This document provides information on acute pancreatitis, including: - It is a common cause of hospitalization in the US, with gallstones and alcohol responsible for 80-90% of cases. - It ranges from mild to severe, with severe cases involving persistent organ failure lasting over 48 hours. - CT imaging can identify necrosis which is associated with increased morbidity and mortality. - The document discusses the etiology, pathogenesis, clinical assessment, management, and classifications of acute pancreatitis.

1. ACUTE PANCREATITIS
-Dr.S.M.B.Sumanth,
1st Year Resident in Internal Medicine,
KIMS R & F

2. GENERAL CONSIDERATIONS
• Recent U.S. estimates indicate that acute pancreatitis is the most common
inpatient principal gastrointestinal diagnosis, responsible for >250,000
hospitalizations per year.
• The annual incidence ranges from 15–45/100,000 persons, depending on the
distribution of etiologies (e.g., alcohol, gallstones, metabolic factors, drugs and
country of study.
• The median length of hospital stay is 4 days,
• Mortality of ~1%.
• From 2000 to 2009, the rate increased by 30%.
• Thus, the incidence of acute pancreatitis continues to rise and is associated with
substantialhealth care costs.

6. ■ETIOLOGY AND PATHOGENESIS
• Gallstones and alcohol account for 80–90% of identified cases of
acute pancreatitis
• The risk of acute pancreatitis in patients with at least one gallstone <5
mm in diameter is fourfold greater than that 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 and genetic predisposition.

7. ERCP & Acute pancreatitis
• Acute pancreatitis occurs in 5–10% of patients following endoscopic retrograde
cholangiopancreatography (ERCP);
• This risk can be decreased with:
• The use of a prophylactic pancreatic duct stent and/or rectal nonsteroidal anti-
inflammatory drugs (NSAIDs;indomethacin).
• Risk factors for post-ERCP pancreatitis
• include minor papilla sphincterotomy,
• suspected sphincter of Oddi dysfunction,
• prior history of post-ERCP pancreatitis,
• age <60 years,
• more than two contrast injections into the pancreatic duct, and
• endoscopistexperience.

8. Hypertriglyceridemia and acute pancreatitis:
• Hypertriglyceridemia is the cause of acute pancreatitis in 1–4% of
cases;
• serum triglyceride levels are usually >1000 mg/dL.
• Most patients with hypertriglyceridemic pancreatitis have
undiagnosed or uncontrolled diabetes mellitus.
• An additional subset has an underlying derangement in lipid
metabolism, probably unrelated to pancreatitis.

9. • Such patients are prone to recurrent episodes of pancreatitis.
• Any factor (e.g., alcohol or medications, such as oral contraceptives)
that causes an abrupt increase in serum triglycerides can potentially
precipitate a bout of acute pancreatitis.
• Patients with a deficiency of apolipoprotein CII have an increased
incidence of pancreatitis; apolipoprotein CII activates lipoprotein
lipase, which is important in clearing chylomicrons from the
bloodstream.

10. PATHOGENESIS
• Pathologically, acute pancreatitis ranges from interstitial pancreatitis (pancreas
blood supply maintained), which is generally self-limited, to necrotizing
pancreatitis (pancreas blood supply interrupted).
• Autodigestion is a currently accepted pathogenic theory resulting when
proteolytic enzymes (e.g., trypsinogen, chymotrypsinogen, proelastase, and
lipolytic enzymes such as phospholipase A2) are activated in the pancreas
acinar cell compartment rather than the intestinal lumen.
• factors facilitating premature activation of trypsin:
• Endotoxins,
• Exotoxins..............

11. • viral infections,
• ischemia,
• oxidative stress,
• lysosomal calcium,
• direct trauma
• Activated proteolytic enzymes, especially trypsin, not only digest
pancreatic and peripancreatic tissues but can also activate other
enzymes, such as elastase and phospholipase A2.

12. ACTIVATION OF PANCREATIC ENZYMES IN THE
PATHOGENESIS OF ACUTE PANCREATITIS
• Several studies have suggested that pancreatitis is a disease that
evolves in three phases.
• The initial phase is characterized by intrapancreatic digestive enzyme
activation and acinar cell injury.
• Trypsin activation appears to be mediated by lysosomal hydrolases
such as cathepsin B that become colocalized with digestive enzymes
in intracellular organelles; it is currently believed that acinar cell
injury is the consequence of trypsin activation.

