dr. s.p. hewawasam (md) consultant gastroenterologist ...pancreatitis, (2) defines severity of acute...

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Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist/Senior Lecturer in Physiology

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Page 1: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Dr. S.P. Hewawasam (MD)

Consultant Gastroenterologist/Senior Lecturer in Physiology

Page 2: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Incidence - 13–45/100,000 persons (US figures)

The median length of hospital stay - 4 days

mortality - 1%

Hospitalization rates increase with age

higher among males than females

Page 3: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Common Causes Gallstones (including microlithiasis)

Alcohol (acute and chronic alcoholism)

Hypertriglyceridemia (usually >11.3 mmol/L (>1000 mg/dL)

Endoscopic retrograde cholangiopancreatography (ERCP), especially after biliary manometry

Drugs (azathioprine, 6-MP, sulfonamides, estrogens, tetracycline, valproic acid, anti-HIV medications, 5-ASA, corticosteroids

Trauma (especially blunt abdominal trauma)

Postoperative (abdominal and non-abdominal )operations)

Page 4: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Uncommon Causes Vascular causes and vasculitis (ischemic-hypoperfusion states after

cardiac surgery) Connective tissue disorders & TTP CA pancreas Hypercalcemia Periampullary diverticulum Pancreas divisum Hereditary pancreatitis Cystic fibrosis Renal failure Infections(mumps, coxsackie virus, cytomegalovirus, echovirus,

parasites) Autoimmune (e.g., type 1 and type 2)- elevated Ig G4

Page 5: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Alcohol is the commonest cause among males

Gallstones is the commonest cause among femalesIn Sri Lanka

Risk is 4X greater in patients with at least one gallstone <5 mm than in patients with larger stones

The incidence of pancreatitis in alcoholics is surprisingly low (5/100,000), indicating that in addition to the amount of alcohol ingested, other factors affect a person’s susceptibility to pancreatic injury such as cigarette smoking

Post ERCP pancreatitis in 5%-10%o prophylactic pancreatic duct stent & rectal NSAID used for prevention

0.1–2% of cases are drug related

Page 6: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Acute Pancreatitis

Interstitial Pancreatitis

Blood supply maintained

Generally self-limiting

Necrotizing Pancreatitis

Blood supply interrupted

Extent of necrosis may correlate with severity of attack and systemic complications

Page 7: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Autodigestion is the currently accepted pathogenic mechanism

Proteolytic enzymes (e.g., trypsinogen, chymotrypsinogen, proelastase, and lipolytic

enzymes such as phospholipase A2) activated in the pancreas acinar cell rather than in the intestinal lumen

Digest pancreatic and peripancreatic tissues but also can activate other enzymes, such as elastase and phospholipase A2

Number of factors (e.g., endotoxins, exotoxins, viral infections, ischemia, oxidative stress,

lysosomal calcium, and direct trauma) are believed to facilitate premature activation of trypsin

Spontaneous activation of trypsin can also occur

Page 8: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

3 phases of acute pancreatitis

Initial phase - characterized by intrapancreatic digestive enzyme activation and acinar cell injury

Second phase - activation, chemoattraction, and sequestration of leukocytes and macrophages in the pancreas→

→enhanced intrapancreatic inflammation• also evidence to support the concept that neutrophils can activate trypsinogen

Third phase - due to the effects of activated proteolytic enzymes and cytokines released by the inflamed pancreas; on distant organs

Page 9: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

The active enzymes and cytokines → digest cell membranes and cause proteolysis, edema, interstitial H’age, vascular damage, coagulation necrosis, fat necrosis, and parenchymal cell necrosis

Cellular injury and death result in the liberation of bradykinin peptides, vasoactive substances, and histamine → vasodilation, ↑vas. permeability & edema → profound effects on many organs

o SIRS

o ARDS

o Multiorgan failure A number of genetic factors can ↑ the susceptibility and/or modify the severity of

acute pancreatitis, recurrent pancreatitis & chronic pancreatitis- all centred around control of trypsin activity

Page 10: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Abdominal pain is the cardinal symptom o Mild discomfort→severe, constant and incapacitating distress

o In the epigastrium and periumbilical region

o may radiate to the back(interscapular region), chest, flanks, and lower abdomen

o May be slightly relieved by bending forward

o Nausea, vomiting, and abdominal distention due to gastric and intestinal hypomotility

o Features of chemical peritonitis-guarding, rigidity

Physical examination frequently reveals a distressed and anxious patient

Low-grade fever, tachycardia, and hypotension are fairly common

Page 11: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Shock is not unusual-may result fromo hypovolemia IIry to exudation of blood and plasma proteins into the

retroperitoneal space

o increased formation and release of kinin peptides, which cause vasodilation and increased vascular permeability

o systemic effects of proteolytic and lipolytic enzymes released into the circulation.

