47 PANCREAS

# PANCREAS

The pancreas is a retroperitoneal gland that performs two unrelated jobs in the same organ: it secretes digestive enzymes into the duodenum (exocrine) and hormones into the bloodstream (endocrine). For MRCS Part A, examiners test it from every angle — embryology (divisum, annular), surgical anatomy (relation to SMV and portal vein), pathology (acute and chronic pancreatitis, adenocarcinoma) and the islet-cell tumours. Master the anatomy first; everything else builds on it.

Gross anatomy

The pancreas lies transversely across the posterior abdominal wall at the level of L1–L2, behind the lesser sac. It is retroperitoneal except for the tail, which sits within the lienorenal (splenorenal) ligament between the two layers of peritoneum running to the splenic hilum. Remember this: a tail injury during splenectomy causes a pancreatic fistula.

It has four parts, each defined by what lies behind it:

- Head — sits in the C-loop of the duodenum. The uncinate process is a hook of pancreatic tissue projecting posteriorly from the head, passing behind the superior mesenteric vessels.

- Neck — overlies the superior mesenteric vein (SMV). The SMV and splenic vein unite posterior to the neck to form the portal vein. This is the surgical key landmark in a Whipple's.

- Body — passes anterior to the aorta, left renal vein, left kidney and left adrenal.

- Tail — ends at the splenic hilum within the lienorenal ligament.

──────────────────────────────

Ducts and the ampulla

Two ducts drain the exocrine pancreas:

- Main pancreatic duct (of Wirsung) — runs the length of the gland and joins the common bile duct at the ampulla of Vater, opening into the second part of the duodenum (D2) at the major duodenal papilla. The sphincter of Oddi controls flow.

- Accessory duct (of Santorini) — drains the upper head and opens separately at the minor papilla, about 2 cm proximal to the major papilla.

The ducts and their fusion patterns are explained by embryology (below), and failure of fusion is the basis for pancreas divisum.

Blood supply, venous and lymphatic drainage

- Arterial: head — superior and inferior pancreaticoduodenal arteries (from gastroduodenal and SMA respectively, forming an anastomotic arcade). Body and tail — branches of the splenic artery (including the dorsal pancreatic and great pancreatic arteries).

- Venous: drains entirely to the portal venous system — splenic vein (body/tail) and SMV (head). This is why pancreatic cancer metastasises early to the liver.

- Lymphatic: head → pancreaticoduodenal and pyloric nodes → coeliac and SMA nodes. Body and tail → pancreaticosplenic nodes → coeliac nodes.

- Innervation: parasympathetic (vagus, secretomotor) and sympathetic (T6–T10 via the coeliac plexus). Pain from pancreatitis and pancreatic cancer refers to the back via these splanchnic pathways — the rationale for coeliac plexus block.

Histology

The pancreas is 98% exocrine and 2% endocrine by mass, but the endocrine portion is hugely important clinically.

Exocrine — arranged as acini draining into ducts:

- Acinar cells secrete digestive enzymes as inactive zymogens (trypsinogen, chymotrypsinogen, proelastase) plus active lipase and amylase. Stimulated by cholecystokinin (CCK).

- Ductal cells secrete a bicarbonate-rich alkaline fluid that neutralises gastric acid in the duodenum. Stimulated by secretin.

Zymogens are activated only in the duodenum, where enterokinase on the brush border converts trypsinogen to trypsin; trypsin then activates the rest of the cascade. Premature intra-pancreatic activation is the trigger for acute pancreatitis.

Endocrine — Islets of Langerhans, concentrated in the tail:

Cell	Hormone	Function
α (alpha)	Glucagon	Raises blood glucose
β (beta)	Insulin	Lowers blood glucose (most abundant)
δ (delta)	Somatostatin	Inhibits insulin and glucagon
PP	Pancreatic polypeptide	Inhibits pancreatic exocrine secretion
ε (epsilon)	Ghrelin	Appetite stimulation

Embryology

The pancreas develops from two endodermal buds of the foregut:

- Dorsal bud — gives the upper head, body, tail and accessory duct (Santorini).

- Ventral bud — develops next to the bile duct and gives the lower head, uncinate process and main duct (Wirsung). The ventral bud rotates posteriorly with the duodenum, swinging round to fuse with the dorsal bud.

