Hepatobilary and pancreas

Question 1

Definition of iatrogenic

Answer 1

induced inadvertently by a doctor
or by medical treatment
or diagnostic procedures

Question 2

What are the three classifications of jaundice?

Answer 2

Pre-hepatic = too much bilirubin produced
Hepatic = too few functioning liver cells
Post hepatic = bile duct obstruction

Question 3

Cause of pre-hepatic jaundice

Answer 3

too much bilirubin produced

eg. Haemolytic anaemia

Question 4

Causes of hepatic jaundice

Answer 4

too few functioning liver cells, eg:
Acute diffuse liver cell injury
End stage chronic liver disease
Inborn errors of metabolism

Question 5

Causes of post hepatic jaundice

Answer 5

bile duct obstruction, eg:
stone,
stricture,
tumour – bile duct, pancreas

Question 6

What is the pathway of bilirubin metabolism?

Answer 6

1. Bilirubin produced by red blood cell breakdown
   = unconjugated.
2. Metabolised in liver – conjugated
   and excreted in bile
3. Some bilirubin is re-absorbed
   from gut along with bile salts in Enterohepatic circulation

Question 7

What symptoms are associated with pre hepatic jaundice and why?

Answer 7

Patient notices yellow eyes/skin only

Because the bilirubin is unconjugated – bound to albumin, insoluble, not excreted

Question 8

What are the symptoms associated with hepatic jaundice and why?

Answer 8

Patient notices yellow eyes/skin and dark urine

Because the bilirubin is mainly conjugated

Question 9

What are the symptoms associated with post hepatic jaundice and why?

Answer 9

Patient notices yellow eyes, dark urine and pale stools

Because the bilirubin is conjugated so soluble and excreted, but can’t get into gut

Question 10

Which LFTs indicate hepatocyte damage?

Answer 10

ALT and AST

Alanine aminotransferase more specific for liver than Aspartate aminotransferase (also found in muscle and red blood cells)

Question 11

Which LFT indicated damage to the bile ducts?

Answer 11

Alkaline phosphatase

Question 12

How is jaundice investigated?

Answer 12

Ultrasound scan to check for dilated ducts in obstruction

Only if no dilated ducts do a liver biopsy to find out the cause of jaundice

Most (non-obstructive) cases are due to acute hepatitis

Question 13

How does mild acute hepatitis look histologically compared to intermediate and severe acute hepatitis?

Answer 13

Mild = lobular disarray - due to injury and death of individual hepatocytes

Intermediate = Bridging necrosis - between portal tracts and hepatic vein

Severe = confluent panacinar necrosis

Question 14

How is chronic hepatitis defined clinically?

Answer 14

‘chronic hepatitis’ is a persistence of abnormal liver tests for more than 6 months.

Question 15

What is the progression of chronic liver disease to cirrhosis ?

Answer 15

normal
Portal fibrosis
Bridging fibrosis
Cirrhosis - hepatocytes form nodules surrounded by fibrous tissue

Question 16

What are the hepatotrophic viruses?

Answer 16

Hepatitis A, B, C, D E
D only affects people with B

Epstein Barr virus, Cytomegalovirus, Herpes simplex virus also as part of a systemic disease, usually in immunocompromised

Question 17

How are Hep A, B and C transmitted?

Answer 17

Hep A = faecal oral

Hep B and C = parenteral

Question 18

How does alcohol abuse change the liver?

Answer 18

Steatosis = Fatty change
Alcoholic steatohepatitis
Cirrhosis

Question 19

What is seen in histologically in steatohepatitis?

Answer 19

fatty change plus hepatocyte injury – ballooning, Mallory Denk body, inflammation, sinusoidal fibrosis

Question 20

What is NAFLD and what is it associated with?

Answer 20

Non-alcoholic fatty liver disease

Associated with Metabolic syndrome – obesity, type 2 diabetes, hyperlipidaemia, also some drugs

Question 21

What is DILI and how is it classified?

Answer 21

Drug Induced Liver Injury

Intrinsic – anyone taking this drug is likely to get liver damage eg. paracetamol

Or idiosyncratic – depends on individual susceptibility. Rare and can be severe.

Question 22

What is the mechanism of Parecetamol toxicity ?

Answer 22

Parecetamol has two safe metabolic pathways
Too much and it is also metabolised by Cytochrome P450 pathway to a toxic metabolite, N-acetyl-p-
benzoquinone-imine (NAPQI)

NAPQI binds covalently to
tissue membrane proteins causing necrosis.

Treatment = Acetylcysteine
Increases Glutathione which neutralises NAPQI

Question 23

What three inborn errors of metabolism cause liver cirrhosis?

Answer 23

Alpha 1 antitrypsin deficiency
Hemochromatosis
Wilsons disease

Question 24

What is Alpha 1 antitrypsin deficiency?

