EXOCRINE PANCREAS:
Endocrine cells make up 1-2% of pancreas:
Islets of Langerhans – insulin, glucagon, somatostatin
Exocrine pancreas is responsible for secreting digestive enzymes:
Acinar cells contains digestive enzymes in zymogen granules = zymogen are inactive enzyme /
proenzymes
Enzymes are all stored as pro-enzymes in zymogen granules
o When the acinar cells are stimulated to secrete enzymes → granule fuses with plasma
membrane → release contents into lumen of ducts → to duodenum via ducts
Enzymes are only activated in duodenum
o Trypsinogen is activated by enteropeptidase into trypsin → catalyses cleavage of other
enzymes
Duct cells secrete:
Bicarbonate-rich fluid in the small ductules
Mucin in the large ducts
o CFTR – cystic fibrosis transmembrane conductance factor is found in the large ducts
Changed with cystic fibrosis → changes the viscosity of pancreatic secretions
Pancreas has a retroperitoneal location
Pancreatic disease has vague signs & symptoms → diagnosis is usually late in the course of the
disease / cancer
CONGENITAL ANOMALIES:
Pancreatic agenesis
Pancreas divisum
o Main pancreatic duct (duct of Wirschung) is short – drains small part of head of gland
o Bulk of gland drains through minor sphincter
o Predisposed to pancreatitis
Annular pancreas
o Pancreas develops as a ring of pancreatic tissue around duodenum → causes duodenal
obstruction → gastric distension, vomiting
Ectopic pancreatic tissue
o Pancreatic tissue is a different location – stomach, duodenum, jejunum, Meckel
diverticulum, ileum
o Ranges from mm to several cm diameter
o Contains pancreatic acinar cells and islet cells
Polycystic disease
o Multiple cysts in kidney, liver, pancreas
o Range from microscopic in size to about 5cm
o Unilocular – benign
o Multilocular – cancer
ACUTE PANCREATITIS:
Acute inflammation of the pancreas can return to normal if cause is removed
Trivial focal inflammation, oedema & fat necrosis → widespread necrosis & haemorrhage
Aetiology of acute pancreatitis:
o Metabolic:
NB! Alcoholism
Hyperlipoproteinaemia, hypercalcaemia, drugs
Genetic – gene mutations of pancreatic enzymes & their inhibitors
o Mechanical:
Gallstones (biliary tract disease & obstruction)
Trauma & iatrogenic injury, e.g. operative or endoscopic
o Vascular, e.g. shock, atheroembolism, polyarteritis nodosa
o Infectious, e.g. mumps, Coxsackie virus
Acute pancreatitis involves changes and inflammation in the pancreas from auto-digestion due to
inappropriately activated pancreatic enzymes:
o Microvascular leakage → oedema
o Fat necrosis by lipases
o Acute inflammation
o Proteolytic destruction of parenchyma
o Blood vessel destruction with haemorrhage
Can be triggered by:
o Pancreatic duct obstruction, e.g. gall stones
o Primary acinar cell injury, e.g. alcohol
o Defective intracellular transport of proenzymes within acinar cells
Signs and symptoms have a sudden and dramatic onset!!
o May follow heavy meal / alcohol binge
o Abdominal pain:
Severe (sometimes mild) epigastric & abdominal
Radiates to upper back
< lying down
> sitting & leaning forward
Acute abdomen – pain, rigidity, no bowel sounds, distention
Medical emergency!! Systemic release of digestive enzymes & explosive activation of inflammatory
response →
o ↑ vascular permeability
o Leukocytosis
o DIC
o Acute respiratory distress syndrome
o Fat necrosis
o Peripheral vascular collapse & shock
o Endotoxaemia (GI flora into blood stream)
Diagnosis:
o Laboratory tests
↑ serum amylase – most commonly used & ↑ serum lipase
↑ urinary clearance of amylase
↑ WBC
o Hypocalcaemia, hyperglycaemia, ↑ bilirubin
o CT scan – necrosis & fluid accumulation, enlarged & inflamed pancreas
o X-ray – visualise gall stones, complications, and helps with differential diagnosis
Exclusion of other causes for abdominal pain
E.g. acute appendicitis, perforated peptic ulcer, acute cholecystitis with
rupture, bowel infarction
o COD: Shock, respiratory distress (ARDS), renal failure (acute tubular necrosis)
Rx:
o Supportive – manage pain, maintain BP, etc
o NO food / fluids
CHRONIC PANCREATITIS:
Longstanding inflammation & fibrosis results in irreversible destruction of exocrine pancreatic
parenchyma (complete at end)
