Dr/ Mohammed HussienAssistant Lecturer of Gastroentrology &

Hepatology Kafrelsheikh University

Acute pancreatitis

2016 By Dr Mohammed Hussien

Objectives

Definition

Pathogenesis

Diagnosis

Pervention

Treatment

Acute pancreatitis

Objectives

o Establish the Diagnosis of Acute Pancreatitis

o Establish the Etiology of Acute Pancreatitis

o Initial Management of Acute Pancreatitis

ALL RECOMMENDATIONS ARE BASED ON THE LATEST ACG MANAGEMENT

2016 By Dr Mohammed Hussien

Acute pancreatitisDefinition

• Acute pancreatitis (AP) is an inflammatory syndrome initiated by pancreatic injury and activation of pancreatic digestive enzymes, leading to direct and indirect activation of the immune system

• ACG ----Acute pancreatitis requires 2 of 3 diagnostic signs

• – Amylase or lipase 3× upper limit of normal values

• – Characteristic sudden onset abdominal pain

• – Characteristic changes on abdominal images

• Contrast-enhanced computed tomographic (CECT) and / or magnetic resonance imaging (MRI) of the pancreas should be reserved for patients in whom the diagnosis is unclear or who fail to improve clinically within the fi rst 48 – 72 h after hospital admission

Epidemiology

Mohammed Hussien 2016

Acute pancreatitis is the third most common inpatient gastrointestinal diagnosis in the United States.

While most patients have a benign course, approximately 15% either present with or develop single or multiple organ involvement and/or pancreatic necrosis within the first 72 hours, resulting in prolonged hospitalization and significant morbidity and mortality

In the United States, more than 80% of the cases of acute pancreatitis are caused by binge drinking of ethanol or by biliary stones

Causes and pathogenesis

• Biliary (eg, gallstones, gallbladder microlithiasis/sludge)

Biliary pancreatitis is most commonly caused by the passage of a stone from the gallbladder through the cystic duct into the common bile duct; impaction at the ampulla of Vater causes reflux of bile into the pancreatic duct.premature activation of intracellular trypsinogen (which causes acinar cell injury) and the release of chemokines and cytokines

• Post ERCP Hyperamylasemia and abdominal pain are common after endoscopic retrograde cholangiopancreatography (ERCP) , but evidence of significant pancreatitis occurs in less than 5% of patients undergoing ERCP.

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• Alcohol consume large quantities of alcohol for 5 to 10 years before the first attack. may occur with as little as 25 g (or two drinks) per day.

• A polymorphism in the detoxifying enzyme uridine 5-diphosphate (UDP) glucuronyl transferase (UGT1A7★3) confers an increased risk for alcoholic pancreatitis

• Environmental factors or cofactors such as smoking and consumption of a high-fat diet may also affect a person's susceptibility to the disease.

• Sphincter of Oddi spasm in the presence of stimulated pancreatic secretion, obstruction of small ductules by proteinaceous plugs,

• oxidative and nonoxidative processes

• Direct toxic effects of alcohol metabolic byproducts

• Alcohol may also change the amounts of potentially damaging proteases in pancreatic secretions

• Increased amounts of lysosomal enzymes

• increased trypsinogen–pancreatic trypsin ratio have been reported in the pancreatic juice of alcoholic patients

Mechanism

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Autoimmune disease:

Iatrogenic:

Drug-induced:

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Surgery (eg, common bile duct exploration, sphincterotomy,splenectomy, distal gastrectomy)

Idiopathic

Infectious (eg, ascariasis, clonorchiasis, mumps, toxoplasmosis, coxsackievirus, cytomegalovirus, tuberculosis, Mycobacterium avium complex)Inherited (Genetic)•CFTR (cystic fibrosis transmembrane conductance regulator)•mutations•SPINK1 (serine protease inhibitor Kazal type 1) mutations•PRSS1 (cationic trypsinogen) mutations

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Metabolic (eg, hypercalcemia, hypertriglyceridemia)

Serum triglyceride levels higher than 1000 mg/dL may precipitate attacks of acute pancreatitis, and lowering serum triglyceride levels to less than 200 mg/dL can prevent pancreatitis. It is currently believed that pancreatitis occurs as a result of the harmful effects of fatty acids released into the pancreatic circulation or parenchyma by the action of pancreatic lipase.

