Hepatobiliary - biliary tract diseases + neoplastic conditions Flashcards
cause of pre-hepatic jaundice
excess production of bilirubin:
- haemolysis (breakdown of RBC)
- ineffective erythropoiesis
cause of hepatic jaundice (3)
- reduced hepatic uptake e.g. drugs
- impaired bilirubin conjugation:
physiologic/ neonatal jaundice
genetic deficiency
diffuse hepatocellular disease - impaired bile flow
AI (autoimmune) cholangiopathies
cause of post-hepatic jaundice
- impaired bile flow
- large duct obstruction
what causes bile duct obstruction (5)
- Gallstones (extrahepatic cholelithiasis)
- Malignancies of biliary tree / head of pancreas
- Inflammatory bile duct strictures
- Porta hepatis lymphadenopathy
- Bile duct malformations/ loss (children)
choledochal cysts, biliary atresia (EHBA), Fibropolycystic disease
bile duct obstruction
- complications
- presentation
intrahepatic cholangitic abscesses/ sepsis
chronic obstruction: Biliary cirrhosis
jaundice, pale stools, tea-coloured urine
hepatholithiasis
intrahepatic biliary stone formation
primary hepatholithiasis complications
recurrent ascending cholangitis, progressive inflammatory destruction / collapse and scarring of hepatic parenchyma
progress to form Biliary Intraepithelial Neoplasia (BilIN) and cholangiocarcinoma (bile duct cancer)
causes of neonatal (14-21 days) cholestasis (5) **
- Cholangiopathies: Extrahepatic biliary atresia (atresia = blocked passageway like a dead end)
- EHBA (Extrahepatic biliary atresia)
- Toxic: Drugs, parenteral nutrition
- Metabolic disease: Tyrosinemia (cannot breakdown tyrosine)
- Infections: CMV, bacterial sepsis
EHBA (Extrahepatic biliary atresia)
- definition
- caution
- presentation
Complete/ partial obstruction of the lumen of the extrahepatic biliary tree within the first 3 months of life
- needs to be identified early and corrected by surgery
jaundice, pale stools, tea-coloured urine (high conjugated bilirubin)
Choledochal cyst
- definition
- complications
Developmental malformation of biliary tree, usually CBD (common bile duct)
stones stenosis strictures pancreatitis risk of bile duct carcinoma
Fibropolycystic disease
- definition
- complications
lesions causing congenital malformations of the biliary tree
- Von Meyenburg complex (small bile duct hamartomas/tumours)
- extra hepatic biliary cysts
- Caroli disease (dilation of bile ducts -> formation of stones
- Congenital hepatic fibrosis
- polycytic renal disease
- cholangiocarcinoma
benign lesions of the liver
HF-BBC
affecting hepatocytes:
- Hepatocellular adenoma
- Focal nodular hyperplasia
affecting bile duct:
- Bile duct hamartoma
- Bile duct adenoma
Cavernous hemangioma**
malignant lesions of the liver
affecting hepatocytes:
- Hepatocellular carcinoma (HCC)**
- Hepatoblastoma
affecting bile duct:
- Cholangiocarcinoma (CC)**
adenocarcinoma - metastasis from the colon/lung/breast -> identify primray site
Angiosarcoma
Focal nodular hyperplasia
- cause
- gross/micro features
- caused by focal alterations in hepatic blood supply
gross:
- well-demarcated but poorly encapsulated
pale nodule with central fibrous scar
non-cirrhotic liver
Micro:
- Fibrous scar with radiating fibrous septa
large misshapen arterial vessels and accompanying ductular reaction, separating hyperplastic hepatocytes No normal bile ducts
Cavernous hemangioma**
- gross/micro features
- complications
most common benign liver tumour
gross:
Subcapsular, discrete, red-blue, soft
spongy appearance
Micro:
- Large vascular channels separated by thin fibrous connective tissue
Complications: **
rupture -> intraperitoneal bleeding, thrombosis, DIVC (Disseminated intravascular coagulation)
is a blood forming tumour - will bleed a lot. DO NOT BIOPSY
Hepatocellular adenoma
- clinical presentation
- risk factor
- incidental, abdominal pain from rapid growth or haemorrhage
- intraabdominal bleeding due to rupture
risk factors: oral contraceptive pill, anabolic steroids
hepato-carcinogenesis
hepatocellular adenoma -> hepatocellular carcinoma
due to mutations:
- beta-catenin activation causing genetic instability
- p53 inactivation
HCC clinical presentation
- Asymptomatic
- Ill-defined upper abdominal pain, malaise, fatigue, weight loss
- Hepatomegaly, abdominal mass or fullness
- distended abdomen
- hematemesis (vomiting of blood)/ black tarry stools
HCC diagnosis
- Serum alpha-fetoprotein (AFP) (insensitive as screening test)
- imaging to detect tumours (taken w/ contrast)
[dont need biopsy to diagnose HCC]
HCC gross features
- Unifocal (usually large) mass
- Multifocal, widely distributed nodules of variable size
- Diffusely infiltrative cancer
apeears pale/ varied (depends on bile production, fatty change, stroma)
HCC micro features
- poorly differentiated
- Trabecular-sinusoidal, pseudoacinar and compact growth patterns
- Polygonal cells with eosinophilic cytoplasm and central round nucleolus with distinct nucleolus
