LECTURE 5 Acute Pancreatitis National O. Bogomolets Medical University Faculty Surgery Department N1 Kyiv 2007 Prof. Kucher M.
Pancreas embryology The ventral pancreas develops in association with the biliary tree, and its duct joins the common bile duct before emptying into the duodenum through the papilla of Vater. During gestation, the duodenum rotates clockwise on its long axis, and the bile duct and ventral pancreas pass round behind it to fuse with the dorsal pancreas. Most of the duct that drains the dorsal pancreas joins the duct draining the ventral pancreas to form the main pancreatic duct (of Wirsung); the rest of the dorsal duct becomes the accessory pancreatic duct (of Santorini) and enters the duodenum 2.5 cm proximal to the main duct.
Surgical anatomy. The pancreas lies retroperitoneally, behind the lesser sac and stomach. The head of the gland lies within the C-loop of the duodenum, with which it shares a blood supply from the coeliac and superior mesenteric arteries. The superior mesenteric vein runs upwards to the left of the uncinate process, and joins the splenic vein behind the neck of the pancreas to form the portal vein. The body and tail of the pancreas lie in front of the splenic vein as far as the splenic hilum, and receive arterial blood from the splenic artery. The close association between the common bile duct and the head of pancreas explains why obstructive jaundice is so common in cancer of the head of the pancreas, and why gallstones frequently give rise to acute pancreatitis.
The exocrine pancreas is essential for the digestion of fat, protein and carbohydrate. The pancreas secretes 1-2 litres of alkaline (pH 7.5-8.8) enzyme-rich juice each day.
The enzymes are synthesized by the acinar cells and stored there as zymogen granules .
Trypsin is the key proteolytic enzyme; it is released in an inactive form (trypsinogen) and is normally only activated within the duodenum by the brush border enzyme, enterokinase . Once trypsin has been activated, a cascade is established whereby the other proteolytic enzymes become activated in turn.
Lipase and amylase are secreted as active enzymes. The alkaline medium required for the activity of pancreatic enzymes is provided by the bicarbonate secreted by the ductal epithelium.
Pancreatic secretion is stimulated by eating. Hormonal and neural (vagal) mechanisms are involved. Food entering the duodenum (notably fat and protein digestion products) releases cholecystokinin (CCK), which stimulates pancreatic enzyme secretion, while at the same time causing the gallbladder to contract and increase bile flow into the intestine. Acid in the duodenum releases the hormone secretin, which stimulates the pancreas to secrete watery alkaline juice. .
The islets of Sobolev-Langerhans are distributed throughout the pancreas. Although they account for only 2% of the weight of the gland, they receive 10% of its blood supply.
Four types of islet cell are recognized:
A cells produce glucagons ;
B cells, insulin ;
D cells, somatostatin ;
PP cells, pancreatic polypeptide .
Glucagon and insulin have well-established physiological roles; the function of the other islet products is uncertain, but somatostatin and pancreatic polypeptide may serve as local (paracrine) regulators, rather than as circulating (endocrine) messengers. Gastrin-producing (G) cells are not normally found in the pancreas, except in the rare Zollinger-Ellison syndrome
Pancreatitis may be acute or chronic. After an attack of acute pancreatitis, the gland usually returns to anatomical and functional normality,
whereas chronic pancreatitis is associated with a fibrosis, permanent derangement of structure and function. Some patients suffer from recurrent acute pancreatitis but enjoy relatively normal health between attacks.
The exact mechanism responsible for acute pancreatitis remains uncertain. Reflux of duodenal juice and/or bile into the pancreatic duct and obstruction to the flow of pancreatic juice may trigger premature activation of pancreatic enzymes within the duct system. Intraduct activation of trypsin, chymotrypsin, phospholipase, catalase and elastase may then unleash a chain reaction of cell necrosis,
further enzyme release and changes in the microcirculation.
