Liver III Lecture (& Gallbladder too..) Rob Edwards November 16, 2011
Jan 02, 2016
Liver III Lecture(& Gallbladder too..)
Rob EdwardsNovember 16, 2011
Rob EdwardsNovember 16, 2011
Reading Assignment• Particular emphasis should be placed on the following topics:•• Primary Biliary Cirrhosis vs. Primary Sclerosing Cholangitis
(pp. 867-869)
• Hepatic Venous Outflow Obstruction (p. 873)•• Nodular Hyperplasias, Benign and Malignant Neoplasms (pp.
875-880)•• Cholelithiasis (Gallstones) & Cholecystitis (pp. 882-886)•• Carcinoma of the Gallbladder (pp.888)
Outline
• Obstructive biliary disease • Circulatory Disorders• Liver Masses and Neoplasms• Biliary Tract
– Gallstones– Cholangitis– Cholangiocarcinoma
Imaging the Bile Ducts:
ERCP• Scope thru Stomach
to 1st segment of Duodenum
• Cannulate CBD via major papilla (duct of Wirsung)
• Shoot contrast, light up CBD, intrahepatic R&L bile ducts, branches by fluoroscopy
Obstructive Biliary Disease• May be extrahepatic
– 2o Biliary Cirrhosis (chronic obstruction of the extrahepatic bile ducts)
• Or intrahepatic– 1o Biliary Cirrhosis– 1o Sclerosing Cholangitis– 2o to other liver dz- drug toxicity,
viral hepatitis
• All can lead to development of cirrhosis:
Secondary Biliary Cirrhosis
• Prolonged extrahepatic obstruction– Most often due to cholelithiasis, malignancy,
post-op strictures
-In kids: biliary atresia, CF, choledochal cysts
• Early: reversible cholestasis, inflammation• Late: Periportal fibrosis/scarring
– Complications: 2o enteric bacterial infection = ascending cholangitis
Primary Biliary Cirrhosis• PF: Autoimmune• Chronic progressive
cholestasis• 40’s-50’s 6:1 F>M• Insidious onset; pruritis, skin
pigmentation, jaundice (late) Granulomatous Inflammatory destruction of intrahepatic bile ducts, periductal autoreactive T-cells
• Many years’ progression to cirrhosis, portal HTN, varices, encephalopathy
Primary Biliary Cirrhosis• Lab:
Hyperbilirubinemia late, implies liver dysfunction
• Hypercholesterolemia = xanthelasmas
• 90% have Antimitochondrial antibodies (anti-PDC E2, leaks from damaged hepatocytes
• Other AI sx: Sicca, RA
Primary Sclerosing Cholangitis• 3rd-5th decade, 2:1 M:F• Segmental inflammation
and fibrosis of intra- and extrahepatic BD’s with intervening dilatations
• PF: Unknown, cytokine-mediated vs. ischemia?
• AI: 75% have anti-SM Ab
• 70% w/ PSC have UC• Micro: Onion-skin fibrosis,
obliteration of duct. Severe cholestasis
• Long term: Inc. Risk of cholangiocarcinoma
http://www.hopkins-gi.org/pages/latin/templates/index.cfm?pg=disease3&organ=6&disease=20&lang_id=1&pagetype=13&pagenum=179
Common Final Pathway: Biliary Cirrhosis
Review - Normal Lobule Flow
Circulatory Disorders (P. 870)
Circulatory Disorders- Inflow• Impaired Arterial Inflow:
– Infarcts rare, but intrahepatic artery occlusion by embolism, tumor compression, vasculitis = Infarct
• Portal Vein Obstruction:– Sx: Abd pain, portal HTN,
varices– Rare, – 50% idiopathic. 2o to
intrabdominal sepsis, hypercoagulable states, trauma
Circulatory Disorders- Intrahepatic• Impaired INTRAhepatic
flow:– Cirrhosis– Sludging in Sickle Cell Dz
• 2o to systemic circulatory compromise:– Right CHF = passive
centrilobular congestion– (NUTMEG LIVER)– Left heart failure: hypoxia,
centrilobular necrosis
Circulatory Disorders-Outflow
• Budd-Chiari Synrdome = Hepatic Vein Thrombosis– Must block multiple main
veins– Assoc w/ hypercoagulable
states (ATIII deficiency, Factor V Leiden, etc)
– Assoc with pregnancy, OCP’s; 10% idiopathic
Liver Masses – Hyperplasias & Neoplasms
• Schema:– Nodular Hyperplasias (NOT neoplastic)
• Focal Nodular Hyperplasia• Nodular Regenerative Hyperplasia
– Benign Neoplasms• Cavernous Hemangioma• Liver cell adenoma
– Malignant Neoplasms• Mets• Hepatocellular Carcinoma• Angiosarcoma
Focal Nodular Hyperplasia
– Congenital vascular abnormality?
