5. Pancreatic Exocrine Dysfunction
Pancreatic enzyme replacement therapy is currently the
mainstay of treatment for nutrient malabsorption secondary to
pancreatic insufficiency.
The leading cause of pancreatic insufficiency is chronic
pancreatitis in adults.
In children, the most common cause of pancreatic insufficiency is
cystic fibrosis.
Prevalence of exocrine pancreatic insufficiency :
Chronic pancreatitis - 30% to 40%
Cystic fibrosis - 80% to 90%
* Bruno et al , Maldigestion associated with exocrine pancreatic insufficiency: implications of gastrointestinal physiology and properties of enzyme preparations for
a cause-related and patient-tailored treatment. Am J Gastroenterol. 2005;90(9):1383– 1393.
6. Etiology
Pancreatic causes :
Chronic pancreatitis
Cystic fibrosis
Obstructions of the pancreatic duct
Shwachman-Diamond syndrome (SDS)
7. Nonpancreatic causes:
Celiac disease
Crohn disease
Autoimmune pancreatitis
Zollinger-Ellison syndrome
GI and pancreatic surgical procedures
8. Diagnosis of PED
Exocrine pancreatic insufficiency (EPI) is largely a clinical
diagnosis.
A patient with a known cause of pancreatic insufficiency who
presents with weight loss and fatty diarrhea is usually begun on
treatment without extensive testing.
The diagnostic options include
Indirect measures 72-hour fecal fat and fecal elastase
Direct measures Secretin– cerulein or
Secretin– pancreozymin tests
9. Steatorrhea is classically defined as at least 7 g of fecal fat over
24 hours, in the context of a 72-hour stool test while on 100 g of
fat daily
Fecal elastase testing may be used to demonstrate a lack of
endogenous enzyme. 72% sensitive for severe pancreatic
insufficiency and 90% specific.
Direct measurements with the secretin–cerulein or secretin–
pancreozymin tests are the gold standard for accurate
assessment of the exocrine function of the pancreas
* Hahn JU, Kerner W, Maisonneuve P, Lowenfels AB, Lankisch PG. Low fecal elastase 1 levels do not indicate exocrine pancreatic insufficiency in
type-1 diabetes mellitus. Pancreas. 2008;36(3):274–278.
10. Impairment of fat digestion first . Why?
Impairment of pancreatic lipase synthesis and secretion occurs
earlier;
More rapid and complete inactivation of lipase occurs in the
acidic duodenum as a result of impaired bicarbonate output;
Proteolytic degradation of lipase occurs earlier during aboral
transit than that of amylase and proteases;
Impairment of pancreatic bicarbonate secretion decreases
duodenal pH, resulting in precipitation of glycine-conjugated
bile acids and further deterioration of fat digestion; and
Extrapancreatic sources of lipase are unable to compensate for
loss of pancreatic lipase activity.
11. Clinical presentation
Patients usually will present for evaluation when <10% of
exocrine pancreatic function remains.
Steatorrhea is the leading symptom in patients with pancreatic
exocrine insufficiency.
Dyspepsia, diarrhea, meteorism, and malabsorbtion of fats,
proteins and carbohydrates and resulting deficiencies of fat
soluble vitamins (A, D, E, K)
12. Pancreatic Exocrine Enzyme
Supplementation
Indications* :
Weight loss and/or steatorrhea (≥15 g/day)
Dyspepsia
Diarrhea
Meteorism
Malabsorbtion of proteins and carbohydrates
No benefit in Pain management in Chronic Pancreatitis ( meta-
analysis result)
*Blumgart Hepatobiliary surgery
13. The main goal of the treatment of pancreatic exocrine
dysfunction is to ensure that optimal amounts of lipase reach
the duodenum with the delivered food.
With the currently available pancreatic enzyme supplement
preparations, azotorrhea (protein malabsorption) can be
eliminated (Brady et al, 1991), whereas steatorrhea usually can
be reduced but not totally corrected.