Rupture of the duct system permits autodigestion of the gland. The continued release of activated proteolytic enzymes is responsible for increased capillary permeability, protein exudation, retroperitoneal oedema and peritoneal exudation. Vasoactive kinins such as kallikrein are also released, and activated macrophages may release cytokines.
Alcohol induces spasm of the sphincter of Oddi and increases the sensitivity of acinar cells to CCK hyperstimulation, resulting in enhanced intracellular protease activation.
Pancreatic inflammation ranges in severity from mild oedema to severe necrosis and haemorrhage .
In general, oedematous pancreatitis is usually mild and settles on conservative treatment, whereas necrotizing pancreatitis is frequently severe, often leading to complications, the need for operation and death.
The majority of patients who develop severe pancreatitis have evidence of early organ dysfunction at the time of admission or soon thereafter. Worsening organ failure is associated with a poor outcome.
Profound hypovolaemic shock may follow the fluid, protein and electrolyte loss that results from altered capillary permeability, and metabolic upsets result from cytokine release.
Endotoxin can be detected in the systemic circulation in many patients, indicating that bacteria and their products may also be implicated in the circulatory upset.
Other factors that contribute to the systemic upset include
acute renal failure (possibly due to a combination of hypovolaemia, endotoxaemia and local intravascular coagulation),
acute respiratory distress syndrome (ARDS, due to altered permeability in pulmonary capillaries),
consumptive coagulopathy, and
altered liver function (due to hepatocyte depression and/or obstruction of the common bile duct by a gallstone or pancreatic oedema).
Aetiology Traumatic (5%) Operative trauma Blunt or penetrating injury Investigation (ERCP or angiography) Idiopathic (20%) Table 19-1. CAUSES OF ACUTE PANCREATITIS
Gallstones are present in some 40% of patients in the UK who develop acute pancreatitis. Most of these have many small stones in the gallbladder, a wide cystic duct, and a common channel between the common bile duct and the main pancreatic duct.
It is now believed that stones or biliary sand may impact transiently in the common channel and so promote the reflux of bile into the pancreatic duct and/or impair the normal flow of pancreatic juice. It has also become apparent that many patients with 'idiopathic acute pancreatitis' are actually suffering from pancreatitis caused not by stones per se, but by debris containing microcrystals of cholesterol and calcium bilirubinate granules (so-called biliary sludge). The causal significance of gallstones and biliary sludge in acute pancreatitis is underlined by the fact that further attacks are exceptional once biliary tract disease has been eradicated
The proportion of cases of acute pancreatitis linked to alcohol varies in different parts of the world. In Scotland the figure is around 30%, whereas in some parts of France and North America it may be as high as 50-90%.
The mechanism responsible is uncertain. Alcohol consumption normally exceeds 80 g day immediately prior to an attack, but genetic vulnerability is likely. Alcohol may cause the secretion of unduly viscid juice, with the formation of protein plugs and impairment of flow, and may also generate toxic free radicals that directly damage the gland. Alcohol-associated pancreatitis frequently causes permanent damage to the gland, with progression to chronic pancreatitis.
Acute pancreatitis is a common cause of emergency admission to hospital. Britain has 100-200 new cases per million of the population each year and the incidence continues to rise, possibly as a result of increasing alcohol consumption.
The disease is relatively rare in children, but all adult age groups may be affected.
Roughly 1 in 4 patients proves to have severe disease, and of these 1 in 4 will die.
Most patients with severe attacks have some evidence of systemic organ dysfunction at presentation. This may be obvious clinically from the shocked state of the patient, or formal 'prognostic factor scores', such as the Glasgow system, Ranson criteria, APACHE II score etc.
Urea and electrolyte measurements reflect the state of hydration and are helpful in managing fluid and electrolyte balance.
Liver function tests (LFTs) may show hyperbilirubinaemia and elevation of liver enzymes, particularly in patients with gallstone pancreatitis.
Hyperglycaemia and glycosuria can occur transiently in severe disease.
Arterial blood gas analysis may reveal severe hypoxia.
Moderate polymorphonuclear leucocytosis is common .
