Acute Chronic Pancreatitis

ACUTE PANCREATITIS PROF. DR. SALİH PEKMEZCİ

PATHOGENESIS pancreatic enzymes and activation of cascade systems Proelastase, Kimotrypsinogen, Prekallikrein, C3, Prophospholipase Plazminogen, Factor 12 trypsinogen Enterokinase and lisosomal katepsin

TRYPSİN Kininogen Elastase Kimotrypsin Phospholipase

Kallikrein C3a Plasmin Factor 12a

Kinin

MECHANISMS OF PANCREATITIS •OBSTRUCTION OF PANCREATIC DUCT •COMMON CHANNEL HYPOTHESIS •REFLUX OF ACTIVATED PANCREATIC ENZYMES •INCREASED DUCTAL PERMEABILITY •OTHERS

ETIOLOGY • • • • • • • • • • •

ALCOHOL GALLSTONES TRAUMA DUCTAL OBSTRUCTION INFECTION DRUGS METABOLIC DISTURBANCES ISCHEMIA HYPERPARATHYROIDISM IDIOPATIC OTHERS

ETIOLOGY • • • • • • • • • •

ALCOHOL GALLSTONE TRAUMA DUCTAL OBSTRUCTION INFECTION DRUGS METABOLIC DISTURBANCES ISCHEMIA OTHER IDIOPATIC

PATHOGENESIS OF ALCOHOL INDUCED PANCREATITIS • PARTIAL OBSTRUCTION IN AMPULLA • HYPERSECRETION OF PANCREAS • PROTEIN PLUGS IN PANCREATIC DUCT • PANCREATIC ISCHEMIA

THE PATHWAY OF ALCOHOL INDUCED PANCREATITIS BY ISCHEMIA ALCOHOL

PANCREATIC ISCHEMIA

XANTHINE DEHYDROGENASE

XANTHINE OXIDASE

metabolysme ACETALDEHYDE

FREE OXYGEN RAD

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

RISK FACTORS IN BILIARY PANCREATITIS • MULTIPLE SMALL GALLSTONES IN GALLBLADDER • LARGE CYSTIC DUCT • CHOLEDOCOLITHIASIS • LARGE CHOLEDOC-WIRSUNG ANGLE • COMMON CHANNEL > 5 MM

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

COMMON CHANNEL IS OBSERVED IN %90 OF PATİENTS WITH BILIARY PANCREATITIS, WHEREAS ONLY IN %20 OF PATIENTS WHO DID NOT PRESENT PANCREATITIS

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

TRAUMA A- POSTOPERATIVE OR POSTERCP B- FOLLOWING BLUNT OR PENETRATING TRAUMA

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA

ETIOLOGY IN

POSTOPERATIVE PANCREATITIS

• DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

• DIRECT TRAUMA • ISCHEMIA • MICROEMBOLI AND TROMBUS • DRUGS USED POSTOPERATIVELY (Azathioprine,steroids, calcium vs.)

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

ETIOLOGY IN PANCREATITIS

POST-ERCP

• OVER MANIPULATION • DIATHERMIA • FORCED IRRIGATION OR CONTRAST AGENT INFUSION

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

DUCTAL OBSTRUCTION • • • • •

PANCREATIC TUMORS DUCTAL STRICTURE PENETRATED DUODENAL ULCER AFFERENT LOOP SYNDROME ANATOMICAL OR PHYSIOLOGICAL ANOMALIES

ETIOLOGY

VIRAL Mumps, Coxsackie B, Enterovirus, EBV, CMV, Hepatitis B, Hepatitis A,

• ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

Hepatitis C BACTERIAL Staphylococcus, E.Coli, Enterococcus, Enterobacteriae, Proteus, P.

Aeruginosa, Spyrocets, C. dyphteria, Legionella, Yersinia, Campylobacter, Salmonella, Mycobacteria, Mycoplasma FUNGAL Aspergillosis, Actyomycosis PARASYTES

