jaundice and cholestasis - school of medicine conference1...jaundice and cholestasis carlos saad,...
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Jaundice and Cholestasis
Carlos Saad, M.D.
H.H. Chao Comprehensive Digestive
Disease Center
UC Irvine Health
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Today’s Goal
• A brief review of the normal metabolism of
bilirubin.
• The pathophysiological approach to the
patient with hyperbilirubinemia and
cholestasis.
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• Jaundice means increased serum bilirubin
with a subsequent yellowish tinge of the
skin and sclera.
• Cholestasis is defined as failure of normal
amounts of bile to reach the duodenum. It
may cause jaundice, not all jaundice is
cholestatic.
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Campbell, 1985
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Campbell, 1985
Pre-Hepatic
Unconjugated Bilirubin
Hepatic
Conjugated Bilirubin
Cholestatic
Bile unable to reach the duodenum
Conjugated Bilirubin
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Pre-hepatic Jaundice (Unconjugated Hyperbilirubinemia)
• Less apparent
• No itching
• Normal color urine
• Unconj. bilirubin
• Normal AST and ALT
• LDH, reticulocytes
• Haptoglobin
• Fragmented RBCs
• Hemolysis
• Intra or extravascular
• Bilirubin uptake
• Shunts, CHF
• Gilbert’s syndrome
• Bilirubin conjugation
• Crigler-Najjar I & II
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Hepatic Jaundice (Conjugated and Unconjugated Hyperbilirubinemia)
• Apparent jaundice
• CB and UB
• Dark urine
• ALT & AST
• Signs and symptoms
of liver disease
Excretion
• Dubin-Johnson
• Rotor
Hepatocellular injury
• Hepatitis
• Cirrhosis
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Hepatic Jaundice (Conjugated and Unconjugated Hyperbilirubinemia)
Excretion
• Dubin-Johnson
• Rotor
Hepatocellular injury
• Hepatitis (viral, ETOH,
autoimmune)
• Wilson Disease
• Drugs
• Sepsis
• Postoperative jaundice
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Cholestatic Jaundice
• Pruritus
• Bili, alk phos, AST,
ALT, cholesterol, bile
acids
• Steatorrhea
• Vit. A, D, E, K,
malabsorption
• Primary Biliary Cholangitis
• Primary Sclerosing Cholangitis
• CBD stone
• Neoplasia
• Strictures
• HIV
• PFIC I, II, III
• Parasites
• Systemic
• Medications
• TPN
Chole = bile Stasis = stop
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Cholestasis
Intrahepatic
• Alteration of the patterns
of the secretion of bile
by the hepatocytes
• Obstruction of the
intrahepatic bile ducts
Extrahepatic
• Obstruction of the
extrahepatic bile ducts
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Hepatocellular Cholestasis
Genetic
• 1-antitrypsin deficiency
• Benign recurrent
intrahepatic cholestasis
• Byler syndrome
• Cholestasis of pregnancy
• Abnormal bile acid
synthesis
• Porphyrias
Acquired
• Medications
• Cholestatic hepatitis
• Bacterial infections
• TPN
• Paraneoplastic cholestasis
• Postoperative cholestasis
• Miscellaneous
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Hepatocellular Cholestasis
Normal HIDA scan
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Obstruction of Intrahepatic Bile Ducts
• Primary biliary cholangitis
• Space occupying lesions
Primary or metastatic liver cancer, lymphoma,
amyloidosis
• Vanishing bile duct syndrome
Allograft rejection, GVHD, Alagille’s syndrome,
Idiopathic adult ductopenia, PSC, Hodgkin’s disease,
Augmentin
• Cystic fibrosis
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Obstruction of Extrahepatic Bile Ducts
• CBD stone
• Pancreatic CA
• Ampullary CA
• Cholangiocarcinoma
• Benign strictures
• Parasites
• PSC
• HIV cholangiopathy
• Lymphoma
• Choledocal cyst
• Biliary atresia
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Signs and Symptoms
• Jaundice, dark urine, pale stool
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Pruritus
• Generalized, constant or intermittent,
exacerbated at night or during warm
weather
• Distressing symptom, has lead to suicide
• Pathogenesis controversial
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Pruritus
Bile Acids Theory
• Bile acids in skin and blood
• Bile acid-binding resin is effective
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Pruritus
Opioid Receptors Theory
• Opiates induce facial scratching in animals
• Endogenous opioids accumulate in cholestasis
• Plasma extracts induce facial scratching in monkeys
• Opioid antagonists relieve pruritus
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Steatorrhea
Bile acid concentration in the intestine
Impaired micelle formation
Inadequate fat solubilization
Malabsorption of dietary fats
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Vitamin Deficiencies
Malabsorption of dietary fats
Fat soluble vitamin malabsorption
Vitamin A night blindness
Vitamin D bone disease
Vitamin E cerebellar ataxia, peripheral neuropathy, retinal
degeneration (in children)
Vitamin K Coagulopathy
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Xantomas
• Due to
hypercholesterolemia
• Resolve after relieving
the obstruction
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Hepatic Osteodystrophy
• Osteopenia and osteoporosis
• Multifactorial: Vitamin D, calcitonin, hormonal factors, immobility, reduced muscle mass
• Prevalence: 30%-50%
• Fractures: 7%-10%
• Improves after OLT
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Biliary Cirrhosis
• From longstanding obstruction
• Complications of portal hypertension are very common
• Hepatocellular carcinoma is rare
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Laboratory Tests
• Hyperbilirubinemia
• Alkaline phosphatase
• 5’nucleotidase
• ALT and AST
• Bile acids
• Cholesterol
• Copper
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Diagnostic Approach
• Careful history and physical examination
• Laboratory tests (LFTs, AMA, pANCA, CA 19-9)
• Imaging: US, CT, MRCP/ERCP/PTC
• Liver biopsy
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Management
Pruritus
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Management Pruritus
• Plasmapheresis/hemoperfusion Transiently
effective
• Phototherapy Benefit in anecdotal reports
• OLT Pruritus associated with chronic liver
disease, refractory and impacting on quality of
life.
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Management
Fat and Vitamin Malabsorption
• Adequate caloric intake
• 30-40 grams of fat a day
• Medium-chain triglycerides
• Calcium supplements
• Parenteral vitamin K
• Document and replace vitamins A, D and E
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Management
Bone Disease
• Bone densitometry
• Correct vitamin D deficiency
• Calcium supplements
• Biphosphonates Alendronate
• Calcitonin and fluoride experimental
• HRT?????
• Prevention through physical exercise, avoid
steroids
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Management
Extrahepatic Biliary Obstruction
• Relieve the obstruction (ERCP, PTC,
surgery)
• Treat the underlying condition
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Isolated bilirubin
Indirect Direct
Hemolysis Dubin Johnson
Medications Rotor Syndrome
Inherited diseases
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Bilirubin with LFTs
ALT AST Alk phos
Viral serologies Non dilated Dilated ducts
ANA, SMA (US)
Tox screen
Ceruloplasmin Liver bx
CT/MRCP
ERCP
Liver biopsy?
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Cholestatic vs Hepatocellular
Observed ALT Observed Alk Phos
Normal ALT Normal Alk Phos
If R > 5 = Hepatocellular
R
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• Suggested reading:
• Harrison’s Principles of Internal Medicine
Chapter 45: Jaundice
• Sherlock Sheila. Diseases of the Liver and
Biliary System
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