etiology & diagnosis

1. ACUTE PANCREATITIS: ETIOLOGY
& DIAGNOSIS
B D Soni
SIDSS JAIPUR

2. Various etiology
1. Mechanical ampullary obstruction
2. Alcohol
3. Smoking
4. Hypertriglyceridemia
5. Post ERCP
6. Hypercalcemia
7. Genetic mutation
8. Drugs
9. Infection & toxins
10. Trauma
11. Pancreatic divisum
12. Vascular disease
13. Autoimmune
14. others

3. Machenical ampullary obstruction
• Gall stone
reflux of bile into the pancreatic duct/
obstruction due to stone or edema
Gall stones (including microlithiasis) are most
common cause of AP ( 35-40%)
• Risk factor – male gender and stone size (3-
5mm)

4. • A serum ALT value 150 IU/L or more (3 times
of normal upper value) carries PPV of 95% for
the diagnosis of Billiary pancreatitis
• Rule – All pt with first attack of AP should have
an USG UA to search for Gall stone, CBD stone
or signs of extrahepatic billiary tract
obstruction

5. GB sludge
• Billiary sludge is a viscous suspension, may
contains microliths
• Microscopic analysis of bile in setting of GB
sludge often shows cholesterol monohydrate
crystal or calcium bilirubinate granuales
• Sludge typically found in patients with
functional or machenical bile stasis –prolong
fasting, with distal bile duct obstruction, TPN

6. Billiary sludge or microlithiasis
• Most patient – asymptomatic
• Billiary sludge is commonly found in 20-40% of
patient with acute pancreatitis with no
obvious cause
• In the absence of any other etiology billiary
sludge should be suspected as the cause in
patients with AP with a transient elevation in
Liver test.
• Microlithiasis defined as a stone size ≤ 3 mm

7. • Ceftriaxone can complex with bile to form
biliary shudge/ microlithiasis
• On ultrasound, sludge appears as a mobile,
low-amplitude echo that layers in the most
dependent part of the gallbladder and without
a DAS

8. Other causes- Ampullary obstruction
• biliary ascariasis
• Periampullary diverticula
• pancreatic and periampullary tumors
• Intraductal papillary mucinous neoplasms
(IPMN) of the pancreas

9. ALCOHOL
• Approximately 30 % of cases of AP
• Only 5% to 10% of patients who drink alcohol develop AP
• Act by increasing the synthesis of enzymes by pancreatic
acinar cells (digestive & lysosomal)
• Over-sensitization of acini to cholecystokinin
• Other machenism –
- It triggers proinflammatory pathways such as nuclear factor
κB (NF-κB)
- Also increases the expression and activity of caspases
- Alcohol decreases pancreatic perfusion
- Induces sphincter of Oddi spasm
- obstructs pancreatic ducts through the precipitation of
proteins inside the ducts
Med Clin North Am 92:889–923, 2008, Cappell MS

10. SMOKING
cigarette smoking is an independent risk factor
for acute and chronic pancreatitis by
mechanisms that are unclear

11. HYPERTRIGLYCERIDEMIA
• Serum concentrations above 1000 mg/dL-ppt
attacks of acute pancreatitis
• A triglyceride level higher than 2000 mg/dL
confirms the diagnosis in a setting of AP
• Reported in children with inherited disorders of
lipoprotein metabolism
• Acquired causes – obesity, diabetes mellitus,
hypothyroidism, pregnancy, estrogen or tamoxifen
therapy, glucocorticoid excess, nephrotic
syndrome, and beta blockers

12. HYPERCALCEMIA
• Hypercalcemia of any cause can lead to acute
pancreatitis
• Proposed mechanisms include deposition of
calcium in the pancreatic duct and calcium
activation of trypsinogen within the pancreatic
parenchyma
Mithöfer K, J Gastroenterology. 1995;109(1):239.
• Hyperparathyroidism

