A useful slide for postgraduate general surgery residents about Acute Pancreatitis.

1. Acute Pancreatitis
Nabin Paudyal

2. Introduction
• Most of the patients with acute pancreatitis (AP) have milder course
• 10-20% of patients have severe, rapid progressive course
• Mortality of patients with AP varies from < 1 % in milder cases to 10-50% in
severe cases.
• Mortality is usually bimodal
• Early phase Within first 2 weeks  death occurs due to Multiple Organ Dysfunction
caused by the intense inflammatory cascade triggered by pancreatic inflammation
• Late phase After 2 weeks caused by septic complication.

4. Pathophysiology
• Exact etiology is unknown
• AP is the final result of abnormal pancreatic enzyme activation inside acinar
cells.
• Immunolocalization studies have shown that after 15 minutes of pancreatic injury both
zymogen granules and lysosome colocalize inside the acinar cells.
• The fact that the colocalization occurs before amylase level elevation, pancreatic
edema and other markers of pancreatitis are evident suggests that COLOCALIZATION
is an early step in the pathophysiologic process of pancreatitis.
• Lysosomal enzyme cathepsin B activates trypsin in these colocalization
organelles. Trypsin activation leads to acinar cell death.

7. Pathophysiology continued..
• Increased inflammation increased permeability of interstitial fluids
Increased microcirculation damage Edema
• In severe cases Persistence of inflammation leads to local hemorrhage and
pancreatic necrosis.
• 80% cases are self limited. In remaining 10%, there is persistence of vicious
circle of inflammation-anti inflammation cascade Leads to local and
systemic complication ALI and ARDS occurs.
• In early phase mortality is due to persistence of inflammatory response.

8. Risk factors
• Gall stone and ethanol abuse [about 70-80% of cases]
• In pediatric age group Blunt abdominal trauma, Systemic disease
• Autoimmune / Drug induced in patients with rheumatologic
conditions such as SLE and Sjogren syndrome.

9. a. Gallstone pancreatitis
Obstructive theory
• Obstruction of the pancreatic
duct by biliary stones Causes
increased pressure inside
pancreatic duct alteration of
tight junctions via calcineurin
signaling  Initiation of
pancreatitis
Reflux theory
• Stones impacted in the ampulla of
Vater  form a common channel that
allows bile salt to reflux into the
pancreas Bile salt induces direct
acinar cell necrosis
• 40% of cases of pancreatitis are due to gallstones in US. Overall 3-8% of cases are caused
• Mostly, women of age 50-70 years have gallstone pancreatitis.

10. Alcohol and smoking induced injury
• Second most common cause of AP
worldwide
• 35% of cases of AP
• Young men, 30-45 years age group
• Of the people who drink heavy alcohol (>
100g/day for at least 5 years), 5-10% of
patients develop AP
• RR of smokers to non-smokers for
developing AP is 4.9:1
• Mechanism of alcohol induced
pancreatitis
• Multifaceted
a. Trigger proinflammatory pathways via
upregulation of nuclear factor XB, TNF-α and
IL-1
b. Inappropriate basolateral exocytosis of
pancreatic zymogens
c. Increased autophagy possibly due to
dysregulation of cathepsin L and B
d. Increased oxidative stress leading to
mitochondrial dysfunction
e. Activation of pancreatic stellate cells (PSC)
causing increased secretion of MMP
f. Impaired pancreatic cell repair due to
dysregulation in developmental factors
PDX1, PTF1a and Notch
g. Shift in cell death caused by apoptosis to
necrosis by decreasing caspase 3/8 activity
and loss of ATP production via mitochondrial
depolarization.

11. Mechanism of alcohol induced AP

12. Anatomic obstruction
• Abnormal flow of pancreatic juice into the duodenum
• Usually described in patients with pancreatic tumors, parasites and
congenital defects
• Pancreatic divisum 5-10% lifetime risk
• Occurs due to defect in pancreatic secretion from the minor papilla
• Ascaris lumbricoides infection, annular pancreas are also associated
with development of AP

13. ERCP induced pancreatitis
• Up to 5% of cases have AP following ERCP
• Mostly occurs in female, young patients with prior history of ERCP induced
pancreatitis
• Patients undergoing therapeutic procedures have more risk of AP compared to
patients undergoing diagnostic procedures
• Patients with multiple attempts at cannulation, SOD dysfunction, abnormal
visualization of the secondary pancreatic ducts after injection of contrast material
have increased risk
• Management of ERCP induced pancreatitis
• Perform ERCP only when absolutely necessary
• Use of indomethacinto prevent ERCP-induced pancreatitis
• Use of pancreatic stents
• Use of minimal pressure while performing ERCP.

