Pathology of extrahepatic
biliary tract and pancreas
MUDr. Helena Skálová
Normal biliary tract
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Liver produces 1 liter of bile per day
Storage of concentrated bile in gallbladder
Release after meal
Bile ducts are essential
Gallbladder is not
Pathology of biliary tract
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Inborn malformations
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Cholelithiasis
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Cholecystitis, cholangoitis
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PBC, PSC
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Tumors
Inborn malformations
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Atresia of biliary ducts:
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narrowing or total closure of the whole lenght of extrahepatic bile ducts
or segmetally
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ethiopathogenesis variable, often unknown (chromosomal defects, viral
infections)
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symptoms: cholestatis in days-weeks after birth, progresses to biliary
cirrhosis
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most frequent cause od death from liver disease in early childhood
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therapy: surgery, liver transplantation
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Cyst of choledochus:
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mostly females, up to 10 years old
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tumor-like mass
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symptoms: asymptomatic, pain, icterus
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therapy: surgery
Cholesterolosis
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Strawberry gallbladder
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Macrophages with cholesterol
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Clinically insignificant
Cholelithiasis
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Bile stones in biliary tract
10-20% of adults in developed countries
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Risk factors: age, female, pregnancy, obesity, bile stasis,
hyperlipidemia, biliary infection
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Cholesterol stones
Pigment stones
Mixed stones
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Cholesterol stones
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80% of bile stones
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Pathogenesis:
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supersaturation of bile with cholesterol
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slow motility of gallbladder
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nucleation into cystals
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aggregation into stones in mucous
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Yellow - white, transparent
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Solitary / a few
Pigment stones
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Pathogenesis:
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inflammation (↑ acidicity)
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hemolysis (overload with bilirubin)
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Black, hard or brown, soft
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Factes, multiple
Mixed stones
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Cholesterol core, pigmented surface
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Solitary / multiple
Location
Cholecystolithiasis, hepaticolithiasis, choledocholithiasis
Cholecystolithiasis
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Most common
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70% asymptomatic
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Cholecystitis, hydrops
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Carcinoma of gallbladder
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No icterus
Stools and urine normal
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!
Choledocholithiasis
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Intrahepatic cholestasis
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Obstructive icterus
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Pale stools
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Dark urine
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Bile colic / strong constant
pain
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Long-term → secondary
biliary cirrhosis
Complications of cholelithiasis
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Acute / chronic cholecystitis,
cholangoitis
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Hydrops of gallbladder
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Empyema of gallbladder
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Decubital ulcers
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Perforation, peritonitis
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Fistula to duodenum, colon
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Biliary ileus
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Obstructive icterus (conjugated
hyperbilirubinemia)
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Biliary cirrhosis
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Pancreatitis
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Carcinoma of gallbladder
Acute cholangoitis
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Suppurative inflammation
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Infection + stones or tumor
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May spread to intrahepatic ducts →
cholangiogenic abscesses → sepsis
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Obstructive icterus
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Therapy: restore bile drainage, atb
Chronic cholangoitis
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Chronic inflammation
accompanying obstruction of bile
ducts
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Prominent fibrosis
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Stenosis
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Attacks of icterus, sepsis
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Secondary biliary cirrhosis
Acute cholecystitis
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Calculous (90%):
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obstruction of gallbladder neck or ductus cysticus
→ ischemia, toxic agents from bile → aseptic
inflammation → infection (E.coli)
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rarely primarily bacterial (Salmonella typhi)
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older women
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Acalculous:
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severly ill patients (surgery, trauma, burns …)
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ischemia
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Suppurative (empyema)
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Decubital necrosis, ulcer
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Gangrenous
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Complications: rupture (esp. acalculous), peritonitis
Chronic cholecystitis
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Very common
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Traumatization by bile stones, repeated
mild acute cholecystitis, mild infection
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Wall thicker (fibrosis, hypertrophy of
mucosa) or thinner (atrophy)
