Exocrine Pancreas: Functions and Diseases

Question 1

basic components of the pancreas

Answer 1

• exocrine: acini, which secrete enzymes (inactive zymogens) into ducts, which join to form pancreatic duct which joins with bile duct
• endocrine: islets of langerhaans, secrete hormones into the bloodstream

Question 2

what do cells of pancreatic acini do vs. duct cells?

Answer 2

• remember, these are both exocrine!
• acinar cells secrete hormones
• duct cells secrete bicarbonate in response to secretin, a hormone from the SI mucosa

Question 3

what does CCK do?

Answer 3

• this is a hormone from the SI mucosa
• stimulates exocrine pancreatic acinar cells to secrete enzymes
• also stimulates gallbladder to move/expel bile into duodenum

Question 4

what is an annular pancreas?

Answer 4

• congenital anomaly
• during embryonic development, ventral and dorsal pancreatic buds may become abnormally fused
• one in 12-15,000 live births
• the annulus is a flat band of pancreatic tissue that completely encircles the second portion of the duodenum

Question 5

symptoms/manifestations of annular pancreas

Answer 5

• newborns: projectile vomiting in the first few days of life because food not entering small intestine
• adults: very rare cause of chronic pancreatitis

Question 6

acinar secretions

Answer 6

enzyme-rich secretions that provide enzymes for digestion

Question 7

ductal secretions

Answer 7

• bicarbonate-rich secretions that neutralize acidic chyme

Question 8

describe the mechanism of bicarbonate secretion by pancreatic duct cells

Answer 8

• it is the same concept as HCl secretion in the stomach
• however, the directions are flipped
• here, H+ is put into the bloodstream, not the lumen
• bicarbonate goes into lumen of pancreatic duct

Question 9

where do the H+ ions that are secreted out of duct cells come from?

Answer 9

• they come from carbonic anhydrase rxn between carbon dioxide and water
• these H+ ions are actively transported out of duct cells by H+/K+ ATPase and released into blood
• bicarbonate goes into duct lumen

Question 10

what does CCK do in the pancreas?

Answer 10

• CCK is released from si in response to fat and proteins entering the duodenum. it stimulates acinar cells to secrete digestive enzymes
• secretin also comes from si due to acidic chyme entering the duodenum. it stimulates ductal cells to secrete bicarbonate

Question 11

how does cystic fibrosis affect the pancreatic ducts?

Answer 11

thick secretions into the pancreatic duct can cause obstruction and result in pancreatic insufficiency

Question 12

pancreatic juice consists of…

Answer 12

• around 100 hydrolytic enzymes
• most important are trypsinogen and trypsin inhibitor, which tightly binds to the active site of trypsin

Question 13

three isoforms of trypsinogens that are found in human pancreatic juice

Answer 13

• cationic trypsinogen (23.1%)
• anionic trypsinogen (16%)
• meso trypsinogen (0.5%)

Question 14

describe the pathway of hereditary pancreatitis

Answer 14

• start with mutations in cationic trypsinogen
• causes intracellular activation of trypsinogen (in pancreatic acinar cells)
• causes intracellular activation and retention of other proenzymes
• overall, injures acinar cells
• see another card for what this injury does

Question 15

two results of of injury to acinar cells in acute pancreatitis

Answer 15

1. proteolysis (by proteases) + fat necrosis (lipase, phospholipase) + hemorrhage (elastase)
2. acinar cell injury response, which leads to interstitial inflammation
   - combined, these lead to acute pancreatitis

Question 16

two main things that happen in hereditary pancreatitis

Answer 16

1. premature activation of pancreatic enzymes, specifically trypsinogen to trypsin
2. inactivation of trypsin inhibitor, which causes autodigestion of pancreatic acini
   - note, either of these (regardless of how they are caused) can cause autodigestion of pancreatic acini

