PANCREATITIS RICHARD L. MONES MD HARLEM HOSPITAL

PANCREATITISRICHARD L. MONES MDHARLEM HOSPITAL

Classification of pancreatitis

Acute· Acute inflammation· Abdominal pain · Elevated pancreatic

enzymes in serum

· Self-limiting

Chronic· Chronic inflammation· Chronic abdominal

pain· Progressive loss of

pancreatic endocrine and exocrine function

BASIC ANATOMY

Ampullary Anatomy

Papilla of Vater

Bile duct sphincter

Sphincter of Oddi

Pancreatic duct sphincter

Ampullary Anatomy

Secretory productsProenzymes

and enzymes

Secretory productsWater and electrolytesDuct

Acinus

Major Functional Units

Regulation

Ach

AchGRPVIPSubstance P

NeurocrineEndocrine

Secretin

CCKSecretin

Secretory Pattern

E. DiMagno and P. Layer, 1993

Pancreas

Trypsinoutput

Midnight 6 am Noon

0

5

10

15Meal

Fasting (interdigestive) Fed

Classes of Enzymes in Pancreatic Juice

Proteases90%

Lipases - 2%

Amylase - 7%

Nucleases <1%

G. Scheele, et al., Gastroenterology 1981; 80:461

Coupled Water and Bicarbonate Secretion

Pancreas

Volumeof H2O

HCO3- output

HCO3-

H2O

GRP: activated enzymes secreted

Supraphysiologic CCK: activated enzymes not secreted

PancreatitisNo Pancreatitis

T. Grady, Am.J.Phy. 1998; 275:G1010

Enzyme Activation and Inhibited Secretion are Both Needed to Initiate Disease

Acinar Cell Zymogen Activation

Protective Mechanisms

· Synthesis of enyzmes as inactive zymogens· Trypsin inhibitor packaged in zymogen granule· Segregation of enzymes in membrane-bound

compartments· Enterokinase restricted to small intestine

Pancreatic cytokine productionCytokine Production

Anti-inflammatory

IL-10IL-1raC5a

Pro-inflammatory

Pancreatic cytokine production

TNFaIL-6IL-1bsIL-2RIL-8ICAM-1iNOS MCP-1MIF PAFSub PPLA2

Histology mild disease

Histology severe disease

Gross specimen in severe pancreatitis

Duodenum

Hemorrhage

Necrosis

Acute Pancreatitis

Other

· Autoimmune· Drug-induced· Iatrogenic· IBD-related· Infectious· Inherited· Metabolic· Neoplastic· Structural· Toxic· Traumatic· Vascular

Alcoholic

Biliary

Idiopathic

Etiologies of acute pancreatitis expanded

Etiologies in Childhood

·Traumatic· Infectious ·Structural·Drug-induced·Metabolic·Others

Acute Pancreatitis

Acute Pancreatitis INFECTIONS

Class Example Mechanism

Viral Coxsackie Unclear

Parasitic Ascaris Obstructive

Fungal Candida Unclear

Bacterial Salmonella Toxin

Inherited Causes

Altered enzyme activityTrypsinogen mutations

Abnormal ion movementCystic fibrosis transmembrane regulator (CFTR) mutations

MetabolicFamilial hypertriglyceridemia

Acute and Chronic Pancreatitis

Hereditary Pancreatitis

· Mutations in cationic trypsinogen

· Autosomal dominant· Incomplete penetrance · Early onset· Frequent calcification· Increased pancreatic cancer

affected

Most Common Mutation - R122H

Hereditary Pancreatitis

Activationpeptide

Trypsin

- Lys - Ile - - Arg122 -Val-

Normal

NH2 - - COOH

- Lys - Ile - - His122 -Val-

Disease Activation Degradation

Resistant to degradationActivation

NH2 - - COOH

Acute Pancreatitis

tetracyclinethiazidesvalproate

nitrofurantoinsulfasalazinepentamidine

minocyclinefurosemidedidanosine (DDI)

estrogens5-amino ASA6-mercaptopurine

corticosteroidsacetaminophenazathioprine

carbamazepineACE inhibitorsasparaginase

RareUncommonCommon

Drug Induced Pancreatitis Sorted by Incidence

Acute Pancreatitis

· Rare cause of acute pancreatitis

· Serum triglycerides usually >1000 mg/dL

· May cause chronic disease· Can be drug-induced:

