Acute Pancreatitis XUE Huiping
Pancreatitis is an inflammatory process in which pancreatic enzymes autodigest the gland.
√The gland can sometimes heal without any impairment of function or any morphologic changes. This process is known as acute pancreatitis. √It can recur intermittently, contributing to the functional and morphologic loss of the gland, the pathological change referred to as chronic pancreatitis.
√Acute pancreatitis refers to an attack involving a previously normal pancrease.√Chronic pancreatis is applied to an attack involving a previously, permanently damaged pancrease.
√Acute pancreatitis is an acute inflammatory process of the pancreas, with variable involvement of other regional tissue or remote organ systems. √ Although pancreatic function and structure usually return to normal, the risk of recurrent attacks is 20 to 50% unless the precipitating cause is removed. √ The disease includes a broad spectrum of pancreatic disease, which varies from mild parenchymal edema to severe hemorrhagic pancreatitis associated with subsequent gangrene and necrosis.急性胰腺炎（acute pancreatitis）是指胰酶在胰腺内激活后引起胰腺组织自身消化的急性化学性炎症。
A sensible classification system separates pancreatitis into mild and severe disease based on physiologic findings, laboratory values, and radiologic imaging.
Mild pancreatitis is not associated with organ dysfunction or complications, and recovery is uneventful. Severe pancreatitis is associated with decreased function of the pancreas, local and systemic complications, and a complicated recovery.
Severe pancreatitis is defined as a local complication and/or organ failure.
Local complications are defined as (1) acute fluid collections;(2) pancreatic necrosis;(3) pancreatic abscess;(4) pancreatic pseudosyst
√The clinical presentation of acute pancreatitis is variable, from episodes of mild abdominal discomfort alone to a severe illness associated with hypotension, metabolic derangements, sepsis, fluid sequenstration, multiple organ failure or even death. √ It is always accompanied by an increased concentrations of pancreatic enzymes in blood and in urine.
EtiologyApproximately 70-80% of patients either have gallstones or a history of sustained alcohol abuse.
√Choledocholithiasis(胆总管石病) and ethanol abuse account for 70 to 80% of all cases.
√Gallstones may cause pancreatitis by impacting in the ampulla of Vater.√The incidence of gallstone-associated pancreatitis parallels that of cholelithiasis(胆石症): it peaks at ages 50 to 70, and women outnumber men by 2 to 1.
Causes of Acute PancreatitisObstruction:Biliary tract disease: cholelithiasis, tumor, ascarid, stenosis pancreatic duct obstruction: neoplasms, cysts,pancreas divisum annular pancreas ampullary stenosis, duodenal diverticulum Duodenal obstructionAlcoholHyperlipidemiaHypercalcemiaHereditaryTrauma:external, operative,ERCPIschemia:hypotension,cardiopulmonary bypass, atheroembolism,vasculitisInfectious causes: parastic bacterial viral fungalDrugs:steroids,azathioprine 6-mercaptopurine, Idiopathic
Obstructive Causes • Choledocholithiasis胆总管石病 • Ampullary obstruction by tumor or sphincter of Oddi hypertension • Choledochocele胆总管囊肿 • Periampullary duodenal diverticulum(憩室) • Pancreas divisum : annular(环状的) pancreas • Primary or metastatic pancreatic tumor • Parasites in pancreatic duct: Clonorchis(支睾吸虫), Ascaris
Drugs • azathioprine硫唑嘌呤/6-mercaptopurine6-巯基嘌呤; • valproic acid丙戊酸; • estrogens雌激素; • metronidazole灭滴灵，甲硝唑; • loop diuretics, including thiazides 噻嗪类, furosemide速尿; • pentamidine; • sulfonamides, including sulfasalazine; • methyldopa: L-asparaginase; • tetracyclines, etc.
Pathogenesis1.A complicated pathophysiologic process2.Enzyme autoactivation and self-digestion (key point)3. Many agents participating in the process4. Complete mechanism remaining unknown
Pancreatic self-protective mechanism1.mucopolysaccharide on pancreatic duct epithelia2.proenzyme3.pancreatin inhibitor4.acinus metabolism activity5. Anti-reflux mechanism: oddi’s sphincter pancreatic duct sphincter
1. Pancreatic Enzyme Abnormally Activated⑴Bile refluxBile common channel pancreatic duct1.hypertension in pancreatic duct 2.premature activation of pancreatic enzymes 3.injury to the lining of the pancreatic ducts pancreatic edema or necrosis MODS
⑵ Duodenal Refulxduodenal enterokinase pancreatic ducttrypsinogen trypsinelastasnogen elastasephospholipasogen phospholipase lecithin lysolecthin
2.Alcohol Toxicity⑴stimulate the pancreas to secrete pancreatic hypertention tiny pancreatic duct and acinus rupture pancreatic juice spillage ⑵spasm of the sphinctor of oddi⑶direct injury to pancreas
3.Pancreatic Microcirculation Disorder⑴systemic hypotension⑵hyperlipidemia: triglycerides lipase free acid fatty acids injure pancreatic microcirculation⑶artheroembolism⑷vasculitis
Aggravatiing factors in later period⑴Infection: pancreatic abscess⑵Intestinal bacteria translocation⑶Cytokine and systemic inflammation reaction syndromeTNF IL-1 IL-6 PAF MSOF⑷Free radicals
PATHOGENESIS • Premature activation of zymogens(酶原) and the escape of activated enzymes from acinar cells and pancreatic ducts set the stage for the autodigestive process that represents acute pancreatitis.
