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. acute pancreatitis

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.

Etiology Approximately 70-80% of patients either have gallstones or a history of sustained alcohol abuse.

Choledocholithiasis( ) 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 gallstoneassociated pancreatitis parallels that of cholelithiasis(): it peaks at ages 50 to 70, and women outnumber men by 2 to 1.

Causes of Acute Pancreatitis

Obstruction: Biliary tract disease: cholelithiasis, tumor, ascarid, stenosis pancreatic duct obstruction: neoplasms, cysts,pancreas divisum annular pancreas ampullary stenosis, duodenal diverticulum Duodenal obstruction Alcohol Hyperlipidemia Hypercalcemia Hereditary Trauma:external, operative,ERCP Ischemia:hypotension,cardiopulmonary bypass, atheroembolism,vasculitis Infectious causes: parastic bacterial viral fungal Drugs:steroids,azathioprine 6-mercaptopurine, Idiopathic

Obstructive Causes
Choledocholithiasis Ampullary obstruction by tumor or sphincter of Oddi hypertension Choledochocele Periampullary duodenal diverticulum() Pancreas divisum : annular() pancreas Primary or metastatic pancreatic tumor Parasites in pancreatic duct: Clonorchis(), Ascaris

Drugs
azathioprine/6-mercaptopurine6- ; valproic acid; estrogens; metronidazole; loop diuretics, including thiazides , furosemide; pentamidine; sulfonamides, including sulfasalazine; methyldopa: L-asparaginase; tetracyclines, etc.

Pathogenesis
1.A complicated pathophysiologic process
2.Enzyme autoactivation and self-digestion (key

point)
3. Many agents participating in the process

4. Complete mechanism remaining unknown

Pancreatic self-protective mechanism

1.mucopolysaccharide on pancreatic duct epithelia 2.proenzyme 3.pancreatin inhibitor 4.acinus metabolism activity 5. Anti-reflux mechanism: oddis sphincter pancreatic duct sphincter

Initiation factor in Earlier period

1. Pancreatic Enzyme Abnormally Activated

Bile reflux Bile common channel

pancreatic duct

1.hypertension in pancreatic duct 2.premature activation of pancreatic enzymes 3.injury to the lining of the pancreatic ducts pancreatic edema or necrosis MODS

 Duodenal Refulx
duodenal enterokinase pancreatic duct trypsinogen trypsin elastasnogen elastase phospholipasogen phospholipase lecithin lysolecthin

2.Alcohol Toxicity
stimulate the pancreas to secrete
pancreatic hypertention tiny pancreatic

duct and acinus rupture

spillage

pancreatic juice

spasm of the sphinctor of oddi direct injury to pancreas

3.Pancreatic Microcirculation Disorder

systemic hypotension hyperlipidemia: triglycerides lipase free acid fatty acids injure pancreatic microcirculation artheroembolism vasculitis

Aggravatiing factors in later period

Infection: pancreatic abscess
Intestinal bacteria translocation

Cytokine and systemic inflammation

reaction syndrome TNF IL-1 IL-6 PAF Free radicals MSOF

PATHOGENESIS
Premature activation of zymogens( ) 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() released into the blood are inactivated by circulating inhibitors, including 2macroglobulin(). 1antitrypsin(), and the C1esterase() inhibitor.

PATHOGENESIS
In addition, trypsin() activates kallikrein(), a peptidase(), which then cleaves several peptides, including bradykinin() and kallidin( ), from their inactive precursors in blood plasma.

PATHOGENESIS
These peptides, termed kinins( ), have various deleterious effects including vasodilatation, increased vascular permeability, pain, and neutrophil( ) 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.

 ()

Pathology
1.Edematous pancreatitis: *interstitial edema *inflammatory cell infiltration of the gland parenchyma 2.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. The acinar cells comprise over 80% of the pancreas and they synthesize and secrete pancreatic enzymes.

Overview of the pancreatic gland

The islet 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.

 Interstitial edema and inflammatory cells within the parenchyma

Hemorrhagic
Macroscopically, marked tissue necrosis and hemorrhage are apparent. Surrounding areas of fat necrosis are also prominent. These are chalky areas of dead adipose tissue that are found within the peripancreatic tissue and throughout the abdomen. Large hematomasoften are located in the retroperitonealspace.

