Pathology of extrahepatic billiary tract and pancreas
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Transcript Pathology of extrahepatic billiary tract and pancreas
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 stones
Pigment stones
Mixed 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
Mixed stones
Cholesterol core, pigmented surface
Solitary / multiple
Location
Cholecystolithiasis, hepaticolithiasis, choledocholithiasis
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:
Chronic:
Sudden onset
Milder course
Pain
Recurrent atacks of steady
Signs of sepsis
Nausea, vomiting
Subsides in 1-10 days
Relapses more intensively
Therapy: cholecystectomy
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
Primary sclerosing cholangitis
(PBC):
(PSC):
Autoimmune nonsupurrative
destruction of small and
medium-sized intrahepatic bile
ducts, portal inflammation
Etiopathogenesis unknown
Association with IBD
(70% of patients have UC)
Fibrosis, biliary cirrhosis
Inflammation and obliterative fibrosis of
intra- and extrahepatic larger bile ducts
Middle-aged women
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)
Cystic fibrosis in lungs
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
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
Acute cholangitis
Biliary cirrhosis
Chronic cholangitis
Cholelithiasis
Acute cholecystitis
Chronic cholecystitis
Carcinoma of gallbladder
Acute pancreatitis
Chronic pancreatitis