14. Drug-induced pancreatitis
• Most common agents
• Sulfonamides
• Metronidazole
• Erythromycin
• Tetracycline
• Didanosine
• Thiazides
• Furosemide
• HMG-CoA reductase inhibitors
• Azathioprine
• 6-MP
• 5-ASA
• Sulfasalazine
• Valproate
• HAART drugs

15. Metabolic factors
• Hypertriglyceridemia and Hypercalcemia
• Hypertriglyceridemia
• Direct pancreatic injury is caused by triglyceride metabolites
• More common in patients with triglyceride level more than 1000 mg/dl
• Familial hypertriglyceridemia Type I, II and V
• Hypertriglyceridemia secondary to hypothyroidism, DM and alcohol does not typically
induce AP
• Hypercalcemia
• Calcium activates trypsinogen into active trypsin AP
• Primary hyperparathyroidism Intraductal calcium deposition ductal obstruction and
pancreatitis

16. Miscellaneous conditions causing AP
• Blunt/ penetrating abdominal trauma (0.2/1% respectively)
• Prolonged intraoperative hypotension
• Excessive pancreatic manipulation during abdominal surgery
• Pancreatic ischemia following splenic artery embolization
• Scorpion venom
• Perforated duodenal ulcers

17. Types of acute pancreatitis
• Interstitial edematous pancreatitis
• Characterized by the inflammation and edema of the pancreatic parenchyma
and peripancreatic tissues
• Necrotizing pancreatitis
• Inflammation and edema of pancreas progresses to pancreatic parenchymal
tissue death
• Leads to necrotic collection around pancreas containing solid and fluid
components
• Infection may occur around the necrotic collection leading to infected Acute
Necrotic Collection (ANC)

20. Clinical features
History
• Epigastric/ periumbilical pain
that radiates to the back
• Nausea or vomiting
• Pain in acute pancreatitis is
constant. Any disappearance of
pain/ decrease of pain should
warrant revision of diagnosis and
other illness MUST be considered.
Physical examination
• Dehydration, poor skin turgor,
tachycardia, hypotension and
dry mucous membrane are
commonly seen in AP.
• Abdomen: Normal to rebound
tenderness and abdominal
rigidity may be seen
• Gray Turner and Cullen signs
may be seen

21. • Concomitant choledocholithiasis or significant edema in head of pancreas
may compress the intrapancreatic portion of the CBD jaundice may be
seen in such patients
• Dullness to percussion and decreased breathing sounds in left (more
commonly) or right hemithorax suggests pleural effusion secondary to AP.

22. Diagnosis
• As per the revised Atlanta Classification (RAC)
• 2/3 of the following
• Abdominal pain consistent with AP (acute, persistent, severe, sharp, epigastric often
radiating to the back)
• A threefold or higher elevation of serum amylase or lipase levels above the upper
laboratory limit of normal
• Characteristic findings of pancreatitis by imaging
• Serum half-life of amylase (10 hours) is shorter than that of lipase (6.9-13.7 hours) and
normalizes faster.
• In patients who present within first 24-48 hours after symptoms, lipase is more
sensitive.

23. • Conditions causing rise in level of serum amylase

24. • Acute pancreatitis patients have
• Hyperglycemia
• Leukocytosis
• Abnormal LFT
• Elevation of alanine aminotransferase levels in the serum in context of AP confirmed by high
pancreatic enzyme levels has a PPV of 95% in the diagnosis of acute biliary pancreatitis.