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 Distention
resulting from a paralytic ileus arising from retroperitoneal irritation or ascites or a retroperitoneal phlegmon

Jaundice
distal common bile duct obstruction by gallstones compression of the distal CBD by pancreatic head edema or by other uncommon findings

Abdominal Distention
Paralytic ileus() with abdominal distention may develop during the first few days, signifying extension of the inflammatory process into the small intestinal and colonic() mesentery().

Clinical Presentation of Sever Pancreatitis

Circulatory Derangements: hypotention,

hypovolemia, hypoeffusion

circulating myocardial depressant factor decreased preload to the heart reduced systemic vascular resistance sepsis-like syndrome hyperdynamic state elevated cardiac output lowered systemic vascular resistance lowered arteriovenous oxgen difference

Clinical Presentation of Sever Pancreatitis

left pleural effusion pulmonary failure tachypnea, dyspnea and cyanosis cerebral abnormalities belligerence, confusion, psychosis and coma Turner sign and Cullen sign a bluish color in the flanks or around the umbilicus, (representing blood dissecting to those areas from the retroperitoneum near the pancreas along fascial planes)

 One to 2 weeks after the onset, large ecchymoses() may appear in the flanks (Grey Turners sign) or the umbilical area (Cullens sign);

 One to 2 weeks after the onset, large ecchymoses() may appear in the flanks (Grey Turners sign) or the umbilical area (Cullens sign);

 One to 2 weeks after the onset, large ecchymoses() may appear in the flanks (Grey Turners sign) or the umbilical area (Cullens sign);

Physical Examination
Initial physical examination reveals mild fever and tachycardia(); Hypotension is present in 30 to 40% of patients.

Physical Examination
epigastria tenderness, rigidity and rebound tenderness (There is marked tenderness to deep palpation of the upper abdomen, but signs of peritoneal irritation are frequently absent.) bowel sounds decreased or absent palpable mass
swollen pancreas Pseudocyst abscess

Laboratory Test

Serum Amylase
Total serum amylase activity is the test most frequently used to diagnose acute pancreatitis. The level rises 6 to 12 hours after onset of symptoms and remains elevated for 3 to 5 days in most cases. (hyperamylasemia is
observed within 24-48 hrs; gradually return to normal values during the subsequent 2-5days)

Serum Amylase
Values more than 3 times the upper limit of normal are highly specific for acute pancreatitis but are found in only 80 to 90% of cases. The magnitude of the rise in serum amylase does not correlate with the severity of the attack, nor does prolonged hyperamylasemia indicate developing complications. the absence of hyperamylasemia cant exclude the diagnosis of acute pancreatitis (extensive pancreatic necrosis)

Disorders Associated with hyperamylasemia

Intra-Abdominal
Pancreatic disorders acute pancreatitis chronic pancreatitis trauma carcinoma pseudocyst pancreatic ascites abscess Nonpancreatic disorders biliary tract disease intestinal obstruction mesenteric infarction perforated peptic ulcer peritonitis afferen loop syndrome acute appendicitis euptured ectopic pregnancy salpingitis ruptured aortic aneurysm Salivary gland disorders mumps parotitis trauma calculi irradiation sialoadenitis impaired amylase excretion renal failure mecroamylasemia Miscellaneus pneumonia pancreatic pleural effusion mediastinal pseudocyst cerebral trauma severe burns diabetic reto acidosis pregnancy drugs bisal buminemia

Extra-Abdominal

Urinary Amylase
a sensitive index of the pancreatitis elevations persist for a longer period than serum amylase some other diseases also manifest hyperamylasuria a normal urinary amylase cant preclude the pancreatitis

 Separation of total serum amylase into its pancreatic (P) and salivary (S) isoenzymes and measurements of urinary amylase output add little to the diagnostic information.

 The amylase-creatinine clearance ratio (ACR) (the ratio of amylase concentration in urine over plasma, divided by the corresponding values for creatinine) is useful in diagnosing asymptomatic macroamylasemia, in which aggregates of circulating amylase escape glomerular filtration and the ACR is abnormally low.