– May be symptomatic (if large) or‘incidentalomas’
– Spontaneous, F>M (8:1) 3rd-5th decade. 75% Asx.
– Solitary circumscribed Pale Yellowish mass w/ central scar
– ‘Spoke and Wheel’ pattern on angiography-hyperperfused.
– Thick plates of hepatocytes ONLY!
Nodular Hyperplasias-II• Nodular Regenerative
Hyperplasia:– 2o to portal HTN,
associated w/ altered intrahepatic blood flow:
• Renal Tx, BMT (Veno-occlusive disease)
• Vasculitides
– Involves entire liver – Multiple spherical
nodules, NO fibrosis
Benign Neoplasms- I• Cavernous
Hemangioma• Most common benign
stromal liver neoplasm (1-20% in autopsy studies)
• 1-2 cm subcapsular mass, may be symptomatic if larger (record = ~30cm….)
• DON’T LET A PATHOLOGIST BIOPSY THEM!
• DDX: Mets
Benign Neoplasms- II• Liver Cell Adenomas
– Seen in women using OCP’s. Regress w/ discontinuation.
– May be up to 30 cm!
• Clinical Significance:– ~10% risk of HCC– Subcapsular adenomas
rupture during pregnancy (~20% mortality)
– MICRO: Disorganized hepatocyte cords, very vascular. NO portal tracts within mass!
Malignant Neoplasms
• Primary Carcinomas– HCC (derived from hepatocytes) – 80-90%– Cholangiocarcinoma (derived from BD epithelium)
• 10-20%
Hepatocellular Carcinoma - I
• Hepatocellular Carcinoma– Relatively rare in US (1-2% of cancers, ~14,000
cases, ~14,000 deaths/yr)– 5% of ALL cancer worldwide (75% of cases in
Asia; 0.5-1M deaths/yr worldwide)
• “Two Diseases”:– 85% cases occur in areas endemic for chronic
HBV infection, half have cirrhosis, occurs in 20’s-40’s
– In US – Complicates other liver dz, 90% have cirrhosis, rare before age 60.
Hepatocellular Carcinoma - II
• Pathogenesis:– Three major etiologies:
• Viral Infection (HBV, HCV)• Chronic Alcoholism• Food (Aflatoxins (A. flavus) in grains/peanuts)• Areca nuts (remove from candy dish in waiting room…)
• Path-o-Fizz:– Repeated cell death/regeneration– Mutations in GF genes, LOH in TS genes– Genomic instability with integrated HBV genome
Hepatocellular Carcinoma - III
• Clinical Features of HCC:– Often obscured by comorbid sx of cirrhosis/hepatitis– Upper abdominal pain/fullness, malaise, WT loss– Variable degrees of jaundice, fever, variceal
bleeding
• Lab: Elevated serum -fetoprotein in 50-75%– Lots of false-positives (cirrhosis, liver necrosis)
• Imaging most valuable for small (resectable) lesions
Hepatocellular Carcinoma - IV• Gross: Unifocal or multifocal,
diffusely infiltrative.• Pale, greenish if making bile• Tend to invade major vessels
(IVC up to right atrium!)• Intrahepatic metastasis• Late mets to lung• Death from cachexia,bleeds
• Micro:– Wide degree of differentiation– Cords with >3 cells’ thick– Glandular formations– Poorly diff/anaplastic
Hepatocellular Carcinoma - V
Hepatocellular Carcinoma - VI
• Variant: Fibrolamellar Carcinoma– Seen in younger patients (20-40, M=F)– No association with HBV or Cirrhosis– Better Prognosis (often resectable)– Gross: Solitary, Hard nodule with fibrous
bands, central scar. Characteristic on CT, MR– Micro: Well differentiated cells & dense
collagen bundles
Fibrolamellar Carcinoma - VII
Hepatocellular Carcinoma - VIII
• Most Common Malignancy in the Liver in US?– Metastatic Carcinoma
• Most often from colon
Hepatoblastoma
• Most common liver neoplasm of young childhood
• 2 types:– Epithelial – small polygonal fetal cells
recapitulating liver development– Mixed epithelial-mesenchymal – foci of
primitive mesnchyme/osteoid/cartilage/skeletal muscle
• Death by 1 year if unresectable
Angiosarcoma• Malignant neoplasm of
endothelial cells• Rare • Most common in H&N,
legs. Liver most common visceral site.