- Pleomorphism
- Bile production
spread of HCC
- vascular (intrahepatic metastasis) forming satellite lesions
- through portal/hepatic vein
prognosis of HCC
factors determining prognosis: Stage, number and size of tumour nodules (tumour burden) vascular spread histologic grade presence of cirrhosis
most die within 2 yrs via
- cachexia (muscle/fat wasting)
- variceal bleeding
- liver failure or hepatic coma
- tumour rupture with fatal haemorrhage
treatment of HCC
- Surgical resection
- Locoregional ablation
- Immunotherapy
- Liver transplantation
hepatoblastoma
- who does it affect
- 2 types
- treatment
- early childhood (<3yrs)
- epithelial
- Mixed epithelial and mesenchymal
Surgical resection and chemotherapy
(fatal if untreated)
cholangiocarcinoma
- causes
- pathogenesis
Carcinoma of bile duct
- Liver fluke infestation** (Opisthorchis, Clonorchis sp. in Thailand, Laos)
- Primary sclerosing cholangitis
- Hepatolithiasis
- Fibropolycystic liver disease
- HBV, HCV infection
- NAFLD
premalignant lesions that progress to form CC:
- Biliary intraepithelial neoplasia (BilIN) 1-3
- intraductal papillary biliary neoplasia
- mucinous cystic neoplasms
chronic inflammation and cholestasis -> promotes somatic mutations or epigenetic alterations
cholangiocarcinoma
- clinical presentation
- prognosis
Extrahepatic tumours:
- present earlier and smaller with biliary obstruction, cholangitis and RUQ pain
- poor prognosis
extrahepatic: 15% at 2 yrs
intrahepatic: 6 mths
gallbladder diseases
- cholelithiasis (gallstones)
- cholecystitis (inflammation)
types of gallstones
- risk factors + pathogenesis
- cholesterol: made of cholesterol, phospholipids, bile salts
caused by supersaturation of bile -> bile stones
gallbladder hypomotility/
mucus hypersecretion - pigmented:
black: caused by increase in secretion of conjugated bilirubin -> hydrolysis
brown: hydrolysed bilirubin glucronides
cholecystitis
- definition
- 3 types
- gallbladder inflammation
- acute/ chronic/ acute on chronic
acute cholecystitis
- clinical presentation
- 2 types
- progressive RUQ pain >6 hrs
- mild fever, tachycardia, sweating, nausea and vomiting
may also progress to be more severe or recur
usually not presented w/ jaundice unless there is CBD obstruction
- Calculous (more common) / acalculous [involvement of gallstones}
Calculous acute cholecystitis (more common) pathogenesis
caused by gallstones obstructing the cystic duct
-> Mucosal phospholipases hydrolyze some toxic product
-> Disruption of normal protective glycoprotein mucus layer
-> mucosal epithelium gets
exposed to direct detergent action of bile salts
-> release of prostaglandins
-> mucosal and mural inflammation
-> Distension and increased intraluminal pressure compromise blood flow to mucosa
-> bacterial contamination
acalculous acute cholecystitis pathogenesis
cause by ischemia - decrease in blood flow from cystic artery
ischemia causes the inflammation -> Inflammation and oedema of wall further compromises blood flow, with gallbladder stasis, biliary sludge and gallbladder mucus causing cystic duct obstruction in the absence of stones
(vicious cycle)
gross features of acute cholecystitis
- Enlarged, tense edematous and congested
- Violaceous to green-black
- Fibrinous/ fibrinopurulent serosal exudates
- GB mucosa ulcerated
- calculous AC will present w/ gallstones
acute cholecystitis complications (5)
- Gangrene (with perforation and peritonitis) or empyema (pus in pleural cavity)
- Pericholecystic and subdiaphragmatic abscesses
- Ascending cholangitis
- liver abscesses
- Septicaemia
chronic cholecystitis
gross and micro features
- caused by progression of acute cholecystitis
- Contracted, thickened wall, smooth mucosa +/-calculi
- Chronic inflammatory infiltrates
- Fibromuscular hypertrophy
- Rokitansky-Aschoff sinuses
- Subserosal fibrosis
gallbladder carcinoma
- males/females more affected
- risk factors
- affects females more
risk factors
- gallstones
- chronic infections: bacterial/parasitic
gallbladder carcinoma
- metastasis
- prognosis
Direct invasion: liver, stomach and duodenum (surrounding organs)
Metastases: liver, regional lymph nodes, lungs
Prognosis is poor
gallbladder carcinoma
- gross and micro features
Diffuse (70%) / infiltrating
Polypoid (30%) / exophytic
micro: usually adenocarcinoma (glandular)
most common cause of HCC
hep C viral infection
acute cholecystitis pathogenesis
- mucosal phospholipases hydrolyse luminal lecithins, forming toxic lysolecithins
- disruption of normal protective glycogen mucus layer:
mucosal epithelium exposed to direct detergent action of bile salts - prostaglandins released within the wall of distended gallbladder causes mucosal and mural inflammation
- distension and increased intraluminal pressure compromise blood flow to mucosa
- risk of bacterial contamination
