Hepatobiliary - biliary tract diseases + neoplastic conditions

Question 1

cause of pre-hepatic jaundice

Answer 1

excess production of bilirubin:

• haemolysis (breakdown of RBC)
• ineffective erythropoiesis

Question 2

cause of hepatic jaundice (3)

Answer 2

• reduced hepatic uptake e.g. drugs
• impaired bilirubin conjugation:
  physiologic/ neonatal jaundice
  genetic deficiency
  diffuse hepatocellular disease
• impaired bile flow
  AI (autoimmune) cholangiopathies

Question 3

cause of post-hepatic jaundice

Answer 3

• impaired bile flow

- large duct obstruction

Question 4

what causes bile duct obstruction (5)

Answer 4

• 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

Question 5

bile duct obstruction

• complications
• presentation

Answer 5

intrahepatic cholangitic abscesses/ sepsis

chronic obstruction: Biliary cirrhosis

jaundice, pale stools, tea-coloured urine

Question 6

hepatholithiasis

Answer 6

intrahepatic biliary stone formation

Question 7

primary hepatholithiasis complications

Answer 7

recurrent ascending cholangitis, progressive inflammatory destruction / collapse and scarring of hepatic parenchyma

progress to form Biliary Intraepithelial Neoplasia (BilIN) and cholangiocarcinoma (bile duct cancer)

Question 8

causes of neonatal (14-21 days) cholestasis (5) **

Answer 8

• 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

Question 9

EHBA (Extrahepatic biliary atresia)

• definition
• caution
• presentation

Answer 9

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)

Question 10

Choledochal cyst

• definition
• complications

Answer 10

Developmental malformation of biliary tree, usually CBD (common bile duct)

stones
stenosis
strictures
pancreatitis
risk of bile duct carcinoma

Question 11

Fibropolycystic disease

• definition
• complications

Answer 11

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

Question 12

benign lesions of the liver

Answer 12

HF-BBC
affecting hepatocytes:
- Hepatocellular adenoma
- Focal nodular hyperplasia

affecting bile duct:

• Bile duct hamartoma
• Bile duct adenoma

Cavernous hemangioma**

Question 13

malignant lesions of the liver

Answer 13

affecting hepatocytes:

• Hepatocellular carcinoma (HCC)**
• Hepatoblastoma

affecting bile duct:
- Cholangiocarcinoma (CC)**

adenocarcinoma - metastasis from the colon/lung/breast -> identify primray site

Angiosarcoma

Question 14

Focal nodular hyperplasia

• cause
• gross/micro features

Answer 14

• 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

Question 15

Cavernous hemangioma**

• gross/micro features
• complications

Answer 15

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

Question 16

Hepatocellular adenoma

• clinical presentation
• risk factor

Answer 16

• incidental, abdominal pain from rapid growth or haemorrhage
• intraabdominal bleeding due to rupture

risk factors: oral contraceptive pill, anabolic steroids

Question 17

hepato-carcinogenesis

hepatocellular adenoma -> hepatocellular carcinoma

Answer 17

due to mutations:

• beta-catenin activation causing genetic instability
• p53 inactivation

Question 18

HCC clinical presentation

Answer 18

• Asymptomatic
• Ill-defined upper abdominal pain, malaise, fatigue, weight loss
• Hepatomegaly, abdominal mass or fullness
• distended abdomen
• hematemesis (vomiting of blood)/ black tarry stools

Question 19

HCC diagnosis

Answer 19

• Serum alpha-fetoprotein (AFP) (insensitive as screening test)
• imaging to detect tumours (taken w/ contrast)
  [dont need biopsy to diagnose HCC]

Question 20

HCC gross features

Answer 20

• Unifocal (usually large) mass
• Multifocal, widely distributed nodules of variable size
• Diffusely infiltrative cancer

apeears pale/ varied (depends on bile production, fatty change, stroma)

Question 21

HCC micro features

Answer 21

• poorly differentiated
• Trabecular-sinusoidal, pseudoacinar and compact growth patterns
• Polygonal cells with eosinophilic cytoplasm and central round nucleolus with distinct nucleolus
• Pleomorphism
• Bile production

Question 22

spread of HCC

Answer 22

• vascular (intrahepatic metastasis) forming satellite lesions
• through portal/hepatic vein

Question 23

prognosis of HCC

Answer 23

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

Question 24

treatment of HCC

Answer 24

• Surgical resection
• Locoregional ablation
• Immunotherapy
• Liver transplantation

Question 25

hepatoblastoma - who does it affect - 2 types - treatment

Answer 25

- early childhood (<3yrs) - epithelial - Mixed epithelial and mesenchymal Surgical resection and chemotherapy (fatal if untreated)

Question 26

cholangiocarcinoma - causes - pathogenesis

Answer 26

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

Question 27

cholangiocarcinoma - clinical presentation - prognosis

Answer 27

Extrahepatic tumours: - present earlier and smaller with biliary obstruction, cholangitis and RUQ pain - poor prognosis extrahepatic: 15% at 2 yrs intrahepatic: 6 mths

Question 28

gallbladder diseases

Answer 28

- cholelithiasis (gallstones) | - cholecystitis (inflammation)

Question 29

types of gallstones | - risk factors + pathogenesis

Answer 29

- 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

Question 30

cholecystitis - definition - 3 types

Answer 30

- gallbladder inflammation | - acute/ chronic/ acute on chronic

Question 31

acute cholecystitis - clinical presentation - 2 types

Answer 31

- 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}

Question 32

Calculous acute cholecystitis (more common) pathogenesis

Answer 32

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

Question 33

acalculous acute cholecystitis pathogenesis

Answer 33

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)

Question 34

gross features of acute cholecystitis

Answer 34

- Enlarged, tense edematous and congested - Violaceous to green-black - Fibrinous/ fibrinopurulent serosal exudates - GB mucosa ulcerated - calculous AC will present w/ gallstones

Question 35

acute cholecystitis complications (5)

Answer 35

- Gangrene (with perforation and peritonitis) or empyema (pus in pleural cavity) - Pericholecystic and subdiaphragmatic abscesses - Ascending cholangitis - liver abscesses - Septicaemia

Question 36

chronic cholecystitis | gross and micro features

Answer 36

- caused by progression of acute cholecystitis - Contracted, thickened wall, smooth mucosa +/-calculi - Chronic inflammatory infiltrates - Fibromuscular hypertrophy - Rokitansky-Aschoff sinuses - Subserosal fibrosis

Question 37

gallbladder carcinoma - males/females more affected - risk factors

Answer 37

- affects females more risk factors - gallstones - chronic infections: bacterial/parasitic

Question 38

gallbladder carcinoma - metastasis - prognosis

Answer 38

Direct invasion: liver, stomach and duodenum (surrounding organs) Metastases: liver, regional lymph nodes, lungs Prognosis is poor

Question 39

gallbladder carcinoma | - gross and micro features

Answer 39

Diffuse (70%) / infiltrating Polypoid (30%) / exophytic micro: usually adenocarcinoma (glandular)

Question 40

most common cause of HCC

Answer 40

hep C viral infection

Question 41

acute cholecystitis pathogenesis

Answer 41

- 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