Constant severe or agonizing pain in the epigastrium, with radiation through to the back, is usually prominent. Pain can also be experienced in either hypochondrium.
Nausea, vomiting and retching are often marked.
Clinical examination often reveals much less tenderness, guarding and rigidity than might have been expected from the patient's history.
Shock is often present in severe pancreatitis.
Bruising around the umbilicus (Cullen's sign) or brawny discoloration of the flanks (Grey-Turner's sign) is an uncommon, relatively late sign of severe pancreatitis but is indicative of a poor prognosis.
Obstructive jaundice may be apparent in patients with pancreatitis due to an impacted gallstone, but is usually transient.
A pleural effusion may be detected in about 20% of cases, and is almost always left-sided; it probably represents the effect of inflammation tracking retroperitoneally to involve the pleura.
Although amylase is widely available and provides acceptable accuracy of diagnosis, where lipase estimation is available it is preferred for the diagnosis of acute pancreatitis.
Available prognostic features which predict complications in acute pancreatitis are
clinical impression of severity, obesity or
APACHE II . 8 in the first 24 hours of admission,
C-reactive protein > 150 mg/l,
Glasgow score 3 or more or persisting organ failure after 48 hours in hospital.
Patients with persisting organ failure, signs of sepsis or deterioration in clinical status 6-10 days after admission will require computed tomography.
W orking Party of the British Society of Gastroenterology; Association of Surgeons of Great Britain and Ireland; Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland. Gut 2005; 54 suppl 3:iii 1-9.
A left-sided pleural effusion or features of ARDS may be seen on chest X-ray. A bowel empty of gas except for a 'sentinel loop' of jejunum may reflect local ileus, and in some cases gas is seen in the hepatic and splenic flexures but not the transverse colon-the 'colon cut-off' sign. Radio-opaque gallstones may be seen in some patients with gallstone pancreatitis.
Balthazar Scoring for the Grading of Acute Pancreatitis The CT Severity Score is the sum of the CT Grade and Necrosis Grade Scores. CT Grade Score : 4 points Two or more fluid collections and / or gas bubbles in or adjacent to pancreas Grade E 3 points Fluid collection in a single location Grade D 2 points Pancreatic gland abnormalities and peripancreatic inflammation Grade C 1 point Focal or diffuse enlargement of the pancreas Grade B 0 points Normal CT Grade A CT Grade Points Appearance on CT CT Grade
Balthazar Scoring for the Grading of Acute Pancreatitis The CT Severity Score is the sum of the CT Grade and Necrosis Grade Scores. Necrosis Grade Score : 6 points Over 50% necrosis 4 points 30 to 50% necrosis 2 points 0 to 30% necrosis 0 points No necrosis Points Necrosis Percentage
A ) A pancreas with mild pancreatitis and no signs of pancreatic necrosis (CTSI: Grade A, 0 points). ( B ) Diffuse enlargement of the gland, including contour irregularities and inhomogeneous attenuation with peripancreatic inflammation consistent with edematous post-ERCP pancreatitis 24 h after ERCP (CTSI: Grade B, 2 points). ( C ) The patient in (B) 20 days after ERCP. The scan shows pancreatic and peripancreatic fluid collection as well as peripancreatic fat necrosis, extra-pancreatic complications, such as pleural effusion and ascites, and vascular complications, such as the embolic obstruction of the superior mesenteric artery resulting in infarction of the spleen (CTSI: Grade E, 4 points plus 2 additional points for extra-pancreatic complication plus 4 points for >30% pancreatic necrosis). ( D ) Pancreatic and peripancreatic fluid collection as well as peripancreatic fat necrosis (CTSI: Grade D, 4 points plus 4 points for pancreatic necrosis [more than 30% necrotic pancreatic parenchyma]). ( E ) Scan suggesting peripancreatic and complete pancreatic necrosis. Placement of a percutaneous drain into the pancreatic fluid collection (CTSI: Grade E, 6 points plus 4 additional points for pancreatic necrosis). ( F ) Organized pancreatic fluid collection and a developing pseudocystic wall, complete obstruction of the duodenum and no signs of superinfection 8 weeks after biliary necrotizing pancreatitis (Balthazar score or modified CTSI are not applicable). CTSI, CT severity index (here, the modified CTSI of Silverman and Banks and colleagues); ERCP, endoscopic retrograde cholangipancreatography.
