ACUTE PANCREATITIS.ppt in clinical surgery

Acute pancreatitis in clinical surgery

1. Acute PancreatitisAcute Pancreatitis
DR. Maulid Abdalla KhamisDR. Maulid Abdalla Khamis
MBBS,MMED SURGERYMBBS,MMED SURGERY

2. Normal Anatomy & PhysiologyNormal Anatomy & Physiology
•neutralize neutralize
chymechyme
•digestive digestive
enzymesenzymes
•hormoneshormones

3. Exocrine FunctionExocrine Function
pancreatic duct
common bile
duct
ampulla
pancreatic enzymes
TAIL
BODY
HEAD
UNCINATE

4. Enzyme SecretionEnzyme Secretion
pancreatic duct
duodenum
acinus
microscopic view
of pancreatic acini

5. Enzyme SecretionEnzyme Secretion
Hormonal
CCK
gastrin
Neural
acetylcholine
VIP
GRP
Secretin (hormonal)
H
2
O
bicarbonate

6. Digestive Enzymes in the Digestive Enzymes in the
Pancreatic Acinar CellPancreatic Acinar Cell
PROTEOLYTICPROTEOLYTIC LIPOLYTIC ENZYMESLIPOLYTIC ENZYMES
ENZYMESENZYMES LipaseLipase
TrypsinogenTrypsinogen Prophospholipase A2Prophospholipase A2
ChymotrypsinogenChymotrypsinogen Carboxylesterase lipaseCarboxylesterase lipase
ProelastaseProelastase
Procarboxypeptidase AProcarboxypeptidase A NUCLEASESNUCLEASES
Procarboxypeptidase BProcarboxypeptidase B Deoxyribonuclease (DNAse)Deoxyribonuclease (DNAse)
Ribonuclease (RNAse)Ribonuclease (RNAse)
AMYOLYTIC ENZYMESAMYOLYTIC ENZYMES
AmylaseAmylase OTHERSOTHERS
ProcolipaseProcolipase
Trypsin inhibitorTrypsin inhibitor

7. Normal Enzyme ActivationNormal Enzyme Activation
trypsinogen trypsin
chymotrypsin
elastase
phospholipase
carboxypeptidase
enterokinase
chymotrypsinogen
proelastase
prophospholipase
procarboxypeptidase
duodenal lumen

8. Exocrine StimulationExocrine Stimulation
•The moreThe more proximal the nutrient infusion…the greater the proximal the nutrient infusion…the greater the
pancreatic stimulation pancreatic stimulation (dog studies)(dog studies)
-stomachstomach – maximal stimulation – maximal stimulation
-duodenumduodenum – intermediate stimulation – intermediate stimulation
-jejunumjejunum – minimal / negligible stimulation – minimal / negligible stimulation
•Elemental formulas tend to cause less stimulation than Elemental formulas tend to cause less stimulation than
standard intact formulasstandard intact formulas
-intact proteinintact protein > > oligopeptidesoligopeptides > > free amino acidsfree amino acids
•Intravenous nutrients (even lipids) do not appear to Intravenous nutrients (even lipids) do not appear to
stimulate the pancreasstimulate the pancreas

9. Protective MeasuresProtective Measures
•COMPARTMENTALIZATIONCOMPARTMENTALIZATION - digestive enzymes are - digestive enzymes are
contained within contained within zymogen granuleszymogen granules in acinar cells in acinar cells
•REMOTE ACTIVATIONREMOTE ACTIVATION - digestive enzymes are secreted as - digestive enzymes are secreted as
inactive proenzymesinactive proenzymes within the pancreas within the pancreas
•PROTEASE INHIBITORSPROTEASE INHIBITORS – – trypsin inhibitortrypsin inhibitor is secreted is secreted
along with the proenzymes to along with the proenzymes to suppresssuppress any premature any premature
enzyme activationenzyme activation
•AUTO “SHUT-OFF”AUTO “SHUT-OFF” – trypsin – trypsin destroysdestroys trypsin in high trypsin in high
concentrationsconcentrations

