Pancreas I

Question 1

How does acute pancreatitis occur?

Answer 1

Patho physi starts with intracellular activation of enzymes and local and systemic disease results from inflammatory processes and enzyme injury

Question 2

Describe the morphology of the cells in the pancreas

Answer 2

90% are acinar cells which are protein/enzyme-synthesizers in the pancreas which are secreted as inactive proenzymes in membrane enclosed vesicles to prevent damage to the cells

Question 3

What is SPNK-1?

Answer 3

An inhibitor produced in the pancreas designed to prevent activation of trypsin from trypsinogen

Question 4

How are pancreatic enzymes stimulated to be released from acinar cells?

Answer 4

Either via Gs (cAMP) via VIP or Gq (Ca2+) via Ach secondary messengar pathways that promote exocytosis of vesicles in the pancreatic lumen to be circulated to the GI

Question 5

It is generally accepted that the earliest event in the pathogenesis of acute pancreatitis is what?

Answer 5

the conversion of pancreatic zymogens to their active forms within the acinar cell.

Question 6

Answer 6

Co-localization of ZG and lysosomes cause enzymes like cothepsin B to activate trypsin from the zymogen granules which then stimulate autodigestion of the acinar cells

Question 7

How does early activation of pancreatic proteases cause a localized inflammatory response?

Answer 7

Proteases activate complement, causing recruitment for C3a and C5a and thus PMNs and macrophages. These cells then release cytokines such as TNF-a, IL-1, PAF, and NO which produce vascular injury and inflammatory responses

Question 8

So how do the local effects of acute pancreatitis present clinically?

Answer 8

There will be pancreatic swelling and liquid extravasation due to inflammatory induced swelling as well as local fat necrosis and hemorrhage leading to pain that raidates to the back and N/V

Question 9

Acute pancreatitis= FAT necrosis

Answer 9

Islets are typically spared until it becomes very severe

Question 10

Hemorrhage can occur if vessels are digested!

Answer 10

More hemorrhage here and islet destruction

Question 11

Question 12

What mainly causes the fat necrosis seen in acute pancreatitis?

Answer 12

lipase production

Question 13

Obviously if pancreatic enzymes reach circulation, the initial local inflammation caused by acute pancreatitis will become widespread. How is this prevented?

Answer 13

Circulating enzymes, such as a1-antitrypsin, which inactivates proteases, and a-macroglobulin, which binds to circulating trypsin and facilitates monocyte clearance of the complex, prevent systemic spread

Question 14

What are the signs and mediators of a poorly contained pancreatitis?

Answer 14

fever, malaise, and confusion via TNFa and Il-6 activation

Hypotension via kallikrein activation

DIC and hemorrhage via thrombin activation, and elastase and chymotrypsin activity

hypoxemia via activation of phospholipase A2 which damage surfactant

hypocalcemia from calcium binding to circulating lipids via a fat saponification process

Question 15

What percentage of pancreatitis events become disseminated?

Answer 15

Only about 20%

Question 16

Acute pancreatitis

Question 17

What are the main causes of acute pancreatitis?

Answer 17

gallstones and EtOH

Question 18

What are the main symptoms of acute pancreatitis?

Answer 18

abdominal pain that radiates to the back, N/V

Question 19

How is acute pancreatitis diagnosed?

Answer 19

Two of the following Three required:

1. abdominal pain, nausea/vomiting
2. Notably elevated serum amylase and lipase more than 3x upper limit of normal
3. CT imaging showing pancreatic inflammation

Question 20

How is acute pancreatitis managed/tx?

Answer 20

IV fluids, pain meds, and remove stones if causative

Question 21

How is trypsin activated?

Answer 21

A Lysine-IlE bond is broken at the N-terminal of trypsinogen

Question 22

How is trypsin deactivated and what is the basis of hereditary pancreatitis?

Answer 22

Cleavage of a arg-val bond at the C-terminal deactivates trypsin and in hereditary pancreatitis the Arg is replaced by a His which cant be degraded

Question 23

More on hereditary pancreatitis

Answer 23

AD disorder and the shared feature of most forms is a defect that increases or sustains the activity of trypsin

Genes implicated in hereditary pancreatitis deserve special note: PRSS1 , and CFTR (cystic fibrosis).

Question 24

What does the gene PRSS1 (7q34) do?