13. • The second phase of pancreatitis involves the activation,
chemoattraction, and sequestration of leukocytes and macrophages
in the pancreas, resulting in an enhanced
intrapancreatic inflammatory reaction.
• The third phase of pancreatitis is due to the effects of activated
proteolytic enzymes and cytokines, released by the inflamed
pancreas, on distant organs.
• Activated proteolytic enzymes, especially trypsin, not only digest
pancreatic and peripancreatic tissues but also activate other enzymes
such as elastase and phospholipase A2.

14. • The active enzymes and cytokines then digest cellular membranes and
cause proteolysis, edema, interstitial hemorrhage, vascular damage,
coagulation necrosis, fat necrosis, and cellular necrosis in the
parenchyma.
• Cellular injury and death result in the liberation of bradykinin
peptides, vasoactive substances, and histamine that can produce
vasodilation, increased vascular permeability, and edema with
profound effects on other organs.

15. • The systemic inflammatory response syndrome (SIRS) and
acute respiratory distress syndrome (ARDS), as well as
multiorgan failure, may occur as a result of this cascade of
local and distant effects.

16. The genes that have been identified include
• (1) cationic trypsinogen gene (PRSS1),
• (2) pancreatic secretory trypsin inhibitor (SPINK1),
• (3) the cystic fibrosis transmembrane conductance regulator gene
(CFTR),
• (4) the chymotrypsin C gene (CTRC),
• (5) the calcium-sensing receptor (CASR),
• (6) claudin-2 (CLDN2).

17. APPROACHTO THE PATIENT
• Abdominal pain is the major symptom of acute pancreatitis.
• Pain may vary from mild discomfort to severe, constant, and
incapacitating distress.
• Characteristically, the pain, which is steady and boring in character,
• is located in the epigastrium region
• may radiate to the back, chest, flanks, and lower abdomen.
• Nausea, vomiting, and abdominal distention due to gastric and
intestinal hypomotility are also frequent complaints.

18. Physical examination
• Low-grade fever,
• tachycardia,
• and hypotension are common.
• Shock
• Jaundice

19. • Erythematous skin nodules due to subcutaneous fat necrosis rarely
occur.
• In 10–20% of patients, there are pulmonary findings, including basilar
rales, atelectasis, and pleural effusion, the latter most frequently left-
sided.
• Abdominal tenderness and muscle rigidity
• Bowel sounds are usually diminished or absent.
• An enlarged pancreas from an acute fluid collection, walled-off
necrosis, or a pseudocyst may be palpable in the upper abdomen
later in the course of the disease (i.e., 4–6 weeks).

20. • A faint blue discoloration around the umbilicus (Cullen’s sign) may
occur as the result of hemoperitoneum,
• a blue-red-purple or greenbrown discoloration of the flanks (Turner’s
sign) reflects tissue breakdown of hemoglobin from severe
necrotizing pancreatitis with hemorrhage; both findings are rare but
reflect an increased clinical severity.

21. ■LABORATORY DATA
• Serum amylase and lipase values threefold or more above normal are strongly
supportive of the diagnosis if alternate etiologies, including gut perforation,
ischemia, and infarction, are excluded.
• there is no correlation between the severity of pancreatitis and the degree of
serum lipase and amylase elevations or serial trends.
• After 3–7 days, even with continuing evidence of pancreatitis, total serum
amylase values tend to return toward normal.
• However, pancreatic lipase levels may remain elevated for 7–14 days.

22. • It should be recognized that amylase elevations in serum and urine
occur in many conditions other than pancreatitis
• Importantly, patients with acidemia (arterial pH ≤7.32)may have
spurious elevations in serum amylase.
• This finding explains why patients with diabetic ketoacidosis may have
marked elevations in serum amylase without any other evidence of
acute pancreatitis.
• On the other hand, serum amylase levels can be spuriously low in the
setting of severe hypertriglyceridemia.

23. Other lab findings
• Leukocytosis (15,000–20,000 leukocytes/μL)
• Hemoconcentration
• Hyperglycemia
• Hypocalcemia
• Hyperbilirubinemia (serum bilirubin >4.0 mg/dL)
• Elevations of alanine aminotransferase (ALT) >3× the upper limit of normal are strongly
associated with a gallstone etiology in patients with acute pancreatitis.
• Hypoxemia (arterial Po2 ≤60 mmHg)
• The electrocardiogram is occasionally abnormal in acute pancreatitis with ST-segment
and T-wave abnormalities simulating myocardial ischemia.

24. The diagnosis is established by two of the following three criteria:
• (1) typical abdominal pain in the epigastrium that may radiate to the
back,
• (2) threefold or greater elevation in serum lipase and/or amylase,
• (3) confirmatory findings of acute pancreatitis on cross-sectional
abdominal imaging.