10. Acute PancreatitisAcute Pancreatitis
DefinitionDefinition
•Acute inflammatory process involving the Acute inflammatory process involving the
pancreaspancreas
•Usually painful and self-limitedUsually painful and self-limited
•Isolated event or a recurring illnessIsolated event or a recurring illness
•Pancreatic Pancreatic functionfunction and and morphologymorphology return return
to normal after (or between) attacksto normal after (or between) attacks

11. EtOH
35%
Idiopathic
10%
Other
10%
Gallstones
45%
Acute PancreatitisAcute Pancreatitis
EtiologyEtiology

12. •CholelithiasisCholelithiasis
•Ethanol abuseEthanol abuse
•IdiopathicIdiopathic
•MedicationsMedications
•HyperlipidemiaHyperlipidemia
•ERCPERCP
•TraumaTrauma
•Pancreas divisumPancreas divisum
•HereditaryHereditary
•HypercalcemiaHypercalcemia
•Viral infectionsViral infections
-MumpsMumps
-CoxsackievirusCoxsackievirus
•End-stage renal failureEnd-stage renal failure
•Penetrating peptic ulcerPenetrating peptic ulcer
Acute PancreatitisAcute Pancreatitis
Associated ConditionsAssociated Conditions

13. Acute PancreatitisAcute Pancreatitis
Causative DrugsCausative Drugs
•AIDS therapy:AIDS therapy: didanosine, pentamidine didanosine, pentamidine
•Anti-inflammatory:Anti-inflammatory: sulindac, salicylates sulindac, salicylates
•Antimicrobials:Antimicrobials: metronidazole, sulfonamides, tetracycline, metronidazole, sulfonamides, tetracycline,
nitrofurantoinnitrofurantoin
•Diuretics:Diuretics: furosemide, thiazides furosemide, thiazides
•IBD:IBD: sulfasalazine, mesalamine sulfasalazine, mesalamine
•Immunosuppressives:Immunosuppressives: azathioprine, 6-mercaptopurine azathioprine, 6-mercaptopurine
•Neuropsychiatric:Neuropsychiatric: valproic acid valproic acid
•Other:Other: calcium, estrogen, tamoxifen, ACE-I calcium, estrogen, tamoxifen, ACE-I

14. Pancreas divisumPancreas divisum

15. Hereditary PancreatitisHereditary Pancreatitis
•Autosomal dominant with 80% phenotypic Autosomal dominant with 80% phenotypic
penetrancepenetrance
•Recurrent acute pancreatitis, chronic pancreatitis, Recurrent acute pancreatitis, chronic pancreatitis,
and 50-fold increased risk of pancreatic cancerand 50-fold increased risk of pancreatic cancer
•Mutation in cationic trypsinogen gene (R122H)Mutation in cationic trypsinogen gene (R122H)
•Other genetic defectsOther genetic defects
-CFTRCFTR
-SPINK1SPINK1

16. failed protective
mechanisms
acinar cell
injury
premature
enzyme activation
Acute PancreatitisAcute Pancreatitis
PathogenesisPathogenesis

17. autodigestion of pancreatic tissue
release of
enzymes into
the circulation
activation
of white
blood cells
local
complications
local
vascular
insufficiency
premature enzyme activation
distant
organ failure
Acute PancreatitisAcute Pancreatitis
PathogenesisPathogenesis

18. •STAGE 1: Pancreatic InjurySTAGE 1: Pancreatic Injury
-EdemaEdema
-InflammationInflammation
•STAGE 2: Local EffectsSTAGE 2: Local Effects
-Retroperitoneal edemaRetroperitoneal edema
-IleusIleus
•STAGE 3: Systemic ComplicationsSTAGE 3: Systemic Complications
-Hypotension/shockHypotension/shock
-Metabolic disturbancesMetabolic disturbances
-Sepsis/organ failureSepsis/organ failure
SEVERITYSEVERITY
MildMild
SevereSevere
Acute PancreatitisAcute Pancreatitis
PathogenesisPathogenesis