Two important developmental anomalies:

- Pancreas divisum — failure of fusion of the dorsal and ventral ducts. Most pancreatic secretion drains through the smaller accessory duct and minor papilla, predisposing to recurrent acute pancreatitis. Commonest pancreatic congenital anomaly (~5–10% of population, most asymptomatic).

- Annular pancreas — the ventral bud rotates abnormally and encircles D2, causing duodenal obstruction. Presents in neonates with bilious vomiting and a double-bubble sign on AXR (alongside duodenal atresia in the differential).

Acute pancreatitis

Premature intra-acinar activation of trypsinogen → trypsin → cascade of enzyme activation → autodigestion, inflammation and a systemic inflammatory response.

Causes — GET SMASHED:

- Gallstones (commonest in UK, ~50%)

- Ethanol (second commonest, ~25%)

- Trauma (including blunt abdominal — pancreas crushed against vertebrae)

- Steroids

- Mumps (and other viruses)

- Autoimmune (IgG4-related)

- Scorpion sting (classic exam trivia — Trinidadian Tityus)

- Hyperlipidaemia / Hypercalcaemia / Hypothermia

- ERCP (~3–5% post-procedure risk)

- Drugs (azathioprine, thiazides, valproate, tetracyclines)

Enzyme roles in pathology:

- Trypsin — initiates and propagates the cascade (the autodigestion trigger).

- Elastase — degrades vascular elastin, causing haemorrhagic pancreatitis and retroperitoneal bleeding (Grey-Turner's and Cullen's signs).

- Lipase — produces fat necrosis (saponification with calcium → hypocalcaemia).

- Phospholipase A2 — implicated in ARDS via surfactant damage.

Diagnosis — two of the three: (1) characteristic epigastric pain radiating to the back, (2) amylase or lipase >3× upper limit, (3) imaging findings. Lipase is more sensitive and specific and stays elevated longer.

> Pearl: If amylase is only mildly raised (≤3× normal), it is NOT pancreatitis. Think acute intermittent porphyria, mesenteric ischaemia, perforation, parotitis or ectopic pregnancy.

Severity scoring — the modified Glasgow (Imrie) score, ≥3 within 48h = severe. Mnemonic PANCREAS: PaO₂ <8 kPa, Age >55, Neutrophils (WCC) >15, Calcium <2, uRea >16, Enzymes (LDH >600, AST >200), Albumin <32, Sugar (glucose) >10. CRP >150 at 48h also predicts severity. BISAP is the modern alternative.

Imaging — contrast-enhanced CT is best done after 72h; earlier scans underestimate necrosis. AXR may show a sentinel loop or colon cut-off sign. USS is first-line to detect gallstones as a cause.

Complications:

- Early (<1 week) — shock, ARDS, AKI, DIC, hypocalcaemia, hyperglycaemia.

- Local (later) — acute peripancreatic fluid collection (no wall, <4 weeks) → pseudocyst (wall of granulation tissue, takes ≥4 weeks to mature, no epithelial lining), pancreatic necrosis (non-enhancing tissue on CT), infected necrosis, walled-off necrosis (encapsulated necrosis, ≥4 weeks), abscess, splenic vein thrombosis (→ gastric varices), pseudoaneurysm of splenic artery.

Management — supportive: aggressive IV fluids, analgesia, oxygen, early enteral nutrition, treat the cause. Antibiotics only for proven infected necrosis. Gallstone aetiology → cholecystectomy on the same admission (mild) or after recovery (severe). ERCP if there is concurrent cholangitis or persistent obstruction.

Chronic pancreatitis

Irreversible inflammation, fibrosis and calcification of the gland. Alcohol is the commonest cause (~70%), followed by recurrent acute pancreatitis, idiopathic, cystic fibrosis (commonest in children), autoimmune and ductal obstruction.

Clinical features — chronic epigastric pain radiating to the back, weight loss, and the late triad of:

- Exocrine insufficiency → steatorrhoea (lipase lost first; floating, foul, sticky stools).

- Endocrine insufficiency → diabetes mellitus (β-cells destroyed late).

- Calcification on imaging (pathognomonic).