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES

DRUGS ASSOCIATED WITH PANCREATITIS

ABSOLUTE RELATIONSHIP • AZOTHIOPRYNE • CHLOROTIAZIDE • ESTROGENS • FUROSEMIDE • SULFONAMIDES • TETRACYCLINE

• ISCHEMIA

• VELPROATE

• OTHER

• PENTHAMIDINE AND DDL

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

DRUGS ASSOCIATED WıTH PANCREATITIS POSSIBLE RELATIONSHIP • • • •

L-ASPARAGYNASE CORTICOSTEROIDS ETACRYNIC ACID PHENPHORMINE

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES

THOUGHT TO BE RELATED WITH PANCREATITIS

• AMPHETAMINE • CHOLESTYRAMINE • PROPOXYPHENE • INDOMETASYNE • ISONIASYDE • MERCAPTOPURINE • OPIADS • RYFAMPISINE

• ISCHEMIA

• SALISILATES

• OTHER

• CIMETIDINE

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

METABOLIC DISTURBANCES • HYPERLIPIDEMIA • HYPERCALCEMIA

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA

ISCHEMIA • EMBOLIZATION OF PANCREATICODUODENAL ARTERY IN AORTOGRAPHY

• DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

• STENOSIS OF TRUNCUS COELIACUS • RUPTURE OF ANEURYSM OF AORTA ABDOMINALIS • MYOCARDIAL INFARCT

ETIOLOGY • ALCOHOL • GALLSTONE • TRAUMA • DUCTAL

OBSTRUCTION

• INFECTION • DRUGS • METABOLIC DISTURBANCES • ISCHEMIA • OTHER

OTHERS • OTOIMMUN DISEASES • PROTEIN ANOMALIES • SCORPION VENOM • PREGNANCY

CLINICALPRESENTATION • ABDOMINAL PAIN • NAUSEA-VOMITMENT • ANOREXIA • FEVER • ABDOMINAL MASS • ILEUS • JAUNDICE

PHYSICAL EXAMINATION • LOCALIZED/GENERALIZED ABDOMINAL TENDERNESS • ABDOMINAL DISTENTION • FEVER • TACHYCARDIA • HYPOTENSION • GREY-TURNER VE CULLEN SIGNS • CONFUSION, PSYCHOSE AND COMA

DIAGNOSIS BIOCHEMICAL MARKERS • • • • • •

SERUM AMYLASE AND ISOFORMES URINE AMYLASE AMYLASE-CREATININE CLEARANCE RATIO SERUM LIPASE AND ISOFORMES TRYPSINE PHOSPHOLIPASE-A

AMYLASE CONTAINING TISSUES • PANCREAS

P-ISOAMYLASE

• • • • • • • • •

S-ISOAMYLASE

SALIVARY GLANDS TUBA OVER ENDOMETRIUM PROSTATE BREAST LUNG LIVER SMALL BOWEL

DISEASES ASSOCIATED WITH HYPERAMYLASEMIA INTRAABDOMINAL CAUSES • PANCREATIC DISEASES ACUTE PANCREATITIS, CHRONIC PANCREATITIS, TRAUMA CARCINOMA, PSEUDOCYST, PANCREATIC ASCITES, ABCESS • NON-PANCREATIC DISEASES BILIARY DISEASES, BOWEL OBSTRUCTIONS, MESENTERIC INFARCT, PERFORATED PEPTIC ULCER,PERITONITIS, AFFERENT LOOP SYNDROME, ACUTE APPENDICITIS RUPTURE OF ECTOPICAL PREGNANCY, SALPENGITIS, RUPTURATED ANEURYSM OF AORTA

DISEASES ASSOCIATED WITH HYPERAMYLASEMIA EXTRAABDOMINAL CAUSES • DISEASES OF SALIVARY GLANDS, MUMPS, PAROTITIS, TRAUMA, PAROTIS STONES, RADIATION SIALADENITIS • AMYLASE CLEARANCE DEFECTS: RENAL FAILURE, MACROAMYLASEMIA

• OTHER: PNUEMONIA, PANCREATIC PLEURAL EFFUSION,

MEDIASTINAL PSEUDOCYST, CEREBRAL TRAUMA, SEVERE BURNS, DIABETIC KETOACIDOSIS, PREGNANCY, DRUGS

AMYLASE-CREATININE CLEARANCE RATIO =

URINE AMYLASE SERUM AMYLASE

X

SERUM CREATININE URINE CREATININE

X

100

OTHER LABORATORY EXAMINATIONS • • • • • • • •

WHOLE BLOOD COUNT SGOT, SGPT ALKALINE PHOSPHATASE BILIRUBINE BLOOD GLUCOSE BLOOD UREA AND CREATININE SERUM ELECTROLYTES DIAGNOSTIC PERITONEAL LAVAGE