19. •Abdominal painAbdominal pain
-EpigastricEpigastric
-Radiates to the backRadiates to the back
-Worse in supine positionWorse in supine position
•Nausea and vomitingNausea and vomiting
•FeverFever
Acute PancreatitisAcute Pancreatitis
Clinical PresentationClinical Presentation

20. Acute PancreatitisAcute Pancreatitis
Differential DiagnosisDifferential Diagnosis
•CholedocholithiasisCholedocholithiasis
•Perforated ulcerPerforated ulcer
•Mesenteric ischemiaMesenteric ischemia
•Intestinal obstructionIntestinal obstruction
•Ectopic pregnancyEctopic pregnancy

21. •SymptomsSymptoms
-Abdominal painAbdominal pain
•LaboratoryLaboratory
-Elevated amylase or lipase Elevated amylase or lipase
•> 3x upper limits of normal> 3x upper limits of normal
•RadiologyRadiology
-Abnormal sonogram or CTAbnormal sonogram or CT
Acute PancreatitisAcute Pancreatitis
DiagnosisDiagnosis

22. Causes of IncreasedCauses of Increased
Pancreatic EnzymesPancreatic Enzymes
AmylaseAmylase LipaseLipase
PancreatitisPancreatitis ↑↑ ↑↑
ParotitisParotitis ↑↑ NormalNormal
Biliary stoneBiliary stone ↑↑ ↑↑
Intestinal injuryIntestinal injury ↑↑ ↑↑
Tubo-ovarian Tubo-ovarian
diseasedisease
↑↑ NormalNormal
Renal failureRenal failure ↑↑ ↑↑
MacroamylasemiaMacroamylasemia ↑↑ NormalNormal

23. Acute PancreatitisAcute Pancreatitis
DiagnosisDiagnosis
•EtOH: historyEtOH: history
•Gallstones: abnormal LFTs & sonographic Gallstones: abnormal LFTs & sonographic
evidence of cholelithiasisevidence of cholelithiasis
•Hyperlipidemia: lipemic serum, Tri>1,000Hyperlipidemia: lipemic serum, Tri>1,000
•Hypercalcemia: elevated CaHypercalcemia: elevated Ca
•Trauma: historyTrauma: history
•Medications: history, temporal associationMedications: history, temporal association

24. Acute PancreatitisAcute Pancreatitis
Clinical ManifestationsClinical Manifestations
PANCREATICPANCREATIC
PERIPANCREATICPERIPANCREATIC
SYSTEMICSYSTEMIC
Mild:Mild: edema, inflammation, fat necrosis edema, inflammation, fat necrosis
Severe:Severe: phlegmon, necrosis, hemorrhage phlegmon, necrosis, hemorrhage
(Cullen,gray tunner, fox sign )infection, (Cullen,gray tunner, fox sign )infection,
abscess, fluid collectionsabscess, fluid collections
Retroperitoneum, perirenal spaces, mesocolon, Retroperitoneum, perirenal spaces, mesocolon,
omentum, and mediastinumomentum, and mediastinum
Adjacent viscera:Adjacent viscera: ileus, obstruction, perforation ileus, obstruction, perforation
Cardiovascular:Cardiovascular: hypotension hypotension
Pulmonary:Pulmonary: pleural effusions, ARDS pleural effusions, ARDS
Renal:Renal: acute tubular necrosis acute tubular necrosis
Hematologic:Hematologic: disseminated intravascular coag. disseminated intravascular coag.
Metabolic:Metabolic: hypocalcemia, hyperglycemia hypocalcemia, hyperglycemia

25. Predictors of SeverityPredictors of Severity
•Why are they needed?Why are they needed?
-appropriate patient triage & therapyappropriate patient triage & therapy
-compare results of studies of the impact of compare results of studies of the impact of
therapytherapy
•When are they needed?When are they needed?
-optimally, within first 24 hours (damage control optimally, within first 24 hours (damage control
must begin must begin earlyearly))
•Which is best?Which is best?