25. Imaging studies
• Not mandatory for diagnosis, but may be helpful in determining the
need for intervention in severe AP or elucidating an elusive etiology
• Abdominal X-ray
• Non-specific
• Findings include air-fluid levels suggestive of ileus
• Cutoff colon sign D/t colonic spasm at the splenic flexure
• Sentinel loop sign
• Widening of C-loop of duodenum D/t severe pancreatic head edema

26. Colon ‘cut-off’ sign refers to mild distension of
transverse colon with collapsed descending
colon.

27. • USG
• Limited by the intraabdominal fat and increased intestinal gas
• USG is done to diagnose gallstones
• Elevated Liver enzymes, pancreatic enzymes and gall stones is 97% sensitive and 100% specific
for acute biliary pancreatitis
• CECT abdomen-pelvis
• Best modality for evaluation of pancreas
• Indications for CT include
• Diagnostic uncertainty
• Confirmation of severity based on clinical predictors
• Failure to respond to conservative treatment
• Clinical deterioration
• CT evaluation is done in portal venous phase (65-70 seconds after contrast)
• CT comments on
• Pancreatic parenchyma
• Amount of peripancreatic inflammation
• Presence of intraabdominal air/ collection
• CT scan can detect necrotizing pancreatitis from 72-96 hours after the onset of symptoms
• If diagnostic uncertainty, it can be performed at the time of admission.

28. • Abdominal MRI
• Evaluating the extent of necrosis, inflammation, and presence of free fluid
• Costly
• MRI requiring patients are often times critically ill and ICU restricted. Hence, use
of MRI in AP is limited.
• MRCP however is important in evaluation of patients with unexplained or
recurrent pancreatitis because it allows complete non-invasive visualization of the
biliary and pancreatic duct anatomy.
• Intravenous (IV) administration of secretin can be injected prior to imaging to
stimulate pancreatic juice secretion, thereby causing a transient distention of
the pancreatic duct. This helps in visualizing difficult pancreatic ducts

29. EUS role in AP
• Evaluation of persistent choledocholithiasis
• Routine ERCP may not reveal evidence of infection, and in fact may
increase the severity of the disease
• EUS>>ERCP for identifying choledocholithiasis
• EUS allows examination of biliary tree and pancreas with no risk of
worsening of the pancreatitis

30. Assessment of severity of Disease
• Ranson scoring
• Ranson and colleagues in 1974 identified 11 parameters (at the time of
admission and after 48 hours) to predict the severity of disease
• Mortality correlates with the number of positive parameters
• If > 3 parameters are fulfilled, we define as severe pancreatitis
• Disadvantage is that severity of the disease is not identified at the time of admission at
assessed 48 hours later
• PPV 50%, NPV 90%
• APACHE II (Acute physiology and chronic health evaluation)
• A GENERAL MEASURE OF SEVERITY OF THE DISEASE
• >8 SCORE defines severe pancreatitis
• PPV of 43%, NPV 89%

31. Assessment of severity of Disease
• Ranson scoring
@After 48 hours
Pa F C ks Ha Bi Bi

32. Assessment of severity of Disease
• CT severity index

33. Assessment of severity of Disease
• Most of the prognostic indices have been hindered by the
complexity, need for imaging and inability to be calculated at the
time of admission
• SIRS has been advocated as a tool to replace other scoring systems
SIRS Criteria Mortality prediction (%)
Meeting SIRS criteria 25
Transient SIRS 8
No SIRS 0

34. CRP and AP
• CRP peaks 48-72 hours after onset of pancreatitis
• Elevated CRP correlates with the severity of disease
• A CRP level of > 150 mg/ml or higher defines severe pancreatitis

35. Management of AP

37. Treatment-Fluid therapy
• Regardless of the severity, the cornerstone of treating AP is aggressive
fluid resuscitation with isotonic crystalloid solution, pain control, early
nutrition
• Rate of fluid should be individualized and adjusted as per age,
comorbidities, vital signs, mental status, skin turgor and urine output.
• Non-responsive patients to fluid therapy or have significant renal,
cardiac or respiratory comorbidities often require invasive monitoring
with central venous access and a Foley catheter.
• RL is the fluid of choice

38. • Intravascular volume depletion from fluid sequestration associated with
pancreatic, peripancreatic and systemic edema is characteristic of
patients with acute pancreatitis
• IV repletion should begin as soon as the diagnosis of acute pancreatitis is
made.
• Recommendations for fluid therapy in AP
• As per American Pancreatic Association/ International Association of
Pancreatology, fluid given should be a crystalloid 5-10 ml/kg/h until the
resuscitation goals are met
• Resuscitation goals include HR <120 bpm, MAP of 65-85 mmHg, Urine output >0.5-1
ml/kg/hr

39. Nutrition in acute pancreatitis
• Nutrition is paramount
• Acute pancreatitis is a state of intense inflammatory response
resulting in a catabolic state, increasing the caloric and nutritional
requirements
• Reduced intestinal vascular perfusion in AP results in gut mucosal
damage bacterial translocation and entry into portal circulation and
portal lymphatics Organ failure, sepsis and secondary pancreatic
infection and peripancretic necrosis
• Early nutrition reduces the bacterial migration, replenishes nutritional
requirements, increases GI blood flow, preserves integrity of bowel
mucosa and stimulates GI motility.

