Acute pancreatitis

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ACUTE PANCREATITIS DR.BARUN KUMAR

Transcript of Acute pancreatitis

Page 1: Acute  pancreatitis

ACUTE PANCREATITIS

DR.BARUN KUMAR

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At a glance

• Etiology• Pathogenesis• Diagnostic assessment

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DEFINITIONS

• An acute inflammatory process of pancreas that may also involve peripancreatic tissue or remote organ system

• Requires 2 out of following 3 features:1. Abdominal pain characteristic of acute pancreatitis2. Serum amylase and/or lipase level >/ 3 times the

upper limit of normal3. Characteristic findings of acute pancreatitis on

ultrasonography or CT scan

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ETIOLOGY

• Alcohol• Gallstone• Post-ERCP• Drugs• Autoimmune• Genetic• Abdominal trauma• Post operative• Infections • Metabolic - hypercalcemia, hyperparathyroidism,

hypertriglyceridemia• Miscellaneous- scorpion bite, worm infestations

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A.ALCOHAL

• Along with gallstone, alcohol is the major etiological agent of acute pancreatitis

• Heavy ethanol abuse >100g/day for at least 5 years, smoking and genetic predisposition bears strong risk for alcohol induced injury.

• Alcohol has both direct(caspases ,sphincter of oddi obst,dec perfusion) and indirect (nf-kb, tnf-alpha, IL-1) effects on exocrine pancreas

• N34S , SPINK-1 mutation association

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B.GALLSTONE

• Responsible for as many as 40% of cases, especially in northern belts of india and woman aged 50-70 years.

• OBSTRUCTIVE THEORY: excessive pressure inside the pancreatic duct due to obstruction and subsequent activation of enzymatic and inflammatory cascade

• REFLUX THEORY: stones impacted in ampulla of vater resulting in reflux of bile in pancreatic duct.

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C.POST-ERCP

• Occurs in as high as upto 5% of patients • Most common complication of ERCP• More common in therapeutic ERCP than diagnostic• Major risk factors include use of precut sphincterotomy,

number of pancreatic duct cannulation, and duct opacification.

• 2 theories have been proposed: a)Traumatic intubatiuon of ampulla causing sphincter spasmb)Excessive hydrostatic pressure during contrast injection

causing acinar cell damage

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D.MICROLITHOIASIS : association with idiopathic recurrent acute pancreatitis

E.GENETICS : IRAP and idiopathic chronic pancreatitis shows strong genetic association PRSS1 (cationic trypsinogen gene) , SPINK1 (42% association) , CFTR (9% association) F. HYPERTRIGLYCERIDEMIA: a level of >1000 mg/dl is suggestive >2000 mg/dl is diagnostic

G.CONGENITAL ANAMOLIES: pancreas divisum needs modifiers or cofactors

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H. DRUG INDUCED PANCREATITIS:

I. HYPERSENSITIVITY : 5-aminosalicyclic acid, azathioprine, 6-mercaptopurine,metronidazole, tetracycline

II.DURG INDUCED HYPERTRIGLYCERIDEMIA: thiazide, isotretinoin, tamoxifen

III. TOXIC METABOLITE: pentamidine, valproic acid, didanosine

IV. OVERDOSE REACTION: acetaminophen, erythromycin

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I. INFECTIONS: hep A , HEP B (well recognised) HEP C, HEV mumps, EBV,VZ,CMV

J. ASCARIASIS: KASHMIR is the most affected area with as high as 23% cases of acute pancreatitis due to ascariasis

K. HYPERPARATHYROIDISM: the primary mechanism is calcium mediated activation of trypsinogen or calcium depostion in pancreatic duct

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L. AUTO-IMMUNE PANCREATITIS:

• auto immune infiltration of pancreas lymphoplasmacytic cells resulting in focal or diffuse enlargement of pancreas.

• However, there is no features of pancreatitis. Instead there are features of obstructive jaundice.

• Serum IgG4 levels > 1400 mg/l OR IgG4 positive cells in IHC

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PATHOGENESIS

• The exact mechanism and detailed understanding is still unknown.

