Sa Med Pancreas Anatomy & Physiology

Front 1

How can you tell the difference between the right and left side of the pancreas?

Back 1

Left side tends to be fatter
Right side tends to have a flap

Front 2

What are the 3 functional & anatomical divisions of the pancreas?

Back 2

1) Endocrine pancreas
2) Exocrine pancreas
3) Pancreatic duct

Front 3

98% of the pancreatis mass is _______ tissue that produces digestive enzymes.

Back 3

Exocrine

Front 4

What cells make up the endocrine pancreas? What do they produce?

Back 4

Islet cells produce:
insulin, glucagon, somatostatin

Front 5

What cells make up the exocrine pancreas?

Back 5

Acinar cells

Front 6

What are the 4 products of the acinar cells in the exocrine pancreas?

Back 6

1) Digestive enzymes
2) Intrinsic factor
3) Pancreatic polypeptide
4) Pancreatic secretory trypsin inhibitor

Front 7

What are the 2 secretions of the pancreatic duct epithelium when stimulated?

Back 7

**Produces large volumes of bicarbonate and fluid

Front 8

What is intrinsic factor important for?

Back 8

Vit B12 absorption

Front 9

What is the function of the bicarbonate and fluid secreted by the pancreatic duct epithelium?

Back 9

Neutralizes gastric acid in the duodenum, provides pH optimum for digestive enzymes (neutral is best), also protective against gastric acid mediated damage
-if excess acid in upper part of SI then some enzymes don't work effectively

Front 10

What are pancreatic acini?

Back 10

Lobules of secretory epithelial cells arrange around the termination of the pancreatic ductules

Front 11

What shape are pancreatic acinar cells?

Back 11

Pyramidal

Front 12

The secretory epithelial cells of the pancreatic acini contain a large number of _______.

Back 12

Secretory granules

Front 13

What do the secretory granules of the pancreatic acini contain?

Back 13

Zymogens of proteases, active amylase/ lipase, and pancreatic secretory trypsin inhibitor

Front 14

What stimulates the secretory granules in the pancreatic acini to go from the apex into the pancreatic ductule?

Back 14

Cholecystokinin

Front 15

Why is it so important for proteases to be contained as zymogens in the secretory granules and not get activated ?

Back 15

Because active proteases cause a runaway cascade in activation of proteases--> proteases destroy the cell

Front 16

Why is pancreatic secretory trypsin inhibitor important in the secretory granules of the pancreatic acinar cells?

Back 16

Inhibits any protease zymogens that may accidentally get activated

Front 17

What are the 6 enzymes/ zymogens that are the most damaging form a disease perspective?

Back 17

1) Trypsinogen
2) chymotrypsinogen
3) Elastase
4) Lipase
5) Amylase
6) Gelatinase

Front 18

What is the function of trypsinogen?

Back 18

Precursor to trypsin, the major proteolytic enzyme
-trypsin breaks down proteins and peptides

Front 19

What is the function of chymotrypsinogen?

Back 19

Precursor to chymotrypsin-an important proteolytic enzyme

Front 20

What's the difference b/w trypsin and chymotrypsin?

Back 20

Prefer to break down different peptide binds

Front 21

What is the function of elastase?

Back 21

Degradation of elastin

Front 22

What is the function of lipase?

Back 22

Hydrolysis of triglycerides to free fatty acids and monoglyceride

Front 23

What is the function of amylase?

Back 23

Hydrolyses starch molecules to di- and trisaccharides and small branched polysaccharides

Front 24

What is the function of gelatinase?

Back 24

Degradation of collagen and gelatin

Front 25

What are 3 different mechanisms that exist in the pancreas to reduce the risk of pancreatic autodigestion?

Back 25

1) zymogens
2) Pancreatic secretory trypsin inhibitor
3) SERPIN's (serine protease inhibitors)

Front 26

Where and how is trypsin initially activated? What happens once its activated?

Back 26

-Within the small intestinal lumen trypsin is initially activated by enterokinase
-trypsin can then autocatalytically activate & also activates chymotrypsin

Front 27

What is the main protective mechanism against pancreatic autodigestion?

Back 27

Synthesis, storage and secretion as zymogens

Front 28

Where is pancreatic secretory trypsin inhibitor synthesized and secreted?

Back 28

Along with trypsinogen

Front 29

What is the function of pancreatic secretory trypsin inhibitor?

Back 29

Rapidly inhibits any trypsinogen that becomes activated within the cell

Front 30

What are SERPIN's? What is the main one?

Back 30

Serine proteinase inhibitors
-Most important is the blood protein alpha1-proteinase inhibitor

Front 31

What is the function of SERPIN's?

Back 31

Main target is neutrophil elastase, but can inhibit trypsin if released into insteritiium, limits local damage

Front 32

What are the 3 hormones responsible for endocrine STIMULATION of the exocrine pancreas?

Back 32

Cholecystokinin, secretin, gastrin

Front 33

In addition to endocrine factors, what else can increase pancreatic secretions?