26. Severity Scoring SystemsSeverity Scoring Systems
•Ranson and Glasgow Criteria (1974)Ranson and Glasgow Criteria (1974)
-based on clinical & laboratory parametersbased on clinical & laboratory parameters
-scored in first 24-48 hours of admissionscored in first 24-48 hours of admission
-poor positive predictors (better negative predictors)poor positive predictors (better negative predictors)
•APACHE Scoring SystemAPACHE Scoring System
-can yield a score in first 24 hourscan yield a score in first 24 hours
-APACHE II suffers from poor positive predictive valueAPACHE II suffers from poor positive predictive value
-APACHE III is better at mortality prediction at > 24 APACHE III is better at mortality prediction at > 24
hourshours
•Computed Tomography Severity IndexComputed Tomography Severity Index
-much better diagnostic and predictive toolmuch better diagnostic and predictive tool
-optimally useful at 48-96 hours after symptom onsetoptimally useful at 48-96 hours after symptom onset

27. Ranson CriteriaRanson Criteria
Alcoholic PancreatitisAlcoholic Pancreatitis
AT ADMISSIONAT ADMISSION
1.1.Age > 55 yearsAge > 55 years
2.2.WBC > 16,000WBC > 16,000
3.3.Glucose > 200Glucose > 200
4.4.LDH > 350 IU/LLDH > 350 IU/L
5.5.AST > 250 IU/LAST > 250 IU/L
WITHIN 48 HOURSWITHIN 48 HOURS
1.1.HCT drop > 10HCT drop > 10
2.2.BUN > 5BUN > 5
3.3.Arterial PO2 < 60 mm HgArterial PO2 < 60 mm Hg
4.4.Base deficit > 4 mEq/LBase deficit > 4 mEq/L
5.5.Serum Ca < 8Serum Ca < 8
6.6.Fluid sequestration > 6LFluid sequestration > 6L
NumberNumber
MortalityMortality
<2<2
1%1%
3-43-4
16%16%
5-65-6
40%40%
7-87-8
100%100%

28. Glasgow CriteriaGlasgow Criteria
Non-alcoholic PancreatitisNon-alcoholic Pancreatitis
1.1.WBC > 15,000WBC > 15,000
2.2.Glucose > 180Glucose > 180
3.3.BUN > 16BUN > 16
4.4.Arterial PO2 < 60 mm HgArterial PO2 < 60 mm Hg
5.5.Ca < 8Ca < 8
6.6.Albumin < 3.2Albumin < 3.2
7.7.LDH > 600 U/LLDH > 600 U/L
8.8.AST or ALT > 200 U/LAST or ALT > 200 U/L

29. CT Severity IndexCT Severity Index
appearanceappearance normalnormal enlargedenlargedinflamedinflamed
1 fluid 1 fluid
collectioncollection
2 or more 2 or more
collectionscollections
gradegrade AA BB CC DD EE
scorescore 00 11 22 33 44
necrosisnecrosis nonenone < 33%< 33% 33-50%33-50% > 50%> 50%
scorescore 00 22 44 66
scorescore morbiditymorbidity mortalitymortality
1-21-2 4%4% 0%0%
7-107-10 92%92% 17%17%
Balthazar et al. Radiology 1990.Balthazar et al. Radiology 1990.

30. Severe Acute PancreatitisSevere Acute Pancreatitis
•Scoring systemsScoring systems
 3 Ranson criteria3 Ranson criteria
 8 APACHE II points8 APACHE II points
 5 CT points5 CT points
•Organ failureOrgan failure
-shock (SBP < 90 mmHg)shock (SBP < 90 mmHg)
-pulmonary edema / ARDS (PaOpulmonary edema / ARDS (PaO
22 < 60 mmHg) < 60 mmHg)
-renal failure (Cr > 2.0 mg/dl)renal failure (Cr > 2.0 mg/dl)
•Local complicationsLocal complications
-fluid collections fluid collections  pseudocysts pseudocysts
-necrosis (mortality 15% if sterile, 30-35% if necrosis (mortality 15% if sterile, 30-35% if
infected)infected)
-abscessabscess

