Pancreatic exocrine insufficiency

Question 1

Key facts about the pancreas (where is it, length, function and distribution of cells, description of exocrine function)

Answer 1

• Retroperitoneal organ lying transversely across L2 on lumbar spine
• 12-15 cm long with head (exocrine end- 50%) and body and tail (50%- more endocrine)
• 99% of cells are exocrine and 1% endocrine
• CHO enzymes: alpha-amylase, secreted in active form
• Lipase enzymes: phospholipase A2, pancreatic lipase, secreted in active form (10-fold greater than needed- great reserve capacity. 90% of enzyme excretion are lipases)
• proteases: secreted in ‘pro’ form. Trypsinogen secreted and luminal enterokinase converts to trypsin (active) which in turn acts on producing active forms of carboxypeptidase. This means that enzymes are active at the right time
• pancreas also secretes NaHCO3 which neutralises stomach acid and ensures enzymes aren’t denatured
• enzymatic secretions peak at 30-60 mins after a meal and return to normal by 3-4 hours

Question 2

Phases of pancreatic activation

Answer 2

1) cephalic phase: sight and smell of food, pancreas prepares to release pro-forms of enzymes
2) gastric phase: presence of food in the stomach and gastric distention, enzymes begin to fill pancreatic ducts
3) intestinal phase: presence of food in duodenum. Release of enzymes and NaHCO3 is stimulated by cholecystokinin and secretin

Question 3

Epidemiology of pancreatic exocrine insufficiency

Answer 3

• incidence: pancreatic cancer (80-90%), chronic pancreatitis (50-80%), distal pancreatectomy (19-80%)
• prevalence: IBD (14-74%), untreated coeliac disease (4-80%), chronic pancreatitis without follow-up (64%)

Question 4

Causes of PEI: primary, secondary, tertiary

Answer 4

• primary causes: surgical resection/damage to pancreas, chronic pancreatitis, necrotizing pancreatitis, cystic fibrosis, cancer to head of pancreas
• secondary causes: gastric/duodenal resection which reduces activation of the pancreas, excess gastric acid denatures enzymes, radiation enteropathy damages pancreas
• tertiary causes: coeliac disease (4-80%), IBS/IBD (14-74%), older age (wear and tear), diabetes type 3C (reduces insulin and exocrine function as a consequence of fibrosis to the islets)

Question 5

Identifying PEI: faecal fat quantification, faecal elastase, C13 breath test, direct tests

Answer 5

• faecal fat quantification: ‘gold-standard’. Eat 100g fat every day for 72 hours and measure faecal fat (normally would expect 93% recovered). But burdensome on patients so rarely done
• faecal elastase: elastase-1 produced by pancreas for connective tissue digestion and not digested by the intestinal transit. <100 ug/g severe, <200 ug/g moderate, 200-500 ug/g mild
• C13 breath test: mix 200mg of C13 in 20g butter and ingest, measure C13 breath every 30 minutes for 6 hours. If <58% recovered=PEI
• direct test: imaging (CT, endoscopy), pancreatic ductal stimulation with secretin/cholecystokinin and measure what comes out of the pancreas

Question 6

Medical and dietetic assessment of PEI

Answer 6

• full clinical history to ascertain aetiology of PEI
• clinical history of PEI: GI symptoms such as bloating, cramping, steatorrhoea
• anthropometry: weight loss, weight gain, SF thickness
• biochemistry: urea, electrolytes, Mg, K, PO4, vitamin/mineral screen
• dietary assessment: 24 hour recall, see if certain foods are triggering symptoms, see if they are restricting
• functional tests such as faecal elastase and nutritional screen (serum deficiencies) would be sufficient to diagnose PEI and start treatment

Question 7

Consequences of PEI

Answer 7

• poor QoL, lack of energy
• pain, cramping, steatorrhoea, bloating
• nutrient deficiencies, malnutrition, places increased risk of infections, decreased bone mineral density
• increased risk of cardiovascular events

Question 8

Management of PEI

Answer 8

1) if PEI suspected, and there is weight loss (with or without steatorrhea) then start on PERT (Creon most commonly used)
2) Encourage eating healthy diet- they don’t need to restrict fat if they are on PERT
3) Encourage healthy lifestyle behaviours i.e. quitting smoking
4) give a multivitamin and mineral supplement
5) monitor and follow up (every 12 months, or every 6 months if under age of 16)

Question 9

PERT administration, dosage, side effects, efficacy

Answer 9

• Usually need 40-50,000 lipase units with a meal and 25,000 lipase units with a snack (may need to titrate up if eating very fatty food or if pancreatic resection)
• need to take as start eating (if gastroparesis may need to take sometime before)
• should not sprinkle on foods- if cannot swallow mix in powder with acidic (pH<5.5 foods)
• if still symptomatic, try proton pump inhibitor to reduce gastric secretions (i.e. omeprazole)
• generally well tolerated, but can get irritation at anus on very high doses, and porcine-origin so may interfere with beliefs
• meta-analysis found PERT to be very efficacious in reducing faecal fat excretion in chronic pancreatitis

Question 10

Enteral feeds and PERT considerations

Answer 10

• Size of tube: small tubes can be blocked with PERT
• continuous feeds, PENG recommends PERT every 2 hours
• with NG tubes may be able to take PERT orally, with NJ or jejunostomy need to administer straight into the jejunum (crush and mix with NaHCO3 first)

Question 11

Type 3C diabetes and PEI

Answer 11

• commonly misdiagnosed as T2DM which leads to poor management, these patients have worse glycaemic control and are more insulin dependent
• mechanisms explaining link: insulin is trophic factor for acinar cells (exocrine) and lack leads to atrophy, islets cells somehow mediate activity of exocrine cells, diabetic neuropathy may inhibit pancreatic reflexes and exocrine dysfunction