14. Management of PED
Lifestyle modifications (eg, avoidance of fatty foods, limitation of
alcohol intake, cessation of smoking, and consumption of a well-
balanced diet)
Vitamin supplementation (primarily the fat-soluble vitamins A,
D, E, and K)
Pancreatic enzyme replacement therapy (PERT), which is the
therapeutic mainstay
15. Long-term monitoring of patients with EPI should focus on the
following 2 issues:
Correction of nutritional deficiencies
Treatment of causative diseases (when possible)
16. Pancreatic Enzyme Replacement
Therapy
Endpoints of treatment are normalization of gut absorption and
correction of nutritional deficiencies.
The typical indications for initiating PERT are progressive
weight loss and steatorrhea.
PERT’s efficacy may be increased through the use of higher
enzyme doses and enteric-coated enzymes, the administration
of therapy during food, and the suppression of acid.*
* Daniel et al, Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis, Gut j .2016
17. PERT causes improvement in:
Coefficient of fat absorption (CFA),
Serum nutritional parameters,
GI symptoms,
Quality of life
18. Approved agents
The pancreatic enzyme products (PEPs) used for PERT are
extracts of porcine pancreas that contain all 3 pancreatic
enzymes (i.e., amylase, protease, and lipase) in varying
proportions.
Lipase plays the paramount role in therapy
6 PEPs have been approved by the US Food and Drug
Administration (FDA) for the treatment of maldigestion in
patients whose bodies do not produce sufficient pancreatic
enzymes:
19. Creon (Abbott Laboratories, North Chicago, IL)
Zenpep (Eurand Pharmaceuticals, Yardley, PA)
Pancreaze (Janssen Pharmaceuticals, Titusville, NJ)
Ultresa (Aptalis Pharma US, Birmingham, AL)
Viokace (Aptalis Pharma US, Birmingham, AL)
Pertzye (Digestive Care, Bethlehem, PA)
* These PEPs are not interchangeable.
20.
21.
22. Pakreoflat ( tab & Syrup)
170 mg pancreatin from porcine pancreas
6 500 FIP units lipase
5 500 FIP units amylase
400 FIP units protease
&
80 mg dimethicone
23. PEPs are administered together with meals and snacks.
PEP dosing for PERT is based on the content of lipase units
The pancreatic lipase replacement dose should be adjusted on
the basis of body weight, clinical symptoms, and stool fat
content.
Several days should be allowed between dose adjustments
24. Dosage Recommendations*
Total daily dose reflects ~3 meals per day and 2 to 3 snacks per
day, with half the mealtime dose given with a snack.
Dosing should not exceed recommended maximum dosage set
forth by the Cystic Fibrosis Foundation Consensus Conferences
Guidelines.
Doses of lipase >2,500 units/kg/meal, lipase >10,000
units/kg/day, or lipase >4,000 units/g fat daily should be used
with caution and only with documentation of effectiveness by 3-
day fecal fat measures indicating a significantly improved
coefficient of fat absorption
Doses of lipase >6,000 units/kg/meal are associated with
colonic stricture and should be decreased.
25. Pancreatic insufficiency due to conditions such as cystic fibrosis
Oral (Creon, Pancreaze, Pertzye, Ultresa, Zenpep):
Initial: Lipase 500 units/kg/meal. Dosage range: Lipase 500 to 2,500
units/kg/meal.
Maximum: Lipase ≤2,500 units/kg/meal or lipase ≤10,000
units/kg/day or lipase <4,000 units/g of fat daily
26. Pancreatic insufficiency due to chronic pancreatitis or
pancreatectomy:
Oral:
Creon , Viokace (administer in combination with a proton pump
inhibitor): :
Initial: Lipase 500 units/kg/meal with individualized dosage
titrations. Usually, half the prescribed dose for an
individualized full meal should be given with each
snack.