Chronic pancreatitis is characterised by progressive destruction of the pancreas
o Can be divided into 2 x types:
Chronic calcifying pancreatitis = calcified protein plugs (calculi) form in pancreatic
ducts
Usually seen in alcoholics, and in cystic fibrosis
Chronic obstructive pancreatitis = due to stenosis / blockage of sphincter of
pancreatic duct → usually due to cholelithiasis
i.e. remove gall stones → relieve pancreatitis
Usually due to:
o Long term alcohol abuse
o Long term pancreatic duct obstruction – e.g. gall stones, pancreas divisum, annular
pancreas, cystic fibrosis
o Other causes – tropical pancreatitis, hereditary pancreatitis
40% - no predisposing factors
Results is parenchymal fibrosis with reduced number & size of acini
o Variable dilation: pancreatic ducts
o Relative sparing of islets
Presentation is variable…
o Similar, but less severe episodes, than acute pancreatitis
o Persistent, recurring episodes of:
Abdominal / back pain = epigastric / LUQ – same modalities as acute pancreatitis
o Precipitated / triggered by:
Alcohol abuse
Overeating
Opiates / drugs that ↑ tone of sphincter of Oddi
o Anorexia, nausea, vomiting, constipation, flatulence, vague indigestion
o Jaundice
Silent → pancreatic insufficiency (malabsorption) & DM
Diagnosis:
o During pain attack there may be mild fever & ↑ serum amylase
BUT: After many years at end stage disease there is no ↑ amylase d/t destruction of
pancreas
o If caused by gallstone obstruction:
Jaundice
↑ serum alkaline phosphatase
o CT / US: See calcifications in pancreas
Eventually results in:
o Exocrine insufficiency →malabsorption
o DM
o Chronic pain
o 40% risk of developing pancreatic cancer
PANCREATIC CANCER:
Considered to be one of the most deadly malignancies
Death to incidence ratio = about 0.98-0.99 : 1
5 year survival rate = < 6%
Median survival from diagnosis = 6 months
Risk factors:
Cigarette smoking – major risk factor!!
Diet
o Total calorie intake
o High intake of fat, meat, salt, dehydrated foods, fried foods, refined sugars, soybean,
nitrosamines
o Protective effect seen from high fibre diet, vitamin C, fruit & vegetables, no preservatives
DM
Chronic pancreatitis
Genetics
o Link btw pancreatic cancer & colon cancer, familial breast cancer with the BRCA2 gene
mutation, hereditary pancreatitis, and a few other conditions
80% = 60-80 years
Black > white
Morphology:
o 60% of pancreatic cancers are found in the head of the pancreas
15% body, 5% tail, 20% whole organ
o Head = obstruct common bile duct & ampulla of Vater → causes a distended biliary tree /
gall bladder
Pain
Jaundice + pruritis
May find cancer due to jaundice!
o Body & tail = silent for long time → disseminated at discovery
Body = impinges on coeliac ganglion → pain
< eating food, lying supine
Tail → usually metastasises before any symptoms appear
Mostly ductal adenocarcinoma
Very invasive
o Extend through retroperitoneal space → nerves → spleen, adrenals, vertebral column,
transverse colon, stomach
o Lymph nodes – periportal, gastric, mesenteric, omental, portal-hepatic
o Enlarged liver due to metastases & distant metastases – lungs, bones
Silent & insidious onset = silent till growth impinges on adjacent structures
Classic presentation:
o Pain may be the 1st symptom – often already beyond cure
Dull epigastric pain – may have back pain
Often < supine and > sitting forward
o Jaundice – obstructive
o Weight loss
Duodenal obstruction → nausea & vomiting = late sign
Weight loss, anorexia, malaise, weakness = seen in advanced disease
Migratory thrombophlebitis – 10%
Diagnosis:
o There are no specific / sensitive markers for pancreatic cancer
o US / CT / MRI
Preferred method for imaging pancreas is IV / oral contrast-enhanced spiral CT
o Biopsy – usually done as a percutaneous FNA cytology
o ERCP (endoscopic retrograde cholangiopancreatography) – see gall bladder section
Used to evaluate patients with suspected pancreatic cancer and obstructive jaundice
Endoscope → catheter into pancreatic and biliary ducts → look for stones, tumours
etc
o PET scan – look for metastases
Rx:
o Surgery (although usually not resectable at time of diagnosis), radiation, chemotherapy
o Pain management & palliation
