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