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Embryology, Anatomy, and Physiology of the Pancreas
The human pancreas develops from the ventral and dorsal domains of the primitive duodenal endoderm beginning at about the 5th wk of gestation ( Fig. 374.1 ). The larger dorsal anlage, which develops into the tail, body, and part of the head of the pancreas, grows directly from the duodenum. The smaller ventral anlage develops as 1 or 2 buds from the primitive liver and eventually forms the major portion of the head of the pancreas. At about the 17th wk of gestation, the dorsal and ventral anlagen fuse as the buds develop and the gut rotates. The ventral duct forms the proximal portion of the major pancreatic duct of Wirsung, which opens into the ampulla of Vater. The dorsal duct forms the distal portion of the duct of Wirsung and the accessory duct of Santorini, which empties independently in approximately 5% of people. Variations in fusion might account for pancreatic developmental anomalies. Pancreatic agenesis has been associated with a base pair deletion in the insulin promoter factor 1- HOX gene, PDX1 (PAGEN1) , PTF1A (PAGEN 2), GATA 6 haploinsufficiency and FS123TER genes. Other genes involved in pancreatic organogenesis include the IHH , SHH or sonic hedgehog gene, SMAD2 , and transforming growth factor-1β genes.
Development of the exocrine pancreas.
A, Gestational age 6 wk. B, Gestational age 7-8 wk. The ventral pancreas has rotated but has not yet fused with the dorsal pancreas. C, The ventral and dorsal pancreatic ductal systems have fused.
(From Werlin SL: The exocrine pancreas. In Kelly VC, editor: Practice of pediatrics, vol 3, Hagerstown, MD, 1980, Harper and Row, Fig. 16.1.)
The pancreas lies transversely in the upper abdomen between the duodenum and the spleen in the retroperitoneum ( Fig. 374.2 ). The head, which rests on the vena cava and renal vein, is adherent to the C loop of the duodenum and surrounds the distal common bile duct. The tail of the pancreas reaches to the left splenic hilum and passes above the left kidney. The lesser sac separates the tail of the pancreas from the stomach.
Anterior view of the pancreas: relationship to neighboring structures.
(From Werlin SL: The exocrine pancreas. In Kelly VC, editor: Practice of pediatrics , vol 3, Hagerstown, MD, 1980, Harper and Row, Fig. 16.2.)
By the 13th wk of gestation, exocrine and endocrine cells can be identified. Primitive acini containing immature zymogen granules are found by the 16th wk. Mature zymogen granules containing amylase, trypsinogen, chymotrypsinogen, and lipase are present at the 20th wk. Centroacinar and duct cells, which are responsible for water, electrolyte, and bicarbonate secretion, are also found by the 20th wk. The final 3-dimensional structure of the pancreas consists of a complex series of branching ducts surrounded by grape-like clusters of epithelial cells. Cells containing glucagon are present at the 8th wk. Islets of Langerhans appear between the 12th and 16th wk.
Pancreatic Anatomic Abnormalities
Complete or partial pancreatic agenesis is a rare condition. Complete agenesis is associated with severe neonatal diabetes and usually death at an early age (see Chapter 607 ). Partial or dorsal pancreatic agenesis is often asymptomatic but may be associated with diabetes, congenital heart disease, polysplenia, and recurrent pancreatitis. Pancreatic agenesis is also associated with malabsorption.
An annular pancreas results from incomplete rotation of the left (ventral) pancreatic anlage, which may be a result of recessive mutations in the IHH or SHH genes. Patients usually present in infancy with symptoms of complete or partial bowel obstruction or in the 4th or 5th decade. There is often a history of maternal polyhydramnios. Other congenital anomalies, such as Down syndrome, tracheoesophageal fistula, intestinal atresia, imperforate anus, malrotation and cardiorenal abnormalities, and pancreatitis may be associated with annular pancreas. Some children present with chronic vomiting, pancreatitis, or biliary colic. The treatment of choice is duodenojejunostomy. Division of the pancreatic ring is not attempted because a duodenal diaphragm or duodenal stenosis often accompanies annular pancreas.
Ectopic pancreatic rests in the stomach or small intestine occur in approximately 3% of the population. Most cases (70%) are found in the upper intestinal tract. Recognized on barium contrast studies by their typical umbilicated appearance, they are rarely of clinical importance. On endoscopy, they are irregular, yellow nodules 2-4 mm in diameter. A pancreatic rest may rarely be the lead point of an intussusception, produce hemorrhage, or cause bowel obstruction.
Pancreas divisum , which occurs in 5–15% of the population, is the most common pancreatic developmental anomaly. As the result of failure of the dorsal and ventral pancreatic anlagen to fuse, the tail, body, and part of the head of the pancreas drain through the small accessory duct of Santorini rather than the main duct of Wirsung. Some researchers believe that this anomaly may be associated with recurrent pancreatitis when there is relative obstruction of the outflow of the ventral pancreas. Diagnosis is made by endoscopic retrograde cholangiopancreatography or by magnetic resonance cholangiopancreatography. Pancreatitis in patients with pancreas divisum is associated with mutations in the CFTR gene. Sphincterotomy is not recommended unless other anomalies are present or the patient has classic pancreatobiliary-type pain, recurrent pancreatitis, or chronic pancreatitis and no other etiology is found.
Choledochal cysts are dilations of the biliary tract and usually cause biliary tract symptoms, such as jaundice, pain, and fever. On occasion, the presentation may be pancreatitis. The diagnosis is usually made with ultrasonography, CT or biliary scanning, or magnetic resonance cholangiopancreatography. Similarly, a choledochocele—an intraduodenal choledochal cyst—may manifest with pancreatitis. The diagnosis can be difficult and require magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, or endoscopic ultrasound.
A number of rare conditions, such as Ivemark (mutation in GDF gene) and Johanson-Blizzard (mutation in UBR1 gene) syndromes, include pancreatic dysgenesis or dysfunction among their features. Many of these syndromes include renal and hepatic dysgenesis along with the pancreatic anomalies.
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