Alcohol, estrogens,isotretinoin, HIV-protease inhibitors

TG

TG lipase

Free fatty acids

Cell damage

Hypertriglyceridemia

V Khurana and J Barkin, Pancreas 2001; 22:103

Pancreatitis

Environmental Toxic Causes

· Definite· Methanol· Ethylene glycol· Organophosphorus insecticides· Scorpion toxins

· Probable· Pentachlorophenol· Trichloroethylene

Gallstone Migration

Gallstone migration

Pancreatitis

· 5-15% of population

· Impaired duct drainage in minority

· Benefit of endoscopic treatments limited to

specific subgroups

PANCREATIC DIVISUM

ImagingDiffuse pancreatic duct narrowing

Diffuse pancreatic enlargement

ImmunityAutoantibodies

Elevated gammaglobulins or IgG4

Histology Periductular lymphoblastic infiltrate

PhlebitisFibrosis

AUTOIMMUNE PANCREATITS

Diagnostic Criteria: I

Patient Characteristics

Gender· Male > female

Age· Wide range (20-80 years), most > 50

years

Comorbidity· Autoimmune diseases

Autoimmune Pancreatitis

0

20

40

60

80

1200

IgG4 (mg/dl)

1000

Pancreatic cancer CP AIP PBC PSC Sjögren’s

syndrome

IgG4

Hamano H, N Engl J Med 2001;8;344:732

Autoimmune PancreatitisAutoimmune Pancreatitis – IgG4

Clinical features of acute diseaseAcute Pancreatitis

· Abdominal Pain· Pancreatic

Enzymes in Serum

Presenting Features

Acute Pancreatitis

% patients

Abdominal painNausea / vomiting

TachycardiaLow grade fever

Abdominal guardingLoss of bowel sounds

Jaundice

0 20 40 60 80 100

Gray Turner SignAcute Pancreatitis

Acute Pancreatitis

Test Sensitivity Specificity Comment

Serum enzymes high moderate >3x normalincreasesspecificity

Ultrasound moderate high best for gallstones

CT moderate high detects edema, fluid collections

CT with IV moderate high detects contrast necrosis

Time Course of Enzyme ElevationsAcute Pancreatitis

Hours after onset

Fold increase over normal

0 6 12 24 48 72 960

2

4

6

8

10

12

Lipase

Amylase

MechanismsAcute Pancreatitis: Mechanisms

Insult

· Zymogen activation· Generation of

inflammatory mediators· Ischemia

· Inflammation· Ischemia

· Necrosis· Apoptosis

· Systemic inflammatory response

· Multi-organ failure

· Neurogenic stimulation

Acute Pancreatitis - Natural History

MildSevere

Death

Organ failure

Infection

Causes of mortalityAcute Pancreatitis

DEATH

Early (< one week)· Systemic

inflammatory response syndrome (SIRS)

· Multiorgan failure

Late (> one week)· Multiorgan

failure· Pancreatic

infections/sepsis

MORTALITY IN CHINREN-ACUTE PANCREATITISCx BONE MARROW

TPLANTALLBOWEL

PERFORATION/SEPSIS

CONG. HEART DISEASE

LUNG TPLANTMULTIVISCERAL

TPLANTPOLYARTERITS

NODOSA

Treatment

Acute Pancreatitis

Supportive care· Aggressive fluid and

electrolyte replacement· Monitoring

Vital signs

Urine output

O2 saturation

Pain

· Analgesia, anti-emetics

Other treatments· Acid suppression· Antibiotics · NG tube· Nutritional support· Urgent ERCP