25. • Although not required for diagnosis, markers of severity may
include:
• Hemoconcentration (hematocrit >44%),
• Admission azotemia (BUN >22 mg/dL)
• SIRS, and signs of organ failure

27. The differential diagnosis should include the following disorders:
• (1) perforated viscus, especially peptic ulcer;
• (2) acute cholecystitis and biliary colic;
• (3) acute intestinal obstruction;
• (4) mesenteric vascular occlusion;
• (5) renal colic

28. • (6) inferior myocardial infarction;
• (7) dissecting aortic aneurysm;
• (8) connective tissue disorders with vasculitis;
• (9) pneumonia; and
• (10) diabetic ketoacidosis

29. • It may be difficult to differentiate acute cholecystitis from acute pancreatitis,
because an elevated serum amylase may be found in both disorders.
• Pain of biliary tract origin is more right sided or epigastric than periumbilical or left
upper quadrant and can be more severe; ileus is usually absent.
• Ultrasound is helpful in establishing the diagnosis of cholelithiasis and cholecystitis.
• Intestinal obstruction due to mechanical factors can be differentiated from
pancreatitis by the history of crescendo-decrescendo pain, findings on abdominal
examination, and CT of the abdomen showing changes characteristic of mechanical
obstruction.

30. • Acute mesenteric vascular occlusion is usually suspected in elderly
debilitated patients with leukocytosis, abdominal distention, and
bloody diarrhea, confirmed by CT or magnetic
resonance angiography.
• Vasculitides secondary to systemic lupus erythematosus and
polyarteritis nodosa may be confused with pancreatitis, especially
because pancreatitis may develop as a complication of these diseases.
• Diabetic ketoacidosis is often accompanied by abdominal pain and
elevated total serum amylase levels, thus closely mimicking acute
pancreatitis; however, the serum lipase level is often not elevated in
diabetic ketoacidosis, and pancreas imaging is normal.

31. ■CLINICAL COURSE, DEFINITIONS, AND CLASSIFICATIONS
• The Revised Atlanta Criteria define :
• (1) phases of acute pancreatitis,
• (2) severity of acute pancreatitis, and
• (3) radiographic definitions,

32. (1) phases of acute pancreatitis,
• Two phases of acute pancreatitis have been defined,
• Early (<2 weeks) and late (>2 weeks),whichprimarily
describe the hospital course of the disease.

33. Early phase of acute pancreatitis
• In the early phase of acute pancreatitis, which lasts 1–2 weeks,
severity is defined by clinical parameters rather than morphologic
findings.
• Most patients exhibit SIRS, and if this persists, patients are
predisposed to organ failure.
• Three organ systems should be assessed to define organ failure:
• respiratory,
• cardiovascular,and renal.

34. • Organ failure is defined as a score of 2 or more for one of these three
organ systems using the modified Marshall scoring system.
• Persistent organ failure (>48 h) is the most important clinical finding
regarding severity of the acute pancreatitis episode.
• Organ failure that affects more than one organ is
considered multisystem organ failure.
• CT imaging is usually not needed or recommended during the first
48 h of admission in acute pancreatitis.

35. The late phase
• The late phase is characterized by a protracted course of illness and
may require imaging to evaluate for local complications.
• The critical clinical parameter of severity, as in the early phase, is
persistent organ failure.
• These patients may require supportive measures such as:
• renal dialysis,
• ventilator support, or need for supplemental nutrition via a
nasojejunal or parenteral route.

36. • The radiographic feature of greatest importance to recognize in this
phase is the development of necrotizing pancreatitis on CT imaging.
• Necrosis is associated with prolonged hospitalization and, if infected,
may require intervention (percutaneous, endoscopic, and/or surgical)

37. (2) severity of acute pancreatitis
• Three classes of severity have been defined:
• Mild,
• Moderately severe,
• Severe.

38. Mild acute pancreatitis
• It is without local complications or organ failure.
• Most patients with interstitial acute pancreatitis have mild
pancreatitis.
• the disease is self-limited and subsides spontaneously, usually within
3–7 days after onset.

39. • Oral intake can be resumed if the patient is hungry, has normal
bowel function, and is without nausea and vomiting.
• Typically, a clear or full liquid diet has been recommended for the
initial meal;
• However, a low-fat solid diet is a reasonable choice following recovery
from mild acute pancreatitis.

40. Moderately severe acute pancreatitis
• It is characterized by transient organ failure (i.e., it resolves in <48 h)
or local or systemic complications in the absence of persistent organ
failure.
• These patients may or may not have necrosis but may develop a local
complication such as a fluid collection that requires a prolonged
hospitalization >1 week.
• As with mild acute pancreatitis, the mortality rate for these patients
remains low.