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Mucosa – metaplasia (gastric, intestinal),
dysplasia (low / high grade)
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Hydrops – chronic obstruction, atrophy,
fibrosis, clear secretion
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Porcelain gallbladder – calcified
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Decubital necrosis
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RF for carcinoma of gallbladder
Symptoms of cholecystitis
Acute:
Chronic:
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Sudden onset
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Milder course
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Pain
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Recurrent atacks of steady
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Signs of sepsis
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Nausea, vomiting
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Subsides in 1-10 days
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Relapses more intensively
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Therapy: cholecystectomy
or colicky pain
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Nausea, vominting
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Intolerance for fatty food
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Therapy: cholecystectomy
Icterus – present ONLY if the inflammation spreads to choledochus
or common hepatic duct and obstructs them
Diseases involving intrahepatic bile ducts
Primary biliary cirrhosis
Primary sclerosing cholangitis
(PBC):
(PSC):
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Autoimmune nonsupurrative
destruction of small and
medium-sized intrahepatic bile
ducts, portal inflammation
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Etiopathogenesis unknown
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Association with IBD
(70% of patients have UC)
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Fibrosis, biliary cirrhosis
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Inflammation and obliterative fibrosis of
intra- and extrahepatic larger bile ducts
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Middle-aged women
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Dilatation of preserved segments
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Biliary cirrhosis
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Middle-aged men
Tumors of gallbladder
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Adenoma:
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tubular, vilous, tubulovilous
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low / high grade dysplasia
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Adenocarcinoma:
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7th decade, slightly more women
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80% associated with gallstones
(chronic inflammation)
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Asia: higher % of pyogenic and parasitic
diseases (without gallstones)
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infiltrating (scirrhotic) / exophytic
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fundus, neck
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invades directly into bile ducts, liver,
peritoneum, LN
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metastases: LN, peritoneum, GIT, lungs
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symptoms: similar to cholecystitis
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diagnosis: late, after cholecystectomy
Adenocarcinoma of extrahepatic bile ducts
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Uncommon
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Older age, slightly more men
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30% associated with gallstones
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RF: PSC, UC, choledodal cyst, fluke infection (Asia)
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Symptoms: painless, progressive jaundice, nausea,
vomiting, weight loss, hepatomegaly, palpable
gallbladder
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Diagnosis: early, but tumor is usually not resectable
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Spreads along bile ducts, metastases in LN
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Klatskin tumor:
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slowly growing sclerotizing tumor from large ducts
at liver hilus, rare metastases
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Carcinoma of the ampula of Vater:
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origin may be also in pancreas or duodenum
Normal pancreas
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Exocrine component (80%):
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Acinar cells – cca 20 digestive
enzymes (trypsin, chymotripsin,
aminopeptidases, lipasis, amylasis,
fosfolipasis …)
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Ductules, dutcs – bicarbonate
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Regulation by secretin and
cholecystokinin (produced by duodenal
mucosa) and n. vagus
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1-3 l of pancreatic juice / day
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Protective mechanisms (inactive
precursors, inhibitors)
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Endocrine component:
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Langerhans islets (insulin, glucagon,
somatostatin)
Inborn malformations
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Agenesis
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rare, associated with widespread
malformations
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Pancreas divisum
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common, failure of fusion of dorsal and
ventral part
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Annular pancreas
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ring around duodenum
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Ectopic pancreas
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common in stomach, duodenum
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Inborn cysts – solitary, multiple
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Polycystosis – kidney, liver, pancreas
Cystic fibrosis
= mucoviscidosis, cystic pancreatofibrosis
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White rase, incidence in CR 1:2500
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AR, mutation in CFTR gene
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2-5% of people are heterozygots
(carriers)
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Defective ion (chloride)
transportation
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Highly viscous mucous
→ obstruction of ducts in exocrine
glands
→ dilatation of terminal ducts and
acini (cysts)
→ atrophy → fibrosis
Symptoms of cystic fibrosis
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Pancreas: malabsorption, steatorrhea, hypovitaminosis, DM (10%)
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Intestine: meconium ileus in newborns
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Bile ducts: cholestasis, biliary cirrhosis
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Salivary, lacrimal glands: xerostomia, xerophtalmia
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Epidydimis: infertility
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Skin: salty sweat (diagnostic)
Cystic fibrosis in lungs
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Most severe changes (90% of deaths)