Investigations — faecal elastase is the first-line non-invasive test for exocrine insufficiency. CT shows calcifications, ductal dilatation and atrophy. MRCP defines duct anatomy.

Management — alcohol cessation, smoking cessation, analgesia (paracetamol → NSAIDs → opioids → coeliac plexus block for intractable pain), pancreatic enzyme replacement (Creon), fat-soluble vitamin supplementation, insulin for diabetes, surgery (Frey, Beger, Puestow procedures) for refractory pain.

Pancreatic adenocarcinoma

Ductal adenocarcinoma of the exocrine pancreas. Aggressive, late-presenting, poor prognosis (<5% 5-year survival overall).

Risk factors — smoking (strongest modifiable), age, chronic pancreatitis, diabetes, obesity, family history, BRCA2, Lynch syndrome, hereditary pancreatitis.

Location and presentation:

- Head (~70%) — obstructs the CBD → painless progressive obstructive jaundice, dark urine, pale stools, pruritus. Courvoisier's sign: a palpable, non-tender gallbladder with jaundice — pancreatic head cancer until proven otherwise. (Courvoisier's law: in gallstone disease the gallbladder is fibrotic and not palpable.)

- Body and tail (~30%) — present late with epigastric pain radiating to the back, weight loss and depression. Trousseau's sign of malignancy = migratory thrombophlebitis.

Tumour marker — CA 19-9 (not specific, but useful for monitoring; falsely low in Lewis-antigen-negative individuals).

Imaging — contrast CT pancreas protocol is the staging investigation; EUS-guided biopsy for histology.

Management:

- Resectable head tumours → Whipple's procedure (pancreaticoduodenectomy) — removes the pancreatic head, duodenum, gallbladder, distal CBD and proximal jejunum, with or without distal stomach (classical vs pylorus-preserving). Reconstructed with three anastomoses: pancreatico-jejunal, hepatico-jejunal, gastro/duodeno-jejunal.

- Resectable body/tail tumours → distal pancreatectomy ± splenectomy.

- Unresectable / metastatic → palliation: ERCP biliary stenting for jaundice, duodenal stenting or gastrojejunostomy for gastric outlet obstruction, chemotherapy (FOLFIRINOX or gemcitabine-based), coeliac plexus block for pain.

Pancreatic neuroendocrine tumours (PNETs)

Rare islet-cell tumours. Often associated with MEN1 (parathyroid, pituitary, pancreas). Diagnosed by hormone-specific tests; localised by CT, EUS or octreotide scanning.

Tumour	Cell	Syndrome	Key feature
Insulinoma	β	Whipple's triad	Hypoglycaemia + symptoms + relief with glucose; high insulin AND high C-peptide
Gastrinoma	non-β (often duodenal)	Zollinger-Ellison	Recurrent/multiple/atypical peptic ulcers, diarrhoea, raised fasting gastrin
Glucagonoma	α	4 Ds	Dermatitis (necrolytic migratory erythema), Diabetes, DVT, Depression
VIPoma	δ-like	Verner-Morrison / WDHA	Watery Diarrhoea, Hypokalaemia, Achlorhydria
Somatostatinoma	δ	Inhibitory triad	Diabetes, steatorrhoea, gallstones

> Pearl: Insulinoma vs factitious hypoglycaemia — both have high insulin. C-peptide is high in insulinoma, low with exogenous insulin (because injected insulin has no C-peptide).


Test yourself

What is the enzyme responsible for autodigestion in acute pancreatitis?

• ((Trypsin::☑️ Premature intra-acinar activation of trypsinogen triggers the whole enzyme cascade.))
• ((Lipase::Activated by trypsin; causes fat necrosis but not the initiator.))
• ((Elastase::Activated by trypsin; degrades vessel walls causing haemorrhage.))
• ((Amylase::A diagnostic marker, not the cause of autodigestion.))

👩‍⚕️ Normally trypsinogen is activated in the duodenum by enterokinase — not in the pancreas.

A man is admitted with haemorrhagic pancreatitis. Which enzyme causes haemorrhagic pancreatitis?

• ((Elastase::☑️ Degrades elastin in vessel walls, producing retroperitoneal haemorrhage.))
• ((Trypsin::Initiates the cascade but does not directly degrade vessels.))
• ((Lipase::Causes fat necrosis and saponification, not bleeding.))
• ((Phospholipase A2::Damages cell membranes and surfactant (ARDS); elastase is the classic haemorrhage answer.))