Question 17

acute pancreatitis general overview

Answer 17

• known to occur as acute hemorrhagic pancreatitis
• follows heavy meals or excessive alcohol ingestion
• about 80% of acute pancreatitis cases are associated with gall stones (cholelithiasis) or alcohol abuse

Question 18

describe 6 causes of acute pancreatitis

Answer 18

1. bile stones: pancreatic enzymes back up into pancreas
2. alcohol
3. overeating (increased demand of pancreatic enzymes)
4. viruses
5. drugs
6. trauma, injury

Question 19

describe changes in acute pancreatitis

Answer 19

• activated enzymes
• acinus: necrosis, leakage of enzymes
• vessel wall: necrosis, hemorrhage, enzymes (amylase and lipase) released into the bloodstream
• enzymatic fat tissue necrosis

Question 20

what enzymes get released into the bloodstream upon acinar cell injury in acute pancreatitis?

Answer 20

• amylase
• lipase

Question 21

describe pathway of pancreatitis

Answer 21

can start with cholelithiasis, ampullary obstruction, chronic alcoholism, or ductal concretions
- leads to interstitial edema
- this impairs blood flow
- this causes ischemia
- following ischemia there is necrosis, fibrosis, and calcifications (caused by recurrent acute states)

Question 22

two results of chronic pancreatitis?

Answer 22

• ischemia (caused by recurrent acute states)
• oxidative stress (idiopathic)

Question 23

typical diagnostic features of acute pancreatitis

Answer 23

• severe abdominal pain, nausea, vomiting
• rapid elevation of serum amylase and lipase (within 24-72 hours)

Question 24

what is the most common form of pancreatic cancer?

Answer 24

pancreatic ductal adenocarcinoma
- only about 5% of patients with this cancer are alive 5 years after diagnosis
- carcinoma cells frequently spread to the liver via the portal vein

Question 25

why are pancreatic cancers so difficult to operate on?

Answer 25

• close association of pancreas with large vessels
• lots of abdominal drainage to lymph nodes

Question 26

describe the role of CD40 as a target in treating pancreatic carcinoma in mice and humans

Answer 26

• tumor has an immunosuppressive microenvironment, meaning it can suppress intervention from the immune system (we say it this can restrain antitumor immunity, meaning that it can suppress the body’s immune response to the tumor)
• this is particularly true in PDA (pancreatic ductal adenocarcinoma)
• original theory was that T cells were involved in reversing this immune suppression by the tumor
• however, research revealed that it is macrophages activated by CD40. these macrophages infiltrated tumors and depleted tumor stroma
• this lends itself to a CD40-dependent mechanism for targeting tumor stroma in treating cancer

Question 27

issues with the GI tract that can lead to development of malabsorption

Answer 27

A. deficient digestion in the lumen
B. inadequate digestion on the membrane of enterocytes
C. impaired transport in enterocytes
D. blockage in the path of nutrients from enterocytes to lymphatics

Question 28

clinical manifestations of deficient intraluminal digestion

Answer 28

• achlorhydria (could be from atrophic gastritis)
• steatorrhea (fat in poop, could be caused by chronic bile insufficiency, bile duct obstruction, or cirrhosis)

Question 29

clinical manifestations of inadequate digestion on cell membrane of enterocytes

Answer 29

an example would be lactose intolerance, which is due to a deficiency of lactase (brush border enzyme)

Question 30

clinical manifestations of impaired transcellular transport in enterocytes

Answer 30

defective chylomicron assembly (as seen in abetalipoproteinemia)

Question 31

clinical manifestations of blocked passage of nutrients from enterocytes to lymphatics

Answer 31

lack of lipoproteins in circulation (can be caused by amyloidosis and scleroderma)

Question 32

what do symptoms of malabsorption occur from?

Answer 32

deficiency of proteins, lipids, carbs, vitamins, and minerals

Question 33

review malabsorption syndromes on slide 87

Answer 33

LET’S GOOOOO