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Retention of viscous mucous in respiratory tract
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Squamous metaplasia
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Chronic bronchitis
→ bronchiectasias
→ repeated bronchopneumonia
→ lung abscesses
→ fibrosis
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Staphylococcus aureus
Pseudomonas aeruginosa
Burkholderia cepacia
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Cor pulmonale chronicum
Cystic fibrosis
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Therapy:
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substitution of pancreatic enzymes
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vaccination, atb, NSAID
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mucolytics, oxygenotherapy
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lung transplantation
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Prognosis:
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without therapy death in childhood
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with advanced therapy between 30-40
years
Acute pancreatitis
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Common (Western countries)
Etiology:
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Biliary diseases
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Alcoholism (exacerbation of chronic pancreatitis)
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Others: obstruction of pancreatic ducts, drugs, infections, parasites,
ischemia, trauma, genetics
Types of acute pancreatitis:
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Intersticial nonsuppurative – accompanies systemic infections (e.g. endemic
parotitis)
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Intersticial suppurative – after hemorrhagic necrotizing, hematogenous
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Hemorrhagic necrotizing
Pathogenesis and morphology of acute hemorrhagic
necrotizing pancreatitis
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Obscure
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Key role of activation of tripsinogen, which then activates other enzymes
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Autodigestion – necrosis and liquefaction of pancreas
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Lipase – fatty tissue necroses
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Hypocalcemia – precipitation of Ca soaps in fat necroses
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Elastase – vascular destruction, hemorrhage
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Coagulative cascade – DIC
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Enzymes enter blood circulation:
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Lipase - fatty tissue necroses in distant sites
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Phospholipids – surfactant destruction, ARDS
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Loss of blood volume, electrolyte disturbance, release of cytokines, vasoactive factors
- shock
Symptoms of full-blown acute hemorrhagic
necrotizing pancreatitis
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Severe constant abdominal pain, vomiting
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Rapidly progresses to shock and circulatory failure, DIC, acute tubular
necrosis, ARDS
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Lab: ↑ amylase, lipase in plasma, leucocytosis, hypocalcemia
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20% mortality
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Therapy: total restriction of food
and fluid, supportive therapy
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Consequences in surviving patients:
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pancreatic abscess (G- bactieria)
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pancreatic pseudocyst
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scarring
Chronic pancreatitis
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Etiology:
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alcoholism (most common)
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chronic obstruction of pancreatic ducts (pseudocyst, concrements,
tumor…)
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hereditary
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autoimmune
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tropical (malnutrition, Africa, Asia)
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idiopathic
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Chronic inflammation, fibrosis, duct dilation, destruction of
exocrine and much later also endocrine parenchyma
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Irreversible destruction and decrease of function
Chronic pancreatitis
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Symptoms:
attacks of pain
maldigestion
jaundice
malabsorption, weight loss, hypoalbuminemic edema
diabetes mellitus
pseudocyst
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RF for pancreatic carcinoma
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Tumors
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Pseudotumors:
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Congenital cyst
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Pseudocyst
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Benign tumors:
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Serous cystadenoma
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Tumors of variable behaviour (low, high grade dysplasia, malignant):
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Mucinous cystic neoplasm (MCN)
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Intraductal papillary mucinous neoplasm (IPMN)
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Malignant tumors:
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Carcinoma
Precancerous lesions
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Pancreatic intraepithelial
neoplasia (PanIN):
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Low grade (PanIN 1)
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Intermediate grade (PanIN 2)
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High grade (PanIN 3)
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Mucinous cystic neoplasm (MCN)
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Intraductal papillary mucinous
neoplasm (IPMN)
Pancreatic carcinoma
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6. – 8. decade, slightly more common in black race
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Association with smoking, chronic pancreatitis, diabetes mellitus
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High mortality
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Ductal adenocarcinoma with abundant desmoplastic stroma
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Symptoms - late:
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long-term silent
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60% in head → obstructive jaundice (tail, body without jaundice)
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weight loss, weakness, anorexia, cachexia
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thrombophlebitis migrans
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pain (perineural spread)
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Metastases: LN, liver, lungs, bones
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Dif. dg.: chronic pancreatitis
Summary:
Consequences of cholelithisis
Acute cholangitis
Biliary cirrhosis
Chronic cholangitis
Cholelithiasis
Acute cholecystitis
Chronic cholecystitis
Carcinoma of gallbladder
Acute pancreatitis
Chronic pancreatitis