A man with chronic pancreatitis reports stools that stick to the commode and will not flush. Loss of which enzyme is responsible?

• ((Lipase::☑️ Lost first in chronic pancreatitis; undigested fat causes floating, sticky steatorrhoea.))
• ((Trypsin::Deficiency causes protein malabsorption, not steatorrhoea.))
• ((Amylase::Deficiency causes carbohydrate malabsorption.))
• ((Elastase::Faecal elastase is a diagnostic marker; not the cause of steatorrhoea.))

In suspected chronic pancreatitis, what is the first non-invasive test?

• ((Serum lipase::Often normal in chronic disease (gland is burnt out).))
• ((Serum amylase::Frequently normal once acinar mass is lost.))
• ((Faecal elastase::☑️ First-line non-invasive marker of exocrine insufficiency.))
• ((Secretin stimulation test::Sensitive but invasive; not first-line.))

A patient presents with an acute abdomen. Amylase 110 U/L, calcium 2.4 mmol/L, normal LFTs. Diagnosis?

• ((Acute intermittent porphyria::☑️ Severe abdominal pain with bland labs — amylase not >3× upper limit excludes pancreatitis.))
• ((Perforation::Would expect free air and peritonism.))
• ((Pancreatitis::Requires amylase >3× upper limit.))
• ((Lead poisoning::Causes colic but with anaemia and basophilic stippling.))

👩‍⚕️ AIP is precipitated by drugs (OCP, barbiturates), alcohol, fasting and infection; treat with IV haem arginate and glucose.

An 18-year-old woman recently started the COCP and presents with abdominal pain, vomiting, muscle weakness, BP 160/85. Amylase 110, calcium 2.41, glucose 5, triglycerides 1.5. Diagnosis?

• ((Acute intermittent porphyria::☑️ Young woman, drug trigger (OCP), neuro signs and hypertension with non-diagnostic labs.))
• ((Diabetic ketoacidosis::Glucose is normal and no acidosis.))
• ((Hypoparathyroidism::Calcium is normal.))
• ((Mumps::Would produce parotitis; presentation does not fit.))
• ((Pancreatitis::Amylase not >3× upper limit.))

A patient with epigastric pain has amylase 900, normal GGT/ALP, slightly raised bilirubin. Diagnosis?

• ((Alcoholic pancreatitis::☑️ Amylase >3× normal with no cholestatic picture points to a non-obstructive cause.))
• ((Choledocholithiasis::Would raise ALP and GGT (cholestatic pattern).))
• ((Biliary colic::Does not produce amylase of 900.))
• ((Gallstone pancreatitis::Would show cholestatic LFTs.))

A patient with acute pancreatitis has a CT after 4 days showing diffuse peripancreatic fluid and non-enhancing pancreatic tissue. Diagnosis?

• ((Pseudocyst::Needs ≥4 weeks to form a defined wall.))
• ((Abscess::Rim-enhancing fluid with systemic sepsis.))
• ((Pancreatic necrosis::☑️ Non-enhancement on contrast CT = ischaemic necrotic tissue.))
• ((Walled-off necrosis::Encapsulation takes ≥4 weeks.))

👩‍⚕️ CT is best timed at ≥72h — earlier scans underestimate necrosis.

A patient with chronic pancreatitis has intractable back pain unresponsive to medication. Management?

• ((NSAIDs::Often ineffective for deep visceral pain.))
• ((Coeliac plexus block::☑️ Targets the splanchnic visceral afferents responsible for pancreatic pain.))
• ((Opioids::Cause tolerance and dependence; not preferred long-term.))
• ((Thoracic epidural::Temporary, not definitive.))

A 50-year-old woman has progressive painless jaundice, pale stools, dark urine and a palpable RUQ mass. Diagnosis?

• ((Pancreatic head carcinoma::☑️ Courvoisier's sign — palpable non-tender gallbladder with jaundice is malignant until proven otherwise.))
• ((Cholangiocarcinoma::Possible but pancreatic head cancer is the classic Courvoisier answer.))
• ((Gallstone obstruction::Courvoisier's law — gallbladder is fibrotic and not palpable.))
• ((Hepatocellular carcinoma::Does not typically cause obstructive jaundice and palpable gallbladder.))