Maximum: Lipase ≤2,500 units/kg/meal or lipase ≤10,000
units/kg/day or lipase <4,000 units/g of fat daily
27. Pancreatic insufficiency (exocrine) due to pancreatic cancer
(off-label dosing):
Oral:
Initial: 25,000 to 50,000 units (lipase) per meal or 1,000 units
(lipase)/kg/day or 4,000 units/5 to 7 g fat at each meal; escalate
dose based on relief of symptoms;
Maximum dose: 2,500 units (lipase)/kg/meal
29. Use with caution in Pregnancy , Renal
dysfunction and hepatic dysfunction
30. Summary
Pancreatic enzyme replacement therapy is currently the
mainstay of treatment for nutrient malabsorption secondary to
pancreatic insufficiency.
The leading cause of pancreatic insufficiency is chronic
pancreatitis in adults.
Exocrine pancreatic insufficiency (EPI) is largely a clinical
diagnosis.
Steatorrhea is the leading symptom in patients with pancreatic
exocrine insufficiency.
Lipase plays the paramount role in therapy
Dosage range: Lipase 500 to 2,500 units/kg/meal with half the
dose with snacks.
Notas do Editor
A very welcome good morning to all my teachers ,seniors , colleagues and juniors . I am going to present my presentation on ……………….
First of all we will have a brief review of physiology of secretion of pancreatic enzymes
As we all know that pancreas secretes all classes of enzymes required for digestion of fats, proteins & carbohydrates.
Of these, Lipases and Amylase are secreted in the active form, proteases are secreted as pro-enzymes.
These secretions are under the control of GI hormones and vagal stimuli.
The presence of peptides and fatty acids from food triggers the release of cholecystokinin (CCK).
As already mentioned, Proteases are secreted as pro-enzymes.
Trypsinogen is converted to the active enzyme trypsin by enterokinase, which is present in intestinal epithelium when the pancreatic juice enters the duodenum.
In an Auto protective mechanism, acinar cells synthesize pancreatic secretory trypsin inhibitor, which also protects acinar cells from autodigestion because it counteracts premature activation of trypsinogen inside acinar cells.
Pancreatic secretory trypsin inhibitor is encoded by serine protease inhibitor Kazal type 1 (SPINK1) gene. SPINK1 gene mutations are associated with the development of chronic pancreatitis, especially in childhood.
Shwachman-Diamond syndrome (SDS): This is a rare autosomal recessive disorder characterized by EPI, bone marrow dysfunction, leukemia predisposition, and skeletal
abnormalities.
Obstructions of the pancreatic duct (eg, from pancreatic cancer or ampullary tumors)
Celiac disease (secondary to decreased pancreatic stimulation)
Crohn disease: This is associated with pancreatic autoantibodies that lead to impaired Pancreatic exocrine function.
Autoimmune pancreatitis: This is often caused by immunoglobulin G4 (IgG4)-related disease and can progress to EPI.
Zollinger-Ellison syndrome: This can produce EPI through acid inactivation of pancreatic enzymes; it is corrected by controlling the acid secretion
A Secretin- cerulein test was performed after overnight fast by infusing intravenously secretin (1 U/kg/h) and caerulein (100 ng/kg/h) over 90 min. The duodenal content was continuously aspirated and separated at 15-min intervals and immediately analyzed for pH, bicarbonate, amylase, lipase, elastase, carboxypeptidase A
Ceruletide, also known as cerulein or caerulein, is a ten amino acid oligopeptide that stimulates smooth muscle and increases digestive secretions. Ceruletide is similar in action and composition to cholecystokinin.
Cholecystokinin, previously called pancreozymin
limitations of the direct functional tests are that they are usually performed only at specialized centers, and they are time consuming and expensive
Among the three nutrient components : carbohydrates, fats and proteins; the impairment of fat digestion occurs first . The main reason behind this are :
Meteorism medical condition in which excess gas accumulates in the gastrointestinal tract and causes abdominal distension.
Also called as flatulence
Three main components of managements are :
All these contain different combinations of lipase/amylase/protease , so these PEPs ( Pancreatic enzyme products) are not interchangeable