Acute Pancreatitis

2.10.06

Definition:
• Acute inflammatory process of pancreas, with variable involvement of other regional tissues or remote organ systems.

Why is it important?
• Common abdominal disease:
-Always a differential in abdominal pain.
-Common admission on acute surgical take.
• Spectrum of clinical presentations:
-Mild, self-limiting disease.
-Apocalyptic destruction of pancreas, multi-organ failure and death.
• Therapy essentially limited to supportive care.

Pancreas - a little history
• "Discovered" by Herophilos (335-280 BC).
-Alexandrian physician and anatomist.
-"Father of anatomy."
• Named by Ruphos.
• Galen:
-Claimed pancreas was cushion - to protect vessels behind.
-Word was "law" - not questioned for ~1500 years.
• Wirsung:
-Discovered pancreatic duct named after him.
• Langerhans.
• Banting and Best:
-Discovered insulin (in dog).
-6 months later, 14-year-old boy with diabetes treated with insulin.
-18 months later, mass-marketed.
-Nobel prize in 1923 (Best omitted).
• Digestive enzymes.
-Discovered throughout mid-late 19th Century.
• Wohlgemuth:
-Discovered amylase.
-Introduction to potential to diagnose pancreatitis.

Embryology
• Ventral bud - close to bile duct.
• Dorsal bud - in dorsal mesentery.
• Both have own duct.
• Duodenum rotates to right.
• Ventral and dorsal portions fuse.
• Ventral portion form uncinate process and inferior head.
• Dorsal portion forms rest of head, neck and tail.
• Ventral and dorsal ducts fuse to form main pancreatic duct (Wirsung's).

Anatomy
• Retroperitoneal.
• Immediately posterior to stomach.
• Space between stomach and pancreas form anterior and posterior borders of lesser sac.

Physiology
• Endocrine:
-Mainly body and tail.
-Islets of Langerhans.
-Insulin - β cells.
-Glucagon - α cells.
-Somatostatin - δ cells.
• Diabetes mellitus.
• Exocrine secretion:
-1500ml per day.
-Digestive proenzymes (zymogens):
§Carbohydrates (amylase).
§Proteins (pro-trypsin, pro-chymotrypsin, pro-carboxypeptidase, pro-elastase).
§Fats (pro-lipase, pro-phospholipase).
-HCO3- - alkalinises duodenal contents.
-Stimulated by CCK, secretin, vagal tone (ACh).

Pathogenesis
Idiopathic.
Gallstones.
Ethanol.
Trauma.
Steroids.
Mumps (and other viruses).
Autoimmune disease.
Scorpion sting (tityus trinitatis).
Hyper- Ca2+/lipids (and hypothermia).
ERCP.
Drugs (SAND - steroids/sulphonamides, azathioprine, NSAIDS, and something beginning with 'D' that I didn't get because he was started to panic about the time.)

• Gallstones:
-Impacting at ampulla.
-Flow of bile up pancreatic duct.
-?Increased pressure up duct.
• Most passed by time of admission.
• Other complications of obstructed bile duct.
• ERCP.
• Scorpion:
-South American scorpion.
-Venom causes haemorrhagic pancreatitis.

• Most common in Western world.
• Rising alcohol consumption in young.
• Leads to chronic pancreatitis.

• Premature enzyme activation within acinar cell.
• Normally trypsin activated in duodenum by enterokinase.
• Mechanisms in acute pancreatitis unknown.
-Disordered Ca2+ signalling shown to be crucial.
-Bile salts and alcohol metabolites shown to lead to enzyme activation in experimental pancreatitis.
• Exact site controversial - many theories e.g.
-Activation within zymogen granules.
-Disordered manufacture, storage or packing of zymogen etc.

Events in acinar cell
• Premature enzyme activation.
• Disruption of cell structure.
• Loss of apical enzyme secretion.
• Formation of apical vacuoles.
• Lysosomes fuse with granules.
• Inflammatory signals released.
• Cell death ensues at later stage.

Local
• Destruction of pancreas:
-Malabsorption.
-Diabetes mellitus.

Regional
• Pseudocyst (after 4 weeks):
-Obstruction.
-Haemorrhage.
• Splenic artery thrombosis.

Systemic
• Cytokines response.
• Multi-organ failure.
• Cardio-respiratory/coagulopathy/renal failure etc.

Incidence
• 3% of all cases of abdominal pain admitted in UK.
• Incidence ~15-420 cases per million per year.
• Overall mortality has dropped:
-From 30% to 6-10%.
-No further drop over decade.
-80% have mild, self-limiting attack/20% have severe disease.
-Up to 40% mortality in severe group.

Presentation
• Symptoms:
-Severe abdominal pain.
-Radiation through to back.
-Nausea +/- vomiting.
• Signs:
-Biliary pancreatitis.
-Alcoholic pancreatitis.
-Ecchymosis to abdominal wall.
§Cullen's sign.

Clinical assessment
• Majority: increased temperature, increased respiratory rate, increased pulse, decreased blood pressure.
• Shock - inadequate tissue perfusion leading to cellular hypoxia.
• SIRS:
-Temperature >380C (or <360C).
-Heart rate >90 bpm.
-Respiratory rate >20 per minute.
-White cell count >12 x 103.
• Sepsis.

Bloods
• Diagnostic.
• Amylase (4X upper limit of normal) - rises 2-12 hours/normalises <7 days, ~10% normal in acute-onset pancreatitis.
• Lipase (2X upper limit of normal) - rises 4-8 hours/normalises 8-14 days - more acute than amylase, but less available.
• FBC.
• U + Es/LFTs/serum Ca2+.
• Arterial blood gas:
-Pa O2, acidosis.

Investigations
• Plain radiographs.
-Erect chest and plain supine abdomen.
-Exclude other pathology.
-Baseline films (especially with later events).
• USS.
-Detects free fluid, gallstones, dilatation of CBD.
• CT.
-Not in first 48 hours.
-Intrapancreatic.
-Shows necrosis/acute fluid collections/abscesses.

Scoring
• Ransom criteria.
• Glasgow score modified from Ransom criteria for all patients.
• APACHE-II.
• APACHE-0.

Management
• General measures.
• Specific measures:
-ITU.
-Antibiotic therapy.
-Nutrition:
§"Drip and suck" - old thinking.
§Early nutrition.
§Use enteral route if possible (oral/NG/NJ feeding).
§"More physiological" - protective "gut barrier."

Interventions
• ERCP.
• Surgery:
-Infected necrosis.
-Pseudocyst:
§Collection of inflammatory fluid > weeks.
§Enzymes, blood, necrotic tissue.
§Symptomatic - obstruction/infection.
§Endoscopic.

Surgery
• Open versus closed.
• Open necrosectomy:
-Conventional procedure.
-Laparotomy.
-Pancreatic necrosectomy.
• Closed necrosectomy.