Hereditary Pancreatitis

Genetic condition characterized by recurrent episodes of painful pancreatic attacks, which can progress to chronic pancreatitis.

Inherited disorder characterized by relapsing chronic pancreatitis. First described by Comfort and Steinberg in 1952.

It is the most common form of chronic relapsing pancreatitis in childhood. May account for approximately 25% of adult cases with chronic idiopathic pancreatitis. Equal sex predilection. At least 1000 individuals in the United States are affected with hereditary pancreatitis.

Autosomal dominant disorder with incomplete penetrance. Hereditary pancreatitis is mainly caused by a mutation of exon 3 of the cationic trypsinogen gene (protease-serine 1 gene, PRSS-1), resulting in an arginine to histidine substitution. Gene map locus is 7q35.

Inherited condition characterized by typical symptomatology and laboratory features of pancreatitis. Pancreatitis results from inappropriate activation of pancreatic proenzymes. Active trypsin is normally inhibited by a limited supply of trypsin inhibitor. If trypsin activity exceeds the inhibitory capacity of pancreatic secretory trypsin inhibitor, then proenzymes, including mesotrypsin and enzyme Y, are activated. The activation of these enzymes is postulated to be part of a feedback mechanism for inactivating wild-type trypsinogen, trypsin, and other zymogens. When the Arg117 cleavage site for mesotrypsin, enzyme Y, and trypsin is replaced by histidine, trypsin continues to activate trypsinogen and other zymogens unabated, leading to autodigestion of the pancreas and pancreatitis. Congenital anomalies of the pancreatic duct or biliary duct system may play a role. The histopathologic findings of pancreatitis are related to the release of activated proteolytic and lipolytic enzyme. Interstitial edema and blood vessel disruption (thrombosis in the portal or splenic vein occurs with an inflammatory response) may appear early. As pancreatitis progresses, necrosis may appear, leading to hemorrhage hereditary pancreatitis with hyperparathyroidism in the multiple endocrine adenomatosis syndrome.

Based on a positive family history of pancreatitis and early onset of symptoms. Characterized by the presence of calculi in pancreatic ducts. Serum amylase (measured up to 4 days) is elevated and lipase activity may be elevated for 8 to 14 days. A puzzling feature is the urinary excretion of lysine and cystine by about half the members of affected kindred (with or without pancreatitis). Endoscopic retrograde cholangiopancreatography is diagnostic for chronic pancreatitis and shows a distorted duct with multiple strictures and dilatations similar to a “chain of lakes” pattern. Children may have complications seen in pancreatitis—pseudocysts, diabetes mellitus, thrombosis of portal or splenic veins, coagulopathy, pleural effusions, and pulmonary edema.

May present with symptoms of pancreatitis late in the first decade. Typical recurrent abdominal pain starting in childhood. Diagnosis confirmed by laboratory studies. Children may be well during attacks. The attacks were characterized by severe abdominal pains, fever, and marked elevation of serum amylase. Pancreatic insufficiency (5.5%), diabetes mellitus (12.5%), pseudocysts (5.5%), and hemorrhagic pleural effusion were observed in a review of 72 patients. Portal vein thrombosis occurred in two patients and was suspected in three other patients. Patients seemed to improve later in life. Attacks were precipitated by emotional upset, alcohol, or high fat intake. The link with adenocarcinoma is unclear. Treatment is conservative, but treatment of complications must be individualized.

Assess pancreatic exocrine and endocrine functions. Evaluate the severity of diabetes mellitus and its sequelae, particularly the presence of cardiovascular, renal, and autonomic impairment. Optimize diabetic control. Patients with stable, well-controlled diabetes undergoing relatively minor surgery may be admitted as “day admit” cases, whereas patients with brittle diabetes may require preoperative admission for stabilization and optimal preparation. Derangement in intravascular volume status is not uncommon during an acute attack of pancreatitis and should be corrected. Chronic exocrine pancreatic insufficiency may result in malnutrition and fat-soluble vitamin deficiencies. Electrolyte abnormalities are common, particularly calcium and potassium homeostasis, and any abnormalities should be corrected preoperatively. Many of these patients with chronic pancreatitis are opioid dependent and alcoholics. Investigations include complete blood count, serum electrolytes, urea and creatinine levels, serum albumin and proteins, coagulation studies, urine ketones, and chest radiography (pleural effusion or pulmonary edema). Anxiety and stress result in an increased sympathetic discharge with its sequelae on substrate metabolism and cardiovascular system; a sedative premedication is advocated. Consider insulin-dependent diabetes mellitus precautions if diabetes mellitus is established. Consider antithrombotic prophylaxis if history of venous thrombosis.

Drainage of pseudocysts is now mainly done percutaneously. Thus patients are presenting increasingly less often for surgery of the pancreas, which usually is very tedious, technically difficult, and fraught with potential complications of hypothermia, significant fluid shifts and electrolyte imbalances, massive blood loss, and hyperglycemia. In addition, systemic complications may arise from the release of multiple cytokines and other toxic factors from the pancreatitis process or during manipulation of the pancreas, because renal failure, hepatic failure, neurologic dysfunction, and cardiorespiratory failure are possible. Although an epidural technique may offer excellent postoperative analgesia and avoid prolonged ventilatory support because of inadequate pain control, the presence of preoperative clotting studies and the potential for postoperative coagulation derangements may be relative contraindications to the wider use of this option. One of the primary goals is preventing hypoglycemia and hyperglycemia with ketosis.

No particular anesthetic agents are specifically beneficial or contraindicated for diabetes. Avoid alcohol and alcohol-containing solutions.