Answer 24

The abnormal anti-protease cannot be exported from hepatocyte

It accumulates in liver cells and injures them – cirrhosis

Insufficient A1AT in blood leads to a failure to inactivate neutrophil enzymes, causing lung emphysema, especially in smokers

Question 25

What is Haemochromatosis?

Answer 25

Any abnormality in the HFE gene which leads to a failure of iron absorption regulation, and excess iron is stored in various organs Patients have high serum levels of transferrin. Treatment = venesection

Question 26

What is Wilsons disease?

Answer 26

Inborn error of copper metabolism Copper accumulates in Liver - causing cirrhosis. Eyes – Kayser-Fleischer rings Brain – ataxia, etc. Treatment to chelate copper and enhance its excretion

Question 27

What are the systemic effects of liver failure?

Answer 27

``` Ascites Muscle wasting Bruising Gynaecomastia Spider naevi Caput medusae ```

Question 28

What is portal hypertension? list its main complications

Answer 28

``` Increased pressure of blood in the portal veins (a gradient of at least 12mmHg). Complications: Splenomegaly – low platelets Oesophageal varices – haemorrhage Piles (perianal varices) Part of cause of ascites ```

Question 29

What are the causes of portal hypertension?

Answer 29

Post-sinusoidal – Hepatic vein thrombosis (Budd Chiari syndrome) Sinusoidal - cirrhosis Pre-sinusoidal - due to disease of the portal vein or its intrahepatic branches

Question 30

What are the risk factors for Hepatocellular carcinoma?

Answer 30

Cirrhosis Male > female, Obesity, Alcohol, viral hepatitis

Question 31

What blood test can be used to detect Hepatocellular carcinoma?

Answer 31

alpha feto-protein

Question 32

What tumours commonly metastasise to the liver?

Answer 32

Few large nodules: Large bowel ``` Multinodular or infiltrative: Lung Pancreas Breast Stomach Melanoma ```

Question 33

What is cholangiocarcinoma?

Answer 33

Adenocarcinoma arising in the bile ducts, can be: Intrahepatic - from small intrahepatic ducts, mass forming, presents late RF = cirrhosis Perihilar - from large ducts, Causes obstructive jaundice early RF = bile duct disease

Question 34

What are the main types of gall stones?

Answer 34

Mixed stones (most common) Cholesterol stones – yellow, opalescent Pigment stones – small black – in haemolytic anaemia 10% contain calcium – visible on plain Xray

Question 35

What is acute and chronic cholecystitis?

Answer 35

Acute cholecystitis – duct blocked by stone, Initially sterile, later infected. Large, swollen, congested, ulcerated. Complications = empyema, rupture Chronic cholecystitis – repeated small gall stones Complications = Fibrosis, Rokitansky Aschoff sinuses

Question 36

What are the clinical features of acute pancreatitis?

Answer 36

Sudden onset of severe abdo pain radiating to back Nausea and vomiting If severe: Grey Turner’s sign – haemorrhage into the subcutaneous tissues of flank, Cullen’s sign – periumbilicus haemorrhage Raised serum amylase/lipase (>3x normal)

Question 37

What is the pathogenesis of acute pancreatitis?

Answer 37

Leakage and activation of pancreatic enzymes- Amylase released into blood Mild = swollen gland with fat necrosis Severe = + necrotic gland and haemorrhage Hypocalcaemia (fatty acids bind calcium ions), hyperglycaemia, abscess formation, pseudocysts (collections of pancreatic juice secondary to duct rupture)

Question 38

What is chronic pancreatitis?

Answer 38

Irreversible destruction of parenchyma of pancreases, exocrine first followed by endocrine tissue, replaced by fibrosis tissue

Question 39

Aetiology of chronic pancreatitis

Answer 39

Alcohol, idiopathic cigarette smoke, Cystic fibrosis, CFTR gene

Question 40

Complications of chronic pancreatitis

Answer 40

Malabsorption of fat due to lack of lipases, causes: Steatorrhoea Impairment of fat soluble vit absorption –A,D, E and K Diarrhoea, weight loss and cachexia Also Diabetes (late feature) and Pseudocysts

Question 41

How does pancreatic adenocarcinoma present

Answer 41

Usually between 60-80yrs Non-specific symptoms: Epigastric pain radiating to back, Weight loss, painless jaundice, pruritis and nausea Trousseau’s syndrome = migratory thrombophlebitis due to hypercoagubility Courvoisier’s sign = palpable gallbladder without pain (suggests nit stones)

Question 42

What are pancreatic neuroendocrine tumours?

Answer 42

Islet cell tumours, very rare often produce multiple hormones but usually single hyperfunctional syndrome eg. Gastrinoma = Zollinger-Ellison syndrome, too much gastrin causes excess acid secretion on the stomach

Question 43

What are the direct (invasive) pancreatic function tests?

Answer 43

Intubation to collect aspirates in the duodenum.

Question 44

What are the indirect (non-invasive) pancreatic function tests?

Answer 44

Pancreatic enzyme analysis in stools (Elastase) Trypsinogen (IRT) measured in blood in CF screening