13. ERCP
• AP is the most common complication after ERCP,
occurring in up to 5% of patients
• 90% to 95% of patients – mild pancreatitis
• An elevation in the serum amylase concentration is
common after ERCP occurring in up to 75 % of patients ,
but acute clinical pancreatitis after ERCP is much less
common (5% among those who asymptomatic
hyperamylasemia)
Gastroenterol Clin North Am. 1990;19(4):793,Pieper-Bigelow C
• Important factors are mechanical injury from
instrumentation of the pancreatic duct and hydrostatic
injury from contrast injection

14. Post ERCP AP
• 3 % of patients undergoing diagnostic ERCP
• 5 % undergoing therapeutic ERCP
• Up to 25 percent undergoing sphincter of Oddi
manometric studies
Clin Endosc. 2012 Sep;45(3):305-12. Epub 2012 Aug 22. Kahaleh M,

15. Post-ERCP pancreatitis
• factors increase the risk of post-ERCP pancreatitis –
 Operator-related factors –
Inadequate training
Lack of experience
 Patient-related factors –
Younger age
Female sex
Normal serum bilirubin
Recurrent pancreatitis
Prior ERCP-induced pancreatitis
Sphincter of Oddi dysfunction

16. Post ERCP AP
 Procedure-related factors –
Difficult cannulation, multiple attempts
Inadvertent MPD canulation and contrast injection
Sphincter of Oddi manometry
Precut sphincterotomy
Pancreatic sphincterotomy
Minor papilla sphincterotomy
Biliary balloon sphincteroplasty
Ampullectomy
Thermal injury from electrocautery- pancreatic orifice
edema

17. Diagnosis
• Post-ERCP pancreatitis is typically diagnosed when a
patient with signs and symptoms of pancreatitis (eg,
abdominal pain and tenderness) has elevated
pancreatic enzymes (amylase and lipase) usually within
the first 24 to 48 hr after the procedure
• Patients who have undergone pancreatogram should
be admitted if four-hour amylase (Amylase after 4 hour
of procedure) level is greater than 2.5 times the upper
limit of reference

18. Prevention
All patients In high-risk patients Unclear efficacy
Careful patient selection Pancreatic duct
stent placement
Nitrates
Consider alternative
modalities
Single-dose rectal
indomethacin
Protease inhibitors
Provider training
and experience
Intravenous fluid
hydration
Guide wire-assisted
cannulation

19. GENETIC MUTATIONS
• Inherited forms of pancreatitis may present as
recurrent acute pancreatitis but eventually
progress to chronic pancreatitis
-Serine protease 1 gene (PRSS1)
-cystic fibrosis gene (CFTR)
-serine protease inhibitor Kazal type 1 (SPINK1)

20. DRUGS
Various machenism –
 Immunologic reactions - 6-mercaptopurine,
aminosalicylates, sulfonamides
 Direct toxic - diuretics, sulfonamides
 Accumulation of a toxic metabolite - valproic
acid, didanosine, pentamidine, tetracycline
erythromycin, metronidazole
 Ischemia - diuretics, azathioprine
 Intravascular thrombosis - estrogen
 Increased viscosity of pancreatic juice - diuretics and
steroids

21. Anti cancer drugs
• 6- Mercaptopurine
• Azathioprine
• L- Asparginase
• Oxaliplatin
• Rarely by Ifosfamide

22. INFECTIONS
• Viruses – Mumps, coxsackievirus, hepatitis B,
cytomegalovirus, varicella-zoster, herpes
simplex, HIV
• Bacteria – Mycoplasma, Legionella, Leptospira,
Salmonella
• Fungi – Aspergillus
• Parasites – Toxoplasma, Cryptosporidium,
Ascaris

23. Miscellaneous Conditions
• Blunt and penetrating abdominal trauma can be
associated with AP in 0.2% and 1% of cases,
respectively
• Prolonged intraoperative hypotension and
excessive pancreatic manipulation during
abdominal surgery can also result in AP
• Pancreatic ischemia in association with acute
pancreatic inflammation can develop after splenic
artery embolization
• Other rare causes include scorpion venom stings
and perforated duodenal ulcers

24. Revised Atlanta 2012
ORIGINAL ARTICLE
Peter A Banks, Acute Pancreatitis Classification Working Group

25. Definition of diagnosis of acute
pancreatitis
• Diagnosis requires any 2 of the following –
a. Abdominal pain consistent with acute
pancreatitis
b. Serum lipase activity (or amylase activity) at least
three times greater than the upper limit of
normal
c. Characteristic findings of acute pancreatitis on
contrast-enhanced computed tomography
(CECT) and less commonly magnetic resonance
imaging (MRI) or transabdominal
ultrasonography.