Jaundice occurs infrequentlyo usually due to edema of the head of the pancreas with compression of the

intrapancreatic portion of the CBD or passage of a biliary stone or sludge

Erythematous skin nodules due to fat necrosis may rarely occur

pulmonary findings in 10–20% of patientso basilar rales, atelectasis, and pleural effusion, mostly left sided.

Page 12: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Abdominal tenderness, guarding and rigidity of variable degree

Bowel sounds - diminished or absent

Upper abdominal mass-o An enlarged pancreas from acute fluid collection, walled off necrosis, or a

pseudocyst in the upper abdomen later on(4–6/52)

Cullen’s sign Grey-Turner sign

as the result of

hemoperitoneum

reflects tissue catabolism of Hb from

severe necrotizing pancreatitis with H’age

Page 13: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

3x or more rise in serum amylase and lipase

o virtually diagnostic if gut perforation, ischemia & infarction excluded

o Amylase >1000 also virtually diagnostic

o no correlation between the severity & the level of lipase/amylase

o serum amylase tend to return toward normal after 3–7 days, despite

ongoing pancreatitis

o isoamylase and lipase levels may be elevated for 7–14 days

o many other causes for amylase elevations, incl. acidaemia(pH <7.32)

o serum lipase is the preferred test

Page 14: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Leukocytosis With more severe disease

o Hemoconcentration with PCV >44%

o prerenal azotemia o Hemoconcentration may be the harbinger of more severe disease (i.e.,

pancreatic necrosis),o Whereas azotemia is a significant risk factor for mortality

Hyperglycemia is common and multifactorialo ↓ insulin, ↑glucagon, ↑ adrenal glucocorticoids & catecholamines

Hypocalcemia occurs in ~25% o pathogenesis incompletely understoodo Intraperitoneal saponification of Ca++ by fatty acids in areas of fat necrosis

occurs occasionally, with large amounts (up to 6.0 g) dissolved or suspended in ascitic fluid

from loss of plasma into the retroperitoneal space and peritoneal cavity

Page 15: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Hyperbilirubinemia in ~10% of patientso However, jaundice is transient

Alk. Phos. & AST also transiently elevated, o parallel serum bilirubin values and may point to GB-related disease or

inflammation in the pancreatic head

Hypertriglyceridemia in 5–10% of patients, o serum amylase levels in these individuals are often spuriously normal d

5–10% of patients have hypoxemia

ECG abnormalities –occasional o ST-segment and T-wave abnormalities simulating myocardial ischemia

Page 16: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Abdominal ultrasound o Recommended as the initial diagnostic imaging modality o Useful to evaluate for gallstone disease and the pancreatic heado The revised Atlanta criteria have clearly outlined the morphologic features

of acute pancreatitis on computed tomography

Contrast Enhanced CT (CECT) abdomeno Imaging modality of choice

• Wider availability, Faster examination time-good images in critically ill, Relatively cheaper

MRI o for multiple follow-up examinations to reduce exposure to radiationo when CECT is contraindicated o when characterisation of specific lesions, mainly fluid collections, is

warranted

Page 17: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Revised Atlanta criteria have clearly outlined the morphologic features of acute pancreatitis on CT o (1) interstitial pancreatitis

o (2) necrotizing pancreatitis

o (3) acute pancreatic fluid collection

o (4) pancreatic pseudocyst

o (5) acute necrotic collection (ANC)

o (6) walled-off pancreatic necrosis (WON)

Page 18: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

2 out of 3 criteriao (1) typical abdominal pain in the epigastrium that may radiate to the backo (2) threefold or greater elevation in serum lipase and/or amylaseo (3) confirmatory findings of acute pancreatitis on cross-sectional abdominal

imaging

Differential Diagnosis (DD of acute abdomen) (1) perforated viscus, especially peptic ulcer (2) acute cholecystitis and biliary colic; (3) acute intestinal obstruction (4) mesenteric vascular occlusion (5) renal colic (6) inferior myocardial infarction (7) dissecting aortic aneurysm (8) connective tissue disorders with vasculitis (9) pneumonia (10) diabetic ketoacidosis

Page 19: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Clinicians have been largely unable to predict severity All severity scoring systems are cumbersome, needs 48 hrs to be

accurate When the score demonstrates severe disease, the patient’s

condition is obvious regardless of the score The new scoring systems, such as the BISAP, have not shown to be

more accurate than the other scoring systems In general, AP-specific scoring systems have a limited value, as

they provide little additional information to the clinician in the evaluation of patients and may delay appropriate management

Essence : o Do not bother too much about the scoring systemso Use APACHE II

Page 20: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Clinical findings associated with a severe course for initial risk assessment

Patient characteristics

Age >55 years

Obesity (BMI >30 kg/m2)

Altered mental status

Comorbid disease

The systemic inflammatory response syndrome (SIRS) Presence of ≥2 of the following criteria:

– pulse >90 beats/min

– respirations >20/min or PaCO2 >32 mm Hg

– temperature >38 °C or <36 °C

– WBC count >12,000 or <4,000 cells/mm3 or >10% immature neutrophils (bands)

Laboratory findings

BUN >20 mg/dl

Rising BUN

HCT >44%

Rising HCT

Elevated creatinine

Radiology findings

Pleural effusions

Pulmonary infiltrates

Multiple or extensive extrapancreatic collections

The presence of organ failure and/or pancreatic necrosis defines severe acute pancreatitis.