• However, most researchers believe abnormal activation of pancreatic enzymes inside the pancreatic acinar cells is the basic pathology

• This further leads to immune response which then is responsible for both local changes and systemic response

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FIG. pathophysiology of acute pancreatitis

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MAJOR STEPS IN PATHOPHYSIOLOGY :

A. INTRA-ACINAR EVENTS

B. INNATE IMMUNE RESPONSE

C. MICROCIRCULATORY DISTURBANCES

D. BACTERIAL INFECTIONS

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A. INTRA – ACINAR EVENTS The key event is intra pancreatic activation of the digestive enzymes either through : i. Ach mediated vagal stimulation ii. Enterokinase activation under pH dependant reaction iii. Trypsin is the first enzyme to get activated which then in turn activates other enzymes

Protecting factors:i. SPINK 1 : packing of inactive intracellular enzymes away from

proteolytic enzymesii. Low intracellular pH- prevents trypsin activationiii. Maintenance of particulate subcellular Ca gradient

COLOCALIZATION THEORY: colocalization of zymogen granules and lysosomes in presence of increased cytosolic Ca gradient

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B. INNATE IMMUNE RESPONSE :

Activation of vascular adhesion molecules

Attraction of neutrophils neutrophil elastase mediated injury ( measured by MPO)

Monocyte mediated injury (through IL-1, IL-6 and TNF-alpha)

Results in damage and further inactivation and the cycle continues (Levels of TNF-alpha and IL-6 correlates with the degree of severe pancreatitis )

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C. MICROCIRCULATORY DISTURBANCE

Leucocyte adhesion, hemoconcentration and vasoconstriction

Reduced capillary perfusion and ischemia

Further pancreatic injury Pancreatic necrosis

Effects on systemic circulation with circulatory failure, hypotension and acute renal failure

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D. BACTERIAL INFECTION

The necrosed pancreatic tissue and peripancreatic fluid collection are susceptible sites for bacterial infection

The most common source of infection is gut through transmigration of bacteria

Most common organsim : E.Coli , pseudomonas, klebsiella

Infected pancreatic necrosis carries a high mortality of as high as 40%

Institution of early enteral feeding is instrumental of preventing transmigration of bacteria

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DIAGNOSTIC ASSESSMENT

A. CLINICAL DIAGNOSISB.LABOROTORY DIAGNOSISC. ASSESSMENT OF SEVERITY

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Clinical Presentation• Pain (95%)

– Acute onset – Mid-abdominal or mid-epigastric – Radiates to the back (50%)– Peak intensity in 30 minutes– Lasts for several hours

• Nausea and vomiting (80%)• Fever• Shock• Abdominal distension (75%)• Abdominal guarding and tenderness (50%)• Restlessness and agitation• Grey-Turner's sign (hemorrhagic discoloration of the flanks)

• Cullen's sign (hemorrhagic discoloration of the umbilicus)

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Cullen's sign Grey-Turner's sign

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LABORATORY DIAGNOSIS

• Serum amylase : alone cannot be used reliably for the diagnosis of AP and serum lipase is preferred.

• Serum lipase is more specific and remains elevated longer than amylase after disease presentation.

• Increased amylase and/or lipase >3 times – Amylase levels rise w/in 2-12h

• Peak w/in first 48hr • Remain elevated 3-5days before return to baseline

– Lipase much more specific

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.• Abdominal ultrasound US should be performed in all patients with AP

• In the absence of gallstones and / or history of significant history of alcohol use, a serum triglyceride should be obtained and considered the etiology if >1000 mg/dl

• In a patient > 40 years old, a pancreatic tumor should be considered as a possible cause of AP

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CT SCAN/ MRI• CT/MRI is the modality of choice for diagnosis and

evaluation and diagnosis of acute pancreatitis • However, patients with mild acute pancreatitis need not

undergo ct/mri • CT/MRI is indicated when:1. Clinical diagnosis is doubtful2. Failure to respond to medical management in 48-72 hrs3. Any change in clinical status suggestive of complication

CT/MRI offers the advantage of evaluation of extent and severity of disease

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MDCT PROTOCOL FOR ACUTE PANCREATITIS

60 SEC DELAYDome of

diaphragm to symphysis

pubis

PORTAL VENOUS PHASE

35 SEC DELAYCOVERAGE THROUGH

PANCREAS TO LOOK FOR

NECROSIS

PANCREATIC PARENCHYMAL

PHASE

10 SEC DELAYTop of the vertetbral

body T12 to sup edge of L4

(in suspected vascular

complications)

Arterial phase CONTRAST – 150 ml of 60% iodinated non-ioinc iv @3-4 ml/sec

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MODIFIED CT SEVERITY INDEX

PROGNOSTIC INDICATOR POINTSPANCREATIC INFLAMMATION

• NORMAL PANCREAS• INTRINSIC PANCREATIC ABNORMALITIES WITH/WITHOUT

INFLAMMATORY CHANGES IN PERIPANCREATIC FAT

0

2• PANCREATIC OR PERIPANCREATIC FLUID COLLECTION OR

PERIPANCREATIC FAT NECROSIS 4

PANCREATIC NECROSIS

• NONE 0

• <30% 2

• >=30% 4

EXTRAPANCREATIC COMPLICATIONS

one or more of pleural effusion, ascites , vascular complications, parenchymal complications, or gastrointestinal tract involvement

2

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.