41. Severe acute pancreatitis
• It is characterized by persistent organ failure (>48 h), involving one or
more organs.
• A CT scan or magnetic resonance imaging (MRI) should be obtained
to assess for necrosis and/or complications.
• If a local complication is encountered, management is dictated by
clinical symptoms, evidence of infection, the maturity of fluid
collection, and clinical stability of the patient.
• Prophylactic antibiotics are no longer recommended for severe
acute pancreatitis

42. (3) radiographic definitions
• Two types of pancreatitis are recognized on imaging as:
• interstitial or necrotizing based on pancreatic perfusion.
• CT imaging with IV contrast is best evaluated 3–5 days into
hospitalization if patients are not responding to supportive care to
assess for local complications such as necrosis.
• The Revised Atlanta Criteria also outline the terminology for local
complications and fluid collections along with a CT imaging template
to guide reporting of findings.

44. Interstitial vs necrotising pancreatitis:
• Interstitial pancreatitis occurs in 90–95% of admissions for acute
pancreatitis and is characterized by:
• Diffuse gland enlargement,
• Homogenous contrast enhancement, and
• Mild inflammatory changes or peripancreatic stranding.
• Symptoms generally resolve with a week of hospitalization.

45. • Necrotizing pancreatitis occurs in 5–10% of acute pancreatitis
admissions and may not evolve until several days of hospitalization.
• It is characterized by:
• lack of pancreatic parenchymal enhancement by intravenous
contrast agent and/or presence of findings of peripancreatic necrosis.

46. Natural history
• The natural history of pancreatic and peripancreatic necrosis is
variable because:
• It may remain solid or liquefy,
• Remain sterile or become infected, and persist or disappear over
time.

47. • Importantly, those with only extrapancreatic necrosis have a
more favorable prognosis than patients with pancreatic necrosis (with
or without extrapancreatic necrosis).
• CT identification of local complications, particularly necrosis, is
critical in patients who are not responding to therapy because
patients with infected and sterile necrosis are at greatest risk
of mortality

48. CT scan of the abdomen without IV contrast performed on admission
for a patient with acute gallstone pancreatitis, showing mild peripancreatic
stranding.

49. Contrast-enhancedCT scan of the abdomen performed on the same patient1 week after admission shows
extensive intrapancreaticnecrosis, evidenced by the lack of contrast enhancement in the pancreaticbody with
very minimal enhancement noted at the distalmost aspect of the pancreatictail.

50. Contrast-enhanced CT scan of the abdomen performed on the same patient 2 weeks after
admissiondemonstrates a semiorganized, heterogeneous fluid collection, referred to as an acute
necrotic collection. On this image, a small area of viable pancreatic parenchyma is seen at the tail
of the pancreas

51. Contrast-enhanced CT scan of the abdomen performed on the same patient 5
weeks after admission demonstrates a well-encapsulated fluid collection,
essentially replacing the pancreas, referred to as walled-off necrosis.

53. ■ACUTE PANCREATITIS MANAGEMENT
• It is important to recognize that 85–90% of cases of acute pancreatitis
are self-limited and subside spontaneously, usually within 3–7 days
after onset, and do not exhibit organ failure or local complications.
• The management of acute pancreatitis begins in the emergency
ward.
• After a diagnosis has been confirmed, early and aggressive fluid
resuscitation is critical.

54. • Additionally, intravenous analgesics are administered, severity is
assessed, and a search for etiologies that may impact acute care
is begun.
• Patients who do not respond to aggressive fluid resuscitation in the
emergency ward should be considered for admission to a step-down
or intensive care unit for :
• aggressive fluid resuscitation,
• hemodynamic monitoring,
• management of any organ failure.

55. Fluid Resuscitation and Monitoring Response to Therapy
• The most important treatment intervention for acute pancreatitis is
early, aggressive intravenous fluid resuscitation to prevent systemic
complications from the secondary systemic inflammatory response.
• The patient is initially made NPO to minimize nutrient-induced
stimulation of the pancreas and is given intravenous narcotic
analgesics to control abdominal pain and supplemental oxygen (as
needed).

56. • Intravenous fluids of lactated Ringer’s or normal saline are
initially bolused at :
• 15–20 mL/kg (1050–1400 mL), followed by 2–3 mL/kgper hour (200–
250 mL/h),
• to maintain urine output >0.5 mL/kg per hour.
• Serial bedside evaluations are required every 6–8 h to assess:
• vital signs,
• oxygen saturation, and
• change in physical examination to optimize fluid resuscitation.