26. Imaging when: for diagnosis
• If abdominal pain suggests strongly that acute
pancreatitis is present, but the serum amylase
and/or lipase activity is less than three times
the upper limit of normal, as may be the case
with delayed presentation, imaging will be
required to confirm the diagnosis

27. Definition of onset of acute pancreatitis
• The onset of acute pancreatitis is defined as
the time of onset of severe abdominal pain at
first during entire course of disease (not the
time of admission to the hospital).

28. Definition of types of acute pancreatitis
• Acute pancreatitis can be subdivided into two
types –
1. Interstitial oedematous pancreatitis
2. Necrotising pancreatitis.

29. Interstitial oedematous pancreatitis
• Defined as diffuse (or occasionally localised)
enlargement of the pancreas due to
inflammatory oedema.

30. CECT: Interstitial oedematous
pancreatitis
• Pancreatic enlargement
due to edema
• pancreatic parenchyma
shows relatively
homogeneous
enhancement, and the
peripancreatic fat
stranding
• There may also be some
peripancreatic fluid

31. Outcome: AIOP
• The clinical symptoms of interstitial
oedematous pancreatitis usually resolve within
the first week

32. Necrotising pancreatitis
• Defined as pancreatic inflamation associated with
necrosis of the pancreatic parenchyma, the
peripancreatic tissue or both
• Necrotising pancreatitis most commonly
manifests as necrosis involving both the pancreas
and peripancreatic tissues and less commonly as
necrosis of only the peripancreatic tissue, and
rarely of the pancreatic parenchyma alone

33. Necrotising pancreatitis
• The impairment of pancreatic perfusion and signs
of peripancreatic necrosis evolve over several
days – early CECT may underestimate the
eventual extent of pancreatic and peripancreatic
necrosis.
• After the first week of the disease, a non-
enhancing area of pancreatic parenchyma should
be considered to be pancreatic parenchymal
necrosis.

34. Necrotising pancreatitis
• The natural history of pancreatic and
peripancreatic necrosis is variable, because it
may remain solid or liquefy, remain sterile or
become infected, persist, or disappear over
time.

35. Infected pancreatic necrosis
• Pancreatic and peripancreatic necrosis can
remain sterile or become infected
• No absolute correlation between the extent of
necrosis and the risk of infection and duration
of symptoms
• Rare during the first week
• The diagnosis of infected pancreatic necrosis is
important because of the need for antibiotic
treatment and likely active intervention

36. Infected pancreatic necrosis
• The presence of infection can be presumed –
When there is extraluminal gas in the pancreatic
and/or peripancreatic tissues on CECT
OR
When percutaneous, image-guided, fine-needle
aspiration (FNA) is positive for bacteria and/or
fungi on Gram stain and culture

37. Fate of PN
Necrosis Liquefaction Suppuration (PUS)

38. The original Atlanta Classification proposed the
term ‘pancreatic abscess’ to define a ‘localised
collection of purulent material without
significant pancreatic/peripancreatic necrosis’
This finding is extremely uncommon, and
because the term is confusing and has not
been adopted widely, the term ‘pancreatic
abscess’ is not used in the current classification

39. Infected pancreatic necrosis
• The development of secondary infection in
pancreatic necrosis is associated with
increased morbidity and mortality

40. A 47-year-old man with acute necrotising pancreatitis complicated by infected
pancreatic necrosis. There is a heterogeneous, acute necrotic collection (ANC) in the
pancreatic and peripancreatic area (white arrows pointing at the borders of the ANC)
with presence of gas bubbles (white arrowheads), usually a pathognomonic sign of
infection of the necrosis

