Presented by:

Ahmad Pourhosseini

pancreatic duct

common bileduct

ampulla

pancreatic enzymes

TAILTAIL

BODYBODY

HEADHEAD

UNCINATEUNCINATE

PROTEOLYTICPROTEOLYTIC LIPOLYTIC ENZYMESLIPOLYTIC ENZYMES ENZYMESENZYMES LipaseLipaseTrypsinogenTrypsinogen Prophospholipase A2Prophospholipase A2ChymotrypsinogenChymotrypsinogen Carboxylesterase lipaseCarboxylesterase lipaseProelastaseProelastaseProcarboxypeptidase AProcarboxypeptidase A NUCLEASESNUCLEASESProcarboxypeptidase BProcarboxypeptidase B Deoxyribonuclease (DNAse)Deoxyribonuclease (DNAse)

Ribonuclease (RNAse)Ribonuclease (RNAse)AMYOLYTIC ENZYMESAMYOLYTIC ENZYMESAmylaseAmylase OTHERSOTHERS

ProcolipaseProcolipaseTrypsin inhibitorTrypsin inhibitor

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

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

EtOH35%

Idiopathic10%

Other10% Gallstones

45%

CholelithiasisEthanol abuse IdiopathicMedicationsHyperlipidemiaERCPTrauma

Pancreas divisumHereditaryHypercalcemiaViral infections

MumpsCoxsackievirus

End-stage renal failurePenetrating peptic ulcer

AIDS therapy: didanosine, pentamidineAnti-inflammatory: sulindac, salicylatesAntimicrobials: metronidazole, sulfonamides,

tetracycline, nitrofurantoinDiuretics: furosemide, thiazides IBD: sulfasalazine, mesalamine Immunosuppressives: azathioprine, 6-mercaptopurineNeuropsychiatric: valproic acidOther: calcium, estrogen, tamoxifen, ACE-I

http://www.uni-ulm.de/klinik/radklinik/rad1/intervention97/radpath/panc2a.gif

Autosomal dominant with 80% phenotypic penetrance

Recurrent acute pancreatitis, chronic pancreatitis, and 50-fold increased risk of pancreatic cancer

Mutation in cationic trypsinogen gene (R122H)

Other genetic defectsCFTRSPINK1

failed protectivemechanisms

acinar cellinjury

prematureenzyme activation

autodigestion of pancreatic tissue

release ofenzymes intothe circulation

activationof white

blood cells

localcomplications

localvascular

insufficiency

premature enzyme activation

distantorgan failure

STAGE 1: Pancreatic InjuryEdemaInflammation

STAGE 2: Local EffectsRetroperitoneal edemaIleus

STAGE 3: Systemic ComplicationsHypotension/shockMetabolic disturbancesSepsis/organ failure

SEVERITYSEVERITYMildMild

SevereSevere

Abdominal painEpigastricRadiates to the backWorse in supine position

Nausea and vomitingFever

Acute PancreatitisAcute PancreatitisClinical PresentationClinical Presentation

CholedocholithiasisPerforated ulcerMesenteric ischemiaIntestinal obstructionEctopic pregnancy

SymptomsAbdominal pain

LaboratoryElevated amylase or lipase

> 3x upper limits of normal

RadiologyAbnormal sonogram or CT

Acute PancreatitisAcute PancreatitisDiagnosisDiagnosis

Grey Turner sign - flank discoloration due to retroperitoneal bleed in pt. with pancreatic necrosis (rare)

Cullen’s sign - periumbilical discoloration (rare)

Grey Turner sign Cullen’s sign

AmylaseAmylase LipaseLipase

PancreatitisPancreatitis ↑↑ ↑↑

ParotitisParotitis ↑↑ NormalNormal

Biliary stoneBiliary stone ↑↑ ↑↑

Intestinal injuryIntestinal injury ↑↑ ↑↑Tubo-ovarian Tubo-ovarian

diseasedisease ↑↑ NormalNormal

Renal failureRenal failure ↑↑ ↑↑

MacroamylasemiaMacroamylasemia ↑↑ NormalNormal

EtOH: historyGallstones: abnormal LFTs & sonographic

evidence of cholelithiasisHyperlipidemia: lipemic serum, Tri>1,000Hypercalcemia: elevated CaTrauma: historyMedications: history, temporal association

Acute PancreatitisAcute PancreatitisClinical ManifestationsClinical Manifestations

PANCREATICPANCREATIC

PERIPANCREATICPERIPANCREATIC

SYSTEMICSYSTEMIC

Mild:Mild: edema, inflammation, fat necrosis edema, inflammation, fat necrosisSevere:Severe: phlegmon, necrosis, hemorrhage, phlegmon, necrosis, hemorrhage, infection, abscess, fluid collectionsinfection, abscess, 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 hypotensionPulmonary:Pulmonary: pleural effusions, ARDS pleural effusions, ARDSRenal:Renal: acute tubular necrosis acute tubular necrosisHematologic:Hematologic: disseminated intravascular coag. disseminated intravascular coag.Metabolic:Metabolic: hypocalcemia, hyperglycemia hypocalcemia, hyperglycemia

0 12 24 36 48 60 72 84 96

hours from pain onset

ER presentation cytokine release organ failure

Why are they needed?appropriate patient triage & therapycompare 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?

Ranson 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

NumberNumberMortalityMortality

<2<21%1%

3-43-416%16%

5-65-640%40%

7-87-8100%100%

appearanceappearance normalnormal enlargedenlarged inflamedinflamed 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.

Scoring systems 3 Ranson criteria 8 APACHE II points 5 CT points

Organ failureshock (SBP < 90 mmHg)pulmonary edema / ARDS (PaO2 < 60

mmHg)renal failure (Cr > 2.0 mg/dl)

Local complicationsfluid collections pseudocystsnecrosis (mortality 15% if sterile, 30-35%

if infected)abscess

Pancreatic rest Supportive care

fluid resuscitation – watch BP and urine output

pain controlNG tubes and H2 blockers or PPIs are

usually not helpful Refeeding (usually 3 to 7 days)

bowel sounds presentpatient is hungrynearly pain-free (off IV narcotics)amylase & lipase not very useful here

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++)

Rule-out necrosis contrasted CT scan at 48-72 hours prophylactic antibiotics if present surgical debridement if infected

Nutritional support may be NPO for weeks TPN vs. enteral support (TEN)

Abdominal pain with food aversionNausea and vomitingGastric atonyIleusPartial duodenal obstruction

ParameterParameterMildMild

PancreatitisPancreatitis

SevereSevere

PancreatitisPancreatitis

AdmissionsAdmissions 80%80% 20%20%

Pancreatic Pancreatic necrosisnecrosis NoNo YesYes

Oral diet within 5 Oral diet within 5 daysdays 80%80% 0%0%

MorbidityMorbidity 8%8% 38%38%

MortalityMortality 3%3% 27%27%

Acute pancreatitis is a self-limited disease in which most cases are mild.

Gallstones and alcohol are the leading causes of acute pancreatitis.

In mild pancreatitis, nutritional support is usually not required

In severe pancreatitis, nutritional support will likely be required with the enteral route preferred over TPN because of both safety and cost.