Pancreatic & Liver Pathology

Question 1

What are the Exocrine & Endocrine functions of the Pancreas?

Answer 1

Exocrine= (85% role). Secrete digestive enzymes -trypsin, lipase, phospholipase, amylase (marker of pancreatic inflammation) which require activation.
Endocrine= islets of Langerhans, secrete peptide hormones into blood (insulin, glucagon)

Question 2

Features of acute pancreatitis?

Answer 2

Sudden onset of severe abdo pain radiating to back.
May be mild (5-7 days) but can be serious with high mortality
Raised serum amylase/lipase

Question 3

What are some causes of pancreatitis?

Answer 3

Gallstones (50%)
Alcohol (25%)
Rare causes (vascular insufficiency, viral infections)
Idiopathic

Question 4

What is the pathogenesis behind severe pancreatitis?

What is Grey Turner’s sign and Cullen’s sign?

Answer 4

Leakage & activation of pancreatic enzymes, amylase released into blood.
Swollen, necrotic gland with fat necrosis & haemorrhage (Grey Turner’s Sign- haemorrhage into the subcutaneous tissues of flank. Cullen’s sign- periumbilicus)

Question 5

What are some features of chronic pancreatitis?

Answer 5

• Progressive inflammatory disorder: parenchyma of pancreas is destroyed & replaced by fibrous tissue.
• Irreversible destruction of exocrine tissue, followed by destruction of endocrine tissue
• Leads to malnutrition & diabetes

Question 6

Causes of chronic pancreatitis?

Answer 6

Toxic (alcohol, drugs, hypercalcaemia)
Genetic (CFTR, PRSS1, SPINK 1 mutations)
Obstruction of main duct (cancer, scarring)

Question 7

What is the most common type of pancreatic cancer?

Answer 7

Pancreatic adenocarcinoma (ductal adenocarcinoma)

Question 8

What are some symptoms of pancreatic adenocarcinoma?
What is Trousseau’s syndrome?
What is Courvoisier’s sign?

Answer 8

• Epigastric pain, radiating to back
• Weight loss, jaundice, pruritus & nausea
• Trousseau’s syndrome (migratory thrombophlebitis)
• Courvoisier’s sign (palpable gallbladder without pain)
• Diabetes increased risk

Question 9

Hereditary Cancer Syndromes… genetics involved?
HNPCC?
Familial Breast Cancer
Familial Pancreatitis

Answer 9

HNPCC= DNA mismatch repair
Familial Breast Cancer= BRCA1
Familial Pancreatitis= Cationic trypsinogen, SPINK1

Question 10

What are some Neuroendocrine Tumours of the Pancreas?

Answer 10

Insulinoma (beta cell)
Glucagonoma (alpha cell)
Gastrinoma (G cell)
Somatostatinoma (gamma cell)

Question 11

What are 2 indicators of hepatocyte damage?

Answer 11

Aminotransferases: Alanine/ALT and Aspartate/AST
(found in the cell and only released by cellular damage)
ALT is more specific to liver than AST (AST also found in muscle & rbc)

Question 12

What indicates impared excretory function in Biliary Tract Damage?

Answer 12

Increased CONJUGATED bilirubin (as the bilirubin has already been conjugated and so solube & excreted, however it is blocked after)
Yellow eyes, pale stools and dark urine.

Question 13

What may an elevated Alkaline phosphatase (ALP) be due to? (elevated due to increased production by cells lining the bile canaliculi, overflow into the blood)

Answer 13

• Cholestasis
• Infiltrative diseases
• Space occupying legions (tumours)
• Cirrhosis

Question 14

What may an elevated Gamma glutamyltransferase (gammaGT) be due to? (elevated due to structural damage)

Answer 14

• Enzyme inducing agents eg)anti-epileptics
• Fatty liver (alcohol, diabetes or obesity)
• Heart failure
• Prostatic disease
• Pancreatic disease
• Kidney damage

Question 15

Clinical manifestations of :
a) Pre hepatic
b) Hepatic
c) Post hepatic
(jaundice)

Answer 15

a) Pre hepatic= yellow eyes/ skin (unconjugated bilirubin, bound to albumin, not excreted)
b) Hepatic= yellow eyes, dark urine (mainly conjugated, soluble)
c) Post hepatic= yellow eyes, pale stools & dark urine (conjugated, soluble, excreted but cant get into gut)

Question 16

When does jaundice manifest?

Answer 16

Hyperbilirubinaemia… serum bilirubin > 40-50micromol/L

Question 17

Causes of pre-hepatic jaundice?

Answer 17

• Haemolysis (eg. Rhesus incompatibility)
• Ineffective erythropoeisis (eg spherocytosis)
• Gilbert’s Syndrome- enzyme deficiency

Question 18

Causes of post-hepatic (obstructive) jaundice?

Answer 18

Gallstones
Biliary Stricture
Cancer
Cholangitis

Question 19

Causes of hepatic jaundice?

a) Unconjugated
b) Conjugated

Answer 19

a) Inherited disorders of conjugation eg) Gilberts, Crigler-Najjar
b) Intrahepatic obstruction, Inherited disorders of excretion eg) Dubin-Johnson, Rotor

Question 20

What are some inborn errors of bilirubin metabolism associated with?

Answer 20

Decreased activity of UDP glucuronyl transferase= Gilberts, Crigler-Najjar
Reduced ability to excrete bilirubin glucuronide= Dubin-Johnson, Rotor

Question 21

Blood tests & jaundice…

a) AST/ALT elevated & normal ALP?
b) AST/ALT normal & elevated ALP?

Answer 21

a) approx 90% have hepatitis

b) approx 90% have obstructive jaundice

Question 22

What is the link between urine and bilirubin?

a) prehepatic
b) hepatic
c) posthepatic

Answer 22

a) unconjugated bilirubin= no urinary bilirubin
b) hepatocellular= variable depending on degree of obstruction
c) obstruction= dark urine (& pale stools)

Question 23

What are the a)Endocrine and b)Exocrine secretions of the pancreas?

Answer 23

a) Endocrine secretions (Islets of Langerhans)= insulin, glucagon, pancreatic polypeptide
b) Exocrine secretions (Ductal & acinar cells)= bicarbonate, digestive enzymes, trypsin & elastase, carboxypeptidases, amylase, lipase

Question 24

What does diagnosis of acute pancreatitis use?

Answer 24

Uses tests of amylase/ lipase (exocrine function)

Question 25

Pancreatic Function Tests…

a) Direct (invasive) tests?
b) Indirect (Non-invasive) tests?

Answer 25

a) Intubation to collect aspirates in the duodenum
Secretin, CCK, Lundh test
b) Pancreatic enzyme analysis in stools (elastase)
Trypsinogen measured in blood in CF screening