256500 6124872 1224 35


Oddi

-ACR
ACCR3.85.3%5 6% ACCR ACCR ACCR // 100

Serum Lipase
a more accurate indicator of acute pancreatitis lipase is solely of pancreatic origin The serum lipase levels tend to remain elevated longer than the amylase levels during the healing phase of pancreatitis. some other diseases also manifest elevated serum lipase
perforated peptic ulcer acute cholecystitis intestinal ischemia

The combination of serum amylase and lipase determinations is more accurate than either test alone).

Hypocalcemia
the consequence of dilutional hypoalbuminemia calcium desposition in areas of fat necrosis resistance of skeletal bone to parathyroid hormone stimulation The ionized calcium concentration remains normal, and symptoms of tetany() are extremely rare.

Other laboratory Test

Elevated white cell count
Leukocytosis ()

> 10000 cells per mm3

Hyperglycemia

Mild azotemia: related to fluid sequestration Abnormalities of liver function test

 Serum triglyceride levels should be obtained in all patients because of their etiologic implications and to help interpret unexpectedly normal serum amylase and lipase levels.

 Elevated alanine() aminotransferase( ) (ALT) and alkaline phosphatase values suggest gallstone-associated pancreatitis. The serum aspartate(()) aminotransferase (AST) is elevated in approximately 50% of patients, owing to alcoholic liver disease or to the pancreatic inflammation itself.

Imaging Tests
1. A plain Abdominal Film
* not specific
* dilatation of an isolated loop of intestine adjacent to the pancreas

* calcification in the pancreas

* left pleural effusions Plain films should be obtained routinely to rule out the presence of free air caused by perforation of a viscus.

2. Ultrasound Examination
* no trauma

* pancreatic and peripancreatic

edema of fluid collection

* pseudosyst
* dilation of pancreatic duct

* GB stone and CBD stone

 Ultrasound examination showing two large pancreatic pseudocysts. Both cysts are indicated by the large white arrows.

3. CT Scans
* confirm diagnosis of pancreatitis

* confirm diagnosis of complications such

as abscess or pseudocyst * reveal extension of inflammation and necrosis * imply prognosis * a needle aspiration under CT guide

 With rapid intravenous bolus injection of contrast material, a dynamic CT scan will reveal extension of peripancreatic inflammation, involvement of adjacent organs, venous thrombosis, and fluid collections.
Most importantly, pancreatic necrosis can be identified and quantitated by the lack of contrast medium enhancement after the bolus injection. The abdominal CT scan may be normal, however, in about 10% of patients with early, mild pancreatitis.

Computed Tomographic Findings in Acute pancreatitis pancreatic changes nonspecific findings

parenchymal enlargement
diffuse focal

bowel distention pleural effusion mesenteric edema

parenchymal edema necrosis peripancreatic changes

blurring of fat planes thickening of fascial planes presence of fluid collections

This CT scan shows poor perfusion of the pancreas.

Abdominal Ultrasonography (US) and Computed Tomography (CT)

US is the method of choice for detecting cholelithiasis() and for determining the diameter of the extrahepatic and intrahepatic bile ducts. Dilatation of these ducts suggests recent or persisting impaction of a stone in the distal common bile duct or the ampulla of Vater. When the clinical diagnosis is made, the CT scan is far superior to US for assessing the extent and local complications of pancreatitis.

 Two pancreatic pseudocysts (arrows). Computed tomography following the intravenous administration of contrast material demonstrates four sharply marginated, fluid-filled collections.

 Large arrow indicates inflamed pancreas. Small arrow denotes areas of peripancreatic inflammation extending toward the hilum of the spleen.

A large pseudocyst (open arrows), which is being percutaneously drained (closed arrow). Pseudocysts that develop in chronic pancreatitis are most commonly caused by duct obstruction, with the formation of a "retention" cyst in the upstream duct or side branch. Unlike the pseudocysts associated with acute pancreatitis, these pseudocysts do not contain activated enzymes, and are usually not a reflection of a necrotizing inflammatory process. These pseudocysts are less likely to produce complications than those associated with acute necrotizing pancreatitis, but they are paradoxically also less likely to resolve. Many of these pseudocysts remain asymptomatic, but they may be complicated by infection, rupture or leak, bleeding, or obstruction of a neighboring hollow viscus (eg, duodenum, bile duct, colon, or ureter, among others). Pseudocysts may also worsen chronic pain or even initiate a wasting syndrome.Recent clinical experience suggests that in patients with pseudocysts smaller than 6 cm, if there is a mature pseudocyst wall on radiographic imaging that does not resemble a cystic neoplasm, minimal symptoms, and no evidence of active alcohol abuse, the risk of complications is extremely small (< 10%). These patients may be safely observed with little risk of serious complication

