Lecture 28 Flashcards
Exocrine Pancreatic Structure
Acini: secrete enzymes
Endocrine Pancreatic Structure
Islets of Langerhans
Pancreatic Duct Cells
Secrete bicarbonate
Cholecystokinin (CCK)
Hormone from SI mucosa (stimulates)
Secretin
Hormone from SI mucosa (stimulates)
Annulus
Flat band of pancreatic tissue completely encircling the second portion of the duodenum
Fusion of the ventral and dorsal pancreatic buds
- May occur during embryologic development
- Newborns: projectile vomiting in the first few days of life
- Adults: very rare cause of chronic pancreatitis
Acinar Secretions
Enzyme-rich secretions that provide the enzymes necessary for digestion
Ductal Secretions
Bicarbonate rich and neutralize acidic chyme
Explain the process of bicarbonate secretion by pancreatic ducts.
- H ions (derived from carbonic anhydrase reaction between CO2 and water) are actively transported out of the duct cells by an H+/K+-ATPase pump and released into the blood
- Bicarbonate ions are secreted into the duct lumen
Cystic fibrosis and pancreatic secretions
Thick secretions into the pancreatic duct may obstruct the duct and cause pancreatic insufficiency
What are the three isoforms of trypsinogen?
- Cationic (23.1%)
- Anionic (16%)
- Meso (0.5%)
Trypsin Inhibitor
Tightly bound to the active site of trypsin
What is the cause of autodigestion of pancreatic acini?
- Premature activation of pancreatic enzymes (trypsinogen to trypsin)
- Inactivation of trypsin inhibitor
Explain the process that causes acute pancreatitis.
- Mutations in cationic trypsinogen (hereditary pancreatitis)
- Intracellular activation of trypsinogen
- Intracellular activation and retention of other proenzymes
- Acinar cell injury
- Acinar cell injury response (-> Interstitial inflammation) OR proteolysis, fat necrosis (lipase, phospholipase), and hemorrhage (elastase)
- Acute pancreatitis
Acute Pancreatitis
- Acute hemorrhagic pancreatitis
- Heavy meals or excessive alcohol ingestion
- 80% of cases associated with gall stones and alcohol abuse
- Clinical features: severe abdominal pain, nausea, vomiting, rapid elevation of amylase and lipase in serum
What structures are impacted with acute pancreatitis?
- Vessel wall: necrosis, hemorrhage, enzymes in bloodstream (Increased amylase and lipase)
- Enzymatic fat tissue necrosis
- Acinus: necrosis and leakage of enzymes
Chronic Pancreatitis
- Ischemia (perpetuates cycle): necrosis, fibrosis, calcifications (recurrent acute states)
- Oxidative stress (idiopathic)
Pancreatic Ductal Adenocarcinoma
- Most common form
- 5% of cases are alive 5 years after diagnosis
- Carcinoma cells frequently spread to the liver via the portal vein
- Close association of pancreas with large blood vessels and the extensive and diffuse abdominal drainage to lymph nodes -> ineffectiveness of surgical removal
CD40 and Pancreatic Ductal Adenocarcinoma (PDA)
- CD40 activation can reverse immune suppression and drive antitumor T cell response
- Tumor regression required macrophages but not T cells or gemcitabine
- CD40 activated macrophages rapidly infiltrated tumors -> tumoricidal -> depletion of tumor stroma
What defects in the GI tract cause malabsorption?
- Deficient intraluminal digestion
- Inadequate digestion on the luminal cell membrane of the enterocytes
- Impaired transcellular transport in the enterocytes
- Blocked passage of nutrients from the enterocytes to the lymphatics
Example of deficient intraluminal digestion.
Achlorhydria (atrophic gastritis), Steatorrhea (chronic pancreatic insufficiency, bile duct obstruction, cirrhosis)
Example of inadequate digestion on the luminal cell membrane of the enterocytes.
Lactose intolerance: lactase deficiency
Example of impaired transcellular transport in the enterocytes.
Defective chylomicron assembly (abeta-lipoproteinemia)
Example of blacked passage of nutrients from the enterocytes to the lymphatics.
Lack of lipoproteins in circulation (amyloidosis, scleroderma)
Why do malabsorption syndromes develop?
Due to disease involving stomach, pancreas, hepatobiliary system, or intestines
What do the symptoms of malabsorption result from?
Deficiency of proteins, lipids, carbs, vitamins, and minerals