Page 21: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (
Page 22: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

The Revised Atlanta Classification (1) defines phases of acute pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions

Two phases o Early (<2 weeks)

• primarily describes the hospital course of the disease• severity is defined by clinical parameters rather than morphologic findings• CT imaging is usually not needed or recommended during the first 48 h of admission

in acute pancreatitis

o Late (>2 weeks)• protracted course of illness • may require imaging to evaluate for local complications• parameter of severity is persistent organ failure• may require supportive measures such as renal dialysis, ventilator support, or need

for supplemental nutrition via the nasojejunal or parenteral route• important to recognize the development of necrotizing pancreatitis on CT

Page 23: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (
Page 24: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Initial Management

Early Aggressive Intravenous Hydrationo 250–500 ml/ hour of isotonic crystalloid to provided to all patients

o unless CVS, renal, or other related comorbidity exist

o most beneficial during the first 12–24 h, little benefit beyond this time period

o Lactated Ringer’s solution may be preferred

o The goal of aggressive hydration should be to decrease the BUN

ERCP in Acute Pancreatitiso Pt’s with AP and concurrent acute cholangitis should undergo ERCP within 24 h

o ERCP is not needed early in most patients with gallstone pancreatitis who lack laboratory or clinical evidence of ongoing biliary obstruction

o In the absence of cholangitis and/or jaundice, MRCP or EUS rather than diagnostic ERCP should be used to screen for choledocholithiasis

o Prophylaxis for post ERCP pancreatitis

Page 25: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Use for any extrapancreatic infectiono cholangitis, catheter-acquired infections, bacteremia, UTI, pneumonia

Routine prophylactic antibiotics for patients with severe AP is not recommended

Not recommended for sterile necrosis to prevent infected necrosis

Infected necrosis considered in patients with pancreatic or extrapancreatic necrosis who deteriorate or fail to improve after 7–10 days of hospitalizationo CT-guided fine-needle aspiration (FNA) for Gram stain and culture to

guide use of appropriate antibiotics

or o Empiric antibiotics after obtaining necessary cultures for infectious agents,

without CT FNA

Page 26: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

In infected necrosis, antibiotics that penetrate pancreatic necrosis, (carbapenems, quinolones, and metronidazole) may be useful in delaying or sometimes totally avoiding interventions

Routine administration of antifungals not recommended

Why not to use routine antibioticso Because of the consistency of pancreatic necrosis few antibiotics penetrate

when given intravenously

o From A meta-analysis NNT was 1429 for 1 patient to benefit

Page 27: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (
Page 28: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

In mild AP, oral feedings started immediately if there is no N & V and the abdominal pain has resolvedo low-fat solid diet appears as safe as a clear liquid diet

In severe AP, enteral nutrition is recommended to prevent infectious complicationso Parenteral nutrition only if enteral nutrition not available, not tolerated,

or not meeting caloric requirements

o NG and NJ comparable in efficacy and safety

Page 29: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Cholecystectomy before discharge(or within 4-6 weeks) if gallstones are found in the GB to prevent recurrence

cholecystectomy deferred until active inflammation subsides and fluid collections resolve or stabilize in necrotizing pancreatitis due to stones

Asymptomatic pseudocysts and pancreatic and/or extrapancreatic necrosis do not warrant intervention regardless of size, location, and/or extension

In stable patients with infected necrosis, surgical, radiologic, and/or endoscopic drainage may be delayed preferably for more than 4 weeks to allow liquefication of the contents and the development of a fibrous wall around the necrosis (walled-off necrosis

In symptomatic patients with infected necrosis, minimally invasive methods of necrosectomy are preferred to open necrosectomy

Page 30: Dr. S.P. Hewawasam (MD) Consultant Gastroenterologist ...pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies imaging definitions Two phases o Early (

Hypertriglyceridemiao Initial therapy include insulin, heparin, or plasmapheresis

o Outpatient therapies

Hypercalcemiao Treatment of hyperparathyroidism or malignancy is effective at reducing

serum calcium

Autoimmune pancreatitiso Glucocorticoids

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Harrison's Principles of Internal Medicine, 19e

American College of Gastroenterology Guideline: Management of Acute Pancreatitis 30 July 2013; doi: 10.1038/ajg.2013.218

2012 revision of the Atlanta Classification of acute pancreatitis POLSKIE ARCHIWUM MEDYCYNY WEWNĘTRZNEJ 2013

Acute Pancreatitis N Engl J Med 2006;354:2142-50