Hypercalcemia secondary to hyperparathyroidism, immobilization, multiple myeloma, or total parenteral nutrition has been linked to hyperamylasemia but probably causes pancreatitis infrequently.

Malignancy (eg, pancreatic or ampullary tumors)

Structural (eg, pancreatic divisum Pancreas divisum results from failure of the ventral and dorsal ducts to join during fetal development; the small accessory duct of Santorini and minor papillae may produce high outflow resistance, Sphincter of Oddi dysfunction or pancreas divisum has been reported in more than 25% of patients with idiopathic pancreatitis in some series, although whether this association is causal or coincidental is difficult to determine, annular pancreas, sphincter of Oddi dysfunction, periampullary diverticula, duodenal duplication cysts, choledochocele, anomalous pancreaticobiliary junction, regional enteritis

Toxic (eg, organophosphates, scorpion venom)

Traumatic (especially motor vehicle accidents)----- Reduced vascular perfusion (e.g., shock), as may occur when surgical procedures are associated with hypotension or hypoperfusion.

Vascular : hypotension or hypoperfusion.

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Pathobiology Pathologically, two morphologic classifications are recognized: acute interstitial pancreatitis and acute hemorrhagic pancreatitis. The latter type is associated with much higher morbidity and mortality.

The fundamental mechanism for transformation of the initial injury into pancreatitis appears to be intracellular activation of digestive enzymes and autodigestion. The complex cascade of cellular events leading to acute pancreatitis begins in the pancreatic acinar cells. Intracellular conversion of pancreatic zymogens into active enzymes most likely involves several pathways, including

(1) cleavage of trypsinogen to trypsin by the lysosomal hydrolase cathepsin B,

(2) disruption of intracellular Ca2+ signaling, and

(3) trypsinogen autoactivation.

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Clinical Manifestations

The typical symptoms of acute pancreatitis are abdominal pain, nausea, and vomiting.

Pain usually develops first and remains constant, without the waxing and waning pattern typical of intestinal or renal colic). The pain is frequently located in the epigastrium with radiation to the midback region; it typically lasts for hours to days and is not relieved by vomiting. Increased pain when supine prompts many patients to sit leaning forward in an effort to minimize discomfort. However, 5% of patients with acute pancreatitis present without abdominal pain.

vary with the severity of the attack, from minimal

local tenderness to marked generalized rebound tenderness, guarding, and abdominal distention. Bowel sounds are frequently diminished or absent because of intestinal ileus.

Jaundice can occur even without stone-induced pancreatitis as a result of compression of the common bile duct by the edematous pancreas. With severe attacks, hypotension, tachypnea, tachycardia, and hyperthermia may be noted.

Fever is usually less than 38.5° C.

large ecchymoses may occasionally appear in the flanks (Grey Turner's sign) or the umbilical area (Cullen's sign);

Abdominal findings

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Common complications in acute pancreatitis

Pancreatic Ductal• Duct disruption

_ With fluid collections– Unorganized (previously called phlegmon)– Organized (pseudocysts)_ With fistula– Pancreatic ascites– Pleural effusion

• Duct obstruction_ Pancreatic Stone, stricture, or other with upstream ductal dilation– Stone, stricture, or other with upstream fluid leak_ Biliary Stone, stricture, or other with abnormal liver injury tests– Stone, stricture, or other with bacterial cholangitis

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Vascular• Pancreatic necrosis• Portal vein thrombosis• Splenic vein thrombosis• Hemorrhage from pseudoaneurysms– Hemosuccus pancreaticus– Pseudocysts– Retroperitoneal Inflammatory• Pancreatic abscess• Pseudocysts• Post-necrotic fluid collections– Sterile pancreatic necrosis– Infected pancreatic necrosis• Inflammatory mass Peripancreatic• Peripancreatic fat necrosis• Duodenal stenosis – obstruction• Colonic stenosis – obstruction