Severe Acute PancreatitisPrevent nutritional depletion Negative nitrogen balance Shorten recovery Reduce inflammation

Mild to moderate pancreatitisNo benefit

RouteTPN v/s Enteral

Type of NutritionComplex v/s Elemental

Acute Pancreatitis

Picture feeding tube

Nutrition Issues

Route of Alimentation

TPNCost – high No pancreas stimulationIncreased infectionsElectrolyte disturbancesDetrimental to gut

integrity

EnteralCost – moderateMay stimulate

pancreasReduced infectionsElectrolytes

undisturbedMay retain gut integrity

Acute Pancreatitis: Nutrition

· Early feeding (48 to 72 hrs) may be important

· Low-fat elemental diet may be preferable

· Not necessary to achieve total caloric requirement immediately

· Monitor for hyperglycemia

· NG v/s NJ feeding

Enteral Feeding: Clinical IssuesSevere Acute Pancreatitis

Naso-Gastric Tube Delivery

Acute Pancreatitis: Enteral nutrition

Issues·Difficult to position/maintain NJ·Lack of evidence that low-level

pancreatic stimulation is harmful

Outcome·Prospective trial NG vs NJ in 50

pts with APACHE II avg 11·Semi-elemental diet low fat·Similar mortality, APACHE

changeEatock Am J. Gastro 100: 432, 2005

Systemic· Pulmonary· Renal· CNS· Multiorgan failure

Metabolic· Hypocalcemia· Hyperglycemia

Major Complications

Local· Fluid collections· Necrosis· Infection· Ascites· Erosion into adjacent

structures· GI obstruction· Hemorrhage

Acute Pancreatitis

Necrosis: Sterile

Acute Pancreatitis - Infections

Antibiotics

Therapeutic

· Cholangitis

· Pancreatic infection

Prophylactic

· Prevent infection of necrosis

· Prevent infectious complications (e.g. urinary tract infection)

Antibiotic use in acute pancreatitis

Bacteria in Infected Necrosis

Escherichia coli

Pseudomonas sp.

Anaerobic sp.

Staphylococcus aureus

Klebsiella sp.

Proteus sp.

Streptococcus faecalis

Enterobacter sp.

Beger, et al., Gastroenterology 1986; 91:433

Pseudocyst

Organized Pancreatic Necrosis

Day 1 Day 7 Day 28

Possible Strategies for Altering Severity

· Relieve ductal obstruction· Protease inhibition· Modulate secretion· Inhibit inflammation· Reduce chemokines / cytokines· Modulate cell death

RETROSPECTIVE SRUDY OF 271 CHILDRENYALE- 1995-2006INCREASED INCIDENCE OF PANCREATITIS

BY 53 %15 % recurrence rateMean age 13 yearsNo stat. difference of BMI

CAUSESBILIARY – 32%

STONESMICROLITHIASIS/SLUDGECHOLEDOCAL/PANCREATIC CYSTSANNULAR PANCREASTUMOR COMPRESSION

CAUSESDRUGS- 25%

VALPROIC ACIDPREDNISONEAZATHIAPRINE

CAUSESTRAUMASYSTEMIC ILLNESS/PICUVIRAL INFECTION-7.95%METABOLIC-DKA (5),

HYPERTIGLYCERIDEMIA (3)IDIOPATHIC 23%

SUMMARYINDEX OF SUSPICIONDO ULTASOUND NO CT AT PRESENTATION !!NUTRITION IF ANTICIPATE > 7 DAYSDON’T TREAT LAB DATAMORPHINE FOR PAINNO NG SUCTIONACID SUPPRESSIONSUPPORTIVE CARE

CHANGING REFERRAL TRENDS OF ACUTE PANCREATITS IN CHILDREN: A 12 YEAR SINGLE-CENTER ANALYSIS: JPGN 2009 SEPT.49(3): 316-322

PANCRESATITIS IN CHILDREN JPGN 37; (5)NOV.591-595

AGA MEDICAL POSITION ON ACUTE PANCREATITS: GASTRO, MAY 2007 201902021

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