5.Pancreatic Enzymes. Exocrine function of pancreas Enzyme of pancreas

Exocrine function of pancreas
Enzyme of pancreas

1. Pancreatic Enzymes
Muzamil Mohammed
clinical chmistry 2024
In clinical chemistry, serum or
plasma measurement of
pancreatic enzyme provides
valuable information for
diagnosing and managing
pancreatic diseases,
particularly acute pancreatitis
and chronic pancreatic
disorders.

2. Pancreatic Enzymes Overview:
•The pancreas plays a crucial role in both
endocrine systems and exocrine pancreatic
(enzyme-secreting) fluid (secretes about 1.5 to 2
L/d), which is rich in essential digestive enzymes
for carbohydrates, proteins, and fats.
•Amylase: Breaks down carbohydrates (starch)
into simpler sugars.
•Lipase: Breaks down triglycerides (fats) into fatty
acids and glycerol.
•Proteases (e.g., trypsin, chymotrypsin): Break
down proteins into amino acids (less commonly
measured in clinical labs).

3. α-Amylase (AMY, EC 3.2.1.1)
•Location:Amylase is found in many
tissues, with the highest amount in
the acinar cells of the pancreas and in
the salivary glands.
•Function:Amylase catalyzes the
hydrolysis of 1,4-a-glycosidic bonds in
straight and branched polysaccharide ,
releasing various types of sugars (i.e
maltose and dextrin). initiates by
salivary isoform of amylase (s-AMY) in
the mouth to be continue by
pancreatic isoenzyme of amylase (p-
AMY) in intestine.
1,4-α-glycosidic bonds
1,6-α-glycosidic bonds
o

4. Clinical Relevance
•Serum amylase levels are measured
primarily to diagnose and monitor
acute pancreatitis. Amylase levels rise
within 2-12 hours of onset, peak at
12-72 hours, and return to normal
within 3-5 days.
•Hyperamylasemia is not exclusive to
pancreatitis; it can also occur in
conditions like salivary gland disorders
(e.g., mumps), renal failure (due to
decreased clearance), and
macroamylasemia.

5. Clinical Significance
•Amylase is the only enzyme that is
filtered through the glomerulus.
•Macroamylasemia: A benign condition
where amylase binds to large
molecules (usually immunoglobulins),
leading to elevated serum amylase
with normal urine amylase.
•Limitations: Amylase is not specific to
the pancreas, as it can also originate
from the salivary glands. This can lead
to false-positive elevations in non-
pancreatic conditions.

6. Diseases of the Pancreas
•Other than trauma, only three diseases cause more than 95% of pancreatic
medical attention. All result in severely diminished pancreatic exocrine function.
is an inherited autosomal recessive disorder characterized by
dysfunction of mucous and exocrine glands throughout the body. Approximately 65-
80% of diagnosed children have pancreatic insufficiency
the fourth most frequent form of fatal cancer. Most
pancreatic tumors arise as adenocarcinomas of the ductal epithelium.
, or inflammation of the pancreas, is ultimately caused by autodigestion
as a result of bile or duodenal contents reflux into the pancreatic duct.
•Pancreatic insufficiency can be detected by enzyme tests when 50% of the acinar
cells are destroyed, but clinical symptoms appear after 90% of cells are destroyed
•Pancreas has a rich nerves supply, so pain is a prrominent feature of the disease.

7. Measurments
Based on the
hydrolysis of small oligosaccharides as
substrates catalyzed by amylase,
result in a color change.

Measure the real time conversion of
specific substrates into products
detectable by spectrophotometry.

Differentiates between pancreatic and
salivary amylase isoenzymes.
•Reference Range: Typically 25-125 U/L.
Sample: Serum, heparinized Plasma.
: in macroamylasemia or
for prolonged elevations in acute
pancreatitis.

8. Lipase (LPS, EC 3. 1.1.3)
•Function: Lipase catalyzes the
breakdown of triglycerides into free
fatty acids and glycerol. It is primarily
produced by the pancreas and plays a
critical role in fat digestion.
•The enzymatic activity of human
lipase is specific for the ester bonds at
positions 1 and 3; it generates a 2-
acylglycerol and releases fatty acids.
•Location: Lipase exists exclusively in
the pancreas. The complete catalytic
activity is achieved in the presence of
bile salts and the coenzyme colipase.

9. Clinical Significance:
•Acute Pancreatitis: Lipase levels rise
within 4-8 hours of symptom onset,
peak at 24 hours, and remain elevated
longer than amylase, typically up to 7-
14 days. It’s particularly useful in
diagnosing late-presenting cases of
acute pancreatitis.
•Chronic Pancreatitis:Lipase levels may
not be significantly elevated due to
reduced pancreatic enzyme production
over time.
•Also rise in pancreatic cancer, renal
failure & Peptic ulcer disease

10. Measurements
: Most common involves the
hydrolysis of a triglyceride substrate and the
quantification of the resulting fatty acids. (i.e.,
titrimetric methods) to produce a blue-purple
chromogen with peak absorption at 580 nm
: Use specific antibodies to detect
lipase, offering high specificity.
: measuring light scattering
by turbidity change as the triglyceride substrate
is hydrolyzed
: Typically 0-160 U/L, serum is
preferable

11. Amylase and Lipase Together:
Both enzymes should be tested in suspected acute pancreatitis. Lipase is generally
preferred due to its higher specificity and longer duration of elevation.
Chronic Conditions: Enzyme levels might be normal or only mildly elevated in chronic
pancreatitis due to the progressive loss of pancreatic tissue.
Limitations and Considerations:
Non-Specificity: Elevated amylase is not always indicative of pancreatic disease;
correlation with lipase, imaging, and clinical findings is essential.
Timing: Enzyme levels must be interpreted in the context of time since symptom
onset, as peak levels vary between amylase and lipase.
•Hemolysis: can interfere leading to falsely elevated results.