• Higher CTSI score associated with protracted clinical course, a higher complication rate and a higher mortality

• CTSI 0-1 = no morbidity or mortality• CTSI 2 = morbidity rate of 4% and no mortality• CTSI 7-10% = 17% mortality and 92%

complication rate

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CT Findings

Tail Indistinct

Intraperitoneal fluid

PANC

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CT FindingsSevere Pancreatitis

NonenhancingNecrosis

Peripancreatic edemaand inflammation

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CLINIAL ASSESSMENT HISTORY PLUS EXAMINATIONS SYMPTOMPS OUT OF PROPORTION THAN SIGNS

SERUM AMYLASE + SERUM LIPASE USG W/A

CT SCAN / MRI

ASSESSEMENT OF RISK

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RISK ASSESSMENT

A. ATLANTA SCORING

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ATLANTA CRITERIA ( CONTD.)

CHARACTERISTICS DEFINING POINT

ORGAN FAILURE SHOCK (SBP <90mm of Hg)Pulmonary insufficiency (PaO2<60 mm oh Hg)Renal failure (serum creatinine level >2mg/dl after rehydration)Gastrointestinal bleeding (>500 mL/24 hr)

LOCAL COMPLICATIONS

PANCREATIC NECROSIS (>30% of the parenchyma or >3 cm)PANCREATIC ABSCESS ( circumscribed collection of pus containing little or no pancreatic necrosis)PANCREATIC PSEUDOCYST (collection of pancreatic juices enclosed by a wall of fibrous tissue or granulation tissue)

UNFAVOURABLE PROGNOSTIC SIGNS

RANSONS SCORE >=3APACHE II SCORE >=8

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ATLANTA CRITERIA ( CONTD.)

CHARACTERISTIC DEFINING POINT

SYSTEMIC COMPLICATIONS

DIC (platelet count <100000)

FIBRINOGEN (1GR/L

FIBRIN SPLIT PRODUCTS >80 ug/dl

METABOLIC DISTURBANCE ( calcium level <7.5 mg/dl)

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B.RANSON SCOREAt admission• age in years > 55 years• white blood cell count > 16000 cells/mm3• blood glucose > 11 mmol/L (> 200 mg/dL)• serum AST > 250 IU/L• serum LDH > 350 IU/L At 48 hours• Calcium (serum calcium < 2.0 mmol/L (< 8.0 mg/dL)• Hematocrit fall > 10% (as compared with admission value)• Oxygen (hypoxemia PO2 < 60 mmHg)• BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid

hydration• Base deficit (negative base excess) > 4 mEq/L• Sequestration of fluids > 6 L

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C.APACHE-II SCORE

• ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION

• predicts severity of any acute disease • consists of 11 parameters reflecting functions of

major organ system also taking age amd baseline chronic disease into account

• allow for monitoring of disease progression and response to therapy

• Has been shown superior to ranson and glasgow

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I.MARSHALL SCORING SYSTEM

ORGAN SYSTEM 0 1 2 3 4

RESPIRATORY (P02/FiO2) >400 301-400 201-300 101-200

<=100

RENALSerum creatinine, mg/dl

<1.4 1.4-1.8 1.9-3.6 3.6-4.9 >4.9

CARDIOVASCULARSystolic blood pressure, mm oh Hg

>90 <90Fluid responsive

<90 Not fluid responsive

<90pH<7.3

<90pH<7.2

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D. SIRS SCORE • hr>90/min, • TEMP >38 or <36 celcius• Resp rate >20 breaths/min or PaCO2>32 mm oh Hg• Blood cell count >12000 or <4000 cells/microlit or >10% band form

E. BISAP SCOREo BUN> 25 mg/Dlo Impaired mental status (gcs<15)o SIRS >=2o Age>60 yrso Pleural effusion

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F. Panc 3 score • Hemotocrit >44 , bmi>30kg/m2, pleural effusion

G.JAPANESE SEVERITY SCORE• Has 9 components • Score of 3 or more reflects severe acute pancreatitis

H. HARMLESS ACUTE PANCREATITIS SCORE• Absence of rebound tenderness and/or guarding• Normal hematocrit• Normal serum creatinine

Enables scoring within 30 mins of admn In a cohort of 394 patients, has shown the accuracy to predict a mild

course of acute pancreatitis as high as 98%

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BIOCHEMICAL PREDICTORS OF PANCREATIC NECROSIS AND SEVERITY

1. C-reactive protein (CRP) - >150 mg/ml 2. Proclcitonin (PCT)3. Serum amyloid –a (SAA)4. Serum macrophage migration inhibitory factor (MIF)5. Trypsionogen activation peptide (TAP)6. Polymorphonuclear granulocyte elastase (PMN)7. Interleukin8. Hematocrit9. Bun

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