Computed tomogram of a patient with pancreatic abscess. The pancreas is diffusely involved, and its margins are difficult to define because of the massive peripancreatic inflammation, which is reflected in the streaking seen in this scan. Toward the tail of the pancreas, numerous small and large bubbles are noted (arrows) in the peripancreatic inflammatory mass. Bubbles, caused by gas-forming microorganisms, indicate that the pancreatic abscess is infected.

4. Diagnostic Paracentesis
1. not an ideal test * an invasive procedure * complications * lack of complete specificity of peritoneal fluid enzyme elevations 2. Help diagnosis * elevations in peritoneal fluid amylase and lipase

Edematous pancreatitis

nercotizing pancreatitis

abdominal pain + vomiting and nausea + fever low jaundice (-)-(+) psychiatric symptom no signs of peritonitis + cullens sign no Grey Turners sign no hemorrhagic ascites no WBC <16000/mm3 blood glucose normal serum calcium normal amylase PaO2 normal Bun.Cr no ARDS no DIC no ARF no mortality low

+++ ++ high ++ - +++ yes ++ - +++ yes yes yes >16000/mm3 > 11.1mmol/L > 2.0 mmol/L or (-) < 8.0 kpa yes yes yes yes high

Differential Diagnosis
1.Intestinal perforation 2.Peptic ulcer 3.Cholecystitis

4.acute intestinal obstruction

5.renal colic

6.myocardial ischemia
7.acute gastroenteritis

Treatment

Nonoperative Management
1. Dietary Control

Oral intake is initially prohibited;

Oral intake can be resumed during the

first week of treatment when abdominal

pain and tenderness have improved, ileus has resolved and hyperamylasemia is normalizing.

2. Nasogastric Suction
reduce vomiting and abdominal
distension reduce pancreatic exocrine secretion by reducing secretion release

3. Intravenous fluid therapy and electrolyte replacement

* hypokalemia, hypochoremia, hypocalcaemia and hypomagnesemia should be corrected * Causes of hypovolemia: paralytic ileus vomiting extensive exudation in abdominal cavity and peripancreatic region Generous fluid resuscitation is very

important
* mild hyperglycemia: insulin treatment

4. Nutritional Support
* fasting for a long time
* persistent pain, ileus or the occurrence of a complication such as pseudocyst, phlegmon or abscess * enteral alimentation is better than that through the parenteral route


4 34 X 4.184 J/ml

5. Antibiotics
* prophylaxis * prevent intestinal bacteria translocation * Treat suppurative

complication


500 mg3/ 2

6. Analgesia
* Meperidine (, ) is the
preferred drug;

* Morphine () should be avoided:

causing spasm of the sphincter of oddi

7.

Pancreatic Exocrine Secretion Suppression 1.nasogastric suction

2.histamine(H2)-receptor antagonists
3.antacids 4.anticholinergics

5.glucagon
6.somatostatin, octreotide and sandostatin (250g 3000 g 24h) (0.1mg , 0.6mg 24h) 7.proglumide (cck-receptor antagonists)

8. Pancreatic enzyme inhibitor

* aprotinin
* gabexate * camostat

Surgical Treatment

Operative indication
1. secondary pancreatic infection 2. correction of associated biliary tract disease 3. progressive clinical deterioration
Surgery

is contraindicated in uncomplicated acute pancreatitis.

Surgical Procedure
1. peritoneal lavage: remove toxins and various metabolites 2. pancreatic drainage 3. debridement of necrotic tissue 4. biliary procedure:
endoscopic sphincterotomy cholecystectomy remove the CBD stone

Complications
Systemic complications ARDS Renal failure Cardiovascular failure MOSF Local complications pancreatic abscess pancreatic psuedocysts pancreatic phlegmon pancreatic ascites pleural effusion pancreatic fistula intestinal fistula

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