12. Other Pancreatic Enzymes and Tests
•A. Trypsin and Chymotrypsin
•Trypsin and chymotrypsin are proteolytic enzymes produced by the pancreas.
These are typically measured in stool samples, particularly in patients with
suspected pancreatic insufficiency.
•B. Fecal Elastase
•Fecal elastase is a marker of pancreatic exocrine function. It is used to
diagnose exocrine pancreatic insufficiency (EPI), which can occur in chronic
pancreatitis or cystic fibrosis. Unlike serum enzymes, fecal elastase is low in
pancreatic insufficiency.

13. Diagnostic Evaluation of Pancreatic Diseases
•A.Acute Pancreatitis: Acute pancreatitis is an
inflammatory condition of the pancreas that can
range from mild to life-threatening.
•Diagnosis: besides characteristic abdominal pain
(Typically in the epigastric region, radiating to the
back) & Imaging findings, amylase and lipase
levels both rise during acute pancreatitis, but
lipase is preferred due to its higher specificity and
longer duration of elevation.

14. Diagnostic Evaluation of Pancreatic Diseases
•B. Chronic Pancreatitis: Chronic pancreatitis is characterized by
progressive pancreatic inflammation and fibrosis, leading to
permanent damage. Unlike acute pancreatitis, enzyme levels may be
less elevated, especially in advanced cases where the pancreatic
tissue is significantly damaged.
•Diagnostic Challenges: Amylase and lipase levels may be normal or
only mildly elevated, especially in late-stage chronic pancreatitis.
Therefore, additional diagnostic tools like imaging and fecal elastase
testing may be required.

15. Diagnostic Evaluation of Pancreatic Diseases
•C. Pancreatic Cancer :
•Pancreatic cancer often presents with nonspecific symptoms, and by
the time enzyme levels are elevated, the disease may be advanced.
Lipase may be elevated, but it is not a primary diagnostic marker for
pancreatic cancer. Instead, imaging and tumor markers like CA 19-9
are more commonly used.

16. Case 1: Acute Pancreatitis
•A 45-year-old male presents with sudden onset of severe epigastric
pain radiating to the back. He has a history of alcohol use.
•Lab Results: Serum amylase = 450 U/L (normal: 25-125 U/L), serum
lipase = 900 U/L (normal: 0-160 U/L).
•Interpretation: Elevated amylase and lipase suggest acute pancreatitis,
likely related to alcohol use. Lipase is preferred for monitoring due to
its specificity and prolonged elevation.

17. Case 2: Chronic Pancreatitis
•A 50-year-old female with a history of chronic alcohol use presents
with recurrent episodes of abdominal pain and weight loss.
•Lab Results: Serum amylase = 90 U/L (normal), serum lipase = 120 U/L
(normal).
•Interpretation: Normal enzyme levels do not rule out chronic
pancreatitis. Further diagnostic evaluation, including imaging and
fecal elastase, is warranted.

18. Case 3: Pancreatic Cancer
•A 65-year-old male presents with jaundice and weight loss.
•Lab Results: Serum lipase = 180 U/L (mildly elevated), CA 19-9 = 400
U/mL.
•Interpretation: Mildly elevated lipase, in the context of jaundice and a
high CA 19-9 level, raises suspicion for pancreatic cancer. Imaging and
biopsy are necessary for confirmation.

20. SAQ
1. Which enzyme is primarily responsible for the breakdown of proteins
in the stomach and small intestine?
A) Amylase
B) Lipase
C) Pepsin
D) Trypsin

21. 2. Pancreatic lipase is crucial for the digestion of which type of nutrient?
A) Proteins
B) Carbohydrates
C) Fats
D) Nucleic acids

22. 3.What type of molecule does pancreatic amylase primarily act upon?
A) Proteins
B) Fats
C) Carbohydrates
D) Nucleic acids

23. 4. Which enzyme is secreted in an inactive form as trypsinogen to
prevent autodigestion of pancreatic tissue?
A) Amylase
B) Trypsin
C) Lipase
D) Chymotrypsin

24. 5.The most specific and sensitive blood test for detection of acute
pancreatitis is
a. Serum amylase
b. Serum lipase
c. Immunoreactive trypsinogen
d. Fasting blood glucose

25. 6.Which of the following is a sensltlve, specific, and noninvasive way to
detect pancreatic insufficiency?
a. Fecal fat test
b. Pancreatic elastase 1 test
c. Serum trypsin test
d. Secretin-cholecystokinin test

26. 7. Which enzyme level can remain elevated for a longer period
following an episode of acute pancreatitis?
A) Amylase
B) Lipase
C) Both A and B equally
D) Neither A nor B

27. 8. Which of the following is NOT a typical cause of elevated pancreatic
amylase levels?
A) Pancreatic cancer
B) Acute pancreatitis
C) Salivary gland inflammation
D) Renal failure

28. 9. Which of the following scenarios would most likely lead to a
significant increase in lipase but not amylase?
A) Gastroenteritis
B) Acute pancreatitis
C) Salivary gland inflammation
D) Gallbladder disease

29. 10.Elevations in pancreatic amylase and lipase levels are typically seen
in which type of pancreatitis?
A) Chronic pancreatitis
B) Acute pancreatitis
C) Autoimmune pancreatitis
D) All types of pancreatitis