Exocrine Pancreas PDF - UAG School of Medicine

Exocrine Pancreas By: Sergio R. Ortiz MD, MPH, CPH Objectives: • To understand the different manifestations of exocrine pancreatic pathologies. • Differentiate between different exocrine pancreatic pathologies • Know the relevant studies to diagnose each pathology • Explain how to interpret clini...

Exocrine Pancreas By: Sergio R. Ortiz MD, MPH, CPH Objectives: • To understand the different manifestations of exocrine pancreatic pathologies. • Differentiate between different exocrine pancreatic pathologies • Know the relevant studies to diagnose each pathology • Explain how to interpret clinical features Congenital Malformations: • Pancreas divisum • Most common congenital anomaly of the pancreas. • Incidence of 3% to 10%. In most individuals, the main pancreatic duct (the duct of Wirsung) joins the common bile duct just proximal to the papilla of Vater, and the accessory pancreatic duct (the duct of Santorini) drains into the duodenum through a separate minor papilla. • Caused by a failure of fusion of the fetal duct systems of the dorsal and ventral pancreatic primordia. As a result, the bulk of the pancreas (formed by the dorsal pancreatic primordium) drains into the duodenum through the small-caliber minor papilla. The duct of Wirsung in individuals with divisum drains only a small portion of the head of the gland through the papilla of Vater. • 95% of individuals are asymptomatic. The remaining 5% develop acute or chronic pancreatitis, possibly related to inadequate drainage of pancreatic secretions through the minor papilla. Illustration of Pancreas Divisum: Pancreatitis: General Features: • It is an inflammatory disorder of the pancreas that is divided into acute and chronic forms. • Acute pancreatitis, function can return to normal if the underlying cause of inflammation is removed. • Chronic pancreatitis causes irreversible destruction of exocrine pancreas. Acute Pancreatitis: • Acute pancreatitis is a reversible inflammatory disorder that varies in severity, from focal edema and fat necrosis to widespread hemorrhagic necrosis. • It is a relatively common and serious condition, with an annual incidence of 33 to 74 per 100,000 globally. In the Western world the incidence is 5 to 35 per 100,000. Overall mortality is about 5%. The incidence of acute pancreatitis is increasing due to the obesity epidemic and related increase in gallstone disease. • Acute pancreatitis is caused by autodigestion of the pancreas by intra-acinar activation of pancreatic enzymes. • Etiology and Pathogenesis: • The most common cause of acute pancreatitis in the United States is the impaction of gallstones within the common bile duct, impeding the flow of pancreatic enzymes through the ampulla of Vater (“gallstone pancreatitis”); this is closely followed by pancreatitis secondary to excessive alcohol intake. Overall, gallstones and chronic excessive alcohol use account for close to 80% of acute pancreatitis cases, with the remainder caused by a multitude of factors. Gross Anatomy Findings: Chronic Pancreatitis: • Characterized by long-standing inflammation that leads to irreversible destruction of the exocrine pancreas, followed eventually by loss of the islets of Langerhans. • The prevalence of chronic pancreatitis is difficult to determine but probably ranges between 0.04% and 5% of the U.S. population and 9 to 62 per 100,000 globally. • The most common cause of chronic pancreatitis is chronic excessive alcohol consumption, especially among middle-aged men. How alcohol triggers chronic pancreatic injury and inflammation is not known; it may alter the activation of digestive enzymes, increase the production of oxygen-derived free radicals, or exert direct toxic effects on acinar cells. Other predisposing factors include functional or anatomic duct obstruction. • As many as 40% of individuals with chronic pancreatitis have no recognizable predisposing factors. It is increasingly being recognized that many “idiopathic” cases are associated with germline mutations in CFTR , PRRS1 , and SPINK1 genes, the very same genes that are often found to be mutated in familial acute pancreatitis. As discussed earlier, mutations in PRRS1 (encoding trypsinogen) and SPINK1 (encoding a trypsin inhibitor) both allow excessive activation of trypsin. Pancreatic Neoplasms: • Can be cystic or solid. • Some tumors are benign, while others are among the most lethal of all malignancies. Cystic Neoplasm: • Are diverse tumors that range from harmless benign cysts to invasive, potentially lethal, cancers. Approximately 5% to 15% of all pancreatic cysts are neoplastic; these constitute less than 5% of all pancreatic neoplasms. • There are three variants of cystic neoplasms. Some, such as serous cystic neoplasms, are almost always benign, whereas others, such as intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms, are precancerous. Most cystic neoplasms are detected incidentally when abdominal imaging is done for other reasons. IPMNs account for 38% of lesions, mucinous cystic neoplasms for 23%, and serous cystic tumors for 16%. Each of these is described next. • Serous Cystadenomas • Composed of glycogen-rich cuboidal cells surrounding small cysts containing clear, straw-colored fluid. • The cysts are small (1–3 mm) and can be solitary, multiple, or present as a honeycomb of microcystic lesions. They typically manifest in the seventh decade of life with nonspecific symptoms such as abdominal pain; the female-to-male ratio is 2 : 1. They are almost uniformly benign, and surgical resection is curative in the vast majority of patients. Most serous cystadenomas carry somatic loss-of-function mutations of the von Hippel-Lindau (VHL) tumor suppressor gene, which you will recall is a negative regulator of hypoxia-inducible factor-α (HIFα). Pancreatic Carcinoma: • Infiltrating ductal adenocarcinoma of the pancreas (more commonly referred to as pancreatic cancer ) is the third leading cause of cancer deaths in the United States, exceeded only by lung and colon cancers. Although it is substantially less common than the other two malignancies, pancreatic carcinoma is near the top of the list of killers because it carries one of the highest mortality rates. • Close to 60,000 Americans were diagnosed with pancreatic cancer in 2021, and virtually all will die in a short period after diagnosis; the 5-year survival rate is a dismal 8%. The global rate is 8 to 14 per 100,000 with 6.92 per 100,000 dying. • The most common antecedent lesions of pancreatic cancer arise in small ducts and ductules and are called pancreatic intraepithelial neoplasias (PanINs). Cystic Fibrosis: • The epithelial cells lining the ducts are also active participants in pancreatic secretion. • The cuboidal cells that line the smaller ductules secrete bicarbonate-rich fluid, while the columnar cells lining the larger ducts produce mucin. • Ductal epithelial cells also express the cystic fibrosis transmembrane conductance regulator (CFTR) ; aberrant function of this membrane protein affects the biochemical, in particular bicarbonate, content and viscosity of pancreatic secretions. CFTR dysfunction has a fundamental role in the pathophysiology of pancreatic disease in individuals with cystic fibrosis Bibliography: • Robbins & Kumar Basic Pathology, 15, 572-581