IMAGING • • • • •

PLAIN X-RAY (THORAX AND ABDOMEN) ABDOMINAL ULTRASONOGRAPHY COMPUTERIZED TOMOGRAPHY MAGNETIC RESONANCE IMAGING ERCP

SCORING SYSTEMS IN ACUTE PANCREATITIS • RANSON CRITERIA • IMRIE CRITERIA • APACHE II (acute physiologic and chronic health enquiry) • MRCS (medical research council sepsis) • SAP (simplified acute physiologic)

RANSON CRITERIA

(GALLSTONE PANCREATITIS) ADMISSION • AGE >70 • LEUCOCYTE >18000/mm3 • BLOOD GLUCOSE >220mg/dl • SERUM LDH >400 IU/dl • AST >250 U/dl

IN THE FIRST 48 HOURS • DECREASED LEVEL OF HEMATOCRIT BY %10 • INCREASED LEVEL OF BUN >2mg/dl • DECREASED SERUM CALCIUM VALUE BELOW <8 mg/dl • BASE DEFICIT >5 mEq/L • ESTIMATED FLUID LOSS >4 L

RANSON CRITERIA

(NON-GALLSTONE PANCREATITIS) ADMISION • AGE >55 • LEUCOCYTE >16000/mm3 • BLOOD GLUCOSE >200mg/dl • SERUM LDH >350 IU/dl • AST >250 U/dl

IN THE FIRST48 HOURS • DECREASED LEVEL OF HEMATOCRIT BY %10 • INCREASED LEVEL OF BUN >5mg/dl • DECREASED SERUM

CALCIUM <8 mg/dl

• BASE DEFICIT >4 mEq/L • ESTIMATED FLUID LOSS >6 L • ARTERIAL PaO2 <60 torr

ASSESSMENT OF THE SEVERITY OF PANCREATITIS BIOCHEMICAL MARKERS • • • • • • • • • • •

NEUTROPHIL ELASTASE ACUTE PHASE PROTEINS TAP (tripsinogen activation peptide) PANCREATITIS RELATED PROTEIN (PAP) COMPLEMENT IL-6 TNF (tumor necrosis factor) RIBONUCLEASE ANTI-PROTEASES PHOSPHOLIPASE-A METHEMALBUMIN

ASSESSMENT OF THE SEVERITY OF PANCREATITIS RADIOLOGICAL EVALUATION • • • •

ULTRASONOGRAPHY CONTRAST ENHANCED CT ERCP ANGIOGRAPHY

COMPLICATIONS LOCAL COMPLICATIONS • BLEEDING • PSEUDOCYST • ABCESS • PHLEGMON • NECROSIS • PANCREATIC ASCITES

COMPLICATIONS SYSTEMIC COMPLICATIONS • RESPIRATORY FAILURE • CARDIOVASCULAR COMPLICATIONS • HEPATOBILIARY COMPLICATIONS • GASTROINTESTINAL COMPLICATIONS • RENAL FAILURE • MULTI-ORGAN FAILURE • METABOLIC DISTURBANCES • LESIONS OF SKIN AND BONE

TREATMENT • • • •

SUPPORTIVE TREATMENT SUPPRESSION OF EXOCRINE SECRETION OF PANCREAS INHIBITION OF PANCREATIC ENZYMES PROTECTION OF PANCREAS FROM FREE OXYGEN RADICALS • ELIMINATION OF TOXIC AGENTS IN PERITONEAL CAVITY

TREATMENT SUPPORTIVE TREATMENT • • • • • •

FLUID RESUSCITATION ELECTROLYTE REPLACEMENT ANALGESIA NUTRITIONAL SUPPORT ANTIBIOTICS RESPIRATORY SUPPORT

TREATMENT SUPPRESSION OF EXOCRINE SECRETION OF PANCREAS

• NASOGASTRIC SUCTION • H2 RECEPTOR ANTAGONISTS • ANTIACIDS • ANTICHOLINERGICS • GLUCAGON • CALCITONIN • SOMATOSTATIN

TREATMENT INHIBITION OF PANCREATIC ENZYMES • INHIBITORS OF PROTEASES • APROTININE • GABEXATE • CHAMOSTATE • FRESH FROZEN PLASMA • ANTIFIBRINOLITICS • CHLOROQUINE

TREATMENT PROTECTION OF PANCREAS FROM FREE OXYGEN RADICALS • CLEANSING AGENTS OF FREE OXYGEN RADICALS • XANTHINE OXYDASE INHIBITORS • ISOVOLEMIC HEMODILUTION

TREATMENT ELIMINATION OF TOXIC AGENTS • PERITONEAL DIALYSIS

Abdominal pain history physical examination serum enzyme levels Acute pancreatitis CRP, LDH, BT edematous pancreatitis

Necrotizing pancreatitis

daily follow-up until the symptoms disappear

ICU daily CRP, LDH

response +

response -

Ultrasonography Biliary pancreatitis Medical treatment

ERCP/papillotomy Elective biliary surgery

CT

(No complication, Focal necrosis -<%50)

Sepsis parameters

FNA - Culture

Surgery

TREATMENT SURGERY

•Necrosectomy in necrotizing pancreatitis •Cholecystectomy •ERCP •Surgery in complications (pseudocyst, ascites vs.)

