Pathology of extrahepatic biliary tract and pancreas

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Pathology of extrahepatic biliary tract and
pancreas

• MUDr. Helena Skálová

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Normal biliary tract

• Liver produces 1 liter of bile per day
• Storage of concentrated bile in gallbladder
• Release after meal
• Bile ducts are essential
• Gallbladder is not

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Pathology of biliary tract

• Inborn malformations
• Cholelithiasis
• Cholecystitis, cholangoitis
• PBC, PSC
• Tumors

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Inborn malformations

• Atresia of biliary ducts
• narrowing or total closure of the whole lenght of
  extrahepatic bile ducts or segmetally
• ethiopathogenesis variable, often unknown
  (chromosomal defects, viral infections)
• symptoms cholestatis in days-weeks after birth,
  progresses to biliary cirrhosis
• most frequent cause od death from liver disease
  in early childhood
• therapy surgery, liver transplantation
• Cyst of choledochus
• mostly females, up to 10 years old
• tumor-like mass
• symptoms asymptomatic, pain, icterus
• therapy surgery

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Cholesterolosis

• Strawberry gallbladder
• Macrophages with cholesterol
• Clinically insignificant

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Cholelithiasis

• Bile stones in biliary tract
• 10-20 of adults in developed countries
• Risk factors age, female, pregnancy, obesity,
  bile stasis, hyperlipidemia, biliary infection
• Cholesterol stones
• Pigment stones
• Mixed stones

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Cholesterol stones

• 80 of bile stones
• Pathogenesis
• supersaturation of bile with cholesterol
• slow motility of gallbladder
• nucleation into cystals
• aggregation into stones in mucous
• Yellow - white, transparent
• Solitary / a few

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Pigment stones

• Pathogenesis
• inflammation (? acidicity)
• hemolysis (overload with bilirubin)
• Black, hard or brown, soft
• Factes, multiple

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Mixed stones

• Cholesterol core, pigmented surface
• Solitary / multiple

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LocationCholecystolithiasis, hepaticolithiasis,
choledocholithiasis
? ? symptoms, complications
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Cholecystolithiasis

• Most common
• 70 asymptomatic
• Cholecystitis, hydrops
• Carcinoma of gallbladder
• No icterus
• Stools and urine normal

!
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Choledocholithiasis

• Intrahepatic cholestasis
• Obstructive icterus
• Pale stools
• Dark urine
• Bile colic / strong constant pain
• Long-term ? secondary biliary cirrhosis

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Complications of cholelithiasis

• Acute / chronic cholecystitis, cholangoitis
• Hydrops of gallbladder
• Empyema of gallbladder
• Decubital ulcers
• Perforation, peritonitis
• Fistula to duodenum, colon
• Biliary ileus
• Obstructive icterus (conjugated
  hyperbilirubinemia)
• Biliary cirrhosis
• Pancreatitis
• Carcinoma of gallbladder

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Acute cholangoitis

• Suppurative inflammation
• Infection stones or tumor
• May spread to intrahepatic ducts ? cholangiogenic
  abscesses ? sepsis
• Obstructive icterus
• Therapy restore bile drainage, atb

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Chronic cholangoitis

• Chronic inflammation accompanying obstruction of
  bile ducts
• Prominent fibrosis
• Stenosis
• Attacks of icterus, sepsis
• Secondary biliary cirrhosis

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Acute cholecystitis

• Calculous (90)
• obstruction of gallbladder neck or ductus
  cysticus
• ? ischemia, toxic agents from bile ? aseptic
  
• inflammation ? infection (E.coli)
• rarely primarily bacterial (Salmonella typhi)
• older women
• Acalculous
• severly ill patients (surgery, trauma, burns )
• ischemia
• Suppurative (empyema)
• Decubital necrosis, ulcer
• Gangrenous
• Complications rupture (esp. acalculous),
  peritonitis

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Chronic cholecystitis

• Very common
• Traumatization by bile stones, repeated mild
  acute cholecystitis, mild infection
• Wall thicker (fibrosis, hypertrophy of mucosa) or
  thinner (atrophy)
• Mucosa metaplasia (gastric, intestinal),
  dysplasia (low / high grade)
• Hydrops chronic obstruction, atrophy, fibrosis,
  clear secretion
• Porcelain gallbladder calcified
• Decubital necrosis
• RF for carcinoma of gallbladder

