1. ACUTE PANCREATITIS
CHAIR OF FACULTY SURGERY # 2
FIRST MOSCOW STATE MEDICAL UNIVERSITY
NATROSHVILI A.G.

2. ANATOMY AND PHYSIOLOGY
• DIGESTIVE ENZYMES
• HORMONES
microscopic view
of pancreatic acini
pancreatic duct
duodenum

3. ANATOMY AND PHYSIOLOGY
trypsinogen trypsin
chymotrypsin
elastase
phospholipase
carboxypeptidase
enterokinase
chymotrypsinogen
proelastase
prophospholipase
procarboxypeptidase
duodenal lumen
Normal Enzyme Activation

4. ANATOMY AND PHYSIOLOGY
Exocrine Stimulation
• THE MORE PROXIMAL THE NUTRIENT INFUSION…THE GREATER THE PANCREATIC STIMULATION
(DOG STUDIES)
• STOMACH – MAXIMAL STIMULATION
• DUODENUM – INTERMEDIATE STIMULATION
• JEJUNUM – MINIMAL / NEGLIGIBLE STIMULATION
• ELEMENTAL FORMULAS TEND TO CAUSE LESS STIMULATION THAN STANDARD INTACT FORMULAS
• INTACT PROTEIN > OLIGOPEPTIDES > FREE AMINO ACIDS
• INTRAVENOUS NUTRIENTS (EVEN LIPIDS) DO NOT APPEAR TO STIMULATE THE PANCREAS

5. ANATOMY AND PHYSIOLOGY
Protection
• COMPARTMENTALIZATION - DIGESTIVE ENZYMES ARE CONTAINED
WITHIN ZYMOGEN GRANULES IN ACINAR CELLS
• REMOTE ACTIVATION - DIGESTIVE ENZYMES ARE SECRETED AS INACTIVE
PROENZYMES WITHIN THE PANCREAS
• PROTEASE INHIBITORS – TRYPSIN INHIBITOR IS SECRETED ALONG WITH
THE PROENZYMES TO SUPPRESS ANY PREMATURE ENZYME ACTIVATION
• AUTO “SHUT-OFF” – TRYPSIN DESTROYS TRYPSIN IN HIGH
CONCENTRATIONS

6. ACUTE PANCREATITIS
Definition
• ACUTE INFLAMMATORY PROCESS INVOLVING THE PANCREAS
• USUALLY PAINFUL AND SELF-LIMITED
• ISOLATED EVENT OR A RECURRING ILLNESS
• PANCREATIC FUNCTION AND MORPHOLOGY RETURN TO
NORMAL AFTER (OR BETWEEN) ATTACKS

7. ACUTE PANCREATITIS
Etiology
Gallstones
45%
Alcohol
[ПРОЦЕНТ]
Idiopathic
10%
Other
10%

8. ACUTE PANCREATITIS
Associated conditions
• CHOLELITHIASIS
• ETHANOL ABUSE
• IDIOPATHIC
• MEDICATIONS
• HYPERLIPIDEMIA
• ERCP
• TRAUMA
• END-STAGE RENAL
FAILURE
• PENETRATING PEPTIC
ULCER

9. ACUTE PANCREATITIS
Pathogenesis
Acinar cell injury
Premature enzyme
activation
Failed protective
mechanisms
Audodigestion of
pancreatic tissue
Local vascular
insufficiency
Activation of white
blood cells
Release of enzymes
into the circulation
Local complications Distant organ failure

10. ACUTE PANCREATITIS
Pathogenesis
• STAGE 1: PANCREATIC INJURY
• EDEMA
• INFLAMMATION
• STAGE 2: LOCAL EFFECTS
• RETROPERITONEAL EDEMA
• ILEUS
• STAGE 3: SYSTEMIC COMPLICATIONS
• HYPOTENSION/SHOCK
• METABOLIC DISTURBANCES
• SEPSIS/ORGAN FAILURE
SEVERITY
Mild
Severe

11. • MILD AP (NO NECROSIS) – 0%
 Sterile necrosis – 10%
 Infected necrosis – 25%
ACUTE PANCREATITIS