Extrapancreatic• Abdominal compartment syndrome – (intra-abdominal pressure of20–25 mmHg or higher)• Systemic inflammatory complications– Systemic inflammatory response syndrome (SIRS)– Compensatory anti-inflammatory response syndrome (CARS)– Infections• Distant organ dysfunction/failure_ Vascular leak syndrome_ Cardiovascular– Hypotension– Shock_ Pulmonary– Pulmonary edema (capillary leak rather than heart failure)– Adult respiratory distress syndrome_ Intestine– Ileus– Leaky gut syndrome_ Renal– Pre-renal azotemia– Acute tubular necrosis

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Laboratory Findings Serum AmylaseTypically, the serum amylase level rises rapidly over the initial 2 to 12 hours of an attack and then slowly declines to its normal values over the next 3 to 5 days.

Hyperamylasemia is not specific to pancreatitis, but marked elevations in serum amylase (more than three times the upper limit of normal)The magnitude of hyperamylasemia has no prognostic valueHyperamylasemia may result from small bowel obstruction, perforation, or infarction; a perforated duodenal ulcer; or liberation of amylase into the circulation from nongastrointestinal sources such as the lung, fallopian tubes, and salivary & release of amylase from certain tumors or be caused by reduced renal clearance of amylase secondary to renal failure

Diagnosis

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Macroamylasemia, an unusual but not rare condition, can occasionally cause isolated elevation of the serum amylase level. In this condition, amylase is bound to an abnormal serum protein; the complex is not cleared by the kidney and results in hyperamylasemia..

Differentiation from pathological hyperamylasemia relies on calculating the amylase-to-creatinine clearance ratio (ACCR), which equals (serum creatinine × urine amylase)/(urine creatinine × serum amylase) × 100. An ACCR less than 1% suggests macroamylasemia.

Amylase activity in blood is composed of isoenzymes from both the pancreas and salivary glands. Pancreatic isoamylase normally accounts for approximately 40% of total serum amylase activity. In acute pancreatitis, serum pancreatic isoamylase increases substantially. Unfortunately, such increases can also occur in conditions other than acute pancreatitis, including intestinal injury and renal insufficiency, thereby rendering its measurement nonspecific.

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Serum Lipase During acute pancreatitis, serum lipase levels increase in parallel with serum amylase levels. The lipase level remains elevated longer and thus may help diagnose pancreatitis after an attack has passed. Additionally, lipase levels are normal in patients with macroamylasemia and parotitis.

Routine laboratory tests in patients with moderate to severe acute pancreatitis usually reveal leukocytosis. Transient mild hyperglycemia is common and occurs when excess glucagon is released from alpha cells of the islets of Langerhans. Hypocalcemia is generally caused by extravasation of nonionized, albumin-bound calcium from inflamed retroperitoneal and, at times, peritoneal surfaces; this form of hypocalcemia is common, usually causes no symptoms, and requires no treatment. In necrotizing pancreatitis, hypocalcemia can be more severe because of loss of ionized calcium within areas of fat necrosis in the pancreas and peripancreatic tissue. Correlates with severity of the disease. Levels lower than 7 mg/dL (1.75 mmol/L) (when serum albumin is normal) are associated with tetany and an unfavorable prognosis. Hyperbilirubinemia and elevations in serum aminotransferase and alkaline phosphatase levels are seen in up to 50%

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Imaging Chest radiographs may show pleural effusions and basilar atelectasis. Bilateral pulmonary opacification with a normal-sized heart is the hallmark of adult respiratory distress syndrome (ARDS;

Abdominal radiographs should be obtained to exclude nonpancreatic diseases such as intestinal perforation. Intestinal gas patterns may indicate ileus, which may sometimes appear as an isolated dilated loop of small bowel overlying the pancreas (a sentinel loop) or dilation of the transverse colon with abrupt termination of the gas column at the splenic flexure (colon cutoff sign) when the inflammatory process affects the phrenicocolic ligament.