Back 33

parasympathetic input via the vagus nerve and cholinergic fibers from the enteric nervous system

Front 34

What is the source of cholecystokinin?

Back 34

Duodenal mucosa (when exposed to fat and protein)

Front 35

What is the effect of cholecytokinin release from the duodenal mucosa in response to fat & proteins?

Back 35

Increases digestive enzymes

Front 36

What is the source of secretin?

Back 36

Duodenal mucosa, released when exposed to low pH

Front 37

What is the effect of secretin release?

Back 37

Increases bicarbonate and fluid secretion (from pancreatic ductules)

Front 38

What is the source of gastrin?

Back 38

Gastric mucosa releases gastrin in response to gastric distension
-tells pancreas has full stomach & needs digestive enzymes

Front 39

What is the effect of gastrin release?

Back 39

increases digestive enzymes

Front 40

What are the 2 hormones/mechanisms that are responsible for downregulation of the exocrine pancreas?

Back 40

1) Somatostatin** (major one)
2) small intestinal negative feedback

Front 41

What is the source of somatostatin?

Back 41

-Pancreatic islet D cells
-intestinal mucosal D cells

Front 42

What are the effects of somatostatin release?

Back 42

Inhibits CCK & secretin effects
-somatostatin cells are farther down the intestine than CCK releasing cells
-stimulation happens bc of CCK release

Front 43

What is the source of small intestinal negative feedback on the exocrine pancreas?

Back 43

Intestinal mucosa

Front 44

What is the effect of the small intestinal negative feedback via the intestinal mucosa?

Back 44

Inhibition of pancreatic enzyme synthesis and release

Front 45

What activates the small intestinal feedback on the exocrine pancreas?

Back 45

Presence of proteolytically active enzymes in the jejunum & ileum leads to decreased pancreatic enzyme synthesis and release

Front 46

What stops the small intestinal feedback on the exocrine pancreas once it starts?

Back 46

Inhibition of proteases within the GI lumen blocks this feedback inhibition, leading to persistent enzyme synthesis & release

Front 47

What are the 3 main phases of pancreatic secretion?

Back 47

1) Cephalic phase -before feeding
2) Gastric phase- peak, ~1-2 h after feeding
3) Intestinal phase- peak ~8-12 h after feeding
~varying amount of enzymes vs fluids and bicarbonate released during the different phases

Front 48

In most dogs, the majority of the pancreatic secretions enters the duodenum via the _____ duct at the _____ papilla.

Back 48

-Accessory duct (Duct of --santorini)
-Minor duodenal papilla

Front 49

What empties into the major duodenal papilla in the dog?

Back 49

The pancreatic duct, which is a minor duct that enters the duodenum in close association to the biliary duct at the major duodenal papilla

Front 50

Does biliary obstruction usually cause pancreatic disease in the dog? Why or why not?

Back 50

No, but the pancreatic duct which is in close association to the biliary duct is the minor duct, the majority of pancreatic secretions is via the accessory duct

Front 51

Describe the pancreatic duct anatomy of the cat. Where do does the pancreatic duct(s) drain?

Back 51

In most cats there is a single duct that fuses w/ the bile duct and enters the duodenum at the major duodenal papilla
-pancreatic secretions go through cystic duct --> common bile duct--> major duodenal papilla

Front 52

Does biliary obstruction usually cause pancreatic disease in the cat?

Back 52

Yes, and pancreatic disease can cause biliary obstruction (can flatten bile duct--> cholestasis) because in the cat there's a single pancreatic duct that fuses with the biliary duct

Front 53

What small animals get acute pancreatitis?

Back 53

dogs and cats

Front 54

What small animals get chronic pancreatitis?

Back 54

Dogs & cats
-dominant form in cats

Front 55

What are the 4 major pancreatic diseases?

Back 55

1) Acute pancreatitis
2) Chronic pancreatitis
3) Pancreatic adenocarcinoma
4) Exocrine pancreatic insufficiency

Front 56

Of the 4 major pancreatic diseases, which has the greatest short-term risk?

Back 56

Acute pancreatitis

Front 57

Clinical pathologic testing for pancreatic disease is usually directed towards identification of ______________.

Back 57

The pancreatic inflammation

Front 58

What are the 2 traditional specific clinical pathology tests for inflammation of the pancreas?

Back 58

1) Serum amylase activity
2) Serum lipase activity

Front 59

What are the 2 pancreas specific enzymes that we measure the mass amount of to test for inflammation of the pancreas?

Back 59

1) Serum trypsinogens (TLI)
2) Serum pancreatic lipase immunoreactivity

Front 60

What do we assume when we measure pancreatic diagnostic tests? (3)

Back 60

1) That expression of the enzyme is constant
2) That the clearance mechanisms are normal
3) That there is no minimal absorption from the lumen of the intestine
*in pancreatic and gastrointestinal disease all of these assumptions may be false

Front 61

How is trypsin eliminated from the system?

