg/dL

Need to:

  • First line ERCP
41
Q

What is ERCP?

A

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
42
Q

Describe endoscopic ultrasound

  • Equipment
  • Imaging of what
A
  • 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
43
Q

What is MRCP?

  • Method
  • Pros
  • Limitations
A

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
44
Q

Pros/Cons of TUS?

A

Pros

  • Inexpensive
  • Safe
  • Widely available
  • Portable

Cons:

  • Low sensitivity
  • Operator dependent
45
Q

Pros/Cons of CT?

A

Pros

  • Detection of concomitant intrahepatic duct stones, liver parenchymal lesions, and pancreatic lesions

Cons

  • Radiation exposure
  • Contrast allergy
  • Renal impairment
46
Q

Pros/Cons of MRC?

A

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
47
Q

Pros/Cons of EUS?

A

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
48
Q

Pros/Cons of ERC?

A

Pros:

  • High accuracy
  • Therapeutic potential

Cons:

  • Higher risk than EUS
  • False positives (air bubbles)
  • False negatives with small stones in dilated duct
  • Unsuccessful cannulation
49
Q

How is choledocholithiasis treated?

A

Endoscopic:

  • ERCP with sphincterotomy and stone extraction

Surgical

  • Laprascopic bile duct exploration at time of cholecystectomy
50
Q

What can cause malignant biliary obstruction?

A
  • Primary bile duct tumor: cholangiocarcinoma
  • Extrinsic compression or invasion of bile duct
  • Pancreatic head adenoCA
  • Gallbladder CA
  • Ampullary CA
  • Porta hepatis lymphadeonopathy
51
Q

How should malignant biliary obstruction be managed?

A
  • Depending on overall management of the underlying malignancy, biliary drainage may be required
  • Percutaneous vs. endoscopic drainage/stent placement
52
Q

What is acute cholangitis/how does it develop?

A
  1. Ascending bacterial entry into bile duct from duodenum
  2. Biliary obstruction
    - Stones
    - Prior biliary surgery >> stricture, stent
    - Malignant obstruction
  3. Biliary stasis and bacterial growth
  4. Increased intraductal pressure >> translocation of bacteria into bloodstream (may cause sepsis, not simple infection; emergency!)
53
Q

What are symptoms of acute cholangitis?

A

Charcot’s Triad:

  1. Fever (90%)
  2. RUQ pain
  3. Jaundice

Also:

  • Elevated WBC
  • Abnormal LFTs

Often positive blood cultures (50%)

  • Enteric Gm (-): E. coli, Klebsiella, Enterococcus
  • Gm (+), anaerobes
  • Prior intervention: VRE, Pseudomonas, MRSA
54
Q

What is therapy for acute cholangitis: mild disease?

A

Empiric Antibiotics : 80% will resolve

  • Biliary excretion: ampicillin/sulbactam, piperacillin/tazobactam, quinolones
  • Anaerobe +/- resistant organisms

Biliary drainage within 24-48 hours

55
Q

What is therapy for acute cholangitis: severe disease (SIRS, shock, unstable)?

A

Urgent biliary drainage

56
Q

What is biliary decompression?

  • Method
  • Goal
  • Risks
A

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
57
Q

What are alternate options for biliary drainage?

A

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
58
Q

What is chronic pancreatitis?

A

Benign stricture of the intra-pancreatic CBD

59
Q

What is primary sclerosing cholangitis (PSC)

  • Associations
A
  • Inflammatory disorder with multiple intra- and extra-hepatic strictures
  • Associated with IBD
60
Q

What is AIDS cholangiopathy?

A

Focal narrowings of bile duct due to infection

61
Q

What is Mirizzi’s syndrome?

A

Impaction of gallstone in cystic duct causing CBD obstruction

62
Q

What is ischemic stricture? (what causes it)

A
  • Hepatic artery injury
  • Liver transplantation
63
Q

Summary

A
  • 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

MS2 GI (26 decks)

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