12. ACUTE PANCREATITIS
Clinical presentation
• ABDOMINAL PAIN
• EPIGASTRIC
• RADIATES TO THE BACK (“BELT PAIN”
• WORSE IN SUPINE POSITION
• NAUSEA AND VOMITING
• FEVER
• LABORATORY
• ELEVATED AMYLASE OR LIPASE
• > 3X UPPER LIMITS OF NORMAL
• LIPASE HAS SLIGHTLY HIGHER SENSITIVITY AND
SPECIFICITY AND GREATER OVERALL ACCURACY THAN
AMYLASE (EVIDENCE CATEGORY A)
• RADIOLOGY
• ABNORMAL SONOGRAM OR CT
• DIFFERENTIAL DIAGNOSIS
• CHOLEDOCHOLITHIASIS
• PERFORATED ULCER
• MESENTERIC ISCHEMIA
• INTESTINAL OBSTRUCTION
• ECTOPIC PREGNANCY

13. ACUTE PANCREATITIS
Clinical presentation
Mild: edema, inflammation, fat necrosis
Severe:
phlegmon, necrosis, hemorrhage, infection, abscess, fluid
collections
Retroperitoneum, perirenal
spaces, mesocolon, omentum, and mediastinum
Adjacent viscera: ileus, obstruction, perforation
Cardiovascular: hypotension
Pulmonary: pleural effusions, ARDS
Renal: acute tubular necrosis
Hematologic: disseminated intravascular coag.
PANCREATIC
PERIPANCREATIC
SYSTEMIC

14. ACUTE PANCREATITIS
Predictors of severity
• WHY ARE THEY NEEDED?
• APPROPRIATE PATIENT THERAPY
• COMPARE RESULTS OF STUDIES OF THE IMPACT OF THERAPY
• WHEN ARE THEY NEEDED?
• OPTIMALLY, WITHIN FIRST 24 HOURS (DAMAGE CONTROL MUST BEGIN
EARLY)
• WHICH IS BEST?

15. ACUTE PANCREATITIS
Scoring systems
• RANSON AND GLASGOW CRITERIA (1974)
• BASED ON CLINICAL & LABORATORY PARAMETERS
• SCORED IN FIRST 24-48 HOURS OF ADMISSION
• POOR POSITIVE PREDICTORS (BETTER NEGATIVE PREDICTORS)
• APACHE SCORING SYSTEM
• CAN YIELD A SCORE IN FIRST 24 HOURS
• APACHE II SUFFERS FROM POOR POSITIVE PREDICTIVE VALUE
• APACHE III IS BETTER AT MORTALITY PREDICTION AT > 24 HOURS
• COMPUTED TOMOGRAPHY SEVERITY INDEX
• MUCH BETTER DIAGNOSTIC AND PREDICTIVE TOOL
• OPTIMALLY USEFUL AT 48-96 HOURS AFTER SYMPTOM ONSET

16. ACUTE PANCREATITIS
Scoring systems: Ranson criteria for alcoholic pancreatitis
AT ADMISSION
1. AGE > 55 YEARS
2. WBC > 16,000
3. GLUCOSE > 200
4. LDH > 350 IU/L
5. AST > 250 IU/L
WITHIN 48 HOURS
1. HCT DROP > 10
2. BUN > 5
3. ARTERIAL PO2 < 60 MM HG
4. BASE DEFICIT > 4 MEQ/L
5. SERUM CA < 8
6. FLUID SEQUESTRATION > 6L
Number
Mortality
<2
1%
3-4
16%
5-6
40%
7-8
100%

17. ACUTE PANCREATITIS
Scoring systems: CT severity index
appearance normal enlarged inflamed
1 fluid
collection
2 or more
collections
grade A B C D E
score 0 1 2 3 4
necrosis none < 33% 33-50% > 50%
score 0 2 4 6
score morbidity mortality
1-2 4% 0%
7-10 92% 17%
Balthazar et al. Radiology 1990.

