Pathology of extrahepatic biliary tract and pancreas MUDr. Helena Skálová.
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Transcript of Pathology of extrahepatic biliary tract and pancreas MUDr. Helena Skálová.
Pathology of extrahepatic biliary tract and pancreas
MUDr. Helena Skálová
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
Pathology of biliary tract
Inborn malformations
Cholelithiasis
Cholecystitis, cholangoitis
PBC, PSC
Tumors
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
Cholesterolosis Strawberry gallbladder Macrophages with cholesterol Clinically insignificant
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 stonesPigment stonesMixed stones
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
Pigment stones Pathogenesis:- inflammation (↑ acidicity)- hemolysis (overload with
bilirubin)
Black, hard or brown, soft Factes, multiple
Cholesterol core, pigmented surface Solitary / multiple
Mixed stones
LocationCholecystolithiasis, hepaticolithiasis, choledocholithiasis
→ → symptoms, complications
Cholecystolithiasis Most common
70% asymptomatic
Cholecystitis, hydrops
Carcinoma of gallbladder
No icterus Stools and urine normal!
Choledocholithiasis
Intrahepatic cholestasis
Obstructive icterus
Pale stools
Dark urine
Bile colic / strong constant pain
Long-term → secondary biliary cirrhosis
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
Acute cholangoitis
Suppurative inflammation Infection + stones or tumor
May spread to intrahepatic ducts → cholangiogenic abscesses → sepsis
Obstructive icterus
Therapy: restore bile drainage, atb
Chronic cholangoitis
Chronic inflammation accompanying obstruction of bile ducts
Prominent fibrosis Stenosis
Attacks of icterus, sepsis
Secondary biliary cirrhosis
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
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
Symptoms of cholecystitis
Acute:
Sudden onset Pain Signs of sepsis Nausea, vomiting
Subsides in 1-10 days Relapses more intensively
Therapy: cholecystectomy
Chronic:
Milder course Recurrent atacks of steady
or colicky pain Nausea, vominting Intolerance for fatty food
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
(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
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
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
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)
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
Cystic fibrosis= mucoviscidosis, cystic pancreatofibrosis White rase, incidence in CR
1:2500 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
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)
Most severe changes (90% of deaths)
Retention of viscous mucous in respiratory tract
Squamous metaplasia
Chronic bronchitis
→ bronchiectasias
→ repeated bronchopneumonia
→ lung abscesses
fibrosis Staphylococcus aureus
Pseudomonas aeruginosa
Burkholderia cepacia
Cor pulmonale chronicum
Cystic fibrosis in lungs
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
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
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
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
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
Chronic pancreatitis Symptoms:- attacks of pain- maldigestion- jaundice- malabsorption, weight loss, hypoalbuminemic edema- diabetes mellitus- pseudocyst
RF for pancreatic carcinoma
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
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)
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
Summary:Consequences of cholelithisis
Cholelithiasis
Acute cholecystitis
Chronic cholecystitis
Carcinoma of gallbladder
Acute pancreatitis
Chronic pancreatitis
Chronic cholangitisAcute cholangitis
Biliary cirrhosis