40. • Persistent ileus, pain, intubation may cause oral feeding impossible. Pain may
also recur when the oral route is resumed
• Nutritional support pathway
• Enteral feeding
• TPN
• Whenever possible, enteral nutrition should be used rather than a TPN
• TPN should be used only when there is intolerance to enteral feeding
• NJ feeding tube is currently favored
• It is unnecessary to wait until the pain has resolved before resuming diet in patients
with pancreatitis.
• It is recommended to begin initiating enteral feeding within 24-72 hours
• Low fat soft diet is the diet of choice.
• Patients unable to tolerate oral feed NJ/ NG feeding
• Unable to feed within 72 hours Start TPN

41. Antibiotics and pancreatitis
• Prophylactic antibiotics do not decrease the frequency of surgical
intervention, infected necrosis OR mortality in patients with severe
pancreatitis
• Use of antibiotics in pancreatitis is associated with increase in Gram
Positive Cocci infection Staphylococcus aureus and Candida.
• Use antibiotics only in
• Pre-existing infections
• Radiologic findings suggestive of infected peripancreatic fluid collection

42. Special considerations

44. Laparoscopic cholecystectomy after
pancreatitis
• If no definitive management of gallstone induced pancreatitis is done,
30% will recur
• Laparoscopic cholecystectomy is indicated for all patients with mild
acute biliary pancreatitis
• Early laparoscopic cholecystectomy (laparoscopy during the initial
admission to the hospital) is safe procedure that decreases
recurrence of the disease.
• IOC, MRCP or EUS helps in exclusion of the choledocholithiasis.
• For severe cases Conservative management for at least 6 weeks f/b
laparoscopic cholecystectomy.

45. ERCP and Acute pancreatitis
• Do NOT use ERCP during any form of pancreatitis
• ERCP is indicated only in cholangitis, persistent bile duct obstruction
• In old age patients who have poor performance status OR several
comorbidities, ERCP with sphincterotomy is a safe alternative to
prevent recurrent biliary pancreatitis

46. Complications of Acute
Pancreatitis

47. Sterile and infected peripancreatic fluid
collection
• 30-57% of patients with AP have peripancreatic fluid collection
• Peripancreatic fluid collection are not surrounded or encased by
epithelium or fibrotic capsule
• Usually self resolving, may become infected
• Evidence of gas within a fluid collection on imaging and acute
decompensation/ failure to improve after 14 days suggests infective
contamination
• CT guided fluid sampling must be done
• Drainage and IV antibiotics (carbapenem, quinolones, cephalosporins)
are indicated.

48. Necrotizing pancreatitis

49. Pancreatic necrosis and infected necrosis
• Pancreatic necrosis is defined as Non-viable pancreatic parenchyma OR
peripancreatic fat
• Can be focal necrosis OR diffuse necrosis of pancreas
• CECT is the most reliable tool to diagnose ANC. Areas of low attenuation
are seen (<40-50 HU is seen) in such conditions.
• Normal pancreatic attenuation= 100-150 HU
• In autopsy studies, about 80% of patients with death secondary to AP had
necrotic pancreas. Hence, timely identification is paramount.
• Main complication of ANC is infection. Amount of necrosis is proportional
to the risk of infection.
• Mostly infection occurs due to translocation of the enteric flora E coli,
Klebsiella, Pseudomonas and Enterococcus

50. When to suspect pancreatic necrosis?
• Prolonged fever
• Elevated WBC
• Progressive clinical deterioration
• Sepsis/SIRS/ Organ failure (> 7 days from the day of onset of AP)
• On CT scan, presence of air in pancreas confirms Necrotic Pancreatitis

51. Management of Necrotizing pancreatitis
• If Necrosis of pancreas is suspected, FNAC is done Culture is
done if a positive Gram stain/ culture is present, diagnosis is
established as “infected necrosis of the pancreas”.
• Indications for intervention
• Persistent pain
• Failure to improve clinically with conservative management
• Symptomatic biliary/ enteric obstruction
• Documented infected necrotic collection with clinical deterioration