Back 61

Renal clearance, accumulates w/ renal failure

Front 62

How are amylase and lipase eliminated form the system?

Back 62

**Renal clearance
-so if azotemic and lipase/ amylase is high could be due to decreased clearance

Front 63

Acute pancreatitis clinically presents the same as what 3 other diseases?

Back 63

1) acute renal failure
2) Acute gastritis
3) foreign body
-in all these cases may see elevation in amylase & lipase activity in dogs that do not have pancreatitis

Front 64

Serum amylase and lipase activity is easy to measure in serum w/ automated tests and is elevated in many cases of acute pancreatitis in dogs. So why isn't it a reliable indicator of pancreatitis?

Back 64

Not specific to the pancreas
-hepatic, gastric and duodenal lipases

Front 65

What are 4 other causes of increased serum lipase activity in dogs other than pancreatitis?

Back 65

1) Duodenitis
2) Viral enteritis
-sky high in parvo puppies
3) Gastritis
4) Hepatitis

Front 66

Where is trypsin synthesized?

Back 66

Only in the pancreas
-so trypsinogen in serum can only come from the pancreas

Front 67

What happens to trypsinogen expression when the pancreas is inflamed?

Back 67

Dramatically decreases

Front 68

What is the downfall to tests that measure trypsin?

Back 68

Test is specialized so takes longer to get results

Front 69

What are the pancreas specific enzymes? (2)

Back 69

Trypsin
Pancreas specific lipase

Front 70

What test is used to measure pancreas specific lipase? What type of assay is this

Back 70

Pancreatic lipase immunoreactivity= spec cPL and spec fPL
-total mass assay

Front 71

How can the lipase from the pancreas be measured and not lipase from other parts of the body?

Back 71

Lipase from pancreas has a different tertiary structure to the other lipases, antibodies raised against this protein can be used to measure PLI specifically in serum sample

Front 72

What is the difference b/w a total mass assay and an activity assay?

Back 72

-Total mass assays use immunoassay where measure amount of substrate binding by enzyme= much more specific, don't rely on presence of an active site
-Activity assay: detects catalytic activity against a substrate, substrates vary in specificity*

Front 73

What are 2 examples of activity assays?

Back 73

traditional lipase and amylase measurements

Front 74

Are total mass assays or lipase/amylase tests more specfiic?

Back 74

Total mass assays are species specific = much much more specialized test

Front 75

What is the benefit of an activity assay over a total mass assay?

Back 75

Activity assay are common in many in-house systems

Front 76

What pancreatic test is available as a SNAP test?

Back 76

Specific pancreatic lipase
-not quantitative

Front 77

How are the specific pancreatic lipase SNAP tests different from all other SNAP tests?

Back 77

A dot doesn't mean positive, the dot needs to be darker than the control dot to indicate increase, darker the dot, the higher the level- lots of subjectivity!!

Front 78

What should you do after you get what you think is a positive SNAP test for pancreatic specific lipase?

Back 78

Mail out for a quantitative assay

Front 79

Compare the clearance, size and charge of TLI to PLI.

Back 79

TLI molecules are relatively small and negatively charged so can pass through glomerulus---< renal clearance
-PLI is larger and positively charged so doesn't undergo renal clearance so taken up by Kupffer cells

Front 80

Is TLI or PLI more likely to be elevated in an animal with pancreatitis?

Back 80

PLI because TLI has a shorter half life so it's often already eliminated
-PLI stays elevated for 10 days
-TLI reduced to normal in 3 days so may be normal by the time you see animal after bout of pancreatitis

Front 81

***What is the test of choice for pancreatitis? exocrine pancreatic insufficiency?

Back 81

Pancreatitis: PLI (greater relative increase in concentration and longer duration of elevation)
EPI: TLI

Front 82

What is a high TLI in cats usually associated with?

Back 82

small intestinal disease

Front 83

What are 4 other methods used to assess the pancreas other than looking at its enzyme activity/ content?

Back 83

1) Radiographs
2) Ultrasonography
3) CT
4) Endoscopic retrograde cholecystopancreatography

Front 84

How can you assess the pancreas via radiographs?

Back 84

-Pancreas is typically not visible
-Pancreatitis causes a local peritonitis

Front 85

How does local peritonitis due to pancreatitis appear on radiographs?

Back 85

-loss of detail & contrast, increased density in cranial abdomen (hazy and fuzzy)
-May see increased angle of pylorus (pancreas sits in pylors so can open up angle)
-ileus
-abdominal effusion (in bad cases)

Front 86

What are 4 signs of pancreatitis that can be seen using ultrasonography?

Back 86

1) pancreatic enlargement
2) Local effusions
3) Peripancreatic fat is often hyperechoic
4) Mesentery often hyperechoic
*findings very operator dependent
-can rule in disease but not rule out

Front 87

What is the method of choice to assess human patients for pancreatic disease?

Back 87

Computed tomography