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The pancreas is a retroperitoneal gland that facilitates digestion and metabolism. The pancreatic head and uncinate process adjoin the duodenal curvature; its neck positioned posterior to the pylorus and anterior to the portal venous confluence. The pancreatic body lies posterior to the stomach; the tail enters the peritoneum near the splenic hilum. Unique for a foregut organ, the pancreas receives blood supply from branches of both the celiac trunk and superior mesenteric artery. Autonomic nerves forming the pancreatic plexus arise from the celiac ganglia, which coordinate sympathetic and parasympathetic synapses from the greater splanchnic and vagus nerves, respectively. Pancreatic tissue is largely composed of acini which secrete digestive proenzymes into a system of ducts that coalesce to form the main and accessory pancreatic ducts. Most exocrine secretions drain into the second part of the duodenum at the level of the major duodenal papilla where they aid in digestion through proteolysis and lipolysis. There is dispersed endocrine tissue throughout the pancreatic parenchyma in functional units known as islets of Langerhans. These conglomerates secrete a host of hormones directly into the circulation, notably insulin, glucagon, and somatostatin. Derived from the foregut, the pancreas has endodermal origins and undergoes nuanced development in utero to become an organ with dual endocrine and exocrine functions. This embryologic review focuses on human pancreatic morphogenesis, physiologic maturation, and relevant congenital malformations in a clinical context.[1][2]

Developmental anomalies of the pancreas can cause obstructive jaundice, pancreatitis, bilious emesis, failure to thrive, and more. The physiologic underpinnings of these clinical presentations will be explored here. While more than one mechanism can cause these presentations, the pathophysiology described in this section is relevant for patients with embryologic malformations of the pancreas. These concepts are broad; specific diagnoses will be discussed in the following section. Anatomical misconfigurations can impinge the common bile duct, leading to biliary tree obstruction and stasis. Increased intraluminal pressure eventually overwhelms biliary canaliculi in the liver. Intercellular junctions between hepatocytes leak, allowing bile to infiltrate the hepatocyte cords. Bile fills the perisinusoidal space of Disse and subsequently diffuses into the hepatic sinusoid system. From there, it drains into hepatic veins, the inferior vena cava, and circulates systemically. Biliary compounds deposit and accumulate in capillary beds of the skin and mucosa, causing the yellow skin tone known as jaundice. Another complication of prolonged bile duct stasis is microbial growth and ascending cholangitis, generally with gram-negative enteric flora.[14] Similar to the biliary tree, the pancreatic duct system can also become obstructed. Abnormal ductal architecture or insufficient sphincter function at the level of the duodenum can cause stasis of exocrine secretions. Increasing intraluminal pressure then promotes the activation of digestive proenzymes within the pancreatic ductal system. Parenchymal inflammation ensues, triggering positive-feedback cytokine cascades that further exacerbate pancreatitis. Exocrine enzymes, notably alpha-amylase and lipase, spill over into the circulation. Lipase itself is a sensitive and specific serum marker for diagnosing pancreatitis.[15]

Similar to the biliary tree, the pancreatic duct system can also become obstructed. Abnormal ductal architecture or insufficient sphincter function at the level of the duodenum can cause stasis of exocrine secretions. Increasing intraluminal pressure then promotes the activation of digestive proenzymes within the pancreatic ductal system. Parenchymal inflammation ensues, triggering positive-feedback cytokine cascades that further exacerbate pancreatitis. Exocrine enzymes, notably alpha-amylase and lipase, spill over into the circulation. Lipase itself is a sensitive and specific serum marker for diagnosing pancreatitis.[15] Pancreatic tissue can anomalously encircle or ectopically implant along the alimentary canal. In these cases, encroaching tissue can cause varying degrees of sticture or, in rare scenarios, small bowel obstruction. Owing to its regional proximity, the duodenum is the most commonly affected site with the highest potential for symptomatic stricture development. Bile entering into the second part of the duodenum encounters resistance distally at the site of stricture or obstruction. Proximal backflow through the pylorus causes bilious emesis, a hallmark of duodenal (or jejunal) obstruction. While other causes of bilious emesis are far more common than pancreatic etiologies, the pathophysiology behind the clinical presentation is similar.[16] Failure to thrive predominantly occurs in neonates and children with metabolic and malabsorptive conditions. Congenital pancreatic disease is among the most critical causes of malabsorptive etiology. Pancreatic peptidases, lipases, and amylases catabolize large nutrients into small peptides, fatty acids, and oligosaccharides that are readily absorbable. Children with obstructive pathology or exocrine insufficiency cannot catabolize nutrients to forms that are suitable for handling by the intestinal brush border. While patients may have an appropriate nutritional intake, they become malnourished by this mechanism.[17]