PATHOGENESIS • Proteases(蛋白酶) released into the blood are inactivated by circulating inhibitors, including α2-macroglobulin(巨球蛋白). α1-antitrypsin(抗胰蛋白酶), and the C1-esterase(酯酶) inhibitor.
PATHOGENESIS • In addition, trypsin(胰蛋白酶) activates kallikrein(激肽释放酶), a peptidase(肽酶), which then cleaves several peptides, including bradykinin(缓激肽) and kallidin(胰激肽), from their inactive precursors in blood plasma.
PATHOGENESIS • These peptides, termedkinins(激肽), have various deleterious effects including vasodilatation, increased vascular permeability, pain, and neutrophil(嗜中性粒细胞) accumulation.
Two mechanisms may trigger pancreatic autodigestion • zymogen activation within the pancreatic acinar cell. • increased pancreatic duct permeability
PATHOGENESIS • After the acinar cell is triggered, it provokes an intense inflammatory response in the pancreas. • Weeping of pancreatic juice into the peripancreatic space or microperforations of the pancreatic ductal system can lead to pseudocyst formation.
PATHOGENESIS • Subsequent hypoperfusion to the gland can convert mild edematous/interstitial pancreatitis to necrotizing pancreatitis. • At this point, release of toxic factors into the systemic circulation, such as trypsin, elastase, phospholipase A2, and platelet activating factor or other cytokines, can lead to cardiovascular and pulmonary collapse. • The necrotic pancreas can become secondarily infected from hematogenous or transperitoneal sources.
Pathology1.Edematous pancreatitis:*interstitial edema*inflammatory cell infiltration of the gland parenchyma2.Hemorrhagic or necrotizing pancreatitis*extensive pancreatic and peripancreatic fat necrosis *parenchymal necrosis
Overview of the pancreatic gland • The pancreatic gland contains three major types of cells. • The duct cells make up about 10% of the pancreas and secrete solutions rich in bicarbonate. • Theacinar cells comprise over 80% of the pancreas and they synthesize and secrete pancreatic enzymes.
Overview of the pancreatic gland • Theislet cells make up about 10% of the pancreas and form the endocrine portion of the pancreas. • The four major types of islet cells secrete the hormones insulin, glucagon, somatostatin, and pancreatic polypeptide.
Interstitial • The gross architecture of the gland is preserved, but it is edematous. • Hemorrhage is absent. • Interstitial edema and inflammatory cells within the parenchyma are prominent. • Disruption of the normal acinar cell architecture is common and may contribute to characteristically reduced enzyme secretion.
Hemorrhagic • Macroscopically, marked tissue necrosis and hemorrhage are apparent. • Surrounding areas of fat necrosis are also prominent. These are chalky白垩的areas of dead adipose tissue that are found within the peripancreatic tissue and throughout the abdomen. • Large hematomas血肿often are located in the retroperitoneal腹膜后的space.
Hemorrhagic • The microscopic appearance of the pancreas parallels the gross changes, with marked fat and pancreatic necrosis. • Vascular inflammation and thrombosis are common.
Fat necrosis • Fat necrosis seen at surgery is associated with peripancreatic release of lipase, with hydrolysis of triacylglycerols (triglycerides) to toxic fatty acids.
Clinical Presentation • Steady, dull, or boring midepigastric pain associated with nausea and vomiting is the classic presentation of acute pancreatitis.
Abdominal pain • predominant clinical feature • midepigastrium, in the right or left upper quadrants • The pain reaches peak intensity within 15 minutes to 1 hour from onset, in contrast to the more abrupt onset of pain with a perforated viscus. • a penetrating pain, radiating to the back (It radiates straight to the midline of the lower thoracic vertebral region in about 50% of patients and is usually worse in the supine position.)
Abdominal pain • rare patients without abdominal pain but with a severe systemic illness ( hypotension, hypoperfusion and depression of mental status) ---- Painless acute pancreatitis is very rare but carries a grave prognosis because the patients frequently present in shock.
Clinical Presentation • Nausea and vomiting • Abdominal Distentionresulting from a paralytic ileus arising from retroperitoneal irritation or ascites or a retroperitoneal phlegmon • Jaundicedistal common bile duct obstruction by gallstones’ compression of the distal CBD by pancreatic head edema or by other uncommon findings