Answer 24

Serine protease 1 (trypsinogen 1)- Cationic trypsin. Gain-of-function mutations prevent self-inactivation of trypsin

Question 25

How does mutation of CFTR (7q31) cause pancreatitis?

Answer 25

Epithelial anion channel. Loss-of-function mutations alter fluid pressure and limit bicarbonate secretion, leading to inspissation of secreted fluids and duct obstruction Mutations in CFTR: 1. decrease bicarbonate secretion by pancreatic ductal cells 2. promoting protein plugging, 3. duct obstruction, and 4. the development of pancreatitis.

Question 26

chronic/long-standing bouts of pancreatitis can lead to what?

Answer 26

40% risk of malignancy, due to chronic inflammation

Question 27

The common dile duct and the main pancreatic duct exit into the duodenum at the ampulla of vater

Answer 27

ERCP- endoscopy retrograde pancreatogram

Question 28

What factors suggest a gallstone etiology of pancreatitis?

Answer 28

1) Age 50+ 2) Female 3) Amylase over 400 Iu/L 4) AST over 100 U/L 5) Alk phos over 300 Iu/L

Question 29

Gotta get the gallstones out!

Question 30

Question 31

NPO= nothing per oral. I.e. dont want to feed these pts. with acute pancreatitis IVs= many liters of fluids rapidly

Question 32

What are some lab predictors of poor outcome with pancreatitis?

Answer 32

* Admission Hematocrit \> 44% with failure to decrease after 24 hours of IV fluids. * Admission BUN \> 25 mg/dl with an increase after 24 hours of IV fluids. * C-reactive protein (CRP) \> 150 mg/L at 48 hours.

Question 33

Why would kidney failure be associated with pancreatitis?

Answer 33

because damage to vessel walls can cause edema and hypotension to develop and the kdineys are not perfused as well (hence the need for fluids)

Question 34

MS= mental status

Answer 34

Question 35

T or F. A CT scan can differentiate between interstitial and necrotizing pancreatitis

Answer 35

T.

Question 36

What are the complications of acute pancreatitis?

Answer 36

* Fluid collections * Pseudocysts * Fistulas –ascites –pleural effusions •Splenic vein thrombosis

Question 37

What causes chronic pancreatitis?

Question 38

What is the main cause of chronic pancreatitis?

Answer 38

chronic alcohol consumption

Question 39

What are the symptoms of chronic pancreatitis?

Answer 39

chronic abdominal pain and other evidence of pancreatic dysfunction including diabetes and/or steatorrhea

Question 40

How is chronic pancreatitis diagnosed and tx?

Answer 40

Diagnosis- imaging Tx: Pain meds, insulin, and enzyme supplements

Question 41

Alcohol makes protein secretions thicker and cause obstruction and they can also calcify

Question 42

Answer 42

Question 43

marked by less inflammation and more fibrosis the pain is more chronic and probably more like a 5/10 while the pain associated with acute pancreatitis is much more severe

Answer 43

Ducts can also rupture and form pseudocyts that can get large the fibrotic pancreas causes increased pressure which irritates nerves and causes more inflammation obstuction of the common bile duct can also cause pain and infection

Question 44

Can try to 'rest' the pancreas with exogenous enzymes but its not that effective blocking the splanchnic nerves (via alcohol injection) does help with pain

Question 45

T or F. Fat malabsorption occurs before protein or carbohydrate in chronic pancreatitis

Answer 45

T. it is primarily due to lipase deficiency

Question 46

How is the fat malabsorption associated with chronic pancreatitis managed?

Answer 46

–reduce dietary fat intake. – oral enzyme supplementation- pretty effective (contain lipases and proteases). – acid suppression therapy (acid will degrade any pancreatic acids you have if you are taking them orally)

Question 47

When does diabetes occur in chronic pancreatitis?

Answer 47

•Only seen in severe disease (\>80% of gland destroyed).

Question 48

What is unique about pancreatitic induced diabetes?

Answer 48

You see loss of the WHOLE islet- leading to loss of both insulin and glucagon, hence difficult to control (brittle)- **glucose can get high or low**. Its better to keep glucose higher than lower due to the severity of hypoglycemic events

Question 49

T or F. Ketoacidosis is rare in chronic pancreatitis induced diabetes

Answer 49

T. Not sure why