18. ACUTE PANCREATITIS
Severe pancreatitis
• SCORING SYSTEMS
• 3 RANSON CRITERIA
• 8 APACHE II POINTS
• 5 CT POINTS
• ORGAN FAILURE
• SHOCK (SBP < 90 MMHG)
• PULMONARY EDEMA / ARDS (PAO2 < 60 MMHG)
• RENAL FAILURE (CR > 2.0 MG/DL)
• LOCAL COMPLICATIONS
• FLUID COLLECTIONS PSEUDOCYSTS
• NECROSIS (MORTALITY 15% IF STERILE, 30-35% IF
INFECTED)
• ABSCESS

19. ACUTE PANCREATITIS
Additional diagnostic tests: Ultrasonography
• LITTLE PART IN THE DIAGNOSIS OF THE ACUTE PANCREATITIS DUE TO BOWEL DILATATION
MAIN SIGNS: ENLARGED HYPOECHOGENIC PANCREAS, POSSIBLE FLUID COLLECTIONS
• ROLE IN BILIARY PANCREATITIS
• STONES IN GALLBLADDER
• COMMON BILE DUCT DILATION
US FINDINGS SHOULD BE EXAMINED IN ALL PATIENTS WITH POSSIBLE ACUTE
PANCREATITIS ON ADMISSION (EVIDENCE CATEGORY B)

20. ACUTE PANCREATITIS
Additional diagnostic tests: CT-scan
• HIGHLY INFORMATIVE
• NORMAL
• HOMOGENEOUS ENHANCEMENT OF THE WHOLE PANCREAS
• ABNORMAL
• NON-VISUALIZATION OF A PART OF THE PANCREAS
• SENSITIVITY OF 90-95%
• SPECIFICITY – 100%
• ROUTINE USE OF CT SCAN WITHIN 24-48 HOURS OF ADMISSION (EVIDENCE CATEGORY C)
• A DYNAMIC CT SCAN SHOULD BE PERFORMED IN ALL (PREDICTED) SEVERE CASES BETWEEN 3 AND 10
DAYS AFTER ADMISSION (EVIDENCE CATEGORY B)

21. ACUTE PANCREATITIS
Additional diagnostic lab tests
• AMYLASE AND LIPASE
• PLASMA LEVEL PEAK WITHIN 24 HOURS
• T1/2 OF AMYLASE << LIPASE
Sensitivity Specificity
Amylase 67-100 85-98
Lipase 82-100 86-100
• AMYLASE/ LIPASE
• DEGREE OF ELEVATION SHOWS LITTLE
CORRELATION WITH DISEASE SEVERITY
AND PROGNOSIS
• MAY HAVE AN INVERSE RELATIONSHIP
WITH SEVERITY
• TRYPSINOGEN 2
• EXCRETED INTO THE URINE
• USED AS A SCREENING TEST FOR
ACUTE PANCREATITIS

22. ACUTE PANCREATITIS
Additional diagnostic lab tests
• ACUTE PHASE REACTANT
• SYNTHESIZED BY THE HEPATOCYTES
• SYNTHESIS IS INDUCED BY THE RELEASE OF INTERLEUKIN 1 AND 6
• PEAK IN SERUM IS THREE DAYS AFTER THE ONSET OF PAIN
• MOST POPULAR SINGLE TEST SEVERITY MARKER USED TODAY
• GOLD STANDARD FOR THE PREDICTION OF THE NECROTIZING COURSE OF THE DISEASE
• ACCURACY OF 86%
• READILY AVAILABLE
C-REACTIVE PROTEIN (CRP)
Isenmann et al Pancreas 1993;8:358-61

23. ACUTE PANCREATITIS
Initial management of acute pancreatitis
• PANCREATIC REST & SUPPORTIVE CARE
• FLUID RESUSCITATION* – MAY REQUIRE 5-10 LITERS/DAY
• CAREFUL PULMONARY & RENAL MONITORING – ICU
• MAINTAIN HEMATOCRIT OF 26-30%
• PAIN CONTROL – PCA PUMP
• CORRECT ELECTROLYTE DERANGEMENTS (K+, CA++, MG++)
• PROTON PUMP INHIBITORS
• SANDOSTATINE
• RULE-OUT NECROSIS
• CONTRASTED CT SCAN AT 48-72 HOURS
• PROPHYLACTIC ANTIBIOTICS IF PRESENT
• SURGICAL DEBRIDEMENT IF INFECTED
• NUTRITIONAL SUPPORT

