Hepatobiliary cancers, pancreas, pancreatic secretions, pancreatic ductal adenocarcinoma, pancreatitis, malabsorption, fates of nutrients in the fed state

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Biomedical Science
BMS 460
D.Rao Veeramachaneni

18 October Hepatobiliary Cancers Liver can give rise to tumors, but it is even more often involved by tumor metastases (because the liver receives blood from two sources) – most often related to primary tumors of GI tract, lungs, and breast Malignant tumors Carcinomas Hepatocellular Worldwide, it is probably the most common human malignant disease Cholangiocellular Gallbladder Extrahepatic bile duct Sarcomas Kupffer cells Extremely rare but has been associated with vinyl chloride Benign tumors Adenomas Hepatocellular and biliary tract Are of limited clinical significance; >90% have been associated with oral contraceptives Pancreatic cancer – live 5-7 years after diagnosis Pancreas Secretin, a hormone from SI mucosa, stimulates duct cells (secrete bicarbonate) Cholecystokinin (CCK), a hormone from SI mucosa, stimulates exocrine cells (secrete enzymes) Annular Pancreas Congenital anomaly During embryologic development, the ventral and dorsal pancreatic buds may become abnormally fused 1 in 12,000 – 15,000 live births Newborns: Projective vomiting in the first few days of life Adults: A very rare cause of chronic pancreatitis The annulus is often a flat band of pancreatic tissue completely encircling the second portion of the duodenum Pancreatic Secretions Acinar secretions are enzyme-rich secretions that provide the enzymes necessary for digestion Ductal secretions are HCO ric3 and neutralize acidic chyme In cystic fibrosis, thick secretions into the pancreatic duct may obstruct the duct and cause pancreatic insufficiency The mechanism of bicarbonate secretion by pancreatic ducts is analogous to that of HCl secretion by the stomach, except that the directions of the H ion and bicarbonate ion are reversed. H ions, derived from carbonic-anhydrase reaction between CO and wat2r, are actively + + transported out of the duct cells by a H /K -ATPase pump and released into blood, while the bicarbonate ions are secreted into the duct lumen Duodenal fat and proteins → CCK → acinar cells (in pancreatic acinar) produce digestive enzymes - Duodenal acidic chyme → secretion → ductal cells (in pancreatic duct) produce HCO 3 Pancreatic ductal adenocarcinoma The most common form of pancreatic cancer Only about 5% of patients with pancreatic ductal adenocarcinoma are alive 5 years after diagnosis Carcinoma cells frequently spread to the liver via the portal vein. The close association of the pancreas with large blood vessels and the extensive and diffuse abdominal drainage to the lymph nodes are factors contributing to the ineffectiveness of surgical removal of pancreatic tumors CD-40 activation can reverse immune suppression and drive antitumor T cell responses Patients with surgically incurable PDA Tumor regression required macrophages but not T cells CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma Demonstrate a CD-40 dependent mechanism for targeting tumor stroma in the treatment of cancer Acute Pancreatitis Known to occur also as acute hemorrhagic pancreatitis Follows heavy meals or excessive alcohol ingestion The clinical features of acute pancreatitis (severe abdominal pain, nausea, and vomiting) and rapid elevation of amylase and lipase in serum (within 25 to 72 hours) are typical diagnostic features ~80% of acute pancreatitis cases are associated with gall stones (50%) and alcohol abuse Acute hemorrhagic pancreatitis Acinus: necrosis, leakage of enzymes Enzymatic fat tissue necrosis Vessel wall necrosis Hemorrhage Enzymes in bloodstream ↑↑ amylase and lipase, among a variety of others; pancreas secretes ~100 hydrolytic enzymes Hereditary pancreatitis Mutations in cationic trypsinogen → intracellular
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