A woman has jaundice and liver metastases from a pancreatic head carcinoma. Management?

• ((ERCP and biliary stent::☑️ Palliative decompression of the CBD in inoperable disease.))
• ((Whipple's procedure::Contraindicated by metastatic disease.))
• ((Surgical bypass::Reserved for failed/contraindicated endoscopic stenting.))
• ((Chemotherapy alone::Does not relieve the biliary obstruction.))

A patient has hypoglycaemia, confusion, sweating, relieved by eating. Insulin high, C-peptide high. Diagnosis?

• ((Exogenous insulin::High insulin but low C-peptide — injected insulin has none.))
• ((Insulinoma::☑️ Autonomous β-cell secretion gives high insulin and high C-peptide; Whipple's triad.))
• ((Glucagonoma::Causes hyperglycaemia, dermatitis and DVT.))
• ((Type 1 diabetes::Low insulin and low C-peptide.))

👩‍⚕️ Whipple's triad (insulinoma) ≠ Whipple's procedure (pancreaticoduodenectomy). Easy MRCS trap.

Which structure passes posterior to the neck of the pancreas?

• ((Coeliac trunk::Arises from the aorta above the pancreas.))
• ((Formation of the portal vein::☑️ SMV and splenic vein unite behind the neck to form the portal vein.))
• ((Inferior vena cava::Lies behind the head, not the neck.))
• ((Left renal vein::Crosses behind the body of pancreas, not the neck.))

A neonate presents with bilious vomiting and a double-bubble on AXR. The pancreas encircles D2. Diagnosis?

• ((Pancreas divisum::Failure of duct fusion; usually asymptomatic in adults.))
• ((Annular pancreas::☑️ Abnormal rotation of the ventral bud encircles D2 causing obstruction.))
• ((Ectopic pancreas::Aberrant tissue in stomach/Meckel's; not obstructive in this pattern.))
• ((Duodenal atresia::Also gives double-bubble but no encircling pancreatic tissue.))

Which islet cell secretes glucagon?

• ((β cell::Secretes insulin.))
• ((α cell::☑️ Secretes glucagon, raising blood glucose.))
• ((δ cell::Secretes somatostatin, inhibiting insulin and glucagon.))
• ((PP cell::Secretes pancreatic polypeptide, inhibiting exocrine secretion.))

Revision summary

- Anatomy — head + uncinate (in duodenal C-loop, behind SMA/SMV), neck (over SMV; portal vein forms posteriorly), body, tail (lienorenal ligament to spleen). Retroperitoneal except tail.

- Ducts — main (Wirsung) + accessory (Santorini); ampulla of Vater opens at major papilla of D2.

- Histology — exocrine (acinar = enzymes via CCK; ductal = HCO₃⁻ via secretin); endocrine islets (α glucagon, β insulin, δ somatostatin, PP).

- Embryology — ventral + dorsal buds; ventral rotates. Divisum = failed fusion (recurrent pancreatitis). Annular = ring around D2 (neonatal obstruction, double-bubble).

- Acute pancreatitis — GET SMASHED; diagnose with amylase/lipase >3× ULN. Trypsin starts cascade; elastase bleeds; lipase = steatorrhoea + hypocalcaemia. Glasgow ≥3 = severe; CRP >150 at 48h. CT at >72h. Pseudocyst wall matures at ≥4 weeks.

- Chronic pancreatitis — alcohol; calcification + steatorrhoea + diabetes. Faecal elastase first; Creon, alcohol cessation, coeliac plexus block.

- Adenocarcinoma — head, painless jaundice, Courvoisier's sign, CA 19-9; resectable → Whipple's; metastatic → ERCP stent.

- PNETs — insulinoma (Whipple's triad; high insulin + high C-peptide), gastrinoma (ZES), glucagonoma (4 Ds), VIPoma (WDHA), somatostatinoma (DM + steatorrhoea + gallstones). MEN1 association.

- One-liner traps — amylase not >3× → think AIP; Courvoisier = cancer; Whipple's triad ≠ Whipple's procedure; insulinoma C-peptide high, factitious low.