Ultrasound and Computed Tomography US is the single best noninvasive test for detecting cholelithiasis ,although it is less reliable for direct visualization of a bile duct stone. An inflamed pancreas

CT is the primary modality for evaluating the extent and local complications of pancreatitis. Pancreatic inflammation may be seen as pancreatic enlargement, inhomogeneity of the pancreatic parenchyma, or fluid infiltrating the peripancreatic fat in 90% of patients

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Magnetic Resonance Imaging and Endoscopic Retrograde Cholangiopancreatography

Magnetic resonance imaging (MRI)

MRI is better than CT for distinguishing between an uncomplicated pseudocyst and one that contains necrotic debris. Though more expensive and less accessible, MRI is preferred in patients who are pregnant or have contrast allergies. In patients with suspected biliary pancreatitis, magnetic resonance cholangiopancreatography (MRCP) may identify more than 90% of bile duct stones.

ERCP is not useful for establishing the diagnosis of acute pancreatitis

very useful to diagnose and treat persistent bile duct stones in acute pancreatitis. It should also be used in the investigation of patients with unexplained recurrent pancreatitis. It is especially useful for the diagnosis of mild chronic pancreatitis, pancreas divisum, or sphincter of Oddi disease. However, it should be noted that pancreatitis occurs in about 5% of patients undergoing ERCP. This risk for pancreatitis increases significantly in female patients with normal serum bilirubin, patients suspected of sphincter of Oddi dysfunction, and those with a previous history of post-ERCP pancreatitis. In fact, patients with the lowest probability of harboring truly obstructive pathology are at the highest risk for the development of pancreatitis after ERCP, even if the procedure is performed for diagnosis alone.

Endoscopic ultrasound (EUS) have accuracy rates rivaling that of ERCP, they may be preferable to ERCP for patients with equivocal evidence of biliary obstruction, especially those at high risk for post-ERCP pancreatitis.

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Scoring systems (Evaluation of Severity)

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Prognostic Criteria for Acute Pancreatitis (Ranson Criteria)

Ranson Criteria

At admission 48 hr after admission

Age >55

Hematocrit decrease >10%

Leukocyte count >16,000/µL

Serum urea nitrogen increase >5 mg/dL

Lactate dehydrogenase >350 IU/L

Calcium <8 mg/dL

Glucose >200 mg/dL

Arterial PO2 <60 mm Hg

Aspartate aminotransferase >250 IU/L

Base deficit >4 meq/L

Estimated fluid

sequestration >6 L

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Simplified Glasgow Criteria

Within 48 hr of admission

Age >55

Leukocyte count >15,000/µL

Lactate dehydrogenase >600 IU/L

Glucose >180 mg/dL

Albumin <3.2 g/dL

Calcium <8 mg/dL

Arterial PO2 <60 mm Hg

Serum urea nitrogen >45 mg/dL

The Acute Physiology and Chronic Health Evaluation (APACHE) II system uses 14 routinely measured parameters to produce a numerical score based on a patient's deviation from the normal range; however, it is more complex and difficult to use outside an intensive care unit.

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Harmless Acute Pancreatitis Score

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(BISAP)

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Atlanta Classification

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Balthazar Scoring

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Initial assessment and risk stratification Hemodynamic status should be assessed immediately upon presentation and resuscitative

measures begun as needed Risk assessment should be performed to stratify patients into higher- and lower-risk categories to assist triage, such as admission to an intensive care setting

Patients with organ failure should be admitted to an intensive care unit or intermediary care setting whenever possible

Initial management Aggressive hydration, defined as 250-500 ml per hour of isotonic crystalloid solution

should be provided to all patients, unless cardiovascular and / or renal comorbidities exist. Early aggressive intravenous hydration is most beneficial the first 12 – 24 h, and may have little benefit beyond

In a patient with severe volume depletion, manifest as hypotension and tachycardia, more rapid repletion (bolus) may be needed