CT scanning is used to recognise abscess or pseudocyst formation or necrosis. Even if a CT scan is not required for diagnostic purposes, it should be performed 3–10 days after the start of a severe attack. If signs of necrosis are seen, a fine needle aspirate of the pancreatic fluid is indicated to identify whether the tissue is infected or not. Sterile necrosis should be managed conservatively but, if there is infection, open necrosectomy is indicated. Repeat CT scanning is recommended every 1–2 weeks
Pain relief . Severe pain requires the administration of opiates; pethidine is frequently prescribed.
Treatment of shock. Large volumes of crystalloid solution, plasma or dextran may be needed to maintain circulating blood volume and to correct intravascular hypovolaemia. Oxygen is essential in shocked patients, in whom pulse, blood pressure, urine output and central venous pressure should be monitored.
Suppression of pancreatic function. Oral fluids and diet are withheld. A nasogastric tube may relieve vomiting but there is no evidence that routine nasogastric intubation is beneficial.
Inhibition of pancreatic secretion or enzymes. There is no evidence to support the use of the somatostatin analogue, octreotide. Similarly, several trials have shown no advantage to the use of the antiprotease, aprotinin (Trasylol), and gabexate mesylate in the treatment of pancreatitis.
Prevention of infection. Antibiotic prophylaxis has been advocated as a means of reducing the risk of secondary infection, but it may result in an increased incidence of severe fungal infection. Consensus supports the use of a prophylactic antibiotic such as an intravenous cephalosporin or imipenem for predicted severe disease. Fluconazole is currently investigated.
Inhibition of inflammatory response. There is currently no evidence to support the use of agents such as the platelet-activating factor (PAF) antagonist, lexipafant, as a means of reducing the inflammatory response in acute pancreatitis.
Nutritional support. A reduction in acute-phase response and septic complications may result from enteral support rather than intravenous nutrition, although this requires the passage of a nasojejunal tube. There remains doubt as to whether outcome is affected, but enteral nutrition should be favoured where possible in patients with severe pancreatitis and its complications
Other measures. Peritoneal lavage with isotonic crystalloid solutions was once advocated as a means of removing enzymes and vasoactive substances from the peritoneal cavity and so preventing their absorption. However, recent trials have shown no reduction in mortality or morbidity in patients with severe acute pancreatitis.
When gallstones are suspected to be the cause of acute pancreatitis, consideration may be given to the endoscopic retrieval of such stones from the biliary tree using a basket or balloon following endoscopic sphincterotomy.
When patients are admitted with a mild attack of pancreatitis, there is no need to institute such active therapy, as in most cases the offending gallstone will pass on into the duodenum spontaneously.
In patients with severe disease that does not settle promptly on conservative management, endoscopic stone retrieval may abort the attack and reduce morbidity and mortality. All patients with predicted severe disease and any patient with suspected cholangitis should therefore undergo urgent endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy
Acute pancreatitis is defined as an attack of pancreatic inflammation, after which the gland returns to anatomical and functional normality
Gallstones (50% of cases) and alcohol (30% of cases) are the outstanding causes of acute pancreatitis
In 1 in 4 cases, the attack is severe, as assessed by prognostic factor scoring; in 1 in 4 patients with severe pancreatitis, the attack proves fatal
In most cases, the pancreatic inflammation is mild and oedematous, and settles on conservative management. Necrotizing pancreatitis is frequently severe and often leads to complications, the need for surgery, and death
Severe attacks of gallstone pancreatitis can often be aborted if a stone occluding the lower end of the biliary tree can be removed by endoscopic papillotomy. Once gallstones have been eradicated, recurrent attacks of gallstone pancreatitis are exceptional