Pancreatitis + Cholestatitis

Question 1

CHRONIC PANCREATITIS
What it is + symptoms

Answer 1

-Chronic, inflammatory disease of the pancreas, with
irreversible morphologic changes

• Symptoms arise from loss of glandular function and
  inflammation
   Pain
   Diarrhoea
   Weight loss

Question 2

CHRONIC PANCREATITIS
Etiology

Answer 2

Etiology
 Alcohol abuse
 Toxins
 Oxidative stress
 Autoimmune disorders
 Genetic disorders (e.g. cystic fibrosis)

Question 3

Chronic. Pancreatitis management

Answer 3

-No cure
- Treatment aimed at relieving pain and
malabsorption
- Malabsorption occurs at >90% loss of
enzymes
- Pancreatic enzymes
- Pancrelipase (Creon)
- Contains lipase, protease and amylase

Question 4

MANAGEMENT of Chronic Pancreatitis

Answer 4

Pain relief
- Pancreatic enzymes may also alleviate pain
- May be caused by cholecystokinin-CCK
(normally denatured by pancreatic trypsin)

-Other analgesics: paracetamol, NSAIDs,
opioids, TCAs
- Surgery

Question 5

DRUG-INDUCED PANCREATITIS

Answer 5

Relatively rare
 Accounts for about 2% of cases
 Usually mild
 Associated drugs:
1. Azathioprine
2. Sulfonamides
3. Tetracycline
4. Methyldopa
5.Estrogens
6. Furosemide
7. 6-Mercaptopurine
8. 5-aminosalicylic acid compounds
9. Corticosteroids
10. GLP-1 (Glucagon-like peptide) analogues

Question 6

CHOLESTATIC HEPATITIS

What type of liver abnormality do these feature suggest?

Answer 6

 Biochemical block of bilirubin excretion
 Clinical picture of obstructive jaundice
 Typically recognized by predominant elevations in alkaline phosphatase and bilirubin
 Mostly reversible, minimal liver damage

Question 7

BILIRUBIN formation + EXCRETION

Answer 7

Red blood cells -haem -> Biliverdin-> Bilirubin ->
Transported to hepatocytes -> Conjugated with glucuronic acid (glucuronyl transferase) ->Excreted in bile

Question 8

BILIRUBIN EXCRETION

Answer 8

Formed from haem
 Biliverdin broken down into unconjugated
bilirubin
 Conjugated with glucuronic acid in liver
 Now water soluble, can be excreted in bile
! In intestine, bacteria convert it to urobilinogen
which can be reabsorbed or stercobilinogen
excreted in faeces/reabsorbed

Question 9

CHOLESTASIS

Pathophysiology

Answer 9

 Retention of hydrophobic bile salts
-Pruritus

 Retention of cholesterol
- Impairs membrane function
 Reduction of bile into intestines
-Malabsorption

 Retention of damaging substances

Question 10

Cholestasis management: how does it help?
•Pruritus
• does what to bile formn
• dissolves what
•

Answer 10

Generally disease-specific

 Pruritus
- Drugs of choice for moderate/severe pruritus
•Ursodeoxycholic acid (UDCA) and bile salt resins

 UDCA
 Increases bile formation
 Antagonizes effects of hydrophobic bile acids on membranes
 Used to dissolve gallstones
- Decreases cholesterol content
 Bile salt resins
- Cholestyramine
- Form a non-absorbable complex with bile acids
- Increases faecal loss of bile acids

Question 11

Cholestasis management

Other drugs for pruritus

Answer 11

 Opioid antagonists
 Phenobarbital/rifampicin
- Induce CYP450 system to decrease serum
bilirubin
 Fat malabsorption
- Dietary modifications (including vitamin
supplementation)

Question 12

DRUG-INDUCED CHOLESTASIS

Answer 12

1. Conjugation in liver makes drugs water-soluble
2. Transport into bile
3. Excretion in feces

Question 13

‘DRUG-INDUCED CHOLESTASIS
Caused by which drugs

Answer 13

 Dicloxacillin
 Nafcillin
 Amoxicillin-clavulanate
 Erythromycin
 Chlorpromazine
 Naproxen(nsaid)
 Terbinafine
Everything else is antibiotics