52. Management of Necrotizing pancreatitis
• Once the infection is demonstrated IV antibiotics
• Antibiotics Carbapenem, quinolones, Metronidazole, 3rd generation
Cephalosporins and piperacillin

53. • Step up approach
• Percutaneous drainage followed by minimally invasive video-assisted retroperitoneal
debridement
• In 2018, a companion study

54. Current management protocol for Necrotic
pancreatitis [based on step-up approach]

55. Pseudocyst of pancreas

56. Pseudocyst of pancreas
• 5-15% of patients with acute
peripancreatic fluid collection (APFC)
have pseudocyst
• Pseudocyst is composed of collagen and
granulation tissue and is not lined by
epithelium
• Pseudocyst typically develops at least 4-
8 weeks later after APFC
• Nonspecific complains of patients
• Persistent pain, Early satiety,
nausea, weight loss, Elevated
pancreatic enzymes in plasma
suggest the diagnosis
• CT/MRI  Support the diagnosis
• EUS with FNA is indicated in
patients with diagnostic
uncertainty.
• High levels of amylase with
absence of mucin and low CEA
suggests characteristic feature of
pseudocyst

57. Classification of pseudocyst of pancreas

58. Management of pseudocyst
• Observation
• Spontaneous regression in 70% for
pseudocysts < 4cm, located in tail,
and no evidence of pancreatic duct
obstruction OR communication with
MPD.
• Indications for invasive therapy
• Symptomatic patients
• Diagnostic confusion [pseudocyst vs
cystic disease of pancreas]
• Endoscopic approach when
pseudocyst is present < 1cm away
from stomach/duodenum
• Trans gastric drainage
• Transduodenal drainage
• Trans papillary drainage
• If pancreatic duct stricture
endoscopic dilation and stent
placement
• Percutaneous drainage of fistula is
indicated only for septic patients
secondary to pseudocyst infection.

59. Management of pseudocyst
• Surgery indications
• Pancreatic pseudocyst not treatable by
endoscopy due to complex anatomy
• Failure to respond to endoscopic treatment
• Management depends upon the location
of the cyst
• Tail Cystogastrostomy
• Jejunum Cystojejunostomy
• Head Cystoduodenostomy
• For pseudocysts not present near the contact
of stomach/ duodenum Roux-en-Y
Cystoduodenostomy
• Cyst drainage is obtained in > 90%
following surgery
• Recurrence 12%

60. Complications of pseudocyst
• Bleeding
• Pancreaticopleural fistula
• Bile duct and duodenal
obstruction
• Rupture into abdominal cavity
• Infection

62. Pancreatic ascites and Pancreaticopleural
fistula (PPF)
• Complete disruption of the pancreatic
duct can cause fluid accumulation.
• Patient with AP who develop
significant abdominal distention and
free intraabdominal fluid Suspect
pancreatic ascites
• Management
• Drainage with endoscopic placement of
stent across the disruption
• Failed cases surgical treatment
consisting of distal resection and closure
of proximal stump.
• Posterior rupture of MPD leads to
development of PPF
• Dyspnea, chest pain, cough, abdominal pain
are usual presenting complaints
• Diagnosis by CXR, Thoracentesis, CT scan
• Usually left sided pleural effusion
• Amylase of pleural fluid > 50,000 IU
• PPF is a/w pseudocyst in about 70% patients
• Management
• Chest drainage
• Parenteral nutritional support
• Administration of octreotide
• If persistent
• Endoscopic sphincterotomy
• Stent placement
• Failure to heal
• Surgical treatment similar to pancreatic ascites

63. Vascular complications
Pseudoaneurysm
• Splenic A, SMA, Cystic A, GDA
pseudoaneurysm
• Pancreatitis elastase
pseudoaneurysm formation
• Rupture causes massive bleeding
• Hypotension and tachycardia,
sudden onset abdominal pain may
suggest rupture
• Management involves
embolization/ ligation
Vascular thrombosis
• Splenic vein, Portal vein thrombosis
• Splenomegaly and gastric varices
may occur due to splenic vein
thrombosis/ portal HTN
• Management
• Thrombolytics
• Conservative management
• If recurrent UGI bleeding due to
venous HT Splenectomy

64. Pancreatocutaneous fistula
• 0.4% of patients with acute pancreatitis may have
Pancreatocutaneous fistula
• May be coexistent with other complications
• Treatment is conservative, yet patients may require surgical
debridement