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Symptoms of cholecystitis

• Chronic
• Milder course
• Recurrent atacks of steady
• or colicky pain
• Nausea, vominting
• Intolerance for fatty food
• Therapy cholecystectomy

• Acute
• Sudden onset
• Pain
• Signs of sepsis
• Nausea, vomiting
• Subsides in 1-10 days
• Relapses more intensively
• Therapy cholecystectomy

Icterus present ONLY if the inflammation
spreads to choledochus or common hepatic duct
and obstructs them
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Diseases involving intrahepatic bile ducts

• Primary biliary cirrhosis
• (PBC)
• Autoimmune nonsupurrative destruction of small
  and medium-sized intrahepatic bile ducts, portal
  inflammation
• Fibrosis, biliary cirrhosis
• Middle-aged women

• Primary sclerosing cholangitis
• (PSC)
• Etiopathogenesis unknown
• Association with IBD
• (70 of patients have UC)
• Inflammation and obliterative fibrosis of intra-
  and extrahepatic larger bile ducts
• Dilatation of preserved segments
• Biliary cirrhosis
• Middle-aged men

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Tumors of gallbladder

• Adenoma
• tubular, vilous, tubulovilous
• low / high grade dysplasia
• Adenocarcinoma
• 7th decade, slightly more women
• 80 associated with gallstones (chronic
  inflammation)
• Asia higher of pyogenic and parasitic diseases
  (without gallstones)
• infiltrating (scirrhotic) / exophytic
• fundus, neck
• invades directly into bile ducts, liver,
  peritoneum, LN
• metastases LN, peritoneum, GIT, lungs
• symptoms similar to cholecystitis
• diagnosis late, after cholecystectomy

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Adenocarcinoma of extrahepatic bile ducts

• Uncommon
• Older age, slightly more men
• 30 associated with gallstones
• RF PSC, UC, choledodal cyst, fluke infection
  (Asia)
• Symptoms painless, progressive jaundice, nausea,
  vomiting, weight loss, hepatomegaly, palpable
  gallbladder
• Diagnosis early, but tumor is usually not
  resectable
• Spreads along bile ducts, metastases in LN
• Klatskin tumor
• slowly growing sclerotizing tumor from large
  ducts at liver hilus, rare metastases
• Carcinoma of the ampula of Vater
• origin may be also in pancreas or duodenum

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Normal pancreas

• Exocrine component (80)
• Acinar cells cca 20 digestive enzymes (trypsin,
  chymotripsin, aminopeptidases, lipasis, amylasis,
  fosfolipasis )
• Ductules, dutcs bicarbonate
• Regulation by secretin and cholecystokinin
  (produced by duodenal mucosa) and n. vagus
• 1-3 l of pancreatic juice / day
• Protective mechanisms (inactive precursors,
  inhibitors)
• Endocrine component
• Langerhans islets (insulin, glucagon,
  somatostatin)

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Inborn malformations

• Agenesis
• rare, associated with widespread malformations
• Pancreas divisum
• common, failure of fusion of dorsal and ventral
  part
• Annular pancreas
• ring around duodenum
• Ectopic pancreas
• common in stomach, duodenum
• Inborn cysts solitary, multiple
• Polycystosis kidney, liver, pancreas

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Cystic fibrosis mucoviscidosis, cystic
pancreatofibrosis

• White rase, incidence in CR 12500
• AR, mutation in CFTR gene
• 2-5 of people are heterozygots (carriers)
• Defective ion (chloride) transportation
• Highly viscous mucous
• ? obstruction of ducts in exocrine
• glands
• ? dilatation of terminal ducts and
• acini (cysts)
• ? atrophy ? fibrosis

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Symptoms of cystic fibrosis

• Pancreas malabsorption, steatorrhea,
  hypovitaminosis, DM (10)
• Intestine meconium ileus in newborns
• Bile ducts cholestasis, biliary cirrhosis
• Salivary, lacrimal glands xerostomia,
  xerophtalmia
• Epidydimis infertility
• Skin salty sweat (diagnostic)