31. Goals of TreatmentGoals of Treatment
•Limit systemic injuryLimit systemic injury
-support and resuscitation – support and resuscitation – effectiveeffective
-decrease pancreatic secretion – decrease pancreatic secretion – ineffective / ineffective /
harmful?harmful?
-inhibit inflammatory mediators – inhibit inflammatory mediators – ineffectiveineffective
-inhibit circulating trypsin – inhibit circulating trypsin – ineffective (too late)ineffective (too late)
-removing gallstones – removing gallstones – mostly ineffectivemostly ineffective
•Prevent necrosisPrevent necrosis – – how?how?
•Prevent infectionPrevent infection
-antibiotics (imipenem and ciprofloxacin) – antibiotics (imipenem and ciprofloxacin) –
probablyprobably effective in necrotic pancreatitiseffective in necrotic pancreatitis
-prevent colonic bacterial translocationprevent colonic bacterial translocation
-removing gallstones – removing gallstones – variably effectivevariably effective

32. Treatment of Treatment of MildMild
PancreatitisPancreatitis
•Pancreatic restPancreatic rest
•Supportive careSupportive care
-fluid resuscitation – watch BP and urine outputfluid resuscitation – watch BP and urine output
-pain controlpain control
-NG tubes and HNG tubes and H
22 blockers or PPIs are usually blockers or PPIs are usually
not helpfulnot helpful
•Refeeding Refeeding (usually 3 to 7 days)(usually 3 to 7 days)
-bowel sounds presentbowel sounds present
-patient is hungrypatient is hungry
-nearly pain-free (off IV narcotics)nearly pain-free (off IV narcotics)
-amylase & lipase not very useful hereamylase & lipase not very useful here

33. Treatment of Treatment of SevereSevere
PancreatitisPancreatitis
•Pancreatic rest & supportive carePancreatic rest & supportive care
-fluid resuscitationfluid resuscitation** – may require 5-10 liters/day – may require 5-10 liters/day
-careful pulmonary & renal monitoring – ICUcareful pulmonary & renal monitoring – ICU
-maintain hematocrit of 26-30%maintain hematocrit of 26-30%
-pain control – PCA pumppain control – PCA pump
-correct electrolyte derangements (Kcorrect electrolyte derangements (K
++
, Ca, Ca
++++
, Mg, Mg
++++
))
•Rule-out necrosisRule-out necrosis
-contrasted CT scan at 48-72 hourscontrasted CT scan at 48-72 hours
-prophylactic antibiotics if presentprophylactic antibiotics if present
-surgical debridement if infectedsurgical debridement if infected
•Nutritional supportNutritional support
-may be NPO for weeksmay be NPO for weeks
-TPN vs. enteral support (TEN)TPN vs. enteral support (TEN)

34. Role of ERCPRole of ERCP
•Gallstone pancreatitisGallstone pancreatitis
-CholangitisCholangitis
-Obstructive jaundiceObstructive jaundice
•Recurrent acute pancreatitisRecurrent acute pancreatitis
-Structural abnormalitiesStructural abnormalities
-NeoplasmNeoplasm
-Bile sampling for microlithiasisBile sampling for microlithiasis
•Sphincterotomy in patients not suitable for Sphincterotomy in patients not suitable for
cholecystectomycholecystectomy

35. Nutrition in Acute Nutrition in Acute
PancreatitisPancreatitis
•Metabolic stressMetabolic stress
-catabolism & hypermetabolism seen in 2/3 of catabolism & hypermetabolism seen in 2/3 of
patientspatients
-similar to septic state similar to septic state (volume depletion may (volume depletion may
be a major early factor in the above be a major early factor in the above
derangements)derangements)
•Altered substrate metabolismAltered substrate metabolism
-increased cortisol & catecholaminesincreased cortisol & catecholamines
-increased glucagon to insulin ratioincreased glucagon to insulin ratio
-insulin resistanceinsulin resistance
•Micronutrient alterationsMicronutrient alterations
-calcium, magnesium, potassium, etccalcium, magnesium, potassium, etc