41. ? Infection from where
• Translocation of bacteria
• Percutaneous procedure- FNA, PCD
• Endoscopic intervention- internal drainage
• Rarely -Worms causing acute pancreatitis

42. COMPLICATION OF AP

43. Definition of organ failure
• Three organ systems should be assessed to
define organ failure:
respiratory, cardiovascular and renal
• Organ failure is defined as a score of 2 or more
for one of these three organ systems using the
Modified Marshall Scoring System (MMSS)

45. Local complication of acute pancreatitis
Local complications are –
1. Acute peripancreatic fluid collection (AFC)
2. Pancreatic pseudocyst (PP)
3. Acute necrotic collection (ANC)
4. Walled-off necrosis (WOPN)

46. Local complication
• Other local complications of acute pancreatitis
include gastric outlet dysfunction, splenic and
portal vein thrombosis, and colonic necrosis.

47. Local complication
Local complications should be suspected –
- There is persistence or recurrence of abdominal
pain,
- Secondary increases in serum pancreatic enzyme
activity,
- Increasing organ dysfunction,
- Development of clinical signs of sepsis, such as
fever and leucocytosis.
Prompt CECT to be done in these cases

48. CECT
• The morphologic description of local
complications is necessary for accurate
diagnosis However Local complications alone,
do not define the severity of acute
pancreatitis.

49. APFC (Acute Peripancreatic Fluid
Collection)
• Peripancreatic fluid associated with interstitial
oedematous pancreatitis with no associated
peripancreatic necrosis, usually seen within
the first 4 weeks after onset of interstitial
oedematous pancreatitis.

50. CECT: APFC
• Occurs in the setting of interstitial oedematous
pancreatitis
• Homogeneous collection with fluid density
• Confined by normal peripancreatic fascial
planes
• No definable wall encapsulating the collection
• Adjacent to pancreas (no intrapancreatic
extension)

51. acute interstitial oedematous pancreatitis and acute peripancreatic fluid collection
(APFC) in the left anterior pararenal space. The pancreas enhances completely, is
thickened, and has a heterogeneous appearance due to oedema. APFC has fluid
density without an encapsulating wall

52. A follow up CT shows complete resolution of the APFC with minimal residual
peripancreatic fat stranding.

53. APFC
• Most acute fluid collections remain sterile and
usually resolve spontaneously without
intervention
• When a localised APFC persists beyond 4
weeks, it is likely to develop into a pancreatic
pseudocyst

54. PSEUDOCYST OF PANCREASE
An encapsulated collection of fluid with a well
defined inflammatory wall usually outside the
pancreas with minimal or no necrosis, usually
appears more than 4 weeks after onset of
interstitial oedematous pancreatitis

55. CECT : PP
• Well circumscribed, usually round or oval
• Homogeneous fluid density
• No solid component
• Well defined wall, completely encapsulated
• Maturation usually requires >4 weeks after
onset of acute pancreatitis; occurs after
interstitial oedematous pancreatitis

56. A 40-year-old man with two pseudocysts in the lesser sac 6 weeks after an episode of acute
interstitial pancreatitis on CT (A, B).Note the round to oval, low-attenuated, homogeneous fluid
collection with a well defined enhancing rim (white arrows pointing at the borders
of the pseudocysts), but absence of areas of greater attenuation indicative of non-liquid
components. White stars denote normalenhancing pancreas

57. PP
• If aspiration of cyst content is performed, there is
usually a markedly increased amylase activity
• A pancreatic pseudocyst is thought to arise from
disruption of the main pancreatic duct or its intra-
pancreatic branches without any recognisable
pancreatic parenchymal necrosis
• Although CECT is the imaging modality used most
commonly to describe pseudocysts, MRI or
ultrasonography may be required to confirm the
absence of solid content in the collection.