TREATMENT SURGERY

NECROSECTOMY •Necrosis infected / sterile ? •Presence of sepsis

TREATMENT SURGERY NECROSECTOMY 3. Laparotomy • packing • closed lavage - drainage 2. CT-guided percutaneous necrosectomy

TREATMENT SURGERY

CHOLECYSTECTOMY Laparoscopic or open (during the same hospitalization period, if possible) Biliary drainage is best accomplished by ERCP

TREATMENT SURGERY

Treatment of pancreatic pseudocyst: 1.Conservative management 2.Percutaneous drainage (radiological) 3.Endoscopic (stenting vs.) 4.Surgical (cystogastrostomy or cystoduodenoostomy or cystojejunostomy) • Laparotomy • Laparoscopy

TREATMENT SURGERY

Pancreatic ascites 1. Endoscopic (pancreatic stent) 2. Surgical (drainage to jejunum,resection)

CHRONIC PANCREATITIS

DEFINITION Irreversible damage to the pancreas and the development of histologic evidence of inflammation and fibrosis and destruction of exocrine (acinar cell) and endocrine (islets of Langerhans) tissue

HISTOPATHOLOGY • Pancreas is normal at the initial period of the disease • As the disease progresses pancreas become wide and stiff • There are narrow and wide segments into the pancreatic ducts; the ducts become dilated and curled in time • Calcified stones may be present into the pancreatic ducts

ETIOLOGY • Alcohol • Pancreatic duct obstruction (trauma, acute pancreatitis, tumor etc.) • Hereditary pancreatitis • İnfantil malnütrisyon • İdyopatik

Classification of Chronic Pancreatitis •

Alcoholic

•

Tropical

Tropical calcific pancreatitis

Fibrocalculous pancreatic diabetes •

Genetic

Hereditary pancreatitis Cystic fibrosis Others? •

Metabolic

Hypercalcemia

Hypertriglyceridemia, acquired or inherited (e.g.,apoprotein C-II deficiency, lipoprotein lipase deficiency) Obstructive •

Benign pancreatic duct obstruction

Traumatic stricture

Stricture after necrotizing pancreatitis Stenosis of sphincter of Oddi

Pancreas divisum (with inadequate accessory papilla) Sphincter of Oddi dysfunction?

Malignant pancreatic duct stricture

Pancreatic, ampullary, or duodenal carcinoma •

Autoimmune

Isolated autoimmune chronic pancreatitis

Associated with autoimmune diseases (Sjögren’s syndrome, primary biliary cirrhosis, primary sclerosing cholangitis) •

Idiopathic

Early-onset Late-onset •

Asymptomatic pancreatic fibrosis

Chronic alcoholic patients Aged individuals

CLINICAL PRESENTATION • Abdominal pain • Nausea - vomiting • Weight loss • Infections • Steatorrhea • Diabetes

DIAGNOSIS • Laboratory: serum amylase and other laboratory examinations of pancreatic function – direct ve indirect) • Imaging: (Plain abdominal X-ray, CT, MRCP, ERCP) • Biopsy

TREATMENT • • • • • •

Cessation of alcohol Low fat diet Pancreatic enzyme supplements Morphine and tobacco should be avoided Analgesics Endoscopic interventions (sphincterotomy, stone removal, stent therapy vs.) • Surgery

TREATMENT surgery

Ampullary operations • Transduodenal sphincteroplasty • Septoplasty of pancreatic duct Denervation operations • Alcohol injection Drainage procedures • Puestow procedure Resection • Whipple procedure • Beger procedure • Total pancreatectomy

Complications • •

Pancreatic Pseudocyst Bleeding

• • •

Common Bile Duct Obstruction Duodenal Obstruction Pancreatic Fistula

• •

Cancer Dysmotility

Pseudocyst Wall, Pseudoaneurysms, Variceal Bleeding from Splenic Vein Thrombosis

External Pancreatic Fistula, Internal Pancreatic Fistulas