57. Fluid resuscitation
• RL has been shown to decrease systemic inflammation (lower C-
reactive protein levels from admission) and may be a better
crystalloid than normal saline.
• A targeted resuscitation strategy with measurement of hematocrit
and BUN every 8–12 h is recommended to ensure adequacy of fluid
resuscitation and monitor response to therapy, noting that a less
aggressive resuscitation strategy may be needed in milder forms of
pancreatitis.

58. • A rising BUN during hospitalization is not only associated
with inadequate hydration but also higher in-hospital mortality.
• A decrease in hematocrit and BUN during the first 12–24 h is strong
evidence that sufficient fluids are being administered.
• Serial measurements and bedside assessment for fluid overload are
continued, and fluid rates are maintained at the current rate.
• Adjustments in fluid resuscitation may be required in patients with
cardiac, pulmonary, or renal disease.

59. • A rise in hematocrit or BUN during serial measurement should be
treated with a repeat volume challenge with a 2-L crystalloid bolus
followed by increasing the fluid rate by 1.5 mg/kg per hour.
• If the BUN or hematocrit fails to respond (i.e., remains elevated or
does not decrease) to this bolus challenge and increase in fluid rate,
consideration of transfer to an intensive care unit is strongly
recommended for hemodynamic monitoring.

60. Assessment of Severity and Hospital Triage
• The Bedside Index of Severity in Acute Pancreatitis (BISAP) incorporates five
clinical and laboratory parameters obtained within the first 24 h of hospitalization
• BUN >25 mg/dL,
• impaired mental status (Glasgow coma scale score <15),
• SIRS,
• age >60 years,
• pleural effusion on radiography
• The presence of three or more of these factors was associated with substantially
increased risk for in-hospital mortality among patients with acute pancreatitis.
• In addition, an elevated hematocrit >44% and admission BUN >22 mg/dL are
also associated with more severe acute pancreatitis.

61. Indications for ICU admission:
• Higher BISAP scores
• Elevations in hematocrit and admission BUN
• No response to initial fluid resuscitation
• Evidence of respiratory failure,
• Hypotension,
• Organ failure

62. Special Considerations Based on Etiology
GALLSTONE PANCREATITIS
• Patients with evidence of ascending cholangitis (rising white blood cell count, increasing
liver enzymes) should undergo ERCP within 24–48 h of admission.
• Patients with gallstone pancreatitis are at increased risk of recurrence, and
consideration should be given to performing a cholecystectomy during the same
admission in mild acute pancreatitis.
• An alternative for patients who are not surgical candidates would be to perform an
endoscopic biliary sphincterotomy before discharge.

63. • HYPERTRIGLYCERIDEMIA
• Serum triglycerides >1000 mg/dL are associated with acute
pancreatitis.
• Initial therapy should focus on treatment of hyperglycemia with
intravenous insulin, which often corrects the hypertriglyceridemia.
• Adjunct therapies may also include heparin or plasmapheresis
• administration of lipid-lowering agents,
• weight loss

64. • Hypercalcemia
• Treatment of hyperparathyroidism or malignancy is effective at
reducing serum calcium.
• POST ERCP PANCREATITIS:
• Pancreatic duct stenting and rectal indomethacin administration are
effective at decreasing pancreatitis after ERCP.

65. Nutritional Therapy
• A low-fat solid diet can be administered to subjects with mild acute
pancreatitis once they are able to eat.
• Enteral nutrition should be considered 2–3 days after admission in
subjects with more severe pancreatitis instead of total parenteral
nutrition (TPN).
• Enteral feeding maintains gut barrier integrity, limits bacterial
translocation, is less expensive, and has fewer complications than
TPN.

69. ■RECURRENT ACUTE PANCREATITIS
• Approximately 25% of patients who have had an attack of acute pancreatitis have a recurrence.
• The two most commonetiologic factors are alcohol and cholelithiasis.
• In patientswith recurrent pancreatitiswithout an obviouscause, the differentialdiagnosisshould
encompass:
• occult biliary tract disease,
• including microlithiasis,
• hypertriglyceridemia,
• pancreatic cancer,
• and hereditary pancreatitis (Table 348-1).
• approximately two-thirds of patients with recurrent acute pancreatitis without an obvious cause
actually have occult gallstonedisease due to microlithiasis.

70. • Genetic defects as in hereditary pancreatitisand cystic fibrosis mutations
can result in recurrent pancreatitis.
• Other diseases of the biliary tree and pancreatic ducts that can cause acute
pancreatitis include
• choledochocele;
• ampullary tumors;
• pancreas divisum; and
• pancreatic duct stones,
• Stricture,
• Tumor.

71. THANK YOU