58. PP
• A pseudocyst may also arise in the setting of acute
necrotising pancreatitis as a result of a
‘disconnected duct syndrome’, whereby
pancreatic parenchymal necrosis of the neck or
body of the gland isolates a still viable distal
pancreatic remnant
• A pseudocyst may be evident many weeks after
operative necrosectomy due to localised leakage
of the disconnected duct into the necrosectomy
cavity

59. ANC (acute necrotic collection)
• During first 4 week, a collection containing
variable amounts of both fluid and necrosis
associated with necrotising pancreatitis
• The necrosis can involve the pancreatic
parenchyma and/or the peripancreatic tissues

60. CECT: ANC
• Occurs only in the setting of acute necrotising
pancreatitis
• Single Or multiple loculated Heterogeneous
collection and non-liquid density of varying
degrees in different locations (some appear
homogeneous early in their course)
• No definable wall encapsulating the collection
• Location—intrapancreatic and/or
extrapancreatic

61. Acute necrotic collections (ANC) in a 44-year-old man with acute necrotising
pancreatitis involving only the peripancreatictissues. Note enhancement of the entire
pancreatic parenchyma (whitestars) and the heterogeneous, non-liquid
peripancreatic components in the retroperitoneum (white arrows pointing at the
borders of the ANC).

62. The ANC in the same patient as (A) but imaged a few weeks later demonstrate a heterogeneous
collection with areas of fat (black arrowheads) surrounded by fluid density, and areas which
have a slightly greater attenuation (black arrows) than seen in collections without necrosis
White arrows denote border of ANC; white stars denote enhancement of pancreatic
parenchyma

63. ANC
• An ANC may be associated with disruption of the
main pancreatic duct within the zone of
parenchymal necrosis and can become infected
• Sequential imaging may be useful to characterise
acute collections
• Within the first week of the disease, it may be
difficult to differentiate an APFC from an ANC, as
both types of collections may appear as areas
with fluid density

64. ANC
• After the first week, the distinction between
these two important types of collections
becomes clear, such that at this stage of
necrosis, a peripancreatic collection associated
with pancreatic parenchymal necrosis can be
properly termed an ANC and not an APFC
• MRI, USG or EUS may be helpful to confirm the
presence of solid content in the collection.

65. WON
• A mature, encapsulated collection of
pancreatic and/or peripancreatic necrosis that
has developed a well defined inflammatory
wall, usually appears >4 weeks after onset of
necrotising pancreatitis.

66. CECT: WON
• Heterogeneous with liquid and non-liquid
density with varying degrees of loculations
(some may appear homogeneous)
• Well defined wall, that is, completely
encapsulated
• Location—intrapancreatic and/or
extrapancreatic
• Maturation usually requires 4 weeks after
onset of acute necrotising pancreatitis

67. A heterogeneous, fully encapsulated collection is noted in the pancreatic and peripancreatic
area Non-liquid components of high attenuation (black arrowheads) in the collection are noted.
The collection has a thin, well defined, and enhancing wall (thick white arrows).

68. A heterogeneous, fully encapsulated collection is noted in the pancreatic and
peripancreatic area. A largely liquefied collection in the bed of the pancreas is
observed with non-liquid components representing areas of trapped fat (black
arrowheads).

69. T2-weighted MRI showing the true heterogeneity of the collection. Black
arrowheads denote areas of necrotic debris surrounded by fluid (white on T2-
weighted image).

70. WON
• WON derives from necrotic pancreatic
parenchyma and/or necrotic peripancreatic
tissues and may be infected, may be multiple, and
may be present at sites distant from the pancreas
• CECT may not readily distinguish solid from liquid
content and, for this reason, WOPN may be
misdiagnosed as a pancreatic pseudocyst
• MRI, USG or EUS may be required for this
distinction.

71. Definition of systemic complications
• Exacerbation of pre-existing co-morbidity, such
as coronary artery disease or chronic lung
disease, precipitated by the acute pancreatitis
is defined as a systemic complication.