24. ACUTE PANCREATITIS
Initial management of acute pancreatitis: ERCP
• GALLSTONE PANCREATITIS
• CHOLANGITIS
• OBSTRUCTIVE JAUNDICE
• RECURRENT ACUTE PANCREATITIS
• STRUCTURAL ABNORMALITIES
• NEOPLASM
• BILE SAMPLING FOR MICROLITHIASIS
• SPHINCTEROTOMY IN PATIENTS NOT SUITABLE FOR CHOLECYSTECTOMY
• NOT INDICATED IN CASE OF MILD PANCREATITIS OF
SUSPECTED OR PROVEN BILIARY ETIOLOGY IN THE ABSENCE OF
THE BILIARY OBSTRUCTION (EVIDENCE A)
Neoptolemos et al 1988; Fan NEJM 1993; Folsch NEJM 1997

25. ACUTE PANCREATITIS
Antibiotics
• SEPSIS
• ACCOUNTS FOR > 80% OF DEATHS
• INTESTINAL FLORA
• GRAM NEGATIVE BACTERIA
• MECHANISM – TRANSLOCATION OF THE BACTERIA ACROSS THE GUT WALL
• PROPHYLACTIC ANTIBACTERIAL TREATMENT IS STRONGLY RECOMMENDED IN SEVERE PANCREATITIS (EVIDENCE B)
• NO EVIDENCE WHEN TO START PROPHYLACTIC TREATMENT OR HOW LONG TO CONTINUE THERAPY
• APPROPRIATE ANTIBIOTICS ARE THOSE THAT ARE ACTIVE AGAINST IN PARTICULAR GRAM-NEGATIVE ORGANISMS
• COMMENCE AS EARLY AS POSSIBLE AFTER THE IDENTIFICATION OF A SEVERE ATTACK

26. ACUTE PANCREATITIS
Pancreatic necrosis
• STERILE NECROSIS – SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS) (FIRST WEEK)
• MORTALITY RATE OF 10-40%
• STERILE PANCREATIC NECROSIS – SURGERY IN SELECTED CASES
SELECTED CASES
• MASSIVE PANCREATIC NECROSIS (>50%) WITH A DETERIORATING CLINICAL
COURSE (EVIDENCE C)
• PATIENTS WITH PROGRESSION OF ORGAN DYSFUNCTION
• NO SIGNS OF THE IMPROVEMENT (GRADE B)

27. ACUTE PANCREATITIS
Pancreatic necrosis
Infected necrosis – Sepsis (After 3 weeks)
Mortality – 20-70%
• US OR CT GUIDED FNA WITH GRAM STAIN AND CULTURE IS A
CONFIRMATORY TEST (EVIDENCE A)
SUSPECT IF:
• EXACERBATION OF CLINICAL SIGNS
• LABORATORY BLOOD TEST CHANGES
• SHIFT TO IMMATURE CELLS
• ELEVATION OF CRP
• INCREASED APACHE II
• POSITIVE BLOOD CULTURE
• NECROSECTOMY IS INDICATED IN A CONFIRMED INFECTED
PANCREATIC NECROSIS (EVIDENCE A)

28. ACUTE PANCREATITIS
Pancreatic necrosis
Infected necrosis – Sepsis (After 3 weeks)
Mortality – 20-70%
• US OR CT GUIDED FNA WITH GRAM STAIN AND CULTURE IS A
CONFIRMATORY TEST (EVIDENCE A)
SUSPECT IF:
• EXACERBATION OF CLINICAL SIGNS
• LABORATORY BLOOD TEST CHANGES
• SHIFT TO IMMATURE CELLS
• ELEVATION OF CRP
• INCREASED APACHE II
• POSITIVE BLOOD CULTURE
• NECROSECTOMY IS INDICATED IN A CONFIRMED INFECTED
PANCREATIC NECROSIS (EVIDENCE A)

29. ACUTE PANCREATITIS
Algorithm
Confirm acute
pancreatitis
Amylase/Lipase
Trypsinogetn2
CT scan in atypical cases
Initial management
Severity stratification
IV fluid/pain conrol
Scoring systems
C-reactive protein
Mild acute
pancreatitis
Severe acute
pancreatitis

30. ACUTE PANCREATITIS
Algorithm
Mild acute
pancreatitis
Severe acute
pancreatitis
RECOMMENDED
Admit to general ward
Refeed when pain
subsides
NOT RECOMMENDED
Antibiotics
CT scan
RECOMMENDED
Admit to ICU
Antibiotics
CT-scan – day 3
NECROSIS
Sterile – observe (CT, US)
Infection suspected – fine needle aspiration/drainage
under US or CT control
Infected necrosis – necrosectomy
Open drainage of abscesses, retroperitoneal space