36. Systemic Changes in Acute Systemic Changes in Acute
PancreatitisPancreatitis
•HyperdynamicHyperdynamic
-Increased cardiac outputIncreased cardiac output
-Decreased systemic vascular resistanceDecreased systemic vascular resistance
-Increased oxygen consumptionIncreased oxygen consumption
•HypermetabolismHypermetabolism
-Increased resting energy expenditureIncreased resting energy expenditure
•CatabolismCatabolism
-Increased proteolysis of skeletal muscleIncreased proteolysis of skeletal muscle

37. TPN in Acute PancreatitisTPN in Acute Pancreatitis
•delay until volume repleted & electrolytes correcteddelay until volume repleted & electrolytes corrected
•check triglycerides first – goal <400check triglycerides first – goal <400
•lipids are OK to use lipids are OK to use (possible exception of sepsis)(possible exception of sepsis)
•monitor glucose levels carefullymonitor glucose levels carefully
-can see insulin insufficiency can see insulin insufficiency andand resistance resistance
-may need to limit calories at firstmay need to limit calories at first
-separate insulin drip may be neededseparate insulin drip may be needed

38. TPN in Acute PancreatitisTPN in Acute Pancreatitis
•Benefit or harm?Benefit or harm?
-early uncontrolled studies suggested benefitearly uncontrolled studies suggested benefit
-two retrospective studies (70’s & 80’s) two retrospective studies (70’s & 80’s)
showed showed no benefitno benefit with TPN in pancreatitis with TPN in pancreatitis
-1987 – randomized study of early TPN vs. IVF 1987 – randomized study of early TPN vs. IVF
alone showed more sepsis, longer stays, & no alone showed more sepsis, longer stays, & no
fewer complications with TPNfewer complications with TPN
•When to use TPN?When to use TPN?
-jejunal access is unavailablejejunal access is unavailable
-ileus prevents enteral feedingileus prevents enteral feeding
-patients in whom TEN clearly exacerbates patients in whom TEN clearly exacerbates
pancreatitispancreatitis

39. Enteral Nutrition in Acute Enteral Nutrition in Acute
PancreatitisPancreatitis
•studiesstudies
-late 80’slate 80’s – patients who received jejunal feeding tubes – patients who received jejunal feeding tubes
at the time of surgery, did well with earlyat the time of surgery, did well with early
post-op enteral supportpost-op enteral support
-19911991 – randomized study of early TPN vs. early TEN – randomized study of early TPN vs. early TEN
post-op showed no short-term differencepost-op showed no short-term difference
-19971997 – early TPN vs. early TEN (Peptamen) via – early TPN vs. early TEN (Peptamen) via
nasojejunal tube in 32 patients showed no difference nasojejunal tube in 32 patients showed no difference
except 4x less cost & less hyperglycemiaexcept 4x less cost & less hyperglycemia
-19971997 – similar study showed fewer complications and – similar study showed fewer complications and
lower cost without change in length of staylower cost without change in length of stay
-19981998 – similar study showed more sepsis and organ – similar study showed more sepsis and organ
failure in the TPN groupfailure in the TPN group

40. Total Enteral Nutrition in Total Enteral Nutrition in
Severe PancreatitisSevere Pancreatitis
•may start as early as possiblemay start as early as possible
-when emesis has resolvedwhen emesis has resolved
-ileus is not presentileus is not present
•nasojejunal route preferred over nasojejunal route preferred over
nasoduodenalnasoduodenal
•likely decreases risk of infectious likely decreases risk of infectious
complications by reducing complications by reducing
transmigration of colonic bacteriatransmigration of colonic bacteria

41. ConclusionsConclusions
•Acute pancreatitis is a self-limited disease in Acute pancreatitis is a self-limited disease in
which most cases are mild.which most cases are mild.
•Gallstones and alcohol are the leading causes of Gallstones and alcohol are the leading causes of
acute pancreatitis.acute pancreatitis.
•In mild pancreatitis, nutritional support is usually In mild pancreatitis, nutritional support is usually
not required not required
•In severe pancreatitis, nutritional support will In severe pancreatitis, nutritional support will
likely be required with the enteral route preferred likely be required with the enteral route preferred
over TPN because of both safety and cost.over TPN because of both safety and cost.