72. Phases of acute pancreatitis
• two overlapping phases in this dynamic
disease process with two peaks of mortality:
early and late
• The early phase, which usually lasts for the
first week, is followed by a second late phase
which can run a protracted course from weeks
to months

73. Early phase
• During the early phase, systemic disturbances
result from the host response to local pancreatic
injury
• This early phase is usually over by the end of the
first week but may extend into the second week
• Cytokine cascades are activated by the pancreatic
inflammation which manifest clinically as the
systemic inflammatory response syndrome
• When SIRS is persistent, there is an increased risk
of developing organ failure

74. SIRS
Signs of systemic inflammatory response syndrome (SIRS)
SIRS—defined by presence of two or more criteria of following
Heart rate >90 beats/min
Core temperature <36°C or >38°C
White blood count <4000 or >12000/mm3
Respirations >20/min or PCO2 <32 mm Hg

75. Early phase
• During the early phase, organ failure described
as “ transient OF” and “persistent OF”
• ‘Transient organ failure’ if the organ failure
resolves within 48 h with supportive Rx
• ‘Persistent organ failure’ if organ failure
persists for >48 hrs
• If organ failure affects more than one organ
system, it is termed multiple organ failure
(MOF).

76. Late phase
• The late phase is characterised by persistence of
systemic signs of inflammation or by the presence of
local complications
• Late phase occurs only in patients with moderately
severe or severe acute pancreatitis
• Local complications evolve during the late phase
• It is important to distinguish the different morphologic
characteristics of the local complications by radiologic
imaging, because these local complications may have
direct implications for management

77. Definition of severity of acute
pancreatitis
• First, on admission, it is important to identify
patients with potentially severe acute pancreatitis
who require aggressive early treatment
• Second, in a secondary care setting, clinicians
need to identify such patients for possible transfer
to specialist care
• Third, for specialists who receive such referrals,
there are advantages to stratifying these patients
into subgroups based on the presence of
persistent organ failure and local or systemic
complications

79. Why not early CECT
• First, the presence and extent of pancreatic and
peripancreatic necrosis may not be defined clearly on
imaging during the first few days of disease. When
necessary, a CECT 5–7 days after admission is more
reliable in establishing the presence and extent of
pancreatic necrosis
• Second, the extent of morphologic changes and necrosis
is not directly proportional to the severity of organ
failure
• Third, even if imaging during the first week identifies the
presence of peripancreatic fluid collections or pancreatic
necrosis, in general no treatments are required for these
conditions at that time.

80. CTSI (balthazar’s)
• CTSI Depends on degree of pancreatic
imflamation and percentage of pancreatic
necrosis

81. Computed Tomography Severity Index (CTSI) for Acute Pancreatitis
Features points
Pancreatic Inflammation
Normal pancreas 0
Focal or diffuse pancreatic enlargement 1
Intrinsic pancreatic alterations with peripancreatic 2
fat inflammatory changes
Single fluid collection/or phlegmon 3
Two or more fluid collections or gas, in or 4
adjacent to the pancreas
Pancreatic Necrosis
None 0
≤30% 2
30%-50% 4
>50% 6

82. CTSI
CTSI Morbidity Mortality
0-3 8% 3%
4-6 35% 6%
7-10 92% 17%

83. Take home msg
• Gall stone and alcohol consist most common cause
accounting 70-75% of all cause
• All pt with first attack of AP should have an USG UA to
search for Gall stone, CBD stone or signs of extrahepatic
billiary tract obstruction
• AP is the most common complication after ERCP, occurring
in up to 5% of patients
• Post ERCP pancreatitis requires high suspicion for the
diagnosis , need to be suspected & evaluated if any
inadvertent event occurs during the procedure.

84. Take home msg
• Acute pancreatitis is an evolving, dynamic condition
and that the severity may change during the course of
the disease
• AP has got two peak of mortality in early phase due to
MOF and in late phase due to infective complications
• The accurate description of local complications,
including the presence of fluid or necrosis in or around
the pancreas, the presence or absence of infection is
necessary to decide need for an intervention

85. Take home msg
• Although local complications may be identified
during the early phase, they are not the
predominant determinants of severity
• Extent of morphologic changes is not directly
proportional to the severity of organ failure
• The definition of severe or moderately severe
acute pancreatitis in the early phase depends on
the presence and duration of organ failure

86. THANK YOU….