Lactated Ringer’s solution may be the preferred isotonic crystalloid replacement fluid Fluid requirements should be reassessed at frequent intervals within 6 h of admission

and for the next 24 – 48 h. The goal of aggressive hydration should be to decrease the blood urea nitrogen

Treatment (According to ACG)

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ERCP in acute pancreatitis Patients with acute pancreatitis and concurrent acute cholangitis should undergo ERCP

within 24 h of admission ERCP is not needed in most patients with gallstone pancreatitis who lack laboratory or

clinical evidence of ongoing biliary obstruction In the absence of cholangitis and / or jaundice, MRCP or endoscopic ultrasound (EUS)

rather than diagnostic ERCP should be used to screen for choledocholithiasis if highly suspected.

Pancreatic duct stents and / or postprocedure rectal nonsteroidal anti-infl ammatory drug (NSAID) suppositories should be utilized to prevent severe post-ERCP pancreatitis in high-risk patients

The role of antibiotics in acute pancreatitis Antibiotics should be given for an extrapancreatic infection, such as cholangitis, catheter-

acquired infections, bacteremia, urinary tract infections,

pneumonia Routine use of prophylactic antibiotics in patients with severe acute pancreatitis is not

recommended The use of antibiotics in patients with sterile necrosis to prevent the development of

infected necrosis is not recommended

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Infected necrosis should be considered in patients with pancreatic or extrapancreatic necrosis who deteriorate or fail to improve after 7 – 10 days of hospitalization. In these patients, either

(i) initial CT-guided fineneedle aspiration (FNA) for Gram stain and culture to guide use of appropriate antibiotics or

(ii)empiric use of antibiotics without CT FNA should be given

In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis, such as carbapenems, quinolones, and metronidazole, may be useful in delaying or sometimes totally avoiding intervention, thus decreasing morbidity and mortality

Routine administration of antifungal agents along with prophylactic or therapeutic antibiotics is not recommended

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Nutrition in acute pancreatitis

In mild AP, oral feedings can be started immediately if there is no nausea and vomiting, and abdominal pain has resolved (conditional recommendation,

moderate quality of evidence). In mild AP, initiation of feeding with a low-fat solid diet appears as safe as a clear

liquid diet (conditional recommendations, moderate quality of evidence).

28. In severe AP, enteral nutrition is recommended to prevent infectious complications. Parenteral nutrition should be avoided unless the enteral route is not available, not tolerated, or not meeting caloric requirements

Nasogastric delivery and nasojejunal delivery of enteral feeding appear comparable in efficacy and safety

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The role of surgery in acute pancreatitis In patients with mild AP, found to have gallstones in the gallbladder, a

cholecystectomy should be performed before discharge to prevent a recurrence of AP

In a patient with necrotizing biliary AP, in order to prevent infection, cholecystectomy is to be deferred until active inflammation subsides and fluid collections resolve or stabilize

The presence of asymptomatic pseudocysts and pancreatic and / or extrapancreatic necrosis do not warrant intervention, regardless of size, location, and / or extension

In stable patients with infected necrosis, surgical, radiologic, and / or endoscopic drainage should be delayed preferably for more than 4 weeks to allow liquefaction of the contents and the development of a fibrous wall around the necrosis (walled-off necrosis)

In symptomatic patients with infected necrosis, minimally invasive methods of necrosectomy are preferred to open necrosectomy

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Prognosis The natural history of pancreatitis is unpredictable and depends on

the cause. In gallstone pancreatitis, cholecystectomy will prevent further attacks.

Hyperparathyroidism, hyperlipidemia, and implicated drugs may cause or contribute to pancreatitis; elimination of these precipitants should prevent reoccurrence. With the exception of alcoholic pancreatitis, progression from acute to chronic pancreatitis is rare.

In most cases of alcoholic pancreatitis, structural and functional abnormalities have generally already occurred, so pancreatic structure and function may continue to deteriorate despite alcohol abstinence, albeit at a slower pace. Nevertheless, alcohol abstinence will decrease the risk for future episodes