• Arises in exposure to vinyl chloride, arsenic, thorotrast (not used anymore!)
• Several decades lag time
• Recur locally
• High grade neoplasms, poor survival
Normal Biliary Tract
• Liver makes 1 L bile/day, concentrated and stored in GB
• GB: Undulating simple columnar epithelium, no submucosa.
Biliary Atresia
• 1/3 of neonatal cholestasis, 1:10,000 live births• = COMPLETE obstruction of extrahepatic biliary
tree in first 3 months of life• Induces rapid (~6 weeks) 2o biliary cirrhosis,
causes 50% of pedi liver transplant.• Fetal form (20%): Congenital, other anomalies• Perinatal form (80%): Normal, but destroyed
postnatally. (toxic insult or Reovirus/rotavirus?)• Rx: Surgical- Kasai procedure
Choledochal Cysts• Congenital dilation of the
CBD• F:M 4:1• Present <10 yo w/ jaundice
or biliary colic• Dilation may be segmental,
or form diverticuli• Predispose to stone
formation, stricture, pancreatitis
• Risk of cholangiocarcinoma in elderly pts.
Cholelithiasis
• Affects 10-20% of Adults wherever calories are not a limiting factor
• ~50 tons of gallstones currently roaming the U.S. as we speak.
• 80% are cholesterol, rest are bilirubin salts• Most are asymptomatic• Risk: Native Americans (>75%), age, ♀• PF: cholesterol supersaturation, GB
hypomotility, crystal nucleation, accretion
Gallstones
• Cholesterol Stones– Multiple, large– Radiolucent if >90%
cholesterol
• Pigmented stones• Smaller• Black if sterile• Brown if 2o cholangitis• Most radioopaque
Cholelithiasis/Cholecystitis
• May be Asx for decades, 1-3% per year become symptomatic– Biliary pain: Colicky (spasmodic due to
contractions), also from cholecystitis
• Complications:• Empyema• Perforation• Cholangitis• Gallstone Pancreatitis
Cholecystitis
• Acute: – 2o to stone obstructing the cystic duct– Rarely seen in post-op pts, trauma, burns, MOF– GB enlarged, Inflammation, serosal fibrin/exudate
• Chronic:– Arises following repeated bouts of acute disease– Smooth serosa, thickened/fibrotic wall– Rokitansky-Aschoff sinuses
Chronic Cholecystitis
Choledocholithiasis • Choledocholithiasis =
Stones in the bile ducts– In US, almost all from
GB– In Asia, pigmented
stones form de novo in ducts, 2o to infection
– May be Asx or cause obstruction, pancreatitis, cholangitis, hepatic abscess, 2o biliary cirrhosis
Cholangitis
• = Bacterial Infection of the Bile Ducts– Can follow any obstruction (stones, tumors,
stents, pancreatitis, strictures)– Iatrogenic: Post-ERCP, T-tube placement– Usually Gram-negative aerobes– May be complicated by sepsis, significant
mortality.
Gallbladder Carcinoma• Uncommon• 7th decade, F>M• Rarely resectable at Dx,
poor prognosis• Sx: Indistiguishable
from cholelithiasis• Infiltrates deep thru
wall, into adj. liver.
Cholangiocarcinoma• DEF: Malignancy of the biliary tree• Risks: PSC, congenital biliary cystic dz, chronic liver fluke
infection• Arise in non-cirrhotic liver, nodular or arborizing• Micro: Adenocarcinoma,well to mod-diff, prominent
desmoplasia• 50% Mets to lung, bone, brain• Advanced at Dx, bad prognosis• Klatskin tumor: CA @ confluence of L+R intrahepatic bile ducts