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Cystic fibrosis in lungs

•  

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Cystic fibrosis

• Therapy
• substitution of pancreatic enzymes
• vaccination, atb, NSAID
• mucolytics, oxygenotherapy
• lung transplantation
• Prognosis
• without therapy death in childhood
• with advanced therapy between 30-40 years

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Acute pancreatitis

• Common (Western countries)
• Etiology
• Biliary diseases
• Alcoholism (exacerbation of chronic pancreatitis)
• Others obstruction of pancreatic ducts, drugs,
  infections, parasites, ischemia, trauma, genetics
• Types of acute pancreatitis
• Intersticial nonsuppurative accompanies
  systemic infections (e.g. endemic parotitis)
• Intersticial suppurative after hemorrhagic
  necrotizing, hematogenous
• Hemorrhagic necrotizing

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Pathogenesis and morphology of acute hemorrhagic
necrotizing pancreatitis

• Obscure
• Key role of activation of tripsinogen, which then
  activates other enzymes
• Autodigestion necrosis and liquefaction of
  pancreas
• Lipase fatty tissue necroses
• Hypocalcemia precipitation of Ca soaps in fat
  necroses
• Elastase vascular destruction, hemorrhage
• Coagulative cascade DIC
• Enzymes enter blood circulation
• Lipase - fatty tissue necroses in distant sites
• Phospholipids surfactant destruction, ARDS
• Loss of blood volume, electrolyte disturbance,
  release of cytokines, vasoactive factors - shock

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Symptoms of full-blown acute hemorrhagic
necrotizing pancreatitis

• Severe constant abdominal pain, vomiting
• Rapidly progresses to shock and circulatory
  failure, DIC, acute tubular necrosis, ARDS
• Lab ? amylase, lipase in plasma, leucocytosis,
  hypocalcemia
• 20 mortality
• Therapy total restriction of food
• and fluid, supportive therapy
• Consequences in surviving patients
• pancreatic abscess (G- bactieria)
• pancreatic pseudocyst
• scarring

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Chronic pancreatitis

• Etiology
• alcoholism (most common)
• chronic obstruction of pancreatic ducts
  (pseudocyst, concrements, tumor)
• hereditary
• autoimmune
• tropical (malnutrition, Africa, Asia)
• idiopathic
• Chronic inflammation, fibrosis, duct dilation,
  destruction of exocrine and much later also
  endocrine parenchyma
• Irreversible destruction and decrease of function

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Chronic pancreatitis

• Symptoms
• attacks of pain
• maldigestion
• jaundice
• malabsorption, weight loss, hypoalbuminemic edema
• diabetes mellitus
• pseudocyst
• RF for pancreatic carcinoma

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Tumors

• Pseudotumors
• Congenital cyst
• Pseudocyst
• Benign tumors
• Serous cystadenoma
• Tumors of variable behaviour (low, high grade
  dysplasia, malignant)
• Mucinous cystic neoplasm (MCN)
• Intraductal papillary mucinous neoplasm (IPMN)
• Malignant tumors
• Carcinoma

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Precancerous lesions

• Pancreatic intraepithelial neoplasia (PanIN)
• Low grade (PanIN 1)
• Intermediate grade (PanIN 2)
• High grade (PanIN 3)
• Mucinous cystic neoplasm (MCN)
• Intraductal papillary mucinous neoplasm (IPMN)

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Pancreatic carcinoma

• 6. 8. decade, slightly more common in black
  race
• Association with smoking, chronic pancreatitis,
  diabetes mellitus
• High mortality
• Ductal adenocarcinoma with abundant desmoplastic
  stroma
• Symptoms - late
• long-term silent
• 60 in head ? obstructive jaundice (tail, body
  without jaundice)
• weight loss, weakness, anorexia, cachexia
• thrombophlebitis migrans
• pain (perineural spread)
• Metastases LN, liver, lungs, bones
• Dif. dg. chronic pancreatitis

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SummaryConsequences of cholelithisis
Biliary cirrhosis
Chronic cholangitis
Acute cholangitis
Cholelithiasis
Acute cholecystitis
Acute pancreatitis
Chronic cholecystitis
Chronic pancreatitis
Carcinoma of gallbladder